Protective Effect of Epigallocatechin Gallate in Ischemia-Reperfusion Injury of Rat Skeletal Muscle.

BACKGROUND: Reactive oxygen species-induced cell injury has been considered to be one of the main etiologic factors in ischemia-reperfusion injury (IRI). As a potential antioxidant agent, epigallocatechin gallate (EGCG) was examined in skeletal muscle of the rats after IRI with or without treatment. MATERIALS AND METHODS: Tourniquet application applied to the rats' hind limbs was selected as the appropriate IRI method. Animals were randomly distributed to one of the following groups: (1) sham control + SF (saline) (10 mg/kg/i.p.) (SC-SF), (2) IRI (4 + 2 h) + SF (10 mg/kg/i.p.) (IRI-SF), (3) IRI and EGCG (25 mg/kg/i.p.) (IRI-EG25), and (4) IRI and EGCG (50 mg/kg/i.p) (IRI-EG50). In another set of experiments with identical groups, the only difference was that the reperfusion period was 24 h. A number of different parameters relating to the damage seen in the skeletal muscles, lungs, kidneys, and liver and particular cytokines were measured by proper analytical methods. RESULTS: In comparison with the SC-SF group, IRI (4 + 2 h) induced an increase in the total oxidative status of skeletal muscle (10.17 ± 0.61 versus 15.74 ± 1.10) and blood creatine phosphokinase (CPK) (669.88 ± 50.23 versus 7202.38 ± 766.13) and lactate dehydrogenase levels (686.00 ± 67.48 versus 1343.00 ± 113.01). Although 25 mg/kg EGCG could not reverse these parameters to their normal levels, the higher dose of EGCG, that is, 50 mg/kg, was sufficient to prevent the increases seen in total oxidative status (8.55 ± 0.85) and CPK levels (4741.63 ± 339.40). In addition, reduced total antioxidant status of skeletal muscle in the IRI-SF group (0.50 ± 0.06) was elevated by the administration of EGCG (50 mg/kg) (0.85 ± 0.04). Regarding remote organ injury, only alanine transaminase (ALT) and aspartate transaminase (AST) levels were found to be increased, showing a slight damage in liver tissue. However, neither dose of EGCG was able to prevent this deleterious effect. As for cytokines (interleukin-1ß, IL-6, IL-8, tumor necrosis factor-α, and monocyte chemotactic protein-1), there were no differences between the study groups. In regard to long-term IRI (i.e., 4 + 24 h), statistically significantly elevated parameters in the IRI-SF group were as follows: CPK, lactate dehydrogenase, creatinine (Cr), and blood urea nitrogen. On the other hand, none of them were influenced by either dose of EGCG. According to the results, EGCG demonstrates a considerable protective effect toward IRI (4 + 2 h) of skeletal muscle. CONCLUSIONS: Although oxidative stress seems to play a significant role both in the pathogenesis of IRI and in the mechanism of action of EGCG, there is no evidence that inflammatory cytokines are, at least in our model, crucial mediators regarding the former events.

Isotretinoin: Still the cause of anxiety for teratogenicity.

Isotretinoin is known as a potent teratogenic agent. Pregnancy should be ruled out before isotretinoin is prescribed. In this study, we evaluated the fetal outcomes of pregnant women who had inadvertently been exposed to isotretinoin during or before pregnancy. We collected data of pregnant women who had admitted to the Teratology Information Service due to isotretinoin exposure. Data regarding medications and comorbidities were documented. Outcomes were grouped as: live births, stillbirths, live births with congenital malformations, induced abortions (due to fetal abnormalities), spontaneous abortions, and elective abortions. We found that three women had gone to elective abortions. Three babies were live born without birth defects, of which, maternal exposure periods were between 0 and 3 weeks, 9 and 10 weeks before last menstrual period. One woman, exposed to isotretinoin up to the fourth week of gestation, decided ongoing her pregnancy with no current drug-related complications. Although many risk management programs worldwide have been used to prevent isotretinoin-related teratogenicity, the results of the present study showed that women became pregnant during isotretinoin intake and opted for pregnancy termination. Attention should be paid to the risk management programs mandating effective contraceptions, in order to lessen the drug-related terminations.

Comparison of Amniotic Fluid Cytokine Levels in Postterm and Term Pregnancy: a Prospective Study.

BACKGROUND: To evaluate amniotic fluid pro- and anti-inflammatory cytokine levels in women with postterm and term pregnancies in labor and not in labor. METHODS: The study involved three groups: postterm (Group 1, n = 29), term in labor (Group 2, n = 28), and control (Group 3, n = 30). All groups were compared with respect to age, gravidity, parity, obstetric history, gestation week, cervical dilatation and effacement, maternal serum C-reactive protein and white cell count, amniotic interleukin 4, 6, and 10 levels, birthweight, and cord blood pH. RESULTS: The amniotic fluid interleukin 10 level was 24.4 ± 8.8 pg/mL in the postterm group, 13.5 ± 5.1 pg/mL in the term in labor group, and 19.8 ± 5.4 pg/mL in the control group (p < 0.001). The amniotic fluid interleukin 4 level was 86.5 ± 57.7 pg/mL in the postterm group, 38.2 ± 29.2 pg/mL in the term in labor group, and 81.9 ± 68.4 pg/mL in the control group (p = 0.002). The amniotic fluid interleukin 6 level was 329 ± 135.1 pg/mL in the postterm group, 252.8 ± 138.7 pg/mL in the term in labor group, and 227.9 ± 114.4 pg/mL in the control group (p = 0.02). There was a positive correlation between gestational age and IL-10 levels (p < 0.05). CONCLUSIONS: Amniotic fluid IL-10 and IL-4 cytokine levels were increased in postterm pregnancy and they decreased with active labor.

Lidocaine for pain control during intrauterine device insertion.

AIM: The aim of this study was to compare the effects of topical lidocaine spray, cream and injection on pain perception during intrauterine device (IUD) insertion. METHODS: Multiparous women of reproductive age were randomized into control, lidocaine cream, spray and injection groups. A 10 cm visual analog scale was used for all patients to evaluate pain during the three steps of the IUD insertion procedure. Baseline pain assessment was made immediately after the administration of analgesics, the second pain assessment was performed immediately after use of the tenaculum, and the third pain assessment was performed after IUD insertion. RESULTS: Two hundred patients were enrolled in the study. The groups were similar in terms of demographic characteristics. The lidocaine injection group exhibited higher baseline pain scores (P < 0.001). Pain associated with tenaculum use was lower in the lidocaine spray group. Pain related to IUD insertion was lower in the lidocaine spray and injection groups (P < 0.001); however, lidocaine spray was superior to injection for the reduction of IUD insertion related pain (P = 0.001). CONCLUSION: Lidocaine spray is a good option for reducing the pain experienced during insertion of an IUD. It reduces pain related to both tenaculum use and IUD insertion. Spray application is both easy and rapid. Paracervical lidocaine injection also reduces pain during IUD insertion, but has no effect on tenaculum-related pain; moreover, the injection itself is painful. Therefore, this option is not a plausible method for reducing pain during IUD insertion.

Comparison of single-incision and conventional laparoscopic surgery for benign adnexal masses.

BACKGROUND: Our aim was to compare single incision and conventional laparoscopic surgeries performed for benign adnexal masses with regard to their intraoperative characteristics and postoperative pain levels. MATERIAL AND METHODS: The main outcome measures were laparoscopic entry time, total operation time, amount of bleeding, intraoperative complications, post-operative pain scores, additional analgesic requirements, and length of hospital stay. RESULTS: A total of 71 women, 39 in the conventional laparoscopy group and 32 in the SILS group, participated in the study. Demographic findings did not differ between the two groups. Similarly, rates of intraoperative complications, rates of conversion to laparotomy, pre- and postoperative hematocrit levels were not significantly different between the groups. Laparoscopic entry time was shorter in the SILS group (10.4 ± 5.9 min. vs. 5.28 ± 1.7 min.). However, total operation time was similar in the two groups. The groups did not show significant differences regarding additional analgesic requirements, or postoperative pain scores after 24 h. However, pain scores in the recovery room and after six and 12 h were lower in the SILS group. CONCLUSION: SILS seems to be effective and safe for the treatment of benign adnexal masses. SILS appears to be advantageous regarding postoperative pain especially in the early period.

A rare case of leiomyosarcoma localized in the Bartholin's gland area and review of the literature.

Sarcomas of the vulva in the Bartholin's gland area are extremely rare in adults and only a few cases have been reported in the literature. A 65-year-old female patient without any previous complaint presented to our hospital complaining of a genital lump with progressive enlargement over the last six months. Pelvic examination revealed a 6 × 5 cm solid mass lesion with irregular margins localized in the left Bartholin's gland. Preoperative pathology results indicated a benign lesion, which was subsequently totally excised. Histopathological examination of the lesion revealed leiomyosarcoma. When a lesion is localized in the Bartholin's gland area, preoperative biopsy may suggest benign cytology, which can lead to a delay in diagnosis and curative treatment. Total local excision is the first choice for vulvar-complicated masses in the Bartholin's gland area. The present case is the ninth well-documented case reported in the literature.

Isolated hydatid cyst of uterine cervix: A case report.

Hydatid disease is an endemic infection which can affect any organ, mainly the liver and lungs. Peritoneal echinococcosis is usually known to occur secondary to hepatic hydatid cyst rupture into the peritoneal cavity. An isolated cyst in the pelvic cavity is considered as primary only when there are no other hydatid cysts. Herein, we report an isolated pelvic-cervical hydatid cyst which presented without any involvement of the other abdominal organs or lungs. Our patient, a 27-year-old woman with the primary complaints of dyspareunia and chronic pelvic pain, had thin-walled large cystic mass originating from the cervix, diagnosed by ultrasonography. She underwent surgery with the most likely initial diagnosis of exophytic fibroid with cystic degeneration. Gynecologists should be aware of the possibility of isolated primary hydatid cyst of the pelvic cavity and should consider this condition in the differential diagnosis of cystic pelvic masses, especially in areas where the disease is endemic.

Cross-sectional evaluation of prescription of valproate and other antiepileptic drugs to pregnant women.

Drug counseling is important in women with epilepsy since data about the effects of maternal antiepileptics on the developing fetus are limited. Although pregnant patients on the most teratogenic drugs are treated in accordance to the European Medicines Agency guidelines, a large amount of them may be exposed to the teratogenic medications unintentionally. We performed a tertiary center observational study about medications of pregnant women who were consulted to Teratology Information Service (TIS) unit for evidence-based teratogenic risk analysis. The registration records of 134 pregnant women between 2014 and 2018 were examined. We evaluated the diagnoses, prescriptions, usage of antiepileptic drugs, and distribution of drug subtypes and investigated the drug-related congenital anomalies after delivery. Women were recontacted after delivery to obtain information about health status of infants. We found that 33 women were diagnosed with neurological disorders. A total number of 60 neurologic drugs was prescribed, including 13 antiepileptics. Antiepileptic drugs covered 38.4% valproate (n = 5), 15.4% pregabalin/gabapentin (n = 2), 15.4% levetiracetam (n = 2), 15.4% lamotrigine (n = 2), 7.7% phenytoin (n = 1), and 7.7% carbamazepine (n = 1). Delivery outcomes revealed that valproate exposure resulted in one baby with congenital cataracts, one postnatal exitus with cardiac dysfunction, and one therapeutic abortion. Various antiepileptic drugs were prescribed to pregnant women prenatally or at different times of pregnancy and valproate was the most common antiepileptic drug consulted to TIS for teratogenic risk analysis. Disseminating TIS units and reporting the outcomes to the teratogenesis literature provide proper evaluation of teratogenic risks of drugs accordingly.

Ischemia-reperfusion injury in skeletal muscle: comparison of the effects of subanesthetic doses of ketamine, propofol, and etomidate.

BACKGROUND: Interest in the effects of anesthetics in skeletal ischemia-reperfusion injury (IRI) has recently emerged. Thus, the objective was to compare the effects of subanesthetic doses of ketamine, propofol, and etomidate in a skeletal IRI model. METHODS: IRI was applied to rats by tourniquet method. Under thiopental anesthesia, five experimental groups were established as follows: (1) sham-control, (2) IRI, (3) IRI+Ketamine, (4) IRI+Propofol, and (5) IRI+Etomidate. Malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were measured in skeletal muscle via a spectrophotometer. Zinc, iron, copper, and selenium were evaluated by atomic absorption spectrophotometer. RESULTS: While the values of malondialdehyde and glutathione peroxidase were higher and lower, respectively, those of superoxide dismutase and catalase were identical in IRI group in comparison with sham-control. Zinc displayed a decrease in IRI group; however, no differences in iron and copper levels were determined. In rats treated with subanesthetic doses of ketamine, elevated malondialdehyde levels in IRI group were reversed to control levels by each dose. While each dose of ketamine decreased superoxide dismutase activities in comparison with IRI group, a reduction in catalase activity was only seen in 3mg/kg ketamine-treated rats. The attenuated glutathione peroxidase activity seen in IRI was greatly reversed by ketamine administration in all doses. No differences in zinc, copper, and iron levels were detected between IRI and ketamine-treated groups. Similar results were obtained either by the administration of propofol or etomidate. CONCLUSIONS: Subanesthetic doses of ketamine, propofol and etomidate displayed beneficial effects in IRI.

Bisoprolol and linagliptin ameliorated electrical and mechanical isometric myocardial contractions in doxorubicin-induced cardiomyopathy in rats.

BACKGROUND: Doxorubicin is an anthracycline chemotherapeutic agent that causes cardiomyopathy as a side effect. Here, we aimed to investigate the effects of linagliptin and bisoprolol on the management of doxorubicin-induced cardiomyopathy in rats. METHODS: Wistar rats were divided into six groups (n = 8). Group I received saline for 4 weeks; group II received 1 mg/kg bisoprolol for 8 weeks; group III received 3 mg/kg linagliptin for 8 weeks; group IV received 1.25 mg/kg doxorubicin for 4 weeks for the induction of cardiomyopathy; group V received 1.25 mg/kg doxorubicin for 4 weeks plus 1 mg/kg bisoprolol for 8 weeks; and group VI received 1.25 mg/kg doxorubicin for 4 weeks plus 3 mg/kg linagliptin for 8 weeks. Electrocardiography and isometric mechanography were conducted to measure ventricular contractile responses. Myocardial tissue and serum samples were analyzed for oxidative and cardiotoxic markers by ELISA. RESULTS: Electrocardiography revealed that QRS, QT and Tp intervals were longer in group IV than group I. Doxorubicin caused a significant decrease in ventricular contraction, which was significantly prevented by bisoprolol. Doxorubicin resulted in myocardial fiber disorganization and disruption, but bisoprolol or linagliptin improved this myocardial damage. Glutathione peroxidase was significantly decreased in groups IV and V. Bisoprolol or linagliptin treatment attenuated the significant doxorubicin-mediated increase in malondialdehyde. Doxorubicin and linagliptin provided significant elevations in CK-MB activity and troponin-I levels. CONCLUSIONS: Doxorubicin resulted in pronounced oxidative stress. The beneficial effects of bisoprolol and linagliptin on myocardial functional, histopathological and biochemical changes could be related to the attenuation of oxidative load.

Knowledge attitude and practice of Turkish health professionals towards pharmacovigilance in a university hospital.

BACKGROUND: Pharmacovigilance and spontaneous reporting of adverse drug reactions (ADRs) have pivotal roles in drug safety. This study aimed to evaluate the knowledge, attitude and practice of health professionals towards pharmacovigilance in a university hospital in Turkey. METHODS: An observational, cross-sectional study via a 25-item self-administered questionnaire was conducted among physicians (n=161) and nurses (n=321). RESULTS: Although 66% (320/482) of the subjects were aware of the 'pharmacovigilance' term, the awareness of the Turkish Pharmacovigilance Center was as low as 30% (161/482). Similarly, 41% (198/482) of the subjects did not know the pharmacovigilance contact point of the hospital. Defining and determining new ADRs and improving patient safety were associated with the importance of spontaneous reporting by the subjects. According to the physicians, unawareness of the national pharmacovigilance system was the first discouraging factor, as was the unawareness of the need for spontaneous reporting of ADRs for the nurses. Although the frequency with which the nurses encountered ADRs was lower than that of the physicians, their claimed reporting ratio (21%; 68/321) was more than the physicians (8%; 12/161). CONCLUSIONS: There is significant potential under-reporting of ADRs, which seems to be the result of several factors, including the lack of the knowledge of the national pharmacovigilance system.

Combination therapy of imipramine and melatonin: additive antidepressant effect in mouse forced swimming test.

Although there are tools to treat depressive patients, a considerable amount of the cases remains to be untreated. These drug-resistant patients need new drugs or drug combinations to overcome this problem. Thus, the potential synergistic effect of melatonin on a classical drug, imipramine was evaluated in the present study. To test this hypothesis, porsolt swim test, a test predictive of antidepressant-like action, was conducted in mice. Imipramine at doses of 20 and 40 mg/kg caused no alteration and statistically significant reduction in the duration of immobility in forced swim test, respectively. While 5 mg/kg melatonin had no effect, 10 mg/kg melatonin slightly reduced the duration of immobility. When sub-effective doses of imipramine and melatonin (20 and 5 mg/kg, respectively) were co-administered, there was no alteration in responses compared with those of each drug alone. Likewise, the effective dose of melatonin (10 mg/kg) did not cause any increase in responses to 20 mg/kg imipramine. Although combination of imipramine (40 mg/kg) and melatonin (5 mg/kg) did not exert an antidepressant effect above that of imipramine alone, co-administration of the effective doses (10 and 40 mg/kg for melatonin and imipramine, respectively) displayed an additive effect. There were no significant differences between groups in relation with locomotor activity test. The results show that co-administration of imipramine and melatonin exhibits an additive effect and that there seems to be no interaction between the drugs.

Body iodine status in women with postmenopausal osteoporosis.

OBJECTIVE: Postmenopausal osteoporosis is a frequent cause of morbidity and can negatively impact life expectancy; iodine is an essential element for bone mineralization, and iodine deficiency is frequently observed. The aim of the present study was to understand the connection between postmenopausal osteoporosis and the level of iodine in the body. METHODS: A total of 132 participants were divided into three groups: group 1 consisted of healthy postmenopausal women (n = 34), group 2 comprised osteopenic women (n = 38), and group 3 included women with postmenopausal osteoporosis (n = 60). The three groups were compared according to demographic, clinical, and laboratory findings. RESULTS: The urinary iodine levels were recorded as 216.1 ±â€Š125.2 in the control group, 154.6 ±â€Š76.6 in the osteopenic group, and 137.5 ±â€Š64.9 in the postmenopausal osteoporosis group (P < 0.001). These differences were maintained after adjustment for body mass index (P < 0.001). The urinary iodine level accurately correlated with the total T-score for the lumbar spine (r = 0.236, P = 0.008). Multiple regression analysis showed that corrected for body mass index, alkaline phosphatase isoenzyme, and urinary deoxypyridinoline, the urinary iodine level was significantly associated with total T-score (beta coefficient = 0.270, P = 0.006). CONCLUSIONS: The urinary iodine level was significantly lower in women with postmenopausal osteoporosis, and iodine replacement may be important in preventing osteoporosis in areas where iodine deficiency is endemic.

Prevention of pro-depressant effect of L-arginine in the forced swim test by NG-nitro-L-arginine and [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one].

Previous studies have shown that l-arginine, the precursor of nitric oxide, has a dual effect (antidepressant and pro-depressant) in the forced swim test. The aim of the present study was to investigate whether nitric oxide-cGMP pathway was involved in this dual effect. Porsolt swim test was conducted to resemble the symptomatology of major depressive disorder. An open field locomotor activity test was also used. L-arginine exerted a U-shape effect in the forced swim test: doses of 30, 100, 300, and 1000 mg/kg caused no alteration, statistically significant reduction, no alteration, and non-significant enhancement, respectively. Neither N(G)-nitro-L-arginine (NNA) nor [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) at doses of 3 mg/kg was found to be effective in the forced swim test, whereas 10 mg/kg ODQ significantly reduced the immobility time. In the presence of NNA, the antidepressant and pro-depressant effects of L-arginine disappeared, however, only the pro-depressant component of l-arginine effect was prevented by ODQ (3 and 10 mg/kg). Saline, the solvent of L-arginine and NNA, and dimethyl sulfoxide (15% in saline), the solvent of ODQ, had no effect on the duration of immobility. None of the drugs or solvents used in the present study had any effect on locomotor activity over the dose range applied. The results show that L-arginine exerts its paradoxical effects by producing nitric oxide and that cGMP seems to have a role only in the pro-depressant component.

Ureaplasma urealyticum: Presence among Sexually Transmitted Diseases.

The aim of this study was to detect the presence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Trichomonas vaginalis, and Ureaplasma urealyticum in genital specimens of symptomatic patients. This study also examined the role of U. urealyticum in infections of the lower genital tract. Cervical and urethral samples from 96 patients (46 males, 50 females) were tested using the Seeplex(®) STD6 ACE kit. Consent forms were received and a questionnaire was applied. All statistical analyses were performed using the SPSS statistical software program (version 17.0). Among the samples tested, at least 1 pathogen was detected in 49% of the samples; specifically, the rate of detection of U. urealyticum, M. hominis, C. trachomatis, N. gonorrhoeae, M. genitalium, and T. vaginalis was 29.1%, 10.4%, 8.3%, 7.3%, 6.3%, and 4.2%, respectively. U. urealyticum was detected as the sole pathogen in samples from 10% of female patients and 28.3% of male patients (p = 0.035). U. urealyticum was present in 54.5% (18/33) of samples in which a single pathogen was detected and 71.4% (10/14) of samples in which multiple pathogens were detected. Among men, significant differences in discharge, dysuria, and pruritus were not noted among those with negative results (84.6%, 69.2%, and 38.5%, respectively), among those positive for only U. urealyticum (100%, 66.7%, and 26.7%, respectively), and those positive for N. gonorrhoeae, C. trachomatis, M. genitalium, and T. vaginalis (100%, 93.3%, and 26.7%, respectively). Detection of U. urealyticum, either alone or together with other pathogens, in a symptomatic group of patients is an important finding, particularly in men.

Placental Elasticity and Histopathological Findings in Normal and Intra-Uterine Growth Restriction Pregnancies Assessed with Strain Elastography in Ex Vivo Placenta.

The aim of this study was to investigate the differences of placental elasticity between intra-uterine growth restriction (IUGR) and normal pregnancies to show whether or not there is any association between histopathological changes and placental elasticity. Fifty-five human placentas were collected at delivery, including 25 with IUGR and 30 controls. Strain elastography (SE) was performed ex vivo and all placentas were examined histopathologically. Elasticity index (EI) and histopathological findings were compared between groups. The placental stiffness and presence of histopathological changes were higher in the IUGR group than in controls (p < 0.05). Also, histopathological findings were associated with decreased EI values, but no specific patterns of histologic abnormalities were identified except villitis and delayed villous maturity. Distinct reduced placental elasticity could be the result of the cumulative effects of all the histologic findings in IUGR.

Antioxidant effect of Legalon(r) SIL in ischemia-reperfusion injury of rat skeletal muscle.

PURPOSE: To evaluated the potential antioxidant agent Legalon (r) SIL (silibinin-C-2',3-bis(hydrogensuccinat)) in the skeletal muscle of rats. METHODS: IRI was achieved via tourniquet application in Wistar-albino rats. Experimental groups were chosen as (i) sham control, (ii) IRI (3+2 h), (iii) IRI and Legalon (r) SIL-50 (50 mg/kg/i.p.), (iv) IRI and Legalon (r) SIL-100 (100 mg/kg/i.p.), and (v) IRI and Legalon (r) SIL-200 (200 mg/kg/ i.p.). Muscle viability (evaluated by triphenyltetrazolium chloride dye method), malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were assessed in muscle samples using a spectrophotometer. RESULTS: Although viability of the injured limb non-significantly declined in the IRI group, administration of Legalon (r) SIL did not prevent injury. However, dramatic increase observed in malondialdehyde levels in the IRI group was prohibited by Legalon (r) SIL in a statistically significant manner. In comparison with the sham-control group, IRI and Legalon (r) SIL administration did not cause any significant alterations in the levels of superoxide dismutase, catalase, and glutathione peroxidase. CONCLUSION: Although Legalon (r) SIL was not sufficient to prevent muscle injury in terms of viability, it is found to be an effective option to reduce reactive oxygen species-induced cell injury.

Does metoclopramide exposure alter endometrial receptivity and decrease pregnancy rates?

OBJECTIVE: The aim of this study was to investigate the effect of metoclopramide on endometrial receptivity with an immunohistochemical investigation of integrin ß3 expression in pregnant rats. MATERIALS AND METHODS: In the present study, the pregnant mice administrated by different doses of metoclopramide were used to explore the effect of metoclopramide on embryo implantation, especially on the endometrial receptivity. RESULTS: The statistical results showed that the number of implanted embryos was gradually declining along the increasing dose of metoclopramide. When the administrated dose of metoclopramide was 3 mg/kg per day, great changes were observed in the exposed uterine morphology and down-regulated integrin ß3 were also found in high dose metoclopramide-exposed mice. CONCLUSION: Metoclopramide exposure, especially in high doses may alter endometrial receptivity by effecting integrin expression on decidual tissue which can decrease pregnancy rates. This drug should only be recommended for use during pregnancy when benefit outweighs the risk.

Hidden function of neuronal nicotinic acetylcholine receptor beta2 subunits in ganglionic transmission: comparison to alpha5 and beta4 subunits.

Neuronal nicotinic acetylcholine receptors (nAChR), which modulate fast excitatory postsynaptic potentials (f-EPSP), are located on both pre- and postganglionic sites in the autonomic nervous system (ANS). The receptor subunits alpha3, alpha5, alpha7, beta2 and beta4 are present in autonomic ganglia in various combinations and modulate acetylcholine (ACh) transmission. In the present study, autonomic functions were systemically examined in mice lacking beta2 subunits (beta2-/-) to further understand the functional role of beta2 subunits in modulating ganglionic transmission. The results show normal autonomic functions, both under physiological conditions and in perturbed conditions, on thermoregulation, pupillary size, heart rate responses and ileal contractile reactions. This suggests that the function of beta2-containing receptors in ganglionic transmission is hidden by the predominant beta4 containing receptors and confirms previous studies which suggest that alpha3alpha5beta4 nAChRs are sufficient for autonomic transmission. On the other hand, beta2-containing receptors have only a minor function on postsynaptic responses to ACh, but may modulate ACh release presynaptically, although there is no evidence for this.

Selective modifiers of glutathione prevent restoration of photorelaxations in mouse gastric fundus.

S-nitrosoglutathione (GSNO) has previously been shown to have a role in ultraviolet (UV) light-elicited relaxations and proposed to account for the photosensitive store in the mouse gastric fundus. Furthermore, the depletion of this photosensitive store and its replenishment via long-term electrical field stimulation were demonstrated in the same tissue. In relation to these results, the aim of the present study was to investigate the putative role of S-nitrosothiols in the restorative effect of long-term electrical field stimulation on the reduced photosensitive store. Two series of UV light-elicited relaxations (photorelaxations) were obtained, and the magnitudes of the responses were 53 +/- 6 and 26 +/- 3%, respectively. The second series of photorelaxations attenuated statistically when compared with those in the first series. Ethacrynic acid (1 microm), diamide (1 microm) and glutathione (1 microm) had no effect on the photorelaxations occurred in the second series of responses. Electrical field stimulation (4 Hz, 25 V, 1 ms, 60 min), applied between two series of photorelaxations, revealed a complete recovery of the attenuated photorelaxations appeared in the second series. N(G)-monomethyl-L-arginine (100 microm), ethacrynic acid (1 microm) and diamide (1 microm) extensively prevented the restorative effect of electrical field stimulation on photorelaxations. In addition, glutathione (1 microm) reversed the prevention achieved by ethacrynic acid and diamide. The conclusion is that the restoration accomplished by electrical field stimulation is because of the activation of nitric oxide synthase, which in turn brings about the regeneration of GSNO proposed to be the photodegradable material store.