Pharmacokinetics and safety of TBAJ-876, a novel antimycobacterial diarylquinoline, in healthy subjects.

TBAJ-876, a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile compared with bedaquiline, is under development for the treatment of drug-susceptible and drug-resistant tuberculosis (TB). A phase 1, first-in-human study of TBAJ-876, comprising a single-ascending dose (SAD) part including a food effect cohort, a multiple-ascending dose (MAD) part, and a relative bioavailability part of tablets versus oral suspension, was conducted on 137 healthy adults. A drug-drug interaction study was conducted on 28 healthy adults to evaluate the effects of TBAJ-876 on a cytochrome P450 3A4 substrate (midazolam) and a P-glycoprotein substrate (digoxin).

Circulation of Pestiviruses in Small Ruminants from Greece: First Molecular Identification of Border Disease Virus.

The incidence of small ruminant pestivirus infections in Greece remains unknown as they have not been diagnosed in the country since 1974 when the most recent Border Disease Virus (BDV) outbreak was reported. The objective of our study was to explore the possible occurrence of pestiviral infections among sheep and goat farms in Greece and to further determine the variants of major concern. Thus, serum samples were collected from 470 randomly selected animals belonging to 28 different flocks/herds.

Whole-genome re-sequencing provides key genomic insights in farmed Arctic charr () populations of anadromous and landlocked origin from Scandinavia.

Arctic charr () is a niche-market high-value species for Nordic aquaculture. Similar to other salmonids, both anadromous and landlocked populations are encountered. Whole-genome re-sequencing (22X coverage) was performed on two farmed populations of anadromous (Sigerfjord;  = 24) and landlocked (Arctic Superior;  = 24) origin from Norway and Sweden respectively.

Characterizing Absorption Properties of Dispersible Pretomanid Tablets Using Population Pharmacokinetic Modelling.

Background And Introduction: The dispersible tablet formulation (DTF) of pretomanid has been developed to facilitate future use in children. This work aimed to assess the pharmacokinetics (PK) and relative bioavailability of the DTF compared to the marketed formulation (MF) and the potential influence of dose.

Methods: Pretomanid DTF was investigated in a single-dose, randomized, four-period, cross-over study, with 7 days of washout between doses.

Single Ascending-Dose Study To Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid in Healthy Adult Subjects.

The primary objective of the study was to evaluate the safety and tolerability of single oral doses of sutezolid tablets administered under fasting conditions in healthy adult subjects. The secondary objective was to determine the pharmacokinetics (PK) of sutezolid and two metabolites, PNU-101603 and PNU-101244. Overall, sutezolid was well tolerated when administered as a 300-mg, 600-mg, 1,200-mg, or 1,800-mg dose in healthy adult subjects under fasting conditions.

Genotyping Strategies Using ddRAD Sequencing in Farmed Arctic Charr ().

Incorporation of genomic technologies into fish breeding programs is a modern reality, promising substantial advances regarding the accuracy of selection, monitoring the genetic diversity and pedigree record verification. Single nucleotide polymorphism (SNP) arrays are the most commonly used genomic tool, but the investments required make them unsustainable for emerging species, such as Arctic charr (), where production volume is low. The requirement to genotype a large number of animals for breeding practices necessitates cost effective genotyping approaches.

Fourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosis.

Linezolid is increasingly used for the treatment of tuberculosis resistant to first-line agents, but the most effective dosing strategy is yet unknown. From November 2014 to November 2016, we randomized 114 drug-sensitive treatment-naive pulmonary tuberculosis patients from Cape Town, South Africa, to one of six 14-day treatment arms containing linezolid at 300 mg once daily (QD), 300 mg twice daily (BD), 600 mg QD, 600 mg BD, 1,200 mg QD, 1,200 mg three times per week (TIW), or a combination of isoniazid, rifampin, pyrazinamide, and ethambutol. Sixteen-hour sputum samples were collected overnight, and bactericidal activity was characterized by the daily percentage change in time to positivity (TTP) and the daily rate of change in log(CFU).

HLA-A29-POSITIVE BIRDSHOT CHORIORETINOPATHY IN AN AFRICAN AMERICAN PATIENT.

Purpose: To report the first documented case of HLA-A29-positive birdshot chorioretinopathy in an African American patient.

Methods: A 51-year-old African American woman presented with a 10-year history of photopsia, progressive decrease in visual acuity, metamorphopsia, and new nyctalopia. Both fundi showed evidence of periphlebitis, arterial attenuation, macular edema, and diffuse chorioretinal atrophy.

Multimodal Imaging and Choroidal Volumetric Changes After Half-fluence PDT in Central Serous Chorioretinopathy.

Purpose: The purpose of this study was to identify SD-OCT changes that correspond to leakage on fluorescein (FA) and indocyanine angiography (ICGA) and evaluate effect of half-fluence photodynamic therapy (PDT) on choroidal volume in chronic central serous choroidoretinopathy (CSC).

Methods: Retrospective analysis of patients with chronic CSC who had undergone PDT. Baseline FA and ICGA images were overlaid on SD-OCT to identify OCT correlates of FA or ICGA hyperfluorescence.

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis.

Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis.

Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group).

A systemic type I 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris.

Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme.

Occupational exposure to cholinesterase inhibiting pesticides: a Greek case.

The determination of plasma or serum cholinesterase is absolute and it is considered as a reliable index of exposure in workers of organophosphorus pesticides industries. In the present study the plasma cholinesterase of 28 persons working in the packaging of an ortho-thio-phosphate was determined, before and after their exposure to this agent. The results of this study showed a plasma cholinesterase depression of 37%, a decrease which was statistically significant (P<0.

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia.

Objectives: To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important.

Methods: The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands.

Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia.

Objectives: To evaluate the effects of finasteride, a specific type II 5-alpha-reductase inhibitor, on symptoms of benign prostatic hyperplasia, prostate volume, and urinary flow during a 7 to 8-year period.

Methods: A total of 190 men with symptomatic benign prostatic hyperplasia and enlarged prostates entered one of two Phase II double-blind 3 to 6-month studies. Of these, 156 patients continued taking open-label finasteride, and more than 70 patients completed 7 to 8 years of treatment.

Lead content of fresh milk samples from different sites in Athens.

Milk and dairy products constitute a major food, especially for infants and children, and relatively low levels of toxic elements can contribute significantly to dietary intakes and be hazardous for public health. The purpose of this survey was to define the levels of lead in milk samples of different origin, to establish the presence or absence of contamination. The milks from different sites of the metropolitan area of Athens contained negligible traces of lead and thus are safe for the public health.

Prostate volume and serum prostate-specific antigen as predictors of acute urinary retention. Combined experience from three large multinational placebo-controlled trials.

Objectives: We evaluated prostate volume and prostate-specific antigen (PSA) as predictors of acute urinary retention (AUR) in men with benign prostatic enlargement (BPE).

Methods: Data were pooled from 3 identical 2-year, multinational, multicenter, non-US, placebo-controlled finasteride trials in 4,222 men with BPE and no evidence of prostate cancer.

Results: The 2-year incidence of spontaneous AUR was higher in placebo patients with enlarged prostates (4.

Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia.

Background: Finasteride, an inhibitor of type 2 5alpha-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated.

Objective: The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA.

Impact of baseline symptom severity on future risk of benign prostatic hyperplasia-related outcomes and long-term response to finasteride. The Pless Study Group.

Objectives: To evaluate the long-term effects of finasteride on symptoms, acute urinary retention (AUR), and the need for benign prostatic hyperplasia (BPH)-related surgery in relationship to baseline symptom severity.

Methods: A total of 3040 men with BPH were treated for 4 years with finasteride or placebo. The changes from baseline in symptoms and the incidence of BPH-related surgery and AUR were determined in men with mild (less than 8), low-moderate (8 to 12), high-moderate (13 to 19), and severe (greater than 19) baseline quasi-American Urological Association symptoms for all patients and for the subgroup with a baseline prostate-specific antigen (PSA) level of 1.

Bee pseudocholinesterase as an indicator of exposure to anticholinesterase insecticides.

The inhibition of pseudocholinesterase (butyrylcholinesterase) activity is a valid and sensitive biochemical indicator of exposure to anticholinesterase insecticides and is often mandatory of the agricultural use of these pesticides. In the present work we developed a modification of an easy and sensitive technique to detect the pseudocholinesterase inhibition due to pesticide exposure. Small amounts of head tissue are needed and low concentrations of the enzyme can be detected.

Bee head acetylcholinesterase as an indicator of exposure to organophosphate and carbamate insecticides.

Insect acetylcholinesterase has received special attention following the discovery that inhibition of the enzyme is the mechanism of activity of the organophosphate and carbamate insecticides. Apiculture is an important source of Greek income and as the detection of anticholinesterase insecticides in bees is very difficult, investigation of the cause of death of honeybees due to acetylcholinesterase inhibition is of great value and will contribute to the differential diagnosis of bee diseases. The enzymatic assay is not capable of distinguishing between individual pesticides', but is an indicator of the exposure of bees to anticholinesterase insecticides.

Proscar: five-year experience.

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire.

Prolonged treatment with finasteride (a 5 alpha-reductase inhibitor) does not affect bone density and metabolism.

Objective: Since it is not clear whether testosterone or dihydrotestosterone is the active hormone in bone metabolism, we wished to assess the effect of finasteride, a 5 alpha-reductase inhibitor, or vertebral bone mineral density and parameters of bone and mineral metabolism.

Design: Patients were treated in a randomized, double-blind controlled study with either placebo, 1 or 5 mg/day finasteride.

Patients: Twenty-three men with benign prostatic hyperplasia (BPH) were included in this study; eight received placebo, seven were allocated to treatment with 1 mg/day, and eight to 5 mg/day finasteride for 12 months.

Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia.

The oral administration of finasteride, a 4-aza-steroid inhibitor of 5 alpha-reductase, decreases serum dihydrotestosterone levels, but has little effect on serum testosterone. The current study was designed to assess the effect of finasteride on dihydrotestosterone levels in the prostates of men with benign prostatic hyperplasia. In a double blind, placebo-controlled study, 69 men with symptomatic prostatic hyperplasia were treated with placebo or 1, 5, 10, 50, or 100 mg/day finasteride for 7 days before transurethral resection of the prostate.