Efficacy of omega-3 in the treatment of polycystic ovary syndrome.

The purpose of this study was to evaluate the efficacy and safety of omega-3 in the treatment of polycystic ovary syndrome and to compare the clinical, hormonal, TNF-α and resistin levels in the patients treated with omega-3. A total of 45 non-obese PCOS women were studied. Women were treated with daily oral 1,500 mg of omega-3 for 6 months. Body mass index (BMI), hirsutism score, fasting glucose and insulin levels were noted for each case. Hirsutism was assessed at 6-month intervals using the Ferriman-Gallwey (F-G) scoring system. Hormonal, TNF-α and resistin levels at 6 months of therapy were compared with baseline values. BMI, F-G scoring, insulin and HOMA levels decreased significantly during treatment, but glucose levels did not change. In the hormonal profile, serum LH and testosterone levels decreased and sex hormone-binding globulin levels increased significantly after the 6 months of therapy. On the other hand, TNF-α levels showed a significant increase, whereas resistin levels showed no change. Omega-3 may be also effective in improving hirsutism and insulin resistance in patients with PCOS.

The influence of obesity on ICSI outcomes in women with polycystic ovary syndrome.

The objective of the study was to compare intracytoplasmic sperm injection (ICSI) outcome and gonadotropin doses between obese women with PCOS and non-obese patients with PCOS. This follow-up study represents ICSI outcomes in obese women with PCOS (BMI ≥ 30 kg/m(2)) compared with non-obese women with PCOS (BMI < 30 kg/m(2)). Obese (n = 18) and non-obese (n = 26) women with PCOS underwent long protocol pituitary suppression, ovarian stimulation and ICSI with fresh embryo transfer. Obese patients with PCOS required higher doses of gonadotropin (2994 IU vs 1719 IU; p < 0.001). Miscarriage rate was significantly higher in obese women compared with the non-obese women with PCOS (60% vs 6.7%, p = 0.002). Our results are valuable for counselling couples before initiation of assisted reproduction techniques (ART).

Effects of silica on mitochondrial functions of the proximal tubule cells in rats.

AIM: Despite the belief that silica (Si) is an inert and non-toxic ingredient, latest studies indicated that it is a potent mitochondria activator and Si-induced ROS generation is involved in the inflammatory reactions of silicotic lungs. Si cytotoxicity has been well studied in phagocytic cells, but its effects on the mitochondria of proximal tubule cells which are continuously exposed to filtered blood-borne soluble Si were not known. METHODS: Using renal cortical slices and isolated mitochondria, the effect of high dietary Si on the mitochondrial functions of proximal tubule cells was studied in rats exposed to 50 mg/kg sodium metasilicate-containing water for 8 days. RESULTS: Digested Si did not accumulate in kidney cortex, it was totally eliminated in the urine. Glomerular filtration rate as well as urine output were normal. Despite unaltered blood and cortex Si levels, ammonia production of cortical slices and isolated mitochondria was increased significantly and this was further increased by L-NAME pre-treatment. Elevated mitochondrial oxygen utilization was associated with increased ammonia production. Cyclosporin-A-sensitive mtPTP increase was associated with unchanged K(ATP) channels in the mitochondria of Si-exposed rats. CONCLUSION: These results suggested that dietary Si increases both extracellular and intracellular ammoniagenesis by elevating mitochondrial oxygen utilisation.

Dietary L-arginine restores aspirin-induced endothelial dysfunction in rat aorta.

L-Arginine induced elevation of the vascular prostanoid led us to think that the risk of coronary spasm may increase in L-arginine consumers when they are subjected to cyclooxygenase inhibitors and this limits the therapeutic value of aspirin. So the aim was to investigate the interaction of aspirin and dietary L-arginine in male rats. Animals were divided into four groups and fed with normal food. The first group received tap water while the second, third and fourth groups were subjected daily to aspirin (8.6 mg/kg), L-arginine (143 mg/kg) and aspirin + L-arginine combination in their drinking water respectively for 7 days. Vasomotor responses were recorded in the aortic rings suspended for isometric-force recordings. Aspirin treatment significantly reduced the dilation to acetylcholine and sodium nitroprusside. Attenuated phenylephrine contractility was associated with normal acetylcholine response in L-arginine group. Addition of L-arginine to aspirin treatment completely prevented aspirin-induced endothelial dysfunction but defective response to sodium nitroprusside persisted. Dietary L-arginine without affecting maximal dilation to acetylcholine significantly increased the share of dilator prostanoid which appears to resist aspirin. These results demonstrated that dietary L-arginine increases dilator prostaoid in rat aortic rings. Contrary to our expectation, co-administered L-arginine protected aspirin induced endothelial dysfunction and ruled out the limitation of aspirin use in L-arginine consumers.

L-arginine-induced changes in the characteristics of endothelial relaxation.

The importance of the functional integrity of endothelium in maintaining vessel tone and the reversibility of its dysfunction by L-arginine (Arg) treatment has made this amino acid very unique and a topic of many experiments. As the behavior of normal vessels against L-Arg was not known properly, we studied the effect of 10(-2) M L-Arg on the dilating effect of Ach and on its characteristics in 10(-6) M phenylephrine-contracted rings prepared from normal rat thoracic aortae, where nitric oxide (NO) mediates most acetylcholine (Ach)-induced relaxation. L-arginine attenuated PE-induced contraction, and the pD2 value for phenylephrine shifted to the right from -log M 7.10 +/- 0.1 to -6.67 +/- 0.16. L-arginine supplementation also caused a tremendous change in the characteristics of Ach-induced dilation. The share of the indomethacin-sensitive part in the 10(-5) M Ach-induced dilation of L-Arg pretreated rings increased from 26.0 +/- 0.1 to 42.0 +/- 4.6%, whereas the L-NAME-sensitive component decreased from 74.0 +/- 1.6 to 29.0 +/- 3.8% (p<0.001). L-arginine led to the occurrence of a non-NO, non-PGI2 component (29.0 +/- 1.1%) in Ach dilation. When regarding the NO-based relaxing response of thoracic aortic rings to Ach in physiological situations, L-Arg-induced changes in the components of endothelial derived relaxation seems an important issue to be considered during L-Arg supplementation in the clinic.

Effects of cadmium on the hearing system.

The functional resemblance between kidney proximal tubular and inner ear epithelial cells which has often been pointed out in the literature led us to hypothesize that nephrotoxic agents that cause renal tubular injury might also impair the function of inner ear cells. As one of the most toxic environmental nephrotoxic agents is cadmium, we aimed to study its effects on hearing experimentally in rats. In this study, increased blood and renal cortical cadmium levels were associated with high cadmium accumulation in ear ossicles and labyrinth in rats exposed to cadmium. The changes in auditory brainstem response (ABR) and otoacoustic emission in 2-month-old male rats exposed to drinking water containing 5 and 15 ppm CdCl2 for 30 days showed that cadmium-induced nephrotoxicity was associated with signs of defective hearing at a concentration of 15 ppm CdCl2 but that 5 ppm CdCl2 caused hearing loss without affecting kidney function. The mean latency of ABR wave 1, which indicates the function of the cochlea, was 1.335 +/- 0.31 ms in the control group and 1.641 +/- 0.052 and 1.74 +/- 0.88 ms in the rats subjected to 5 and 15 ppm CdCl2, respectively (p < 0.001). In the cadmium-treated groups short interpeak wave I-III latencies (p < 0.01) indicated cochlear dysfunction and this was also supported by the distortion product otoacoustic emission results (p < 0.001). Non-significant changes in wave III and V latencies were accepted as evidence of unaltered function of the other parts of the auditory system. These results suggest that hair cells are more sensitive to cadmium than kidney tubule cells and that the cochlear component of hearing is more vulnerable to cadmium toxicity than other parts of the auditory system.

Cadmium-induced changes in epithelial cells of the rat stomach.

The aim of this study was to determine the changes in the function and fine structure of the gastric mucosa following exposure to high cadmium (Cd) for 30 d in rats. In the present study, control animals were fed with normal food and tap water and the remaining animals received Cd (15 ppm CdCl2) in drinking water for the same period. Receiving Cd for 30 d increased the mean blood (p < 0.01) and mucosa (p < 0.001) Cd levels, while decreased mucus thickness, mucin content (p < 0.01) significantly. Basal acid output fell significantly (p < 0.01). Light and electron microscopic examination revealed the following: (1) Cd decreases the mean number of surface mucous, isthmic-neck, parietal cells (p < 0.05) and chief cells (p < 0.001) per unit from the control value and (2) in some cells of zymogenic unit, the Cd-induced alterations were characterized with dilated Golgi cisternae, focal enlarged endoplasmic reticulum, broken tubulovesicles, degenerated mitochondria, dense nuclei, as well as lysosomal structures. We concluded that Cd augments the elimination rate of zymogenic unit's cells by increasing the alteration rate, and the reduced basal acid output, mucin content, and mucus thickness can be explained easily with the loss of zymogenic unit's cell population.

Cadmium-induced changes in parietal cell structure and functions of rats.

The aim of this study was to determine the cadmium (Cd)-induced functional and structural changes in gastric parietal cells of male rats exposed to high Cd for 30 d. In the present study, control animals were fed with normal food and tap water; the remaining animals received Cd (15 ppm CdCl2) in drinking water for the same period. Receiving Cd for 30 d increased the mean blood Cd level, the mean tissue Cd content, and the mean blood pressure (p < 0.01, p < 0.001, p < 0.01, respectively). The basal acid output fell; however, the increases in stimulated acid output were not statistically significant. Light and electron microscopic examination revealed respectively that (1) Cd decreases the mean parietal cell number per unit from the control value of 23.46 +/- 3.84 to 19.46 +/- 2.12 (p < 0.05) and it affected preferentially the cells located at the distal half of the zymogenic unit and (2) in parietal cells, the Cd-induced alterations were characterized with swollen canalicular profiles, broken-down tubulovesicles, or degenerated mitochondria. We concluded that Cd augments the elimination rate of parietal cells by increasing the alteration rate and reduced basal acid output can be explained easily with the loss of parietal cell population.

Mosaic rearrangement of chromosome 18: characterization by FISH mapping and DNA studies shows trisomy 18p and monosomy 18p both of paternal origin.

Structural abnormalities of chromosome 18p mainly consist of isochromosomes of the short arm, which result in tetrasomy 18p. Trisomy 18p is much rarer, and less well characterized. We report on a 12-year-old girl with minor facial anomalies, delayed development, abnormal hands, atopic dermatitis, and hearing loss. She was mosaic for two abnormal cell lines in peripheral blood. In 90% of cells, a dicentric chromosome with duplication of the whole short arm of chromosome 18 resulted in trisomy 18p; 10% of cells had monosomy 18p, arising from a t(14;18)(p11;q11). FISH mapping, with multiple region specific and locus specific probes from the short and long arm of chromosome 18, showed that the structure of the dicentric chromosome 18 was 18pter-->18q23::18q11-->18pter. DNA polymorphisms for chromosome 18 showed that the abnormalities of chromosome 18 were paternal in origin. Combining all results, we could link the trisomy 18p and monosomy 18p to a common origin via a complex series of events in an early mitosis.

The effect of developmental exposure to cadmium (Cd) on visual evoked potentials (VEPs) and lipid peroxidation.

Pregnant Swiss albino rats were divided into three groups: control (C), gestational exposure of Cd (G-Cd), and gestational/postnatal exposure of Cd (GP-Cd) groups. Control animals received tap water, and the rats of GP-Cd group received Cd as CdC12 in their drinking water during the experimental period. The G-Cd group was given Cd during pregnancy, but given tap water after birth. Twenty-two days after birth, 15 rats (for each group) were taken from their mothers and continued to be treated with Cd (GP-Cd group) or tap water (C and G-Cd groups) for an additional 38 days. On postnatal day (PND) 60, flash visual evoked potentials (FVEPs) were recorded with disc electrodes attached with collodion 0.5 cm in front of and behind bregma. The mean latencies on N1, P2, and P3 were prolonged in the GP-Cd group compared with controls. The mean latency of P3 was also significantly different between G-Cd and GP-Cd groups. P1-N1 and N1-P2 amplitudes of VEPs were significantly decreased in the GP-Cd group compared with control group. N1-P2 amplitude of the G-Cd group was significantly lower than that of the control group. Thiobarbituric acid reactive substances (TBARS) were determined as an indicator of lipid peroxidation. Our data showed that pre- and postnatal Cd treatment caused a significant increase of lipid peroxidation in the brain.

The effect of manganese-induced hypercholesterolemia on learning in rats.

Since the exact mechanism of manganese (Mn)-induced learning disability is not known, we investigated the role of elevated cholesterol in rats exposed daily to 357 and 714 micrograms Mn/kg for 39 d. Significant Mn accumulation was accompanied by increased cholesterol content in the hippocampal region of Mn-treated rats. The learning, which is based on the time needed to reach food placed at the exit of a T-maze after a 1-d training period, was significantly slower in exposed rats than in unexposed rats. The rats receiving 357 and 714 micrograms Mn/kg reached the food in 104.5 +/- 13.8 and 113.3 +/- 25.7 s, respectively, on d 30, whereas their untreated counterparts reached the food in 28.7 +/- 11.4 s. This delay was completely corrected to 29.3 +/- 7.8 and 30.7 +/- 6.0 s in rats with coadministration of an inhibitor of cholesterol biosynthesis with 357 and 714 micrograms/kg of Mn. The correction of impaired learning was associated with the normalization of hippocampal cholesterol, but the Mn level in this region of the brain was not influenced in rats treated with a drug that inhibits cholesterol biosynthesis. These results suggested that Mn-induced hypercholesterolemia is involved in Mn-dependent learning disability.

Role of cadmium-induced lipid peroxidation in the kidney response to atrial natriuretic hormone.

In order to investigate the role of increased lipid peroxidation in the development of cadmium-induced hypertension, 30 male albino rats were exposed to drinking water containing 15 micrograms/ml cadmium for 30 days, and the results were compared with those of 30 controls. Water containing high cadmium concentrations caused a significant accumulation of the element in blood and kidneys, associated with an obvious elevation in blood pressure. The systolic and diastolic blood pressures rose from 102.8 +/- 7.0 and 81.2 +/- 3.8 mm Hg to 128.1 +/- 4.6 and 107.9 +/- 7.4 mm Hg, respectively, in cadmium-treated rats (p < 0.01). A decreased glomerular filtration rate and increased serum creatinine levels were accompanied by elevated levels of cortical and medullary thiobarbituric acid reactive substances in cadmium-induced hypertensive rats. The mean thiobarbituric acid reactive substance level rose from a control value of 211.5 +/- 64.1 to 303.3 +/- 46.3 nmol/g protein (p < 0.01) in the renal cortex due to the high intake of cadmium. Despite its obvious diuretic and natriuretic action in control animals, the bolus injection of 1.2 and 2.4 micrograms/kg atrial natriuretic peptide corrected neither elevated blood pressure nor the reduced glomerular filtration rate in rats exposed to cadmium. However, the tubular response to atrial natriuretic peptide remained unaltered. These data suggest that a lack of vascular response to atrial natriuretic peptide is one of the many putative causes of cadmium-induced hypertension, and cadmium-mediated increased lipid peroxidation may be involved in this unresponsiveness.

Reversibility of manganese-induced learning defect in rats.

In this study the mechanism by which manganese (Mn) induces learning defect and its reversibility has been investigated in rats. Female albino rats were dosed orally with 357 micrograms Mn/kg body weight for 15 or 30 days. Attempts were made to correct the Mn-induced learning defect by (1) co-administration of mevinolin and Mn for 30 days; (2) administration of mevinolin for 15 days after 15 days of dosing with Mn, and (3) by withdrawal of Mn treatment (15 days dosing with Mn followed by 15 days without Mn). Mevinolin was given orally at 235.7 micrograms/kg body weight. Significant increases in the Mn and cholesterol levels in the hippocampus were accompanied by an obvious slowness in learning of rats exposed to Mn. After one training period (day 29) the time required to reach the exit of a T-maze was 104.5 +/- 13.8 sec for rats dosed with Mn for 30 days, whereas that of the controls was 28.7 +/- 11.4 sec on day 30. This delay was completely corrected (to 30.7 +/- 6.0 sec) in rats co-administered mevinolin (an inhibitor of cholesterol biosynthesis) with Mn. Withdrawal of Mn, with or without inhibiting the cholesterol biosynthesis, also corrected the Mn-induced learning defect. These results suggest that Mn toxicity produces learning disability by increasing cholesterol biosynthesis and this reversible disability in learning can be corrected by withdrawal of Mn exposure.

The role of cadmium in the peroxidative response of kidney to stress.

Since the kidney is a main target for cadmium, its accumulation in the kidney tissue by increasing peroxidative damage make the kidney functions vulnerable to stress. For this reason, the effect of cadmium-induced peroxidative damage to kidney responses to stress was investigated in this study. Two-month-old albino rats receiving 15 micrograms/mL containing Cd drinking water for 30 d were exposed to restraint and cold stress for 6 h, and their responses were compared with those of unstressed counterparts. Lipid peroxidation was found to be significantly higher in the cortical portion of kidney in cadmium-exposed rats than that of unexposed animals. The mean thiobarbutyric acid reactive substance (TBARS) level rose from 211.6 +/- 64.2 to 303.4 +/- 46.4 nmol/g protein (p < 0.01). Six hours of cold and restraint stress caused an elevation in the cortical TBARS level in control animals without affecting its level in cadmium-exposed rats. Despite unaltered cortical TBARS, its medullar levels increased significantly in cadmium-exposed rats because of stress. These results suggested that cadmium accumulation in the kidney increases the susceptibility of medulla against peroxidative damage. However, further functional studies are necessary to explain the role of cadmium in the stress-induced deterioration of medullar functions.

The susceptibility to stress-induced gastric injury of rats exposed to cadmium.

In this experimental study, the effect of cadmium on cold and restraint stress-induced gastric lesions has been studied. Rats received 15 micrograms/mL cadmium-containing water for 30 d, and at the end of this period, they were subjected to cold and restraint stress. Cadmium accumulation in gastric mucosa was associated with increased mucosal lesions, as well as decreased mucin and PGE2 levels in rats exposed to cadmium. Stress-induced mucosal injury was more pronounced, and the hemoglobin leakage into gastric lumen owing to breakdown in the barrier was 17.30 +/- 3.45 micrograms/mL in control and 35.71 +/- 6.18 micrograms/mL in treated rats. Our data suggest that high cadmium intake facilitates the occurrence of stress-induced mucosal lesions by diminishing the mucin content and PGE2 generation in gastric mucosa.

Role of lipid peroxidation in cadmium-induced impairment of the gastric mucosal barrier.

Peroxidative tissue damage has been reported to contribute to several pathological disorders. Despite high exposure to both exogenous and endogenous oxidant stress, the strong cell defence mechanism of the gastric mucosa protects mucosal epithelial cells against these noxious stimuli. However, some environmental factors involved in lipid peroxidation (such as cadmium), which disrupt gastric mucosal protection, may impair the mucosal barrier and facilitate the occurrence of gastric ulcers. In an experimental study to investigate this hypothesis, the level of cadmium-induced lipid peroxidation products (TBARS) and an antioxidant enzyme (SOD) were investigated. The mucin content (P < 0.01) and prostaglandin levels (P < 0.05) of mucosa as components of the gastric mucosal barrier were found to be significantly reduced in rats exposed to 15 ppm of cadmium in water for 30 days when compared with those of unexposed controls. TBARS levels in blood (P < 0.05) and mucosa (P < 0.001) increased markedly in cadmium-exposed animals whereas blood SOD levels remained unchanged. The significant correlation between TBARS and mucosal cadmium (r = 0.664, P < 0.01), as well as between cadmium and PGE2 (r = -0.719, P < 0.01), led to the conclusion that cadmium-induced lipid peroxidation is involved in the increased vulnerability of gastric mucosa to injurious stimuli in rats. This susceptibility may be responsible for the high incidence of stress-induced gastric ulcer in the population.

Cadmium induced lipid peroxidation in kidney function.

Since the kidney is the main target organ for many metals including cadmium, the generation of the products of lipid peroxidation due to accumulation of these toxic metals in the kidney may have importance in the mechanism of their nephrotoxicity. In order to test this hypothesis, we carried out an experimental study in rats. The functions and the levels of tiobarbituric acid reactive substances (TBARS) of the kidney were investigated in animals receiving 15 micrograms/ml aqueous Cd solution for 30 days. Due to cadmium accumulation in kidney cortex, the ratio of Cd/Zn increased significantly and this increase was associated with elevated TBARS in both renal cortex and medulla. The content of TBARS in renal cortex rose from 211.6 +/- 64.2 to 303.4 +/- 46.4 nmol/g protein (p<0.01) and GFR decreased to 390.5 +/- 109.4 from 1008.7 +/- 4.8 microliters/min (p<0.01) in cadmium exposed animals. Daily coadministration of selenium, vitamins A, C, E did not reverse the adverse effect of cadmium on kidney function, despite the significant decrease in cortex TBARS levels (p<0.01). In conclusion, these data suggest to us that lipid peroxidation assessed by TBA test may not be the only mechanism in cadmium induced nephrotoxicity.

The role of diet cholesterol changes on EEG.

Thirty three male albino rats, weight between 200 and 220 g were used in this experiment. Control animals consisting of 11 rats were fed with a normal lab diet for a period of 14 weeks and the others (22) were fed with a diet containing 1% cholesterol for the same period. At the end of the experimental period, plasma cholesterol level (Mean +/- SD) was 141.29 +/- 34.5 mg/dl in the cholesterol group and 70.66 +/- 10 mg/dl in the control group. Eleven of the rats from the cholesterol group were transferred to the normal diet for 14 weeks (normocholesterolemic group). Spectral analysis of EEG records from parietal lobes of animals showed that there was an obvious depression in the brain waves of hypercholesterolemic rats whereas no depression in normocholesterolemic rats.

SEP spectral analysis of cholesterol rich rats.

In this study, twenty four albino rats, weighing between 180 and 200 g were tested. One half was fed with a diet containing 1% cholesterol for 12 weeks and the other half was fed with a normal lab diet for the same period. After the experimental period, the plasma cholesterol level in the diet group was 134.04 +/- 21.11 mg/dl compared with the control group 72.72 +/- 10.5 mg/dl. In the two groups, SEPs were recorded from central (Cz) referenced to frontal (Fz) following left posterior tibial nerve (PTN) stimulation. Amplitude spectra of SEPs were computed by Fast Fourier Transform (FFT) algorithm. Their amplitude maxima were found to occupy the frequency bands of 1-3.5, 4-5, 6-7, 8-10, 11-12, 13-20, 20.5-36 and 36 Hz and above. The decibel (dB) values of the maxima were statistically lower for hypercholesterolemia than for the normals in the all the frequency bands.

The effect of hypercholesterolemia on SEPs recorded from rats.

Twenty-four albino rats, weighing 180-200 g were studied. Twelve of them were fed with a diet containing 1% cholesterol for 12 weeks and the others were fed with a normal lab diet for the same period. As a result, plasma cholesterol level was found in the diet group 134.04 +/- 21.11 mg/dl with respect to control 72.72 +/- 10.5 mg/dl. In the two groups, following left posterior tibial nerve (PTN) stimulation, SEPs were recorded from central (Cz) referenced to frontal (Fz). In the hypercholesterolemic group, the first negative component (N24) was found to be prolonged (p less than .001) and the peak-to-peak amplitudes (N24P40, P40N80) were observed to be decreased (p less than .001). These results have shown that the latency and amplitude can be changed by hypercholesterolemia.