[Correlations of CT and MRI imaging of the lateral pterygoid muscle]. On the basis of 15 CT scan and MRI studies of normal volunteers, the authors describe the features the lateral pterygoid muscle. A good correlation appears between CT and MR images which would be useful in the staging of tumors in this space, and in the pathophysiology of internal derangements of the temporomandibular joint (TMJ).


[Unusual sites of Pott's disease. Apropos of fourteen cases]. The diagnosis of Pott's disease is generally easy exception unusual sites whose diagnosis is requires cross-section imaging and needle biopsy. The authors report 14 cases of atypical forms of Pott's disease: 7 cases of centro-somatic forms 4 cases of sub-occipital Pott's disease, 2 cases of posterior arch and one case of sub-ligamentous vertebral tuberculosis. The radiological diagnosis of Pott's disease is suggested by the presence of a paravertebral abscess noted in 12 cases tuberculous spondylitis associated in 3 cases and multifocal involvement in 9 cases.


[Cystic lymphangioma of the neck in adults. Contribution of ultrasonography and computed tomography. Apropos of a case]. Authors present a case of cystic lymphangioma of the neck in an adult patient. Cystic lymphangioma of the neck can simulate other benign lesions and occasionally extend into the mediastinum. Using computed tomography and ultrasound, the authors are able to confirm the suspected diagnosis, exclude other diagnostic considerations, and demonstrate absence of mediastinal extension. Opportunity of such diagnosis in adult is no frequent.


[Cervico-mediastinal cystic lymphangioma]. Anterior cervico-mediastinal tumors in children, especially if they are cystic, often correspond to the diagnosis of cystic hemolymphangioma. CT and Chest US are contributive for the diagnosis and the pre-operative staging.


[Post-traumatic gas in children. Apropos of a case]. The authors report a case of post-traumatic gas in the portal vein in a child. They stress the rarity of this lesion in such circumstances and recall the radiological signs together with the differential diagnoses and the principal aetiologies.


[Vertebral osteosclerosis, sacro-iliitis and palmoplantar dermatitis. Apropos of a case]. The authors report a case of aseptic vertebral osteitis which they classify in the context of SAPHO in view of the association with unilateral sacro-ileitis and palmoplantar dermatitis. They stress the importance of recognizing this disease which is initially suggestive of either a bone disease (Paget's disease, bone metastasis) or infectious discospondylitis.


[Disorders of relaxation of the lower esophageal sphincter appearing after resection of a mid-thoracic esophageal pulsion diverticulum]. A pulsion diverticulum of the mid-thoracic oesophagus was resected because of severe dysphagia. A subdiverticular myotomy was associated for the treatment of non-propagated oesophageal contractions, without oesophageal low-sphincter abnormalities. Three months post-operatively, the dysphagia was still present and manometry showed the absence of lower sphincter relaxation after 45 percent of deglutitions; a lower oesophageal sphincter myotomy was performed, resulting in correction of the dysphagia and of the sphincter relaxation abnormalities. The deficit of the inhibitory nervous mechanism, responsible for abnormalities of lower oesophageal sphincter relaxation, was present in the entire intramural oesophageal plexus, but, was not symptomatic at the level of the IOS prior to resection of the diverticulum.


[Atypical pleural effusion by transdiaphragmatic communication. Apropos of two cases: chylothorax and hydrothorax]. We report two cases of pleural effusion in which a subdiaphragmatic cause was noted. In both cases it was necessary to obliterate a defect in the diaphragm via a thoracic incision. In one case, a left chylothorax occurred in a patient with hepatic cirrhosis. In this case, it was postulated that the normal lymphatic pathway through the right hemidiaphragm could have been stopped by pleural sequelae from right lobectomy. In the other case, a right pleural effusion occurred after peritoneal dialysis. It is a well known pathological entity: the structural defect can be observed by separation of collagen bundles in the tendinous diaphragm. This type of pleuro-peritoneal communication is well known in women suffering from menstrual pneumothorax or in patients treated by peritoneal dialysis.


[Thymus in posterior mediastinal localization. Apropos of a case in a child]. Posterior and upper mediastinal localization of the thymus gland is uncommon in young children. Presenting symptoms and signs are very variable from incidental diagnosis to bronchopneumonial with atelectasias of the left upper Chest X-Ray and CT Scan are sufficient to make the diagnosis. Treatment of complicated forms with bronchial compression requires thoracotomy and surgical excision.


[Is ex situ surgery of the liver useful for difficult hepatic resections?]. Five cases of hepatic tumor deemed unresectable by conventional techniques are presented to illustrate the potential benefit offered by complete hepatic vascular exclusion (Pringle maneuver associated with inferior vena cava clamping below and above the liver). The most extensive and difficult liver resections may be achieved, with possible venous reconstruction, if the clamping period is not interrupted. Hepatic vascular exclusion may exceed one hour, up to 85 minutes in this series, with a good liver tolerance, in the absence of preoperative liver dysfunction. The advantages and disadvantages of the ex situ extracorporeal liver resections performed under similar circumstances are discussed. The authors consider that the role of ex situ liver procedures should be very limited.


[Primary colonic intussusception protruding from the anus in adults. Two cases]. The authors report two cases of colonic intussusception in the adult protruding from the anus--or colon-anal intussusception--, not due to a tumor. The first case was a chronic ileo-caeco-colique intussusception, the second case was an acute colo-rectal intussusception. Colo-anal intussusceptions are very rare: less than twenty cases have been described since 1925 in adults. The absence of a tumor origin in our cases represents a special feature, as only three other similar cases have been described. The surgical treatment in both cases was primary colonic resection without colostomy. The surgical treatment of the first case was subtotal colectomy with ileo-rectal anastomosis. The second case was primarily reduced by barium enema which allowed optimal secondary surgical resection of a prepared colon.


[Radiological anatomy of the wrist].

[Radiological anatomy of the wrist]. The wrist is an articular complex composed of the radio-carpal, distal radio-ulnar and all of the carpal joints. Despite progress in imaging techniques, conventional radiology with plain x-rays and arthrography are still very widely used. Plain x-rays, numerous because of the anatomical complexity of the wrist, must be selected in relation to the clinical context and suspected diagnosis and must be performed according to a perfect technique. Contrast arthrography may be uni-, bi-, or tri-compartmental depending on the information required. It allows assessment of the integrity of the intra-articular synovial and ligamentous structures. The specific indications for computed tomography are uncommon, but those of MRI are becoming increasingly frequent due to refinement of the machines, especially the development of surface coils.


[Arthrography of the wrist].

[Arthrography of the wrist]. The procedure, followed by the normal radiological anatomy of the various joint compartments of the wrist are described. The main indications (especially post-traumatic indications) and abnormal findings are then investigated.


[MRI of the wrist joint].

[MRI of the wrist joint]. Due to the development of new surface coils and the use of thin slices, MRI has become an essential diagnostic tool in wrist pathology. After several technical considerations, the authors describe the normal MRI appearance of the various anatomical structures of the wrist, particularly the triangular fibrocartilaginous complex of the wrist and the elements of the carpal tunnel. They review the principal indications for MRI: chronic diseases such as carpal tunnel syndrome and traumatic ligamentous and cartilaginous lesions. The bone marrow lesions detected in the presence of occult fractures and osteonecrosis of the lunate or scaphoid are then briefly considered. The diagnostic criteria of median nerve compression (carpal tunnel syndrome) include morphological and signal changes in the nerve, abnormal palmar convexity of the flexor retinaculum and signs of tenosynovitis of the intracarpal flexor tendons. However, in practice, MRI is only useful when there is disagreement between the clinical and EMG findings and in postoperative recurrences, in which case it may reveal insufficient section of the retinaculum or the presence of exuberant postoperative fibrosis responsible for persistent nerve compression. Traumatic tears of the triangular fibrocartilage are characterised by a linear high signal intensity image (on T1 and T2 weighted sequences), usually situated in the periphery of the articular disk. Degenerative lesions tend to be central, within the disk and are frequently observed after the age of 40 years.


[Instability of the carpal bones].

[Instability of the carpal bones]. The understanding of carpal instability and their radiological signs are based on a knowledge of the anatomy and complex physiology of the wrist. This article successively deals with the physiological anatomy, radiological technique, normal static and dynamic radiological features, radiographic signs of various types of instability and therapeutic principles.


[Scaphoid bone].

[Scaphoid bone]. The scaphoid is the most important carpal bone due to the frequency of its pathological involvement. Two points of radiological anatomy are stressed: the presence of the scaphoid tubercle whose projection gives rise to the scaphoid ring, the solid radio-capitatum ligament which bridges the scaphoid. Scaphoid fracture represents 70% of all carpal bone fractures and its presence must therefore be meticulously investigated on appropriate x-rays or on tomographies or CT scans, rather than by the classical repeat examination a fortnight later. CT provides good analysis of scaphoid fragments when consolidation is delayed (pseudarthrosis), allowing earlier and more justified indications for surgery. The wrist ligaments are poorly visualised by MRI at the present time; but it allows study of the cartilage and, most importantly, is a decisive examination when there is a doubt about bone vitality.


[Kienböck's disease. Current data].

[Kienböck's disease. Current data]. Aseptic osteonecrosis of the lunate bone is a rare disease of unknown aetiology. The mechanical theory of shearing of the lunate underneath the radius is generally accepted, especially in the presence of a short ulna, even if it is insufficient. The diagnosis is exclusively radiographic and requires, in the early stages, the use of MRI which is more sensitive and specific than bone scan. Plain X-rays allow the disease to be classified into various stages, which determine the therapeutic indications. Many treatments have been proposed, but the follow-up is often inadequate. Simple immobilization is atraumatic, but its efficacy is highly controversial. Equalization of the two bones, usually by shortening the radius, is the most widely used technique and, with a follow-up of more than 20 years, appears to be effective in 80% of subjects. Revascularization of the lunate has been proposed in the early forms. Partial arthrodeses are indicated in the advanced forms. Radio-carpal arthrodesis or denervation of the wrist are indicated in the presence of osteoarthritis. Functional sequelae are frequent in these young subjects, who are often manual workers.


[Distal radio-ulnar joint. Traumatic and degenerative diseases]. The distal radio-ulnar joint participates in the biomechanics of the wrist both by transmission of carpal stresses and by its role in the mobility of the wrist. Fractures of the distal radio-ulnar joint are often missed as they are frequently only a radiation of fractures of the radius to the distal radio-ulnar joint. Computed tomography is the most useful examination to assess the severity of these lesions. Distal radio-ulnar dislocations may also be associated with fractures of the radius, but usually occur in isolation. The diagnosis is difficult, as the slightest rotation on plain X-rays interferes with the evaluation criteria. A CT scan in the neutral position and in pronation and supination is the examination of choice for dislocations and subluxations, but must be interpreted according to strict criteria. In contrast, a tea of the triangular ligament can only be assessed on arthrography and the distinction between traumatic and degenerative rupture is difficult. The patient's age, the site of the perforation and the length of the ulna are important elements in the diagnostic decision. MRI appears to be a promising examination for investigation of this joint, but the quality of the images is not yet perfectly reproducible.


[Rheumatic wrist].

[Rheumatic wrist]. The wrist is frequently involved in the course of inflammatory rheumatism. The clinical and radiological features of the arthritis may guide the diagnosis when wrist involvement is isolated. The rheumatoid wrist may associate articular and tendon sheath synovitis, nerve compressions, muscle atrophy and deformities. X-rays reveal increased volume of the soft tissues, followed by cartilaginous destruction. Magnetic resonance imaging may detect the lesions early in their course. RS3PE, rheumatoid arthritis of the elderly, never induces destructive lesions. Still's disease is distinguished from rheumatoid arthritis by the predominant involvement of the radiocarpal and intercarpal joints with relative sparing of the metacarpo-phalangeal and proximal interphalangeal joints. Jaccoud's hand may be observed in the course of lupus with metacarpo-phalangeal dislocation of capsulo-ligamentous origin without cartilaginous destruction. Wrist involvement is often asymmetrical in ankylosing spondylitis. In psoriatic rheumatism, arthritis of the wrist is similar to that observed in rheumatoid arthritis, but demineralization is less common and occurs later and constructive lesions are associated with pinching.


New alcohol resistant strains of Saccharomyces cerevisiae species for potable alcohol production using molasse. Two alcohol resistant strains of Saccharomyces cerevisiae species were isolated from a Greek vineyard plantation. The strain AXAZ-1 gave a concentration of 17.6% v/v alcohol and AXAZ-2 16.5%, when musts from raisin and sultana grapes, respectively, were employed in alcoholic fermentations. They were found to be more alcohol tolerant and fermentative in the fermentation of molasse than the traditional baker's yeast. Specifically, using an initial [symbol: see text] Be density of 16 [symbol: see text] Be at the repeated batch fermentation process, in the first as well as fourth batch, the better AXAZ-1 gave final [symbol: see text] Be densities of 6.0 and 10.5 respectively, and the baker's yeast 11.6 and 14.5.


Effect of mixture of surfactants and adsorbents on anaerobic digestion of water hyacinth-cattle dung. In an effort to improve the anaerobic digestion of water hyacinth-cattle dung with enriched methane content, the effects of mixtures of surfactant-surfactant, adsorbent-adsorbent and surfactant-adsorbent have been studied in various combinations. Among the combinations tested, bentonite and gelatin, gelatin and Tegoprens 43, sodium lauryl sulfate and Tegoprens 42, and Tegoprens 47 and Tegoprens 63 showed more than a 100% increase in gas production with higher methane yield.


Purification and characterization of lamb pregastric lipase. Lamb pregastric lipase was purified from a commercial source using delipidation, solubilization with KSCN, acid-precipitation, pepsin-digestion, affinity chromatography with agarose-Cibacron Blue F3GA, gel filtration, and elution from a native 10% (w/v) polyacrylamide gel. The enzyme had a single subunit of 68,000 Da with maximum esterase activity when measured at pH 6.0 and 30 degrees C. The enzyme preferentially hydrolyzed short- and medium-chain (C4, C6, and C8) synthetic esters and short-chain (C4 and C6) monoacid triglycerides. The NH2-terminal sequence demonstrated high homology with gastric and lingual lipases.


A biosensor for L-proline determination by use of immobilized microbial cells. A biosensor to quantify L-proline within 10(-5)-10(-3) mole/L concentration is described. Immobilized Pseudomonas sp. cells grown in a medium containing L-proline as the only source of carbon and nitrogen were used to create the biosensor. The cells oxidized L-proline specifically consuming O2 and did not react with other amino acids and sugars. The change in oxygen concentration was detected with a Clark oxygen membrane electrode. The cells were immobilized by entrapment in polyvinyl alcohol (PVA) cryogel. The resultant biocatalyst had a high mechanical strength and retained its L-proline-oxidizing ability for at least two months.


A biocompatible needle-type glucose sensor based on platinum-electroplated carbon electrode. A biocompatible needle-type glucose sensor with a 3-electrode configuration was constructed. A platinum-electroplated carbon stick was used as the working electrode, Ag/AgCl as the reference electrode, and a disposable hypodermic needle made of stainless steel as the counter electrode. A Nafion membrane, an immobilized glucose oxidase (GOD) membrane, and a biocompatible membrane with diffusion-limiting effect were coated successively onto the working electrode. The sensor showed a rapid response (< 120 s in batch operation), good reproducibility (RE < 3%), good stability (over 36 h in control serum), a wide dynamic range (5-600 mg/dL glucose), and superior biocompatibility. It was used to determine glucose in serum. The data obtained from the sensor showed good agreement with that from a clinical autoanalyzer (R > 0.95).


Ethanol production from cellulose by coupled saccharification/fermentation using Saccharomyces cerevisiae and cellulase complex from Sclerotium rolfsii UV-8 mutant. Using cellulase/hemicellulase complex of Sclerotium rolfsii UV-8 mutant and Saccharomyces cerevisiae for fermentation, the coupled saccharification/fermentation (CSF) of 15% AT-rice straw was carried out at 40 degrees C, pH 4.5 for the first 24 h and further incubation was performed at 30 degrees C for 72 h. Increasing the amount of cellulase activity from 3-12 IU FPA/g of substrate resulted in increased yields of ethanol from 1.5-3.6% in 96 h. It has been observed that the coupled system was advantageous over the two stage (separate hydrolysis/fermentation) system as it produced higher amounts of ethanol from cellulose (3.6% as compared to 2.3% ethanol from rice straw).


Effects of potassium on the ethanol production rate of Saccharomyces cerevisiae carrying the plasmid pCYG4 related with ammonia assimilation. The influence of potassium on ethanol production by Saccharomyces cerevisiae wild type and AR5 cells carrying the plasmid pCYG4 was investigated. This plasmid carries the glutamate dehydrogenase gene conferring an 11-fold higher level of expressed enzyme activity over the wild type cells. All experiments were carried out in batch culture with medium supplemented to different potassium concentrations up to 180 mM. Maximum ethanol production rate was observed in the AR5 cells grown in medium supplemented with 3.5 mM of potassium ions. Glucose uptake rate increased with increasing potassium up to 60 mM, but higher concentrations depressed glucose uptake rate in both strains. Furthermore, the wild type cells showed higher growth rate, ethanol production, and glucose consumption rate than the AR5 cells. These lower rates in the AR5 cells could be explained by repression of potassium uptake by an enhancement of ammonium feeding, and greater energy requirements by these cells due the presence of the plasmid.


Protection of Aspergillus niger cellulases by urea during growth on glucose or glycerol supplemented media. The cellulase enzymes of Aspergillus niger were found to undergo catabolite repression in the presence of glucose and glycerol accompanied by sudden drop in pH of the fermentation medium below 2.0. This sudden drop in pH caused inactivation of cellulolytic enzymes produced by Aspergillus niger. The supplementation of nitrogen sources, especially urea, protects A. niger cellulases from inactivation caused by a sudden drop in pH, since urea helped to maintain the pH of the fermentation medium between 3.5 and 4.5. The role of urea in the protection of cellulase was more prominent when it was used in combination with glycerol (5%).


Adsorption of phenylalanine from casein hydrolysates. The specific diet therapy for phenylalaninemies requires special hydrolysates of proteins where phenylalanine content is reduced to approx 0.53% of the amino acids present. In previous work, Amberlite XAD-4 resin was used to retain phenylalanine from an acid hydrolysate of casein. It was also observed that the adsorption isotherm of phenylalanine on the resin showed a convex pattern that allowed a frontal chromatography. In the present study, this technique was improved, aiming at the processing of larger hydrolysates volumes. This was achieved with the use of two sequential columns (50 x 1 cm), each containing 34 cm3 of the resin, and joined through a 1-cm long tygon, tube 1 mm diameter. This system was used to process 100 mL of casein acid hydrolysate containing 12 g of free amino acid and allowed the reduction of phenylalanine content from 4.39 to 0.14% of the total amino acids present, within 1 h. It was also observed that this technique could not be directly applied to enzymatic hydrolysates of casein unless they were especially produced for this purpose, which means that in this kind of hydrolysate, phenylalanine should be free or linked in small adsorptive peptides.


Protoplast fusion of beta-glucosidase-producing Aspergillus niger strains. Protoplast fusion, induced by polyethylene glycol and Ca2+, was carried out between two auxotrophic strains of Aspergillus niger. The fusion frequency ranged from 6.2 x 10(-2) - 9.1 x 10(-2). After induced haploidization of a diploid, various segregants showing combinations of the parental genetic markers were isolated. Unlike diploids, haploid segregants exhibited greater variations in their morphology and beta-glucosidase activities. One segregant showed a 2.5-fold increase in beta-glucosidase activity over those of the parents. Thus, this method appears promising for creating new recombinant strains of A. niger with improved beta-glucosidase activities.


Synergism between Clostridium thermocellum cellulases cloned in Escherichia coli. We have obtained a synergistic effect during degradation of Avicel and filter paper by Clostridium thermocellum cellulases (two endoglucanases and one cellobiohydrolase) cloned in Escherichia coli. The highest degree of synergism was found at early stages of reaction, during the first 20 h: 2.5 and 2.9 on Avicel and filter paper, respectively. During combined action of all three cellulases the main product is cellobiose.


Purification and characterization of a cystatin-type cysteine proteinase inhibitor in the human hair shaft. We found a cysteine proteinase inhibitor in human hair shaft extract treated with 0.01 M Tris HCl buffer, pH 8.0. A yield of 0.2 mg of purified cysteine proteinase inhibitor was obtained from 86 g of hair shaft. The cysteine proteinase inhibitor had a molecular mass of 13 kDa as determined by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was more stable to heat and pH than most proteins and had a pI of 4.7. Immunologically, its antigenicity was the same as that of cystatin A, but differed from that of cystatin B and C, and kininogen. The amino-acid sequence of the first 30 residues from the NH terminus of the inhibitor was identical to that of cystatin A from human epidermis. Hair shaft cysteine proteinase inhibitor is thus considered to be identical to epidermal cystatin A.


Epidermal expression of the calcium binding surface antigen 27E10 in inflammatory skin diseases. The expression of the heterodimeric complex of the calcium-binding proteins MRP-8 and MRP-14 was investigated in various inflammatory dermatoses using immunohistochemical staining with the monoclonal antibody 27E10. In addition to the inflammatory infiltrate, a positive staining was repeatedly found in the involved epidermis from patients with lichen planus, lupus erythematosus and psoriasis vulgaris, but not in normal skin epidermis and/or in epidermis from leucocytoclastic vasculitis patients. The keratinocytic expression of the 27E10 antigen was dissimilar to that of the MHC class-II molecules and the adhesion molecule ICAM-1. These data indicate that the 27E10 antigen is a distinct activation marker of inflammatory keratinocytes and may have proinflammatory properties.


Clinical evaluation of scleroderma spectrum disorders using a points system. We have established a new diagnostic method using a points system to evaluate patients with early scleroderma and those with scleroderma spectrum disorders (SSD). To examine the clinical usefulness of this method, it was applied to a total of 215 cases including 97 patients with scleroderma, 32 with SSD, 28 with presumed primary Raynaud's phenomenon (RP) and 58 with other connective tissue disorders (CTD). A total score was obtained for each patient as the sum of the following five factors: (1) extent of skin sclerosis (maximum, 10 points); (2) pulmonary changes (maximum, 4 points); (3) antinuclear antibodies (maximum, 5 points); (4) pattern of Raynaud's phenomenon (maximum, 3 points); and (5) nailfold bleeding (maximum, 2 points). Of the 97 scleroderma patients, 86 (89%) had 9 or more points, and of the 32 SSD patients, 28 (88%) had 5 to 8 points. In contrast, all patients with presumed primary RP and 54 of 58 (93%) patients with other CTD had 0 to 4 points. These data suggest that this diagnostic method is very useful not only for clinical evaluation of SSD, but also for the differentiation of scleroderma and SSD from other CTD and primary RP.


Anticentromere-protein-B--DNA complex activities in anticentromere antibody-positive patients. Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often those with scleroderma). In this study, we analysed activities of anti-CENP-B-DNA complex in anticentromere antibody (ACA)-positive patients using DNA immunoprecipitation with purified CENP-B. The activities correlated with ACA titres and were closely associated with Raynaud's phenomenon. Patients with CREST symptoms (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) showed higher activities than those with no symptoms. Our results suggest that autoimmune responses to native CENP-B may have an important role in the pathogenesis of scleroderma.


Biochemical responses of skin to allergenic and non-allergenic nitrohalobenzenes. Evidence that an NADPH-dependent reductase in skin may act as a prohapten-activating enzyme. Using a selection of 'classic' haptens (dinitrohalobenzenes and picryl chloride) and related non-sensitizing analogous, we examined changes in levels of glutathione (GSH) and glutathione disulphide (GSSG) in mouse skin 12 h after their epicutaneous application. We observed that elevation of GSSG levels and/or depletion of GSH levels correlated well with contact allergenic potential. Non-sensitizing analogous failed to perturb GSH/GSSG status. In vitro assays using mouse skin and rat liver microsomal preparations indicated that only the allergenic nitrohalobenzenes initiated NADPH-dependent oxygen utilization, with the activity falling off in the order picryl chloride >> DNIB > DNBB > DNCB > DNFB. In addition, an examination of the colour of mouse skin homogenates ex vivo after application of the dinitrohalobenzenes showed significant yellowing (consistent with aromatic nucleophilic substitution) only with DNFB. Our results indicate that, while an aromatic nucleophilic substitution reaction with skin protein can possibly account for the allergenicity of DNFB, it does not seem to occur with DNCB, DNBB or DNIB. These may instead behave mainly as prohaptens which are activated enzymically by NADPH-dependent reductase(s) within the skin, with the concomitant generation of superoxide and hydrogen peroxide, to form potentially protein-reactive free radical and other metabolites. Picryl chloride appears capable of both conjugating directly with proteins by aromatic nucleophilic substitution and undergoing NADPH-dependent metabolism to other potentially protein-reactive metabolites.


Rosin allergy: identification of a dehydroabietic acid peroxide with allergenic properties. A peroxide of dehydroabietic acid was isolated from rosin using flash chromatography and preparative HPLC. It was identified by 1H-NMR and MS. In animal experiments, this peroxide cross-reacted with a previously identified allergen in rosin, 15-hydroperoxyabietic acid (15-HPA), despite differences in molecular weight and unsaturation. Both substances are able to react via a radical mechanism generating structurally similar molecules. In patch testing of patients, no reactions were observed to the peroxide. Low skin penetration of the peroxide could be the explanation for this. The peroxide seems of little clinical importance. The observed cross-reactivity is an indication of antigen generation via a radical mechanism. Only a few compounds that react with radical mechanisms to form antigens are described in the literature.


Effects of thermal shocks on interleukin-1 levels and heat shock protein 72 (HSP72) expression in normal human keratinocytes. Interleukin-1 expression is reported to be modified under a number of cell conditions including physiological stress, injury and activation. We report the effects of the physiological stresses cold and heat shock on IL-1 levels in keratinocytes. Having observed that normal human skin obtained from plastic surgery, usually stored at 4 degrees C for a few hours, highly expressed HSP72, a constant feature of stressed human keratinocytes, we wondered whether this induction could be linked to a cold shock and to modification of IL-1 levels in keratinocytes. Cultured keratinocytes were incubated at 4, 37, 40 and 43 degrees C for 1.5, 4, 8 and 16 h in a defined medium. HSP72 expression was studied by immunohistochemistry and immunoblot and IL-1 was quantified using specific and sensitive radioimmunoassay. Our findings showed that intracellular IL-1 alpha and IL-1 beta levels are not significantly modified by thermal shock. HSP72 is only induced after cell exposure to 43 degrees C and is not a cold-shock protein. These results demonstrate that thermal stress is not an inductive signal for IL-1 modification in keratinocytes.


Retinoic acid provokes a regeneration-like proliferative response in murine epidermis. A bivariate DNA/bromodeoxyuridine flow cytometric study. Retinoic acid (RA) is an inducer of epidermal proliferation by a mechanism of action which is not fully known. We examined the proliferative response of hairless mouse epidermis to a single topical application of different doses of RA (0.1-1000 nmol). The mitotic rate was assessed using the stathmokinetic method, and change in epidermal cell numbers were scored per microscopic vision field in tissue sections. Cell cycle parameters were measured by bivariate bromodeoxyuridine/DNA flow cytometry on isolated epidermal basal cells after pulse labelling up to 10 days after RA treatment. The results showed a dose-dependent increase in mitotic activity with a maximum at 3 days after RA application, and a dose-dependent hyperplasia with a maximum at 4 days after RA application. Cell-cycle analysis showed an immediate proliferative response after RA application similar to that following various skin irritants. Although differences in the G2 phase transit were seen, this indicates a similar mechanism of action of RA-induced epidermal proliferation and that associated with epidermal regeneration in general.


In vitro activity of pyronaridine against African strains of Plasmodium falciparum. The in vitro activity of pyronaridine was determined and compared with the activity of monodesethylamodiaquine and amopyroquine against 31 clinical isolates and two clones of Plasmodium falciparum originating from Central and West Africa using a semi-micro drug susceptibility test. Pyronaridine and amopyroquine were 2.5 and four times less active, respectively, against the highly chloroquine-resistant clone, than against the chloroquine-susceptible clone but were equally active against chloroquine-susceptible and chloroquine-resistant clinical isolates. Compared with chloroquine-susceptible isolates, monodesethylamodiaquine was three times less active against chloroquine-resistant parasites. Pyronaridine is highly active against chloroquine-resistant strains of P. falciparum and may be a promising candidate for the treatment of resistant malaria.


The chemotherapy of rodent malaria. XLVII. Studies on pyronaridine and other Mannich base antimalarials. The activities of Mannich base antimalarials, including pyronaridine, have been explored against drug-sensitive (Plasmodium berghei N) and chloroquine-resistant (Plasmodium yoelii NS) rodent malaria parasites in vivo. Lines of these parasites have been developed with resistance to pyronaridine, amodiaquine, or WR 228,258. The responses and patterns of cross-resistance of these lines to Mannich bases and other blood schizontocides are inconsistent. It is concluded that some Mannich bases may prove still to be of value inthe treatment of chloroquine-resistant Plasmodium falciparum infection.


Treatment of chloroquine-resistant malaria in monkeys with a drug combination that reverses resistance in vitro. Compounds that inhibit the P-glycoprotein-related efflux mechanism of multidrug-resistant cells reverse chloroquine resistance in vitro. Hence, the co-administration of chloroquine and an efflux-blocking drug could potentially treat chloroquine-resistant malaria infections. We administered a drug combination (chloroquine and a tiapamil analogue), that has been shown to reverse chloroquine resistance in vitro, to Aotus monkeys but failed to safely clear experimentally-induced chloroquine-resistant Plasmodium falciparum parasitaemias.


Complement (C3) levels and activation in rabbits experimentally infected with Trypanosoma evansi. Rocket immunoelectrophoresis was used to monitor the levels of the third complement component (C3) in the blood of rabbits experimentally infected with Trypanosoma evansi. Although a reduction in the circulating levels of C3 was associated with C3 activation in rabbits with high levels of parasitaemia, there was no evidence for C3 activation in uninfected rabbits, rabbits with early-stage, light infections or rabbits cleared of infection by drug treatment. Host-tolerance to current infection and to re-exposure to the parasite are probably affected by such changes in C3.


Visceral leishmaniasis in southern Sudan: status of healthy villagers in epidemic conditions. A combination of interview, serology and skin testing was used to investigate the status of apparently healthy villagers during a visceral leishmaniasis epidemic in southern Sudan. The number of people who had died equalled the number who were alive at the time of the survey. The direct agglutination test (DAT) identified 10% of the people as being serologically positive. Most young children (36/39) and 34% (22/64) of adults had neither positive serology nor skin test. About 64% (42/66) of adults had positive skin tests. In two villages, 54% and 76% of those over four years of age showed evidence of having been infected. The mortality associated with infection was estimated as at least 69%; 25% of those infected appeared to have cured spontaneously. The outcome for the remaining 6% was still doubtful. Even in this devastating epidemic there is, therefore, evidence of a considerable amount of infection without severe disease. Serological tests, while useful clinically, are apparently not useful for detecting early cases. Combined skin testing and serology produces a comprehensive though partially hypothetical picture.


Axenic cultivation of amastigotes of Leishmania donovani and Leishmania major and their infectivity. Two clones of promastigotes, one of Leishmania donovani and one of L. major, and an uncloned stock of L. major were axenically transformed to heat-shock amastigotes, at 35 and 37 degrees C, respectively. Of the four different culture media tested, a relatively cheap, liquid medium, RBLM, was found to be the best, both for the transformation of the promastigotes and the serial, axenic cultivation of the amastigotes. In an experiment of 30 days duration, serial cultivation, in an atmosphere with 5% CO2, was possible by subculturing every three days. There were significant differences in virulence in BALB/c mice between axenically-cultured amastigotes and promastigotes, both in terms of the weights, lengths and parasite burdens of the spleens of mice infected intraperitoneally (ip) with L. donovani or L. major and of the appearance, type and size of the cutaneous lesions which developed in mice given L. major by intradermal inoculation.


Analysis of host components in hydatid cyst fluid and immunoblot diagnosis of human Echinococcus granulosus infection. To improve serodiagnosis of cystic hydatidosis, immunoblotting studies were performed to look for a highly specific parasite antigen(s). First, commercially available hydatid cyst fluid antigen preparations were characterized by SDS-PAGE and by immunoblotting with sera specific for parasite and host animal proteins. One preparation, designed for use in complement fixation tests, did not appear to be suitable for immunoblotting because of the low concentrations of parasite antigens. Several host proteins, including serum albumin and IgG, were detected in the cyst fluid. Sera from patients with Echinococcus granulosus infections and other parasitic diseases were examined by immunoblotting for antibodies against specific cyst fluid parasite antigens. Several parasite antigens were variably recognized. Only one antigen, a 40 kDa protein, was recognized by all E. granulosus-infected patients. Reactivity against this antigen was also observed in all sera from E. multilocularis, cysticercosis, and schistosomiasis patients as well as in some filariasis cases. Two E. granulosus antigens, molecules of 12.5 and approximately 17 kDa, were only recognized by antibodies from some E. granulosus patients.


Evaluation of hepatic fibrosis after oxamniquine therapy of murine schistosomiasis. Chemical and histological indices of liver fibrosis were measured after eight, 18 and 28 weeks in mice infected with Schistosoma mansoni and treated at eight weeks with oxamniquine, in mice infected with S. mansoni and not treated and in mice not infected with S. mansoni. Total worm burdens and liver egg counts were determined in the infected mice to determine severity of infection. Treatment with oxamniquine resulted in near total eradication of S. mansoni worms after 10 weeks and in their complete killing and marked reduction of eggs in the liver at 10 and 20 weeks. Liver fibrosis 10 weeks after oxamniquine treatment was not significantly different than in the untreated, infected group but there was no progression between 10 and 20 weeks after oxamniquine treatment. Fibrosis did however increase between 10 and 20 weeks in the untreated infected group. In the murine model, oxamniquine is an effective treatment for S. mansoni and prevents progression of liver fibrosis.


Observations on Culex quinquefasciatus Say in relation to transmission of filariasis due to subperiodic Wuchereria bancrofti in Samoa. Observations on Culex quinquefasciatus Say in Samoa during a study of the epidemiology and control of subperiodic bancroftian filariasis are reported. The man-biting rate of C. quinquefasciatus was comparable with that of Aedes (Finlaya) samoanus Gruenberg in one indicator village and lower in another. The house-frequenting behaviour of the two species was similar. Culex quinquefasciatus was active throughout the night with peak biting during midnight hours, and its survivorship, estimated by two methods, was higher than those of the main vectors, A. (Stegomyia) polynesiensis Marks and A. samoanus. Culex quinquefasciatus showed low susceptibility to subperiodic Wuchereria bancrofti, compared with the two main vectors, in laboratory feeding experiments on volunteers with three levels of microfilaraemia. This agrees with the observed very low natural infection rate, suggesting that C. quinquefasciatus is an inefficient vector of subperiodic W. bancrofti in Samoa.


The diel pattern of entry to outdoor oviposition sites by female Aedes aegypti (L.) (Diptera: Culicidae) that then laid eggs there: a preliminary study. Experimental observations, made outdoors during the dry and wet seasons in Trinidad, demonstrate that more than 70% of female Aedes aegypti that are destined to oviposit within the next two hours enter ovitraps during the first and last two-hour periods in the day, a finding consistent with the diel pattern of oviposition recorded earlier at the same site. It is possible that proportionately more eggs are laid in the morning peak during the dry season than the wet season. Fewer eggs are laid within a two-hour experimental period if an open ovitrap is not accessible to females before the experimental period begins. It is inferred that, during the early afternoon, ovitraps are entered by females destined to lay eggs there more than two hours later in the same day.


The nature of the teneral state in Glossina and its role in the acquisition of trypanosome infection in tsetse. Teneral Glossina morsitans morsitans from outbred and susceptible stocks infected with Trypanosoma (Nannomonas) congolense developed, respectively, three and six times higher midgut infection rates than flies of the same stock which had previously taken a bloodmeal. Non-teneral G. m. morsitans remained relatively refractory to infection when infected at subsequent feeds. Differences in susceptibility to midgut infection between teneral flies from susceptible and outbred lines of G. m. morsitans disappeared in non-teneral flies, showing that maternally inherited susceptibility to midgut infection is a phenomenon restricted to the teneral state of the fly. Laboratory reared G. m. morsitans were found to have become significantly more susceptible to trypanosome infection than wild flies from the population from which the colony was derived. The likely role of rickettsia-like organisms (RLO) in potentiating teneral susceptibility to midgut infection is discussed. The addition of the specific midgut lectin inhibitor D-glucosamine to the infective feed of non-teneral flies increased midgut infection rates to levels comparable with those achieved in teneral flies. It is concluded that the peritrophic membrane does not act as a barrier preventing non-teneral flies becoming infected. The relative refractoriness of non-teneral flies suggests that they do not play a significant part in the epidemiology of Trypanozoon or T. congolense infections.


A survey of mites on farm animals in Libya. In 1985-1988, 2287 farm animals (cattle, camels, sheep, goats, horses, donkeys, dogs and rabbits) suspected of carrying parasitic mites were examined at 58 farms throughout Libya. Mites were identified on 1303 of these animals. The commonest parasites on cattle were Psoroptes and Chorioptes, on camels and sheep were Sarcoptes and Psoroptes, and on goats were Sarcoptes and Demodex. Infested horses carrier Psoroptes or Chorioptes, and one donkey carried Sarcoptes. Otodectes was common on dogs, but Sarcoptes was rare and no Demodex were seen. Rabbits often had psoroptic ear mange or sarcoptic body mange. Dermanyssus gallinae and Ornithonyssus bursa were seen on chickens, but no mites were found on pigeons, ducks or turkeys.


A survey of ticks on farm animals in Libya. Thirteen species of ixodid ticks and two species of argasid ticks were collected during a three-year survey of 58 farms in Libya. These included Boophilus annulatus, B. microplus, B. decoloratus, seven species of Hyalomma, Rhipicephalus sanguineus, Rh. evertsi, Rh. bursa, Argas persicus and Ornithodoros foleyi. This is the first recording of B. microplus, B. decoloratus and Rh. bursa in Libya. Of 20,391 animals examined by random sampling, 2020 (9.6%) had ticks; particularly common were Hy. dromedarii on camels, Hy. impeltatum on sheep and Hy. excavatum on cattle. The tick found most frequently overall was Hy. dromedarii.


Prothrombin and factor X activating properties of Bothrops erythromelas venom. The enzymatic properties of Factor II (FII) and Factor X (FX) activators from Bothrops erythromelas venom were investigated. Both activators were inhibited by ethylenediaminetetraacetate (EDTA) and 1,10-phenanthroline, and are thought to be metalloproteinases with molecular weights of 90 kDa and 70-90 kDa, respectively. The activity of the FII activator in the crude venom was about 30 times greater than that in Oxyuranus scutellatus venom and the level of FX activator activity, which was CA2+ ion dependent, was similar to that in Daboia russelli venom. The venom also had two haemorrhagic factors (58 and 105 kDa) and two fibrinolytic enzymes (18 and 58 kDa).


The effect of exposure to selected numbers of Schistosoma mansoni miracidia on survival of cohorts of Biomphalaria pfeifferi. Cohorts of 25 specimens of Biomphalaria pfeifferi were each exposed to batches of one, three, five, seven and 10 Schistosoma mansoni miracidia per snail. The effect on survival was evaluated by calculating the weekly per capita mortality rates and the mean life expectancy of the exposed snails. No statistically significant difference could be demonstrated between the mean per capita mortality rates of cohorts exposed to one and three miracidia per snail. Likewise there was no significant difference between the values obtained for cohorts exposed to five, seven and 10 miracidia per snail. In general, however, survival of the cohorts showed an inverse relationship with the number of miracidia to which each individual snail was exposed.


Human articular cartilage in osteoarthrosis. I. The matrix. Transmission electron microscopic study. The present research has been carried out with the aim of contributing to the understanding of morphological changes in human articular cartilage during osteoarthrosis and to evaluate the usefulness of TEM in this application. Only the matrix was examined in this first phase of study. Fragments from the femoral head of 20 patients subjected total hip arthroplasis, were studied by TEM after treatment with current procedures. The images obtained were considered observing the division of cartilage into superficial, intermediate and deep layers. Patients were divided according to the gravity of their clinical conditions. The least severe forms of pathology seem to involve only the superficial layer, which quickly loses the lamina splendens and may be affected by rarefactions of the matrix, which becomes fissured, while the deep layers are only slightly involved. During the later stages, the pathology progresses with irregularity of disposition and size of the collagen fibres and an increase in the number and size of fissures. The intermediate layer shows architectural disorder in the collagen fibres, even reaching the deep layer. The interfibrillar distance appears greater. As pathology progresses, the superficial layer tends to disappear, while the successive layers undergo progressive alteration in disposition and size of the collagen fibres. Globular aggregations of various dimensions and electron density similar to collagen are present in the deep layer.


The myenteric plexus of the rat colon: a methodological approach for scanning electron microscopical study. In the present research four different procedures were tested for the Scanning Electron Microscopic identification of Auerbach's myenteric plexus in the distal colon of the rat. The specimens were processed as follows: enzymatic and chemical digestion (trypsin and HCl); fixation with glutaraldehyde; fixation and staining with zinc iodide/osmium tetroxide (ZIO); fixation and staining with zinc iodide/osmium tetroxide (ZIO) followed by maceration in NaOH solution. All the procedures required microdissection to separate the different layers of the colonic wall. Light microscopic controls were prepared with the ZIO technique. Among the methods utilized, fixation and staining with ZIO appeared to be by far the best as regards the preservation of the architectural arrangement of the myenteric plexus as well as of the fine structural details.


Vasculature of bovine placentas studied by scanning electron microscopy of corrosion casts. Corrosion casts, obtained after injection of Tensol or Mercox, from 10 placentas of Holstein breed cows, were studied. The investigation was performed in fetal cotyledons, which are attached to uterine caruncles to form units, called placentons. Arteries and veins form, together, vascular cylinders, with the venous half cartridge partially surrounding the arterial one. The morphological differences between arterioles and venules concern the type of distribution, branching, surface (nuclei, oblique folds, anular narrowings).


Stereology of the pterygopalatine ganglion of the rat. The right pterygopalatine ganglia (PG) of 9 male Wistar-strain rats were dissected, embedded in Epon (3 specimens) or paraffin (6 specimens), and prepared for stereological examination under light microscopy. The perikarya were quantitatively characterized, and the ganglionic volume was determined. Stereology is an efficient method for the quantitative evaluation of the perikarya of the PG. The results(expressed as mean +/- standard deviation) were: a) areal fraction occupied by the perikarya = 53.8 +/- 7.4%; b) the perikaryal surface area per volume = 0.101 +/- 0.013 microns-1; c) the number of perikarya per volume x 10(-5) = 5.26 +/- 0.99 microns-3; d) the mean profile area of the perikarya (apk) = 505.93 +/- 78.29 microns 2; e) the mean perikaryal volume (vpk) = 9,179.33 +/- 1,533.52 microns 3; and f) the ganglionic volume = 0.210 +/- 0.127 mm3. The low coefficient of variation the apk and vpk values suggests the presence of only one population of neurons in the PG of the rat. The number of perikarya in the PG is about 11,046 per ganglion. As compared to analogous data in the otic ganglion of the rat, the PG did not show statistically significant stereological differences, but the relatively higher number of neurons found in the PG is probably associated with the higher functional activity of this ganglion.


Endocrinologic effects of the anaesthetic propofol. Because of the similarities of the adrenal glands of mammals and of the lizard Podarcis s. sicula, the latter has already been the subject of various studies on the effects of Propofol and other anaesthetics. Because a relationship between the activities of the thyroid and adrenal glands of this species has been demonstrated, the authors administered Propofol to a species of lizard to investigate its effects on the thyroid gland. Propofol inhibited thyroid activity, promoted steroid synthesis, and caused the contemporaneous appearance of both adrenaline and noradrenaline granules in the cytoplasm of the chromaffin cells. These results suggest that inhibition of the activity of the thyroid gland is secondary to the action of Propofol on the adrenal gland.


[Liddle syndrome (or pseudo-hyperaldosteronism). Long-term development and erythrocyte potassium flow study in 4 cases]. Liddle's syndrome (or pseudoprimary aldosteronism) is a rare hereditary disease; only 18 cases have been reported since 1963. Its cause remains unclear, but one of its features is increased cell membrane permeability to ions. A diagnosis of Liddle's syndrome was made in 4 new cases, all female, two of them sisters (cases n0 3 and 4), at the ages of 2, 12, 5 and 4 years. The first manifestations were dehydratation with hypokalemia at 6 months (case n0 1), hypertension at 2 years (case n0 2), polydipsia with poor weight and height gain at 5 and 4 years of age (cases n0 3 and 4). At diagnosis, all the patients had severe hypertension, metabolic alkalosis, hypokalemia and hyperkaliuria, low plasma renin activity and serum aldosterone levels. Administration of antihypertensive agents was without effect, but the hypertension was reduced when triamterene and low-sodium diet were used. Hypercalciuria was observed in 2 cases and nephrocalcinosis in 2 (case n0 1 had both hypercalciuria and nephrocalcinosis). The 2 oldest patients (n0 3 and 4) developed progressive kidney failure, possibly due to reno-vascular disease secondary to hypertension. Patient n0 3 underwent kidney transplantation 18 years after the first symptoms of the disease. This resulted in the complete disappearance of her hypokalemia and hypertension. The red blood cell membrane permeability to K+ and Cl- was studied in all 4 cases before triamterene treatment. The passive permeability to K+ and (K+/Cl-) cotransport were both elevated. A second study, 3 years (cases n0 2 and 3) and 8 years (cases n0 1 and 4) later, of patients treated with triamterene showed low values for passive K+ permeability and (K+/Cl-)-cotransport. The 4 new cases of Liddle's syndrome had the classic features of the disease, except for hypercalciuria and nephrocalcinosis in 2 of them. The cell membrane permeability data are difficult to interpret. Hypokalemia and hypertension were immediately corrected after kidney transplantation in one case and remained so for 4 years, suggesting that this disease is tubular in origin.


Quantitative growth of the eye in the human fetus. Eye weight growth was studied in 50 human fetuses aged 14 to 39 weeks after conception. The collected date was correlated with fetal maturity parameters (festational age and fetal weight) using the allometric method. Normal eye weight curves were obtained. The results indicate that eye weight growth present negative allometry. These curves may be important for the diagnosis of fetal eye malformations, and may indicate that noninvasive method such as ultrasounds can be used.


[Influenza A infection in children. Clinical spectrum and comparison with respiratory syncytial virus infection during the winter 1989-1990]. Respiratory syncytial viral (RSV) infection can be rapidly differentiated from influenza viral infection by immunofluorescence techniques. These tests were used to identify some epidemiological and clinical characteristics of both infections. 77 RSV and 22 influenza viral infections were detected during an outbreak (November 1989 to March 1990) in 210 children less than 6 years admitted for lower respiration tract infections. The fluorescent antibody assay was performed on nasal aspirates. The RSV outbreak ran from November to March, while the influenza outbreak was shorter, during December and January. The patients infected with RSV were younger (mean age: 6.7 months) than those infected with influenza virus (mean age: 20.9 months) (p < 0.001). Those with influenza virus infection presented with higher temperatures, more often had initial seizures (p < 0.05) and displayed fewer clinical or X-ray respiratory symptoms (p < 0.001). Mean durations of hospitalization were 9.9 days for RSV infection and 7.7 days for influenza virus infection. The therapeutic use of bronchial dilators, oxygen and steroids was correlated with the degree and duration of respiratory manifestations. A 3 month follow-up was insufficient to show any difference between recurrences or complications in the two groups. The clinical and radiological differences in these two groups of patients viral-infected are similar to those described in the literature. Variability from one outbreak to another precludes any extrapolation to other populations and justifies the systematic use of the fluorescent antibody assay, especially when a specific antiviral therapy is considered.


[Phenotypic expression of 12 mutations of the phenylalanine hydroxylase gene]. Several mutations in the human phenylalanine hydroxylase (PAH) gene have been described and it may be interesting to tentatively correlate mutant genotypes and clinical phenotypes of phenylketonuria (PKU). Twelve mutations were searched for using classical techniques of molecular biology in a total of 126 patients. 3 phenotypes were arbitrarily defined: typical PKU, atypical PKU or Mediterranean form, and persistent mild hyperphenylalaninemia. The patients were classified according to the residual in vivo PAH activity. Mutations were found in 64 patients. One mutation was found in each of the 2 alleles in 20 children. Only one mutation could be identified in the other 44. Only 45 children could be assigned to a phenotype. Mutations leading to total loss of PAH activity were associated with typical PKU (in homozygotes or compound heterozygotes). Mutations leading to residual PAH activity were associated in homozygotes with atypical PKU; they were also associated in compounded heterozygotes with atypical PKU, irrespective of the fact that the other allele suppressed enzyme activity or was unknown. A mutation which changed the affinity of PAH for phenylalanine was associated with mild hyperphenylalaninemia. The clinical heterogeneity of PKU can be correlated with identified mutations of the human PAH gene. Molecular studies do not help to predict either the phenotype or the long-term outcome. However, description of the biochemical changes combined with identification of the mutation should lead to a better understanding of consequences of mutation for PAH activity.


[Risk factors of sudden infant death and of death by accidents. According to a national survey in the total postneonatal death]. The incidence of sudden infant death syndrome (SIDS) peaks at 2-4 month of age and during the colder months of the year. Other risk factors such as sex, birth weight, maternal age and multiple pregnancy also seem to be shared by the other causes of death after the neonatal period. A retrospective, exhaustive survey of all deaths of infants aged 28 days-one year was carried out between September 1986 to December 1987. The control group was a representative sample of the live births in France during 1989. The deaths were classified into 3 groups: group I, 1184 SIDS, group II 228 SIDS remaining unexplained after autopsy (out of 315 autopsied SIDS), and group III 83 accidental deaths. The factors studied were: sex, birth weight, maternal age, number of infants born from the pregnancy. The risk factors were measured by Odds Ratios and the variables related to mortality were introduced into a logistic model. Incidence of deaths peaked between the 2nd and the 4th month of age in groups I and II while deaths were evenly distributed throughout the first year in group III. Colder months, male gender, low birthweight, multiple birth and the young age of the mother all increased the risk of death in SIDS (groups I and II) but the same factors were also linked to accidental deaths. The results confirm those of earlier reports and raise the question why the risk factors for accidental deaths are similar to those for explained or unexplained SIDS, except for infant age.


[Evaluation of vaccine coverage in children under two years of age in Kinshasa (Zaire)]. Despite efforts to make immunization against preventable diseases available to all children in Zaire, only about 33% of the children living at Kinshasa were immunized in 1986. The compliance with the vaccination schedules was evaluated in 211 children less than 2 years of age consulting in the largest medical center of Kinshasa during one week in September 1989. Socio-demographic data on the parents and histories of infectious preventable diseases in children were also collected. 93% of the children were immunized against tuberculosis, 85% against diphtheria, tetanus, pertussis and poliomyelitis, 76% against measles. Compliance with the vaccination schedule was higher when the mothers were better educated, or when they worked in the public service. 25% of the children had not been immunized against measles at the age of 9 months. The vaccine schedule and the strategy must still be improved.


[Chronic intestinal pseudo-obstruction and delayed myenteric ganglion cell maturation]. Enteric nerve cells begin to mature during the last trimester of pregnancy and become mature only after birth. The degree of maturation seems to be related to bowel motility. A girl was born from a pregnancy complicated by hydramnios, and did not pass meconium before the 64th hr of life. Barium enema on day 4 showed a left microcolon with no distension of the transverse colon. Tests for cystic fibrosis were negative. On day 12, the patient presented with septicemia due to Pseudomonas maltophylia. Parenteral alimentation by central catheter was instituted. Surgical rectal biopsy showed that the number of ganglion cells was normal but the cells were immature. Progressive feeding was possible for the 3rd month of life. A second rectal biopsy at 3 1/2 months showed some remaining immature ganglion cells. Immature ganglion cells can account for neonatal functional intestinal obstruction, as has been established for the small left colon syndrome. The progressive loss of symptoms seems to be correlated with histological maturation of the neurological apparatus of the large bowel. Severe complications, such as occlusion, sepsis, nutritional disorders can occur during this long period of functional intestinal obstruction.


[Systemic gas embolism in the greater circulation in a ventilated premature infant]. Pneumothorax is common complication in newborns; its incidence is increased by intubation, particularly when high pressure ventilation is necessary. Systemic air embolism is a rare and usually fatal form of "displaced air". A preterm newborn, 27 weeks of gestational age, weighing 940 g, with respiratory distress syndrome was treated by intubation at 1 min of life and high pressure ventilation (Peak 36 cmH2O, PEP 6 cmH2O, FiO2 = 1). Bilateral pulmonary interstitial emphysema was seen on X-rays at 4 hr of life. Acute cyanosis and bradycardia occurred at 7 hr of life; large amounts of air mixed with blood were withdrawn from the umbilical vein catheter. There was no pneumothorax, pneumomediastinum or subcutaneous emphysema. The newborn died at 9 hr of life. Post mortem injection of contrast fluid into umbilical vein catheter indicated no cardiac perforation: this finding was confirmed by autopsy. This is a new case of systemic air embolism that may be due to high pressure ventilation in an extremely underweight newborn. Preventive measures consist of monitoring ventilation, possibly using new techniques, but their efficacy remain to be demonstrated.


[Amiodarone and fetal supraventricular tachycardia. Apropos of a case with neonatal hypothyroidism]. Fetal tachycardia can be a cause of in utero death. Its detection is not always easy and its treatment is still controversial. Paroxysms of supraventricular tachycardia were detected on echocardiography at the 25th week of a second pregnancy. The mother was given sotalol, but the supraventricular tachycardia became permanent. At the 27th week of gestation, sotalol was stopped and the mother was given digoxin and the foetus received 2 injections of digoxin, 10 micrograms/kg, via the umbilical cord. As this treatment was only partially effective, the mother was also given amiodarone 800 mg/day at week 28, then the dose was reduced to 400 mg/day. However, at the 31st week, the mother showed signs of digoxin intolerance, and it was replaced by sotalol. Fetal blood tests at week 34 showed a high placental transfer of digoxin and sotalol and a low fetal level of amiodarone. The newborn, a girl, was born at the 36th week having a sinus rhythm. She developed signs of hypothyroidism (T4: 4 micrograms/ml; TSH:325 microliters U/ml at 5 days of life). The placental transfers of sotalol, digoxin and amiodarone are in the range of values known to be effective. The amiodarone responsible for hypothyroidism was given to the mother because she was intolerant to digoxin. Its use must be limited to arrhythmias that are resistant to other drugs or complicated by hydrops fetalis. When used, amiodarone should not be given for more than 6 weeks, and at the lowest possible dose.


Haematological values of rusa deer (Cervus timorensis russa) in New Caledonia. Blood samples were collected from 91 rusa deer (Cervus timorensis russa), immediately after being shot, to define their mean haematological values (red cell count, white cell count, differential leucocyte count, packed cell volume, haemoglobin concentration, mean cell volume, mean cell haemoglobin, and mean cell haemoglobin concentration). Male deer had a significantly higher red cell count and haemoglobin concentration, and a lower mean cell volume and mean cell haemoglobin content, than did female deer.


Serum biochemical values of rusa deer (Cervus timorensis russa) in New Caledonia. Blood samples were collected from 91 rusa deer (Cervus timorensis russa), immediately after being shot. Serum mean biochemical values from shot deer are presented for blood urea nitrogen, creatinine, creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein, albumin, calcium, and phosphorus. Mean total protein and albumin increased with age. There was an age-associated increase of gamma globulins. Mean creatine kinase activity and creatinine, albumin and phosphorus concentrations were higher in stags than in hinds. Pregnant hinds had lower mean creatine kinase activity and phosphorus and higher mean alanine aminotransferase and total protein than non-pregnant hinds. Mean calcium concentration increased when deer were agitated before bleeding.


Mesothelioma in horses.

Mesothelioma in horses. Pleural mesothelioma and pericardial mesothelioma with spread to the pleural cavity were diagnosed in 2 horses. Clinical signs included respiratory distress, depression and pleural pain. The affected body cavities contained copious, serous effusions containing very large neoplastic mesothelial cells with densely-staining cytoplasm, hyperchromic nuclei and prominent, often multiple, nucleoli. Ultrastructurally, the neoplastic cells appeared as solid aggregates, with profuse microvillous borders and neolumen formation. Cytological examination, together with confirmative ancillary diagnostic tests, including electron microscopy and immunocytochemistry, may be used to obtain an ante-mortem diagnosis of mesothelioma.


Within and between observer agreement on ultrasonic evaluation of bovine ovarian structures. A diagnostic ultrasound unit with a 5 MHz probe was used to examine ovarian structures in vitro from 32 reproductive tracts obtained at slaughter from young cows. Agreement between and within observers, and between observers and dissection results was evaluated using the kappa statistic. Agreement was high (kappa from 0.531 to 0.969) for all evaluations of corpora lutea. The sensitivity, specificity and predictive value of both positive and negative findings for presence of a corpus luteum was > 0.9. Agreement between and within observers was little better than chance for follicles measuring 4 to < 6 mm and for follicles measuring 6 to < 10 mm. However, agreement between observers and dissection results indicated that observers could detect follicles 4 to < 6 mm and 6 to < 10 mm (kappa 0.301 to 0.731 and 0.414 to 0.612, respectively). Kappa values within and between observers and between observers and dissection results for observations of follicles measuring > or = 10 mm were almost all > 0.4 indicating that large follicles can be readily detected using ultrasound. It is suggested that further validation of ultrasound methods is needed to determine whether follicles measuring < 4 mm can be accurately identified, and whether follicles can be accurately identified and monitored over a number of days. The ultrasound unit was useful for detecting the presence of corpora lutea and follicles. However, agreement between and within observers on the presence of follicles measuring < 10 mm was poor.


The survival and fecundity of buffalo flies after treatment of cattle with three anthelmintics. Two anthelmintics with known insecticidal action (ivermectin and closantel) and one with no recorded effect on insects (levamisole) were tested to evaluate their effects on buffalo fly (Haematobia irritans exigua). Blood from animals given closantel or levamisole had no significant effect on mortality of buffalo flies in an in-vitro assay. In contrast, blood from animals given ivermectin showed a dose-dependent effect on the mortality of buffalo flies. At 24 h after one injection of the recommended dose of ivermectin, 98% of the flies applied to cattle in an in-vivo assay are killed. Blood from cattle injected with ivermectin killed 95% of flies 8 d after injection and still killed 15% of flies at 18 days after injection. Surviving flies laid almost no eggs and this effect on flies was significant up to 33 d after injection. The results indicate that ivermectin may be useful to control buffalo fly populations in the field.


Reduced growth of Lucilia cuprina larvae fed serum from sheep treated with anthelmintics. The effect of three commonly used anthelmintics, levamisole hydrochloride, ivermectin and closantel, on the development of the sheep blowfly, Lucilia cuprina, was determined. Sheep were treated with each anthelmintic using the manufacturers' recommended dose for helminth control. Both ivermectin and closantel significantly (p < 0.05) reduced the growth rate of larvae of L cuprina cultured in vitro on serum from these sheep. Levamisole hydrochloride had no effect. Ivermectin was effective for less than 6 days after treatment, whereas closantel significantly reduced larval growth 21 days after treatment. Dose-response experiments showed that lower concentrations of both ivermectin and closantel were not as effective in reducing larval growth.


Adverse drug reactions: report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1992. Fifty-nine reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee of the Australian Veterinary Association from February 1991-March 1992 inclusive. The number of reports received/number of animals involved per species was: dogs (23/24); cats (20/30); horses (4/4); cattle (7/10); sheep (3/745); poultry (1/580); pigs (1/8). Of these, 38 (64%) were classified as definite ADRs and 9 (15%) as probable ADRs. In 10 (17%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Two reports involved veterinarians inadvertently overdosing animals. Eighteen reports involved apparent hypersensitivity reactions and 6 reports involved probable drug interactions. Four reports involved the use of drugs at appropriate doses but in inappropriate clinical situations, and 3 reports were associated with 'off-label' use.


Salting-out behaviour of the domains of ovomucoid. The solubility of ovomucoid and of four fragments comprising domain I, I+II, and III of the protein in concentrated ammonium sulphate solution were studied at different pHs (25 degrees C) and at various temperatures (pH 7.0), and the salting-out parameters Ks and beta were determined for the five proteins. The aqueous solubilities of ovomucoid and the four fragments were highly dependent on temperature which causes structural alteration due to thermal unfolding of the proteins. The values of KS and beta for domain III and domain II+III at different pHs were similar to those of other globular proteins whereas those of ovomucoid and domain I and domain I+II were atypical. They were explained in terms of the lack of structural stability and the presence of carbohydrate moieties in domains I and II.


Beta-glucosidase of a white-rot fungus Trametes gibbosa. Extracellular beta-glucosidase was purified from a white-rot fungus, Trametes gibbosa by 50% ammonium sulphate saturation and Sephadex G-100 column chromatography. It showed maximum activity towards p-nitrophenyl- beta-D- glucopyranoside (pNpG). The pH optimum was 3.5. Temperature optimum was 40 degrees C but shifted to 50 degrees C on preincubation with pNpG. Hg2+, Fe3+ and Cu2+ strongly inhibited the activity. The enzyme was competitively inhibited by glucose with a Ki of 5.2 mM. The apparent molecular mass as determined by gel filtration chromatography was 640 kDa.


Characterization of lipoprotein lipase activators from equine plasma. Equine plasma lipoproteins were fractionated into VLDL, LDL-1, LDL-2 and HDL by density gradient ultracentrifugation. From each lipoprotein fraction, five apo C like peptides of approx. M(r) 1400, 10000, 9500, 9000 and 8000 were detected by SDS-polyacrylamide gel electrophoresis. After partial purification by Sephadex G-75, one fraction, showing a strong activation of lipoprotein lipase, was further purified by Mono Q anion exchange column. Two of the apo C like peptides (M(r) 10000 and 8000) activated the bovine milk lipoprotein lipase in vitro; only one (M(r) 9500) inhibited the lipolytic activity. This work confirms that many mammals present two apo C-II components with different molecular weights.


Lower susceptibility of low density lipoprotein to in vitro oxidation in diabetic patients. The susceptibility to peroxidative stress of low density lipoprotein (LDL), induced by incubation with CuSO4, has been studied in eleven diabetic patients and eleven control subjects. Our results suggest that oxidized LDL (OX-LDL) of diabetic patients have a significant higher reactivity to 2,4,6-trinitrobenzene sulfonic acid (TNBS) than controls, that indicates a lower susceptibility of LDL to oxidative stress. Furthermore using the fluorescence polarization (Pf) of 1,6-diphenyl-1,3,5-hexatriene (DPH) and its phosphatidylcholine derivative (DPH-PC) we have shown that peroxidation induces a decrease of fluidity in OX-LDL of controls and diabetic patients, both at the lipoprotein surface, where is localized DPH-PC and at the interface between lipoprotein surface and core which is probed by DPH.


Isolation and partial characterization of hyaluronan-protein-collagen complex (HA-PC) from fetal sheep skin of different gestational ages. Hyaluronic acid (HA) has a positive effect on cell migration, differentiation and wound healing. Earlier work from our laboratory has shown the presence of biologically active proteins associated with HA. The protein associated with HA of fetal sheep skin varies in molecular weight depending on its gestational age. Specifically, the protein profile changes at 125 days of gestation, from a 60 KDa protein to a smaller protein of about 21 KDa. This time period coincides with the time that scarring becomes apparent in fetal sheep skin wounds. In this study, we have quantified changes in the proteins associated with HA with increasing gestational age, obtained amino acid profiles of these proteins with increasing gestational age, and proposed the existence of an HA-associated protein-collagen complex (HA-PC) which may serve as a scaffold for wound healing. Our results indicate that HA-PC content decreases from 42% of the dry weight at 75 days of gestation to 22% at 125 days of gestation. Protein content, in contrast, increases to 40% of the dry weight at 140 days of gestation. At the same time, collagen content increases from < 1% of the dry weight at 75 days to > 10% at 140 days. The increase in collagen content may account for the increase in total protein seen at 140 days. The expression of varying HA-PC's at different gestational ages may influence the kinetics of collagen fibrillogenesis and thus account for the previously noted late gestational change from "scarless" wound healing to "adult-like" wound healing in fetal sheep.


The cholinergic agonist carbachol reduces intracellular beta-amyloid precursor protein in PC 12 and C6 cells. Amyloid beta-protein, the major constituent of amyloid plaques in Alzheimer's disease, is derived from larger amyloid precursor proteins (APP). Changes in the rates and or pathways of APP synthesis and degradation may be central to the deposition of beta-amyloid. We explored the possibility that APP processing is regulated by activation of endogenous cell-surface neurotransmitter receptors by stimulating C6, PC12 and neuroblastoma cells with the cholinergic agonist carbachol. We measured the intracellular APP in these cell lines by western blotting using three antibodies against different regions of APP. When cells were treated with carbachol for different periods, PC12 and C6 cells responded with a sharp decrease of APP bands. Similar blots probed with an antibody against heat-shock protein (HSP), showed no change in the intensity of the immunoreactive HSP-70 band. These results suggest that the decrease in intracellular APP seen after stimulation by carbachol has some specificity and that APP processing may be regulated by stimulation of cholinergic receptors on the surface of cells.


Substrate binding properties of L-glycerol-3-phosphate dehydrogenase in isolated liver mitochondria of hyperthyroid rats. In isolated, intact liver mitochondria from hyperthyroid rats, the L-glycerol-3-phosphate binding site(s) of the L-glycerol-3-phosphate dehydrogenase was (were) found to be influenced by the nature of the electron acceptor, as well as by the pH and the presence of calcium ions. With the hydrophobic electron acceptor menadione a single L-glycerol-3-phosphate binding site was detected kinetically at bulk pH values between 6.5 and 9.0. With the hydrophilic phenazine methosulfate, on the other hand, two L-glycerol-3-phosphate binding sites were distinguishable at pH > or = 7.5 and pH > or = 7.0, in the presence and absence of Ca2+, respectively. The kinetic mechanism of the reaction catalyzed by L-glycerol-3-phosphate dehydrogenase is ping pong Bi Bi with a hydrophilic electron acceptor, where as with the hydrophobic substance, a sequential Bi Bi mechanism was observed. We suggest that the latter mechanism has physiological relevance.


Stimulation of Nb2 mitogenesis by an analogue of human growth hormone (110-127). Two 18-mer peptides were synthesized. Peptide E117 had the same amino acid sequence as that in the region 110-127 of human growth hormone [hGH (110-127)]. In the second peptide (L117), E117 was replaced with leucine. Biological activity of the peptides was assessed in cultured Nb2 lymphoma cells. L117 stimulated cell division and DNA synthesis in a concentration-dependent manner. Maximum stimulation was equivalent to that noted with native hGH although L117 was much less potent (L117; EC50 approximately 1 microM vs. hGH; EC50 approximately 20 pM). No demonstrable activity was found with peptide E117. These results suggest that the amphipathic helical structure of hGH (110-127) is crucial for biological activity.


Distribution and antioxidant activity of a palm oil carotene fraction in rats. The aim of this study was to determine the tissue distribution of carotenoids in palm oil and to correlate the accumulation of carotenoids with protection against oxidative stress. We found that: (i) After 2 weeks beta-carotene in the liver increased from 7.3 to 30 ng/g wet tissue; alpha-carotene and lycopene after 10 weeks of feeding were 74 and 49 ng/g wet tissue respectively; (ii) Beta-carotene content in heart and hind limb skeletal muscles increased after 10 weeks to 17 and 6 ng/g wet tissue respectively; (iii) No carotenoids were detected in the brain, adipose and skin during the period of feeding; (iv) After in vitro induction of lipid peroxidation in liver homogenates by an azo-initiator of peroxyl radicals an inverse correlation between tissue carotenoid level and accumulation of lipid peroxidation products was observed; alpha-carotene > lycopene > beta-carotene.


Nucleotide sequence of cDNA for porcine heme oxygenase and its expression in Escherichia coli. The nucleotide sequence of a cDNA for porcine heme oxygenase was determined. The open reading frame encoded a polypeptide of 288 amino acid residues with a molecular mass of 33,074 Da. A prokaryotic expression plasmid carrying porcine heme oxygenase cDNA was constructed and transfected into Escherichia coli cells. The full-length heme oxygenase expressed was localized in the bacterial membranes. Two small-sized heme oxygenases with no membrane-bound properties were also detected, suggesting that in E. coli cells a considerable amount of the enzyme expressed was degraded.


Myotoxicity and physiological effects of three Trimeresurus flavoviridis phospholipases A2. When basic proteins I and II from Trimeresurus flavoviridis (Habu snake) venom, which are Lys-49-phospholipase A2 (PLA2) with low activity, were injected intramuscularly into mice, myonecrosis was induced accompanied by a rapid increase of plasma creatine kinase level. This increase was about 2 times greater than that raised by highly active T. flavoviridis Asp-49-PLA2 which has been regarded as a myotoxic factor. Calcium-dependent depolarization of frog muscle fibers was observed with basic proteins I and II but not with Asp-49-PLA2. Indirect hemolysis of rat erythrocytes was induced by Asp-49-PLA2 but not by basic proteins I and II. Myotoxicity and depolarization effects appear to be not necessarily related to lipolytic activity of proteins although hemolytic effects is in parallel to lipolytic potency. Light microscopic observations of muscle preparations treated with three PLA2s showed similar histological changes, i.e., myolytic necrosis without hemorrhage and infiltration of polymorphonuclear cells. The structural and functional elements of PLA2s for eliciting myotoxicity are discussed.


In vitro transfer of N-acetylglucosamine to endogenous glycoprotein acceptors catalyzed by the nucleus and the cytoplasmic membranes prepared from L1210 cells. The non-nuclear membranes and the nuclei prepared from L1210 cells catalyze the in vitro transfer of N-acetyl(14C)glucosamine from UDP-N-acetyl(14C)glucosamine to endogenous glycoprotein acceptors. Adequate analysis of these acceptors have demonstrated that the nucleus has its own N-acetylglucosaminyltransferase system that leads to the formation of N-N'-diacetylchitobiosylated proteins.


Immunodetection of tubulin carboxypeptidase activity on nitrocellulose membrane after gel electrophoresis and blotting. It was found that the detyrosination of tyrosinated tubulin by tubulin carboxypeptidase can occur when both the enzyme and the substrate are adsorbed on nitrocellulose. This, and the use of a specific antibody that recognizes detyrosinated tubulin allowed us to localize tubulin carboxypeptidase on a nitrocellulose membrane after agarose gel electrophoresis and blotting. The method was also extended to detect pancreatic carboxypeptidase A.


Interaction between phenylalanine and antisense nucleosides and the effect of pH and salts on the strength of interaction. The interaction of 12 antisense nucleosides with phenylalanine (Phe), and the effect of pH and salts on the strength of interaction was studied by charge-transfer reversed-phase thin-layer chromatography. Phe significantly decreased the lipophilicity of nucleosides. This effect may be due to the interaction between the more hydrophilic Phe and the more lipophilic nucleosides, resulting in charge-transfer complexes of moderate lipophilicity. The relative strength of interaction was the weakest in acidic and the strongest in alkaline environment. This finding indicates the partially or entirely hydrophilic character of the interaction. Salts influenced to a lesser extent the interaction, their effect depended both on the concentration and on the type of cation. The relatively low impact of salts on the strength of interaction suggests that other than hydrophilic forces are involved in the Phe - antisense nucleoside interaction.


Identification of human salivary protease activity toward mucin: differences with caries. A protease activity directed toward high molecular weight salivary mucus glycoprotein was identified in the secretion of human submandibular salivary gland. The protease exhibited maximum activity at pH 7.0-7.4, and following ammonium sulfate fractionation yielded an active enzyme at 60% saturation which on SDS-PAGE gave 48 and 53kDa protein bands. The enzyme exhibited serine-protease properties by showing susceptibility to phenyl methyl sulfonyl fluoride, alpha 1-antitrypsin, and egg white and soybean inhibitors. The protease activity in submandibular saliva of caries-resistant subjects was found to be 3.8-fold greater than that in saliva of caries-susceptible individuals, thus suggesting that the enzyme expression may be linked to the resistance to caries.


Hammett rho sigma correlation for the inhibition by indoles of coniferyl alcohol oxidation catalyzed by cell wall peroxidases. The inhibitory effect of indole-3-acetic acid, and of its peroxidase-mediated degradation products of an indole nature, on the oxidation rate of coniferyl alcohol catalyzed by cell wall peroxidases has been studied. The results show that the inhibitory effect of indole-3-acetic acid and indole-3-carbinol may be explained, in part, by their properties as peroxidase substrates. However, I50 values for a series of indole compounds not regarded as peroxidase substrates show a good correlation with the electron-donating or electron-withdrawing nature of the 3-substituents, as judged by the linearity of the Hammett rho sigma plot. These results suggest that although the properties of indole compounds as peroxidase substrates may be responsible, in part, for their inhibitory effects on the peroxidase-mediated oxidation of coniferyl alcohol, the inhibitory effect appears to be mainly determined by the acidity of the imino group of the indole nucleus.


Toxicity studies of the non-sulfhydryl angiotensin converting enzyme inhibitor N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline in rats. The acute and subacute toxicities of N-[8-amino-1(S)-carboxyoctyl]-L- alanyl-L-proline (AB-47, CAS 120008-53-9), which is a non-sulfhydryl angiotensin converting enzyme inhibitor, were studied in male and female Fischer 344 rats. In the acute study, male and female rats were orally given 5000 mg/kg of AB-47. No rats were dead during the observation period (14 days) after the administration. The LD50 values of AB-47 were more than 5000 mg/kg in both male and female rats. Although only diarrhoea as toxic sign was observed 2 to 7 h after the administration, this sign disappeared within 24 h after the administration. Necropsy at the termination of observations revealed no macroscopic lesions in any rats. In the subacute study, male and female Fischer 344 rats were orally given 40, 200 or 1000 mg/kg/d of AB-47 for 4 weeks. Neither toxic signs nor death due to drug effects were observed at any dosage levels of AB-47. Furthermore, AB-47 did not influence body weight, food consumption, food efficiency, urinalytical and hematological parameters in both male and female rats. The minor changes of serum parameters, which consisted of very slight increases in serum potassium and decreases in serum albumin/globulin ratio, occurred in male rats given 200 and 1000 mg/kg/d of AB-47. Serum urea nitrogen values were elevated in both male and female rats given 1000 mg/kg/d of AB-47. Slight decreases of heart weight and heart weight/body weight ratios were observed at all dosage levels of AB-47.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of slow release nifedipine tablets in patients with essential hypertension. The antihypertensive effect of slow release nifedipine (CAS 21829-25-4) tablets (20 mg, Adalat) administered once or twice daily was studied in patients with essential hypertension of WHO stage I or II. Ambulatory blood pressure was monitored by a finger volume oscillometric device every 5 min for 24 h before and during the treatment with nifedipine. Whether administered once or twice daily, nifedipine tablets dit not change the pattern of circadian blood pressure variation; i.e. diurnal rise and nocturnal fall. Twice daily administration induced a significant downward shift in the blood pressure pattern. In other words, further hypotensive effect was observed during the night when the blood pressure was already low. On the other hand, administration once daily in the morning lowered daytime blood pressure without affecting blood pressure during the night. The duration of action of nifedipine tablets administered once daily was 12 h or more. In the acute experiment using 20 mg tablets of nifedipine, plasma concentration of nifedipine was well correlated with the percentage change in mean blood pressure. The minimal effective plasma concentration of nifedipine was estimated to be 13.4 ng/ml. However, in chronic treatment, nifedipine lowered blood pressure at the plasma concentration of 10 ng/ml. The results indicate that nifedipine tablets administered once daily provide an effective antihypertensive regimen for controlling daytime hypertension with minimal antihypertensive effect during the night.


Structure/histotoxicity relationship of parenteral iron preparations. Commercial iron preparations with different chemical structures and stabilities which are indicated for parenteral application were analyzed. After intravenous application in mice, toxic effects were screened by histological examination of liver, kidney, adrenal, lung and spleen. The various iron complexes were classified into four groups according to their physicochemical properties (molecular mass, kinetic and thermodynamic stability). It was found that the toxic effects can be forecasted by the chemical properties. The results clearly show that not all iron preparations tested can be recommended for intravenous application. After injection, the ideal iron preparation is deposited in the reticulo-endothelial system, and not in the parenchyma of the liver, nor mainly in the periportal area. Furthermore, its renal elimination rate should be below 1% of the dose, and there should be practically no iron detectable in the tubuli. The molecular mass of an optimal product is between 30,000 and 100,000 Daltons, and the preparation does not contain any slowly degradable biopolymers, so that the incidence of allergic side effects is reduced to a minimum. Iron preparations consisting only of weak iron complexes, which liberate iron ions stochastically, should not be used for intravenous application.


Studies on some 10-[2-(N,N-disubstituted thiocarbamoylthio)acetyl]phenothiazine derivatives. Nineteen 10-[2-(N,N-disubstituted thiocarbamoylthio) acetyl]phenothiazine derivatives have been synthesized by the reaction of 10-chloroacetylphenothiazine with potassium salt of N,N-disubstituted dithiocarbamic acid derivatives. The structures of the compounds have been elucidated by UV, IR, 1H-NMR spectra and microanalysis. The anticholinergic activity of the compounds was determined by assessing the inhibition of acetylcholine using atropine sulfate as a control. Results are discussed in relation to the activity and structure of the synthesized compounds.


Ultrasound studies of the effect of trospium chloride on gall-bladder kinetics. In a randomized double-blind study the effects of increasing doses of trospium chloride (Spasmo-lyt, CAS 10405-02-4), 0.2, 0.5, 1.0, and 1.5 mg i.v., on gall-bladder contractility were compared among themselves and against placebo and n-butylscopolamine bromide (20 mg i.v.) by an intraindividual 5-fold crossover technique. Gall-bladder volumes after drug-induced contraction (fat stimulus with sodium iopodate) were measured by ultrasound scanning conducted by a single examiner. Serial measurements, carried out in 6 female subjects without any evidence of gall-bladder disease, demonstrated a dose-dependent trend of inhibition of gall-bladder motility produced by trospium chloride. In the maximal doses employed (1.0 and 1.5 mg i.v.) trospium chloride effected almost total inhibition of motility. The response to n-butylscopolamine bromide tested in a nonblind comparison, showed a dose-effect ratio of roughly 40:1 between trospium chloride and n-butylscopolamine bromide given intravenously. This work confirms that ultrasound measurement of gall-bladder volume is a suitable pharmacodynamic model for testing the dose-effect relationships of antispasmodic agents.


Effects of propiverine hydrochloride on the spontaneous contractions of isolated guinea-pig urinary bladder strip and rhythmic urinary bladder contractions of anesthetized dog. The effects of propiverine hydrochloride (P-4, CAS 60569-19-9), a new drug to treat pollakiuria, was investigated on the spontaneous contractions of isolated guinea-pig urinary bladder strip and rhythmic urinary bladder contractions of anesthetized dog. At 10(-6)-10(-5) mol/l P-4 raised the base line of an isolated guinea-pig urinary bladder strip and accelerated its spontaneous contraction. At 10(-4) mol/l P-4 raised, and then lowered the baseline, and accelerated then suppressed its spontaneous contractions. Papaverine at 10(-6)-10(-4) mol/l also showed a similar action as P-4 in the isolated guinea-pig urinary bladder strip. Flavoxate at 10(-6)-10(-4) mol/l raised its base line and accelerated its spontaneous contractions. Those of P-4 at 10(-5) mol/l were not inhibited by tetrodotoxin 10(-6) mol/l). At doses of 50 mg/kg or more, intraduodenal administration of P-4 suppressed the frequency of rhythmic urinary bladder contractions of anesthetized dog in a dose-dependent manner. These results indicate that P-4 shows mainly an accelerating action on the endogenous spontaneous contractions of urinary bladder, but on exogenous contractions induced by the Balloon's method it shows an suppressing action and regulates the functions of the urinary bladder, so P-4 might become a useful drug for the clinical treatment of micturitional dysfunction, for example, pollakiuria.


Comparison of the efficacy and tolerance of a garlic preparation vs. bezafibrate. The efficacy and tolerance of a garlic preparation (Sapec, Kwai) was investigated in a randomized double-blind study vs. bezafibrate. This multi-centre study was conducted in 5 general medical practices and involved 98 patients with primary hyperlipoproteinaemia. The daily doses of the active substances were 900 mg of garlic powder (standardized as to 1.3% alliin) and 600 mg of bezafibrate, respectively. The pre-phase with placebo lasted 6 weeks, the treatment period covered 12 weeks. All patients were advised to observe a low-fat "step-1 diet" for the duration of the study. The 98 case report forms allowed the statistical evaluation of total cholesterol, HDL cholesterol and triglyceride levels for 94 patients, and of LDL cholesterol values for 92 patients. In the course of the treatment both study medications caused a statistically highly significant reduction in total cholesterol, in LDL cholesterol and triglycerides, and an increase in HDL cholesterol. However, there was no significant difference in the efficacies of both medication groups. Side effects were mentioned by 5 patients each in both treatment groups, none of which led to the withdrawal of the patients. Concerning the garlic preparation, there was no correlation between the perception of garlic odour and the influence on the cholesterol level.


[Plasma- and tissue concentrations following intramuscular administration of etofenamat. Pharmacokinetics of etofenamat and flufenamic acid in plasma, synovium, and tissues of patients with chronic polyarthritis after administration of an oily solution of etofenamat]. Studies on Plasma and Tissue Concentrations of Etofenamate following Intramuscular Application/Pharmacokinetics of etofenamate and flutenamic acid in plasma, synovia and tissues of patients with chronic polyarthritis after application of oily etofenamat solution Pharmacokinetics of etofenamate (ETO, CAS 30544-47-9; Rheumon i.m.) and flufenamic acid (FLU, CAS 530-78-9) were investigated in plasma, synovial fluid, and tissues after single intramuscular application of etofenamate to patients with rheumatoid arthritis. 62 patients with indicated operative procedure in the knee-joint received a single dose of etofenamate dissolved in oil before operation. At definite times between 1.5 and 48 h post injectionem samples from 6 patients of each time group were collected. Samples of plasma, synovial fluid, synovial membrane, muscle, bone, hyaline cartilage, and fat tissue and in some cases meniscus cartilage were taken. Concentrations of ETO and its active metabolite, FLU, were determined by HPTLC. In all tissues investigated, concentration/time courses of ETO and FLU were observed. ETO and FLU were measured first in all matrices 1.5 h at the latest 3 h post injectionem. Pharmacokinetics in tissues follows that in plasma. Rate-limiting step is the liberation of drug from the oil depot. For a long period pharmacokinetics of ETO and FLU is mainly determined by the constant liberation from the oil depot (zero order kinetics of liberation). Zero order kinetics is deduced from the linear ascent of the cumulated AUC (in percent) vs. time plot. It is directly related to the liberation of drug from the galenical formulation.(ABSTRACT TRUNCATED AT 250 WORDS)