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排序方式: 共有683条查询结果,搜索用时 15 毫秒
1.
Chakraborty Bhaswat S. Sardessai Manik S. Jaworski Theodore J. Midha Kamal K. Hawes Edward M. 《Pharmaceutical research》1987,4(3):207-213
For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized. 相似文献
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Studies have demonstrated that lipid rafts ultimately regulate the endocytosis of anthrax toxin via clathrin dependent pathway. Interestingly, GPI-anchored protein rich rafts have also been shown to be transported down to the endocytic pathway to reducing late endosomes. Taking advantage of this parallelism, we tried translating the anthrax toxin natural intoxication mechanism by administering a DNA chimera that encoded protective antigen attached to a mammalian GPI-anchor sequence at its C-terminus (pGPI-PA63). We also designed a chimera that had an additional N-terminal TPA leader sequence (pTPA.GPI-PA63) with an aim to target GPI-PA63 to ER where new CD1 molecules are synthesized. Analysis of antibody titers demonstrated successful priming and potential IgG titers after the first boost. In vitro cell proliferation studies in the presence of GPI-attached PA63 peptides revealed that there was a clonal expansion of CD4+ NK1.1+ helper T cell population which rapidly produced IL-4 in response to T cell receptor ligation. These cells provided direct B cell help that aided IgG formation. Effector responses generated by NKT cells were found to be MHC II-independent and CD1d-restricted. In addition, the group pTPA.GPI-PA63 also displayed low magnitude MHC-II restricted (CD1d-independent) NKT cell and CD4+ T cell helper responses in response to non-GPI attached PA63 peptides which overall resulted in the heightened responses seen for this group. Importantly, DNA vaccination mediated the generation of high avidity neutralizing antibodies that mediated protection against lethal toxin challenge. 相似文献
4.
Ajit Sood Vandana Midha Neena Sood Manu Bansal 《Indian journal of gastroenterology》2006,25(6):283-285
BACKGROUND: The treatment of hepatitis C virus (HCV)-related cirrhosis is difficult due to high frequency of adverse effects. We retrospectively reviewed the case records of patients with HCV cirrhosis to evaluate the efficacy and tolerability of pegylated (peg) interferon and ribavirin treatment in these patients. METHODS: Medical records of 28 patients with HCV-related compensated cirrhosis were reviewed. The treatment protocol was a combination therapy of peg interferon alfa-2b (1 microg/Kg/week) plus oral ribavirin (10-12 mg/Kg/day). Primary endpoint was sustained virological response, with additional endpoints of drug tolerance, clinical or biochemical worsening and death. RESULTS: End-of-treatment virlogic response was seen in 24 of 28 patients (85%) and sustained virologic response in 15 of 28 (53%) patients. Biochemical end-of-treatment response and sustained response were seen in 20 and 16 patients (71% and 57%), respectively. Treatment had to be stopped in 3 patients due to decompensation of liver status in two and drug intolerance in one, while dose modification was required in two patients. CONCLUSIONS: Combination therapy with peg interferon plus ribavirin seems effective in patients with liver cirrhosis. High relapse rate, poor biochemical recovery and possibility of decompensation are issues that need to be kept in mind. 相似文献
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K K Midha E M Hawes J W Hubbard E D Korchinski G McKay 《Journal of clinical psychopharmacology》1989,9(1):4-8
Interpatient variation in response to therapy with antipsychotic drugs is a major problem. This study was designed to assess the extent of variation in disease-free subjects in whom known sources of variance were controlled as much as possible. The subjects were 32 healthy, nonsmoking males of European origin, aged 18-25 years, and weighing no more than +/- 15% from the ideal weight for height. After an overnight fast, each subject ingested 50 mg of chlorpromazine. Plasma samples were harvested over a 24-hour period during which the subjects were on a standardized, caffeine-free diet. Plasma levels of chlorpromazine were measured by gas-liquid chromatography-mass spectrometry. The results showed wide intersubject variation in all pharmacokinetic parameters including maximum concentration, area under the curve, and oral clearance. Furthermore, none of the data were normally distributed. For each pharmacokinetic parameter, the distribution was leptokurtotic and skewed. As a consequence, the geometric means provided better estimates of central tendency than the arithmetic means. It seems that a major proportion of intersubject variation is an inherent problem that cannot be accounted for by differences in race, diet, smoking habits, or concomitant drug ingestion. 相似文献
10.
This paper describes the tragic case of a young woman who died of cancer of
the colon after successfully donating eggs to her younger sister. Although
there is no direct link between her operation and the subsequent
development of bowel carcinoma, this case imparts a feeling of unease when
seen in conjunction with other cases reported during the last few years. It
is a reminder that little is known of the long-term consequences of some
aspects of assisted conception. Women undergoing ovarian stimulation for
themselves or a matched recipient have the right to be advised, in an
agreed format, that there is some concern about unproven potential risks
from the stimulatory drugs. The safety of egg donors must assume priority
over all other considerations, including lack of donors or any moral
position. The recent decision by the Human Fertilisation and Embryology
Authority (HFEA) to withdraw any form of payment or recompense to egg
donors does not seem to us to be based on a balance of scientific advances,
patient needs and the ethics of gamete supply. They state that the
intention to withdraw payments was implicit in the 1990 Human Fertilisation
and Embryology (HFE) Act. However the Act was based on the Warnock report
made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility
drugs had not yet caused any unease. The Act provided the HFEA with
discretionary powers to issue directions so that the future policies would
be consistent with any emerging new medical evidence. It is imperative that
the HFEA provide convincing evidence on how the current policy of payment
to donors harms society, donors or recipients, and how in the UK the new
policy will improve medical practice in assisted conception. Successful
pilot studies must precede the implementation of any new policy. Failure to
do this could cause irreversible harm to the practice of assisted
conception using donor gametes, which will ultimately be against the basic
aims of the 1990 HFE Act.
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