Effects of lipoic acid in an experimentally induced hypertensive and diabetic rat model.

In this study, experimental diabetes and nephrectomy have been applied separately and together in order to investigate the possible therapeutic effects of lipoic acid (LA) on hypertensive and diabetic rat kidneys. Wistar rats were divided into eight groups: control, diabetes mellitus (DM), 5/6 nephrectomy, DM + 5/6 nephrectomy, LA administration, DM + LA treated, 5/6 nephrectomy + LA treated, and DM + 5/6 nephrectomy + LA-treated groups, respectively. Renal damage was evaluated histomorphometrically, ultrastructurally, and biochemically. Our findings supported that diabetes and hypertension together increased the rate of renal injury, and LA had therapeutic effects on hypertensive and diabetic rat kidneys.

A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid.

The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

The only effects of recombinant follicle-stimulating hormone for ovulation induction in the pre-implantation period of rats.

OBJECTIVE: The aim of this study was to evaluate the changes in follicular development, serum hormonal levels, and endometrium in the pre-implantation period of rats by using recombinant FSH (rFSH) without human chorionic gonadotropin (hCG). METHODS: Thirty female rats were studied in six groups of five specimens. Two groups determined as controls (groups 1 and 2). Two groups received constant doses of rFSH (groups 3 and 4) and other two decreasing doses (groups 5 and 6). One of the paired groups was mated. Uterus, ovaries, and blood samples were taken from non-mated groups (groups 1, 3, and 5) at the proestrus period and from mated groups (groups 2, 4, and 6) in the pre-implantation period. RESULTS: In non-mated groups antral follicles and corpus luteum periodicum and in mated groups antral follicles, corpus luteum periodicum, and corpus luteum graviditatis were increased in rFSH groups, especially in decreasing dose groups. Estradiol (E2) levels were increased and progesterone (P)/E2 ratio was significantly decreased in decreasing dose groups. Endometrium surface epithelium was columnar, irregular, and folded in rFSH groups. Endometrium glandular epithelium was cuboidal in all groups. In decreasing dose groups endometrial stroma was smooth and fibroblastic. Mitotic indices of endometrium surface, glandular epithelium, and stroma were significantly decreased in rFSH groups. Primary follicles and P levels showed no change. CONCLUSION: It seems likely that decreasing doses of rFSH might be used in order to improve follicular development, although it has negative effects with E2 on endometrium in the pre-implantation period of rats.

In vitro release--in vivo microbiological and toxicological studies on ketoconazole lipid granules.

In some multidrug therapy programs, ketoconazole (KTZ) may be administered with some antacids that could modify its dissolution rate and reduce its absorption, thus leading to therapeutic failures. The primary aim of this study was to evaluate the influence of Compritol HD5 ATO and Compritol 888 ATO on this interaction in comparison with commercial KTZ tablets. The second aim was to prepare lipid granules of KTZ that could be an alternative to the commercial formulation. Therefore, six KTZ sustained-release granules were prepared with different lipid concentrations, because they were found to be more suitable than tablets that are dissolved only in gastric medium. The results confirmed that the dissolution rate of KTZ granules was significantly reduced in the presence of antacids. The ideal formulation was selected as granules including 5% of Compritol lipids in relation to the suitability of the target profile. Therapeutic effects of orally administered, ideal KTZ granule formulations, and commercial tablets were evaluated in vivo by the experimental model of murine vulvo-vaginal candidiasis (VVC) with and without antacids. It was found that formulations were very effective on VVC, and the therapeutic effect decreased significantly in the presence of antacids. Histopathological studies were carried out for vagina, stomach, and liver tissues and hepatoxicity was also examined. The levels of reduced glutathione (GSH) were measured to assess the oxidative stress induced by KTZ and function of the liver. It was observed that orally administered formulations of KTZ were successful in treating candidiasis in mice without irritancy in stomach. However, liver tissues were damaged. The decreased GSH levels indicated toxicity in our study. This study suggested that in vitro release and in vivo microbiological-toxicological properties of KTZ were affected by antacids and drug-excipient interactions. Lipid granules of KTZ prepared with Compritol 888 ATO could be proposed as a new KTZ solid dosage form with optimum dissolution and therapeutic characteristics.

Bioadhesive controlled release systems of ornidazole for vaginal delivery.

Our objective was to develop a bioadhesive vaginal tablet formulation of ornidazole by using different polymer mixtures, to evaluate the bioadhesive tablet properties, and to investigate the irritation potential of the formulations to the rat vaginal tissue. Vaginal tablets of ornidazole were directly compressed with bioadhesive and swellable polymer mixtures as release-controlled agents. Carbopol 934 (Cp), pectin (Pc), hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (Na CMC), and guar gum (GG) were used in different ratios. Bioadhesive properties, swelling capacity, release studies, and histological studies of the formulations were carried out. The bioadhesive strength between bovine vagina and surface of the tablets was determined by tensile experiments, and it was found to be dependent on Cp content. The release mechanism was described and found to be non-Fickian for all formulations. Dissolution data were evaluated statistically. No histological damage was found except one formulation containing high amount of guar gum.