The effect of horse simulator riding on visual analogue scale, body composition and trunk strength in the patients with chronic low back pain.

BACKGROUND: Chronic low back pain (CLBP) is one of the most common musculoskeletal disorders, and thus effective treatments are required. Recently, real horseback riding has been reported to be beneficial for the patients. However, it has some limitations, such as limited approaches and safety issues. OBJECTIVE: The purpose of this study was to investigate the effect of horse simulator riding on back pain, body composition and trunk strength in the patients with CLBP. PARTICIPANTS: Forty-seven men with CLBP (mean age 20.55 ± 1.38 years) were randomly divided into a control group (n = 23) and a horse simulator riding group (n = 24), and visual analogue scale (VAS), body composition and isokinetic trunk strength were measured after 8 weeks for which subjects in a horse simulator riding group had performed the horse simulator exercise (HSE). RESULTS: Horse simulator exercise significantly reduced pain scores of VAS and enhanced isokinetic torques of trunk at 30 and 90°/s. There were also significantly increased muscle mass and decreased fat mass in horse simulator riding group. CONCLUSION: It can be inferred that HSE may be helpful in relief of back pain and recovery of back function through developing trunk strength and balancing the ratio of trunk flexor/extensor muscles.

DA-9601 inhibits activation of the human mast cell line HMC-1 through inhibition of NF-kappaB.

Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-alpha, IL-1beta, and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601 attenuated PMA- and A23187-induced activation of NF-kappaB as indicated by inhibition of degradation of IkappaBalpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases.

Effects of cysteine on the pharmacokinetics of intravenous phenytoin in rats with protein-calorie malnutrition.

The effects of cysteine on the pharmacokinetics of phenytoin and one of its metabolites, 5-(p-hydroxyphenyl)-5-phenylhydantoin (pHPPH) were investigated after intravenous administration of phenytoin, 25 mg/kg, to control rats (4-week fed on 23% casein diet) and rats with PCM (protein-calorie malnutrition, 4-week fed on 5% casein diet) and PCMC (PCM with oral cysteine supplementation, 250 mg/kg, twice daily starting from the fourth week). In rats with PCM and PCMC, the phenytoin hydroxylation (to form pHPPH) activities were significantly smaller (164, 103 and 95.3 pmol/min per mg protein for the control rats, and rats with PCM and PCMC, respectively) than that in control rats. In rats with PCMC, the intrinsic clearance of phenytoin, CL(int) was significantly slower than those in control rats and rats with PCM (0.175, 0.131 and 0.044 ml/min). The above data suggested that the formation of pHPPH could be reduced in rats with PCM and PCMC. This was supported by significantly smaller 24-h urinary excretion of pHPPH (54.7, 35.6 and 32.5% of intravenous dose of phenytoin) in rats with PCM and PCMC than that in control rats. In rats with PCM, the maximum velocity (0.344, 0.203 and 0.196 microg/min), apparent volume of distribution in central compartment (44.4, 65.4 and 72.2 ml/kg) of phenytoin, and total area under the plasma concentration-time curve from time zero to time infinity (609, 714 and 1210 microg min/ml), renal clearance (20.5, 13.4 and 4.67 ml/min per kg) and 24-h urinary excretion (54.7, 35.6 and 32.5% of intravenous dose of phenytoin) of pHPPH were not returned to control levels by cysteine supplementation (rats with PCMC). This could be mainly due to the fact that the phenytoin hydroxylation activity in rats with PCMC was not returned to control level.

Effects of cysteine on the pharmacokinetics and pharmacodynamics of intravenous and oral azosemide in rats with protein-calorie malnutrition.

The effects of cysteine on the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous (10 mg/kg) and oral (20 mg/kg) administration to male Sprague-Dawley rats fed on 23% protein diet (control rats), and 5% protein diet with (rats with PCMC) or without (rats with PCM) oral cysteine (250 mg/kg, twice daily for the fourth week) for 4 weeks. After intravenous administration to rats with PCMC, some pharmacokinetic parameters restored fully or more than the level of control rats; the time-averaged nonrenal clearance (2.70 versus 2.32 ml/min/kg) and apparent volume of distribution at steady state (160 versus 189 ml/kg) were comparable to those in control rats, however, the terminal half-life (34.7 versus 57.2 min) and mean residence time (73.3 versus 99.3 min) were significantly shorter, area under the plasma concentration-time curve from time zero to time infinity (AUC, 1930 versus 2680 microg min/ml) was significantly smaller, and time-averaged renal (2.24 versus 1.21 ml/min/kg) and total body (CL, 4.98 versus 3.65 ml/min/kg) clearances were significantly faster than those in control rats. This could be mainly due to significantly faster renal clearance and at least partly due to increased cytochrome P450 1A2 activity by cysteine supplementation. After intravenous administration to rats with PCMC, the total amount of 8-hr urinary excretion of unchanged azosemide was significantly greater (457 versus 305 microg/g body weight), however, the 8-hr urine output (15.3 versus 31.1 ml/g kidney) was not significantly different between control rats and rats with PCMC. This could be due to the fact that urine output seemed to reach an upper plateau from 10 mg/kg dose of azosemide in rats.

Costunolide induces apoptosis by ROS-mediated mitochondrial permeability transition and cytochrome C release.

Costunolide is an active compound isolated from the root of Saussurea lappa Clarks, a Chinese medicinal herb, and is considered a therapeutic candidate for various types of cancers. Nevertheless, the pharmacological pathways of costunolide are still unknown. In this study, we investigate the effects of costunolide on the induction of apoptosis in HL-60 human leukemia cells and its putative pathways of action. Using apoptosis analysis, measurement of reactive oxygen species (ROS), and assessment of mitochondrial membrane potentials, we show that costunolide is a potent inducer of apoptosis, and facilitates its activity via ROS generation, thereby inducing mitochondrial permeability transition (MPT) and cytochrome c release to the cytosol. ROS production, mitochondrial alteration, and subsequent apoptotic cell death in costunolide-treated cells were blocked by the antioxidant N-acetylcystein (NAC). Cyclosporin A, a permeability transition inhibitor, also inhibited mitochondrial permeability transition and apoptosis. Our data indicate that costunolide induces the ROS-mediated mitochondrial permeability transition and resultant cytochrome c release. This is the first report on the mechanism of the anticancer effect of costunolide.

Prevention of c-Jun/activator protein-1 activation and microsomal epoxide hydrolase induction in the rat liver by cysteine during protein-calorie malnutrition.

Protein-calorie malnutrition (PCM), a major global health problem, arises during protein and/or energy deficit due to disease and nutritional inadequacy. To date, cellular adaptive responses and gene expression associated with PCM remain poorly understood. In view of the primary role of the liver in energy conversion, the present study was designed to investigate changes in hepatic morphology and molecular alterations during PCM. PCM caused marked decreases in the cytoplasmic eosinophilic content and nuclear shrinkage in the hepatocytes with a decrease in glutathione content. The nuclear activator protein-1 (AP-1) complex was activated in the liver of PCM rats. AP-1-binding activity of nuclear extracts produced from PCM rats was reduced by the presence of anti-c-Jun antibody. Microsomal epoxide hydrolase (mEH), a phase II detoxifying enzyme, was 4-fold induced, with a 20-fold increase in the mRNA level during PCM. In contrast to the PCM-induced changes in hepatic morphology, PCM rats supplemented with cysteine showed an increase in the GSH level and well-preserved hepatic structures with mild fat degeneration. Cysteine supplementation inhibited the activation of AP-1 and the induction of mEH in PCM rats. These results provided evidence: (i) that PCM alters liver morphology with a decrease in the glutathione level; (ii) that cysteine may serve as a key element responsible for preserving hepatic morphology and maintaining the glutathione level; and (iii) that cysteine was active in preventing the activation of AP-1 and mEH induction in the liver during PCM.

Effects of cysteine on the pharmacokinetics of intravenous adriamycin in rats with protein-calorie malnutrition.

In rats with protein-calorie malnutrition (PCM, 5% caseine diet for 4 weeks), hepatic cytochrome P450 levels suppressed markedly and cytochrome P450 mRNAs decreased significantly compared with those in control rats (23% caseine diet for 4 weeks), however, the values completely (or partially) returned to control levels by a week (from fourth week) of cysteine supplementation (rats with PCMC) (Cho, Kim et al., Arch. Biochem. Biophys. 1999, 372: 150-158). The formation of aglycone metabolites of adriamycin and adriamycinol, M3 and M4, respectively, seemed to be induced (Lee and Lee, Res. Commun. Mol. Pathol. Pharmacol. 1999, 105: 87-96) by pretreatment with dexamethasone (possibly by hepatic cytochrome P450 RL 33/cDEX, Komori and Oda, J. Biochem. 1994, 116: 114-120) in rats. Adriamycin, 16 mg/kg, was administered intravenously in 1-min to control rats and rats with PCM and PCMC. In rats with PCM, the plasma concentrations of adriamycin was higher (the area under the plasma concentration-time curve from time zero to 12 hr, AUC(0-12 hr), tended to be higher) and 24-hr urinary excretion of M3 (including its 'conjugates') seemed to increase than those in control rats, suggested that the formation of M3 was inhibited in rats with PCM. In rats with PCMC, the plasma concentrations of adriamycin were lower (the AUC(0-12 hr) was significantly smaller) and 24-hr urinary excretion of M3 (including its 'conjugates') were significantly greater than those in rats with PCM, suggested that the formation of M3 increased significantly by cysteine supplementation by restoring the enzyme system(s) that metabolize adriamycin to M3. The altered pharmacokinetic parameters of adriamycin mentioned above in rats with PCM returned to greater than those of control rats after cysteine supplementation (rats with PCMC). Above data suggested that other hepatic cytochrome P450 isozyme(s) which catalyze(s) the formation of M3 from adriamycin could be induced by cysteine supplementation.

Suppression of rat hepatic cytochrome P450s by protein-calorie malnutrition: complete or partial restoration by cysteine or methionine supplementation.

Pharmacokinetic profiles of therapeutic agents are altered by protein-calorie malnutrition (PCM). The current study was designed to determine the expression of hepatic cytochrome P450s in rats after protein restriction and to investigate its molecular basis. Western blot analysis revealed that rats with protein restriction for 4 weeks exhibited marked suppression in the hepatic P450 1A2, 2C11, 2E1, and 3A1/2 levels. Northern blot analysis showed that hepatic P450 1A2, 2C11, and 3A1/2 mRNAs were significantly decreased in the state of PCM. The P450 2E1 mRNA level was slightly decreased in PCM rats, suggesting the possibility that expression of P450 2E1 affected by PCM might result from the transcriptional and/or posttranscriptional regulation. PCM-induced changes in most P450 expression completely or partially returned to control levels by a week of cysteine supplementation. Cysteine also prevented decreases in P450 1A2, 2C11, 2E1, and 3A1/2 mRNA levels by PCM. Methionine was minimally active in restoring the P450 expression. A metabolic change in hepatic ethoxyresorufin dealkylase activity in PCM rats was consistent with the P450 apoprotein and mRNA levels. Although the plasma concentrations of azosemide, a loop diuretic, primarily metabolized by cytochrome P450 1A, increased in protein-deprived rats, cysteine supplementation significantly reduced the increased plasma concentrations of the drug. The altered pharmacokinetic parameters of azosemide in PCM rats returned to those of control after cysteine supplementation, corroborating the conclusion that cysteine was effective in restoring cytochrome P450 expression and metabolic activities.

Use of illicit drugs among high-school students in Jamaica.

Reported are the results of a survey to assess the prevalence of illicit drug use among high-school students in Jamaica. A total of 2417 high-school students in 26 schools were covered: 1063 boys and 1354 girls of whom 1317 were grade-10 students (mean age 15.7 years) and 1100 were grade-11 students (mean age 16.8 years). Of the students, 1072 and 1345 were from rural and urban schools, respectively, while 1126 and 1291 were children of parents who were professionals and nonprofessionals, respectively. The following drugs were used by the students: marijuana (10.2%), cocaine (2.2%), heroin (1.5%) and opium (1.2%). Illicit drug use among males, urban students and children of professionals was higher than that among females, rural students and children of nonprofessionals, respectively.

Determination of a new antiulcer agent, eupatilin, in rat plasma, bile, urine, and liver homogenate by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a new antiulcer agent, eupatilin, in rat plasma, urine, bile, and liver homogenate. The method involved deproteinization of biological sample with the same volume of acetonitrile. A 100 microl aliquot of the supernatant was injected onto a C18 reversed-phase column. The mobile phase employed was ammonium acetate buffer (1% ammonium acetate and 0.5% acetic acid) - acetonitrile (58:42, v/v) and the flow rate was 1.0 ml/min. The column effluent was monitored by a ultraviolet detector set at 350 nm. The retention time for eupatilin was approximately 6.5 min. The detection limits for eupatilin in rat plasma, urine, bile, and liver homogenate were 50, 50, 100, and 100 ng/ml, respectively. The coefficients of variation of the assay were generally low (below 7.46%) for rat plasma, urine, bile, and liver homogenate. No interferences from endogenous substances were observed.

Usefulness of CT in patients with ischemic colitis proximal to colonic cancer.

OBJECTIVE: The purpose of this study was to assess the usefulness of CT scans for distinguishing ischemic from tumoral segments in patients with colonic carcinoma complicated by proximal bowel ischemia. MATERIALS AND METHODS: CT scans of 20 patients with ischemic colitis proximal to obstructing colonic carcinoma were reviewed retrospectively. The concomitant presence of ischemia was proven on pathologic examinations in 12 patients and on barium enema studies in the remaining eight patients. CT scans were analyzed for the involved site and length, bowel wall thickness, enhancing pattern of both tumoral and ischemic segments, and changes in the pericolic space. The results of tumor staging on CT scans were compared with those of pathologic findings. RESULTS: Distinction of ischemic from tumoral segments could be made on CT in 15 (75%) of the 20 patients. Of the 20 patients, 18 had ischemic segments contiguously proximal to the tumoral segment, and the remaining two patients had a skipped zone with intervening normal mucosa. Tumoral segments were irregularly thickened in most patients. Maximum thickness ranged from 0.8 to 4.5 cm (mean, 2.0 cm). Most often the ischemic segment was concentrically and smoothly thickened, ranging from 0.6 to 1.5 cm (mean, 1.0 cm). The tumoral segments enhanced heterogeneously in 12 patients and enhanced homogeneously in the remaining eight, whereas ischemic segments enhanced homogeneously in 14 (70%) patients and heterogeneously in six. On CT scans, we saw the target or double halo sign in four (20%) patients. Pericolic vascular engorgement was 19 patients, two of whom were overstaged because pericolic vascular engorgement was interpreted as tumor infiltration. CONCLUSION: Although CT findings are not specific for certain groups of patients, they are often helpful in distinguishing tumoral from ischemic segments in patients with ischemic colitis proximal to colonic carcinoma. An understanding of this pathologic entity may increase the accuracy of CT for staging colonic carcinoma.

Comparison of three bowel preparations for sigmoidoscopy.

The efficacy of three lower bowel preparations in 96 patients undergoing rigid sigmoidoscopy was studied. The maximal length of insertion and clarity of view were assessed in each group and compared to patients without bowel preparation. Blood per rectum and diarrhoea were the main indications for sigmoidoscopy. The maximal insertion of the instrument was similar for all groups and the rectosigmoid junction was examined in the majority. The clarity of view was good in 71% of patients receiving Fleet enema, 68% of those receiving Dulcolax micro-enema, 36% in the Dulcolax suppository group and 16% in the group without bowel preparation. There were no adverse effects or complications arising from bowel preparation or sigmoidoscopy. Bowel preparation significantly improves the number of satisfactory sigmoidoscopic examinations, and the use of simple disposable enemas is safe and effective.

Colonoscopy in Jamaica--a 12-year experience.

Four hundred and nine colonoscopic examinations were performed in 335 patients over a 12-year period in Jamaica. The main indications were suspected polyps (34%) rectal bleeding (22%) and suspected carcinoma (11%). Total colonoscopy was performed in 33% of cases. The ascending colon and hepatic flexure were examined in a further 25%, and the transverse colon in another 21%. Endoscopic examination of the suspected abnormal area was possible in all cases. In 142 examinations, no abnormality was detected, reflecting a false positive Barium enema in some. Polyps were found in 135 examinations, diverticula in 69 and carcinoma in 13. There were no complications. Colonoscopy was more sensitive and specific than Barium enema. The Barium enema findings were incorrect in 91 of 224 examinations (41%). Colonoscopy is a safe and accurate procedure which enables improved patient management.

Colonoscopy in Jamaica: a 12 year experience

Four hundred and nine colonoscopic examinations were performed in 335 patients over a 12-year period in Jamaica. The indications were suspected polyps (34%), rectal bleeding (22%), and suspected carcinoma (11%). Total colonoscopy was performed in 33% of cases. The ascending colon and hepatic flexure were examined in a further 25%, and the transverse colon in another 21%. Endoscopic examination of the suspected abnormal area was possible in all cases. In 142 examinations, no abnormality was detected, reflecting a false positive Barium enema in som. Polyps were found in 135 examinations, diverticula in 69 and carcinoma in 13. There were complications. Colonoscopy was more sensitive and specific than Barium enema. The Barium enema findings were incorrect in 91 of 224 examinations (41%). Colonoscopy is a safe and accurate procedure which enables improved patient management