Comparative Evaluation of Serum Copeptin in Obesity with Non Alcoholic Fatty Liver Disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a major cause of liver disease in India. NAFLD is regarded as the metabolic syndrome's hepatic component. AVP has a significant impact on glucose and lipid metabolism by stimulating hepatic glycogenolysis, gluconeogenesis, and fat production by modulating insulin and glucagon release from the pancreatic Langerhans' islets. AVP has a relatively short half-life of about 20 minutes, and more than 90% of AVP in circulation is bound to platelets. As a result, AVP is ineffective as a biomarker in clinical practice. Copeptin is a cleavage product of the AVP precursor, pre pro-vasopressin, which is secreted by the posterior pituitary gland in response to hypotension and hyperosmolality. We aimed to compare the serum copeptin level in obese with NAFLD patients with obese without NAFLD patients. MATERIALS: We collected data from 80 obese patients which were divided into two groups based on the presence and absence of NAFLD. Serum copeptin levels were measured by a Human Copeptin ELISA kit (Shanghai Coon Koon). The level of serum Copeptin was compared between two groups and also in three different grades of NAFLD. RESULT: Out of 80 subjects in our study, the mean value of serum copeptin in the group of obese with NAFLD was 24.96 pmol/L and in the group of obese without NAFLD was 15.38 pmol/L. The median (IQR) of serum copeptin in obese with NAFLD group was 24.5 pmol/L and in obese without NAFLD group was 12.25 pmol/L. The highest median S. Copeptin in pmol/L was seen in the obese with NAFLD group with a significant difference between 2 groups (W = 1388.500, p = ≤ 0.001). Strength of Association (Point-Biserial Correlation) = 0.44 (Large Effect Size). The mean value of serum copeptin was 20.00, 24.14, and 31.77 pmol/L in NAFLD grade 1, grade 2, and grade 3 respectively. The highest median S. Copeptin in pmol/L is seen in NAFLD Grade 3 group with a significant difference between 3 groups (χ2 = 23.446, p = ≤ 0.001). CONCLUSION: Serum copeptin can be used as an additional tool to predict the severity of the nonalcoholic fatty liver disease. Measurement of serum copeptin levels can be used as an additional, simple, non-invasive, easily accessible, and cost effective parameter to predict the severity of the nonalcoholic fatty liver disease.

Combined saposin deficiency: A rare occurrence.

Combined saposin deficiency (OMIM #611721), an exceedingly rare lysosomal storage disorder, is caused by a mutation in the gene PSAP. This gene encodes a protein, prosaposin, that cleaves into four constituent proteins, each of which has a role as a cofactor for the enzymes whose deficiency results in Krabbe disease, metachromatic leukodystrophy, Gaucher disease, and Farber disease, respectively. Intact prosaposin itself is essential for neuronal survival. The typical manifestation of combined saposin deficiency is of severe neurological features in the neonatal period, hepatosplenomegaly, thrombocytopenia, and early death. We report, to the best of our knowledge, the first Indian case with these clinical manifestations and confirmation by genetic and enzymatic testing.

Plants and their Bioactive Compounds as a Possible Treatment for Traumatic Brain Injury-Induced Multi-Organ Dysfunction Syndrome.

BACKGROUND & OBJECTIVE: Traumatic brain injury is an outcome of the physical or mechanical impact of external forces on the brain. Thus, the silent epidemic has complex pathophysiology affecting the brain along with extracranial or systemic complications in more than one organ system, including the heart, lungs, liver, kidney, gastrointestinal and endocrine system. which is referred to as Multi-Organ Dysfunction Syndrome. It is driven by three interconnected mechanisms such as systemic hyperinflammation, paroxysmal sympathetic hyperactivity, and immunosuppression-induced sepsis. These multifaceted pathologies accelerate the risk of mortality in clinical settings by interfering with the functions of distant organs through hypertension, cardiac arrhythmias, acute lung injury, neurogenic pulmonary edema, reduced gastrointestinal motility, Cushing ulcers, acute liver failure, acute kidney injury, coagulopathy, endocrine dysfunction, and many other impairments. The pharmaceutical treatment approach for this is highly specific in its mode of action and linked to a variety of side effects, including hallucinations, seizures, anaphylaxis, teeth, bone staining, etc. Therefore, alternative natural medicine treatments are widely accepted due to their broad complementary or synergistic effects on the physiological system with minor side effects. CONCLUSION: This review is a compilation of the possible mechanisms behind the occurrence of multiorgan dysfunction and reported medicinal plants with organoprotective activity that have not been yet explored against traumatic brain injury and thereby, highlighting the marked possibilities of their effectiveness in the management of multiorgan dysfunction. As a result, we attempted to respond to the hypothesis against the usage of medicinal plants to treat neurodegenerative diseases.

Doppler hemodynamic liver index and hepatic elastic modulus: Advanced ultrasonographic techniques for non-invasive prediction of esophageal varices in cirrhosis.

PURPOSE: Currently esophagoscopy is the gold standard for assessment of esophageal varices in cirrhosis. Predicting the presence of esophageal varices, varices needing treatment (VNT) and variceal grade by advanced ultrasonographic techniques using a combination of Doppler hemodynamic liver index (HDLI) (quantifying portal hypertension) and hepatic elastic modulus (quantifying hepatic fibrosis) would be a cost-effective and non-invasive alternative to routine endoscopy. METHODS: Our cross-sectional study consisted of cirrhotic patients diagnosed using clinical features and laboratory parameters. Portal venous Doppler and liver sonoelastography were performed in selected subjects for obtaining measurements of HDLI (portal vein diameter/mean velocity) and hepatic elastic modulus respectively. Within 3 days of ultrasound, the subjects underwent upper GI endoscopy for assessment of presence, VNT and grade (F1, F2, F3) of varices. Subjects were divided into two groups (without and with varices) and data analyzed using XLSTAT. RESULTS: A total of 60 subjects (26 without and 34 with varices) were evaluated. Mean Doppler HDLI of subjects with varices was significantly higher (0.72 vs. 0.59, p < 0.0001) with progressive increase in values with variceal grade, being highest in grade-F3 (mean 0.77). Likewise, mean hepatic elastic modulus was also higher in subjects with varices (28.9 vs. 12.6 kPa, p < 0.0001) and showed progressive increase with grade (51.1 kPa for F3). For predicting presence of varices, maximum accuracy of elastic modulus was at cut-off of 14.5 kPa (sensitivity, specificity 83% and 84.6%) and Doppler HDLI was at 0.66 (66% and 92.3%). Good inter-rater agreement was present (κ 0.66). CONCLUSION: Combination of Doppler HDLI and hepatic elastic modulus is an excellent non-invasive method for predicting the presence, VNT, and variceal grade and may obviate need for routine endoscopic screening in cirrhosis.

Use of steroids in COVID-19 patients: A meta-analysis.

BACKGROUND: Emerging reports have shown the benefits of steroids in hospitalized COVID-19 patients as life-saving drugs. However, the use of steroids in COVID-19 patients is confusing among many physicians. AIM: The aim of the current study was to find out the exact association of steroids in the deaths of COVID-19 patients. METHODS: The relevant studies were searched in PubMed, Google scholar, and Clinical trials registries till May 25, 2021 and sorted out based on inclusion and exclusion criteria. The quality of studies was assessed using a standard scale. The pooled odds ratio was calculated with a 95% confidence interval. The sensitivity and sub-group analyses were also done. The publication bias was assessed qualitatively. The Rev Man 5 was used for all analyses with a random-effect model. RESULTS: The quantitative analysis was done with 9922 patients (6265-male and 3657-females) from 21 relevant studies. The pooled estimate results i.e. 0.52 [0.34, 0.80] have shown a significant reduction in deaths of COVID-19 patients in the steroidal group as compared to the non-steroidal group. The sensitivity analyses did not alter our conclusions. In subgroup analysis, methylprednisolone has shown a significant reduction in deaths of COVID-19 patients as compared to the non-steroidal group, however, more clinical evidence is required for dexamethasone and hydrocortisone. CONCLUSION: The use of steroids in hospitalized COVID-19 patients is useful to reduce deaths.

Gamma irradiations induced morphological and biochemical variations in in vitro regenerated ginger (Zingiber officinale rosc.)- an invaluable medicinal spice.

PURPOSE: To evaluate the effect of gamma irradiations on morphological and biochemical variations of in vitro shoots, regenerated plants and rhizomes of ginger (Zingiber officinale Rosc.) var. Himgiri. MATERIALS AND METHODS: In vitro established shoot cultures were treated with different doses of gamma irradiations (10-100 Gy). Nonirradiated shoots were used as controls. Radio sensitivity of shoots and in vitro growth parameters were recorded. Surviving shoots along with controls were multiplied, rooted and hardened. Irradiation effect on chromosomes was evaluated by comparing with controls. Various morphological and biochemical observations were recorded in regenerated plants and rhizomes and compared to controls. RESULTS: Irradiated shoots showed decline in survival percentage (95% in 10 Gy to 12.33% in 100 Gy) with increase in dose rate after 4 weeks of irradiation. Shoot survival significantly decreased with irradiation dose rate above 20 Gy. Shoot multiplication rate showed an increase from 1:2 in 1st subculture to 1:9 after 5th subculture, in 10 Gy irradiated cultures with 4.5 cm average length of shoots and 8.19 number of leaves after 5th subculture. Average rooting showed an increase from 15.55% after 2nd subculture to 100% after 5th subculture, in 10 Gy irradiated shoots; however, no multiplication and rooting was observed in higher doses. In vitro rooted shoots were subjected to hardening with 100 percent survival in a mixture comprised of soil, cocopeat and FYM. One-year-old hardened plants when observed for morphological variations showed nonsignificant variations in comparison to controls. Rhizomes obtained from 10 Gy irradiated plants showed enhanced concentration of 6-gingerol and reduced crude fiber content when compared with controls. CONCLUSIONS: Gamma irradiation doses up to 10 Gy resulted in nonsignificant phenotypic variations but can positively affect biochemical composition of rhizomes leading to development of biochemically improved mutant lines of ginger with increased 6-gingerol and lowered crude fiber content. Therefore, suggesting the lower doses of gamma irradiations for improvement of biochemical constituents in vegetatively propagated plants.

Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions.

Arsenic is a key environmental toxicant having significant impacts on human health. Millions of people in developing countries such as Bangladesh, Mexico, Taiwan, and India are affected by arsenic contamination through groundwater. Environmental contamination of arsenic leads to leads to various types of cancers, coronary and neurological ailments in human. There are several sources of arsenic exposure such as drinking water, diet, wood preservatives, smoking, air and cosmetics, while, drinking water is the most explored route. Inorganic arsenic exhibits higher levels of toxicity compared its organic forms. Exposure to inorganic arsenic is known to cause major neurological effects such as cytotoxicity, chromosomal aberration, damage to cellular DNA and genotoxicity. On the other hand, long-term exposure to arsenic may cause neurobehavioral effects in the juvenile stage, which may have detrimental effects in the later stages of life. Thus, it is important to understand the toxicology and underlying molecular mechanism of arsenic which will help to mitigate its detrimental effects. The present review focuses on the epidemiology, and the toxic mechanisms responsible for arsenic induced neurobehavioral diseases, including strategies for its management from water, community and household premises. The review also provides a critical analysis of epigenetic and transgenerational modifications, mitochondrial oxidative stress, molecular mechanisms of arsenic-induced oxidative stress, and neuronal dysfunction.

Reciprocal relation between reporter gene transcription and translation efficiency in fission yeast.

The fission yeast, Schizosaccharomyces pombe, is an excellent model for basic research but is not useful for commercial scale protein expression due to lack of strong expression vectors. Earlier, we showed that the lsd90 promoter elicited significantly greater GFP expression level than the adh1 and nmt1 promoters, albeit in different vector backbones. Here, we have systematically investigated the contribution of selectable markers, LEU2 and URA3m to GFP expression: while LEU2 elicited very low expression, the URA3m gene, with truncated promoter, elicited much greater GFP expression level with all promoters. Paradoxically, an inverse correlation was observed between the GFP transcription and translation efficiency. This system can be useful for understanding the factors governing recombinant gene expression and optimization of protein production.

Phytohormone Priming of Tomato Plants Evoke Differential Behavior in Rhizoctonia solani During Infection, With Salicylate Priming Imparting Greater Tolerance Than Jasmonate.

In the field of phytohormone defense, the general perception is that salicylate (SA)-mediated defense is induced against biotrophic pathogens while jasmonate (JA)-mediated defense functions against necrotrophic pathogens. Our goals were to observe the behavior of the necrotrophic pathogen Rhizoctonia solani in the vicinity, on the surface, and within the host tissue after priming the host with SA or JA, and to see if priming with these phytohormones would affect the host defense differently upon infection. It was observed for the first time, that R. solani could not only distinguish between JA versus SA-primed tomato plants from a distance, but surprisingly avoided SA-primed plants more than JA-primed plants. To corroborate these findings, early infection events were monitored and compared through microscopy, Scanning Electron Microscopy, and Confocal Laser Scanning Microscopy using transformed R. solani expressing green fluorescence protein gene (gfp). Different histochemical and physiological parameters were compared between the unprimed control, JA-primed, and SA-primed plants after infection. The expression of a total of fifteen genes, including the appressoria-related gene of the pathogen and twelve marker genes functioning in the SA and JA signaling pathways, were monitored over a time course during early infection stages. R. solani being traditionally designated as a necrotroph, the major unexpected observations were that Salicylate priming offered better tolerance than Jasmonate priming and that it was mediated through the activation of SA-mediated defense during the initial phase of infection, followed by JA-mediated defense in the later phase. Hence, the present scenario of biphasic SA-JA defense cascades during R. solani infection, with SA priming imparting maximum tolerance, indicate a possible hemibiotrophic pathosystem that needs to be investigated further.

Commercial application of cellulose nano-composites - A review.

Cellulose is the biosynthetic product from plants, animals and bacteria. Cellulose is the most abundant polymer having long linear chain like structure composed of (1,4) linked ß-D glucopyranosyl units assembled into hierarchical structures of microfibrils with excellent strength and stiffness. And 'nanocellulose' refers to the cellulosic materials with defined nano-scale structural dimensions. They may be cellulose nanocrystal (CNC or NCC), cellulose nanofibers (CNF) or bacterial nanocellulose. Nanocellulose is non-toxic, biodegradable and biocompatible with no adverse effects on health and environment. Due to its low thermal expansion coefficient, high aspect ratio, better tensile strength, good mechanical and optical properties, they find many applications in thermo-reversible and tenable hydrogels, paper making, coating additives, food packaging, flexible screens, optically transparent films and light weight materials for ballistic protection, automobile windows. It also find potential in biopharmaceutical applications such as in drug delivery and for fabricating temporary implants with PHB like sutures, stents etc.

Oxidative Stress: Major Threat in Traumatic Brain Injury.

BACKGROUND & OBJECTIVE: Traumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity worldwide. It represents mild, moderate and severe effects of physical assault to brain which may cause sequential, primary or secondary ramifications. Primary injury can be due to the first physical hit, blow or jolt to one of the brain compartments. The primary injury is then followed by secondary injury which leads to biochemical, cellular, and physiological changes like blood brain barrier disruption, inflammation, excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of oxidative stress. Apart from this, there is also an immediate increase in glutamate at the synapses following severe TBI. Excessive glutamate at synapses in turn activates corresponding NMDA and AMPA receptors that facilitate excessive calcium influx into the neuronal cells. This leads to the generation of oxidative stress which further leads to mitochondrial dysfunction, lipid peroxidation and oxidation of proteins and DNA. As a consequence, neuronal cell death takes place and ultimately people start facing some serious disabilies. CONCLUSION: In the present review we provide extensive overview of the role of reactive oxygen species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.

An amperometric H2O2 biosensor based on hemoglobin nanoparticles immobilized on to a gold electrode.

The nanoparticles (NPs) of hemoglobin (Hb) were prepared by desolvation method and characterized by transmission electron microscopy (TEM), UV spectroscopy and Fourier-transform IR (FTIR) spectroscopy. An amperometric H2O2 biosensor was constructed by immobilizing HbNPs covalently on to a polycrystalline Au electrode (AuE). HbNPs/AuE were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectra (EIS) before and after immobilization of HbNPs. The HbNPs/AuE showed optimum response within 2.5 s at pH 6.5 in 0.1 M sodium phosphate buffer (PB) containing 100 µM H2O2 at 30°C, when operated at -0.2 V against Ag/AgCl. The HbNPs/AuE exhibited Vmax of 5.161 ± 0.1 µA cm-2 with apparent Michaelis-Menten constant (Km) of 0.1 ± 0.01 mM. The biosensor showed lower detection limit (1.0 µM), high sensitivity (129 ± 0.25 µA cm-2 mM-1) and wider linear range (1.0-1200 µM) for H2O2 as compared with earlier biosensors. The analytical recoveries of added H2O2 in serum (0.5 and 1.0 µM) were 97.77 and 98.01% respectively, within and between batch coefficients of variation (CV) were 3.16 and 3.36% respectively. There was a good correlation between sera H2O2 values obtained by standard enzymic colorimetric method and the present biosensor (correlation coefficient, R2 =0.99). The biosensor measured H2O2 level in sera of apparently healthy subjects and persons suffering from diabetes type II. The HbNPs/AuE lost 10% of its initial activity after 90 days of regular use, when stored dry at 4°C.

Autonomic status and pain profile in patients of chronic low back pain and following electro acupuncture therapy: a randomized control trial.

Pain is a syndrome characterized by several neurophysiological changes including that of the autonomic nervous system. Chronic low back pain (LBP) is a major health problem and is a frequent reason for using unconventional therapies especially acupuncture. This study was conducted to evaluate the autonomic status and pain profile in chronic LBP patients and to observe the effect of electro acupuncture therapy. Chronic LBP patients (n=60) were recruited from the Department of Orthopaedics, GTB Hospital, Delhi. Age and sex matched healthy volunteers were selected as controls (n=30). Following a written consent, LBP patients were randomly allocated into two study groups - Group A received 10 sittings of electro acupuncture, on alternate days, at GB and UB points selected for back pain, while the Group B received a conventional drug therapy in the form of oral Valdecoxib together with supervised physiotherapy. Controls were assessed once while the patients were assessed twice, before and after completion of the treatment program (3 weeks). The autonomic status was studied with non-invasive cardiovascular autonomic function tests which included E: I ratio, 30:15 ratio, postural challenge test and sustained handgrip test. Pain intensity was measured with the visual analogue scale (VAS) and the global perceived effect (GPE). Statistical analysis was performed using repeated measure's ANOVA with Tukey's test. Pain patients showed a significantly reduced vagal tone and increased sympathetic activity as compared to the controls (P<0.05 to P<0.001 in different variables). Following treatment, both the study groups showed a reduction in vagal tone together with a decrease in the sympathetic activity. There was also a considerable relief of pain in both groups, however, the acupuncture group showed a better response (P<0.01). We conclude that there is autonomic dysfunction in chronic LBP patients. Acupuncture effectively relieves the pain and improves the autonomic status and hence can be used as an alternative/additive treatment modality in these cases.

Load of heavy metals in the airborne dust particulates of an urban city of central India.

The geographical and temporal distribution patterns of airborne dust particulates have been studied in different representative areas of Raipur City. Dust fall samples from different sites were collected and some selected toxic metals namely Cr, Mn, Fe, Ni, Cu, Zn, Sb and Pb in them were determined by AAS. Total annual flux of 11.7, 541.4, 2751.0, 14.2, 9.8, 90.9, 17.6, and 17.7 kg km(-2) y(-1) were measured for Cr, Mn, Fe, Ni, Cu, Zn, Sb, and Pb respectively. The occurrence of metal concentration were generally in the order industrial > heavy traffic > commercial > residential area in Raipur city. The results of analysis show the existence of toxic metal concentration in the order Fe > Mn > Zn > Pb approximately Sb > Ni > Cr > Cu in Raipur city. These large levels of metal pollutants have also been correlated with some meteorological parameters like temperature, relative humidity and wind velocity, and strong positive correlations have been observed.

In vitro regeneration of Acacia catechu Willd. from callus and mature nodal explants--an improved method.

Callus was derived from cultured cotyledons on MS medium supplemented with 2,4-D (0.25 mg/l) and NAA (0.25 mg/l). Plantlets were regenerated from the callus and nodal explants on MS medium containing BAP (2.0 mg/l) and Kn (2.0 mg/l), and further multiplied on the same medium. Addition of adenine sulphate (25.0 mg/l), ascorbic acid (20.0 mg/l) and glutamine (150.0 mg/l) in the medium resulted in enhanced axillary branching. Multiple shoots formed after 6 weeks were separated and subcultured in the fresh medium of same composition. For rhizogenesis, microshoots of 2.0-2.5 cm length were dipped in sterilized IAA solution (10 mg/l) for 24 hr followed by transfer to half strength MS medium containing activated charcoal (0.02%) resulting in rooting (75%) within 8 weeks. The rooted plants were transferred to pots containing sterilized soil and sand mixture for hardening and 71% survival was recorded. Fifty true to type plantlets of A. catechu could be obtained within seven months of culture establishment.