Supplementation with Alpha-Tocopherol and Ascorbic Acid to Nonalcoholic Fatty Liver Disease's Statin Therapy in Men.

Oxidative stress and inflammation contribute to the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD), and the control of lipid status by statins may help to stop the progression of NAFLD. We hypothesized that the addition of antioxidant vitamins C and E to atorvastatin therapy is associated with improved serum enzyme antioxidant status. NAFLD-related serum parameters and the activity of antioxidant enzymes, before and after 3 months of treatment, were determined in patients receiving atorvastatin alone or atorvastatin plus antioxidants. Compared to healthy controls, the patients, before receiving therapy, had increased catalase and glutathione reductase, with no significant difference in glutathione peroxidase activity. After the treatment, the levels of all three antioxidant markers were reduced to the same degree in both groups of patients, indicating therapy-induced lower level of reactive oxygen species production and/or improved nonenzymatic antioxidant mechanisms. Both therapies led to the normalization of the serum lipid profile and aminotransferase levels in the patients, but the reduction in CRP, although significant, did not reduce levels to those of the controls. The obtained results favor the notion that therapy with atorvastatin alone is equally efficient during the early stages of NAFLD, regardless of the addition of antioxidant vitamins. This trial is registered with TCTR20180425001.

The impact of vitamin C on the relationship among inflammation, lipid peroxidation and platelet activation during analgesic nephropathy in rats.

BACKGROUND: Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F2α (8-iso-PGF2α) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1ß and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated. METHODS: Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation. RESULTS: The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1ß. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B2. CONCLUSIONS: Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B2 excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.

Sheep and goats as indicator animals for the circulation of CCHFV in the environment.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus, which causes a serious illness with case-fatality rates of up to 80% in humans. CCHFV is endemic in many countries of Africa, Asia and Southeastern Europe. Next to the countries with endemic areas, the distribution of CCHFV is unknown in Southeastern Europe. As the antibody prevalence in animals is a good indicator for the presence or absence of the virus in a region, seroepidemiological studies can be used for the definition of risk areas for CCHFV. The aim of the present study was to reveal which ruminant species is best suited as indicator for the detection of a CCHFV circulation in an area. Therefore, the prevalence rates in sheep, goats and cattle in different regions of Albania and Former Yugoslav Republic of Macedonia were investigated. As there are no commercial tests available for the detection of CCHFV-specific antibodies in animals, two commercial tests for testing human sera were adapted for the investigation of sera from sheep and goats, and new in-house ELISAs were developed. The investigation of serum samples with these highly sensitive and specific assays (94-100%) resulted in an overall prevalence rate of 23% for Albania and of 49% for Former Yugoslav Republic of Macedonia. Significant lower seroprevalence rates for CCHFV were found in cattle than in small ruminants in given areas. These results indicate that small ruminants are more suitable indicator animals for CCHFV infections and should therefore be tested preferentially, when risk areas are to be identified.

Circulation of Crimean-Congo Hemorrhagic Fever Virus in the former Yugoslav Republic of Macedonia revealed by screening of cattle sera using a novel enzyme-linked immunosorbent assay.

BACKGROUND: There are only few assays available for the detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)-specific antibodies in animals, and data about diagnostic sensitivity and specificity are incompletely documented for most of these tests. This is unfortunate since CCHFV antibodies in animals can be used as indicator for virus circulation in a geographic area and therewith potential risk of human exposure. This paper therefore reports on a novel ELISA for the detection of CCHFV-specific antibodies in cattle and on its application for testing ruminant sera from the Former Yugoslav Republic of Macedonia. PRINCIPAL FINDINGS: A highly sensitive and specific ELISA was developed to detect CCHFV-specific IgG antibodies in cattle. The assay was validated by using 503 negative serum samples from a country where CCHFV has never been detected until now, and by using 54 positive serum samples. The positive sera were verified by using two commercially available assays (for testing human serum) which we have adapted for use in animals. The sensitivity of the novel ELISA was 98% and its specificity 99%. The presence of Hyalomma ticks was demonstrated in the Former Yugoslav Republic of Macedonia and depending on the region antibody prevalence rates up to 80% were detected in the cattle population. CONCLUSION: This article describes a fully validated, highly sensitive and specific ELISA for the detection of CCHFV-specific IgG antibodies in cattle. Using this assay, CCHFV-specific antibodies were detected for the first time in cattle in the Former Yugoslav Republic of Macedonia, giving evidence for an active circulation of this virus in the country. Supporting this conclusion, the occurrence of the main vector of CCHFV was demonstrated in the present work for the first time in Former Yugoslav Republic of Macedonia.

D-galactose induced inflammation lipid peroxidation and platelet activation in rats.

BACKGROUND: To investigate events possibly related to the development of D-galactose induced senescence, we examined whether 8-iso PGF(2α) formation, a marker of in vivo lipid peroxidation is altered and whether its biosynthesis is associated with 11-dehydro-TXB(2) excretion rate, as a marker of in vivo platelet activation. In this setting, we also investigated the relationship between proinflammatory mediators (IL-6 and TNF-α from one, and lipid peroxidation and platelet activation, from another aspect. METHODS AND RESULTS: Forty animals were divided, depending on treatment with d-galactose into: placebo and D-galactose treated rats. 8-iso-PGF(2α), IL-6 and TNF-α were measured in plasma, while 11-dehydro-TXB(2) was determined in the urine after a six week treatment with d-galactose. Compared to placebo, d-galactose treated animals showed significantly higher levels of all measured parameters. CONCLUSIONS: D-galactose induced changes in the rate of F(2)-isoprostane formation are associated with the changes in the excretion rate of 11-dehydro-TXB(2).

Gaps in brucellosis eradication campaign in sheep and goats in Republic of Macedonia: lessons learned.

AIM: To identify why "test and slaughter policy" for eradication of brucellosis did not significantly reduce the prevalence in sheep and goats in Macedonia. METHOD: Coverage of sampled vs expected number of sheep and goats, absolute number of positive animals, prevalence, frequency distribution, and classes of disease prevalence were retrospectively analyzed at the village level for 2004-2006. A comparative analysis of the disease prevalence in the investigated villages was also performed. The percentage of slaughtered animals was analyzed for 2000-2006. RESULTS: We found differences between the expected and actual number of sampled animals, which were related to the type of livestock breeding. Traditionally maintained flocks and migratory flocks were considered to be responsible for the transmission of the disease. The absolute number of positive animals and the number of infected vs non-infected holdings did not decrease over the study period. Most of the villages had between 1 and 10 positive animals. Between 2000 and 2006, 55% of the positive animals were slaughtered, 41% in 2001 and up to 79% in 2002. Moreover, in 2005 and 2006, 34% and 53% of sheep and goats were found to be positive at the slaughter line, respectively, demonstrating that only 21%-23% of the infected animals were correctly removed from the herds. CONCLUSION: Based on the findings of this study, Macedonia changed its control strategy from "test and slaughter" to a vaccination policy for sheep and goats in 2008.