Diabetes alters aromatase enzyme levels in gonadal tissues of rats.

Diabetes mellitus (DM) is associated with increased risk of reproductive problems. Estrogens have important roles in reproductive processes in both genders. Aromatase catalyzes the conversion of androgens to estrogens and is expressed in a variety of tissues. Although it is known that insulin regulate the activity of aromatase, there are few data about the effects of diabetes on this enzyme. The aim of the present study was to investigate the effects of experimental diabetes on aromatase expression levels in ovary, testis, uterus, and vas deferens tissues of female and male rats. Rats were injected with streptozotocin to induce diabetes. At the end of 4 and 12 weeks, tissue homogenates were prepared and evaluated for aromatase proteins by western blot. Uterus and vas deferens smooth muscle responses were also evaluated. Aromatase expression levels in ovary were significantly decreased both in 4 and 12 weeks of diabetes. In testis, enzyme levels were not altered at 4 weeks, but significantly decreased at 12 weeks of diabetes. In uterus and vas deferens tissues, no significant differences were observed at aromatase immunoreactivity but uterus and vas deferens smooth muscle responses were altered. These results indicated for the first time that DM altered the expression levels of aromatase both in ovary and testis but did not affect enzyme levels in uterus and vas deferens tissues. Altered smooth muscle responses did not correlate with tissue aromatase levels. Altogether, these findings lead us to suggest that aromatase might be an important target molecule in sexual dysfunction seen in DM.

Synthesis of some new 1-acylthiosemicarbazides, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones and their anti-inflammatory activities.

Sixteen 1-(1-naphthyloxy)acetyl-4-substituted-3-thiosemicarbazides, 2-substituted amino-5-(1-naphthyloxy)methyl-1,3,4-oxadiazoles, 2-substitutedamino-5-(1-naphthyloxy) methyl-1,3,4-thiadiazoles and 3-(1-naphthyloxy)methyl-4-substituted-1,2,4-triazole-5-thiones were synthesized. The structures of the compounds have been elucidated by UV, IR, 1H-NMR, 13C-NMR spectra and elemental analysis. The anti-inflammatory activities of the compounds were evaluated by carregeenan induced hind paw edema and air-pouch inflammation tests in mice. In carrageenan induced hind paw edema test, compounds 1a, 1d, 3d, 4a showed equivalent or higher activity compared to naproxen and phenylbutazone. In the air-pouch inflammatory model, compounds 1a, 1b, 1d, 2c, 3c, 3d, 4a and 4d showed marked anti-inflammatory activity. The ED50 values of these compounds ranged between 24-36 mg/kg. Side effects of the compounds on gastrointestinal system and kidneys were examined and none of the compound showed significant side effects.

Studies on synthesis, chromatographic resolution, and antiinflammatory activities of some 2-thioxo-1,2,3,4-tetrahydropyrimidines and their condensed derivatives.

In this study, the synthesis of some new 2-thioxo-1,2,3,4-tetrahydropyrimidines and their condensed derivatives, thiazolo[3,2-a]pyrimidines, are described. The structures of the compounds were confirmed by 1R, 1H-NMR, 13C-NMR, and mass spectroscopy. The direct high-performance liquid chromatographic separation of the compounds on derivatized cellulose chiral stationary phases such as cellulose tris(3,5-dimethylphenylcarbamate) (OD), cellulose tris(4-methylphenylcarbamate) (OG), and cellulose tris(4-methylbenzoate) (OJ) was studied. All of the compounds were screened for their antiinflammatory activity and also investigated histopathologically. Compounds 3 and 1a were found to be the most promising antiinflammatory agents in this group.

Synthesis and anti-inflammatory activities of some thiazolo[3,2-a]pyrimidine derivatives.

Sixteen new 2-benzylidene-7-methyl-3-oxo-5-(substituted phenyl)-2, 3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl esters (1a-4d) have been synthesized by reacting 1,2,3,4-tetrahydropyrimidine-2-thiones (1-4) with chloroacetic acid and appropriate benzaldehydes in a single step. Their structures have been proved by IR, 1H NMR, mass spectra and elemental analysis. The compounds were tested for their anti-inflammatory activities. Test results revealed that compounds 1b, 1c, 4a and 4c exerted moderate anti-inflammatory activity at the 100 mg/kg dose level compared with indomethacin.

Synthesis and evaluation of anti-inflammatory activity of some thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and their Michael addition products.

Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones (4-10) were obtained in a one step synthesis by heating 3-aryl-5-mercapto-1,2,4-triazoles (3a-d) with chloroacetic acid and appropriate aromatic aldehyde in acetic acid and acetic anhydride in the presence of anhydrous NaOAc. Michael type addition of cyclic secondary amines (N-methylpiperazine, piperidine) to 4-10 gave 2-phenyl-6-(alpha-aminoarylmethyl)thiazolo[3,2-b]-1,2,4-triazole-5 -ols (4a-10b). The structures of the compounds were confirmed by spectral and elementary analysis. The compounds synthesized in previous and present studies were investigated for their anti-inflammatory activities.

Condensed heterocyclic compounds: synthesis and antiinflammatory activity of novel thiazolo[3,2-alpha] pyrimidines.

In this study, thirty six new 2-benzylidene-7-methyl-3-oxo-5- phenyl-2,3-dihydro-5H-thiazolo[3,2-alpha]pyrimidine-6-carboxylic acid methyl esters were synthesized and characterized by spectral, crystallographic, and elemental analysis. The antiinflammatory activity of the compounds was tested by the carrageenan hind paw edema test. It was found that compound 6a having a 2-meth-oxyphenyl group at position 5 and a benzylidene group at position 2 was the most potent compound in this series. All the compounds that were tested for ulcer activity gave positive results.

The effect of propofol and thiopentone on impairment by reactive oxygen species of endothelium-dependent relaxation in rat aortic rings.

The effect in isolated rat aorta of propofol, thiopentone, midazolam, etomidate and fentanyl on the impairment of endothelium-dependent relaxation by reactive oxygen species is reported. Aortic rings were exposed to reactive oxygen species by the electrolysis of the bathing physiological buffer, and endothelium-dependent relaxation in response to acetylcholine was inhibited. This inhibition was countered by incubation before electrolysis with propofol (2 x 10(-5) and 6 x 10(-5) M) or thiopentone (10(-5)-10(-4) M), but not with midazolam (3 x 10(-4) M), etomidate (3 x 10(-4) M) or fentanyl (3 x 10(-5) M). We suggest that the protective effect of propofol and thiopentone against the loss of endothelium-dependent relaxation caused by reactive oxygen species may be because of their antioxidant and free radical scavenging properties, which could be clinically relevant during surgical procedures in which ischaemia is unavoidable.