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Biomedical subjects

K Saga

Publications and source records attributed to K Saga.

At least 55 records · Page 3Linked to original sources

Biology of sweat glands and their disorders. I. Normal sweat gland function.

The basic mechanisms of sweat gland function and an updated review of some relatively common disorders of sweat secretion, are presented. Although sweat secretion and ductal absorption are basically biophysical and biologic cellular processes, a detailed description of the basic biophysical principles of membrane transport has been avoided to make the discussion more readable. The cited references will, however, help those readers primarily interested in the basic details of sweat gland function. Part I of this article includes a discussion of morphologic characteristics, central and peripheral nervous control of sweat secretion, neurotransmitters, intracellular mediators and stimulus secretion coupling, Na-K-Cl cotransport model for the ionic mechanism of sweat secretion, ingredients of sweat, ductal function, the pathogenesis of abnormal sweat gland function in cystic fibrosis, and the discovery of the apoeccrine sweat gland. Part II, to be published in the May issue of the Journal, reviews reports of all those major disorders of hyperhidrosis and hypohidrosis that have appeared in the literature during the past 10 years. It is hoped that this review will serve as a resource for clinicians who encounter puzzling disorders of sweating in their patients, as well as for investigators who wish to obtain a quick update on sweat gland function.

Humans↗

Biology of sweat glands and their disorders. II. Disorders of sweat gland function.

Part I of this article (J Am Acad Dermatol 1989; 20:537-63) focused on normal sweat gland function. Part II provides a discussion of hyperhidrosis and hypohidrosis. Hyperhidrotic disorders affect the palms and soles and the axillae and are associated with previous spinal cord injuries, peripheral neuropathies, brain lesions, intrathoracic neoplasms, systemic illness, and gustatory sweating. Hypohidrotic disorders include anhidrotic ectodermal dysplasia, hereditary sensory neuropathy, Holmes-Adie syndrome, and generalized anhidrosis.

Humans↗

Effect of beraprost sodium on peripheral circulation insufficiency in rats and rabbits.

Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is a chemically and biologically stable epoprostenol analogue which possesses both potent antiplatelet and peripheral vasodilating actions. Its effect on obstruction of the peripheral artery was studied in three different models: 1. acute thrombosis induced by electrical-stimulation of the femoral artery in rabbits, 2. occlusion induced by intra-arterial injection of sodium laurate in rats and 3. tail gangrene induced by subcutaneous injections of both ergotamine and epinephrine in rats. Oral administration of beraprost sodium resulted in suppression of thrombus formation in the acute thrombosis model, marked improvement of macroscopic and histological observations in the laurate-occlusion model and inhibition of tail gangrene extension. In contrast, ticlopidine improved thrombus formation in the acute thrombosis model and slightly improved histological observation in the laurate-occlusion model, but not in the tail gangrene model. Cilostazol suppressed lesions in the acute thrombosis model, but not in the tail gangrene model. These findings suggest that beraprost sodium may be very useful clinically for the therapy of peripheral circulation insufficiency diseases such as Buerger's disease and Raynaud's disease.

Acute Disease↗

[Studies on transfer of vitamin K into human breast milk].

We studied whether the administration of vitamin K to mothers could increase the concentration of vitamin K in breast milk and prevent idiopathic vitamin K deficient bleeding in breast-feeding infants. Sixty puerperal women were divided into three groups, the control group, Menaquinone-4 (MK-4) administered group and vitamin K1 administered group. We measured the concentrations of vitamin K1, MK-4 and MK-7 in maternal plasma and breast milk on the fourth day after delivery. In the MK-4 group, the concentrations of MK-4(2.13 ng/ml in plasma, 49.3 ng/ml in milk) were significantly higher than in the control group (0.28 ng/ml, 1.51 ng/ml). In the vitamin K1 group, the concentrations of vitamin K1 (49.0 ng/ml in plasma, 71.6 ng/ml in milk) were significantly higher than in the control group (1.17 ng/ml, 2.41 ng/ml). The concentration rates (milk/plasma ratio) of vitamin K1, MK-4 and MK-7 were 2.52, 5.43 and 0.52 in the control group, 1.60, 40.2 and 0.67 in the MK-4 group and 1.65, 10.8 and 0.71 in the vitamin K1 group, respectively. The concentration rate of MK-4 was higher than that of vitamin K1 and was increased by MK-4 administration. After delivery, the daily concentration of MK-4 in milk was increased from 1.69 ng/ml on the first day to 49.3 ng/ml on the fourth day in the MK-4 group. These results indicate that MK-4 is accumulated and concentrated into breast milk, and continuous MK-4 administration can increase the concentration of vitamin K in milk, preventing idiopathic vitamin K deficient bleeding in infants.

Female↗

K+ efflux from the monkey eccrine secretory coil during the transient of stimulation with agonists.

1. Using a K+-sensitive extracellular electrode, we attempted to determine whether cholinergic stimulation of the simian palm eccrine sweat gland is associated with transient net K+ efflux as in other exocrine glands. 2. When isolated secretory coils placed in a glass capillary were continuously superfused (method A), 32% of total cellular K+ was lost during 3 min of stimulation with methacholine (MCh) followed by K+ reuptake when stimulation was stopped. 3. When secretory coils were stimulated in a small chamber (without continuous superfusion, method C), MCh (5 x 10(-6) M)-induced maximal K+ efflux as determined by the peak level of extracellular K+ concentrations was dose dependent, inhibited by atropine but not altered by a cholinesterase inhibitor, physostigmine (1.3 x 10(-5) M). Thus the peak K+ level was used as a measure of K+ efflux throughout the study. 4. Phenylephrine (10(-4) M) and A23187 (5 x 10(-6) M) also induced K+ efflux but to a lesser extent than did MCh. 5. Ouabain (10(-3) M)-induced K+ loss was 2.4-fold higher than the peak level of MCh-induced K+ efflux. 6. In a Ca2+-free medium with added EGTA, inhibition of K+ efflux was only partial in the first MCh stimulation but progressively increased on repeated stimulation, suggesting that cytoplasmic or membrane Ca2+ not readily accessible to EGTA may be important for K+ efflux. Inhibition of K+ efflux in the Ca2+-free medium was completely reversed on subsequent addition of Ca2+. 7. Five millimolar Ba2+ partially inhibited MCh-induced K+ efflux. 8. 10(-4) M-bumetanide itself caused a small K+ loss and strongly inhibited the subsequent MCh-induced K+ loss. 9. MCh-induced K+ loss was drastically inhibited in the low-Cl- (by replacing with gluconate- or methylsulphate-) or low-Na+ (by replacing with Tris+) medium. 10. K+ efflux occurs predominantly across the basolateral membrane. 11. Vinblastine at 10(-4) M, which completely inhibits sweat secretion (our unpublished results), however, showed no effect on MCh-induced K+ efflux. 12. We conclude that the transient net K+ efflux associated with MCh stimulation constitutes a crucial primary ionic event in cholinergic eccrine sweat secretion as in other exocrine secretory cells.

Animals↗

Ultrastructural localization of ouabain-sensitive, K-dependent p-nitrophenyl phosphatase activity in monkey eccrine sweat gland.

We studied the electron microscopic localization of ouabain-sensitive, potassium-dependent p-nitrophenyl phosphatase (K-pNPPase) activity of the Na K-ATPase complex in Rhesus monkey eccrine sweat gland by use of the one-step lead citrate method of Mayahara et al. (Histochemistry 1980; 67:125). Reaction product was observed predominantly in the cytoplasmic side of the basolateral membranes of clear (secretory) cells, especially in the interdigitating membrane folds in the basal labryinth, and were completely abolished by 10 mM ouabain or by removal of K+. Little or no enzyme activity was noted in membrane processes in the intercellular canaliculi and in the secretory coil lumen. Basolateral membranes of the dark cells also showed moderate enzyme activity. The myoepithelial cell membrane was devoid of reaction product, except in a few membrane processes arising from the inner aspect of myoepithelial cells. In the coiled duct, K-pNPPase activity was present predominantly in the entire cell membrane of the peripheral ductal cells. The predominantly basolateral distribution of Na-K-ATPase in the eccrine sweat secretory cells is consistent with the concept that a Na-K-Cl co-transport model may be involved in the mechanism of eccrine sweat secretion.

4-Nitrophenylphosphatase↗

Effect of theophylline on the transport of tyrosine in cultured B-16 mouse melanoma cells.

The effect of theophylline, an inhibitor of phosphodiesterase, on tyrosine (Tyr) transport across cell membrane was studied using cultured B-16 mouse melanoma cells. 1.5 mM Theophylline in culture medium increased Tyr uptake velocity in linear fashion up to 36 h, after which it reached a plateau at which the cells showed about a 60% increase in Tyr transport velocity. This increase was independent of extracellular Na, essentially unaffected by cell density, and partially inhibited by concomitantly added cycloheximide. These results suggested that biosynthesis of macromolecules, probably acting as System L transporter, was induced by theophylline treatment.

Animals↗

Toxicology of mabuterol.

The acute, subacute and chronic toxicity of dl-1- (4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butyl-amino-ethanol hydrochloride (mabuterol), a new beta 2-selective adrenoceptor stimulant, was studied in mouse, rat, rabbit and dog. The acute oral LD50 was between 199.9 and 319.3 mg/kg in all four species used and did not differ significantly between the sexes. Intravenous LD50 was between 18.3 and 51.1 mg/kg (four species), i.p. between 60 and 78.3 mg/kg and s.c. between 113 and 125.7 mg/kg (mouse and rat only). In subacute and chronic studies in Wistar rats, mabuterol was dosed by gavage at 0, 10, 20, 40, 80 and 120 mg/kg for 1 month, and 0, 1, 2.5, 10 and 40 mg/kg for 3 (interim) and 6 months or in food at 0, 2.5, 10 and 40 mg/kg for 6 (interim) and 12 months. Beagle dogs were dosed by gelatine capsule with 0, 0.05, 0.5, 5 and 50 (25) mg/kg for 6 (interim) and 24 months. In rats, 1 and 2.5 mg/kg were well tolerated. At 10 mg/kg and above, irritability and hypersalivation were seen dependent on dose. Two males and one female given 120 mg/kg died from the test substance. In dogs, 0.05, 0.5 and 5 mg/kg were well tolerated. 50 mg/kg caused vomiting, diarrhoea, tonic-clonic convulsions and increased salivation. One male had to be killed because of severe convulsions. At term, 3 of 56 female rats of the one-year study had benign mesovarian leiomyomas. No other substance-related changes were discovered but all findings belonged to the spontaneous pathology of rat and dog, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

Studies on the transport of tyrosine, leucine, and methionine in cultured B-16 mouse melanoma cells.

1. Linear uptake of tyrosine lasted for 1 min in cultured B-16 mouse melanoma cells preloaded with an amino acid such as tyrosine. 2. The tyrosine uptake increased markedly on preincubating the cells with 0.1 mM methionine, tyrosine, histidine or tryptophan and moderately with 1 mM phenylalanine, valine, isoleucine, or leucine. The effects of the preincubation on leucine uptake were similar to those on tyrosine uptake. 3. The tyrosine uptake was Na-independent under the experimental conditions used (0.05-1.0 mM); Km 75 micrometers and Vmax 15 nmol/min/mg protein. The methionine uptake (0.1-0.5 mM) was also Na-independent (Km 150 micrometers and Vmax 25 nmol/min/mg protein), whereas Na-dependent uptake could contribute at 2 mM methionine. 4. Inhibitions of tyrosine uptake by tryptophan, phenylalanine, leucine, isoleucine, methionine, valine, and histidine were competitive, giving K1 values of 70, 80, 100, 130, 160, 350, and 900 micrometers, respectively. 5. Exchange between intracellular methionine and extracellular tyrosine and vice versa was equimolar. Potencies of amino acids in stimulating tyrosine efflux were in the following order: methionine greater than tyrosine greater than histidine greater than tryptophan greater than phenylalanine greater than leucine greater than isoleucine much greater than valine. 6. The amino acid affinity of the system in the intracellular surface was suggested to be different from that in the extracellular surface. 7. The theophylline-treated cells showed a marked increase in tyrosine-uptake rate with elevated Vmax and unchanged Km.

Animals↗

Annular hemosiderotic histiocytoma.

A 35-year-old woman was examined because of a symptomless multiple annular eruption. The lesion consisted of rings of closely set, smooth, firm papules that were brown in color. Hemosiderotic histiocytoma was diagnosed by light and electron microscopy. Ultrastructurally, the lesion consisted of fibroblastic and histiocytic cells with marked hemosiderin and lipid deposition.

Adult↗

Pharmacological and toxicological studies of a new non-steroidal anti-inflammatory drug: KC-8973.

A benzophenone derivative, 4-butyl-2'-fluorobenzophenone (KC-8973), having anti-inflammatory effects has been studied pharmacologically and toxicologically. On the carrageenin-induced paw edema, KC-8973 had the most potent activity of the tested commercial non-steroidal anti-inflammatory drugs. KC-8973 had a moderate effect on bradykinin-induced capillary permeability and lesser effect on dextran-, egg white- and serotonin-induced paw edemas in rats, respectively. From the detailed studies of prophylactic and therapeutic effects on the adjuvant-induced arthritis in rats, it was demonstrated that KC-8973 has an immuno-suppressive activity in addition to an anti-inflammatory effect. KC-8973 had a local-analgesic and antipyretic effect on the rat paw edema induced by brewer's yeast. KC-8973 caused no undesirable side effect at pharmacologically effective dose in the 1-month sub-acute toxicological study.

Animals↗