Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome

Background Patients with liver diseases often have some form of anemia. Hematological dyscrasias are known side effects of antipsychotic drug medication and the occurrence of agranulocytosis under clozapine is well described. However, the sex-dependent impact of clozapine and haloperidol on erythrocytes and symptoms like anemia, and its association with hepatic iron metabolism has not yet been completely clarified. Therefore, in the present study, we investigated the effect of both antipsychotic drugs on blood parameters and iron metabolism in the liver of male and female Sprague Dawley rats. Methods After puberty, rats were treated orally with haloperidol or clozapine for 12 weeks. Blood count parameters, serum ferritin, and liver transferrin bound iron were determined by automated counter. Hemosiderin (Fe3+) was detected in liver sections by Perl’s Prussian blue staining. Liver hemoxygenase (HO-1), 5’aminolevulinate synthase (ALAS1), hepcidin, heme-regulated inhibitor (HRI), cytochrome P4501A1 (CYP1A1) and 1A2 (CYP1A2) were determined by Western blotting. Results We found anemia with decreased erythrocyte counts, associated with lower hemoglobin and hematocrit, in females with haloperidol treatment. Males with clozapine medication showed reduced hemoglobin and increased red cell distribution width (RDW) without changes in erythrocyte numbers. High levels of hepatic hemosiderin were found in the female clozapine and haloperidol medicated groups. Liver HRI was significantly elevated in male clozapine medicated rats. CYP1A2 was significantly reduced in clozapine medicated females. Conclusions The characteristics of anemia under haloperidol and clozapine medication depend on the administered antipsychotic drug and on sex. We suggest that anemia in rats under antipsychotic drug medication is a sign of an underlying liver injury induced by the drugs. Changing hepatic iron metabolism under clozapine and haloperidol may help to reduce these effects of liver diseases.

Rat leukocyte population dynamics predicts a window for intervention in aging.

Age-associated changes in human hematopoiesis have been mostly recapitulated in mouse models; but not much has been explored in rats, a physiologically closer model to humans. To establish whether rat hematopoiesis closely mirrors humans’, we examined the peripheral blood of rats throughout their lifespan. Significant age-associated changes showed distinctive population shifts predictive of age. A divergence between predicted versus chronological age changes was indicative of fragility; thus, these data may be a valuable tool to identify underlying diseases or as a surrogate predictor for intervention efficacy. Notably, several blood parameters and DNA methylation alterations defined specific leverage points during aging, supporting non-linear aging effects and highlighting a roadmap for interventions at these junctures. Overall, we present a simple set of rat blood metrics that can provide a window into their health and inform the implementation of interventions in a model system physiologically relevant for humans.

Effects of Knotweed-Enriched Feed on the Blood Characteristics and Fitness of Horses

The aboveground biomass of dry knotweed was administered daily to large groups of young (1- to 3-year-old) stallions of the Czech Warmblood, Czech-Moravian Coldblood and Silesian Norik breeds, fed individually for 4 and 6 months in two successive winter experiments. Their fitness was compared with control groups consisting of equally numerous subgroups comparable in age, breed, body mass and initial blood parameters. The effects of knotweed on the horses’ fitness were evaluated based on changes in blood characteristics. Even if administered in small amounts, 150 g per day, knotweed could (1) increase the thrombocyte numbers, (2) increase the globulin content (thus improving the horses’ immunity, which is desired in large groups of animals), (3) stimulate lipid metabolism in cold-blooded horses and (4) decrease the concentration of cholesterol. The long-lasting effect of knotweed on both the urea and triglyceride–cholesterol ratio presumably reflected, between the two experiments, the temporary protein starvation of horses on pastures with poor quality of grass in a dry summer.

The landscape of antibiotic usage among COVID-19 patients in the early phase of pandemic: a Malaysian national perspective

Background During the early phase of the COVID-19 pandemic, antibiotic usage among COVID-19 patients was noted to be high in many countries. The objective of this study was to determine the prevalence of antibiotic usage and factors affecting antibiotic usage among COVID-19 patients during the early phase of the COVID-19 pandemic in Malaysia. Methods This was a cross-sectional study that involved reviewing medical records of COVID-19 Malaysian patients aged 12 and above who were diagnosed with COVID-19 and received treatment in 18 COVID-19 hospitals from February to April 2020. A minimum sample of 375 patients was required. A binary logistic regression analysis was performed to determine factors associated with antibiotic usage. Variables with p < 0.05 were considered statistically significant. Results A total of 4043 cases were included for analysis. The majority of the patients (87.6%) were non-smokers, male (65.0%), and had at least one comorbidity (37.0%). The median age was 35 years (IQR: 38). The prevalence of antibiotic usage was 17.1%, with 5.5% of them being prescribed with two or more types of antibiotics. The most frequent antibiotics prescribed were amoxicillin/clavulanic acid (37.8%), ceftriaxone (12.3%), piperacillin/tazobactam (13.3%), azithromycin (8.3%), and meropenem (7.0%). Male patients (adjusted OR 1.53), who had a comorbidity (adjusted OR 1.36), associated with more severe stage of COVID-19 (adjusted OR 6.50–37.06), out-of-normal range inflammatory blood parameters for neutrophils, lymphocytes, and C-reactive protein (adjusted OR 2.04–3.93), corticosteroid use (adjusted OR 3.05), and ICU/HDU admission (adjusted OR 2.73) had higher odds of antibiotic use. Conclusions The prevalence of antibiotic usage in the early phase of the COVID-19 pandemic was low, with amoxicillin/clavulanic acid as the most common antibiotic of choice. The study showed that clinicians rationalized antibiotic usage based on clinical assessment, supported by relevant laboratory parameters.

Effect of Long-Acting Selenium Preparation on Health and Productivity of Sheep

The aim of this study was to determine the effects of long-acting selenium (Se) preparation in sheep. The experimental material comprised Skudda ewes and their lambs. The animals were divided into two equal groups: C-control, and E-experimental. Between days 70 and 80 of pregnancy, group E ewes were injected with Se preparation (Barium Selenate Injection, BVP Animal Care, Ireland) at f 1 mL/50 kg body weight. Hematological, biochemical and immunological blood parameters as well as Se levels were analyzed in ewes. The growth rate of lambs, the dimensions of the musculus longissimus dorsi (MLD) cross-section, and fat thickness over the loin-eye area were also determined. It was found that barium selenate stimulated the mechanisms of humoral and cellular immunity. The injection was an effective form of Se supply, which was confirmed by its increased concentration in the blood serum of lactating ewes. The offspring of the experimental ewes were characterized by a faster growth rate, and they achieved significantly higher body weight (p ≤ 0.05) at 100 days of age. The lambs also had significantly higher parameters of MLD (p ≤ 0.05) at similar carcass fat content.

Ecotoxicological Effects of Silver Nanoparticles (Ag-NPs) on Parturition Time, Survival Rate, Reproductive Success and Blood Parameters of Adult Common Molly (Poecilia sphenops) and Their Larvae

Nanoparticles (NPs) can display toxicological effects on aquatic organisms. This study investigates ecotoxicological effects of Ag-NPs on reproductive and blood parameters of adult common molly (Poecilia sphenops) and their larvae. During the LC50 96 h test, female fish were exposed to concentrations of 0, 5, 15, 25, 35, 45 and 60 mg L−1 of Ag-NPs, while larvae were exposed to 0, 3, 5, 10 and 15 mg L−1. Finally, we aim to evaluate the effects of 0, 5, 10 and 15 mg L−1 of Ag-NPs on parturition time, reproductive success and hematological parameters of the mature fish exposed to sub-lethal concentration during a 62-day period. We also evaluated the survival rate of larvae. The results show a positive correlation between mortality rate and Ag-NP concentration. Values for LC50 96 h in adult fish and larvae were 26.85 mg L−1 and 6.22 mg L−1, respectively. A lack of parturition and reproductive success were seen in fish that underwent chronic exposure to Ag-NPs (15 mg L−1). The results show that RBC, WBC and hematocrit were significantly decreased in fish exposed to Ag-NPs. In addition, the serum concentrations of total protein, albumin, cholesterol and triglycerides were significantly increased in fish submitted to Ag-NPs (concentrations of 5–15). In conclusion, submitting a fish to higher concentration than 10 mg L−1 has adverse effects on reproductive system and blood parameters.

Influence of Sodium Humate on the Growth Performance, Diarrhea Incidence, Blood Parameters, and Fecal Microflora of Pre-Weaned Dairy Calves

This study aimed to evaluate the effects of the administration of sodium humate (NaH) on the growth performance, diarrhea incidence, and fecal microflora of pre-weaned Holstein calves. In a 53-day experiment, forty healthy newborn female calves were randomly allocated to the following four treatment groups: (1) control (basal diet); (2) 1-gram NaH (basal diet extra orally supplemented with 1 g of NaH dissolved in 100 mL of milk or milk replacer daily); (3) 3-gram NaH (basal diet extra orally supplemented with 3 g of NaH dissolved in 100 mL of milk or milk replacer daily); and (4) 5-gram NaH (basal diet extra orally supplemented with 5 g of NaH dissolved in 100 mL of milk or milk replacer daily). NaH was mixed with milk (d 2–20) or milk replacer (d 21–53). Calves in the 5-gram NaH group had a higher ADG during d 1 to 21 and d 21 to 53 than the other groups did (p < 0.05). Fecal scores and diarrheal incidence were significantly lower in the 3-gram and 5-gram NaH groups than the 1-gram NaH and control groups during d 1 to 20 (p < 0.05). The serum IgA, IgG and IL-4 concentrations, and T-SOD and T-AOC activities were higher, and the serum IL-6, TNF-α, D-lactic acid, and MDA concentrations were lower in the 5-gram NaH group than the control group (p < 0.05). Furthermore, NaH supplementation increased the abundances of Bifidobacterium and Lactobacillus but decreased the abundance of Escherichia coli in feces (p < 0.05). These encouraging findings indicated that supplementation with 5 g of NaH effectively improved the immune status, antioxidant capacity, and intestinal beneficial bacteria, and further improved the growth performance and reduced the diarrhea incidence of the pre-weaned dairy calves.