The present study aimed to compare the effect of gender difference on hemodynamic consequences in the development of monocrotaline (MCT)-induced pulmonary hypertension in rat. The effect of antioxidant enzyme systems on the development of pulmonary hypertension mediated by the phytotoxin MCT and the effect of gender on these antioxidant systems were also investigated. For this purpose, the right ventricular pressures (RVPs) and right ventricular/heart weight (HW) ratios were compared between groups and the glutathione (GSH) level and superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were determined in lung and liver tissue samples of rats. RVP and right ventricular/HW ratios significantly increased in the MCT group compared to the control group. In the MCT group, RVP was significantly higher in males than females. MCT-induced pulmonary hypertension resulted in decreased GSH level, decreased GST and SOD activities and increased CAT activity in lung and liver tissues of both male and female rats. In addition, the lung and liver GSH level and GST and SOD levels were higher in female control rats compared to male control rats. The results of the present study, that antioxidant enzyme activities were different between the groups, highlight the possible role of oxidative stress in the pathogenesis of MCT-induced pulmonary hypertension in rats. Moreover, the lower antioxidant defense capacity of male rats than female rats may be considered as a cause of more aggressive course of MCT-induced pulmonary hypertension in males compared to females.

Although neuroregeneration is detected in PHO grafts with minor degradation in 60 d, autologous nerve graft is found to be superior in axonal regeneration compared to PHO nerve tube grafts. PHO conduits were found to create minor inflammatory reaction in vivo, resulting in good soft tissue response.

No abstract

The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of coumaric acid on spinal cord ischemia injury in rats. Rats were divided randomly into four groups of eight animals as follows: control, ischemia, ischemia + coumaric acid, and ischemia + methylprednisolone. In the control group, only a laparotomy was performed. In all other groups, the spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. Levels of malondialdehyde and nuclear respiratory factor 1 were analyzed, as were the activity of superoxide dismutase. Histopathological and immunohistochemical evaluations were performed. Neurological evaluation was performed with the Tarlov scoring system. The ischemia + coumaric acid group was compared with the ischemia group, and a significant decrease in malondialdehyde and levels was observed. Nuclear respiratory factor 1 level and superoxide dismutase activity of the ischemia + coumaric acid group were significantly higher than in the ischemia group. In histopathological samples, the ischemia + coumaric acid group is compared with the ischemia group, and there was a significant increase in numbers of normal neurons. In immunohistochemical staining, hypoxia-inducible factor-1α and NF-kappa B immunopositive neurons were significantly decreased in the ischemia + coumaric acid group compared with that in the ischemia group. The neurological deficit scores of the ischemia + coumaric acid group were significantly higher than the ischemia group at 24 h. Our results revealed for the first time that coumaric acid exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord.

Our results indicate that aqp-4 is not up-regulated during the initial stages of hydrocephalus. This implies that aqp-4 may not play a significant role in hydrocephalus compensation until severe ventricular dilatation occurs.

Pineal cyst apoplexy is a very rare entity with previously reported symptoms of severe frontal or occipital headache, gaze paresis and visual field defects, nausea or vomiting, syncope, ataxia, hearing loss and sudden death. The treatment options for symptomatic pineal cysts are observation, shunting, aspiration via stereotactic guidance or endoscopy, third ventriculostomy, ventriculocysternostomy, and/or surgical resection by craniotomy and microsurgery. Here, the authors report an unusual case of a 28-year-old male patient with pineal cyst apoplexy, presenting with headache, insomnia, and sexual dysfunction symptoms who is being managed conservatively and observed for two years by an academic tertiary care unit.

Object Aquaporins (aqp) are protein channels providing water transport across cell membranes. The main member of this family expressed in the CNS is aqp-4. The pattern and amount of expression of this channel suggest a dominant role in bulk water movement into the nervous tissue. It has also been shown to play a role in several water balance disorders in the CNS. In this study, the authors investigated the possible role of aqp-4 in syringomyelia. Methods Twenty-five male Wistar-Hannover rats were divided into experimental (20 rats) and control (5 rats) groups. Syringomyelia was induced in the experimental group by kaolin injection into the cisterna magna. Eight weeks later, the animals were killed, and their spinal cords were removed. Central canal dilations were noted in all experimental animals. Immunohistochemistry and Western blot analysis were performed to evaluate aqp-4 expression. Results Both groups demonstrated positive immunoreactive signals to aqp-4. Western blot analysis revealed a slight decrease in the mean aqp-4 value in the experimental group; however, the difference did not reach statistical significance (p > 0.05). Immunohistochemical analysis showed a similar pattern and intensity of aqp-4 staining in both groups. Conclusions The results of this study indicate that aqp-4 most likely does not play a major role in chronic syringomyelia. Its slight downregulation during the initial stage of syrinx formation is possibly a compensatory mechanism. This effect is not present during the late stage of syringomyelia, and aqp-4 is most likely not involved in the pathophysiology of syrinx cavity formation.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic blistering disorder, caused by mutations in the COL7A1 gene encoding for type VII collagen (C7) protein. These mutations result amongst other complications in fragility of the skin and mucosal membranes. RNA exon-skipping is the modulation of splicing of a pre-mRNA in order to prevent inclusion of a targeted exon into the mRNA. Many RDEB patients harbour a mutation in exon 73 of the COL7A1 gene. We aimed to identify an antisense oligonucleotide (AON) that would exclude the in-frame exon 73 from the COL7A1 mRNA. Exon-skipping in COL7A1 can result in a slightly shortened C7 protein. QR-313, a fully phosphorothioated and 2'O-methylated AON, composed of 21 bases was selected. This sequence is optimized for length, sequence, lack of immunogenicity and optimal manufacturability. We have tested the effectiveness of QR-313 using multiple cell-types, including primary wild type fibroblasts, (modified) HaCaT cells and dermal fibroblasts compound heterozygous RDEB patient, harbouring a mutation in exon 73. These cells were examined for their ability to induce exon 73 skipping from the COL7A1 mRNA using an in vitro transfection system. Products were analysed using PCR and results demonstrate that QR-313 efficiently excludes exon 73 from the COL7A1 mRNA. Secondly, we have assessed the RNA exon skip potential of QR-313 in human skin equivalents (HSEs). HSEs are composed of a dermal layer, harbouring fibroblasts, with a differentiated epidermal layer on top. Before application of QR-313, HSEs were wounded by partial removal of the epidermis, to mimic the blistered skin of RDEB patients. Topical application of QR-313 in a carbomer-based hydrogel for 24-48 hrs, resulted in the exclusion of exon 73 from the COL7A1 mRNA in dermal fibroblasts and epidermal keratinocytes. QR-313 is a potential novel RNA oligonucleotide that could treat RDEB due to exon 73 mutations by exon-skipping. 195The identification of a postzygotic GJA1 mutation in a patient with an inflammatory linear verrucous epidermal nevus suggests that the disease is a mosaic of erythrokeratodermia variabilis et progressiva An inflammatory linear verrucous epidermal nevus (ILVEN) is a keratinocytic epidermal nevus (KEN) that runs along the lines of Blaschko, characterized by pruritic erythematous papules with massive inflammatory cell infiltrates. ILVEN is not currently classified as either an epidermolytic or a non-epidermolytic subtype of KEN, and no causative gene has been identified. Here, we identified a postzygotic mutation in the gene encoding gap junction protein alpha-1 (GJA1) in an ILVEN patient. The patient, a 14 year-old female without any relevant family history, developed erythematous and verrucous plaques along the Blaschko's lines of the extremities and buttocks commencing in the first year of life; the plaques gradually increased in both number and size. A skin biopsy revealed verrucous hyperkeratosis and acanthosis, without epidermolytic degeneration, but with lymphocyte infiltration of the s...