Puumala Orthohantavirus Reassortant Genome Variants Likely Emerging in the Watershed Forests.

Hemorrhagic fever with renal syndrome (HFRS) remains a prevalent zoonosis in the Republic of Tatarstan (RT), Russian Federation. Puumala orthohantavirus (PUUV), carried by bank voles (Myodes glareolus), is the principal zoonotic pathogen of HFRS in the RT. In this study, we sought to demonstrate the similarity of the PUUV genetic sequences detected in HFRS case patients and bank vole samples previously collected in some areas of the RT. Furthermore, we intended to identify the reassortant PUUV genomes and locate a potential site for their emergence. During 2019 outbreaks, the PUUV genome sequences of the S and M segments from 42 HFRS cases were analysed and compared with the corresponding sequences from bank voles previously trapped in the RT. Most of the PUUV strains from HFRS patients turned out to be closely related to those isolated from bank voles captured near the site of the human infection. We also found possible reassortant PUUV genomes in five patients while they were absent in bank voles. The location of the corresponding HFRS infection sites suggests that reassortant PUUV genomes could emerge in the bank voles that inhabit the forests on the watershed between the Kazanka River and Myosha River. These findings could facilitate the search for the naturally occurring reassortants of PUUV in bank vole populations.

Analysis of Puumala orthohantavirus Genome Variants Identified in the Territories of Volga Federal District.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease commonly diagnosed in the Volga Federal District (VFD). HFRS is caused by Puumala orthohantavirus (PUUV), and this virus is usually detected in bank voles as its natural host (Myodes glareolus). The PUUV genome is composed of the single-stranded, negative-sense RNA containing three segments. The goal of the current study is to identify genome variants of PUUV strains circulating in bank voles captured in the Udmurt Republic (UR) and Ulyanovsk region (ULR). The comparative and phylogenetic analysis of PUUV strains revealed that strains from Varaksino site UR are closely related to strains previously identified in the Pre-Kama area of the Republic of Tatarstan (RT), whilst strains from Kurlan and Mullovka sites ULR are similar to strains from the Trans-Kama area of the RT. It was also found that Barysh ULR strains form a separate distinct group phylogenetically equidistant from Varaksino and Kurlan−Mullovka groups. The identified groups of strains can be considered as separate sub-lineages in the PUUV Russian genetic lineage. In addition, the genomes of the strains from the UR, most likely, were formed as a result of reassortment.

Interaction of the pitavastatin with model membranes.

Pitavastatin is a statin drug that, by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can lower serum cholesterol levels of low-density lipoprotein (LDL) accompanied by side effects due to pleiotropic effects leading to statin intolerance. These effects can be explained by the lipophilicity of statins, which creates membrane affinity and causes statin localization in cellular membranes. In the current report, the interaction of pitavastatin with POPC model membranes and its influence on the membrane structure were investigated using H, H and P solid-state NMR spectroscopy. Our experiments show the average localization of pitavastatin at the lipid/water interface of the membrane, which is biased towards the hydrocarbon core in comparison to other statin molecules. The membrane binding of pitavastatin also introduced an isotropic component into the 31P NMR powder spectra, suggesting that some of the lamellar POPC molecules are converted into highly curved structures.

The Distribution of Puumala orthohantavirus Genome Variants Correlates with the Regional Landscapes in the Trans-Kama Area of the Republic of Tatarstan.

In the European part of Russia, the highest number of hemorrhagic fever with renal syndrome (HFRS) cases are registered in the Volga Federal District (VFD), which includes the Republic of Tatarstan (RT). Puumala orthohantavirus (PUUV) is the main causative agent of HFRS identified in the RT. The goal of the current study is to analyze the genetic variations of the PUUV strains and possible presence of chimeric and reassortant variants among the PUUV strains circulating in bank vole populations in the Trans-Kama area of the RT. Complete S segment CDS as well as partial M and L segment coding nucleotide sequences were obtained from 40 PUUV-positive bank voles and used for the analysis. We found that all PUUV strains belonged to RUS genetic lineage and clustered in two subclades corresponding to the Western and Eastern Trans-Kama geographic areas. PUUV strains from Western Trans-Kama were related to the previously identified strain from Teteevo in the Pre-Kama area. It can be suggested that the PUUV strains were introduced to the Teteevo area as a result of the bank voles' migration from Western Trans-Kama. It also appears that physical obstacles, including rivers, could be overcome by migrating rodents under favorable circumstances. Based on results of the comparative and phylogenetic analyses, we propose that bank vole distribution in the Trans-Kama area occurred upstream along the river valleys, and that watersheds could act as barriers for migrations. As a result, the diverged PUUV strains could be formed in closely located populations. In times of extensive bank vole population growth, happening every 3-4 years, some regions of watersheds may become open for contact between individual rodents from neighboring populations, leading to an exchange of the genetic material between divergent PUUV strains.

Cardioprotective effect of caffeic acid phenethyl ester on cardiac contusion following blunt chest trauma in rats.

We investigated the effects of caffeic acid phenethyl ester (CAPE) on cardiac damage after blunt chest injury. Forty male adult Wistar albino rats were divided into four groups; control, cardiac contusion, cardiac contusion + CAPE, and CAPE. CAPE, 10 mmol/kg, was administered intraperitoneally for 7 days following cardiac contusion. Heart tissue and blood were obtained at the end of the experimental period. Cardiac histopathology was determined using hematoxylin & eosin (H & E) staining. Expression of tumor necrosis factor-alpha (TNF-α) in cardiomyocytes was determined using immunohistochemistry. Cardiac apoptosis was determined using the TUNEL method. Serum creatine kinase (CK), creatine kinase-muscle/brain (CK-MB) and lactate dehydrogenase (LDH) levels were determined using spectrophotometric methods. The serum cardiac troponin I (C-TI) level was measured using the ELISA method. Myofibril loss was detected in the cardiomyocytes of the cardiac contusion group. Increased apoptosis and TNF-α expression were observed in the cardiac contusion group compared to the control group. Increased CK, CK-MB, LDH and C-TI levels were found in the cardiac contusion group. We found that CAPE administration improved myocardial function. Compared to the cardiac contusion group, CK, CK-MB, LDH and C-TI levels decreased significantly in the cardiac contusion + CAPE group. Administration of CAPE significantly inhibited apoptosis and cardiac TNF-α expression. Our findings demonstrate the therapeutic effects of CAPE for cardiac contusion damage after blunt chest trauma.

Midkine levels and its relationship with atherosclerotic risk factors in essential hypertensive patients.

BACKGROUND AND OBJECTIVES: Hypertension (HT) is one of the risk factors associated with atherosclerosis. Midkine (MK) plays a role as a growth factor in various biologic and pathologic events. In some reports, MK expression has been shown to be linked with vascular smooth muscle proliferation and neo-angiogenesis in atherosclerotic vessels. The aim was to research relationship of MK serum levels with some atherosclerotic risk factors in hypertensive patients. METHODOLOGY: This study examined 60 patients with essential HT and 30 healthy controls. Serum biochemistry, including lipid profile, MK, Vitamin B12, C-reactive protein, zinc and copper levels were obtained. RESULTS: MK levels of the HT patients were significantly higher than the control group (24.8 ± 6.8 ng/mL vs. 18.39 ± 5.6 ng/mL, respectively, P < 0.01). Lipid profile parameters such as total cholesterol, triglyceride, low-density lipoprotein (LDL) were also significantly higher in HT patients (P < 0.021, P < 0.01, and P < 0.01, respectively). Zinc levels were 179.13 ± 34.06 µg/dL and 172.55 ± 45.47µg/dL in the HT and control group, respectively. Serum MK levels were positively correlated with diastolic (r = 0.288, P < 0.05) and systolic blood pressures (r = 0.390, P < 0.002), and also with serum total cholesterol (r = 0.406, P < 0.002) and LDL cholesterol (r = 0.318, P < 0.015) levels. Furthermore MK was also negatively correlated with zinc and Vitamin B12levels (r = -0.298, P < 0.023, r = -0.334, P < 0.027, respectively). CONCLUSION: This study has demonstrated an important association between increased serum MK levels and risk factors of atherosclerosis such as HT, increased total and LDL cholesterol.

Biological properties and pathogenicity factors of Helicobacter pylori.

The unexpected discovery of Helicobacter pylori (H. pylori) has revolutionised the history of microbiology as well as of gastroenterology in the last 30 years, with an invaluable benefit for millions of persons worldwide. The confirmation that this Gram-negative spiral bacterium could live in the stomach has rendered out-of-date the concept of inhospitality of micro-organisms in the gastric environment, after a long history of unheard reports on the presence of spiral bacteria in the stomach. The pathogenicity of H. pylori depends on its ability to colonize as well as the capability to survive in the harsh gastric environment. This is possible by a coevolution between the pathogen itself and the host. Any perturbation of this equilibrium disrupts the host-pathogen interaction, promoting the pathological effects. H. pylori has a wide range of pathogenicity factors, in particular cytotoxins, enzymes of aggression, and factors providing protection against human defense systems. The most well-characterized cytotoxins contributing to epithelial cell damage are the vacuolating cytotoxin A (VacA) and the cytotoxin-associated gene A (CagA). Only detailed knowledge of the microbiology and genomics of H. pylori infection will allow a vaccine to be produced. Today, we know that H. pylori induces strong humoral and cellular immune responses, but these are incapable of eliminating the bacterium, raising doubts about the possibility of developing an effective vaccine easily. This review highlights microbiological findings concerning H. pylori infection, focusing on colonization, survival and pathogenicity.

RED CELL DISTRIBUTION WIDTH AND ACUTE COMPLICATIONS OF DIABETES.

CONTEXT: Red cell distribution width (RDW) has been associated with type 2 diabetes (T2DM), however data in relation to diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar non-ketotic acidosis (HONK) remains unclear. OBJECTIVE: The aim of this study was to evaluate the association between RDW, MCV, and RDW/MVC values and acute complications in T2DM. PATIENTS AND METHODS: RDW was measured in 90 T2DM patients (30 DKA, 30 HONK and 30 T2DM without acute complications). Clinical variables were analyzed by One -Way ANOVA, Kruskal-Wallis and Pearson analysis with SPSS software. Diagnostic screening tests and ROC curve analysis determined the cut-off point of MCV,RDW and RDW/MCV values. RESULTS: DKA patients had higher levels of plasma glucose (524.20±201.43mg/dL, p<0.001), HbA1c (10.73±2.29%, p<0.001), osmotic pressure (310.32 mosm/L, p<0.001), RDW (14.61±1.75g/L, p<0.01), and the RDW/MCV ratio (0.17±0.04%, p<0.01), compared to HONK patients. RDW/MCV cut-off value was 0.15 with 90% sensitivity 50% specifity these values for only MCV were 76.67%-70%, for only RDW were 76.67%-63.33% respectively. The area under curve values for the ability to reflect DKA for RDW and the RDW/MCV ratio were 0.708 and 0.766, respectively (p<0.001). CONCLUSIONS: RDW and RDW/MCV ratio were found associated with DKA and valuable in predicting DKA. However these parameters were not valuable in predicting HONK.

Evaluation of human chaperonin 10 and high-sensitivity C-reactive protein levels of infertile women who underwent ovulation induction and intra-uterine insemination.

INTRODUCTION: The implantation of embryo is one of the crucial steps of a successful pregnancy. The foetus should be protected from maternal immune system, for the appropriate implantation and modification in maternal immunity is crucial. We investigated high-sensitivity C-reactive protein (hs CRP), which is an indicator of low-grade inflammation and Cp10 that has immunosuppressant and growth-promoting capabilities at embryo levels in ovulation induction and intra-uterine insemination (IUI)applied in infertile women. The ovulation induction was maintained by clomiphene citrate or gonadotropins for 42 infertile patients. After successful ovulation induction, IUI was carried out. The blood samples were taken 2 and 8 days after IUI to evaluate Cp10 and hs CRP levels. The pregnant and non-pregnant groups' results were analyzed. The Cp10 levels 8 days after IUI were higher in pregnant group, whereas there was no difference for the 2 days after levels between pregnant and non-pregnant group. The hs CRP levels were similar for both 2nd and 8th days when we compared pregnant and non-pregnant groups. The Cp10 levels increased from day 2 to day 8 in pregnant group. In contrast, the Cp10 levels decreased in non-pregnant group. The change in hs CRP levels from day 2 to day 8 was not significant in pregnant and non-pregnant groups. The Cp10 levels were higher in early phases of fertilisation and elevated through the preceding days of conception in pregnant patients, while it decreased in non-pregnant patients with failed cycles.

Atherosclerosis, some serum inflammatory markers in psoriasis.

AIM: Psoriasis is an autoimmune inflammatory disease which is associated with increased inflammatory markers and atherosclerosis. We wanted to investigate whether there is a relationship between some inflammatory markers and subclinical atherosclerosis markers. METHODS: We studied 60 psoriasis patients and 50 healthy controls. Demographic, biochemical parameters, C3, C4, d-dimer, CRP, fibrinogen and YKL-40 (human cartilage glycoprotein-39) levels were measured. After measuring carotid intima-media thickness (cIMT) and aortic elasticity parameters such as aortic strain, (beta) stiffness index and compliance, statistical comparisons were done. RESULTS: Patients with psoriasis had significantly higher diastolic blood pressure, CRP, fibrinogen, C3, uric acid levels, ß-stiffness index, and cIMT values than the control group. cIMT was correlated with CRP, YKL-40 and psoriasis area and severity index (PASI) score (r=0.219, P=0.038; r=0.225, P=0.033 and r=0.275, P=0.034). Aortic strain (%), aortic compliance and aortic stiffness index were correlated with C3 (r=-0.349, r=-0.526 and r=0.235) and fibrinogen (r=-0.354, r=-0.275 and r=0.289), all P values <0.05, but not with PASI score. The presence of psoriasis was related to aortic strain (ß±SE: -2.055±0.861, P=0.019) and ß-stiffness index (ß±SE: 2.934±1.143, P=0.012). CONCLUSION: Serum C3, CRP, fibrinogen and YKL-40 levels are elevated as well as increased cIMT and impaired aortic elasticity in psoriasis. CRP, YKL-40 and PASI score are correlated with cIMT. Increased serum C3 and fibrinogen levels correlate negatively with aortic strain and aortic compliance, and correlate positively with the ß-stiffness index.

The relationship between fibroblast growth factor 23 and osteoporosis in postmenopausal women.

AIM: A lack of estrogen in postmenopausal women is an important factor causing the development of osteoporosis. Our purpose is to investigate the effects of Fibroblast Growth Factor 23 (FGF-23) on bone mineral metabolism and bone turnover. METHODS: Twenty-eight patients with postmenopausal osteoporosis (PMO), 32 patients with postmenopausal osteopenia and 30 healthy control subjects (postmenopausal non-osteoporosis) were included in this study. In order to assess the bone mineral metabolism; FGF 23, parathyroid hormone, vitamin D, calcium, phosphate, osteocalcin, alkaline phosphatase and hydroxyproline levels were measured. RESULTS: FGF 23 levels were found significantly higher in PMO group compared with postmenopausal osteopenia and control groups (P<0.01 and P<0.05 respectively). Urine hydroxyproline level was detected to be significantly lower in PMO patients compared with control group (P<0.01). Lomber and femur BMD levels were found to be significantly lower in PMO patients compared with postmenopausal osteopenia and control groups (P<0.001, P<0.001; P<0.001, P<0.001 respectively). On the other hand, when we categorized the PMO group subjects according to the age of menopause, the FGF 23 levels were found to be significantly higher in the group of menopausal age <5 years compared to the group of menopausal age >10 and to the group of menopausal age 5-10 years (P<0.05, P<0.05). CONCLUSION: We think our findings indicate that serum FGF 23 level is a significant determinant of increased bone turnover at early periods in PMO patients.

Trace elements and toxic heavy metals play a role in Buerger disease and atherosclerotic peripheral arterial occlusive disease.

AIM: The aim of the present study was to define the roles of trace elements and toxic heavy metals in Buerger disease and atherosclerotic peripheral arterial occlusive disease (PAOD). METHODS: Seventy-five subjects who were identical in demographic charecteristics were selected for the study; 25 with Buerger disease, 25 with PAOD, 25 healthy volunteers. Serum selenium (Se), zinc (Zn), copper (Cu), iron (Fe),whole blood cadmium (Cd) and lead (Pb), erythrocyte glutathione (GSH), erythrocyte glutathione peroxidase (GSH-Px), erythrocyte and plasma malondialdehyde (MDA) levels were measured. RESULTS: Serum Se and Zn levels were significantly low in patients with Buerger disease compared to patients with PAOD and controls (P<0.001 and P<0.001 respectively). Serum levels of Fe and Zn were also significantly low in patients with PAOD compared to controls (p<0.001 and p<0.05 respectively). In contrast, Cu and Pb levels in Buerger disease group were significantly high compared to PAOD and control groups (P<0.001 and P<0.001 respectively). Erythrocyte GSH and GSH-Px levels were significantly lower in patients with Buerger disease compared to patients with PAOD and controls (P<0.001 and P<0.001 respectively), while erythrocyte and plasma MDA levels were significantly higher (P<0.001 and P<0.001 respectively). CONCLUSION: It can be concluded that the levels of trace elments and toxic heavy metals and oxidative stress influence the disease process in Buerger disease more than PAOD.

Effects of amylin on bone development and egg production in hens.

Amylin is a member of the calcitonin family of hormones cosecreted with insulin from the pancreatic beta-cells that can act as an osteoblast mitogen and as an inhibitor of bone resorption in mice and humans. The aim of this study was to investigate the role of amylin on bone formation and some egg parameters in hens. The study was performed in 60 hens aged 10 wk. Thirty hens constituting the treatment group were s.c. injected with amylin at a 75 microg/kg dose every other day. The remaining hens were used as the control group. Five birds from the treatment and control groups were slaughtered at 14, 16, 18, and 20 wk of age and serum and bone parameters were compared between the treatment and control groups. The remaining 20 hens were fed without any amylin injection until 35 wk. All hens at the end of the 35th week were slaughtered and then serum, bone, and egg parameters were assessed. In the treatment group, bone calcium levels increased, whereas serum calcium levels decreased. This dose of amylin also increased the cortical width of tibiotarsuses in hens. Eggshell thickness was found thicker in the treatment group than in the control group. Overall, the results of this study suggest that amylin may stimulate the bone and eggshell quality by increasing calcium uptake from the bloodstream and may influence the sustainability of yield in hens.

Serum leptin and ghrelin concentrations of maternal serum, arterial and venous cord blood in healthy and preeclamptic pregnant women.

Preeclampsia, a common complication of pregnancy, is associated with alteration in the concentration of leptin in maternal blood. The action of leptin is antagonistic to that of ghrelin. Here, we compared the levels of leptin and ghrelin in maternal serum and in arterial and venous cord blood between healthy pregnant women and those suffering from mild and severe preeclampsia. The levels of leptin in maternal and newborn's blood were elevated in both mild and severe preeclamptic patients (p < 0.05). Moreover, serum ghrelin levels were negatively correlated with blood pressure and leptin/ghrelin ratio was decreased in preeclampsia (p < 0.05). We concluded that increased production of ghrelin may represent a compensatory hypotensive mechanism in preeclamptic women.

Serum leptin and ghrelin concentrations of maternal serum, arterial and venous cord blood in healthy and preeclamptic pregnant women

Preeclampsia, a common complication of pregnancy, is associated with alterationin the concentration of leptin in maternal blood. The action of leptin is antagonisticto that of ghrelin. Here, we compared the levels of leptin and ghrelin in maternalserum and in arterial and venous cord blood between healthy pregnant women andthose suffering from mild and severe preeclampsia. The levels of leptin in maternaland newborn’s blood were elevated in both mild and severe preeclamptic patients(p<0.05). Moreover, serum ghrelin levels were negatively correlated with blood pressureand leptin/ghrelin ratio was decreased in preeclampsia (p<0.05). We concludedthat increased production of ghrelin may represent a compensatory hypotensivemechanism in preeclamptic women (AU)

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DNA damage in metabolic syndrome and its association with antioxidative and oxidative measurements.

The purpose of this study was to assess DNA damage levels in subjects with metabolic syndrome (MetS). Sixty-five subjects with MetS and 65 controls were enrolled in this study. Levels of DNA damage, total antioxidant capacity (TAC), total peroxide and oxidative stress index (OSI) were measured. We found that DNA damage levels were significantly increased [155.5 (60-264) vs. 93.2 (0-208) arbitrary units; p < 0.001] and TAC levels were significantly decreased in MetS than in control (1.34 +/- 0.27 vs. 55 +/- 0.33 mmol Trolox equivalent/l; p < 0.001). A significant falling trend in TAC levels and a significant rising trend in DNA damage values with the increase in the number of metabolic disturbances (anova p < 0.001 for both) were observed. Total peroxide (30.9 +/- 4.9 vs. 21.3 +/- 2.5 micromol H2O2/l; p < 0.001) and OSI levels [2.4 (1.3-3.8) vs. 1.4 (0.7-2.3) arbitrary units; p < 0.001] were significantly higher in the subjects with MetS than in controls. We found significant negative correlation between DNA damage and TAC levels in MetS (r = -0.656, p < 0.001) and in control (r = -0.546, p < 0.001). In multiple linear regression analysis, age, body mass index, presence of MetS and number of the components of MetS were independent predictors of log-transformed DNA damage (p < 0.05, for all). DNA damage is increased in patients with MetS. The increase in DNA damage might be occur because of the increase in the imbalance between the production of oxidants and antioxidant defences in subjects with MetS.

Ghrelin immunohistochemistry of gastric adenocarcinoma and mucoepidermoid carcinoma of salivary gland.

Ghrelin (G-HH) synthesized in several tissues including salivary and stomach glands stimulates appetite in humans by modulating neuropeptide Y neurons in the hypothalamic arcuate nucleus. Loss of appetite is one of the most important symptoms of stomach cancer. We conducted a study using immunohistochemistry to determine whether salivary glands and stomach cancer tissues produce ghrelin. We determined that negative ghrelin immunohistochemistry discriminates tumors from normal tissues and may therefore further our understanding of the clinically important problem of reduced food intake and anorexia in cancer patients. Radioimmunoassay analyses confirmed that cancer cells do not produce a G-HH peptide, whereas normal cells yield this peptide.

Comparison of oxidative stress indicators in plasma of recent-onset and long-term type 1 diabetic patients.

Oxidative stress was compared in plasma of 15 recently diagnosed (<2 mo) or 15 longstanding (>5 yr) type 1 diabetic patients with 15 healthy volunteers. Lipid peroxidation indices measured in plasma included thiobarbituric acid-reactive substances (TBARS), conjugated dienes, and lipid hydroperoxide (ROOH). The values obtained were corrected for phospholipid to minimize this as a confounding factor. In recently diagnosed diabetics, plasma conjugated lipid dienes were significantly elevated. However, in longstanding diabetics there was a marked increase in TBARS, conjugated dienes, and lipid hydroperoxide levels. Our findings showed increased oxidative stress in type 1 diabetics regardless of metabolic control and that conjugated diene measurement appeared to be the most sensitive bioindicator of oxidant stress in our population.