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Biomedical subjects

K Kanda

Publications and source records attributed to K Kanda.

At least 91 records · Page 5Linked to original sources

Catecholamine response to stress: age related modifications in tail-suspended rats.

The catecholamine response to acute stress has been shown to change with age. However, alterations under chronic stress conditions have not been established. This study attempted to determine whether aging modifies the catecholamine response to chronic stress load in rats subjected to tail suspension. Urinary excretions of epinephrine (E) and norepinephrine (NE) were monitored before and during the tail suspension experiments in rats at two different ages: 5 weeks old (young) and 18 months old (aged). Basal excretions of E and NE before the suspension were higher in the aged rats, indicating that sympathetic-adrenal medullary activities increase with age under resting conditions. The chronic stress load elicited E responses in the aged rats similar to those in the young rats. The NE responses, however, were completely different in that tail suspension caused a greater increase in NE excretion in the young rats than in the aged rats. This finding suggests that the sympathetic response to chronic stress load changes with age.

Adrenal Glands↗

Effects of stress on Kv1.5 K+ channel gene expression in the left ventricle of rat hearts.

Voltage-dependent K+ channels contribute to the repolarization phase of the cardiac action potential. An increase in Kv1.5 K+ channel gene expression by a pharmacological dose of glucocorticoid was reported recently in the heart of an adrenalectomized rat. In this study, we examined whether physiological elevations of glucocorticoid induced by tail suspension affects the K+ channel gene expression. Five-week-old male Wistar rats were subjected to tail suspension for three days. Total RNA was extracted from the ventricle, and the level of Kv1.5 mRNA was determined by Northern blot analysis. On the first day, the Kv1.5 mRNA had increased over the non-suspended rat. By the third day, mRNA had increased significantly by more than 3-fold. knowing that urinary excretions of glucocorticoid increase in tail-suspended rats, these findings suggest that physiologically elevated glucocorticoid may upregulate Kv1.5 K+ gene expression.

Action Potentials↗

[Experimental study on organ perfusion by intraaortic balloon counterpulsation with double balloon catheter].

Newly-developed catheter for the intraaortic balloon counterpulsation with cardio-renal assist was examined on animal model. The catheter consists of two balloon segments between which the celiac trunk, the superior mesenteric artery and the renal artery are to be placed. Statistical comparison on each hemodynamic element was carried out between the catheter (DBC), conventional single balloon catheter (SBC) of the same balloon volume as DBC and no assist (None) groups. There were no significant changes between SBC and DBC in cardiac output, femoral arterial flow and central venous pressure. Renal arterial flow and urinary output were significantly increased in DBC (None 14.4 +/- 3.9, SBC 22.6 +/- 5.6, DBC 31.0 +/- 6.9 ml/min in renal arterial flow, None 33 +/- 9, SBC 64 +/- 14, DBC 78 +/- 20 ml/h in urinary output, p < or = 0.05). After the remodeling adjust to the human stature, a clinical application would be considered.

Animals↗

Developmental alterations in NMDA receptor-mediated [Ca2+]i elevation in substantia gelatinosa neurons of neonatal rat spinal cord.

Using spinal cord slices prepared from neonatal rats, the intracellular free Ca2+ concentration ([Ca2+]i) in neurons located in the dorsal horn substantia gelatinosa (SG) was measured with microscopic fluorometry by loading fura 2-AM into neurons. Developmental alterations in the elevation of [Ca2+]i elicited by the glutamate analogs, NMDA and AMPA, were investigated from postnatal day (PNDs) 1 to 17. During the 1st week of postnatal life, when neuronal maturation of the SG is known to take place, the NMDA response remained large or even slightly increased. It subsequently showed a gradual decline. This pattern of postnatal changes is consistent with previously reported autoradiographic studies on NMDA-binding sites. The affinity of receptors for NMDA was found to decrease constantly during the period examined. The AMPA response and resting [Ca2+]i showed no significant developmental changes. Neonatal treatment with capsaicin, which has been shown to degenerate fine primary afferent fibers terminating in the SG, delayed the developmental decline in the NMDA-induced [Ca2+]i response. It is suggested that the number and the molecular properties of NMDA receptors expressed in the SG change during early postnatal neuronal maturation. The temporal coincidence between postnatal alteration in NMDA-induced [Ca2+]i elevation and neuronal maturation of the SG may indicate that intracellular Ca2+ regulated by NMDA receptor activation is related to postnatal neuronal maturation. Activation of fine primary afferent fibers may contribute to the observed developmental alterations in the NMDA response of SG neurons.

Animals↗

A targeting model of boron neutron-capture therapy to hepatoma cells in vivo with a boronated anti-(alpha-fetoprotein) monoclonal antibody.

We described previously that 10B atoms delivered by monoclonal antibody (mAb) exerted a cytotoxic effect on AH66 cells in a dose-dependent manner upon thermal neutron irradiation in vitro. In the present study, the delivering capacity of boronated anti-(alpha-fetoprotein) (AFP) mAb to carry 10B atoms to AFP-producing tumor xenografts in nude mice was determined. Boronated mAb was prepared by conjugating 50 mM 10B compound to an anti-AFP mAb (2 mg/ml) using N-succinimidyl-3-) (2-pyridyldithio) propionate. The number of 10B atoms conjugated directly to the mAb was estimated to be 459/antibody by prompt gamma-ray spectrometry. Boron concentrations in tumor tissue obtained 12, 24, 72, and 120 h after injection of 3.0 mg 10B-conjugated anti-AFP mAb were 11.10 +/- 3.12 (SD, n = 6). 29.30 +/- 5.11, 33.02 +/- 11.8, and 12.91 +/- 5.62 ppm respectively. For control 10B-conjugated anti-dinitrophenol (DNP) mAb, the values were 9.59 +/- 0.99, 10.37 +/- 2.86, 10.00 +/- 2.95, and 8.83 +/- 4.71 ppm respectively. The concentrations in blood were less than 0.40 +/- 0.10 ppm with anti-AFP mAb and less than 0.51 +/- 0.15 ppm with anti-DNP mAb at each sampling time (12, 24, 72, and 120 h). The number of 10B atoms delivered to the tumor cells was calculated to be 0.62 x 10(9), 1.63 x 10(9), 1.84 x 10(9) and 0.72 x 10(9) at each sampling time after injection of 10B-anti-AFP mAb. The amount of 10B atoms necessary for effective boron neutron-capture therapy was estimated to be 10(9)/tumor cell. We were able to carry 1.84 x 10(9) 10B atoms to AH66 tumor cells by using 10B-anti-AFP mAb. The accumulation reached its peak 72 h after injection. These data indicated that the 10B-conjugated antitumor mAb could deliver a sufficient amount of 10B atoms to the tumor cells to induce cytotoxic effects 72 h after injection upon thermal neutron irradiation.

Animals↗

Glucocorticoids potentiate the action of atrial natriuretic polypeptide in adrenalectomized rats.

Adrenal insufficiency in human and rat is associated with an impairment of the diuretic response to water load, and only glucorticoids (GCs) restore this deficit. Our observation that GCs potentiate atrial natriuretic polypeptide (ANP)-stimulated cGMP production in cultured renal cells prompted us to examine the possibility that GCs may restore the diuretic response through the potentiation of ANP action. Initially, changes in urine volume and ANP levels were studied in adrenalectomized (Adx) and sham-operated intact rats after an oral water load of 5 ml/100 g BW. Urine volume after water load was 4.5 +/- 0.5 ml/30 min in the intact rats, whereas it was 0.8 +/- 0.2 ml/30 min in the Adx rats. In the intact rats, a significant increase in plasma ANP level was observed 30 min after the water load, whereas no increase was observed in Adx rats. This defective ANP response may be involved in the impairment of the diuretic response in Adx rats. Indeed, pretreatment of Adx rats with dexamethasone (Dex, 20 micrograms/100 g BW) increased plasma ANP levels even before water load and improved diuretic response. Subsequently, effect of iv administration of human or rat ANP at a pharmacological dose (2.5 micrograms/100 g BW) on urine volume, osmolarity, and urinary excretion of cGMP, and sodium was studied in Adx rats that received an oral water load 30 min before ANP. Dex treatment was achieved by per os administration 3 h before the ANP injection. In Adx rats, the urine volume after ANP administration was 1.2 +/- 0.1 ml/30 min, and pretreatment with Dex markedly increased the urine volume to 6.3 +/- 0.4 ml/30 min. Dex also increased ANP-induced osmolar and sodium excretion by 2.6- and 2.9-fold, respectively. Although urinary excretion of cGMP was increased in Adx rats by ANP administration, a further significant increase was observed by the pretreatment with Dex. Injection of (Bu)2cGMP to Adx rats pretreated with Dex resulted in a significant increase in urine volume and osmolar and sodium excretion. However, no significant increase in urine volume was observed in Adx rats not pretreated with Dex. The present study suggests that GCs restore the diuretic response to acute water load not only by increasing the secretion of ANP but also by potentiating ANP-stimulated cGMP production. Furthermore, GCs may augment ANP action at one or more steps other than cGMP formation because administration of (Bu)2cGMP to Adx rats did not correct the diuretic response to water load.

Adrenalectomy↗

Adrenocortical response to tail-suspension in young and old rats.

We recently showed that increased glucocorticoid secretion aggravates disuse atrophy when induced by skeletal unloading. Disuse atrophy in the elderly is becoming a serious problem in many developed countries. In this study we attempted to examine how aging affects the glucocorticoid response to skeletal unloading. Three groups of rats (aged 5 weeks, 12 months and 18 months) were subjected to 7 days of hind limb unloading by tail-suspension. Urinary excretion of corticosterone over a 24-hr period were monitored every other day. Corticosterone excretion in the control group of 5-week-old rats was initially 87.4 +/- 12.8 ng/day and did not change throughout the experiment. Tail-suspension experiments yielded a significant increase (more than 3 fold) in excretion on days 1 and 3 of the suspension before returning to control levels. In the 12-month-old rats, a marked increase in the basal corticosterone level was observed in the control rats throughout the experiment, while the increase by tail-suspension was attenuated with a transient, significant increase on day 5. In 18-month-old rats, a further increase in the basal level was observed in the control group, although excretions tended to increase steadily from day 1 to day 3 and remained high until day 7. Urinary excretion of corticosterone among the 18-month-old suspension group was similar to those observed in the control group. These results indicate that the younger (5-week-old) rats adapted the stress load caused either by tail-suspension or manipulation alone faster than the older rats did (12 or 18 months old). The observation that basal corticosterone excretion increases with age suggests, alterations in the hypothalamic-pituitary-adrenal axis among the aged rats which might aggravates disuse atrophy induced by skeletal unloading.

Adaptation, Physiological↗

Changes in serum 1,25-dihydroxyvitamin D3 and mRNAs for osteocalcin and alkaline phosphatase in femur unloaded by tail suspension in rats.

To elucidate the mechanism involved in the development of disuse atrophy of bone by skeletal unloading, changes in osteocalcin and alkaline phosphatase mRNAs, markers for bone formation, were studied in the hind limb bones of tail-suspended rats. Tail suspension for 8 and 14 days resulted in a significant decrease in osteocalcin mRNA in the femur when compared with age-matched non-suspended controls. Serum 1,25-dihydroxyvitamin D3 decreased to 60% of the control level after 8 days of skeletal unloading but regained almost normal levels over the next 7 days. Since it is known that vitamin D3 up regulates and glucocorticoid down regulates transcription of the osteocalcin gene, the endocrine response evoked by tail suspension may have aggravated the disuse atrophy caused by skeletal unloading in this study.

Alkaline Phosphatase↗

Boron neutron capture therapy of malignant melanoma using 10B-paraboronophenylalanine with special reference to evaluation of radiation dose and damage to the normal skin.

A treatment regimen for boron neutron capture therapy of malignant melanomas is described using 10B-paraboronophenylalanine as the tumor-targeting compound. As a therapeutic dose, we adopted the maximum tolerable dose for the skin regardless of tumor 10B concentration. In practice, the maximum neutron fluence should be decided prior to starting irradiation. For this purpose, the kinetics of the concentration of 10B in the blood and skin and the skin-to-blood ratios were analyzed in the six patients who received 170 mg/kg of the compound intravenously, and skin concentrations during irradiation were predicted using a standard skin factor curve. This yields a skin concentration at time T based on the blood concentration at time 0. We calculated the maximum tolerable fluence yielding but not exceeding 18 RBE-Gy by assuming that the RBE of 14N(n,p)14C and 10B(n, alpha)7Li reaction for skin damage is 2.5. Actual skin reactions in three of five patients treated with the therapy were, as predicted, within tolerable limits, and we were able to obtain complete tumor regression in four cases. The results indicate that application of our logical approach will be useful for subsequent cases and further development of this therapy.

Aged↗

[Manometric study of the biliary sphincter zone: a comparison between the length of phasic activity and the narrow distal segment].

Motor activity of the sphincter of Oddi has been evaluated in 26 patients who underwent ERCP examination. Manometric recordings from the common bile duct and the sphincter of Oddi were performed with a single end-lumen perfused catheter. The number of successive 3 mm spaced black marks, observed during the pull-through from the first appearance of the proximal sphincter activity to that of duodenal pressure, was used to measure the length of the sphincter zone. In 14 of 26 patients, the length of phasic activity zone of the sphincter of Oddi was 9 mm. However, the narrow distal segment of the common bile duct was 15.1 +/- 3.6 mm in length. In same patients, the length of phasic activity zone was shorter than the anatomical one. The mean sphincter of Oddi pressure (SOP) at the distance of 6 mm from the papillary pore (77.8 +/- 22.1 mmHg) was greater than that of 9 mm (58.4 +/- 27.0 mmHg) and 12 mm (51.0 +/- 16.9 mmHg). These results suggest that the location of the orifice of catheter should be taken into consideration when comparing the SOP.

Adult↗

Suppression of rabbit VX-2 subcutaneous tumor growth by gadolinium neutron capture therapy.

VX-2 tumors growing in hind legs of New Zealand White rabbits (n = 4) were exposed to thermal neutrons for 40 min (2.1 x 10(12) neutrons cm-2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5-6 fold higher than that in the contralateral tumor. Growth of gadolinium-infused tumors was significantly inhibited compared to that of control tumors (P < 0.05) between the 16th and 23rd days after treatment.

Animals↗

Effects of isosorbide in patients with Menière's disease.

The effects of isosorbide on vertigo, disability, hearing loss and tinnitus in 32 patients with Menière's disease were evaluated after a 24-month observation period. Vestibular symptoms in 80% of patients were assessed as improved according to the 1985 AAO-HNS post-treatment reporting criteria. In contrast, the effect of this osmotic diuretic on cochlear symptoms was limited.

Administration, Oral↗

Autonomic nervous system disturbance as etiological background of vertigo and dizziness.

In order to investigate whether dysautonomia lies behind vertigo and/or dizziness in the neurotological clinic, an electrocardiogram (ECG) R-peak to R-peak test (R-R test) along with the Schellong test were simultaneously performed in 136 subjects. ECG data were analyzed by a microcomputer, and R-R intervals were calculated. In a dynamic test performed during postural changes from the supine to the standing position, there were 23 of 55 (41.8%) positive test results in patients with peripheral vestibular disorders, 28 of 51 (54.9%) with central vestibular disorders, and 15 of 18 (83.3%) with spinocerebellar degeneration. In a static test with the patient in the standing position, there were 13 of 55 (29.1%) positive test results in patients with peripheral vestibular disorders, 16 of 51 with central vestibular disorders, and 8 of 18 (44.4%) with spinocerebellar degeneration. A significant difference in the positive rate between spinocerebellar degeneration and both other central and peripheral vestibular disorders in the dynamic test was observed. These results also demonstrated that dysautonomia upon postural changes might play an important role in the development of vertigo and dizziness and that it is provoked by disorders of the autoregulatory mechanisms of the cerebral blood flow. This test is presumed to be excellent for detecting dysautonomia by virtue of being non-invasive, having good reproducibility and being readily available to quantitative evaluation by using a microcomputer.

Autonomic Nervous System↗

[Factors effecting medication errors].

The purpose of this paper is to reveal factors that may occur or that may prevent medication errors, and to consider some measures of patients' safety. For this aim, we explored the characteristics of each ward and the characteristics of each nurse as well as their experiences about medication errors. The investigation was conducted at a approximately 650-bed university hospital located in a large urban center in Tokyo, and at a approximately 150-bed private hospital located in a suburb of Tokyo. Questionnaires were distributed in October 1991 and asked nurses to identify medication errors in which they had been personally committed within the past one-month. A response rate was approximately 70%. We were informed other information of each unit from head nurses--such as the unit size, case mix, nurse staffing and working schedule of nurses. Results indicate that on the questionnaires the nurses reported 10 times medication errors than they reported to head nurses. 56 percent of 155 nurses (except nurses who were working at an ICU and a mental ward) stated they had made medication errors or near misses during the 1-month reporting period. 30 percent of 155 stated they actually dealt with medication errors occurred by others. Several factors that effect medication errors have been identified by a stepwise discriminant analysis. The proportion of serious patient and the bed occupancy rate influenced the occurrence of medication errors. The educational career of a nurse, especially whether the nurse had been offered an assistant nursing program or not, related to dealing with and/or preventing medication errors.(ABSTRACT TRUNCATED AT 250 WORDS)

Discriminant Analysis↗

Urinary excretion of stress hormones of rats in tail-suspension.

Tail-suspension of rats has been employed for the study of disuse atrophy of hindlimb muscles and bones. From our study, it is suggested that stress exacerbates muscle and bone atrophy; however, the determination of stress hormones has been inappropriately performed. For assessing the effect of tail suspension on stress hormone secretion, suspension was performed for 7 days in a metabolic cage. Urinary excretions of corticosterone, catecholamines and antidiuretic hormone were determined during the 7-day suspension. Urine volume was unchanged during the suspension period, whereas water consumption was decreased during suspension. Urinary excretion of corticosterone and catecholamines increased significantly during the initial 3 days of suspension. The excretion of antidiuretic hormone increased throughout the suspension period. Our results demonstrated that the determination of urinary excretion of these hormones is useful for evaluating the stress reaction.

Adrenal Glands↗

Electron-equivalent dose for the effect of gadolinium neutron capture therapy on the growth of subcutaneously-inoculated Ehrlich tumor cells in mice.

The present in vivo study estimates the dose resulting from the gadolinium neutron capture reaction and the gadolinium enhancement extent of the thermal neutron effect. The assay is based on the time required from cell inoculation to the formation of tumors with an arbitrary size of 200 mm2. Mice were inoculated subcutaneously with Ehrlich tumor cells with or without meglumine gadopentetate (1.2 mg 157Gd/0.2 ml), and were exposed to 1.1 x 10(12) thermal neutrons cm-2(n 8), or 3 MeV electrons at three dose levels (each n 10). To reach 200 mm2 in size, it took 18.8 days for tumors treated with neutrons only and 34.7 days for those treated with gadolinium and neutrons. From the time-dose relation obtained with 3 MeV electrons, the equivalent doses corresponding to delays of 34.7 and 18.8 days were 15.0 and 7.4 Gy, respectively. Thus, gadolinium enhanced the thermal neutron effect two-fold (15.0/7.4) in the present study.

Animals↗

[Renal autotransplantation and graft replacement for DeBakey IIIb dissecting aneurysm--a case report].

A successfully repaired case, a 53-years old man, who suffered DeBakey IIIb type dissecting aneurysm and renal dysfunction was reported. The right kidney, of which artery was originated from the false lumen, was autotransplanted to the right iliac system to improve the renal blood circulation. Then the descending aorta was segmentally replaced with the prosthesis under profound hypothermia, circulatory arrest and retrograde cerebral perfusion without cross-clamping the aortic arch. Three months later, aortography and catheterization study suggested that the reperfused left kidney resulted in renin-dependent hypertension. Kidney, therefore, was resected to improve blood pressure control. Patient recovered successfully, with no evidence of neurological complication.

Aortic Dissection↗

Neutron-capture therapy of murine ascites tumor with gadolinium-containing microcapsules.

Gadolinium-containing microcapsules were evaluated as an agent for gadolinium neutron-capture therapy. Mice were inoculated intraperitoneally with 10(7) Ehrlich ascites tumor cells and gadolinium microcapsules and exposed to thermal neutrons for 12 min (approximately 1.86 x 10(12) neutrons cm-2). Significantly more mice given gadolinium microcapsules than those given placebo microcapsules or control survived for 60 days and considerably longer (P < 0.0001), indicating that gadolinium neutron-capture reactions effectively suppressed the growth of ascites tumor cells in mice. The results suggest that these microcapsules are an effective gadolinium carrier for neutron-capture therapy.

Animals↗