Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

KD025 Shifts Pulmonary Endothelial Cell Bioenergetics and Decreases Baseline Lung Permeability.

KD025 is a ROCK2 inhibitor currently being tested in clinical trials for the treatment of fibrotic lung diseases. The therapeutic effects of KD025 are partly due to its inhibition of profibrotic pathways and fat metabolism. However, whether KD025 affects pulmonary microvascular endothelial cell (PMVEC) function is unknown, despite evidence that alveolar-capillary membrane disruption constitutes major causes of death in fibrotic lung diseases. We hypothesized that KD025 regulates PMVEC metabolism, pH, migration, and survival, a series of interrelated functional characteristics that determine pulmonary barrier integrity. We used PMVECs isolated from Sprague Dawley rats. KD025 dose-dependently decreased lactate production and glucose consumption. The inhibitory effect of KD025 was more potent compared with other metabolic modifiers, including 2-deoxy-glucose, extracellular acidosis, dichloroacetate, and remogliflozin. Interestingly, KD025 increased oxidative phosphorylation, whereas 2-deoxy-glucose did not. KD025 also decreased intracellular pH and induced a compensatory increase in anion exchanger 2. KD025 inhibited PMVEC migration, but fasudil (nonspecific ROCK inhibitor) did not. We tested endothelial permeability in vivo using Evans Blue dye in the bleomycin pulmonary fibrosis model. Baseline permeability was decreased in KD025-treated animals independent of bleomycin treatment. Under hypoxia, KD025 increased PMVEC necrosis as indicated by increased lactate dehydrogenase release and propidium iodide uptake and decreased ATP; it did not affect Annexin V binding. ROCK2 knockdown had no effect on PMVEC metabolism, pH, and migration, but it increased nonapoptotic caspase-3 activity. Together, we report that KD025 promotes oxidative phosphorylation; decreases glycolysis, intracellular pH, and migration; and strengthens pulmonary barrier integrity in a ROCK2-independent manner.

Physiological performance, secondary metabolite and expression profiling of genes associated with drought tolerance in Withania somnifera.

Physiological, biochemical, and gene expression responses under drought stress were studied in Withania somnifera. Photosynthesis rate, stomatal conductance, transpiration rate, relative water content, chlorophyll content, and quantum yield of photosystems I and II (PSI and PSII) decreased in response to drought stress. Comparative expression of genes involved in osmoregulation, detoxification, signal transduction, metabolism, and transcription factor was analyzed through quantitative RT-PCR. The genes encoding 1-pyrroline-5-carboxylate synthetase (P5CS), glutathione S-transferase (GST), superoxide dismutase (SOD), serine threonine-protein kinase (STK), serine threonine protein phosphatase (PSP), aldehyde dehydrogenase (AD), leucoanthocyanidin dioxygenase/anthocyanin synthase (LD/AS), HSP, MYB, and WRKY have shown upregulation in response to drought stress condition in leaf tissues. Enhanced detoxification and osmoregulation along with increased withanolides production were also observed under drought stress. The results of this study will be helpful in developing stress-tolerant and high secondary metabolite yielding genotypes.

Morphological, chemical and molecular characterization of Centella asiatica germplasms for commercial cultivation in the Indo-Gangetic plains.

Centella asiatica germplasm collected from north, north-eastern and southern parts of India was compared for biomass and centellosides productivity under uniform agro-climatic conditions of the Indo-Gangetic plains at Lucknow. The highest biomass accumulation (411.9 g FW/m2 area) was recorded in accession A from north India, followed by 284.0, 135.7 and 29.2 g FW/m2 in accessions M, B and E from southern, eastern and north-eastern regions, respectively. Accession M possessed the highest asiaticoside content (52.1 mg/gDW) that was 1.58, 2.34 and 21.7 folds more than accessions A, B and E, respectively. The madecassoside level in leaves of accessions B and M was comparable (28.9 and 25.7 mg/gDW) and two folds more than accession A (13.9 mg/gDW). The madecassic and asiatic acid content in leaf tissue of all four accessions remained low in Lucknow. Amplified fragment length polymorphism (AFLP) analysis with 23 primers yielded 696 fragments, 563 of which were polymorphic. Accession M out-grouped with genetic dissimilarity indices of 83, 85 and 95% from accessions A, E and B, respectively. Commercial cultivation of accessions M and A through a four months growth cycle (June to September) in agro-climatic conditions of the Indo-Gangetic plains is suggested.

Evaluation of antiulcer potential of Mimusops hexandra in experimental gastro duodenal ulcers.

The study was aimed to investigate antiulcer effects of acetone extract and its different fractions Mimusops hexandra against experimental gastro-duodenal ulcers. 80% acetone extract of stem bark of Mimusops hexandra (Extract A, p.o.) and its different fractions namely diethyl ether (Extract A1, p.o.), ethyl acetate (Extract A2, p.o.) and aqueous (Extract A3, p.o.) were tested for the presence of preliminary phytoconstituents and were screened for their antiulcer potential in experimental animals using ethanol-HCl and aspirin-induced gastric damage at the dose of 500 mg kg-1p.o. Extract A2 being the most active fraction amongst all the fractions tested was also studied at different doses to find its ED50. Further, to establish the mechanism of action, Extract A2 was also tested for its effects in acetic acid-induced gastric ulcer models and cysteamine-induced duodenal ulcer. The effect was compared with cimetidine. Flavonoids (quercetin), procyanidins, saponins and triterpenoids were found to be present in bark. Oral administration of Extract A2 inhibited formation of gastric lesions induced by aspirin in a dose dependent manner. Elevated level of lipid peroxidation due to ethanol-HCl and aspirin induced gastric damage was significantly (p<0.05) reduced by the treatment with Extract A2. Further, Extract A2 at the dose of 100 mg kg-1 (p.o.) reduced extent of acetic acid induced gastric ulcer in experimental animals. Moreover, protection afforded by Extract A2 against cysteamine-induced duodenal lesions was evident from dose dependent decrease in ulcer index (p<0.05), score for intensity (p<0.05) and total lesion area (p<0.05), when compared with the control group. The antiulcer activity shown by Extract A2 in experimental gastro-duodenal ulcer could be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms.

Effect of Woodfordia fruticosa on dexamethasone induced insulin resistance in mice

Diabetes is a group of syndrome characterized by hyperglycemia, altered metabolism of lipids, carbohydrates and proteins, resulting in an increased risk of complications from vascular disease. The flowers of Woodfordia fruticosa (L.) Kurz, Lythraceae, have been used traditionally in the treatment of diabetes, dysentery, diarrhea, other bowel complaints, internal haemorrhages, in leucorrhoea and menorrhagia. Externally powdered flower is sprinkled over foul ulcers and wounds for diminishing their discharge and promoting granulations. In Konkan leaves are used in bilious sickness. W. fruticosa is also reported to have DNA topoisomerase inhibitor, antibacterial, antifertility, antipeptic ulcer, free radical scavenging, and hepatoprotective activity. W. fruticosa is a medicinal plant used to treat a wide range of disorder including diabetes. The present work investigates the effects of the WF in dexamethsone induced insulin resistance in mice. The results of animal study revealed that the extract at dose 100, 200 and 400 mg/kg was found to be significant (p<0.01) after 22 days of treatment. Further isolation studies afforded an anthraquinone glycoside, chrysophanol-8-O-β-D-glucopyranoside. Moreover further experiments will be required to identify their exact mechanism of action.

Renal toxicity of lisinopril and rosuvastatin, alone and in combination, in Wistar rats.

The aim of study was to evaluate the effect of commonly used lisinopril, rosuvastatin and their combined action on site-specific nephrotoxicity in rats using clusterin and microalbumin nephrotoxic biomarkers and other related parameters using oral gavage. Rosuvastatin at 2 different doses showed increase in urinary microalbumin levels whereas lisinopril and its combination with rosuvastatin at 2 different doses did not show urinary microalbumin excretion indicating beneficial effects of lisinopril in terms of reducing microalbumin. Urinary clusterin levels significantly increased in high-dose treated animals of lisinopril and rosuvastatin. The use of lisinopril plus rosuvastatin at low dose also led to worsened renal function by raising urinary clusterin levels (217 ± 4.6 ng/ml) when compared with the control (143 ± 3.3 ng/ml). Renal histopathology showed multifocal regeneration of tubules indicating proximal tubule damaged. These results indicate that lisinopril (50 mg/kg), rosuvastatin (100 mg/kg), lisinopril+rosuvastatin (20+40 mg/kg) and lisinopril+rosuvastatin (50+100 mg/kg) showed toxicity only on proximal tubules.

A novel herbal formulation in the management of diabetes.

BACKGROUND AND AIM: Momordica charantia Linn. is traditionally used as a medicine for diabetes. The present investigation was aimed to formulate and evaluate transdermal patchesof Momordica charantia Linn. MATERIALS AND METHODS: The transdermal films containing the herbal drug component fractionated fromethanolicextract of M. charantia fruits were prepared by using hydroxy propyl methyl cellulose as a polymer. The films were evaluated for folding endurance, thickness, weight variation, drug contents and in vitro diffusion studies and in vivo parameterslike acute and sub-acute antihyperglycemic activity in diabetic rats, biochemicalstudies, skin irritation in rats and stability studies. RESULT AND DISCUSSION: The weightof transdermal patches of M. charantia (2 cm(2); 10 mg/patch) and was found to be 0.03 gm.Thickness of patches of M. charantia (2 cm(2); 10 mg/patch) was found to be satisfactory. The percentage release of active constituents from transdermal patches of M.charantia (2 cm(2); 10 mg/patch) was found to be 47.59% in 10% hydroalcoholic phosphate buffer pH 7.4 at the end of 6 h.The transdermal route exhibited negligible skin irritation and in vivo results revealed that the patches successfully decrease the blood glucose level. CONCLUSION: From the results, we concluded that the well-known herbal drug M. charantia Linn. have been found to be effective for diabetes through modern pharmaceutical formulation techniques.

Functional specialization of domains tandemly duplicated within 16S rRNA methyltransferase RsmC.

RNA methyltransferases (MTases) are important players in the biogenesis and regulation of the ribosome, the cellular machine for protein synthesis. RsmC is a MTase that catalyzes the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to G1207 of 16S rRNA. Mutations of G1207 have dominant lethal phenotypes in Escherichia coli, underscoring the significance of this modified nucleotide for ribosome function. Here we report the crystal structure of E. coli RsmC refined to 2.1 A resolution, which reveals two homologous domains tandemly duplicated within a single polypeptide. We characterized the function of the individual domains and identified key residues involved in binding of rRNA and SAM, and in catalysis. We also discovered that one of the domains is important for the folding of the other. Domain duplication and subfunctionalization by complementary degeneration of redundant functions (in particular substrate binding versus catalysis) has been reported for many enzymes, including those involved in RNA metabolism. Thus, RsmC can be regarded as a model system for functional streamlining of domains accompanied by the development of dependencies concerning folding and stability.

A novel use of methylene blue as a pharmacological tool.

INTRODUCTION: A new use of methylene blue as an ulcerogenic agent and the mechanisms involved were identified with an objective to exploit methylene blue as a pharmacological tool to study investigational antiulcer agents. METHODS: Ulcerogenic potential was assessed using electron microscopy and measurement of an ulcer index after administering methylene blue (5-125 mg kg(-1), p.o.) or absolute ethanol (99%v/v, 2 ml, p.o.) to fasted rats. Estimation of thiobarbituric acid reactive substances, superoxide dismutase, reduced glutathione and catalase was used to assess oxidative stress. H(+)/K(+) ATPase activity, gastric mucosal blood flow and gastric acid secretion were measured to study the mechanism of methylene induced gastric ulcer. RESULTS: Methylene blue (100 mg kg(-1), p.o.) produced marked ulceration of the gastric mucosa due to increased levels of thiobarbituric acid reactive substances, activities of the H(+)/K(+) ATPase and superoxide dismutase, and decreased blood flow to the gastric mucosa, activity of catalase combined with reduced glutathione levels. DISCUSSION: It may be concluded that methylene blue activates the H(+)/K(+) ATPase to increase gastric acid secretion and reduces blood supply to gastric mucosa to produce oxidative stress that subsequently causes ulceration of gastric mucosa. Methylene blue can be used as an ulcerogenic agent to study mechanisms of investigational antiulcer agents.

Study of Mimusops elengi bark in experimental gastric ulcers.

The present study was designed to investigate the effect of Mimusops elengi (Sapotaceae) against experimental gastric ulcers. The 50% alcoholic extract of Mimusops elengi (Ext E) and its different fractions namely ethyl acetate (Ext E1), n-butanol (Ext E2), methanol (Ext E3) and aqueous (Ext E4) were studied (p.o.) against ethanol-induced gastric damage. Ext E1 was also studied in ethanol-induced, pylorus-ligated and water-immersion plus stress-induced gastric ulcer models. Ranitidine HCl (80 mg kg(-1)) was used as a reference standard. In ethanol-induced gastric ulcer model, pantoprazole (20 mg kg(-1)) was also used as a reference standard. Ext E1 tested in mice up to the dose of 5000 mg kg(-1) (p.o.) did not produce any sign of toxicity. Ext E at the doses of 50, 100, 300 and 500 mg kg(-1) and its different fractions (100 mg kg(-1)) showed reduction in gastric ulceration (P < 0.05). Ext E1 at the doses of 10, 50 and 100 mg kg(-1) showed dose-dependent inhibition of gastric lesions against ethanol-induced gastric damage. In 19 h pylorus-ligated animals, Ext E1 at 50 and 100 mg kg(-1) doses showed significant reduction in ulcer index (P < 0.05). Significant reduction was also observed in total acidity, volume of gastric acid secretion, total acid output and pepsin activity (P < 0.05) when compared with the control group. Besides, Ext E1 showed increase in the mucosal glycoproteins that was evident from significant rise in total carbohydrates to protein ratio (TC:PR ratio) (P < 0.05), which is an indication of mucin activity. Ext E1 also showed protection against water-immersion plus stress-induced gastric lesions that was evident from dose-dependent decrease in ulcer index (P < 0.05), score for intensity (P < 0.05) and total lesion area (P < 0.05) when compared with the control group. It can be concluded from our study that Ext E1 possesses anti-ulcer activity against experimental gastric ulcers. The mechanism of anti-ulcer activity can be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms.