Levels of Amyloid Beta-42, Interleukin-6 and Tumor Necrosis Factor-Alpha in Alzheimer’s Disease and Vascular Dementia

Amyloid β42 (Aβ42) and proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been suggested to contribute to the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Our aim was to examine whether the changes in these parameters would be able to discriminate the patients with AD from those with VaD and from healthy individuals. We have analyzed the levels of Aβ42, IL-6 and TNF-α in the serum of newly diagnosed 28 AD patients, 16 VaD patients and 26 healthy non-demented controls. We also investigated whether there is an association between Aβ42, IL-6 and TNF-α levels and mini-mental state examination (MMSE) scores and body mass indexes (BMI) of patients. Our data showed a significant decrease in serum Aβ-42 levels in AD patients compared to VaD patients and controls. Levels of IL-6 and TNF-α were not different between AD patients, VaD patients and controls. We observed a correlation between Aβ-42 levels and MMSE scores and BMI levels in both AD and VaD patients. However, Aβ-42 levels were not correlated with IL-6 and TNF-α levels. Significantly lower levels of Aβ42 found in the serum of AD patients than that of VaD patients and controls suggests that it can be a specific biochemical marker for AD.     

Phytochemical Composition and Antioxidant Activities of the Essential Oil and Extracts of Satureja subspicata Vis. Growing in Bosnia and Herzegovina

The phytochemical composition and the antioxidant activities of the essential oil, as well as methanol and hot water extracts of endemic Satureja subspicata Vis . growing in Bosnia and Herzegovina (BiH), were described. β‐Caryophyllene, cis‐β‐ocimene, and α‐pinene, identified by GC/MS and GC‐FID, were the dominant oil components. The major compound of both of extracts, identified by HPLC‐DAD, was rosmarinic acid. The analyzed essential oil showed moderate antioxidant activity. In this first report on the extracts of S. subspicata growing in BiH, the obtained results showed a high content of rosmarinic acid, as well as considerable amount of total phenols and flavonoids. Compared to the hot water extract, the methanol extract exhibits higher antioxidant potential, measured by DPPH and FRAP assay (IC₅₀ = 0.45 g/l and 1879.43 equiv. Fe²⁺ μm ), while the hot water extract showed higher potential in inhibition of linoleic acid oxidation (51.7% and 61.5% for 1 and 10 g/l). A good antioxidant potential of the tested extracts indicates their potential use as antioxidants, particularly for lipid protection, and partly explains the justification of the use of this plant in traditional medicine of BiH.     

Assessment of serum thiol/disulfide homeostasis in multiple myeloma patients by a new method

Objectives: The etiology of multiple myeloma (MM) is not exactly known. This study investigated the role of thiol/disulfide homeostasis in the etiopathogenesis of MM.

Methods: Some 50 patients with MM (aged 39–84 years) and 50 sex-matched healthy volunteer controls (aged 50–91 years) participated in this study. Venous blood samples were collected, and levels of native thiols, total thiols, and disulfide were measured.

Results: Native and total thiol levels in the control group were determined to be higher than in the study and patient groups (P<0.001). Disulfide levels were found to be higher in the control group than in the study group and higher in newly diagnosed patients than in outpatients who were undergoing treatment (P=0.002). The ratios of thiol levels were found to be similar in both the study and control groups (P>0.05).

Discussion: The results of the study show that although there was a decrease in the levels of disulfide, native thiol, and total thiol, the balance of thiol/disulfide was maintained. This is the first study to research the homeostasis of dynamic thiol/disulfide from the perspective of the new method that was used. We hope that this study will encourage and facilitate further studies in this area.     

Effects of carvacrol on defects of ischemia-reperfusion in the rat liver

Many plants found in nature have been used to treat various illnesses. One such plant is oregano (Kekik in Turkish). Health beneficial effects of carvacrol obtained from oregano oil have been shown scientifically. We have investigated the comparative effects of carvacrol in the liver of rats subjected to ischemia-reperfusion defect, with silymarin. To test the effects we formed four groups using male Wistar albino rats. Group I was control. The other three groups of animals were administered 60 min prior to surgical operation single doses of physiological serum, carvacrol and silymarin, respectively. Group II, III and IV animal were subjected to 45 min long liver ischemia and 60 min reperfusion. Blood and tissue samples were collected for biochemical and histological analysis following the test.AST and ALT values obtained after biochemical analysis of the serums showed statistically significant difference in group II than the other three groups. A statistical evaluation of the serum AST levels among the groups II, III and IV showed that both groups III and IV which had no difference in between were significantly different in a positive way from group II (p<0.001). As to the serum ALT levels, difference between group II and group III (p<0.001) and group II and group IV (p<0.01) was found significant. No statistical difference was observed in groups I, III and IV for GSH, MDA and CAT levels of the liver. A statistical evaluation of the GSH level in group III and group IV was found to be significantly different from group II (p<0.001) without any difference between them. A similar evaluation for MDA and CAT levels among the revealed no difference between group III and group IV, however, group II showed difference with group II and group IV (p<0.05).Histological findings were in harmony with the biochemical results. We conclude that carvacrol protects the liver against defects caused by ischemia and reperfusion, and carvacrol is not hepatotoxic at the applied dosage.     

Effects of Aminoguanidine on Glomerular Basement Membrane Thickness and Anionic Charge in a Diabetic Rat Model

We investigated the effect of aminoguanidine (AG) administration on GBM thickness, glomerular heparan sulfate (HS) content, and urinary albumin and HS excretion in diabetic rats. After induction of diabetes, female Wistar rats were divided into 2 groups: Group AGDM (n=11) received 1g/L aminoguanidine bicarbonate in drinking water, group DC (n=12) was given only tap water. Control rats received AG (group AGH, n=8) or tap water (group HC, n=8). At the end of a period of 8 weeks, urinary albumin and glycosaminoglycan (GAG) excretion was detected. GBM heparan sulfate distribution and count was determined under the electron microscope. The AGDM group had lower urinary albumin and GAG excretion than diabetic controls. GBM thickness was increased in diabetic rats compared to groups of AGDM and HC. In AGDM group alcian blue stained particle distribution and count in the GBM was similar to healthy controls. In conclusion AG prevents the decrease of anionic charged molecules in the GBM and GBM thickening. This can be one of the mechanisms by which AG decreases albuminuria in diabetic rats.     

Effects of vitamin C and vitamin E on lipid peroxidation, blood serum metabolites, and mineral concentrations of laying hens reared at high ambient temperature

This study was conducted to determine the effects of vitamin C (L-ascorbic acid) and vitamin E (alpha-tocopherol acetate) on serum concentrations of lipid peroxidation (MDA) and triiodothyronine (T3), thyroxine (T4), adrenocorticotropic hormone (ACTH), and some metabolite and mineral in laying hens reared at high ambient temperatures ranging from 25 degrees C to 35 degrees C. One hundred twenty laying hens (18 wk old; Hy-Line) were divided into 4 groups, 30 hens per group. The laying hens were fed either a basal diet (control) or the basal diet supplemented with either 250 mg of L-ascorbic acid/kg of diet (vitamin C), 250 mg of alpha-tocopherol acetate/kg of diet (vitamin E), or 250 mg of L-ascorbic acid plus 250 mg alpha-tocopherol acetate/kg of diet (combination). Separately or as a combination vitamins C and E increased serum vitamin C and vitamin E concentrations (p < 0.001) but decreased serum MDA concentration (p < 0.05). Serum concentrations of vitamin E and vitamin C were found highest but serum MDA concentration was lowest in the combination group. Supplemental vitamins C and E either separately or in a combination increased serum T3 and T4 concentrations (p < 0.05), whereas decreased serum ACTH concentration (p < 0.01). Serum glucose and cholesterol concentrations decreased, whereas serum protein concentration increased (p < 0.05) when vitamins C and E singly or together were added to the diet. Vitamin C and vitamin E supplementation resulted in an increase in serum concentrations of Ca, P, and K (p < 0.01) but a decrease in serum concentration of Na (p < 0.05). The results of the present study suggest that supplemental vitamin C and vitamin E alter serum lipid peroxidation, vitamin C, vitamin E and metabolite status, and diets supplemented with a combination of these two vitamins offer a good management practice in laying hens reared at high temperatures. In addition, the results suggest that dietary vitamin C and vitamin E act synergistically.     

Interferon-alpha reduces the development of experimental necrotizing enterocolitis

Cytokines had important role in the pathogenesis of necrotizing enterocolitis (NEC). The aim of this study is to investigate if IFN-alpha has a prophylaxic effect on experimental NEC development in newborn rat pups. Twenty eight Wistar Albino newborn rat pups were divided into three groups. Control group rats were breast-fed, NEC group and interferon (IFN) group rat pups were hand-fed with premature newborn formula. IFN-alpha was administered subcutaneously at a dose of 50,000 IU/rat/day in IFN group. NEC was induced experimentally by cold stress twice a day in IFN and NEC groups. On the fourth day, the rats were killed, and all the intestine were removed to determine the tissue level of malonaldehyde (MDA) and histologic changes. The microscopic lesions in the NEC group rats were virtually the same as those seen in neonatal NEC, with severe separation of submucosa and/or lamina propria, loss of villi and in some cases necrosis to extention the muscularis. In contrast, in the rats treated with IFN, lesions were moderate separation of submucosa and/or lamina propria, edema in submucosal and muscular layers. Intestinal injury score and MDA levels in NEC group were significantly higher than in the IFN group (P<0.05). In conclusion it was suggested that IFN-alpha was effective in reducing the severity of NEC in rat pups.     

Investigating Voluntary Medical Male Circumcision Program Efficiency Gains through Subpopulation Prioritization: Insights from Application to Zambia

Background

Countries in sub-Saharan Africa are scaling-up voluntary male medical circumcision (VMMC) as an HIV intervention. Emerging challenges in these programs call for increased focus on program efficiency (optimizing program impact while minimizing cost). A novel analytic approach was developed to determine how subpopulation prioritization can increase program efficiency using an illustrative application for Zambia.

Methods and Findings

A population-level mathematical model was constructed describing the heterosexual HIV epidemic and impact of VMMC programs (age-structured mathematical (ASM) model). The model stratified the population according to sex, circumcision status, age group, sexual-risk behavior, HIV status, and stage of infection. A three-level conceptual framework was also developed to determine maximum epidemic impact and program efficiency through subpopulation prioritization, based on age, geography, and risk profile. In the baseline scenario, achieving 80% VMMC coverage by 2017 among males 15–49 year old, 12 VMMCs were needed per HIV infection averted (effectiveness). The cost per infection averted (cost-effectiveness) was USD $1,089 and 306,000 infections were averted. Through age-group prioritization, effectiveness ranged from 11 (20–24 age-group) to 36 (45–49 age-group); cost-effectiveness ranged from $888 (20–24 age-group) to $3,300 (45–49 age-group). Circumcising 10–14, 15–19, or 20–24 year old achieved the largest incidence rate reduction; prioritizing 15–24, 15–29, or 15–34 year old achieved the greatest program efficiency. Through geographic prioritization, effectiveness ranged from 9–12. Prioritizing Lusaka achieved the highest effectiveness. Through risk-group prioritization, prioritizing the highest risk group achieved the highest effectiveness, with only one VMMC needed per infection averted; the lowest risk group required 80 times more VMMCs.

Conclusion

Epidemic impact and efficiency of VMMC programs can be improved by prioritizing young males (sexually active or just before sexual debut), geographic areas with higher HIV prevalence than the national, and high sexual-risk groups.