Adverse and hormetic effects in rats exposed for 12 months to low dose mixture of 13 chemicals: RLRS part III.

The aim of the current study was to evaluate the effects of a mixture of thirteen common chemicals on rats, after a one-year exposure to doses around the acceptable daily intake (ADIs), using blood and urinary tests. The influence of low doses of the mixture on weight gain, water consumption, feed consumption and feed efficiency, biochemistry parameters, haematological parameters, blood lymphocytes subsets, serum inflammation profile and urine parameters was evaluated. Our mixture caused a moderate monotonic increase of the males' appetite and a non-monotonic increase of anabolism and a monotonic increase of appetite for the females. Regarding biochemical parameters, the exposure to the test mixture caused non-monotonic increases of AST and ALT, a decrease of PChE in males and plausibly a monotonic biliary obstruction in both sexes. Monocytes significantly increased in low dose groups of both sexes. A significant decrease of all the lymphocytes subclasses and an increased expression of TNF-α protein associated with an increased expression of IFN-γ protein observed in various groups. It became apparent that after twelve months of exposure very low doses of the tested mixture had both non-monotonic and monotonic harmful effects on different levels on rats.

Six months exposure to a real life mixture of 13 chemicals' below individual NOAELs induced non monotonic sex-dependent biochemical and redox status changes in rats.

This study assessed the potential adverse health effects of long-term low-dose exposure to chemical mixtures simulating complex real-life human exposures. Four groups of Sprague Dawley rats were administered mixtures containing carbaryl, dimethoate, glyphosate, methomyl, methyl parathion, triadimefon, aspartame, sodium benzoate, calcium disodium ethylene diamine tetra-acetate, ethylparaben, butylparaben, bisphenol A, and acacia gum at doses of 0, 0.25, 1 or 5 times the respective Toxicological Reference Values (TRV): acceptable daily intake (ADI) or tolerable daily intake (TDI) in a 24 weeks toxicity study. Body weight gain, feed and water consumption were evaluated weekly. At 24 weeks blood was collected and biochemistry parameters and redox status markers were assessed. Adverse effects were observed on body weight gain and in hepatotoxic parameters such as the total bilirubin, alanine aminotransferase (ALT) and alkaline phosphatase (ALP), especially in low dose and affecting mainly male rats. The low dose group showed increased catalase activity both in females and males, whereas the high dose group exhibited decreased protein carbonyl and total antioxidant capacity (TAC) levels in both sex groups. Non-monotonic effects and adaptive responses on liver function tests and redox status, leading to non-linear dose-responses curves, are probably produced by modulation of different mechanisms.

A guide to acquired vitamin K coagulophathy diagnosis and treatment: the Russian perspective.

Physicians often come across with cases of vitamin K antagonists-dependent coagulopathy for reasons such as accidental use of the vitamin K antagonists (VKA), excessive administration of prescribed anticoagulants of indirect action or not reported administration of vitamin K antagonists due to memory impairment and/or other mental disorders, even deliberate use thereof (attempt to murder or suicide). Rodenticide-poisoning (coumarins, warfarins) via food or occupational accidents are difficult to diagnose. This article discusses different types of acquired vitamin K-dependent coagulopathy. Differential diagnosis is primarily based on patient statements before additional causes of vitamin K deficiency are explored. Even when pathological vitamin K deficiency is not determined, appropriate and urgent medical treatment is necessary: administration of fresh frozen plasma or concentrated factors of the prothrombin complex, administration of vitamin K remedies along with symptomatic therapy. With early diagnosis and prescription of appropriate therapy, prognosis is favorable. Reasons for vitamin K antagonists-dependent coagulopathy cases.

Antimicrobial resistance development following surgical site infections.

Surgical site infections (SSIs) determine an increase in hospitalization time and antibiotic therapy costs. The aim of this study was to identify the germs involved in SSIs in patients from the Clinical Emergency County Hospital of Craiova (SCJUC) and to assess their resistance to antimicrobials, with comparisons between surgical wards and the intensive care unit (ICU). The biological samples were subjected to classical bacteriological diagnostics. Antibiotic resistance was tested by disc diffusion. We used hierarchical clustering as a method to group the isolates based upon the antibiotic resistance profile. The most prevalent bacterial species isolated were Staphylococcus aureus (S. aureus; 50.72%), followed by Escherichia coli (E. coli; 17.22%) and Pseudomonas aeruginosa; 10.05%). In addition, at lower percentages, we isolated glucose-non-fermenting, Gram-negative bacteria and other Enterobacteriaceae. The antibiotic resistance varied greatly between species; the most resistant were the non-fermenting Gram­negative rods. E. coli exhibited lower resistance to third generation cephalosporins, quinolones and carbapenems. By contrast, Klebsiella was resistant to many cephalosporins and penicillins, and to a certain extent to carbapenems due to carbapenemase production. The non-fermenting bacteria were highly resistant to antibiotics, but were generally sensitive to colistin. S. aureus was resistant to ceftriaxone (100%), penicillin (91.36%), amoxicillin/clavulanate (87.50%), amikacin (80.00%) and was sensitive to levofloxacin, doxycycline, gentamycin, tigecycline and teicoplanin. The Enterobacteriaceae resistance was only slightly higher in the ICU, particularly to carbapenems (imipenem, 31.20% in the ICU vs. 14.30% in the surgical wards; risk ratio = 2.182). As regards Staphylococcus species, but for non-fermenting bacteria, even if the median was almost the same, the antibiotic resistance index values were confined to the upper limit in the ICU. The data gathered from this study may help infection control teams to establish effective guidelines for antibiotic therapies in various surgical procedures, in order to minimize the risk of developing SSIs by the efficient application of the anti-infection armamentarium.

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well­designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.

Immunohistochemical expression of TGF beta (TGF-ß), TGF beta receptor 1 (TGFBR1), and Ki67 in intestinal variant of gastric adenocarcinomas.

Although in the last decades the incidence of gastric cancer declined, at present it is ranked worldwide on the fourth place between all human cancer pathology. Also, it has an aggressive behavior, the majority of patients being diagnosed in advanced stages. One of the key factors to control survival improvement of those patients is to clarify the molecular mechanisms involved in initiation, progression, invasion, and metastasis of gastric cancer. We thus investigated the immunoreactivity for TGF-ß, TGFBR1, and Ki67 of 25 specimens of intestinal gastric adenocarcinomas, and compared this with the correspondent reactivity for three specimens of diffuse gastric carcinomas; in the end, we tried to establish a statistical correlation with major clinicomorphological parameters. As a result, we noticed that the highest reactivity was present in the diffuse type compared with the intestinal variant, in which the TGF-ß reactivity progressively increased along the normal epithelium-intestinal metaplasia-dysplasia-carcinoma sequence. Also, we found for intestinal variant that TGF-ß immunoreactivity correlated significantly with tumor degree of differentiation and proliferative activity measured based on Ki67 immunoreactivity. In conclusion, TGF-ß is implicated in the progression of intestinal type of gastric adenocarcinomas and its immunoreactivity assessment for these targets has a prognostic value.

Antiviral therapy effects upon hepatitis C cholestatic syndrome.

Cholestasis includes, as a syndrome, all clinical and biological manifestations caused by the deficient or simply absent biliar secretion or caused by the obstruction of the biliary ducts. The hepatic cholestasis from the chronic hepatitis C (HC VHC) is a result of the altered interlobular biliary canalicules, caused by the modified cellular transport mechanisms and it is associated with a medium to severe degree of fibrosis. The aim of this study was to evaluate the efficiency of antiviral therapy in HC VHC patients. The study included a number of 37 HC VHC patients admitted at the Medical Department no. 1 of the Emergency County Hospital of Craiova; they were treated with Pegasys, 180 microg/week and Copegus, 1000 or 1200 mg/day, taking in consideration their weight, for 48 weeks and they were monitored for 24 weeks after the treatment. The following parameters were analyzed: direct bilirubine, total cholesterol, alkaline phosphatase, gamma-glutamiltranspeptidase and leucin-aminopeptidase. Under treatment, the clinical status caused by the cholestasis (pruritus, icteric syndrome, hemoragipary syndrome) was improved in six of the given cases (16.22%). Before therapy, the hepatic cholestasis was present in 20 patients (54.05%), and after treatment in 14 patients (37.83%). During therapy, the average values for all the monitored parameters decreased: direct bilirubine (0.38 +/- 0.18 mg/dl vs. 0.34 +/- 0.24 mg/dl, p = 0.0867), total cholesterol (198.53 md/dl vs. 183.16 mg/dl, p = 0.0808), alkaline phosphatase (236.99 +/- 79.09 iu/l vs. 227.82 +/- 87.59 iu/l, p = 0.0845), gamma-glutamiltranspeptidase (47 +/- 32.89 iu/l vs. 43.91 +/- 29.66 iu/l, p = 0.1509), and leucin-aminopeptidase (32.33 +/- 13.22 iu/l vs. 28.95 +/- 14.22 iu/l, p = 0.0038). Under antiviral treatment there was noticed an improvement of the cholestasis clinical status in a small number of cases. Antiviral therapy favorably influenced the liver cholestasis associated in patients with chronic hepatitis C in a rather small proportion. Under Interferon pegylate and Ribavirine treatment, low levels of direct bilirubine, cholesterol and enzymes were found. Hepatic cholestasis and, especially, the high serum values of gamma-glutamiltranspeptidase have a negative influence upon antiviral therapy, causing the low sustained virological response.