Phosphorus supplementation modulates nitric oxide biosynthesis and stabilizes the defence system to improve arsenic stress tolerance in mustard.

The interaction of mineral nutrients with metals/metalloids and signalling molecules is well known. In the present study, we investigated the effect of phosphorus (P) in mitigation of arsenic (As) stress in mustard (Brassica juncea L.). The study was conducted to investigate potential of 30 mg P·kg-1 soil P supplement (diammonium phosphate) to cope up with the adverse effects of As stress (24 mg As·kg-1 soil) in mustard plants Supplementation of P influenced nitric oxide (NO) generation, which up-regulated proline metabolism, ascorbate-glutathione system and glyoxalase system and alleviated the effects of on photosynthesis and growth. Arsenic stress generated ROS and methylglyoxal content was scavenged through P-mediated NO, and reduced As translocation from roots to leaves. The involvement of NO under P-mediated alleviation of As stress was substantiated with the use of cPTIO (NO biosynthesis inhibitor) and SNP (NO inducer). The reversal of P effects on photosynthesis under As stress with the use of cPTIO emphasized the role of P-mediated NO in mitigation of As stress and protection of photosynthesis The results suggested that P reversed As-induced oxidative stress by modulation of NO formation, which regulated antioxidant machinery. Thus, P-induced regulatory interaction between NO and reversal of As-induced oxidative stress for the protection of photosynthesis may be suggested for sustainable crops.

Effect of different levels of protein concentrates supplementation on the growth performance, plasma amino acids profile and mTOR cascade genes expression in early-weaned yak calves.

OBJECTIVE: This study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to changes occurring in the plasma- amino acids, -insulin profile, and signaling activity of mammalian target of rapamycin (mTOR) cascade to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks. METHODS: For this study, 48 early (3 months old) weaned yak calves were selected, and assigned into four dietary treatments according to randomized complete block design. The four blocks were balanced for body weight and sex. The yaks were either grazed on natural pasture (control diet) in a single herd or the grazing yaks was supplemented with one of the three protein rich supplements containing low (17%; LP), medium (19%; MP), or high (21%; HP) levels of crude proteins for a period of 30 days. RESULTS: Results showed that the average daily gain of calves increased (0.14 vs 0.23-0.26 kg; p<0.05) with protein concentrates supplementation. The concentration of plasma methionine increased (p<0.05; 8.6 vs 10.1-12.4 µmol/L), while those of serine and tyrosine did not change (p>0.05) when the grazing calves were supplemented with protein concentrates. Compared to control diet, the insulin level of calves increased (p<0.05; 1.86 vs 2.16-2.54 µIU/mL) with supplementation of protein concentrates. Addition of protein concentrates up-regulated (p<0.05) expression of mTOR-raptor, mammalian vacuolar protein sorting 34 homolog, the translational regulators eukaryotic translation initiation factor 4E binding protein 1, and S6 kinase 1 genes in both Longissimus dorsi and semitendinosus. In contrast, the expression of sequestosome 1 was down-regulated in the concentrate supplemented calves. CONCLUSION: Our results show that protein supplementation improves the growth performance of early weaned yak calves, and that plasma methionine and insulin concentrations were the key mediator for gene expression and protein deposition in the muscles.

Moringa olifeira Lam. Stimulates Activation of the Insulin-Dependent Akt Pathway. Antidiabetic Effect in a Diet-Induced Obesity (DIO) Mouse Model.

We investigated the antidiabetic effect of Moringa olifeira Lam. in a diet-induced obesity (DIO) mouse model. Six mice were randomly selected as normal controls. Moringa olifeira Lam. leaf extract at a dose of 200, 400 or 600 mg/kg body weight, glibenclamide (Glib) at the dose of 10 mg/kg (positive control) and distilled water at 10 ml/kg (control group) were administered orally by gastric intubation, and each group consisted of six mice. Insulinsensitive tissues (liver, skeletal muscle) were collected to investigate antidiabetic effects and examine the plant's molecular mechanisms. Moringa olifeira Lam. leaf extract prevented weight gain. It also reduced blood glucose in DIO mice. Glib and Moringa olifeira Lam. leaf extract, 400 mg/kg, treatments restored insulin levels towards normal values (P < 0.05 versus diabetic control group). Western immunoblot analysis of different tissues, collected at the end of the study, demonstrated that Moringa olifeira Lam. stimulated activation of the insulin-dependent Akt pathway and increased the protein content of Glut 4 in skeletal muscle. The improvement of hepatic steatosis observed in DIO-treated mice was associated with a decrease in the hepatic content of SREBP-1, a transcription factor involved in de novo lipogenesis. The hepatic PPARα protein content in the plant extract- treated mice remained significantly higher than those of the control group (P < 0.05). In conclusion, this study provides the first evidence for direct action of Moringa olifeira Lam. on pancreatic ß-cells, enhancing glucose-stimulated insulin secretion. This correlated with hypoglycaemic effects in diabetic mice associated with restored levels of plasma insulin.

Moringa oleifera-rich diet and T cell calcium signaling in spontaneously hypertensive rats.

Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physicochemical analysis shows that Moringa oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was diminished in both strains of rats fed the Moringa oleifera. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. Studies of platelets from patients with primary hypertension and from SHR support the notion that the concentration of intracellular free calcium [Ca(2+)](i) is modified in both clinical and experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T cells of SHR than in those of WKY rats fed the control diet. Feeding the diet with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of IL-2 and modulates T cell calcium signaling in hypertensive rats.

Improving management of type 2 diabetes in South Asian patients: a systematic review of intervention studies.

OBJECTIVES: Optimal control of type 2 diabetes is challenging in many patient populations including in South Asian patients. We systematically reviewed studies on the effect of diabetes management interventions targeted at South Asian patients with type 2 diabetes on glycaemic control. DESIGN: Systematic review of MEDLINE, EMBASE and CINAHL databases for randomised controlled trials (RCTs) and pre-post-test studies (January 1990 to February 2014). Studies were stratified by where interventions were conducted (South Asia vs Western countries). PARTICIPANTS: Patients originating from Pakistan, Bangladesh or India with type 2 diabetes. PRIMARY OUTCOME: Change in glycated haemoglobin (HbA1c). Secondary end points included change in blood pressure, lipid levels, anthropomorphics and knowledge. RESULTS: 23 studies (15 RCTs) met criteria for analysis with 7 from Western countries (n=2532) and 16 from South Asia (n=1081). Interventions in Western countries included translated diabetes education, additional clinical care, written materials, visual aids, and bilingual community-based peers and/or health professionals. Interventions conducted in South Asia included yoga, meditation or exercise, community-based peers, health professionals and dietary education (cooking exercises). Among RCTs in India (5 trials; n=390), 4 demonstrated significant reductions in HbA1c in the intervention group compared with usual care (yoga and exercise interventions). Among the 4 RCTs conducted in Europe (n=2161), only 1 study, an education intervention of 113 patients, reported a significant reduction in HbA1c with the intervention. Lipids, blood pressure and knowledge improved in both groups with studies from India more often reporting reductions in body mass index and waist circumference. CONCLUSIONS: Overall, there was little improvement in HbA1c level in diabetes management interventions targeted at South Asians living in Europe compared with usual care, although other outcomes did improve. The smaller studies in India demonstrated significant improvements in glycaemic and other end points. Novel strategies are needed to improve glycaemic control in South Asians living outside of India.

Evaluation of anti-inflammatory potential of leaf extracts of Skimmia anquetilia.

OBJECTIVE: To evaluate anti-inflammatory potential of leaf extract of Skimmia anquetilia by in-vitro and in-vivo anti-inflammatory models. METHODS: Acute toxicity study was carried out to determine the toxicity level of different extract using acute toxic class method as described in Organization of Economic Co-operation and Development Guidelines No.423. Carrageenan (1% w/w) was administered and inflammation was induced in rat paw. The leaf extracts of Skimmia anquetilia were evaluated for anti-inflammatory activity by in-vitro human red blood cell (HRBC) membrane stabilization method and in-vivo carrangeenan-induced rat paw edema method. RESULTS: The in-vitro membrane stabilizing test showed petroleum ether (PE), chloroform (CE), ethyl acetate (EE), methanol (ME) and aqueous extracts (AE) showed 49.44%, 59.39%, 60.15%, 68.40% and 52.18 % protection, respectively as compared to control groups. The in-vivo results of CE, EE and ME showed 58.20%, 60.17% and 67.53% inhibition of inflammation after 6h administration of test drugs in albino rats. The potency of the leaf extracts of Skimmia anquetilia were compared with standard diclofenac (10 mg/kg) which showed 74.18% protection in in-vitro HRBC membrane stabilization test and 71.64% inhibition in in-vivo carrangeenan-induced rat paw edema model. The ME showed a dose dependent significant (P< 0.01) anti-inflammatory activity in human red blood cell membrane stabilization test and reduction of edema in carrageenan induced rat paw edema. CONCLUSIONS: The present investigation has confirmed the anti-inflammatory activity of Skimmia anquetilia due to presence of bioactive phytoconstitutes for the first time and provide the pharmacological evidence in favor of traditional claim of Skimmia anquetilia as an anti- inflammatory agent.

Serum lipoprotein composition, lecithin cholesterol acyltransferase and tissue lipase activities in pregnant diabetic rats and their offspring receiving enriched n-3 PUFA diet.

The effects of dietary n-3 polyunsaturated fatty acids on lipoprotein concentrations and on lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL) and lecithin cholesterol acyltransferase (LCAT) activities were studied in streptozotocin-induced diabetic rats during pregnancy and in their macrosomic offspring from birth to adulthood. Pregnant diabetic and control rats were fed Isio-4 diet (vegetable oil) or EPAX diet (concentrated marine omega-3 EPA/DHA oil), the same diets were consumed by pups at weaning. Compared with control rats, diabetic rats showed, during pregnancy, a significant elevation in very low density lipoprotein (VLDL) and low and high density lipoprotein (LDL-HDL(1))-triglyceride, cholesterol and apoprotein B100 concentrations and a reduction in apoprotein A-I levels. HTGL activity was high while LPL and LCAT activities were low in these rats. The macrosomic pups of Isio-4-fed diabetic rats showed a significant enhancement in triglyceride and cholesterol levels at birth and during adulthood with a concomitant increase in lipase and LCAT activities. EPAX diet induces a significant diminution of VLDL and LDL-HDL(1) in mothers and in their macrosomic pups, accompanied by an increase in cholesterol and apoprotein A-I levels in HDL(2-3) fraction. It also restores LPL, HTGL and LCAT activities to normal range. EPAX diet ameliorates considerably lipoprotein disorders in diabetic mothers and in their macrosomic offspring.

N-3 fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring.

OBJECTIVE: We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring. DESIGN: Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days. MEASUREMENTS: Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in erythrocytes. The plasma lipid concentrations and fatty acid composition were also determined. RESULTS: Diabetes increased plasma triglyceride and cholesterol concentrations, whereas macrosomia was associated with enhanced plasma cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N-3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC values in diabetic rats and their macrosomic offspring. EPAX diet increased the diminished vitamin A levels in diabetic mothers and vitamin C concentrations in macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide dismutase and glutathione peroxidase activities in diabetic and macrosomic animals. CONCLUSION: Diabetes and macrosomia were associated with altered lipid metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA diet improved hyperlipidemia and restored antioxidant status in diabetic dams and MAC offspring.

Effect of Aralia cachemirica Decne root extracts on blood glucose level in normal and glucose loaded rats.

An aqueous and alcoholic extract of the roots of Aralia cachemirica (Araliaceae) were evaluated for hypoglycemic activity in normal fasted and glucose induced hyperglycemic rats. The aqueous and alcoholic extracts at a dose of 250 mg/kg showed statistically significant (p < 0.01) hypoglycemic activity in glucose loaded animals however no effect was observed in normal fasted rats.

Diuretic and nephroprotective effect of Jawarish Zarooni Sada--a polyherbal unani formulation.

A number of drugs, both single and compound preparations are used widely in Tibb-e-Unani (Unani medicine) in the management of renal diseases. But such drugs mostly, have not been investigated for their described effects. Jawarish Zarooni Sada (JZS) is one such polyherbal preparation containing 15 ingredients, mainly described to be diuretic and nephroprotective. Therefore, in the present study ethanol and water extracts of JZS (300 mg each) were investigated for diuretic activity by measuring the total urine output over a period of 6h. Sodium and potassium level in urine sample was also estimated. Nephroprotective activity of JZS against gentamicin-induced nephrotoxicity was investigated by administering JZS along with high dose of gentamicin (40 mg/kg) and elevation of serum urea and serum creatinine was taken as the index of nephrotoxicity. JZS showed significant diuretic and nephroprotective effect.

Dietary (n-3) polyunsaturated fatty acids exert antihypertensive effects by modulating calcium signaling in T cells of rats.

After 10 wk of feeding an experimental diet enriched with (n-3) polyunsaturated fatty acids (PUFA), i.e., eicosapentaenoic acid [EPA, 20:5(n-3)] and [DHA, 22:6(n-3)] (EPAX), blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats was reduced relative to rats fed an unsupplemented control diet. Concanavalin A-stimulated T-cell proliferation was diminished in both strains of rats fed the PUFA/EPAX diet. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. To determine whether there was a defect in calcium homeostasis in T cells during hypertension, we employed the following agents: caffeine, which recruits calcium from the cytosolic Ca(2+)-induced Ca(2+)-release pool; ionomycin, which at low concentrations opens calcium channels; and thapsigargin (TG), which mobilizes [Ca(2+)]i from the endoplasmic reticulum (ER) pool. Caffeine-induced increases in [Ca(2+)]i were not modified by the PUFA/EPAX diet. The ionomycin-induced increases in [Ca(2+)]i in T cells from SHR were greater than in those from WKY rats; consumption of the PUFA/EPAX diet did not modify Ca(2+) influx in cells of either strain. The TG-induced increases in [Ca(2+)]i in T cells from SHR were greater than those in cells from WKY rats. Interestingly, consumption of the experimental diet reduced TG-evoked increases in [Ca(2+)]i in T cells from SHR and increased those in T cells from WKY rats, indicating that the PUFA/EPAX diet could reverse the calcium mobilization from the ER pool in T cells. These results suggest that (n-3) PUFA exert antihypertensive effects and modulate T-cell calcium signaling during hypertension in rats.

Use of unconventional methods of therapy by cancer patients in Pakistan.

Most of the studies related to the use of unconventional methods of therapy by cancer patients have been carried out in the developed countries. This study was conducted to ascertain the frequency, type, and duration of use of unconventional methods of therapy by cancer patients in Pakistan. We also wanted to identify individuals who are most likely to use these methods and to compare the findings with those reported from the developed countries. Between 1 April and 30 May 1994, all patients with histologically proven cancer who visited the oncology unit were interviewed. A printed questionnaire with questions and options was used as an interview guide. Informed consent was obtained. One hundred and ninety-one patients were interviewed, on average, for 25 minutes each. Use of unconventional methods of therapy by cancer patients was widespread (54.5% of all patients). The majority (83.7%) were influenced by family members to use these methods. Traditional herbal medicines (70.2%) and homeopathy (64.4%) were the most commonly employed methods. Thirty-six percent of the users employed these methods before receiving any conventional therapy. Only 15% used these methods after conventional therapeutic options had been exhausted. Patients generally perceived these methods as useful, non-toxic and inexpensive. Age, marital status, socio-economic background, education level and status of underlying neoplasm did not influence the frequency of use of unconventional methods. The use, however, was influenced by gender, family size, and type of underlying malignancy. Patients aware of their diagnosis were less likely to use these methods. This study suggests that use of unconventional methods by cancer patients in Pakistan is widespread. Unlike western countries, these methods are often employed before receiving any conventional therapy. This probably results in a significant delay which can be expected to adversely influence the subsequent disease management and survival. Public education, reduction of cost and easy availability of conventional therapy may be helpful in reducing the use of methods which otherwise may have no proven value.

Methemoglobinemia induced by topical anesthesia: a case report and review.

Topical anesthetic drugs are widely used by clinicians during hospital and outpatient procedures and are also available to the public in a variety of over-the-counter preparations. Although generally safe, they may cause potentially life-threatening methemoglobinemia. We describe a patient who developed repeated episodes of severe methemoglobinemia after administration of topical Cetacaine spray (a proprietary mixture of benzocaine, tetracaine, and butamben) employed for pharyngeal anesthesia before endotracheal intubation, and briefly review the etiology and pathophysiology of this disorder. Cautious interpretation of oxyhemoglobin saturation values obtained by pulse oximetry or estimated from arterial blood gas analysis is crucial lest the diagnosis of severe methemoglobinemia and the resulting hypoxemia are overlooked. If necessary, the condition is usually readily corrected by intravenous administration of methylene blue.

The anti-stress activity of a gem-containing Unani formulation against diverse stressors.

Drugs of mineral origin, especially gems, are extensively used in Tibb-e-Unani (Unani Medicine), both as single drugs and as compound formulations. But such drugs have not yet been adequately studied scientifically. Jawahir Mohra (JM) is one such, as yet unstudied, anti-stress Unani preparation, containing a few herbal and animal ingredients also. Therefore in the present study, a modified JM preparation was investigated for its anti-stress activity against physical, chemical and metabolic stimuli. The non-gem complement (NGC) of JM was also studied for action against physical stress. In albino rats stressed by swimming and subsequently tested for motor function by Rota rod (muscle coordination), activity wheel (forced motor activity) and photoactometer (spontaneous motor activity), JM treatment for 7 days produced a striking and significant increase in activity. The NGC also increased the activity significantly which was however less than JM. JM also produced a striking increase in cold swimming endurance and in the latency of post-anoxia convulsions, while pentylentetrazol (PTZ)-induced defecation and urination in an open field arena under continuous stimulation by intense light and sound was significantly decreased. Therefore, the present investigation indicates that the gem-containing Unani compound JM has significant anti-stress activity of a non-specific type against diverse stressors. This could be due to adaptogenic activity of the preparation. The study also shows that the gems in JM contribute significantly to its anti-stress activity.