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Biomedical subjects

Y C Kim

Publications and source records attributed to Y C Kim.

At least 235 records · Page 13Linked to original sources

Biological and pharmacological effects of pinusolide, a novel platelet activating factor antagonist.

Pinusolide, a potent platelet activating factor (PAF) receptor binding antagonist, inhibited PAF-induced aggregation of rabbit platelets with an IC50 value of 5 microM, whereas no inhibitory effects on the aggregation induced by ADP, thrombin, and collagen were observed. Pinusolide protected the mice from PAF-induced lethality with ED50 values of 1.1 mg/kg, i.v. and 69 mg/kg, p.o. Topically given pinusolide at 2 mg/ear effectively inhibited croton oil induced mouse ear edema. All the pinusolide treated ears recovered to normal healthy appearance in a sharp contrast to totally necrotized untreated ears. These results indicated that pinusolide is a potent and specific PAF antagonist in all experimental models as shown in vitro, in vivo, and in animal tests.

Animals↗

Antihepatotoxic activity of icariin, a major constituent of Epimedium koreanum.

In an attempt to identify compounds with antihepatotoxic activity, carbon tetrachloride-induced cytotoxicity in primary cultured rat hepatocytes has been adopted as a screening system. Using this screening system, an antihepatotoxic compound from the aerial parts of Epimedium koreanum has been isolated. This compound, icariin, is a flavonol glycoside. Its antihepatotoxic activity was first evaluated by measuring the release of glutamic pyruvic transaminase and sorbitol dehydrogenase from CCl4-intoxicated rat hepatocytes into the culture medium. Icariin significantly reduced the level of glutamic pyruvic transaminase and sorbitol dehydrogenase released resulting in a 76% protection from toxicity at concentration ranges from 1 microM to 20 microM. The antihepatotoxic activity of icariin was also estimated by the determination of total cytochrome P-450 content and glutathione-S-transferase activity in the CCl4-intoxicated hepatocytes.

Animals↗

Comparison of nuclear bone and gallium scans in the therapeutic evaluation of bone lymphoma.

The objective of this study was to compare Tc-99m MDP bone and Ga-67 scans for the therapeutic response to bone lymphoma in 40 patients. The authors retrospectively compared 40 Tc-99m MDP bone scans and 20 Ga-67 scans before therapy, 29 bone scans and 13 Ga-67 scans during the therapy, and 33 bone scans and 15 Ga-67 scans after therapy. Tc-99m MDP and Ga-67 whole body scans were obtained within 2 weeks of each study and were graded visually (grades 1-4) in which grade 3 means similar count density to that of normal iliac alar activity on bone scans and normal liver activity on Ga-67 scans, respectively. The findings of lesion improvement during and after therapy were found in 66.0% (19 of 29) and 72.7% (24 of 33) with Tc-99m MDP bone scans, 84.6% (11 of 13) and 86.7% (13 of 15) with Ga-67 scans, respectively. The mean grades of Tc-99m MDP uptake were 3.06 before, 2.34 during, and 1.75 after therapy. The mean grades of Ga-67 uptake were 3.22 before, 1.42 during, and 1.30 after therapy. Ga-67 scans appear to be more reliable than Tc-99m MDP bone scans in evaluating the therapeutic response of bone lymphoma.

Adult↗

Characterization and function of histamine receptors in corpus cavernosum.

Widespread clinical use of H2 antagonists for peptic ulcer disease has been associated with reports of impotence. Histamine is a vasoactive amine which is endogenously produced in many organs including the penis. To date, 3 histamine receptor subtypes (H1, H2 and H3) have been identified. However, the role and function of histamine in the corpus cavernosal physiology are poorly understood. This study evaluates the in vitro functional characteristics of the 3 histamine receptor subtypes in the isolated corpus cavernosal strips from New Zealand White rabbits. The isometric responses to histamine and specific histamine receptor subtype agonists were assessed, following cyclooxygenase (indomethacin, 10(-5) M.), adrenergic (guanethidine, 5 x 10(-6) M.) and cholinergic (atropine, 5 x 10(-6) M.) blockade, at resting tension and after submaximal precontraction with norepinephrine (NE, 2 x 10(-5) M.). Histamine (10(-8) M. to 10(-3) M.) produced concentration-dependent contraction from basal and precontracted states and did not relax precontracted tissue. The H1 agonist, 2-(2-thiazolyl)ethylamine (10(-8) M. to 10(-3) M.), produced a contractile response from both basal and precontracted states, while the corporal tissue did not respond to either dimaprit, an H2 agonist (10(-8) M. to 10(-5) M.) or R(-)-alpha-methyl-histamine, an H3 agonist (10(-8) M. to 10(-5) M.). The response to histamine was progressively attenuated by an H1 antagonist (mepyramine; 10(-8) M. to 10(-5) M.), while neither an H2 antagonist (cimetidine; 10(-4)M.) nor an H3 antagonist (thioperamide; 10(-4)M.) had any inhibitory effects. H1 antagonism enhanced relaxation induced by electrical field stimulation (neurally mediated). Such relaxation increased after preincubation with 10(-6) M. or greater of mepyramine (p < 0.05). This study suggests that the principal histamine receptor subtype that mediates smooth muscle cell contraction in the corpus cavernosum is the H1 subtype. Since histamine H1 receptor antagonism increased NANC neurally mediated corporal relaxation, it possesses potential as an intracavernosal pharmacotherapeutic agent for the treatment of erectile dysfunction. This study, therefore, strongly indicates that H2 receptor antagonists are unlikely to have direct effects on penile erection.

Acetylcholine↗

Three cases of primary hyperparathyroidism associated with nonmedullary thyroid carcinoma.

Nonmedullary thyroid carcinoma was diagnosed in three of nine cases of primary hyperparathyroidism. In all three cases, diagnosis of primary hyperparathyroidism was made before that of thyroid carcinoma. In the first case, follicular carcinoma was incidentally detected during parathyroidectomy. In the second case, thyroid tumor was discovered during imaging studies for hyperparathyroidism. Papillary carcinoma and ectopic parathyroid was diagnosed postoperatively. In the third case, a thyroid lesion had been mistaken for a putative parathyroid lesion, but the diagnosis of papillary carcinoma was obtained. These cases suggest that preoperative examination for hyperparathyroidism should be carefully evaluated, considering possible concomitant thyroid lesions.

Adenocarcinoma↗

Profound hypotension immediately following insertion of methyl methacrylate during bipolar endoprosthesis in a patient with long-term levodopa-treated paralysis agitans.

Insertion of methyl methacrylate polymer into newly reamed bony cavities has sometimes resulted in profound hypotension, cardiac arrest, or sudden death which are more common in patients with hemodynamic instability or hypovolemia. In paralysis agitans(Parkinson's disease), dramatic worsening of the disease often occurs when another illness or trauma accompanies it. And it is possible that chronic medication with levodopa can cause the loss of ability to support blood pressure. So, it involves some risk to use methyl methacrylate in chronic levodopa-treated paralysis agitans. We present a case of paralysis agitans who demonstrated profound hypotension immediately following insertion of methyl methacrylate polymer in spite of normovolemia and proper anesthetic management.

Aged↗

Modulation of vasoactive intestinal polypeptide (VIP)-mediated relaxation by nitric oxide and prostanoids in the rabbit corpus cavernosum.

The polypeptide VIP has been proposed as an inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter involved in the relaxation of cavernosal smooth muscle during erection. However, the specific mechanism(s) by which VIP exerts its effect is unknown. To determine whether VIP is involved in NANC-mediated cavernosal relaxation, strips of corpus cavernosum from New Zealand White rabbits were hung in tissue baths; atropine and guanethidine were added to block cholinergic and adrenergic neurotransmission, respectively. The tissue was then submaximally precontracted with norepinephrine (NE) and relaxed by electrical field stimulation (EFS; 10 V square waves, 0.5 msec. duration, 10 second trains at 5, 15 and 40 Hz) before and after preincubation with the VIP antagonist, VIP 10-28. To evaluate the role of nitric oxide (NO) and prostaglandins on the relaxant effect of VIP in the corpus cavernosum, the strips were contracted with NE and subsequently relaxed with cumulative doses of VIP (10(-10) to 10(-6) M.). After VIP dose-response curves were obtained, the strips were preincubated with N omega-nitro-L-arginine (NOARG, an inhibitor of nitric oxide synthase, 10(-4) M.) and the VIP dose-response curve was repeated. Indomethacin (10(-5) M.) was added to one-half of the NOARG treated strips to inhibit prostaglandin synthesis. VIP 10-28 inhibited EFS-induced relaxation (p < 0.05) and produced dose-dependent relaxation, which was inhibited by NOARG (p < 0.05). In contrast, the VIP-induced relaxation was more pronounced in the presence of indomethacin (p < 0.05). Moreover, indomethacin substantially reversed the NOARG inhibition of VIP relaxation (p < 0.05). These results suggest that VIP is a mediator of NANC cavernosal relaxation and that NO synthesis is involved in VIP-induced NANC relaxation in the corpus cavernosum. In addition, the presence of vasoconstrictive prostanoids modulates this VIP-mediated NANC relaxation. Therefore, VIP appears to contribute to NANC neurally mediated cavernosal relaxation, and its mechanisms of relaxation are dependent on prostanoid and involve the generation of NO.

Animals↗

Metabolic fate of the new antithrombotic agent aspalatone in rats. In vivo and in vitro study.

In order to determine whether aspalatone ([3-(2-methyl-4-pyronyl)]-2- acetyloxybenzoate, CAS 147249-33-0), a new antiplatelet agent, behaves as a prodrug of acetylsalicylic acid (ASA), metabolism studies in rats were carried out in vivo and in vitro using the whole animal and tissue homogenates. The ASA molecule was not detected in the plasma samples taken after oral administration of aspalatone at 80 mg/kg. Instead, salicylic acid maltol ester (SM), the deacetylated metabolite of aspalatone, was detected in the plasma and it was rapidly hydrolyzed to salicylic acid. In in vitro experiments with rat serum, intestinal fluid, liver and gastric mucosal homogenates, SM was the only compound formed after 4 min incubation at 37 degrees C. From these results it was concluded that aspalatone does not behave as a prodrug of ASA in rats. In addition, the results of experiments using certain esterase inhibitors, suggested the major contribution of B-esterase(s) in the metabolism of aspalatone to SM particularly in serum and intestinal fluid.

Animals↗

Effect of intracellular cAMP on K current in single gastric myocytes of guinea-pig.

In guinea-pig stomach, the effect of increased intracellular cAMP induced by forskolin, 8-Br-cAMP, or isobuthyl-methylxanthine (IBMX) on K current was studied in whole-cell currents. In enzymatically dispersed single cells, agents elevating [cAMP]in showed quite different effects on the IK depending on the recording conditions. Though using the same recording pipette containing 0.1 mM EGTA, agents elevating [cAMP]in reduced IK(Ca) recorded at various membrane potentials, while forskolin increased the spontaneous transient outward currents (STOCs) recorded at fixed holding potential, 0 mV. Such a reduction of K currents was not observed in the cells dialysed with heparin contained in the recording pipette. These results suggested the possibility that the cAMP modulate the internal Ca(2+)-store. To assess the effect of cAMP on the internal Ca2+ store, carbachol or caffeine was used to mobilize intracellular Ca2+ store. Using the carbachol- or caffeine-induced IK(Ca), the effects of forskolin on [Ca2+]in was investigated. Forskolin inhibited the carbachol-induced K current, while the caffeine-induced current was not affected. From the above results, it might be suggested that increased intracellular cAMP might modulate the release of Ca2+ from IP3-sensitive Ca2+ store to- reduce the Ca(2+)-activated K currents.

Animals↗

Lack of effect of carbon monoxide inhibitor on relaxation induced by electrical field stimulation in corpus cavernosum.

Carbon monoxide has been proposed as a possible neurotransmitter because of its ability to bind to the iron atom of the heme of guanylyl cyclase, which is similar to that of nitric oxide. To determine whether carbon monoxide exerts an effect on the penis, strips of rabbit corpus cavernosum were mounted in an organ bath for isometric tension studies and the effect of zinc deuteroporphyrin, an inhibitor of heme oxygenase which metabolizes hemoprotein and releases carbon monoxide, on relaxation induced by electrical field stimulation (neurally mediated) was determined. Also observed was relaxation induced by electrical field stimulation after incubation with atropine and guanethidine to isolate nonadrenergic noncholinergic neurotransmission. Zinc deuteroporphyrin (10(-6) M, 10(-5) M, 10(-4) M and 3 x 10(-4) M) did not affect relaxation induced by electrical field stimulation in the absence or presence of guanethidine and atropine. Therefore, it appears that carbon monoxide does not contribute to neurally mediated relaxation of the rabbit corpus cavernosum.

Animals↗

Tc-99m MIBI uptake in simultaneous thyroid and lung cancers.

The authors present a patient with simultaneous follicular thyroid and small-cell lung cancers, both of which showed Tc-99m MIBI uptake. CT scans showed two masses: one involving the right lower neck including the right supraclavicular area and the right superior mediastinum, and the other involving the peripheral portion of the right upper lobe of the lung. I-131 imaging showed increased uptake in the right neck mass only. Tc-99m MIBI imaging, which was performed for evaluation of chest pain, showed intense uptake in the neck mass (tumor to heart ratios in planar and tomographic images were 0.92 and 0.96, respectively), and less uptake in the lung mass (tumor to heart ratios in planar and tomographic images were 0.53 and 0.40, respectively). Biopsy of the right supraclavicular mass revealed a follicular carcinoma, and a bronchoscopic biopsy of the right upper lobe mass revealed a small cell carcinoma.

Adenocarcinoma, Follicular↗

Experimental evidence for endothelium dependent relaxation and neuronal nitric oxide in corpus cavernosum.

It is known that penile erection is mediated primarily through the release of a nonadrenergic noncholinergic (NANC) neurotransmitter which has been recently identified as nitric oxide (NO). To evaluate whether the endothelium is involved in neurally mediated relaxation in corpus cavernosum, we determined electrical field stimulation (EFS) induced relaxation in both the presence and absence of endothelium, and we tested the effect of an inhibitor of NO synthase, NG-nitro-L-arginine (NOARG), in the absence of endothelium to examine if de-endothelialized tissue can still generate NO. Isolated corpus cavernosal strips from New Zealand White rabbits were used for isometric tension study using organ chambers. The endothelium was removed through denuding tissue. After the tissue was contracted with norepinephrine, EFS was performed at frequencies of 5, 15 and 40 Hz in the presence of guanethidine and atropine to evaluate NANC-selective nerural relaxation. The relaxation induced by EFS was observed after preincubation with NOARG(10(-4) M) for 30 minutes. L-arginine (10(-3) M) was then added for 30 minutes in the presence of NOARG before a second set of EFS studies were performed. Following norepinephrine precontraction, EFS relaxed corporal strips in both the intact and de-endothelialized strips. However, deendothelialization significantly impaired EFS induced relaxation (p < 0.05). NOARG attenuated relaxation induced by EFS and the addition of L-arginine reversed the inhibitory effect of NOARG in the strips with endothelium. In the strips without endothelium, NOARG still inhibited EFS induced relaxation. This relaxation was reversed by the addition of L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synthesis and antiplatelet effects of the new antithrombotic agent aspalatone with low ulcerogenicity.

A new compound, aspalatone (acetylsalicylic acid maltol ester), was synthesized by esterification of acetylsalicylic acid (ASA) and maltol, an antioxidant, and studied for its bleeding time prolongation effect in rats, for its antiplatelet aggregation activity in vitro and ex vivo in rats, and for its antithrombotic activity in vivo using the mouse thromboembolism test. Aspalatone treatment (15 mg/kg p.o.) for 10 days prolonged bleeding time by 57% (p < 0.005) in Sprague-Dawley rats vs control, while ASA treatment (15 mg/kg p.o.) prolonged by 44%. At the low dose of 15 mg/kg p.o. at least 8 days of treatment were necessary for aspalatone and ASA to prolong the bleeding time significantly. On the other hand, salicylic acid maltol ester which lacks the acetyl group did not significantly affect bleeding time at a dose of 15 mg/kg. Aspalatone produced a potent inhibition of collagen-induced platelet aggregation in vitro with IC50 of 1.8 x 10(-4) mol/l, but, similar to ASA, did not significantly inhibit ADP-induced aggregation. The ability of oral aspalatone to inhibit platelet aggregation in rats ex vivo was compared with other reference antiplatelet drugs. Relative potency was ASA > dipyridamole approximately equal to aspalatone > ticlopidine. A single dose of aspalatone potently prevented death due to collagen-induced platelet aggregation in mice in vivo with ED50 value of 32 mg/kg p.o., but failed to prevent death due to ADP-induced platelet aggregation. When given for 10 days, aspalatone prevented collagen-induced death by 90% (p < 0.001) at 20 mg/kg, and this antithrombotic effect lasted after 4 days of wash-out period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Psychogenic versus primary organic impotence.

The origin of impotence in unmarried patients is believed to be mostly psychogenic and has been diagnosed as such. However, we occasionally found that some of these patients showed clinical findings strongly suggesting an organic cause. We investigated the clinical spectrums of 160 unmarried impotent patients (145 psychogenic impotent patients and 15 primary organic impotent patients). The primary organic impotent patients had a history of unsuccessful sustained erections and intercourse without any trauma or definite associated medical disease, and showed abnormal findings in the audiovisual stimulation penogram (AVS-penogram), whereas only 66% (96/145) of the psychogenic group showed abnormal classification. The most common cause of primary organic impotence was vasculogenic. Primary organic impotence should be considered a specific disease for which comprehensive diagnostic methods are needed in unmarried impotent patients to differentiate it from psychogenic impotence.

Adult↗

Insulin increases vascular smooth muscle recovery from intracellular calcium loads.

Insulin has previously been shown to attenuate vasoconstrictor responses to pressor agonists and accelerate vascular smooth muscle relaxation and vascular smooth muscle Ca2+ efflux. To further determine the role of insulin in regulating vascular smooth muscle Ca2+, quiescent A7r5 cultured vascular smooth muscle cells and human vascular smooth muscle cells were incubated with or without 10(-7) or 10(-8) M insulin for 1 hour and then loaded with fura 2-AM; intracellular Ca2+ responses to and rates of recovery from angiotensin II (200 nM) and arginine vasopressin (AVP) (10 microM) were studied fluorometrically in stirred suspension. Insulin (10(-7) M) caused an increase in the peak intracellular Ca2+ response to angiotensin II (peak/baseline x 100 = 469 +/- 96 versus 288 +/- 74, P < .05) and a decrease in the peak Ca2+ response to vasopressin (288 +/- 50 versus 389 +/- 33, P < .025). However, insulin also caused a marked increase in the rate of intracellular Ca2+ recovery to baseline after stimulation with both angiotensin II (77.3 +/- 13.8 versus 30.6 +/- 6 nM/min, P < .03) and vasopressin (P < .05), such that the cumulative exposure to elevated intracellular Ca2+ after stimulation with either agonist (ie, area under the intracellular Ca2+ curve) was reduced with insulin treatment. Insulin (10(-8)) caused small but still significant effects on all parameters in the A7r5 cells. Insulin also caused comparable effects on Ca2+ recovery in the human cells but was without significant effect on peak Ca2+ responses to AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

[A case of angiosarcoma of the scalp with numerous thin-walled cavitary pulmonary lesions].

A 69-year-old man was diagnosed as having angiosarcoma of the scalp. Under local radiotherapy he developed a left pneumothorax, then a right pneumothorax three weeks later, making treatment difficult. Numerous thin-walled cavitary lesions throughout both lung fields were demonstrated on chest CT scans. The bilateral pneumothorax were probably due to the numerous lung metastases. Despite various treatments, he died of respiratory failure one month after the development of pneumothorax.

Aged↗