THE THERAPEUTIC EFFECT OF ALLOPURINOL IN FATTY LIVER DISEASE IN RATS.

Background: Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD). Aim: We therefore aimed at evaluating the influence of allopurinol on the course of NAFLD in rats. Study Design: We divided 21 mature albino Sprague Dawley rats into three groups: controls (n = 7, normal diet for 12 weeks); NAFLD rat models (by feeding water containing 30% fructose for first 8 weeks) treated with allopurinol subsequently for the next 4 weeks (n = 7); and similar case treated with placebo (saline) subsequently for the next 4 weeks (n = 7). Methods: We compared the histopathological scores, IL-1 and IL-2 immunoexpression levels across the groups. Liver histopathological score was determined by observing the steatosis (the percentage of liver cells containing fat): <25% = 1+, 25% - 50% = 2+, 51% - 75% = 3+, >75% = 4+; inflammation and necrosis: 1 focus per low-power field = 1+; and 2 or more foci = 2+. The number of liver IL-1 and IL-2 positive cells was measured by systematically scoring at least 100 hepatocyte cells per field in 10 fields of tissue sections by a magnification of 100. Results: Xanthine oxidase (XO) activity and lipid peroxidation was significantly different in the allopurinol group compared to the saline group (XO; 0.098 ± 0.006 mU/mg vs. 0.162 ± 0.008 mU/mg, p = 0.01, 0.116 ± 0.040 nmol malondialdehyde/mg versus 0.246 ± 0.040 nmol malondialdehyde /mg, p = 0.01). The allopurinol group had lower histopathological scores, IL-1 and IL-2 immunoexpression levels in the liver compared to the saline group (2.13 ± 0.35 against 5.45 ± 0.24, p = 0.003, IL-1; 5.76 ± 0.43 against 12.85 ± 3.26, p = 0.023, IL-2; 8.55 ± 1.14 against 56.23 ± 7.12, p = 0.002). Conclusions: Allopurinol has a therapeutic role against the progression of NAFLD of the rats.

Effects of sunitinib on immunoreactivity of vimentin, E-cadherin and S100 in kidneys of streptozotocin induced diabetic mice.

Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We investigated the possible effects of sunitinib on the kidney of streptozotocin (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1 was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment. Kidneys were removed after 8 weeks. The immunoreactivities of vimentin, E-cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100 was located in both the glomeruli and tubules of the kidney. We found that the number of vimentin and E-cadherin positive glomeruli and tubules were increased after sunitinib treatment compared to saline treated diabetic mice. The number of vimentin labeled tubules was decreased in the sunitinib treated group compared to diabetic + saline groups. Differences in the number of S100 positive tubules and glomeruli between groups 3 and 4 were not statistically significant. The effect of sunitinib on experimental diabetic mice appears to be related to levels of vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and sunitinib may protect against renal damage from DM.

The long pentraxin-3 is a useful marker for diagnosis of ovarian torsion: An experimental rat model.

Pentraxin-3 (PTX3) plays an important role in the primary inflammatory response. We aim to evaluate PTX3 as a diagnostic marker of ovarian torsion in an experimental rat model. In this study, 16 female Sprague Dawley albino mature rats were randomly allocated to Group 1 (control, sham operated) and Group 2 (experimental ovarian torsion model). A torsion model was set up using atraumatic vascular clips just above and below the right ovary for a 3-h ischaemia. Blood samples were collected before and three hours after ovarian torsion. Three hours after ovarian torsion, right ovary was surgically removed for histopathological examination in both groups. There was no significant difference in preoperative PTX3 level in both groups (1.05 ± 0.20 ng/mL vs 1.09 ± 0.28 ng/mL, p > 0.05). Three hours after the operation, mean plasma level of PTX3 was significantly higher in ovarian torsion group than the control group (2.13 ± 0.49 ng/mL vs 1.07 ± 0.22 ng/mL, p = 0.001). Also, the mean total histopathological score was significantly increased in the torsion group. PTX3 can be used in clinical practice as a useful marker for early diagnosis of ovarian torsion.

Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat model.

In this study, possible thyrotoxicosis-related histological changes in testicular tissues of rats with experimentally induced thyrotoxicosis model were evaluated on cellular connections and stem cell markers. Two experimental groups, thyrotoxicosis and control, each consisting of eight animals were used. Rats in the thyrotoxicosis group were injected intraperitoneally with 3,3',5-triiodo-l-thyronine (50 µg/100 g body weight/day) for 10 days. At the end of the study, animals in both groups were anesthetized, and blood samples were collected for biochemical analyses. Their testes were dissected out and histological procedure was conducted to perform further histochemical, immunohistochemical analyses and tissue expression analysis by real-time polymerase chain reaction. Expression of the stem cell markers such as c-kit and Thy-1 significantly decreased in the testes of the thyrotoxicosis group compared with the control group; however, Nanog expression was not detected in any of the groups. Similarly, connexin 43 and occludin expressions were also found to be significantly lower in the thyrotoxicosis group. These results on cellular connections are supported with the tissue expression analysis. Our findings are indicative of supporting microenvironmental tissue decay rather than parenchyma damage, which has been actually ignored in the literature. In conclusion, experimental thyrotoxicosis model may have adverse effects on the cell junctional complexes, cell-cell interactions, and pluripotency capacity.

Nephro-protective effect of granulocyte colony-stimulating factor in streptozotocin induced diabetic rats.

Diabetic nephropathy is one of the most serious complications of diabetes and the major cause of end-stage renal failure. Consequences of diabetic nephropathy include increased kidney size and glomerular volume, thickening of basement membranes and progressive accumulation of extracellular matrix. Reports in the literature support an association between increased secretion of inflammatory molecules, such as cytokines, growth factors and metalloproteinases, and development of diabetic nephropathy. We investigated the potential of granulocyte colony- stimulating factor (G-CSF) as a therapeutic candidate for preventing diabetic nephropathy. We used 21 8-week-old male rats; 14 were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. The rats were divided into three groups of seven: group 1, control; group 2, diabetic; group 3, diabetic plus G-CSF treatment. After 4 weeks, immunoexpressions of transforming growth factor ß1 (TGF-ß1), Akt and CD34 levels were measured in the kidney tissue. Blood glucose, urine protein and the glomerular area also were measured for each group. We found that G-CSF treatment decreased TGF-ß1 immunoexpression, urine protein and glomerular area in kidneys of diabetic rats, and increased CD 34 and Akt immunoexpression in kidneys of diabetic rats. The effects of G-CSF were independent of blood glucose levels. G-CSF may be a useful therapeutic agent for preventing diabetic nephropathy.

Comparison of the use of conventional, hydrophilic and gel-lubricated catheters with regard to urethral micro trauma, urinary system infection, and patient satisfaction in patients with spinal cord injury: a randomized controlled study.

BACKGROUND: Management of the lower urinary tract is crucially important in patients with spinal cord injuries in order to prevent damage to the upper urinary tract and to preserve renal function. AIM: This study was designed to compare the use of standard polyvinyl chloride (PVC), hydrophilic-coated, and gel-lubricated non-hydrophilic catheters with regard to urethral micro trauma, urinary system infection, and patient satisfaction in patients with spinal cord injuries. Study design. Randomized, controlled study. SETTING: University hospital, inpatient clinic. POPULATION: Twenty-five male patients with spinal cord injuries. METHODS: The patients were asked to use 3 different types of catheters. The selection of catheter order was determined randomly, and all 3 catheters were used for 6 weeks consecutively. All patients were assessed at the beginning of treatment and at weeks 6, 12, and 18, in terms of urethral cytology, urinalysis, urine culture, and patient satisfaction (Visual Analog Scale, VAS). RESULTS: Ten patients completed the study. Regarding the urethral trauma evaluation, urethral cell counts were reduced with gel-lubricated non-hydrophilic catheter use (P<0.05), increased with PVC catheter use (P<0.05), and showed no change with hydrophilic-coated catheter use (P>0.05). The number of leucocytes in the urine sediment was significantly reduced after gel-lubricated catheter use (P<0.05). There was significantly less microhematuria with hydrophilic-coated and gel-lubricated non-hydrophilic catheter use compared with PVC catheter use (P<0.05). There were no significant differences among catheters with respect to symptomatic urinary tract infection and microbiological analysis of urine culture (P>0.05). The mean VAS was better with the gel-lubricated non-hydrophilic catheter than with the other two catheter types (P<0.05). CONCLUSION: The hydrophilic-coated catheter and especially the gel-lubricated non-hydrophilic catheter reduce trauma to the urethral surfaces and enable easy and comfortable catheterization. CLINICAL REHABILITATION IMPACT: The hydrophilic and gel-lubricated catheters represent an attractive alternative to standard PVC catheters for urological rehabilitation in patients with spinal cord injuries.

Postpubertal testicular/epididymal epithelial thickness alterations in unilateral epididymal/vasal obstruction of prepubertal rats.

This study was conducted to evaluate postpubertal testicular and epididymal epithelial changes induced by unilateral epididymal and vasal obstruction in rats by measuring epithelium thickness of seminiferous tubuli (MSTet) and epithelium thickness of ductus epididymis (MDEet). Rats were randomly divided into 3 groups: group I underwent unilateral epididymal ligation; group II underwent unilateral vasal ligation and group III received sham operations. MDEet on the ipsilateral side of the epididymal ligation group significantly decreased compared to the contralateral side and sham group. For the contralateral side of the ligated vas, MDEet significantly decreased compared to the ipsilateral side and sham group. MSTet was less on the side of the operation than the contra lateral side and the sham group after both surgical procedures. The obstruction point of the male genital tract affect sperm parameters for clinical extraction or aspiration procedures.

Evaluation of the relationship between inducible nitric oxide synthase (iNOS) activity and effects of melatonin in experimental osteoporosis in the rat.

Inducible nitric oxide synthase (iNOS) plays a critical role in the pathogenesis of osteoporosis. iNOS generates nitric oxide (NO), a free radical contributing to the imbalance between bone formation and resorption caused by estrogen depletion. Melatonin is the major product of the pineal gland which is known to diminish iNOS expression and NO production significantly. The aim of this study was to determine the distribution of iNOS and the amount of apoptotic cells after melatonin treatment in ovariectomized rats. Since previous studies have shown that constitution of bone formation is primarily sustained in nucleus pulposus and epiphyseal cartilage, experiments were carried out on nucleus pulposus and epiphyseal cartilage; additional quantitation of osteoblasts and osteoclasts were evaluated on vertebral area as well. Vertebral sections of ovariectomized rats were obtained from formalin-fixed and parafin-embedded blocks. iNOS expression and quantitation of apoptotic cells in nucleus pulposus and epiphyseal cartilage were evaluated using indirect immunoperoxidase and TUNEL techniques, respectively. The number of osteoclasts and osteoblasts in trabecular bone was determined using histomorphometry. Ovariectomy increased iNOS expression and the number of apoptotic cells in nucleus pulposus and epiphyseal cartilage, whereas a 4-week treatment with melatonin (10 mg/kg/day) resulted in the reduction of both effects. These data indicate that there is strong influence of melatonin application on expression of iNOS, apoptosis, osteoclast and osteoblast numbers after ovariectomy. In conclusion, melatonin besides its usual use as an antiaging hormone, may also be an effective hormone in treatment of bone changes in estrogen deficiency states.