Ulnar artery aneurysm in a patient with Behçet’s disease

Behçet’s disease is a systemic disease characterized by oral aphthosis, genital ulcers, ocular lesions, gastrointestinal, musculoskeletal, neurological and major vessel involvement. Arterial involvement, aneurysms and arterial thrombosis have been reported in 1.5–3% of patients. In this case report, we present a patient with ulnar arterial aneurysm associated with Behçet’s disease.     

The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus

Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes‐associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes‐associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high‐titre anti‐glutamic acid decarboxylase (GAD)—compared with single and low‐titre autoantibody—is associated with an early age of onset, low fasting C‐peptide values as a marker of reduced pancreatic B‐cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut‐off points of anti‐GAD for differentiating clinically relevant diabetes mellitus subgroups.     

A substituted tetrahydro-tetrazolo-pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion

The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals are thought to play a role in suppressing the HBV-specific immune response. Current therapeutics are not directed at reducing this viral antigenemia; thus, our group has focused on identifying inhibitors of HBsAg secretion. By using the HBV-expressing cell line HepG2.2.15, high-throughput screening of an 80,288-compound synthetic small-molecule library identified HBF-0259, an aromatically substituted tetrahydro-tetrazolo-(1, 5-a)-pyrimidine. Following resynthesis, HBF-0259 had a 50% effective concentration of approximately 1.5 microM in a secondary, HBV-expressing cell line, with a concentration that exhibited 50% cytotoxicity of >50 microM. The equilibrium concentration of HBF-0259 in aqueous solution at physiological pH was 15 to 16 microM; the selective index was thus >9. As intended by our screening paradigm, HBF-0259 is a selective, potent inhibitor of secretion of both subviral and DNA-containing viral particles, while the secretion of alpha-1-acid glycoprotein and alpha-1-antitrypsin was unaffected. The HBV e antigen, which is not a constituent of HBV particles, was also unaffected, suggesting that the secretion of particles bearing HBV structural glycoproteins is targeted directly. Inhibitory activity was also confirmed by transfection of HBsAg, indicating that the action of the compound is independent of those of other viral proteins. HBF-0259 had no effect on HBV DNA synthesis, demonstrating that inhibition is independent of viral genomic replication. Finally, HBF-0259 had little or no effect on the cell-to-cell spread of two unrelated viruses, suggesting that it is a specific inhibitor of secretion of HBsAg. Possible mechanisms of action and the implications for its development are discussed.     

Lymphocytic Colitis Associated with Lansoprazole Treatment

Introduction: There have been several reported cases of lansoprazole-associated collagenous colitis (CC) reported in the literature but only 1 reported case of lansoprazole-associated lymphocytic colitis (LC) in the literature. Both CC and LC are considered inflammatory bowel diseases, but they are distinctly classified based on the condition of the colon, which is typically confirmed through biopsy.Case summaries: A 52-year-old white male (Patient 1), with a height of 178 cm and weight of 75 kg, presented to Gazi University Hospital, Ankara, Turkey, with a 3-month history of abdominal pain and nonbloody, watery diarrhea. The patient reported receiving PO lansoprazole 30 mg/d to treat heartburn ~1 week prior to the onset of diarrhea. The patient's medical history revealed that he did not have any preexisting conditions, other than gastroesophageal reflux disease (GERD) for which lansoprazole was prescribed. The medical history report also revealed that the patient was not receiving any concomitant medications or treatments at the time. A colon biopsy confirmed LC. Additionally, a 43-year-old white female (Patient 2), with a height of 168 cm and weight of 61 kg, presented to the same facility with a 6-month history of nonbloody, watery diarrhea and mild lower abdominal cramping. The patient reported that initial onset began ~2 months after receiving a 10-day Helicobacter pylori eradication combination treatment regimen that included lansoprazole, amoxicillin, and clarithromycin, followed by lansoprazole monotherapy to treat GERD. The patient's medical history revealed no other concomitant medications were being adminstered at the time. A colon biopsy confirmed LC.Discussion: A search of the literature using the MEDLINE database and all relevant English-language articles with key words lansoprazole and lymphocytic colitis, found that there were several cases of lansoprazole-associated CC reported and 1 reported case of lansoprazole-associated LC. Histologic findings from laboratory tests and colon biopsies confirmed diagnoses of LC in both patients in this case report. Patient 1 presented with diarrhea and cramping, which the patient reported had been ongoing for ~3 months, following lansoprazole administration. However, after lansoprazole was discontinued, the symptoms completely resolved within 7 days. Patient 2 presented with diarrhea and cramping, which had been occurring for ~6 months. That patient reported that initial onset commenced ~2 months after a 10-day H pylori eradication combination treatment regimen that included lansoprazole, amoxicillin, and clarithromycin, followed by lansoprazole monotherapy to treat GERD. However, after sulfasalazine (3 g/d) was prescribed for 2 months immediately upon diagnosis of LC, there was little improvement in the effort to control the diarrhea in this patient. After omeprazole 20 mg/d was substituted for lansoprazole, the patient's diarrhea ceased. Follow-up sigmoidoscopy 2 months later revealed normal mucosa and complete normalization of histologic findings. The patient remains diarrhea-free while on omeprazole. A causality assessment using the Naranjo adverse reaction algorithm produced scores of 6 for both patients, suggesting that LC was probably associated with lansoprazole treatment.Conclusions: Here we report 2 cases of LC in patients probably associated with the administration of lansoprazole treatment. Complete remission occurred after lansoprazole was discontinued.     

Screening of Tissue Transglutaminase Antibody in Healthy Blood Donors for Celiac Disease Screening in the Turkish Population

Celiac disease (CD) is a disease having the characteristic pathology of the mucosa of the small intestine. The prevalence of CD in the Turkish population has not been investigated previously. The present study was designed to determine the prevalence of CD in healthy blood donors. Serum samples of 2000 healthy blood donors presenting to Hacettepe University Faculty of Medicine Hospital Blood Bank were tested for tissue transglutaminase (tTG) IgA and IgG antibodies with enzyme-linked immunosorbent assay (ELISA; Euroimmune, Germany). The histopathological findings for the cases with positive serology were evaluated. The distribution of sex was 95.7% male, and 4.3% female. The mean age was 33 +/- 9. Among 2000 donors, 23 (1.15%) were positive for tTG IgA antibody and 3 (0.15%) were positive for tTG IgG antibody. None of the samples was positive for both antibodies. Serum total IgA was measured in two cases with only tTG IgG positivity and was found to be low in one case. Twelve subjects positive for tTG agreed to endoscopy and biopsy. Histopathological examination revealed changes classified as Marsh III-II in one, Marsh II in two, Marsh I in seven, and Marsh 0 in two donors. This was the first study conducted to determine the prevalence of tTG positivity in the Turkish population. The tTG antibody positivity prevalence in healthy blood donors was as high as 1.3%. This study shows that the prevalence of CD in the Turkish population is relatively high in comparison to that in the Western world.     

Rosiglitazone,peroxisome proliferator receptor-gamma agonist,ameliorates gentamicin-induced nephrotoxicity in rats

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe gram-negative infections. Reactive oxygen spaces (ROS) are important mediators of gentamicin-induced nephrotoxicity. Peroxisome proliferator-activated receptors (PPARs) have different activities including antioxidant properties. This study was performed to investigate the protective role of PPAR-γ agonist against GEN-induced nephrotoxicity. Male Wistar Albino rats were randomly divided into the following four groups, each of which consisted of six animals: (1) control; (2) intraperitoneally injected with GEN for 14 consecutive days (100 mg/kg/day); (3) treatment with rosiglitazone (RSG) via nasogastric gavage (10 mg/kg/daily for 14 days); (4) treatment with GEN + RSG combination for 14 day. Rats were decapitated on the 15th day and kidneys were removed. Urine was collected for every 24 h for the determination of daily urine volume. Urea, creatinine, Na⁺ and K⁺ levels were measured in blood. Malondialdehyde (MDA), reduced glutathion (GSH), and nitric oxide (NO) levels along with glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activities were determined in the renal tissue. Changes in body weight were recorded. GEN treatment was found to cause nephrotoxicity as evidenced by elevation of serum urea and creatinine levels. Renal impairment was also assessed by the renal histology. The significant decrease in GSH and increases in MDA and NO levels as well as a decrease in GSH-Px, CAT, and SOD activities indicated that GEN-induced renal damage was mediated through oxidative reactions. On the other hand, RSG administration protected kidney tissue against GEN-induced and free radical-mediated oxidative renal damage in rats.