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Biomedical subjects

T Coşkun

Publications and source records attributed to T Coşkun.

At least 19 recordsLinked to original sources
PubMed2006

Audiologic findings in children with biotinidase deficiency in Turkey.

OBJECTIVE: Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous features, including sensorineural hearing loss. Although many features of the disorder are reversible following treatment with biotin, the hearing loss appears to be irreversible. In the present study, hearing status of patients with biotinidase deficiency is characterized in a Turkish population. METHODS: Subjective and objective audiologic tests were performed on 20 children with profound biotinidase deficiency. RESULTS: Sensorineural hearing loss occurs in approximately 55% of the children with biotinidase deficiency. The hearing loss varies in severity from mild to profound hearing loss. In children diagnosed immediately after birth because they had an older sibling with the disorder, statistically significant differences were found between ABR results and age of diagnosis (p<0.05). Greater prolongation in ABR latencies were observed in the late-diagnosed children compared to that in the early-diagnosed children (p<0.05). CONCLUSION: Early diagnosis is important to prevent peripheral and central hearing loss. Children with biotinidase deficiency who have hearing loss are likely at increased risk for having speech and language problems. If hearing aids do not provide sufficient amplification, cochlear implantation may be indicated in these children. Therefore, it is important to test the hearing thresholds of these children with hearing aids and evaluate their language development.

Adolescent↗
PubMed2005

Xanthoma disseminatum: a child with respiratory system involvement and bronchiectasis.

Xanthoma disseminatum (XD) is a rare normolipemic mucocutaneous xanthomatosis due to the proliferation of non-x histiocytes. Occasional involvement of the upper respiratory system has been reported, but lower respiratory tract involvement is very rare. Here, we present a child with severe involvement of the upper and lower respiratory tract by XD and bronchiectasis in the lower lobes of both lungs. The patient was an 8-year-old boy who was admitted to our hospital because of red-brown papules which developed on the skin and progressive dyspnea. He was diagnosed as having XD by skin biopsy. Physical examination revealed disseminated, numerous yellow-reddish brown papular xanthomas on the forehead and eyelids, around the neck and axillary area, and in the oral cavity and pharynx. He had respiratory distress and clubbing of the fingers. Chest x-rays showed hyperaeration and segmental atelectasis. High-resolution CT of the thorax revealed diffuse thickening of the whole tracheal and bronchial wall, and bronchiectasis in the lower lobes. Flexible fiberoptic bronchoscopy revealed numerous xanthomatous lesions in the nasal cavity, nasopharynx, oropharynx, subglottic area, trachea, bifurcation, both main bronchi, and smaller bronchi. To the best of our knowledge, this is the first report of a child with typical lesions of XD with severe involvement of the lower respiratory tract and bronchiectasis.

Bronchiectasis↗
PubMed2005

The effect of oral L-carnitine supplementation on the lipid profiles of hyperlipidaemic children.

AIM: To investigate the carnitine status and the effect of carnitine supplementation on serum lipid profiles in children with hyperlipoproteinaemia, a clinical open trial was conducted at Hacettepe University Ihsan Dogramaci Children's Hospital, Section of Nutrition and Metabolism. METHODS: Patients were given carnitine at a dose of 100 mg/kg/d for 12 wk. Blood samples for the determination of lipid profile and carnitine levels and urine samples for carnitine levels were obtained on admission, at week 4 and week 12 of the study period. RESULTS: A total of 41 children were enrolled in the study: 20 patients had type II heterozygotes, eight patients had type II homozygotes, three patients had type III, six patients had type V and four patients had secondary hyperlipidaemias. Serum and urine carnitine levels were within normal limits on admission. No significant correlations were found between serum carnitine levels and serum lipid profiles. Serum HDL and apolipoprotein A-I decreased significantly during the 12 wk of intervention in type II heterozygotes. In type II homozygotes, total cholesterol and LDL levels at weeks 4 and 12 increased significantly compared to initial levels. No significant change was noted for lipid parameters in hyperlipoproteinaemia type V. CONCLUSION: The results of this trial demonstrated that carnitine supplementation was of no benefit for children with hyperlipidaemias, especially in primary hyperlipoproteinaemia type II heterozygotes, homozygotes and type V.

Administration, Oral↗
PubMed2002

Maple syrup urine disease: mutation analysis in Turkish patients.

Maple syrup urine disease (MSUD), the most frequently occurring organic acidaemia in Turkey, is caused by a deficiency of the activity of branched-chain keto acid dehydrogenase enzyme (BCKAD) complex. Mutation analysis of the E1alpha, E1beta, and E2 genes of the BCKAD complex in 12 Turkish MSUD patients yielded three disease-specific mutations and a polymorphism in the E1alpha gene, none in the E1beta gene and one mutation in the E2 gene. Among them, three missense mutations (Q80E, C213Y, T106M) and the F280F polymorphism occurring in the E1alpha gene and the splice site mutation (IVS3 - 1G>A) in the E2 gene were novel. Three of the missense mutations and the splicing mutation occurred homozygously and caused classical MSUD. One patient carried the splicing mutation homozygously and the T106M mutation in the heterozygous state; this patient is the first case having simultaneously two different mutations in two different genes in the BCKAD complex. IVS3 - IG>A splicing mutation detected on the E2 gene causes deletion of the first 14 bp of exon 3 in the mutant mRNA extending between 190 and 204 nt. The deletion spans the cleavage point between mitochondrial targeting and lipoyl-bearing site of the E2 protein.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2001

Inflammatory response to cold injury in remote organs is reduced by corticotropin-releasing factor.

Current experimental evidence concerning the potential activity of corticotropin releasing factor (CRF) in inflammatory processes still remains controversial. To determine whether CRF has protective effects on three remote organs (liver, lung and stomach) affected by cold injury and to characterize the role of neutrophils in cold-induced inflammation, dorsums of anesthetized rats were exposed for 5 min to a 22% NaCl solution maintained at -20+/-0.5 degrees C and the rats were sacrificed at 24 h after the cold injury. The results indicate that cold-exposure-induced edema in the liver, lung and stomach was blocked by subcutaneous (s.c.; 1.2 and 12 nmol/kg; 30 min before cold trauma) CRF pretreatment, while the central administration of CRF (intracisternally (i.c.); 0.30 and 1.5 nmol/rat; 15 min before cold) had the similar effect at the higher dose. Histological assessment and the tissue myeloperoxidase activities also revealed that CRF given peripherally has a protective role in damage generation. Moreover, CRF had a facilitatory effect in the recovery of the body temperature following cold exposure. In conclusion, CRF is likely to act on its peripheral receptors in the inflamed remote organs, suppressing the edematogenic effects of inflammatory mediators, some of which are neutrophil-derived.

Animals↗
PubMed2001

Evaluation of a fetus at risk for dihydropteridine reductase deficiency by direct mutation analysis using denaturing gradient gel electrophoresis.

Dihydropteridine reductase (DHPR) is an enzyme involved in the recycling of tetrahydrobiopterin (BH(4)), which is an obligate co-factor of the aromatic amino acid hydroxylases. DHPR deficiency is a rare, autosomal recessive disorder caused by mutations in the QDPR gene. DHPR-deficient patients are diagnosed by a lack of response to a low phenylalanine diet and by severe neurological symptoms. Final diagnosis is made by measurements of neurotransmitters and pterin metabolites in cerebrospinal fluid (CSF) and urine, in addition to DHPR enzyme activity, which can be assessed in whole red blood cells. Treatment of DHPR deficiency can be difficult and the outcome is not always satisfying, even if all treatment strategies are followed. Therefore prenatal diagnosis is of great importance in affected families. Prenatal diagnosis is possible by measuring DHPR activity in different cell types but this is time consuming. More than 25 different mutations have to date been identified in the QDPR gene and direct identification of a mutation in a fetus would be easy and rapid. We have developed a method based on denaturing gradient gel electrophoresis (DGGE) for the analysis of the QDPR gene. The method is useful for rapid and simultaneous scanning of all exons and flanking intronic sequences of the QDPR gene. We describe the first prenatal diagnosis conducted using this method.

Alleles↗
PubMed2001

Factor V Leiden mutation in Turkish patients with homozygous cystathionine beta-synthase deficiency.

Venous and arterial thromboembolism can occur in patients with homocystinuria. Resistance to activated protein C, which is caused by a single point mutation in the gene for factor V, renders an individual at risk for thrombosis. It has been suggested that coexistence of hereditary homocystinuria and factor V Leiden mutation might jointly play a role in the development of thrombosis. We analysed six patients with homocystinuria due to cystathionine beta-synthase deficiency for factor V Leiden and prothrombin G20210A mutations. Only one patient was found to have the factor V Leiden mutation in homozygous form and this patient had suffered from severe thrombosis. One patient was found to be heterozygous with no documented thrombosis. None of the patients had prothrombin G20210A mutation. We stress the necessity for screening for known thrombophilic risk factors in patients with cystathonine beta-synthase deficiency. The coexistence of the factor V Leiden mutation can cause severe thrombotic events in patients with homocystinuria.

Adolescent↗
PubMed2001

Mutation analysis in Turkish patients with hereditary fructose intolerance.

Thirteen Turkish patients with hereditary fructose intolerance (HFI) were screened for the three common mutations, A149P, A174D and N334K, in the aldolase B gene that have been detected frequently in European population. We found that nine of the patients carry the A149P mutation in both alleles, which corresponds to a frequency of about 55%. Single-strand conformation analysis of all coding exons of the gene was also performed to detect unknown mutations in four patients not carrying the three common mutations. No aberrant migration patterns were observed in these patients.

Alleles↗
PubMed2001

Low serum carnitine concentrations in healthy children with iron deficiency anemia.

Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship.

Anemia, Iron-Deficiency↗
PubMed2000

Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE).

Dihydropteridine reductase (DHPR) catalyses the conversion of quinonoid dihydrobiopterin (qBH2) to tetrahydrobiopterin (BH4), which serves as the obligatory cofactor for the aromatic amino acid hydroxylases. DHPR deficiency, caused by mutations in the QDPR gene, results in hyperphenylalaninemia and deficiency of various neurotransmitters in the central nervous system, with severe neurological symptoms as a consequence. We have studied, at the clinical and molecular levels, 17 patients belonging to 16 Turkish families with DHPR deficiency. The patients were detected at neonatal screening for hyperphenylalaninemia or upon the development of neurological symptoms. To identify the disease causing molecular defects, we developed a sensitive screening method that rapidly scans the entire open reading frame and all splice sites of the QDPR gene. This method combines PCR amplification and "GC-clamping" of each of the seven exonic regions of QDPR, resolution of mutations by denaturing gradient gel electrophoresis (DGGE), and identification of mutations by direct sequence analysis. A total of ten different mutations were identified, of which three are known (G23D, Y150C, R221X) and the remaining are novel (G17R, G18D, W35fs, Q66R, W90X, S97fs and G149R). Six of these mutations are missense variants, two are nonsense mutations, and two are frameshift mutations. All patients had homoallelic genotypes, which allowed the establishment of genotype-phenotype associations. Our findings suggest that DGGE is a fast and efficient method for detection of mutations in the QDPR gene, which may be useful for confirmatory DNA-based diagnosis, genetic counselling and prenatal diagnosis in DHPR deficiency.

Adolescent↗
PubMed2000

Glucagon-like peptide (GLP-1) is involved in the central modulation of fecal output in rats.

In addition to its insulinotropic action, exogenously administered glucagon-like peptide (GLP-1) inhibits gastropancreatic motility and secretion via central pathways. The aims of the present study were to evaluate the effects of exogenous GLP-1-(7-36) amide on fecal output and to investigate the role of endogenous GLP-1 on stress-induced colonic activity. With the use of a stereotaxic instrument, adult male Sprague-Dawley rats weighing 200-250 g were fitted with stainless steel cerebroventricular guide cannulas under ketamine anesthesia. A group of rats were placed in Bollman-type cages to induce restraint stress. Fecal output monitored for 2 h was increased significantly by intracerebroventricular GLP-1 to 500, 1, 000, and 3,000 pmol/rat (P < 0.05-0.01), whereas intraperitoneal GLP-1 had no effect. Intracerebroventricular administration of the GLP-1 receptor antagonist exendin-(9-39) (10 nmol/rat) reversed the increases induced by GLP-1 (500 pmol/rat; P<0.01). Similar results were also observed with the injection of corticotropin-releasing factor receptor antagonist astressin (10 microg/rat icv). The significant increase in fecal pellet output induced by restraint stress was also decreased by both intracerebroventricular exendin (10 nmol/rat) and astressin (10 microg/rat; P<0.01-0.001). These results suggest that GLP-1 participates in the central, but not peripheral, regulation of colonic motility via its own receptor and that GLP-1 is likely to be a candidate brain-gut peptide that acts as a physiological modulator of stress-induced colonic motility.

Animals↗
PubMed2000

Endothelin-1-induced PMN infiltration and mucosal dysfunction in the rat small intestine.

The objectives of this study were to characterize the effects of endothelin (ET)-1 on intestinal mucosal parameters and to assess the contribution of polymorphonuclear leukocytes (PMNs), intercellular adhesion molecule-1 (ICAM-1), and a platelet-activating factor (PAF) to the mucosal dysfunction induced by ET-1. Different concentrations of ET-1 (100, 200, and 400 pmol/kg) were infused into the superior mesenteric artery for 10 min, and tissue samples were obtained 30 min after terminating the infusion. ET-1 administration significantly elevated tissue myeloperoxidase activity, plasma carbonyl content, and tissue chemiluminescence intensity, indicating that ET-1 produces PMN infiltration and oxidant stress. Blood-to-lumen clearance of (51)Cr-EDTA significantly increased after ET-1 infusion (400 pmol/kg). Monoclonal antibodies against ICAM-1 (1A29, 2 mg/kg), antineutrophil serum, and PAF antagonist (WEB-2086, 10 mg/kg) attenuated the mucosal barrier dysfunction induced by ET-1. Overall, our data indicate that ET-1 causes PMN accumulation, oxidant stress, and mucosal dysfunction in the rat small intestine and that ET-1-induced mucosal dysfunction involves a mechanism that includes a role for PMNs, ICAM-1, and PAF.

Animals↗
PubMed1999

Capsaicin-sensitive vagal fibres and 5-HT3-, gastrin releasing peptide- and cholecystokinin A-receptors are involved in distension-induced inhibition of gastric emptying in the rat.

The present study was undertaken to investigate how the activation of gastric mechanoreceptors by distension of the stomach in conscious gastric fistula rats influences gastric emptying; and the roles of capsaicin sensitive vagal afferent fibres and the 5-HT3, GRP and CCK-A receptors involved in mediating these responses. To activate mechanoreceptors by non-nutrient dependent pathways, methylcellulose in saline was used to distend the stomach (5 cm H2O) and the subsequent emptying of saline was examined immediately, and at 3, 5 and 10 min following distension. Prior distension delayed the subsequent emptying of saline instilled into the stomach compared with non-distended controls (2.28+/-0.09 ml/5 min; P < 0.001). Topical application of capsaicin, completely abolished the distension-induced inhibition of gastric emptying when compared with vehicle treated rats (2.82+/-0.09 vs. 2.38+/-0.04 ml/5 min; P < 0.001). Peripheral administration of a GRP antagonist (2258 U89UJ, 1 mg/kg), and a 5-HT3 antagonist (BRL4369UA, 50 microg/kg) significantly reversed (2.56+/-0.14 ml/5 min; P < 0.05 and 2.61+/-0.07 ml/5 min; P < 0.01; respectively) the delay in gastric emptying induced by distension. When the rats were treated with the CCK-A antagonist, gastric emptying of saline following distension was also significantly facilitated (2.56+/-0.07 ml/5 min; P < 0.001). In contrast, the CCK-B/gastrin receptor antagonist had no significant effect on the distension induced delay in gastric emptying (1.95+/-0.12 ml/5 min). The present results suggest that gastric distension in conscious gastric fistula rats delays gastric emptying by activating capsaicin-sensitive extrinsic afferent nerve fibres. Moreover, the results also indicate that distension-induced mechanisms involve GRP, 5-HT3 and CCK-A receptors, but not CCK-B receptors.

Animals↗
PubMed1999

Rehydration of moderately dehydrated children with transient glucose intolerance using rice oral rehydration solution.

Following the successful rehydration of two moderately dehydrated patients with transient glucose intolerance (TGI) using rice-oral rehydration solution (R-ORS), R-ORS has been used in Hacettepe University Ihsan Dogramaci Children's Hospital Diarrhea Training and Treatment Unit (DTTU) to rehydrate moderately dehydrated children with TGI. The files of children with moderate dehydration and glucose intolerance admitted to the unit were reviewed retrospectively within two periods according to the availability of R-ORS. The clinical and laboratory findings were analysed where available. Before R-ORS became available (September 1993) 6 patients were admitted, all of whom deteriorated with glucose (G)-ORS treatment in 7.0 +/- 3.8 h and were hospitalized for i.v. fluid treatment. During the second period 22 moderately dehydrated children with TGI were admitted. The clinical and laboratory characteristics on admission of the children in the two periods were not statistically different (p > 0.05). Among the 22 patients admitted during the second period 10 were administered G-ORS in the unit and 12 had already received G-ORS at home. Clinical and laboratory deterioration was observed in these 10 patients while receiving G-ORS in the unit within 6.3 +/- 3.7 h and rehydration was continued with R-ORS. Clinical and laboratory improvement were demonstrated in 8 patients within 18.2 +/- 6.5 h. Overall, 17 patients were rehydrated successfully with R-ORS, with a mean time of 18.0 +/- 7.2 h. Five patients were hospitalized. The overall success rate of R-ORS was 77.3%. R-ORS may be considered as an alternative mode of therapy to i.v. treatment in the rehydration of moderately dehydrated children with TGI.

Dehydration↗