Osman Sulak

Lithium-induced renal toxicity in rats: Protection by a novel antioxidant caffeic acid phenethyl ester

Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li2CO3 solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 μM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-β-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.

Androgens and the Development of the Vagina

Abstract Today it is generally held that the vagina develops from sinovaginal bulbs and that the lower third of the definitive vagina is derived from the urogenital sinus. Here we show that the entire vagina arises by downward growth of Wolffian and Müllerian ducts, that the sinovaginal bulbs are in fact the caudal ends of the Wolffian ducts, and that vaginal development is under negative control of androgens. We designed a genetic experiment in which the androgen receptor defect in the Tfm mouse was used to examine the effects of androgens. Vaginal development was studied by 3D reconstruction in androgen-treated female embryos and in complete androgen-insensitive littermates. In androgen-treated females, descent of the genital ducts was inhibited, and a vagina formed in androgen-insensitive Tfm embryos as it does in normal females. By immmunohistochemical localization of the androgen receptor in normal mouse embryos, we demonstrated that the androgen receptor was expressed in Wolffian duct and urogenital sinus-derived structures, and was entirely absent in the Müllerian duct derivatives. We conclude that the Wolffian ducts are instrumental in conveying the negative control by androgens on vaginal development. The results are discussed under evolutionary aspects at the transition from marsupial to eutherian mammals.

The effects of methidathion on liver: role of vitamins E and C

Methidathion (MD) is one of the most widely used organophosphate insecticides (OPIs) for public health programmes and agricultural purposes. However it causes side effects such as liver disorders. We examined the ameliorating effects of a combination of vitamins E and C against MD induced liver toxicity in rats. MD was given orally with a single dose of 8 mg/kg body weight at 0 h. Vitamin E and vitamin C were injected 30 min after the treatment of MD at doses of 150 mg/kg body weight i.m. and 200 mg/kg body weight i.p., respectively. Liver tissue samples were taken 24 h after the MD administration. In MD treated group, some histopathological changes like infiltration with mono-nuclear cells at parenchymal tissue, sinusoidal dilatation, focal necrotic areas, granular degeneration and picnotic nuclei in the hepatocytes were observed. The severity of these lesions was reduced by administration of vitamins. It is concluded that MD caused liver damage and single-dose treatment with a combination therapy of vitamins E and C after the administration of MD can reduce the toxic effects of MD on liver tissue of rats.

Lithium-induced lung toxicity in rats: the effect of caffeic acid phenethyl ester (CAPE)

Aims: We aimed to evaluate the effects of caffeic acid phenethyl ester (CAPE) on lithium (Li)‐induced lung toxicity. Methods: Twenty‐two adult male Wistar albino rats weighing between 280 and 300 g were used. The rats were randomly divided into three groups: control, Li and Li+CAPE groups. Li and CAPE were co‐administered intraperitoneally twice daily for 4 weeks. Control rats were given 0.9% NaCl during the same period. All the rats were allowed to feed ad libitum until midnight after they had received the proposed treatment. Results: In the Li group, peribronchial and intraparenchymal lymphocyte and macrophage infiltration were observed. Atypical type II pneumocytes, alveolar destruction and emphysematous changes were also detected. Lymphocyte and macrophage infiltration was significantly decreased in the Li+CAPE group compared with the Li group. Alveolar destruction, emphysematous changes and intraparenchymal mononuclear cell infiltration were also recovered to a level close to the control group. Malondialdehyde (MDA) levels were increased in the Li group compared with the control group. CAPE administration decreased the MDA levels in the Li+CAPE group. Conclusions: CAPE was found to associate with histopathological changes recovery in the lungs and oxidative stress due to Li treatment.

Growing of caecum and vermiform appendix during the fetal period.

Objective: The aim of this study is to investigate the growing of the caecum and the vermiform appendix during the fetal period in human fetuses and the relation between growing and shape of the caecum and the localization of the vermiform appendix. Methods: 40 male and 40 female externally normal-looking fetuses were studied between 10 and 40 weeks of gestation and were subdivided into fetuses of the 1st, 2nd, and 3rd trimesters and full-term fetuses. The parameters of interest included covering of the caecum with peritoneum, shape of the caecum (long tube, symmetric saccule, asymmetric saccule, extremely large right side – atypical), axial length and width of the caecum localization of the vermiform appendix, length of vermiform appendix and length of the meso-appendix. Results: There was a difference in covering of the caecum with peritoneum between males and females; the caecum was predominantly tube shaped during the fetal period, with the asymmetric saccule towards the end of the fetal period; the localization of the vermiform appendix was subcaecal (39%) during the fetal period and postileal (34%) in female fetuses and subcaecal (48%) in male fetuses – the localization of the vermiform appendix changed according to the caecum shape during the fetal period; we found significant differences in the measurements of vermiform appendix, meso-appendix, and caecum among 1st-, 2nd-, and 3rd-trimester fetuses and full-term fetuses. Conclusions: There was an increase in the measurements for vermiform appendix, meso-appendix, and caecum with increasing gestational age; the localization of the vermiform appendix depended on the shape of the caecum, was different from that of adults and different between sexes, and there was also a significant difference in covering of the caecum with peritoneum between both sexes.

The development of jejunum and ileum during the fetal period

OBJECTIVE In our study, the morphologic structures of the jejunum and ileum sections of small intestine were investigated in human fetuses during the fetal period. MATERIALS AND METHODS The study was realised on 131 human fetuses (male: 69; female: 62) with ages between 10 and 40 weeks, which have got no external pathology and anomalies. The external sizes of fetuses were measured, and then the structures in the abdominal cavity were determined by the abdominal dissection. The localization of jejunum and ileum, duodenojejunal flexure and ileal orifice points, the measurements of macroscopic diameters, types of the mass of jejunum and ileum and the localization according to the abdominal regions of the mass of jejunum and ileum were determined. Also, the samples of the jejunum and ileum were examined both macroscopically and microscopically. The thickness of tunica serosa, tunica muscularis and tunica mucosa was determined under the light microscope. RESULTS According to the sexes, gestational ages and groups, the averages and the standard deviations of the all parameters were determined. The correlations between the parameters were determined. The percentage of parameters was compared according to sex and among groups. No differences were found in parameters between sexes (p<0.05). The macroscopic parameters were increased according to the gestational age. The thickness of tunica serosa did not change according to the gestational age. CONCLUSION It is thought that the data we have will help the evaluation of jejunum and ileum in intrauterine period; we also believe that the data in our study may help in the diagnosis and treatment of anomalies and pathologies in fetal period that belongs to jejunum and ileum.

Estimating the testis volume during the fetal period using the stereological method

The purpose of the present study is to assess the development of seminiferous tubule volume, stromal volume and total testis volume in the human fetal testis during the fetal period using the stereological method. In this study, we examined 90 testes of 45 human fetuses with no congenital anomalies and pathologies. They were aged between 12 and 40 weeks and localized between the scrotum and the abdomen. Total testis volume, seminiferous tubule volume, and stromal volume were estimated using Cavalier Principles. The weight and density of the testes were calculated as well. During the fetal period, the testes were firstly found on the right in the 27th week and on the left in the 32nd week in the scrotum. At the end of the third trimester and full term, the migration of the testes into scrotum was completed (98%). When the second trimester, third trimester and full term fetuses were compared, the differences between testis volumes were significant (p<0.001). The density of the testes between the groups was not significant (p>0.05). Testis parameters during the fetal period were not significantly (p>0.05) different between the right and left testes localization. The correlation between the fetal testis parameters was significant (p<0.001). Towards the end of the fetal period, the rate of seminiferous tubule volume to stromal volume changed in the favor of seminiferous tubule volume. It was observed that interstitial tissue became more regular and had a good organized structure with the progress of gestational age. In the third trimester, the lumen in the seminiferous tubules became more regular and clear and the interstitial tissue had a clear appearance.

Anatomical development of urinary bladder during the fetal period

The aim of this study was to determine the development, location, and size of the urinary bladder during the fetal period. The study was performed on 149 human fetuses between 9 and 40 weeks of gestation. The location of the urinary bladder with respect to transverse plane between the highest point of pubic symphysis and the sacral promontory and median sagittal plane was first determined. The dimensions and the angle of the urinary bladder were measured, and bladder shapes were determined. In addition, the edges of the vesical trigone were measured. There was no significant difference between sexes for any of the parameters (P > 0.05). A significant correlation was observed between all parameters and gestational age (P < 0.001). The urinary bladder was located above the transverse plane in most of the cases (83%) and in the median sagittal plane in every case. It was determined that the angle of bladder did not change and the mean value of the angle was 151° during the fetal period. Bladder was categorized into four different shapes (ellipsoid, round, cuboid, and triangular), and the most common shape found during the fetal period was cuboid. The vesical trigone was an isosceles triangle during the fetal period. The new data provided by this study will enable evaluation of the development of the fetal urinary bladder, and should be useful in several fields such as anatomy, fetopathology, medical imaging, obstetrics, and pediatric urology. Clin. Anat. 21:683–690, 2008.

The morphometry of patella and patellar ligament during the fetal period.

This study aims to determine the development and morphology of the patella and patellar tendon and to obtain morphometric data about these structures during the fetal period. One hundred five human fetuses (55 males and 50 females) aged 9–40 weeks were used in this study. Fetuses were divided into four groups between gestational weeks; Group I (9–12 weeks), Group II (13–25 weeks), Group III (26–37 weeks), and Group IV (38–40 weeks). The patella and patellar ligament were exposed via anatomical dissection; the dimensions (length, width, thickness) and the width of the lateral and medial articular surfaces of the patella, and the length and width of the patellar ligament, were measured using a Verniers caliper. No significant differences were observed between genders or sides for any of the parameters (P > 0.05), and a significant correlation was found between gestational age and all parameters (P < 0.001). All parameters of the patella and patellar ligament were found to be different statistically between trimesters (P < 0.05). This study reveals the development, morphological changes, and the morphometric measurements of the patella and patellar ligament during the fetal period. We hope that the present results can be useful for future studies. Clin. Anat. 24:225–231, 2011.

Size and location of the fetal human ovary

Objective: To determine the development and the localization of the ovaries during the fetal period. Material and Methods: One hundred and fifty-four ovaries obtained from 77 human fetuses aged between 9 and 40 weeks of gestation were used in this study. Firstly, the shapes and the positions of the ovaries were established. Second, the localization of the ovaries with respect to linea terminalis, ureters, and the iliac arteries were determined. Finally, the dimensions and the weight of the ovaries were measured. Findings: In the fetal period, the ovaries were most commonly almond shaped and had an oblique orientation. In the 1st trimester the midpoint of the long axis of the fetal ovaries were at the level of linea terminalis. In the 2nd and 3rd trimester and full-term fetuses, it was observed that the ovaries were not in ovarian fossa, suggesting that descensus ovary was in progression during these times. During the intrauterine period, the ovaries were most commonly located anterior to the ureters and over the common iliac artery, only to migrate to its final location between the internal and external iliac arteries towards the end of the 40th week. Conclusion: We found that the ovaries did not assume the position of the adults at the end of the fetal period, rather continued its descent after the birth. We believe our findings about the fetal ovaries will be useful in obstetrics, fetal pathology, and forensic pathology.