Outcome and Genetic Factors in IgG4-Associated Autoimmune Pancreatitis and Cholangitis: A Single Center Experience

Introduction. Most investigations on autoimmune pancreatitis (AIP) were published on Asian cohorts while those on Caucasians are limited. However, there might be differences related to the origin. Patients and Methods. We analyzed 36 patients and compared type 1 (AIP1) with type 2 (AIP2). Results. The majority of patients suffered from AIP1 (55.6%). AIP1 patients were significantly older than AIP2 patients (54.4 versus 40.8 years). Moreover, 85.0% of AIP1 patients had concurrent autoimmune cholangitis (AIC) while 18.8% of AIP2 patients suffered from overlap to ulcerative colitis (UC). However, AIP1 patients revealed a cholestatic course and had significantly higher immunoglobulin G4 levels (IgG4). When compared to allele frequencies in healthy controls, in patients with AIP1 HLA-B8 reached statistical significance. Response to steroids was excellent in both groups, but we noticed high rates of relapse especially in AIP1 patients. Finally, 3 patients with AIP1 were diagnosed with cholangiocellular carcinoma (CCC). Conclusion. In contrast to Asian studies, we found an almost equal distribution of AIP1 and AIP2 patients in our German cohort. AIP2 patients were younger and mostly of female gender whereas AIP1 patients revealed higher IgG4 levels and involvement of the biliary tract in sense of IgG4-associated cholangitis.

Multiple Spontaneous Intracranial-Extracranial Arterial Dissections in a Patient with Osteogenesis Imperfecta

A 40-year-old male with osteogenesis imperfecta (OI) was admitted to the hospital with an acute right monoparesis. Diffusion-weighted MRI showed infarction in the territory of the left anterior cerebral artery (ACA) and in the left posterior cerebral artery (PCA). In his vascular imaging, occlusion of the left vertebral artery (VA) starting from V2 segment was consistent with dissection and pseudoaneurysm in the right ACA. We presented this case because of the presence of spontaneous and simultaneous occurrence of both intracranial and extracranial arterial dissections in OI.

Synthesis of Peripherally Tetrasubstituted Phthalocyanines and Their Applications in Schottky Barrier Diodes

New metal-free and metallophthalocyanine compounds (Zn, Co, Ni, and Cu) were synthesized using 2-hydroxymethyl-1,4-benzodioxan and 4-nitrophthalonitrile compounds. All newly synthesized compounds were characterized by elemental analysis, FT-IR, UV-Vis, 1H-NMR, MALDI-TOF MS, and GC-MS techniques. The applications of synthesized compounds in Schottky barrier diodes were investigated. Ag/Pc/p–Si structures were fabricated and charge transport mechanism in these devices was investigated using dc technique. It was observed from the analysis of the experimental results that the charge transport can be described by Ohmic conduction at low values of the reverse bias. On the other hand, the voltage dependence of the measured current for high values of the applied reverse bias indicated that space charge limited conduction is the dominant mechanism responsible for dc conduction. From the observed voltage dependence of the current density under forward bias conditions, it has been concluded that the charge transport is dominated by Poole-Frenkel emission.

Chemopreventive and Antitumor Efficacy of Curcumin in a Spontaneously Developing Hen Ovarian Cancer Model

We investigated the effect of daily dietary curcumin intake on the development and progression of spontaneous ovarian cancer in a galline (hen) model, as the chicken is the only nonhuman animal in which ovarian cancer spontaneously develops with a high prevalence. At the end of 12 months, ovarian cancer had spontaneously developed in 39% (35/90) of control hens not fed curcumin ( n = 90). In comparison, it spontaneously developed in 27% (24/90) and 17% (15/90) of hens given curcumin at 25.8 ( n = 90) and 53.0 mg/day ( n = 90), respectively ( P = 0.004). This represented significant dose-dependent reductions in overall ovarian cancer incidence in the 25.8 and 53.0 mg/day curcumin-fed groups (31% and 57%, respectively). Daily curcumin intake also reduced ovarian tumor sizes ( P = 0.04) and number of tumors ( P = 0.006). Evaluation of the molecular mechanisms underlying the chemopreventive and antitumor effects of curcumin revealed that NF-κB and STAT3 signaling pathways were significantly inhibited but that the nuclear factor erythroid 2/heme oxygenase 1 antioxidant pathway was induced by curcumin intake in a dose-dependent manner in ovarian tissues ( P < 0.05). Sequencing of the Ras family genes ( KRAS, NRAS , and HRAS) revealed less frequen KRAS and HRAS mutations in ovarian tumors in the curcumin-fed animals. In conclusion, our results demonstrated for the first time that daily curcumin intake leads to a significant and dose-dependent reduction in spontaneous ovarian cancer incidence and tumor growth, indicating a tremendous role for curcumin as a chemopreventive strategy for ovarian cancer. Cancer Prev Res; 11(1); 59-67. ©2017 AACR .

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.

Contents Vol. 153, 2017

MicroRNA Signature of Cigarette Smoking and Evidence for a Putative Causal Role of MicroRNAs in Smoking-Related Inflammation and Target Organ Damage

Background— Cigarette smoking increases risk for multiple diseases. MicroRNAs regulate gene expression and may play a role in smoking-induced target organ damage. We sought to describe a microRNA signature of cigarette smoking and relate it to smoking-associated clinical phenotypes, gene expression, and lung inflammatory signaling. Methods and Results— Expression profiling of 283 microRNAs was conducted on whole blood–derived RNA from 5023 Framingham Heart Study participants (54.0% women; mean age, 55±13 years) using TaqMan assays and high-throughput reverse transcription quantitative polymerase chain reaction. Associations of microRNA expression with smoking status and associations of smoking-related microRNAs with inflammatory biomarkers and pulmonary function were tested with linear mixed effects models. We identified a 6-microRNA signature of smoking. Five of the 6 smoking-related microRNAs were associated with serum levels of C-reactive protein or interleukin-6; miR-1180 was associated with pulmonary function measures at a marginally significant level. Bioinformatic evaluation of smoking-associated genes coexpressed with the microRNA signature of cigarette smoking revealed enrichment for immune-related pathways. Smoking-associated microRNAs altered expression of selected inflammatory mediators in cell culture gain-of-function assays. Conclusions— We characterized a novel microRNA signature of cigarette smoking. The top microRNAs were associated with systemic inflammatory markers and reduced pulmonary function, correlated with expression of genes involved in immune function, and were sufficient to modulate inflammatory signaling. Our results highlight smoking-associated microRNAs and are consistent with the hypothesis that smoking-associated microRNAs serve as mediators of smoking-induced inflammation and target organ damage. These findings call for further mechanistic studies to explore the diagnostic and therapeutic use of smoking-related microRNAs.

Stroke and Circulating Extracellular RNAs

There is increasing interest in extracellular RNAs (ex-RNAs), with numerous reports of associations between selected microRNAs (miRNAs) and a variety of cardiovascular disease phenotypes. Previous studies of ex-RNAs in relation to risk for cardiovascular disease have investigated small numbers of patients and assayed only candidate miRNAs. No human studies have investigated links between novel ex-RNAs and stroke.

TÜRKİYE’DE FAALİYET GÖSTEREN MEVDUAT BANKALARININ BİREYSEL VE SEKTÖREL RİSK DERECELENDİRMESİ: BİR CAMELS ANALİZİ UYGULAMASI

A nationwide multicentre study in Turkey for establishing reference intervals of haematological parameters with novel use of a panel of whole blood

A nationwide multicentre study was conducted to establish well-defined reference intervals (RIs) of haematological parameters for the Turkish population in consideration of sources of variation in reference values (RVs).