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Biomedical subjects

M Ichikawa

Publications and source records attributed to M Ichikawa.

At least 199 records · Page 11Linked to original sources

Nitric oxide increases renal blood flow by interacting with the sympathetic nervous system.

To investigate whether changes in renal blood flow induced by nondepressor doses of L-arginine, the precursor of nitric oxide, are mediated by a sympathetic neural mechanism, we examined the following in conscious rabbits: (1) the effects of intravenous infusion of L- or D-arginine (15 to 200 mumol/kg per minute) on renal blood flow and renal sympathetic nerve activity with or without intravenous infusion of a nonpressor dose of NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase inhibitor, and (2) the effects of L-arginine on renal blood flow after renal denervation with or without L-NMMA pretreatment. In renal innervated rabbits, L-arginine (100 and 200 mumol/kg per minute) increased renal blood flow by 9 +/- 2 and 16 +/- 3 mL/min (P < .05, respectively) and decreased renal sympathetic nerve activity by 12 +/- 4% and 19 +/- 3% of control (P < .05, respectively). In contrast, no changes occurred in any variable during D-arginine infusion. L-NMMA attenuated the renal blood flow and renal sympathetic nerve activity responses to L-arginine (P < .05). In renal denervated rabbits, L-NMMA also attenuated the renal blood flow responses to L-arginine (P < .05) and abolished them (P < .05) compared with those in renal innervated rabbits. All renal blood flow responses to L-arginine were accompanied by parallel changes in plasma L-citrulline concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of antihypertensive agents on baroreceptor function in early hypertensive rats.

To investigate the effects of antihypertensive treatment with four currently used agents (trichlormethiazide, atenolol, nicardipine, and enalapril) on the arterial baroreceptor function at the early phase of hypertension, we administered the agents to spontaneously hypertensive rats and Wistar-Kyoto rats from 8 to 10 weeks of age and examined the aortic nerve activity function. In untreated spontaneously hypertensive rats, the relation between the arterial pressure and aortic nerve activity was shifted to the right, that is, to a higher pressure level (threshold pressure, 90 +/- 3 versus 76 +/- 1 mm Hg, P < .05), and the maximum gain which was obtained by logistic function analysis was depressed (1.55 +/- 0.08% versus 2.18 +/- 0.13% maximum/mm Hg, P < .01) as compared with untreated Wistar-Kyoto rats. An equivalent decrease in arterial pressure with each of the four agents (-20 +/- 1 mm Hg, P < .01) produced a leftward shift of the arterial pressure-aortic nerve activity relation to a similar extent (threshold pressure, 77 +/- 1 mm Hg, P < .05) in spontaneously hypertensive rats. In addition, treatment with the four agents equally augmented the maximum gain in spontaneously hypertensive rats (2.13 +/- 0.09% maximum/mm Hg, P < .05). The antihypertensive agents affected neither the blood pressure nor the aortic nerve activity in Wistar-Kyoto rats. These findings suggest that antihypertensive treatment with the four classes of agents equally enhances the arterial baroreceptor function through blood pressure reduction but not through specific depressor mechanisms at the early stage of hypertension.

Animals↗

In vivo microdialysis for the transdermal absorption of valproate in rats.

The suitability of sampling via microdialysis for a lipophilic drug, valproate (VPA), was evaluated by the elimination rate constant of VPA solution in an in vitro experimental first-order elimination system. The elimination rate constant of VPA in dialysate was found to be 0.43 +/- 0.05h-1, which was in good agreement with the real elimination rate constant (0.46 +/- 0.02h-1). A change in VPA concentration in the solution surrounding a microdialysis probe was well maintained by the microdialysis method, suggesting no adsorption between the membrane of the microdialysis probe and VPA. On the basis of the in vitro experiment, the effect of a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), on the transdermal absorption of VPA was examined in rats by the use of microdialysis in vivo. An intradermal microdialysis was performed at a flow rate of 1.0 microliter/min for 7h after the dermal application of 50 mM VPA solution with or without 3% (w/v) HPE-101. HPE-101 increased the transdermal absorption rate of VPA by 80 times compared with the control. The microdialysis system was found to be quite useful for assessing the in vivo transdermal absorption of a lipophilic VPA.

Animals↗

Antihypertensive effects of a novel calcium antagonist, semotiadil fumarate (SD-3211), alone and in combination with enalapril or trichlormethiazide in spontaneously hypertensive rats.

Semotiadil fumarate, a novel benzothiazine calcium antagonist, was given alone or in combination with either enalapril or trichlormethiazide to conscious, spontaneously hypertensive, rats daily for 2 weeks. Systolic blood pressure and heart rate were recorded 24 h before the start of the regimen and then every 2 and 24 h after the 1st, 3rd, 7th, 10th and 14th doses. When given alone, the antihypertensive effects of semotiadil (10 mg/kg, p.o.) and enalapril (5 mg/kg, p.o.) first became apparent after the 3rd dose and thereafter the effects appeared to develop daily although this effect had waned by the time of the next dose. When given in combination, however, these drugs appeared to potentiate each other and after the 7th dose, the antihypertensive effect persisted. Trichlormethiazide (30 mg/kg, p.o.) alone failed to exert any significant antihypertensive effect and in combination was not always additive to that of semotiadil. In contrast to the effect on blood pressure, the heart rate remained resistant to all these drugs. These results indicate that combined daily dosing of semotiadil, especially with enalapril, each at relatively low doses may be able to control hypertension in a continuous manner.

Administration, Oral↗

In vivo microdialysis for pharmacokinetic investigations: a plasma protein binding study of valproate in rabbits.

The use of microdialysis to study the binding of valproate (VPA) to plasma proteins was evaluated in rabbits. Prior to an in vivo microdialysis, in vitro relative recovery of VPA respectively from Ringer's solution, 5% (w/v) of albumin solution and plasma sample via a microdialysis probe was examined. The in vitro relative recovery was defined as a ratio of the VPA concentration determined in the dialysate to the free VPA concentration in the sample solution surrounding the membrane of the microdialysis probe. When the sample solution was well stirred at 700 rpm and maintained at 37 degrees C, the in vitro relative recovery of VPA was significantly different among them. It increased in the order of Ringer's solution (34.3 +/- 2.6%) > 5% (w/v) of albumin solution (25.7 +/- 4.6%) > rabbit plasma sample (15.8 +/- 1.2%). Thereafter, pharmacokinetics of VPA was determined using both microdialysis sampling via the rabbit femoral vein and collection of whole blood via the rabbit ear vein after intravenous administration of VPA at a dose of 43 mg/kg. Free concentrations of VPA in plasma were determined by ultrafiltration method as opposed to microdialysis method. There was no difference in the elimination half-life of VPA determined by microdialysis, 1.09 +/- 0.22 h, or ultrafiltration, 1.22 +/- 0.21 h. The AUC of VPA in dialysate was 15 +/- 4 micrograms.h/ml, which corresponded to 15% of that in ultrafiltrate (103 +/- 17 micrograms.h/ml). The value was in good agreement with the in vitro relative recovery of VPA from plasma sample (15.8 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anti-osteopenic effect of nasal salmon calcitonin in type 1 osteoporotic rats: comparison with subcutaneous dosing.

The anti-osteopenic effect of nasal salmon calcitonin (SCT) was investigated in a type 1 osteoporotic model, Wistar rats which were ovariectomized (OVX) at age of 12 weeks, and compared with that of subcutaneous SCT. It was proved that nasal (5, 10, 20 and 40 U/rat) and subcutaneous (5, 10 and 20 U/kg) administration of SCT on alternate days for 3 weeks, starting a week after OVX, prevented the osteopenic changes of tibia and lumbar vertebra; this was proved by physicochemical parameters and histomorphometrically. A clear dose-dependent effect was seen in the trabecular bone volume of a selected regions of the 5th lumbar vertebra, and the ED50s of nasal and subcutaneous SCT calculated were 7.4 U/rat and 3.5 U/kg, respectively. The results indicate that nasal SCT is absorbed efficiently in rats with increased bone turnover to prevent rapidly developing osteopenia and that the administration route is a suitable standard method for chronically giving biodegradable anti-osteoporotic peptides to rats.

Administration, Intranasal↗

Effect of family group psychotherapy on alcoholic families.

We examined the effect of family group psychotherapy on 14 alcoholic families. Family group psychotherapy helped alcoholic families be aware of their anxiety and conflict and enabled them to share their feelings with a group. Alexithymia for a cognitive-affective disturbance significantly decreased after group psychotherapy. Moreover, participation in family group psychotherapy over six months increased family cohesion and allowed anxiety and conflict to be more easily expressed within the family.

Adult↗

Frequency of synchronous oscillations of neuronal activity increases during development and is correlated to the number of synapses in cultured cortical neuron networks.

It has been proposed that synchronous oscillations of groups of neurons corresponding to sensory information and changes in temporal pattern of oscillations are important for processing of the information in the cortex. However, it has not been determined yet how the temporal or spatial pattern of such oscillations are regulated. We observed spontaneous synchronous oscillations of Ca2+ transients, which were caused by bursts of action potentials of neurons, even in cultured cortical neurons. The frequency of synchronous Ca2+ oscillations increased with development of synapses in cultured neurons and was highly correlated to the number of synapses formed in the same culture.

Animals↗

Effect of differential rearing on synapses and soma size in rat medial amygdaloid nucleus.

The effects of differential rearing on synaptic morphology and neuronal size were examined in the medial amygdaloid nucleus (MAN) of adult rats. Forty-day-old male rats were housed in one of three ways: individually (isolated condition, IC); with four males per cage (unisexual condition, UC); or with two males and two females per cage (social condition, SC). After 2 months, the animals were prepared for electron and light microscopy. Although there was no statistically significant difference in number of synapses per unit volume in MAN, the number of perforated (P) synapses, which are characterized by discontinuities in the postsynaptic density, were significantly greater in the UC and the SC than in the IC. The length of synaptic contact zone of P synapses was also longer in both the UC and the SC compared with the IC, whereas the length of nonperforated synapses was longer only in the SC. Soma area was also larger in the SC compared with the IC. These results demonstrate that exposure to different rearing conditions, in which the pheromonal environment can be substantially different, can induce striking morphological changes in both synapses and neurons in the MAN of adult rats.

Amygdala↗

Specific tropism of Japanese encephalitis virus for developing neurons in primary rat brain culture.

Among all the neural cells in fetal rat brain culture developing neurons showed the highest rate of infection by Japanese encephalitis virus (JEV). JEV specifically bound to these cells as measured by immuno-staining. These results indicate that developing neurons are the major target of JEV, and that the initial specific binding of virus to these cells may be one of the reasons for the neurotropism of JEV.

Animals↗

Sequence and gene structure of the hepatitis E virus isolated from Myanmar.

Hepatitis E virus (HEV) is a causative agent of enterically transmitted non-A, non-B hepatitis. Hepatitis E occurs not only in sporadic forms but also in epidemic outbreaks in the developing world. We have revealed the nucleotide and predicted amino acid sequences of full cDNA of HEV isolated from sporadic hepatitis E of Myanmar. The genome is 7194 nucleotides long, followed by a poly(A) tail, and has three open reading frames. The nonstructural gene is located in the 5' terminus, while the structural gene is situated in the 3' terminus. Our HEV strain has 98.5% nucleic acid identity with the HEV strain cloned by workers at Genelabs Incorporated from Myanmar. The difference is point nucleotide substitutions. There is a high degree of nucleotide relatedness among HEVs isolated from the same geographical location.

Amino Acid Sequence↗

The dynamics of intramembranous particles in the degradative pathways of the phagocytosed erythrocyte.

The present study was designed to reveal membrane events during an erythrophagocytosis by electron microscopy. The erythrocytes, which were extravasated into rats' mesenteric lymph node sinuses by short clamping of the portal-vein and phagocytosed by fixed macrophages, were analysed at 0.5, 1, 3, 4 and 6 hr after reopening of the vein by using freeze-fracture and thin-section techniques. The results were as follows: the intramembranous particles of the phagocytosed erythrocyte aggregated after injection of lysosomal enzymes into the phagosome. The digested cytoplasm accumulated in the space between the phagosomal and erythrocyte membranes and was removed from the phagosome by bleb formation or invagination. Subsequently, the erythrocyte membranes lost their intramembranous particles and fragmented. The phagosome lost its density and erythrocyte-structure and became a vacuole (phagosomal ghost), which fractured lamellarly.

Animals↗

Hypercalcemia associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia.

Recent reports have described clinical benefits of all-trans-retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL). This paper describes severe hypercalcemia (serum calcium: 18.7 mg/dl) in association with ATRA treatment in a 14 year old girl with APL. Serum parathyroid hormone (PTH) concentrations were normal (0.21 ng/ml), which precludes the possibility of primary hyperparathyroidism or ectopic PTH secretion as a cause of the hypercalcemia. As for the factors which can accelerate mineral resorption, there were no apparent increases in the levels of PTH-related protein (PTH-rP), prostaglandins and vitamin D metabolites. In our in vitro experiment, ATRA did not stimulate the leukemic cells to produce PTH-rP. We speculate that ATRA, like PTH, may increase osteoclastic activity and induce hypercalcemia.

Adolescent↗

Formation and maturation of synapses in primary cultures of rat cerebral cortical cells: an electron microscopic study.

Cerebral cortical cells from fetal rats (18 days) were cultured for 3, 7, 14, 21, 28, 35 days in vitro (DIV) and the development of synapses was examined morphologically by electron microscopy. At 3 DIV, no synapses could be recognized. An immature type of synapse was found at 7 DIV which thereafter developed morphologically. The length of the synaptic contact zone (SCZ) increased with DIV from 271 +/- 11.4 nm (mean +/- SEM) at 7 DIV to 410 +/- 11.4 nm at 35 DIV. The number of synaptic vesicles per terminal also increased with DIV: 10.0 +/- 1.2 at 7 DIV, 35.7 +/- 3.4 at 21 DIV, and 53.3 +/- 4.5 at 35 DIV. The time course of numerical density of synapses was examined quantitatively by electron microscopy. Synaptic density was very low at 7 DIV. It was significantly increased at 14 DIV and thereafter showed variable changes. Four culture series showed decreases after 14 DIV, but one series showed a further increase at 21 DIV followed by a decrease at 28 DIV. The mean density of synapses at each DIV was as follows: 1780 +/- 86/10(6) microns3 at 7 DIV, 4244 +/- 595/10(6) microns3 at 14 DIV, 2285 +/- 674/10(6) microns3 at 21 DIV, 2552 +/- 646/10(6) microns3 at 28 DIV, and 2080 +/- 532/10(6) microns3 at 35 DIV. Neuronal cell density was counted in each culture to calculate the relative number of synapses per neuron. The cell density decreased with age from 301 +/- 51/10(6) microns3 at 7 DIV to 39 +/- 9/10(6) microns3 at 35 DIV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of differential rearing on the structure of perforated synapses in the granule cell layer of the rat's accessory olfactory bulb.

The effects of differential rearing on synaptic morphology in the granule cell layer of the accessory olfactory bulb (AOB) were examined in adult rats. Forty-day-old male rats were housed in one of three ways: individually (isolated condition, IC); with four males per cage (unisexual condition, UC); or with two males and two females per cage (social condition, SC). After 2 months, the animals were killed for electron microscopy. Two types of synapses were classified: (1) perforated synapses, which are characterized by discontinuities in their postsynaptic thickenings, and (2) non-perforated synapses. The length of the synaptic contact zone as well as the area and the length of the perimeter of both the pre- and postsynaptic terminals were measured in each observed synapse. For perforated synapses, the length of the synaptic contact zone was significantly greater in the UC and the SC than in the IC. For the presynaptic terminals of perforated synapses, the area was greater in the UC and the SC than in the IC, and the length of the perimeter was greater in the UC than in the IC. In contrast, there was no difference in the area and the length of the perimeter among the three groups for postsynaptic terminals. For non-perforated synapses, there was no statistically significant difference in either the area or the length of the perimeter of pre- and postsynaptic terminals among the three experimental groups, although the length of the synaptic contact zone was greater in the SC than in the IC.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

How is depth perception affected by long-term wearing of left-right reversing spectacles?

The plasticity of binocular depth perception was investigated. Six subjects wore left-right reversing spectacles continuously for 10 or 11 days. On looking through the spectacles, the relation between the direction of physical depth (convex or concave) and the direction of binocular disparity (crossed or uncrossed) was reversed, but other depth cues did not change. When subjects observed stereograms through a haploscope and were asked to judge the direction of perceived depth, the directional relation between perceived depth and disparity was reversed both in the two line-contoured stereograms and in the random-dot stereogram in the middle of the wearing period, but the normal relation often returned late in the wearing period. When subjects observed two objects while wearing the spectacles and were asked which appeared the nearer, veridical depth perception increased as the wearing-time passed. These results indicate that the visual transformation reversing the direction of binocular disparity causes changes both in binocular stereopsis and in processes integrating different depth cues.

Depth Perception↗

An epidemic outbreak of hepatitis E in Yangon of Myanmar: antibody assay and animal transmission of the virus.

An epidemic outbreak of hepatitis E occurred in an army recruit camp of Yangon, Myanmar, in October 1989. One hundred and eleven patients among 600 residents were hospitalized. As high as 83.7% of these patients were positive for the acute phase antibody against hepatitis E virus by an enzyme-linked immunosorbent assay developed in our laboratory. Also, 30.6% of 49 symptom-free residents examined were positive for the antibody. We prepared a stool extract from six patients and inoculated it into 10 rhesus monkeys for a series of three sub-passages. All of them developed acute biochemical hepatitis along with an elevation of antibody levels. A rechallenge with viruses of the present outbreak failed to provoke hepatitis in two monkeys that had previously recovered from acute hepatitis caused by an isolate of sporadic hepatitis E of the same area. Similarly, the rechallenge of the sporadic strain did not induce hepatitis in two monkeys that had been previously infected with the epidemic virus. These data suggested that the subjects would obtain neutralizing antibodies against the hepatitis E virus once infected, and many adult inhabitants of the endemic area had no protective antibodies and were still susceptible to hepatitis E infection.

Adult↗