Effects of N-acetyl-L-cysteine on Teratogenicity of Cadmium in Mice

ABSTRACT Embryotoxicity and teratogenicity of cadmium (Cd) and modulation of its effects by N-acetyl-L-cysteine (NAC) were evaluated in mice. Pregnant ICR mice were intraperitoneally injected with 3.5 mg/kg of CdCl₂ on day 10 or 11 of gestation (vaginal plug = day 0). Pregnant mice were pretreated with 160 mg/kg of NAC intravenously 2 hours before dosing with CdCl₂. Pregnant mice were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations, cleft palate and abnormal palatal rugae. There was little difference in body weight gain of dams during the gestation period in the groups treated with NAC plus Cd as compared with the groups treated with Cd alone. Pretreatment with 160 mg/kg of NAC decreased the fetal mortality, incidence of cleft palate and abnormal palatal rugae induced by Cd on day 11. On day 10, pretreatment with NAC decreased the incidence of Cd induced abnormal palatal rugae. These results clearly indicate that NAC exerts protective effects against embryotoxicity and teratogenicity of Cd.     

Factors associated with contraceptive practices of married women in Bangladesh with respect to their employment status.

OBJECTIVE: There might be a difference between non-working and working women in their perception of rights and privileges which may influence their contraceptive behavior. The purpose of this study was to examine contraceptive behavior among non-working and working women in Bangladesh determining associated factors. METHOD: Analysis was based on data from the 1999-2000 Bangladesh Demographic and Health Survey which employs nationally representative sample. RESULTS: The prevalence of current contraceptive use (any method) was 58.2% among non-working women and 65.5% among working women. Both rates are still low for the country. Some factors, such as discussed family planning with husband, husband approves family planning, desire for more children, and husband lives together, were influential determinants of lower contraceptive prevalence among the non-working women. CONCLUSION: The results indicate a necessity for social activities promoting husband-wife communication and women's participation in employment to enhance the use of contraceptives among Bangladeshi women, especially non-working women.     

A double-blind dose-ranging study of risedronate in Japanese patients with osteoporosis (a study by the Risedronate Late Phase II Research Group)

To determine the clinical recommended dosage regimen of risedronate for the treatment of involutional osteoporosis in Japanese patients, dose-response relationships for the efficacy and safety of this drug were investigated using a multi-center, randomized, double-blind, parallel group comparative design with four dose levels of risedronate (placebo, 1 mg, 2.5 mg and 5 mg per day). A total of 211 patients diagnosed with involutional osteoporosis according to the criteria proposed by the Japanese Society for Bone and Mineral Research were randomized and received one of the four doses once daily for 36 weeks. All patients were supplemented with 200 mg of calcium daily in the form of calcium lactate. The primary efficacy endpoint was the percent change in bone mineral density of the lumbar spine (L2-L4 BMD) determined by dual-energy X-ray absorptiometry (DXA) from baseline to the time of final evaluation. Changes in biochemical markers of bone turnover and safety profile were also compared. Percent changes in L2-L4 BMD at final evaluation in the placebo, and 1-, 2.5-, and 5-mg risedronate groups were 0.79+/-5.30, 2.71+/-4.93, 5.29+/-3.96, and 5.15+/-4.25% (mean+/-SD), respectively. A linear dose-response relationship was obtained up to a dose of 2.5 mg, whereas no further increase in BMD was observed at 5 mg. The decrease in bone turnover markers, including N-terminal osteocalcin, phosphorus, and urinary deoxypyridinoline, also showed a linear dose-response relationship up to a dose of 2.5 mg. Alkaline phosphatase level decreased linearly up to a dose of 5 mg. Risedronate was well tolerated in this 36-week study with 1- to 5-mg doses. Neither the overall incidence of adverse events nor the percentage of patients without problem in overall safety assessment differed significantly among the dose groups including the placebo group. Based on these results, a once-daily dose of 2.5 mg of risedronate, which is half that used in Caucasians, is recommended for the treatment of involutional osteoporosis in Japanese patients.     

Atrial septal defect repair through limited lateral thoracotomy in children

Objective We have developed a surgical method for atrial septal defect repair through a limited right lateral thoracotomy in which the incision line begins 2 cm caudal from the lower angle of the scapula and ends at the midaxial line, thereby improving patient satisfaction with the cosmetic results of treatment. Methods We performed a retrospective review of 28 patients who underwent isolated atrial septal defect repair through a limited right lateral thoracotomy between January 2002 and August 2004. The mean age and mean body weight at the time of the operation were 85.8 months (range 9–236 months) and 23.0 kg (range 8.0–56.0 kg), respectively. All repaired defects were the ostium secundum type. Results There was no operative or late mortality and no late morbidity after a mean follow-up of 26 months (range 12–41 months). Echocardiography showed no residual shunt in any of the patients. The mean length of the skin incision was 7.8 cm (range 5.0–11.0 cm), and almost all the patients had satisfactory cosmetic results. Conclusion The atrial septal defect repair through a limited right lateral thoracotomy in pediatric patients showed satisfactory surgical results and excellent cosmetic results.     

Inhibitory effect of activated protein C on platelet aggregation induced by the prothrombin-converting reaction

The present study was undertaken to elucidate the effect on platelet aggregation of the prothrombin-converting reaction on platelets with or without activated protein C (APC). A reaction mixture of washed platelets from human individuals, Factor Xa and prothrombin markedly induced platelet aggregation; maximum aggregation rates, 31.3–92.5%, and times to reach to maximum aggregation, 11.6 to 20.1 min. This aggregation was inhibited by the addition of APC with 50% inhibition concentration (IC₅₀) value of 14.4 U/ml. APC also inhibited thrombin generation in the reaction mixture in a dose-dependent manner with IC50 value of 0.96 U/ml. However, APC did not inhibit the thrombin (0.1 CU/ml)-induced platelet aggregation at concentrations of up to 30 U/ml. These findings suggest that APC has no direct inhibitory effect on platelet aggregation and that APC inhibits platelet aggregation through inhibition of thrombin generation.     

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line.

Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype.     

Antiinflammatory properties of the new antirheumatic agent 4-acetylaminophenylacetic acid

The antiinflammatory activity of 4-acetylaminophenylacetic acid (MS-932) was investigated. MS-932 did not suppress the acute inflammation of carrageenin-induced paw edema in rats or of primary swelling in adjuvant arthritic rats. However, prophylactic treatment with MS-932 inhibited secondary inflammation in adjuvant arthritic rats. MS-932 also restored to normal the weight of the spleen and the serum albumin/globulin ratio of adjuvant arthritic rats. In addition to its prophylactic effect, MS-932 had a therapeutic effect on adjuvant arthritis. In in vitro tests, MS-932 did not inhibit prostaglandin E2 biosynthesis from arachidonic acid by sheep seminal vesicle microsomal enzyme or superoxide generation by guinea pig neutrophils stimulated with opsonized zymosan. MS-932 had no analgesic effect in mice and no antipyretic effect in rats. These results indicate that MS-932 suppresses adjuvant arthritis through modulation of the immune system.     

Late massive hemoptysis after transbronchial biopsy of hamartoma: an involvement of pulmonary artery and vein.

Pulmonary hamartoma is a common benign neoplasm that is usually asymptomatic and that arises in the periphery of the lung. However, when the tumor is growing without showing characteristic findings of hamartoma, such as involving calcification, fat density, and chondromatous contents in chest X-rays or computed tomography, the diagnosis is sometimes that problematic and definitive histological diagnosis should be established. We herein report a case with a massive hemoptysis 10 days after a successful transbronchial biopsy. A 69-year-old man who underwent mitral valve plasty 6 years earlier presented a left lung shadow during a routine chest X-ray. The shadow was seen to be growing by a series of chest X-rays. A week after warfarin had been stopped, a bronchoscopic biopsy was performed. No bronchial hemorrhage was observed during the procedure, and warfarin was not restarted. The patient began noticing bloody sputa once or twice a day, and 10 days after the biopsy, 400 mL of hemoptysis was suddenly disgorged. An emergency left upper lobectomy of the lung was performed, and the hemoptysis soon disappeared postoperatively. The patient is well without respiratory symptoms 36 months after the surgery.     

Associations of brachial-ankle pulse wave velocity and carotid atherosclerotic lesions with silent cerebral lesions.

Silent cerebral lesions are increasingly found in mass screenings using MRI and magnetic resonance angiography (MRA). The purpose of this paper is to assess the usefulness of two non-invasive clinical tests-carotid ultrasound examination and brachial-ankle pulse wave velocity (baPWV) measurement-for predicting silent cerebral infarction (SCI) and silent intracranial arterial stenosis. Data were collected on 480 asymptomatic adult subjects who participated in a brain screening program at a single hospital between April 2003 and March 2006. All participants underwent baPWV measurement, B-mode ultrasonography of carotid arteries, MRI, and MRA. Data on 476 (99.1%) subjects were included in the analysis. Among these, 273 (57.4%) were male and the mean age was 51.5 years; 161 (33.8%) had carotid plaque; 33 (6.9%) had increased intima-media thickness (IMT); 99 (20.8%) had SCI; and 7 (1.5%) had intracranial arterial stenosis. The multivariate analysis showed that age (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.08-1.17), carotid plaque (OR: 2.69; 1.59-4.56), increased IMT (OR: 2.40; 1.02-5.65), and a history of hypertension treatment (OR 2.22; 1.11-4.43) were significantly associated with SCI. Also, increased IMT (OR 9.70: 1.48-63.71) was related to intracranial arterial stenosis. Brachial-ankle PWV was related to SCI (p<0.01) and intracranial stenosis (p=0.01) in univariate analysis but not in multivariate analysis. The presence of carotid plaque and that of increased IMT on ultrasound examination are useful for assessing the risk of SIC. Increased IMT is also predictive of intracranial arterial stenosis.     

Epicardial radiofrequency ablation for chronic atrial fibrillation undergoing simultaneous on-pump beating coronary artery bypass grafting

Off-pump coronary artery bypass grafting has become an attractive surgical alternative for myocar-dial revascularization because of the advantage of myocardial protection and other benefits of patients. However, it is still regarded as a controversial treatment for the coronary artery disease accompanied by atrial fibrillation (AF). A significant number of patients in need of coronary revascularization have chronic AF. Although the Cox-Maze III procedure is the gold standard for the surgical treatment of AF, few of these patients undergo AF operations at the time of their coronary bypass grafting. We report herein a case of the pulmonary vein isolation to eliminate the AF by means of epicardial radiofrequency ablation combined with 2 vessels coronary artery bypass grafting on the beating heart with the aid of cardiopulmonary bypass.