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101.
Mohd. Rais Mustafa Rohaini Mohamad Laily Din Shamsuddin Wahid 《Phytotherapy research : PTR》1995,9(8):555-558
Muscle relaxant activities of six compounds isolated from Malaysian medicinal plants were investigated on the smooth muscles of the rat aorta and longitudinal muscle of the guinea-pig ileum. Except for goniothalamin, the other five compounds exhibited varying degrees of muscle relaxant activities on the two smooth muscles. Dicentrine, isocorydine, altholactone and usnic acid reduced the contractions to KCI and phenylephrine in the rat aorta, whilst atranorin slightly reduced the contractions to phenylephrine but not KCI. In addition, dicentrine and isocorydine markedly reduced the contractile response to phenylephrine in Ca2+-free Krebs solution. In the longitudinal muscle of the guinea-pig ileum, altholactone, atranorin, dicentrine and isocorydine inhibited to a greater extent the phasic than the tonic responses to KCI. All four compounds similarly inhibited the contractions induced by ACh. The results suggest that the relaxant activities of the compounds are attributed mainly to inhibition of Ca2+ influx via the calcium channels in the membrane of the smooth muscles. Furthermore, the greater sensitivity of dicentrine, isocorydine and altholactone against phenylephrine-induced contractions or KCI-induced phasic contractions are due to their abilities to inhibit intracellular Ca2+ release in these muscles. 相似文献
102.
E. W. Eijdems G. J. Zaman M. de Haas C. H. Versantvoort M. J. Flens R. J. Scheper E. Kamst P. Borst F. Baas 《British journal of cancer》1995,72(2):298-306
We have analysed the contribution of several parameters, e.g. drug accumulation, MDR1 P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and topoisomerase (topo) II, to drug resistance in a large set of drug-resistant variants of the human non-small-cell lung cancer cell line SW-1573 derived by selection with low concentrations of doxorubicin or vincristine. Selection with either drug nearly always resulted in MDR clones. The resistance of these clones could be explained by reduced drug accumulation and was associated with a decrease rather than an increase in the low MDR1 mRNA level. To test whether a decrease in MDR1 mRNA indirectly affected resistance in these cells, we introduced a MDR1-specific hammerhead ribozyme into wild-type SW-1573 cells. Although this led to a substantial reduction in MDR1 mRNA, it did not result in resistance. In all resistant clones we found an altered form of the multidrug resistance-associated protein (MRP), migrating slightly slower during SDS-polyacrylamide gel electrophoresis than MRP in parental cells. This altered MRP was also present in non-P-gp MDR somatic cell hybrids of the SW-1573 cells, demonstrating a clear linkage with the MDR phenotype. Treatment of crude cellular membrane fractions with N-glycanase, endoglycosidase H or neuraminidase showed that the altered migration of MRP on SDS-PAGE is due to a post-translational modification. There was no detectable difference in sialic acid content. In most but not all doxorubicin-selected clones, this MDR phenotype was accompanied by a reduction in topo II alpha mRNA level. No reduction was found in the clones selected with vincristine. We conclude from these results that selection of the SW-1573 cell line for low levels of doxorubicin or vincristine resistance, predominantly results in MDR with reduced drug accumulation associated with the presence of an altered MRP protein. This mechanism can be accompanied by other resistance mechanisms, such as reduced topo II alpha mRNA in case of doxorubicin selection. 相似文献
103.
Greenfield LJ Zaman SH Sutherland ML Lummis SC Niemeyer MI Barnard EA Macdonald RL 《Neuropharmacology》2002,42(4):502-521
All GABA(A) receptor (GABAR) subunits include an invariant proline in a consensus motif in the first transmembrane segment (M1). In receptors containing bovine alpha1, beta1 and gamma2 subunits, we analyzed the effect of mutating this M1 proline to alanine in the alpha1 or beta1 subunit using 3 different expression systems. The beta1 subunit mutant, beta1(P228A), reduced the EC(50) for GABA about 10-fold in whole cell recordings in HEK293 cells and L929 fibroblasts. The corresponding alpha1 subunit mutant (alpha1(P233A)) also reduced the GABA EC(50) when expressed in Xenopus oocytes; alpha1(P233A)beta1gamma2S receptors failed to assemble in HEK293 cells. Binding of [(3)H]flumazenil and [(3)H]muscimol to transfected HEK293 cell membranes showed similar levels of receptor expression with GABARs containing beta1 or beta1(P228A) subunits and no change in the affinity for [(3)H]flumazenil; however, the affinity for [(3)H]muscimol was increased 6-fold in GABARs containing beta1(P228A) subunits. In L929 cells, presence of the beta1(P228A) subunit reduced enhancement by barbiturates without affecting enhancement by diazepam or alfaxalone. Single channel recordings from alpha1beta1gamma2S and alpha1beta1(P228A)gamma2L GABARs showed similar channel kinetics, but beta-mutant containing receptors opened at lower GABA concentrations. We conclude that the beta1 subunit M1 segment proline affects the linkage between GABA binding and channel gating and is critical for barbiturate enhancement. Mutation of the M1 proline in the alpha1 subunit also inhibited receptor assembly. 相似文献
104.
Najib N Idkaidek N Beshtawi M Bader M Admour I Alam SM Zaman Q Dham R 《Biopharmaceutics & drug disposition》2002,23(5):197-202
A randomized, two-way, crossover, bioequivalence study in 24 fasting, healthy, male volunteers was conducted to compare two brands of gliclazide 80 mg tablets, Glyzide (Julphar, UAE) as test and Diamicron (Servier Industries, France) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in joint venture with Speciality Hospital, Amman, Jordan. The drug was administered with 240 ml of 20% glucose solution after a 10 h overnight fasting. After dosing, serial blood samples were collected for a period of 48 h. Plasma harvested from blood was analyzed for gliclazide by validated HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0- proportional, variant), C(max), T(max), T(1/2), and elimination rate constant were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were applied to AUC(0-t), AUC(0- proportional, variant), and C(max) for bioequivalence evaluation of the two brands which revealed no significant difference between them, and 90% CI fell within US FDA accepted bioequivalence range of 80-125%. Based on these statistical inferences, Glyzide was judged bioequivalent to Diamicron. 相似文献
105.
Najib N Idkaidek N Beshtawi M Bader M Admour I Alam SM Zaman Q Dham R 《Biopharmaceutics & drug disposition》2002,23(7):301-306
A randomized, two-way, crossover study was conducted in 24 fasting, healthy, male volunteers to compare the bioavailability of two brands of metformin 500 mg tablets; Dialon (Julphar, UAE) as test and Glucophage (Lipha Pharmaceutical Industries, France) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in joint venture with Al-Mowasah Hospital, Amman, Jordan. The drug was administered with 240 ml of water after a 10-h overnight fasting on two treatment days separated by 1-week washout period. After dosing, serial blood samples were collected for a period of 30 h. Plasma harvested from blood was analyzed for metformin by validated HPLC method with UV-visible detector capable to detect metformin in the range of 0.05-5.0 microg/ml with limit of quantitation of 0.05 microg/ml. Various pharmacokinetic parameters including AUC(0-t), AUC(0-proportional to), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-proportional to) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval (97.9-110.8% for AUC(0-t), 97.4-110.7% for AUC(0-proportional to); 95.3-110.5% for C(max)) of test/reference ratio for these parameters were found within bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Dialon is bioequivalent to Glucophage. 相似文献
106.
107.
Kearney MT Nolan J Lee AJ Brooksby PW Prescott R Shah AM Zaman AG Eckberg DL Lindsay HS Batin PD Andrews R Fox KA 《European journal of heart failure》2003,5(4):489-497
BACKGROUND: Mortality in patients with mild to moderate chronic heart failure remains high. At present there is no easy way of identifying patients within this population at increased risk of death in the medium to long term. AIMS: To develop a prognostic index to identify outpatients with mild to moderate chronic heart failure at increased risk of death. METHODS AND RESULTS: Five hundred and fifty-three outpatients mean (S.D.) age 63(+/-10) years with symptoms of chronic heart failure (mean New York Heart Association functional class, 2.3(+/-0.5)), were recruited between December 1993 and April 1995. By April 2000, 201 patients had died. Using data from non-invasive measurements of cardiac size, electrical and autonomic function, renal function and plasma biochemistry we identified eight independent predictors of mortality (all P<0.01). To develop a prognostic index, predictors were dichotomised by group median and awarded 0 or 1 point accordingly. Serum sodium =140 mmol/l (1 point), creatinine >/=111 micromol/l (1 point), cardiothoracic ratio >/=0.52 (1 point), SDNN =112 ms (1 point), maximum corrected QT interval >/=487 ms (1 point), QRS dispersion>/=42.7 ms (1 point), the presence of non-sustained ventricular tachycardia (1 point) and voltage criteria for left ventricular hypertrophy on 12-lead ECG (1 point). We calculated risk scores for patients by adding the points of each independent risk factor. In the low-risk group (0-3 points) mortality at 5 years was 20% and in the high-risk group (4-8 points) 53%. The area under the receiver-operator characteristic curve using dichotomised variables was 0.74 and for continuous model 0.78. CONCLUSIONS: Our prognostic index which uses eight non-invasive measurements and a straightforward additive points system, has good discrimination and stratifies outpatients with chronic heart failure into high and low risk. This index may be useful in clinical care and risk stratification. 相似文献
108.
Pelvic lipomatosis in a child 总被引:4,自引:0,他引:4
We report a 10-year-old boy with pelvic lipomatosis causing chronic urinary retention. CT scan features, therapy and review of the literature are discussed. 相似文献
109.
Recco RA Zaman MM Cortes H Colucci J Poomkudy G Kaplan EL 《Epidemiology and infection》2002,129(2):303-306
Invasive group A streptococcal (GAS) infections have been of increasing concern worldwide during the past 15 years. Spread of group A streptococci to contacts with resulting invasive infection has been reported in families, in residential nursing homes, and even from patients to health care workers. We report an instance of temporally related life-threatening group A streptococcal infection in a husband and 2 weeks later in his wife. This example further emphasizes the need for careful observation among family members and other close contacts of patients with invasive group A streptococcal infection. Although at present there are no universal recommendations for monitoring or for antibiotic prophylaxis of close contacts of persons with invasive GAS infection, when added to existing literature, this report suggests additional consideration is required. 相似文献
110.
A patient presented to a district general hospital with a type B dissection of the aorta. He was deemed too unwell for surgical intervention. An endovascular stent repair was successfully carried out. The case shows that such a procedure can be safely performed by a multidisciplinary team within a district general hospital. 相似文献