Neuroprotective effects of amantadine for experimental acute carbon monoxide poisoning.

OBJECTIVE: Amantadine is known to have a neuroprotective effect in many neurological diseases. This study aims at investigating the neuroprotective effect of amantadine in rats exposed to carbon monoxide (CO) poisoning. MATERIALS AND METHODS: Rats were maintained under standard experimental laboratory conditions and randomized into 4 different groups of 7 each namely control, amantadine only, CO exposure, and amantadine + CO exposure. For immunohistochemical analysis, tissues taken from the prefrontal and hippocampal regions were taken into formalin and kept for at least one day. Afterward, the tissue was followed and blocked for paraffin blocking. N-Methyl D-Aspartate (NMDA) levels in homogenates were studied by the Enzyme-Linked Immunosorbent Assay (ELISA) method. Superoxide dismutase (SOD) and catalase (CAT) activities in the supernatants were studied with commercial kits. Nitric oxide (NO) and Asymmetric Dimethyl Arginine (ADMA) levels were studied by the ELISA method. Enzyme activity values were calculated by dividing the protein values in the supernatants and normalizing them. RESULTS: CAT, SOD, NMDA, ADMA, and NO levels were statistically significantly different between the groups (p < 0.05). According to post-hoc pairwise comparison test results, the values of the control and amantadine groups for CAT, SOD, NMDA, ADMA, and NO parameters were significantly higher than that of CO group. Similarly, values in the control and amantadine groups were considerably higher than values for the amantadine + CO group. NMDA values were significantly lower in group amantadine + CO than in CO group (p: 0.049). CONCLUSIONS: Apoptosis and endothelial damage after CO poisoning is a complex process, and amantadine administration has a limited contribution in preventing this process.

New αIIbß3 variants in 28 Turkish Glanzmann patients; structural hypothesis for complex activation by residues variations in I-EGF domains.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by impaired platelet aggregation due to defects in integrin αIIbß3, a fibrinogen receptor. Platelet phenotypes and allelic variations in 28 Turkish GT patients are reported. Platelets αIIbß3 expression was evaluated by flow cytometry. Sequence analyzes of ITGA2B and ITGB3 genes allowed identifying nine variants. Non-sense variation effect on αIIbß3 expression was studied by using transfected cell lines. 3D molecular dynamics (MDs) simulations allowed characterizing structural alterations. Five new alleles were described. αIIb:p.Gly423Asp, p.Asp560Ala and p.Tyr784Cys substitutions impaired αIIbß3 expression. The αIIb:p.Gly128Val substitution allowed normal expression; however, the corresponding NM_000419.3:c.476G>T variation would create a cryptic donor splicing site altering mRNA processing. The ß3:p.Gly540Asp substitution allowed αIIbß3 expression in HEK-293 cells but induced its constitutive activation likely by impairing αIIb and ß3 legs interaction. The substitution alters the ß3 I-EGF-3 domain flexibility as shown by MDs simulations. GT variations are mostly unique although the NM_000419.3:c.1752 + 2 T > C and NM_000212.2:c.1697 G > A variations identified in 4 and 8 families, respectively, might be a current cause of GT in Turkey. MD simulations suggested how some subtle structural variations in the ß3 I-EGF domains might induce constitutive activation of αIIbß3 without altering the global domain structure.

Comparison of interfragmentary pinning versus the extension block technique for acute Doyle type 4c mallet finger.

The aim of this study was to compare the closed reduction interfragmentary pinning method (IPM) with the extension block technique (EBT) for bony mallet finger. Patients who underwent mallet finger operations were screened retrospectively for the following inclusion criteria: Doyle type 4c, age between 18 and 75 years, less than 4 weeks to surgery, and more than 1 year of follow-up time. Group I underwent a closed reduction IPM, and group II underwent the EBT. Lateral radiographs taken during the preoperative and final examination were used to evaluate the size and amount of displacement from the distal interphalangeal (DIP) joint and the dorsal fragment as well as the articular surface. Operation times were compiled from patient records. During the final examination, pain and DIP joint range of motion (ROM) were assessed and complications were recorded. The Crawford criteria were used for functional results. Fifteen patients in group I (8 men, 7 women) and 17 patients in group II (10 men, 7 women) were evaluated. Age, gender, time to surgery and follow-up time showed no statistically significant differences between the two groups. The differences in fragment size, preoperative and postoperative joint displacement, amount of dorsal displacement and DIP joint ROM were not statistically significant between the two groups. However, the operation time was significantly shorter time in group I than in group II (p=0.000). The average time to fracture union was significantly longer in group I (7.3 weeks) than in group II (6 weeks) (p=0.013). The EBT has faster time to union and is a safer method with lesser risk of arthritis and fragmentation. The IPM can be an alternative with shorter operation time, less pin bed infection and nail bed damage, especially in Doyle type 4c cases with large fragments.

Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms.

BACKGROUND AND AIMS: Whether single nucleotide polymorphisms (SNPs) of homocysteine metabolism enzymes influence the rate of cardiovascular (CV) events in coronary artery disease (CAD) patients remains controversial. METHODS AND RESULTS: In this analysis, 1126 subjects from the AtheroGene study with CAD and 332 control subjects without known CAD were included. The following SNPs were investigated: methylentetrahydrofolate reductase (MTHFR-C667T), methionin synthetase (MS-D919G), and cystathionin beta synthetase (CBS-I278T). The endpoint was the combination of cardiovascular death, stroke, and non-fatal myocardial infarction (N = 286). The median follow-up time was 6.4 years. Kaplan-Meier curve analysis showed an increasing event rate with rising homocysteine levels (p < 0.001) in CAD patients. Further, in Cox-Regression analysis homocysteine was a predictor of the endpoint with a hazard ratio (HR) of 6.5 (95% CI: 2.9-14.6, p < 0.001) in the adjusted model including cardiovascular risk factors. Of the three SNPs, homozygous MTHFR SNP increased homocysteine levels significantly in patients with CAD and individuals without CAD (both p < 0.001). The SNPs in MS and CBS were not related to relevant changes in homocysteine levels in CAD patients or controls. The different SNPs of MTHFR, MS, and CBS were not related to an increased event rate. CONCLUSION: Homocysteine level is a strong predictor of CV events. Subjects with and without CAD and SNPs in the enzyme MTHFR had increased homocysteine levels. This was not observed for MS and CBS SNPs. Although MTHFR SNPs alter homocysteine levels in patients and controls, these polymorphisms had no impact on prognosis in CAD patients.

The predictive value of different equations for estimation of glomerular filtration rate in patients with coronary artery disease - Results from the AtheroGene study.

BACKGROUND: Impaired renal function leads to dramatically increased risk for the development and progression of coronary artery disease (CAD). Therefore we aimed to assess the predictive value of different equations for estimated glomerular filtration rate (eGFR) in CAD-patients. METHODS: From the AtheroGene study 2135 patients were included. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (4MDRD) equation for serum creatinine (sCr), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for sCr and cystatin C (CysC) each alone, and in combination (CysC/sCr). eGFR was assessed regarding the combined outcome of cardiovascular death and non-fatal myocardial infarction and regarding complex CAD represented by a SYNTAX score ≥23. Median follow-up was 4.3years. RESULTS: Only the CKD-EPI equation using CysC could differentiate between eGFR >90ml/min/1.73m(2) vs. eGFR 60-90ml/min/1.73m(2) according to the occurrence of an endpoint event (log-rank test p=0.009). In the Cox regression analysis only eGFR calculated by CKD-EPI equation for CysC (Hazard ratio per 1 standard deviation (HR) 1.27 (95% CI 1.07-1.50); p=0.007) and for CysC/sCr (HR 1.22 (95% CI 1.02-1.46); p=0.026) were predictive regarding the outcome after adjustment for cardiovascular risk factors and Nt-proBNP. Furthermore, only eGFR calculated by CKD-EPI equation for CysC (odds ratio (OR) 1.57 (95% CI 1.36-1.78); p<0.001) and for CysC/sCr (OR 1.32 (95% CI 1.13-1.53); p<0.001) were significantly associated with a SYNTAX score ≥23. CONCLUSION: In patients with CAD the CKD-EPI equation for CysC and for CysC/sCr provided the best predictive value regarding the prognosis and the severity of CAD.

Extension block technique for mallet fractures: a comparison of one and two dorsal pins.

The aim of this study was to compare the clinical and radiological outcomes of one or two dorsal pins for extension blocking of mallet fractures. We treated 36 mallet fractures with the extension block technique. A single pin was used in 19 fractures (Group 1) and two pins in 17 fractures (Group 2). The mean age was 33.6 years and the mean follow-up time was 12.2 months. All patients were assessed by the Crawford outcome score. Extensor lag and other complications were noted. All fractures united with a mean time of 6.0 weeks (4-9) in Group 1, and 6.1 weeks (4-7) in Group 2. We obtained 74% and 71% excellent and good outcome scores in Group 1 and in Group 2, respectively. The final extension lag was 6° in Group 1, and 7° in Group 2. No difference was found between the two groups in terms of clinical outcomes, radiological values and complications.Level 3 non-randomized controlled study.

[Multiple abscesses after a cruise along the Latin American coast]. / Multiple Abszesse nach Südamerikakreuzfahrt.

We report a case of an extracutaneous involvement of pyoderma gangrenosum. The patient initially presented with multiple sterile abscesses of the skin, heart, prostate, and kidney. Extracutaneous involvement in pyoderma gangrenosum is very rare. Confirmation of the diagnosis was only possible after exclusion of other relevant differential diagnoses. Continuous search for microbes proved negative and after an empiric therapeutic attempt with prednisolone, the patient improved quickly. However, each time we reduced the steroids even in combination with methotrexate or with azathioprine the patient relapsed. Only after therapy with the tumor necrosis factor-α-inhibitor infliximab was permanent remission achieved.

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia.

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated ß-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When ß-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.

Reduced left uncinate fasciculus fractional anisotropy in deficit schizophrenia but not in non-deficit schizophrenia.

AIMS: Schizophrenia is a psychiatric disorder manifesting with heterogeneous symptom clusters and clinical presentations. The deficit syndrome is the condition defined by the existence of primarily negative symptoms, and patients with the deficit syndrome differ from non-deficit patients on measures of brain structure and function. In the current study, by using diffusion tensor imaging (DTI), we investigated the frontotemporal connectivity that is hypothesized to differ between deficit and non-deficit schizophrenia. METHODS: Twenty-nine patients and 17 healthy controls were included in the study. The patients had deficit (n = 11) or non-deficit (n = 18) schizophrenia and they were evaluated clinically with the Schedule for Deficit Syndrome (SDS) and Positive and Negative Syndrome Scale (PANSS). Diffusion-based images were obtained with a 1.5T Siemens Magnetic Resonance Imaging machine and analyses were carried out with Functional Magnetic Resonance Imaging of the Brain Library Software - Diffusion tool box software. RESULTS: The fractional anisotropy values in the left uncinate fasciculus of schizophrenia patients with the deficit syndrome were lower than those of non-deficit patients and the controls. There were no differences between non-deficit schizophrenia patients and controls. CONCLUSION: These findings provide evidence of left uncinate fasciculus damage resulting in disrupted communication between orbitofrontal prefrontal areas and temporal areas in deficit schizophrenia patients.

Attitude and behavior related to organ donation and affecting factors: a study of last-term students at a university.

AIM: The aim of this study was to detect the behavior and attitude of our last-term students. METHODS: The study group for this cross-sectional research consisted of 1690 last-term students. We applied a questionnaire about sociodemographic features, behaviors, and attitudes about organ donation. Data were evaluated with SPSS 11.0. RESULTS: We accessed 1287 students among whom 1.3% stated that they would donate their organs. Among students who did not agree, 58.7% were considering donation. The main reasons for not agreeing to donation were fear of commercial use (45.7%) and the belief of inappropriateness related to religion (25.7%). In contrast, 62.3% stated that they would donate their organ when needed for their relatives. Also, 50.6% indicated that if one of their relatives died, they would donate their relative's organs; there was no significant difference based on gender. In addition, favorable thoughts about donation were significantly more prevalent for female subjects (P = .001). Organ donation behavior and thoughts were significantly higher among the group with better economic position (P = .001, .018); and for students whose mother had an education higher than high school (P = .003, .004). Higher donation ratios were observed for students who had a relative working in the medical field (P = .04) and the group who stated they were well informed about organ donation (P < .001). CONCLUSION: When we take into account that our study group consisted of university students, organ donation rates were low. To overcome the difficulties, we have to inform the community and collaborate with religious organizations. To prevent fear that organs will be used commercially we must prove confidence in the system.

Clinical manifestations of infants with nutritional vitamin B deficiency due to maternal dietary deficiency.

AIM: In developing countries, nutritional vitamin B(12) deficiency in infants due to maternal diet without adequate protein of animal origin has some characteristic clinical features. In this study, haematological, neurological and gastrointestinal characteristics of nutritional vitamin B(12) deficiency are presented. METHODS: Hospital records of 27 infants diagnosed in a paediatric haematology unit between 2000 and 2008 were evaluated retrospectively. RESULTS: The median age at diagnosis was 10.5 months (3-24 months). All the infants were exclusively breast fed and they presented with severe nonspecific manifestations, such as weakness, failure to thrive, refusal to wean, vomiting, developmental delay, irritability and tremor in addition to megaloblastic anaemia. The diagnosis was confirmed by complete blood counts, blood and marrow smears and serum vitamin B(12) and folic acid levels. The median haemoglobin level was 6.4 g/dL (3.1-10.6) and mean corpuscular volume (MCV) was 96.8 fL (73-112.3). Some patients also had thrombocytopaenia and neutropaenia. All the infants showed clinical and haematological improvement with vitamin B(12) administration. Patients with severe anaemia causing heart failure received packed red blood cell transfusions as the initial therapy. CONCLUSION: Paediatricians must consider nutritional vitamin B(12) deficiency due to maternal dietary deficiency in the differential diagnosis of some gastrointestinal, haematological, developmental and neurological disorders of infants with poor socioeconomic status. Delay in diagnosis may cause irreversible neurological damage.

Investigation of zinc and copper levels in methimazole-induced hypothyroidism: relation with the oxidant-antioxidant status.

Thyroid hormones are associated with the oxidative and antioxidative status of the organism. Depression of metabolism by hypothyroidism has been reported to decrease oxidant production and thus protect tissues against oxidant damage. The purpose of the present study was to investigate Zn and Cu levels in MMI-induced hypothyroidism and to show whether there is a connection between these trace elements and the oxidant-antioxidant status in experimental hypothyroidism. 3-Nitrotyrosine was measured as a marker of nitro-oxidative stress. In order to examine the antioxidant status of MMI-induced hypothyroidism in rats, GSH and SOD levels were determined as well. Significantly decreased 3-nitrotyrosine, Cu and Zn levels were observed in our experimental model when compared with the controls. On the other hand, GSH and SOD levels remained constant. It may be suggested that Cu and Zn serve as antioxidant molecules and exert their effects in an indirect manner to reduce oxidative stress in experimental hypothyroidism.

A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis.

BACKGROUND: Thyroid dysgenesis is the most frequent cause of congenital hypothyroidism (CH), and its genetic basis is largely unknown. Hitherto, two mutations in the human thyroid transcription factor 2 (TTF-2) gene have been described in unrelated cases of CH with cleft palate, spiky hair, variable choanal atresia, and complete thyroid agenesis. Here, we describe a novel TTF-2 mutation in a female child resulting in syndromic CH in the absence of thyroid agenesis. RESULTS: The index case is homozygous for an arginine to cysteine mutation (R102C) of a highly conserved residue within the forkhead, DNA binding domain of TTF-2. Her consanguineous, heterozygous parents are unaffected, and the mutation was not detected in 100 control chromosomes. Consonant with its location, the R102C mutant TTF-2 protein showed loss of DNA binding and was transcriptionally inactive. CH in the proposita was associated with cleft palate, spiky hair, and bilateral choanal atresia. However, radiological studies showed the presence of thyroid tissue in a eutopic location. CONCLUSION: Our findings indicate that human thyroid development can occur despite loss of TTF-2 function and suggest that TTF-2 gene defects should also be considered in cases of syndromic CH without total athyreosis.