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Biomedical subjects

D L Taylor

Publications and source records attributed to D L Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1999

Oxidative metabolism, apoptosis and perinatal brain injury.

Perinatal hypoxic-ischaemic injury (HII) is a significant cause of neurodevelopmental impairment and disability. Studies employing 31P magnetic resonance spectroscopy to measure phosphorus metabolites in situ in the brains of newborn infants and animals have demonstrated that transient hypoxia-ischaemia leads to a delayed disruption in cerebral energy metabolism, the magnitude of which correlates with the subsequent neurodevelopmental impairment. Prominent among the biochemical features of HII is the loss of cellular ATP, resulting in increased intracellular Na+ and Ca2+, and decreased intracellular K+. These ionic imbalances, together with a breakdown in cellular defence systems following HII, can contribute to oxidative stress with a net increase in reactive oxygen species. Subsequent damage to lipids, proteins, and DNA and inactivation of key cellular enzymes leads ultimately to cell death. Although the precise mechanisms of neuronal loss are unclear, it is now clear both apoptosis and necrosis are the significant components of cell death following HII. A number of different factors influence whether a cell will undergo apoptosis or necrosis, including the stage of development, cell type, severity of mitochondrial injury and the availability of ATP for apoptotic execution. This review will focus on some pathological mechanisms of cell death in which there is a disruption to oxidative metabolism. The first sections will discuss the process of damage to oxidative metabolism, covering the data collected both from human infants and from animal models. Following sections will deal with the molecular mechanisms that may underlie cerebral energy failure and cell death in this form of brain injury, with a particular emphasis on the role of apoptosis and mitochondria.

Animals↗
PubMed1999

Anti-human immunodeficiency virus type 1 activity, intracellular metabolism, and pharmacokinetic evaluation of 2'-deoxy-3'-oxa-4'-thiocytidine.

The racemic nucleoside analogue 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC) is in clinical development for the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection. dOTC is structurally related to lamivudine (3TC), but the oxygen and sulfur in the furanosyl ring are transposed. Intracellular metabolism studies showed that dOTC is phosphorylated within cells via the deoxycytidine kinase pathway and that approximately 2 to 5% of dOTC is converted into the racemic triphosphate derivatives, which had measurable half-lives (2 to 3 hours) within cells. Both 5'-triphosphate (TP) derivatives of dOTC were more potent than 3TC-TP at inhibiting HIV-1 reverse transcriptase (RT) in vitro. The K(i) values for dOTC-TP obtained against human DNA polymerases alpha, beta, and gamma were 5,000-, 78-, and 571-fold greater, respectively, than those for HIV RT (28 nM), indicating a good selectivity for the viral enzyme. In culture experiments, dOTC is a potent inhibitor of primary isolates of HIV-1, which were obtained from antiretroviral drug-naive patients as well as from nucleoside therapy-experienced (3TC- and/or zidovudine [AZT]-treated) patients. The mean 50% inhibitory concentration of dOTC for drug-naive isolates was 1.76 microM, rising to only 2.53 and 2.5 microM for viruses resistant to 3TC and viruses resistant to 3TC and AZT, respectively. This minimal change in activity is in contrast to the more dramatic changes observed when 3TC or AZT was evaluated against these same viral isolates. In tissue culture studies, the 50% toxicity levels for dOTC, which were determined by using [(3)H]thymidine uptake as a measure of logarithmic-phase cell proliferation, was greater than 100 microM for all cell lines tested. In addition, after 14 days of continuous culture, at concentrations up to 10 microM, no measurable toxic effect on HepG2 cells or mitochondrial DNA replication within these cells was observed. When administered orally to rats, dOTC was well absorbed, with a bioavailability of approximately 77%, with a high proportion (approximately 16.5% of the levels in serum) found in the cerebrospinal fluid.

Animals↗
PubMed1999

Pyrido [1,2a] indole derivatives identified as novel non-nucleoside reverse transcriptase inhibitors of human immunodeficiency virus type 1.

Pyrido [1,2a] indole derivatives were identified as potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication during a random screening programme. The compounds showed no antiviral activity against HIV-2 or in cells chronically infected with HIV-1, but had good inhibitory effect against purified HIV-1 reverse transcriptase (RT) in an in vitro assay. They were therefore classified as non-nucleoside RT inhibitors (NNRTI). The synthesis of additional compounds of the same class revealed a structure-activity relationship. The most potent compound of the series, BCH-1, had similar antiviral activity to the licensed NNRTI nevirapine against laboratory strains of HIV-1 cultured in cell lines and primary clinical isolates of HIV-1 cultured in peripheral blood mononuclear cells. However, BCH-1 showed greater cytotoxicity, providing a narrow selectivity index in the order of 35. BCH-1 had equivalent antiviral activity against viruses resistant to the nucleoside RT inhibitors zidovudine, didanosine and lamivudine and maintained better activity (less than threefold change in IC50) than nevirapine against viruses resistant to a range of NNRTIs with the single amino acid changes L100I, K103N, E138K or Y181C in the RT. Viruses with single V106A or Y188C amino acid changes showed five- and 10-fold resistance to BCH-1, respectively, in contrast to nevirapine, which had a > 100-fold change in IC50. However, virus with both V106A and Y188C amino acid changes showed higher level resistance (> 15-fold) to BCH-1. Virus with > 10-fold resistance to BCH-1 was rapidly selected for after growth in increasing concentrations of compound and was shown to be cross-resistant to nevirapine. Sequencing of this virus revealed two amino acid changes at positions 179 (V to D) and 181 (Y to C) in the RT. BCH-1 represents a new class of NNRTI, which may act as a lead to identify more selective compounds.

Amino Acid Substitution↗
PubMed1999

Increased nitric oxide synthesis is not involved in delayed cerebral energy failure following focal hypoxic-ischemic injury to the developing brain.

This study addressed the hypothesis that the delayed impairment in cerebral energy metabolism that develops 10-24 h after transient hypoxia-ischemia in the developing brain is mediated by induction of increased nitric oxide synthesis. Four groups of 14-d-old Wistar rat pups were studied. Group 1 was subjected to unilateral carotid artery ligation and hypoxia followed immediately by treatment with the nitric oxide synthase (NOS) inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg). Group 2 underwent hypoxia-ischemia but received saline vehicle. Group 3 received L-NAME without hypoxia-ischemia, and group 4, saline vehicle alone. At defined times after insult, the expression of neuronal and inducible NOS were determined and calcium-dependent and -independent NOS activities measured. Cerebral energy metabolism was observed using 31P magnetic resonance spectroscopy. At 48 h after insult, the expression of inducible NOS increased, whereas neuronal NOS at 24 h decreased on the infarcted side. Calcium-dependent NOS activity was higher than calcium-independent NOS activity, but did not increase within 36 h after insult, and was significantly inhibited by the administration of L-NAME. However, L-NAME did not prevent delayed impairment of cerebral energy metabolism or ameliorate infarct size. These results suggest that the delayed decline in cerebral energy metabolism after hypoxia-ischemia in the 14-d-old rat brain is not mediated by increased nitric oxide synthesis.

Animals↗
PubMed1999

Symptom experience of Filipino American midlife women.

OBJECTIVE: The purpose of this study was to describe the perimenopausal symptom experience of Filipino American midlife women with particular emphasis upon estrogen-related menopause symptoms (day sweats, hot flashes, night sweats, and vaginal dryness). DESIGN: A cross-sectional, descriptive survey was used to generate symptom experience data for 165 Filipina Americans between the ages of 35 and 56 who self-identified as Filipina American and were English-language proficient. The community-based sample completed questionnaires composed of sample characteristic questions and a 51-item menstrual symptom checklist with menopause-related symptoms embedded in it. RESULTS: Sample characteristics and symptom experience were compared among age groups of 35 to 39 (n = 39), 40 to 44 (n = 40), 45 to 49 (n = 37), and 50 to 56 (n = 49) and by perimenopausal phase, defined as premenopausal (n = 85), transitional (n = 33), and menopausal/postmenopausal (n = 47). The most reported individual symptoms were "felt energetic" (86.1%) and "well-being" (83.6%). Estrogen-related menopause symptoms were reported as "vaginal dryness" (39.4%), "hot flashes" (37.6%), "day sweats" (27.9%), and "night sweats" (24.2%) by the total sample. Distress associated with estrogen-related menopause symptoms was reported by 17% (n = 28) of all women. Subjects' chi 2 tests indicated that 50-to-56-year-old women were more likely to report fatigue/sleep symptoms, physical symptoms, and estrogen-related menopause symptoms than all other age groups. When compared by perimenopausal phase, transitional women were more likely to report moderate or extreme severity for day sweats. Premenopausal women were more likely to report minimal or mild severity and women in the perimenopausal transition were more likely to report moderate or extreme severity on estrogen-related menopause symptoms. CONCLUSIONS: Filipino American midlife women appear to consider the perimenopausal transition in a positive light and experience little distress associated with estrogen-related menopause symptoms experienced. Findings from this study suggest that Filipina Americans view perimenopausal symptoms as part of a normal life stage that does not warrant concern.

Adaptation, Physiological↗
PubMed1999

Symptom responses of midlife Filipina Americans.

OBJECTIVE: The purpose of this study was to describe the perimenopausal symptom responses of Filipino American midlife women. DESIGN: This cross-sectional, descriptive survey collected symptom response information on Filipino American midlife women aged 35 to 56 years (n = 165) who self-identified as Filipina American and were proficient in the English language. Women were recruited from community churches and social groups. A survey questionnaire comprised of health history questions and a symptom checklist with symptom response questions were completed by the participants. RESULTS: The symptom responses of women were compared by age groups of 35 to 39 (n = 39), 40 to 44 (n = 40), 45 to 49 (n = 37), and 50 to 56 (n = 49) and by perimenopausal phases of premenopausal (n = 85), transitional (n = 33), and menopausal/postmenopausal (n = 47). Indications from chi 2 tests showed that women in the 35-to-39- and 50-to-56-year groups were more likely to take acetaminophen (Tylenol) or aspirin for symptoms, and women in the 45-to-49- and 50-to-56-year groups were more likely to be on hormone replacement therapy. Surprisingly, women in the 50-to-56-year group were less likely to use talking with friends as a symptom management strategy. CONCLUSIONS: Nonpharmacologic symptom management strategies exceeded the use of medications (hormones, over-the-counter) by Filipina Americans. This may be a strong indicator of their positive attitude toward this phase in their life and sends a message to clinicians about the choices that these women make for symptom management. Culturally relevant care would include alternatives to hormone replacement therapy in education materials about the perimenopausal transition for midlife Filipinas.

Adaptation, Physiological↗
PubMed1999

Changing women's health, changing nursing practice.

Women's health is a field of study and health care that is of the highest concern for nurses, both from a professional and personal standpoint. It is imperative that those in nursing practice, education, and research be knowledgeable about, prepared for, able to advocate for, and participate in the transformation of health care policy and practice. The changing health care patterns and changing health care delivery system influencing the future of women's health are discussed. Recommendations for nursing practice, education, and research are proposed to advance women's health care.

Adolescent↗
PubMed1998

Fluorescent-protein biosensors: new tools for drug discovery.

Recent improvements in target discovery and high-throughput screening have increased the pressure at key points along the drug-discovery pipeline. High-content screening was developed to ease the bottlenecks formed at the target-validation and lead-optimization points, and a new generation of reagents that report on specific molecular processes in living cells (fluorescent-protein biosensors) have been important in its development. Creative designs of fluorescent-protein biosensors have emerged and been used to measure the molecular dynamics of macromolecules, metabolites and ions. Recent applications of fluorescent-protein biosensors to biological problems have provided a foundation for their use in biotechnology.

Biosensing Techniques↗
PubMed1998

Isolation and characterization of the fungal metabolite 3-O-methylviridicatin as an inhibitor of tumour necrosis factor alpha-induced human immunodeficiency virus replication.

The cytokine tumour necrosis factor alpha (TNF-alpha) has been shown to play a role in human immunodeficiency virus (HIV) replication by activating transcription of the provirus in both T cells and macrophages. Therefore, agents that block TNF-alpha-induced HIV expression could have therapeutic value in the treatment of AIDS. We have sought to identify antiviral agents that block TNF-alpha induction of HIV LTR-directed transcription, using a cell-based, virus-free assay system in automated high-throughput screening. HeLa cells were transfected with an HIV LTR-luciferase reporter plasmid and a stable line was isolated in which TNF-alpha increased luciferase production by two- to threefold. This cell line was used to screen approximately 15,000 fungal extracts. An inhibitory activity specific for TNF-alpha-induced HIV LTR transcription was observed in culture OS-F67406. The active component was isolated and identified as a known metabolite, 3-O-methylviridicatin, by NMR and mass spectrometry. No biological activity has been associated with this compound previously. This compound blocks TNF-alpha activation of the HIV LTR in the HeLa-based system, with an IC50 of 5 microM, and inhibited virus production in the OM-10.1 cell line, a model of chronic infection responsive to induction by TNF-alpha, with an IC50 of 2.5 microM.

Anti-HIV Agents↗
PubMed1997

Effects of probenecid on the elicitation of spreading depression in the rat striatum.

Spreading depression (SD) is a wave of cellular depolarization which contributes to neuronal damage in experimental focal ischaemia, and may also underlie the migraine aura. The purpose of this study was to examine the effects of probenecid, an inhibitor of organic anion transport, on K+-evoked SD in vivo. Microdialysis electrodes were implanted in the rat striatum, and recurrent SD elicited by perfusion of artificial cerebrospinal fluid containing 160 mM K+ for 20 min. Probenecid was administered either directly through the microdialysis probe, starting 50 min before application of high K+, or intravenously. SD was markedly reduced by perfusion of 5 mM probenecid through the microdialysis probe. In contrast, a high intravenous dose of probenecid (250 mg/kg) only slightly inhibited SD elicitation 90 min after treatment, despite clear changes in the amplitude and spectrum of the electroencephalogram, as early as 10 min after drug administration, confirming that probenecid readily penetrated the central nervous system. As SD is inhibited by hypercapnia, we have examined the possibility that probenecid may inhibit SD through extracellular acidification subsequent to blockade of lactate transport. Perfusion of 1-20 mM probenecid increased dose-dependently the dialysate levels of lactate, but without extracellular acidosis since the dialysate pH was not significantly reduced. How probenecid inhibits SD deserves further investigation because it may help identify novel strategies to suppress this phenomenon, now recognized deleterious to neuronal function and survival.

Animals↗
PubMed1997

Independent, specialized invasions of ectomycorrhizal mutualism by two nonphotosynthetic orchids.

We have investigated the mycorrhizal associations of two nonphotosynthetic orchids from distant tribes within the Orchidaceae. The two orchids were found to associate exclusively with two distinct clades of ectomycorrhizal basidiomycetous fungi over wide geographic ranges. Yet both orchids retained the internal mycorrhizal structure typical of photosynthetic orchids that do not associate with ectomycorrhizal fungi. Restriction fragment length polymorphism and sequence analysis of two ribosomal regions along with fungal isolation provided congruent, independent evidence for the identities of the fungal symbionts. All 14 fungal entities that were associated with the orchid Cephalanthera austinae belonged to a clade within the Thelephoraceae, and all 18 fungal entities that were associated with the orchid Corallorhiza maculata fell within the Russulaceae. Restriction fragment length polymorphism and single-strand conformational polymorphism analysis of ectomycorrhizal tree roots collected adjacent to Cephalanthera showed that (i) the fungi associated internally with Cephalanthera also form typical external ectomycorrhizae and that (ii) ectomycorrhizae formed by other Basidiomycetes were abundant where the orchid grows but these fungi did not associate with the orchid. This is the first proof of ectomycorrhizal epiparasitism in nature by an orchid. We argue that these orchids are cheaters because they do not provide fixed carbon to associated fungi. This view suggests that mycorrhizae, like other ancient mutualisms, are susceptible to cheating. The extreme specificity in these orchids relative to other ectomycorrhizal plants agrees with trends seen in more conventional parasites.

Basidiomycota↗
PubMed1997

Traction forces of cytokinesis measured with optically modified elastic substrata.

Animal cells dividing in culture undergo a dramatic sequence of morphological changes, characterized by cytoskeletal disassembly as cells round up, redistribution of actin, myosins and other cytoplasmic and surface molecules into the cleavage furrow, and respreading, before daughter cells finally separate at the mid-body. Knowledge of forces governing these movements is critical to understanding their mechanisms, including whether formation of the cleavage furrow results from increased force generation at the equator or relaxation at the poles, and whether traction force subsequently mediates cytofission of the intercellular bridge. We have quantitatively mapped traction forces in dividing cells, by extending the silicone-rubber substratum method to detect forces of nanonewtons to micronewtons. We used a new silicone polymer to fabricate substrata whose compliance can be adjusted precisely by ultraviolet irradiation. We show that traction force appears locally at the furrow in the absence of relaxation at the poles during cleavage. Force also rises as connected daughter cells respread and attempt to separate, suggesting that tension contributes to the severing of the intercellular bridge when cytokinesis is completed.

3T3 Cells↗
PubMed1997

Comparison of a high power diode laser with the Nd:YAG laser using in situ wound strength analysis of healing cutaneous incisions.

BACKGROUND AND OBJECTIVE: The laser-tissue interaction of a high power semiconductor diode laser was compared to the continuous wave neodymium yttrium aluminum garnet (Nd:YAG) laser by evaluating primary wound healing of cutaneous incisions in rats. STUDY DESIGN/MATERIALS AND METHODS: Full thickness incisions were made in rat skin using a diode laser (805 nm, 10 W, contact mode), an Nd:YAG laser (1,064 nm, 10 W, contact mode), and a stainless steel scalpel blade (control). In situ wound breaking strength measurements were obtained at 7, 14, and 21 days using a specially designed tensiometer. Cross sectional area of non-disrupted wounds was calculated in two groups prior to testing to allow for calculation of tensile strength. Blinded histopathologic analysis was also performed. RESULTS: Analysis of variance (P < or = 0.05) was used to determine differences in breaking strengths and tensile strengths due to incision method. There was no significant difference in the breaking strengths (group 1) or tensile strengths (groups 2 and 3) of the diode and Nd:YAG laser incisions. As predicted, breaking strengths and tensile strengths of scalpel blade incisions were significantly greater than those of incisions made with laser energy. Histopathologic evaluation revealed that through day 14, the degree of inflammation and collagen production was similar for diode and Nd:YAG laser incisions. Laser incisions had greater inflammation and a lag in fibroblast invasion and collagen production compared with scalpel incisions. By day 21, all incisions were similar in fibroblast population and collagen production, but laser incisions had slightly more inflammation than scalpel incisions. CONCLUSION: In the primary wound healing model described, the tissue effect, cellular response, and development of wound strength were essentially the same for the high power diode laser at 10 W and the Nd:YAG laser at 10 W.

Animals↗
PubMed1997

Head and neck squamous cell growth suppression using adenovirus-p53-FLAG: a potential marker for gene therapy trials.

The recombinant wild-type p53 adenovirus has been proven effective against the growth of human head and neck squamous cell cancer (SCCHN) cell lines iir vitro and in a nude mouse model. The addition of a FLAG peptide sequence was used in this study, along with the p53 adenovirus vector as a marker of the site of the gene therapy activity. It provides clear evidence of the exogenous gene product within the transduced carcinoma cells. No alterations in transcription or translation of the p53 gene product were noted with the addition of the FLAG sequence to the original p53 adenovirus vector. Immunohistochemical analysis displayed simultaneous expression of the p53 and FLAG proteins in the infected cells. The p53 protein remained localized to the nucleus, whereas the FLAG protein was additionally noted in the cytoplasm. In vitro growth suppression assays and in vivo microscopic residual tumor model experiments in nude mice showed a similar tumoricidal effect with the p53-FLAG adenovirus vector to that with the previously studied p53 adenovirus vector without the addition of the FLAG sequence. We conclude that the addition of the FLAG octapeptide sequence allows identification of those cells that have been affected by the molecular therapy independent of the endogenous gene expression of the cells. This novel molecular tracer may prove useful in characterizing infection efficiency and in gene therapy trials.

Adenoviridae↗
PubMed1996

Changes in extracellular acid-base homeostasis in cerebral ischemia.

The purpose of this study was to examine the changes in extracellular CO32- and lactate concentration produced by ischemia, especially in relation to the occurrence of anoxic depolarization, and how some of these changes are altered by the inhibition of organic acid transport systems with probenecid. These data demonstrate that (i) the transmembrane mechanisms contributing to intracellular acid-base regulation (Na+/H+ and HCO3-/Cl- exchanges, and lactate/H+ cotransport) are markedly activated during ischemia; (ii) the efficacy of these mechanisms is abolished as the cellular membrane permeability to ions, including H+ and pH-changing anions, suddenly increases with anoxic depolarization; and (iii) efflux of intracellular lactate during ischemia, and its reuptake with reperfusion, mainly occur via a transporter. These findings imply that residual cellular acid-base homeostasis persists as long as cell depolarization does not occur, and strengthen the concept that anoxic depolarization is a critical event for cell survival during ischemia.

Acid-Base Equilibrium↗
PubMed1996

Myosin II transport, organization, and phosphorylation: evidence for cortical flow/solation-contraction coupling during cytokinesis and cell locomotion.

The mechanism of cytokinesis has been difficult to define because of the short duration and the temporal-spatial dynamics involved in the formation, activation, force production, and disappearance of the cleavage furrow. We have investigated the structural and chemical dynamics of myosin II in living Swiss 3T3 cells from prometaphase through the separation and migration of daughter cells. The structural and chemical dynamics of myosin II have been defined using the semiautomated, multimode light microscope, together with a fluorescent analogue of myosin II and a fluorescent biosensor of myosin II regulatory light chain (RLC) phosphorylation at serine 19. The correlation of image data from live cells using different modes of light microscopy allowed interpretations not possible from single-mode investigations. Myosin II transported toward the equatorial plane from adjacent regions, forming three-dimensional fibers that spanned the volume of the equator during anaphase and telophase. A global phosphorylation of myosin II at serine 19 of the RLC was initiated at anaphase when cortical myosin II transport started. The phosphorylation of myosin II remained high near the equatorial plane through telophase and into cytokinesis, whereas the phosphorylation of myosin II at serine 19 of the RLC decreased at the poles. The timing and pattern of phosphorylation was the same as the shortening of myosin II-based fibers in the cleavage furrow. Myosin II-based fibers shortened and transported out of the cleavage furrow into the tails of the two daughter cells late in cytokinesis. The patterns of myosin II transport, phosphorylation, and shortening of fibers in the migrating daughter cells were similar to that previously defined for cells migrating in a wound in vitro. The temporal-spatial patterns and dynamics of myosin II transport, phosphorylation at serine 19 of the RLC, and the shortening and disappearance of myosin II-based fibers support the proposal that a combination of the cortical flow hypothesis and the solation-contraction coupling hypothesis explain key aspects of cytokinesis and polarized cell locomotion.

3T3 Cells↗
PubMed1996

MDL 74,968, a new acyclonucleotide analog: activity against human immunodeficiency virus in vitro and in the hu-PBL-SCID.beige mouse model of infection.

The novel acyclonucleotide derivative of guanine, 9-[2-methylidene-3-(phosphonomethoxy)propyl] guanine (MDL 74,968), had antiviral activity comparable to those of 9-(2-phosphonomethoxyethyl) adenine (PMEA) and 2',3'-dideoxyinosine against laboratory strains of both human immunodeficiency virus (HIV) types 1 and 2 cultured in MT-4 cells and several clinical HIV isolates cultured in human peripheral blood mononuclear cells (PBMCs). MDL 74,968 was at least fourfold less toxic than PMEA to MT-4 cells or PBMCs, thereby producing a more favorable in vitro selectivity index for the former compound. Studies of acute toxicity in CD-1 mice showed that MDL 74,968 was not toxic at doses of 1,600 mg/kg of body weight via the intraperitoneal route or at doses of 500 mg/kg via the intravenous route. Furthermore, no adverse effects of MDL 74,968 were apparent when mice were treated at doses of 200 mg/kg twice daily for 5 days. Treatment by continuous subcutaneous infusion of MDL 74,968 or PMEA at the daily dose of 20 mg/kg in the hu-PBL-SCID.beige murine model of HIV infection significantly reduced the severity of infection compared with that in placebo-treated controls. Quantitation of virus recovery by endpoint titration of spleen cells in coculture with mitogen-activated PBMCs demonstrated that MDL 74,968 as well as PMEA significantly reduced the amount of virus (P < 0.02). Moreover, by using DNA extracted from spleens, the mean HIV:HLA PCR product ratio, which takes into account individual variation in immune system reconstitution, were 0.50 and 0.40 for MDL 74,968 and PMEA treatments, respectively, whereas animals receiving the placebo control had significantly higher levels of HIV proviral DNA (mean 0.78; P < 0.02). Taken together, these promising findings suggest that an orally bioavailable prodrug of MDL 74,968 should be developed for the treatment of HIV infection.

Adenine↗