Nevzat Gözel

Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients in eastern Turkey: still a serious problem to consider

Summary.  Hepatitis delta virus (HDV) is a serious cause of liver‐related morbidity and mortality. Coexistent infection with HDV tends to aggravate the course of hepatitis B virus (HBV)‐associated liver disease. The aim of this study was to determine the prevalence of HDV infection among patients chronically infected with HBV in the Elazig region, which is in eastern Turkey. A group of 282 patients infected with chronic HBV were investigated for the study. Anti‐HDV seropositivity was evaluated in all patients. The anti‐HDV‐positive patients were further tested for HDV RNA. Severity of liver disease was assessed by liver biopsy. Regression analysis was used to determine the relationship between independent variables and HDV positivity. Of 282 chronic HBV patients, 192 were men (68.1%) and 90 were women (31.9%). The mean age was 43.8 ± 12.7 (between 18 and 73 years). Anti‐HDV was positive in 45.5% of the patients (128/282). Among the 128 anti‐HDV‐positive patients, 116 were checked for HDV RNA and 56.9% were found positive (66/116). Chronic HDV infection rate was therefore present in at least 23.4% of the whole study group (66/282). There were 83 patients with cirrhosis (29.4%) in the study group. Anti‐HDV seroprevalence and HDV RNA presence were higher in those with cirrhosis (61.4% and 42.2%, respectively). No significant relationship was found between anti‐HDV seropositivity and demographic factors such as age, sex and operation or transfusion history except family history. HDV‐RNA‐positive patients had significantly higher ALT and lower albumin levels when compared to HDV‐RNA‐negative patients. HDV‐RNA‐positive patients also had a significantly higher fibrosis stage. In conclusion, these findings demonstrated that HDV infection is endemic and still a serious problem in the Elazig region of eastern Turkey. HDV infection is significantly related to the family exposure and increases the risk of severe liver fibrosis in this region.

The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity

Abstract The polyphenol curcumin has several pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer features. In this study, we evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7 mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100 mg/kg via gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats exhibited kidney injury manifested by increased serum urea and creatinine (p < 0.05). The kidney tissue from the cisplatin treated rats also exhibited a significant increase in the malondialdehyde (MDA) levels (p < 0.05). The treatment with curcumin prevented a rise in the serum urea, creatinine and MDA levels when compared to the control group kidneys (p < 0.05). The analysis the nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and SIRT4), which play important roles in the resistance to stress and the modulation of the threshold of cell death, showed similar trends (p < 0.05). In the cisplatin-only treated rats, the induced renal injury decreased the levels of the NAMPT and SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and SIRT proteins in the cisplatin-treated rats (p < 0.05). These data suggest that curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity, thereby enhancing the therapeutic window of cisplatin.

Chromium modulates expressions of neuronal plasticity markers and glial fibrillary acidic proteins in hypoglycemia-induced brain injury.

AIMS This experiment investigated if chromium (Cr) as Cr-histidinate (CrHis) and Cr29 picolinate (CrPic) have a protective role in rats with hypoglycemia-induced brain injury, assessed by neuronal plasticity and regeneration potential. MAIN METHODS Male Sprague-Dawley rats were prospectively divided into 2 groups: control and hypoglycemic (induced by insulin administration, 15U/kg, i.p., n=56). Hypoglycemic rats were then received randomly 1) none, 2) dextrose (on the day of sampling), 3) CrHis, or 4) CrPic. Cr-chelates were delivered via drinking water (providing 8μg elemental Cr per day) for one week prior to the hypoglycemia induction. The expressions of neuroplasticity markers [neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP-43), glial fibrillary acidic protein (GFAP)], glucose transporters (GLUT), and nuclear transcription proteins [nuclear factor-kappa (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and 4-hydroxyl nonenal (HNE)] were determined using Western blot. KEY FINDINGS Hypoglycemia caused increases in the expressions of GLUT-1, GLUT-3, GFAP, NF-κB and HNE and decreases in the expression of NCAMs, GAP-43 and Nrf2 in the hippocampus, cerebellum, and cortex. Cr-chelates suppressed expressions of GLUTs, GFAP, NF-κB and HNE expressions and enhanced expressions of NCAM, GAP-43 and Nrf2, which were more notable for CrHis than for CrPic. SIGNIFICANCE In conclusion, hypoglycemia leads to cerebral injury and Cr-chelates, particularly CrHis have protective and regeneration potential in cerebral tissues through modulating neuroplasticity markers and nuclear transcription proteins as well as facilitating glucose transporters.

Hematological Indices May Be Useful in the Diagnosis of Systemic Lupus Erythematosus and in Determining Disease Activity in Behçet's Disease

Objectives: The aim of this study was to investigate the relationships between clinical features of rheumatic diseases and hematologic indices, including mean platelet volume (MPV), MPV/platelet ratio (MPR), platelet/lymphocyte ratio, and neutrophil/lymphocyte ratio (NLR). Subjects andMethods: Rheumatoid arthritis (RA; n = 91), systemic lupus erythematosus (SLE; n = 51), systemic sclerosis (SSc; n = 39), and Behçets disease (BD; n = 53) patients, and 55 healthy controls (HC) were enrolled. Hematological indices were calculated and one-way analysis of variance, Mann-Whitney U and χ2 tests, and receiver operating characteristic (ROC) analyses were performed. Results: The MPV and MPR were higher in the SLE group than the RA group (p < 0.05 and p < 0.01, respectively). ROC analysis indicated that MPV (area under the curve, AUC, 0.68, 95% CI 0.58-0.77) and MPR (AUC 0.69, 95% CI 0.59-0.78) were sensitive and specific markers for SLE against RA. The NLR was higher in the RA, SLE, and SSc groups compared to the HC group (p < 0.05, p < 0.001, and p < 0.01, respectively). The NLR was higher in the active BD patients than those that were inactive (p = 0.008). Besides, NLR was higher in patients with neuro-BD and patients with active genital ulcers compared to patients without neurological involvement (p < 0.01) and active genital ulcers (p < 0.05). Conclusion: The MPV and MPR were significantly higher in the SLE group than in the RA group. They were also higher in the active than in the inactive BD patients. The MPV and MPR are useful diagnostic tools for SLE, and NLR reflects disease activity in BD. However, further research should be performed to standardize these tools.

The Protective Effects of Bevacizumab in Bleomycin-Induced Experimental Scleroderma

BACKGROUND The capillary networks are less dense and have irregular structures in scleroderma. These abnormalities result in lower capillary blood flow causing severe tissue hypoxia, which is a major stimulus for angiogenesis. However, current knowledge about compensatory angiogenesis is ambiguous in scleroderma. Bevacizumab is an inhibitor of vascular endothelial growth factor (VEGF). OBJECTIVES The aim of the present study is to evaluate the protective effects of bevacizumab in bleomycin (BLM)- -induced dermal fibrosis. MATERIAL AND METHODS This study involved 4 groups of Balb/c mice (n = 10 per group). Mice in the control group received 100 μL/day of phosphate-buffered saline (PBS) subcutaneously, while the other 3 groups were given 100 μg/day of BLM (dissolved in 100 μL PBS) subcutaneously, for 4 weeks. Mice in BLM-treated 3rd and 4th groups also received bevacizumab (1 or 5 mg/kg twice a week, intraperitoneally). At the end of the fourth week, all mice were sacrificed and blood and tissue samples were obtained. RESULTS The BLM applications increased the dermal thicknesses, tissue hydroxyproline contents, and α-smooth muscle actin-positive (α-SMA+) cell counts, and led to histopathologically prominent dermal fibrosis. The bevacizumab treatments decreased the tissue hydroxyproline contents and dermal thicknesses, and these improvements were more prominent at doses by which α-SMA+ cell counts were markedly decreased, in the BLM-injected mice. CONCLUSIONS In our study, inhibition of VEGF with bevacizumab treatments prevented the BLM-induced dermal fibrosis suggesting that VEGF expression contributes to the pathogenesis of scleroderma.

Octreotide ameliorates dermal fibrosis in bleomycin-induced scleroderma

Background/aim Insulin-like growth factor (IGF)-I is a differentiation and growth factor. Antifibrotic action of octreotide has been reported in pulmonary fibrosis. The present study aimed to research the prophylactic and therapeutic potential of octreotide on a bleomycin (BLM)-induced experimental scleroderma model. Materials and methods Sixty Balb/c female mice were divided into 6 groups. Daily subcutaneous BLM (100 μg) was injected for 3 weeks in groups II and III and for 6 weeks in groups V and VI. Octreotide (100 μg/kg per day) was injected subcutaneously for the first 3 weeks in group III (prophylactic) and the second 3 weeks in group VI (therapeutic). Mice in groups I, II, and III were sacrificed at the end of the third week, while mice in groups IV, V, and VI were sacrificed at the end of the sixth week. Results Repeated BLM applications increased dermal inflammatory cell counts and dermal thickness, and led to dermal fibrosis at both the third and sixth weeks. Moreover, mRNA expressions of TGF-β1 and IGF binding protein (IGFBP)-3 and -5 were higher in the BLM- injected sham groups. On the other hand, IGFBP-3 and -5 mRNA expressions were significantly decreased in both the prophylactic and therapeutic octreotide groups. Similarly, octreotide decreased dermal inflammatory infiltrations and dermal thickness. Conclusion Octreotide has antifibrotic actions on experimentally induced dermal fibrosis. It can be suggested that IGF-I plays pathogenic roles, and octreotide is a candidate for research in the treatment of scleroderma.

Association of clinical and laboratory parameters with ambulatory arterial stiffness index in acromegaly patients

Objective: In this study, we determined the relationship between the ambulatory arterial stiffness index (AASI) and clinical and laboratory parameters in patients with acromegaly. Methods: Sixty-five patients with acromegaly, who visited to Dicle University Medical Faculty Department of Endocrinology (33 females and 32 males), were included in this study. The study control group consisted of 65 subjects. Demographic and clinical data were recorded. Laboratory data (complete blood count, blood urea nitrogen, creatinine, electrolytes, albumin, lipid profile, growth hormone [GH], insulin-like growth factor-1, and the 75-g oral glucose tolerance test) performed over the last year were evaluated. The AASI was obtained from 24-hour ambulatory blood pressure monitoring records of all patients. This study was completed in 15 months from 2013 to 2015. Results: Twelve patients (18.4%) had diabetes and 21 patients (32%) had hypertension. The mean AASI value was 0.41 ± 0.14. The mean AASI value in the control group was 0.25 ± 0.09. Growth hormone (GH) levels were positively correlated with the AASI values. AASI values tended to be higher in hypertensive subjects than that in normotensive individuals. Conclusions: Our results show that the AASI value increased in patients with acromegaly, independent of the increase in blood pressure. The AASI was strongly dependent on the degree of the GH increase in patients with acromegaly and may have an important role predicting cardiovascular risk in patients with acromegaly.

The effects of Mucuna pruriens on the renal oxidative stress and transcription factors in high-fructose-fed rats

In the present study, we evaluated the effects of M. pruriens administration on metabolic parameters, oxidative stress and kidney nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways in high-fructose fed rats. Male rats (n = 28) were divided into 4 groups as control, M. pruriens, fructose, and M. pruriens plus fructose. All rats were fed a standard diet supplemented or no supplemented with M. pruriens (200 mg/kg/d by gavage). Fructose was given in drinking water for 8 weeks. High fructose consumption led to an increase in the serum level of glucose, triglyceride, urea and renal malondialdehyde (MDA) levels. Although M. pruriens treatment reduced triglyceride and MDA levels, it did not affect other parameters. M. pruriens supplementation significantly decreased the expression of NF-ҡB and decreased expression of Nrf2 and HO-1 proteins in the kidney. This study showed that the adverse effects of high fructose were alleviated by M. pruriens supplementation via modulation of the expression of kidney nuclear transcription factors in rats fed high fructose diet.

Sorafenib Reveals Anti-Arthritic Potentials in Collagen Induced Experimental Arthritis Model

Objectives This study aims to examine the effects of sorafenib on a collagen-induced arthritis model. Materials and methods The study included 50 randomly selected female Wistar-albino rats (8-10-week-old, weighing between 200 g to 250 g). The rats were divided into five equal groups as control, arthritis, etanercept, sorafenib high-dose, and sorafenib low-dose groups, respectively. Arthritis was induced by injecting mixed intradermal chicken type II collagen and incomplete Freunds adjuvant. Twenty-four hours after the advent of arthritis; rats in group 3 were injected subcutaneous etanercept (6 mg/kg/week), while those in groups 4 and 5 were given sorafenib (10 or 30 mg/ kg/day) orally until they were sacrificed on the 34th day. The rat claws and trunk bloods were carefully examined to note perisynovial inflammation and cartilage/bone injury through histopathology. Tissue vascular endothelial growth factor (VEGF) and VEGF receptor levels were carefully checked using western blot analysis. Results Analysis of the experimental data showed that collagen-induced arthritis decreased in treatments groups after 12-13 days and 34th day in contrast with the arthritis group. Histopathological examination revealed broad perisynovial inflammation and cartilage/bone break down in the arthritis group. Compared to the control group, tissue VEGF and VEGF receptor levels increased in the arthritis group. Sorafenib and etanercept decreased tissue VEGF and VEGF receptor levels, perisynovial inflammation, damage of cartilage/bone. Conclusion Our findings indicate that sorafenib treatment ameliorates collagen-induced arthritis with anti-VEGF effectiveness.

Paricalcitol Inhibits Wnt/β-Catenin Signaling Pathway and Ameliorates Dermal Fibrosis in Bleomycin Induced Scleroderma Model

Objectives This study aims to determine the prophylactic and therapeutic efficacy of inhibition of Wnt/β-catenin signaling pathway with paricalcitol in an experimental scleroderma model created with bleomycin (BLM). Materials and methods Sixty female BALB/c mice (8-week old and weighing 25 g to 30 g) were divided into six groups as prophylactic-early [group 1 (control I)], sham I (group 2), paricalcitol I (group 3), therapeutic-late [group 4 (control II)], sham II (group 5), and paricalcitol II (group 6) groups. Subcutaneous BLM (100 μg/day) injections were used to induce dermal fibrosis and paricalcitol (0.3 μg/kg/day) was applied subcutaneously to BLM-injected mice during the first three weeks for preventive interventions and in the second three weeks for therapeutic interventions. Tissue samples were harvested for subsequent pathological and real-time polymerase chain reaction analysis. Tissue transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions were determined by real-time polymerase chain reaction. Results Repeated BLM applications increased the dermal inflammatory cell infiltration and dermal thickness, and led to dermal fibrosis, in both early and late stages. Similarly, transforming growth factor-beta 1, axin-1, and Wnt-2 expressions were significantly increased in the sham groups compared to the own control group (p<0.05 for all). Contrarily, prophylactic and therapeutic paricalcitol applications decreased the transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions compared to the own sham group (p<0.05 for all). In addition, the regressions in dermal necro-inflammation and dermal fibrosis on pathological views were also observed in the paricalcitol applied groups. Conclusion In this model, increased axin-1 and Wnt-2 messenger ribonucleic acid expressions suggest that Wnt/β-catenin pathway is active in dermal fibrosis.