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Chicken liver is a potential source of campylobacteriosis in humans. Therefore, we determined the number of Campylobacter in chicken liver. In total, 33 vacuum-packed liver products were obtained from retail stores, and found that 27 of the 33 products (81.8%) were contaminated with Campylobacter. Moreover, Campylobacter was isolated from 138 of 149 livers (92.6%) collected from the 27 Campylobacter-positive products. The mean Campylobacter count was 2.3 log 10 CFU/g, while Campylobacter count in 22 of the 138 contaminated livers (15.9%) was >3.0 log 10 CFU/g. Furthermore, gastrointestinal tract, liver, and bile samples were collected from 35 broilers at chicken processing plants. We isolated Campylobacter from the gastrointestinal tract of 27 broilers (77.1%). Of these 27 broilers, liver of 24 broilers (88.9%) was Campylobacter-positive, with a mean Campylobacter count of 2.8 log 10 CFU/g. Of these 24 broilers, bile of 13 broilers (54.2%) was contaminated with Campylobacter (mean Campylobacter count, 3.5 log 10 CFU/mL). Among them, bile of 2 broilers had a Campylobacter count of >8.3 log 10 CFU/mL. Collectively, these results indicate that livers derived from broilers colonized with Campylobacter are contaminated with Campylobacter at the time of evisceration. Therefore, to prevent foodborne campylobacteriosis in humans, chicken livers should be thoroughly heated before consumption.

Meat derived from spent hens as well as broilers is destined for human consumption. There are many reports on the prevalence and antimicrobial resistance of Campylobacter and Salmonella in broiler meat, but few in spent hen meat. Therefore, we investigated the prevalence and antimicrobial resistance of these genera in spent hen meat collected at chicken processing plants. Campylobacter and Salmonella were isolated from 47 (92.2%) and 18 (35.5%), respectively, of breast meat derived from 51 spent hen flocks. Campylobacter jejuni accounted for 87.5% of Campylobacter isolates. The highest resistant rate in C. jejuni isolates was found for ampicillin (45.3%), followed by tetracycline (14.3%) and ciprofloxacin (14.3%). There was no Campylobacter isolate resistant to erythromycin, which is recommended as a first-choice antimicrobial for humans when Campylobacter enteritis is strongly suspected. Of Salmonella isolates, the first and second most frequent serovars were Salmonella Corvallis (30.4%) and S. Braenderup (21.7%), respectively. Of Salmonella isolates, 30.4% were resistant to streptomycin. There was no Salmonella isolate resistant to ciprofloxacin, which is one of the recommended antimicrobials for humans against Salmonella enteritis. This study shows that one third of spent hen meat is contaminated with Campylobacter or Salmonella, and administration of erythromycin or cefotaxime is an effective option for patients with Campylobacter- or Salmonella- enteritis, respectively, caused by consumption of spent hen meat.

Background: The "zero death from asthma strategy" in the medical treatment for bronchial asthma has been promoted by the Ministry of Health, Labour, and Welfare from 2006, and it indicates that medical and non-medical specialists, as well as pharmacists, should cooperate, and strives to build cooperation which is suited the actual conditions of an area. It is also important for COPD. Although hospitals in some areas cooperate with clinics and pharmacies, the overall concept of cooperation appears to be absent in most Japanese hospitals., Method: A questionnaire was administered in early March, 2012 to 477 allergology institutions, and was authorized by an educational establishment., Result: Among 246 replies from the institutions, cooperation between hospitals and clinics was carried out by 98 institutions (39.8%) specializing in bronchial asthma, and in 64 institutions (37.2%) specializing in COPD. However, cooperation tools were used in only 37 of these institutions (15.0%). The ability to fill prescriptions outside the hospital was available in 209 institutions (85.0%). One-hundred and seventeen institutions (47.6%) replied that they have no tools for hospital-pharmacy cooperation. Direct indications were written in prescriptions by 82 institutions (33.3)., Conclusion: In order to build inter-regional association and to equalize medical treatment, we suggest that developing tools and organization for cooperation between health professionals who treat patients with bronchial asthma and COPD is necessary.

Appropriate handling and controlled temperature prevent cross-contamination and proliferation of contaminants in foods, thereby reducing the incidences of food-borne gastroenteritis in Japan. However, the incidence of Campylobacter jejuni/coli infection did not markedly decrease and has become one of the major causes of food-borne diseases. C. jejuni and C. coli are widespread in warm-blooded domestic animals; therefore, food products may easily become contaminated during processing. C. jejuni and C. coli do not proliferate in foods, nor resistant to freezing, drying and oxidative stresses, and the number is greatly reduced under such conditions. These properties should be considered for risk management of Campylobacter in food processing and manufacturing.

Aim: Pain management is vital for both the maintenance and improvement of the quality of life of residents, in Japanese long-term care facilities. However, few studies examining pain assessment in older populations have been published. The purpose of this study is to investigate the actual conditions related to pain assessment of residents by nurses in Japanese long-term care facilities. Included in this investigation are the actual frequency of pain assessments, the nurses own perceptions of the pain assessment of their residents, whether or not nurses have undertaken any training related to pain assessment, and the need for a pain assessment training period., Methods: A questionnaire was distributed to 487 nurses in 60 Japanese long-term care facilities., Results: A total of 443 valid responses were collected. The data revealed that 74.7% of these nurses lack the confidence to suitably assess the residents' pain and 44.2% of these nurses do not conduct pain assessments on a regular basis. Additionally, only 9.9% of the nurses surveyed have participated in seminars concerning pain in older people., Conclusion: The results indicate that over 70% of nurses lack the confidence to suitably assess their residents' pain. In addition, the number of residents who cannot self-report their pain because of cognitive impairment is increasing. Therefore, it is necessary to develop new approaches which provide nurses with sufficient knowledge and confidence to conduct appropriate pain assessments on their residents.

Alcohol consumption impairs Th1-mediated cellular immune responses and enhances serum IgE levels. It has been reported that the elevated IgE levels are associated with a Th2 polarization response, but the mechanisms for enhancing Th2 polarization by the ethanol treatment remain to be elucidated. The aim of this review is to present and discuss the mechanism of Th2 polarization response by alcohol. IL-12 production by APCs such as monocytes, macrophages, and dendritic cells (DCs) preferentially leads to Th1 polarization. Acute ethanol consumption results in a significant decrease in IL-12 production in LPS-stimulated DCs and a CD40/CD40L interaction between CD40 on the DCs and CD40 ligand expressed on activated T cells. This suggests that Th2 polarization by ethanol is caused by impaired IL-12 production from APCs. In contrast, the induction of IL-10 by LPS is enhanced by ethanol treatment, suggesting that elevated IL-10 may play a role in ethanol-induced suppression of IL-12. However, ethanol inhibited IL-12 production in LPS-stimulated DCs devoid of IL-10 (IL-10/DC), suggesting that down-regulation of IL-12 by ethanol is independent of the IL-10 levels. Furthermore, several studies report that PGE2, cAMP and linolic acid, and endogenous lipid mediators released in inflammatory conditions, also inhibit IL-12 production. These inhibitory effects are similar to the IL-12 inhibition by ethanol. In addition, increase in the levels of these lipid mediators is induced by ethanol treatment. Alternatively, cytokine signaling studies indicate that IL-12 production by DCs is negatively regulated by PI3K and GSK-3, but positively regulated by p38 MAPK, mTOR, and NF-kappa B. Thus, it seems possible that ethanol may interact on the upstream of IL-12 producing a signal pathway. In fact, ethanol alters the stability of cell membrane, and suppresses clustering of TLR4 and recruitment of signaling molecules into lipid rafts, where it associates with the Ser/Thr kinase and the adaptor proteins, and forms a signaling complex. Down-regulation of lipid raft signaling is results in the impaired IL-12 production leading to the Th1 polarization, and causes CD4+ T cells to differentiation toward the Th2 lineage.

A 68-year-old man was admitted to our hospital in the mid-October of 2006 because of a one-month history of peculiar movements of the left hand, which had been preceded by one month by awkward motions in the left leg. Upon neurological examination, spontaneous involuntary movement of the left hand was found. His left hand with his index finger stretched moved toward his right side spontaneously. He could not control his left leg freely. Although he showed mild ataxia in his left hand, there was no weakness, no dystonia, and no apraxia. No sensory abnormality was detected except for mild deep-sensation impairment in his left foot. The results of magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) were normal; however, single-photon emission computed tomography (SPECT) showed hypoperfusion in the right hemisphere. At the time of admission, although a clinical diagnosis could not be made, we considered that the involuntary movements of his left hand were consistent with alien hand sign (AHS). Two and a half months after its onset, with the development of rapidly progressive dementia and generalized myoclonus, AHS gradually disappeared. Three months after the AHS onset, MRI with DWI showed restricted diffusion within the cortex involving the cingulated gyrus and bilateral temporal lobes, which was more prominent on the right than on the left side. Four months after the AHS onset, 14-3-3 protein level of the cerebrospinal fluid was elevated, and EEG recordings showed diffuse slowing of basic activity with periodic complexes. The patient was clinically diagnosed as having CJD. The patient died of pneumonia four and a half months after the AHS onset. AHS has rarely been reported in patients with CJD. Our case illustrates the importance of considering CJD in the differential diagnosis, if the patient showed AHS, even with normal MRI findings.

After a single oral dose of silodosin in male rats, male dogs and healthy human male volunteers, C(max) occurred within about 2 h, indicating rapid absorption. The elimination half-life was about 2 h in rat and dog, but 4.7 h (fasted) and 6.0 h (non-fasted) in humans. Absolute bioavailability values in rat, dog and human were about 9, 25 and 32%, respectively. In rat and dog, total blood clearance was almost equivalent to the hepatic blood flow, but that in human was low (20%), demonstrating a large species difference in hepatic clearance. In each species, the apparent volume of distribution exceeded the volume of total body water. After an oral dose of (14)C-silodosin to male rats, radioactivity was rapidly and widely distributed to most tissues. The highest concentrations outside the gastrointestinal tract were found in liver and kidney, with only low concentrations in brain tissues. The in vitro plasma protein binding of silodosin was about 80% in rat and dog, and 95.6% in humans, with alpha(1)-acid glycoprotein (AGP) contributing to the binding profile. Silodosin was found to be a dual substrate for CYP3A4 and p-glycoprotein. In human plasma, two major metabolites generated by UDP-glucuronosyltransferase (UGT; UGT2B7) and alcohol/aldehyde dehydrogenase (ADH/ALDH) were found, but no glucuronide conjugates were detected in rat or dog plasma. After a single oral dose of (14)C-silodosin in rat, dog and human, the urinary excretion of radioactivity was 15-34%, with that of unchanged silodosin being less than 4%. The radioactivity was predominantly excreted via the feces.

Background: Sevoflurane causes QT interval prolongation clinically, but its precise mechanism has not been clarified. We examined the mechanism of QT interval prolongation induced by sevoflurane by means of electrophysiological technique in guinea-pig ventricular myocyte., Methods: Electrocardiogram was recorded in guinea-pig and effect of sevoflurane (1, 2, 4%) was examined. Action potential (AP), delayed rectified potassium current (IKr), and L-type calcium channel current (ICa) were monitored as whole-cell current and by voltage clamp techniques in guinea-pig single ventricular myocytes. Sevoflurane was applied by bubbling into the bathing solution., Results: Sevoflurane (1, 2, 4%) increased QTc value. Sevoflurane prolonged the duration of AP at 2%, but shortened it at 6%. IKr was reduced to 35% of control in the presence of 2% sevoflurane, but a higher concentration (6%) did not show further inhibition. ICa was reduced only to 87% of control in the presence of 2% sevoflurane and the reduction was dose-dependent (4, 6%)., Conclusions: Sevoflurane 2% inhibited IKr, but it showed only slight inhibition on ICa. Because the duration of AP is regulated by ICa (plateau phase) and IKr (repolarization), greater inhibition of IKr than ICa could result in prolongation of AP. It is suggested that this mechanism may play a role in QT interval prolongation under sevoflurane anesthesia.

Objective: We conducted a population-based study to examine differences in risk of developing chronic atrophic gastritis in association with Helicobacter pylori (H. pylori) infection, with and without the presence of cytotoxin-associated gene A (CagA) antibodies, as well as to determine associations with the lifestyle factors., Method: Seventy hundred and thirty eight residents (295 men and 443 women) aged 30-64 living in a village in the southern part of Fukuoka Prefecture had an annual health checkup, and all participated in our study. We obtained information on their lifestyle with informed consent and measured the levels of serum pepsinogen I (PGI) and pepsinogen II (PGII), H. pylori and CagA antibodies. Chronic atrophic gastritis was defined as both PGI < 70 micrograms/l and PGI/PGII < 3.0., Results: The odds ratios for development of chronic atrophic gastritis were 4.26 (95% CI, 2.22-8.17) for CagA-positive H. pylori infection and 3.87 (95% CI, 1.95-7.68) for CagA-negative H. pylori infection in males, and 4.92 (95% CI, 3.06-7.92) and 3.02 (95% CI, 1.69-5.41) respectively for females, as compared with H. pylori-negative subjects. Regarding the relationship between chronic atrophic gastritis and lifestyle factors, high consumption of green tea was found to be negatively associated with risk, particularly with CagA-positive H. pylori infection., Conclusions: Our results suggest that a CagA-positive H. pylori infection is associated with an elevated risk for developing chronic atrophic gastritis as compared with Cag-negative H. pylori infection.

After the advent of levodopa, treatment of Parkinson's disease has changed and the activity of daily life of patients has been remarkably improved; whereas, many patients experience various problems such as wearing-off, dyskinesia, dystonia, neuropsychiatric problems, and dysautonomia. Especially, wearing-off and dyskinesia emerge with the change of absorptional pattern of levodopa and could be solved by regulating the timing and the dose of it. Recently, some new drugs for Parkinson's disease have been available and we physician have a wide choice of them. It is important to make a careful choice of and manipulate of doses of drugs after understanding daily life of each patient enough.

An 80-year-old man who had was administered antihypertensive medication showed repeated transient unresponsiveness during standing and/or walking. Neurological examination showed no focal neurological signs except mild dementia. Head-up tilting examination induced unresponsiveness and a decrease of systolic blood pressure from 111 mmHg to 86 mmHg. This unresponsiveness disappeared 3 minutes later when the blood pressure recovered to 102/64 mmHg. Cerebral angiography demonstrated occlusion in the right internal carotid artery and the right vertebral artery. Severe stenosis was observed at the left internal carotid artery and the left vertebral artery. Discontinuance of the antihypertensive medication reduced the frequency of orthostatic transient unresponsiveness. Elastic stockings in the lower extremities completely prevented the attack; head-up tilting did not induce hypotension with elastic stockings. The transient unresponsiveness in the present case was probably correlated to hemodynamic failure under the condition of severe cerebral arteriosclerosis.

Leptin, a product of the ob gene, is thought to play a key role in the regulation of adiposity. However, it is unclear in humans as to whether or not leptin influences the blood pressure, serum lipids, physical activity level, or eating behavior in relation to obesity. Recent reports have indicated both gender-based differences in the leptin levels and a correlation of the percentage of body fat with leptin levels has been observed among obese subjects. As far as we know, these relationships among non-obese young adults have yet to be studied. Therefore, the serum leptin concentrations among 107 non-obese students (72 males and 35 females) were measured by a radioimmunoassay(RIA). Fasting leptin levels ranging between 1.2 and 23.4 ng/mL were observed in all subjects, and the levels among females were 2.6 times higher than in males (7.64 vs 2.95 ng/mL; p < 0.001). A close correlation was observed regarding the log-transformed leptin levels with the percentage of body fat as determined by the bioelectrical impedance analysis method(r = 0.734, p < 0.001 in males and r = 0.579, p < 0.001 in females). In conclusion, these data thus suggest the serum leptin levels among non-obese students show significant gender-based differences while, in addition, the leptin levels also correlate positively with the percentage of body fat. However, it remains unclear as to whether or not the leptin levels are independently related to the blood pressure, serum lipids, physical activity level (sports activity and leisure-time activity), and eating behavior (eating breakfast, mid-day snacking and nighttime snacking).

We conducted a prospective study to clarify the relationship between mortality and body mass index (BMI) in a middle-aged and elderly population in Japan. The subjects included 12,649 people (5,686 males and 6,963 females) aged from 40-69 years, who were identified by a mail survey between 1987 and 1989, and thereafter were followed up from the date of the survey until February 28, 1995. Cox's proportional hazards model was used to adjust for age, smoking status, drinking habit and occupation, and hazard ratios were calculated for total mortality and cancer mortality based on levels of BMI, while using a BMI of 22 to approximately 24 as a reference level. Results showed a U shaped relationship between BMI and total mortality in females. Females demonstrated a minimal total mortality in the reference group, but a significantly high hazard ratio in the lowest group of BMI < 20 (hazard ratio = 1.95, p < 0.01) and the highest group of BMI > or= 26 (hazard ratio = 1.71, p < 0.01). On the other hand, males did not demonstrate such a U shaped relationship, but instead showed an L shaped relationship between BMI and total mortality. Males showed a minimal total mortality at a BMI of 24 of approximately 26 (hazard ratio = 0.92), but a significantly high hazard ratio in the lowest BMI group (hazard ratio = 1.57, p < 0.01). In contrast, an elevated hazard ratio was not observed in the highest BMI group (hazard ratio = 1.05). The relationship between BMI and cancer mortality was found to be similar to the relationship between BMI and total mortality in both males and females. Our findings suggest that moderate overweight may be a sign of good health among both middle-aged and elderly men in Japan.

We assessed the effects of propofol on contraction, action potentials and Ca2+ currents (Ica) in single ventricular cells in dog. Low concentrations of propofol 10(-5)M had no effects on contractile responses, but high doses above 10(-4)M of propofol decreased contractions. Propofol 10(-3)M reduced the duration of action potentials (time to 90% repolarization). Ica was decreased by propofol 10(-4)M without accompanying use-dependent manner. The present study indicates that clinical concentrations of propofol do not exert direct negative inotropic effects, but at supratherapeutic concentrations it inhibits cardiac contractility.

The purpose of this study was to determine if a relationship exists between 'sekentei' and utilization of health, social and nursing services. 'Sekentei' is the level of a person's self-consciousness of others observing one's behavior and endeavoring to meet the perceived norms of behavior. A questionnaire assessing 'sekentei' was developed and utilized in a survey with 1,294 persons responding to the questionnaires. The results of this study were as follows: (1) 'Sekentei' was related to the place of birth, former occupation and education of persons. (2) Respondents who had a higher 'sekentei' score showed a tendency to have a sense of resistance concerning the use of services. (3) There was a significant relationship between 'sekentei' and utilization of services. These results show the importance of considering individual consciousness of 'sekentei' and characteristics of a community to facilitate use of services and remove the stigma related to social services in a community.

The effects of bupivacaine on Na+ and Ca2+ currents in single canine isolated left ventricular cells were examined using whole-cell voltage clamp technique to reveal the mechanism of its negative inotropism. The cells were isolated by enzymatic dispersion and superfused in an oxygenated Tyrode's solution. Bupivacaine 10(-6) M decreased the amplitude of INa and delayed the peak time. These effects were dose and frequency dependent. At a concentration of 10(-3) M, bupivacaine abolished INa. Meanwhile, bupivacaine did not modify ICa at a concentration of 10(-6) M. At 10(-5) M bupivacaine, the amplitude of ICa was depressed by 22% and the depression was dose dependent. These results suggest that low concentration (10(-6) M) of bupivacaine depresses contraction, by reducing intracellular Ca2+ secondary to reduction in intracellular Na+ activity and the Na+-Ca2+ exchange mechanism. At higher concentrations, the reduction in contraction caused by bupivacaine may result partly from a reduced influx of Ca2+.

Although volatile anesthetic is known as a cerebral vasodilator, its mechanism is not clear. The purpose of this study was to investigate effects of sevoflurane or halothane on contractions induced by high K+ and serotonin in the isolated canine basilar artery. Cylindrical segments of canine basilar artery were placed in Krebs solution oxygenated with 95% O2 and 5% CO2 at 37 degrees C. They were then constricted with cumulative administration of 10 to 60 mM KCl, or with 10(-9) to 10(-6) M serotonin and exposed to either sevoflurane or halothane at concentration of 1.0 and 2.0 MAC. Halothane and sevoflurane at concentration of 1.0 and 2.0 MAC decreased contractile responses evoked by KCl to a similar degree. The attenuation by either of the two anesthetics at concentration of 2.0 MAC were equivalent to the inhibitions by diltiazem 2 x 10(-7) M. Contractile responses to serotonin above 3 x 10(-7) M were depressed by halothane 1.0 MAC, but not by sevoflurane 1.0 MAC. Sevoflurane and halothane at concentration of 2.0 MAC decreased contractile responses evoked by serotonin at concentrations above 3 x 10(-8) M and 10(-8) M. Removal of the endothelium did not alter the response of the basilar artery contracted by serotonin to either anesthetic. These findings suggest that sevoflurane and halothane depress the voltage-dependent Ca2+ channels due to decreases of contractile responses to high K+. Our results also demonstrate that sevoflurane is a less potent vasodilator of the basilar artery contracted by serotonin than halothane.

The effects of sevoflurane (SV) on contraction, membrane ionic currents and intracellular cAMP concentration were studied in single canine ventricular cells. The authors demonstrated first that SV depressed contractile response of single ventricular cells in a dose-dependent manner. In electrophysiological studies, SV depressed the plateau height and duration of action potentials. Whole-cell voltage clamp experiments revealed that SV depressed voltage-dependent Ca2+ currents in a dose-dependent manner but SV (1%, 2%) did not change Na+ currents. Further, SV (1%, 2%) did not reduce intracellular cAMP concentrations. We conclude that the decrease of myocardial contractile response in single canine cardiac cells by SV is mainly due to the inhibition of voltage-dependent L-type of Ca2+ channels at the sarcolemma and not through changes in intracellular cAMP levels.

The effects of sevoflurane on contraction and membrane potentials were studied in isolated canine ventricular muscle strips. Sevoflurane depressed electrically-induced contraction in a dose-dependent manner. The inhibitory effect was more pronounced in high-K+ Tyrode solution than in normal Tyrode solution suggesting that sevoflurane inhibits transmembrane Ca2+ influx. In electrophysiological studies, sevoflurane depressed both overshoot and the plateau phase of action potentials. Resting membrane potential was not affected by sevoflurane. We conclude that the depression of myocardial contractility by sevoflurane may be due to block of transmembrane calcium influx.

We studied the effects of bupivacaine on the contractility and membrane potentials in isolated dog papillary muscle. Bupivacaine (10(-6)-10(-4) M) produced dose-dependent depression of twitch tension elicited by electrical stimulation. These inhibitory effects were greater at high frequencies of stimulation (2, 3 Hz) than at low frequencies (less than 1 Hz). Bupivacaine did not alter the resting membrane potential, but produced a reduction in Vmax of the action potentials, in a dose-dependent and reversible manner (concentrations from 10(-6) to 10(-4) M). Bupivacaine 10(-4) M often blocked the fast action potentials in normal Tyrode's solution. In high K+ (26 mM) Tyrode's solution, bupivacaine inhibited both slow action potentials and associated contractions in the presence of isoproterenol. These results suggest that low concentrations of bupivacaine decreases the contraction mainly due to Na+ channel block, whereas at higher concentration, this anesthetic may block Ca2+ channels. In addition, isoproterenol may be clinically effective in the treatment of bupivacaine cardiotoxicity due to stimulation of Ca2+ mediated slow action potentials through beta-receptors.

The effects of ketamine on Ca(2+)-activated K+ channel currents were studied in dispersed single smooth muscle cells from rabbit portal vein using inside-out patch clamp technique. In a near physiological K+ and Ca2+ gradient, three populations of outward rectangular single currents were recorded in isolated cell membrane of rabbit portal vein at +60 mV membrane potential. These currents were judged as Ca(2+)-activated K+ channel currents since application of EGTA or Apamin in the internal solution inhibited these currents. Application of 10(-5)M or 10(-4)M ketamine inhibited the number of occurrences of channel opening and decreased open times, but did not reduce the amplitudes. When the 10(-3)M ketamine was applied, the Ca(2+)-activated K+ channel currents were abolished. We suggest that the depression of Ca(2+)-activated K+ channel currents may explain the continuous contraction observed in rabbit portal vein at a clinical concentration of ketamine from a point of electrophysiological K+ current study.

The effect of the ophthalmic solution of tranilast, an anti-allergic agent, on allergic conjunctivitis was studied in passively sensitized guinea pigs. We determined the content of uranine dye and histamine in tears and histopathologically examined palpebral conjunctiva. After instillation of antigen into the conjunctival sac, inflammation of the palpebral conjunctiva, an increase in leaked dye and the release of histamine were found. In the histopathological study, tranilast (1.0%) suppressed the appearance of edema and infiltration of inflammatory cells. Tranilast suppressed the leakage of uranine in a dose-dependent manner. A 0.5% solution of diphenhydramine also showed the inhibitory effect on the leakage of uranine. The inhibitory effect of 0.5% tranilast on antigen-induced dye leakage and histamine release lasted for 6 hr. These results suggest that topically applied tranilast is effective for allergic conjunctivitis.

We studied the inhibitory effects of tranilast, an anti-allergic drug, on the human keloid tissues implanted into the dorsal skin of athymic nude mice and on the growth of keloid fibroblast in vitro. In the keloid tissue-implanted model, tranilast (50-200 mg/kg, p.o.) decreased the weight of the keloid tissue as triamcinolone (25 mg/kg, p.o.) did. Tranilast (200 mg/kg, p.o.) reduced the hydroxyproline content of implanted tissues. Tranilast (3-300 microM) also inhibited the collagen synthesis by keloid fibroblast in vitro. Only a high concentration of tranilast (300 microM) suppressed the glycosaminoglycan synthesis and cell proliferation of keloid fibroblasts. Moreover, tranilast scarcely affected the fibronectin production. Triamcinolone (10 microM) also inhibited glycosaminoglycan synthesis and cell proliferation. These results suggest that the inhibitory effect of tranilast on the keloid tissues is related to its inhibition of the collagen synthesis of fibroblasts. Tranilast would be useful as a therapeutic drug for the treatment of keloids.

In order to analyze direct action of isoflurane on myocardium, we studied effects of isoflurane on membrane potentials and transmembrane ionic currents in single ventricular myocytes isolated enzymatically from rabbit hearts. Membrane potentials were recorded with a suction microelectrode technique, and an action potential was elicited by a brief intracellular stimulus. Isoflurane 3% depressed the action potential overshoot, plateau phase and duration without changing resting potential. Isoflurane decreased the refractory period of the action potential and prolonged the time-constant (tau) of the recovery process. In corresponding voltage clamp experiments, isoflurane significantly depressed the Ca2+ current (ICa), which generates the plateau phase. However, isoflurane had no effect on the transient outward current (I(t)), which triggers repolarization of the action potential. In rabbit ventricular cells, the time- and voltage-dependent outward K+ current (IK) was nearly absent. In conclusion, the depression of the action potential plateau by isoflurane is due to the decrease of ICa. Since isoflurane has no effect on It, the depression of the plateau phase by isoflurane may explain the shortening in the duration and the refractory period of the action potential.

In order to assess directly the actions of halothane on myocardium, especially on the Ca2+ channel we studied effects of halothane on electrophysiological and biochemical properties in single ventricular myocytes isolated enzymatically from guinea pig hearts. Membrane potentials and the slow inward Ca2+ current (ICa) were recorded with a suction microelectrode technique and a whole cell voltage clamp technique. The plateau duration of the action potential, maintained by ICa, and ICa was depressed by 2% halothane (to 58% and 29% of control respectively). To define the site on which halothane acts in the cell membrane, we measured cyclic adenosine monophosphate (cAMP) content of single ventricular myocytes using radioimmunoassay. One percent (1%) and 2% halothane directly produced a dose-dependent decrease in myocardial cAMP content (79% and 65% of control respectively). In conclusion, the present results suggest that the decrease of ICa by halothane participates in the observed depression of the action potential plateau phase and demonstrate that halothane depression of ICa is in part due to an inactivation of phosphorylation dependent gate in the Ca2+ channel resulting from the decrease in cAMP content by halothane.

The effects of ketamine on membrane potentials and voltage-dependent Ca2+ current were studied in dispersed single smooth muscle cells from rabbit portal vein. The resting membrane potential (-56.2 +/- 1.5mV) was not affected by ketamine (10(-5)-10(-3)M). The duration and the amplitude of the action potential evoked by intracellular stimulation were significantly decreased by ketamine in the concentrations of 10(-4)M and 10(-3)M. Voltage-gated Ca2+ current in single smooth muscle cells was apparently decreased by ketamine at concentrations of between 10(-5)M to 10(-3)M. The activation threshold of Ca2+ current (approx. -30mV) was also decreased by ketamine. Therefore, these results suggest that inhibition of the contractile response by ketamine in vascular smooth muscle from rabbit portal vein may be attributable to the inhibition of the Ca2+ current.

The effects of ketamine on contraction induced by depolarization of cell membrane (high K+-induced contracture) were studied in isolated vascular smooth muscle from rabbit portal vein. Ketamine in concentrations above 5 x 10(-4) M caused relaxation in phasic contraction, and above 10(-4) M caused relaxation in tonic contraction. These effects of ketamine at concentrations of between 10(-5) to 10(-3) M were dose dependent and reversible. In concentration above 10(-5) M, ketamine decreased the contractile response (tonic contraction) induced by 2.5 mM Ca2+ after the temporary contracture in Ca2+-free, high K+ solution. The contractile responses to norepinephrine (10(-6) M) or serotonin (10(-6) M) were also inhibited by ketamine. From these findings, it is concluded that ketamine decreases contractile responses due to transmembrane Ca2+ influx after depolarization of cell membrane and may decrease the contractile responses in concentration above 5 x 10(-4) due to Ca2+ release inhibition from sarcoplasmic reticulum.