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Biomedical subjects

N Kawashima

Publications and source records attributed to N Kawashima.

At least 91 records · Page 5Linked to original sources

Paradoxical analgesia produced by naloxone in diabetic mice is attributable to supersensitivity of delta-opioid receptors.

The effects of naloxone on the analgesic response were examined using the tail-flick test, in mice with streptozotocin-induced diabetes. Subcutaneous injection of naloxone (5 mg/kg, s.c.) produced a marked analgesia in diabetic mice but not in age-matched non-diabetic mice. Naloxone-induced analgesia in diabetic mice was significantly reduced by pretreatment with naltrindole (0.1 mg/kg, s.c.), a selective antagonist of delta-opioid receptors. By contrast, no significant naloxone-induced increase in tail-flick latency in diabetic mice was observed after chronic treatment with naloxone (5 mg/kg, s.c.) for 5 days. However, the tail-flick latency was significantly increased by chronic treatment with naloxone in non-diabetic mice. Furthermore, the significant naloxone-induced increase in tail-flick latency in non-diabetic mice that had been chronically treated with naloxone was also antagonized by pretreatment with naltrindole. Chronic pretreatment with 5 mg/kg of naloxone for 5 days markedly attenuated the analgesic effect of the delta-agonist DPDPE in diabetic mice, whereas this pretreatment significantly enhanced the effect of DPDPE in non-diabetic mice. These results suggest that naloxone-induced 'paradoxical' analgesia in mice may be mediated predominantly by delta-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Effects of diabetes on stress-induced analgesia in mice.

The present studies were designed to determine whether streptozotocin-induced (STZ-induced) diabetes in mice can attenuate the development of antinociception induced by exposure to both foot shock and forced swimming stress. Foot shock stress produced significant analgesia both in control and diabetic mice. However, the extent of foot shock stress-induced analgesia (FSSIA) in diabetic mice was significantly lower than that in control mice. Naloxone (2 mg/kg, i.p.) significantly attenuated FSSIA in control mice, but was without effect on FSSIA in diabetic mice. One-minute swimming stress had no significant effect on tail-pinch latency in control mice, whereas 3-min swimming stress produced significant analgesia in these mice. Diabetic mice exhibited robust swimming stress-induced analgesia (SSIA): one-min swimming stress produced significant analgesia in diabetic mice. These analgesic effects were blocked by naltrindole, a selective antagonist of delta-opioid receptors, but not by pretreatment with beta-funaltrexamine, an irreversible and selective antagonist of mu-opioid receptors. These results suggest that the deficiency in the functioning of mu-opioid receptors caused by diabetes results in significant activation of an endogenous analgesic system, which is mediated mainly by delta-opioid receptors.

Animals↗

Role of spleen or spleen products in the deficiency in morphine-induced analgesia in diabetic mice.

We examined the possibility that the spleen or factor(s) derived from spleen mononuclear cells are involved in the deficient mu-opioid receptor-mediated analgesia encountered in diabetic mice. Splenectomized diabetic mice had a significantly higher sensitivity to morphine analgesia than untreated or sham-operated diabetic mice. Naive recipient mice injected with mononuclear spleen cells from diabetic mice exhibited a lower sensitivity to morphine analgesia than vehicle-treated naive mice. These results suggest that some factor(s) derived from spleen mononuclear cells may play an important, direct or indirect role in the selective reduction in mu-agonist-mediated analgesia in diabetic mice.

Analgesia↗

Naloxone-induced analgesia in diabetic mice.

We evaluated the effects of s.c. administration of naloxone in mice with streptozotocin-induced diabetes, compared to those in age-matched naive mice. Naloxone injected s.c. produced a dose-related increase in tail-flick latency in diabetic mice but not in naive mice. Naloxone-induced analgesia in diabetic mice was significantly reduced by pretreatment with naltrindole, a selective antagonist of delta-opioid receptors. These results indicate that naloxone-induced 'paradoxical' analgesia in diabetic mice may be mediated by delta-opioid receptors.

Analgesia↗

An immunohistochemical study of the distribution of immunocompetent cells, especially macrophages and Ia antigen-expressing cells of heterogeneous populations, in normal rat molar pulp.

The precise distribution of various immunocompetent cells in rat molar pulp was immunohistochemically examined by use of seven anti-rat monoclonal antibodies. It was demonstrated that rat molar pulp contained many OX6 (anti-Ia antigen)-positive cells and a large number of ED1 (anti-monocytes, macrophages, and dendritic cells)-positive, ED2 (anti-tissue macrophages)-positive, and/or OX35 (anti-macrophages and CD4+ lymphocytes)-positive cells. Macrophage-like cells predominated in the central portion of the pulp, while cells of dendritic appearance usually existed in the periphery of the pulp. Double-immunoperoxidase staining revealed that these cells showed some heterogeneity, but the majority could be classified as ED1+/OX6-/ED2+ cells, which may be Ia-histiocytes. Findings also suggested that true dendritic cells may be included in the ED1+/OX6+/ED2- category of cells. A small number of T lymphocytes and plasma cells were also detected. These results suggest that the normal dental pulp contains a variety of immunocompetent cells, with macrophages as the most dominating. Following the exogenous invasion of pathogenic stimuli in the pulp, these cells may participate in the defense reaction by acting as phagocytes or antigen-presenting cells, which are essential for the initiation of immune responses.

Animals↗

Antinociceptive effect of mexiletine in diabetic mice.

We examined the effect of mexiletine on the threshold for pain perception as determined by the application of mechanical noxious stimuli (tail-pinch) in diabetic mice. Mexiletine produced a pronounced analgesic effect in diabetic mice in a dose-dependent manner. Mexiletine (10(-5)M) significantly inhibited the K(+)-evoked release of substance P from the slices of spinal cord of diabetic mice. These results suggest that the reduction of release of substance P from the nociceptive afferent terminal in the spinal cord is involved in the mechanisms of mexiletine analgesia in diabetic mice.

Animals↗

[Effect of maternally derived antibody levels on antibody responses to canine parvovirus, canine distemper virus and infectious canine hepatitis virus after vaccinations in beagle puppies].

Antibody titers against canine parvovirus (CPV), canine distemper virus (CDV) and infectious canine hepatitis virus (ICHV) in serum were measured in 6 beagle dams and their 38 puppies bred in our colony, in order to clarify the effects of maternally derived antibodies to antibody responses against the viruses after vaccinations in puppies. Correlation coefficient on antibody titers between puppies and dams were CPV: r = 0. 7935, CDV: r = 0.8194 and ICHV: r = 0.8105. Mean maternal antibody positive rates in 7-day-old puppies from their dams were CPV: 67%, CDV: 46% and ICHV: 45%. Mean half-lives of the maternal antibodies in puppies were estimated to be CPV: 13.5 days, CDV: 15.1 days and ICHV: 15.4 days. The antibody response against CPV vaccination in puppies was mainly observed in dogs being titers of less 1:5 and positivity was 39% (15/38 puppies) after 1st vaccination at 42 days after birth, and 82% (31/38 puppies) after 2nd vaccination at 70 days. That against CDV vaccination (at 56 days after birth) was seen highly in dogs being titers of less 1:10 and positivity was 53% (20/38). Also that against ICHV vaccination (at 56 days after birth) was seen frequently in dogs being titers of less 20 holds and the rate was 87% (33/38). From these results, it was estimated that the age when high antibody response against each vaccination could be expected in puppies might be CPV: between 40 and 69 days, CDV: between 32 and 92 days and ICHV: between 31 and 52 days, respectively.

Age Factors↗

[Changes in concentration of cefotetan in blood and lung tissue after intravenous administration].

Cefotetan (CTT), a newly-developed cephamycin antibiotic, has been used widely for the treatment of various infectious diseases because of its excellent antibacterial potency and dynamic transport in vivo. Although the drug transfer to almost every organ, tissue, and body fluid has been studied, only a few reports are available regarding the transfer to lung tissue. In the present study, 1 g of CTT was intravenously injected in a single dose to each of 22 patients subjected to pulmonary resection. Subsequently, its concentrations in blood and lung tissue were measured in sequence. The degree of transfer of the drug to the lung tissue was calculated to evaluate the pharmacodynamics of CTT in vivo. The following results were obtained in this analysis. 1. The T1/2(beta) of the concentration in blood was 4.18 hours, and AUC0-infinity was 478.7 micrograms.hr/ml. 2. Cmax in the lung tissue was 31.5 micrograms/g, and Tmax was 0.83 hour, and tissue concentrations decreased in parallel to blood concentrations. CTT was transferred to the lung tissue to achieve high concentrations following an intravenous administration. Since high concentrations are maintained for a long period of time, this antibiotic is expected to exert an excellent effect in the prevention and the treatment of respiratory infections.

Aged↗

Immunopathological studies of an autopsy case with Goodpasture's syndrome and systemic necrotizing angiitis.

A rare autopsy case of Goodpasture's syndrome with systemic necrotizing angiitis is reported. The patient, a 56-year-old male, died of respiratory failure with massive pulmonary hemorrhage and renal failure. The autopsy showed widespread hemorrhage in both lungs, diffuse crescentic glomerulonephritis, and systemic necrotizing angiitis in the small arteries. Immunofluorescence studies demonstrated a linear deposition of IgG along the glomerular basement membrane (GBM) as well as the alveolar basement membrane. A granular deposition of C3 was also found along the GBM. Electron microscopy showed that the GBM was irregularly thickened and wrinkled, but electron-dense deposits were indistinct. Anti-GBM antibody activity was detected in the patient's serum and had cross reactivity with normal alveolar basement membrane. The renal eluates contained IgG antibody activity for normal human GBM. These results suggest that glomerulonephritis and pulmonary hemorrhage in the present case were mediated by anti-basement membrane antibodies. We also discussed whether anti-basement membrane antibody is involved in the pathogenesis of systemic necrotizing angiitis.

Anti-Glomerular Basement Membrane Disease↗

Endogenous indole-3-acetic Acid in the stem of tobacco in relation to flower neoformation as measured by mass spectroscopic assay.

The contents of free indole-3-acetic acid (IAA) and alkali-labile, conjugated IAA were measured in relation to a ;floral gradient' present in epidermis and subepidermis tissues of flowering plants of Nicotiana tabacum by capillary gas-chromatographic spectrometric analysis by selected ion monitoring (GC-SIM-MS) using 2,4,5,6,7-penta deutero IA ((2)H(5)-IAA) as an internal standard. In floral axes, floral branches and stems with floral branches, free IAA levels (dry weight) were 387, 253, and 417 nanograms, and bound IAA levels were 99, 1089, and 268 nanograms. In vegetative tissue of the first plus second internodes (measured from top), and of the 11th to 13th internodes, free IAA levels were 826 and 500 nanograms, and bound IAA levels were 1421 and 286 nanograms, respectively. Since flower-forming ability of excised cells from the epidermis and subepidermis shows a gradient in an in vitro system, but levels of IAA in these tissues do not, there thus appears to be no correlation between flower-forming ability (in vitro) and endogenous IAA levels (at the time of excision) in tobacco stem tissues.

Journal Article↗

Late effects of whole or partial body x-irradiation on mice: life shortening.

Life table data were obtained on 2400 ddY/SLC female mice exposed at 10 weeks of age to a single dose of X-rays. Doses given to the whole body were 95, 190, 380 and 570 rad, and to head, trunk or lower body, 190, 380, 570 and 760 rad. The mean survival time of unirradiated controls was 73 weeks. The mean survival times after whole body exposure decreased linearly with increasing dose. The estimate of life shortening per 100 rad was 7.2 per cent for whole body exposure. The life shortening after head or lower body exposure to a dose of 190 rad was 6.2 and 7.1 weeks respectively, and almost no further life shortening up to 760 rad. After trunk irradiation with 190 rad, life shortening was 10.4 weeks and beyond that dose life shortening was 1.1 per cent per 100 rad.

Actuarial Analysis↗