Favipiravir-induced inflammatory and hydropic degenerative liver injury in rats.

BACKGROUND: Favipiravir is very effective in the treatment of many viral infections, especially at high doses. It was used at such doses to treat coronavirus disease 2019 (COVID-19) during the pandemic. However, liver damage was reported in patients undergoing such treatment. OBJECTIVES: This study aimed to investigate the effects of low and high doses of favipiravir on the liver of rats, using biochemical and histopathological methods. MATERIAL AND METHODS: Wistar albino rats were allocated to one of 3 groups, namely a healthy group (HG), a 100 mg/kg favipiravir (FAV-100) group and a 400 mg/kg favipiravir (FAV-400) group. Favipiravir was administered orally at 100 mg/kg and 400 mg/kg doses to the FAV-100 (n = 6) and FAV-400 (n = 6) groups, respectively. Distilled water was administered orally (1 mL) using the same method to the HG (n = 6). This procedure was repeated twice a day for 1 week. At the end of this period, the animals were euthanized with a high dose of thiopental anesthesia (50 mg/kg) and their liver tissues were removed. RESULTS: Favipiravir caused an increase in malondialdehyde (MDA), nuclear factor kappa B (NF-κB) and interleukin 6 (IL-6) levels in the liver tissue, as well as elevated alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) levels in the blood. Moreover, favipiravir caused a decrease in total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. In addition, severe edema, lymphocyte infiltration and hydropic degeneration were observed in the liver tissue of the FAV-400. CONCLUSIONS: High-dose favipiravir caused more significant oxidative and inflammatory damage in the liver tissue of rats than low-dose favipiravir.

Beneficial interaction of pycnogenol with indomethacin in rats.

Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.

Amelioration of oxidative damage parameters by carvacrol on methanol-induced liver injury in rats.

The methanol metabolite that causes hepatotoxicity is formic acid, generating reactive oxygen radical formation and cell damage. Carvacrol is an antioxidant monoterpenic phenol produced from Thymus vulgaris. This study aimed to investigate the effects of carvacrol on methanol-induced oxidative liver damage in rats. Eighteen rats were divided into three groups. Methotrexate was administered orally for 7 days to methotrexate+methanol (MTM) and methotrexate+methanol+carvacrol (MMC) groups. Methotrexate was given before methanol to cause methanol poisoning. Distilled water was given to the healthy group (HG) as a solvent. At the end of the 7th day, 20% methanol was administered orally at a dose of 3 g/kg to the MTM and MMC groups. Four hours after methanol administration, 50 mg/kg carvacrol was injected intraperitoneally into the MMC group. Animals were sacrificed 8 h after carvacrol injection. Biochemical markers were studied in the excised liver tissue and blood serum samples, and histopathological evaluations were made. Severe hemorrhage, hydropic degeneration, pycnosis, and mononuclear cell infiltration were observed in the liver of the MTM group. Additionally, the levels of malondialdehyde (MDA), total oxidant status (TOS), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly higher, and total glutathione (tGSH) and total antioxidant status (TAS) were significantly lower in the MTM group compared to HG (P<0.001). Carvacrol prevented the increase in MDA, TOS, ALT and AST levels with methanol and the decrease in tGSH and TAS levels (P<0.001), and alleviated the histopathological damage. Carvacrol may be useful in the treatment of methanol-induced liver damage.

The role of protein oxidation in the development of diabetic microvascular complications.

OBJECTIVE: The role of protein oxidation in the development of diabetic microvascular complications was investigated. METHODS: In total, 266 participants were split into five groups: Group 1; diabetes mellitus for at least 10 years without any complications, Group 2; diabetic nephropathy, Group 3; diabetic neuropathy, Group 4; diabetic retinopathy, and Group 5; control group. Thiol, disulfide, ferroxidase, and ischemia-modified albumin (IMA) levels were analyzed in the serum. RESULTS: Native thiol, total thiol, and native thiol/total thiol were lower in Group 4 than Groups 1, 3, and 5 (p<0.001). However, disulfide/native thiol and disulfide/total thiol were higher in Group 4 than all other groups (p<0.001). IMA was higher in Groups 3 and 4 than all other groups (p<0.001). Ferroxidase was lower in Groups 3 and 4 than Group 2 (p<0.001). CONCLUSION: Thiol-disulfide homeostasis impairment in favor of disulfide may have a function in the progress of diabetic retinopathy. Furthermore, the disruptions of IMA and ferroxidase levels involve in the development of diabetic retinopathy and neuropathy.

Oxidative and pro-inflammatory lung injury induced by desflurane inhalation in rats and the protective effect of rutin.

BACKGROUND: Desflurane is a mainstay of general inhaled anesthetics with a methyl ethyl ether structure and is widely used in clinical practice. It has been reported to induce inflammation and lipid peroxidation in rat pulmonary parenchyma, to increase alveolar macrophages, and to cause peribronchial infiltration and edema. Rutin, a flavonoid vitamin P1, is known to have biological properties including acting as an antioxidant, an anti-inflammatory, and an inhibitor of bronchoalveolar polymorphonuclear leukocyte (PNL) infiltration. OBJECTIVES: The aim of this study is to examine the effects of rutin on desflurane-induced pulmonary injury using biochemical and histopathological methods. MATERIAL AND METHODS: The rats were divided into 3 groups (n = 6 each): healthy control (HC), rutin+desflurane-treated (DRT) and desflurane-only (DSF). Briefly, 50 mg/kg of rutin was given orally to the DRT group and an equal volume of normal saline was given to the DSF and HC groups. After 1 h, anesthesia was induced and maintained in the DRT and DSF groups for 2 h. After the rats had been sacrificed, the lungs were removed. Malondialdehyde (MDA), total glutathione (GSH), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF-κB) levels were measured in the excised lung tissue. The removed tissues were also fixed in 10% formalin, and the obtained sections were stained with hematoxylin and eosin (H&E) and evaluated under light microscopy. The biochemical and histopathological results of the DRT group were compared with those obtained from the DSF and HC groups. RESULTS: Desflurane increased MDA, TNF-α and NF-κB, and decreased GSH in lung tissue. The PNL infiltration, alveolar macrophages, hemorrhage, alveolar damage, and edema were observed in the lung tissue of the DSF group. Rutin was histopathologically shown to protect lung tissue from oxidative stress by preventing an increase in oxidant parameters and a decrease in antioxidants. CONCLUSIONS: The results suggest that rutin may be useful in the treatment of desflurane-associated lung injury.

The Relationship Between Visceral Adiposity Index and Epicardial Adipose Tissue in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION AND AIM: Cardiovascular diseases remain the most common cause of morbidity and mortality in patients with diabetes. Epicardial adipose tissue (EAT), visceral fat depot of the heart, was found to be associated with coronary artery disease in cardiac and non-cardiac patients. Increased visceral adiposity is associated with proinflammatory activity, impaired insulin sensitivity, increased risk of atherosclerosis and high mortality. In the present study we aimed to investigate the relationship between EAT and visceral adiposity index (VAI) in patients with diabetes. METHODS: This was a cross-sectional study involving 128 patients with type 2 diabetes mellitus (73 females, 55 males; mean age, 54.09+±+9.17 years) and 32 control subjects (23 females, 9 males; mean age, 50.09+±+7.81 years). EAT was measured by using a trans-thoracic echocardiograph. Parameters such as waist circumference (WC), body mass index (BMI), triglyceride and high density lipoprotein (HDL) cholesterol were used to calculate VAI. RESULT: EAT and VAI measurements were significantly higher in patients with diabetes when compared to control subjects. In the bivariate correlation analysis, VAI was positively correlated with uric acid level (r=0.214, p=0.015), white blood cell count (r= 0.262, p=0.003), platelet count (r=0.223, p=0.011) and total cholesterol levels (r= 0.363, p<0.001). Also, VAI was found to be the independent predictor of EAT. CONCLUSION: Simple calculation of VAI was found to be associated with increased EAT in patients with type 2 diabetes.

Effects of anakinra on the small intestine mucositis induced by methotrexate in rats.

Intestinal mucositis is an important problem in the patients receiving cancer treatment. We aimed to investigate the effect of anakinra, which is a well known anti-oxidant and anti-inflammatory agent, on methotrexate-induced small intestine mucositis in rats. Forty rats were divided into 4 groups with 10 in each group. The healthy group (HG) and the methotrexate group (MTXG) were given distilled water, while the methotrexate + anakinra 50 (MTX+ANA50) and the methotrexate + anakinra 100 (MTX+ANA100) groups were intraperitoneally administered 50 and 100 mg/kg of anakinra. After one hour, the MTXG, MTX+ANA50 and MTX+ANA100 groups were given oral methotrexate at a dose of 5 mg/kg. This procedure was repeated once a day for 7 days. After the rats had been sacrificed, the small intestine tissue of rats were removed for the assesment of biochemical markers, histopathological evaluation and gene expression analyze. Statistical analyses of the data were performed using one-way ANOVA. Malondialdehyde (MDA), myeloperoxidase (MPO) and interleukin-6 (IL-6) levels were significantly higher, whereas total glutathione (tGSH) levels were significantly lower in MTXG (P<0.001) compared to other groups. MTX also increased IL-1ß and TNF-α gene expression levels in MTXG (P<0.001). Inflammatory cell infiltration and damage to the villus were observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the MTX+ANA100 group. A dose of 100 mg/kg of anakinra prevented the increase of the biochemical markers and gene expression levels better than a dose of 50 mg/kg. Intestinal mucositis caused by MTX may be preventible by co-administered anakinra.

The effect of anakinra to nephrotoxicity with cisplatin induced in rats: Biochemical, gene expression and histopathological evaluation.

BACKGROUND: Oxidative stress and interleukin-1 beta (IL-1ß) have been reported to play a role in the pathogenesis of nephrotoxicity induced by cisplatin. OBJECTIVES: The objective of this study was to investigate the effect of anakinra, which is an IL-1ß receptor antagonist, on cisplatin-induced nephrotoxicity in rats, through biochemical, gene expression and histopathological analyses. MATERIAL AND METHODS: The study was designed with 4 groups. For 1 week, the control group (C) and the cisplatin (Cis) group received distilled water, while the cisplatin + anakinra 50 (Cis + ANA50) group and the cisplatin + anakinra 100 (Cis + ANA100) group were intraperitoneally administered 50 mg/kg and 100 mg/kg of anakinra, respectively. The Cis, Cis + ANA50 and Cis + ANA100 groups were intraperitoneally injected with a 2.5 mg/kg dose of cisplatin for 7 days. After sacrifice, the kidney tissue of each rat was extracted for the assessment of the malondialdehyde (MDA) and total glutathione (tGSH) levels, and for gene expression analyses of IL-1ß. The kidney tissues were histopathologically evaluated. Statistical analyses of the data were performed using one-way analysis of variance (ANOVA). RESULTS: The administration of cisplatin (the Cis group) yielded a higher level of MDA (4.75 ±0.25 nmol/mL; p < 0.001) and lower levels of tGSH (1.80 ±0.35 mg/L; p < 0.001) compared to other groups. Cisplatin also increased IL-1ß gene expression (6.33 ±0.27 gene expression levels; p < 0.001) compared to other groups. The impact of anakinra on the MDA and tGSH levels, and on IL-1ß gene expression induced by cisplatin was observed as a reversal of these findings (p < 0.05). Anakinra better prevented an increase of the levels of MDA and IL-1ß at a dose of 100 mg/kg compared to a 50 mg/kg dose. CONCLUSIONS: Anakinra prevents oxidative kidney damage induced by cisplatin, in a dose-dependent manner. This result suggests that anakinra may be useful in the treatment of cisplatin-induced kidney damage.

The effect of rutin on cisplatin-induced oxidative cardiac damage in rats.

OBJECTIVE: Cisplatin is an anticancer drug used for treating childhood solid tumors. Symptoms related to cisplatin-induced cardiovascular adverse effects may be mild or severe. Rutin (vitamin P1) has many properties, including as antioxidant, anticancer, antidiabetic, antimicrobial, antiulcer, and tissue renewal properties. Therefore, we aimed to biochemically, histopathologically, and immunohistochemically demonstrate the effect of rutin on cisplatin-induced cardiotoxicity in rats. METHODS: The rats included in our study were divided into four groups: Healthy group (HE), 5-mg/kg cisplatin group (CP), 50 mg/kg rutin+5-mg/kg cisplatin (CR-50), 100-mg/kg rutin+5-mg/kg cisplatin (CR-100) group. RESULTS: CP group administered cisplatin had significantly increased blood, serum, and cardiac tissue malondialdehyde (MDA), interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), troponin I, creatine kinase (CK), and CK-MB levels compared to the HE group, whereas there was a significant decrease in the total glutathione (tGSH) levels. Rutin was observed to prevent the increase in MDA, IL-1ß, TNF-α, troponin I, CK, and CK-MB levels as well as prevent the decrease in tGSH levels more significantly when administered at a 100-mg/kg dose than at a 50-mg/kg dose. Histopathologically, cardiac necrosis, dilated/congested blood vessels, hemorrhage, polymorphonuclear leukocyte, edema, and cells with pyknotic nuclei were observed in the CP group. Rutin was shown to prevent cisplatin-induced cardiac damage more effectively when used at a100-mg/kg dose than at a 50-mg/kg dose. CONCLUSION: These results suggest that rutin is useful for preventing cisplatin-related cardiovascular damage.

The seroprevalence of Coxiella burnetii in Erzincan, Turkey: Identification of the risk factors and their relationship with geographical features.

BACKGROUND & OBJECTIVES: Coxiella burnetii (C. burnetii) bacterium, the causative agent of Q fever has regained importance due to the increasing cases of infections and outbreaks. A cross-sectional descriptive study was conducted to investigate the seroprevalence of C. burnetii in human populations of Erzincan province located in the eastern Turkey, identify the risk factors, and to explore the relationship between geographical features. METHODS: A total of 368 people residing in the rural (306) and urban (62) areas of the province were included in the study. Serum samples were analyzed for the presence of C. burnetii phase II IgG antibody using ELISA (Virion/ Serion, Wurzburg, Germany). Spatial analyses were performed to evaluate correlations between seroprevalence and geographical features. RESULTS: The overall seroprevalence of C. burnetii was found to be 8.7% (32/368). In rural residents it was 8.5% (26/306), while in urban population it was 9.7% (6/62). Cattle breeding and contact with animal afterbirth waste were found to be major risk factors, and were significantly correlated with seropositive cases (p<0.05). The seropositive cases were only observed in the areas between 1067 and 1923 masl. Of the total seropositive cases, 65.6% were within 1000 m and 87.5% within 4000 m of rivers and their main tributaries. Around 59.4% cases were observed in areas with a slope of 0 to 5°. INTERPRETATION & CONCLUSION: The results of the study showed that C. burnetii seroprevalence was higher than expected, and significantly differs according to geographical features of a region. Significant risk factors include raising cattle and exposure to infected animals or their birth products/secretions. It is also more frequent in areas with higher number of rivers and streams, higher altitude and lower slope.

Neutrophil-to-lymphocyte ratio as a possible indicator of epicardial adipose tissue in patients undergoing hemodialysis.

INTRODUCTION: Chronic inflammation is a major risk factor in the pathogenesis of cardiovascular disease in end-stage renal disease (ESRD) patients. Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between coronary artery disease and EAT was shown in healthy subjects and ESRD patients. In the present study we aimed to investigate the relationship between EAT and inflammation parameters including neutrophil-to-lymphocyte ratio (NLR) in hemodialysis (HD) patients. MATERIAL AND METHODS: Forty-three HD patients (25 females, 18 males; mean age: 64.1 ±11.9 years) receiving HD and 30 healthy subjects (15 females, 15 males; mean age: 59.1 ±10.8 years) were enrolled in the study. Epicardial adipose tissue measurements were performed by echocardiography. RESULTS: Neutrophil-to-lymphocyte ratio levels were significantly higher in HD patients than in the healthy control group. Hemodialysis patients were separated into two groups according to their median value of NLR (group 1, NLR < 3.07 (n = 21) and group 2, NLR ≥ 3.07 (n = 22)). Group 2 patients had significantly higher EAT, C-reactive protein and ferritin levels, while albumin levels were significantly lower in this group. In the bivariate correlation analysis, EAT was positively correlated with NLR (r = 0.600, p < 0.001) and ferritin (r = 0.485, p = 0.001) levels. CONCLUSIONS: Neutrophil-to-lymphocyte ratio was found to be an independent predictor of EAT in HD patients (odds ratio = 3.178; p = 0.008). We concluded that this relationship might be attributed to increased inflammation in uremic patients.

Vitamin D and inflammation: evaluation with neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

INTRODUCTION: Association of vitamin D, inflammation and endothelial dysfunction, beside the classic bone metabolism disorders, may explain the pathogenesis of numerous diseases associated with vitamin D deficiency. While large numbers of reports support the relationship of vitamin D with inflammation, several reports fail to confirm this relationship. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel and inexpensive markers of inflammation that can be studied in all centers. The goal of this study was to investigate the association between 25-hydroxy vitamin D (25(OH)D) and inflammation with the novel inflammatory markers NLR and PLR. MATERIAL AND METHODS: This study was performed retrospectively. Results of the simultaneously performed 25(OH)D, parathyroid hormone, albumin, calcium, phosphorus, alkaline phosphatase and creatinine level measurements and complete blood count were recorded. The data of 4120 patients were included in the study. RESULTS: Between vitamin D deficient and non-deficient groups there were significant differences in PLR (p < 0.001) and NLR (p = 0.001). Vitamin D had a significant negative correlation with PLR (p < 0.001) and NLR (p < 0.001). Multiple regression analysis indicated that 25(OH)D was independently and negatively correlated with PLR (OR = 0.994, 95% CI 0.991-0.998, p = 0.02). CONCLUSIONS: Platelet-to-lymphocyte ratio and NLR were significantly associated with 25(OH)D levels, and PLR was found to be an independent predictor of 25(OH)D levels. Our study revealed an inverse association of vitamin D levels and inflammation with these inexpensive and universally available markers.

What Is the Best Pulmonary Physiotherapy Method in ICU?

Objective. Effects of high frequency chest wall oscillation technique were investigated on intubated ICU patients. Background. Thirty intubated patients were included in the study. The control group (n = 15) received routine pulmonary rehabilitation technique. In addition to the pulmonary rehabilitation technique, the study group (n = 15) was given high frequency chest wall oscillation (HFCWO). APACHE II, dry sputum weight, lung collapse index, and blood gas values were measured at 24th, 48th, and 72nd hours and endotracheal aspirate culture was studied at initial and 72nd hour. The days of ventilation and days in ICU were evaluated. Results. There is no significant difference between APACHE II scores of groups. The dry sputum weights increased in the study group at 72nd hour (p = 0.001). The lung collapse index decreased in study group at 48th (p = 0.003) and 72nd hours (p < 0.001). The PO2 levels increased in the study group at 72nd hour (p = 0.015). The culture positivity at 72nd hour was decreased to 20%. The days of ventilation and staying in ICU did not differ between the groups. Conclusions. Although HFCWO is very expensive equipment, combined technique may prevent the development of lung atelectasis or hospital-acquired pneumonia more than routine pulmonary rehabilitation. It does not change intubated period and length of stay in ICU. However, more further controlled clinical studies are needed to use it in ICU.

Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats.

Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide.

[A case of brucellosis and Crimean-Congo hemorrhagic fever coinfection in an endemic area]. / Endemik bir bölgede bruselloz ve Kirim Kongo kanamali atesi koenfeksiyonu olgusu.

Brucellosis, a zoonotic disease which is especially seen in developing countries is still an important public health problem worldwide. Crimean-Congo hemorrhagic fever (CCHF) is another zoonotic disease that transmits to humans by infected tick bites as well as exposure to blood or tissue from infected animals. Both of the diseases are common among persons who live in rural areas and deal with animal husbandry. Since brucellosis usually presents with non-specific clinical symptoms and may easily be confused with many other diseases, the diagnosis of those infections could be delayed or misdiagnosed. In this report, a case of coinfection of brucellosis and CCHF has been presented to emphasize the possibility of association of these infections. A 70-year-old female patient with a history of dealing with animal husbandry in a rural area admitted to our hospital with the complaints of fever, malaise, generalized body and joint pains, and headache. Her complaints had progressed within the past two days. She also reported nausea, vomiting, abdominal pain and bloody diarrhea. She denied any history of tick bites. Her physical examination was significant for the presence of 38.8°C fever, increased bowel sounds and splenomegaly. Laboratory analysis revealed leukopenia, thrombocytopenia and high levels of liver enzymes. The patient was admitted to our service with the prediagnosis of CCHF. Serum sample was sent to the Department of Microbiology Reference Laboratory at Public Health Agency of Turkey for CCHF testing. During patient's hospitalization in service, more detailed history was confronted and it was learned that she had fatigue, loss of appetite, sweating, joint pain, and intermittent fever complaints were continuing within a month and received various antibiotic treatments. The tests for brucellosis were conducted and positive results for Brucella Rose Bengal test, tube agglutination (1/160 titers) and immune capture test with Coombs (1/320 titers) were determined. The tests performed in the reference laboratory revealed CCHF virus-specific IgM positivity by immunofluorescence assay and viral RNA positivity by real-time polymerase chain reaction. Two blood cultures remained sterile during hospitalization, this situation was considered to be the cause of antibiotic usage in the last month. Doxycycline and rifampicin therapy were initiated for brucellosis, and close monitoring with supportive therapy for CCHF. On the second day of admission, the patient was transfused with 5 units random platelets and 2 units fresh frozen plasma due to dramatic decline of platelet count (37.000/mm(3)). Early clinical response to brucellosis therapy was confirmed with resolution of fever and improved blood counts and the treatment was completed in eight weeks on an outpatient basis. No other problems were encountered during follow-ups after completion of treatment. According to accessible literature search, coinfection of brucellosis and CCHF has not been reported previously. In conclusion, as our country is endemic for both brucellosis and CCHF, it is important to consider both infections in the differential diagnosis. Physicians should keep in mind that, likewise in our case, coinfection of brucellosis and CCHF can be detected.

Seroprevalence of Crimean-Congo Hemorrhagic Fever Virus in Erzincan Province, Turkey, Relationship with Geographic Features and Risk Factors.

To determine the seroprevalence and risk factors associated with Crimean-Congo hemorrhagic fever virus (CCHFV) in residents of Erzincan, Turkey. Although CCHFV is endemic in Erzincan, this is the first study to evaluate its seroprevalence in this region. This study included a total of 372 subjects, 174 of whom had been exposed to or bitten by ticks, 145 of whom worked with livestock, and 53 of whom resided in the city and did not have exposure to livestock. Data on CCHFV IgG and IgM antibodies were extracted from serum samples collected from all subjects using an ELISA. All samples were tested for CCHFV IgG and CCHFV IgM. Only IgM-positive samples were processed for detection of viral RNA through RT-PCR. Using seropositive cases only, we performed spatial analyses to evaluate correlations between seroprevalence and geographic location (i.e., proximity to rivers, altitude, and slope angle of land). In this study, 14.0% (52/322) of the total subjects were positive for CCHFV IgG. Seven of the individuals were positive both for CCHFV IgG and CCHFV IgM. Of these seven, only one sample tested positive for CCHFV RNA. Individuals who worked with livestock in the rural areas and had a history of tick exposure were statistically more likely to test positive for CCHFV IgG than individuals from the city and not exposed to ticks (p < 0.05). Seroprevalence was affected by geographic characteristics, including distance to rivers, altitude, and slope angle of land. We observed a high seroprevalence of CCHFV in Erzincan, which is similar to that observed in other endemic regions of Turkey. CCHFV seroprevalence rates are found to be quite high in the people who live in the sloping fields at certain heights and where there are a lot of rivers and streams.

Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus.

The prevalence of diabetes mellitus (DM) is increasing secondary to increased consumption of food and decreased physical activity worldwide. Hyperglycaemia, insulin resistance and hypertrophy of pancreatic beta cells occur in the early phase of diabetes. However, with the progression of diabetes, dysfunction and loss of beta cells occur in both types 1 and 2 DM. Programmed cell death also named apoptosis is found to be associated with diabetes, and apoptosis of beta cells might be the main mechanism of relative insulin deficiency in DM. Autophagic cell death and apoptosis are not entirely distinct programmed cell death mechanisms and share many of the regulator proteins. These processes can occur in both physiologic and pathologic conditions including DM. Besides these two important pathways, endoplasmic reticulum (ER) also acts as a cell sensor to monitor and maintain cellular homeostasis. ER stress has been found to be associated with autophagy and apoptosis. This review was aimed to describe the interactions between apoptosis, autophagy and ER stress pathways in DM.

The Impact of Resveratrol on Oxidative Stress Induced by Methotrexate in Rat Ileum Tissue: Evaluation of Biochemical and Histopathological Features and Analysis of Gene Expression.

OBJECTIVE: The aim of this study was to assess the impact of resveratrol (RST) on oxidative stress induced by methotrexate in rat ileum tissue. MATERIALS AND METHODS: Twenty-four rats were divided into 4 groups with 6 in each group. Each rat was orally administered the following every day for 30 days: group 1 (MTXG), methotrexate (MTX; 5 mg/kg); group 2 (RMTXG), MTX (5 mg/kg) plus RST (25 mg/kg/day); group 3 (RSTG), RST alone (25 mg/kg/day), and group 4 (controls), distilled water. After the rats had been sacrified, the ilea were removed for the assessment of malondialdehyde (MDA), total glutathione (tGSH) and glutathione peroxidase (GSH-Px). Gene expression analyses for interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffin-embedded sections of the ileum were analyzed under a light microscope and the findings were recorded. Statistical analyses of the data were performed using one-way ANOVA. RESULTS: The administration of MTX in group 1 yielded a higher level of MDA (8.33 ± 2.5 µmol/g protein, p < 0.001) and lower levels of tGSH (0.97 ± 0.29 nmol/g protein) and GSH-Px (5.22 ± 0.35 U/g protein, p < 0.001) compared to the other groups. MTX also increased IL-1ß (40.33 ± 5.43 gene expression levels), TNF-α (6.08 ± 0.59) and MPO gene expression (9 ± 1.41) in group 1 compared to the controls (11.33 ± 2.07, 2.15 ± 0.33 and 3.43 ± 0.48, respectively, p < 0.001). The impact of RST on IL-1ß, TNF-α and MPO gene expression induced by MTX was observed as a reversal of these findings (p < 0.05). Severe inflammation, damage to the villus epithelium and crypt necrosis was observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the RMTXG group. CONCLUSION: In this study, ileal damage caused by MTX was inhibited by RST.

Association of hematological indicies with diabetes, impaired glucose regulation and microvascular complications of diabetes.

In recent years, there has been renewed interest in hematological parameters as predictors of endothelial dysfunction and inflammation. The aim of our study is to evaluate the relationship between HbA1c and hematological indices, and to evaluate the relationship between these parameters and microvascular complications of diabetes. Three hundred and seven diabetic patients (124 male, 183 female; mean age 50.8±8.5), and 187 controls (76 male, 111 female; mean age 51.1±10.1) were included in the study. In the diabetic group, mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), white blood cell count (WBC), platelet count, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) were significantly higher than the control group (P<0.05). Diabetic patients were divided into two group according to their HbA1c levels (Group 1; HbA1c <7 (n=82) and group 2; HbA1c ≥7 (n=225)). Mean platelet volume, PCT and PDW levels were significantly increased in group 2. Mean platelet volume was significantly increased in diabetic patients with retinopathy compared to those without retinopathy (P=0.006). The neutrophil to lymphocyte ratio and PLR levels were significantly higher in patients with nephropathy (P=0.004, P=0.004 respectively). There was statistically significant difference of lymphocyte count between patients with and without neuropathy. In correlation analysis, positive correlation between HbA1c and PCT (rs=0.192, P<0.001), HbA1c and PDW (rs=0.305, P<0.001), HbA1c and MPV (rs=0.352, P<0.001) were determined. In binary logistic regression analysis; WBC, PDW and PLR levels were found to be independently associated with diagnosis of diabetes while WBC, MPV, PLR and NLR levels were found to be independently associated with impaired glucose regulation. This study demonstrates that altered hematological indices are closely associated with HbA1c levels in individuals with and without diabetes and some of these parameters are associated with diabetic microvascular complications. These associations may be explained by connection between these easy accessible and inexpensive hematological indices and inflammation, tendency to coagulation and thrombosis in patients with diabetes.

Comparison of dexmedetomidine and propofol used for drug-induced sleep endoscopy in patients with obstructive sleep apnea syndrome.

UNLABELLED: Backround: Surgical operations are alternative treatments in persons with Obstructive Sleep Apnea Syndrome who cannot tolerate continuous positive airway pressure therapy. Drug-Induced Sleep Endoscopy is a method with which somnolence is pharmacologically induced and collapse is evaluated through nasal endoscopy in patients with Obstructive Sleep Apnea Syndrome. AIMS: We aimed to evaluate efficiency of dexmedetomidine or propofol used for sedation in patients undergoing drug-induced sleep endoscopy. METHODS: A total of 40 patients aged between 18 and 65 years old in the ASA STATUS I-II group were included in the study. After premedication with midazolam 0.05 mg/kg intravenously, patients were randomly divided into two groups and administered intravenous (iv) propofol with the loading dose of 0.7 mg/kg for 10 minutes, followed 0.5 mg/kg/h infusion (Group P); or dexmedetomidine with the loading dose of 1 mcg/kg for 10 minutes, followed by 0.3 mcg/kg/h infusion (Group D). Haemodynamic and respiratuary parameters, Bispectral index score, Ramsey sedation score, time to achieve sufficient sedation, surgeon's and patients' satisfaction, postoperative Aldrete score and side effects were recorded. RESULTS: Time to achieve sufficient sedation, Bispectral index scores at 5, 10 and 15th. minutes intraoperatively, first Aldrete score in the recovery room, SpO2 values and respiratory rates all over the surgical procedure and in the recovery room were found lower in Group P (P<0.05). Bispectral index scores, mean arterial pressure and heart rate in the recovery room were significantly lower in Group D (P<0.05). CONCLUSION: Dexmedetomidine may be preferred as a safer agent with respecting to respiratory function compared with propofol in obstructive sleep apnea patients who known to be susceptible to hypoxia and hypercarbia.