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Biomedical subjects

T C Chou

Publications and source records attributed to T C Chou.

243 records · Page 14Linked to original sources

Combined antiviral effects of paired nucleosides against guinea pig cytomegalovirus replication in vitro.

Several promising antiviral nucleosides have been tested in paired combinations against guinea pig cytomegalovirus (GPCMV) replication in guinea pig embryo (GPE) cells by plaque reduction assay; these are [9-(2-hydroxy-1-3-2-dioxaphosphorinan-5-yl)oxymethyl]-guanin e P-oxide (2'nor-cGMP, compound 164), [4-amino-5-bromo-7-(2-hydroxyethoxymethyl)-pyrrolo(2,3-d)pyrimidine] (compound 102), (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), 9-(2-hydroxyethoxymethyl)-guanine (acyclovir, ACV) and 3'-azido-3'-deoxythymidine (zidovudine, AZT). Various degrees of interactions were observed; i.e. synergistic reactions were noted in the presence of compound 164/compound 102 and compound 164/DHPG combinations at all concentrations tested. HPMPC/DHPG combinations were synergistic at relatively lower concentrations of DHPG, but became antagonistic as the concentration of DHPG increased. Combinations of compound 164/ACV and DHPG/AZT were antagonistic.

Animals↗

Earthworm muscle preparation for studying several potent compounds--the possible existence of a "Soman receptor.".

A new model of earthworm (Eisenia foedida) dorsal muscle preparation was studied. It is a specific preparation for testing GABA and its agonist muscimol. The response of muscle could be recorded through mechanical functional changes instead of potential variations. Thus, it is a direct and simple means for measuring GABA activity. ChE-deactivated preparation was suggested for this purpose. By mild membrane modifications of earthworm muscle preparation, it was possible to remove or inactivate GABA, glutamic acid or Soman combining protein. In conjunction with superfusion of Ach-receptor antagonist (alpha-Bungaratoxin) or GABA antagonist (picrotoxin, isopropylbicyclophosphate), we could differentiate Soman receptor from Ach and GABA receptor. The possible existence of a Soman receptor in the earthworm muscle was therefore proposed.

Animals↗

Evaluation of high density DRAMs as a nuclear radiation detector.

The research is based on the nuclear radiation induced soft error phenomenon associated with dynamic random access memory devices (DRAMs). Samples of 256 kbit and 1 Mbit decapped DRAMs from several manufactures were exposed to standard alpha sources and showed a linear response with an intrinsic detection efficiency approaching 10%. Sensitivity studies were performed to evaluate the effects of DRAM operating voltage, refresh frequency and the data pattern stored prior to irradiation. The associated mechanism of soft error phenomenon is discussed. Samples were also exposed to gamma rays up to 10(5) rad to examine the total dose effect. The annealing phenomenon after gamma exposure is also presented.

Alpha Particles↗

Emergency endoscopic nasobiliary drainage for acute calculous suppurative cholangitis and its potential use in chemical dissolution.

Acute suppurative cholangitis is one of the common causes of acute abdomen in Taiwan. Emergency decompression is a life-saving procedure if patients fail to respond to antibiotic treatment. From July 1988 to June 1991, 224 patients were encountered with concomitant bile duct stones and cholangitis; 40 were brought to the emergency service with shock or mental confusion or responded poorly to antibiotic treatment. The patients consisted of 20 males and 20 females aged 21-81 years (mean age 64 years); 55% had intrahepatic duct stones, 50% had positive blood culture, 38% had undergone previous biliary surgery, 25% had concomitant medical illnesses and 20% presented with mental confusion. Emergent endoscopic nasobiliary drainage (ENBD) was performed within 48 h of each patient's arrival in the emergency room. In 3 days all the patients exhibited significant improvement as defined by body temperature, vital signs, white blood cell count, serum bilirubin and alkaline phosphates levels. When their condition had stabilized, 21 patients underwent elective surgery. Six patients received ethylenediaminetetraacetic acid infusion through an ENBD tube. Two of the patients' stones dissolved completely. Six patients received papillotomy with stone removal. The remaining patients refused further treatment. There was no hospital mortality. It is therefore concluded that ENBD offers an effective treatment for acute calculus suppurative cholangitis and it is a potential route of administration for the chemical dissolution of bile duct stones.

Abdomen, Acute↗

Chemical dissolution of gallstones in Taiwan: an in vitro study.

To evaluate the potential for the chemical dissolution of gallstones, 480 stones from 214 patients were studied. The stones were obtained via surgery or endoscopically. They were classified into cholesterol-rich mixed stones, brown pigment stones and black stones. The composition of bilirubin and cholesterol was determined by Fourier transformed infrared spectroscopy. Two per cent tetrasodium ethylenediamine acetate (EDTA), dimethylsulfoxide (DMSO) or methyl-tert-butyl-ethylene (MTBE) were used to dissolve the stones. To enhance solubility, surfactant polysorbate-20 was used to mix two of the individual three solvents. Methyl-tert-butyl-ethylene was found to have the best dissolution ability (by dry weight) 94, 13.4 and 20% for mixed, brown and black stones, respectively. Dimethylsulfoxide resulted in 13, 14 and 25% dissolution and EDTA 9.5, 13 and 16.5%. In contrast, pure water dissolved 4, 6 and 10.4% of the stones, respectively. A combination of the dissolution agents did not enhance the dissolution rate. In fact, the combination of solvents unexpectedly reduced the solubility of the stones: EDTA/MTBE was 17.5, 6.7 and 16.0%; DMSO/MTBE 43.2, 21.9 and 18.0%; DMSO/EDTA 9.1, 7.0 and 9.6%. In conclusion, cholesterol-rich mixed stones were able to be dissolved using MTBE but results of contact dissolution for gallstones are still far from satisfactory.

Cholelithiasis↗

Enhanced dissolution of gallstone by combining ethanol with two commonly used cholelitholytic solvents.

BACKGROUND/AIMS: Contact dissolution therapy is one of the non-surgical treatments for patients with gallstone. Among the various solvents, methyl tert-butyl ether (MTBE) is used for cholesterol gallstone, while tetrasodium ethyl-dimethyl tetraacetate (EDTA-4Na) solution is used to dissolve calcium bilirubinate stones. However, the contents of gallstone cannot be precisely predicted while they are still present in the human body. This study was designed to test if the MTBE and EDTA can be mixed together and to test the solubility of different kinds of gallstone in each original solution and mixture. METHODOLOGY: Each 0.1 gm of mixed cholesterol stone, brown stone and pigment stone from 18 patients was used. Pure ethanol was chosen to enhance the miscibility between the organic phase of MTBE and the aqueous phase of EDTA. The contents of gallstone after dissolution were examined with scanning electromicroscopy. RESULTS: We found the mixture of ethanol, MTBE and EDTA to be the most efficient solvent in gallstone dissolution in comparison with the other two original solvents. The mixture reached a dissolution percentage of 97.96 +/- 1.00, 88.96 +/- 6.51 and 67.75 +/- 14.26 for cholesterol, brown and black pigment gallstone, respectively. CONCLUSIONS: We concluded that ethanol can be used to mix the MTBE and EDTA with good preservation in their litholytic effects on gallstone. The ethanol-MTBE-EDTA solvent is, therefore, a promising universal cholelitholytic agent which deserves further tests for its safety and efficacy in the in vivo study.

Cholagogues and Choleretics↗

Rational approach to the clinical protocol design for drug combinations: a review.

Based on the median-effect equation of Chou and the combination index (CI) equation of Chou-Talalay, a computer software for automated dose-effect analysis has been developed. This method provides quantitation of synergism (CI < 1) and antagonism (CI > 1) at different dose and effect levels. Therefore, it allows the selection of the best pair (or triplet) of combination, optimal combination ratio, and the best schedule of treatment. These analyses has been shown to be useful for the clinical protocol design. (Chang et al. Cancer Res. 45: 2434-2439, 1985). The user-friendly computer program also gives dose-reduction index (DRI) which determines how many fold of dose-reduction is allowed for each drug in synergistic combinations. Dose reduction leads to reduced toxicity while maintaining the desired efficacy (Chou et al. Encyclopedia of Human Biology 2:675-683, 1997; Encyclopedia of Cancer 1:368-379, 1997). The Chou-Talalay method distincts from all other methods by the fact that it not only takes into account the "potency" but also the "shape" of dose-effect curves of each drug and their combinations (Chou & Hayball, CalcuSyn for Windows, Biosoft, Cambridge UK, 1996). This method has been applied in combination of anticancer agents, anti-HIV agents, purging leukemic cells for autologous bone marrow transplantation (Chang et al. Cancer Res. 47:119-122, 1987) and combination of immunosuppressants for organs transplants. Specific examples of the theoretical equations, the median-effect plot, the CI plot, the isobologram, and the polygonogram are illustrated.

Antineoplastic Combined Chemotherapy Protocols↗

Potent neutralization of primary human immunodeficiency virus clade C isolates with a synergistic combination of human monoclonal antibodies raised against clade B.

OBJECTIVES: We investigated the ability of several human neutralizing monoclonal antibodies (mAbs), originally raised against human immunodeficiency virus (HIV) clade B isolates, to neutralize primary clade C isolates as single agents and in combination. STUDY DESIGN/METHODS: HIV clade C isolates from five different countries were tested for susceptibility to neutralization by anti-clade B mAbs in human peripheral blood mononuclear cells. Monoclonal antibody combinations were evaluated for possible synergy. RESULTS: All 20 primary HIV clade C isolates could be neutralized 97.5% to 100% by a quadruple combination of mAbs IgG1b12, 2G12, 2F5, and 4E10. These mAbs recognized conserved epitopes and were highly synergistic, resulting in strong cross-clade neutralization. CONCLUSIONS: In our previous experiment, a synergistic combination of human neutralizing mAbs protected all macaque neonates against oral challenge with a simian-human immunodeficiency virus encoding HIV env. Together, our data suggest that passive immunization with currently available anti-clade B mAbs could play a role in preventing HIV clade C transmission through breastfeeding.

Antibodies, Monoclonal↗