Environmental Cd and Zn Concentrations in Liver and Kidney of European Hare from Different Serbian Regions: Age and Tissue Differences

A total of 84 European hares collected from eleven Serbian regions investigated upon cadmium (Cd) and zinc (Zn) presence. Strong statistically significant correlations between Cd concentrations in kidney and liver were registered in animals older than 12 months. Significant differences between Zn concentrations in liver in comparison to kidney were found within every single age group with exception of the oldest. Negative correlation (Ps—Pearson’s correlation) between Zn and Cd concentrations were found in liver samples within the age group of 12 months (Ps = ?0.67, p = 0.004).     

Human induced pluripotent stem cells and their use in drug discovery for toxicity testing

Predicting human safety risks of novel xenobiotics remains a major challenge, partly due to the limited availability of human cells to evaluate tissue-specific toxicity. Recent progress in the production of human induced pluripotent stem cells (hiPSCs) may fill this gap. hiPSCs can be continuously expanded in culture in an undifferentiated state and then differentiated to form most cell types. Thus, it is becoming technically feasible to generate large quantities of human cell types and, in combination with relatively new detection methods, to develop higher-throughput in vitro assays that quantify tissue-specific biological properties. Indeed, the first wave of large scale hiSC-differentiated cell types including patient-derived hiPSCS are now commercially available. However, significant improvements in hiPSC production and differentiation processes are required before cell-based toxicity assays that accurately reflect mature tissue phenotypes can be delivered and implemented in a cost-effective manner. In this review, we discuss the promising alignment of hiPSCs and recently emerging technologies to quantify tissue-specific functions. We emphasize liver, cardiovascular, and CNS safety risks and highlight limitations that must be overcome before routine screening for toxicity pathways in hiSC-derived cells can be established.     

Mutational analysis of three tumor suppressor genes in two models of rat hepatocarcinogenesis.

An albumin-simian virus 40 (SV40) large T-antigen (T-Ag) transgenic model and a chemically induced model of multistage hepatocarcinogenesis were created in our laboratory to study the molecular mechanisms involved in the genesis and progression of neoplasia in the rat liver. In the study presented here, these two models of rat hepatocarcinogenesis were used to perform a comparative mutational analysis of three tumor suppressor genes involved in hepatic neoplastic growth. By using polymerase chain reaction-single strand conformation polymorphism analysis and sequencing, exons 5-8 of the p53 tumor suppressor gene and a region between nt 4325 and 4479 of the rat mannose 6-phosphate/insulin-like growth factor 2 receptor (M6p/Igf2r) coding sequence were screened. The latter is homologous to the human M6P/IGF2r coding sequence which is mutated in human hepatocellular carcinoma. A complete single strand conformation polymorphism analysis of the entire coding region of the rat adenomatous polyposis coli (Apc) gene was also performed for the first time in rat tumorigenic samples. Twenty-six chemically induced rat hepatocellular carcinomas, 21 neoplasms from the livers of SV40 T-Ag animals, and five immortalized hepatic cell lines from the transgenic rats were evaluated. None of the hepatic tumors exhibited mutations in the regions analyzed. The albumin-SV40 T-Ag transgenic cell line L-60, derived from normal hepatic tissue, had two mutations in contiguous codons of exon 5 of the p53 gene: a GGT --> GTT missense transversion in codon 183 and a silent mutation in codon 184. The transversion, which may affect the DNA binding domain of the p53 protein, probably originated during cell culture and may have been positively selected because it gave a growth advantage to the mutated cells. The studied region of the M6p/Igf2r gene was not found to be mutated in these two models of rat hepatocarcinogenesis. Although M6p/Igf2r, Apc, and p53 have been shown to be mutated in a variety of human hepatic proliferative diseases, our results indicate that aberrations in these genes may not be necessary for liver carcinogenesis in the rat.     

Range of motion in the joints of the upper extremity at different stages of sympathetic reflex dystrophy (SRD)]

Sympathetic reflex dystrophy of the upper extremity is among the most serious complications of trauma injuries. The aim of this paper was to assess the effectiveness of mobilization treatment, augmented by cryogenic temperatures of post trauma SRD of the upper extremity. The material comprised 113 patients treated at the Orthopedic Outpatient Clinic of the J. Babiński Hospital in Breslau during the years 1987-1995. All patients underwent conservative treatment because of post trauma SRD. The effectiveness of cryo-therapy was based on pre- and post-therapy ROM examination. These results were compared to the ROM of the healthy extremity and the degree of ROM limitation was hence calculated. Limitation of ROM was found in all joints of the upper extremity regardless to the stage of the disease. The greatest limitations were found in the joints directly adjacent to the area were the disease was most pronounced. The applied therapy in these cases was found to increase ROM in all patients, with the greatest increase of ROM during stage I and II of the disease.     

Prothrombogenic factors and reduced antioxidative defense in children and adolescents with pre-metabolic and metabolic syndrome.

BACKGROUND: The aim of this study was to examine prothrombogenic factors and antioxidative defense in obese children and adolescents with pre-metabolic and metabolic syndrome, and to analyze insulin secretion and resistance, early glycoregulation disorders and lipid status. METHODS: Insulin sensitivity was determined using the homeostasis model assessment for insulin resistance (HOMA-IR), while insulin secretion was determined using the homeostasis model assessment beta (HOMA-beta). Prothrombogenic factors analyzed were plasma plasminogen activator inhibitor-1 (PAI-1) and fibrinogen. Superoxide dismutase and glutathione peroxidase were measured as markers of antioxidative defense. RESULTS: Patients with metabolic syndrome were characterized with increased body mass index (BMI), waist circumference, and HOMA-IR and HOMA-beta levels, and all had increased blood pressure and triglyceride levels, low high-density lipoprotein cholesterol levels, increased PAI-1 levels and reduced antioxidative defense levels. Patients with pre-metabolic syndrome had higher levels of basal and mean insulinemia during an oral glucose tolerance test, higher levels of HOMA-beta and lower levels of antioxidative defense compared to patients with metabolic syndrome. CONCLUSIONS: Negative correlations between antioxidative defense parameters and BMI, abdominal obesity, insulin secretion, systolic blood pressure and atherogenic lipid factors, as well as correlations between PAI-1 and insulin resistance and basal glycemia in the metabolic syndrome group contribute to accelerated atherosclerosis. Positive correlations between PAI-1 and waist circumference and BMI, and negative correlations between BMI and antioxidative defense in the pre-metabolic syndrome patients show that this early stage preceding the metabolic syndrome is also characterized by atherosclerotic complication risks and evident hyperinsulinism and insulin resistance.