Asphyxiophilic death due to masochistic behaviour in a video game addict teen: A case report and reviews.

The disorder of internet gaming is increasingly being blamed on major psychological problems affecting youth. Action video games are enjoyable for masochists. Video game chores that practise bondage and other acts that cause pain and anoxia may be masochistic in nature in order to promote player satisfaction. Asphyxia will result in pleasure in asphyxiophilia, a dangerous and occasionally lethal form of sexual masochism. Constriction of the neck with ligature materials is a frequent method of causing hypoxia. The subject of this case study was a compulsive player of online video games. During the masochistic act, along with a recording of it, he unintentionally died. Given that he was naked, had a ligature around his neck, had his wrists and legs bound, and had two fabric-holding clamps on his scrotum, asphyxiophilia was determined to be the cause of his death. At the scene of death, neither pornographic materials nor proof of frequent use of this kind of behaviour were discovered. Along with recording, the subject's cell phone's flash was on to help with the dim lighting and he may have been videotaping these masochistic acts as part of a videogame task. The results of the autopsy, circumstantial evidence, police inquiry and witness accounts all support accidental death.

Sukshmjeevanu in Vedas: The Forgotten Past of Microbiology in Indian Vedic Knowledge.

No one questions the existence of presumptive knowledge of invisible organisms causing disease, decay and destruction mentioned before the discovery of the microbial world by Antonie Van Leeuwenhoek, who was the first to describe the invisible world as per literature available today. However, the knowledge about microbial world by Indian Rishis presented in Sanskrit shlokas or suktas of our traditional manuscripts such as Vedas remained unseen, where the Rishis had predicted the role of microorganisms known as Krimi or Jeevanu years before Leeuwenhoek. This note is an attempt to bring an emphasis to revisit our traditional Vedic knowledge and establish them through research based facts for wider acceptance globally.

Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species.

BACKGROUND: Candida species are the important etiologic agents for candidiasis, the most prevalent cause of opportunistic fungal infections. Candida invasion results in mucosal to systemic infections through immune dysfunction and helps in further invasion and proliferation at several sites in the host. The host defence system utilizes a wide array of the cells, proteins and chemical signals that are distributed in blood and tissues which further constitute the innate and adaptive immune system. The lack of antifungal agents and their limited therapeutic effects have led to high mortality and morbidity related to such infections. METHODS: The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. RESULTS: This article sheds light on novel drug delivery approaches to target the immunological axis for several Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. rugose, C. hemulonii, etc.). CONCLUSION: It is clear that the novel drug delivery approaches include vaccines, adoptive transfer of primed immune cells, recombinant cytokines, therapeutic antibodies, and nanoparticles, which have immunomodulatory effects. Such advancements in targeting various underpinning mechanisms using the concept of novel drug delivery will provide a new dimension to the fungal infection clinic particularly due to Candida species with improved patient compliance and lesser side effects. This advancement in knowledge can also be extended to target various other similar microbial species and infections.

Gonadotropin-releasing hormone agonist induces downregulation of tensin 1 in women with endometriosis.

INTRODUCTION: Many cell migration-related molecules are associated with endometriosis. Tensin 1 (TNS1), which has been implicated in cell migration, may play a role in endometriosis. The study goal was to evaluate the TNS1 expression in endometrial tissue and serum from women with endometriosis treated with gonadotropin-releasing hormone agonist (GnRHa). MATERIAL AND METHODS: Tissue and serum samples were collected from women with endometriosis who were treated (n = 29) with GnRHa or untreated (n = 30). TNS1 mRNA was examined using quantitative PCR. TNS1 protein levels in tissue and serum samples were investigated using Western blot, immunohistochemistry and ELISA. Eleven women with endometriosis participated in a follow-up investigation of serum TNS1 before and after GnRHa treatment. RESULTS: TNS1 mRNA (P = 0.006) and protein (P = 0.001) were significantly downregulated in endometriotic tissue from women with endometriosis who received GnRHa. Immunolocalization of TNS1 showed strong expression in the epithelial and stromal cells of endometriotic tissue from women untreated with GnRHa, whereas endometriotic tissue from GnRHa-treated women showed low TNS1 expression. Follow-up monitoring of serum TNS1 concentration in 11 women showed an average decrease in concentration of 53%, from 294.9 ± 66.69 to 140.3 ± 55.21 pg/mL, following GnRHa treatment (P = 0.003). CONCLUSIONS: GnRHa induces downregulation of TNS1 in tissue and serum in women with endometriosis. These results emphasize the importance TNS1 as a potential therapeutic molecular target for the treatment of endometriosis with GnRHa.

Peripheral levels of superoxide dismutase and glutathione peroxidase in youths in ultra-high risk for psychosis: a pilot study.

IntroductionOxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset. OBJECTIVE: This work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC). METHODS: Thirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits. RESULTS: After adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities. CONCLUSION: Our results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.

Oxidative, inflammatory, genetic, and epigenetic biomarkers associated with chronic obstructive pulmonary disorder.

A large body of evidence indicates that chronic obstructive pulmonary disorder (COPD) is accompanied by oxidative stress and inflammatory and genetic pathways. Epidemiological studies indicate that COPD is a major cause of mortality and morbidity in the world. Recent research development in COPD focuses on accelerated aging and various oxidative stress biomarkers. It involves the clinical manifestation of the disease process and may also contain biochemical, immunological, physiological, morphological, and genetic aspects that add to the progressiveness of the disease. Herein, we summarize findings that highlight the role of dimensions of COPD in the investigation of oxidative stress, inflammatory responses, genetic and epigenetic studies, and pharmacological and dietary antioxidant intervention.

Peroxisomes: role in cellular ageing and age related disorders.

Peroxisomes are dynamic organelles essential for optimum functioning of a eukaryotic cell. Biogenesis of these organelles and the diverse functions performed by them have been extensively studied in the past decade. Their ability to perform functions depending on the cell type and growth conditions is unique and remarkable. Oxidation of fatty acids and reactive oxygen species metabolism are the two most important functions of these ubiquitous organelles. They are often referred to as both source and sink of reactive oxygen species in a cell. Recent research connects peroxisome dysfunction to fatal oxidative damage associated with ageing-related diseases/disorders. It is now widely accepted that mitochondria and peroxisomes are required to maintain oxidative balance in a cell. However, our understanding on the inter-dependence of these organelles to maintain cellular homeostasis of reactive oxygen species is still in its infancy. Herein, we summarize findings that highlight the role of peroxisomes in cellular reactive oxygen species metabolism, ageing and age-related disorders.

Prospects of Nanostructure Materials and Their Composites as Antimicrobial Agents.

Nanostructured materials (NSMs) have increasingly been used as a substitute for antibiotics and additives in various products to impart microbicidal effect. In particular, use of silver nanoparticles (AgNPs) has garnered huge researchers' attention as potent bactericidal agent due to the inherent antimicrobial property of the silver metal. Moreover, other nanomaterials (carbon nanotubes, fullerenes, graphene, chitosan, etc.) have also been studied for their antimicrobial effects in order ensure their application in widespread domains. The present review exclusively emphasizes on materials that possess antimicrobial activity in nanoscale range and describes their various modes of antimicrobial action. It also entails broad classification of NSMs along with their application in various fields. For instance, use of AgNPs in consumer products, gold nanoparticles (AuNPs) in drug delivery. Likewise, use of zinc oxide nanoparticles (ZnO-NPs) and titanium dioxide nanoparticles (TiO2-NPs) as additives in consumer merchandises and nanoscale chitosan (NCH) in medical products and wastewater treatment. Furthermore, this review briefly discusses the current scenario of antimicrobial nanostructured materials (aNSMs), limitations of current research and their future prospects. To put various perceptive insights on the recent advancements of such antimicrobials, an extended table is incorporated, which describes effect of NSMs of different dimensions on test microorganisms along with their potential widespread applications.

Oxidative Stress and Accelerated Aging in Neurodegenerative and Neuropsychiatric Disorder.

BACKGROUND: Neurodegenerative diseases are becoming more and more common in today's world. As people are continuously being exposed to exogenous factors like UV radiations, gamma rays, X-Rays, environmental pollutants and heavy metals, the cases of increased oxidative damage are increasing. Even though some amount of oxidative damage occurs in all metabolic reactions but their increase from the normal level in organisms causes neurodegenerative diseases. These neurodegenerative disorders like Alzeimers, Parkinsons disease and neuropsychiatric disorders such as schizophrenia, bipolar, depression are caused due to the decline in physiological and psychological functions caused by ROS and RNS. These ROS and RNS are formed as the result of excess oxidative damage in the system. METHODS: The following article goes into detail explaining all the effects caused by excess oxidative damage like ROS/RNS formation and telomere shortening. Further, it explains the pathways of neurodegenerative diseases and neuropsychiatric diseases. This article also sheds light on the effective treatments of such disorders by changing lifestyle and activating antioxidant pathways. CONCLUSION: It is clear that neurodegenerative diseases are caused due to excess oxidative stress and alter the functioning of the central nervous system. The central nervous system undergoes neurodegenerative or neuropsychiatric changes.

Socioeconomic Disadvantage Moderates the Association between Peripheral Biomarkers and Childhood Psychopathology.

BACKGROUND: Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF. METHODS AND FINDINGS: Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-demographic characteristics and mental health problems using the Child Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a cumulative risk model. Generalized linear models were used to assess associations between SED, biomarkers levels and psychopathology. SED was significantly associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020) and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066, p = 0.077). SED was also significantly associated with all CBCL DSM-oriented scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were associated with specific subscales. Moreover, the associations between serum biomarkers and domains of psychopathology were moderated by SED, with stronger correlations between mental health problems, IL6, TBARS, and BDNF being observed in children with high SED. CONCLUSIONS: In children, SED is highly associated with mental health problems. Our findings suggest that this association may be moderated via effects on multiple interacting neurobiological systems.

Peripheral immuno-inflammatory abnormalities in ultra-high risk of developing psychosis.

BACKGROUND: Immuno-inflammatory imbalances have been documented in schizophrenia, but very little is known about the immunological changes prior to the onset of disease. OBJECTIVE: This work aimed to compare serum levels of pro- and anti-inflammatory cytokines in young subjects at ultra-high risk (UHR) of developing psychosis with age- and sex-matched healthy controls. METHODS: A total of 12 UHR and 16 age- and sex-matched healthy controls (HC) subjects were enrolled in this study. Clinical profile was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS), Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and Global Assessment of Functioning (GAF) scale. Serum interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, IFN-γ, and IL-17 were measured by flow cytometry using the Th1/Th2/Th17 cytometric bead array. RESULTS: Compared with the healthy control group, patients in UHR showed increased IL-6 levels (Z=-2.370, p=0.018) and decreased IL-17 levels in serum (Z=-1.959, p=0.050). Levels of IL-17 positively correlated to the values in GAF symptoms (rho=0.632, p=0.028). CONCLUSION: Our results suggest that immunological imbalances could be present in the early stages of psychosis, including in at-risk stages. Future studies should replicate and expand these results.

Evaluation of polysaccharide-based chiral stationary phases in quality control of (S)-mirtazapine.

High-performance liquid chromatographic methods were developed for separation of the enantiomers of mirtazapine and its four process-related substances. The direct separations were achieved on chiral stationary phases containing amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H), cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and cellulose tris(4-methylbenzoate) (Chiralcel OJ-H ). The experimental data were utilized to discuss the effects of the mobile phase composition, the nature of the alcoholic modifier and the specific structural features of the analytes on retention and separation. The elution sequence was determined under the optimized separation conditions.

Molecularly imprinted polymer for selective extraction of 3-methylflavone-8-carboxylic acid from human urine followed by its determination using zwitterionic hydrophilic interaction liquid chromatography.

A novel water-compatible molecularly imprinted SPE combined with zwitterionic hydrophilic interaction liquid chromatography method for selective extraction and determination of 3-methylflavone-8-carboxylic acid (MFA), the main active metabolite of flavoxate in human urine, was developed and validated. The effects of progenic solvents, pH, cross linker and amount of monomer were studied to optimize the efficiency and selectivity. The molecularly imprinted polymer showed good specific adsorption capacity with an optimum of 200 µmol/g at pH 7.5 and selective extraction of MFA from human urine. The recovery of MFA from human urine was >98%. The lower limit of quantification was 1.20 µg/mL. The proposed method overcomes the matrix effects of endogenous substances generally encountered during direct analysis of urine sample.

Development of a validated liquid chromatographic method for determination of related substances of telmisartan in bulk drugs and formulations.

A simple and rapid reversed phase liquid chromatographic method for separation and determination of the related substances of telmisartan (TLM) was developed and validated. The chromatographic separation was achieved on Lichrospher RP-18 column (250 × 4.6 mm, 5 µm), using 20 mM ammonium acetate containing 0.1% (v/v) triethylamine (pH adjusted to 3.0 with trifluoroacetic acid) and acetonitrile as mobile phase at 25°C. The detection was performed at 254 nm. The method was validated and found to be robust, precise, specific and linear between 0.37 and 500 µg/mL. The limits of detection and quantification of telmisartan were 0.11 and 0.37 µg/mL, respectively. The method was successfully applied to quantify related substances and assay of TLM in bulk drugs and commercial tablets. The related substances relate to a novel synthetic route and different from those A-H impurities reported by European Pharmacopeia.

Development of a molecularly imprinted polymer for selective extraction followed by liquid chromatographic determination of sitagliptin in rat plasma and urine.

A novel water-compatible molecularly imprinted solid-phase extraction (MISPE) combined with zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) method for selective extraction and determination of sitagliptin in rat serum and urine was developed and validated. The effects of progenic solvents, pH, cross linker and amount of monomer were studied to optimize the efficiency and selectivity. The adsorption kinetics and isotherms were measured. The molecularly imprinted polymer (MIP) showed good specific adsorption capacity with an optimum of 180 mg/g at pH 7.5 and selective extraction of sitagliptin from rat plasma and urine. The recovery of sitagliptin from rat urine and plasma was >98%. The limits of detection (LOD) and quantification (LOQ) were 0.03 and 0.10 µg/L respectively. The proposed method overcomes the matrix effects of phospholipids generally encountered while preparation of plasma samples by precipitation of proteins.

Rapid determination of rifaximin on dried blood spots by LC-ESI-MS.

The use of blood spot collection cards is a simple way to obtain specimens for therapeutic drug monitoring, assessing adherence to medications and preventing toxicity in a clinical setting. A high-throughput liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) method for determination of rifaximin on dried blood spots (DBS) was developed and validated. It involves solvent extraction of a punch of DBS followed by reversed-phase LC on a monolithic column consisting of a silica rod with bimodal pore structure and detection by ESI-MS. Rifampicin was used as an internal standard (IS). The run time was within 5.0 min with a very low back-pressure at a flow rate of 0.5 mL/min. The assay was linear from 0.1 to 10 ng/mL. The mean recovery was 98.42%. The developed method is very simple, rapid and useful for clinical applications.

Precolumn derivatization followed by liquid chromatographic separation and determination of tramiprosate in rat plasma by fluorescence detector: application to pharmacokinetics.

Alzheimer disease (AD) is characterized pathologically by extracellular amyloid deposits composed of amyloid ß (Aß) protein. A simple and rapid method using HPLC with fluorescence detector was developed and validated for determination of tramiprosate in rat plasma. Pre-column derivatization of the deproteinized rat plasma was carried out using o-phthaldialdehyde (OPA) as a fluorescent reagent in presence of 3-mercaptopropionic acid. The liquid chromatographic separation was achieved on a Kromasil C18 column using methanol:acetonitrile: 20 mM phosphate buffer pH 7.5 (8.0:17.5:74.5 v/v/v) as a mobile phase in an isocratic elution mode. The eluents were monitored by a fluorescence detector set at 330 and 450 nm of excitation and emission wavelength respectively. Vigabatrin was used as an internal standard. The method was linear within the range 30.0-1000.0 ng/mL. Design of experiments (DOE) was used to evaluate the robustness of the method. The developed method was applied to study the pharmacokinetics of tramiprosate in rats.

High-performance liquid chromatographic determination of anti- hypertensive drugs on dried blood spots using a fluorescence detector--method development and validation.

A selective and sensitive high-performance liquid chromatography method with fluorescence detection for simultaneous determination of irbesartan, losartan and valsartan on dried blood spots (DBS) has been developed and validated. It involves solvent extraction of a punch of DBS followed by reversed-phase liquid chromatography on a Lichrospher(®) 100 RP-18e column. Fluorescence detection was performed at 259 and 385 nm as excitation and emission wavelengths, respectively. The detection limits of irbesartan, losartan and valsartan were 1.8, 3.6 and 1.8 ng/mL respectively. The mean recoveries of irbesartan, losartan and valsartan were 98.68, 98.42 and 97.81%, respectively. The mean inter-day and intra-day precisions of irbesartan, losartan and valsartan were 2.07 and 1.34%, 1.42 and 1.48%, and 3.20 and 2.15% respectively. The proposed method was simple and rapid. Design of experiments was used to evaluate the robustness of the method.

Reversed-phase liquid chromatographic determination of tramiprosate in rat plasma using evaporative light scattering detector.

A simple and reliable method was developed for determining blood concentrations of tramiprosate using reversed-phase HPLC with evaporative light scattering detection. The optimum evaporator and nebulizer temperatures for ELSD were set at 90 and 60°C respectively. The method was linear for a concentration range of 10-1000 µg/mL when 0.3 mL blood was used. The intra-assay precision ranged from 1.84 to 5.24%, and the coefficient of variation (CV) for a quality control sample at 10 µg/mL was 5.24% with a bias of -9.50% from the target value. The inter-assay precision ranged from 2.58 to 5.96%, and the CV for a quality control sample at 10 µg/mL was 5.96% with a bias of -7.50% from the target value. The method described here is suitable for management of tramiprosate in Alzheimer disease therapy.

Development of a validated high-throughput LC-ESI-MS method for determination of sirolimus on dried blood spots.

A high-throughput liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) method for screening of sirolimus on dried blood spots (DBS) was developed and validated. It involves solvent extraction of a punch of DBS followed by reversed-phase LC on a relatively new monolithic column consisting of a silica rod with bimodal pore structure and detection by ESI-MS. The run time was less than 3 min with a very low backpressure at a flow rate of 0.5 mL/min. The method can analyze more than 100 samples in an 8 h working day, including sample preparation. The assay was linear from 1 to 100 ng/mL. The mean recovery was 92.42%. The mean inter-day and intra-day precisions were 1.23 and 1.41%, respectively. The developed method is simple, rapid and useful for clinical applications.