Do teas rich in antioxidants reduce the physicochemical and peroxidative risk factors for calcium oxalate nephrolithiasis in humans? Pilot studies with Rooibos herbal tea and Japanese green tea.

Several experimental and animal studies have demonstrated that substances rich in antioxidants can reduce the physicochemical and peroxidative risk factors for calcium oxalate (CaOx) renal stone formation in urine and blood. However, there are very few such investigations in humans. In the present pilot study, two varieties of tea, a green one from Japan (JGT) and a herbal one from South Africa (Rooibos) (RT), both rich in antioxidants, were administered to a group of CaOx stone formers (SF) (n = 8) for 30 days. Both teas were analysed for polyphenols by high-performance liquid chromatography and for minerals by plasma atomic and optical emission spectroscopy. 24 h urines (baseline and day 30) were analysed for lithogenic factors. CaOx metastable limits and crystal nucleation and growth kinetics were also determined in each urine sample. Deposited crystals were inspected by scanning electron microscopy. Blood samples were collected (baseline and day 30). Biomarkers of oxidative stress including plasma and urinary thiobarbituric acid reactive substances (TBARS) and urinary N-acetyl-ß-D-glucosaminidase (NAG) were also determined. Urinary physicochemical risk factors were also investigated after ingestion of RT for 30 days in two control groups (CG1 and CG2), the latter one of which consisted of habitual JGT drinkers. Statistical analyses were performed using Wilcoxon signed rank tests and Mann-Whitney tests for paired and independent measurements, respectively. Several flavonoids and catechins were quantified in RT and JGT, respectively, confirming that both teas are rich sources of antioxidants. Mineral content was found to be far below dietary reference intakes. There were no significant changes in any of the urinary physicochemical or peroxidative risk factors in the control groups or in SF, except for the supersaturation (SS) of brushite (Bru) which decreased in the latter group after ingestion of JGT. Crystal morphology showed a tendency to change from mixed CaOx mono- and di-hydrate to monohydrate after ingestion of each tea. Since the latter form has a stronger binding affinity for epithelial cells, this effect is not protective. Analysis of the physicochemical and peroxidative risk factors in CG1 and CG2 did not reveal any evidence of a synergistic effect between the two teas. Paradoxically, baseline risk factors in the habitual JGT control group were significantly raised relative to those in CG1. Our preliminary results suggest that ingestion of RT and JGT does not reduce the risk factors for CaOx stone formation in humans, but these findings need to be tested in further studies involving much larger sample sizes.

3-(Arylacetylamino)-N-methylbenzamides: a novel class of selective anti-Helicobacter pylori agents.

After chemical modification preceded by the random screening of our chemical library, a novel class of selective anti-Helicobacter pylori agents was generated. Consequently, the 3-(arylacetylamino)-N-methylbenzamides, which were quite easy to prepare, showed potent inhibitory activity against Helicobacter pylori but exhibited no inhibitory activity against other sorts of bacteria and fungi, e.g., Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Bacteroides fragilis, and Candida albicans. These compounds showed potent anti-H. pylori activity under acidic conditions, whereas amoxicillin and clarithromycin decreased activity. The 3-(3-arylpropionylamino)-N-methylbenzamides, 3-(aryloxyacetylamino)-N-methylbenzamides, and (3-methylcarbamoylphenyl)carbamic acid 1-arylmethyl esters also exhibited potent anti-H. pylori activity. Finally, we selected 7n (BAS-118) as a candidate compound for further evaluation.

Cholinergic mechanisms involved with histamine hyperreactivity in immune rabbit airways challenged with ragweed antigen.

The present study examines the effects of aerosolized ragweed antigen (RAg) on tracheal (TSM) and bronchial (BSM) smooth muscle contraction in rabbits actively immunized with RAg. Airway segments were isolated 48 h after aerosol challenge with either saline or RAg, and airway contractile responses to histamine were measured. Histamine remained a weak agonist in TSM segments after RAg challenge. In contrast, BSM responsivity to histamine was significantly increased after RAg challenge as evidenced by a parallel shift to the left (i.e., Fslope = 3.2; degrees of freedom (df) = 1,224; p = NS and Felev = 19.4; df = 1,225; p less than 0.001) of the mean dose-response relationship. In sham-immunized rabbits, the BSM contractile responses to histamine were similar after aerosol challenge with either RAg or normal saline. After the BSM segments were treated with 10(-6) M atropine, there was no significant difference in histamine reactivity between the RAg- and saline-challenged groups. The augmented BSM contractile response to histamine was only partially inhibited in the presence of either tetrodotoxin or hexamethonium. We conclude that 48 h after a single in vivo exposure to antigen in immune rabbits, the airway contractile responses to histamine in vitro are increased in BSM but not in TSM and that the mechanism of the augmented contractile responses in BSM likely involves the facilitated neural release of acetylcholine from both preganglionic and postganglionic sites.

Factors that affect oxygen affinity of hemoglobin in chronic hemodialysis patients.

To investigate various factors that possibly affect oxygen affinity of hemoglobin (Hb-O2 affinity) in chronic hemodialysis (HD) patients, we determined P50 at standard condition (P50std), 2,3-diphosphoglycerate (2,3-DPG) content in red blood cells, serum inorganic phosphorus (S-Pi), Hb, and arterial blood gas analysis in 55 HD patients. P50std in HD patients was higher than that in normal controls (26.6 +/- 1.6 vs. 25.4 +/- 1.4 mm Hg; p less than 0.001). We could find neither an effect of alkalizating agents for HD (acetate vs. bicarbonate) nor an effect of the underlying disease (diabetics vs. nondiabetics) on Hb-O2 affinity. There were significant positive correlations between P50std and the duration of HD therapy (r = 0.598; p less than 0.001) and between P50std and SPi (r = 0.476; p less than 0.001), contrasting with the absence of correlation between P50std and Hb. Forward stepwise multiple-regression analysis demonstrated that the duration of HD therapy played the most important roles in determining P50std, followed by SPi and PO2. These data suggest that the major factor influencing Hb-Os affinity in chronic HD therapy is the duration of the therapy and that the minor factors are SPi and PO2.

[The effect of thiamine deficiency on the actions of drugs affecting the central nervous system in rats (author's transl)].

Male Wistar rats, 35-days-old, maintained on a thiamine deficient diet for 30 days showed marked growth inhibition and a heart rate less than 70% of that of control rats. We examined the effect of thiamine deficiency on the action of drugs effecting the central nervous system at this period. In thiamine deficient rats treated with chloral hydrate 200 mg/kg, ketamine 100 mg/kg sodium pentobarbital 50 mg/kg, and hexobarbital 100 mg/kg, the sleeping time increased. Pretreatment with 15 mg/kg of the metabolic enzymes inhibitor, SKF-525A, 30 min prior to the hexobarbital administration resulted in prolongation of sleeping time in all groups. The thiamine deficient rats slept almost 3.5 times longer than did the control group. Pretreatment with 100 mg/kg of the metabolic enzyme inducer, sodium phenobarbital, 48 hours prior to hexobarbital treatment resulted in decreased sleeping time in all groups, as compared with only hexobarbital treatment. In the thiamine deficient rats the catalepsy and ptosis induced by the i.p. administration of tetrabenazine 50 mg/kg was reduced even when the control and pair-fed groups responded to this drug at the drug peak time. The spontaneous neuronal activity of lateral hypothalamus was most sensitive to the administration of 5-hydroxytryptophan in thiamine deficient rats.

[Effects of diazepam on rage reaction elicited by the lateral hypothalamus (LH) and on single unit activities in the LH and the basal medial amygdaloid nucleus (Abm) in cats (author's transl)].

Effects of diazepam were examined on the whine reaction elicited by LH stimulation and on unit activities in the LH and Abm in cats. The spontaneous firing frequency of Abm neurons was 5 to 30 spikes/sec and in all 6 neurons isolated the firing frequency increased by non-nociceptive and/or clap-stimulation. Diazepam decreased the spontaneous firing frequency of all Abm neurons isolated and the increased firing frequency elicited by non-nociceptive and/or clap-stimulation was also depressed by diazepam. The spontaneous firing frequency of neurons in the LH was 4 to 5 spikes/sec and all 6 neurons isolated firing frequency increased by non-nociceptive stimulation. Only one of 6 neurons, however, was activated by clap-stimulation. Diazepam decreased the spontaneous firing frequency of all LH neurons. Out of 6 neurons responsive to non-nociceptive stimulation, 3 were also depressed by diazepam. The other neurons were not affected by diazepam. These results suggest that depressed action of diazepam on the whine reaction elicited by the LH stimulation may be related to the decrease of firing in the Abm and/or the LH by diazepam.

[Effects of diazepam on evoked potential recorded from basal medial amygdaloid nucleus, lateral hypothalamus and midbrain reticular formation (author's transl)].

The evoked potential in the lateral hypothalamus (LH) recorded by stimulation of basal medial amygdaloid nucleus (Abm) showed a triphasic pattern and diazepam (2 mg/kg, i. p.) decreased the late component. The evoked potential in the midbrain reticular formation (MRF) recorded by stimulation of Abm showed a fast component with a relatively short latency followed by a biphasic late component and diazepam decreased the late component. Though the evoked potential in the Abm recorded by stimulation of LH showed a triphasic pattern, diazepam had no influence on the amplitude. Diazepam increased markedly the amplitude of evoked potential in the MRF recorded by stimulation of LH. Diazepam was ineffective on the evoked potential in the Abm recorded by stimulation of MRF. Diazepam decreased markedly the late component of evoked potential in the LH recorded by stimulation of MRF. These results suggest that the depression of emotional behavior by diazepam may be particularly related to the fact that the evoked potential in the LH recorded by stimulation of Abm was decreased by diazepam.