Time Course of Reversal of Fentanyl-Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene and Intramuscular and Intranasal Naloxone.

The increase in opioid overdose deaths, particularly involving potent, long-acting synthetic opioids, has led to calls for stronger, longer-acting opioid-overdose-reversal agents. Using an opioid-induced respiratory depression model, we investigated the onset and time course of action of naloxone and a long-acting opioid antagonist, nalmefene, in reversing the effects of an ongoing intravenous fentanyl infusion over a period of up to 100 min. Healthy, moderately experienced opioid users received intramuscular (IM) nalmefene 1 mg, IM naloxone 2 mg, or intranasal (IN) naloxone 4 mg after fentanyl-induced respiratory depression was established based on reduction in respiratory minute volume (MV).

Evaluation of sunobinop for next-day residual effects in healthy participants.

Sunobinop is a novel, potent, selective partial agonist at nociceptin/orphanin FQ peptide (NOP) receptors. The primary objective of this randomized, double-blind, placebo-controlled study was to assess the next-day residual effects of an evening dose of sunobinop in healthy participants. Participants were randomized into 1 of 5 treatment sequences.

Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-Ascending Doses of Sunobinop in Healthy Participants.

Sunobinop is an investigational, potent, selective partial agonist at the nociceptin/orphanin FQ peptide receptor in vitro. Three phase 1 studies were conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating single- and multiple-dose administration of sunobinop in healthy participants. Study 1 was a randomized, double-blind, placebo-controlled, single-ascending dose study.

A case of severe acute respiratory failure after elective abdominoplasty.

Surgical correction of abdominal muscle diastasis may decrease intra-abdominal volume and increase intra-abdominal pressure. The induced changes may ultimately lead to respiratory compromise. In abdominoplasty, one of the most frequently performed esthetic procedures, those changes are believed to be transient and clinically insignificant.

Post hysterectomy mesonephric carcinoma: A case report and literature review.

Mesonephric carcinoma is a rare type of carcinoma seen in the female genital tract. It arises from the mesonephric remnants situated in the broad ligament, lateral wall of the cervix, vagina, and uterine corpus. Very few cases of mesonephric carcinoma have been reported so far in the literature.

Histomorphological and Morphometric Evaluation of Microvessel Density in Nodal Non-Hodgkin Lymphoma Using CD34 and CD105.

 Expression of angiogenic markers determined by microvessel density (MVD) could be used as a reliable predictor of prognosis and as a potential target for antiangiogenic therapy in different categories of non-Hodgkin lymphoma (NHL).  The aim of this study was to evaluate MVD using immunohistochemical methods and computer-assisted quantitative image analysis in nodal NHL patients and compare CD34 and CD105 expression in lymph nodes of NHL patients.  The present study was conducted on 60 lymph node biopsies received in the Department of Pathology at our tertiary care center for histopathological examination.

Bone marrow dyspoiesis associated with severe refractory anaemia in liver cirrhosis.

Background And Aim: Peripheral cytopaenias and dyspoiesis are common in cirrhosis; however, the prevalence of dyspoiesis and its contribution in cirrhosis-related cytopaenias has not been studied. We aimed to study the bone marrow (BM) dyspoiesis and its impact on peripheral blood cell counts and refractory anaemia in patients with cirrhosis.

Patients And Methods: We reviewed all the BM aspirates and biopsies of cirrhotic cases, done from 2011 to 2018 for clinical indications.

Acute Pulmonary Embolism in COVID-19: A Report of Two Cases.

Coronavirus disease 2019 (COVID-19), which is currently causing a global pandemic, is found to be associated with abnormal coagulation parameters and hyper-coagulable state with increased risk of venous thromboembolism (VTE). Here, we present two non-ICU cases of COVID-19, complicated with acute pulmonary embolism (PE). As of now, there are no proper guidelines established on anticoagulation in these patients.

Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: Insights from mathematical modeling and meta-analysis.

Antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (T) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and heat. First-generation (polymodal) TRPV1 antagonists potently block all three TRPV1 activation modes.

National Iron Plus Initiative: Current status & future strategy.

Anaemia is a severe public health problem amongst all vulnerable age groups in India. The National Nutritional Anaemia Prophylaxis Programme initiated in 1970, was revised and expanded to include beneficiaries from all age groups namely children aged 6-59 months, 5-10 yr, adolescents aged 10-19 yr, pregnant and lactating women and women in reproductive age group under the National Iron Plus Initiative (NIPI) programme in 2011. The dose of iron, frequency and duration of iron supplementation and roles and responsibilities of the functionaries were described.

Study the Expression of CD10 in Prostate Carcinoma and its Correlation with Various Clinicopathological Parameters.

Background And Objective: Adenocarcinoma of the prostate is the second most common cause of cancer. The loss of CD10 is a common early event in human prostate cancer and is seen in lower Gleason Score malignancies while increased and altered expression is seen in high Gleason Score tumors, lymph nodes and bone metastasis.

Material And Methods: This was a prospective observational study conducted on 75 patients suspected to have prostate cancer.

Prevention and Control of Anemia Amongst Children and Adolescents: Theory and Practice in India.

Anemia is a major public health problem in India with prevalence of more than 50% amongst children and adolescents. The decline in the burden of anemia has been insignificant over the past 5 decades. The present review assesses the National Guidelines for Prevention and Control of Anemia in India, the current status of the program implementation and possible reasons for the continued high prevalence of anemia in the country.

T cell phenotypes in women with Chlamydia trachomatis infection and influence of treatment on phenotype distributions.

T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38HLA-DR), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3CCR5 and CCR4, respectively), and T cell homing marker (CCR7) for both CD4 and CD8 T cells in CT-infected women.

Distinct peripheral vs mucosal T-cell phenotypes in chlamydia-infected women.

Problem: Differences in circulating (peripheral) and mucosal T-cell phenotypes in chlamydia-infected women remain largely unknown.

Method Of Study: Thirteen paired mononuclear cell specimens from blood and cervicovaginal lavages collected from chlamydia-infected women were stained and analyzed using ten-color cell surface flow cytometry for T-cell distribution, activation status, homing, and T helper (Th)-associated chemokine receptors (CKRs).

Results: A higher proportion of genital mucosal T-cells were activated (CD38 HLA-DR ) and expressed CCR5 and Th1-associated CKR CXCR3 CCR5 compared to peripheral T-cells, but a lower proportion of mucosal T-cells expressed homing CKR CCR7, Th-2 associated CKR CCR4, and CXCR3 CCR4 for both T-cell subsets.

Relationship between Amphipathic β Structures in the β Domain of Apolipoprotein B and the Properties of the Secreted Lipoprotein Particles in McA-RH7777 Cells.

Our previous studies demonstrated that the first 1000 amino acid residues (the βα domain) of human apolipoprotein (apo) B-100, termed apoB:1000, are required for the initiation of lipoprotein assembly and the formation of a monodisperse stable phospholipid (PL)-rich particle. The objectives of this study were (a) to assess the effects on the properties of apoB truncates undergoing sequential inclusion of the amphipathic β strands in the 700 N-terminal residues of the β domain of apoB-100 and (b) to identify the subdomain in the β domain that is required for the formation of a microsomal triglyceride transfer protein (MTP)-dependent triacylglycerol (TAG)-rich apoB-containing particle. Characterization of particles secreted by stable transformants of McA-RH7777 cells demonstrated the following.

The Predominant CD4 Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma.

infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of -specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4 T cells, in protective immunity to chlamydia.

Oral Abuse Potential, Pharmacokinetics, and Safety of Once-Daily, Single-Entity, Extended-Release Hydrocodone (HYD) in Recreational Opioid Users.

Objectives: A once-daily, extended-release hydrocodone bitartrate tablet with abuse-deterrent properties (Hysingla ER [HYD]) is available for the treatment of chronic pain in appropriate patients. This study evaluated the oral abuse potential and pharmacokinetics (PK) of HYD intact, chewed, or milled to fine particles in comparison with hydrocodone solution or placebo.

Design: Single-center, double-blind, randomized, five-period, five-treatment crossover study.

A randomized, double-blind, positive-controlled, 3-way cross-over human experimental pain study of a TRPV1 antagonist (V116517) in healthy volunteers and comparison with preclinical profile.

This experimental, translational, experimental pain, single-center, randomized, double-blind, single-dose, 3-treatment, 3-period cross-over proof-of-concept volunteer trial studied the efficacy of a novel TRPV1 antagonist (V116517) on capsaicin- and UV-B-induced hyperalgesia. Heat and pressure pain thresholds, von Frey stimulus-response functions, and neurogenic inflammation were assessed together with safety. Each treatment period was 4 days.

Intranasal Abuse Potential, Pharmacokinetics, and Safety of Once-Daily, Single-Entity, Extended-Release Hydrocodone (HYD) in Recreational Opioid Users.

Objectives: A once-daily, extended-release hydrocodone bitartrate tablet with abuse-deterrent properties (Hysingla ER® [HYD]) is available for the treatment of chronic pain in appropriate patients. This study evaluated the intranasal abuse potential and pharmacokinetics of HYD coarse and fine particles vs hydrocodone powder or placebo.

Design: Single-center, double-blind, positive- and placebo-controlled, randomized, four-treatment crossover study.