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.
15667066
Oculohypotensive effects of foeniculum vulgare in experimental models of glaucoma.
PURPOSE
Evaluation of oculohypotensive activity of single drop application of aqueous extract of Foeniculum vulgare in experimental models of glaucoma.


METHODS
The evaluation of oculohypotensive activity of Foeniculum vulgare was done in rabbits with normal intraocular pressure (IOP) and with experimentally elevated IOP. The experimental increase in IOP was achieved using water loading and steroid induced glaucoma models.


RESULTS
The aqueous seed extract of Foeniculum vulgare exhibited 17.49, 21.16 and 22.03% reduction of intraocular pressure (IOP) in normotensive rabbits at 0.3%, 0.6% and 1.2% (w/v) concentrations respectively. The 0.6% concentration was further evaluated in acute and chronic models of glaucoma. A maximum mean difference of 31.20% was observed between vehicle treated and extract treated eyes in water loading model while a maximum mean IOP lowering of 31.29% was observed in steroid induced model of glaucoma.


CONCLUSIONS
The aqueous extract of Foeniculum vulgare possesses significant oculohypotensive activity, which was found to be comparable to that of timolol. Further investigations into the mechanism of action, possible toxicity and human clinical trials are warranted before the Foeniculum vulgare finds place in the arsenal of antiglaucoma drugs prescribed by physicians.
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.
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.
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.
38466120
Novel therapeutic agents in ovarian cancer.
AIMS
Epithelial ovarian cancer is responsible for 4% of all cancer deaths in women, and the five-year overall survival of patients with advanced disease is 30-40%. Treatment currently comprises a combination of surgery and chemotherapy with carboplatin and paclitaxel. The main reason for treatment failure is that the majority of patients present with advanced disease, and current drugs are unable to effect a cure even in chemosensitive patients. This article systematically reviews novel therapeutic strategies that have been evaluated in patients with ovarian cancer in the last 5 years.


METHODS
Pubmed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed) and American Society of Clinical Oncology Annual conference abstracts were searched using the terms "(phase I OR phase II OR phase III OR phase 1 OR phase 2 OR phase 3) AND (ovary OR ovarian) AND (cancer OR carcinoma)" from January 2000 to May 2005 to identify studies for potential inclusion in this review. Reviews of novel therapies in ovarian cancer were also used to identify additional clinical trials.


FINDINGS
A wide range of therapeutic strategies are currently being evaluated in ovarian cancer. These include novel cytotoxics, small molecule inhibitors, monoclonal antibodies, gene therapy and immuno-therapy strategies. The rationale for the development of these agents includes enhancement of efficacy by targeting novel biological pathways, re-sensitisation to existing drugs, simplification of drug administration and/or reduction of drug-toxicity.


CONCLUSIONS
Current developments have the potential to result in substantial improvements in the outlook for women with ovarian cancer.
35032978
Cobbled tongue.
39974976
Antiproteinuric effect of oral paricalcitol in chronic kidney disease.
BACKGROUND
Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients.


METHODS
In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N= 107, mean dose 9.5 microg/week) or placebo (N= 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of paricalcitol on proteinuria.


RESULTS
At baseline, proteinuria was present in 57 patients randomized to oral paricalcitol and 61 patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P= 0.004 (odds for reduction in proteinuria 3.2 times greater for paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive > or =30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS).


CONCLUSION
Our results demonstrate that the reduction in proteinuria was associated with paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.
25565003
What is the role of noninvasive ventilation in diastolic heart failure?
26099246
Expression profiling and individualisation of treatment for ovarian cancer.
Ovarian cancer is the commonest cause of gynaecological cancer-related mortality. Patients with this disease generally undergo surgery followed by platinum-taxane chemotherapy, with additional chemotherapy at relapse. Although the prognosis for patients with advanced cancer is poor--a five-year survival of only 30-40%--there is a wide range of outcomes for individual patients. To date, clinico-pathological variables such as age, stage, grade, histology, debulking status and response to chemotherapy continue to provide the basis on which treatment decisions are made for individual patients. Immunohistochemical markers and information on p53 mutation status have been extensively evaluated in ovarian cancer, but have not yet been shown to be sufficiently informative to influence clinical decisions on a routine basis. The recent advent of expression profiling has provided a new impetus to identifying clinically useful prognostic markers. The ambition of personalised medicine through microarray-based profiling appears to be realistic, but further studies on large uniform cohorts are needed before this potential is fully realised.