The use of deep seawater (DSW) in thalassotherapy has begun in Japan. To clarify the health effects of DSW on the human body, we investigated the changes in plasma lactate and pyruvate concentrations, or subjective judgment scores, after bathing at rest in 9 healthy young men. Subjects were immersed for 10 minutes in DSW, surface seawater (SSW), and tap water (TW) heated to 42°C. Plasma samples were collected before bathing, immediately after bathing, and 60 minutes after bathing. The scores were obtained by an oral comprehension test. In the DSW bathing, plasma lactate and pyruvate concentrations showed no significant changes immediately after bathing or 60 minutes after bathing. In contrast, subjects who bathed in SSW showed a significant decrease in lactate concentrations 60 minutes after bathing compared with immediately after bathing. Subjects who bathed in TW showed a significant increase in lactate concentrations immediately after bathing compared with before bathing, and they showed a significant decrease in lactate and pyruvate concentrations 60 minutes after bathing. We found no significant change in the thermal sensation score in the DSW bathing, though significant differences were found between before and immediately after bathing in the SSW and TW groups. Moreover, the score decreased significantly 60 minutes after bathing compared to immediately after bathing in the TW bathing. Higher concentrations of salts contained DSW such as sodium, nitrate-nitrogen, phosphate-phosphorus, and silicate-silicon may have a good influence on human health. Although additional studies are needed to support our findings, DSW is the mildest water to the human body among the three kinds of water, since no significant changes in the items measured were found only in DSW.
This experiment was carried out to investigate the effect of N. sativa L. on histopathology of pancreatic β-cells, and blood insulin and glucose concentrations in streptozotocin-induced diabetic rats. Fifty male Wistar rats (200-250 g) were divided into two experimental groups (diabetics with no treatment and diabetics with N. sativa L. treatment), each containing twenty-five rats. Diabetes was induced in both groups by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg). The experimental animals in both groups became diabetic within 24 hours after the administration of STZ. The rats in N. sativa L.-treated group were given the daily intraperitoneal injection of 0.20 ml/kg of N. sativa L. volatile oil for 30 days starting the day after STZ injection. Control rats received only the same amount of normal saline solution. The rats in both groups received the last injection 24 hours before the sacrification and 5 randomly-selected rats in each group were sacrificed before, and the 1, 10, 20 and 30 days after the STZ injection to collect blood and pancreatic tissue samples. The N. sativa L. treatment caused a decrease in the elevated serum glucose, an increase in the lowered serum insulin concentrations and partial regeneration/proliferation of pancreatic β-cells in STZ-induced diabetic rats with the elapse of the experiment. It is concluded that the hypoglycaemic action of N. sativa L. could be partly due to amelioration in the β-cells of pancreatic islets causing an increase in insulin secretion. More studies are needed to demonstrate the exact mechanism of action of N. sativa L. on ameliorated blood glucose concentration in STZ-induced diabetes.
Levamisole is an immunopotenciator drug which is used as an antihelmintic drug as well as very effective remedy on cellular immunity compared with humoral immunity. A total 71 patients (37 men, 34 women) who referred to our department between March 1997 and December 2001, with a history of the disease for about 1 year, were diagnosed as having chronic brucellosis through those tests brucella serum agglutination test (SAT), SAT with Coombs and SAT with 2-mercaptoethanol. The patients were randomly divided into levamisole group (36 patients) and control group (35 patients). All patients were given rifampicin 600 mg/day + doxycycline 200 mg/day for 6 weeks as a standard classical combined therapy for brucellosis. In the levamisole group, oral levamisole 80 mg every other day for 6 weeks was added to the treatment. There was a statistically significant difference between two groups, in complaints of arthralgia, fatigue and sweats before and 6 months after treatment, as well as in erythrocyte sedimentation rate and C-reactive protein elevations and lymphomonocytosis finding. While it was provided both clinical and serological improvement in all patients in the levamisole group; 11 patients in the control group did not improve both clinically and in view of specific and nonspecific laboratory findings and a recurrence occurred in one case, in this group. In conclusion, levamisole added to classical antibiotic therapy in treatment of chronic brucellosis was found quite efficient in all patients in providing adequate clinical and laboratory response in comparison to classical antibiotic therapy alone.
Mutations of p53 are rare in primary and advanced neuroblastomas. The p53 gene was studied in a TGW cell line established from a TNB1 xenograft, derived from metastasized neuroblastoma. The p53 protein level in TGW was elevated at baseline. Treatment with doxorubicin to induce genotoxic stress neither altered the p53 protein level nor induced p21 protein within 24 hours. DNA sequencing analysis revealed a novel triplet deletion mutation at codon 282 (R282del) of the p53 gene, a mutation also found in TNB1, indicating that the mutation occurred in the relapsed tumor. The mutant was incapable of transactivation and had no effect on the transactivational activity of the wild-type p53 gene product in reporter assays using a plasmid possessing a p53 responsive element of p21, bax or mdm2. These results suggest that the mutant p53R282del found in TGW is a non-functional mutant and has no dominant negative nature.
The current study was designed to characterize the role of Rho and Rho-dependent kinase (Rho-kinase) in isometric contractile responses induced by serotonin (5-HT) and a solution containing 40 mM K+ (high K+) in ring preparations of the middle cerebral artery of bovine. Application of W-7, a Ca2+-calmodulin inhibitor, reversibly and equally attenuated the amplitudes of contractions produced by both 5-HT and high K+. Similar effects were observed with ML-7, an inhibitor of myosin light chain kinase. Surprisingly, the protein kinase C inhibitors, calphostin C and Ro-31-8220, had no effect on the 5-HT-induced contraction. Incubation of preparations with Clostridium difficile toxin A and B or with Clostridium botulinum C3 exoenzyme for 48 hours attenuated the 5-HT-induced response but not the high K+-induced response. Application of the Rho-kinase inhibitor, Y-27632, resulted in marked inhibition of the 5-HT-induced response but had negligible effect on the high K+-induced response. These results suggest that the activation of Rho and Rho-kinase may be involved in the generation of the contraction produced by 5-HT in the bovine middle cerebral artery, while protein kinase C plays, if any, an insignificant role on the contraction.
Fibrates are widely used hypolipidemic agents that activate the peroxisome proliferator-activated receptor α (PPARα) and regulate the expression of many genes involved in lipid metabolism. We studied the mechanism of the effect of clofibrate on cholesterol homeostasis. Rats were fed with chow containing clofibrate, cytochrome P-450 inhibitor ketoconazole, or clofibrate plus ketoconazole. Control rats were fed only with normal chow. The levels of six oxysterols in liver microsome were determined. The levels of mRNAs for liver X receptor alpha (LXRα), ATP-binding cassette A1 (ABCA1), PPARα and cholesterol 7α-hydroxylase (CYP7A) in the liver were analyzed by northern blotting. Clofibrate administration decreased plasma levels of total cholesterol and triglyceride and increased high-density lipoprotein-cholesterol (HDL-C). Clofibrate increased the levels of liver microsomal oxysterols including 25- and 27-hydroxycholesterol, which are potent activators of LXRα. Clofibrate also enhanced the expression of mRNAs for PPARα, LXRα, and ABCA1. Simultaneous administration of ketoconazole suppressed the effects of clofibrate on plasma lipids, hepatic oxysterol levels, and the expression of the genes. Clofibrate increases cytochrome P450 content and the resulting oxysterol generation may partly mediate the clofibrate-induced up-regulattion of LXRα and ABCA1, which are related to reverse cholesterol transport.
The aim of this study was to clarify the relationship between cardiac sympathetic nervous activity (SNA) assessed by radioiodinated metaiodobenzylguanidine (123I-MIBG), an analogue of norepinephrine and cardiovascular functions in patients with chronic heart failure (CHF). Subjects were 17 patients with CHF. A dose of 111 MBq of 123I-MIBG was administered intravenously, and 5-minute anterior planar images were obtained 15 minutes (early image) and 3 hours (delayed image) after the injection. The heart/mediastinum (H/M) count ratio was defined to quantify cardiac 123I-MIBG uptake. The washout ratio (WR) of 123I-MIBG from the heart was calculated as follows: (early counts−delayed counts)/early counts×100 (%). Echocardiography was performed on all patients within 1 week of 123I-MIBG scintigraphy to measure stroke volume index (SVI). Blood pressure and heart rate (HR) in the resting state were also recorded to calculate cardiovascular functions including cardiac output, pulse pressure (PP), and mean blood pressure. Significant linear correlations were found between the early H/M ratio of 123I-MIBG and SVI, and between the delayed H/M ratio of 123I-MIBG and SVI, respectively. WR of 123I-MIBG was correlated with HR, and was inversely correlated with SVI and with PP, respectively. It is likely that a decrease in SVI is associated with enhanced cardiac SNA in severe CHF. 123I-MIBG scintigraphy is effective in assessing the cardiac functional status and SNA in patients with CHF in vivo. Moreover, changes in PP and HR indicate well alteration in SNA.
In this study, we investigated whether the variant of the β3-adrenoceptor gene is associated with accumulation of body fat in Japanese junior high school students. A total of 87 junior high school students, 50 boys and 37 girls, participated in this survey. The β3-adrenoceptor gene variant was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Accumulation of body fat was assessed by skinfold thickness at the triceps and subscapular with a skinfold caliper. There was no difference between boys and girls in the frequency of the β3-adrenoceptor gene allele. There were no significant differences in body mass index and percent body fat between the Arg carriers (Trp/Arg or Arg/Arg) and the Arg noncarriers (Trp/Trp) for either sex. The Trp64Arg variant of the β3-adrenoceptor gene does not seem to have a strong effect on the accumulation of body fat in this group of Japanese junior high school students.
The lumbosacral region, with its manifold variations and anomalies, is one of the most important section of the entire spine. From the fusion defects to the segmentation anomalies, a wide variety of malformation exists in this region. Individuals with such anomalies usually have no physical complaints until their spines undergo pathological conditions. Two patients with a variety of lumbosacral vertebra anomalies are described. Each of them had a different malformation, but low back pain was the common complaint of these patients. According to our knowledge, these cases have never been reported before. We analysed their clinical and radiological features and discussed with the literature.