Body mass index as a determinant of clozapine plasma concentrations: A pharmacokinetic-based hypothesis.

BACKGROUND: Knowledge regarding the impact of body composition measures on pharmacokinetics of antipsychotics is limited. AIMS: Our aim was to investigate the impact of body weight and body mass index on clozapine pharmacokinetics using a therapeutic drug monitoring database. METHODS: A large therapeutic drug monitoring dataset of clozapine plasma concentrations considering three patient subgroups was analysed: a control group (CLZ0, 20-30 kg/m2, n=266), a group with high body mass index (CLZhigh, body mass index ⩾30 kg/m2, n=162) and with low body mass index values (CLZlow, body mass index <20 kg/m2, n=27). Comparisons of plasma and dose-adjusted plasma concentrations (C/D) of clozapine were based on the Spearman's correlation (rs), Kruskal Wallis and Mann-Whitney-U tests. For percentages we used the Pearson chi-square test (χ2). To assess effects of confounders we used bootstrapping analysis of covariates. RESULTS/OUTCOMES: Regarding demographic characteristics, groups differed only for sex percentage with more females than males in CLZlow and CLZhigh compared to CLZ0 (p=0.001 for χ2 test). Plasma and C/D values were positively associated with body mass index (rs=0.108, p=0.022 and rs=0.156, p=0.001 respectively). Intergroup differences were observed for plasma and dose-adjusted concentrations of clozapine (p=0.031 and p=0.029 for Kruskal Wallis respectively): post-hoc pairwise comparisons showed higher plasma concentrations and C/D of clozapine in CLZhigh compared to CLZ0 (p=0.014 and p=0.007 respectively for Mann-Whitney U-test), by mean 21 and 18%, respectively. Differences for C/D values remained after accounting for sex (p=0.02). CONCLUSIONS/INTERPRETATION: In obese patients, bioavailability, distribution or elimination of clozapine may be altered due to increased clozapine deposits in fat tissue and hepatic enzyme activity changes.

The levels of sICAM-1, sELAM-1, TNFα and sTNFR1 proteins in patients with colorectal adenocarcinoma in tumor and corresponding normal mucosa.

Colorectal cancer is a common malign disease of the gastrointestinal tract. The cancer survival rate depends on the stage of the disease at detection time. It is well known that several molecular mechanisms are involved in cancer and some molecules might affect or modulate cancerogenesis. The aim of the study was to assess the levels of sICAM-1, sELAM-1, TNFα and sTNFR1 protein in tumor and corresponding normal mucosa in a group of patients with colorectal adenocarcinoma and also associations of these parameters with demographic and clinical profiles of the patients. Tissue specimens were obtained during resection of neoplastic lesions. Protein levels were assayed in tissue homogenates by ELISA. The protein level of sICAM-1 in tumor was significantly increased in comparison to the corresponding normal mucosa (80.06 ng/mg vs 69.53 ng/mg, p=0.02). Furthermore, a significant positive correlation between sICAM-1 and sTNFR1 proteins levels in tumor (rs=0.58, p<0.001) and in corresponding normal mucosa (rs=0.48, p<0.001) was found. Also, significant correlations in corresponding normal mucosa were found between sELAM-1 and sICAM-1 (rs=0.58, p<0.001) and between sTNFR1 and sELAM-1 (rs=0.57, p<0.001). Significantly higher level of sTNFR1 in corresponding normal mucosa samples of patients with distant metastases was observed (p=0.04). Obtained results suggest that sICAM-1 protein could be considered as colorectal cancer marker. Furthermore, sTNFR1 also has the potential to become a good prognostic marker used during monitoring of the patients. Nevertheless, a further study in this area to confirm this correlation is required.

Mesenchymal Stem Cells-Potential Applications in Kidney Diseases.

Mesenchymal stem cells constitute a pool of cells present throughout the lifetime in numerous niches, characteristic of unlimited replication potential and the ability to differentiate into mature cells of mesodermal tissues in vitro. The therapeutic potential of these cells is, however, primarily associated with their capabilities of inhibiting inflammation and initiating tissue regeneration. Owing to these properties, mesenchymal stem cells (derived from the bone marrow, subcutaneous adipose tissue, and increasingly urine) are the subject of research in the settings of kidney diseases in which inflammation plays the key role. The most advanced studies, with the first clinical trials, apply to ischemic acute kidney injury, renal transplantation, lupus and diabetic nephropathies, in which beneficial clinical effects of cells themselves, as well as their culture medium, were observed. The study findings imply that mesenchymal stem cells act predominantly through secreted factors, including, above all, microRNAs contained within extracellular vesicles. Research over the coming years will focus on this secretome as a possible therapeutic agent void of the potential carcinogenicity of the cells.

The Medical Treatment of Homeless People.

BACKGROUND: The homeless are often in poor health, and their risk of premature death is three to four times that of the general population. This article is intended to provide an overview of the medical care of the homeless in Germany. METHODS: We selectively reviewed pertinent scientific and non-scientific publications from the years 2000-2017 that were retrieved from PubMed, from the reports of the German Homeless Aid Society (Bundesarbeitsgemeinschaft Wohnungslosenhilfe), from the websites of homeless aid organizations, and from Google Scholar. RESULTS: At least 75% of the homeless currently suffer from a mental illness requiring treatment. Common somatic problems include respiratory (6-14%) and cardiovascular disorders (7-20%), injuries and intoxications (5-15%), and infectious and parasitic diseases (10-16%). To circumvent the multiple barriers impeding homeless people's access to standard medical care (lack of health insurance, a feeling of being unwelcome, lack of disease awareness, impaired capacity for compliance), medical help is offered to them outside the system in a number of ways, embedded in an overall scheme of social and practical assistance with daily living. These medical resources differ from region to region. They are often underfinanced and tend to focus on acute general medical care, with limited access to specialists. CONCLUSION: More heath care resources need to be made available to the homeless beyond standard medical care. Concrete suggestions are discussed in the text.