Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine

In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma- globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment.     

A novel NPHS2 gene mutation in Turkish children with familial steroid-resistant nephrotic syndrome

We report in this paper two siblings aged 8 and 17 months who were clinically diagnosed with familial steroid-resistant nephrotic syndrome (SRNS). By mutation screening of the NPHS2 gene, a homozygous missense mutation, P118L, was detected in both children. This study is the first systematic investigation of NPHS2 gene mutations in Turkish children with familial SRNS. If this mutation is a hot spot of mutation in the Turkish population, screening this novel mutation in Turkish children with SRNS may be of great clinical use to prevent unnecessary treatment modalities, provide accurate genetic counselling and predict the prognosis of the disease.     

Protective effect of rutin on mercuric chloride-induced reproductive damage in male rats

This study investigated the effects of rutin against reproductive damage caused by toxic mercury in male rats. Thirty-five Sprague Dawley rats were used. Control group was injected with saline for 7 days. The rutin-100 group received 100 mg/kg/b.w. rutin for 7 days. Mercuric chloride (HgCl₂) group received 1.23 mg/kg/b.w. of HgCl₂ for 7 days. Mercury chloride + rutin-50 group received 50 mg/kg/b.w. rutin and HgCl₂ 1.23 mg/kg/b.w. for 7 days. HgCl₂ + rutin-100 group received 100 mg/kg/b.w. rutin and HgCl₂ 1.23 mg/kg/b.w. for 7 days. It was detected that HgCl₂ treatment increased malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expressions, necrosis and degeneration of spermatogonium, dead and abnormal sperm percentages; tubular walls thinning; and decreased antioxidant enzyme activities and sperm motility. It was determined that rutin application reduced testicular damage caused by HgCl₂. In conclusion, rutin administration may treat HgCl₂ toxicity in testes.     

The effect of fluoxetine on ischemia–reperfusion after aortic surgery in a rat model

Background

Aortic ischemia–reperfusion (IR) is an important factor in the development of postoperative acute lung injury after abdominal aortic surgery. The aim of the present study was to examine the effect of fluoxetine (Flx), a selective serotonin reuptake inhibitor widely used as a preoperative anxiolytic, on lung injury induced by abdominal aortic IR in rats.

Methods

Wistar rats were randomized into three groups (n = 7 per group): (1) control (sham laparotomy); (2) IR without Flx (60-min ischemia and 120-min reperfusion); (3) IR with Flx (Flx + IR) (Flx 20 mg/kg/d, intraperitoneally for 3 d before surgery). Lung tissue samples and bronchoalveolar lavage (BAL) were obtained for biochemical analysis of oxidative status. Ischemia-modified albumin (IMA) level and protein concentrations in BAL and lung wet to dry weight ratios were determined. Histologic evaluation of the lung tissues was also performed.

Results

IR without Flx led to significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant–antioxidant balance and decrease in superoxide dismutase, glutathione, and ferric reducing antioxidant power activities (P < 0.05 versus control), whereas Flx was able to restore these parameters (P > 0.05 versus control) and decrease IMA level (P < 0.01 versus control) and protein concentration (P < 0.05 versus control) in BAL and wet to dry lung weight ratio. Histologic evaluation showed that Flx attenuated the morphologic changes associated with lung injury.

Conclusions

The results indicate that Flx confers protection against aortic IR-induced lung oxidative stress and cellular integrity. IMA levels in BAL may be used as a follow-up marker for the efficacy of treatment in lung injury.     

Magnetic resonance imaging at first episode in pediatric multiple sclerosis retrospective evaluation according to KIDMUS and lesion dissemination in space criteria

Background: Several diagnostic imaging criteria are being described and examined in pediatric multiple sclerosis (MS). Compared to adults, children are more likely to experience acute or relapsing demyelinating episodes of various etiologies which show similar clinical and magnetic resonance imaging (MRI) findings. Aim: To investigate the fulfillment of MRI diagnostic criteria at initial episode in pediatric MS. Methods: We reviewed our series of children and adolescents with the final diagnosis of clinically definite MS and applied the McDonald dissemination in space (DIS) and KIDMUS criteria to their initial MRI scans. Results: Thirty patients (17 girls, 13 boys), most with brainstem dysfunction and polysymptomatic presentation, were included in the study. Twenty-five (83.3%) patients fulfilled both McDonald and KIDMUS criteria. Patients who did not meet any McDonald DIS criteria did not meet KIDMUS criteria either. Only one patient met the McDonald criteria but not the KIDMUS criteria because of the absence of lesions perpendicular to corpus callosum. Conclusions: Our results show 5/30 (16.6%) of MS patients may not present the diagnostic MRI features initially. The variable sensitivity observed for the current MRI criteria in different series can be due to referral biases, differences between populations and length of follow-up, and the definition of MS patients by two attacks only.     

Predictive factors of drug-resistant epilepsy in children presenting under 2 years of age: experience of a tertiary center in Turkey

Population-based studies report that children with epilepsy have relatively better prognosis than those with an onset at infancy, though studies about this period are limited. We aimed to evaluate the etiology in infant epilepsy less than 2 years of age and foreseeable risk factors for anti-epileptic drug resistance. We evaluated the patients who were presented to the division of pediatric neurology in our university hospital with seizures when they were between 1 and 24 months of age and diagnosed as epilepsy. Two hundred and twenty-nine patients (110 male and 119 female) who were diagnosed between the ages of 1–24 months were included in the study. The etiologies were structural (n = 55;24%), genetic (n = 29;12.7%), metabolic (n = 27;11.7%), and infectious (n = 8;3.5%), and it was unknown in 110 patients (48%). One-hundred and forty (61%) patients met the criteria for drug-resistant epilepsy (DRE). Multivariate logistic regression analysis showed that developmental delay at onset (OR 3.9, 95% CI 1.22, 12.47, p = 0.021), multifocal epileptiform discharges (OR 2.8, 95% CI 1.1, 7.44, p = 0.031), and history of status epilepticus (OR 32.9, 95% CI 3.8, 285.35, p = 0.001) were strong predictive factors for DRE. The epilepsy in children under 2 years of age is highly resistant to the anti-epileptic drugs, which could be related to the history of status epilepticus, developmental delay at onset, and multifocal epileptiform discharges.     

Location and incidence of the zygomaticofacial foramen: An anatomic study

The location and incidence of the zygomaticofacial foramen (ZFF) was studied in 80 dry skulls (160 sides) of unsexed adult skulls of West Anatolian people. The average distances from the ZFF to the frontozygomatic suture, to the zygomaticomaxillary suture, and to the inferior orbital rim were found to be 26.2 ± 3.2 mm, 18.6 ± 3.14 mm, and 5.94 ± 1.43 mm, respectively. The zygomas were evaluated for the number of foramina on their facial aspects. There was none in 25 (15.6%), one in 71 (44.4%), two in 45 (28.1%), three in 10 (6.3%), four in seven (4.4%), and five in two (1.3%) sides. The ZFF was also studied for its distribution around the zygoma by dividing the surface into four anatomical areas. There was no statistical difference between the morphometrical results on both sides. Data regarding the location and variation in the number of the ZFF is important in avoiding zygomatic nerve and vessel injury during surgery, but by virtue of the great variability found, ZFF is an unreliable landmark for maxillofacial surgery. Clin. Anat. 22:559–562, 2009. © 2009 Wiley‐Liss, Inc.     

Linkage disequilibrium between glucose-6-phosphate dehydrogenase deficiency and congenital color blindness in Turkish population.

No erythrocyte glucose-6-phosphate dehydrogenase (G6PD)-deficient person was detected among 90 male patients with congenital color blindness (CCB) diagnosed at the Ophthalmology Clinic of our Hospital. Eighteen complete G6PD-deficient subjects had normal color vision. These results suggest that there is a linkage disequilibrium between CCB and G6PD genes.     

The plasma levels of activated thrombin activatable fibrinolysis inhibitor and thrombomodulin in Behçet Disease and their association with thrombosis

Objective

To investigate the plasma levels of activated thrombin activatable fibrinolysis inhibitor (aTAFI) and thrombomodulin (TM) in Behçet disease (BD) and their relationship with thrombosis.

Methods

Plasma aTAFI and TM levels were measured by ELISA in 89 patients with BD (18 having venous thrombosis) and in 86 healthy controls.

Results

Compared with healthy controls, the BD group had significantly lower levels of aTAFI (13.49 ± 8.88 µg/ml vs. 26.76 ± 11.57 µg/ml, p < 0.0001) and significantly higher levels of TM (3.26 ± 1.85 ng/ml vs. 2.6 ± 0.69 ng/ml, p = 0.0003). Neither aTAFI, nor TM levels differed significantly between BD patients with and without thrombosis (p > 0.05). Despite a tendency to positive correlation (r = 0.37, p = 0.0004) between plasma levels of aTAFI and TM in healthy controls, there was a tendency for negative correlation (r = -0.51, p < 0.0001) between these two parameters in BD patients.

Conclusion

The plasma aTAFI and TM levels do not seem to be related with the presence of thrombosis observed in BD. Increased plasma TM levels in BD may simply reflect endothelial cell activation and dysfunction.