Association of BK Virus Titers With Lymphocyte Count in Renal Transplant Patients.

OBJECTIVES: Regular screening for the BK virus (BKV) is recommended for early intervention in renal transplant patients. Identification of predictors for the development of BK viremia would improve their monitoring. We performed a retrospective study investigating whether the lymphocyte count may be a predictor of BKV development in renal transplant patients. PATIENTS AND METHODS: We retrospectively analyzed 268 renal transplant patients who were followed in our clinic from January 2011 to August 2014. The viral loads of BKV in blood detected by quantitative real-time polymerase chain reaction test were performed according to relevant guidelines. We also retrospectively monitored lymphocyte count, creatinine, immunosuppressive drug doses, and tacrolimus/cyclosporine/mTor inhibitors levels during the same time as BKV screening. Demographic and other clinical data were extracted from patients' files. The calculation of correlation coefficients and receiver operating characteristics (ROC) curve analysis were performed. RESULTS: Overall, 16 patients (5.9%) who experienced BKV-DNA positivity were included the study. Mean age of patients was 38.2 ± 12.8 years. All patients received steroid and calcineurin inhibitors (CNIs). Mycophenolate mofetil/mycophenolic acid (MMF/MPA) was administered to 14 patients. BKV-DNA was found in 64 of the 88 (72.7%) plasma samples. The lymphocyte count on the first day of positive BKV-DNA test was significantly lower than in those with negative BKV-DNA results (1700/µl vs 2400/µl, respectively; P = .009). Its AUC of the ROC curve was 0.77 (P = .012). The optimal cutoff point for lymphocyte count was 1900/µl, and sensitivity and specificity for predict BKV positivity were 75% and 78.57%, respectively. We also found that lymphocyte count negatively correlated with the first detectable BKV titers (r = -0.438; P = .015). However, there is no relation between CNI/mTOR inhibitor levels, MMF/MPA doses, lymphocyte count, and all BKV-titers. CONCLUSIONS: Decreased lymphocyte count may be a predictor for preceding BKV viremia. Clinicians should be more careful in terms of the decreased lymphocyte count in case of BKV replication in renal transplant patients.

Sildenafil accelerates liver regeneration after partial hepatectomy in rats.

OBJECTIVE: The regeneration process causes the liver to achieve an adequate volume and function after major hepatectomy or living donor liver transplantation. Sildenafil, a selective phosphodiesterase-5 inhibitor used for erectile dysfunction, impacts the liver by enhancing the effects of nitric oxide. The aim of this study was to investigate the influence of sildenafil on liver regeneration in rats after partial hepatectomy. METHODS: Sixty young female Wistar Albino rats were randomly divided into three equal groups before 70% hepatectomy. Thereafter, we administered intraperitoneal saline to the control group (G1); 10 µg/kg sildenafil to the low-dose group (G2) and 100 µg/kg to the high-dose sildenafil group (G3). Half of the rats per group were sacrificed on the first and the other half on the fifth postoperative day after partial hepatectomy. Regeneration was assessed using three methods: (1) the formula described by Kwon et al formula, (2) the average number of mitotic figures in 10 microscopic fields, and (3) the average of Ki-67-positive nuclei in 1000 cells using immunohistochemistry. RESULTS: Although, the hepatic regeneration and mitosis rates were similar in all three groups, Ki-67 levels were significantly higher in both G2 and G3 than the control group on the first postoperative day. Hepatic regeneration was significantly greater in G2 and G3 than the control group as was the mitosis rate in the G2 group versus the two groups. By the 5th postoperative day Ki-67 levels were similar in the three groups. CONCLUSION: Sildenafil treatment accelerated hepatic regeneration after partial hepatectomy in rats.

Splenic recurrence of liver hydatid cyst and spleen preserving therapy.

Hydatid cyst disease remains a considerable public health problem, especially in pastoral and farming regions. Although the spleen is the third most commonly affected organ after the liver and lungs, splenic hydatid cyst is an uncommon entity even in areas that are endemic for echinococcosis. The recurrence rate after surgical therapy of the liver hydatid cyst is reported as 6.8-22.3 percent. Recurrences most frequently occur in the liver. Extrahepatic recurrences occur in the lung or peritoneum and the serosa of the abdominal organs. Splenic recurrence of liver hydatid cyst has not previously been reported. The most common surgical therapy is splenectomy, and the other option is spleen preserving surgery. We report the first case of recurrent splenic hydatid cyst in the spleen and liver synchronously after surgical therapy for liver hydatid disease. The patient was treated with liver resection and spleen preserving surgery.

Preserving effects of melatonin on the levels of glutathione and malondialdehyde in rats exposed to irradiation.

In this study we investigated whether pretreatment with melatonin was protective against the injury of the central nervous system (CNS) in rats receiving LD(50) whole body irradiation. The wistar rats were randomized into four groups: i) the control group (CG), ii) melatonin-administered group (MG; 1 mg/kg body weight), iii) irradiated group (RG; 6.75 Gy, one dose), and iv) melatonin-administered and irradiated group (MRG). Blood samples were drawn from the rats 24 h after the treatment and plasma glutathione levels were assayed. Plasma glutathione level was significantly higher in RG than CG. The melatonin pretreatment prevented GSH increase induced by irradiation. Lipid peroxidation and glutathione levels of rat cerebral cortex were determined in all groups after 24 h. Cortical malondialdehyde (MDA) was significantly higher in the RG. The melatonin pretreatment prevented cortical MDA increase induced by irradiation. Cortical GSH was significantly lower in RG than the CG. The melatonin pretreatment prevented cortical GSH decrease induced by irradiation. Tissue samples were obtained from cerebral cortex and hypothalamus which also were affected by ionizing irradiation in the CNS and were evaluated with electron microscopy. Histopathological findings showed that LD(50) whole body irradiation resulted in damage of the neuronal cells of CNS. The results obtained from this study demonstrated that pretreatment with melatonin prevented the damage that develops in CNS following irradiation. The beneficial effect of melatonin can be related to protection of the CNS from oxidative injury and preventing the decrease in the level of cortical glutathione.

Melatonin treatment for prevention of oxidative stress: involving histopathological changes.

This study was undertaken to test the effect of irradiation on the histopathology of the hypothalamus and cerebral cortex. In addition, the probable effects of radiotherapy on the activities of antioxidant enzymes and levels of nitric oxide (NO) in the plasma were investigated as well. The effects of melatonin treatment on radiotherapy-based central nervous system (CNS) damage were also studied. For this purpose, the rats were randomized into four groups. The first group was the control group (sham-exposed group), the second group received only melatonin, the third group was irradiated and the fourth group received both melatonin and irradiation. Plasma samples of rats were collected for measuring the activities of superoxide dismutase (SOD), catalase (CAT) and the levels of NO. 24 h after the interventions, tissue samples were obtained from the hypothalamus and the cerebral cortex for the light microscopic investigations. These tissues were mostly affected by radiation. The results indicated that the application of radiation significantly enhanced the levels of plasma SOD and NO. On the other hand, melatonin pretreatment prevented the decrease in plasma CAT activity induced by irradiation. It was found that the application of melatonin could significantly prevent the irradiation-induced damages. Light microscopic results revealed that the damage of the CNS by radiation was prevented by the application of melatonin.

Body fat percent and fat distribution parameters in rheumatic diseases.

Alterations in body composition in chronic rhematologic disorders have been associated with decreased strength, altered energy metabolism and immunologic compromise and may provide a useful indicator of the severity of the disease. However, results of anthropometric parameter studies have been equivocal. The purpose of this study, was to compare body composition parameters of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) with those of healthy controls. Mean age, height, weight and body mass index (BMI) of patients with RA were not found to be different from those of the controls. BMI, body fat percent (BFP) were found to be high in patients with AS, but the differences between this two parameters of AS patients and controls were not statistically significant. Mean BFP of patients with RA was higher than the control subjects, but only the difference between female patients with RA and controls was statistically significant. Mean lean body mass (LBM) was slightly lower in male and female patients with RA compaired to the healthy controls. LBM of AS patients was found to be similar with that of the controls. Upper/lower body fat ratio (U/L BFR) and central/peripheral body fat ratio (C/P BFR) were higher in male patients with RA, but there were no differences between patients and controls. U/L BFR and C/P BFR body fat ratios were higher in AS patients. But, only the differences between C/P body fat distribution of AS patients and control subjects was statistically significant. The results obtained from this preliminary report show some anthropometric parameters of RA and AS patients can differ from those of the healthy controls. Future investigations are needed to determine the metabolic alterations causing the changes in body composition.

Platelet Functions in Patients with Allergic Asthma.

To investigate platelet functions in patients suffering from allergic diseases including asthma, blood was collected from ten asthmatic patients (five females, five males) and ten healthy controls (five females, five males) and by using whole-blood electrical impedance system; platelet count and platelet aggregation studies (maximum aggregation extent, maximum aggregation rate) were performed. Allergy screening was performed with skin test reactions and with high total and specific immunoglobulin E levels (CAP-Phadiatop system). Platelet count (333.1 ± 41.1 x 109/L), collagen induced the response of platelet aggregation (12.95 ± 4.19) and maximum rate of aggregation (8.00 ± 5.22) in allergic patients were found significantly higher than those of controls (252.1 ± 49.1 x 109/L; 8.33 ± 1.19; 4.28 ± 1.31) (p< 0.05). Also ADP induced response of platelet aggregation (18.21 ± 3.56) and maximum rate of aggregation (10.64 ± 2.12) in asthmatic patients were higher than controls (12.37 ± 2.63; 7.80 ± 1.64) with statistical significance (p< 0.01). Secretion products of activated platelets such as histamine, serotonin, PGF2α and PAF may play role in bronchial responsiveness in allergic asthma. The results of this study showed that platelet function tests were effected in asthmatic patients. The changes in platelet functions are thought to be related with increased IgE levels and stimulation of platelets by these antibodies.

A possible mechanism of X-ray-induced injury in rat lens.

PURPOSE: X-ray and other radiation can cause cataract, but the pathogenic mechanism is largely unknown. The aim of this study was to investigate the accumulation of iron in the x-ray-exposed rat lens and its relationship to lens injury. METHODS: Fifty male Wistar rats were divided randomly into five groups of 10. Groups 2 and 4 rats were sham-exposed, groups 3 and 5 were x-ray-treated, and group 1 served as control. X-ray radiation and sham exposure were performed in a similar manner. After 10 and 30 days of exposure, a lens from each rat in groups 2 and 3, and 3 and 5, respectively, were analyzed by flame atomic absorption technique for the assessment of metal content. RESULTS: Significantly decreased zinc and increased iron and calcium concentrations were detected in the lens samples of groups 3 and 5 compared with groups 2 and 4 and controls. Similar results were obtained comparing groups 5 and 3. CONCLUSIONS: We propose that x-ray exposure may cause toxic cell injury of the rat lens via Fenton metals catalyzed damage. Initial lens membrane damage in the radiolytic phase may permit the access of iron resulting in lens damage.

Cataractous changes in rat lens following cigarette smoke exposure is prevented by parenteral deferoxamine therapy.

OBJECTIVES: To test whether iron accumulation in the lens following cigarette smoke exposure is the principal mechanism in smoke-related cataractogenesis and to assess the possible protective effect of deferoxamine mesylate treatment against lenticular degeneration with in vivo exposure to cigarette smoke. METHODS: Thirty-two male Wistar rats were randomly divided into 4 equal groups. Groups 3 and 4 rats were exposed to cigarette smoke for 1 hour each day for 90 consecutive days, and groups 1 and 2 rats were treated in a similar manner but exposed only to room air. In addition, deferoxamine was given subcutaneously to groups 2 and 4 rats. Both eyes of all the animals were then enucleated and 1 eye prepared for histopathological examination. The fellow eye was used to measure iron, calcium, zinc, and copper levels. RESULTS: Significantly higher iron and calcium and lower zinc levels were observed in the lenses of group 3 rats compared with those in the other groups. Similar comparisons performed between groups 1 and 2, 1 and 4, and 2 and 4 did not show any significant difference. Copper concentrations did not differ between groups. Distinct histopathological changes in the anterior lens epithelium, such as hyperplasia, hypertrophy, and epithelial multilayering, and the presence of swollen epithelial cells overlying the posterior lens capsule, observed in group 3 rats, were not present in the other groups. CONCLUSIONS: Cataractogenesis following cigarette smoke exposure in rats was associated with the accumulation of iron, and concurrent deferoxamine therapy prevented such cataract formation. CLINICAL RELEVANCE: Our results may apply to human cataract formation associated with cigarette smoking, so such pathogenesis may be prevented by concurrent parenteral deferoxamine treatment. Clinical studies are needed, however, to determine the value of this suggestion.

Cadmium and iron accumulation in rat lens after cigarette smoke exposure and the effect of vitamin E (alpha-tocopherol) treatment.

PURPOSE: Cadmium accumulation in the lens has been implicated in cataractogenesis of chronic smokers. This study was planned to evaluate whether or not in vivo cigarette smoke exposure causes cadmium accumulation in rat lens, and possible protective effect and mechanism of alpha-tocopherol (vitamin E) treatment on cataractogenesis. METHODS: 28 male Wistar rats were randomly divided into four equal groups. Group 3 and 4 rats were exposed to cigarette smoke over ninety consecutive days, and Group 1 and 2 rats were treated in a similar fashion but exposed only to room air. Additionally, vitamin E was given to Group 2 and 4 rats. RESULTS: Significantly higher iron levels were observed in the lenses of Group 3 rats compared to other groups. With respect to cadmium, Group 3 and 4 rats had significantly higher levels compared to Group 1 and 2 rats. Although vitamin E treatment prevented iron accumulation in Group 4 rats, it had no effect on cadmium concentrations. Distinct histopathological changes observed in Group 3 rats were not present in Group 4 rats. CONCLUSION: Our study demonstrates that in vivo cigarette smoke exposure causes accumulation of cadmium in rat lens and IM vitamin E treatment does not affect this accumulation. The protective effect of vitamin E treatment on smoke exposed rat lens seems to be mediated by blockage of iron accumulation in the lens.

Prevention of lens damage associated with cigarette smoke exposure in rats by alpha-tocopherol (vitamin E) treatment.

PURPOSE: To evaluate the possible protective effect and mechanism of alpha-tocopherol (vitamin E) treatment on lens degeneration associated with in vivo exposure to cigarette smoke and to further clarify the role of iron in cigarette smoke-generated lens damage. METHODS: Twenty-eight male Wistar rats were randomly divided into four equal groups. Rats in groups 3 and 4 were exposed to cigarette smoke for 1 hour each day over 90 consecutive days, and rats in groups 1 and 2 were treated in similar fashion but only exposed to room air. Additionally, vitamin E was given to the rats in groups 2 and 4 via intramuscular route. At the end of the study, both eyes of all the animals were enucleated; one eye was prepared for histopathologic examination, and the fellow eye was used for the measurement of iron and calcium levels. RESULTS: Significantly higher iron and calcium levels were observed in the lenses of group 3 rats than in other groups. Similar comparisons performed between groups 1 and 2, groups 1 and 4, and groups 2 and 4 did not show any significant difference. Distinct histopathologic changes in the anterior lens epithelium, such as hyperplasia, hypertrophy, epithelial multilayering, and the presence of epithelial cells over posterior lens capsule, observed in group 3 rats were not present in other groups. CONCLUSIONS: Cataractogenesis after cigarette smoke exposure was associated with an accumulation of iron and calcium in the rat lens, and vitamin E supplementation protected such accumulations and cataractogenesis.

Determinations of some trace and heavy metals in rat lenses after tobacco smoke exposure and their relationships to lens injury.

Cigarette smoking has been implicated in the pathogenesis of cataract, but the pathogenic mechanism by which cigarette smoke causes cataract is yet to be completely understood. There has been suggestion that oxidative damage caused by accumulation of Fenton reagents (iron and copper) in the lens can cause lens damage and possibly cataract. To investigate the accuracy of this theory the study was planned. A number of twenty-four male Wistar rats were divided randomly into experimental and control groups. The experimental group of rats were exposed to cigarette smoke for two hours in each day over sixty consecutive days and the controls were treated in identical fashion but only exposed to room air. At the end of the study period, both eyes of all the animals were enucleated and one eye prepared for histopathological examination and the other used for the measurement of metal levels. The lenses of experimental animals showed significantly decreased zinc and increased iron, and calcium concentration relative to those of sham exposed controls. However, no significant difference was found in the copper contents of the lenses of both groups. Distinct histopathological changes such as hyperplasia, hypertrophia, and multilayering of epithelial cells and elevations of calcium concentration detected in the lenses of experimental group animals suggested that the lens damage was a result of in-vivo exposure to tobacco smoke. We propose that increased metal contents in the lens can cause lens damage by the mechanism of oxidative stress through formation of oxygen radicals via metal catalysed Fenton reaction.

Histopathological and ultrastructural examination of the rat conjunctiva after exposure to tobacco smoke.

Exposure to tobacco smoke can cause irritation of the conjunctiva. We conducted this study to identify the effect of tobacco on rat conjunctiva. Animals were divided into experimental and control groups and we exposed the experimental group to tobacco smoke. Control group rats inhaled only room air. Spectrophotometric analysis of the smoke-air mixture revealed that many toxic substances were present in this compound. We found very high levels of plasma thiocyanate after exposure to smoke in experimental group animals but no increase in the control group. So, this data indicates that these animals inhaled smoke effectively in our method. After 3 months conjunctivas were examined by light and electron microscopy. In the experimental group, conjunctivas were thinned, atrophied and microvillous projections and desmosomal connections were absent in comparison with the control conjunctivas. This pathologic change is very similar to conjunctival response to chronic irritants of any type.

Long-term effects of cigarette-smoke exposure on plasma testosterone, luteinizing hormone and follicle-stimulating hormone levels in male rats.

OBJECTIVES: To determine the effects of long-term cigarette smoking on the levels of plasma testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in male adult rats and to examine morphological and histological changes in the testes. MATERIALS AND METHODS: Cigarette smoke was generated by a smoking-machine and 12 rats were exposed to cigarette smoke diluted with 90% air for 60 days (2 h/day). Twelve rats were exposed to room air only under similar conditions as controls. The concentrations of plasma testosterone, LH and FSH were measured before and after exposure using a radio-immunoassay and the testes were examined histologically. RESULTS: In rats exposed to smoke, the mean plasma testosterone level decreased significantly but there were no significant changes in testosterone in the control rats. The mean plasma LH and FSH levels of the two groups did not change significantly after exposure. In rats exposed to smoke, histological examination of the testes showed fewer Leydig cells and degeneration of the remaining cells. CONCLUSION: These results indicate that the decrease in plasma testosterone levels induced by exposure to smoke was not associated with changes in plasma gonadotrophin levels. The decrease in testosterone levels may be related to the toxic effects of smoke on Leydig cells.