Levent Tumkaya

Toward Changing of the Pathophysiologic Basis of Acute Hydrocephalus After Subarachnoid Hemorrhage: A Preliminary Experimental Study

BACKGROUND Acute hydrocephalus (ventricular enlargement within 72 hours) is a common complication in patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrospinal fluid (CSF) secretion may be increased in the early phases of SAH, but it has not been proved definitively. We studied the histologic features of choroid plexus (CP) in the early and late phases of SAH. METHODS This study was conducted on 20 rabbits, with 5 rabbits in the control group, 5 rabbits in the sham group, and 10 rabbits in the SAH group. In the SAH group, five of the animals were decapitated after 2 days of cisternal blood injections, and the other five animals were decapitated after 14 days of injections. The CP of lateral ventricles were obtained from coronary sections of brains at the level of the temporal horns of the lateral ventricles. Sections were stained with hematoxylin and eosin and Masson trichrome for SAH-related damage and examined stereologically to discern water-filled vesicles, which were counted. Sections were compared statistically. RESULTS The mean numbers of water vesicles were different after SAH between the early decapitated group (group III) and the late decapitated group (group IV). The mean numbers of water vesicles were 2.80 (± 0.05) in the control group (group I), 2.76 (± 0.02) in the sham group (group II), 14.68 (± 0.06) in the early decapitated group (group III), and 4.78 (± 0.13) in the late decapitated group (group IV). Total number of fluid-filled vesicles of CP was also assessed stereologically; the total numbers were 840 (± 16) in group I, 828 (± 7) in group II, 4404 (± 19) in group III, and 1434 (± 41) in group IV. The numbers of water-filled cisterns were significantly increased in the early phases of SAH (P < 0.05). CONCLUSIONS In SAH with aneurysm rupture, increased CSF secretion seems to be triggered by hemorrhage in the early phase, but it is not possible in the late phase because of CP degeneration. In the early phase of hemorrhage, CSF secretion may be stimulated by the irritant receptor glossopharyngeal and vagal nerve endings, which innervate the healthy CP epithelium and arteries. Our findings may be accepted as being causative. It is likewise possible that CSF blockage per se leads to hydrocephalus, and the morphologic changes are sequelae that occur later in the course of disease. This is the first study to show the water vesicles of CP as a causative factor in the development of acute hydrocephalus after SAH.

Mobile phone radiation during pubertal development has no effect on testicular histology in rats.

Mobile phones are extensively used throughout the world. There is a growing concern about the possible public health hazards posed by electromagnetic radiation emitted from mobile phones. Potential health risk applies particularly to the most intensive mobile phone users—typically, young people. The aim of this study was to investigate the effects of mobile phone exposure to the testes, by assessing the histopathological and biochemical changes in the testicular germ cells of rats during pubertal development. A total of 12 male Sprague Dawley rats were used. The study group (n = 6) was exposed to a mobile phone for 1 h a day for 45 days, while the control group (n = 6) remained unexposed. The testes were processed with routine paraffin histology and sectioned. They were stained with hematoxylin–eosin, caspase 3, and Ki-67 and then photographed. No changes were observed between the groups (p > 0.05). The interstitial connective tissue and cells of the exposed group were of normal morphology. No abnormalities in the histological appearance of the seminiferous tubules, including the spermatogenic cycle stage, were observed. Our study demonstrated that mobile phones with a low specific absorption rate have no harmful effects on pubertal rat testicles.

The effect of exposure of rats during prenatal period to radiation spreading from mobile phones on renal development

Abstract Background: The aim of this study was to investigate the effects of exposure to a 900-MHz electromagnetic field (EMF) produced by mobile phones on the renal development of prenatal rats. Histopathological changes and apoptosis in the kidneys, together with levels of urea, creatinine and electrolyte in serum were determined. Methods: A total of 14 Sprague–Dawley rats were studied. Pregnant rats were divided into two equal groups: a control group and an EMF-exposed group. The study group was exposed to 900-MHz of EMF during the first 20 days of pregnancy, while the control group was unexposed to EMF. Sections obtained from paraffin blocks were stained for caspase-3 by immunohistochemistry, hematoxylin–eosin and Masson’s trichrome. Results: Mild congestion and tubular defects, and dilatation of Bowman’s capsule were observed in the kidney tissues of rats in the exposed group. Apoptosis was evaluated using anti-caspase-3; stronger positive staining was observed in the renal tubular cells in the study group than those of the control group. Although there was a significant difference between the study and control groups in terms of K+ level (p < 0.05), no significant difference was observed in the other parameters studied (p > 0.05). Conclusion: Our study shows that the electromagnetic waves propagated from mobile phones have harmful effects on the renal development of prenatal rats.

Is resveratrol a potential substitute for leuprolide acetate in experimental endometriosis

OBJECTIVE Resveratrol, a phytoalexin polyphenol, has anti-angiogenic, antioxidant, anti-inflammatory properties. We aimed to compare the anti-inflammatory and anti-angiogenic effects of resveratrol and leuprolide acetate (LA) in an experimental endometriosis model. STUDY DESIGN A prospective experimental study was conducted in a University Surgical Research Center. Thirty-three non-pregnant female Sprague-Dawley rats, in which experimental model of endometriosis were surgically induced were randomly divided into four groups. Group 1 was administered 30 mg/kg resveratrol i.m. for 14 days, group 2 was given 1mg/kg s.c. single dose LA, group 3 was administered both resveratrol and LA, and group 4 had no medication. After two weeks medication rats were sacrificed and size, histopathology and immunreactivity to matrix metalloproteinase (mmp)2, mmp9, vascular endothelial growth factor (VEGF) of the endometriotic implants were evaluated. Plasma and peritoneal fluid levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were analyzed. RESULTS The endometriotic implant volumes, histopathological grade and immunreactivity to mmp2, mmp9 and VEGF were significantly reduced (p<0.001), and plasma and peritoneal fluid levels of IL-6, IL-8 and TNF-α were significantly decreased in group 1 and group 2 in comparison to group 3 and group 4 (p < 0.001). CONCLUSION Resveratrol alone is a potential agent for the treatment of endometriosis and may be an alternative to LA. In contrast, the combination of LA and resveratrol decreased the anti-inflammatory and anti-angiogenic effects of each agent. Since resveratrol is widely used as an alternative therapy for a variety of conditions, it can undermine the effectiveness of LA. Therefore, caution should be exercised when used in combination with other agents.

Protective effect of infliximab on methotrexate-induced liver injury in rats: unexpected drug interaction.

AIMS Although methotrexate (mtx) is a widely used agent to treat cancer and inflammatory diseases, its hepatotoxic effect limits for clinical utility. We aimed to investigate whether infliximab (inf), an inhibitor of tumor necrosis factor-alpha (TNF-α) has a protective effect against mtx-induced hepatotoxicity. MATERIALS AND METHODS For mtx group, the animals received an intraperitoneal single dose injection of mtx at a dose of 20 mg/kg. For inf group, the animals received an intraperitoneal single dose injection of inf at a dose of 7 mg/kg. For mtx + inf group, the single dose of inf at a dose of 7 mg/kg was given 72 h prior to mtx injection. After 72 h, a single dose of mtx 20 mg/kg was given. All rats were sacrificed 5 days after mtx injection. RESULTS TNF-α and nitric oxide (NO) levels of mtx group was significantly higher than the control (P < 0.001), inf (P < 0.001) and mtx + inf (P < 0.001) groups. Total score of histological damage was higher in the mtx group when compared with the mtx + inf group. Arginase and carbamoyl phosphate synthetase 1 (CPS-1) of mtx group was suppressed in comparison with the control group and was markedly increased in mtx + inf group. CONCLUSION Inf may partially prevent mtx-induced hepatic damage in rats. However, the combined usage of mtx and inf increases arginase and CPS-1 enzyme activities and at the same time blocks TNF-α. This combination especially in cancer patients may lead to cancer cell invasion and metastasis.

Topiramate ameliorates abdominal aorta cross-clamping induced liver injury in rats.

Background and Aim: Ischemia/reperfusion (I/R) injury in the liver occurs after a prolonged period of ischemia followed by restoration of hepatic blood perfusion. During the surgery of abdominal aorta, I/R injury causes damage to lower extremities and many organs, especially liver. The antioxidant and tumor necrosis factor-alpha (TNF-α) suppression effects of topiramate (TPM) have been reported in several studies. We evaluated the potential protective effect of TPM on cellular damage in liver tissue during I/R injury. Materials and Methods: Thirty male Wistar albino rats were divided into three groups: Control, I/R, and I/R plus TPM (I/R + TPM) groups. Laparotomy without I/R injury was performed in the control group. After laparotomy, cross-ligation of infrarenal abdominal aorta was applied for 2 h in I/R groups that was followed by 2 h of reperfusion. TPM (100 mg/kg/day) was orally administrated to the animals in the I/R + TPM group for seven consecutive days before I/R procedure. Results: The I/R groups TNF-α and interleukin-6 (IL-6) levels were significantly higher than those of the control (P = 0.010; P = 0.002) and I/R + TPM groups (P = 0.010; P = 0.002, respectively). Asymmetric dimethyl arginine (ADMA) levels of I/R group were higher than the control (P = 0.015) and I/R + TPM groups. I/R caused serious histopathological damage to liver tissue; however, TPM led to very low histopathological changes. Conclusion: Our data demonstrated that TPM treatment prominently decreases the severity of liver I/R injury. TPM pretreatment may have preventive effects on liver injury via I/R during intra-abdominal surgery.

Reversal of Rocuronium-Induced Neuromuscular Block with Sugammadex and Resulting Histopathological Effects in Rat Kidneys

Background: This study investigated the effect of injection of rocuronium or sugammadex alone and rocuronium + sugammadex on urea, creatinine, electrolyte levels, and histopathological findings in rats. Methods: Thirty-six Sprague-Dawley male rats were divided to receive intravenously 16 or 96 mg/kg sugammadex, 1 mg/kg rocuronium, 1 mg/kg rocuronium + 16 mg/kg sugammadex, or 1 mg/kg rocuronium + 96 mg/kg sugammadex. The control group received an equal volume of physiological serum. Rats receiving rocuronium were ventilated until resumption of spontaneous ventilation and followed for 72 h. Blood samples were withdrawn from the tail vein to measure urea, creatinine, and electrolyte values; then both kidneys were excised, and the tissues were used for histopathological examination. Results: Rats receiving rocuronium and high doses of sugammadex (96 mg/kg) showed increased glomerular vacuolation, tubular dilatation, vascular vacuolation and hypertrophy, lymphocyte infiltration, and tubular cell sloughing compared to the control group (p = 0.002). Biochemical markers of renal function were not significantly altered after treatment with high doses of sugammadex. Conclusion: The elimination half-life of the rocuronium–sugammadex complex was found to be greater than that of free rocuronium or sugammadex, which led to marginal histopathological changes in the kidney without affecting any renal functions.

Effects of exposure to 2100 MHz GSM-like radiofrequency electromagnetic field on auditory system of rats ☆

INTRODUCTION The use of mobile phones has become widespread in recent years. Although beneficial from the communication viewpoint, the electromagnetic fields generated by mobile phones may cause unwanted biological changes in the human body. OBJECTIVE In this study, we aimed to evaluate the effects of 2100MHz Global System for Mobile communication (GSM-like) electromagnetic field, generated by an electromagnetic fields generator, on the auditory system of rats by using electrophysiological, histopathologic and immunohistochemical methods. METHODS Fourteen adult Wistar albino rats were included in the study. The rats were divided randomly into two groups of seven rats each. The study group was exposed continuously for 30days to a 2100MHz electromagnetic fields with a signal level (power) of 5.4dBm (3.47mW) to simulate the talk mode on a mobile phone. The control group was not exposed to the aforementioned electromagnetic fields. After 30days, the Auditory Brainstem Responses of both groups were recorded and the rats were sacrificed. The cochlear nuclei were evaluated by histopathologic and immunohistochemical methods. RESULTS The Auditory Brainstem Responses records of the two groups did not differ significantly. The histopathologic analysis showed increased degeneration signs in the study group (p=0.007). In addition, immunohistochemical analysis revealed increased apoptotic index in the study group compared to that in the control group (p=0.002). CONCLUSION The results support that long-term exposure to a GSM-like 2100MHz electromagnetic fields causes an increase in neuronal degeneration and apoptosis in the auditory system.

The effect of prenatal exposure to 1800 MHz electromagnetic field on calcineurin and bone development in rats

PURPOSE To investigated the effects of exposure to an 1800 MHz electromagnetic field (EMF) on bone development during the prenatal period in rats. METHODS Pregnant rats in the experimental group were exposed to radiation for six, 12, and 24 hours daily for 20 days. No radiation was given to the pregnant rats in the control group. We distributed the newborn rats into four groups according to prenatal EMF exposure as follows: Group 1 was not exposed to EMF; groups 2, 3, and 4 were exposed to EMF for six, 12, and 24 hours a day, respectively. The rats were evaluated at the end of the 60th day following birth. RESULTS Increasing the duration of EMF exposure during the prenatal period resulted in a significant reduction of resting cartilage levels and a significant increase in the number of apoptotic chondrocytes and myocytes. There was also a reduction in calcineurin activities in both bone and muscle tissues. We observed that the development of the femur, tibia, and ulna were negatively affected, especially with a daily EMF exposure of 24 hours. CONCLUSION Bone and muscle tissue development was negatively affected due to prenatal exposure to 1800 MHz radiofrequency electromagnetic field.

Efectos protectores de infliximab sobre el daño pulmonar inducido por metotrexato

INTRODUCTION Methotrexate (MTX) is used to treat cancers, several forms of arthritis and other rheumatic conditions, although MTX may cause pulmonary toxicity related to the production of free oxygen radicals, various cytokines. Infliximab (IB) with its potent effect on tumor necrosis factor-alpha (TNF-α) inhibition also inhibits the release of endothelin-1 (ET-1). We aimed to investigate whether IB reduces pulmonary damage induced by an overdose of MTX. METHOD The rats were divided into 3 groups of 8 animals. The control group was given only saline. One dose of 20mg/kg MTX intraperitoneal was administered in the MTX group. IB 7 mg/kg was given to the MTX+IB (MI) group. Three days after IB was administered, 20mg/kg MTX was given. Five days after MTX was administered, all rats were sacrificed. RESULTS The TNF-α, ET-1, malondialdehyde (MDA), myeloperoxidase (MPO) and caspase-3 levels in MTX group were significantly higher than in control groups of TNF-α (P=.001), ET-1 (P=.001), MDA (P=.001), MPO (P=.001) and caspase-3 levels (P=.001) and MI groups of TNF-α (P=.009), ET-1 (P=.001), MDA (P=.047), MPO (P=.007) and caspase-3 levels (P=.003). The MI group had less histopathological damage in lung tissue than the MTX group. CONCLUSION Overdose of MTX leads to cytokine release and the formation of reactive oxygen species in addition to increased ET-1 secretion release that causes lung damage. IB, as a potent proinflammatory agent, TNF-α blocker, can decrease ET-1 release and oxidative stress, it may show significant protective effects in lung tissue against damage caused by MTX overdose.