Search

ABSTRACT Context Meditation and related relaxation techniques are good means of alleviating stress and maintaining good health. Osho dynamic meditation decreases several psychopathological variables such as anxious‐depressive syndrome, aggressive behaviors, and depression which is practiced in Nepal and all over the world. Various studies have shown alteration in different hormone levels due to meditation by strengthening adaptive mechanisms. Aim The aim of this study was to evaluate the effect of Osho meditation on serum hormonal levels in pre‐ and postmeditation participants. Methods A pre–post study was conducted among 70 healthy volunteers (42 male and 28 female) where various types of Osho dynamic meditation techniques were incorporated together to understand their combined effects on serum hormone levels in participants attending the 7 days meditation camp. Serum hormones such as cortisol, estrogen, progesterone, free triiodothyronine (fT3), free thyroxine (fT4), thyroid‐stimulating hormone (TSH), testosterone, and growth hormone were measured by chemiluminescence immunoassay. Results Out of 70 participants, 68 participants (97%) had subjective opinion of Osho dynamic meditation being effective in alleviating stress, depression, and anger. Also, there was a significant decline in body weight and body mass index in both male and female populations after a strict vegetarian diet and meditation. Likewise, a significant rise in the level of estrogen (p < 0.001), progesterone (p < 0.001), growth hormone (p < 0.001), testosterone (p = 0.002), and fT3 (p = 0.049) in postmeditation male participants indicates the importance of Osho dynamic meditation on elevating sex hormones such as estrogen, progesterone, testosterone as well as fT3, and growth hormones among Osho meditation practicing participants. Conclusion Our findings suggest significant changes in the hormonal levels and improvement in stress and depression in participants undergoing Osho meditation.

ABSTRACT Acute encephalitis syndrome (AES) causes significant morbidity and mortality worldwide. In Nepal, Japanese encephalitis virus (JEV) accounts for ~5-20% of AES cases, but ~75% of AES cases are of unknown etiology. We identified a gemykibivirus in CSF collected in 2020 from an 8-year-old male patient with AES using metagenomic next-generation sequencing. Gemykibiviruses are single stranded, circular DNA viruses in the family Genomoviridae. The complete genome of 2,211 nucleotides was sequenced, which shared 98.69% nucleotide identity to its closest relative, Human associated gemykibivirus 2 isolate SAfia-449D. Two real-time PCR assays were designed, and screening of 337 cerebrospinal fluid (CSF) and 164 serum samples from AES patients in Nepal collected in 2020 and 2022 yielded 11 CSF and 1 serum sample that were positive in both PCR assays. Complete genomes of seven of the positives were sequenced. These results identify a potential candidate etiologic agent of encephalitis in Nepal.IMPORTANCEViral encephalitis is a devastating disease, but unfortunately, worldwide, the causative virus in many cases is unknown. Therefore, it is important to identify viruses that could be responsible for cases of human encephalitis. Here, using metagenomic sequencing of CSF, we identified a gemykibivirus in a male child from Nepal with acute encephalitis syndrome (AES). We subsequently detected gemykibivirus DNA in CSF or serum of 12 more encephalitis patients by real-time PCR. The virus genomes we identified are highly similar to gemykibiviruses previously detected in CSF of three encephalitis patients from Sri Lanka. These results raise the possibility that gemykibivirus could be an underrecognized human pathogen.

Abstract Background Thyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles. Methods This hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman’s correlation was done to determine the association between variables. Results Out of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal. Conclusion The rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal.

Introduction: Polycystic ovary syndrome is a common hormonal disorder that affects women of reproductive age which is characterized by hyperandrogenism, polycystic ovarian morphology, ovarian dysfunction, and hyperinsulinemia. Increased prevalence of cardiovascular disease and higher cardiovascular morbidity is seen in women with polycystic ovary syndrome. This study aimed to estimate the prevalence of high serum homocysteine levels among women with polycystic ovarian syndrome visiting an infertility clinic of a tertiary care centre. Methods: This was a descriptive cross-sectional study conducted among women with polycystic ovarian syndrome visiting an infertility clinic at the Department of Obstetrics and Gynaecology of a tertiary care centre from 1 June 2023 to 1 September 2023. The study was conducted after obtaining ethical approval from the Institutional Review Committee. Biochemical analysis of gonadal hormones, serum homocysteine and lipid profile was done. A convenience sampling method was used. The point estimate was calculated at a 95% confidence interval. Results: Among 76 women, the prevalence of high serum homocysteine level was found in 54 (71.05%) (60.86-81.25, 95% Confidence Interval). The mean age of patients was 27.46±6.18 years. Conclusions: The prevalence of high homocysteine levels among women with polycystic ovarian syndrome is higher than other studies done in similar settings.

Conclusion: Our study depicted there is a marked alteration in biochemical and hematological parameters specifically thrombocytopenia, leukopenia, increased transaminase levels, and high prothrombin time seen in dengue positive cases.

Introduction: Polycystic ovarian syndrome is the most common endocrine-metabolic disorder, affecting women of reproductive age groups, which shares various symptoms with thyroid dysfunctions. Despite it predisposition of aforesaid cohorts to autoimmunity, these etiologies have not adequately been studied in them. This study aimed to find out the prevalence of positive thyroid peroxidase antibodies among women with polycystic ovarian syndrome visiting an infertility clinic at a tertiary care centre. Methods: This was a cross-sectional study conducted at a tertiary care centre among patients visiting the infertility clinic at the Department of Obstetrics and Gynaecology from 21 September 2022 to 21 February 2023. Biochemical analysis of thyroid hormones, gonadal hormones, anti-mullerian hormone and thyroid peroxidase antibody were done in Abbott ARCHITECT ci4100 and SNIBE Maglumi 800 autoanalyzer. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 70 participants, thyroid peroxidase antibody was positive in 16 (22.86%) (13.02-32.69, 95% Confidence Interval). The mean age of the patients was 28.25±5.26 years. In the individuals with thyroid-stimulating hormone below 2.5 mIU/l, 5 (31.25%) had positive thyroid peroxidase antibody titre. Conclusions: The prevalence of positive thyroid peroxidase antibodies among women with polycystic ovarian syndrome is similar to other studies done in similar settings. Regular monitoring of thyroid peroxidase antibodies is recommended in these women to guide conception in order to evade inevitable adverse pregnancy outcomes.

Abstract Background Prompt diagnosis of metabolic disorders in a resource-limited country like Nepal is daunting. Acute intermittent porphyria is a rare but common hepatic porphyria mostly seen in females of the reproductive age group. As its incidence is quite uncommon, conjectures about porphyria diagnosis are often duped into a diagnostic conundrum. Case presentation Here we unravel a case of a 15-year-old Hindu Nepalese girl distraught by the myriad of symptoms in the setting of severe abdominal pain accompanied by constipation and limb pain as the chief complaints. She presented with acute severe hypertension with marked persistent hyponatremia (up to 109 mEq/L). Despite conservative management of hypertension and electrolytes, unresolved electrolyte imbalance led us to the speculation of disturbance in the renin–angiotensin–aldosterone system. Due to her exacerbating neurovisceral status, she also required intensive care during the disease course. After thorough investigations and exemption of presumed provisional diagnoses, based on sustained symptomatic presentation, the clinical suspicion was driven towards a diagnosis of porphyria-related disorders. Positive Watson-Schwartz test substantiated the diagnosis of acute intermittent porphyria. Her symptoms gradually abated after the consumption of high carbohydrate diets. Conclusion This case highlights the baffling amalgamation of symptoms that simulate common diseases of concern yet are buried in the realm of porphyric disorders. Porphyria can be diagnosed using simple screening tools and timely treatment can diminish serious consequences.

Objectives: This study intends to determine the association of parathormone with vitamin D and other biochemical parameters (calcium and phosphate) and evaluate the relationship between low vitamin D and parathormone levels. Methods: A hospital-based cross-sectional study was conducted among 310 study participants over the period of 1 year. Patients who underwent laboratory investigations for vitamin D, parathormone, calcium, and phosphate in the Clinical Biochemistry Laboratory at the Institute of Medicine, Tribhuvan University Teaching Hospital were included. Serum intact parathyroid hormone, vitamin D, calcium, and phosphate were measured in Abbott Architect (ci4100) integrated system autoanalyzer. Results: Among the 310 study participants, 177 (57%) were males and 43% were females. The mean age of the patient was 47.09 ± 19.01 years. High intact parathyroid hormone (>68 pg/ml) was observed in 73% of the patients. Low vitamin D (

Background: Dengue virus infection is a major source of morbidity and mortality in the majority of tropical and subtropical nations. In Nepal, the first case of dengue was reported in 2004, followed by numerous outbreaks exerting a critical impact on public health. This study aims to describe the clinical and laboratory characteristics of dengue patients visiting a tertiary care hospital to see the trend of presentation. Method: Hospital based cross‐sectional study was conducted among diagnosed cases of dengue from April 2023 to September 2023. A total of 692 patients undergoing testing by commercially available dengue rapid diagnostic tests were recruited and categorized dengue positive (if NS1 and/or IgM positive) and dengue negative (NS1, IgM, and IgG all negative or only IgG positive). The dengue‐positive cases were further subdivided into three groups (only NS1 positive, only IgM positive, both NS1 and IgM positive). Additionally, biochemical and hematological analyses were performed, and results were compared between positive and negative cases by using Mann–Whitney U test while subgroups of dengue‐positive cases were compared using Kruskal–Wallis H test. Results: Most common symptoms were fever (94.5%) followed by headache (79.8%) and myalgia (74.7%). Among 346 dengue‐positive subjects, 53.2% (n = 184) were NS1‐only positive, 21.7% (n = 75) were IgM‐only positive, and 25.1% (n = 87) were both NS1+IgM positive. Thrombocytopenia (n = 179, 51.7%), leucopenia (n = 99, 28.6%), increased SGPT (n = 182, 52.6%), increased SGOT (n = 188, 54.3%) were seen among dengue positive patients. Leukopenia was more severe in patients with only NS1 positive cases (p = 0.008) whereas thrombocytopenia (p ≤ 0.001) was more severe in patients with both IgM and NS1 positive cases. Conclusion: Our study depicted there is a marked alteration in biochemical and hematological parameters specifically thrombocytopenia, leukopenia, increased transaminase levels, and high prothrombin time seen in dengue positive cases. [ABSTRACT FROM AUTHOR]

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52–0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) for at least 3 h. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and produced dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and with significantly reduced signs of naloxone-precipitated withdrawal, which suggested reduced physical dependence compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

Introduction: Major cases of poisoning are associated with organophosphates. Cholinergic effects and an intermediate phase seen with organophosphate poisoning may implicate myopathy. Creatine kinase is a marker of muscle tissue damage. This study aimed to find out the mean serum creatine kinase among organophosphate poisoning cases in a tertiary care centre. Methods: A descriptive cross-sectional study was carried out among organophosphate poisoning cases in a tertiary care hospital from 13 October 2017 to 30 March 2018. Ethical approval was taken from the Institutional Review Committee [Reference number: 117(6-11-E) 2/074/075]. Blood samples were assayed for serum acetylcholinesterase in the pharmacology laboratory and for serum creatine kinase and lactate dehydrogenase in the biochemistry laboratory. Low serum acetylcholinesterase was taken as the basis for the establishment of organophosphate poisoning. A convenience sampling technique was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 103 organophosphate poisoning cases, the mean serum creatine kinase was 931.35±446.60 IU/l (845.10-1017.60, 95% Confidence Interval). Conclusions: The mean serum creatine kinase level among organophosphate poisoning cases was higher than in other studies done in similar settings.

The world’s health in 2020 was in the grip of the COVID-19 pandemic and its adverse consequences and is still continuing in 2021. Most countries have been locked down or going through different forms of lockdown to prevent the transmission of the infectious virus SARS-CoV-2. To date, there is no specific treatment or vaccination preventive measures. World Health Organization has approved few vaccines for emergency use. Still, the emergence of mutations within SARS-CoV has put forward challenges for vaccine developers. Whether infectious or non-infectious, all diseases have an inflammatory aspect to alarm the body system along with an anti-inflammatory counterbalance mechanism to minimize harmful effects whether through immune modulation or antioxidant reserves. An approach to counteract the novel disease, COVID19, was also sought in enhancing the anti-inflammatory aspect, at the level of prevention and at the level of treatment. One of the methodologies was the recommendation of micronutrient Vitamin D whose immune-modulatory role has been well appreciated in many disease conditions. This short review aims to explore the relationship between vitamin D status through susceptibility and clinical outcomes of COVID-19.

The macrocyclic tetrapeptide CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) and its D-Trp isomer exhibit kappa opioid receptor (KOR) antagonism which prevents stress-induced reinstatement of extinguished cocaine-conditioned place preference. Here, we evaluated the effects of substitution of Trp and D-Trp on the peptides’ opioid activity, antinociceptive tolerance, and the ability to prevent relapse to extinguished drug-CPP. Six analogs were synthesized using a combination of solid-phase peptide synthesis and cyclization in solution. The analogs were evaluated in vitro for opioid receptor affinity in radioligand competition binding assays, efficacy in the [35S]GTPγS assay, metabolic stability in mouse liver microsomes, and for opioid activity and selectivity in vivo in the mouse 55 °C warm-water tail-withdrawal assay. Potential liabilities of locomotor impairment, respiratory depression, acute tolerance, and conditioned place preference (CPP) were also assessed in vivo, and the ameliorating effect of analogs on the reinstatement of extinguished cocaine-place preference was assessed. Substitutions of other D-amino acids for D-Trp did not affect (or in one case increased) KOR affinity, while two of the three substitutions of an L-amino acid for Trp decreased KOR affinity. In contrast, all but one substitution increased mu opioid receptor (MOR) affinity in vitro. The metabolic stabilities of the analogs were similar to those of their respective parent peptides, with analogs containing a D-amino acid being much more rapidly metabolized than those containing an L-amino acid in this position. In vivo, CJ-15,208 analogs demonstrated antinociception, although potencies varied over an 80-fold range and the mediating opioid receptors differed by substitution. KOR antagonism was lost for all but the D-benzothienylalanine analog, and the 2′-naphthylalanine analog instead demonstrated significant delta opioid receptor (DOR) antagonism. Introduction of DOR antagonism coincided with reduced acute opioid antinociceptive tolerance and prevented stress-induced reinstatement of extinguished cocaine-CPP.

New strategies facilitate the design of cyclic peptides which can penetrate the brain. We have designed a bicyclic peptide, OL-CTOP, composed of the sequences of a selective μ-opioid receptor antagonist, CTOP (f-cyclo(CYwOTX)T) (X = penicillamine, Pen; O = ornithine) and odorranalectin, OL (YASPK-cyclo(CFRYPNGVLAC)T), optimized its solid-phase synthesis and demonstrated its ability for nose-to-brain delivery and in vivo activity. The differences in reactivity of Cys and Pen thiol groups protected with trityl and/or acetamidomethyl protecting groups toward I2 in different solvents were exploited for selective disulfide bond formation on the solid phase. Both the single step and the sequential strategy applied to macrocyclization reactions generated the desired OL-CTOP, with the sequential strategy yielding a large quantity and better purity of crude OL-CTOP. Importantly, intranasally (i.n.s.) administered OL-CTOP dose-dependently antagonized the analgesic effect of morphine administered to mice through the intracerebroventricular route and prevented morphine-induced respiratory depression. In summary, the results demonstrate the feasibility of our solid-phase synthetic strategy for the preparation of the OL-CTOP bicyclic peptide containing two disulfide bonds and reveal the potential of odorranalectin for further modifications and the targeted delivery to the brain.

Context: Meditation and related relaxation techniques are good means of alleviating stress and maintaining good health. Osho dynamic meditation decreases several psychopathological variables such as anxious‐depressive syndrome, aggressive behaviors, and depression which is practiced in Nepal and all over the world. Various studies have shown alteration in different hormone levels due to meditation by strengthening adaptive mechanisms. Aim: The aim of this study was to evaluate the effect of Osho meditation on serum hormonal levels in pre‐ and postmeditation participants. Methods: A pre–post study was conducted among 70 healthy volunteers (42 male and 28 female) where various types of Osho dynamic meditation techniques were incorporated together to understand their combined effects on serum hormone levels in participants attending the 7 days meditation camp. Serum hormones such as cortisol, estrogen, progesterone, free triiodothyronine (fT3), free thyroxine (fT4), thyroid‐stimulating hormone (TSH), testosterone, and growth hormone were measured by chemiluminescence immunoassay. Results: Out of 70 participants, 68 participants (97%) had subjective opinion of Osho dynamic meditation being effective in alleviating stress, depression, and anger. Also, there was a significant decline in body weight and body mass index in both male and female populations after a strict vegetarian diet and meditation. Likewise, a significant rise in the level of estrogen (p < 0.001), progesterone (p < 0.001), growth hormone (p < 0.001), testosterone (p = 0.002), and fT3 (p = 0.049) in postmeditation male participants indicates the importance of Osho dynamic meditation on elevating sex hormones such as estrogen, progesterone, testosterone as well as fT3, and growth hormones among Osho meditation practicing participants. Conclusion: Our findings suggest significant changes in the hormonal levels and improvement in stress and depression in participants undergoing Osho meditation. [ABSTRACT FROM AUTHOR]

Introduction: Local anesthetic used for dental extraction is 2% lidocaine hydrochloride with adrenaline (1:200000). Lidocaine is cardiac depressant and adrenaline is cardiac stimulant; it decreases or increases blood pressure respectively. Methods: A total of 100 patients (50 controlled hypertensive and 50 non-hypertensive) were selected. The study was conducted over a period of 14 months from January 2020 to February 2021. Blood pressure was measured for patients who were planned for dental extraction by auscultatory method. Following that, 1.5-3 ml (depending upon the nerve block) 2% lidocaine with adrenaline (1:200000) was injected using a 3ml syringe (26 Gauge). Blood pressure was re-recorded after 10 minutes from the time of injection. Visual analog scale pain score was obtained during administration of local anesthesia. Paired t-test was applied to compare blood pressure change before and after administration of local anesthesia in controlled hypertensive and non-hypertensive patients. Results: There was a statistically significant increase in both systolic and diastolic blood pressure in non-hypertensive patients (p = 0.008, p = 0.017). This, however, was not the case with controlled hypertensive patients. There was statistically significant increase in systolic blood pressure (p < 0.001). Pain on injection (50% in non-hypertensive and 48% in controlled hypertensive patients) was the only adverse drug reaction that was reported in both groups. Conclusion: 2% lidocaine hydrochloride with adrenaline (1:200000) increased systolic but not diastolic blood pressure in controlled hypertensive patients

Sigma receptors modulate nociception, offering a potential therapeutic target to treat pain, but relatively little is known regarding the role of sigma-2 receptors (S2R) in nociception. The purpose of this study was to investigate the in vivo analgesic and anti-allodynic activity and liabilities of a novel S2R selective ligand, 1-[4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)butyl]-3-methyl-1,3-dihydro-1,3-benzimidazol-2-one (CM-398). The inhibition of thermal, induced chemical, or inflammatory pain as well as the allodynia resulting from chronic nerve constriction injury (CCI) model of neuropathic pain were assessed in male mice. CM-398 dose-dependently (10–45 mg/kg i.p.) reduced mechanical allodynia in the CCI neuropathic pain model, equivalent at the higher dose to the effect of the control analgesic gabapentin (50 mg/kg i.p.). Likewise, pretreatment (i.p.) with CM-398 dose-dependently produced antinociception in the acetic acid writhing test (ED50 (and 95% C.I.) = 14.7 (10.6–20) mg/kg, i.p.) and the formalin assay (ED50 (and 95% C.I.) = 0.86 (0.44–1.81) mg/kg, i.p.) but was without effect in the 55 °C warm-water tail-withdrawal assay. A high dose of CM-398 (45 mg/kg, i.p.) exhibited modest locomotor impairment in a rotarod assay and conditioned place aversion, potentially complicating the interpretation of nociceptive testing. However, in an operant pain model resistant to these confounds, mice experiencing CCI and treated with CM-398 demonstrated robust conditioned place preference. Overall, these results demonstrate the S2R selective antagonist CM-398 produces antinociception and anti-allodynia with fewer liabilities than established therapeutics, adding to emerging data suggesting possible mediation of nociception by S2R, and the development of S2R ligands as potential treatments for chronic pain.

Controlling receptor functional selectivity profiles for opioid receptors is a promising approach for discovering safer analgesics; however, the structural determinants conferring functional selectivity are not well understood. Here, we used crystal structures of opioid receptors, including the recently solved active state kappa opioid complex with MP1104, to rationally design novel mixed mu (MOR) and kappa (KOR) opioid receptor agonists with reduced arrestin signaling. Analysis of structure-activity relationships for new MP1104 analogs points to a region between transmembrane 5 (TM5) and extracellular loop (ECL2) as key for modulation of arrestin recruitment to both MOR and KOR. The lead compounds, MP1207 and MP1208, displayed MOR/KOR Gi-partial agonism with diminished arrestin signaling, showed efficient analgesia with attenuated liabilities, including respiratory depression and conditioned place preference and aversion in mice. The findings validate a novel structure-inspired paradigm for achieving beneficial in vivo profiles for analgesia through different mechanisms that include bias, partial agonism, and dual MOR/KOR agonism.

Background: Type II Diabetes Mellitus (Type II DM) is a metabolic disorder characterized by glucotoxicity and lipotoxicity. Marker of glycemic control are HbA1c, fasting blood glucose and postprandial blood glucose. There is altered lipid parameters in Type II DM which possess significant cardiovascular risk to the patient. Recent studies have shown that ceruloplasmin, an inflammatory marker having antioxidant property,is ideal marker to know the cardiovascular status, degree of insulin resistance and cancer risk. Aims and Objectives: Present study was carried out to determine the relation between glycemic status and serum ceruloplasmin along with lipid parameters which reflects the cardiovascular status in these patients. Materials and Methods: Blood samples were collected from eighty-eight patients with type II diabetes mellitus along with age and sex matched forty-two healthy controls. Fasting lipid profile and blood glucose, postprandial blood glucose, serum ceruloplasmin and HbA1c levels were determined using auto analyser in the department of clinical biochemistry in Institute of Medicine.Appropriate tests of significance were computed by SPSS version 20. Results: Serum ceruloplasmin was found higher in type II DM than non-diabetic group, median 52.0 (95% CI: 49-53) mg/dl versus median 45.0 (95% CI: 41-47) mg/dl, at significant level of 0.001 probability test. Similarly, fasting blood glucose, post prandial glucose, HbA1c and TG/HDL cholesterol ratio correlated significantly with serum ceruloplasmin.The cut off value of 46.5 mg/dL was obtained for serum ceruloplasmin with sensitivity of 87.5% and specificity of 62% which has good discriminating value for type II diabetic patients versus non-diabetic patients. Conclusion: Findings in our study shows that increased glycation coupled with altered lipid profile in type II DM causes enhanced generation of ceruloplasmin which could be used as potential marker for identifying acceleratedglycation and atherogenesis in these subjects.

Introduction: Samples received in the laboratory are often rejected because of visible hemolysis. Every laboratory has protocols on whether to accept or reject hemolyzed samples based on tests ordered. The objective of the study was to observe and analyze the variations seen in association with hemolyzed samples in liver function test parameters and electrolytes measurement. Methods: This cross-sectional observational study was carried out in 88 laboratory samples in the Clinical Biochemistry Laboratory. Hemolysis was induced by mechanical mixing. This study compared reported values of bilirubin, protein, albumin, aminotransferases (ALT and AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), sodium and potassium between hemolyzed and non-hemolyzed samples. Results: Mean values of total bilirubin (TB) and direct bilirubin (TB), ALT, ALP, GGT and sodium (Na) were found to be significantly decreased post hemolysis (p<=0.001) with mean variances (s2) at 0.30 (TB), 0.38 (DB), 0.56 (ALT), 0.18 (ALP), 0.01 (GGT) and 0.001 (Na). In contrast, mean values of AST (s2= -0.9, p<0.001) and potassium (s2 = -0.3, p<0.001) were found to be significantly elevated post hemolysis. Total protein and albumin were also found to be elevated in hemolyzed samples but the average variance was not statistically significant. Degree of hemolysis had highly varying effects in some parameters like AST and total protein, but less varying and more consistent effects on other measured parameters. Conclusion: Free hemoglobin estimation should be considered before rejecting a clinical sample because of hemolysis. Mathematical equations cannot be expected to reproduce corrected values of the analytes in question because of the large variances, so these tests need to be repeated on non-hemolyzed samples for the analytes that are affected. [ABSTRACT FROM AUTHOR]

HIV-1 Tat (transactivator of transcription) protein disrupts dopaminergic transmission and potentiates the rewarding effects of cocaine. Allosteric modulators of the dopamine transporter (DAT) have been shown to reverse Tat-induced DAT dysfunction. We hypothesized that a novel DAT allosteric modulator, SRI-30827, would counteract Tat-induced potentiation of cocaine reward. Doxycycline (Dox)-inducible Tat transgenic (iTat-tg) mice and their G-tg (Tat-null) counterparts were tested in a cocaine conditioned place preference (CPP) paradigm. Mice were treated 14 days with saline, or Dox (100 mg/kg/day, i.p.) to induce Tat protein. Upon induction, mice were place conditioned two days with cocaine (10 mg/kg/day) after a 1-h daily intracerebroventricular (i.c.v.) pretreatment with SRI-30827 (1 nmol) or a vehicle control, and final place preference assessed as a measure of cocaine reward. Dox-treatment significantly potentiated cocaine-CPP in iTat-tg mice over the response of saline-treated control littermates. SRI-30827 treatment eliminated Tat-induced potentiation without altering normal cocaine-CPP in saline-treated mice. Likewise, SRI-30827 did not alter cocaine-CPP in both saline- and Dox-treated G-tg mice incapable of expressing Tat protein. These findings add to a growing body of evidence that allosteric modulation of DAT could provide a promising therapeutic intervention for patients with comorbid HIV-1 and cocaine use disorder (CUD). [ABSTRACT FROM AUTHOR]