Biomedical subjects

S M Chung

Publications and source records attributed to S M Chung.

At least 37 records · Page 2Linked to original sources

PubMed1999

Menadione-induced vascular endothelial dysfunction and its possible significance.

Although several studies have shown that treatment with menadione leads to endothelial cell cytotoxicity, investigations of menadione's effects on blood vessels are limited. Our previous studies have shown that menadione can indirectly induce alterations in vasomotor tone through platelet cytotoxicity. To determine if menadione affects vascular function, we investigated the effect of menadione on blood vessels using the isolated rat aortic rings in vitro organ bath system. Treatment with menadione directly resulted in contraction of aortic rings with endothelium but did not cause any effect on aortic rings without endothelium. Menadione irreversibly inhibited the acetylcholine- and histamine-induced relaxation of aortic rings with endothelium in a time- and concentration-dependent manner. Menadione treatment potentiated phenylephrine- and serotonin-induced vasoconstriction in aortic rings with endothelium. These in vitro results were observed at concentrations of menadione that are highly relevant to human therapeutics with menadione. When menadione was administrated intravenously to rats, blood pressure increased significantly in a concentration-dependent manner. Furthermore, menadione infusion suppressed the blood pressure reduction induced by acetylcholine. By demonstrating that menadione caused in vitro endothelial dysfunction (i.e., decreased relaxation and increased vasoconstriction in the organ bath experiments) and confirming that these results were consistent with in vivo observations, we have provided evidence suggesting that a quinone such as menadione can alter vasomotor tone through endothelial dysfunction. Such dysfunction could possibly contribute to vascular diseases.

Acetylcholine↗

PubMed1999

Determination of betulinic acid in mouse blood, tumor and tissue homogenates by liquid chromatography-electrospray mass spectrometry.

A rapid and sensitive high-performance liquid chromatography-electrospray MS method has been developed to determine tissue distribution of betulinic acid in mice. The method involved deproteinization of these samples with 2.5 volumes (v/w) of acetonitrile-ethanol (1:1) and then 5 microl aliquots of the supernatant were injected onto a C18 reversed-phase column coupled with an electrospray MS system. The mobile phase employed isocratic elution with 80% acetonitrile for 10 min; the flow-rate was 0.7 ml/min. The column effluent was analyzed by selected ion monitoring for the negative pseudo-molecular ion of betulinic acid [M-H]- at m/z 455. The limit of detection for betulinic acid in biological samples by this method was approximately 1.4 pg and the coefficients of variation of the assay (intra- and inter-day) were generally low (below 9.1%). When athymic mice bearing human melanoma were treated with betulinic acid (500 mg/kg, i.p.), distribution was as follows: tumor, 452.2 +/- 261.2 microg/g; liver, 233.9 +/- 80.3 microg/g; lung, 74.8 +/- 63.7 microg/g; kidney, 95.8 +/- 122.8 microg/g; blood, 1.8 +/- 0.5 microg/ml. No interference was noted due to endogenous substances. These methods of analysis should be of value in future studies related to the development and characterization of betulinic acid.

Animals↗

PubMed1999

Advantages of calcium green-1 over other fluorescent dyes in measuring cytosolic calcium in platelets.

Fluorescent indicators are widely used in the measurements of cytosolic calcium in many cell types for many purposes because they are relatively easy to use. Notwithstanding, they have some defects to prevent accurate measurements under certain conditions, such as significant dye leakage and UV-quenching effect. Menadione, a representative quinone derivative with antiaggregating effect, is also UV-absorbent. To investigate whether menadione can affect the change of cytosolic calcium in platelets by agonist, we measured the change of cytosolic calcium level using calcium green-1. Since this dye has not been used previously in platelets, we determined that the optimal loading of calcium green-1 to platelets was achieved using 3 microM dye incubated for 60 min at 37 degrees C. Our study compared the use of calcium green-1 with fura-2 and fluo-3 (two widely used dyes) in measurements of cytosolic calcium. Fura-2 is UV-excited, so when menadione was treated in fura-2-loaded cells, it had a quenching effect. Fluo-3, the other visible fluorescent indicator, leaked from platelets very rapidly and required the use of anion channel blockers which are known to affect physiological response of platelets. Our study demonstrated that changes in cytosolic calcium levels can be accurately measured without these problems by using calcium green-1. We therefore were able to demonstrate that menadione inhibited calcium increase by thrombin in a dose-dependent manner similar to menadione's antiaggregating effect in platelets.

Aniline Compounds↗

PubMed1999

Replication-competent, nonneuroinvasive genetically engineered herpes virus is highly effective in the treatment of therapy-resistant experimental human tumors.

A genetically engineered, nonneurotropic herpes simplex virus (R7020) with a proven safety profile in both animals and humans was found effective in the treatment of large xenotransplanted tumors arising from a radiation- and chemotherapy-resistant human epidermoid carcinoma and a hormone-refractory prostate adenocarcinoma. R7020 replicated to high titer and caused rapid regression of the human tumor xenografts. Tumor destruction was accelerated in animals given both R7020 and fractionated ionizing radiation. Tumors arising from cells surviving one treatment with R7020 were fully susceptible to a second dose of virus. We conclude R7020 is an effective antitumor agent for non-central nervous system tumor xenografts with an excellent safety profile.

Adenocarcinoma↗

PubMed1999

The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma.

To test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity.

Animals↗

PubMed1999

Ethanol co-exposure increases lethality of allyl alcohol in male Sprague-Dawley rats.

Since allyl alcohol and ethanol are both metabolized by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), ethanol could affect allyl-alcohol induced toxicity under in vivo coexposure conditions. Male Sprague-Dawley rats were treated with ethanol (2 g/kg, i.p.) simultaneously or 2 h before with allyl alcohol (40 mg/kg, i.p.). Coexposure to allyl alcohol and ethanol resulted in neither enhancement nor protection in allyl alcohol-induced hepatotoxicity at 24 h. However, markedly increased lethality was observed under our coexposure conditions. Pretreatment with 4-methylpyrazole (4-MP) to inhibit ADH did not result in increased lethality to allyl alcohol or ethanol alone, but significantly reduced the lethality of the combined treatment. In contrast, ALDH inhibition increased the lethality of allyl alcohol alone as well as that of the combined allyl alcohol and ethanol treatment. Kinetic studies revealed that combined treatment with allyl alcohol and ethanol resulted in higher blood allyl alcohol levels compared to allyl alcohol alone, and these were accompanied by greater lethality. ADH inhibition increased allyl alcohol blood levels significantly when rats were treated with allyl alcohol alone or allyl alcohol plus ethanol, leading to protection against lethality. In contrast, ALDH inhibition did not affect blood allyl alcohol levels, but resulted in increased lethality. These data suggest a possible role for a metabolite of allyl alcohol, acrolein, in the increased lethality of allyl alcohol and ethanol coexposure in rats.

Alcohol Dehydrogenase↗

PubMed1999

Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus.

Malignant gliomas remain incurable with current interventions. Encouraging investigational approaches include the use of genetically modified herpes simplex-1 (HSV-1) viruses as direct cytotoxic agents. Combining attenuated HSV-1 with standard therapy, human U-87 malignant glioma xenografts grown in the hind limb or intracranially in athymic nude mice were exposed to ionizing radiation, inoculated with genetically modified HSV R3616, or received both virus and radiation. The combination of virus with fractionated ionizing radiation suggests a synergistic action and results in reduced tumor volumes and longer survivals when compared with treatment with either modality alone.

Animals↗

PubMed1999

Neuro-ophthalmic manifestations of pituitary tumors.

Pituitary tumors manifest with a variety of unique localizing signs and symptoms that neurosurgeons and neuro-ophthalmologists must readily identify. Visual disturbances may be the presenting complaint. Loss of central visual acuity, visual field deficits, and mechanisms of diplopia are discussed with case examples used to highlight each.

Adult↗

PubMed1998

Clinical results of 24 pituitary macroadenomas with linac-based stereotactic radiosurgery.

PURPOSE: To determine the impact of stereotactic radiosurgery (SRS) on the clinical course, hormonal status, and follow-up CT/MRI scan of pituitary macroadenomas. METHODS AND MATERIALS: From July 1988 to March 1996, 24 pituitary macroadenomas had been treated using 6 MV linear accelerator based SRS. They consisted of 11 (45.8%) prolactinomas, 2 (8.3%) growth hormone (GH)-secreting tumors, 1 (4.2%) Cushing's disease, 8 (33.3%) nonsecreting (nonfunctioning: NF) tumors, and 2 (8.3%) mixed prolactin-growth hormone (PRL-GH)-secreting tumors (M:F = 12:12; aged 21-61 years). Postoperative irradiation was performed in all cases except for the instance of Cushing's disease. The prescribed dose to tumor center varied from 10 to 27 Gy (mean 21.1 Gy) using a collimator size of 0.5 to 2.5 cm. The follow-up duration ranged from 13 to 89 months (mean 49.2 months). Results from these patients were compared to our results using conventional radiation. RESULTS: Visual acuity and field defect were improved or became normal in 19 (79.2%) cases. Four (16.7%) remained unchanged after the treatment. One (4.1%) progressed 6 years after SRS and subsequently had repeat surgery with conventional boost irradiation. Of the 13 (46.4%) prolactinomas, including two mixed PRL-GH secreting tumors, 11 (84.1%) revealed normal hormonal levels within 1 year after SRS. In contrast, it took 2 years to become normal after conventional radiation therapy. In four GH-secreting tumors including two mixed PRL-GH secreting tumors, SRS and conventional methods showed similar responses. On follow-up imagings of the 21 patients, the mass was completely resolved in 4 (16.7%), including 3 PRLs and one NF, decreased in 11 (45.8%), and unchanged in 5 (16.7%) with central necrosis or cysts. One (4.2%) progressed and was reoperated 6 years after treatment. The complications related to SRS were comparable to those from conventional method. CONCLUSION: Radiosurgery can be used effectively in patients with pituitary adenoma. In this study, a more rapid hormonal and clinical response was achieved with radiosurgery than with conventional pituitary irradiation treatment.

Adenoma↗

PubMed1998

Chemically induced platelet lysis causes vasoconstriction by release of serotonin.

Our previous studies have shown that menadione is cytotoxic to platelets, leading to substantial release of vasoactive substances. To test whether platelet lysis induced by menadione could cause vasoconstriction, we investigated the effect of platelet lysate induced by menadione on rat aorta in organ bath system. We showed that menadione-induced platelet lysate caused vasoconstriction in a dose- and time-dependent manner. These effects were seen in aortic rings both with and without endothelium, but it was much greater in rings without intact endothelium. The time course of vasoconstriction was well correlated with the time courses of platelet lysis (assessed by lactate dehydrogenase release) as well as serotonin release. The vasoconstriction by platelet lysate was blocked by serotonin antagonists, ketanserin, and LY53,857, but not by thromboxane A2 (TXA2) receptor antagonist, SQ29,548, suggesting that vasoconstriction mainly occurred secondary to the release of serotonin in our in vitro system. However, potentiation of vasoconstriction by combined treatment of serotonin and a stable TXA2 mimic, U46619, suggests the possibility of the increased risk for vasoconstriction in vivo. In addition, the serotonin-induced vasoconstriction was potentiated by residual menadione present in the organ bath. These results suggest that chemically induced platelet cytotoxicity can provoke alteration in vasomotor tone by release of serotonin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

Correlation of plasma clearance of 54 extensively metabolized drugs between humans and rats: mean allometric coefficient of 0.66.

PURPOSE: To evaluate the distribution of allometric exponents for relationship of total plasma clearance of 54 extensively metabolized drugs, with wide-ranging linear clearance values, between humans and rats, to provide a rationale for the observed data, and to discuss potential significance of the findings. METHODS: Human and rat plasma clearance values of 54 drugs with markedly different physicochemical properties were obtained from the literature. Standard allometric analysis was performed for each drug using both rat and human data. Unbound vs. total plasma clearances were obtained for 15 out of 54 drugs and their correlations between humans and rats were compared. RESULTS: The mean+/-SD of the allometric exponent for the 54 drugs studied is 0.660+/-0.190. The median clearance ratio based on unit body weight is 7.41 and the median exponent is 0.645. Excluding two outliers the correlation coefficient of plasma clearance between humans and rats was 0.745 (p < 0.0001). For the 15 drugs, use of unbound plasma clearance approach seems to significantly improve the correlation coefficient compared to total plasma clearance (0.940 vs. 0.841). CONCLUSIONS: The present study indicates that on average, humans and rats may eliminate extensively metabolized drugs at a rate similar to that expected from the allometric or body surface area relationship of basal metabolic rate between the two species. A simple statistical distribution hypothesis is used to rationalize the species difference in plasma drug clearance. Rat may serve as an useful animal model to predict (unbound) plasma clearance of drugs in humans.

Animals↗

PubMed1998

Treatment of total hyphema with relatively low-dose tissue plasminogen activator.

The purpose of this study is to investigate the efficacy of tissue plasminogen activator (tPA) in the treatment of total hyphema following ocular trauma or intraocular surgery. Three patients (3 eyes) representing unresolved total hyphema for more than 5 days and uncontrolled high intraocular pressure received intracameral injections of 10 microgram of recombinant tPA. Intracameral tPA injection resulted in complete resolution of hyphema in all 3 eyes. Resolution occurred mostly within 24 to 48 hours after injection. Possible side effects of tPA injection, such as increased intraocular pressure and corneal edema, were not observed. However, 1 eye had vitreous hemorrhage after repeated injections of tPA. Intracameral injection of tPA seems to be a safe and effective method for the treatment of unresolved total hyphema. However, repeated intracameral tPA injections may cause unwanted complications such as vitreous hemorrhage.

Adult↗

PubMed1997

Ocular neuromyotonia in Graves dysthyroid orbitopathy.

OBJECTIVES: To describe 2 patients with ocular neuromyotonia in association with Graves orbitopathy and to consider the possible underlying mechanisms. DESIGN: Description of the clinical findings in 2 patients with these conditions. SETTING: Neuro-ophthalmology referral centers. PATIENTS: Two patients, aged 55 and 52 years, had episodic, involuntary periods of vertical diplopia and dysthyroid orbitopathy. INTERVENTION: Treatment with carbamazepine in one patient and external beam radiation therapy in the second patient. MAIN OUTCOME MEASURES: Frequency and duration of episodic spasms of the extraocular muscles. RESULTS: Although radiation therapy is the most common association with ocular neuromyotonia, it cannot explain the involuntary contractions of extraocular muscles in all affected patients. Other mechanisms must be involved, such as those discussed in this article. CONCLUSION: Ocular neuromyotonia is described in 2 patients with dysthyroid orbitopathy, confirming previous findings. Possible mechanisms are given.

Analgesics, Non-Narcotic↗

PubMed1997

Evidence of optic pathway gliomas after previously negative neuroimaging.

PURPOSE: The authors emphasize the potential for the development of anterior visual pathway gliomas, evidenced by computed tomography (CT) or magnetic resonance imaging (MRI) scans, in neurofibromatosis type 1 (NF1) patients who previously had normal neuroimaging studies. METHODS: The clinic charts and CT and MRI scans were retrospectively reviewed for all patients evaluated at the neurofibromatosis clinic of one referral center over a period of 7 years. Patients with neuroimaging studies demonstrating anterior visual pathway gliomas who previously had normal scans were identified, and their cases are described in detail. A similar, previously reported series, from the pediatric literature, was also reviewed. RESULTS: Eight percent (28/360) of patients had CT or MRI scans revealing optic gliomas. Two of these patients had normal neuroimaging studies previously. CONCLUSION: A negative neuroimaging study in an NF1 patient does not exclude the future development of an optic glioma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Similarity or discrepancy in pharmacokinetic parameter estimation between bolus and infusion studies.

A recent study by Heatherington and Rowland showing discrepancies in steady-state volume of distribution (Vss) estimation of two barbiturates between bolus and infusion studies in rat hindlimb preparations was reviewed. Their rationale is that increasing the duration of administration may increase the accessibility for tissue distribution and thus increase Vss for compounds showing slow tissue uptake. Such a dosing-duration-dependent distribution concept is, however, inconsistent with the principle in linear kinetics that the fate or disposition function of any drug molecules is independent of time of administration and presence of other molecules. When their well-designed bolus studies were reanalyzed by including extrapolated outflow data from the last sampling time to infinity, the Vss values for the two barbiturates were found to be very similar to those obtained by the infusion method. Our analysis seems to validate a theoretical concept that parameter estimation is independent of the duration of administration in linear kinetics. A potential complication of using the bolus method to study Vss is presented.

Animals↗

PubMed1996

Visual outcome in bilateral nonarteritic anterior ischemic optic neuropathy.

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) is a common cause of visual loss in the older population. Bilateral NAION is a well-documented entity; however, no study to date has compared the visual outcome between affected eyes. METHODS: The authors retrospectively reviewed the charts of 99 patients with diagnoses of NAION over 3 1/2 years. In the 23 patients with bilateral involvement, 16 were included in the study for analysis of final visual outcome between affected eyes. Snellen acuity, Ishihara color plates, and Humphrey automated perimetry were evaluated as the parameters of visual function. Descriptive analysis of the outcome between affected eyes for each parameter is presented as a frequency distribution of pre-defined groups. Statistical significance is established using nonparametric tests. RESULTS: Bilateral NAION was found in 23% (23/99) of the patients studied. The authors identified a high percent agreement between eyes with regard to visual acuity (81% within 3 Snellen lines), color vision (69% within 3 plates), and Humphrey visual field (75% within 5 decibels of mean deviation). Additionally, there was a statistically significant correlation between affected eyes for all three visual parameters: visual acuity (P = 0.043), color vision (P = 0.001), and Humphrey visual field (P = 0.039). CONCLUSION: The authors found a high percent agreement and statistically significant correlation in final outcome between affected eyes of patients with bilateral NAION for visual acuity, color vision, and visual field loss. With a larger series, it may be possible to predict the visual outcome of the second affected eye based on the parameters of the first eye.

Adult↗

PubMed1996

Acute effect of qigong training on stress hormonal levels in man.

We observed the acute effects of Qigong training on the levels of human endogenous opioid peptides, such as beta-endorphin, and other stress hormones [adrenocorticotrophic hormone (ACTH), cortisol, and dehydroepiandrosterone-sulfate (DHEA-S)] in a group of ChunDoSunBup Qigong trainees. At pre (-10 min), mid (40 min) and post (70 min) time of training, blood was taken for the determination of plasma level of hormones. The level of beta-endorphin was significantly increased during the mid-time of training while the level of ACTH declined at the mid- and post-time of training. Cortisol and DHEA-S were not significantly changed during training. This result suggests that Qigong training, as a stress coping method, affects and plays a role in hormonal regulation related to the maintenance of homeostasis in man.

Adrenocorticotropic Hormone↗

PubMed1996

Application of PCR from the fine needle aspirates for the diagnosis of cervical tuberculous lymphadenitis.

Tuberculosis remains a major public health problem worldwide. A definitive and accurate diagnosis of tuberculosis in cervical lymphadenopathy is important because satisfactory results can be achieved with chemotherapy alone, obviating surgery. Recently, fine needle aspiration cytology (FNAC) has provided an alternative and easy procedure for collection of material for cytomorphologic and bacteriologic examination. But the detection rate for M. tuberculosis from the aspirate material is still low with Ziehl-Neelson stain and even with culture. The authors therefore performed polymerase chain reaction (PCR) for mycobacterial DNA sequences in 31 cases of cytodiagnosis of tuberculous lymphadenitis and compared conventional bacteriologic methods. Ziehl-Neelson staining for acid-fast bacilli (AFB) was positive in 3 cases (10%) in direct smears, and the cultures for M. tuberculosis were positive in 6 cases (19%). In 19 (61%) among 31 samples, mycobacterial DNA fragments were detected, using the PCR method. With combined conventional and PCR method, the rate of detection was increased to 68 percent high. In conclusion, PCR is the most sensitive technique in the demonstration of M. tuberculosis in patient with clinically suspected as tuberculosis, who have AFB stain or culture negative cytology. Combined conventional and PCR methods as well as cytologic findings are of further help in the detection and characterization of M. tuberculosis.

Biopsy, Needle↗