Progression of herpesvirus infection remodels mitochondrial organization and metabolism.

Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Here we show extensive transcriptional remodeling of protein-encoding host genes involved in the respiratory chain, apoptosis, and structural organization of mitochondria as herpes simplex virus type 1 lytic infection proceeds from early to late stages of infection. High-resolution microscopy and interaction analyses unveiled infection-induced emergence of rough, thin, and elongated mitochondria relocalized to the perinuclear area, a significant increase in the number and clustering of endoplasmic reticulum-mitochondria contact sites, and thickening and shortening of mitochondrial cristae. Finally, metabolic analyses demonstrated that reactivation of ATP production is accompanied by increased mitochondrial Ca2+ content and proton leakage as the infection proceeds. Overall, the significant structural and functional changes in the mitochondria triggered by the viral invasion are tightly connected to the progression of the virus infection.

Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Comparative evaluation of phenotypic and genotypic methods for the rapid and cost-effective detection of carbapenemases in extensively drug resistant Klebsiella pneumoniae.

PURPOSE: Carbapenemases are the enzymes that can hydrolyze carbapenems and other ß-lactam antibiotics. These enzymes confer resistance to multiple antibiotics and act as a stumbling block in the treatment of infections caused by gram-negative bacteria. Therefore, rapid and specific detection of these enzymes is crucial for deciding the course of treatment and better clinical outcomes. MATERIAL AND METHODS: This study was conducted to compare various phenotypic and PCR based methods for the detection of carbapenemases in carbapenem- and colistin-resistant Klebsiella pneumoniae. One hundred clinical isolates of extensively resistant Klebsiella pneumoniae were included in the study. Phenotypic detection for carbapenemases was performed by Rapidec® Carba NP (Biomerieux), modified carbapenem inactivation method (mCIM), imipenem-ethylenediaminetetraacetic acid disk synergy (EDS), double disk synergy test using mercaptopropionic acid (DDST-MPA), and combined disk method (CD) and for colistin by microbroth dilution method. Genotypic detection for carbapenemases and colistin resistance was performed by targeted PCR. RESULTS: The sensitivity of Carba NP test and mCIM were positive in 95% and 96% respectively and specificity was 100% for both methods. The sensitivity of EDS, DDST-MPA, and CD were 55.6%, 88.9% and 54.5% respectively. Among the carbapenem resistance genes, blaOXA-48 (82%) genes were the most prevalent. Among metallo-beta lactamases, blaVIM (56%) was most common followed by blaNDM (54%) and blaIMP (20%). The mcr-1 gene for colistin resistance was not detected in any isolate. CONCLUSION: Among the five phenotypic assays analyzed, the mCIM is the most simple, inexpensive, accurate and reproducible method for carbapenemase detection in Klebsiella pneumoniae. The DDST-MPA test provides the best sensitivity for the detection of carbapenemases, although specificity is low. These tests, when applied in a clinical laboratory and assessed by the microbiologist, can help in guiding the course of treatment.

Biochemical characterization of clinically relevant mutations of human Translin.

DNA damage in all living cells is repaired with very high efficiency and nucleic acid binding proteins play crucial roles in repair associated processes. Translin is one such evolutionarily conserved nucleic acid interacting protein speculated to be a part of the DNA repair protein network. It is also involved in activation of RNA-induced silencing complex (RISC) along with Translin-associated factor X (TRAX) as the C3PO (component 3 promoter of RISC) complex. In the present work, we characterized ten clinically relevant variants of the human Translin protein using bioinformatic, biochemical, and biophysical tools. Bioinformatic studies using DynaMut revealed 9 out of the 10 selected mutations the Translin protein. Further analysis revealed that some mutations lead to changes in interactions with neighbouring residues in the protein structure. Using site directed mutagenesis, the point substitution variants were generated, corresponding proteins were overexpressed and purified using Ni-NTA affinity chromatography. Purified proteins form octamers similar to wild type (WT) Translin, as observed using native polyacrylamide gel electrophoresis (PAGE), gel filtration, and dynamic light-scattering (DLS) analysis. These octamers are functional and bind to single-stranded DNA (ssDNA) as well as single-stranded RNA (ssRNA) substrates. The mutant Translin proteins interact with wild type TRAX and form corresponding C3PO complexes. The C3PO complexes formed by all Translin variants with TRAX are functional in-vitro and show endoribonuclease activity. However, significant differences were observed in the extent of RNase activity in vitro. In conclusion, the clinically relevant mutations in Translin protein analysed by us exert their effect by modulating the RNase activity of the protein without altering its DNA-dependant function.

Effects of Face Masks on Pulse Rate and Blood Pressure Components During Stairs Climbing.

BACKGROUND: The use of face masks has been associated with physiological changes in body. This study aims to know the changes in pulse rate and blood pressure components after wearing face masks during stairs climbing. METHODS: An experimental study was conducted among 60 apparently healthy young adults between 18-35 years of age. The pulse rate and blood pressure of the participants were recorded during rest at ground floor and after climbing the stairs till 5th floor at brisk and regular pace without wearing the face masks. The uniform KN95 masks were distributed and proper coverage of nose, mouth and chin were ensured. After 5 minutes interval, the pulse rate and blood pressure were recorded again at rest in ground floor and after climbing stairs with use of KN95 masks. RESULTS: At rest, the difference in mean pulse rate was statistically significant after wearing masks in participants between 21-25 years of age (86.46±14.59 bpm, p=0.014). After climbing the stairs, the mean pulse rate (131.16±18.48 bpm), mean systolic blood pressure (137.67±16.13 mmHg) and mean rate pressure product (182.87±41.70) were higher in participants (age group: 26-30 years) wearing masks and the difference was statistically significant (p=0.001; 0.013; 0.001respectively). During stairs climbing, the change in mean systolic blood pressure (32.66±16.73 mmHg), mean pulse pressure (43.77±24.64 mmHg) and mean rate pressure product (96.58±37.23) were higher in participants (age group: 26-30 years) and the difference was statistically significant (p=0.036; 0.047 and 0.009 respectively). CONCLUSIONS: The changes in systolic blood pressure, pulse pressure and rate pressure product are found to increase after wearing face masks during stairs climbing. It can be suggestive of increase workload to the heart by wearing face masks in addition to climbing the stairs.

Design-computer-aided manufacturing guided implant-supported prosthesis in a fibular graft reconstructed mandible: A 7-year follow-up of a case.

Reconstruction of functional occlusion in case of a large surgical defect of the mandible involving partial mandibulectomy remains a significant challenge to the maxillofacial surgeon and prosthodontist. Removable appliances and the conventional implant-supported prosthesis are precluded in this case due to the absence of normal anatomical contours of the bone. In recent years, due to the advancement of technology, bone graft reconstruction with computer-guided rehabilitation of the functional occlusion has been advocated to reverse the debilitating effects of the hemimandibulectomy defect. This clinical report describes the prosthodontic management of fibular graft reconstructed mandible by computer-aided design-computer-aided manufacturing guided implant-supported prosthesis.

Autochthonous nutrient recycling driven by soil microbiota could be sustaining high coconut productivity in Lakshadweep Islands sans external fertilizer application.

The soils of Lakshadweep Islands are formed as a result of the fragmentation of coral limestone, that is carbonate-rich, with neutral pH, but poor in plant nutrients. Coconut palm (Cocos nucifera L.) is the main crop cultivated, supporting the life and livelihood of the islanders. No external fertilizer application or major plant protection measures are adopted for their cultivation as the Islands were declared to go organic decades back. Yet, Lakshadweep has one of the highest productivity of coconut compared with other coconut growing areas in India. Therefore, a question arises: how is such a high coconut productivity sustained? We try to answer by estimating in three main islands (i) the nutrients added to the soil via the litter generated by coconut palms and (ii) the role of soil microbiota, including arbuscular mycorrhizae, for the high productivity. Our results indicated that, besides adding a substantial quantum of organic carbon, twice the needed amount of nitrogen, extra 20% phosphorus to the already P-rich soils, 43-45% of potassium required by palms could be easily met by the total coconut biomass residues returned to the soil. Principal Component Analysis showed that soil organic carbon %, potassium, and organic carbon added via the palm litter and AM spore load scored >± 0.95 in PC1, whereas, available K in the soil, bacteria, actinomycetes, phosphate solubilizers and fluorescent pseudomonads scored above >± 0.95 in PC2. Based on our analysis, we suggest that the autochthonous nutrients added via the coconut biomass residues, recycled by the soil microbial communities, could be one of the main reasons for sustaining a high productivity of the coconut palms in Lakshadweep Islands, in the absence of any external fertilizer application, mimicking a semi-closed-loop forest ecosystem.

Proteomic Perspective of Cadmium Tolerance in Providencia rettgeri Strain KDM3 and Its In-situ Bioremediation Potential in Rice Ecosystem.

In this study, a multi-metal-tolerant natural bacterial isolate Providencia rettgeri strain KDM3 from an industrial effluent in Mumbai, India, showed high cadmium (Cd) tolerance. Providencia rettgeri grew in the presence of more than 100 ppm (880 µM) Cd (LD50 = 100 ppm) and accumulated Cd intracellularly. Following Cd exposure, a comparative proteome analysis revealed molecular mechanisms underlying Cd tolerance. Among a total of 69 differentially expressed proteins (DEPs) in Cd-exposed cells, de novo induction of ahpCF operon proteins and L-cysteine/L-cystine shuttle protein FliY was observed, while Dps and superoxide dismutase proteins were overexpressed, indicating upregulation of a robust oxidative stress defense. ENTRA1, a membrane transporter showing homology to heavy metal transporter, was also induced de novo. In addition, the protein disaggregation chaperone ClpB, trigger factor, and protease HslU were also overexpressed. Notably, 46 proteins from the major functional category of energy metabolism were found to be downregulated. Furthermore, the addition of P. rettgeri to Cd-spiked soil resulted in a significant reduction in the Cd content [roots (11%), shoot (50%), and grains (46%)] of the rice plants. Cd bioaccumulation of P. rettgeri improved plant growth and grain yield. We conclude that P. rettgeri, a highly Cd-tolerant bacterium, is an ideal candidate for in-situ bioremediation of Cd-contaminated agricultural soils.

Sensorial, textural, and nutritional attributes of coconut sugar and cocoa solids based "bean-to-bar" dark chocolate.

The impacts of cocoa solids and coconut sugar on the sensory perception of bean-to-bar dark chocolate were investigated with mixture design using response surface methodology. The maximum and minimum levels of cocoa nib, cocoa butter, and coconut sugar for the preparation of chocolate were 35-50%, 15-30%, and 20-35%, respectively. A suitable mathematical model was used to evaluate each response. Maximum and minimum levels of components caused a poor sensory acceptance of the resultant dark chocolate. The optimum level of independent variables, for the best set of responses, was 44.7% cocoa nib, 25.2% cocoa butter, and 30.2% coconut sugar, with a hedonic score of 8.28 for appearance, 8.64 for mouth feel, 8.71 for texture, 8.68 for taste, and 8.51 for overall acceptability, at a desirability of 0.86. The minimum time for grinding the chocolate mix was 24 hour, which was evident from the microscopic analysis of the chocolate mix. The optimized chocolate (70% dark) per 100 g constitutes 1.06 g moisture, 50.09 g crude fat, 10.37 g crude protein, 35.90 g carbohydrates, and 2.55 g ash content. The L, a, b values indicated a darker color and was stable under ambient condition with a hardness value of 59.52 N, which significantly decreased to 16.23 N within 10 min at ambient temperature (30 ± 2°C). The addition of coconut sugar along with cocoa solids incorporates polyphenols, flavonoids, antioxidant potential, and minerals into bean-to-bar dark chocolate and hence offers a commercial value and health potential for stakeholders.

Follicle-stimulating hormone-mediated decline in miR-92a-3p expression in pubertal mice Sertoli cells is crucial for germ cell differentiation and fertility.

Sertoli cells (Sc) are the sole target of follicle-stimulating hormone (FSH) in the testis and attain functional maturation post-birth to significantly augment germ cell (Gc) division and differentiation at puberty. Despite having an operational microRNA (miRNA) machinery, limited information is available on miRNA-mediated regulation of Sc maturation and male fertility. We have shown before that miR-92a-3p levels decline in pubertal rat Sc. In response to FSH treatment, the expressions of FSH Receptor, Claudin11 and Klf4 were found to be elevated in pubertal rat Sc coinciding with our finding of FSH-induced decline in miR-92a-3p levels. To investigate the association of miR-92a-3p and spermatogenesis, we generated transgenic mice where such pubertal decline of miR-92a-3p was prevented by its overexpression in pubertal Sc under proximal Rhox5 promoter, which is known to be activated specifically at puberty, in Sc. Our in vivo observations provided substantial evidence that FSH-induced decline in miR-92a-3p expression during Sc maturation acts as an essential prerequisite for the pubertal onset of spermatogenesis. Elevated expression of miR-92a-3p in post-pubertal testes results into functionally compromised Sc, leading to impairment of the blood-testis barrier formation and apoptosis of pre-meiotic Gc, ultimately culminating into infertility. Collectively, our data suggest that regulation of miR-92a-3p expression is crucial for Sc-mediated induction of active spermatogenesis at puberty and regulation of male fertility.

Peripheral neurological complications during COVID-19: A single center experience.

BACKGROUND AND AIMS: We highlight the peripheral neurologic complications of coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an ongoing global health emergency. METHODS: We evaluated twenty-five patients admitted to the COVID-19 Recovery Unit (CRU) at New York-Presbyterian Weill Cornell University Medical Center after intensive care hospitalization with confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whom neurology was consulted for weakness and/or paresthesias. All patients were clinically evaluated by a neuromuscular neurologist who performed electrodiagnostic (EDX) studies when indicated. Magnetic resonance imaging (MRI) of the affected regions, along with nerve and muscle biopsies were obtained in select patients to better elucidate the underlying diagnosis. RESULTS: We found fourteen out of twenty-five patients with prolonged hospitalization for COVID-19 infection to have peripheral neurological complications, identified as plexopathies, peripheral neuropathies and entrapment neuropathies. The other eleven patients were not found to have peripheral neurologic causes for their symptoms. Patients with peripheral neurological complications often exhibited more than one type of concurrently. Specifically, there were four cases of plexopathies, nine cases of entrapment neuropathies, and six cases of peripheral neuropathies, which included cranial neuropathy, sciatic neuropathy, and multiple mononeuropathies. CONCLUSIONS: We explore the possibility that the idiopathic peripheral neurologic complications could be manifestations of the COVID-19 disease spectrum, possibly resulting from micro-thrombotic induced nerve ischemia.

Infection-induced chromatin modifications facilitate translocation of herpes simplex virus capsids to the inner nuclear membrane.

Herpes simplex virus capsids are assembled and packaged in the nucleus and move by diffusion through the nucleoplasm to the nuclear envelope for egress. Analyzing their motion provides conclusions not only on capsid transport but also on the properties of the nuclear environment during infection. We utilized live-cell imaging and single-particle tracking to characterize capsid motion relative to the host chromatin. The data indicate that as the chromatin was marginalized toward the nuclear envelope it presented a restrictive barrier to the capsids. However, later in infection this barrier became more permissive and the probability of capsids to enter the chromatin increased. Thus, although chromatin marginalization initially restricted capsid transport to the nuclear envelope, a structural reorganization of the chromatin counteracted that to promote capsid transport later. Analyses of capsid motion revealed that it was subdiffusive, and that the diffusion coefficients were lower in the chromatin than in regions lacking chromatin. In addition, the diffusion coefficient in both regions increased during infection. Throughout the infection, the capsids were never enriched at the nuclear envelope, which suggests that instead of nuclear export the transport through the chromatin is the rate-limiting step for the nuclear egress of capsids. This provides motivation for further studies by validating the importance of intranuclear transport to the life cycle of HSV-1.

Declining levels of miR-382-3p at puberty trigger the onset of spermatogenesis.

A major change in the transcriptome of testicular Sertoli cells (Scs) at the onset of puberty enables them to induce robust spermatogenesis. Through comprehensive literature mining, we generated a list of genes crucial for Sc functioning and computationally predicted the microRNAs regulating them. Differential expression analysis of microRNAs in infant and pubertal rat Scs showed that miR-382-3p levels decline significantly in pubertal Scs. Interestingly, miR-382-3p was found to regulate genes like Ar and Wt1, which are crucial for functional competence of Scs. We generated a transgenic (Tg) mouse model in which pubertal decline of miR-382-3p was prevented by its overexpression in pubertal Scs. Elevated miR-382-3p restricted the functional maturation of Scs at puberty, leading to infertility. Prevention of decline in miR-382-3p expression in pubertal Scs was responsible for defective blood-testis barrier (BTB) formation, severe testicular defects, low epididymal sperm counts and loss of fertility in these mice. This provided substantial evidence that decline in levels of miR-382-3p at puberty is the essential trigger for onset of robust spermatogenesis at puberty. Hence, sustained high levels of miR-382-3p in pubertal Scs could be one of the underlying causes of idiopathic male infertility and should be considered for diagnosis and treatment of infertility.

Metagenomic Investigation Uncovers Presence of Probiotic-Type Microbiome in Kalparasa® (Fresh Unfermented Coconut Inflorescence Sap).

The phloem sap tapped from unopened inflorescence (spadix) of coconut palm using a novel collecting device, "coco-sap chiller," has been branded Kalparasa® (henceforth as Kalparasa in the text) to distinguish its properties not found in sap harvested by traditional methods. To know its hitherto unidentified microbiome profile, we employed high-throughput sequencing to uncover the bacteriome and mycobiome in fresh and 12-h fermented samples. Fresh Kalparasa had a pH of 7.2, which dropped to 4.5 after 12 h, signifying fermentation of the sap. Diversity analysis indicated fresh Kalparasa having higher bacterial species than the fermented one. Contrary to this, fresh sap had lower fungal/yeast diversity than the fermented sample. Fresh Kalparasa had relatively higher abundance of probiotic-type Leuconostoc genus followed by equal proportions of Gluconobacter, Acetobacter, and Fructobacillus. The 12-h fermented Kalparasa showed a significant increase in Gluconobacter with a sharp decrease in Leuconostoc. Mycobiome data revealed fresh Kalparasa to be preponderant in Saccharomyces and Hanseniaspora genera of yeasts while the fermented sap had higher representation of Hanseniaspora and Cortinarius and lesser Saccharomyces. This suggested that the fermentation of Kalparasa was probably driven by symbiotic culture of bacteria and yeasts (SCOBY), particularly acetic acid bacteria and non-Saccharomyces yeasts. The bacteriome-function predictions highlighted the enrichment of glycerophospholipid, ABC transporters, purine, and pyrimidine metabolisms. Based on our findings, Kalparasa containing large population of Leuconostoc mesenteroides, Fructobacillus fructosus, Saccharomyces cerevisiae, and Hanseniaspora guilliermondii can be promoted as a healthy "unfermented" plant edible food containing live probiotic-type microbiome during its consumption.

FSH mediated cAMP signalling upregulates the expression of Gα subunits in pubertal rat Sertoli cells.

Follicle Stimulating Hormone (FSH) acts via FSH-Receptor (FSH-R) by employing cAMP as the dominant secondary messenger in testicular Sertoli cells (Sc) to support spermatogenesis. Binding of FSH to FSH-R, results the recruitment of the intracellular GTP binding proteins, either stimulatory Gαs or inhibitory Gαi that in turn regulate cAMP production in Sc. The cytosolic concentration of cAMP being generated by FSH-R thereafter critically determines the downstream fate of the FSH signalling. The pleiotropic action of FSH due to differential cAMP output during functional maturation of Sc has been well studied. However, the developmental and cellular regulation of the Gα proteins associated with FSH-R is poorly understood in Sc. In the present study, we report the differential transcriptional modulation of the Gα subunit genes by FSH mediated cAMP signalling in neonatal and pubertal rat Sc. Our data suggested that unlike in neonatal Sc, both the basal and FSH/forskolin induced expression of Gαs, Gαi-1, Gαi-2 and Gαi-3 transcripts was significantly (p < 0.05) up-regulated in pubertal Sc. Further investigations involving treatment of Sc with selective Gαi inhibitor pertussis toxin, confirmed the elevated expression of Gi subunits in pubertal Sc. Collectively our results indicated that the high level of Gαi subunits serves as a negative regulator to optimize cAMP production in pubertal Sc.

Awareness of aerosol-related transmission of COVID-19 among the dentists of Nepal.

OBJECTIVE: To access the awareness of dental practitioners of Nepal towards COVID-19 transmission through aerosols. MATERIALS AND METHODS: The study involved 384 dentists from all over Nepal and was conducted for a period of 3 months. A self-reported online questionnaire was developed using Google forms and the link was shared. It emphasized the awareness related to the aerosol and ventilation system in their daily practices was prepared. The data were analyzed in Statistical Package for Social Sciences version 20.0 software. RESULTS: The majority of participants were female 52.9% (n = 203) and within the age groups of <30 years 57% (n = 219). Participants from Bagmati Province were 60.4% (n = 232), with least from Sudurpaschim Province 0.5% (n = 2). 60% of participants provided only emergency services during the COVID-19 pandemic and few (7%) provided consultations via telephone. The current ventilation system used was a well-ventilated room with open windows 65.4% (n = 251). However, 52.8% (n = 203) preferred specialized operatory incorporating high-efficiency particulate air (HEPA) filters and ultraviolet (UV) light. More than 60% of respondents were unaware of the particle size of the aerosol. CONCLUSIONS: The obtained results signify the need for the proper ventilation system with appropriate air filtration systems in dental clinical setups.

Use of virtual reality in the inpatient rehabilitation of COVID-19 patients.

INTRODUCTION: Use of virtual reality (VR) in healthcare has expanded in recent years. The challenges faced by patients with prolonged COVID-19-related hospitalizations - social isolation, disability, neurologic sequelae, adjustment-related anxiety, depression, and stress - may be mitigated by the novel use of VR as one modality of a comprehensive rehabilitation plan. This descriptive study aimed to understand patient satisfaction and perceived benefit of virtual reality on a COVID-19 recovery unit, as well as the logistical and operational feasibility of providing VR content for patients and staff. MATERIALS AND METHODS: During the COVID-19 surge in New York City in 2020, the COVID-19 Recovery Unit (CRU) of a large academic hospital invited patients and staff to participate in VR sessions with three categories of experience: (1) Guided meditation, (2) Exploration of natural environments, (3) Cognitive stimulation games. Patients and staff were surveyed about satisfaction and perceived benefit. RESULTS: 13 patients and 11 staff were surveyed, with median patient satisfaction scores of 9 out of 10, with ten representing "extremely satisfied," and median staff satisfaction scores of 10. 13/13 patients answered "yes" to recommending the therapy to others, and 12/13 answered "yes" to perceived enhancement of their treatment. 11/11 staff answered "yes" to recommending the therapy to others, and 11/11 answered "yes" to perceived enhancement of their wellbeing. DISCUSSION: A VR program implemented on a COVID-19 rehabilitation unit for patients and healthcare providers was rated as highly satisfactory with perceived benefit by survey respondents. Participants commented that the use of VR was useful in coping with isolation and loneliness, and could be implemented within the context of clinical care for COVID-19 patients as part of a comprehensive rehabilitation model. The use of VR was also logistically and operationally feasible on the CRU. Future work to compare benefits of VR to standard neuropsychological rehabilitation is needed.

Combination therapy of N-acetyl-L-cysteine and S-2(2-aminoethylamino) ethylphenyl sulfide for sulfur mustard induced oxidative stress in mice.

INTRODUCTION: Sulfur mustard (SM) is chemically, bis(2-chloroethyl) sulfide and a strong alkylating agent that causes cytotoxicity and blisters on skin. In laboratory animal models, SM is extremely lethal. Since no specific antidote has been proposed, decontamination upon contact is the recommended procedure. Several antidotes have been screened for SM, and in that sulfanyl compounds, N-acetyl-l-cysteine (NAC) and S-2(2-aminoethylamino) ethylphenyl sulfide (DRDE-07) showed good protection. Since they showed protection at high doses, the aim of this study was to evaluate the efficacy in combination at low dose, for percutaneously administered SM in mice. MATERIAL AND METHODS: 4 LD50 of SM (32.4 mg/kg) was administered, and NAC (50 mg/kg), DRDE-07 (25 and 50 mg/kg) and their combinations were evaluated as 30 min pre-treatment by single oral administration. RESULT: After 72 h of SM exposure, significant decrease in body weight, decrease in hepatic reduced glutathione, and increase in hepatic malondialdehyde were observed (P < 0.001), showing oxidative stress. The combination of NAC (100 mg/kg) and DRDE-07 (50 mg/kg) showed significant protection (P < 0.01). The severe histopathological lesions induced by SM in liver, spleen and skin were also considerably reduced by the combination. CONCLUSION: The combination of NAC and DRDE-07 having sulfanyl groups, will be promising antioxidants and an effective antidote for SM toxicity.

Chol-Dex nanomicelles: Synthesis, characterization and evaluation as efficient drug carriers for colon targeting.

Core-shell structures obtained from amphiphilic molecules on self-assembly in a medium have emerged as an important tool in the area of biomedical sciences. Here, we have synthesized cholesteryl-dextran (Chol-Dex) amphiphiles in sufficiently high yields via conjugation of cholesteryl hemisuccinate to dextran in two different concentrations (5 and 10%). After physicochemical and spectral analysis, the nanomicelles were subjected to size measurements. DLS and TEM confirmed the formation of core-shell type of nanomicelles. Hydrophobic drug-entrapped formulations (Metronidazole and Rifampicin) displayed sustained release behaviour of drugs from them. Sustained release at neutral pH demonstrated usefulness of the non-toxic delivery system for colon specific diseases.