High Helicobacter pylori cure rate with sitafloxacin-based triple therapy.

BACKGROUND: Bacterial resistance of Helicobacter pylori to antibiotics is increasing and it often leads to failure of antibiotic treatment. A new sitafloxacin-based triple therapy was developed to counter this situation; the fluoroquinolone sitafloxacin has a low minimum inhibitory concentration for H. pylori. AIM: To investigate the efficacy in Japanese patients of sitafloxacin-based triple therapy and document its efficacy in relation to anti-microbial susceptibility. METHODS: We investigated the efficacy of a 1-week sitafloxicin-based regimen of rabeprazole 10 mg four times daily (q.d.s.), metronidazole 250 mg twice daily (b.d.) and sitafloxacin 100 mg b.d. in 180 H. pylori-positive Japanese patients (first-line treatment: n = 45, second-line; n = 41, third-line: n = 94). At 8 weeks, patients were given the (13) C-urea breath test to assess eradication status. RESULTS: Eradication rate was 92.2% [95% confidence interval (CI): 87.3-95.7%, 166/180] in intention-to-treat analysis. Although the eradication rate was higher in patients treated with first-line therapy [45/45 (100%, 95% CI: 83.4-100%)] than in those with second- [38/41 (92.7%, 80.1-98.5%)] or third-line therapy [83/94 (88.3%, 80.0-94.0%)], no significant differences were noted with respect to the number of previous therapy attempts (P = 0.054). Eradication rates in patients infected with sensitive- and resistant strains to metronidazole were 96.6% (28/29) and 96.3% (77/80) (P = 0.941), respectively, while rates were 98.4% (60/61) in sitafloxacin-sensitive and 50.0% (1/2) in sitafloxacin resistant strains (P < 0.001). CONCLUSION: Sitofloxacin-based triple therapy with metronidazole b.d. and rabeprazole q.d.s. achieved an eradication rate exceeding 88%, irrespective of eradication history, CYP2C19 genotype, or metronidazole resistance status.

Effect of volitional relaxation and motor imagery on F wave and MEP: do these tasks affect excitability of the spinal or cortical motor neurons?

OBJECTIVE: To test if simple motor imagery, like thumb abduction, preferentially influences the excitability of the spinal or cortical motoneurons. METHODS: Ten healthy subjects underwent two separate experiments, each consisting of recording F waves and MEPs from abductor pollicis brevis (APB) in three consecutive sessions: (1) baseline, (2) after immobilizing APB for 3 h, and (3) after brief muscle exercise. During the immobilization, the subjects were instructed to volitionally relax APB in experiment 1 (relaxation task), and mentally simulate thumb abduction without actual movement in experiment 2 (imagery task). RESULTS: Relaxation task suppressed both MEPs and F waves. Motor imagery reduced this suppression, restoring F waves nearly completely (94%) and MEPs only partially (77%). Hence, the rest-induced decline of MEPs in part results from cortical modulation. In contrast, statistical analysis revealed no differences in imagery-induced recovery of motoneuron excitabilities whether assessed by F wave or MEP. Thus, increased excitability of spinal motoneurons responsible for F-wave changes also accounts for recovery of MEPs. CONCLUSIONS: Volitional relaxation depresses the spinal and cortical motoneurons, whereas mental simulation counters rest-induced suppression primarily by restoring spinal excitability. SIGNIFICANCE: The present findings help elucidate physiologic mechanisms underlying motor imagery.

Effect of motion imagery to counter rest-induced suppression of F-wave as a measure of anterior horn cell excitability.

OBJECTIVE: To test if motor imagery prevents the rest-induced suppression of anterior horn cell excitability. METHODS: Ten healthy subjects underwent two separate experiments, each consisting of stimulating the median nerve 100 times and recording F-waves from abductor pollicis brevis (APB) in three consecutive sessions: (1) after muscle exercise to standardize the baseline, (2) after immobilization of APB for 3h and (3) after muscle exercise to check recovery. We instructed the subject to volitionally relax APB in experiment 1 (relaxation task), and to periodically simulate thumb abduction without actual movement in experiment 2 (imagery task). RESULTS: F-wave persistence and amplitude declined after relaxation task and recovered quickly after exercise, but changed little with imagery task. F-wave latencies showed no change when analyzed individually. The frequency distribution of collective F-waves recorded from all subjects remained the same after relaxation task, but showed a shift toward longer latencies after imagery task. CONCLUSIONS: Mental imagery without overt motor output suffices to counter the effect of sustained volitional muscle relaxation, which would, otherwise, cause a reversible reduction in anterior horn cell excitability. SIGNIFICANCE: This finding documents the importance of central drive for spinal excitability, which affects F-wave studies of a paretic muscle.

Antioxidant potential of qizhu tang, a chinese herbal medicine, and the effect on cerebral oxidative damage after ischemia reperfusion in rats.

A traditional Chinese herbal medicine, Qizhu Tang (QZT) was studied for its in vitro antioxidant activity and the effect on cerebral oxidative damage after forebrain ischemia followed by reperfusion in rats. The QZT decoction was shown to have strong hydroxyl radical (*OH) scavenging activity (approx. 0.1 mM as Trolox equivalent) when determined by ESR using DMPO as a spin trap reagent and H2O2/UV as the *OH source. When the QZT decoction was injected into rat duodenum 2 h before cerebral ischemia, the oxidative brain damage after 45 min reperfusion was strongly inhibited in terms of two biochemical indications, thiobarbituric acid reactive substance formation and the loss of glutathione peroxidase. Since the QZT formula consists of 4 herbal constituents (Rhizoma atractylodis, Poria, Radix notoginseng and Radix astragali), each of the component herbs and their combinations were also examined for their protective effects on the cerebral ischemia/reperfusion injury and the effects were compared with their in vitro antioxidant potential. Although some of the incomplete formulas showed as strong antioxidant activities as complete QZT in vitro, only the complete QZT formula was effective in preventing cerebral oxidative injury in rats, and other preparations showed limited activity in vivo.

Clinical evaluation of leukocyte-depleted blood cardioplegia for pediatric open heart operation.

BACKGROUND: Blood cardioplegia (BCP) is widely used for myocardial protection during open heart operation. However, BCP may have a chance to induce neutrophil-mediated myocardial injury during aortic cross-clamping. We clinically evaluated the myocardial protective effect of leukocyte-depleted blood cardioplegia (LDBCP) for initial and intermittent BCP administration in pediatric patients. METHODS: Fifty patients undergoing open heart operation for congenital heart disease between January 1997 and March 1999 were reviewed. Twenty-five were administered LDBCP for myocardial protection during ischemic periods (LDBCP group), and the remaining 25 were given BCP without leukocyte depletion (BCP group). RESULTS: The difference in plasma concentrations of malondialdehyde between coronary sinus effluent blood and arterial blood just after reperfusion in the LDBCP group (1.68 +/- 0.56 micromol/L) was significantly lower than that in the BCP group (2.35 +/- 0.62 micromol/L; p < 0.01). The LDBCP group showed significantly lower plasma concentrations of human heart fatty acid-binding protein at 50 minutes after reperfusion (LDBCP group, 103.5 +/- 38.7 IU/L; BCP group, 144.8 +/- 48.8 IU/L; p < 0.01) and the peak value of creatine kinase-MB during the first 24 postoperative hours (LDBCP group, 17.0 +/- 8.5 IU/L; BCP group, 26.0 +/- 11.6 IU/L; p < 0.01) than did the BCP group. The maximum dose of catecholamine was significantly smaller in the LDBCP group (LDBCP group, 3.20 +/- 2.18 microg x kg(-1) x min(-1); BCP group, 5.60 +/- 2.83 microg x kg(-1) x min(-1); p < 0.01). CONCLUSIONS: These results suggest the usefulness of LDBCP for protection from the myocardial injury that can be induced by BCP administration during aortic cross-clamping.

Effect of vitamin E on aspirin-induced gastric mucosal injury in rats.

We investigated the effect of vitamin E on aspirin-induced gastric mucosal injury in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups and were fed for 20 weeks with a diet containing <0.1 mg/100 g of alpha-tocopherol (vitamin E-deficient), 2 mg/100 g of alpha-tocopherol (normal and vitamin E-sufficient), or 50 mg/100 g of alpha-tocopherol (vitamin E-supplemented). In vitamin E-deficient rats, oral administration of aspirin (200 mg/kg) plus HCI created more severe hemorrhagic erosions than in other rats. Vitamin E-deficient rats had higher levels of thiobarbituric acid reactive substances, myeloperoxidase activity, and cytokine-induced neutrophil chemoattractant in the gastric mucosa. Flow cytometry showed that CD18 expression on stimulated neutrophils was higher in vitamin E-deficient rats than in vitamin E-supplemented rats. These results suggest that vitamin E protects against aspirin-induced gastric mucosal injury by inhibiting lipid peroxidation and accumulation of activated neutrophils.

Neonatal primary neuronal death induced by capsaicin and axotomy involves an apoptotic mechanism.

To clarify the mechanism of capsaicin-induced primary neuronal cell death, newborn and adult rats were given a subcutaneous injection of capsaicin (50 mg/kg). Neonatal capsaicin injection induced neuronal apoptosis in the trigeminal ganglion. Apoptotic neurons had peripheral stacks of long parallel endoplasmic reticulum that are characteristic to primary neurons of the B-type, and exhibited nucleoplasmic condensation, nuclear shrinkage and cytoplasmic fragmentation. Light microscopically, apoptotic neurons exhibited a sign of DNA fragmentation as revealed by a nick end labelling method. The proportion of apoptotic cells was quite low during the first 12 h after capsaicin injection (<1%), rapidly increase to 10.44% by 24 h, and decreased to 0.29% by 48 h. Normal and vehicle control levels of apoptosis were <1%. Nerve growth factor (NGF, 0.5 mg/kg) simultaneously administered with capsaicin reduced the incidence of apoptosis by about 35% at 24 h post-injection. Neonatal transection of the infraorbital nerve induced neuronal apoptosis similar to that produced by the neonatal capsaicin in the maxillary division of the trigeminal ganglion. Unlike capsaicin, however, the neurotomy-induced apoptosis was seen in neurons of both the A- and B-types. Neither the capsaicin injection nor the neurotomy induced apoptosis in adult rats, though mitochondrial swelling similar to that seen at 0.5 h after neonatal capsaicin was observed after capsaicin injection in adults. The results indicate that the capsaicin-induced and nerve injury-induced primary neuronal damages in newborn rats share a common final pathway, apoptosis.

Circadian rhythm sleep disorders in adolescents: clinical trials of combined treatments based on chronobiology.

Delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake rhythm are circadian rhythm sleep disorders that are common in adolescents. Most patients have difficulty adjusting to school life, poor class attendance or refuse to go to school. Since a treatment has not been established, the present paper is presented to propose a strategy for treating circadian rhythm sleep disorders in adolescents, based on our clinical studies. Twenty subjects (12 males and eight females, mean age 16.2+/-1.7 years) participated in the study. The onset of sleep disorder occurred between the ages of 11 and 17. The most common factors affecting the onset of disorders were changes in social environment. The subjects kept a sleep-log for the periods before and during treatments. The treatments were based on chronobiology: resetting the daily life schedule, chronotherapy, regulation of the lighting environment, methylcobalamin, and/or melatonin. Bright light exposure was successful in 10 patients, of whom four were treated with methylcobalamin. Melatonin treatment was successful in two patients (one with and one without chronotherapy). Thirteen of the 20 patients were successfully, treated with therapies based on chronobiology. After consideration of these results, a step-by-step procedure of combined treatments for the circadian rhythm sleep disorders is proposed.

Role of lipid peroxidation and antioxidants in gastric mucosal injury induced by the hypoxanthine-xanthine oxidase system in rats.

Free radical-induced gastric mucosal injury was caused by severe depletion of glutathione and alpha-tocopherol. Intravenous infusion of hypoxanthine (HX) via the jugular vein and local intra-arterial infusion of xanthine oxidase (XO) via the left gastric artery caused marked gastric mucosal injury in the antrum and the corpus. This study was performed to determine whether antioxidants in the gastric mucosa are mobilized during oxidative stress in the rat stomach. The level of thiobarbituric acid (TBA) reactive substance in the gastric mucosa was not significantly changed. The levels of total glutathione and alpha-tocopherol in the gastric mucosa significantly decreased. Total superoxide dismutase (Cu/Zn-and Mn-SOD) and glutathione peroxidase activities were not significantly changed. Administration of SOD reversed the glutathione level but not the alpha-tocopherol level in the gastric mucosa. To determine the role of glutathione and alpha-tocopherol in oxidative stress, the stomach was removed from a normal, alpha-tocopherol supplemented, and glutathione-depleted rat and used for experimentation. Frozen slices of the rat stomach were infused with HX-XO then examined histochemically using cold Schiff's reagent for signs of lipid peroxidation. It was found that the alpha-tocopherol supplemented stomach inhibited lipid peroxidation induced by HX-XO. Biochemical measurements and histochemical examination showed that the glutathione-depleted frozen tissue section and the homogenate had increased by lipid peroxidation induced by HX-XO. These findings suggested that alpha-tocopherol and glutathione may play a role in protecting the gastric mucosa against oxygen free radicals.

[Hemorheological effects of autologous blood storage before surgery for cardiac valvular diseases].

The hemorheological effects of autologous blood storage with or without the use of erythropoietin were examined before surgery for valvular disease. There was no rheological difference between patients with aortic (16 cases) or mitral (10 cases) valve disease. Before storage, the levels of hematocrit, whole blood viscosity, and especially coefficient of rheology, were lower (p < 0.05) in the blood stored with erythropoietin, but this difference disappeared after storage. The plasma viscosity of both groups did not change before and after storage. The viscosity of blood was equalized after the storage of blood, irrespective of the use of erythropoietin.

Bax protein-like immunoreactivity in primary sensory and hypothalamic neurons of adult rats.

Bax protein-like immunoreactivity (Bax-ir) was examined in the perfusion-fixed, cryosectioned rat nervous system. In the central nervous system, hypothalamic neurons were the only neurons that exhibited Bax-ir in the cell body. Their axons traveled toward the median eminence, suggesting that the Bax-like immunoreactive (Bax-ir) hypothalamic neurons included neurosecretory ones. Bax-ir axons were observed in the solitary tract nucleus, and spinal and medullary dorsal horns. They appear to have been derived from Bax-ir primary sensory neurons in the viscerosensory nodose ganglion and somatosensory dorsal root and trigeminal ganglia. In the somatosensory ganglia, smaller cells exhibited stronger Bax-ir. Accordingly, the ir axons in the dorsal horn were most concentrated in lamina II.

Effect of tea polyphenols on fecal flora and fecal metabolic products of pigs.

The effects of tea polyphenols on fecal flora and fecal metabolic activities were studied in eight 30-day-old pigs fed a basal diet (control) or the diet supplemented with 0.2% of tea polyphenols for 2 weeks. During tea polyphenol administration compared to before administration, the levels of lactobacilli were increased significantly (P < 0.05 and P < 0.01 on days 7 and 14 of administration, respectively), whereas the levels of total bacteria (P < 0.01) and bacteroidaceae (P < 0.01 and P < 0.001 on days 7 and 14 of administration, respectively) were decreased significantly. The detection rate of lecithinase positive clostridia including Clostridium perfrigens showed a tendency to decrease during administration. No detectable change occurred in the levels of other organisms throughout the experimental period. Fecal concentrations of ammonia were decreased significantly (P < 0.05 and P < 0.01 on days 7 and 14 of administration, respectively). Fecal phenol (P < 0.001), p-cresol (P < 0.05), and skatol (P < 0.01) were reduced significantly on day 14 of administration compared to before administration. The amounts of fecal short chain fatty acids, acetic acid (P < 0.05) and lactic acid (P < 0.05) were increased significantly on day 14 of administration. The pH values were decreased slightly during administration. The odour of the feces was reduced remarkably during tea polyphenol administration.

[Studies on antiulcer agents. I. The effects of various methanol and aqueous extracts of crude drugs on antiulcer activity].

The antiulcer activities of 59 methanol and aqueous extracts obtained from 59 crude drugs on the ethanol-HCl-induced ulceration in rats were investigated. Among them 15 extracts were selected and they were further examined for their effects on indomethacin-, aspirin- and the water-immersion stress-induced ulcer. From these results, the methanol extract of root of Iris germanica was found to, show potent antiulcer activities. The above methanol extract was separated into 3 portions by solvent extraction, and the ether soluble portion was fractionated into 5 fractions (1 to 5) by chromatography. Fractions 4 and 5 showed significant antiulcer activities. Fraction 4 was further purified and the obtained gamma-irigermanal exhibited a potent antiulcer activity. However, further investigations are required to understand the mechanism.

Antioxidative effects of a processed grain food.

Antioxidant biofactor: AOB is a unique processed grain food. It is a yellow-green powder. It contains the following extracts: germ extracts, soybean, rice bran, tear grass, sesame, wheat, citron, green tea, green leaf extract, and malted rice. These materials were slowly roasted under a powdered oure at less than 60 degrees C and fermented with Aspergillus oryzae over 3 days to transform each ingredient into low molecular weight substances. These conditions were different by each material, environmental humidity and temperature. It probably contains a variety of substances having antioxidant activity including flavonoids, alpha-tocopherol, vitamin C, and tannins. We investigated its antioxidative properties using electron spin resonance (ESR) and autoxidation of rat brain homogenates. The superoxide, hydroxyl radical, and the stable free radical, diphenyl-p-picrylhydrazyl (DPPH) radical scavenging activity of AOB was investigated using ESR spectrometry. In an in vitro study, a suspension of AOB was added directly to a superoxide generating system (hypoxanthine-xanthine oxidase; HX/XO) and investigated using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trapping agent. At final concentrations of 0.01, 0.05, and 0.1 mg/ml, AOB dose-dependent scavenging activity was observed as 0.103, 0.619, and 1.369 U/ml, respectively. A concentration of 1.0 mg/ml completely scavenged DMPO-OOH signals; 1.0 mg/ml of AOB inhibited the DMPO-OH signal generated by Fenton's reaction, but its inhibitory effect was not competitive, and was inhibition of the Fenton's reaction. 1.0, 3.0, and 5.0 mg/ml of AOB were significantly inhibited the DPPH radical. In an in vivo study, rats were fed AOB orally at doses of 1 or 5 g/day for 24 h or for 3 days and the superoxide scavenging activity was measured in plasma. With the administration of 1 g/day for 3 days, the superoxide scavenging activity was about 1.8 times that of the control group fed a basal diet; 1.5 times the control with 5 g/day for 1 day, and 2.6 times the control with 5 g/day for 3 days, all of which represented significant increases in superoxide scavenging activity. AOB strongly inhibited the autoxidation of rat brain homogenates in vitro in a dose-dependent manner. However, each ingredient before roast and fermentation little inhibited lipid peroxidation. Roasting and fermentation with A. oryzae way be important to transform each ingredient into low molecular weight substances. Therefore, it was suggested that AOB possesses strong antioxidant and free radical scavenging activities.

Isolation and identification of an antifungal naphthopyran derivative from Rhinacanthus nasutus.

Rhinacanthus nasutus (Acanthaceae) gave a new antifungal naphthopyran derivative. The structure of the compound was elucidated by spectroscopic methods as 3,4-dihydro-3,3-dimethyl-2H-naphtho[2,3-b]pyran-5,10-dione [1].

[Chemo-embolization using degradable starch microspheres and regional hyperthermia in unresectable hepatocellular carcinoma].

Antitumor effects and prognosis of the patients with unresectable hepatocellular carcinoma were investigated in the treatment of chemo-embolization using degradable starch microspheres (DSM) and regional hyperthermia. Twenty-six cases were treated with chemo-embolization using DSM alone (Group A) and eighteen cases were treated with combination of chemo-embolization and hyperthermia (Group B). Tumor regression rates over 50% were 42% (11/26) and 56% (10/18) in Group A and Group B, respectively. In the patients with tumors over 7 cm in diameter, no favorable response was obtained in Group A (0/11), but the response rate was increased to 56% (5/9) by the combination of hyperthermia. In the patients with arterio-portal shunt, therapeutic effects were observed in 17% (1/6) and 50% (1/2) of Group A and Group B, respectively. In the patients with portal invasion (Vp2 and Vp3), no favorable response was demonstrated in Group A (0/4), but tumor response was demonstrated in one out of 3 cases in Group B. One- and two-year survival rates were 59% and 53%, respectively, in Group A, and 93% and 45%, respectively, in Group B. The DSM, temporary embolus, is suitable for the combination of hyperthermia because chemo-embolization using DSM can be performed many times. Therefore, these results suggested that chemo-embolization using DSM should be beneficial as combination therapy for unresectable hepatocellular carcinoma.

[Antitumor effect and indication of chemoembolization using degradable starch microspheres and regional hyperthermia in patients with hepatocellular carcinoma].

Antitumor effects and indications of chemoembolization using degradable starch microspheres (DSM) and regional hyperthermia were investigated in patients with unresectable hepatocellular carcinoma. Chemoembolization using DSM was performed in 40 cases and fourteen cases were treated with the combination of hyperthermia. Tumor regression rate over 50% was 48% (chemoembolization alone: 42%, combined hyperthermia: 57%). Though one and two year survival rates were 62% and 54% respectively in the treatment with chemoembolization alone, one year survival rate was 91% in the treatment with combined hyperthermia. From the viewpoint of antitumor effect, it was thought that effectual indications of chemoembolization using DSM alone were the cases whose tumor size were below 7 cm and portal invasion were negative. These indications however were spread by the combination of hyperthermia. The DSM, temporary embolus, is suitable for combination of hyperthermia because chemoembolization using DSM can be performed many times. The cases with clinical stage III and obstruction of the first branch of portal veins did not become severe hepatic failure because DSM was temporary embolus. Therefore, from the viewpoint of safety, chemoembolization using DSM has almost the same indications as intra-arterial infusion therapy. These results suggested that chemoembolization using DSM will be a beneficial methods as combination therapy for unresectable hepatocellular carcinoma.

Persistent light reaction: induction in the guinea pig.

Persistent light reactions similar to those in humans were observed in the study of photoallergenicity of chemicals in guinea pigs. The animals photoinduced with chemicals reacted to long-wavelength ultraviolet (UVA) radiation in the absence of test materials at the challenge stage. The sensitivity of the animals to UVA persisted for more than 1 year. The minimum erythema dose to UVB of animals in the treated group was less than that in the control group. Our investigations indicate that the main factors influencing the elicitation of persistent light reaction were the amount of Freund's complete adjuvant (FCA) used to enhance the allergic response in animals, and the UVA dose at the induction stage. Based on these findings, we have developed a method to make animals persistent light reactors with high frequency. This method consists of 1 intradermal injection of 1.2 ml emulsified FCA, 5 irradiations with 20.4 J/cm2 of UVA, and topical applications of 5% p-aminoethylbenzoate (benzocaine) at the induction stage. We also found that photosensitivity could be induced using FCA and UVA without photosensitizers.