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Biomedical subjects

N Inaba

Publications and source records attributed to N Inaba.

At least 19 recordsLinked to original sources

Suppressive effects of F-1322 on the antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs.

We investigated the effects of F-1322 (N-[2-[4-(benzhydryloxy)piperidino]ethyl]-3-hydroxy-5-(3-pyridylmethoxy)-2-naphthamide), a new compound that inhibits both thromboxane A2 synthetase and 5-lipoxygenase and that functions as a histamine antagonist, on the Ascaris antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs. Oral administration of F-1322 (10-100 mg/kg) inhibited the antigen-induced late asthmatic response in a dose-dependent manner. Histological analysis revealed that F-1322 prevented the accumulation of eosinophils in the airways and this was paralleled by a decrease in the number of eosinophils and lymphocytes recovered in bronchoalveolar lavage fluid. F-1322 (0.1-10 microM) inhibited eotaxin-induced chemotaxis and actin polymerization of eosinophils in vitro in a concentration-dependent manner, while oral administration of F-1322 dose-dependently suppressed the migration of eosinophils into the airways in vivo in response to infusion of interleukin 5 and eotaxin in combination. F-1322 may, thus, improve the late asthmatic response in this model, in part, by preventing the accumulation of eosinophils in the airways. The pharmacological profile of F-1322 indicates that this drug is likely to be useful in the treatment of allergic diseases such as asthma.

Airway Resistance↗

Increased excretion of N-acetyl-beta-D-glucosaminidase and beta2-microglobulin in gestational week 30.

BACKGROUND: Little is known about when the urinary excretion of a combination of N-acetyl-beta-D-glucosaminidase (NAG) and beta2-microglobulin (beta2MG) concentration [relative to creatinine (Cr)] reaches maximal values during uncomplicated normotensive pregnancy. This study was thus designed to analyze when urinary excretion of biochemical parameters was increased during normotensive pregnancy. METHODS: NAG, beta2MG, total protein, albumin, and Cr were simultaneously measured in random (untimed) midstream urine samples from 22 healthy nonpregnant women and from 82 normotensive pregnant women (22 in gestational week 20, 25 in week 30, and 35 in week 37). RESULTS: NAG/Cr and beta2MG/Cr ratios were significantly higher (P < 0.01-0.05) in the normotensive pregnant women in gestational week 30 than in the nonpregnant control subjects and normotensive pregnant women in gestational week 20. The NAG/Cr and beta2MG/Cr ratios showed maximal values in gestational week 30. The total protein/Cr ratio was significantly higher in gestational weeks 20, 30, and 37 than in the control subjects. The albumin/Cr ratio was significantly higher in women in gestational week 30 and 37 than in women in gestational week 20 and in the control subjects. CONCLUSIONS: The excretion of both NAG and beta2MG relative to Cr was increased and showed the maximal values in gestational week 30 during normotensive pregnancy. The increase in a tubular enzyme (NAG) might be caused by renal tubular damage, and that in a low molecular weight protein (beta2MG) might result from decreased renal tubular reabsorption. These findings suggest that renal tubular damage and reabsorption dysfunction were increased in gestational week 30.

Acetylglucosaminidase↗

[Pressure wire guide provisional coronary stent implantation].

OBJECTIVES: Whether coronary artery lesion successfully dilated by balloon angioplasty should be stented or not is unclear. The purpose of this study is to evaluate the provisional stent implantation method assessing residual ischemia by pressure wire. METHODS: Thirty-one patients with de-novo lesions suitable for stenting were enrolled in a pressure wire guided provisional stent study. The pressure wire was used to assess the fractional flow reserve(FFR) before and after balloon angioplasty. When the FFR after angioplasty was less than 0.75, stent implantation was planned. Patients with lesions consisting of an intermediate stenosis proximal to the target lesion, chronic total occlusion, bypass graft and left main lesion were excluded from the study. Stent implantation was permitted even if the FFR was more than 0.75 when the operator thought stenting was necessary. Medical treatment was given with aspirin 162 mg/day, cilostazol 200 mg/day for 6 months and additional ticlopidine 200 mg/day for a month after stenting the lesion. RESULTS: Target vessel was the left anterior descending coronary artery in 19 lesions, the right coronary artery in 3, and the circumflex coronary artery in 9. Stent implantation was performed in seven (23%) of 31 lesions and the other 24(77%) lesions were treated with only balloon angioplasty. The FFR before intervention was 0.58 +/- 0.16, and improved to 0.87 +/- 0.07 (p < 0.0001). Percentage diameter stenosis before intervention was 70.7 +/- 12.6% and improved to 20.1 +/- 13.3% (p < 0.0001) after intervention. There was no major cardiac event (death, coronary artery bypass grafting, myocardial infarction, stent thrombosis). Six months follow-up angiography was performed in 27 patients (87%). Angiographic restenosis (percentage diameter stenosis > or = 50%) was found in four patients (15%). A new lesion was found in two patients. Target vessel revascularization was performed in six patients (21%). CONCLUSIONS: Lesions successfully dilated by balloon angioplasty with FFR > or = 0.75 do not require stenting.

Angioplasty, Balloon, Coronary↗

The fertility and pregnancy outcomes of the patients who underwent preservative operation followed by adjuvant chemotherapy for malignant ovarian tumors.

The fertility and pregnancy outcomes of the patients were studied, who previously underwent preservative operation for malignant tumors, including those of borderline malignancy, in our ward from 1981 to 1995. For each of the 9 patients, unilateral ovary was preserved, the range of their ages before operation was 10 to 28 years old, and histologically, 7 patients had tumors derived from germ cells, and 2 had those from epithelial cells. As for clinical stages according to the FIGO's criteria, 5, 1, 2 and 1 patients were in stage I, II, III and IV, respectively. The regimens of the combination chemotherapy for patients with germ cell tumors were PVB (cisplatin, vinblastine and bleomycin), PEP (cisplatin, etopside and pepleomycin), PVP (cisplatin, vinblastine and pepleomycin), AVAC (doxorubicin, vincristine, actinomycin-d and cyclophosphamide). Those for the patient with epithelial tumors were CAP (cyclophosphamide, doxorubicin and cisplatin), CP (cyclophosphamide and cisplatin). Eight patients have been doing well, although 1 of them experienced recurrence and died. Amenorrheic periods of 2 to 12 months were noticed in 3 patients, although in all of them, ovulatory cycles recovered. Eight pregnancies were reported: 5 term delivery with normal babies, and others were preterm termination due to abruptio placenta with a baby of appropriate for date, spontaneous abortion, and artificial termination. We suppose that the combination chemotherapy applied for the patients in the present study affected neither the fertility of the patients nor the outcomes of the pregnancies.

Adolescent↗

Changes in plasma soluble CD26 and CD30 during pregnancy: markers of Th1/Th2 balance?

The theory that the Th1 and Th2 cell ratio shifts towards Th2 dominance during pregnancy may improve fetal survival has gained support from recent studies. Also, the variation in the Th1/Th2 cell ratio is reportedly associated with intrauterine growth retardation and preeclampsia. On the basis of these findings, the analysis of the Th1/Th2 balance may be useful in predicting severe complications during pregnancy. However, simple methods for the analysis of Th1/Th2 balance are presently not available. Recently, it has been reported that regulation of CD26 cell surface expression correlates with the production of Th1-like cytokines. On the other hand, previous studies proposed that the sCD30 molecule is an activation marker useful for evaluation of a Th2 immune response. It is, therefore, possible that the analysis of the Th1/Th2 balance during pregnancy by measuring plasma sCD26 and sCD30 simultaneously is a simple and useful method. We herein demonstrate that combined analysis of sCD26 and sCD30 is a potent surrogate tool to evaluate the Th1/Th2 balance during pregnancy.

Adult↗

Placenta accreta/increta. Review of 10 cases and a case report.

A review of the patients seen at the Department of Obstetrics at Dokkyo University Hospital who had suffered placenta accreta/increta in the past 18 years, was performed. There were 10 such cases out of 9,716 deliveries during this period. This incidence is higher than that which has been reported in other Western countries. Forty percent of the patients in our study had placenta accreta/increta accompanied by placenta previa or low lying; 30% had had a prior cesarean section (C/S); 70% had previously experienced dilatation and curettage (D & C); 80% had previously undergone a C/S and/or D & C: and 40% had a history of miscarriage. Three of the ten patients with placenta accreta/increta required a hysterectomy; 2 patients were successfully treated with hemostatic stitches on the endometrium; and the remaining 5 mild cases were treated with removal of the placenta, either manually or with the use of forceps. There was no case of maternal death. In 2 cases, neonatal asphyxia was noted, but the neonate immediately recovered.

Adult↗

Gastroprotective mechanism of lafutidine, a novel anti-ulcer drug with histamine H2-receptor antagonistic activity.

Lafutidine (CAS 118288-08-7, FRG-8813) is a novel histamine H2-receptor antagonist with gastroprotective activity. The aim of this study was to investigate the property of the gastro-protective activity of lafutidine by examining the effect on ammonia-induced change in transmucosal potential difference (PD), basal gastric mucosal blood flow (GMBF) and noxious agent-induced cell damage. Intragastrical application of lafutidine accelerated the recovery of the PD reduction after exposure of the mucosa to 0.25% ammonia solution and the accelerating effect was abolished by chemical deafferentation, but not with indometacin, a cyclooxygenase inhibitor. The application of capsaicin, as a reference compound, significantly promoted the recovery of the ammonia-induced PD reduction and this effect was not altered with indometacin. Lafutidine given intragastrically caused a sustained increase in GMBF in a dose-dependent fashion, which was also completely inhibited in the deafferentated rats. In vitro studies revealed that, in contrast to 16,16-dimethyl prostaglandin E2, lafutidine did not protect isolated gastric superficial epithelial cells from ethanol- or ammonia-induced damage. In conclusion, the gastroprotection of lafutidine is induced by promoting the restitution of the damaged mucosa after a noxious agent, not by directly protecting the epithelial cells and this effect may be caused through the mechanism of capsaicin-sensitive afferent nerves.

16,16-Dimethylprostaglandin E2↗

Antiulcer effect of lafutidine on indomethacin-induced gastric antral ulcers in refed rats.

Lafutidine is a new type antiulcer agent with antisecretory and gastroprotective activities. We investigated the effect of lafutidine on indomethacin-induced antral ulcer in refed rats. Subcutaneous indomethacin injection resulted in the formation of gastric antral ulcer. Lafutidine (1-10 mg/kg, p.o.) reduced the area of ulcer in a dose-dependent manner when administered immediately after the indomethacin injection. Capsaicin at 3 mg/kg, p.o. and 16,16-dimethyl prostaglandin E2 at 3 microg/kg, p.o. also reduced the ulcer area. Chemical deafferentation of capsaicin-sensitive neurons or N(G)-nitro-L-arginine treatment aggravated the ulcer formation and abolished the preventive effect of lafutidine and capsaicin. After the induction of gastric ulcer, lafutidine given twice daily for 2.5 days reduced the area of ulcer in a dose-dependent manner with a significant effect at 10 mg/kg, p.o., as compared with that of the control group. In chemically-deafferentated rats, lafutidine did not show any healing effect. Cimetidine (30 mg/kg, p.o.) and famotidine (1 mg/kg, p.o.) had no significant effect on indomethacin-induced antral ulcer. These results may suggest that lafutidine, unlike cimetidine and famotidine, can prevent the indomethacin-induced antral ulcer formation and accelerate the healing of the ulcer in refed rats through mechanisms involving the capsaicin-sensitive afferent neurons and nitric oxide.

16,16-Dimethylprostaglandin E2↗

[TTV materno-infantile infection--a study on the TTV frequency in Japanese pregnant women and the natural history of TTV mother-to-infant infection].

We preliminarily describe the frequency of TTV in Japanese pregnant women, non-parenteral, postnatal materno-infantile transmission of TTV, and 2 cases in which infantile development of the TTV carrier-state seemed to have occurred by vertical infection. The sera of 85 hepatitis B, C and G-positive and 36 non-pathological pregnant Japanese women were screened for the presence of TTV DNA with a use of semi-nested PCR. The positive rates were 25.9 and 27.8%, respectively. No significant differences were gained between these two groups. Twenty-one infants were born to the TTV carrier women. Of them, 9 infants (42.9%) sero-converted to TTV DNA-positive after their age of 4 months. Among the infants who were breast-fed, the positive sero-conversion rate of TTV DNA tended to increase as the length of the breast feeding period increased. Serum AST/ALT levels stayed within normal upper limits in the 9 infants. This study indicates the frequent, and furthermore, certain possibility of non-parenteral (i.e., via breast milk), postnatal vertical infection of TTV.

Biomarkers↗

Nasal absorption kinetic behavior of azetirelin and its enhancement by acylcarnitines in rats.

PURPOSE: The long-term stability and nasal absorption characteristics of a basic nasal formulation of azetirelin, a thyrotropin-releasing hormone analog and its absorption enhancement by incorporation of acylcarnitines in the formulation were investigated. METHODS: The long-term stability of basic nasal azetirelin formulations at 25 degrees C was predicted by calculation from the Arrhenius plot of the data on 6 months' storage at 40, 50 and 60 degrees C. Nasal azetirelin absorption characteristics were kinetically examined by intranasal administration to rats, determination of plasma azetirelin level by radioimmunoassay, and fitting the data to a two-compartment model including absorption rate. RESULTS: Basic nasal azetirelin formulations of pH 4.0 and pH 5.1 were predicted to be highly stable. Residual azetirelin after 2 years storage at 25 degrees C was greater than 95%. Nasal absorption characteristics of this formulation in the pH 4.0-6.3 range showed pH-dependency, with pH 4.0 showing the highest absolute bioavailability (Bioav) of 17.1%. This nasal Bioav was 21 times greater than that of oral administration (0.8%). Acylcarnitines with 12 or more carbon atoms in the acyl chain greatly enhanced nasal absorption of azetirelin: Bioavs with lauroylcarnitine chloride (LCC) and palmitoylcarnitine chloride were 96.9% and 72.9%, respectively. This enhancement by LCC plateaued at the low concentration of 0.1%. CONCLUSIONS: The basic nasal azetirelin formulation at pH 4.0 is stable and shows adequate absorption, with nasal absorption having greater Bioav than oral absorption. The 12-carbon acylate LCC was the strongest enhancer among acylcarnitines and provided near-total delivery of the administered dose to the blood.

Absorption↗

Vertical transmission of hepatitis C virus: risk factors and infantile prognosis.

OBJECTIVES: To clarify the incidence and risk factors of the vertical transmission of hepatitis C virus (HCV) and to determine the prognosis of the carrier infants. METHODS: At our hospital, 1,941 non-pathological (non-HIV carriers) Japanese pregnant women were screened for anti-HCV antibodies. Sera of the antibody-positive women were examined by the reverse transcription polymerase chain reaction (RT-PCR) method, and the positive women and their infants were followed by testing HCV-related markers. RESULTS: The HCV carrier rate among the pregnant women was 3.5% (68/1,941). Four among the 65 infants (6.2%) who were successfully followed for more than 6 months developed the HCV carrier-state. Of all the risk factors examined, only the elevation (> or = 110 IU/l) of maternal serum alanine aminotransferase (ALT) was found to be significant for HCV vertical transmission. Seventy-five and 50% of the carrier infants manifested chemical hepatitis and seroconverted to an HCV-RNA-negative status, respectively, during the follow-up period. CONCLUSIONS: The frequency of HCV vertical transmission was 6.2%. Half of the carrier infants became seronegative for HCV-RNA. HCV vertical transmission was significantly affected by the maternal serum ALT level prior to delivery.

Adolescent↗

Modulation of the inspiratory-related activity of hypoglossal premotor neurons during ingestion and rejection in the decerebrate cat.

Single-unit activities of the bulbar reticular inspiratory neurons directly projecting to hypoglossal motoneurons were studied during fictive ingestion (e.g., swallowing) and rejection elicited by repetitive stimulation of the superior laryngeal nerve and by application of water to the pharynx in immobilized decerebrated cats. The single-unit activity was recorded during 113 episodes of fictive ingestion from 25 inspiratory neurons directly projecting to hypoglossal motoneurons (single projection neurons) and 7 inspiratory neurons directly projecting to both hypoglossal and phrenic motoneurons (dual projection neurons) in the regions ventrolateral to the nucleus tractus solitarii and dorsomedial to the nucleus ambiguus. All of single projection neurons ceased inspiratory-related rhythmical discharges coincidentally with the onset of repetitive stimulation of the superior laryngeal nerve. The majority of them (19/25, 76%, type A) showed a spike burst during ingestion, whereas the minority (6/25, 24%, type B) kept silent until the end of repetitive stimulation of the superior laryngeal nerve. During fictive ingestion elicited by application of water to the pharynx, the type-A neurons showed a spike burst activity, whereas the type-B neurons kept silent. All dual projection neurons (7/7, 100%, type C) ceased inspiratory-related rhythmical discharges at the onset of repetitive stimulation of the superior laryngeal nerve and showed no activity during fictive ingestion. Likewise, the type-C neurons kept silent during fictive ingestion elicited by application of water to the pharynx. A spike burst was induced during 33 episodes of fictive rejection in all of 5 tested type-A, 3 tested type-B, and 6 tested type-C neurons. It is concluded that the premotor neurons involved in the respiratory-related rhythmical activity of hypoglossal motoneurons is responsible for switching from respiration to ingestion and rejection.

Animals↗

Maternal-infant transmission of hepatitis G virus.

By a reverse transcriptase-polymerase chain reaction assay, we studied the risk of hepatitis G virus vertical infection in seven infants born to women positive for hepatitis G virus ribonucleic acid and hepatitis C virus antibody. Of these, three (42.9%) tested positive for hepatitis G virus ribonucleic acid and two (28.6%) had a carrier state. Intrauterine or birth canal infection seemed much more significant than the infection by breast-feeding.

Breast Feeding↗

Effects of several denervation procedures on distribution of calcitonin gene-related peptide and substance P immunoreactive in rat stomach.

The effect of chemical deafferentation, vagotomy (VGX), and gangliosympathectomy (GSX) on the density of fibers containing calcitonin gene-related peptide (CGRP) and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation by capsaicin abolished the density of CGRP-immunoreactive (IR) fibers, not Sub.P-IR fibers. Ten days after VGX, the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reduction of CGRP-IR and Sub.P-IR fibers was seen in submucosal and muscular layers. GSX significantly reduced the density of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosal and muscular layers. Pretreatment with 6-hydroxydopamine, a neurotoxin for noradrenergic nerves, did not affect the density of CGRP-IR fibers in the gastric wall. The density of Sub.P-IR fibers in the gastric wall was not affected by GSX. These studies indicate that the CGRP-IR and Sub.P-IR fibers in the mucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and muscle layers, that a major portion of the CGRP-IR fibers in the mucosa is of both vagal and spinal origin, and that a major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, the present results support that CGRP-IR fibers, not Sub.P-IR fibers, in the rat stomach are capsaicin-sensitive.

Animals↗

[Effect of a novel antiulcer drug, lafutidine, on experimental chronic gastritis in rats].

Oral administration of an ammonia solution (0.01%) or a sodium taurocholate solution (TCA solution, 5 mM) as drinking water for 4 weeks or 13 weeks, respectively, resulted in gastric mucosal thinning and decreased parietal cell numbers. Oral administration of TCA solution also caused cell infiltration in the lamina propria of the mucosa and mucosal fibrosis. When lafutidine (3, 10 mg/kg) was administered orally once daily for one week after the withdrawal of ammonia or TCA solution, the recovery of the mucosal thickness in the fundic gland area and the parietal cell number were significantly accelerated, and the recovery of mucosal thickness in the pyloric gland area also tended to be accelerated. Lafutidine at 10 mg/kg for 1 week had no influence on normal mucosal thickness and parietal cell numbers. At the doses that produce equal or greater acid antisecretory effect than lafutidine, oral administration of cimetidine (30 mg/kg) and famotidine (1 mg/kg) had no effect on either of these atrophy indexes. These results demonstrate that lafutidine, unlike cimetidine and famotidine, can accelerate the healing of mucosal injuries in ammonia- and TCA-induced chronic gastritis models.

Acetamides↗

Increased susceptibility of rat gastric mucosa to ulcerogenic stimulation with aging. Role of capsaicin-sensitive sensory neurons.

We examined the influences of aging on gastric damage and gastric mucosal blood flow (GMBF) responses induced by acid back-diffusion, following the barrier disruption, and investigated the relation of capsaicin-sensitive sensory nerves to these changes. Male Fischer rats 3, 13, and 24 months old were used. Under urethane anesthesia, a rat stomach was mounted on a chamber, and gastric potential difference (PD), luminal H+ loss, and GMBF were measured before, during, and after exposure to 20 mM sodium taurocholate (TC) for 30 min, in the presence of 50 mM HCl. Mucosal exposure to TC caused surface cell damage, PD reduction, and acid back-diffusion (luminal H+ loss) in all groups of rats; delta PD reduction and the amount of H+ loss were not significantly different between young and aged rats. In young rats, a marked increase of GMBF was observed with luminal acid loss following TC treatment, yet it resulted in less damage in the gastric mucosa. In aged rats, however, such GMBF responses were apparently mitigated, leading to a significant worsening of gastric mucosal lesions induced by TC. Mucosal application of capsaicin (0.1 mg/ml) caused an increase of GMBF in young rats, but this response was significantly attenuated in aged rats. In addition, the amount of calcitonin gene-related peptide (CGRP) released in the isolated stomach in response to capsaicin (1 X 10(-5) M) was significantly lower in aged animals when compared to young rats. These findings suggest that the gastric mucosa of aged rats is more vulnerable to acid back-diffusion following the barrier disruption, partly because of dysfunction of GMBF responses mediated by capsaicin-sensitive sensory neurons in the acidic conditions.

Aging↗