Zinc supplementation prolongs the latency of hyperthermia-induced febrile seizures in rats.

Some studies have shown a relationship between febrile seizures and zinc levels. The lowest dose zinc supplementation in pentylenetetrazole seizure model has a protective effect. But, zinc pretreatment has no effect in maximal electroshock model. However, it is unclear how zinc supplementation affects hyperthermia-induced febrile seizures. The aim of the present study was to investigate the effects of zinc supplementation on febrile seizures in male Sprague-Dawley rats. The rats were randomly assigned to four groups. Zinc supplementation was commenced 5 days prior to febrile seizure induction by placing the animals in a water bath at 45°C. We measured the rectal temperature and determined the febrile seizure latency, duration, and stage. In the zinc-supplemented group, both the seizure latency and the rectal temperature triggering seizure initiation were significantly higher than in the other groups. We suggest that zinc supplementation can positively modulate febrile seizure pathogenesis in rats.

Angiogenesis inhibition impairs testicular morphology in experimental left varicocele rat model.

INTRODUCTION: It has been reported that varicocele might promote angiogenesis. However, it is not clearly identified how angiogenesis affect testicular morphology or spermatogenic activity. The objective of the study is to investigate the effect of spironolactone, as an angiogenesis inhibitor, on the ipsilateral testis morphology in left varicocele-induced rats. MATERIALS AND METHODS: Twenty four adult (12-14 mo), male Wistar albino rats were randomly assigned to four groups (n=6, for each): 1. Control group, 2. Sham-operated group, 3. Experimental left varicocele group and, 4. Spironolactone (20mg/kg/day)-treated experimental left varicocele group. Histopathological findings in rat testis were investigated. RESULTS: Microvessel density increased in varicocele group and spironolactone inhibited angiogenesis neither by antimineralocorticoid, nor by antiandrogenic effect. However, spermatogenesis impaired in spironolactone treated varicocele group. CONCLUSION: Angiogenesis seems to be a protective process in varicocele. Spironolactone treatment, probably by inhibiting angiogenesis, impairs testicular morphology.

The effect of long-term oral tadalafil treatment on corpus cavernosum function in an experimental spinal cord transection rat model.

OBJECTIVES: The aim of this study was to investigate the pharmacological effects of long-term oral tadalafil treatment on the corpus cavernosum function in rats subjected to experimental spinal cord transection (SCT). METHODS: Thirty young adult, male Sprague­Dawley rats were randomly divided into five groups (n» 6, each), as follows: (1) Control,(2) Control surgery (Sham), (3) Tadalafil (Td), (4) Experimental SCT, and (5) SCT + Tadalafil (SCT + Td). SCT rat model: after removal of T8-T9 spinal processes and laminates, a full-thickness scalpel incision was made in the spinal cord. SCT + Td rat model:rats subjected to SCT were given tadalafil (5mg kg(-1), p.o.) for 4 weeks. Next, the penile cavernous tissues obtained by en blocexcision were trimmed free of the surrounding tissue to isolate cavernosal smooth muscle strips, which were then transferred into the isolated organ baths to investigate isometric tension changes in response to various bioactive agents and electrical field stimulation (EFS). RESULTS: The relaxation response to acetylcholine at 0.01 mM concentration was significantly less in the SCT group compared with other groups. EFS-induced relaxation in the basal and precontracted cavernous tissue preparations was greater in the SCT + Td group than in the SCT group. CONCLUSION: This study demonstrated that long-term tadalafil administration preserves relaxation responses probably by affecting through the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in SCT-applied rats. This treatment strategy might preserve the erectile process and prevent the SCT-induced permanent damage in the cavernosal tissue.

The association between intron 4 VNTR, E298A and IVF 23+10 G/T polymorphisms of ecNOS gene and sildenafil responsiveness in patients with erectile dysfunction.

The objective of the study was to determine the association between intron 4 variable number of tandem repeats (VNTR), E298A and IVF 23+10 G/T polymorphisms of ec-NOS gene and sildenafil responsiveness in patients with erectile dysfunction (ED). Ninety-six patients who were evaluated for ED between November 2003 and June 2004 and 167 healthy individuals representing the normal population as controls were included in the present study. The patients were evaluated by medical history, five-item version of International Index of Erectile Function, serum glucose, testosterone levels and lipid profiles. Sixty-seven patients received four consecutive doses of sildenafil from 25 to 100 mg according to the response. The ec-NOS gene intron 4 VNTR, E298A and IVF 23+10 G/T polymorphisms were evaluated in the isolated DNA blood samples obtained from the patient group with ED (n=96), from the group received sildenafil (n=67) and from the healthy group (n=167). Genotype distributions of ec-NOS gene intron 4, E298A and IVF 23+10 G/T polymorphisms in the patient group were similar to those in the healthy group. The frequency of the ec-NOS gene intron 4 genotype were found as bb=41.7%, ab=50% and aa=8.3% in the sildenafil responders and bb=93.5% and ba=6.5% in the sildenafil non-responders. This finding was statistically significant. Statistical analysis of ec-NOS gene E298A and IVF 23+10 G/T polymorphisms did not reveal any significant difference between sildenafil responders and non-responders. These findings may indicate that 'a' allele of ec-NOS gene intron 4 VNTR polymorphism associates with a better sildenafil response.

Relaxation induced by serotonin and sumatriptan in isolated guinea pig gallbladder strips.

The effects of 5-hydroxytryptamine (5-HT) and sumatriptan were investigated on isolated guinea pig gallbladder strips. While 0.1 microM-50 mM of 5-HT exhibited contractile and/or relaxant effects in quiescent preparations, the same concentrations of sumatriptan did not. On the other hand, carbachol-precontracted tissues were relaxed by the same amounts of 5-HT and sumatriptan in a concentration-dependent manner. The relaxant responses to 5-HT were not antagonized or changed by tetrodotoxin, indomethacin, capsaicin, NG-nitro-L-arginine (L-NOARG), GR55562 [(+/-)-propranolol, 3-[3-(N,N-dimethylamino)propyl 1-4-hydroxy-N-[4-(pyridin-4-yl)phenyl]benzamide , S(-)-propranolol, methysergide, ketanserin. tropisetron, GR 113808 ([1-[2-(methylsulphonylamino)ethyl -4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate maleate salt). pargyline, and fluvoxamine. The relaxant responses to sumatriptan were antagonized by GR55562 but not by S(-)-propranolol. These results suggest that 5-HT and sumatriptan cause relaxation in carbachol-precontracted isolated guinea pig gallbladder strips by yet undefined mechanisms.

Does serotonin relax the rat anococcygeus muscle via 5-HT7 receptors?

The mechanisms of serotonin (5-HT)-induced contraction and relaxation were studied in the rat anococcygeus muscle. In the presence of prazosin (1 nM) and ketanserin (10 nM), concentration/response curves to 5-HT were shifted to the right and the maximum effects were not affected (pKB values 9.09+/-0.29 and 8.66+/-0.06 for prazosin and ketanserin, respectively). On contrary, guanethidine (10 microM) antagonised the 5-HT-induced contractions non-competitively. In the presence of guanethidine, prazosin or ketanserin further inhibited the responses to 5-HT at lower concentrations. The serotonergic receptor agonists 5-carboxamidotrypamine, metoclopramide and sumatriptan did not produce any effect in tissues under baseline conditions. 5-HT caused concentration-dependent relaxation in phenylephrine (1 microM) -precontracted preparations in the presence of guanethidine (10 microM). Tetrodotoxin (1 microM), N(G)-nitro-L-arginine (100 microM) and capsaicin (1 microM) were ineffective in antagonising the relaxation induced by 5-HT. The serotonergic receptor antagonists: ketanserin (0.1 microM), ICS 205930 (10 microM), GR 113808 (10 microM), GR 55562 (10 microM), methiothepin (10 nM), mesulergine (10 microM), ritanserin (0.1 microM) and spiperon (0.1 microM) did not antagonise 5-HT-induced relaxation. On the other hand, clozapine (0.01-0.1 microM) and metergoline (0.1-1 microM) attenuated the relaxation induced by 5-HT. These results demonstrate that 5-HT contracts rat anococcygeus muscle directly by an action on alpha1-adrenergic receptors and indirectly by releasing noradrenaline from adrenergic nerve endings. None of the 5-HT receptors plays a role in the 5-HT-induced contractions. Moreover 5-HT induces concentration-dependent relaxation in the precontracted preparations which apparently are not mediated through known 5-HT receptor types.

The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats.

BACKGROUND: Taurine, which is the major intracellular free beta-amino acid, is known to be an endogenous antioxidant and a membrane-stabilizing agent. In this study, we wished to know whether taurine altered the concentration of gentamicin in kidney tissue and could protect against gentamicin-induced acute proximal tubular injury. METHODS: Wistar albino rats of both sexes were assigned to three groups, which all received one of the following daily intraperitoneal injections for 8 days: (i) 0.9% sodium chloride (NaCl) alone at the same volume as gentamicin treated rats (group C; n=8); (ii) 100 mg/kg/day gentamicin alone (group G; n=8, four male, four female); or (iii) 100 mg/kg/day gentamicin plus 7.5 ml/kg/day taurine (group G+T; n=9, five male, four female). Urine was collected for 24 h for the determination of urine volume and creatinine. Intracardiac blood was collected for blood urea nitrogen (BUN) and serum creatinine determination. The kidneys were removed, weighed, and the left kidneys were subjected to biochemical analysis for the determination of thiobarbituric acid-reactive substance (TBARS) and lactate levels, and glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities. The right kidneys were divided vertically in half. The upper halves were used for histopathological examination, by light and electron microscopy. The lower halves were used to detect the gentamicin concentration within the kidney tissue, by high-performance liquid chromatography (HPLC). Changes in body weight and normalized kidney weight were recorded. RESULTS: Taurine treatment reduced gentamicin-induced increases in serum creatinine, 24 h urine volume, BUN and tissue lactate and TBARS levels (0.57+/-0.02 vs 1.06+/-0.08 mg/dl, P<0.001; 9.00+/-1.46 vs 20.9+/-2.73 ml, P<0.001; 25.3+/-1.87 vs 54.1+/-6.99 mg/dl, P<0. 001; 2.56+/-0.10 vs 3.44+/-0.08 micromol/g wet tissue, P<0.001; and 66.4+/-3.41 vs 79.5+/-5.07 nmol/g wet tissue, P>0.05, respectively). Taurine reduced the accumulation of gentamicin within the kidney tissue (233+/-29 vs 494+/-93 microg/g wet tissue, P<0.05). Taurine treatment also prevented body weight loss due to gentamicin administration (17.8+/-1.64 vs -10.0+/-7.08 g, P<0.01) and normalized reduced Gpx and SOD activities (3.46+/-0.16 vs 2.37+/-0. 15 U/g wet tissue, P<0.01; and 15577+/-377 vs 12662+/-577 U/g wet tissue, P<0.01, respectively). Light microscopic examination of the renal tissues from gentamicin-treated rats revealed severe histopathological changes, whereas specimens obtained from taurine-treated rats revealed only mild changes. This finding was supported by electron microscopic examination. CONCLUSIONS: Our observations suggest that taurine treatment attenuates the accumulation of gentamicin within kidney tissue and counteracts the deleterious effect of gentamicin on renal tubular function. They may have potentially important clinical implications.

Cyclosporine A preparations and their vehicles induce contraction of the guinea pig gallbladder in vitro: the role of cyclooxygenase metabolites.

The aim of this study was to establish whether prostanoids play a role in the contraction induced by cyclosporine A (CyA) preparations in the guinea pig isolated gallbladder strips. It was also aimed to study the effects of the preparations and their solvents on the acetylcholine-evoked rhythmic contractions of the guinea pig isolated sphincter of Oddi (SO). Isometric contractions were recorded. CyA parenteral and oral preparations and their vehicles, Cremophor-EL and Labrafil caused concentration-dependent and sustained contractions (74.2 +/- 6.2, 58.4 +/- 6.3, 88.9 +/- 4.9 and 47.5 +/- 6.2% of maximum KCl contraction, respectively) of gallbladder strips, but not of SO. Quinacrine, indometacin and ridogrel inhibited the contraction induced by CyA preparations and their vehicles in gallbladder strips (for CyA parenteral preparation, 34.7 +/- 6.7, 1.4 +/- 0.9, 19.0 +/- 6.4% of maximum KCl contraction, respectively). The drug and its vehicles changed neither the initial contraction nor the amplitude and frequency of the phasic contractions induced by acetylcholine in SO preparations. The results indicate that the drug is able to contract the gallbladder strips and the vehicles contribute to the contracting effect of CyA. Prostanoids may be responsible for the CyA-induced contraction of the gallbladder.

The possible role of endothelin(s) in cyclosporine A preparations--induced contraction of guinea pig isolated gallbladder strips.

1. In guinea-pig isolated gallbladder strips, both cyclosporine A (CyA) preparations and their vehicles (10(-7) M-4 x 10(-5) M) caused stable, long-lasting and concentration-dependent contractions. 2. Some gallbladder strips showed spontaneous rhythmic activity. CyA and its vehicles increased this rhythmic activity. Furthermore, they elicited rhythmic activity in the strips that did not show any spontaneous rhythmic activity. 3. Bosentan (10(-5) M) and verapamil (10(-5) M) partly but significantly inhibited the contractions due to CyA preparations and their vehicles except the effect of verapamil on Labrafil-induced contraction. 4. Neither parenteral and oral solutions of CyA nor their vehicles caused any contractile response on the sphincter of Oddi preparations.