MKS3/TMEM67 mutations are a major cause of COACH syndrome, a joubert syndrome related disorder with liver involvement

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/ aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs

The node of Ranvier in CNS pathology.

Healthy nodes of Ranvier are crucial for action potential propagation along myelinated axons, both in the central and in the peripheral nervous system. Surprisingly, the node of Ranvier has often been neglected when describing CNS disorders, with most pathologies classified simply as being due to neuronal defects in the grey matter or due to oligodendrocyte damage in the white matter. However, recent studies have highlighted changes that occur in pathological conditions at the node of Ranvier, and at the associated paranodal and juxtaparanodal regions where neurons and myelinating glial cells interact. Lengthening of the node of Ranvier, failure of the electrically resistive seal between the myelin and the axon at the paranode, and retraction of myelin to expose voltage-gated K(+) channels in the juxtaparanode, may contribute to altering the function of myelinated axons in a wide range of diseases, including stroke, spinal cord injury and multiple sclerosis. Here, we review the principles by which the node of Ranvier operates and its molecular structure, and thus explain how defects at the node and paranode contribute to neurological disorders

The effects of low-high doses of dexmedetomidine on erythrocyte deformability in rats

Arslan, Mustafa/0000-0003-4882-5063WOS: 000305723300003PubMed: 22693969Background: Dexmedetomidine is an anesthetic agent frequently used for sedation, intensive care units, and general anesthesia. The purpose of our study was to investigate the effect of two different doses of dexmedetomidine on erythrocyte deformability in rats. Materials and methods: The study was performed on 21 male rats, with 7 rats in each study group and the control group. The rats in the study groups were administered dexmedetomidine (low dose 5 mu g.kg(-1), high dose 10 mu g.kg(-1)) intraperitoneally, and the rats in the control group were administered physiological saline. Erythrocyte packs were prepared using heparinized total blood samples. Deformability measurements were done by erythrocyte suspensions in phosphate buffered saline (PBS) buffer. A constant flow filtrometer system was used to measure erythrocyte deformability, and the relative resistance was calculated. Results: Use of a high dose dexmedetomidine resulted in an increase in relative resistance, which is an indicator for erythrocyte deformability in control rats (p=0.014). Conclusions: High dose dexmedetomidine via negative change in erythrocyte deformability may cause a functional deterioration in blood flow and tissue perfusion. Our results showed that low dose dexmedetomidine protects erythrocyte deformability better than the high dose (Fig. 1, Ref. 23). Full Text in PDF www.elis.sk

The effect of peritoneal wrapping on colonic anastomosis healing in rats with impaired wound healing due to superior mesenteric artery occlusion

45th Congress of the European-Society-for-Surgical-Research -- JUN 09-12, 2010 -- Geneva, SWITZERLANDWOS: 000281136400435…European Soc Surg Re

Effect of dexmedetomidine on erythrocyte deformability during ischemia-reperfusion injury of liver in diabetic rats

Arslan, Mustafa/0000-0003-4882-5063WOS: 000312349000001PubMed: 23173624Aim: The aim of this study is to evaluate the effect of dexmedetomidine on erythrocyte deformability during IR injury of liver in diabetic rats. Methods: Twenty-eight Wistar Albino rats were included in the study after a 4 week streptozocin (65 mg/kg) treatment to observe the existence of diabetes. The animals were randomly assigned to one of the four experimental groups: GroupC and DC (sham-control group): The abdomen was dissected with a median laparotomy and the liver was collected. GroupDIR: The liver was collected after IR following the abdominal median laparotomy. GroupDIRD: The liver was collected after IR following the abdominal median laparotomy and 30 min of infusion of dexmedetomidine 100 mu g/kg ip The deformability measurements were performed in erythrocyte suspensions containing Htc 5% in PBS buffer. Results: The deformability index was significantly increased in diabetic rats, however it was similar in the GroupC and DIRD. It was significantly increased in the GroupDIR when compared to the GroupC, DIRD and DC. The relative resistance was increased in IR models. Conclusion: Erythrocyte deformability was damaged in rats having diabetes and IR injury. This injury might lead to further problems in microcirculation. It was shown that dexmedetomidine may be useful in enhancing the adverse effects of this injury (Tab. 1, Fig. 2, Ref. 41). Full Text in PDF www.elis.sk

Evaluation of erythrocyte deformability in experimentally induced osteoporosis in female rats and the effects of vitamin C supplementation on erythrocyte deformability

Arslan, Mustafa/0000-0003-4882-5063WOS: 000296929900002PubMed: 22180984Objective: The aim of this study was to evaluate the possible variations in antioxidant enzymes, lipid peroxidation and erythrocyte deformability in experimentally induced osteoporosis in female rats and to assess the effects of vitamin C supplementation on those variations. Material: A total of 20 female Wistar Albino Rats were randomized into the three groups as controls (Group C, n=6), ovariectomized rats (Group 0, n=7) and ovariectomized rats receiving vitamin C supplementation (Group OVC, n=7). After the surgical procedure of ovariectomy, group OVC received 1 g ascorbic acid in 500mL water daily. After 100 days following the ovariectomy, bone mineral density (BMD) was measured by using dual-energy X-ray absorptiometry. Results: BMD was significantly lower in the group 0 than in the group C (p=0.015), whereas it was significantly higher in the group OVC than in the group 0 (p=0.003). MDA activity was significantly higher in the group 0 than in the group C (p=0.032), whereas it was significantly lower in the group OVC than in the group 0 (p=0.025). SOD activity was significantly higher in the group 0 than in the group C (p=0.032). Erythrocyte deformability was significantly higher in the group 0 than in the group C and OVC (p=0.008, p=0.021, respectively). Conclusion: Erythrocyte deformability may show negative variations, suggesting a causative role in disruption of blood flow and tissue perfusion, which also negatively affect bone metabolism. Vitamin C supplementation seems to reverse those negative effects of variations in erythrocyte deformability. However, our preliminary results should be confirmed in more experimental studies and clinical trials (Tab. 3, Ref. 28). Full Text in free PDF www.bmj.sk

Does vitamin C prevent the effects of high dose dexmedetomidine on rat erythrocyte deformability?

Arslan, Mustafa/0000-0003-4882-5063; PAMPAL, HASAN KUTLUK/0000-0003-4664-391XWOS: 000302385900002PubMed: 22428760Purpose: Dexmedetomidine is an anesthetic agent frequently used for sedation at the intensive care units and during general anesthesia. The purpose of our study was to investigate whether vitamin C prevents the effect of high dose dexmedetomidine on erythrocyte deformability in rats. Methods: The study was performed on 21 male rats, with 7 rats in each study groups and the control group. The rats in the study groups were treated with intraperitoneal dexmedetomidine (10 mu g/kg) and intraperitoneal dexmedetomidine plus Vitamin C (ascorbic acid) (100 mg/kg ascorbic acid administered 1 hour before administration of 10 mu g/kg dexmedetomidine), respectively. Intraperitoneal physiological saline was administered in the control group. Erythrocyte packs were prepared using heparinized total blood samples. Deformability measurements were done by erythrocyte suspensions in phosphate buffered saline (PBS) buffer. A constant flow filtrometer system was used to measure erythrocyte deformability and the relative resistance was calculated. Results: Erythrocyte deformability was significantly higher in dexmedetomidine group than in control and vitamin C plus dexmedetomidine groups (p=0.003, p=0.013, respectively). Erythrocyte deformability indexes were found similar in the control group and in the vitamin C plus dexmedetomidine group (p=0.383) Conclusions: High dose dexmedetomidine may cause functional deterioration in blood flow and tissue perfusion with negative effects in erythrocyte deformability. Vitamin C supplementation seems to reverse those negative effects and variations in erythrocyte deformability. However, our preliminary results should be confirmed in wider serious of experimental and clinical trials (Fig. 1, Ref. 27). Full Text in PDF www.elis.sk

Effect of iloprost on erythrocyte deformability in rat's lower extremity undergoing an ischemia reperfusion injury

Arslan, Mustafa/0000-0003-4882-5063WOS: 000318058700002PubMed: 23514550Aim: Ischemia reperfusion injury (I/R) in lower extremity is a frequent and important clinical phenomenon. The protective effect of iloprost on local and distant organ injury due to I/R has been well documented but its effect on erythrocyte deformability needs further investigation. Our aim was to investigate the effect of iloprost on erythrocyte deformability in the infrarenal aorta of rats undergoing I/R. Materials and methods: Our study was conducted with 18 Wistar albino rats. Rats were divided into the 3 groups; the randomized control group (group C; n=6), I/R group without iloprost (group I/R; n=6) and I/R group with iloprost 10 mcg.kg(-1), 30 min infusion (group I/R-I; n=6). Packs of erythrocytes were prepared from heparinized blood samples and deformability measurements were done. Results: The comparisons of the control and I/R-I groups revealed similar results (p=0.951). The values of the IR group were significantly higher than those of the control and IR-I groups (p=0.006, p=0.011, respectively). Conclusion: In our study, we detected the unfavourable effects of I/R on erythrocyte deformability, which may lead to disturbance in blood flow and hence tissue perfusion in the infrarenal rat aorta. We also found that Iloprost had beneficial effects by reversing the undesirable effects of I/R (Fig. 1, Ref. 15). Full Text in PDF www.elis.sk