Serum paraoxonase activity is decreased in the active stage of Behçet's disease

AIMS: To evaluate paraoxonase1 (PON1) activities and malondialdehyde (MDA) levels, one of the end products of lipid peroxidation induced by reactive oxygen species in patients with Beh?et's disease (BD) in the active stage. METHODS: Serum MDA levels and PON1 levels were measured spectrophotometrically in 16 patients with BD in the active stage of the disease and in 15 healthy subjects who constituted the control group. RESULTS: In the BD group, median (range) serum PON1 and MDA levels were 149.64 U/l (88.02-281.68) and 1.21 nmol/ml (0.90-3.42), respectively. In the control group, median (range) serum PON1 and MDA levels were 206.86 U/l (114.43-422.52) and 0.72 nmol/ml (0.50-1.12), respectively. There was a statistically significant decrease in serum PON1 levels (p = 0.02) and an increase in serum MDA levels (p<0.001) in patients with BD in the active stage when compared to controls. CONCLUSION: Endothelial damage and increased polymorph nuclear leucocyte activity in the active stage of BD could result in a pro-oxidation environment which, in turn, results in decreased antioxidant PON activity and increased lipid peroxidation as evidenced by increased MDA levels.     

Glandular hamartoma of the larynx

Glandular hamartoma of the larynx is an extremely rare lesion, and the number of well-documented and acceptable cases is limited. Presenting symptoms may include changes in voice, eating and activity levels, and respiratory complaints. We report on a 14-month-old infant with this rare clinical entity. Direct laryngoscopy revealed a well-mucosalized, encapsulated, firm, 0.5 cm wide and 2.5 cm long lesion that originated from the right aryepiglottic fold and reached into the nasopharynx. The mass was completely excised endoscopically. Histopathological examination revealed a hamartoma, which was composed of glandular elements, mixed with mesodermal tissues. After endoscopic removal of the hamartoma, the child was relieved of the obstruction.     

Effect of Weight Loss on Bone Metabolism: Comparison of Vertical Banded Gastroplasty and Medical Intervention

Background: We studied the effects of weight loss on bone metabolism. Methods: 16 consecutive surgically-treated (14 female, 2 male) morbidly obese patients and 65 obese (53 male, 12 female) medically-treated patients were enrolled in an observational study. Surgical treatment for morbidly obese patients was vertical banded gastroplasty (VBG). Studies were performed prior to and 12 months after the start of treatment. Bone mineral density (BMD), bone turnover markers, sex steroids, calcium excretion and parathyroid hormone measurements were done at each visit. Results: Weight loss was more prominent with surgical than with medical treatments. Bone loss was also pronounced in the surgical treatment group, and occurred at the hip level only (P<0.05). Compared to previously reported studies, where the effects of malabsorptive treatments for obesity on bone metabolism were studied, calcium excretion and parathyroid hormone levels did not change after VBG or medical therapy. For both groups, bone markers indicated an increased bone turnover, evidenced by increased urinary excretion of deoxypyridinoline and serum levels of osteocalcin (P<0.05). Sex steroid measurements revealed a decrease in estradiol levels in the surgical treatment group, but not in medical treatment group. This finding was thought to be secondary to less weight loss in the medical group. Conclusion: Our data indicate that weight loss causes bone loss. The bone loss is independent of the method of weight reduction. However, the mechanism of the bone loss is not clear. It may be explained partly by reduced estradiol levels in female patients. Because the mechanisms of bone disease after weight loss remain unclear, it is difficult to determine the most effective treatment. It is important to detect osteopenia early, before fractures occur. Measuring BMD appears to be the only reliable method for screening.     

Adductor T reflex abnormalities in patients with decreased patellar reflexes

The adductor reflex (AR) is a tendon reflex that has various features that differ from other tendon reflexes. This reflex was tested in different disorders presenting with diminished patellar reflexes such as diabetic lumbosacral radiculoplexus neuropathy (DLRPN), L2–L4 radiculopathy, and distal symmetric diabetic neuropathy (diabetic PNP). The AR and crossed‐AR (elicited by tapping the contralateral patellar tendon) were recorded using concentric needle electrodes. Additionally, the patellar T reflex (vm‐TR) and vastus medialis H reflex (vm‐HR) were recorded using surface electrodes. AR was recorded in only one out of eight patients with DLRPN, but it was recorded in 21 out of 22 patients with L2–L4 radiculopathy (95.5%). Of these reflexes, only AR showed prolonged latency in the L2–L4 radiculopathy group. The latencies of AR, vm‐TR, and vm‐HR were prolonged in patients with diabetic PNP. We conclude that AR can be useful in the differential diagnosis of some lower motor neuron disorders that present with patellar reflex disturbance. Muscle Nerve 40: 264–270, 2009     

Frequency of hepatitis G virus and transfusion-transmitted virus infection in type II diabetes mellitus

The hepatitis G virus (HGV) and transfusion-transmitted virus (TTV) are recently defined hepatitis viruses that the pathogenic roles in liver diseases are still not clear. It has been well known that some hepatitis virus, such as hepatitis C, might have an affinity to pancreatic islet cells. To investigate the relationship between the newly defined hepatitis viruses and diabetes mellitus (DM), we studied the prevalence of TTV and HGV in a type 2 diabetic patient population. Serum samples of 60 patients with DM and 45 healthy volunteers as control were taken. HGV RNA and TTV DNA was investigated by polymerase chain reaction. HGV was detected in none of diabetic patients (0%) and only one in control group (2.2%). However, TTV DNA was detected in 16 patients with DM (26%) and in five controls (11%). TTV was more prevalent in diabetic patients, but the difference between groups was not statistically significant (p > 0.05). These results revealed that TTV is more common in diabetic patients than in controls. At present, we don't know if this result is only a coincidence or a sign of potential association between TTV and DM. Further studies are certainly needed to elucidate a potential relationship.     

Circulating leptin and body composition in chronic obstructive pulmonary disease

Nutritional depletion and weight loss are two features of chronic obstructive pulmonary disease (COPD), and the association between low body mass index (BMI) and poor prognosis in patients with COPD is a common clinical observation. Mechanisms of weight loss are still unclear in COPD. Excessive energy expenditure partly due to increased work of breathing was shown, but other mechanisms have been searched for. Leptin is a hormone secreted by adipocytes that plays an important role in energy homeostasis and regulates body weight through control of appetite and energy expenditure. The aim of this study was to evaluate the association of circulating leptin levels and measures of body composition in COPD patients. Thirty male COPD outpatients (mean age 66.3 +/- 8.4) and 20 controls (mean age 65.9 +/- 10.8) were included in the study. After standard spirometry and body composition measurements, serum leptin concentration was measured by ELISA assay. COPD patients were grouped according to BMI. Mean BMI was 19.01 +/- 2.26 kg/m2 in group 1 (COPD patients with low BMI), 26.85 +/- 4.51 in group 2 COPD (COPD patients with normal/high BMI) and 27.64 +/- 2.75 kg/m2 in healthy controls (group 3). Mean serum leptin concentration was 1.41 +/- 1.86 ng/ml in group 1, 2.60 +/- 1.38 ng/ml in group 2 and 2.82 +/- 1.46 ng/ml in group 3 (p = 0.002). Leptin correlated to not only BMI but also body weight, waist circumference, triceps and biceps skinfold thickness and body fat percent (p < 0.05 for all). Results of this study suggest that the cause of weight loss is not increased circulating leptin in COPD. Instead, leptin remains regulated in COPD and further decreased in patients with low BMI, probably as a compensatory mechanism to preserve body fat content, which should be evaluated in further studies.     

Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency

Journal of Clinical Immunology - NF-κB essential modulator (NEMO, IKK-γ) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are...     

BRAF Activation Initiates but Does Not Maintain Invasive Prostate Adenocarcinoma

Prostate cancer is the second leading cause of cancer-related deaths in men. Activation of MAP kinase signaling pathway has been implicated in advanced and androgen-independent prostate cancers, although formal genetic proof has been lacking. In the course of modeling malignant melanoma in a tyrosinase promoter transgenic system, we developed a genetically-engineered mouse (GEM) model of invasive prostate cancers, whereby an activating mutation of BRAF^V600E–a mutation found in ~10% of human prostate tumors–was targeted to the epithelial compartment of the prostate gland on the background of Ink4a/Arf deficiency. These GEM mice developed prostate gland hyperplasia with progression to rapidly growing invasive adenocarcinoma without evidence of AKT activation, providing genetic proof that activation of MAP kinase signaling is sufficient to drive prostate tumorigenesis. Importantly, genetic extinction of BRAF^V600E in established prostate tumors did not lead to tumor regression, indicating that while sufficient to initiate development of invasive prostate adenocarcinoma, BRAF^V600E is not required for its maintenance.     

Effect of diffuse fatty infiltration of the liver on hepatic artery resistance index

PURPOSE: This study was conducted to evaluate the effect of various degrees of diffuse fatty infiltration of the liver on the hepatic artery resistance index. METHODS: One-hundred forty subjects were examined using standard color and spectral Doppler sonography protocols. Fatty infiltration of the liver was identified and graded sonographically. The patients were grouped (n = 35 in each of 4 groups) according to the degree of diffuse fatty infiltration of the liver as follows: normal (group 1), mild (group 2), moderate (group 3), and severe (group 4). The resistance index calculated for each patient was the mean of 3 measurements. Mean resistance index of the hepatic artery was then calculated for each group. RESULTS: The mean resistance index was 0.81 +/- 0.04 for group 1, 0.79 +/- 0.06 for group 2, 0.75 +/- 0.05 for group 3, and 0.73 +/- 0.05 for group 4. We found a statistically significant (p < 0.05) decrease in resistance index when comparing groups 3 and 4 with groups 1 and 2 separately. CONCLUSIONS: Hepatic artery resistance index decreases as the severity of diffuse fatty infiltration increases.     

Primary antibody deficiencies in Turkey: molecular and clinical aspects

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n?=?4), CD40L (n?=?1), ICOS (n?=?1), IGHM (n?=?1), and TCF3 (n?=?1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2–10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.