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131.
132.
The aim of the present study was to investigate the stereoselectivity in the kinetic disposition and the transplacental distribution of bupivacaine in term parturients during labor. Maternal age ranged from 18-37 years and fetal gestational age from 37.6-41.5 weeks. Healthy parturients (n = 23) received epidural 0.5% racemic bupivacaine alone (group A) or combined with epinephrine (group B). Maternal venous blood was sampled at regular intervals until 8 h after drug administration and umbilical venous blood was obtained at delivery. Bupivacaine enantiomers were determined in plasma samples by HPLC using a Chiralcel(R) OD-R column and a UV detector. One- or two-compartment models were fitted to data and differences between the (+)-(R) and (-)-(S) enantiomers were compared with the paired Wilcoxon test (P< 0.05). The influence of epinephrine was evaluated using the unpaired Mann-Whitney test (P< 0.05). The disposition of bupivacaine in maternal plasma was stereoselective, with higher V(d/f) (140.60 vs. 132.81 L for group A and 197.86 vs. 169.46 L for group B) and C(l/f) (29.00 vs. 25.43 L/h for group A and 33.15 vs. 26.39 L/h for group B) and lower t(1/2)beta (3.24 vs. 3.30 h for group A and 4.36 vs. 4.45 h for group B) being observed for (+)-(R)-bupivacaine. The combined administration of epinephrine resulted in higher V(d/f) (197.86 vs. 140.60 L for (+)-(R) and 169.46 vs. 132.81 L for (-)-(S)) and t(1/2)beta values (4.36 vs. 3.24 h for (+)-(R) and 4.45 vs. 3.30 h for (-)-(S)). The transplacental distribution of bupivacaine was stereoselective only when bupivacaine was administered without epinephrine (group B), with a higher cord blood/maternal blood ratio being observed for (-)-(S)-bupivacaine (0.40 vs. 0.35). Chirality 16:65-71, 2004. 相似文献
133.
The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria 总被引:5,自引:0,他引:5
Rengarajan J Sassetti CM Naroditskaya V Sloutsky A Bloom BR Rubin EJ 《Molecular microbiology》2004,53(1):275-282
The increasing rate of multidrug-resistant tuberculosis has led to more use of second-line antibiotics such as para-aminosalicylic acid (PAS). The mode of action of PAS remains unclear, and mechanisms of resistance to this drug are undefined. We have isolated PAS-resistant transposon mutants of Mycobacterium bovis BCG with insertions in the thymidylate synthase (thyA) gene, a critical determinant of intracellular folate levels. BCG thyA mutants have reduced thymidylate synthase activity and are resistant to known inhibitors of the folate pathway. We also find that mutations in thyA are associated with clinical PAS resistance. We have identified PAS-resistant Mycobacterium tuberculosis isolates from infected patients, which harbour mutations in thyA and show reduced activity of the encoded enzyme. Thus, PAS acts in the folate pathway, and thyA mutations probably represent a mechanism of developing resistance not only to PAS but also to other drugs that target folate metabolism. 相似文献
134.
Kaizer RR da Silva AC Morsch VM Corrêa MC Schetinger MR 《Neurochemical research》2004,29(12):2251-2255
In the present study we investigated a potential mechanism by which high sugar (HS) and high fat (HF) diets could affect acetylcholinesterase (AChE) activity. The treatment with HS and HF diet was done for six months on male and female rats. The results showed decreased hippocampal AChE activity in male and females receiving HS and HF diets (HS 24% and 36%; HF 38% and 32%, males and females, respectively; P < 0.05). The activity in the cerebral cortex was reduced in males (49 and 40%) and females (19 and 17%) (P < 0.05) on HS and HF diets, respectively. In the hypothalamus AChE activity was decreased on HS diet in males (46%) and female (25%) (P < 0.05) and also on HF diet in males (34%) and females (21%) (P < 0.05). However, in the cerebellum no changes in AChE activity were observed. These results indicate that HS and HF diets produced mainly inhibition in acetylcholine degradation. It probably indicates a chronic alteration induced by these diets on the cholinergic system. 相似文献
135.
Lemperle G Morhenn VB Pestonjamasp V Gallo RL 《Plastic and reconstructive surgery》2004,113(5):1380-1390
Injectable dermal filler materials consist of either fluids, biological fragments, or suspensions of particles or microspheres. Particles and microspheres are said to "migrate," but migration can occur only when they are injected into blood vessels. To evaluate biocompatibility and transport, five nonresorbable polymethylmethacrylate microspheres of various sizes, suspended in different carriers, as well as resorbable polylactic acid and dextran microspheres were injected subcutaneously into mice. The five implantation sites were the right cheek, right axilla, right groin, urethra, and the right quadriceps muscle of the thigh. These sites were excised along with the local lymph nodes, lungs, liver, and spleen at 1, 3, 6, and 9 months after injection. Polymethylmethacrylate microspheres of 4 microm and 8 microm were phagocytosed but not transported to lymph nodes or distant organs. Larger microspheres of 20, 40, and 100 microm were encapsulated by connective tissue, macrophages, and giant cells. Polylactic acid microspheres caused a mild inflammatory response and had disappeared at 6 months. Dextran microspheres caused a pronounced foreign-body reaction and were phagocytosed at 9 months. The extremely large carbon-coated spheres of 200 to 500 microm in diameter "migrated" up to 1 cm from the implantation site. With the exception of an erroneous intravenous injection, no migration or transportation of any of the injected microspheres to lymph nodes or filter organs was seen. Obviously, the collagen glue released no microspheres. After subdermal injection, the collagen carrier substance kept the microspheres apart as a scaffold for tissue ingrowth, whereas all other carrier substances, such as gelatin, hyaluronic acid, or alginate, separated soon after injection, thereby causing agglomeration of the microspheres. 相似文献
136.
137.
Genomic data provide invaluable, yet unreliable information about protein function. However, if the overlap in information among various genomic datasets is taken into account, one observes an increase in the reliability of the protein-function predictions that can be made. Recently published approaches achieved this either by comparing the same type of data from multiple species (horizontal comparative genomics) or by using subtle, Bayesian methods to compare different types of genomic data from a single species (vertical comparative genomics). In this article, we discuss these methods, illustrating horizontal comparative genomics by comparing yeast two-hybrid (Y2H) data from Saccharomyces cerevisiae with Y2H data from Drosophila melanogaster, and illustrating vertical comparative genomics by comparing RNA expression data with proteomic data from Plasmodium falciparum. 相似文献
138.
Dendritic cells (DCs) are the most potent antigen-presenting cells, and are regarded as "natural adjuvants" for the induction of primary T or T-dependent immunity. DCs in the peripheral sites capture and process antigens. Encounter of exogenous or endogenous stimuli mature the function of DCs, and they thus acquire T-cell stimulatory capacity and distinct chemotactic behavior which enables them to migrate to lymphoid tissue. In the secondary lymphoid organs, they present antigens to T- and B-cells and stimulate their proliferation. Dendritic cells are also involved in tolerance induction, in particular, to self antigens. DCs also play a key role in the transmission of many pathogens, and therefore may become targets for designing new therapies. DCs have been manipulated in vitro and in vivo for cancer immunotherapy. In this article, we provide a concise overview of DC biology and its current and future role in clinical settings. 相似文献
139.
Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins 总被引:11,自引:0,他引:11
Chacinska A Pfannschmidt S Wiedemann N Kozjak V Sanjuán Szklarz LK Schulze-Specking A Truscott KN Guiard B Meisinger C Pfanner N 《The EMBO journal》2004,23(19):3735-3746
Mitochondria import nuclear-encoded precursor proteins to four different subcompartments. Specific import machineries have been identified that direct the precursor proteins to the mitochondrial outer membrane, inner membrane or matrix, respectively. However, a machinery dedicated to the import of mitochondrial intermembrane space (IMS) proteins has not been found so far. We have identified the essential IMS protein Mia40 (encoded by the Saccharomyces cerevisiae open reading frame YKL195w). Mitochondria with a mutant form of Mia40 are selectively inhibited in the import of several small IMS proteins, including the essential proteins Tim9 and Tim10. The import of proteins to the other mitochondrial subcompartments does not depend on functional Mia40. The binding of small Tim proteins to Mia40 is crucial for their transport across the outer membrane and represents an initial step in their assembly into IMS complexes. We conclude that Mia40 is a central component of the protein import and assembly machinery of the mitochondrial IMS. 相似文献
140.
Jabor VA Coelho EB Lanchote VL 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,813(1-2):343-346
OBJECTIVE: The enantioselective kinetic disposition of lercanidipine, a dihydropyridine type of third-generation calcium antagonist, was investigated in six healthy male volunteers following a single 20 mg racemic oral dose. METHODS: Serial plasma samples were obtained from 0 to 24 h after drug administration. Lercanidipine enantiomers were analysed using a chiral LC-MS-MS method. RESULTS: The following differences (p < 0.05, Wilcoxon test) between (S) and (R) enantiomers were found (median): C(max) 2.071 ng mL(-1) versus 1.681 ng mL(-1); AUC(0-24)12.352 ng h mL(-1) versus 10.063 ng h mL(-1) and Cl/f 732.16 L h(-1) versus 1891.84 L h(-1). The AUC(0-infinity) values for (S)-LER were 1.21-fold higher than those for (R)-LER. CONCLUSION: The pharmacokinetics of LER was enantioselective in healthy volunteers following a single dose of 20 mg of the unlabeled racemic drug. 相似文献