Dexmedetomidine as an Adjunct to Propofol in Patients Undergoing Elective Endoscopic Retrograde Cholangio-Pancreaticography - A Double-blind Randomized Controlled Study.

Background: Propofol is the drug of choice for procedural sedation. The addition of α2 agonist dexmedetomidine may improve the safety profile of the procedure by providing stable hemodynamics, better sedation quality, and decreasing the side effects of each drug during elective endoscopic retrograde cholangio-pancreaticography (ERCP). Materials and Methods: Eighty patients aged between 18 and 60 years were distributed randomly into two groups. The dexmedetomidine + propofol group (group DP) received an injection of dexmedetomidine at the dose of 1 mcg/kg in 100 mLsaline, and the propofol group (group P) received plain 100 mL normal saline over 10 min. Subsequently, both groups received a bolus dose of injection propofol 1 mg/kg as sedation, and a modified observer's assessment of alertness/sedation score (MOASS) score was assessed, followed by infusion at the rate of 50 mcg/kg/min during the procedure. A rescue bolus dose (20 mg) of propofol was administered when the patient showed signs of inadequate sedation or analgesia in both groups. Cardiovascular and respiratory parameters were recorded every 10 min throughout the procedure. Post-procedure modified Aldrete score was evaluated for 30 min, and the endoscopist's score was noted at the end of the procedure. Results: There was a significant difference (P = 0.001) in the additional number of rescue doses of propofol administered in group DP (3.47 ± 0.77) as compared to group P (8.78 ± 1.11). The total dose of propofol was lower in group DP (316.59 ± 43.29 mg) than in group P (443 ± 41.1 mg) with P value = 0.001. Statistically significant differences in the hemodynamic values were observed in group DP during infusion (P value < 0.05) of dexmedetomidine and throughout the procedure (P < 0.05) when compared with group P. Endoscopists graded the satisfaction score as very high (3.477 ± 0.77) in group DP. Conclusion: The addition of dexmedetomidine to propofol during ERCP provided better and safer sedation.

Targeting AKT2 in MDA-MB-231 Cells by Pyrazole Hybrids: Structural, Biological and Molecular Docking Studies.

Pyrazolic hybrids appended with naphthalene, p-chlorobenzene, o-phenol and toluene have been synthesized using Claisen Schmidt condensation reaction of 1-benzyl-3,5-dimethyl-1H-pyrazole-4-carbaldehyde. All compounds were characterized by various spectroscopic techniques. Compound (E)-3-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-1-(4-chlorophenyl)prop-2-en-1-one crystallizes in monoclinic crystal system with C2/c space group. These synthesized compounds were tested for cytotoxic activity and among these compounds 4b and 5a shows prominent cytotoxic activity against triple-negative breast cancer (TNBC) cells MDA-MB-231 with IC50 values 47.72 µM and 24.25 µM, respectively. Distinguishing morphological changes were noticed in MDA-MB-231 cells treated with pyrazole hybrids contributing to apoptosis action. To get more insight into cytotoxic activity, in silico molecular docking of these compounds were performed and the results suggested that (E)-3-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-1-(p-tolyl)prop-2-en-1-one and 1-(1'-benzyl-5-(4-chlorophenyl)-3',5'-dimethyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazol]-2-yl)ethan-1-one binds to the prominent domain of Akt2 indicating their potential ability as Akt2 inhibitor. Moreover, from in silico ADME studies clearly demonstrated that these compounds may be regarded as a drug candidate for sub-lingual absorption based on log p values (2.157-4.924). These compounds also show promising antitubercular activity. The overall results suggest that pyrazolic hybrids with substitution at less sterically hindered positions have appealing potent cytotoxic activity and antituberculosis activity due to which they may act as multidrug candidate.

Chronic lead exposure disrupts neurometabolic activity in mouse brain: An ex vivo1H-[13C]-NMR study.

Lead poisoning has been identified as a problem in adults as well as in children. Chronic exposure to lead has been implicated in neurological disorders such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. In the present study, we evaluated the impact of chronic lead exposure on cerebral glutamatergic and GABAergic metabolic activity in mice. C57BL6 mice were provided lead acetate in drinking water for two months. The regional cerebral metabolic activity was measured using 1H-[13C]-NMR spectroscopy in conjunction with infusion of [1,6-13C2]glucose. The blood Pb2+ increased significantly in lead acetate treated mice. Concomitantly, there was a significant reduction in the forelimb strength. The level of myo-inositol was elevated in the cerebral cortex of mice chronically exposed to lead. The glutamatergic neurometabolic activity was found to be reduced following chronic lead exposure in the cerebral cortex, hippocampus, and striatum. In contrast, the GABAergic fluxes were impaired in the hippocampus and thalamus only. The metabolic fluxes in the cerebellum were unperturbed to Pb2+ toxicity. In conclusion, we report that chronic lead exposure in mice leads to an impairment in forelimb strength, and a perturbation in neurometabolism in brain regions involving cognition and movement.

EEG Abnormalities and Their Radiographic Correlates in a COVID-19 Inpatient Cohort.

Background and Objectives: To identify the prevalence of EEG abnormalities in patients with coronavirus disease 2019 (COVID-19) with neurologic changes, their associated neuroimaging abnormalities, and rates of mortality. Methods: A retrospective case series of 192 adult COVID-19-positive inpatients with EEG performed between March and June 2020 at 4 hospitals: 161 undergoing continuous, 24 routine, and 7 reduced montage EEG. Study indication, epilepsy history, intubation status, administration of sedatives or antiseizure medications (ASMs), metabolic abnormalities, neuroimaging pathology associated with epileptiform abnormalities, and in-hospital mortality were analyzed. Results: EEG indications included encephalopathy (54.7%), seizure (18.2%), coma (17.2%), focal deficit (5.2%), and abnormal movements (4.6%). Epileptiform abnormalities occurred in 39.6% of patients: focal intermittent epileptiform discharges in 25.0%, lateralized periodic discharges in 6.3%, and generalized periodic discharges in 19.3%. Seizures were recorded in 8 patients, 3 with status epilepticus. ASM administration, epilepsy history, and older age were associated with epileptiform abnormalities. Only 26.3% of patients presented with any epileptiform abnormality, 37.5% with electrographic seizures, and 25.7% patients with clinical seizures had known epilepsy. Background findings included generalized slowing (88.5%), focal slowing (15.6%), burst suppression (3.6%), attenuation (3.1%), and normal EEG (3.1%). Neuroimaging pathology was identified in 67.1% of patients with epileptiform abnormalities, over two-thirds acute. In-hospital mortality was 39.5% for patients with epileptiform abnormalities and 36.2% for those without. Risk factors for mortality were coma and ventilator support at time of EEG. Discussion: This article highlights the range of EEG abnormalities frequently associated with acute neuroimaging abnormalities in COVID-19. Mortality rates were high, particularly for patients in coma requiring mechanical ventilation. These findings may guide the prognosis and management of patients with COVID-19 and neurologic changes.

Anatomy of Covid outbreak of vaccinated: An observational case-control study of Covid breakthrough infections in medical college students at Rural Medical College, India

IntroductionBreakthrough infections about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported worldwide in both partially or completely vaccinated individuals irrespective of the type of vaccine. India, also emerged as the vaccine powerhouse producer, initiating the worlds one of the largest vaccination drives since January 16, 2021, with two vaccines named, BBV-152(COVAXIN) and AZD1222 (COVISHIELD). Breakthrough cases are reported from all over the globe for all kinds of vaccines. This is the investigation report into the outbreak of breakthrough COVID-19 infections at one of the medical colleges in Rural India unraveled in early October 2021. This report underscores the role of COVID-19 appropriate behavior along with vaccination and the role of IgG in evaluating immunity generated through vaccination. ObjectiveThe study objective was to 1. Clinically characterize the recent breakthrough infection of COVID-19 (SARS-CoV-2) infection among (students) vaccinated in BKL Walawalkar Rural Medical College. 2. To evaluate COVID-19 appropriate behavior (CAB) in cases and controls. 3. To evaluate COVID-19 anti spike IgG in the cases in comparison with the control MethodsA total of 74 students studying at BKL Walawalkar Rural Medical College and vaccinated for COVID-19 were included in the study. RT-PCR diagnosis was done from 5 to 10 October 2021. The breakthrough infection in the cases was characterized using self-assessment questionnaires in comparison to the controls. The cases were assessed clinically and also using biochemical parameters. Both cases and controls were also assessed for their adherence to COVID-19 appropriate behavior using a separate semi-quantitative questionnaire and scoring system. ResultsIn our study, out of the total subjects, 50% of Covaxin recipients had experienced vaccine breakthrough infection and 20% of Covishield recipients experienced breakthrough infection. Also, 6 out of the 35 cases were asymptomatic, and the rest were either having mild symptoms. None of them required any hospitalization or O2 therapy. The CAB score was lower in the cases when compared to controls. All the vaccine recipients show seroconversion. Anti-spike IgG antibodies titers are dynamic over time and across the clinically distinct groups. Irrespective of varying IgG titer, the vaccine protects against severity and possibly mortality. ConclusionThe need for better awareness of COVID-19 appropriate methods as an alternative to and additive to vaccination is necessary to control the transmission of COVID-19 infection and decrease the disease severity. Vaccines are effective against preventing severe disease and possibly mortality. The use of serum anti-spike COVID-19 IgG is restricted to know the status of SARS-CoV-2 seroconversion.

CBF oscillations induced by trigeminal nerve stimulation protect the pericontusional penumbra in traumatic brain injury complicated by hemorrhagic shock.

Traumatic peri-contusional penumbra represents crucial targets for therapeutic interventions after traumatic brain injury (TBI). Current resuscitative approaches may not adequately alleviate impaired cerebral microcirculation and, hence, compromise oxygen delivery to peri-contusional areas. Low-frequency oscillations in cerebral blood flow (CBF) may improve cerebral oxygenation in the setting of oxygen deprivation. However, no method has been reported to induce controllable oscillations in CBF and it hasn't been applied as a therapeutic strategy. Electrical stimulation of the trigeminal nerve (TNS) plays a pivotal role in modulating cerebrovascular tone and cerebral perfusion. We hypothesized that TNS can modulate CBF at the targeted frequency band via the trigemino-cerebrovascular network, and TNS-induced CBF oscillations would improve cerebral oxygenation in peri-contusional areas. In a rat model of TBI complicated by hemorrhagic shock, TNS-induced CBF oscillations conferred significant preservation of peri-contusional tissues leading to reduced lesion volume, attenuated hypoxic injury and neuroinflammation, increased eNOS expression, improved neurological recovery and better 10-day survival rate, despite not significantly increasing CBF as compared with those in immediate and delayed resuscitation animals. Our findings indicate that low-frequency CBF oscillations enhance cerebral oxygenation in peri-contusional areas, and play a more significant protective role than improvements in non-oscillatory cerebral perfusion or volume expansion alone.

Adult neurogenesis alters response to an aversive distractor in a labyrinth maze without affecting spatial learning or memory.

Adult neurogenesis has been implicated in learning and memory of complex spatial environments. However, new neurons also play a role in nonmnemonic behavior, including the stress response and attention shifting. Many commonly used spatial tasks are very simple, and unsuitable for detecting neurogenesis effects, or are aversively motivated, making it difficult to dissociate effects on spatial learning and memory from effects on stress. We have therefore created a novel complex spatial environment, the flex maze, to enable reward-mediated testing of spatial learning in a flexibly configurable labyrinth. Using a pharmacogenetic method to completely inhibit neurogenesis in adulthood, we found that rats lacking new neurons (TK rats) and wild type controls completed and remembered most mazes equally well. However, control rats were slower to complete peppermint-scented mazes than other mazes, while neurogenesis-deficient rats showed no effect of mint on maze behavior, completing these mazes significantly faster than control rats. Additional testing found that wild type and TK rats showed similar detection of, avoidance of, and glucocorticoid response to the mint odor. These results suggest that spatial learning and memory in a labyrinth task is unaffected by the loss of new neurons, but that these cells affect the ability of an aversive stimulus to distract rats from completing the maze.

Acute Seizures Occurring in Association With SARS-CoV-2.

Seizures are an infrequent and serious neurological complication of SARS-CoV-2 infection, with limited data describing the etiology and the clinical context in which these occur or the associated electrographic and imaging findings. This series details four cases of seizures occurring in patients with COVID-19 with distinct time points, underlying pathology, and proposed physiological mechanisms. An enhanced understanding of seizure manifestations in COVID-19 and their clinical course may allow for earlier detection and improved patient management.

Electrical Stimulation of the Infraorbital Nerve Induces Diving Reflex in a Dose-Controlled Manner.

The "diving reflex" (DR) is a very powerful autonomic reflex that facilitates survival in hypoxic/anoxic conditions and could trigger multifaceted physiologic effects for the treatment of various diseases by modulating the cardiovascular, respiratory, and nervous systems. The DR can be induced by cold water or noxious gases applied to the anterior nasal mucosa and paranasal regions, which can stimulate trigeminal thermo- or chemo-receptors to send afferent signals to medullary nuclei which mediate the sympathetic and parasympathetic nervous systems. Although promising, these approaches have yet to be adopted in routine clinical practice due to the inability to precisely control exposure-response relationships, lack of reproducibility, and difficulty implementing in a clinical setting. In this study, we present the ability of electrical Trigeminal (Infraorbital) Nerve Stimulation (eTINS) to induce the DR in a dose-controllable manner. We found that eTINS not only triggered specific physiological changes compatible with the pattern of "classic" DR observed in animals/humans, but also controlled the induced-DR at varying levels. This study demonstrates, for the first time, that the intensity of the DR is controllable by dose and opens possibility to investigate its protective mechanism against various pathologies in well-controlled research settings.

Are shed hair genomes the most effective noninvasive resource for estimating relationships in the wild?

Knowledge of relationships in wild populations is critical for better understanding mating systems and inbreeding scenarios to inform conservation strategies for endangered species. To delineate pedigrees in wild populations, study genetic connectivity, study genotype-phenotype associations, trace individuals, or track wildlife trade, many identified individuals need to be genotyped at thousands of loci, mostly from noninvasive samples. This requires us to (a) identify the most common noninvasive sample available from identified individuals, (b) assess the ability to acquire genome-wide data from such samples, and (c) evaluate the quality of such genome-wide data, and its ability to reconstruct relationships between animals within a population.We followed identified individuals from a wild endangered tiger population and found that shed hair samples were the most common compared to scat samples, opportunistically found carcasses, and opportunistic invasive samples. We extracted DNA from these samples, prepared whole genome sequencing libraries, and sequenced genomes from these.Whole genome sequencing methods resulted in between 25%-98% of the genome sequenced for five such samples. Exploratory population genetic analyses revealed that these data were free of holistic biases and could recover expected population structure and relatedness. Mitochondrial genomes recovered matrilineages in accordance with long-term monitoring data. Even with just five samples, we were able to uncover the matrilineage for three individuals with unknown ancestry.In summary, we demonstrated that noninvasive shed hair samples yield adequate quality and quantity of DNA in conjunction with sensitive library preparation methods, and provide reliable data from hundreds of thousands of SNPs across the genome. This makes shed hair an ideal noninvasive resource for studying individual-based genetics of elusive endangered species in the wild.

New neurons restore structural and behavioral abnormalities in a rat model of PTSD.

Post-traumatic stress disorder (PTSD) has been associated with anxiety, memory impairments, enhanced fear, and hippocampal volume loss, although the relationship between these changes remain unknown. Single-prolonged stress (SPS) is a model for PTSD combining three forms of stress (restraint, swim, and anesthesia) in a single session that results in prolonged behavioral effects. Using pharmacogenetic ablation of adult neurogenesis in rats, we investigated the role of new neurons in the hippocampus in the long-lasting structural and behavioral effects of SPS. Two weeks after SPS, stressed rats displayed increased anxiety-like behavior and decreased preference for objects in novel locations regardless of the presence or absence of new neurons. Chronic stress produced by daily restraint for 2 or 6 hr produced similar behavioral effects that were also independent of ongoing neurogenesis. At a longer recovery time point, 1 month after SPS, rats with intact neurogenesis had normalized, showing control levels of anxiety-like behavior. However, GFAP-TK rats, which lacked new neurons, continued to show elevated anxiety-like behavior and enhanced serum corticosterone response to anxiogenic experience. Volume loss in ventral CA1 region of the hippocampus paralleled increases in anxiety-like behavior, occurring in all rats exposed to SPS at the early time point and only rats lacking adult neurogenesis at the later time point. In chronic stress experiments, volume loss occurred broadly throughout the dentate gyrus and CA1 after 6-hr daily stress but was not apparent in any hippocampal subregion after 2-hr daily stress. No effect of SPS was seen on cell proliferation in the dentate gyrus, but the survival of young neurons born a week after stress was decreased. Together, these data suggest that new neurons are important for recovery of normal behavior and hippocampal structure following a strong acute stress and point to the ventral CA1 region as a potential key mediator of stress-induced anxiety-like behavior.

Adult neurogenesis affects motivation to obtain weak, but not strong, reward in operant tasks.

Decreased motivation to seek rewards is a key feature of mood disorders that correlates with severity and treatment outcome. This anhedonia, or apathy, likely reflects impairment in reward circuitry, but the specific neuronal populations controlling motivation are unclear. Granule neurons generated in the adult hippocampus have been implicated in mood disorders, but are not generally considered as part of reward circuits. We investigated a possible role of these new neurons in motivation to work for food and sucrose rewards in operant conditioning tasks using GFAP-TK pharmacogenetic ablation of adult neurogenesis in both rats and mice. Rats and mice lacking adult neurogenesis showed normal lever press responding during fixed ratio training, reward devaluation, and Pavlovian Instrumental Transfer, suggesting no impairment in learning. However, on an exponentially progressive ratio schedule, or when regular chow was freely available in the testing chamber, TK rats and mice showed less effort to gain sucrose tablets. When working for balanced food tablets, which rats and mice of both genotypes strongly preferred over sucrose, the genotype effects on behavior were lost. This decrease in effort under conditions of low reward suggests that loss of adult neurogenesis decreases motivation to seek reward in a manner that may model behavioral apathy.

Aryl-1H-imidazole[4,5f][1,10]phenanthroline Cu(II) complexes: Electrochemical and DNA interaction studies.

The reaction of aryl imidazo[4,5f] [1,10]phenanthrolines with Cu(NO3)2 lead to the formation of Cu(II) complexes of the type [Cu(L)(NO3)2] where L=PIP, 2-(phenyl) [4,5f] imidazo phenanthroline; HPIP=2-(2-hydroxyphenyl)imidazo [4,5f] phenanthroline and NIP=2-(naphthyl) [4,5f] imidazo phenanthroline. The interaction of these complexes with calf thymus DNA has been studied using viscosity measurements, UV-visible and fluorescence spectroscopy. Chemical nuclease activity of these complexes has also been investigated. All complexes cleave DNA via oxidative pathway involving singlet oxygen. Molecular docking studies revealed that these complexes bind to DNA through minor groove.

Fluorescent zinc(ii) complexes for gene delivery and simultaneous monitoring of protein expression.

Two new zinc(ii) complexes, [Zn(l-His)(NIP)]+(1) and [Zn(acac)2(NIP)](2) (where NIP is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, acac = acetyl acetone), have been synthesized and characterized by elemental analysis, UV-vis, fluorescence, IR, 1H NMR and electron spray ionization mass spectroscopies. Gel retardation assay, atomic force microscopy and dynamic light scattering studies show that 1 and 2 can induce the condensation of circular plasmid pBR322 DNA into nanometer size particles under ambient conditions. Treatment of 2 with 5 mM EDTA restored 30% of the supercoiled form of DNA, revealing partial reversibility of DNA condensation. The in vitro transfection experiment demonstrates that the complexes can be used to deliver pCMV-tdTomato-N1 plasmid which expresses red fluorescent protein. The confocal studies show that the fluorescent nature of complexes is advantageous for visualizing the intracellular delivery of metal complexes as well as transfection efficiency using two distinct emission windows.

Anxiolytic Actions of Exercise in Absence of New Neurons.

Physical exercise reduces anxiety-like behavior in adult mice. The specific mechanisms that mediate this anxiolytic effect are unclear, but adult neurogenesis in the dentate gyrus has been implicated because it is robustly increased by running and has been linked to anxiodepressive-like behavior. We therefore tested the effects of long-term wheel running on anxiety-like behavior in GFAP-TK (TK) mice, a transgenic strain with complete ablation of adult neurogenesis. Five weeks of running reduced anxiety-like behavior equally in both TK mice and wild type (WT) control mice on two tests, elevated plus-maze and novelty-suppressed feeding. WT and TK mice also had similar patterns of c-fos expression in the hippocampus following anxiety testing. Following testing on the elevated plus-maze, running reduced c-fos expression in the dorsal dentate gyrus and CA3 in both WT and TK mice. Following testing on novelty-suppressed feeding, running reduced c-fos expression throughout the dentate gyrus and CA3 in both WT and TK mice. Interestingly, following testing on a less anxiogenic version of novelty-suppressed feeding, running reduced c-fos expression only in the dorsal dentate gyrus in both WT and TK mice, supporting earlier suggestions that the dorsal hippocampus is less involved in emotional behavior than the ventral region. These results suggest that although running increases adult neurogenesis, new neurons are not involved in the decreased anxiety-like behavior or hippocampal activation produced by running. © 2016 Wiley Periodicals, Inc.

Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis.

UNLABELLED: Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP-thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus. SIGNIFICANCE STATEMENT: To investigate cellular processes underlying adaptation to social instability, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Unexpectedly, these changes were accompanied by changes in social strategies without evidence of impairments in cognition or anxiety regulation. Restoring adult neurogenesis in disrupted rats using oxytocin and conditionally suppressing the production of new neurons in socially naive GFAP-thymidine kinase rats showed that loss of 6-week-old neurons may be responsible for adaptive changes in social behavior.

Antiproliferative activity of bicyclic benzimidazole nucleosides: synthesis, DNA-binding and cell cycle analysis.

An efficient route was developed for synthesis of bicyclic benzimidazole nucleosides from readily available d-glucose. The key reactions were Vörbruggen glycosylation and ring closing metathesis (RCM). Primarily, to understand the mode of DNA binding, we performed a molecular docking study and the binding was found to be in the minor groove region. Based on the proposed binding model, UV-visible and fluorescence spectroscopic techniques using calf thymus DNA (CT-DNA) demonstrated a non-intercalative mode of binding. Antiproliferative activity of nucleosides was tested against MCF-7 and MDA-MB-231 breast cancer cell lines and found to be active at low micromolar concentrations. Compounds and displayed significant antiproliferative activity as compared to and with the reference anticancer drug, doxorubicin. Cell cycle analysis showed that nucleoside induced cell cycle arrest at the S-phase. Confocal microscopy has been performed to validate the induction of cellular apoptosis. Based on these findings, such modified bicyclic benzimidazole nucleosides will make a significant contribution to the development of anticancer drugs.

Neuroprotective effects of caffeine in MPTP model of Parkinson's disease: A (13)C NMR study.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons with an accompanying neuroinflammation leading to loss of dopamine in the basal ganglia. Caffeine, a well-known A2A receptor antagonist is reported to slow down the neuroinflammation caused by activated microglia and reduce the extracellular glutamate in the brain. In this study, we have evaluated the neuroprotective effect of caffeine in the MPTP model of PD by monitoring the region specific cerebral energy metabolism. Adult C57BL6 mice were treated with caffeine (30 mg/kg, i.p.) 30 min prior to MPTP (25 mg/kg, i.p.) administration for 8 days. The paw grip strength of mice was assessed in order to evaluate the motor function after various treatments. For metabolic studies, mice were infused with [1,6-(13)C2]glucose, and (13)C labeling of amino acids was monitored using ex vivo(1)H-[(13)C]-NMR spectroscopy. The paw grip strength was found to be reduced following the MPTP treatment. The caffeine pretreatment showed significant protection against the reduction of paw grip strength in MPTP treated mice. The levels of GABA and myo-inositol were found to be elevated in the striatum of MPTP treated mice. The (13)C labeling of GluC4, GABAC2 and GlnC4 from [1,6-(13)C2]glucose was decreased in the cerebral cortex, striatum, olfactory bulb, thalamus and cerebellum suggesting impaired glutamatergic and GABAergic neuronal activity and neurotransmission of the MPTP treated mice. Most interestingly, the pretreatment of caffeine maintained the (13)C labeling of amino acids to the control values in cortical, olfactory bulb and cerebellum regions while it partially retained in striatal and thalamic regions in MPTP treated mice. The pretreatment of caffeine provides a partial neuro-protection against severe striatal degeneration in the MPTP model of PD.

Occupational Stress, Salivary Cortisol, and Periodontal Disease: A Clinical and Laboratory Study.

BACKGROUND: Periodontitis is a multifactorial disease, commonly associated with most of the lifestyle diseases. In the recent years, the association between periodontitis with occupational stress has evolved in various studies in many developed settings. This study aims at studying the prevalence of periodontal disease and its relationship with job stress among industrial labor workers covered under Employee's State Insurance Corporation Scheme. MATERIALS AND METHODS: The study included 180 subjects who were informed about the research goals, and also requested to sign consents. The questionnaire included parts from the generic job stress questionnaire from the National Institute of Job Stress and Health. Dental examinations based on community periodontal index protocol were done using WHO probe. Participants with moderate to severe periodontitis (score 3, 4) were informed about the salivary cortisol test. The saliva samples were collected and transported to the lab. Data were entered in EPI info 3.1.1 and analyzed in SPSS 14. The Chi-square analysis was done to measure association, and logistic regression analysis was done to identify the independent association of job stress to periodontitis. RESULTS: The study shows that 48% of the participants reported to have job stress, and 55% had periodontitis. The mean salivary cortisol level was 3.42 ng/dl. The results also indicated a higher odds of having low levels of salivary cortisol among those who reported job stress. Bi-variant regression analyses show the relationship of periodontitis with job stress to be much higher on controlling for other risk factors. The odds of having periodontitis in relation to positive job stress were 6 times higher than those who did not have positive job stress. CONCLUSIONS: This study shows a high prevalence of job stress related periodontitis among industrial workers in India. This research recommends the health and labor ministry to improve access to dental care especially in rural areas and include psychiatric units and oral health care as a part of primary health care. The factories administration should encourage recreation and retreat of the workers so as to reduce the level of stress at work. The factory administrations were recommended to have counselors to help their employees.

Monitoring cellular uptake and cytotoxicity of copper(II) complex using a fluorescent anthracene thiosemicarbazone ligand.

The thiosemicarbazone derivative of anthracene (ATSC, anthracene thiosemicarbazone 1) and its copper(II) complex (CuATSC, 2) were synthesized and characterized by spectroscopic, electrochemical, and crystallographic techniques. Interaction of 1 and 2 with calf thymus (CT) DNA was explored using absorption and emission spectral methods, and viscosity measurements reveal a partial-intercalation binding mode. Their protein binding ability was monitored by the quenching of tryptophan emission using bovine serum albumin (BSA) as a model protein. Furthermore, their cellular uptake, in vitro cytotoxicity testing on the HeLa cell line, and flow cytometric analysis were carried out to ascertain the mode of cell death. Cell cycle analysis indicated that 1 and 2 cause cell cycle arrest in sub-G1 phase.