Mechanism of potentiation by diazepam of adenosine response

Diazepam (3 microM) potentiates the adenosine-induced relaxation of caecum. Other benzodiazepine receptor ligands, such as inosine and hypoxanthine, failed to modify adenosine responses. Diazepam failed to further modify the dose-response curve to adenosine obtained in the presence of dipyridamole, and uptake inhibitor. Diazepam and dipyridamole did not affect the responses to 2-chloroadenosine. The relaxant effect of adenosine was not blocked by Ro 15-1788, a benzodiazepine receptor antagonist. These observations indicated that diazepam potentiated adenosine response by inhibiting the uptake of purine nucleotide and, that the benzodiazepine receptor is not purinergic in nature in the rat caecum.     

Heightened Delta Power during Slow-Wave-Sleep in Patients with Rett Syndrome Associated with Poor Sleep Efficiency

Sleep problems are commonly reported in Rett syndrome (RTT); however the electroencephalographic (EEG) biomarkers underlying sleep dysfunction are poorly understood. The aim of this study was to analyze the temporal evolution of quantitative EEG (qEEG) biomarkers in overnight EEGs recorded from girls (2–9 yrs. old) diagnosed with RTT using a non-traditional automated protocol. In this study, EEG spectral analysis identified high delta power cycles representing slow wave sleep (SWS) in 8–9h overnight sleep EEGs from the frontal, central and occipital leads (AP axis), comparing age-matched girls with and without RTT. Automated algorithms quantitated the area under the curve (AUC) within identified SWS cycles for each spectral frequency wave form. Both age-matched RTT and control EEGs showed similar increasing trends for recorded delta wave power in the EEG leads along the antero-posterior (AP). RTT EEGs had significantly fewer numbers of SWS sleep cycles; therefore, the overall time spent in SWS was also significantly lower in RTT. In contrast, the AUC for delta power within each SWS cycle was significantly heightened in RTT and remained heightened over consecutive cycles unlike control EEGs that showed an overnight decrement of delta power in consecutive cycles. Gamma wave power associated with these SWS cycles was similar to controls. However, the negative correlation of gamma power with age (r = -.59; p<0.01) detected in controls (2–5 yrs. vs. 6–9 yrs.) was lost in RTT. Poor % SWS (i.e., time spent in SWS overnight) in RTT was also driven by the younger age-group. Incidence of seizures in RTT was associated with significantly lower number of SWS cycles. Therefore, qEEG biomarkers of SWS in RTT evolved temporally and correlated significantly with clinical severity.     

MiR-101 Induces Senescence and Prevents Apoptosis in the Background of DNA Damage in MCF7 Cells

Moderately increased DNA damage due to the exogenous miR-101 (4 fold) over-expression in MCF7 cells was substantiated by an increase in the number of γ-H2AX foci, correlating with a simple-to-do Halo-assay. miR-101 induced mild/moderate DNA damage favoured senescence rather than apoptosis. An experimental support emanated from the induced mild/moderate DNA damage with 1 µM/5 µM etoposide in MCF7 cells, which resulted in an endogenous miR-101 over-expression (10/4 fold, respectively), followed by senescence. On the other hand, the severe DNA damage induced with 10 µM etoposide, resulted in a low (<1 fold) endogenous expression of miR-101 and an elevated percentage of apoptotic cells. Using bioinformatics tools along with in-vitro and in-vivo validations, miR-101 was found to target and downregulate the mRNA expression of UBE2N and SMARCA4, involved in DNA damage repair (DDR) pathways. Recovery of the expression of the two novel targets in anti-miR-101 transfection validated the results. We conclude that a threshold range of over-expressed miR-101, capable of inducing mild/moderate DNA damage, is sensed by cells to become senescent. The observation derives further support from in-silico protein-protein network analysis where the two novel targets showed their involvement in senescence pathway.     

Effective bioremoval and detoxification of textile dye mixture by Alishewanella sp. KMK6

Alishewanella sp. strain KMK6 was able to degrade mixture of textile dyes (0.5–2.0 g?l^?1) within 8 h. An initial 28 % reduction in COD was observed immediately after decolorization at static anoxic conditions which on further incubation at shaking conditions reduced by 90 %. Partially purified azoreductase was able to utilize different azo dyes as substrates. The HPLC profile of dye degradation showed formation of metabolic products. Further FTIR analysis showed significant changes in the peaks corresponding to functional groups present in dye mixture and its degradation products. The genotoxicity assessment showed that the dye degradation products were non-toxic compared to dye mixture.     

Proline hydroxylation by soybean lipoxygenase.

The lipoxygenase-catalyzed hydroxylation of proline was studied in vitro in the presence of linoleic acid. The rate of reaction exhibited dependence on the concentration of proline, linoleic acid and the enzyme. The magnitude of hydroxyproline formed per mg of protein was time-dependent. Nordihydroguaiaretic acid at 0.1 mM concentration completely inhibited this reaction. No proline hydroxylation was detected during peroxidation of linoleic acid by vanadyl(IV). It is suggested that free-radical products of linoleic acid peroxidation may co-oxygenate proline in the presence of lipoxygenase.     

Delayed Initiation but Not Gradual Advancement of Enteral Formula Feeding Reduces the Incidence of Necrotizing Enterocolitis (NEC) in Preterm Pigs

Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC) in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of enteral feeding of an intact vs. hydrolyzed protein formula on NEC incidence and severity in preterm pigs. In Experiment 1, preterm pigs received total parenteral nutrition (TPN) at birth with abrupt initiation of enteral formula feeds (50% full intake) on d of life (DOL) 2 (EA) or 5 (LA) while PN continued. Pigs were also fed formula containing either intact or hydrolyzed protein. In Experiment 2, preterm pigs received TPN at birth with enteral, hydrolyzed-protein formula feeds introduced on DOL 2 either abruptly (EA; 50% full feeds) or gradually (EG; 10–50% full feeds over 5 d) while PN continued. NEC incidence and severity were assessed based on macroscopic and histological scoring. In Experiment 1, NEC incidence (41% vs. 70%, P<0.05) and severity were reduced in LA vs. EA groups and LA was associated with a higher survival rate, daily weight gain and jejunum villus height. Piglets fed hydrolyzed vs. intact protein formula had lower stomach content weights and similar NEC incidence. In Experiment 2, NEC incidence and severity were not different between pigs the EG vs. EA group. Proinflammatory gene expression (IL-1β, IL-6 and S100A9) in the ileum was lower in both LA and EG vs. EA groups. In conclusion, delayed initiation but not gradual advancement of enteral feeding is protective against NEC in preterm pigs. Feeding hydrolyzed vs. intact protein formula improved gastric transit without affecting the NEC incidence.     

Profile of Substance Use among Patients Attending De-Addiction Centres in a Coastal City of Southern India

Drug dependence is still to be recognized in developing countries as a significant public health problem and literature on the magnitude of this problem is limited. The present research was planned to study the socio-demographic profile and the reasons for substance use among patients admitted at De-addiction centres in Mangalore, India. In this cross-sectional study, all the patients admitted at the De-addiction centres during the study period were interviewed. The data was analyzed and the results obtained were expressed in proportions. A total of 83 patients were included in the study, all of whom were males. A positive family history of substance use was evident in 63% of the respondents. The mean age of the study participants was 41.9 (SD±11.2) years and the mean age for starting substance use was 20.9 (SD±7.7) years. The most common substance used was alcohol (95.2%). Majority of the subjects (56.6%) cited peer pressure as a reason for initiating substance use. Our findings suggest that the initiation of substance use occurs during late teenage years and mostly due to peer pressure. Our observations point towards the vulnerability of younger age towards substance use and hence, it is proposed that the preventive health policies in this regard should be targeted specifically during teenage years.