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J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):289-94.
Liquid chromatographic method for the determination of ganciclovir and/or acyclovir in human plasma using pulsed amperometric detection.

Kishino S, Takekuma Y, Sugawara M, Shimamura T, Furukawa H, Todo S, Miyazaki K.

Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo, 060-8648, Japan.

We have developed a simple, rapid and highly sensitive method for determining plasma concentrations of ganciclovir and/or acyclovir by using reversed-phase chromatography followed by pulsed amperometric detection. A linear relationship between the amount of ganciclovir (0.05-10 microg/ml plasma) or acyclovir (0.1-20 microg/ml plasma) and peak height ratio was obtained. The relative standard deviations of all standard curves were greater than or equal to 0.999. The limits of detection for ganciclovir and acyclovir quantitation were 10 ng/ml and 50 ng/ml (signal/noise >3), respectively. Daily fluctuations of plasma standard curves (n=5) for the ganciclovir and acyclovir samples were small, with relative standard deviations (RSD) of 3.3 and 4.5% (n=5), respectively. The intra-assay precision for the ganciclovir and acyclovir samples were 6.9 (n=5) and 5.5% (n=5), respectively. Inter-assay precision of ganciclovir (n=3) and acyclovir (n=3) ranged from 2.6 to 6.8% and 3.5 to 5.0%, respectively. Using this method, the pharmacokinetics and removal of ganciclovir during continuous hemodiafiltration (CHDF) in a liver transplant recipient being treated for severe cytomegalovirus infection was investigated. The mean (+/-SD) ratio of ganciclovir concentrations at the inlet and outlet of the dialyzer (C(outlet)/C(inlet)) was 0.56+/-0.09. The areas under the curves of ganciclovir up to 12 h postdosing (AUC(0-->12)) at the inlet and outlet of the dialyzer were 12.54 microg h/ml and 7.16 microg h/ml, respectively. The ultrafiltrate of ganciclovir was 16.6 mg. The terminal elimination half-life (T(1/2)) of ganciclovir during CHDF was 3.6 h. These results demonstrate that CHDF effectively removes ganciclovir. Until formal guidelines have been established, ganciclovir or acyclovir dosage should be adjusted according to the results of monitoring of plasma drug concentration. The method described here is suitable for clinical monitoring of plasma ganciclovir or acyclovir levels in solid organ transplant recipients and for use in studies involving pharmacokinetics. Copyright 2002 Elsevier Science B.V.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12401354&dopt=Abstract

Int J STD AIDS. 1998 Aug;9(8):476-9.
Herpes zoster ophthalmicus and HIV infection in Nigeria.

Umeh RE.

Department of Ophthalmology, College of Medicine, University of Nigeria, Enugu, Africa.

Eight patients, 3 men and 5 women, aged between 24 and 40 years who had herpes zoster ophthalmicus (HZO) were seen in the Eye Department of the University of Nigeria Teaching Hospital, Enugu between 1994 and 1997. One of the patients was already on treatment for active pulmonary tuberculosis at the time he was first seen. All had skin eruptions at different stages of development in the area of distribution of the first trigeminal nerve on the affected side of the face and head. Ocular examination revealed impaired vision in the affected eye (between 6/12 and hand movement) in all the patients. All had lid oedema while 5 had ptosis (3 partial and 2 complete). Various degrees of conjunctival injection were observed in all patients while 6 of them had corneal anaesthesia and keratitis. Uveal inflammation, present in all the patients varied from mild iritis in 4 individuals to severe iridocyclitis in the remaining 4. Pupils reacted to light sluggishly in 2 patients while they were dilated and fixed in 3 others. None had any associated abnormalities in the posterior segment. Six of the patients consented and were screened for human immunodeficiency virus (HIV) infection. Of these, 4, including the patient with pulmonary tuberculosis, tested seropositive while 2 were seronegative. All 8 were treated with topical acyclovir. This was combined with oral acyclovir in one of the patients. Follow-up period was between 2 and 52 weeks. During this period skin eruptions and anterior segment signs improved in 5 patients while remaining stable in 3 others; post-herpetic neuralgia persisted on the affected side in 4 patients. Patients who were HIV seropositive did not recover as quickly or to the same extent as the seronegative ones. It is concluded that HZO infection may indicate underlying HIV infection in young Africans as has been found in whites.

PIP: Manifestations of herpes zoster ophthalmicus (HZO) infection are well known in HIV-seropositive White patients in developed countries, but this association has not been previously noted in African AIDS patients. This paper analyzes 8 cases (3 men and 5 women) 24-40 years of age who were treated at the Eye Department of the University of Nigeria Teaching Hospital, Enugu, for HZO in 1994-97. Of the 6 patients who consented to HIV screening, 4 were HIV-seropositive. One of the HIV-infected patients had been treated for pulmonary tuberculosis a year prior to the present illness, but the remaining 7 were in apparent good health. The patients presented with skin eruptions in the area of distribution of the trigeminal nerve on the affected side of the face and head. Visual acuity was impaired in all 8 cases. The most common ocular findings were lid edema, ptosis, conjunctival infection, corneal anesthesia, keratitis, uveal inflammation, and abnormal pupillary reaction. The severity of presentation was similar in HIV-positive and HIV-negative patients and all improved during follow-up; however, clinical improvement was less rapid or pronounced among the HIV-positive patients. These findings suggest that HZO infection in young Africans should be regarded as a possible indicator of HIV infection.

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nih.go.jp

Twenty-four strains of acyclovir (ACV)-resistant (ACV(r)) herpes simplex virus type 1 (HSV-1) were generated from the HSV-1 TAS strain by exposure to ACV, and the genotype and phenotype of the thymidine kinase (TK) from these mutants were analyzed. The TK polypeptide of the ACV(r) HSV-1 strains was examined by Western blot using an anti-HSV-1 TK rabbit serum. The sensitivity of each strain to ACV, foscarnet and cidofovir (CDV) was also determined. A single guanine (G) insertion or a single cytosine (C) deletion was detected in 12 of the 24 ACV(r) strains at the G or C homopolymer stretches within the TK gene. Genotypic analysis predicted that two thirds of the ACV(r) HSV-1 strains expressed truncated TK polypeptides, while one third expressed viral TK polypeptide with a single amino acid substitution at various sites. Western blot abnormalities in the viral TK polypeptides were identified in 21 ACV(r) strains. There was an inverse correlation between the susceptibility of the HSV-1 mutant strains to ACV and that to CDV. Nucleotide sequencing of the TK gene and Western blot analysis of the viral TK polypeptides are considered to be one of the methods for predicting virus sensitivity to ACV and CDV.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12406508&dopt=Abstract

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