Seyhun Solakoglu

The protective effect of alpha lipoic acid against traumatic brain injury in rats.

Traumatic brain injury (TBI) was induced by a weight-drop device using 300 g–1 m weight-height impact. The study groups were: control, alpha-lipoic acid (LA) (100 mg/kg, po), TBI, and TBI + LA (100 mg/kg, po). Forty-eight hours after the injury, neurological scores were measured and brain samples were taken for histological examination or determination of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na+-K+ ATPase activities, whereas cytokines (TNF-α, IL-1β) were determined in blood. Brain oedema was evaluated by wet–dry weight method and blood–brain barrier (BBB) permeability was evaluated by Evans Blue (EB) extravasation. As a result, neurological scores mildly increased in trauma groups. Moreover, TBI caused a significant decrease in brain GSH and Na+-K+ ATPase activity, which was accompanied with significant increases in TBARS level, MPO activity and plasma proinflammatory cytokines. LA treatment reversed all these biochemical indices as well as histopathological alterations. TBI also caused a significant increase in brain water content and EB extravasation which were partially reversed by LA treatment. These findings suggest that LA exerts neuroprotection by preserving BBB permeability and by reducing brain oedema probably by its anti-inflammatory and antioxidant properties in the TBI model.

A frameshift mutation of ERLIN2 in recessive intellectual disability, motor dysfunction and multiple joint contractures

We present a family afflicted with a novel autosomal recessive disease characterized by progressive intellectual disability, motor dysfunction and multiple joint contractures. No pathology was found by cranial imaging, electromyography and muscle biopsy, but electron microscopy in leukocytes revealed large vacuoles containing flocculent material. We mapped the disease gene by SNP genome scan and linkage analysis to an ∼0.80 cM and 1 Mb region at 8p11.23 with a multipoint logarithm of odds (LOD) score of 12. By candidate gene approach, we identified a homozygous two-nucleotide insertion in ERLIN2, predicted to lead to the truncation of the protein by about 20%. The gene encodes endoplasmic reticulum (ER) lipid raft-associated protein 2 that mediates the ER-associated degradation of activated inositol 1,4,5-trisphosphate receptors and other substrates.

Cysteinyl-leukotriene receptor antagonist montelukast decreases blood–brain barrier permeability but does not prevent oedema formation in traumatic brain injury

Introduction: Traumatic brain injury is highly associated with the over-production of reactive oxygen species. The aim of this study was to investigate the putative neuroprotective effect of montelukast, a cysteinyl-leukotriene receptor antagonist, in a rat model of traumatic brain injury (TBI). Methods: Sprague Dawley rats were subjected to TBI with a weight-drop device using 300 g-1 m weight-height impact. The groups were: control (saline), montelukast (10 mg kg −1 per day, ip), trauma and trauma + montelukast. Two days post-trauma, neurological examination scores were measured and animals were decapitated and the brain tissues were taken for the histologic and biochemical [malondialdehyde (MDA)—an index for lipid peroxidation, reduced glutathione (GSH), myeloperoxidase (MPO)—an index for neutrophil infiltration and Na +/K +-ATPase activity] evaluations. Brain oedema and blood–brain barrier (BBB) permeability were also evaluated. Results: The neurological examination scores mildly increased in trauma groups at 48 hours. Although the scores were decreased in the montelukast treated group, they were still significantly higher than the control. The trauma caused a significant increase in brain water content and Evans blue (EB) extravasation. Montelukast treatment reduced BBB permeability. It also decreased lipid peroxidation and MPO activity. Conclusion: The present study suggests that montelukast may have beneficial effects against TBI-induced oxidative stress of the brain.

EFFECTS OF GRANULOCYTE-MACROPHAGE COLONY -STIMULATING FACTOR ON INCISIONAL WOUND HEALING IN AN EXPERIMENTAL DIABETIC RAT MODEL

The exact nature of poor wound healing in diabetes is uncertain. Neutrophils play a critical role in the host defense mechanism, and it is suggested that impaired neutrophil functions cause healing difficulties with or without infections in diabetic patients. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is used clinically when given systematically to increase the circulating neutrophils, but its wound-healing effects have not been systematically studied. This study was undertaken to examine the effects of GM-CSF on incisional wound healing in an experimental diabetic rat model. Forty rats were randomly divided into three groups, group I receiving saline as control, diabetes-induced group II receiving saline and diabetes-induced group III receiving GM-CSF. The anesthetized rats in all groups were wounded 21 days after diabetes induction by streptozotocin. Blood neutrophil counts and neutrophil fractions were also determined three days after wounding. Tensile strengths of wounded skin and the hydroxyproline (hyp) level of the wound were determined and wound healing processes were evaluated by light and electron microscopy, fourteen days after wounding. Neutrophil counts and phagocytosis were significantly increased in group III and neutrophil counts decreased in group II (p < 0.05). Although the hydroxyproline level of wound tissue significantly decreased in group II as compared with group III (p < 0.05), there was no differences of tensile strength between group II and III (p < 0.05). Wound score in group II was less than that in groups I and III (p < 0.05). It is concluded that PMN may have a role in modulating wound healing. GM-CSF may be useful for creating better wound healing healing. GM-CSF may be useful for creating better wound healing in risky patients such as diabetics.

The Relationship between Neutrophils and Incisional Wound Healing

The systemic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) is used clinically to increase circulating neutrophils, but its wound healing effects after intraperitoneal treatment have not been studied yet. We planned to investigate the effect of neutrophils on wound healing under cyclophosphamide and GM-CSF treatment. Forty rats were divided into three groups: control group (group I, n = 12) receiving saline, group II (n = 14) receiving cyclophosphamide and group III (n = 14) receiving GM- CSF. The rats in all groups underwent incisional wounding and were euthanized after 7 days. Blood neutrophil counts and functions, tensile strengths and the hydroxyproline level of skin were determined, and a histopathological evaluation of healing was made. Neutrophil counts and phagocytosis significantly increased in group III and decreased in group II. Although the skin hydroxyproline level did not differ, there was a difference in tensile strength of the wounded skin between group II and group III. The wound score in group II was lower than that in groups III and I. As a result we suggest that systemically given GM-CSF – by increasing the neutrophil count and neutrophil phagocytosis index – can enhance the tensile strength of surgical incisions.

Effect of COX-2 inhibitor meloxicam against traumatic brain injury-induced biochemical, histopathological changes and blood–brain barrier permeability

Abstract Objective: The overproduction of reactive oxygen species and resultant damage to cellular proteins or lipids of cell membranes and DNA by free radicals are the underlying mechanisms of many neuropathologies. Cyclooxygenase-2 (COX-2) inhibitors have been suggested to be neuroprotective by reducing prostanoid and free radical synthesis, or by directing arachidonic acid metabolism through alternate pathways. This study investigated the putative neuroprotective effect of the COX-2 inhibitor, meloxicam, in a rat model of diffuse brain injury. Methods: Sprague–Dawley rats were subjected to traumatic brain injury with a weight-drop device using 300 g−1 m weight–height impact. The groups were: control, meloxicam (2 mg/kg, i.p.), trauma and trauma + meloxicam (2 mg/kg, i.p.). Forty-eight hours after the injury, neurological examination scores were measured, the animals were decapitated and brain tissues were taken. Brain edema and blood–brain barrier (BBB) permeability were evaluated by wet–dry weight method and Evans blue (EB) extravasation respectively. In brain tissues, malonedialdehyde, glutathione, myeloperoxidase and Na/K-ATPase levels were measured. Results: The neurological examination scores mildly increased in trauma groups 48 hours after the induction of trauma. Meloxicam treatment improved the altered neurological status. The trauma caused a significant increase in brain water content that was partially reversed by meloxicam. Meloxicam also reduced the EB extravasation indicating the preservation of the BBB integrity. Meloxicam treatment also significantly reduced the increase in malondialdehyde and myeloperoxidase levels and restored glutathione content of the brains that had been significantly increased after trauma. Conclusion: Meloxicam exerts neuroprotective effect by preserving BBB permeability and by reducing brain edema (probably by its anti-inflammatory properties) in the diffuse brain injury model.

The Effect of Cultured Autologous Fibroblasts on Longevity of Cross-Linked Hyaluronic Acid Used as A Filler

BACKGROUND Various kinds of biomaterials are being used for soft tissue augmentation in plastic surgery. Organic molecules are usually absorbed in a short amount of time. Inorganic molecules stay in the body for a longer period of time, but are prone to cause various reactions; therefore, none of them are ideal filler substances. OBJECTIVE This study was designed to examine the clinical and histologic effects of injection of cultured fibroblasts in hyaluronic acid as a filler material. The advantages, disadvantages, and side effects of the procedure were examined during the study. METHODS Skin biopsies obtained from the backs of 30 Sprague Dawley rats were used in the study. Dermal fibroblasts obtained from these biopsies were cultured for 21 days and, after 3 weeks, autologous labeled cultured fibroblasts of the rats were injected intracutaneously alone and mixed with hyaluronic acid. Injections of culture medium and hyaluronic acid were also performed as control groups. At the end of the fourth and eighth months, skin biopsies were taken from the injection sites and normal skin and examined under light and electron microscopes. RESULTS The injected fibroblasts, elastin, and collagen production were analyzed and found to be stable, long-lasting, and well tolerated. No complications were observed. CONCLUSIONS Cultured human dermal fibroblasts combined with hyaluronic acid can provide a suitable, biocompatible, and long-lasting material and should be regarded as a new method in dermal renovation even beyond their temporary filling effect.

Nephrotic Syndrome Associated with Agnogenic Myeloid Metaplasia

Extramedullary hematopoiesis being an important feature of agnogenic myeloid metaplasia (AMM), a chronic myeloproliferative disease of clonal origin, may affect the kidneys, but this condition is usually asymptomatic. Until now, there is only one reported case of nephrotic syndrome associated with AMM. We present a patient with AMM who had nephrotic syndrome and whose renal biopsy revealed membranous glomerulonephritis together with renal extramedullary hematopoiesis.

Effects of systemic Thalidomide and intracerebroventricular Etanercept and Infliximab administration in a Streptozotocin induced dementia model in rats

Tumor necrosis factor-alpha (TNF-α) upregulation enhances amyloid β (Aβ) induced neurotoxicity in Alzheimers disease (AD). Intracerebroventricular streptozotocin (STZ) administration causes pathological changes and cognitive deficits similar to those seen in AD by causing impairment of brain glucose and energy metabolism. Recent reports indicate a protective role of Thalidomide, Etanercept, and Infliximab, all of which have anti-TNF-α activity, against cognitive and neuropathological changes in experimental and clinical studies. We aimed to investigate the protective effects of Thalidomide, Etanercept, and Infliximab in a rat model of intracerebroventricular STZ-induced dementia. Sprague-Dawley rats (250-300g) were separated to sham (n=6) and STZ (n=24) groups. The STZ group was divided into four groups (STZ, STZ-thalidomide, STZ-etanercept, and STZ-infliximab). Morriss water maze (MWM) and passive avoidance (PA) tests were performed. At the end of the third week, brain tissues were obtained. Histopathological analysis, immunohistochemistry, and electron microscopic examinations were done. The improvement performance of the STZ group was significantly reduced in the MWM test (p<0.001). Compared with the STZ, STZ-thalidomide, STZ-etanercept, and STZ-infliximab groups had significantly better performance (p<0.001, <0.05 and <0.05, respectively) in the MWM test. STZ administration caused a significant decrease in the mean escape latency in PA reflex (p<0.001). Thalidomide, Etanercept, and Infliximab were associated with better PA reflexes compared to the STZ group (p<0.001 for all). Morphological and immunohistochemical results showed increased neurodegenerative changes compared to sham group. Our findings are in line with the findings reported in the literature and encourage further studies with TNF-α antagonists, in particular Thalidomide.

Comparison of conventional and no-touch techniques in harvesting saphenous vein for coronary artery bypass grafting in view of endothelial damage.

BACKGROUND Optimization of saphenous vein patency for myocardial revascularization. OBJECTIVE The goal of this study was to present the no-touch technique of saphenous vein preparation. This technique consists of harvesting the vein with a pedicle of surrounding tissue, which protects the vein from distension pressure. METHODS We performed a prospective, randomized study that compared 2 techniques for harvesting saphenous vein-conventional and no-touchin 40 patients undergoing coronary artery bypass grafting. We carried out a morphologic study of the endothelium with the aid of light and transmission electron microscopy and an immunohistochemical assessment to identify adenosine, inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) in the vein wall. RESULTS The integrity of endothelial cell and all vascular layers was maintained better with the no-touch technique than with the conventional procedure. The immunohistochemical assessment revealed that adenosine receptor, iNOS, and VEGF immunoexpression levels were normal or lower in the no-touch group than in the conventional-harvest group, as shown by the staining densities in all layers of the vein wall. CONCLUSION Endothelial integrity and adenosine, iNOS, and VEGF immunoreactivities were better preserved when the no-touch technique was used for vein graft harvesting. The mechanical protection provided by the cushion of surrounding tissue in the no-touch group and the vasorelaxation and thromboresistant activities of nitric oxide may be responsible for the reduction in vasospasms and the improved patency rate.