Co-receptor usage of HIV-1 primary isolates, viral burden, and CCR5 genotype in mother-to-child HIV-1 transmission. Rx drugs

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AIDS. 2000 Aug 18;14(12):1721-9.
Co-receptor usage of HIV-1 primary isolates, viral burden, and CCR5 genotype in mother-to-child HIV-1 transmission.

Ometto L, Zanchetta M, Mainardi M, De Salvo GL, Garcia-Rodriguez MC, Gray L, Newell ML, Chieco-Bianchi L, De Rossi A.

Department of Oncology and Surgical Sciences, AISA Reference Center, University of Padua, Italy.

OBJECTIVE: To investigate the relationship between CC chemokine receptor 5 (CCR5) genotype, viral load and co-receptor usage of maternal HIV-1 isolates in perinatal HIV-1 transmission. PATIENTS AND METHODS: A total of 181 mothers and infants were studied at the time of delivery. Wild-type (wt) and delta32 CCR5 alleles were determined by means of polymerase chain reaction (PCR). The viral load in maternal plasma samples was determined by a quantitative reverse transcriptase-PCR assay; co-receptor usage of maternal isolates was determined by viral infection in cells stably expressing CCR5 or CXC chemokine receptor 4 (CXCR4) co-receptors. RESULTS: HIV-1 transmission rates in wt/wt and wt/delta32 mothers (14.7 versus 15.8%), and in wt/wt and wt/delta32 infants (14.6 versus 14.3%) were similar. Mothers transmitting infection to wt/delta32 infants had significantly higher HIV-1-RNA levels than those who transmitted infection to wt/wt infants (5.4 versus 4.1 log10 copies/ml, P = 0.03). In wt/wt children there was a positive relationship between transmission rate and maternal viral load over the entire range of HIV-1 values, whereas in wt/delta32 children transmission occurred only at viral loads greater than 4.0 log10 copies/ml. Logistic regression analysis confirmed that the relationship between viral load and transmission varied according to the child's CCR5 genotype (P = 0.035; adjusted for zidovudine prophylaxis and mode of delivery, P = 0.090). Moreover, the majority of wt/wt transmitting mothers had R5-type isolates, whereas none of the wt/delta32 mothers with an R5-type virus transmitted HIV-1 to their wt/delta32 infants. CONCLUSION: Taken together, these findings suggest that CCR5 delta32 heterozygosity exerts a protective effect against perinatal transmission in children exposed to a low maternal viral burden of an R5-type isolate.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10985308&dopt=Abstract

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daum.net

Enantiomers may confer benefits over racemates in therapeutic uses and we developed a chiral separation method of cetirizine enantiomers, a second generation H1 histamine receptor antagonist, in rat plasma. alpha1-Acidglycoprotein based chiral stationary phase(AGP-CSP), monitored with UV at 230 nm was used to separate the enantiomers. Observed enantioselectivity (alpha) was 2.0. The AGP-CSP was also used at a preparative scale to isolate the enantiomers with an optical purity of greater than ee 99%. In addition, an analysis was carried out for the cetirizine enantiomers in rat plasma to study the differences of enantiomers in pharmacokinetics. Both (+)- and (-)-cetirizine were separated using a reversed-phase column of AGP, and were detected at the range of 2.5-200 microg ml(-1) in plasma. Although there was no recognizable differences in pharmacokinetics between the enantiomers in rat, the method appears to be useful for their pharmacokinetic studies.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10985583&dopt=Abstract

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apclinical.com

The impact of interventions designed to shift prescribing from loratadine to fexofenadine at HMOs was studied. Pharmacy claims data for a six-month preintervention period at four HMOs were analyzed to identify all new and refill prescriptions for loratadine, fexofenadine, astemizole, and cetirizine. The interventions consisted of a mandatory lockout of loratadine in favor of fexofenadine (at HMO A), a voluntary switch to fexofenadine promoted through letters to both physicians and members (HMO B), and a voluntary switch promoted through letters to physicians only (HMO C). There was no intervention at HMO D. Pharmacy claims data for the six months after each intervention program was implemented were analyzed to determine changes in the market share and prescribing of the study drugs. After the intervention programs were implemented, the market share of fexofenadine increased from 18.9% to 65.2% at HMO A, from 14.8% to 21.0% at HMO B, and from 20.7% to 23.8% at HMO C. Loratadine's market share decreased from 62.3% to 8.7% at HMO A, from 67.5% to 58.6% at HMO B, and from 70.5% to 65.3% at HMO C. HMOs A, B, and C each had greater shifts in market share for fexofenadine and loratadine than the control HMO. Changes in prescribing followed a similar pattern for the 25 physicians at each HMO who had most frequently prescribed loratadine during the preintervention period. The average cost per antihistamine prescription decreased 22.3% at HMO A. Prescription costs continued to rise at HMOs B, C, and D. Mandating the use of fexofenadine produced a significant increase in its market share, reduced the cost of nonsedating antihistamines, and successfully influenced prescribing behavior. Voluntary programs had a more modest impact on market share and did not stop increases in prescription costs.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11030030&dopt=Abstract

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