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1.
J Dairy Sci ; 104(9): 9784-9800, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34147220

ABSTRACT

Our objective was to investigate the interactions between starch level and rumen-protected Met, Lys, His (RP-MLH) on milk yield, plasma AA concentration, and nutrient utilization in dairy cows fed low metabolizable protein diets (mean = -119 g/d of metabolizable protein balance). Sixteen multiparous Holstein cows (138 ± 46 d in milk, 46 ± 6 kg/d in milk) were used in a replicated 4 × 4 Latin square with a 2 × 2 factorial arrangement of treatments. Each period lasted 21 d with 14 d for diet adaptation and 7 d for data and sample collection. Dietary starch level varied by replacing (dry matter basis) pelleted beet pulp and soyhulls with ground corn resulting in the following treatments: (1) 20% pelleted beet pulp and 10% soyhulls (reduced starch = RS), (2) RS plus RP-MLH (RS+AA), (3) 30% ground corn (high starch = HS), and (4) HS plus RP-MLH (HS+AA). Dietary starch concentrations averaged 12.3 and 34.4% for RS and HS basal diets, respectively. Diets were supplemented with RP-MLH products to supply digestible Met, Lys, and His. Compared with RS and RS+AA diets, HS and HS+AA diets increased yields of milk (37.9 vs. 40.1 kg/d) and milk protein (1.07 vs. 1.16 kg/d) and decreased dry matter intake (25.9 vs. 25.2 kg/d), milk urea N (12.6 vs. 11.0 mg/dL), and plasma urea N (13.3 vs. 11.6 mg/dL). Milk N efficiency was greater in cows fed the HS and HS+AA than RS and RS+AA diets (28.9 vs. 25%), and RP-MLH supplementation improved milk true protein concentration. Starch level × RP-MLH interactions were observed for plasma concentrations of Arg and Lys, with RP-MLH being more effective to increase plasma Arg (+16%) and Lys (+23%) when supplemented to the RS than the HS basal diet. Replacing pelleted beet pulp and soyhulls with ground corn lowered the plasma concentrations of all essential AA except Met and Thr. In addition, the plasma concentrations of His and Met increased with RP-MLH. The apparent total-tract digestibilities of neutral and acid detergent fiber were lower, and those of starch and ether extract greater in cows offered the HS and HS+AA diets than RS and RS+AA diets. Urinary excretion of urea N decreased by replacing pelleted beet pulp and soyhulls with ground corn. Enteric CH4 production, CH4 yield, and CH4 intensity all decreased in the HS and HS+AA versus RS and RS+AA diets. Diets did not affect the intakes of gross energy, metabolizable energy, and net energy of lactation. In contrast, digestible energy intake increased with feeding the RS and RS+AA diets, whereas CH4 energy decreased in cows fed the HS and HS+AA diets. Supplementation with RP-MLH had no effect on energy utilization variables. Overall, the lack of interactions between dietary starch level and RP-MLH supplementation on most variables measured herein showed that the effects of starch intake and RP-MLH were independent or additive.


Subject(s)
Methionine , Rumen , Animals , Cattle , Diet/veterinary , Diet, Protein-Restricted/veterinary , Female , Histidine , Lactation , Lysine , Nitrogen , Starch , Zea mays
2.
J Dairy Sci ; 102(5): 4138-4154, 2019 May.
Article in English | MEDLINE | ID: mdl-30852019

ABSTRACT

The dairy industry can benefit from low crude protein (CP) diets due to reduced N excretion, but shortages of Met, Lys, and His may limit milk protein synthesis. We studied the effect of incremental amounts of rumen-protected (RP)-His on plasma and muscle AA profile, nutrient utilization, and yields of milk and milk true protein in dairy cows. Eight multiparous Holstein cows (130 ± 30 d in milk) were randomly assigned to treatment sequences in a replicated 4 × 4 Latin square design with 28-d experimental periods. Treatments included a basal diet composed (dry matter basis) of 50% corn silage, 15% haylage, and 35% concentrate supplemented with 0, 82, 164, and 246 g/d of RP-His and 11 g/d of RP-Met. Milk, plasma, and muscle samples were collected weekly or every other week during all 4 periods, whereas spot urine and fecal grab samples were taken only in wk 4 of each period. Data were analyzed individually by week using linear, quadratic, and cubic orthogonal polynomials and repeated measures. Plasma His increased linearly with RP-His during wk 1 (30.3 to 57.2 µM) to wk 4 (33.2 to 63.1 µM). Plasma carnosine increased linearly with supplemental RP-His except in wk 2. No treatment effect was observed for plasma 3-methylhistidine except a quadratic effect in wk 3. Inclusion of RP-His showed linear effects on muscle His in wk 2 (20.1 to 32.5 µM) and 4 (20.3 to 35.5 µM). Whereas muscle anserine and carnosine concentrations were not affected by treatments in wk 4, anserine responded quadratically and carnosine showed a trend for a quadratic response to RP-His in wk 2. During wk 4, treatments did not affect urinary excretion of total purine derivatives, as well as dry matter intake and milk concentrations of fat and true protein. In contrast, milk yield tended to increase linearly (31.2 to 32.7 kg/d) and milk true protein yield responded linearly (0.93 to 0.98 kg/d) and tended to increase quadratically to RP-His supplementation in wk 4. Also, milk urea-N (11.7 to 12.9 mg/dL) and urinary excretion of urea-N (23.7 to 27.0% of N intake) increased linearly with feeding RP-His in wk 4. Overall, RP-His was effective to enhance plasma and muscle concentrations of His and milk protein synthesis. Elevated milk urea-N and urinary excretion of urea-N suggest that plasma His may have exceeded the requirement with excess N converted to urea in the liver. Future research is needed to determine the bioavailability of RP-His supplements to improve the accuracy of diet formulation for AA.


Subject(s)
Cattle/metabolism , Diet, Protein-Restricted , Diet/veterinary , Histidine/pharmacology , Milk Proteins/metabolism , Muscle, Skeletal/metabolism , Rumen/metabolism , Animals , Dairying , Dietary Supplements , Female , Histidine/blood , Histidine/metabolism , Lactation , Methylhistidines , Milk/metabolism , Random Allocation , Silage , Urea/metabolism , Zea mays
3.
Eur J Surg Oncol ; 36(12): 1131-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20933363

ABSTRACT

This review describes the latest surgical treatments for peritoneal carcinomatosis (PC) arising from gastric cancer. Systemic chemotherapy is less effective against PC because of the existence of the blood-peritoneal barrier. Accordingly, perioperative intraperitoneal chemotherapy plus cytoreductive surgery (CRS) is a new trend of multidisciplinary therapy for PC. Intraperitoneally administered drugs penetrate directly into the peritoneal dissemination, resulting in the high loco-regional intensity of drugs. A new bidirectional chemotherapy called neoadjuvant intraperitoneal/systemic chemotherapy (NIPS) has been developed. After NIPS, the disappearance of PFCCs has been reported, and the incidence of complete cytoreduction has increased accordingly. Complete cytoreduction, a low peritoneal carcinomatosis index, and negative PFCCs are significant favorable prognostic factors. Hyperthermic intraperitoneal chemotherapy (HIPEC) after CRS is associated with improved survival with an acceptable postoperative mortality and morbidity. Early postoperative intraperitoneal chemotherapy (EPIC) has also contributed to improving survival after CRS.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Stomach Neoplasms/pathology , Chemotherapy, Adjuvant , Humans , Hyperthermia, Induced , Infusions, Parenteral , Laparoscopy , Lymphatic Metastasis , Neoadjuvant Therapy/methods , Peritoneal Lavage/methods , Peritoneal Neoplasms/secondary
4.
Orthod Craniofac Res ; 8(3): 191-9, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16022721

ABSTRACT

OBJECTIVES: Identification, characterization, and potential application of mesenchymal stem cells (MSC) derived from human dental tissues. METHODS: Dental pulp and periodontal ligament were obtained from normal human impacted third molars. The tissues were digested in collagenase/dispase to generate single cell suspensions. Cells were cultured in alpha-MEM supplemented with 20% fetal bovine serum, 2 mM l-glutamine, 100 microM l-ascorbate-2-phosphate. Magnetic and fluorescence activated cell sorting were employed to characterize the phenotype of freshly isolated and ex vivo expanded cell populations. The developmental potential of cultured cells was assessed following co-transplantation with hydroxyapetite/tricalcium phosphate (HA/TCP) particles into immunocompromised mice for 8 weeks. RESULTS: MSC were identified in adult human dental pulp (dental pulp stem cells, DPSC), human primary teeth (stem cells from human exfoliated deciduous teeth, SHED), and periodontal ligament (periodontal ligament stem cells, PDLSC) by their capacity to generate clongenic cell clusters in culture. Ex vivo expanded DPSC, SHED, and PDLSC populations expressed a heterogeneous assortment of makers associated with MSC, dentin, bone, smooth muscle, neural tissue, and endothelium. PDLSC were also found to express the tendon specific marker, Scleraxis. Xenogeneic transplants containing HA/TCP with either DPSC or SHED generated donor-derived dentin-pulp-like tissues with distinct odontoblast layers lining the mineralized dentin-matrix. In parallel studies, PDLSC generated cementum-like structures associated with PDL-like connective tissue when transplanted with HA/TCP into immunocompromised mice. CONCLUSION: Collectively, these data revealed the presence of distinct MSC populations associated with dental structures with the potential of stem cells to regenerate living human dental tissues in vivo.


Subject(s)
Dental Pulp/physiology , Mesenchymal Stem Cells/physiology , Periodontal Ligament/physiology , Regeneration/physiology , Animals , Cell Differentiation/physiology , Clone Cells/physiology , Humans , Tissue Engineering
5.
Radiat Res ; 163(1): 72-8, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15606309

ABSTRACT

Preclinical studies are in progress to determine the potential of boron neutron capture therapy (BNCT) for the treatment of carcinomas of the head and neck. Recently, it has been demonstrated that various boronated porphyrins can target a variety of tumor types. Of the porphyrins evaluated so far, copper tetracarboranylphenyl porphyrin (CuTCPH) is potentially a strong candidate for clinical use. In the present investigation, the response of the oral mucosa to CuTCPH-mediated boron neutron capture (BNC) irradiation was assessed using the ventral surface of the tongue of adult male Fischer 344 rats, a standard rodent model. CuTCPH was administered by intravenous infusion, at a dose of 200 mg/kg body weight, over a 48-h period. Three days after the end of the administration of CuTCPH, biodistribution studies indicated very low levels of boron (<2 microg/g) in the blood. Levels of boron in tongue tissue were 39.0 +/- 3.8 microg/g at this time. This was the time selected for irradiation with single doses of thermal neutrons from the Brookhaven Medical Research Reactor. The estimated level of boron-10 in the oral mucosa was used in the calculation of the physical radiation doses from the 10B(n,alpha)7Li reaction. This differs from the approach using the present generation of clinical boron carriers, where boron levels in blood at the time of irradiation are used for this calculation. Dose-response curves for the incidence of mucosal ulceration were fitted using probit analysis, and the doses required to produce a 50% incidence of the effect (ED50 +/- SE) were calculated. Analysis of the dose-effect data for CuTCPH-mediated BNC irradiation, compared with those for X rays and thermal neutrons alone, gave a compound biological effectiveness (CBE) factor of approximately 0.04. This very low CBE factor would suggest that there was relatively low accumulation of boron in the key target epithelial stem cells of the oral mucosa. As a consequence, with low levels of boron (<2 microg/g) in the blood, the response of the oral mucosa to CuTCPH-mediated BNCT will be governed primarily by the radiation effects of the thermal neutron beam and not from the boron neutron capture reaction [10B(n,alpha)7Li].


Subject(s)
Boron Neutron Capture Therapy/adverse effects , Metalloporphyrins/therapeutic use , Mouth Mucosa/pathology , Mouth Mucosa/radiation effects , Oral Ulcer/etiology , Oral Ulcer/pathology , Radiation Injuries/etiology , Radiation Injuries/pathology , Animals , Body Burden , Boron Neutron Capture Therapy/methods , Dose-Response Relationship, Radiation , Drug Evaluation, Preclinical , Female , Lethal Dose 50 , Metalloporphyrins/adverse effects , Radiotherapy Dosage , Rats , Rats, Inbred F344 , Relative Biological Effectiveness , Tissue Distribution , Treatment Outcome
6.
J Comp Physiol B ; 172(2): 125-36, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11924562

ABSTRACT

The T-tubules and sarcoplasmic reticulum (SR) serving excitation-contraction (EC) coupling in lobster (Homarus americanus) cardiac muscle are similar to those in mammalian myocardium. Tetanic contraction is elicited by a burst of action potentials from the cardiac ganglion. In this study we evaluated the roles of the sarcolemma and SR in EC coupling of the ostial valve muscle (orbicularis ostii m. or OOM) of lobster heart. The OOM was mounted in a bath with saline on a microscope stage; force was measured by strain gauge. [Ca2+]i was measured using iontophoretically micro-injected fura-2 salt. Peak [Ca+]i, peak tetanic force and time to peak [Ca2+]i increased with that of stimulus train duration (TD), to a maximum at a TD of 500 ms. Force increased with [Ca2+]. Cd2+ reduced force by 90%; ryanodine and caffeine reduced tetanic [Ca2+]i transients by 80% and 70%, and force by 90% and 80%, respectively. Ryanodine, caffeine and cyclopiazonic acid slowed the decline of [Ca2+]i and force during relaxation. Relaxation required [Na+]o. The rate of decline of [Ca2+]i appeared to be a sigmoidal function of the [Ca2+]i and increased for any [Ca2+]i with TD. Inactivity slowed relaxation of force; stimulation accelerated relaxation. These data suggest important contributions of Ca2+ transport both across the sarcolemma and across the SR membrane during EC-coupling of lobster cardiac muscle, while average cytosolic [Ca2+]i regulates the rate of [Ca2+]i elimination during relaxation.


Subject(s)
Heart/physiology , Myocardial Contraction/physiology , Nephropidae/physiology , Sarcolemma/metabolism , Sarcoplasmic Reticulum/metabolism , Animals , Caffeine/pharmacology , Calcium/metabolism , Calcium-Transporting ATPases/metabolism , Fluorescent Dyes , Fura-2 , Muscle Fibers, Skeletal/physiology , Myocardial Contraction/drug effects , Myocardium/cytology , Phosphodiesterase Inhibitors/pharmacology , Ryanodine/pharmacology
7.
J Comp Neurol ; 436(3): 376-88, 2001 Jul 30.
Article in English | MEDLINE | ID: mdl-11438937

ABSTRACT

Localization of neuropeptide Y (NPY) mRNA in the hypothalamus of chickens was studied by in situ hybridization with digoxigenin-labeled chicken NPY cRNA probe. The largest number of perikarya-expressing NPY mRNA was found within the mediobasal hypothalamus, including the infundibular nucleus, inferior hypothalamic nucleus, and median eminence. Many NPY perikarya were noted to surround the nucleus rotundus and to be present in the supraoptic nucleus. Moreover, some perikarya were detected in the nucleus of basal optic root, bed nucleus pallial commissure, and nucleus striae terminalis close to the lateral forebrain bundle. NPY-immunoreactive nerve fibers were densely distributed in these regions containing the NPY mRNA-expressing perikarya. Following food deprivation for four days, perikarya-expressing NPY mRNA and peptide were markedly increased in the mediobasal hypothalamus and particularly so in the infundibular nucleus. No changes, however, were detected in other regions containing NPY-positive perikarya. Water deprivation induced less increase in NPY-positive perikarya in the mediobasal hypothalamus compared to food deprivation. After gonadectomy, the number of NPY-positive perikarya in the mediobasal hypothalamus was unaltered. Northern blot analysis with (32)P-labeled chicken NPY cDNA probe demonstrated that a 2.7-fold increase of NPY mRNA was induced by starvation and a 1.5-fold increase was induced by dehydration, whereas the NPY mRNA band remained unchanged after gonadectomy. Thus, it seems that NPY neurons located in the mediobasal hypothalamus are involved in feeding behavior but not reproductive activity.


Subject(s)
Chickens/physiology , Dehydration/pathology , Food Deprivation/physiology , Hypothalamus/anatomy & histology , Hypothalamus/metabolism , Neuropeptide Y/biosynthesis , Orchiectomy , RNA, Messenger/metabolism , Animals , Blotting, Northern , Hypothalamus/cytology , Image Processing, Computer-Assisted , Immunohistochemistry , In Situ Hybridization , Male
8.
Rinsho Shinkeigaku ; 40(1): 29-33, 2000 Jan.
Article in Japanese | MEDLINE | ID: mdl-10825797

ABSTRACT

We presented a patient with chronic encapsulated intracerebral hematoma. This 49-year-old woman suffered from visual disturbance, and slowly progressive right hemiparesis, sensory disturbance of the right extremities and incongruous right homonymous hemianopia over 2 months. Computed tomography scanning showed high density area and ring enhancement, and magnetic resonance imaging revealed mixed intensity on T1 and T2-weighted images in her left thalamus and internal capsule. Angiographic studies revealed no vascular anomaly or tumor stain. The pathologic pictures indicated well-encapsulated hematoma containing fresh and old hematomas in the left thalamus. Most reported cases of this disease had hematomas in the subcortex and no cases had similar visual disturbance. This report was prepared because this condition is uncommon and may remain unrecognized.


Subject(s)
Cerebral Hemorrhage/complications , Hematoma/complications , Hemianopsia/etiology , Thalamus , Cerebral Hemorrhage/diagnosis , Chronic Disease , Female , Hematoma/diagnosis , Humans , Magnetic Resonance Imaging , Middle Aged , Paresis/etiology , Thalamus/pathology , Tomography, X-Ray Computed
9.
J Neurosci ; 20(6): 2418-26, 2000 Mar 15.
Article in English | MEDLINE | ID: mdl-10704516

ABSTRACT

Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines that are considered to be involved in a variety of neuropsychiatric functions. Here, we report behavioral and neuropsychological deficits in mice carrying a single mutated allele of the TH gene in which TH activity in tissues is reduced to approximately 40% of the wild-type activity. In the mice heterozygous for the TH mutation, noradrenaline accumulation in brain regions was moderately decreased to 73-80% of the wild-type value. Measurement of extracellular noradrenaline level in the frontal cortex by the microdialysis technique showed a reduction in high K(+)-evoked noradrenaline release in the mutants. The mutant mice displayed impairment in the water-finding task associated with latent learning performance. They also exhibited mild impairment in long-term memory formation in three distinct forms of associative learning, including active avoidance, cued fear conditioning, and conditioned taste aversion. These deficits were restored by the drug-induced stimulation of noradrenergic activity. In contrast, the spatial learning and hippocampal long-term potentiation were normal in the mutants. These results provide genetic evidence that the central noradrenaline system plays an important role in memory formation, particularly in the long-term memory of conditioned learning.


Subject(s)
Hippocampus/physiology , Norepinephrine/metabolism , Tyrosine 3-Monooxygenase/genetics , Animals , Association Learning/physiology , Avoidance Learning/physiology , Brain Chemistry/genetics , Chimera , Fear , Female , Frontal Lobe/cytology , Frontal Lobe/enzymology , Heterozygote , Hippocampus/cytology , Long-Term Potentiation/physiology , Male , Memory/physiology , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Neurologic Mutants , Microdialysis , Neurons/enzymology , Space Perception/physiology , Tyrosine 3-Monooxygenase/metabolism
10.
Am J Gastroenterol ; 95(1): 285-8, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10638599

ABSTRACT

Chronic idiopathic intestinal pseudo-obstruction is one of the disorders that is most refractory to medical and surgical treatment. Even when patients are given nutritional support, including total parenteral nutrition, obstructive symptoms seldom disappear. We report a case of chronic idiopathic intestinal pseudo-obstruction, due to myopathy, in which hyperbaric oxygenation therapy was strikingly effective. The presence of myopathy was histologically confirmed on the surgically resected jejunal specimen. Hyperbaric oxygenation resulted not only in relief of the patient's obstructive symptoms but also in a rapid decrease of abnormally accumulated intestinal gas. At last, he could resume oral intake without any critical adverse effects. These observations strongly suggest that hyperbaric oxygenation can be an effective therapy in the management of chronic idiopathic intestinal pseudo-obstruction.


Subject(s)
Hyperbaric Oxygenation , Intestinal Pseudo-Obstruction/therapy , Chronic Disease , Humans , Intestinal Pseudo-Obstruction/diagnostic imaging , Intestinal Pseudo-Obstruction/pathology , Male , Middle Aged , Radiography
11.
J Med Chem ; 42(16): 3163-6, 1999 Aug 12.
Article in English | MEDLINE | ID: mdl-10447961

ABSTRACT

Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Cháng Shan), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-1 (3) and Df-2 (4), respectively, were obtained using silica gel and acetone. They showed high activity against P. falciparum malaria in vitro. Compound 3 was found to be equally effective against P. berghei in vivo as the clinically used drug chloroquine, whereas 4 showed only 1/24 of the activity of 3. Metabolism studies of these compounds revealed that compound 4 is readily metabolized in mouse liver. Accordingly, the dose of 4 must be higher than that of 3 to attain blood levels sufficient for a favorable therapeutic effect.


Subject(s)
Antimalarials/chemical synthesis , Drugs, Chinese Herbal/pharmacology , Plasmodium berghei , Plasmodium falciparum/drug effects , Quinazolines/chemical synthesis , Quinazolines/pharmacology , Quinolizines/chemical synthesis , Animals , Antimalarials/chemistry , Antimalarials/isolation & purification , Antimalarials/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Malaria/drug therapy , Male , Mice , Mice, Inbred ICR , Models, Molecular , Molecular Conformation , Piperidines , Quinazolines/chemistry , Quinazolines/isolation & purification , Quinazolinones , Quinolizines/chemistry , Quinolizines/pharmacology
12.
Jpn Hosp ; (18): 59-66, 1999 Jul.
Article in English | MEDLINE | ID: mdl-11184924

ABSTRACT

Although every medical institution always make efforts to provide best services for the patients, it tends to be insufficient to send the patient's information and share them with other medical institutions. It is partly because in the Japanese medical care system there is no obligation to inform patients' medical information to other medical institutions. To provide effective and cost-effective medical service, we made a local network system between university hospital and other medical institutions. The system contributes to clarify the role of medical institutions and the continuity of medical service. For the next step, we must construct the home-care information service network towards the total service for the patients.


Subject(s)
Community Networks/organization & administration , Delivery of Health Care, Integrated/organization & administration , Program Development , Cooperative Behavior , Health Facility Administration , Hospitals, University/organization & administration , Japan
13.
Arzneimittelforschung ; 48(2): 149-53, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9541725

ABSTRACT

To investigate the efficacy of azelastine hydrochloride (azelastine, CAS 79307-93-0, Azeptin) in suppressing cough, 22 bronchial asthma patients complaining mainly of cough were given the drug for four weeks. Peak flow rates (PEFR), pulmonary function tests, capsaicin cough threshold, and bronchial hyperresponsiveness were compared pre- and post-administration. After four-week's administration of azelastine (2 mg twice daily), cough decreased as demonstrated in a significant progressive improvement of cough points. The morning PEFR (1/min) was improved significantly at one week and two weeks post-administration. Changes were from 434 +/- 26.4 pre-administration to 461 +/- 25.8 at Week 1 (p < 0.05), 462 +/- 26.7 at Week 2 (p < 0.05), 452 +/- 22.5 at Week 3, and 462 +/- 20.8 at Week 4. The evening PEFR (1/min) showed 439 +/- 22.2 pre-administration, 454 +/- 21.4 at Week 1, 464 +/- 22.4 at Week 2, 457 +/- 19.3 at Week 3 and 467 +/- 17.8 at Week 4, improvement being significant at Week 1 (p < 0.05). Regarding pulmonary function tests no significant changes were observed. FVC (liter), FEV1 (liter), and FEV1/FVC (%) were 3.45 +/- 0.86, 2.68 +/- 0.52, and 83.6 +/- 5.93 pre-administration; and 3.48 +/- 0.21, 2.72 +/- 0.65, and 84.1 +/- 6.21 post-administration, respectively. The capsaicin cough threshold [Ccap (mumol/l)] showed significant improvement, changing from 5.95 (0.016-50.0) pre-administration to 19.7 (0.08-50.0) post-administration (p < 0.05). Conversely, an index of bronchial hyperresponsiveness, Dmin (mg/dl;U), showed no significant changes (14.9 +/- 5.2 vs. 19.7 +/- 5.3). These results suggest that azelastine inhibits cough in patients with bronchial asthma by increasing the level of the cough threshold without changing bronchial hyperresponsiveness.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Antitussive Agents/therapeutic use , Asthma/drug therapy , Cough/drug therapy , Phthalazines/therapeutic use , Adolescent , Adult , Aged , Asthma/complications , Asthma/physiopathology , Bronchial Hyperreactivity/drug therapy , Bronchial Hyperreactivity/physiopathology , Capsaicin , Cough/etiology , Cough/physiopathology , Female , Humans , Male , Middle Aged , Peak Expiratory Flow Rate/drug effects , Respiratory Function Tests , Vital Capacity/drug effects
14.
Neuroreport ; 7(15-17): 2649-53, 1996 Nov 04.
Article in English | MEDLINE | ID: mdl-8981440

ABSTRACT

This study aimed at obtaining evidence that cinchophen, an ulcerogenic drug, stimulates the corticotropin-releasing hormone (CRH)-secreting cells in the paraventricular nucleus of the hypothalamus (PVH) to induce c-Fos expression. Without colchicine pretreatment, cinchophen was injected i.p. 60 min before the time of maximum CRH level in the hypothalamus, as decided by radioimmunoassay. Eighty percent of the c-Fos/CRH double-labelled cells were concentrated in the parvicellular subnuclei. In the medial and anterior parvicellular subnuclei, the double-labelled neurones of treated rats significantly outnumbered those of controls. The result shows that cinchophen induces excitation of the CRH-secreting cells.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Corticotropin-Releasing Hormone/metabolism , Hypothalamus/drug effects , Proto-Oncogene Proteins c-fos/drug effects , Quinolines/pharmacology , Animals , Dose-Response Relationship, Drug , Hypothalamus/metabolism , Male , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Wistar
15.
Calcif Tissue Int ; 59(5): 385-91, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8849406

ABSTRACT

We examined the bone turnover and bone mass in adjuvant-induced arthritis in rats and assessed the effects of indomethacin in this model. One hundred ten SD rats, 6 weeks of age, were assigned to 11 groups and injected with adjuvant or solvent in the right foot. Adjuvant-injected rats were orally administered indomethacin at doses of 0 (vehicle), 0.1 (low), 0.5 (medium), and 1.5 (high) mg/kg body weight from the start (day 0). Animals were sacrificed on days 0, 14 (acute phase), and 28 (chronic phase). In the arthritic-control group, serum osteocalcin level and bone mineral content of the fourth lumbar body (L4) and the femur were significantly reduced on day 14. Serum alkaline-phosphatase was increased on day 28. Trabecular bone volume of L4 was decreased on day 14, and the value was further decreased on day 28. Bone formation rate (BFR/BS) was significantly reduced on day 14, and then osteoclast number (Oc.N/BS) increased on day 28. Indomethacin treatment dose-dependently prevented increases in paw volume and osteoclast number. In the high dose group, these indices were maintained at the same level with those in the normal group. However, indomethacin treatments were not able to maintain the parameters of bone formation such as serum osteocalcin and BFR/BS values, and the trabecular bone mass decrease was only partially prevented. These data clearly indicated both reduced bone formation and increased bone resorption as the causes of bone loss in adjuvant-induced arthritis in rats. Increased bone resorption seemed to be due to the increased activity of prostaglandins, but bone formation defect would be related to other factors in this animal model.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Arthritis, Experimental/physiopathology , Bone Density/drug effects , Bone Remodeling/drug effects , Indomethacin/administration & dosage , Administration, Oral , Animals , Arthritis, Experimental/blood , Arthritis, Experimental/chemically induced , Arthritis, Experimental/drug therapy , Female , Osteocalcin/blood , Rats , Rats, Sprague-Dawley
16.
Appl Environ Microbiol ; 62(11): 4066-72, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8899997

ABSTRACT

Four isozymes of manganese peroxidase (MnP) were identified in the culture fluid of the hyperlignolytic fungus IZU-154 under nitrogen starvation conditions. One of them was purified and characterized kinetically. The specific activity and Kcat/K(m) value of the MnP from IZU-154 were 1.6 times higher than those of the MnP from a typical lignin-degrading fungus, Phanerochaete chrysosporium. Two cDNAs encoding MnP isozymes from IZU-154 were isolated. The coding sequence of the two cDNAs, IZ-MnP1 cDNA and IZ-MnP2 cDNA, were 1,152 (384 amino acids) and 1,155 (385 amino acids) bp in length, respectively. They exhibit 96.2% identity at the nucleotide level and 95.1% identity at the amino acid level. Southern blot analysis indicated that two MnP isozyme genes exist in IZU-154 genomic DNA. The primary structures of two MnPs from IZU-154 were similar to those of MnPs from P. chrysosporium. The amino acid sequences including the important residues identified in MnPs from P. chrysosporium, such as the manganese-binding residues, the calcium-binding residues, the disulfide bonds, and the N-glycosylation site, were conserved in the two deduced IZ-MnPs. However, several discrepancies were found in the context around the distal histidine residue between MnP from IZU-154 and MnP from P. chrysosporium, which likely led to the difference in the kinetic parameters for MnP function.


Subject(s)
Basidiomycota/enzymology , Peroxidases/metabolism , Amino Acid Sequence , Base Sequence , Basidiomycota/genetics , Basidiomycota/metabolism , Binding Sites/genetics , Conserved Sequence , DNA Primers/genetics , DNA, Complementary/genetics , DNA, Fungal/genetics , Isoenzymes/genetics , Isoenzymes/isolation & purification , Isoenzymes/metabolism , Kinetics , Lignin/metabolism , Molecular Sequence Data , Peroxidases/genetics , Peroxidases/isolation & purification , Restriction Mapping , Sequence Homology, Amino Acid , Species Specificity
17.
J Neurochem ; 66(6): 2338-49, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8632156

ABSTRACT

The cell adhesion molecule L1 is a multifunctional protein in the nervous system characterizing cell adhesion, migration, and neurite outgrowth. In addition to full-length L1, we found an alternatively spliced variant lacking both the KGHHV sequence in the extracellular part and the RSLE sequence in the cytoplasmic part of L1. This L1 variant was expressed exclusively in nonneuronal cells such as Schwann cells, astrocytes, and oligodendrocytes, in contrast to the expression of the full-length L1 in neurons and cells of neuronal origin. To investigate the functions of the L1 variant, we established cell lines transfected with a cytoplasmic short L1 (L1cs) cDNA that lacks only the 12-bp segment encoding for the RSLE sequence. The promoting activities of homophilic cell adhesion, neurite outgrowth, and neuronal cell migration of L1cs-transfected cells (L4-2) were similar to those of full-length L1-transfected cells (L3-1), but the cell migratory activity of L4-2 itself was clearly lower than that of L3-1. In conclusion, the short form of L1 is a nonneuronal type, in contrast to the neuronal type of the full-length L1. Deletion of the four amino acids RSLE in the cytoplasmic region of L1 markedly reduced cell migratory activity, suggesting an importance of the RSLE sequence for the signaling events of neuronal migration mediated by L1.


Subject(s)
Cell Adhesion Molecules, Neuronal/genetics , Cell Movement/physiology , Membrane Glycoproteins/genetics , Neurons/physiology , Amino Acid Sequence , Animals , Animals, Newborn , Astrocytes/cytology , Astrocytes/physiology , Base Sequence , Cell Adhesion/physiology , Cell Line/physiology , DNA, Complementary/pharmacology , Gene Expression Regulation/genetics , Isomerism , Leukocyte L1 Antigen Complex , Molecular Sequence Data , Mutagenesis/physiology , Neurites/physiology , Neurons/cytology , Neurons/ultrastructure , Oligodendroglia/cytology , Oligodendroglia/physiology , Polymerase Chain Reaction , Rats , Schwann Cells/cytology , Schwann Cells/physiology , Sciatic Nerve/cytology
19.
Pulm Pharmacol ; 9(1): 59-62, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8843511

ABSTRACT

To assess the effects of azelastine in patients with cough-variant asthma, we measured the cough threshold for capsaicin (the concentration required to elicit more than five coughs) in 16 patients with cough-variant asthma before and after 4 weeks of treatment with azelastine (2 mg; b.i.d.) or placebo. After treatment, coughing decreased in all patients and the cough threshold for capsaicin increased significantly, from 0.67 +/- 0.30 microM to 4.76 +/- 1.55 microM (P < 0.01) in the azelastine group. However, the cough threshold for capsaicin did not increase significantly, from 0.86 +/- 0.33 microM to 1.11 +/- 0.35 microM (P > 0.10) in the placebo group. These results suggest that azelastine inhibits coughing in patients with cough-variant asthma.


Subject(s)
Asthma/complications , Bronchodilator Agents/pharmacology , Capsaicin/adverse effects , Cough/chemically induced , Histamine H1 Antagonists/pharmacology , Phthalazines/therapeutic use , Adult , Aged , Cough/prevention & control , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged
20.
Int Urol Nephrol ; 28(5): 643-7, 1996.
Article in English | MEDLINE | ID: mdl-9061423

ABSTRACT

Gross haematuria and severe bleeding from the large intestine occurred after pelvic radiotherapy in an 84-year-old woman with cancer of the uterus. Hyperbaric oxygenation treatment at 2 atmospheric absolute pressures for 60 minutes daily over 30 days and infusion of prostaglandin E1 abolished completely haematuria and tarry stool, and reversed the endoscopic findings of radiation cystitis and colitis.


Subject(s)
Alprostadil/therapeutic use , Colitis/therapy , Cystitis/therapy , Hyperbaric Oxygenation , Radiation Injuries/therapy , Uterine Neoplasms/radiotherapy , Aged , Aged, 80 and over , Colitis/etiology , Combined Modality Therapy , Cystitis/etiology , Cystoscopy , Female , Humans , Pelvis/radiation effects , Radiation Injuries/diagnosis , Radiation Injuries/physiopathology
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