Ulvi Demirel

Allopurinol ameliorates thioacetamide-induced acute liver failure by regulating cellular redox-sensitive transcription factors in rats.

Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-қB ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-κB, AP-1, TNF-α, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.

Nadroparin Sodium Activates Nrf2/HO-1 Pathway in Acetic Acid-Induced Colitis in Rats

Effects of nadroparin sodium, a low molecular weight heparin, in colitis was investigated by analyzing proteins implicated in nuclear factor E2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) and nuclear factor kappa B (NF-κB) pathways. Twenty-eight rats were used. Colitis was induced by acetic acid (AA). Nadroparin sodium was given to prevention and treatment groups in addition to AA. Colitis was assessed histologically and levels of proteins were analyzed with Western blot. Nadroparin not only prevented and ameliorated the AA-induced colitis histopathologically but also decreased expression of colon NF-κB, activator protein-1, cyclooxygenase-2, tumor necrosis factor-alpha, and IL-6, which were significantly increased in group AA compared to control. The accumulation of Nrf2 in nuclear fraction and HO-1 found low in group AA was increased with nadroparin (p < 0.05). The mean malondialdehyde level increased with AA and was decreased significantly with nadroparin prevention and treatment (p < 0.001). Nadroparin sodium has both protective and therapeutic effects against colonic inflammation via exerting anti-oxidative and anti-inflammatory effects by modulating Nrf2/HO-1 and NF-κB pathways.

Pegylated Interferon α Therapy in Chronic Delta Hepatitis: A One-Center Experience

Background: The only established therapy for chronic viral delta hepatitis, the most severe form of viral hepatitis is treatment with pegylated-interferon α (Peg IFN α). Objectives: In this study, we aimed to determine the efficacy of pegylated-interferon α 2a (Peg-IFN α 2a) and 2b (Peg IFN α 2b) in the treatment of patients infected with chronic delta hepatitis virus. Patients and Methods: The sample size was based on available patients potentially to be recruited. Data of 63 patients receiving either Peg IFN alpha 2a or Peg IFN alpha 2b were retrospectively assessed in the present cohort study performed in Turkey. Of 56 patients completed the study, 41 received Peg IFN α 2a and 15 received Peg IFN α 2b for 12 months. Patients were evaluated for biochemical and virological responses at the end of given treatment and six months after the treatment. Results: Stage of fibrosis was found high in both groups (85.4% vs. 86.7%), while cirrhosis was higher in the group of Peg IFN α 2b (53.3% vs. 34.1%). At the end of treatment, either hepatitis delta virus RNA (HDV RNA) alone or both HDV RNA and hepatitis b virus DNA (HBV DNA) had negative results in 32% of patients. Although HDV RNA negativity was sustained in 30.3% of patients, negativity of both HDV RNA and HBV DNA was decreased to 19.6% six months after completion of the treatment. HBV DNA became positive in one third of patients with response at six months after completion of the treatment (10.7% of all patients). HDV RNA negativity at month six was found as a predictor of positive response. No significant difference was found between Peg IFN α 2a and Peg IFN α 2b for virological response rate. Conclusions: Treatment with Peg IFN α achieved a sustained negativity of HDV RNA in about one third of patients. Duration of Peg IFN α therapy might be prolonged to at least 24 months or more to prevent the occurrence of Hepatitis B virus (HBV) relapse encountered six months after completion of the treatment.

PISTACIA TEREBINTHUS COFFEE PROTECTS AGAINST THIOACETAMIDE-INDUCED LIVER INJURY IN RATS

AIM/BACKGROUND Pistacia terebinthus is used as a coffee substitute in the East and Southern Anatolia regions of Turkey. It contains unsaturated fatty acids, tocopherols, polyphenols and carotenoids. P. terebinthus has anti-inflammatory and potential antioxidant activity. In this study we evaluated the protective effects of P. terebinthus coffee (PTC) on thioacetamide (TAA)-induced liver injury in rats. MATERIALS AND METHODS Twenty-eight male Sprague-Dawley rats were equally randomized into four groups. Chronic liver injury was induced with TAA (100 mg/kg i.p. three times weekly). The first group of rats served as control and received only tap water (G1), and the remaining groups of rats received PTC, p.o (G2); TAA (G3); TAA plus PTC, p.o (G4), respectively. RESULTS After 8 weeks, PTC intake significantly reduced fibrosis/inflammation scores (p PTC intake reduced transforming growth factor beta (TGF-β) concentrations in the liver (p PTC intake. DISCUSSION AND CONCLUSION PTC intake provided beneficial effects against TAA-induced liver injury in rats. PTC probably suppresses the proinflammatory cytokines through NF-κB signaling pathway.

Investigation of the association between clinical outcome and the cag pathogenicity-island and other virulence genes of Helicobacter pylori isolates from patients with dyspepsia in Eastern Turkey

The aims of our work were to determine the presence of the cag pathogenicity-island (cag PAI) and other virulence genes of Helicobacter pylori recovered from patients with gastritis and peptic ulcer, and to investigate the correlation of these virulence genes with clinical outcome. The presence of the cagA, the promoter regions of cagA, cagE, cagT, and the left end of cag-PAI (LEC), cag right junction (cagRJ), the plasticity region open reading frames (ORFs), vacA and oipA genes among 69 H. pylori isolates were determined by polymerase chain reaction. Intact cag PAI was detected in only one (1.4%) isolate. The cagA gene was identified in 52.1% and 76.2% of isolates from patients with dyspepsia (gastritis and peptic ulcer), respectively. The plasticity region ORFs i.e. JHP912 and JHP931 were predominantly detected in isolates from peptic ulcer. Less than 25% of the isolates carried other ORFs. Types I, II and III were the most commonly found among the isolates. None of the isolates possessed type Ib, 1c, IIIb, IV and V motifs. The most commonly vacA genotypes were s1am1a and s1m2 in isolates with peptic ulcer and gastritis, respectively. The results confirmed that the prevalence of oipA (Hp0638) gene was 75% and 85.7% in patients with gastritis and peptic ulcer, respectively. Furthermore, vacA s1am1a positivity was significantly related to peptic ulcer (p < 0.05).

Relationship between diverticulosis and nonalcoholic fatty liver disease in elderly patients

Objective To compare clinical and laboratory features of elderly patients with and without diverticulosis and assess factors related to hepatosteatosis. Method This retrospective case–control study analysed the clinical and laboratory data, colonoscopy and abdominal ultrasonography records of patients >65 years who underwent colonoscopies. Subjects were categorized according to the presence and absence of colonic diverticulosis. Univariate/multivariate logistic regression analyses were performed to evaluate the independent predictive factors of hepatosteatosis. Results A total of 355 patients were enrolled in the study: 169 had colonic diverticulosis; and 186 without colonic diverticulosis formed the control group. Age, sex and chronic disorders associated with the metabolic syndrome did not differ between the diverticulosis and control groups. The rate of hepatosteatosis was lower in patients with diverticulosis compared with the control group (27% versus 42%, respectively). Diabetes mellitus, hyperlipidaemia and hepatosteatosis were more common among patients aged <75 years. In the multivariate logistic regression analysis, diverticulosis remained an independent predictor of hepatosteatosis (odds ratio 0.529; 95% confidence interval 0.323, 0.866). Other independent predictive factors in the multivariate analysis were triglyceride and albumin. Conclusion Diverticulosis in the elderly was found to be a negative predictor of hepatosteatosis. Higher values of albumin and triglyceride in conjunction with the absence of diverticulosis may be suggestive of nonalcoholic fatty liver disease in the elderly.

A Neglected Issue in Ulcerative Colitis: Mesenteric Lymph Nodes

Data evaluating the presence and characteristics of mesenteric lymph nodes (LNs) in patients with ulcerative colitis (UC) are scarce. The aim of this study is to determine the presence and characteristics of LNs in UC. The LN characteristics in computed tomography (CT), including LN dimension and attenuation, were evaluated retrospectively in 100 patients with UC (61 active and 39 inactive cases). Clinical characteristics and laboratory parameters, including CBC, biochemical analysis, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were also compared. Mesenteric LNs were evident in all patients with UC. The attenuation and dimension of mesenteric LNs did not differ between active and inactive patients with UC. No correlation was found among patients with UC in terms of LN dimension, attenuation, ESR, CRP, leucocyte, and albumin (all with p > 0.05). The current study suggested that inflammation results in the development of mesenteric LN in UC, similar to Crohn’s disease and other inflammatory disorders.

An Overlooked Potentially Treatable Disorder: Idiopathic Mesenteric Panniculitis

Objective: The aim of this study was to determine the prevalence of mesenteric panniculitis (MP) and to describe its clinical characteristics, therapy, and outcome. Subjects and Methods: This retrospective study was carried out among patients with MP based on computed tomography (CT) scans from January 2012 to December 2015. The CT images were reanalyzed by study radiologists to confirm the previous MP diagnosis. Patients were divided into 2 groups, i.e., idiopathic and secondary, based on the presence or absence of associated predisposing factors such as trauma, malignancy, autoimmune disorders, ischemia, or previous abdominal surgery. The clinical characteristics of the 2 groups, as well as treatments, were assessed. Results: Among the 19,869 CT scans, 36 patients (0.18%) with MP were identified (i.e., 19 [53%] females and 17 [47%] males). The median age was 54 years (range 26 - 76). Twenty-four patients (67%) were categorized into the idiopathic group. Malignancy was the predisposing factor in 8 (22%) of those patients. Furthermore, abdominal pain was the cardinal symptom observed in 22 patients (92%) in the idiopathic group. In the idiopathic group, 15 patients (63%) were treated with antibiotics and 16 (67%) were treated with nonsteroidal anti-inflammatory drugs (NSAID). One unresponsive patient was treated with colchicine. Symptomatic relief was achieved in all of the treated patients. Conclusion: In this study, a symptomatic idiopathic subgroup of patients with MP did not have any associated disorder. The response to treatment with antibiotics and NSAID was effective in most of the patients. Based on these findings, anti-inflammatory treatments beyond NSAID and surgery should be reserved for patients who are unresponsive to antibiotics and NSAID.

Impact of interleukin 28B rs12979860 C/T polymorphism on severity of disease and response to treatment in hepatitis delta

INTRODUCTION Pegylated-interferon alpha (Peg-IFN α) is the therapy most commonly used to treat chronic hepatitis delta virus (HDV) infection. In the present study, we planned to investigate effect of IL28B polymorphism on response to Peg-IFN α therapy and disease progression in patients with chronic HDV. METHODOLOGY A total of 47 patients who received Peg-IFNα therapy for at least one year were investigated. The patients were divided into three groups based on their response to treatment: sustained viral response (SVR) (32%), unresponsive (53%), and relapse (15%). The groups were compared in terms of age, gender, blood biochemistry (albumin, total bilirubin, lactic acid dehydrogenase, ALT, AST, ALP, GGT), complete blood count, HBeAg, HBsAg, HBV-DNA, HDV-RNA, IL28B genotypes (CC, CT, TT), and results of liver biopsy. RESULTS Regarding the investigation of IL28B genotype, the prevalence of CC, CT, and TT showed no difference among the three groups. In the SVR group, the prevalence of CC was 53%, CT was 47%, but there was no patient with TT. In the unresponsive group, prevalence of CC was 52%, CT was 32%, and TT was 16%. In the relapse group, prevalence of CC was 43%, CT was 57%, but there was no patient with TT genotype. No significant difference was found among the groups with sustained response, no response, and relapse in terms of CC and CT polymorphisms (p>0.05). CONCLUSIONS No relationship was found between IL28B rs12979860 polymorphism and response to treatment and disease severity in patients with chronic HDV infection.

Çölyak hastalığı; 5 yıllık takip, antikor-patoloji korelasyonu

Giris ve Amac: Bu calismanin amaci colyak hastaligi tanisi ile takip edilen hastalarin klinik, laboratuvar ve patolojik ozelliklerinin arastirilmasidir. Gerec ve Yontem: Klinigimizde colyak hastaligi tanisi ile takip edilen hastalar retrospektif olarak degerlendirildi. Anti-gliadin antikor immunglobulin A, anti-endomisyum, doku transglutaminaz immunglobulin A ve immunglobulin G antikorlari kaydedildi. Hastalarin tani aninda klinik ve laboratuvar ozellikleri patolojik Marsh siniflamasina gore gruplara ayrilarak gruplar arasi farkliliklar saptanmaya calisildi. Bulgular: Calismaya klinigimizde takip edilen toplam 174 hasta alindi. Hastalarin 107’si (%61,5) kadin, 67’si (%38,5) erkekti. Ortalama tani yasi 30,67 (min/mak:18/73)’tu. Tani aninda hastalarin %24’unde anemi, 118 hastanin 24’unde (%20,3) vitamin B12 eksikligi, 110 hastanin 27’sinde (%24,5) folik asit eksikligi mevcuttu. D vitamini eksikligi 84 hastanin 63’unde (%75) saptandi. Kemik mineral dansitometresi bakilan 53 hastanin %49,1’inde (26/53) osteoporoz, %41,5’inde osteopeni (22/53) saptandi ve %9,4’u normaldi. Endoskopik biyopsi sonuclari Marsh siniflamasina gore; 17’si (%14) sinif 1, 20’si (%16,5) sinif 2, 71’i (%58,6) sinif 3 ve 13’u (%10,7) sinif 4 grubundaydi. Marsh 1’de sirasiyla anti-gliadin antikor immunglobulin A, anti-endomisyum, doku transglutaminaz immunglobulin A, doku transglutaminaz immunglobulin G pozitiflik oranlari %22.2, %50, %54.5 ve %20 iken Marsh 4’te pozitiflik oranlari sirasi ile %100, %100, %81.8 ve %87’ye cikmaktadir. Antikor pozitifliginin Marsh 1’den Marsh 4’e giderek arttigi gozlendi. Sonuc: Marsh 1 hastalarinda dusuk oranda antikor pozitifligi saptanmasi bu grup hastalarin bir kisminin colyak olmayabilecegini dusundurmektedir. Marsh 1 saptanan olgularin kesin colyak hastaligi tanisi oncesi, diger hastaliklar yonunden irdelenmesi gerekmektedir.