Tevfik Noyan

Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects

Objective To evaluate the serum levels of zonulin, which regulates tight junctions between enterocytes and is a physiological modulator controlling intestinal permeability, in patients with autism spectrum disorders (ASDs). Study design Serum zonulin levels were determined in 32 patients with ASD and 33 healthy controls using an enzyme‐linked immunosorbent assay. The severity of ASD symptoms was assessed with the Childhood Autism Rating Scale. Results Serum zonulin levels were significantly higher in the patients with ASD (122.3 ± 98.46 ng/mL) compared with the healthy controls (41.89 ± 45.83 ng/mL). There was a positive correlation between zonulin levels and Childhood Autism Rating Scale score when all subjects were assessed (r = 0.523; P < .001). Conclusions This study suggests that zonulin, which regulates intestinal permeability, plays a role in the development of symptoms of ASD.

Evaluation of serum Neuron-specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder

Brain specific‐proteins are not found in other tissues and measurement non‐invasively in the blood may identify structurally and functionally damaged brain regions and identify the severity and prognosis of neuropsychiatric diseases. For this reason, we aimed to evaluate serum brain‐specific protein values as brain damage markers in children with autism spectrum disorder (ASD).

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

Introduction 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). Materials and methods K2-EDTA whole blood samples (total of 3363) were collected from 12 laboratories. Sera were also collected for measurements of iron, UIBC, TIBC, and ferritin for use in the latent abnormal values exclusion (LAVE) method. The blood samples were analysed within 2 hours in each laboratory using Cell Dyn and Ruby (Abbott), LH780 (Beckman Coulter), or XT-2000i (Sysmex). A panel of freshly prepared blood from 40 healthy volunteers was measured in common to assess any analyser-dependent bias in the measurements. The SD ratio (SDR) based on ANOVA was used to judge the need for partitioning RVs. RIs were computed by the parametric method with/without applying the LAVE method. Results Analyser-dependent bias was found for basophils (Bas), MCHC, RDW and MPV from the panel test results and thus those RIs were derived for each manufacturer. RIs were determined from all volunteers’ results for WBC, neutrophils, lymphocytes, monocytes, eosinophils, MCV, MCH and platelets. Gender-specific RIs were required for RBC, haemoglobin, haematocrit, iron, UIBC and ferritin. Region-specific RIs were required for RBC, haemoglobin, haematocrit, UIBC, and TIBC. Conclusions With the novel use of a freshly prepared blood panel, manufacturer-specific RIs’ were derived for Bas, Bas%, MCHC, RDW and MPV. Regional differences in RIs were observed among the 7 regions of Turkey, which may be attributed to nutritional or environmental factors, including altitude.

Endoplasmic reticulum stress in the livers of BDNF heterozygous knockout mice

Abstract Context: Involvement of endoplasmic reticulum (ER) stress and brain-derived neurotrophic factor (BDNF) in hepatic lipid metabolism has been reported previously. Objective: The effects of chronic BDNF deficiency on ER stress response in the livers were examined in this study. Methods: BDNF(+/−) mice, characterised by BDNF deficiency, and their wild-type (WT) littermates were used. The ER stress was induced by tunicamycin (Tm) (0.5 mg/kg, intraperitoneal). Animals were divided into four groups; WT, WT + Tm, BDNF(+/−), and BDNF(+/−)+Tm. Results: At the basal conditions, BDNF deficiency did not affect hepatic cell death or lipid accumulation. However, during ER stress, BDNF(+/−)+Tm group showed increased apoptosis, GADD153 immunostaining, sterol regulatory element-binding protein-1c (SREBP-1c) level, and steatosis compared to the WT + Tm group. Conclusion: Endogenous BDNF might be protective against apoptosis through GADD153 suppression and steatosis via SREBP-1c suppression during ER stress. This effect of BDNF might be clinically important for type 2 diabetes and obesity, which are related with both ER stress and BDNF deficiency.

The Effect of Tadalafil on Renal Fibrosis Induced by Ureteral Obstruction

Objective: It has been reported that phosphodiesterase-5 (PDE-5) inhibitors improve kidney function during acute and chronic renal failure. This study aimed to determine the possible therapeutic effects of tadalafil, a specific PDE-5 inhibitor, on renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Male Sprague-Dawley rats were used and randomly divided into three groups (n = 6) as sham-operated, UUO and tadalafil-treated (10 mg/72 hours, ig) UUO (UUO+T) groups. Unilateral ureteral obstruction was induced by complete ligation of the left ureter and 14 days after surgery creatinine clearance, urinary cyclic guanosine monophosphate (cGMP), renal alpha-smooth muscle actin (α-sma) and transforming growth factor βeta (TGF-β) levels, as well as histologic changes, were observed in all the animals. Results: Unilateral ureteral obstruction-induced renal fibrosis was confirmed by increased α-sma level, collagen deposition, tubular dilation, inflammatory cell infiltration and necrosis. An increased renal TGF-β level and decreased urinary cGMP level was also observed in obstructed animals in addition to reduced creatinine clearance. Tadalafil treatment, which restored the animals’ urinary cGMP level, significantly attenuated the fibrotic changes and TGF-β increase in their kidneys. Conclusion: This study suggests that tadalafil treatment ameliorates renal fibrosis by reducing TGF-β expression and may have important clinical relevance since tadalafil is currently used clinically to treat erectile dysfunction and pulmonary hypertension.

Comparison of the effects of continuous versus intermittent enteral feeding on plasma leptin and ghrelin levels in Intensive Care Units

Objetivo: Este ensaio aleatorio prospectivo tem por objetivo verificar se existe uma associacao entre o programa de administracao de nutricao enteral e os hormonios leptina e grelina, os quais funcionam no metabolismo energetico. Metodos: Este estudo incluiu 38 pacientes de Unidades de Terapia Intensiva, com idades entre os 18 e os 85 anos, que receberam nutricao enteral. Os pacientes foram escolhidos aleatoriamente para receberem nutricao enteral utilizando infusao continua (n=19) ou intermitente (n=18). Alem de exames bioquimicos de rotina, foram colhidas amostras de sangue dos pacientes para analises dos niveis de leptina e grelina no 1o, 7o e 14o dias de nutricao enteral. Resultados: Nao houve diferenca estatistica significante entre os grupos em relacao a dados descritivos e variaveis categoricas tais como doencas subjacentes, complicacoes, utilizacao de esteroides e outros (p>0,05). A diminuicao no numero de leucocitos e nos niveis de creatinina e proteina C-reativa com o tempo foi estatisticamente significativa (p=0,010, p=0,026, p<0,001, respetivamente). Nao existiu diferenca com significância estatistica entre os grupos em relacao aos niveis de leptina e grelina (p=0,982 e p=0,054). Embora os niveis de leptina nao mudaram com o tempo, os niveis de grelina de ambos os grupos foram significativamente superiores no 7° e 14° dias quando comparados aos verificados na analise do primeiro dia (p=0,003). Conclusao: Este estudo revelou que os programas de nutricao enteral continua e intermitente foram bem tolerados com pequenas complicacoes apresentadas pelos pacientes em Unidades de Terapia Intensiva. O padrao de administracao de nutricao enteral por si so nao afetou os niveis de leptina e grelina. Estudos controlados aleatorios em coortes maiores sao necessarios para verificar qual programa de administracao de nutricao enteral, intermitente ou a continuo, e mais adaptavel ao padrao de secrecao diurno de hormonios metabolicos.

Comparison of serum acetyl hydrolase (PAF-AH) and paraoxonase 1 (PON1) values between prostate cancer patients and a control group

The aim of the study was to measure platelet‐activating factor acetyl hydrolase (PAF‐AH) and paraoxonase (PON1) enzyme activity levels in patients with high Psa values to compare with healthy peers and also to determine the efficacy of these parameters in predicting pathologic results of patients with high Psa values. This study included 66 patients with Psa value > 4 ng/dl (Group 1) and 44 patients with Psa <4 ng/dl (Group 2) for a total of 110 patients. Parameters measured in serum of PON1, PAF‐AH, and MDA were compared between the groups. Additionally the same parameters were compared between patients with prostate biopsy performed due to high Psa and diagnosed with cancer and the control group with normal Psa values. The PAF‐AH activity in Group 1 was 125.17 ± 8.64 and in Group 2 was 120.08 ± 9.23 U/ml (p = 0.003). The PON1 activity was 63.12 ± 6.74 and 65.91 ± 7.77 U/ml in the groups, respectively (p = 0.04). Additionally, there were significant differences identified between the control group and PCa diagnosis group in terms of PAF‐AH and PON1 activities (p = 0.004 and p = 0.02, respectively). The enzyme activity of PAF‐AH and PON1 measured in serum of patients with high Psa value and patients with diagnosis of prostate cancer (PCa) were identified to have changed by a significant amount compared to healthy peers with normal Psa value. It was concluded that these parameters may be beneficial markers for use in assessment of patients with high Psa value.