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Aim: To design and synthesize a series of benzenesulfonamide derivatives, 4-[2-alkylthio-5(4)-(4-substitutedphenyl)imidazole-4(5)-yl]benzenesulfonamides (4a-4j), which are intended to act as cyclooxygenase-2 (COX-2) inhibitors with good COX-2 inhibitor activity, and which will exert anti-inflammatory activities in vivo., Methods: Benzenesulfonamide derivatives were designed and synthesized through multi-step chemical reactions. All the synthesized compounds were evaluated in an in vitro assay. The active compound 4a-4f was selected for further evaluation in a carrageenan-induced rat paw edema model., Results: Docking studies showed that compound 4 bind into the primary binding site of COX-2 with the sulfonamide SO2NH2 moiety interacting with the secondary pocket amino acid residues. In the in vitro assay, compound 4 inhibited COX-2 with an inhibition concentration IC(50) value of 1.23-8 nmol/L, compared to celecoxib with IC(50) value of 1.5 nmol/L. Compound 4b and 4c had good potency and selectivity in comparison to the celecoxib. In the in vivo model, compound 4a-4f exhibited a moderate potency to inhibit 50% carrageenan-induced paw edema with value of 1.58-4.3 mg/kg. In the latter experiment, compound 4c was the most active compound., Conclusion: The anti-inflammatory effects obtained for compound 4a-4j could be due to the presence of fluorine or hydrogen substituents in the para position of the phenyl ring of these compounds.

Purpose: To investigate the effects of gamma-rays on male NMRI mice, in the absence or presence of vitamin E, on abnormalities in chromosome number in 8-cell embryos generated after mating with non-irradiated female mice., Materials and Methods: The 8 - 11 week old male NMRI mice were irradiated whole body with 4 Gy of gamma-rays alone or in combination with 200 international units (IU)/kg vitamin E administered 1 h prior to irradiation. After 4 days, they were mated at weekly intervals with superovulated, non-irradiated female mice in successive 6 weekly periods. About 68 h post coitous (p.c.), 8-cell embryos were fixed on slides using standard methods in order to screen for abnormalities in chromosome number., Results: In control embryos, 8% of metaphases were aneuploid whereas in embryos generated from irradiated mice, the frequency of aneuploidy increased dramatically at all post irradiation sampling times (p < 0.001). Administration of vitamin E one hour before irradiation, significantly decreased chromosomal aberrations in all 6 groups (p < 0.05)., Conclusion: Data indicate that gamma-irradiation affects spermatogenesis and causes DNA alterations in sperm that may lead to chromosome abnormalities in subsequent embryos. Administration of vitamin E before irradiation effectively reduced the frequency of chromosomal abnormalities. The mechanism(s) by which vitamin E reduces genotoxic effects of radiation could be via radical scavenging or antioxidative effects.

Introduction: The goal of this study was to investigate the effect of transurethral resection of the prostate and open prostatectomy on the serum prostate-specific antigen (PSA) level in men with benign prostatic hyperplasia., Materials and Methods: Serum prostate-specific antigen levels were determined before and 6 months after operation in 86 patients with benign prostatic hyperplasia who had undergone transurethral resection of the prostate or open prostatectomy. We measured the prostate volume by means of transrectal ultrasonography and weighed the surgical specimen. Changes in serum PSA levels and their correlation with prostate volume and the resected prostate weight were evaluated., Results: Of 86 patients, 45 underwent transurethral resection of the prostate and 41 underwent open prostatectomy. Mean PSA levels were reduced by 67.4 % (range, 0.40 ng/mL to 7.60 ng/mL) in the patients who had undergone transurethral resection of the prostate and 80.7% (range, 1.00 ng/mL to 14.50 ng/mL) in the patients with open prostatectomy. Removal of 1g of prostate tissue reduced serum PSA levels by an average of 0.15 ng/mL in those who underwent transurethral resection of the prostate and 0.10 ng/mL in those treated with open prostatectomy (P = .018). Forty patients (88.9%) in the group who underwent transurethral resection of the prostate and 39 (95.1%) in the open prostatectomy group exhibited a postoperative PSA level of less than 2.00 ng/mL (P = .20)., Conclusion: A modified reference range seems necessary for the screening of prostate cancer via PSA level in men who have undergone prostatectomy for benign prostatic hyperplasia.

Retrospectively, 41 Iranian patients with Mediterranean abdominal lymphoma (MAL) were studied; 21 patients had received anthracycline-based protocols, and 20 patients had been treated with regimens lacking anthracyclines. The study groups were comparable with respect to several factors, including age, performance status, histology of lymphoma, stage of disease, and the average relative dose intensity of their protocols. Our first group had a complete remission (CR) rate of 62%, mean disease-free interval (DFI) of 16.3 months and a 71% overall survival at 30 months. The second group showed a CR rate of 40%, mean DFI of 11.2 months, and a 35% overall survival at 30 months. The differences were significant in survival (P = .012) and DFI (p < .001). The incidence of serious toxicities and complications was similar.

The effect of ethacrynic acid on the motor function of guinea pig ileum was studied in vitro. Ethacrynic acid produced dose-related (5-160 microgram/ml) contractions in this tissue. Morphine, tetrodotoxin and sodium-free medium prevented the contractions while hexamethonium, diphenhydramine, methysergide or indomethacin did not. Atropine in a high concentration (0.1 microgram/ml) only inhibited the contractions. Ethacrynic acid inhibited the contraction of ileum induced by electrical stimulation of intramural nerves. This was not prevented by pretreatment with reserpine. Repeated exposure to ethyacrynic acid developed tachyphylaxis in contractile response. Inhibition of electrically elicited contraction of guinea pig ileum also diminished with repeated treatment. Ethacrynic acid (80-160 micrograms/ml) inhibited the peristaltic reflex of the guinea pig ileum. It is concluded that the excitatory effect of ethacrynic acid is most probably mediated by the release of neurotransmitter, however, the mechanism of the inhibitory effect remains to be elucidated.

Adrenergic agonists produced a characteristic and definite decrease in the amplitude of spontaneous contractions and tone of the isolated rabbit jejunum. Effect of phenylephrine was abolished either by phenoxybenzamine or phentolamine. Relaxation induced by epinephrine and by norepinephrine was inhibited after combined treatment with phentolamine and propranolol. Phentolamine alone diminished the response to epinephrine and to norepinephrine, but the diminution for epinephrine was greater, indicating that epinephrine has a greater affinity for alpha- than for beta-receptors in the rabbit jejunum. Stimulation of the beta-receptors by isoproterenol was inhibited by propranolol, oxprenolol, sotalol and pindolol, but the block was incomplete. The activity of these four beta-blockers in preventing the inhibitory response to isoproterenol was as follows: inidolol greater than or equal to oxprenolol greater than propranolol greater than sotalol. This demonstrates the fact that not all beta-adrenergic blocking agents possess an identical pharmacologic spectrum of activity. Also it can be suggested that the beta-receptors of jejunum differ in specificity from those of other organs.