Breath sample collection through the nostril reduces false-positive results of 13C-urea breath test for the diagnosis of helicobacter pylori infection.

BACKGROUND: One of the disadvantages of '3C-urea breath test is possible interference by urease activity not related to Helicobacterpylori. AIMS: We design the simple and non-invasive modification to avoid the contamination of 13CO(2) produced in the mouth. PATIENTS AND METHODS: One hundred and twenty-nine patients who underwent diagnostic upper endoscopy were enrolled. Within 1 week of the endoscopic procedure, each patient received the modified 13C-urea breath test. Breath samples were collected at baseline and at 1, 3, 5, 10, 15, 20 and 30 min after ingestion of 100 mg 13C-urea solution through the mouth and the nostril at each time point. RESULTS: The breath delta13CO2 value through the nostril at 1 min was already higher in H. pylori-positive patients than in H. pylori-negative patients. Using 2.5% as the cut-off value, the sensitivity and specificity of the modified 13C-urea breath test at 20 min were both 100%, whereas the sensitivity and specificity of the standard 13C-urea breath test were 97.7 and 94%, respectively, using 3% as the cut-off value. CONCLUSIONS: The modified 13C-urea breath test in which breath samples are collected through the nostril provides an easy way of avoiding false-positive results for the detection of H. pylori infection.

[Unusual transient M-proteinemia (IgG-kappa type) detected using separax membrane. A case report].

We report a patients with squamous cell carcinoma of tongue showing transient M-protein (IgG-kappa type) on electrophoresis using a Separax membrane. The M-protein was detected in the alpha 1 to beta regions as a broad band, and it was detected in the slow gamma region as a monoclonal band on electrophoresis using other types of membranes. The unusual electrophoretic pattern of globulin found in this patient was considered to be caused by alternation of globulin by unusual sugar chains.

[Pharmacological study on hydrocortisone 17-butyrate 21-propionate (author's transl)].

The topical and systemic anti-inflammatory activities of hydrocortisone 17-butyrate 21-propionate (HBP) were studied. The systemic anti-inflammatory activities of HBP and reference steroids were examined for their effects on dinitrochlorobenzene dermatitis, carrageenin edema, cotton pellet granuloma and adjuvant arthritis in rats and by the delayed allergic edema test in mice. The topical anti-inflammatory activities of these steroids were examined for their effects on croton oil dermatitis, croton oil ear edema, carrageenin edema and cotton pellet granuloma in rats. Furthermore, effects of these steroids on liver glycogen deposition in mice, thymolysis, and decrease of serum corticosterone level in rats were examined. Systemically administered HBP was less potent than betamethasone 17-valerate (BV), but was almost equal to hydrocortisone 17-butyrate (HB) in anti-inflammatory activity, and its effects on liver glycogen deposition, thymolysis, and the decrease of serum corticosterone level. However, the topical anti-inflammatory activity of HBP was more potent than that of BV and HB, although in the same experiment, thymolytic activity of HBP was less potent than that of BV, but was almost equal to HB. The inhibitory effect of HBP on hypotonic induced hemolysis was weaker than that of BV, but was stronger than that of HB in vitro. The affinity of HBP was higher than that of BV and HB to polymorphonuclear leucocytes used as the inflammatory cells in vitro. On the other hand no marked difference was observed in the affinity to erythrocytes used as the non-inflammatory cells in vitro. These results suggest that HBP is a useful drug which has superior topical anti-inflammatory activity, but has a weak systemic effect.

[Studies of D-penicillamine (5): effects on rat adjuvant arthritis (author's transl)].

D-Penicillamine (D-PA), 80-100 mg/kg/day enhanced the early phase of adjuvant arthritis (AA) in rats when it was administered orally for about 4 weeks after the adjuvant injection day, whereas dexamethasone (1 mg/kg/day, p.o.) and chloroquine diphosphate (25 mg/kg/day, p.o.) inhibited AA in the same dosing regimen. On the other hand, subcutaneous injection of sodium aurothiomalate (12.5 mg/kg/day) enhanced AA initially, but inhibited it later. The enhancing effect of D-PA on the early phase of AA was observed also at doses of 50 mg/kg/day and 200 mg/kg/day, but, in the case of 200 mg/kg/day, inhibited the later phase of AA. When the administration of D-PA was started before the adjuvant injection, it showed a tendency to suppress AA on proportion to the dosing period. The effect of D-PA, however, was not observed in the model when the drug administration was started after the establishment of arthritis. The co-administration pyridoxine HCl did not influence the effect of D-PA on AA. A good correlation was not obtained between the inflammatory score and the PPD induced skin reaction, serum metals level and histopathological changes of lymph node in the AA rats treated with D-PA. Thus the effect of D-PA on AA was related to dose, timing and duration of the administration. It was suggested that the enhancing and inhibitory effects of D-PA on AA were not based on vitamin B6, depletion, but rather were caused by inhibition of T1 and T2 lymphocytes which may be regulating this arthritis process.

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -1. Acute toxicity of hydrocortisone 17-butyrate 21-propionate and its analogues in mice, rats and dogs (author's transl)].

The acute toxicity of hydrocortisone 17-butyrate 21-propionate (HBP), hydrocortisone 17-butyrate (HB17) and hydrocortisone 21-butyrate (HB21) were investigated by three administration routes (s.c., i. p. and p. o.) in mice, rats and dogs. In the case of HBP, LD50 by oral administration was the highest, and followed by subcutaneous and intraperitoneal administration in mice and rats. And LD50 of HB17 and HB21 were not different from HBP in mice by subcutaneous administration. The depression of spontaneous movement and respiratory rate, ptosis, larcrymation and the collapse were commonly observed in all drugs, and it was independent of administration routes. The autopsy revealed the atrophy of thymus, spleen and adrenal glands, the supprative nodules of heart and liver and the ulcers of alimentary tract in mice and rats. But the changes observed in mice and rats were recognized when 1000 mg/kg of HBP was administered to dogs subcutaneously. Many of these changes were common to glucocorticoids, and the LD50 of HBP was rather high compared with other synthetic steroids; therefore, HBP was among less toxic steroid.

[Influence of hydrocortisone 17-butyrate 21-propionate on the visual and the auditory organs (author's transl)].

The visual toxicity and the ototoxicity of hydrocortisone 17-butyrate 21-propionate (HBP), a newly synthesized anti-inflammatory steroid, was investigated using rats and dogs. (1) Electroretinogram (ERG) and visually evoked potential (VEP) in rats were not changed when HBP was administered intravenously and intraperitoneally, even at the semilethal doses. Consequently, it was suggested that HBP had no effect on the visual nervous system. (2) Similar to other corticosteroids, the intra ocular pressure rose in the dogs received HBP. Nevertheless, these dogs showed neither the remarkable changes in ERG, in the fundus of the eye, in the histological examination, nor the turbidity of the cornea and the lens. Based on these facts, it was reasonable to think that the the rise in the intra ocular pressure caused by HBP was not so severe that induce the secondary influence to other visual functions. (3) The rats received HBP did not show any changes in the auditory function by the audiometry. As the result, HBP was thought to be one of the rather safety corticosteroids concerning the visual toxicity and the ototoxicity.

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -2. Subacute toxicity in rats by subcutaneous administration (author's transl)].

Subacute toxicity of hydrocortisone 17-butyrate 21-propionate (HBP), a new synthetic corticosteroid, was studied in rats, using betamethasone 17-valerate (BV) and hydrocortisone 17-butyrate (HB) as the reference drugs. HBP was subcutaneously injected to rats at the daily doses of 0.08, 0.4, 2.0, 10 and 50 mg/kg for 30 days. BV and HB were also administered at the daily doses of 0.08, 0.4 and 2.0 mg/kg. The recovery test was performed for 4 weeks after administration of HBP, BV and HB. The suppression of body weight gain by HBP was observed at the doses more than 0.08 mg/kg in male and more than 2.0 mg/kg in female rats. In addition, at the doses more than 0.4 mg/kg of HBP induced the dose-dependent symptoms such as decrease in the number of circulating white blood cells, lymphocyte counts and S-ALP level, increase in total cholesterol, GOT and GPT level of serum, and regressive changes in adrenals, lymphatic and hematopoietic tissues. There were fatal cases in rats given 50 mg/kg of HBP. These changes are considered to be common phenomena to other corticosteroids, and less toxic in female than male rats. Changes of symptoms caused by the administration of HBP 2.0 mg/kg were almost recovered after withdrawal. The toxicities of three corticosteroids were in the order of BV greater than HB greater than or equal to HBP in strength. As the result, maximum non-toxic dose of HBP was estimated to be 0.08 mg/kg in female and lower than that in male rats.

[Studies on antigenicity, phototoxicity and other specific toxicities of hydrocortisone 17-butyrate 21-propionate (HBP) (author's transl)].

The present experiments were undertaken to determine the antigenicity and other toxicities of HBP; such as phototoxicity, photosensitivity, ulcerogenicity, adrogenic-myotropic, estrogenic and progestational activities, and mutagenicity. No antibody formation and delayed type skin reaction of HBP were seen in rabbits. Active systemic anaphylaxis was not observed in guinea pigs challenged by HBP. In the phototoxicity and photosensitivity test, 0.1% HBP ointment, 0.1% HBP cream and 10% HBP acetone solution did not show any skin reaction with or without irradiation of ultraviolet light. Repeated subcutaneous administration of HBP irritated the gastric and intestinal mucosa dose dependently in rats as hydrocortisone 17-butyrate and betamethasone 17-valerate (BV). HBP had neither androgenic-myotropic nor estrogenic activity, but antiestrogenic activity was observed. The progestational activity of HBP in immature rabbit pretreated with estrone was less potent than BV. In the mutagenicity test os HBP investigated by the reverse mutation according to the method by Ames, no significant increase in the number of revertants was observed in the presence or absence of S9 mixture.

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -3. Subacute toxicity in rats by percutaneous administration (author's transl)].

Subacute toxicity of hydrocortisone 17-butyrate 21-propionate (HBP) was studied in rats. HBP was percutaneously given to rats with 0.1% and 0.5% creame (0.1% HBP-C, 0.5% HBP-C) and ointment (0.1% HBP-O, 0.5% HBP-O) at the daily dose level of 150 mg per 100 g body weight for 1 month. Rats receiving HBP-C and HBP-O showed some dose-dependent symptoms such as the suppression of body weight gain, emaciation, decrease in the number of white blood cells, hemoglobin, hematocrit, and serum total cholesterol level, regressive changes in adrenals, skin, lymphatic and hematopoietic tissues, which are known as toxic effects of synthetic corticosteroids. These symptoms were comparatively high toxic in male rats and in cream groups, and almost disappeared in rats elapsed recovery time of 1 month after withdrawal of HBP.

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -4. Chronic toxicity in rats by subcutaneous administration (author's transl)].

Chronic toxicity of hydrocortisone 17-butyrate 21-propionate (HBP), a new synthetic corticosteroid, was studied in rats. HBP was subcutaneously injected to rats as the daily doses of 0.001, 0.01, 0.01, 1.0 and 3.0 mg/kg for 6 months, and the following recovery test was carried out for 4 weeks. Hydrocortisone 17-butyrate (HB) and betamethasone 17-valerate (BV) were used as the reference drugs at the doses of 0.1, 1.0 and 3.0 mg/kg. The suppression of body weight gain by the administration of HBP was observed at the doses more than 1.0 mg/kg in male and more than 0.1 mg/kg in female, and the dead animals were sent at the highest dose of HB and BV. Mainly at the doses more than 0.1 mg/kg HBP induced the dose-dependent symptoms such as decrease in the number of white blood cells and total protein level in serum, and increase in total cholesterol, GOT and GPT level in serum, and atrophic changes of adrenals, lymphatic tissues, skin and subsexual organs. No usual abnormality was recognized at the doses less than 0.01 mg/kg of HBP. These symptoms were more toxic in male, and the strength of toxicity was in the order of BV greater than HB greater than HBP. Many of these findings have known as common effects of corticosteroids. The changes observed in this study were almost recovered after withdrawal of HBP at the doses less than 0.1 mg/kg. As the result, it was suggested that the maximum non-toxic dose of HBP was 0.001 mg/kg.

[Studies of toxicity of hydrocortisone 17-butyrate 21-propionate -5. Chronic toxicity in rats by percutaneous administration (author's transl)].

Chronic toxicity of a new synthetic corticosteroid, hydrocortisone 17-butyrate 21-propionate (HBP), was investigated in rats of both sexes. HBP was percutaneously given to rats with 0.1%, 0.5% cream and ointment at the daily dose level of 150 mg per 100 g body weight for 6 months. For the comparison, the percutaneous toxicity with 0.12% betamethasone 17-valerate (BV) cream and ointment, and 0.1% hydrocortisone 17-butyrate (HB) cream and ointment at the daily dose level of 150 mg per 100 g body weight were studied. Rats receiving HBP showed the dose-dependent changes such as the suppression of body weight gain and food intake, emaciation, decrease in the number of white blood cells and lymphocytes, total protein, increase in the number of red cells, hematocrit, hemoglobin, blood sugar and total cholesterol, regressive changes in adrenal cortex, lymphatic and hematopoietic tissues and skin, and gastric erosion, which have been well known as toxic effects of synthetic corticosteroids. These findings were comparatively high toxic in male, and almost disappeared in rats elapsed recovery time of month after withdrawal of HBP. The toxicities of HBP, BV and HB were qualitatively same. However, the grade of effects of HBP toxicity was similar to that of HB, weaker than of BV.

The action of chlorphenesin carbamate on the frog spinal cord.

Studies were carried out to elucidate the mechanism of action of chlorphenesin carbamate (CPC) and to compare the effect of the drug with that of mephenesin on the isolated bullfrog spinal cord. Ventral and dorsal root potentials were recorded by means of the sucrose-gap method. CPC caused marked hyperpolarizations and depressed spontaneous activities in both of the primary afferent terminals (PAT) and motoneurons (MN). These hyperpolarizations were observed even in high-Mg2+ and Ca2+-free Ringer's solution, suggesting that CPC has direct actions on PAT and MN. Various reflex potentials (dorsal and ventral root potentials elicited by stimulating dorsal and ventral root, respectively) tended to be depressed by CPC as well as by mephenesin. Excitatory amino acids (L-aspartic acid and L-glutamic acid) caused marked depolarizations in PAT and MN, and increased the firing rate in MN. CPC did not modify the depolarization but abolished the motoneuron firing induced by these amino acids. However, mephenesin reduced both the depolarization and the motoneuron firing. The dorsal and ventral root potentials evoked by tetanic stimulation (40 Hz) of the dorsal root were depressed by the drugs. These results indicate that CPC has an apparent depressing action on the spinal neuron, and this action may be ascribed to the slight hyperpolarization and/or the prolongation of refractory period.

[Effects of D-penicillamine on vitamin B6 and metal ions in rats (author's transl)].

D-penicillamine, an antirheumatic drug having chelating ability, was investigated for the effects on vitamin B6 and metals at doses ranging from 25 to 600 mg per kg, p.o., or in case of the highest dosing of D-penicillamine, together with s.c. administration of cupric sulfate or pyridoxine hydrochloride for 28 days in rats. The effects were compared with the actions of L- and DL-penicillamine. D-penicillamine increased urinary vitamin B6 excretion and lowered vitamin B6 levels extensively in serum and slightly in the liver. Those changes were also seen with L- and DL-penicillamine. On the other hand, D-penicillamine had no effects on the activities of serum transaminases and alkaline phosphatase and on the urinary excretion of xanthurenic acid after a tryptophan loading. D-Penicillamine, like L- and DL-penicillamine increased the urinary excretion of Cu and Zn and reduced Cu contents both in serum and liver. When Cu was given s.c. concomitantly with D-penicillamine p.o., an enhancement was seen in the effects of D-penicillamine on the urinary excretion of xanthurenic acid and body weight gain, as well as on the serum level of vitamin B6 and serum transaminase activities. Simultaneous injection of vitamin B6 with D-penicillamine produced a recovery in the lowering vitamin B6 levels induced by D-penicillamine in serum and liver and enhanced the urinary excretion of Cu, but did not influence the serum content of Cu. Thus, although the antivitamin B6 activity of D-penicillamine was demonstrated in rats, the degree was slight and was less than that seen with L- or DL-penicillamine. Moreover, the enhancing effect of Cu on the antivitamin B6 activity of D-penicillamine might be explained by the chelate formation between D-penicillamine-pyridoxal complex and Cu.

[Studies on the anti-ulcer effects of isoprenyl flavonoids (1). The anti-ulcer effects of isoprenyl chalcone extracted from Sophora subprostrata (author's transl)].

A series of extracted fractions from sophora subprostrata was screened by determining anti-ulcer effects in pylorus ligated and stressed rats. Fr. [C-2] had the most potent anti-ulcer effects of all fractions extracted. Sophoradin and sophoranone which were isolated from Fr. [C-2] were also found to have inhibitory effects on ulcer formation in pylorus ligated and stressed rats. The anti-ulcer effect of sophoradin was relatively potent in comparison with that of sophoranone and/or Fr. [C-2]. The anti-ulcer effect of sophoranone was approximately the same as that of Fr. [C-2]. The authors examined the effects of sophoradin and sophoranone on gastric secretion in pylorus ligated rats. Sophoradin and sophoranone significantly reduced the volume of gastric juice. Sophoradin but not sophoranone inhibited the free and total acid output of gastric juice. The effect of sophoradin was examined on various secretagogues which induced gastric secretions in rats with acute fistula. Sophoradin showed a tendency to inhibit tetragastrin- and insulin-induced gastric acid secretion, but there were no effects on methacholine- and histamine-induced secretions. These results suggest that sophoradin may have marked anti-ulcer and inhibitory effects on gastric secretion.

[Studies on D-penicillamine (1): Inhibitory effect of D-penicillamine on the heat-Cu++ induced denaturation of human gamma-globulin (author's transl)].

The inhibitory effect of D-penicillamine on the denaturation of human gamma-globulin induced by heat and Cu++ was compared with the action of other agents such as antirheumatic drugs, anti-inflammatory drugs, SH reagents, SH inhibitors and chelating reagents. The denaturation of human gamma globulin was induced by Cu++ at 10 micrometer ("Cu++ induced denaturation") and was further increased by heating at 63 degrees C for 3 hr in the presence of Cu++ ("total denaturation"). Thus the value obtained by subtracting "Cu++ induced denaturation" from "total one" was designated as "thermal denaturation". D-Penicillamine enhanced "thermal denaturation" at a low concentration but inhibited it with increasing the concentration as well as L-cysteine. SH reagents such as thiomalic acid, 6-mercaptopurine inhibited "total" and "thermal" denaturation. SH inhibitors and protein binding reagents such as N-ethylmaleimide, trinitrobenzenesulfonic acid inhibited the "total" and "thermal" denaturation of the protein. Chelating reagents such as ethylenediamine tetraacetic acid, 8-hydroxyquinoline inhibited "total", "Cu++ induced" and "thermal" denaturation of the protein. Au+ inhibited "total denaturation", but not "Cu++ induced denaturation". On the other hand, Au+++ denaturated the protein considerably with or without heating, in the absence of Cu++ but dithiothreitol did so only with heating in the same condition. The anti-inflammatory drugs used herein had no effect on the protein denaturation. D-Penicillamine apparently prevents the denaturation of human gamma-globulin by the chelate formation with Cu++ and the binding to free protein SH, initiator for sulfhydryldisulfide interchange reaction.