39481152
Magnesium deficiency: does it have a role to play in cataractogenesis?
Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of vital ocular tissues such as lens. Presence of high magnesium content especially in the peripheral part of lens as compared to aqueous and vitreous humor has been observed. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body especially those utilizing ATP. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium-dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Furthermore, magnesium deficiency is associated with increased oxidative stress secondary to increased expression of inducible nitric oxide synthase and increased production of nitric oxide. Thus the alterations in lenticular redox status and ionic imbalances form the basis of the association of magnesium deficiency with cataract. In this paper we review the mechanisms involved in magnesium homeostasis and the role of magnesium deficiency in the pathogenesis of cataract.
18999099
Pathogenetic role of magnesium deficiency in ophthalmic diseases
Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of several vital ocular tissues such as cornea, lens and retina. The magnesium content of lens, especially in its peripheral part, is higher than that in aqueous and vitreous humor. Magnesium has also been shown to play critically important role in retinal functions. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body and regulates neuroexcitability and several ion channels. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium-dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Such ionic imbalances in turn alter the other cellular enzymatic reactions and form the basis of the association of magnesium deficiency with ophthalmic diseases such as cataract. In presence of magnesium deficiency, an imbalance between mediators of vasoconstriction and vasorelaxation may underlie the vasospasm, which is one of the pathogenic factors in primary open angle glaucoma. Furthermore, magnesium deficiency is also a contributing factor in increased oxidative stress and inducible NOS stimulation that can further contribute in the initiation and progression of ocular pathologies such as cataract, glaucoma and diabetic retinopathy. In this paper we review the association of disturbances of magnesium homeostasis with several ophthalmic diseases.
22333721
Current concepts in the pathophysiology of glaucoma
Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. A better understanding of the pathophysiological mechanisms involved in the onset and progression of glaucomatous optic neuropathy is crucial in the development of better therapeutic options. This review is an effort to summarize the current concepts in the pathophysiology of glaucoma so that newer therapeutic targets can be recognized. The literature available in the National Medical Library and online Pubmed search engine was used for literature review.
23113580
Future Target Molecules in Antiglaucoma Therapy: TGF-β May Have a Role to Play
Glaucoma, a leading cause of irreversible blindness, is often associated with increased resistance to aqueous outflow in trabecular tissue. Increased outflow resistance has been attributed to increased extracellular matrix (ECM) deposition in trabecular tissue. A critical balance between the synthesis and breakdown of the components of extracellular tissue is important in keeping the intraocular pressure within the normal range. Multiple mechanisms have been shown to affect ECM turnover in trabecular tissue. In this review, we examine the related literature to understand the role of TGF-β in ECM turnover, in the development and progression of glaucoma, and in possible therapeutic strategies that can be devised by targeting the TGF-β signaling pathways.
5792982
Therapeutic potential of Curcuma longa, the golden spice of India, in drug discovery for ophthalmic diseases
Background: Curcuma longa is among the most commonly used spices in India and other Asian countries. The herb has also been used in Ayurveda and other traditional systems of medicine for the prevention and treatment of a variety of ailments. Curcuminoids are the major chemical constituents of C. longa that are of medicinal importance. Today, a large body of scientific evidence exists to indicate potential therapeutic benefits of C. longa. Several preclinical and clinical studies have investigated the pharmacological properties of C. longa and results indicate strong therapeutic potential for anti-inflammatory, antioxidant, antibacterial, anticancer and many other properties. Objective: This review summarizes the scientific evidences showing possible benefits of C. longa in a variety of ophthalmic diseases. Conclusion: Although the putative mechanism(s), molecular targets and range of therapeutic applications have been researched widely, further investigations are needed to explore the true therapeutic potential and future of curcuminoids as novel drug molecules in ophthalmic diseases.
11594402
Intraocular Pressure-Lowering Activity of Topical Application of Aegle Marmelos Fruit Extract in Experimental Animal Models
Aim: The present study was designed to evaluate the intraocular pressure (IOP)-lowering activity of topical application of the aqueous extract of Aegle marmelos fruit in experimental animal models. Materials and Methods: New Zealand white rabbits with normal and experimentally elevated IOP using water loading and steroid-induced models were included in this study. The IOP-lowering effect of A. marmelos fruit extract in rabbits with experimentally elevated IOP was also compared with that of timolol 0.25%. Results: In rabbits with normal IOP, the A. marmelos fruit extract at a concentration of 1% showed the maximum IOP-lowering effect with 22.81% reduction from baseline IOP. The maximum IOP reduction achieved in water loading and steroid-induced models with the same concentration of A. marmelos was 27.57 and 28.41% from baseline, respectively. The efficacy was comparable to that of timolol after 45 min of water loading in the water loading model, and during the first 2 h of treatment in the steroid-induced model. Conclusion: A. marmelos fruit extract showed significant IOP-lowering activity in experimental animal models.
39024721
Efficacy and safety of iodopovidone in chemical pleurodesis: a meta-analysis of observational studies.
The search for an 'ideal' agent for pleurodesis continues. Iodopovidone is a topical antiseptic and has been shown to be safe and effective in many studies. The aim of this study was to evaluate the efficacy and safety of iodopovidone as an agent for chemical pleurodesis. We performed a systematic review of all the observational trials which have used iodopovidone for chemical pleurodesis. Six studies including 265 patients who had undergone chemical pleurodesis with iodopovidone were included for this analysis. Iodopovidone was used for variety of indications, which included pleural effusion (157 patients), and pneumothorax (108 patients). Pleurodesis was performed through tube thoracostomy in 144 patients and through thoracoscopy in 121 patients. The success rate of pleurodesis varied from 64.2% to 100%, and summary success rate of all the studies was 90.6% (95% confidence intervals [CI], 86.4-93.8). The success rate was independent for the procedure (tube thoracostomy [126/144; 87.5%, 95% CI 80.9-92.4] or thoracoscopy [114/121; 94.2%, 95% CI 88.4-97.6]) used for performing pleurodesis or for the indication (pleural effusion [139/157; 88.5%, 95% CI 82.5-93.1] or pneumothorax [101/108; 93.5%, 95% CI 87.1-97.4]). The only significant complication reported was chest pain of varying degree. Systemic hypotension was reported in three patients in only one study. There were no deaths related to chemical pleurodesis with iodopovidone. Overall, this review supports the safety and efficacy of iodopovidone as an agent for chemical pleurodesis in cases of recurrent pleural effusions and pneumothoraces regardless of their etiology.
20628925
Chronic kidney disease is associated with oxidative stress independent of hypertension.
BACKGROUND
Oxidative stress is implicated in the pathogenesis of chronic kidney disease (CKD) and essential hypertension (EHTN). However, the role of hypertension in causing increased oxidative stress in patients with CKD is unknown.


METHODS
We performed a case control study in patients with EHTN and those with equal blood pressure assessed by ambulatory blood pressure monitoring but with concomitant CKD. Those with diabetes mellitus and those taking renin angiotensin inhibitors were excluded. Biomarkers of oxidative stress, malondialdehyde (MDA) and protein carbonylation and total glutathione levels were measured.


RESULTS
Average (SD) 24-hour ambulatory blood pressure in 12 patients with CKD was 134 (17)/75 (16) compared to 134 (10)/80 (9) in 11 patients with EHTN (p = NS). Plasma MDA in CKD was 0.89 +/- 0.38 micromol/l compared to 0.68 +/- 0.16 micromol/l in EHTN (p = 0.07). Urinary MDA/creatinine ratio was 1.78 (0.31) in CKD vs 1.43 (0.69) micromol/g in those with EHTN (p = 0.04). Thus, lipid peroxidation was increased in urine of CKD patients. Patients with CKD had higher (1.04 (0.20) nmol) carbonyl/mg protein compared to those with EHTN (0.80 (0.21) nmol carbonyl/mg protein) (p = 0.03). Thus, protein carbonylation was increased in CKD patients. Total glutathione in CKD and EHTN patients was 6.6 (1.8) ng/ml and 7.3 (3.1) ng/ml (p = NS). There was a good correlation between biomarkers of lipid (MDA) and protein oxidation (protein carbonyls) (r = 0.6, p = 0.004).


CONCLUSIONS
Biomarkers of lipid and protein oxidation are higher in patients with CKD compared to EHTN despite similar blood pressure. Thus, nonhemodynamic factors such as inflammation and altered cellular redox state may play a greater role in the generation of oxidative stress in CKD.
33440140
Supervised atenolol therapy in the management of hemodialysis hypertension.
BACKGROUND
Uncontrolled hypertension continues to be a common problem, particularly in noncompliant hemodialysis patients. Atenolol, a water soluble beta-blocker has a prolonged half-life in renal failure and may serve as a useful antihypertensive agent in these patients.


METHODS
Hypertension was diagnosed by ambulatory blood pressure monitoring for 44 hours during an interdialytic interval in eight chronic hemodialysis patients receiving no antihypertensive therapy. An average daytime blood pressure greater than 140/90 mm Hg or an average nighttime blood pressure greater than 120/80 mm Hg was used to define uncontrolled hypertension. Patients were then administered atenolol (25 mg) following hemodialysis three times a week. The efficacy of therapy was judged by ambulatory blood pressure monitoring three weeks after instituting atenolol therapy. Blood pressure loads above the threshold blood pressures during the day or night were also calculated and compared before and after three weeks of atenolol therapy.


RESULTS
The mean 44-hour ambulatory blood pressure (ABP) fell from 144 +/- 14/80 +/- 7 mm Hg to 127 +/- 13/69 +/- 10 mm Hg (P < 0.001). The heart rate fell from 85 +/- 11 to 70 +/- 11 beats per minute. The systolic and diastolic blood pressure load was reduced from 71 +/- 25% and 30 +/- 24% to 35 +/- 26% and 11 +/- 17%, respectively (P < 0.001). There was a persistent antihypertensive effect over 44 hours. The blood pressure reduction was achieved without any increase in intradialytic symptomatic or asymptomatic hypotensive episodes, reduction in delivered dialysis, or statistically significant changes in serum potassium or glucose.


CONCLUSIONS
A supervised administration of atenolol following hemodialysis effectively and safely controls hypertension in chronic hemodialysis patients. This therapy can be particularly valuable for noncompliant hemodialysis patients.
39272838
Urinary protein binding does not affect response to furosemide in patients with nephrotic syndrome.
Response to loop diuretics in patients with nephrotic syndrome (NS) is subnormal. Studies in animal models of NS have suggested that binding of diuretic to urinary albumin is one of the mechanisms that may be operative in this diuretic resistance. To explore this hypothesis, 12 patients with NS were studied to determine whether displacement from urinary protein binding with sulfisoxazole would restore response to 120 mg of furosemide. The study was stopped after treating seven patients because it was clear that sulfizoxazole had no effect. Sodium excretion (mean +/- SD) from furosemide alone was 239 +/- 90 versus 240 +/- 115 mEq/8 h with sulfisoxazole. Sulfisoxazole had modest effects on serum pharmacokinetics of furosemide but had no effect on either the time course of furosemide urinary excretion or overall amount excreted: 49 +/- 15 mg versus 54 +/- 12 mg for furosemide alone and furosemide plus sulfisoxazole, respectively. It is concluded that urinary protein binding of loop diuretics is not a major mechanism for the diuretic resistance of NS. In turn, strategies aimed at displacing such binding are unlikely to be clinically helpful.
124927
Oxidative stress in hypertension and chronic kidney disease: role of angiotensin II.
Angiotensin II, via the type 1 (AT1) receptor, stimulates oxidative stress. The vasculature, interstitium, juxtaglomerular apparatus, and the distal nephron in the kidney express nicotinamide adenine dinucleotide phosphate (NADPH) oxidase that generates superoxide anion, which is an important component of angiotensin II-induced oxidative stress. The angiotensinogen gene is stimulated by NF-kappaB activation, which is sensitive to the redox ratio, providing a positive feedback loop that can upregulate angiotensin II production. Oxidative stress can accompany hypertension in many models, including the spontaneously hypertensive rat (SHR), angiotensin II-infused rats, renovascular hypertension, and the deoxycorticosterone acetate (DOCA) salt model of hypertension. AT1 receptor antagonists can abrogate the effects of angiotensin II on oxidative stress, thus providing an important mechanistic insight onto the renal protective effects of these agents in conditions associated with angiotensin II excess.