Among the various ways that growth hormone (GH) underlies the growth physiology of teleost fishes, GH stimulates transport pathways that facilitate the absorption of nutrients across intestinal epithelia. The current study investigated the effects of GH on the gene expression of nutrient transporters in an omnivorous teleost, the Mozambique tilapia (Oreochromis mossambicus). We employed pituitary gland removal (hypophysectomy) and hormone replacement to assess whether GH directs the gene expression of the GH receptor (ghr2), the peptide transporters, pept1a, pept1b and pept2, the amino acid transporter, slc7a9, the Na+/glucose cotransporter, sglt1, the glucose transporter, glut2, and the myo-inositol transporter, smit2, in anterior, middle, and posterior intestine. ghr2 was predominantly expressed in posterior intestine, while pept1a, pept1b, slc7a9, sglt1, glut2, and smit2 exhibited the highest mRNA levels in anterior and/or middle intestine. While hypophysectomized tilapia exhibited diminished expression of ghr2, pept1a, pept1b, slc7a9, and glut2 compared with intact and sham-operated controls, only ghr2, pept1a, pept1b and glut2 levels were restored by GH replacement. Our findings indicate that GH supports growth, at least in part, by stimulating the gene expression of its cognate receptor and key nutrient transporters in the intestine. There is a renewed interest in investigating individual variation in hormone levels in relation to fitness metrics, as hormones act as mediators of life-history trade-offs. Hormone concentrations, however, are labile, responding to both internal and external stimuli, so the relationship between hormones and fitness can be non-consistent. One explanation of this inconsistent relationship is that a single hormone sample may not be representative of individual phenotypes in a free-living species. We addressed this issue by repeatedly sampling a free-living population of mountain white-crowned sparrows, Zonotrichia leucophrys oriantha, for baseline and stress-induced corticosterone (cort) and testosterone (T) across different stages of the breeding season. We measured (co)variation using three different methods, taking into account inter- and intra-individual variances, to determine whether hormone levels and the stress response are repeatable. We documented the temporal (over 3 months) and spatial (home-range) ve studies combine both physiological and environmental components to better understand the relationship between hormones and fitness. OBJECTIVES To critically appraise, compare and summarize the quality of the measurement properties of the Dartfish software across various populations and motion tasks. DATA SOURCES Systematic electronic searches were performed in PsychInfo, Embase, Medline@ Ovid, CINAHL and Google Scholar databases from January 1999 to January 2020. STUDY SELECTION Prospective measurement studies published in English peer-reviewed journal that reported on at least one psychometric property (reliability, validity, measurement error) using Dartfish were included. https://www.selleckchem.com/ALK.html Independent reviewer performed searches and identified studies. DATA EXTRACTION We followed the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) 2018 guideline for abstracting and assessing data quality. Independent extraction was performed by two individual authors. The extracted data involved the author, year, study population, setting, sample size, measurement properties, and information on camera positions, analyzed movement vof motion obtained with Dartfish are valid for single plane movements. The lack of effective treatment against multidrug-resistant Klebsiella pneumoniae (MDR-Kp) calls for finding and optimizing the combination therapies of old antibiotics. In this study, we aimed to quantify the combined effect of polymyxin B and minocycline by building an in silico semi-mechanistic pharmacokinetic-pharmacodynamic (PKPD) model and predict the bacterial kinetics when exposed to the drugs alone and in combination at clinically achievable unbound drug concentration-time profiles. A clinical strain resistant to polymyxin B (minimum inhibitory concentration, ****16 mg/L) and minocycline (****16 mg/L) was selected for extensive in vitro static time-kill experiments. The strain was exposed to concentrations of 0.0625 - 48 xMIC with seven samples taken per experiment for viable counts during 0 - 28 h. These observations allowed the development of the PKPD model. The final PKPD model included drug-induced adaptive resistance for both drugs. Both the minocycline-induced bacterial killing and resistance onset rate constant were increased when polymyxin B was co-administered, while polymyxin B parameters were unaffected. Predictions at clinically used dosages from the developed PKPD model showed no or limited antibacterial effect with monotherapy, while combination therapy kept bacteria below the starting inocula for > 20 h at high dosages (polymyxin B 2.5 mg/kg + 1.5 mg/kg q12h; minocycline 400 mg + 200 mg q12h, loading + maintenance doses). Our study suggests that polymyxin B and minocycline in combination may be of clinical benefit in the treatment of infections with MDR-Kp, also for isolates that are non-susceptible to either drug alone. V.Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.
Among the various ways that growth hormone (GH) underlies the growth physiology of teleost fishes, GH stimulates transport pathways that facilitate the absorption of nutrients across intestinal epithelia. The current study investigated the effects of GH on the gene expression of nutrient transporters in an omnivorous teleost, the Mozambique tilapia (Oreochromis mossambicus). We employed pituitary gland removal (hypophysectomy) and hormone replacement to assess whether GH directs the gene expression of the GH receptor (ghr2), the peptide transporters, pept1a, pept1b and pept2, the amino acid transporter, slc7a9, the Na+/glucose cotransporter, sglt1, the glucose transporter, glut2, and the myo-inositol transporter, smit2, in anterior, middle, and posterior intestine. ghr2 was predominantly expressed in posterior intestine, while pept1a, pept1b, slc7a9, sglt1, glut2, and smit2 exhibited the highest mRNA levels in anterior and/or middle intestine. While hypophysectomized tilapia exhibited diminished expression of ghr2, pept1a, pept1b, slc7a9, and glut2 compared with intact and sham-operated controls, only ghr2, pept1a, pept1b and glut2 levels were restored by GH replacement. Our findings indicate that GH supports growth, at least in part, by stimulating the gene expression of its cognate receptor and key nutrient transporters in the intestine. There is a renewed interest in investigating individual variation in hormone levels in relation to fitness metrics, as hormones act as mediators of life-history trade-offs. Hormone concentrations, however, are labile, responding to both internal and external stimuli, so the relationship between hormones and fitness can be non-consistent. One explanation of this inconsistent relationship is that a single hormone sample may not be representative of individual phenotypes in a free-living species. We addressed this issue by repeatedly sampling a free-living population of mountain white-crowned sparrows, Zonotrichia leucophrys oriantha, for baseline and stress-induced corticosterone (cort) and testosterone (T) across different stages of the breeding season. We measured (co)variation using three different methods, taking into account inter- and intra-individual variances, to determine whether hormone levels and the stress response are repeatable. We documented the temporal (over 3 months) and spatial (home-range) ve studies combine both physiological and environmental components to better understand the relationship between hormones and fitness. OBJECTIVES To critically appraise, compare and summarize the quality of the measurement properties of the Dartfish software across various populations and motion tasks. DATA SOURCES Systematic electronic searches were performed in PsychInfo, Embase, Medline@ Ovid, CINAHL and Google Scholar databases from January 1999 to January 2020. STUDY SELECTION Prospective measurement studies published in English peer-reviewed journal that reported on at least one psychometric property (reliability, validity, measurement error) using Dartfish were included. https://www.selleckchem.com/ALK.html Independent reviewer performed searches and identified studies. DATA EXTRACTION We followed the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) 2018 guideline for abstracting and assessing data quality. Independent extraction was performed by two individual authors. The extracted data involved the author, year, study population, setting, sample size, measurement properties, and information on camera positions, analyzed movement vof motion obtained with Dartfish are valid for single plane movements. The lack of effective treatment against multidrug-resistant Klebsiella pneumoniae (MDR-Kp) calls for finding and optimizing the combination therapies of old antibiotics. In this study, we aimed to quantify the combined effect of polymyxin B and minocycline by building an in silico semi-mechanistic pharmacokinetic-pharmacodynamic (PKPD) model and predict the bacterial kinetics when exposed to the drugs alone and in combination at clinically achievable unbound drug concentration-time profiles. A clinical strain resistant to polymyxin B (minimum inhibitory concentration, MIC 16 mg/L) and minocycline (MIC 16 mg/L) was selected for extensive in vitro static time-kill experiments. The strain was exposed to concentrations of 0.0625 - 48 xMIC with seven samples taken per experiment for viable counts during 0 - 28 h. These observations allowed the development of the PKPD model. The final PKPD model included drug-induced adaptive resistance for both drugs. Both the minocycline-induced bacterial killing and resistance onset rate constant were increased when polymyxin B was co-administered, while polymyxin B parameters were unaffected. Predictions at clinically used dosages from the developed PKPD model showed no or limited antibacterial effect with monotherapy, while combination therapy kept bacteria below the starting inocula for > 20 h at high dosages (polymyxin B 2.5 mg/kg + 1.5 mg/kg q12h; minocycline 400 mg + 200 mg q12h, loading + maintenance doses). Our study suggests that polymyxin B and minocycline in combination may be of clinical benefit in the treatment of infections with MDR-Kp, also for isolates that are non-susceptible to either drug alone. V.Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.
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