Factors associated with pathological tumor stage and T3a upstage in clinical T1-2 renal cell carcinoma.

INTRODUCTION: Considering the oncological outcomes, understanding the preoperative factors associated with and predicting advanced stage and T3a upstage will help in risk assessment and selection of the right treatment. MATERIAL AND METHOD: Patients with postoperative pathology of Renal Cell Carcinoma (RCC) and stage T1-2 N0M0 were included in the study. Demographic and pathological characteristics of the patients, Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and De Ritis- the ratio of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were recorded. Patients were classified according to T stage (T1-2 vs T3-4) and T3a upstage (T3a upstaged vs non-T3a upstaged). RESULTS: A total of 289 patients participated in the study when inclusion and exclusion criteria were applied. No difference was found between the groups in terms of age, gender, body mass index, laterality, ABO blood group, Rh positivity and comorbidities. According to multivariate analysis, PLR, AST/ALT, Fuhrman grade, open radical nephrectomy (RN) and Clear Cell pathological subtype were found to be significant-independent factors in predicting advanced stage (T3-4) and T3a upstage (P<0.05). CONCLUSION: It was found that higher PLR and AST/ALT ratios were associated with more advanced stage and postoperative T3a upstage in RCC patients. In addition, these patients more frequently had open RN and had higher Fuhrman grades, while the clear cell subtype was less common.

The therapeutic effect of ALT-711 on erectile function in rats treated with high-level AGEs (advanced glycation end products) containing diet.

To investigate, if advanced glycation end products (AGEs) are involved in erectile dysfunction (ED) and also ALT-711, a cross-link breaker of AGEs, has the therapeutic potential against the development of ED in rats treated with high concentrated AGEs including food. For this purpose, 30 male Harlan Spraque-Dawley rats randomly were divided into three groups; (1) control rats treated with regular diet, (2) rats treated with high-level of AGE specific diet for 6 months, and (3) rats having AGE-diet treated with ALT-711 for the final 3 months of 6 months of AGE-diet period. Erectile response to cavernosal nerve stimulation (CNS), protein expression of neuronal nitric oxide synthase (nNOS) and levels of AGEs, Malondialdehyde (MDA), cyclic guanosine monophosphate (cGMP) were determined in penile tissues. Erectile responses to CNS and penile nNOS and cGMP content were significantly reduced, while AGEs and MDA were elevated in penises of Group-2. Treatment with ALT-711 reversed ED and depletion of both nNOS and cGMP. Additionally, ALT-711 treatment reduced penile tissue AGEs and MDA expression. In present study: rats without any co-morbidity such as diabetes mellitus (DM) and chronic renal failure (CRF) were treated with high-level AGEs containing food. Our results suggest that ALT-711 may be an interesting and promising approach in the treatment of AGEs-related ED.

Does radio frequency radiation induce micronuclei frequency in exfoliated bladder cells of diabetic rats?

OBJECTIVE: For many years there has been a discussion among both experts and the general public regarding the effects of radio frequency (RF) radiation on the human organism. The purpose of the present study was to evaluate the relationship of micronucleui (MN) frequency and RF radiation in exfoliated bladder cells of non-diabetic and diabetic rats. METHODS: Three groups were used in the experiment: Group I (n=6): diabetic group without RF exposure; Group II (n=6): diabetic group exposed 2100 MHz RF radiation and Group III (n=6): control animals (non-diabetic group, no RF exposure). RF exposure in the experiment resulted in a whole body average SAR of 0.24 W/kg with an ERMS field of 17.5 V/m in non-thermal levels. RESULT: Results showed that there was no statistically important differences between non-RF exposed diabetes group and control group; Group I and Group III (p>0.05). There was no statistically important differences between diabetes group and diabetes+RF exposed group (Group I and Group II) (p>0.05). RF exposure did not result in increased MN frequencies in exfoliated bladder cells of diabetic rats with respect to control animals (Group II and Group III), either and this result found no statistically important (p>0.05). CONCLUSIONS: This study suggested no possible genotoxic effects of RF radiation among human beings especially with chronic disorders, such as diabetes.

No genotoxic effect in exfoliated bladder cells of rat under the exposure of 1800 and 2100 MHz radio frequency radiation.

In this study, we aimed to investigate the effects of 1800 and 2100 MHz Radio Frequency (RF) radiation on the number of micronucleus (MN) in exfoliated bladder cells of rat which shows the genotoxic damage. Exposure period was 30 min/day, 6 days/week for a month and two months exposure periods. Thirty male wistar albino rats were used for five groups: Group I (n = 6): 1800 MHz RF exposed animals for one month, Group II (n = 6): 2100 MHz RF exposed animals for one month, Group III (n = 6): 2100 MHz RF exposed for two months, Group IV (n = 6): control group for one month, Group V (n = 6): control group for two months. Rats of the control groups were housed in their home cages during the entire experimental period without subjecting to any experimental manipulation. 1800 and 2100 MHz RF exposures did not result in any significant MN frequencies in rat bladder cells with respect to the control groups (p > 0.05). There was no statistically significant difference between 2100 MHz RF exposed groups, either. Further studies are needed to demonstrate if there is any genotoxic effect, micronucleus formation in other tissues of rats.

Antioxidative and therapeutic effects of spirulina on trichloroethylene induced cutaneous irritation balb/c mice.

OBJECTIVES: To evaluate the antioxidative and therapeutic effects of spirulina on the trichloroethylene induced cutaneous irritation balb/c mice. BACKGROUND: During recent years, an attention has been focused on the antioxidant potential of Spirulina species. METHODS: Balb/c mice were randomized into the four groups. At the end of the each application, the rats were sacrificed and dorsal skin was taken. Histopathologic and immunohistochemical evaluations were conducted, oxidative stress was assessed by the measurement of malondialdehyde (MDA) levels, superoxide dismutase (SOD) activities and nitric oxide (NO) production. RESULTS: There was a statistically significant decreased disruption in epidermal integrity, oedema in intercellular dermis, disorganization in collagen fibres and immunoreactivity in the pre acute dermatitis/ antioxidant and the post acute dermatitis/ treatment groups when compared to the acute dermatitis group (p<0.05). CONCLUSION: The results of the present study indicate the antioxidative and therapeutic effects of Spirulina on trichloroethylene induced cutaneous irritation balb/c mice (Tab. 2, Fig. 8, Ref. 33).

Therapeutic effect of combination of alagebrium (ALT-711) and sildenafil on erectile function in diabetic rats.

Recently, the relationship between advanced glycation end products (AGEs) and erectile dysfunction (ED) has been reported. The present study aimed to investigate whether a combination of an AGE cross-link breaker (alagebrium/ALT-711) and sildenafil could enhance the erectile capacity in streptozotocin (STZ) diabetic rats. Additionally, we assessed the effect of that treatment option on some molecules that have been suggested to have crucial roles in AGE-related ED pathways. Four groups of animals were utilized: (1) age-matched control rats, (2) STZ-induced diabetic rats (40 mg kg(-1) i.p.), (3) STZ rats+sildenafil (5 mg kg(-1) p.o.), (4) STZ rats treated with a combination of sildenafil (5 mg kg(-1) p.o)+alagebrium/ALT-711 (10 mg kg(-1) p.o.) for the final 1 month of the 2 months of diabetes period. At 2 months after i.p. injection of STZ, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue AGEs, MDA (malondialdehyde), cyclic guanosine monophosphate (cGMP) (ELISA), endothelial nitric oxide (NO) synthase (eNOS), inducible NO synthase (iNOS) (western blot), nuclear factor (NF)-κB, mitogen-activated protein (MAP) kinase (immunohistochemistry) and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) analyses were performed in all groups of rats. STZ diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve) after CNS when compared with control rats (P<0.05). The increase in both ICP and area under the erectile curve of STZ diabetic rats treated with a combination of sildenafil+alagebrium/ALT-711 as well as in STZ diabetic rats treated with sildenafil alone was significantly greater than STZ diabetic rats. Additionally, combination treatment decreased AGE, MDA, iNOS, NF-κB, MAP kinase and apoptosis levels, whereas it preserved cGMP contents in diabetic penile tissue. Decreased AGE, MDA, iNOS, NF-κB, MAP kinase and increased cGMP levels at the combination (sildenafil+alagebrium/ALT-711) therapy group increased both the peak ICP and total ICP to CNS in the STZ diabetic rats, which was similar to the response observed in control rats. These results may explain the role of AGEs in diabetes-related ED and the effect of an AGE cross-link breaker alagebrium/ALT-711+sildenafil therapy on some critical molecules related to AGE-related ED pathways.

The study of biochemical and histopathological effects of spirulina in rats with TNBS-induced colitis.

OBJECTIVES: To evaluate the beneficial effects of spirulina on the treatment of experimental colitis. BACKGROUND: Spirulina, a planktonic blue green algae from oascillateriaceae family, has anti-inflammatory, antioxidant, antitumor, anti-viral, and antimicrobial effects, rendering it a natural drug of prophylactic and therapeutic properties. The effects of spirulina on colitis are not known. METHODS: Wistar rats weighing 200-300 g were used. Experimental colitis was created during anesthesia using the trinitrobenzene sulfonic (TNBS) acid. The rats were randomly divided into the 3 groups. In the group 1 (sham; n = 8), saline was administered via oral gavage 7 days after 1 ml of rectal saline was administered. In the group 2 (experimental colitis + spirulina; n = 8), 2 g/kg spirulina was administered via oral gavage 7 days after the rectal 1 ml TNBS was administered. In group 3 (experimental colitis; n = 8), enema was administered via oral gavage 7 days after the rectal 1 ml TNBS was administered. Eight days after the instigation of TNBS colitis, the rats were sacrificed and blood and tissue samples were taken. Histopathologic and immunohistochemical evaluations were conducted, and malondialdehyde (MDA), advanced oxidation protein products (AOPP), catalase (CAT), total antioxidant status (TAS), and glutathione (GSH) levels were determined. RESULTS: Inflammation on mucosa and submucosa, hemorrhage, necrosis, cellular infiltration and crypt abscess formation, immunoreactivity and tissue MDA levels were decreased in the experimental colitis + spirulina group when compared to the experimental colitis group (p < 0.05). CONCLUSION: The results of the present study indicate the beneficial effects of spirulina on TNBS-induced inflammatory bowel disease (Tab. 6, Fig. 10, Ref. 40).

Effects of vitamin C and N-acetylcysteine against cyclophosphamide-induced genotoxicity in exfoliated bladder cells of mice in vivo.

PURPOSE: To investigate the effects of vitamin C and N-acetylcysteine (NAC) against cyclophosphamide (CP) -induced genotoxic damage in exfoliated bladder cells of mice by micronucleus (MN) assay. METHODS: For each experimental step, 6-8 Swiss albino balb/c male mice were used. CP was used as positive control. Vitamin C (10, 30 and 60 mg/kg) and CP (51.6 mg/kg) were administered intraperitoneally to the experimental animals. Vitamin C was administered twice, one dose 24 h prior to the CP administration and the second dose simultaneously with the CP. NAC (200, 400 and 800 mg/kg) was administered by gavage for 7 consecutive days before the injection of CP. Distilled water and normal saline as negative controls I and II were used, respectively. Ten days after CP treatment, the mice were sacrificed and bladders were isolated and cut, and exfoliated cells were scraped from the bladder walls. Air-dried smears were stained by Feulgen reaction. MN frequencies were scored in 1000 epithelial cells per animal and defined as MN per thousand (per thousand). RESULTS: Three doses of vitamin C (10, 30 and 60 mg/ kg) showed a significant inhibitory effect on MN frequencies in mouse bladder cells when compared with those of positive control group (p <0.05). Dose-dependent inhibitory effect of vitamin C was observed only between the doses of 10 and 60 mg/kg (p <0.05). Histopathological changes that depended on CP- induced inflammatory infiltration and haemorrhage in mucosa propria were not observed in all 3 vitamin C doses. Three doses of NAC (200, 400 and 800 mg/kg) inhibited the CP-induced genotoxicity (p <0.05), however, the antigenotoxic effect of NAC was not dose-dependent. Histopathological changes that depended on CP-induced inflammatory infiltration and haemorrhage in mucosa propria were not observed in 200 and 400 mg/kg NAC dosage. The extent of desquamation in bladder was similar in all 3 doses of NAC when compared with the positive control group. CONCLUSION: Our study indicated that vitamin C and NAC reduced the CP-induced MN frequencies in target (bladder) cells of mice by 41-71% in all cases. The modifying effects of vitamin C and NAC against CP-induced genotoxic damage may be due to their antioxidant, nucleophilic properties and to the ability to act as precursors of glutathione.

The relationship between the enzyme activity, lipid peroxidation and red blood cells deformability in hemizygous and heterozygous glucose-6-phosphate dehydrogenase deficient individuals.

Glucose-6-phosphate dehydrogenase (G6PD) activity, red blood cell (RBC) lipid peroxidation and deformability were investigated in hemizygous and heterozygous G6PD deficient subjects and compared with normal individuals. None of the subjects were in acute hemolytic crises. G6PD activity was assessed based on the spectrophotometric determination of generated NADPH. Lipid peroxidation was measured as thiobarbutiric acid reactive substances (TBARS). RBC deformability was analyzed by ektacytometry. RBC lipid peroxidation was found to be significantly higher in hemizygous subjects compared to control and heterozygous subjects, while RBC deformability was found to be significantly impaired. However, although lipid peroxidation was higher than control, RBC deformability was not significantly different from control in heterozygous individuals, characterized by significantly lower RBC G6PD activity. There were no significant correlations between these three parameters when the three groups were analyzed separately, but a significant negative correlation was found to exist between G6PD activity and TBARS when the pooled data from the three groups were used for the analysis. This was also true for the relationship between RBC deformability and G6PD activity. It has been concluded that G6PD activity is not a good predictor of oxidative damage resulting in mechanical impairment in heterozygous individuals.

Effects of heparin on hypertonic potassium chloride-induced bronchoconstriction.

BACKGROUND: Changes in bronchial osmolarity is a well-known factor for bronchoconstricion. Recenty, nonisotonic aerosols have begun to be used for the assessment of bronchial hyperreactivity. Hypertonic KCl can cause bronchoconstriction even in non-symptomatic asthmatic patients. OBJECTIVE: To evaluate the protective role of heparin on hypertonic KCl-induced bronchospasm in asthma. METHODS: Thirty-eight asthmatic patients were included in this double-blind, placebo-controlled study. On day 1 of the study, after performing the respiratory function test (RFT), patients had inhaled KCl 10% and RFTs were done after 20 minutes. On day 2 of the study, after the basal RFT, 18 patents inhaled NaCl 0.9% 0.2 mLkg solution. After the completion of this procedure, patients waited for 20 minutes and inhaled KCl 10% 10 mL, and RFTs were repeated 20 minutes later. The second group consisted of 20patients who inhaled heparn 1,000 units/kg after the RFTs were performed. Twenty minutes later, they inhaled KCl 10% and waited for 20 minutes. Finally, RFTs were done and compared with those from the other group. RESULTS: In the control group, forced expiratory volume in one second (FEV1) decreased 17.4% on day 1 and 16.4% on day 2. In the heparin-treated group, FEV1 decreased 18.6% on day 1, but almost no change occurred after this group was treated with heparin before inhalation of hypertonic KCl on day 2. CONCLUSIONS: Heparin was found to be highly protective against hypertonic KCl induced bronchospasm in bronchial asthma.

Effects of caffeic acid phenethyl ester and epidermal growth factor on the development of caustic esophageal stricture in rats.

BACKGROUND/PURPOSE: An experimental study was performed to modify the healing response in caustic esophageal burns to prevent stricture development. Two different agents with different modes of actions, caffeic acid phenethyl ester (CAPE) and epidermal growth factor (EGF), were studied. CAPE has antiinflammatory, immunomodulatory, antioxidant, and antimitotic properties. EGF has known properties in supporting wound healing and in protecting esophagus from injuries. METHODS: The model described by Gehanno and its modification by Liu was used to create standard esophageal burns with 50% NaOH. The study was performed with 76 rats in 4 main groups (sham, CAPE, EGF, and control) and 2 subgroups in each for 5 and 28 days of observation. Efficacy of treatment was assessed in 28-day subgroups by measuring weight gain, contrast esophagograms on day 27, histologic evaluation by measuring stenosis index (wall thickness/lumen diameter), and collagen deposition, and biochemically by determining tissue hydroxy proline (OHP) content. RESULTS: In the end of the study, increase rates of mean body weights of the animals in the 28-day subgroups were as follows: sham, 30%; CAPE, 23%; EGF, 22%; and control, 14%. Although all the animals in subgroups significantly gained weight, the mean weight gain was significantly low in controls when compared with sham, CAPE, and EGF groups (P <.05). Contrast esophagograms on day 27 showed no stenosis in the sham, mild stenosis in CAPE and EGF, and severe stenosis with proximal dilatation in controls. Stenosis indices of the subgroups were as follows: sham, 0.29; CAPE, 0.41; EGF, 0.41; control, 0.84. Index was significantly higher in controls (P <.05). Collagen accumulation scores in the esophageal wall were as follows: Sham, 0.0; CAPE, 0.87; EGF, 0.30; control, 2.70. Scores also were significantly higher in controls (P <.05). Tissue (OHP) levels were as follows (mg/g dry tissue): Sham, 1.48; CAPE, 1.53; EGF, 1.90; control, 4.01. Production of OHP was significantly higher in controls. CONCLUSIONS: The results of the parameters in the study indicate that administration of CAPE and EGF has beneficial effects in the prevention of caustic esophageal strictures. Those effects of CAPE may occur through its antiinflammatory, immunomodulatory, and antioxidant properties, and EGF may occur through its induced proliferative properties on the esophagus.