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An implant from hydroxyapatite and polyethylene (HA+PE) composite was investigated for the usability in large bone defects. With this aim, the implants were manufactured in blocks by hot compacting the mixture of 80% HA and 20% PE weight ratio. Powders were machined in a lathe in the dimensions of diaphysis of the radius of the mongrel dogs. Then a defect, 1.5 cm in length, was made in the diaphysis of the radius with an operation performed under general anaesthesia in 16 healthy mongrel dogs. The defects were filled with implant as a block. The dogs were observed radiologically in 15-day intervals and examined clinically in certain intervals. The bone samples were taken out from four dogs for the histopatological examinations at the end of the 2nd, 4th, 6th and 12th months, respectively. Clinical examinations indicated the occurrence of slight lameness in all cases at the first month of experiment, but lameness completely disappeared in a further examination. Progressive resorption and new bone formation began in the implants from the first month, but complete resorption was not observed in any case at the end of 12-month period. SEM and optical microscope examinations revealed fibroblast cell with its clear cytoplasmic extensions and osteoblast cells in endosteum in the inner region. Bone formation increasing and extending to the pores of implant in time and blood vessels with lamellar structure and Haversian system were observed. As a result, it was indicated that HA+PE composite implants could be applied with confidence and are useful in treatment of large bone defects in long bone of dogs. [ABSTRACT FROM AUTHOR]

Aluminium (Al) is a toxic metal with frequent exposure because it is a common element in nature and is found in many products used in daily life. L-arginine is a semi-essential amino acid that is involved in many biochemical pathways in the body and has antioxidant effects. The current research evaluated the possible protective effects of L-arginine against aluminium chloride (AlCl 3 ) induced testicular damage. In this animal-based experimental study, 28 male Wistar Albino rats were separated into four groups: control, Al (20 mg/kg/day Al), Al + L-arginine (20 mg/kg/day Al + 50 mg/kg/day L-arginine), and L-arginine (50 mg/kg/day L-arginine). All applications were carried out intraperitoneally (i.p.) for 4 weeks. The histopathological changes caused by exposure to Al in the testicular tissue and the protective effects of L-arginine were investigated by using biochemical, histochemical, immunohistochemical [4-hydroxynonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG)] and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay techniques. The testicles in the AlCl 3 group showed increased 4-HNE, 8-OHdG expressions, apoptotic index, and abnormal sperm content, while serum testosterone levels, sperm motility, and sperm number were decreased (p < 0.05). Furthermore, histomorphometric examinations of testicular tissue indicated significant structural impairments such as vacuolization in the seminiferous tubule epithelium, edema, and vascular congestion in the interstitial area (p < 0.05). However, the structural alterations were largely ameliorated in the Al + L-arginine group (p < 0.05). Thus, L-arginine, which is an antioxidant, may protect against the harmful effects of Al and may help improve male fertility., (© 2022 Wiley-VCH GmbH.)

Antidepressant drugs are globally used to treat several psychiatric disorders in pediatric patients and their prescription has continued to increase in recent years, especially among girls. In addition to its well-known metabolic and gastrointestinal side effects, antidepressants can cause sexual dysfunction in adults. However, the effects of the antidepressants on puberty onset and reproductive system remain unclear in children and adolescents. Therefore, the goal of this study is to examine the effects of chronic postnatal antidepressant drugs, paroxetine or bupropion, treatments on puberty onset and reproductive system components in female rats weaned at postnatal day (PND) 21. Female rats (n = 10 for each group) were exposed to vehicle (0.2 mL of saline), paroxetine (3.6 mg/kg in 0.2 mL of saline) or bupropion (17 mg/kg in 0.2 mL of saline) daily by oral gavage from the PND 21 to PND 90-93. Chronic paroxetine or bupropion treatments advanced the puberty onset, but the difference was statistically significant in only the paroxetine group. The exposure to bupropion significantly decreased the serum anti-Müllerian hormone (AMH) levels and luteinizing hormone (LH) levels. There were increases in serum estradiol levels by both antidepressant treatments and the significance was found in only the paroxetine group. Consistent with these results, histopathologic changes were observed in the ovary and uterus tissues taken from both antidepressant-treated rats. The obtained results of chronic postnatal exposure to paroxetine or bupropion may change the timing of puberty onset and lead to disruption of reproductive functions in females., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Antidepressant use in adolescents has become more common in recent years. We have found several studies stating that prenatal antidepressant exposure can lead to delayed or earlier puberty onset but there was no study on postnatal paroxetine or bupropion. The main aim of this study was to investigate the effect of postnatal exposure to bupropion or paroxetine on puberty onset, reproductive and feeding results. The male rats (n = 8/group) aged 21 days were exposed to paroxetine (3.6 mg/kg) or bupropion (17 mg/kg) orally by gastric gavage every day from postnatal day 21-90. Also, control group received only saline orally as a vehicle. Postnatal exposure to bupropion or paroxetine delayed puberty onset compared to control group, but it was not significant. Sperm counts were significantly lower in the paroxetine and bupropion groups compared to control group. Sperm motility was significantly lower in only bupropion group. In addition, sperm motility was lower in paroxetine group, but it was not significant. In the histopathological examination, there was damage to the testicular structure in both treatments. Taken together, our result indicates that postnatal paroxetine or bupropion exposure may affect puberty onset and contribute to the impairment in fertility in male rats., (© 2019 Blackwell Verlag GmbH.)

Objective: Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. In this study, we investigated whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the nephrotoxic effect of GM in rats., Methods: Rats were divided into five groups. Group 1 and 2 served as control and sham respectively, Group 3 as GM group, Group 4 as GM+CoQ10 and Group 5 as GM+BFT for 8days. At the end of the study, all rats were euthanized by cervical decapitation and then blood samples and kidneys were collected for further analysis. Serum urea, creatinine, cytokine TNF-a, oxidant and antioxidant parameters, as well as histopathological examination of kidney tissues were assessed., Results: Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated serum creatinine, urea and KIM-1 level as compared with the controls. Moreover, a significant increase in serum malondialdehyde, reduced glutathione. Histopathological examination of renal tissue in gentamisin administered group, there were extremly pronounced necrotic tubules in the renal cortex and hyalen cast accumulation in the medullar tubuli. BFT given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and KIM-1 were almost normalized in the GM+BFT group. Benfotiamin treatment was significantly decreased necrotic tubuli and hyalen deposition in gentamisin plus benfotiamin group. CoQ10 given to GM rats did not cause any statistically significant alterations in these nephrotoxicity parameters when compared with GM group but histopathological examination of renal tissue in GM+CoQ10 administered group, CoQ10 treatment was decreased necrotic tubuli rate and hyalen accumulation in tubuli., Conclusion: The results from our study indicate that BFT supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this study, we examined liver damage induced by d-galactosamine (d-GaIN) and the protective effects of vitamin D3 in relation to d-GaIN toxicity. Twenty Wistar albino rats were used in this study. The rats were divided into four groups. Group I rats were used as the control group. Group II rats were given a single intraperitoneal injection of d-GaIN. Group III rats were given a single intraperitoneal injection of d-GaIN, intramuscular vitamin D3 for five days. Group IV rats were given intramuscular vitamin D3 for five days. All of rats were euthanized by cervical decapitation on the fifth day of experiment. Upon completion of the experiment, a midsaggital incision was performed, and the livers of all rats were removed and fixed. The livers were processed to perform TUNEL technique and histochemical staining. During the microscope examination, we observed inflamatory cell infiltration, sinusoidal dilatation, and apoptotic bodies due to d-GaIN exposure. In addition, glycogen content of the group II hepatocytes was significantly decreased. Vitamin D3 treatment provided better structural apperance of the livers in group III. TUNEL positive cells were extremly pervasive in the group II livers. The study found group III TUNEL positive cells at a reduced rate in relation to group II due to vitamin D3 treatment. This findings indicate that d-GaIN causes inflamation in the liver. This inflamation triggers the apoptotic process gradually. Vitamin D3 has potency to decrease the severity of d-GaIN-caused structural liver damage., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Irisin was first identified in skeletal muscle cells, but its precise location has not yet been demonstrated, and there is limited information about irisin protein in other human and rat tissues. The present immunohistochemical study was undertaken to screen skeletal muscle and other tissues for irisin immunoreactivity. İrisin staining was found in the brain (neurons and neuroglia), cardiac and skeletal muscle (fibers) and skin (sebaceous glands) tissues in male rats. In both human adult and fetal skeletal muscle, the most intense immunohistochemical staining was in the perimysium and endomysium, in the peripheral nerve (epineurium) and axon and nerve sheaths spreading among the cells, in the sarcoplasma and subendomysium. Irisin was also demonstrated in the testis (seminiferous tubules, some spermatogenic cells in fetal and Leydig cells in fetal and adult testis, ductus epididymis in fetal human epididymis); pancreas (islets of Langerhans, serous acini cells, intralobular and intralobular ducts cells); liver (hepatocytes; Kupffer cells and sinusoidal endothelial cells); spleen (subcapsular region and periarterial lymphatic sheets); the stomach (gastric parietal cells, tunica muscularis cells). We conclude that the fat-burning protein irisin locally produced in peripheral and central tissues could act as a gatekeeper of metabolic energy regulation in those tissues, since this myokine converts white into brown adipose tissue, enhancing energy expenditure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: This study was designed to determine the impact of the degree of obesity on respiratory mechanics and simple hemodynamic parameters at laparoscopic bariatric surgery., Methods: The patients were divided into two groups, each of which included 24 patients (a morbidly obese group and a super obese group) undergoing laparoscopic bariatric surgery. Dynamic respiratory compliance, respiratory resistance, and peak inspiratory pressures were measured at four time points: 10 min after anesthesia induction (T1: induction), 10 min after pneumoperitoneum (T2: pneumoperitoneum), 10 min after terminating pneumoperitoneum (T3: end-pneumoperitoneum), and before extubation (T4: extubation). The systolic, diastolic, and mean arterial pressures and the heart rate values were measured noninvasively in T0 (10 min before operation)., Results: Obesity was found to cause a statistically significant increase in respiratory resistance and a peak inspiratory pressure and a decrease in dynamic respiratory compliance. In the morbidly obese group, the lowest dynamic respiratory compliance was 37 ± 12 mL/cm H(2)O, but it was 33 ± 13 mL/cm H(2)O in the super obese group. The systolic pressure, diastolic pressure, and mean arterial pressure were found to decrease significantly in both groups., Conclusions: Morbid obesity and super obesity have negative effects on hemodynamics and respiratory mechanics.

Background/aims: The objective of this study is to evaluate the factors effective on mortality and morbidity of the patients operated for liver tumor., Methodology: Thirty-four patients who were operated for liver tumor between January 1st 2008 and December 31st 2009 in Cerrahpasa Medical Faculty have been included in this study. Patient preoperative, perioperative and postoperative characteristics and the effects of these characteristics on mortality, morbidity and the length of hospital stay were evaluated., Results: Most common postoperative complications during the study were fever and surgical site infection. Nineteen of the patients with blood loss over 1, 000 mL had the need for postoperative ICU treatment. The presence of concomitant disease, especially diabetes mellitus, liver disease and cardiovascular diseases and more than 2 units transfusion of erythrocyte suspension and fresh frozen plasma were considered related to mortality and morbidity., Conclusions: Patient preoperative, perioperative and postoperative characteristics affect patient morbidity and mortality in liver resection surgery. Diagnosing liver tumors early and thus reducing surgical site blood loss and use of blood products will decrease mortality and morbidity ratios after liver surgeries.

This study was designed to investigate the protective effects of caffeic acid phenethyl ester on carbon tetrachloride-induced liver damage in rats. Twenty-four male Wistar rats were divided in three groups. Group I was used as control. Rats in group II were injected with carbon tetrachloride every other day for 1 month, whereas rats in group III were injected with carbon tetrachloride and caffeic acid phenethyl ester every other day for 1 month. At the end of the experiment, all animals were killed by decapitation and their livers were removed. Liver tissues were processed for electron microscopy. Histopathologically, hepatocytes of rats treated with carbon tetrachloride had damage in the cytoplasmic organelles and nuclei membranes as well as an excessive lipid accumulation in the hepatocytes. However, those histopathological changes were reduced with the coadministration of carbon tetrachloride and caffeic acid phenethyl ester. We conclude that caffeic acid phenethyl ester treatment has the capability to prevent carbon tetrachloride-induced liver damage in rats.

Object: Even though there have been many efforts to recover neuronal dysfunction following spinal cord injuries, there are limitations to the treatment of these injuries. The purpose of this laboratory investigation was to determine the clinical and neurophysiological effects of human umbilical cord blood (HUCB) transplantation in a rat hemisection model of spinal cord injury., Methods: In this study, experimental hemisection of the thoracic spinal cord was performed in rats. The rats were divided into 4 groups (6 rats in each group). One group of rats (Group 1) underwent thoracic laminectomy only. Rats in Group 2 underwent laminectomy and right hemisection of the thoracic spinal cord. Rats in Group 3 underwent right hemisection and implantation of freshly obtained HUCB on Day 0 postinjury. Rats in Group 4 underwent hemisection and implantation of freshly obtained HUCB on Day 4 postinjury. Clinical evaluations of rat motor function included the following: neurological examination, Rotarod performance, and inclined plane tests. Rats also underwent reflex evaluation., Results: The neurological examinations revealed that the frequency of plegic rats was 70.8% at the beginning of the study across all 4 groups; this value decreased to 20.8% by the end of the study. The percentage of rats with a normal examination increased from 25% to 50%. The results of Rotarod performance and 8-week inclined plane performance tests showed statistical significance (p < 0.05) in an overall group comparison across all time points. At the end of the 8 weeks, a statistically significant difference was found in the inclined plane test results between rats in Groups 1 and 2. There were no statistically significant differences between Groups 1, 3, and 4 (p < 0.05). When the reflex responses of the hemisectioned sides were compared, statistically significant differences were detected between groups (p < 0.05). All groups were significantly different with regard to the right-side reflex response score (p < 0.05). Spinal cord preparations of rats in all groups were examined for histopathological changes., Conclusions: Human umbilical cord blood is stem cell rich and easily available, and it carries less risk of inducing a graft-versus-host reaction in the recipient. Human umbilical cord blood serum is also noted to contain stem cell–promoting factors, which is why cell isolation was not used in this study. Freshly obtained cord blood was also used because storage of cord blood has been reported to have some negative effects on stem cells. Transplantation of freshly obtained HUCB into the hemisectioned spinal cord experimental model demonstrated clinical and neurophysiological improvement.

It was aimed to investigate the histopathological and biochemical changes in kidney tissues of rats exposed to cigarette smoke and possible protective effects of caffeic acid phenethyl ester (CAPE) on these changes. Twenty one male Wistar albino rats were divided into three equal groups. Animals in group I were used as control. Rats in group II were exposed to cigarette smoke and rats in group III were exposed to cigarette smoke and daily administration of CAPE. At the end of the 60-day experimental period, all the animals were sacrificed by decapitation. The serum samples obtained from the animals were studied for uric acid, creatinine and blood urine nitrogen (BUN) levels. Following routine histological procedures, kidney tissue specimens were examined under a light microscope. In addition, dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities and malondialdehyde (MDA) and nitric oxide (NO) contents were determined spectrophotometrically in tissue samples. It was found that serum uric acid and BUN levels of the rats exposed to cigarette smoke alone were elevated, although serum creatinine levels did not significantly change. Furthermore, renal SOD, GSH-Px, NO and MDA levels were significantly increased. These increases in serum BUN, and renal SOD, GSH-Px, NO and MDA levels were significantly inhibited by CAPE treatment. In light microscopic observations of tissues from rats exposed to smoke, mesangial cell proliferation in the renal corpuscles, dilatation and congestion in the peritubular capillaries and degenerative alterations in the proximal tubules were noted. There were also atrophic renal corpuscles. However, these histopathological changes were partially disappeared in the rats exposed to cigarette smoke plus CAPE. The present findings indicate that cigarette smoke causes impairment in renal structure and function, which can be prevented by CAPE administration.

The aim of this study was to investigate the immunolocalization of transforming growth factor beta (TGF-beta2) in rat thymic stromal cells and thymocytes and investigate the roles of TGF-beta2 in thymopoiesis during the late stages of fetal development. Twelve adult pregnant female Wistar rats weighing 250-270 g were used in this study. The rats were killed by cervical dislocation on gestation days 16 (GD16), 18 (GD18) and 20 (GD20). Fetal thymus glands were prepared and examined by an immunohistochemical technique to reveal binding of an anti-TGF-beta2 rabbit polyclonal antibody. The thymic primordium was surrounded with a connective tissue capsule at GD16 and at this stage TGF-beta2 immunoreactivity was not observed. At GD18, the connective tissue capsule had formed septa which subdivided the tissue into lobules and at this stage TGF-beta2 immunolocalization was detected in the capsule and in thymocytes. Lobulation was more evident at GD20 and TGF-beta2 immunoreactivity of thymocytes was more extensive than on GD18. Results indicate that TGF-beta2 may play an important role in the organization or development of thymocytes in the late stages of thymopoiesis.

It is reported that the pineal gland and its main hormone melatonin may have a role in the regulation of ghrelin synthesis in the brain. Stomach is the place where ghrelin is predominantly expressed and secreted. One aim of this study was to investigate possible effects of pinealectomy and melatonin treatment on gastric ghrelin amount. The studies on the effects of the pineal gland on leptin and ghrelin arises the question whether the pineal gland has also effects on the other energy-regulatory peptides such as peptide YY (PYY) and neuropeptide Y (NPY). Therefore, we also aimed to investigate the changes in the immunohistochemical staining of intestinal PYY and hypothalamic NPY following pinealectomy and melatonin treatment. Serum PYY levels were also investigated. Sprague-Dawley rats were divided into four groups as sham-operated (SHAM), sham-operated with melatonin treatment (SHAM-MT), pinealectomised (PNX) and melatonin-treated PNX (PNX-MT) groups. The cells immunostained for ghrelin were abundant throughout the gastric mucosa in all the groups. Neither pinealectomy nor exogenous melatonin affected significantly immunohistochemical staining of ghrelin in stomach. Pinealectomy resulted in a significant increase in immunohistochemical staining of PYY in ileum. The results of serum PYY measurement corresponded closely to the data obtained by immunohistochemical analysis of PYY in ileum, being significantly lower and higher in SHAM and PNX groups, respectively. Pinealectomy caused a decrease in NPY synthesis in ARC as understood from low immunohistochemical staining of NPY. Melatonin treatment increased NPY synthesis in SHAM rats and restored reduction in NPY synthesis caused by pinealectomy. In conclusion, the pineal gland and its main hormone melatonin can be suggested to have a role in the regulation of NPY synthesis in ARC and PYY in gastrointestinal system.

Ultrastructural changes in the kidneys of rats after acute cadmium exposure and the effects of exogenous metallothionein (MT) were studied by transmission electron microscopy. Thirty-six adult Wistar rats were divided into three groups. Cadmium chloride (CdCl2) (3.5 mg/kg/day) was injected subcutaneously in the first group. In the second group, 30 micromol/kg MT was administered in addition to CdCl2. Control rats received 0.5 ml subcutaneous saline solution. Four rats from each group were killed on days 1, 3, 5, and 7 after administration of the compounds. Kidney tissues were taken and fixed in 2.5% glutaraldehyde solution for electron microscopic observations. Tissue damage in kidney increased as time passed since the administration of CdCl2 in the first group. Degeneration in the proximal and distal tubules was observed. Increased apoptosis was seen in the proximal tubules epithelium, especially on day 7. Peritubular capillaries became dilated, there was degeneration of the endothelial cells, and the amount of intertubular collagen fibers was increased. On day 1, irregular microvilli in the proximal tubules, deepening of the basal striations, and myelin figures; on day 3, multiple vesicular mitochondria and regions of edema around tubules; on days 5 and 7, increased apoptotic cell in the proximal tubules and widened rough endoplasmic reticulum of the endothelial cells of glomerular capillaries were observed. We observed that the structural alterations that increased depending on the day of Cd administration decreased after exogenous MT administration, the dilation of the peritubular capillaries persisted, and there were degenerated proximal tubules. It was established that cadmium chloride was toxic for kidney cortex and caused structural damage. Exogenous MT partly prevents CdCl2-induced damage.

The aim of this study was to investigate the histological and biochemical changes in liver of rats exposed to cigarette smoke and effects of caffeic acid phenetyl ester (CAPE) on these changes. For this purpose, 21 male Wistar rats were divided into three groups. Animals in Group I were used as control. Rats in Group II were exposed to cigarette smoke and rats in Group III were exposed to cigarette smoke and injected daily with CAPE. At the end of the 60-days experimental period, all rats were killed by decapitation and blood samples were obtained. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin levels and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px ), malondialdehyde (MDA) contents were determined. Following routine histological procedures, liver tissue specimens were examined under a light microscope. The levels of ALT, AST, total bilirubin, SOD, GSH-Px and MDA were significantly increased in rats exposed to cigarette smoke compared with those of the controls. Light microscopic examination of liver specimens from rats exposed to cigarette smoke revealed mononuclear cell infiltration and that some of the hepatocytes had a hyperchromatic nucleus and enlarged sinusoids. The rats which were treated with CAPE along with cigarettes had partially attenuated histological changes associated with cigarette exposure. In conclusion, the damage inflicted by cigarette in the rat liver can be partially prevented by CAPE administration., ((c) 2005 John Wiley & Sons, Ltd.)

Background: Abdominal aortic surgery can cause ischemic/reperfusion (I/R) injury in not only the lower extremities, but also in the remote organs and tissues such as lungs, kidneys, heart, and liver during abdominal aortic surgery. It can result in mortality and morbidity because of the remote organ injury in early postoperative period. In this study, we investigate the effects of iloprost and vitamin C on the kidney remote organ damage after I/R following abdominal aortic surgery., Material and Methods: Thirty-four adult male Wistar rats were used and divided into five groups. I/R was studied infrarenally in the abdominal aorta following a median laparotomy. The left kidney was excised immediately following the laparotomy in group I (n = 6, normal group). Group II (n = 6) was the sham group. Group III (n = 6, control group) was subjected to 3 h of ischemia followed by an hour of reperfusion. Group IV (n = 8) was given iloprost 20 ng/kg/min during I/R period before aortic-clamping. Group V (n = 8) was given vitamin C 100 mg/kg during I/R period before aortic-clamping. Arterial blood samples were obtained to determine the levels of blood pH, pO(2) (mmHg), pCO2 (mmHg), HCO(3) (mmol/L), and plasma malondialdehyde (MDA, nmol/mL) at the end of reperfusion period in all groups. The left kidneys were used for remote measurements of tissue MDA (nmol/g.w.t) and scored by histopathological examination for acute inflammation., Results: While the arterial blood pO(2) and HCO(3) levels significantly increased, the plasma and renal parenchymal MDA levels significantly decreased in both group IV and group V when compared to group III (P < 0.05). Histopathological and acute inflammation scores statistically decreased in both group IV and V compared with group III (P < 0.05). Although MDA levels, histopathologic and acute inflammation scores in group V were lower than group IV, the differences were not statistically significant (P > 0.05)., Conclusion: Both iloprost and vitamin C decreased remote organ damage on the kidney after I/R of lower extremities in the rat model. However, vitamin C is more effective than iloprost in preventing postoperative renal dysfunction.

There are few data on morphology of light-chain deposition disease (LCDD) of kidney with coexistent light-chain cast nephropathy (LCCN). Here, the authors report the morphology in 23 cases of LCDD and LCCN. They retrospectively evaluated 23 renal biopsies with light (LM), immunofluorescence (IF), and electron microscopy (EM). Twenty-one patients had myeloma, 1 had a monoclonal gammopathy, and in 1 no illness was found. Nodular glomerulosclerosis, the LM lesion suggestive of LCDD, was noted in only 3 of 23 cases. Glomeruli were unremarkable in 16 (69%) cases. The diagnostic casts of LCCN were seen in all biopsies. Linear light chain (LC) immunoreactivity was observed in 23 (100%) cases (18 kappa, 5 lambda); GBM + TBM in 13, TBM only in 7, GBM only in 1, TBM and interstitium in 1, GBM, TBM and mesangium in 1. Casts were positive with same LC in all cases (100%). Fifteen cases (65%) showed granular electron-dense deposits; GBM only in 5, TBM only in 5, GBM and TBM in 4, mesangium in 1. In 8 patients without EM deposits, the diagnosis of LCDD was rendered by IF. Fifteen (65%) had deposits detectable by IF and EM, 8 (37%) had deposits with IF only. LCCN dominated the LM findings in all patients. There were minimal or no glomerular changes by LM. This study shows the lack of characteristic LM findings of LCDD in combined cases of LCDD and LCCN and emphasizes the difficulty for-definitive diagnosis-without IF and EM.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. This study compared effects of two PCB mixtures, Aroclors 1221 (A1221) and 1254 (A1254) on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine and uric acid in female rats. Histopathological changes in the liver and kidney were also examined. A group of adult Wistar rats served as controls. Groups II and III were subcutaneously injected with A1221 and A1254 at 10 mg/kg every other day for 6 weeks. At the end of this period, all animals were decapitated and blood samples were collected. Serum urea, creatinine, uric acid, ALT, AST and ALP levels were determined. Liver and kidney were collected for histopathological examination. They were fixed in formaldehyde and processed for light microscopy. Both A1221 and 1254 significantly elevated serum ALT (p < 0.05) and AST (p < 0.01) levels compared to the control group. Serum ALP values were significantly increased by A1221 (p < 0.05), but they were unaffected in the A1254 group. Treatment with both A1221 and A1254 significantly increased serum levels of urea (p < 0.05), creatinine (p < 0.01) and uric acid (except in the A1221 group; p < 0.005). Distinct histopathological changes including renal corpuscular atrophy, peritubular vascular congestion and dilated cortical tubules, sinusoidal dilatation, congestion and mononuclear cell infiltration were observed. These findings suggest that PCBs may cause nephrotoxicity and hepatotoxicity in female rats., (Copyright 2005 John Wiley & Sons, Ltd.)

Although the main source of circulating ghrelin is the stomach, it is also present in physiologically relevant amounts in the hypothalamus. It is reported that pharmacological doses of melatonin decrease blood levels of ghrelin. Thus, melatonin (MT) may be a candidate for the regulation of ghrelin synthesis in the brain. This study was therefore undertaken to investigate possible effects of pinealectomy and exogenous melatonin on hypothalamic ghrelin amount. Serum ghrelin levels following pinealectomy and administration of melatonin were also sought. Adult male Sprague-Dawley rats were divided into four groups as sham-operated (SHAM), sham-operated with melatonin treatment (SHAM-MT), pinealectomised (PNX) and melatonin-treated PNX (PNX-MT) groups. Ghrelin staining in the hypothalamus was determined by immunohistochemistry. Hypothalamic ghrelin was not observed in PNX rats. Much higher staining was detected in SHAM-MT rats compared to SHAM group. Lack of effect of melatonin on hypothalamic ghrelin in PNX rats implicates that exogenous melatonin requires an intact pineal to exert its effects. Although there were remarkable changes in the immunohistochemical activity of ghrelin in the hypothalamic arcuate nucleus, neither pinealectomy nor exogenous melatonin significantly changed serum levels of ghrelin. We have demonstrated for the first time that the pineal gland may play a role in ghrelin amount in the hypothalamus.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Two PCB mixtures, Aroclors 1221 and 1254 have been suggested to have estrogenic and anti-estrogenic properties, respectively. We have examined whether these PCB mixtures modulate bone turnover and vertebral histology in intact and ovariectomized (ovx) rat models. Thirty-two adult female rats were divided into four groups subcutaneously receiving 4% DMSO (control), A1221 (10 mg/kg), A1254 (10 mg/kg) oestradiol (E2, 30 microg/kg). These compounds were injected to the animals for a period of 6 weeks at two daily intervals. In the second model, rats (n=32) were ovx and allowed to recover for a period of 3 weeks. Control group received vehicle (4% DMSO) alone. Remaining rats were divided into three groups and injected (s.c.) with A1221, A1254 and E2 for 5 weeks. Urine samples were collected prior to end of the experiments. Then, all animals were decapitated. Serum parathyroid hormone (PTH), calcitonin and osteocalcin levels were determined by immunoradiometric method. Serum concentrations of alkaline phosphatase (ALP), calcium and inorganic phosphate were determined by enzymatic-colorimetric method. Urinary deoxypyridinoline (DPD) was measured by ELISA. Lumbar vertebrae (L2) of all animals were dissected out and processed for light microscopy. Levels of urinary DPD were significantly lowered in E2 -treated intact rats (p<0.001). Ovx significantly increased urinary DPD excretion (p<0.01) compared to intact control values. Administration of A1221 and A1254 had no significant effects in intact rats, however, they significantly reduced (p<0.05) and increased (p<0.001) urinary DPD levels in ovx rats, respectively. Neither of the PCB mixtures significantly changed serum osteocalcin and ALP levels in intact or ovx rats (except A1221 increased ALP in intact model, p<0.01). Both PCB mixtures had differential effects on serum PTH, calcitonin, calcium and inorganic phosphate concentrations. Treatment with A1221 reversed the adverse effects of ovariectomy on L2 histology. However, A1254 produced necrotic areas in vertebral bone, and this effect was expanded in ovx animals. Our findings suggest that both Aroclor compounds interfere with bone turnover mechanisms, particularly in ovx rats.

Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/reperfusion (I/R)-induced damage. This study was designed to investigate the effects of melatonin on the renal I/R injury in rats given the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). After right nephrectomy, I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24h reperfusion. The administration of melatonin significantly attenuated BP in NOS-inhibited hypertensive rats. Malondialdehyde (MDA) levels, a stable metabolite of the free-radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (3.48+/-0.2mg/l serum) than in the control group (2.69+/-0.2mg/l serum). L-NAME (40 mgkg(-1) for 15 days)+I/R significantly increased the MDA levels compared to I/R alone. Melatonin administration to L-NAME rats significantly reduced the MDA values resulting from I/R. We also demonstrated that I/R, and especially L-NAME+I/R, lead to structural changes in the kidney and that melatonin attenuates these changes. These results suggest that melatonin reduces BP and I/R injury in NOS inhibited rats by L-NAME.

The aim of this study was to investigate the effects of excess all-trans retinoic acid, a vitamin A metabolite, on pancreatic organogenesis and TGF-beta2 expression during prenatal development in rats. First group of animals used as control while a single dose of 60 mg/kg all-trans retinoic acid was ingested by the mothers, at day 8 of gestation (before the neurulation period) in group II and at day 12 of gestation (after the neurulation period) in group III, and all embryos were sacrificed at day 18 of gestation. TGF-beta2 expression was detected in the capsule, acini and Langerhans islets in the control group. In the pancreas of group II, dilatation and congestion of interlobular vessels were observed. Langerhans islet structures were completely absent. Moreover acinar TGF-beta2 immune reactivity was not determined. In group III, acinar expression of TGF-beta2 in acid was similar to that in the controls but their Langerhans islets TGF-beta2 immune reactivity was significantly less than the controls. In view of the present findings we suggest that TGF-beta2 plays important role in pancreatic morphogenesis and administration of excess all-trans retinoic acid before neurulation inhibit TGF-beta2 expression disrupted pancreatic morphogenesis particularly Langerhans islets. However, its administration after neurulation had less adverse affect on pancreatic organogenesis and TGF-beta2 immune reactivity.

In the present study, protective effects of caffeic acid phenethyl ester (CAPE) have been evaluated on carbon tetrachloride (CCl4)-induced hepatotoxicity in rat. Twenty-four male Wistar rats were divided in three groups. Group I was used as control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and CAPE for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and conjugated bilirubin levels and hepatic malondialdehyde (MDA) contents were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All biochemical parameters in serum and the hepatic MDA content were significantly higher in animals treated with CCl4 than in the controls. Rats treated with CCl4 and CAPE showed a significant reduction in biochemical parameters in serum and hepatic MDA content. Livers of rats treated with CCl4 showed classic histology of cirrhosis, whereas the histopathological changes were reduced after administration of CCl4 and CAPE. A normal lobular appearance was observed in livers in this group except for fatty degeneration. The results of our study indicate that CAPE treatment prevents CCl4-induced liver damage in rats., (Copyright 2004 Elsevier GmbH)

Mutations in p53 gene are the most frequent gene alterations in human cancer. In this study, we have used the monoclonal antibody (DO7) to evaluate the role of the p53 gene mutation in the progression of basal cell carcinomas towards invasion. We tested the positivity for p53 protein in tumor cells in six cases of basosquamous cell carcinoma (BSCC), in twelve cases of infiltrative basal cell carcinoma (IBCC) and twenty-four cases of non-infiltrative basal cell carcinoma (NIBCC) in order to evaluate its potential prognostic significance. We also tested the expression of p53 protein in normal epithelia adjacent to carcinomas in order to determine its role in tumor progression. p53 protein staining with some peripheral accentuation was identified in 42,9% of all groups. No correlation was found between the immunreactivity of p53 protein and recurrence, pattern of tumor, diameter of the tumors and sex. However, there were statistically significant differences in positivity of p53 protein in normal epithelia adjacent to carcinomas and age of patients (t value: 2,21; p: 0,034). Results of the study suggest that the increasein p53 mutation frequency of morphologically normal epidermis was related to age and was independent of the degree of differentiation of BCC.