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K Iwatsuki

Publications and source records attributed to K Iwatsuki.

359 records · Page 20Linked to original sources

Effects of nicardipine on pancreatic exocrine secretion in the dog.

1. The effects of nicardipine on the secretion of pancreatic juice were investigated in dog isolated, blood-perfused pancreas, and compared with those of papaverine, aminophylline and secretin. 2. Intra-arterial administration of nicardipine (1-10 micrograms) elicited a dose-dependent increase in pancreatic secretion. Papaverine (0.1-1 mg), aminophylline (0.3-3 mg) and secretin (0.03-0.1 units) also elicited increased secretion. The secretory activity of nicardipine (10 micrograms) was approximately equal to that of 0.5 mg of papaverine, 1.5 mg of aminophylline and 0.03 units of secretin. 3. The concentration of bicarbonate in the pancreatic juice induced by nicardipine was increased, but the protein concentration was only increased slightly. These effects are analogous to those of secretin. 4. Nicardipine-induced secretion was not modified by pretreatment with relatively large doses of phentolamine, propranolol, atropine, guanethidine, haloperidol or metiamide. 5. Secretin-induced secretion was significantly potentiated by infusion of papaverine, but not by infusion of nicardipine or aminophylline. 6. These results suggest that nicardipine acts on the exocrine cells in the dog pancreas, at least in part, through the increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.

Aminophylline↗

Secretory and vascular effects of the optical isomers of nicardipine.

The effects of optical isomers of nicardipine on the secretion of pancreatic juice and blood flow were investigated in the dog-isolated, blood-perfused pancreas. Intra-arterial administration of (-)-nicardipine (10-300 micrograms) caused a dose-dependent increase in pancreatic secretion. However, the (+)-isomer was much less potent than the (-)-isomer and even in 300 micrograms of (+)-isomer caused only a slight secretion. (+)- And (-)-nicardipine increased perfusion blood flow in a dose-dependent manner, and (+)-nicardipine was approximately five times as potent as the (-)-isomers. The maximum increase in a flow rate was produced by 30 micrograms of (+)-isomer and 100 micrograms of (-)-isomer. Bicarbonate concentration in pancreatic juice induced by (-)- and (+)-nicardipine was increased in a dose-dependent manner, but the protein concentration was only increased slightly. From these results, it is concluded that there is a stereoselectivity in the secretory and vascular actions of optical isomers of nicardipine.

Animals↗

Activities of NAD+-dependent aldehyde dehydrogenase and alcohol dehydrogenase in the liver of spontaneously hypertensive rats in the process of development.

The difference in the basal activities of NAD+-dependent aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) was investigated in the liver of age-matched spontaneously hypertensive (SH) and normotensive Wistar Kyoto (WK) rats. A significant difference between the SH and WK rats in the basal ALDH activity, ADH activity and the protein content of subcellular fractions was observed. The activities of mitochondrial low Km- and high Km-ALDH in the SH rats at 5-8 weeks of age were higher than those in the WK rats. The microsomal high Km-ALDH activity in the SH rats at 5 and 11 weeks of age was higher than that in the WK rats. The ADH activities in the SH rats at 5-14 weeks of age were lower than those in the WK rats. The mitochondrial protein content in the SH rats at 5-14 weeks of age was higher than those in the WK rats. At 14 weeks of age, an increase in the blood acetaldehyde level was observed after an intraperitoneal injection of 1.5 g/kg of ethanol in the SH rats. No difference in blood ethanol level was observed between the SH and WK rats.

Acetaldehyde↗

Effects of bromocriptine on pancreatic secretion in the isolated, blood-perfused pancreas of the dog.

Effects of bromocriptine on the secretion of pancreatic juice were investigated with dog isolated, blood-perfused pancreas. Bromocriptine (1-10 mg) caused dose-dependent increases in the secretion of pancreatic juice. However, bromocriptine did not affect the perfusion blood flow rate. The secretory response to bromocriptine was inhibited by pretreatment with a dopamine antagonist, sulpiride, but not by phentolamine, propranolol, atropine, metiamide, indomethacin or tetrodotoxin. Bromocriptine caused a dopamine-like secretion of the pancreatic juice containing a high concentration of bicarbonate but had little effect on protein output. These results suggest that bromocriptine increases pancreatic secretion stimulating directly on pancreatic dopamine receptors.

Animals↗

Effect of secretagogues on pancreatic exocrine secretion in the monkey and the dog.

The effects of secretin, cholecystokinin, dopamine, histamine and acetylcholine on the secretion of pancreatic juice were investigated in the monkey and the dog. In the resting state, bicarbonate concentration and the volume of pancreatic juice in the monkey were greater than those in the dog. However, the protein concentration of pancreatic juice in the monkey was less than that in the dog. Intravenous administration of secretin, cholecystokinin, histamine and acetylcholine caused a dose dependent increase in pancreatic secretion in both species. The responses in the monkey were greater than those in the dog. Dopamine caused pancreatic secretion only in the dog. The increase in bicarbonate concentrations of pancreatic juice induced by secretin and histamine in the monkey were greater than that in the dog. Increase in protein concentrations of the juice induced by cholecystokinin and acetylcholine in the monkey were less than that in the dog. However, pancreatic juice pH in both species was the same and was not affected by the secretagogues in the resting state or during the stimulation by secretogogues. From these results, it is concluded that there is a species difference in the secretory actions of the secretagogues in the monkey and the dog.

Acetylcholine↗

Metoclopramide enhances bethanechol-induced pancreatic exocrine secretion of the dog.

The effects of metoclopramide on pancreatic exocrine secretion were investigated in the pentobarbitone-anaesthetized dog. All drugs were injected into the femoral vein. Metoclopramide (10-1000 micrograms/kg) did not change the resting rate of pancreatic secretion. Pancreatic secretion, induced by bethanechol (3 micrograms/kg), was dose-dependently enhanced by simultaneous injections of metoclopramide (10 and 30 micrograms/kg), but the protein and bicarbonate concentrations of the pancreatic juice were not affected. Secretions induced by secretin (0.1 units/kg) and dopamine (3 micrograms/kg) were not modified by metoclopramide at up to 30 micrograms/kg. A larger dose of metoclopramide (1000 micrograms/kg) suppressed dopamine-induced secretion to a lesser extent than the same dose of sulpiride. From these results, it is concluded that metoclopramide enhances secretory responses to cholinergic stimulations by peripherally sensitizing the muscarinic receptor-mediated exocrine process and this drug is a weaker antagonist of the dopamine D2 receptors than sulpiride.

Animals↗

Effects of ZSY-27, a synthesized phosphodiesterase inhibitor, on exocrine secretion and cyclic nucleotide concentration in the dog pancreas.

1. Effects of intravenous injections of ZSY-27, a synthesized phosphodiesterase inhibitor, on pancreatic exocrine secretion and on pancreatic cyclic AMP and cyclic GMP concentrations of dogs were investigated. 2. ZSY-27 (0.3 and 1 mg/kg) increased cyclic AMP concentration dose-dependently, which preceded the increase in pancreatic secretion but did not affect cyclic GMP concentration. 3. These results suggest that ZSY-27 causes exocrine secretion from the dog pancreas mediated through an increase in intracellular cyclic AMP concentration.

Animals↗

Effects of peptide histidine isoleucine on pancreatic exocrine secretion in anaesthetized dogs.

1. The effects of peptide histidine isoleucine (PHI) on pancreatic exocrine secretion were investigated in preparations of the isolated and blood-perfused dog pancreas as compared with those of vasoactive intestinal peptide (VIP), secretin and glucagon. 2. Each peptide tested was injected intra-arterially (i.a.) as a single bolus. Graded doses of PHI (3-300 nmol/kg), VIP (1-100 nmol/kg) and secretin (0.01-0.3 nmol/kg) caused dose-dependent increases in the secretion of pancreatic juice and bicarbonate outputs, but had little effect on the protein outputs. Glucagon (0.1-10 mumol/kg) produced a bell-shaped dose-response curve for the secretory rate, bicarbonate and protein outputs. 3. The secretory activity of 30 nmol/kg of PHI corresponded roughly to that of 80 pmol/kg of secretin, 9 nmol/kg of VIP and 0.6 mumol/kg of glucagon, respectively. Thus, based on administered dose, PHI was about 375 x less potent than secretin, 3 x less potent than VIP and 20 x more potent than glucagon. 4. The PHI- and VIP-stimulated secretions were inhibited by a VIP antagonist, but not by a glucagon antagonist, SCH23390 (a dopamine D-1 antagonist), L-364718 (a cholecystokinin antagonist) or atropine. 5. Each peptide increased cyclic AMP concentration, but not cyclic GMP concentration, concomitant with the increase in pancreatic secretion. 6. From these results, it is concluded that PHI produces an increase in pancreatic secretion by acting on VIP-preferring receptors on the exocrine pancreatic gland of the dogs. This may be mediated at least in part through the increase of intracellular cyclic AMP concentrations.

Animals↗

Subtypes of adenosine receptors on pancreatic exocrine secretion in anaesthetized dogs.

Characterization of adenosine receptor subtypes was examined on the canine exocrine pancreas using selective adenosine receptor agonists and antagonists in the isolated and blood-perfused pancreas of anaesthetized dogs. Each drug was injected intra-arterially in a single bolus fashion. Graded doses of CGS21680 (1-300 nmol/kg), a selective adenosine A2A receptor agonist, produced dose-dependent increases in the secretory rate of pancreatic juice, with a maximum effect at approximately 30 nmol/kg. However, CPA (1-300 nmol/kg), a selective adenosine A1 receptor agonist, did not cause the pancreatic secretion. CGS21680 (3-30 nmol/kg) and secretin (0.01-0.03 pmol/kg) increased the bicarbonate concentration in pancreatic juice and decreased the protein concentration. CCK-8 (0.1-0.3 pmol/kg) increased the protein concentration but did not alter the bicarbonate concentration. DMPX (5-50 nmol/kg), a weak adenosine A2A receptor antagonist, caused a progressive parallel shift to the right in the dose response curve for CGS21680-induced pancreatic secretion without changes in the maximal response. DPCPX (100 nmol/kg), a selective A1 adenosine receptor antagonist, did not antagonize the CGS21680-induced pancreatic secretion. Schild analysis of the data indicated that the apparent pA2 value for DMPX was 8.3 using CGS21680 as the agonist. The slope of the Schild regression line was not different from 1. When a phosphodiesterase IV inhibitor rolipram (0.1 nmol/kg) was added, pancreatic secretion induced by CGS21680 (10 nmol/kg) and secretin (0.03 pmol/kg) were potentiated, but not that of CCK-8 (0.3 pmol/kg). These results suggest the existence of adenosine A2A receptors in the exocrine cells of the dog pancreas involved in the water and bicarbonate secretory response.

Adenosine↗

Body fluid oxygen tension and prognosis in patients with ruptured aneurysm.

Body fluid gas pressure and electrolytes of patients with ruptured aneurysm were continuously analyzed. Intracranial pressure (ICP) was regulated at the level of 120-100 mm H2O by cerebral ventricular drainage. There was no significant change in the pH, PCO2, HCO3-, Na+, K+, Ca++ in the cerebrospinal fluid (CSF) of patients with slight or moderate disturbance of consciousness (lethargic-drowsy state). The PcsfO2 of the patients with marked disturbances of consciousness (semicoma-coma) was significantly low. PcsfO2 of the patients with cerebral vasospasm was significantly lower than for those without vasospasms. PcsfO2/PaO2 was 0.27 +/- 0.01 in the patients with vasospasm and 0.50 +/- 0.01 in those with vasospasm. PcsfO2 tended to decrease in patients with markedly bloody CSF. When the bloody CSF was cleared by ventricular drainage, PcsfO2 increased. PcsfO2 did not return to a normal value in the patients with marked disturbances of consciousness despite sufficient arterial oxygen tension. This suggests that PcsfO2 and PcsfO2/PaO2 should provide a convenient index for the prognosis of patients with ruptured aneurysm.

Aged↗

Subcorneal pustular dermatosis-type IgA pemphigus induced by thiol drugs.

We report a case of subcorneal pustular dermatosis (SPD)-type IgA pemphigus arising in a 49 year-old woman with rheumatoid arthritis who had been treated with chrysotherapy. Scaly erythemic plaques containing vesicles and pustules occurred on her chest and abdomen during the course of anti-rheumatic treatments using prednisolone at 11 mg/day and thiol compounds (bucillamine and gold sodium thiomalate). Histological investigations revealed subcorneal pustules containing many neutrophils and a few acantholytic cells, and intercellular IgA deposits at the upper epidermis of the eruptions without any other immunoglobulins and complement component C3. Circulating IgA antibodies directed against intercellular spaces of the epidermis were found by prolonged incubation of normal skin specimens in medium containing 20% patient's serum in an explant culture, although standard indirect immunofluorescence for IgA antibodies was negative. The eruptions were treated successfully with prednisolone, 30 mg/day, dapsone, 50 mg/day, and discontinuance of the thiol compound. In addition to the coexistent rheumatoid arthritis, both thiol compounds might have been responsible for the development of the eruptions.

Abdomen↗

Recalcitrant trichophytic granuloma associated with NK-cell deficiency in a SLE patient treated with corticosteroid.

Although deep trichophytic infection often occurs in immunocompromised patients, the immune deficiency in such patients has not been clarified. A 28-year-old man who suffered from recalcitrant trichophytic granuloma and tinea universalis during treatment for SLE with corticosteroid is described here to define the immunological abnormalities. In addition to routine immunological tests, we evaluated the patient's innate and specific immune functions to dermatophytes, including T cell, natural killer (NK) cell and neutrophil functions and activation of the complement cascade. We measured the minimum inhibitory concentration (MIC) of itraconazole for the isolated fungus and its concentrations in the patient's serum and pus. Trichophyton (T.) rubrum was constantly isolated from the exudates of the patient's skin lesions, although the concentrations of itraconazole in his serum (198 ng/ml) and lesions (210 ng/ml) were sufficient to inhibit the growth of the isolated fungus in vitro. Specific cell-mediated immune responses, determined by T cell stimulation and IFN-gamma production, were evoked following stimulation with trichophytic antigens. The patient's innate immunity, assessed by activation of the complement cascade and neutrophil-mediated phagocytosis, was not impaired. The number of circulating NK cells was markedly decreased (0.2% of the peripheral blood mononuclear cells), and was associated with low NK cell activity against K-562 cells even though lymphopenia had improved. The deficiency of innate immunity mediated by NK cells might be responsible for a part of the persistence of trichophytic granuloma in our case. Dermatophytes usually affect the horny layer of the skin and do not invade the living layers because the host immune system uses various mechanisms to eliminate the fungi. Both specific T cell-mediated immunity and nonspecific immunological mechanisms provide host defense against fungal infections. An adaptive immune response is usually preceded by innate immune responses mediated by neutrophils, NK cells, and circulating proteins such as complement components and anti-microbial peptides. However, in patients with localized or systemic immunological defects, granulomatous cutaneous infection of dermatophytes mostly caused by trichophytic fungi may occur [1]. Trichophytic granuloma includes Majocchi's granuloma [2] and disseminated trichophytic granuloma [3]. Recently, we experienced a patient with trichophytic granuloma and tinea universalis caused by Trichophyton (T.) rubrum infection during treatment with corticosteroid for systemic lupus erythematosus (SLE). We describe the clinical details of this patient, focusing on his immunological defects which led to the persistence of the fungal infection.

Adult↗

Koebner phenomenon on skin graft donor site in cutaneous angiosarcoma.

An 81-year-old woman developed a necrotic plaque and a surrounding purple-red, irregularly shaped macule on her scalp. The diagnosis of angiosarcoma was confirmed histologically. A wide surgical excision was made followed by a split-thickness skin graft from her right buttock. Nine months later, she noticed a dark purple-red lesion on the donor site which grew rapidly into a large mass. Histological examination revealed irregular clefts and vascular channels lined by atypical endothelial cells. Lung metastasis and pneumothorax were also noted. The secondary tumor appeared to represent Koebner phenomenon in a patient with angiosarcoma of the scalp.

Aged↗

E-3123, a new synthetic protease inhibitor, protects against deoxycholic acid-induced acute pancreatitis in dogs.

The effects of intravenous infusion of 4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate (E-3123), a new synthetic protease inhibitor, on deoxycholic acid-induced acute pancreatitis in a canine pancreas were investigated. The retrograde injection of 1% deoxycholic acid into the pancreatic duct significantly and time-dependently increased venous serum amylase and lipase activities. E-3123 significantly decreased these increased amylase and lipase activities. Two hours after deoxycholic acid injection, the amylase activity was reduced by 23 +/- 3% and 34 +/- 4% after infusion of 0.1 and 1 mg/kg/hr of E-3123, respectively, compared to the corresponding values in the control group, and the lipase activity was reduced by 13 +/- 3% and 29 +/- 3%, respectively. The potency of 1 mg of E-3123 to decrease these enzymes was almost the same as that of 5 mg of gabexate, a novel protease inhibitor. Pancreatic wet weight/body weight also decreased after treatment with E-3123 in dogs injected with deoxycholic acid. Histologic examination revealed that injection with deoxycholic acid caused marked interstitial edema, hemorrhage, vacuolization and inflammation as well as focal acinar cell necrosis, while in the E-3123-treated group, only mild changes in these parameters were seen. These results suggest that E-3123 may be useful in suppressing the progression of acute pancreatitis induced by deoxycholic acid, at least in part, through its protease-inhibiting ability.

Acute Disease↗

Dissociation of prostaglandin output from secretin-stimulated exocrine secretion of the pancreas in dogs.

Correlation between pancreatic exocrine secretion and prostaglandin (PG) output was investigated in the isolated and blood-perfused pancreas in pentobarbital-anesthetized dogs. Intraarterial injections of low doses of secretin (0.03-1 units) caused dose-dependent increases in the secretion of pancreatic juice without affecting the output of PGs. Increased secretion was not modified by indomethacin treatment (5 mg/kg, i.v.). Intra-arterial injections of high doses of secretin (4 and 8 units) stimulated the output of both pancreatic secretin and PGE2 and 6-keto-PGF1 alpha into the blood of the pancreaticoduodenal vein dose-dependently. Increased output of PGs was completely inhibited by the indomethacin treatment, but pancreatic secretion was not inhibited. Total amylase and pancreatic isoamylase activities in the blood from the pancreaticoduodenal vein were increased by the injection of secretin (8 units, i.a.). These results suggest that there is no simple correlation between the ability of secretin to increase the pancreatic secretion and its ability to stimulate PGs synthesis in dog pancreas. Increased output of PGs may be due to the consequence of the acute pancreatitis induced by high doses of secretin.

Amylases↗

Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on inflammatory responses in psoriasis.

Topical application of 1alpha,25-dihydroxyvitamin D3 (VD3) is thought to be beneficial in psoriasis because of its action in regulating keratinocyte proliferation and inflammation mediated by various cytokines. We assessed the effect of VD3 on the production levels of interferon (IFN)-alpha, interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in mitogen-stimulated peripheral blood mononuclear cells (PBMC) of psoriatic patients. The results demonstrated that VD3 significantly inhibited IFN- , IL-6, and IL-8 levels produced by concanavalin A (Con A)-stimulated PBMC of psoriatic patients in a dose-dependent manner, and reduced mRNA expression for IFN- and IL-8. These findings suggest that in addition to the direct anti-proliferation effect on keratinocytes, VD3 may down-regulate the inflammatory cytokine production by infiltrating cells in psoriatic lesions.

Adult↗