Refining shape and size of silver nanoparticles using ion irradiation for enhanced and homogeneous SERS activity.

We present green synthesis of silver nanoparticles in water using unirradiated and Ag 15 + ion irradiated phytoextracts of Bergenia Ciliata leaf, Eupatorium adenophorum leaf, Rhododendron arboreum leaf and flower. The use of different plant extracts and their subsequent ion irradiation allow for successful refinement of nanoparticle size and morphology. Due to changes in reducing and capping agents the nanoparticle surface functionalization also varies which not only controls the morphology but also allows for surface oxidation and aggregation processes. In this work, we have synthesized silver nanoparticles which exhibit sizes in the range from 13 to 24 nm and having shapes like spherical, quasispherical, trigonal, hexagonal, cylindrical, dendritic assemblies, and porous nanoparticles. Owing to changes in the size and shape of the nanoparticles, their direct bandgap (2.05 eV - 2.48 eV) and local surface plasmon resonance (420 nm - 490 nm) could also be tuned. These nanoparticles are examined as SERS substrates, where their enhancement factors, limit of detection for methylene blue, and SERS substrate homogeneity have been tested. It has been observed the nanoparticles synthesized using unirradiated plant extracts present an enhancement factor of 10 6 with a limit of detection 10 - 8 M. Whereas nanoparticles with refined morphology and shapes upon irradiation present high enhancement factors of >10 7 and detection limit down to 10 - 9 M. In addition, uniformity in Raman spectra over the SERS substrates has been obtained for selected Ag NPs substrates synthesized using irradiated extracts with minimum relative standard deviation in enhancement factor < 12%.

Dual metal ion (Fe3+ and As3+) sensing and cell bioimaging using fluorescent carbon quantum dots synthesised from Cynodon dactylon.

In this study, water dispersible fluorescent carbon quantum dot (CQD) has been synthesised, having an average size of 8.6 ± 0.4 nm using Cynodon dactylon (CD) following microwave assisted green synthetic one-step method. As-prepared CQD fluoresces strongly at 444 nm having a quantum yield of 1% in water when excited at 350 nm. This fluorescence of CQD is sensitive toward As3+ and Fe3+ metal ions. These CQD are utilized for dual metal ion fluorescence sensing; turn-on fluorescence sensing for As3+ and turn-off fluorescence sensing for Fe3+ ions. Limit of detection for As3+ and Fe3+ ions has been found to be 19 nM and 0.10 µM respectively, which is the lowest value reported for As3+ without any functionalization. The adsorption kinetics of As3+ and Fe3+ ions on CQD have been examined using pseudo-first-order-kinetic model revealing that physical adsorption is dominant over chemical processes in this work. For 0.41 g/L and 1.90 g/L dose of CQD, the equilibrium adsorption capacity was found to be 1.57 × 10-6 mg/g, 2.91 × 10-7 mg/g, and 1.01 × 10-5 mg/g, 1.69 × 10-6 mg/g respectively for As3+ and Fe3+ ions. Despite having low quantum yield in water, as-prepared CQD showed low cytotoxicity and good tolerance against photodegradation of biological cells at concentrations lower than 62.5 µg/mL and when the cells are illuminated up to 12 h. Owing to this, the synthesised CQD have been utilized as fluorescent probes for in itro cell imaging.

Cellular and molecular immune response and production performance of Indian white shrimp Penaeus indicus (H. Milne-Edwards, 1837), reared in a biofloc-based system with different protein levels of feed.

The present study focuses on the immunity and growth of Penaeus indicus fed with varying protein levels (25%, 30%, and 35%) in a biofloc based rearing system. A 120 days growth trial was carried out using juvenile Penaeus indicus (0.71 ± 0.01) with dietary protein level, 25% (LP), 30% (MP), and 35% (HP), and a control diet-fed with 35% acted as control group resulting in 4 treatments each with four replicates and were randomly assigned 16 tank units (7500 L each). A combination of different carbon sources (molasses, wheat flour, and rice bran in 2:1:1 ratio), yeast and a probiotic (Bacillus sp.) consortium were used for the development of biofloc. At the end of the trial, the growth parameters of shrimps viz., initial weight, feed conversion ratio (FCR), and daily growth coefficient (DGC) were computed. The results indicated that shrimp fed with medium (30%) protein (MP) diet recorded significantly (P < 0.05) improved growth performance compared to high protein fed group (35%) and low protein (25%) fed group (LP) in a biofloc system and control group (35%). The immunological parameters such as hemagglutination activity (HA) assay, serum protein, lysozyme, phenol oxidase (PO), and inhibition of superoxide dismutase (SOD) activity were observed in serum, plasma, and hemocyte lysate supernatant (HLS). The HA activity, PO activity in plasma was found to be higher in high protein fed animals, whereas medium protein resulted in enhanced PO activity in serum. Similarly, lysozyme and SOD were inhibited well in high protein fed animals compared to the low protein fed group. The vital immune genes's mRNA profiling showed a potential rise in the expressional pattern in MP and HP treatments compared to LP and control. BGBP (beta-1,3-glucan binding protein) and hemocyanin mRNA transcript levels were highly upregulated in the HP (5 fold) and moderately expressed in MP (2 fold) and LP (1-2 fold). The transcripts of peroxinectin, antimicrobial peptides like crustin showed significant upregulation in HP followed by in MP and LP and control. Likewise, other immune genes, such as SOD, prophenoloxidase (proPO), showed a similar trend in a marginal way, indicating immunomodulation in the biofloc groups. This study suggested that biofloc with high protein (35%) supplementation can substantially enhance the immune response of shrimps, although medium protein level (30%) is optimum for improving the survival, growth, and in turn economic return in Indian white shrimp.

Methanolic Extract of Muntingia Calabura L. Mitigates 1,2-Dimethyl Hydrazine Induced Colon Carcinogenesis in Wistar Rats.

OBJECTIVE: The present study aimed to evaluate the efficacy of methanolic extract of Muntingia calabura L. leaves (MEMC) in ameliorating oxidative stress and inflammation associated with 1,2-dimethyl hydrazine (DMH) induced colon cancer. METHODS: The antioxidant enzymes, oxidative stress markers, liver and renal toxicity markers were evaluated. Histopathological examination of colon tissues was carried out with the aid of alcian blue stain and Hematoxylin and Eosin stain. RESULTS: MEMC supplementation at doses of 100 and 200 mg/kg body weight of rats causes the antioxidant enzymic levels to retain near to its normal range. Meanwhile the oxidative stress markers, which showed an elevation from its normal level upon DMH administration, gets significantly reduced on MEMC treatment. Histopathological observation also revealed that the severity of colorectal cancer was reduced by the supplementation of MEMC. CONCLUSION: The findings from the present study showed that MEMC can exert a potential role to ameliorate the oxidative stress and inflammation associated with colorectal cancer.

Protective effect of Catharanthus roseus plant extracts against endosulfan and its isomers induced impacts on non-targeted insect model, Drosophila melanogaster and live brain cell imaging.

Endosulfan has been recognized as a highly controversial pesticide due to its acute toxicity, potential bioaccumulation, persistency, and long-range atmospheric transport. Several plant extracts act as antioxidant agents against wide-range of pesticide toxicity hazards through the free radicals scavenging properties. Plants' secondary metabolites are considered as efficient protective agents against various cellular toxic injuries. Understanding these properties of botanicals, several researchers currently focused on the detoxification and ameliorative potency of plant extracts against highly toxic chemicals. In our studies, we focused on the endosulfan total and its isomers (alpha and beta) induced changes on Drosophila melanogaster and their ameliorative effects by co-administrated with methanolic and aqueous extracts of Catharanthus roseus whole plant. We selected the 1/5th EC50 concentration of alpha-endosulfan, beta-endosulfan, and endosulfan (total) and co-administrated with 1/50th EC50 concentration of aqueous and methanolic extracts and evaluated their ameliorative effects, in terms of verifying the life stage activities, protein profiling and also by using live brain cells imaging. We finally concluded that, the methanolic and aqueous extracts inhibit the toxic impacts caused by endosulfan and its isomers and also increasing the survival rate of the test organism.

The effect of aloe vera and tea tree oil mouthwashes on the oral health of school children.

PURPOSE: To evaluate the effect of two herbal mouthwashes containing aloe vera and tea tree oil, on the oral health of school children. METHODS: A double-blinded, placebo-controlled prospective interventional study was conducted in school children aged 8-14 years. The study participants were divided into four groups depending upon the mouthwash used: Group 1 (aloe vera), Group 2 (chlorhexidine), Group 3 (tea tree oil) and Group 4 (placebo). The variables studied included plaque index, gingival index and salivary Streptococcus mutans counts, which were recorded at baseline, 4 weeks after supervised mouth rinse and after 2 weeks of stopping the mouth rinse. RESULTS: A total of 89 boys and 63 girls were included. A statistically significant decrease in all variables was noted after the use of both the herbal preparations at the end of 4 weeks which was maintained after the 2-week washout period (p < 0.001). The difference in variables between groups using aloe vera, Tea tree oil and chlorhexidine, was not statistically significant. CONCLUSION: The use of aloe vera and tea tree oil mouthwashes can decrease plaque, gingivitis and S. mutans in the oral cavity in children. The activity of these two agents is comparable to that of chlorhexidine.

FeIn2S4 Nanocrystals: A Ternary Metal Chalcogenide Material for Ambipolar Field-Effect Transistors.

An ambipolar channel layer material is required to realize the potential benefits of ambipolar complementary metal-oxide-semiconductor field-effect transistors, namely their compact and efficient nature, reduced reverse power dissipation, and possible applicability to highly integrated circuits. Here, a ternary metal chalcogenide nanocrystal material, FeIn2S4, is introduced as a solution-processable ambipolar channel material for field-effect transistors (FETs). The highest occupied molecular orbital and the lowest unoccupied molecular orbital of the FeIn2S4 nanocrystals are determined to be -5.2 and -3.75 eV, respectively, based upon cyclic voltammetry, X-ray photoelectron spectroscopy, and diffraction reflectance spectroscopy analyses. An ambipolar FeIn2S4 FET is successfully fabricated with Au electrodes (EF = -5.1 eV), showing both electron mobility (14.96 cm2 V-1 s-1) and hole mobility (9.15 cm2 V-1 s-1) in a single channel layer, with an on/off current ratio of 105. This suggests that FeIn2S4 nanocrystals may be a promising alternative semiconducting material for next-generation integrated circuit development.

Evaluation of anti-hypertensive activity of Ulmus wallichiana extract and fraction in SHR, DOCA-salt- and L-NAME-induced hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus wallichiana Planchon (Himalayan Elm), a traditional medicinal plant, used in fracture healing in folk tradition of Uttarakhand, Himalaya, India. It is also used as diuretic. U. rhynchophylla, native to China, known as Gou Teng in Chinese medicine, is used for hypertension (WHO). U. macrocarpa has antihypertensive and vasorelaxant activity. However, no detailed studies related to hypertension have been reported previously, so we have explored the antihypertensive activity of U. wallichiana. AIM OF THE STUDY: To investigate the pharmacological effect of ethanolic extract (EE) and butanolic fraction (BF) of U. wallichiana in hypertensive rats. MATERIALS AND METHODS: SHR, DOCA-salt- and L-NAME-induced hypertension models were used. Treatment was performed by oral administration of EE and BF of U. wallichiana (500mg/kg/day and 50mg/kg/day) for 14 days. Then blood pressure was measured by non-invasive blood pressure (NIBP) measurement technique. Invasive blood pressure (IBP) was also reported to support the NIBP data. Concentrations of plasma renin, angiotensin II (Ang II), nitrate/nitrite (NO), cGMP were estimated. Angiotensin-converting enzyme (ACE) activity and ROS activity were also estimated. RESULTS: Blood pressure was significantly higher in SHR as compared to normotensive wistar group (170.59±0.83mmHg vs 121.54±1.24mmHg, respectively). SBP was increased in DOCA-salt induced group compared to their control (132.77±3.90mmHg vs 107.85±5.95mmHg, respectively) and L-NAME-induced group compared to their control (168.55±5.07mmHg vs 113.03±4.13mmHg, respectively). The treatment of extract and fraction of U. wallichiana significantly decreased the blood pressure in SHR+EE (151.26±1.85mmHg, p<0.001), SHR+BF (140.44±1.16mmHg, p<0.001); DOCA+EE (113.43±5.44mmHg, p<0.05), DOCA+BF (105.09±5.12mmHg, p<0.05) and L-NAME+EE (119.76±4.39mmHg, p<0.001), L-NAME+BF (117.50±7.27mmHg, p<0.001) compared to their respective diseased control groups. The plasma renin, Ang II and ACE activity were also significantly decreased and augmented the NO and cGMP levels. It also down regulated the expression of Renin, ACE, NOS3 and TGF-ß1 at mRNA levels. CONCLUSIONS: The EE and BF probably reducing the BP via Renin-angiotensin-aldosterone system and NO/cGMP signaling pathway. The decrease in blood pressure may be due to presence of quercetin analogue flavonoids (2S,3S)-(+)-3',4',5,7-tetrahydroxydihydroflavonol-6-C-ß-D-glucopyranoside; 6-Glucopyranosyl-3,3',4',5,7-pentahydroxyflavone; 6-Glucopyranosyl-4',5,7-trihydroxyflavanone and (2S,3S)-(+)-4',5,7-trihydroxydihydroflavonol-6-C-ß-D-glucopyranoside, may be due to its antioxidant activity. Thus EE and BF of U. wallichiana found to have the potential ability to be used as herbal medicament to treat hypertension.

Comparison of efficacy of herbal disinfectants with chlorhexidine mouthwash on decontamination of toothbrushes: An experimental trial.

BACKGROUND: Toothbrushes in regular use can become heavily contaminated with microorganisms, which can cause infection or reinfection. There is a need for toothbrush disinfection methods, which are rapidly effective, cost-effective, nontoxic, and that can be easily implemented. AIM: To compare the efficacy of 3% neem, garlic of concentration 4.15 mg/mL and green tea of concentration 40 mg/mL with 0.2% chlorhexidine mouthwash as toothbrush disinfectants. MATERIALS AND METHODS: The study was a parallel in vitro comparative experimental trial conducted among 75 randomly selected boys aged between 18 years and 21 years. The subjects were divided into five groups, namely, Group I, Group II, Group III, Group IV, and Group V. They were provided with a new set of precoded toothbrushes and nonfluoridated tooth pastes. After 14 days of tooth brushing, the toothbrushes were immersed in antimicrobial solution for 12 h [Group I--distilled water (control), Group II--3% neem, Group III--garlic of concentration 4.15 mg/mL, Group IV--green tea of concentration 40 mg/mL, and Group V--0.2% chlorhexidine] and then subjected to microbial analysis to check the presence of Streptococcus mutans. The t-test and analysis of variance (ANOVA) were done using Statistical Package for the Social Sciences (SPSS) software version 16. RESULTS: All test solutions showed a statistically significant reduction of Streptococcus mutans count (P < 0.001). There was no statistical difference between the efficacies of neem, garlic, and green tea when compared with chlorhexidine mouthwash (P > 0.05). CONCLUSION: Neem, garlic, and green tea are equally efficacious as chlorhexidine and these herbal products can be used as potent alternatives to chlorhexidine as disinfectant for toothbrushes.

Cardioprotective Effect of Ulmus wallichiana Planchon in ß-Adrenergic Agonist Induced Cardiac Hypertrophy.

Ulmus wallichiana Planchon (Family: Ulmaceae), a traditional medicinal plant, was used in fracture healing in the folk tradition of Uttarakhand, Himalaya, India. The present study investigated the cardioprotective effect of ethanolic extract (EE) and butanolic fraction (BF) of U. wallichiana in isoprenaline (ISO) induced cardiac hypertrophy in Wistar rats. Cardiac hypertrophy was induced by ISO (5 mg/kg/day, subcutaneously) in rats. Treatment was performed by oral administration of EE and BF of U. wallichiana (500 and 50 mg/kg/day). The blood pressure (BP) and heart rate (HR) were measured by non-invasive blood pressure measurement technique. Plasma renin, Ang II, NO, and cGMP level were estimated using an ELISA kit. Angiotensin converting enzyme activity was estimated. BP and HR were significantly increased in ISO group (130.33 ± 1.67 mmHg vs. 111.78 ± 1.62 mmHg, p < 0.001 and 450.51 ± 4.90 beats/min vs. 347.82 ± 6.91 beats/min, respectively, p < 0.001). The BP and HR were significantly reduced (EE: 117.53 ± 2.27 mmHg vs. 130.33 ± 1.67 mmHg, p < 0.001, BF: 119.74 ± 3.32 mmHg vs. 130.33 ± 1.67 mmHg, p < 0.001); HR: (EE: 390.22 ± 8.24 beats/min vs. 450.51 ± 4.90 beats/min, p < 0.001, BF: 345.38 ± 6.79 beats/min vs. 450.51 ± 4.90 beats/min, p < 0.001) after the treatment of EE and BF of U. wallichiana, respectively. Plasma renin, Ang II, ACE activity was decreased and NO, cGMP level were increased. The EE and BF of U. wallichiana down regulated the expression of ANP, BNP, TNF-α, IL-6, MMP9, ß1-AR, TGFß1 and up regulated NOS3, ACE2 and Mas expression level, respectively. Thus, this study demonstrated that U. wallichiana has cardioprotective effect against ISO induced cardiac hypertrophy.

In vivo performance of a microfabricated catheter for intraparenchymal delivery.

BACKGROUND: Convection-enhanced delivery (CED) is currently the only effective clinical technique to deliver biological therapeutic agents that would otherwise not cross the blood-brain barrier. Despite the promise of CED, several technical problems have limited its effectiveness. NEW METHOD: Brain infusions into a large mammal (pig) were performed with a catheter that was fabricated using micro-electro-mechanical systems (MEMS) technology (Olbricht et al., 2010). The performance of the catheter was evaluated for infusions at increasing infusion rates. Magnetic resonance (MR) images were acquired in real time to examine the distribution of infused tracers in the parenchyma. RESULTS: Both backflow and the distribution of CED of infusates into a variety of cytoarchitectures in porcine brain were quantified. Concentration profiles were determined for several MR contrast reagents as well as a fluorescent dye that are the sizes of small molecules, therapeutic proteins and an adeno-associated virus (AAV). The reagents can serve as surrogates for assessing the convective distribution of active molecules. Infusion rates up to 20µL/min were attained without evidence of backflow along the catheter. COMPARISON WITH EXISTING METHODS: The device performed well in terms of both backflow and infusion, superior to that of many studies reported in the literature on other catheters. All infused molecules had comparable ratios of distribution to infusion volumes. CONCLUSIONS: The catheter described in this report appears able to target tissue structures with precision, deliver therapeutics at high infusion rates, and resist backflow that can compromise the efficacy of CED therapy. The technology allows development of "smart" catheters for future applications.

Capsaicin 8% patch for treprostinil subcutaneous infusion site pain in pulmonary hypertension patients.

BACKGROUND: Treprostinil sodium improves haemodynamics and symptoms in pulmonary arterial hypertension (PAH) patients, but its subcutaneous (s.c.) administration can produce severe local site pain, and lead to discontinuation of vital treatment. Treprostinil is a prostacyclin analogue which stimulates prostacyclin receptors in skin nociceptor terminals, resulting in pain and cutaneous hypersensitivity, for which current pain remedies have limited effect. Capsaicin 8% patch relieves neuropathic pain for 3 months after a single 60 min cutaneous application; we investigated whether its pre-application can reduce s.c. trepostinil-induced pain. METHODS: A single-centre, double-blind, randomized, placebo-controlled, crossover study was conducted to assess the safety and efficacy of a single capsaicin 8% patch pre-application for s.c. treprostinil pain in 11 PAH patients, relative to control patch with low-dose capsaicin 0.075% cream. RESULTS: The primary efficacy endpoint, mean difference between the two treatment arms in an 11-point numerical pain rating scale from baseline to 2 weeks after patch applications, was significantly lower on the capsaicin 8% patch treatment arm [P=0.01, mean difference=-1.47 units, 95% credible interval (CI): -2. 59 to -0.38] in the patients who completed the study per protocol, although intention-to-treat analysis did not show significant difference (P=0.28). Heat pain thresholds were decreased (P=0.027, mean difference=5.43°C, 95% CI: 0.71-10.21) and laser Doppler flux increased (P=0.016, mean difference=370 units, 95% CI: 612 to 127.9) at the application site immediately after capsaicin 8% patch, confirming activity. CONCLUSIONS: Further investigation of the efficacy of capsaicin 8% patch in this indication is warranted.

Blood levels of folate at birth and risk of childhood leukemia.

BACKGROUND: A role for folate in cancer etiology has long been suspected because of folate's function as a cofactor in DNA methylation and maintenance of DNA synthesis. Previous case-control studies examining the association between risk of childhood acute lymphoblastic leukemia (ALL) and mothers' self-reported folate intake and supplementation have been inconclusive. MATERIALS AND METHODS: We used a quantitative microbiologic assay to measure newborn folate concentrations in archived dried bloodspots collected at birth from 313 incident ALL cases, 44 incident acute myeloid leukemia (AML) cases, and 405 matched population-based controls. RESULTS: Overall, we found no difference in hemoglobin-normalized newborn folate concentrations (HbFol, nmol/g) between ALL cases and controls (2.76 vs. 2.77, P = 0.97) or between AML cases and controls (2.93 vs. 2.76, P = 0.32). Null results persisted after stratification by both birth period (1982-94, 1995-98, and 1999-2002) to account for the start of folate fortification of grain products in the United States, and by self-reported maternal prepregnancy supplement use. Similarly, no association was observed for major ALL subgroups. CONCLUSIONS: Our results do not support an association between birth folate concentrations and risk of childhood AML or major ALL subgroups. IMPACT: However, they do not rule out a role for folate through exposures after birth or in early stages of fetal development.

Allopolyploidization lays the foundation for evolution of distinct populations: evidence from analysis of synthetic Arabidopsis allohexaploids.

Polyploidization is an important mechanism for introducing diversity into a population and promoting evolutionary change. It is believed that most, if not all, angiosperms have undergone whole genome duplication events in their evolutionary history, which has led to changes in genome structure, gene regulation, and chromosome maintenance. Previous studies have shown that polyploidy can coincide with meiotic abnormalities and somatic cytogenetic mosaics in Arabidopsis allotetraploids, but it is unclear whether this phenomenon can contribute to novel diversity or act as a mechanism for speciation. In this study we tested the hypothesis that mosaic aneuploidy contributes to the formation of incipient diversity in neoallopolyploids. We generated a population of synthesized Arabidopsis allohexaploids and monitored karyotypic and phenotypic variation in this population over the first seven generations. We found evidence of sibling line-specific chromosome number variations and rapidly diverging phenotypes between lines, including flowering time, leaf shape, and pollen viability. Karyotypes varied between sibling lines and between cells within the same tissues. Cytotypic variation correlates with phenotypic novelty, and, unlike in allotetraploids, remains a major genomic destabilizing factor for at least the first seven generations. While it is still unclear whether new stable aneuploid lines will arise from these populations, our data are consistent with the notion that somatic aneuploidy, especially in higher level allopolyploids, can act as an evolutionary relevant mechanism to induce rapid variation not only during the initial allopolyploidization process but also for several subsequent generations. This process may lay the genetic foundation for multiple, rather than just a single, new species.

Evaluation of C677T polymorphism of the methylenetetra hydrofolate reductase gene and its association with levels of serum homocysteine, folate, and vitamin B12 as maternal risk factors for Down syndrome.

AIMS AND OBJECTIVE: Evaluation of C677T polymorphisms of the methylenetetra hydrofolate reductase (MTHFR) gene and its association with level of serum homocysteine, folate, and vitamin B12 as possible maternal risk factors for Down syndrome. DESIGN: This was a case-control study. MATERIAL AND METHODS: Fifty-two mothers (mean age 27.6 years) with babies having free trisomy 21 of North Indian ethnicity and 52 control nonlactating mothers (mean age 24.9 years) of same ethnicity attending services of genetic lab for bloodletting for other causes were enrolled after informed written consent. Fasting blood was collected and was used for determination of plasma homocysteine, vitamin B12, and folate (serum and RBC), and for PCR amplification of the MTHFR gene. RESULTS: The prevalence of MTHFR C677T polymorphism in north Indian mothers of babies with trisomy 21 Down syndrome was 15.38% compared to 5.88 % in controls. The difference between two groups was not statistically significant (P = 0.124). Low serum folate was demonstrated in 34.62% of cases vs. 11.54% in controls, which was significant (P = 0.005). Low RBC folate was found in 30.7% of cases versus 11.53% in controls, which was not significant (P = 0.059), when analyzed independently. But on multiple regression analysis the difference was statistically significant. Low serum vitamin B12 was found in 42.31% of cases versus 34.62% in controls, which was not significant (P = 0.118). The mean serum homocysteine in cases was 10.35 ± 0.68 while controls were 9.02 ± 0.535. CONCLUSION: Serum levels of folate were low in cases. The RBC folate levels were comparable in both groups. However the combined serum folate and RBC folate were low in cases compared to control groups. Homocysteine levels in our study were higher in Down syndrome mothers compared to controls; however high-serum level of Homocysteine had no association with MTHFR polymorphism. No association of serum vitamin B12 with MTHFR polymorphism in occurrence of Down syndrome births was found. Peri- or preconceptional folate supplementation may therefore lead to a decline in DS births, if supported by larger studies.

Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch.

Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug-drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as 'defunctionalization' of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies.

Effects of taurine on glutathione peroxidase, glutathione reductase and reduced glutathione levels in rats.

The aim of the present study is to investigate the effects of oral administration of taurine on endogenous glutathione peroxidase (GPx) and Glutathione Reductase (GR) activities and reduced glutathione (GSH) level in normal rats. Normal saline (Group I) or 5% taurine in normal saline was administered in dose of 50 mg (Group II), 250 mg (Group III) or 500 mg kg(-1) of body weight (Group IV) through intragastric intubation for 60 days. GPx and GR enzyme activities and GSH and taurine levels were determined in liver, heart, stomach, kidney and plasma of normal Wistar rats. GPx activity showed an increase in liver, heart, stomach and plasma. GR activity increased in kidney and decreased in liver and plasma. GSH levels increased in liver, stomach and decreased in kidney. Liver showed an increase and heart, stomach and kidney a decrease in taurine level in taurine administered rats when compared to control rats. The results varied from organ to organ and the observed variations among organs might be related to their respective enzymatic, non-enzymatic antioxidant potential and its functions. From the present study it may be concluded that long term oral administration of taurine affects GPx, GR and GSH levels in normal rats.

Adverse health effects due to arsenic exposure: modification by dietary supplementation of jaggery in mice.

Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic.

Investigational drugs targeting FLT3 for leukemia.

FMS-like tyrosine kinase-3 (FLT3) is a member of the class III membrane receptor tyrosine kinase family and is important in survival, proliferation and differentiation of hematopoietic cells. FLT3 is mutated in approximately 30% of acute myelogenous leukemia patients. These mutations involve internal tandem duplications in the juxtamembrane domain of the receptor and tyrosine kinase point mutations in the activation loop. Over the past decade, due to the incidence and poor prognosis associated with FLT3, numerous agents have been developed to directly inhibit the activity of wild type and mutated FLT3. In this review, we focus on the preclinical data demonstrating in vitro activity, inhibition of downstream signaling pathways and potential synergy with traditional chemotherapeutic agents. Also, early clinical trial data specifically focusing on drug toxicity, clinical efficacy and future directions of FLT3-directed anticancer therapy are discussed.

Insulinotropic effect of aqueous extract of Brassica nigra improves glucose homeostasis in streptozotocin induced diabetic rats.

Aqueous extract of BRASSICA NIGRA (AEBN) has been shown to have good antidiabetic effect along with significant decrease (p<0.01) of abnormal serum lipid levels in our previous study. To understand the mechanism of action, effect of oral administration of AEBN for two months on glycolytic and gluconeogenic enzymes was studied in liver and kidney tissues of rats with streptozotocin (STZ) induced diabetes mellitus. The activities of gluconeogenic enzymes were higher and of glycolytic enzymes were decreased in both the liver and kidney tissues during diabetes. However, in diabetic rats treated with AEBN for two months, decrease of serum glucose, increase of serum insulin and release of insulin from pancreas (shown in vitro from isolated pancreas) along with the restoration of key regulatory enzyme activities of carbohydrate metabolism and glycogen content were observed. The therapeutic role of AEBN in STZ induced diabetes as exemplified in this study can be attributed to the release of insulin from pancreas and change of glucose metabolizing enzyme activities to normal levels, thus stabilizing glucose homeostasis in the liver and kidney. The LD50 was found to be more than 15 times the effective dose (ED) implying higher margin of safety for AEBN. These biochemical effects indicate that AEBN could be a possible new therapeutic agent for the treatment of diabetes.