ß-Carboline (FG-7142) modulates fear but not anxiety-like behaviour in zebrafish.

The ß-Carboline FG-7142 is a partial inverse agonist at the benzodiazepine allosteric site on the GABA-A receptor that induces anxiogenic, proconvulsant, and appetite-reducing effects in many species, including humans. Seizure-kindling effects have been well studied, however anxiogenic properties are relatively unexplored. This study aimed to investigate concentration-dependent effects of FG-7142 on anxiety-like behaviour and fear responses in zebrafish (Danio rerio) using the open-field test (OF) and novel object approach test (NOA). A U-shaped distribution was found with maximal responses in increased immobility and reduced distance moved at 10 µM in the NOA but not the OF. Follow up experiments demonstrated a lack of effect in repeated OF testing and no changes in opercular movements. Furthermore, the effect of FG-7142 was reversed with ethanol treatment. These results suggest that FG-7142 elicits a 'freezing' response in zebrafish via the introduction of novelty, suggesting fear-induction. These findings indicate that FG-7142 may act as an agent to promote acute fear responses in zebrafish.

Role of Ultrasonography and Color Doppler in the Assessment of High-Risk Pregnancies and Their Accuracy in Predicting Fetal Outcome.

Introduction Various methods are employed to evaluate the well-being of the fetus in high-risk pregnancies which consists of a biophysical profile (BPP), a non-stress test (NST), and daily fetal movements. Detection of aberrant blood flow in fetoplacental beds has been revolutionized by recent developments in ultrasound technology, such as color Doppler flow velocimetry. The cornerstone of maternal and fetal care is lowering maternal and perinatal mortality and morbidity is antepartum fetal surveillance. Doppler ultrasound is a non-invasive way of obtaining a qualitative and quantitative evaluation of maternal and fetal circulation and is utilized to investigate complications like fetal growth restriction (FGR) and fetal distress. Thus, it is useful in making distinctions between fetuses that are truly growth restricted and small for gestational age and healthy fetuses. The aim of the current study was to determine the role of Doppler indices in high-risk pregnancies and their accuracy in predicting fetal outcomes. Material and methods This prospective cohort study included 90 high-risk pregnancies in the III trimester (after 28 weeks of gestation) on whom ultrasonography and Doppler were performed. Ultrasonography was performed using PHILIPS EPIQ 5, a curvilinear probe of frequency 2-5MHz. Gestational age was determined with a biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femoral length (FL). Placental grading and position were noted. Estimated fetal weight and the amniotic fluid index were calculated. BPP scoring was done. Doppler study was conducted and the findings of Doppler indices that is pulsatility index (PI) and resistive index (RI) of the middle cerebral artery (MCA), umbilical artery (UA), and uterine artery (UTA), and cerebroplacental (CP) ratio in these high-risk pregnancies were documented and compared with standard. The flow patterns in MCA, UA, and UTA were also assessed. These findings were correlated with fetal outcomes.  Results Among 90 cases, the common high-risk factor in pregnancy was preeclampsia without severe features (30%). Growth lag was present in 43 (47.8%) participants. Among the study population, HC/AC ratio was increased in 19 (21.1%) participants which indicates asymmetrical intrauterine growth restriction. Adverse fetal outcomes were seen in 59 (65.6%) of the subjects. CP ratio and UA PI had better sensitivity (83.05% and 79.66%, respectively) and positive predictive value (PPV) (87.50% and 90.38%, respectively) in identifying the adverse fetal outcomes. Diagnostic accuracy of CP ratio and UA PI (Accuracy=81.11%) was highest in predicting adverse outcomes than all the other parameters. Conclusion CP ratio and UA PI had better sensitivity, PPV, and diagnostic accuracy in identifying adverse fetal outcomes than other parameters. The study's findings support that the use of color Doppler imaging in high-risk pregnancies will help in the early identification of adverse fetal outcomes and aid in early intervention. This study is non-invasive, simple, safe, and reproducible. This study can also be performed bedside in high risk and unstable patients. This study is required to accurately assess fetal well-being in all high-risk pregnancies in order to improve fetal outcomes and to incorporate this procedure as a part of the protocol for the assessment of fetal well-being in these patients.

DRR Dhan 58, a Seedling Stage Salinity Tolerant NIL of Improved Samba Mahsuri Shows Superior Performance in Multi-location Trials.

BACKGROUND: Improved Samba Mahsuri (ISM) is an elite, high-yielding, bacterial blight resistant, fine-grained rice variety with low glycaemic index. It is highly sensitive to salt stress, particularly at seedling stage, which significantly reduces its yield potential in coastal areas. A salinity tolerant QTL, Saltol, associated with seedling stage tolerance was previously mapped on chromosome 1 (10.6-11.5 Mb) from the Indian landrace, Pokkali and is effective in different genetic backgrounds. The objective of this study was to enhance salinity tolerance of ISM by incorporating the Saltol QTL through marker-assisted backcross breeding using the breeding line, FL478 (Pokkali/IR29). RESULTS: Foreground selection was carried out at each generation using five Saltol-specific markers and three bacterial blight resistance genes, Xa21, xa13 and xa5. Background selection was conducted using 66 well distributed polymorphic SSR markers and at the BC3F2 generation, a single plant with maximum recurrent parent genome recovery (95.3%) was identified and advanced to the BC3F4 generation. Based on bacterial blight resistance, seedling stage salinity tolerance and resemblance to ISM, four advanced breeding lines were selected for testing in replicated experiments near Hyderabad, India. A promising near-isogenic line, DRR Dhan 58, was evaluated in multi-location trials-coastal salinity and it showed significant salinity tolerance, resistance to bacterial blight disease, high yield and excellent grain quality during the 2019 and 2020 trials. DRR Dhan 58 was 95.1% similar to ISM based on genotyping with the 90 K SNP chip. Whole genome resequencing analysis of Pokkali and FL478 which were salinity tolerant checks, ISM and DRR Dhan 58 showed a high degree of relatedness with respect to the candidate gene loci for Saltol and OsSKC1 (Shoot K+ Concentration 1). CONCLUSION: DRR Dhan 58, possessing Saltol and three bacterial blight resistance genes (Xa21, xa13 and xa5) in the genetic background of the Indian mega-variety of rice, Samba Mahsuri, was developed for potential cultivation in areas prone to seedling stage salinity, as well as areas with endemic bacterial blight disease. This entry had a 24% yield advantage over the recurrent parent ISM under coastal saline conditions in multi-location trials and was recently released for commercial cultivation in India.

Computed Tomography Severity Scoring on High-Resolution Computed Tomography Thorax and Inflammatory Markers With COVID-19 Related Mortality in a Designated COVID Hospital.

Introduction Radiological Society of the Netherlands introduced the coronavirus disease 2019 (COVID-19) Reporting and Data System (CO-RADS) and the corresponding CT severity score (CTSS) to diagnose COVID-19 severity. However, data regarding the same is very limited. Objectives The objective of this study was to correlate the computed tomography severity scoring (CTSS) on high-resolution computed tomography (HRCT) thorax and inflammatory markers with COVID-19 related mortality. Methods A retrospective observational study was conducted in a tertiary center between June 2020 to May 2021 among 2343 adult patients at the department of radio-diagnosis with suspected and confirmed COVID-19 cases who received an HRCT thorax. Data was collected retrospectively from the records regarding age, sex, and information regarding inflammatory markers such as C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), D-dimer, and neutrophil-to-lymphocyte ratio. Information on HRCT thorax of patients was reviewed for radiological suspicion of COVID-19 related lung changes using CO-RADS scoring and severity of lung involvement using CT-severity scoring. Data was analyzed using SPSS version 22 (IBM Inc., Armonk, New York). Results The mean age was 51.69 ± 16.02 years, and most of the study participants were male (1592, 67.95%). The majority (999, 42.64%) had diabetes as a comorbidity. The reverse transcription polymerase chain reaction (RT-PCR) test was positive in 1571 (67.05%) participants. The majority (1571, 67.05%) had a CO-RADS score of six, and only 150 (6.40%) had CO-RADS score of four. The CT severity score was normal in 147 (6.27%), mild in 724 (30.90%), moderate in 903 (38.54%), and severe in 569 (24.29%) participants. The CRP levels were moderate in 1200 (51.22%) and severe in 428 (18.27%) participants. The mean ferritin, D-dimer and interleukin-6 (IL-6) levels were 321.83 ± 266.42 ng/ml, 1.51 ± 0.85mg/l, and 323.05 ± 95.52pg/ml, respectively. The mean length of hospital stay was 10.25 ± 6.52 days. Most of them (1926 out of 2343, 82.20%) survived, and nearly 417 out of 2343 (17.80%) died. Out of 2343, 569 participants had severe CT severity scores, out of which 205 (36.03%) died, and 364 (63.97%) participants survived. Conclusion A positive correlation was found between CT severity scoring on HRCT thorax and inflammatory markers with COVID-19 related mortality and can be used in early diagnosis and timely management of COVID-19 positive patients.

Marker assisted pedigree breeding based improvement of the Indian mega variety of rice MTU1010 for resistance against bacterial blight and blast and tolerance to low soil phosphorus.

Rice production is affected by many biotic and abiotic stresses; among them, bacterial blight (BB) and blast diseases and low soil phosphorous stress cause significant yield losses. The present study was carried out with the objective of combining the BB resistance gene, Xa21, the blast resistance gene, Pi54, and the low soil phosphorous tolerance QTL/gene, Pup1, into the genetic background of the Indian mega-rice variety, MTU1010 (Cottondora Sannalu), through marker-assisted pedigree breeding. RP5973-20-9-8-24-12-7 [a near isogenic line (NIL) of MTU1010 possessing Pup1] and RP6132 [a NIL of Akshayadhan possessing Xa21 + Pi54] were crossed and 'true' F1s were identified, using the target gene-specific markers and selfed. F2 plants, which are homozygous for all the three target genes/QTLs, were identified using PCR based markers and were advanced further through the pedigree method of breeding, with selection based on phenotypic traits specific for MTU1010. At the F5 generation, a set of 15 promising triple positive homozygous lines were identified and screened for their resistance against BB and blast diseases and tolerance to low soil P. Among them, two lines (LPK 30-18-16 and LPK 49-15-22) showed higher yields as compared to MTU1010, along with the desirable long slender grain type in both low soil P and normal soil P plots, and also exhibited high levels of resistance against BB and blast diseases, with lesser grain shattering as compared to MTU1010. These lines are being advanced for multi-location trials for validating their performance.

Zebrafish aversion to infrasound in an open field test.

Aquatic species are capable of detecting infrasound (sub-20 Hz frequencies) which may be a source of anthropogenic pollution and have a detrimental impact on the environmental fitness of fish. Infrasound is generated by infrastructure, producing acoustic frequency peaks that are not discernible by humans. The presence of these frequencies may therefore impact the environmental wellbeing of aquatic laboratory animals, which are often housed in spaces adjacent to facilities producing infrasound. To investigate the potential impact of infrasound, we used wild-type zebrafish (Danio rerio) and exposed them to short periods of infrasound at either 5, 10, 15, or 20 Hz, or 0 Hz as a control group. A motion-tracking software system was used to monitor fish movement in an open field test and arena location, distance moved, and immobility were quantified. There was a significant effect of 15 Hz which caused the fish to spend more time away from the infrasound source. The 20 Hz group also spent significantly less time in the zone closest to the speaker. There were no differences in distance moved or immobility between infrasound and control groups. These findings demonstrate that 15 Hz infrasound has aversive effects on zebrafish, causing them to move away from the sound source. To enhance environmental enrichment and wellbeing of aquatic laboratory animals, sources of infrasound pollution should be investigated and mitigated.

Marker assisted improvement of low soil phosphorus tolerance in the bacterial blight resistant, fine-grain type rice variety, Improved Samba Mahsuri.

Improved-Samba-Mahsuri (ISM), a high-yielding, popular bacterial blight resistant (possessing Xa21, xa13, and xa5), fine-grain type, low glycemic index rice variety is highly sensitive to low soil phosphorus (P). We have deployed marker-assisted backcross breeding (MABB) approach for targeted transfer of Pup1, a major QTL associated with low soil P tolerance, using Swarna as a donor. A new co-dominant marker, K20-1-1, which is specific for Pup1 was designed and used for foreground selection along with functional markers specific for the bacterial blight resistance genes, Xa21, xa13, and xa5. A set of 66 polymorphic SSR marker were used for the background selection along with a pair of flanking markers for the recombination selection in backcross derived progenies and in BC2F2 generation, 12 plants, which are homozygous for Pup1, all the three bacterial blight resistance genes and possessing agro-morphological traits equivalent to or better than ISM were selected and selfed to produce BC2F3s. They were evaluated in plots with low soil P and normal soil P at ICAR-IIRR, Hyderabad for their low soil P tolerance, and bacterial blight resistance and superior lines were advanced to BC2F6. One of the lines, when tested at multiple locations in India was found promising under both normal as well as low soil P conditions.

Polyphenols of Salix aegyptiaca modulate the activities of drug metabolizing and antioxidant enzymes, and level of lipid peroxidation.

BACKGROUND: Salix aegyptiaca is known for its medicinal properties mainly due to the presence of salicylate compounds. However, it also contains other beneficial phytochemicals such as gallic acid, quercetin, rutin and vanillin. The aim of the study was to examine the redox potential, antioxidant and anti-inflammatory activity of these phytochemicals along with acetylsalicylic acid. METHODS: The redox potential and antioxidant activity of gallic acid, quercetin, rutin, vanillin and acetylsalicylic acid were determined by oxidation-reduction potential electrode method and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, respectively. In ex vivo studies, antioxidant activity of these phytochemicals was determined by lipid peroxidation and carbonyl content assay in the liver of mice. Anti-inflammatory activity was determined by protein denaturation method. Six-week old C57BL/6 mice treated with gallic acid (100 mg/kg body weight) and acetylsalicylic acid (25 and 50 mg/kg body weight) to investigate their in vivo modulatory effects on the specific activities of drug metabolizing phase I and phase II enzymes, antioxidant enzymes and level of lipid peroxidation in liver. RESULTS: The order of ability to donate electron and antioxidant activity was found to be: gallic acid > quercetin > rutin > vanillin > acetylsalicylic acid. In ex vivo studies, the similar pattern and magnitude of inhibitory effects of these phytochemicals against peroxidative damage in microsomes and protein carbonyl in cytosolic fraction were observed. In in vivo studies, gallic acid and acetylsalicylic acid alone or in combination, enhanced the specific activities of drug metabolizing phase I and phase II enzymes as well as antioxidant enzymes and also inhibited lipid peroxidation in liver. CONCLUSIONS: These findings show a close link between the electron donation and antioxidation potential of these phytochemicals, and in turn their biological activity. Gallic acid, quercetin, rutin and vanillin were found to be better electron donors and antioxidants and therefore, might be mainly responsible for the antioxidant properties of S. aegyptiaca, while acetylsalicylic acid provided its maximum anti-inflammatory activity.

Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects.

Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 µg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg(-1)) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 µA, 90 µS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation.

Ultrasound irradiation: a robust approach for direct functionalization of graphene oxide with thermal and antimicrobial aspects.

Sonochemical waves as mechanochemical energy was employed to exfoliate graphite oxide and functionalized graphene oxide (GrO), through a reaction of solvent and accountable for top-down and bottom-up approach respectively. The in situ formation of ester intermediate was inferred and a polymeric surface of GrO was further functionalized with 6-Aminoindazole (6-AIND) through sonochemical nucleophilic substitution reaction. As compared to conventional method the effect of ultrasound was verified for the direct functionalization of GrO. The conventional hazardous acylation step for functionalization of GrO was deleted in ultrasound assisted formation of f-(6-AIND) GrO nanocomposite, prepared by stereoselective exploitation of carboxyl groups at edges of GrO. The characterization has ascertained a covalent attachment of 6-AIND onto GrO surface with ATR-FTIR, XPS, SSNMR, TGA, DSC, XRD, AFM, RAMAN, EDX, SEM, BET and elemental analyzer. A weight loss in TGA depicts enhanced thermal stability of f-(6-AIND) GrO and a thermally sensitive behavior. The f-(6-AIND) GrO was studied for in vitro antimicrobial activity to ensure health and environmental safety. Antibacterial activity was identified against human pathogenic gram-positive (Staphylococcus aureus; ATCC 25923) and gram-negative bacteria (Escherichia coli; ATCC 25922). The antifungal activity was observed against Candida albicans (ATCC 10231).

A New Begomovirus Species in Association with Betasatellite Causing Tomato Leaf Curl Disease in Gandhinagar, India.

In December 2012, tomato leaf curl disease (ToLCD) (2) was observed in tomato-growing areas of Gandhinagar District of Gujarat, a state in northwestern India. Incidence of ToLCD was estimated to be between 40 and 70% depending on the cultivars used. Infected plants exhibited symptoms consisting of leaf rolling, leaf curling, and yellowing typical of begomoviruses. Total DNA was isolated from a single affected tomato plant (2). Begomovirus infection in this sample was established by amplification of the expected-size 550-bp DNA fragment from this extract by PCR with degenerate DNA-A primers (3). Rolling circle amplification (RCA) using ϕ29 DNA polymerase was carried out on the total DNA, followed by digestion with Bam HI. An amplicon of ~2.8 kb was gel-eluted and cloned into Bam HI linearized pBluescript II KS(+). Restriction enzyme digestion of plasmid DNA from the resulting clones indicated the presence of one type of molecule. Using PCR and universal betasatellite primers, the expected 1.3-kb fragment was amplified from the DNA extract (1). An amplicon of ~1.3 kb was gel-eluted and cloned into pTZ57RT vector. Sequence analysis revealed that DNA-A (GenBank Accession No. KC952005) is composed of 2,753 nt and showed the highest identity (87.8%) with Tomato leaf curl Kerala virus[India:Kerala:2008] (GenBank Accession No. EU910141). An analysis for recombination showed this begomovirus DNA likely to have originated by recombination between Tomato leaf curl Kerala virus and Tomato leaf curl Karnataka virus. The satellite DNA-ß (GenBank Accession No. KC952006) is composed of 1,365 nt and showed the highest identity (75.6%) with Tomato leaf curl betasatellite[India:Ludhiana:2004] (ToLCB-[IN:Lud:04]) (GenBank Accession No. AY765255). On the basis of DNA-A sequence analysis, the ICTV species demarcation criteria of 89% DNA-A sequence identity, and genome organization, the present isolate was considered as a new begomovirus species and named Tomato leaf curl Gandhinagar virus (ToLCGNV). The betasatellite shares less than 78% identity with (ToLCB-[IN:Lud:04]), it is considered a new species of betasatellite and the name, Tomato leaf curl Gandhinagar betasatellite (ToLCGNB) is proposed. Multimeric clones of the begomovirus and betasatellite DNAs were generated in a binary vector and these plasmids transformed into Agrobacterium tumefaciens. Nicotiana benthamiana and tomato plants agroinoculated with the cloned begomovirus DNA developed leaf curl symptoms, whereas plants co-agroinoculated with the cloned begomovirus and betasatellites developed more severe symptoms, including leaf rolling, leaf curling, and yellowing. The symptoms induced by the begomovirus and betasatellite DNAs were indistinguishable from those observed in the field. Thus, ToLCGNV is a new monopartite begomovirus which, in association with a new species of betasatellite, causes ToLCD in Gandhinagar, India. The presence of ToLCGNV needs to be considered, along with the already reported begomoviruses infecting tomatoes in this state, e.g., Tomato leaf curl Gujarat virus (2), in studies aimed to developing tomato cultivars with stable resistance to these tomato-infecting begomoviruses in India. References: (1) R. W. Briddon et al. Mol. Biotechnol. 20:315, 2002. (2) C. Reddy et al. Arch Virol. 150:845, 2005. (3) S. D. Wyatt and J. K. Brown. Phytopathology 86:1288, 1996.

Radiomodulation by Hoechst 33258 against radiation-induced damage in murine splenocytes.

In this study modulatory effect of Hoechst 33258 on radiation induced membrane related signaling events which ultimately leads to apoptosis has been investigated. Splenocytes from Swiss albino mice were irradiated in air at room temperature in a gamma chamber (240 TBq 60Co Model 4000 A) at the dose-rate of 0.052 Gys(-1). Membrane lipid peroxidation, fluidity, specific activities of antioxidant enzymes, levels of nitric oxide, glutathione and apoptosis in presence and absence of different concentrations of Hoechst 33258 has been assayed. DNA binding activity of nuclear factor kappa B and activator protein-1 was also assayed by electrophoretic mobility shift assay. Modulatory effect of Hoechst 33258 was examined at 3 and 5 Gy using different concentrations (10, 20 and 30 microM). Hoechst 33258 was found to inhibit radiation induced peroxidative damage and fluidity and lowered the level of nitric oxide and apoptosis--as evident by DNA ladder assay and FACS, indicating free radicals scavenging potential. Dot plot diagramme clearly showed that 30 microM Hoechst 33258 caused 14% and 19% decrease in apoptotic cells at 3 Gy and 5 Gy of radiation respectively (compared to irradiated control group). Further DNA binding activity of nuclear factor kappa B and activator protein-1 was also inhibited but the antioxidant potential of the cells was enhanced. These findings support that Hoechst 33258 protects the cell from undergoing apoptosis. Hoechst 33258 may have interacted and has an ability to protect splenocytes against radiation induced apoptosis through modulation of membrane-related signaling events and antioxidant status.

Antihyperglycemic and protective effects of Trigonella foenum graecum seed powder on biochemical alterations in alloxan diabetic rats.

BACKGROUND: Trigonella foenum-graecum, an annual herb belonging to the family Leguminosae, commonly known as fenugreek, has been reported to have hypoglycemic, hypocholesterolemic, hyperinsulinemic and antidiabetic properties. In the present study, the effect of oral feeding of Trigonella foenum-graecum seed powder (TSP) has been studied on blood glucose, monoamine oxidase (MAO), membrane fluidity, neurolipofuscin content, DNA degradation and glucose transporter-4 (GLUT4) accumulation in the alloxan-induced diabetic rat brain. METHODS: Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and diabetic rats were treated with 2 IU insulin, per day and 5% TSP in the diet for 21 days. RESULTS: Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Increased MAO activity with correlated increase in genomic DNA degradation in the diabetic brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress, causing loss of membrane fluidity, increased neurolipofuscin and decreased of GLUT4 expression with diabetes in the brain. The present study showed that TSP treatment reversal the changes to near normal levels in diabetic rat brain. CONCLUSIONS: The present findings indicate that the TSP exerts its anti-diabetic and neuroprotective effects, probably mediated through a decrease in hyperglycemia and oxidative stress thereby ameliorating the control and management of diabetic complications.

Beneficial effects of Trigonella foenum graecum and sodium orthovanadate on metabolic parameters in experimental diabetes.

Oxidative stress in diabetic tissues is accompanied by high-level of free radicals with simultaneously declined antioxidant enzymes status leading to cell membrane damage. The present study was carried out to observe the effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, antioxidant enzymes, lipid peroxidation, pyruvate kinase, lactate dehydrogenase and protein kinase C in heart, muscle and brain of the alloxan-induced diabetic rats to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight), and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for 21 days. Blood glucose levels increased markedly in diabetic rats, animals treated with a combined dose of SOV and TSP had glucose levels almost comparable with controls, similar results were obtained in the activities of pyruvate kinase, lactate dehydrogenase, antioxidant enzymes and protein kinase C in diabetic animals. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP to effectively reverse diabetic alterations in experimental diabetes.

Antidiabetic and neuroprotective effects of Trigonella foenum-graecum seed powder in diabetic rat brain.

Trigonella foenum-graecum seed powder (TSP) has been reported to have hypoglycemic and hyperinsulinemic action. The objective of the study was to examine the antidiabetic and neuroprotective role of TSP in hyperglycemiainduced alterations in blood glucose, insulin levels and activities of membrane linked enzymes (Na+K+ATPase, Ca2+ATPase), antioxidant enzymes (superoxide dismutase, glutathione S-transferase), calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in the diabetic rat brain. Female Wistar rats weighing between 180 and 220 g were made diabetic by a single injection of alloxan monohydrate (15 mg/100 g body weight), diabetic rats were given 2 IU insulin, per day with 5% TSP in the diet for three weeks. A significant increase in lipid peroxidation was observed in diabetic brain. The increased lipid peroxidation following chronic hyperglycemia was accompanied with a significant increase in the neurolipofuscin deposition and Ca2+ levels with decreased activities of membrane linked ATPases and antioxidant enzymes in diabetic brain. A decrease in synaptosomal membrane fluidity may influence the activity of membrane linked enzymes in diabetes. The present study showed that TSP treatment can reverse the hyperglycemia induced changes to normal levels in diabetic rat brain. TSP administration amended effect of hyperglycemia on alterations in lipid peroxidation, restoring membrane fluidity, activities of membrane bound and antioxidant enzymes, thereby ameliorating the diabetic complications.

Chemomodulatory potential of Glycine max against murine skin and cervical papillomagenesis.

In the present study, chemopreventive potential of Glycine max (G. Max) seeds was examined against DMBA-induced skin and MCA-induced cervical papillomagenesis in Swiss albino mice. Different doses (2.5, 5, and 7.5% w/w) of G. max were provided to animals in feed. Results exhibited a significant reduction in skin as well as cervical tumor incidence and tumor multiplicity (up to 75%) at all doses of test diet as compared to the control. Relatively, 7.5% test diet was most effective in protecting the animals against carcinogenesis. Further, detoxifying enzymes and antioxidative status was also evaluated in the liver of mice to understand the role of G. max in prevention of cancer. It was observed that the test diet containing G. max significantly elevated the specific activities of glutathione-S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase (CAT), and glyoxalase I (Gly I). The test diet also elevated the content of reduced glutathione whereas it decreased the level of the peroxidative damage along with the specific activity of lactate dehydrogenase. It appeared that G. max seeds provided chemoprevention against skin and cervical papillomagenesis probably by modulating the detoxifying and antioxidative enzymes. It could be inferred that intake of G. max might help in reducing the risk of cancer.

Prepubertal daidzein exposure enhances mammary gland differentiation and regulates the expression of estrogen receptor-alpha and apoptotic proteins.

Mechanism of chemoprevention by daidzein (500 µg/g bwt) was examined by injecting it subcutaneously at 16th, 18th, and 20th day postpartum, followed by counting of terminal end buds (TEBs), terminal ducts (TDs), and lobules and immunohistochemistry of ER-α, Bcl2, Bax, and caspase-3. DNA fragmentation was also analysed to measure the apoptosis level. Estradiol benzoate (EB) (500 ng/g bwt) and dimethyl sulphoxide (DMSO) were used as reference and vehicle, respectively. Observations show a significant enhancement of mammary gland differentiation at postnatal day 21 (PND21) as well as PND50. There was a significant decrease of ER-α expression at PND21 and increase in its expression at PND50, in daidzein-treated animals. The ratio of expression of Bcl-2 to Bax proteins increased at PND50 the same whereas, it decreased at PND50 due to daidzein. An increased expression of caspase-3 and DNA fragmentation was also seen due to daidzein at PND50. The mammary gland of EB-treated animals showed response a somewhat similar to that of daidzein-treated animals.