Effect of Disturbances of Zinc and Copper on the Physical and Mental Health Status of Patients with Alcohol Dependence.

The concentrations of copper and zinc in the tissues of alcohol-addicted people can significantly correlate with the variables describing their mental state. Studies on the homeostasis of zinc in alcohol-dependent patients have often been characterized by low hypozincemia detection. This may be caused by a low content of zinc in blood serum (1%) compared to the average zinc level in the body. Unfortunately, most authors have identified extracellular zinc in their studies. In the available literature, data on the level of copper in patients suffering from alcohol dependence are inconsistent. Our study included 100 alcohol-addicted patients (the study group) and 50 healthy subjects (the control group). Mental state was measured using appropriate psychometric scales. We used inductively coupled plasma mass spectrometry (ICP-MS) to determine copper and zinc content. Our results confirm the purposefulness of the use of zinc concentration in erythrocytes as a diagnostic parameter for low zinc status in alcohol-dependent patients. Alcohol-dependent patients with reduced concentrations of zinc in erythrocytes/copper in blood plasma differed significantly from alcohol-dependent patients with normal concentrations in terms of clinical parameters. With regard to zinc in blood plasma and copper in erythrocytes, this situation has not been found. The clinical symptoms of hypozincemia and copper deficiency in patients addicted to alcohol usually relate to disorders in central nervous system functioning, and they result in a decreased quality of physical and mental life.

The effect of opioid agonists and antagonists on gastrointestinal motility in mice selected for high and low swim stress-induced analgesia.

BACKGROUND: The opioid system in the gastrointestinal (GI) tract plays an important physiological role, but is also responsible for the side effect of opioid drugs, including troublesome constipation in chronic pain treatment. The aim of this study was to characterize and validate a new mouse model to study the effects of opioid agonists and antagonists in the GI tract. METHODS: Six-week-old male Swiss-Webster mice, divergently bred for high (HA) and low (LA) swim stress-induced analgesia (SSIA), were used in the study. To assess the influence of opioid agonists (morphine and loperamide) and antagonists (naloxone hydrochloride, NLX and naloxone methiodide, NLXM) on GI motility, whole GI transit (whole GIT) and upper GIT assays were conducted. To evaluate the expression of opioid receptors in the ileum and colon of HA and LA mice, immune staining was performed. KEY RESULTS: The effect of morphine was more pronounced in HA line, whereas loperamide exerted a stronger effect in LA mice. Furthermore, NLX and NLXM differentially abolished the inhibitory action of the central and peripheral opioid system on whole and upper GIT in HA and LA mice. The differences in GI motility between HA and LA mice coexisted with parallel changes in the expression of opioid receptors in the ileum and colon. CONCLUSIONS & INFERENCES: Differences in the activity of the endogenous opioid system are responsible for the vulnerability to changes in GI motility during treatment with opioids. Our findings validate the HA/LA model for further studies on opioids in the GI tract.

Genetic and environmental predictors of chronic kidney disease in patients with type 2 diabetes and diabetic foot ulcer: a pilot study.

Chronic kidney disease (CKD) is often observed among patients with type 2 diabetes mellitus (T2DM) and diabetic foot (DF) leading to end stage renal disease. The aim of this pilot study was to determine genetic and environmental factors involved in the etiology of CKD among patients with DF. The following polymorphisms were studied: rs1800469, rs759853, rs1553005, rs1799983, rs1801133, rs3134069, rs2073618, rs8192678, rs6330, rs11466112, rs121917832 in terms of alleles distribution in patients with DF and T2DM, with or without CKD. The study includes 101 patients with T2DM and DF. Studied groups were divided into 39 individuals with CKD (cases) and 62 controls, depending on the presence of kidney failure defined as eGFR < 60ml/min/1.73m(2) and coexistence of microalbuminuria > 30 mg/dl in at least 3 urine samples. Cases and controls were matched according to mean age, gender, mean duration of T2DM, mean duration of insulin therapy, mean duration of DF cholesterol levels and smoking frequencies. The study showed that CKD risk factors were the following variables: creatinine level, body weight, hips circumference, ischemic heart disease, hypertension and diabetic retinopathy. Moreover, the results suggest the protective role of the allele C of rs3134069 polymorphism in CKD development in patients with T2DM and DF in the following allelic variants: [AA] vs. [AC] and [AA] vs. [AC + CC]. The allele C was observed to be less frequent than the allele A in patients with T2DM and DF. None of the other following polymorphisms was observed to be a potential risk factor of CKD in T2DM and DF population: rs6330, rs759853, rs1553005, rs1799983, rs1801133, rs1800469, rs8192678, rs11466112, rs121917832. We concluded that the rs3134069 polymorphism seems to be the most likely protective genetic factor in CKD development in patients with T2DM and DF.

Sampling intervals verification in pharmacokinetics studies.

Regulatory agencies do not specify how to plan the sampling intervals in pharmacokinetics (PK) studies. Every interval between each sampling point forms one of the fractions of the area under the curve (AUC). The aim of this study is to propose a method of qualitative evaluation of PK studies, on the basis of the analysis of the partial AUC fields' values. For the pharmacokinetic analysis, average concentrations of high variability drug-itraconazole were used before (BO) and after sampling intervals optimization (AO). PK calculations were performed using Phoenix(TM) WinNonlin 6.3(®) (Certara L.P.) and in house software Biokinetica 4.0. Arithmetic formula and acceptance limit (AL%) was established, below which the mean of partial fields (MAF) value in PK study can be considered optimal. In case of MAF the CV% value before optimization was 125.35 and after the optimization 46.51. In the cases of AUC fractions for several partial fields BO data, the AL% value was exceeded. The values of AUC fractions did not exceed AL% established for AO data. The paper proposes an empirical method of quality assessment, made on the basis of the percentage of the AUC fractions. This method can be used in the quality assessment of PK studies.