The objective of the present study was to investigate the influence of prostaglandin F(2alpha) (PGF (2alpha)) and nitric oxide (NO) on production of steroids and PGs by culturing bovine luteal cells obtained from ovaries on days 8-12 of the estrous cycle with a nitric oxide (NO) donor (Spermine NONOate), and a NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester dihydrochloride: L-NAME). When the cells were exposed for 24 h to PGF(2alpha) (10(-7)-10(-5) M), production of progesterone (P(4)) increased significantly at all doses used (P0.05) secretion of T, PGF(2alpha) and PGE(2). Estradiol-17beta (E(2)) was detectable on the level of sensitivity of assay and was not significantly altered by any treatments. The overall results suggest that PGF(2alpha) and NO produced locally in bovine CL play roles in the regulation of the secretory function of the bovine CL as auto/paracrine factors.

To test whether nitric oxide (NO) is involved in prostaglandin (PG) F_2α-induced regression of the bovine corpus luteum (CL) in vivo, heifers were treated as follows: Group 1, saline (3 ml/h); Group 2, dinoprost, an analogue of prostaglandin F_2α(aPGF_2α; 5 mg/0.5 h); Group III, Nω-nitro-L-arginine methyl ester (L-NAME; 200 mg/4 h), an inhibitor of nitric oxide synthase; and Group IV, L-NAME (400 mg/4 h) and aPGF_2α(5 mg/0.5 h). All treatments were administered by an intraluteal microdialysis system (MDS) on day 15 of the cycle. Perfusate and jugular plasma samples were collected at half-hour intervals; additionally, jugular plasma samples were collected once daily from day 16 to day 21 of the cycle. In the perfusate samples, aPGF_2αincreased P₄( P < 0.05), PGE₂( P < 0.001), and LTC₄( P < 0.05) concentrations; L-NAME increased P₄( P < 0.05) but did not change PGE₂and LTC₄( P > 0.05) concentrations as compared with the period before treatment. Simultaneous perfusion of CL with L-NAME and aPGF_2αcaused a further increase of P₄concentration ( P < 0.05) induced by L-NAME or aPGF_2αtreatment and increased PGE₂and LTC₄( P < 0.001) concentrations to the level observed after aPGF_2αtreatment. Perfusion of CL with aPGF_2αcaused luteal regression within 24 h, while perfusion with L-NAME prolonged the life span of CL to day 21 ( P < 0.05). Concomitant L-NAME and aPGF_2αtreatment partially counteracted ( P < 0.05) the luteal regression caused by aPGF_2αadministration. These results show that NO is involved in the process of luteolysis in the bovine CL and suggest that the luteolytic effect of aPGF_2αmay be mediated by NO as an important component of an autocrine/paracrine luteolytic cascade.

Deer keds are obligatory hematophagous ectoparasites of birds and mammals. Cervids serve as specific hosts for these insects. However, ked infestations have been observed in non-specific hosts, including humans, companion animals, and livestock. Lipoptena fortisetosa is a weakly studied ectoparasite, but there is evidence to indicate that it continues to spread across Europe. The existing knowledge on deer keds’ impact on wildlife is superficial, and their veterinary importance is enigmatic. Lipoptena fortisetosa is a species with vectorial capacity, but potential pathogen transmission has not been assessed. The objective of this study was to evaluate the prevalence of selected pathogens in L. fortisetosa collected from cervids and host-seeking individuals in the environment. Out of 500 acquired samples, 307 (61.4%) had genetic material from at least one tested pathogen. Our research suggests that L. fortisetosa may be a potential vector of several pathogens, including A. phagocytophilum, Babesia spp., Bartonella spp., Borellia spp., Coxiella-like endosymbionts, Francisiella tularensis, Mycoplasma spp., Rickettsia spp., and Theileria spp.; however, further, more extensive investigations are required to confirm this. The results of the study indicate that keds can be used as biological markers for investigating the prevalence of vector-borne diseases in the population of free-ranging cervids.

Background: The primary objective of this study was to develop a population pharmacokinetic model of meropenem, based on the population of critically ill adult patients undergoing CRRT. The secondary one was to examine the relationship between patient characteristics (covariates) and individual PK parameters. Finally, we aimed to perform Monte Carlo simulations to assess the probability of target attainment (PTA) of %T > MIC considering the uncertainty of PK parameters. Materials and methods: The study population included 19 adult critically ill patients on CRRT, receiving 1 g of meropenem in 1-h infusions every 8 h. Blood samples were collected prior to (time zero) and 15, 30, 45, 60, 75, 90, 120, 180, 240 and 480 min after the start of meropenem administration. Population nonlinear mixed-effects modeling was conducted using NONMEM software, Fortran, and Wings for NONMEM. Results: A two-compartment model was used to describe the available data. Typical values of the central and peripheral volume of distribution, and the CRRT and inter-compartmental clearance for a theoretical patient with 24.6 g/l albumin concertation were V₁ = 27.9 l, V₂ = 33.7 l, Cl_CRRT = 15.1 l/h, and Q = 21.1 l/h. A significant covariate relationship between V₁ and albumin concentration was observed in the data that was described by a power relationship with − 2.87 exponent. Subsequently performed Monte Carlo simulations of the model allowed us to assess the impact of albumin concentration on PTA. The 40%T > 2 mg/l target was reached in more than 90% of subjects after 1-h infusion of 1000 mg q8h and steady-state conditions. The more stringent 100%T > 2 mg/l target requires higher doses and/or longer infusion durations that depend on the albumin concentration. Conclusions: The population PK model was successfully developed to describe the time course of meropenem concentrations. The hypoalbuminemia was found to be associated with higher PTA in the CRRT patients after multiple short-term infusions.

The escalating misuse of antibiotics, particularly broad-spectrum antibiotics, has emerged as a pivotal driver of drug resistance. Among these agents, tetracyclines are widely prescribed for bacterial infections, but their indiscriminate use can profoundly alter the gut microbiome, potentially compromising both their effectiveness and safety. This review delves into the intricate and dynamic interplay between tetracyclines and the gut microbiome, shedding light on their reciprocal influence. By exploring the effects of tetracyclines on the gut microbiome and the impact of gut microbiota on tetracycline therapy, we seek to gain deeper insights into this complex relationship, ultimately guiding strategies for preserving antibiotic efficacy and mitigating resistance development.

The aim of this study was to investigate the influence of nitric oxide (NO) donors (S-nitroso-L-acetyl penicillamine, spermine-NO complex and sodium nitroprusside) and NO synthase inhibitors (N(omega)-nitro-L-arginine methyl ester, N(omega)-nitro-l-arginine, and (+/-)-2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine) on progesterone production by dispersed bovine luteal cells cultured for 24 h. All NO donors inhibited progesterone production and increased nitrite or nitrate concentration in the medium in a dose-dependent manner. Secretion of progesterone was reduced to 75% (P < 0.01), 56% (P < 0.001) and 37% (P < 0.001) by S-nitroso-L-acetyl penicillamine; to 65% (P < 0.001), 45% (P < 0.001) and 33% (P < 0.001) by spermine-NO complex and to 77% (P < 0.05), 74% (P < 0.01) and 54% (P < 0.001) by sodium nitroprusside treatments at concentrations of 10(-5), 10(-4) and 10(-3) mol l(-1), respectively, compared with the concentration of this hormone measured in cells cultured in medium alone. NO synthase inhibitors decreased significantly (P < 0.05) nitrite or nitrate concentration and increased progesterone secretion with different potency at different doses. Significant increases in progesterone production were observed after N(omega)-nitro-L-arginine methyl ester treatment at a concentration of 10(-5) mol l(-1) and 10(-4) mol l(-1), and after N(omega)-nitro-l-arginine administration at a concentration of 10(-6) mol l(-1) (P < 0.01) and 10(-5) mol l(-1) (P < 0.05), compared with the concentration of this hormone measured in control cells. The results indicate that both NO donors and NO synthase inhibitors regulate steroidogenesis in cultured bovine luteal cells from days 10 to 14 of the oestrous cycle; however, the degree of progesterone inhibition by NO donors and stimulation by NO synthase inhibitors was dependent on the drug used.