Effects of food or sleep deprivation during civilian survival training on clinical chemistry variables.

Objective: To describe clinical chemistry and weight changes after short-term food or sleep deprivation or multiple deprivations during civilian survival training.

Methods: Data from one baseline-controlled two-period crossover study designed to compare sleep deprivation for up to 50 hours with food deprivation for up to 66 hours (n = 12) and data from regular multiple-deprivations survival training comparing participants (n = 33) with nondeprived instructors (n = 10).

Results: Food deprivation was associated with decreased body weight, blood glucose, serum triglycerides, sodium, chloride, and urine pH, and there were increases in blood and urine ketones and serum free fatty acids.

Effect of probenecid and quinidine on the transport of alovudine (3'-fluorothymidine) to the rat brain studied by microdialysis.

Microdialysis was used to sample extracellular unbound concentrations of alovudine in order to study the influence of well-known transport inhibitors (probenecid and quinidine) on the transport of alovudine between the blood and the brain extracellular fluid or whole brain tissue. The AUC (area under the time versus concentration curve) ratio brain extracellular fluid/serum was 0.17+/-0.

Neoglycolipid conjugates of foscarnet with enhanced antiviral activity in cells infected with human cytomegalovirus and herpes simplex virus type 1.

The synthesis of a series of neoglycolipid conjugates of foscarnet as potential drug targeting forms or lipophilic prodrugs of foscarnet is described. The compounds were obtained from suitably protected neoglycolipids, in which the lipid chain consisted of 12 to 20 carbon atoms, by ethoxycarbonylphosphonylation at the 6-hydroxyl or 4-hydroxyl group followed by deprotection. The in vitro antiviral activity of the compounds was determined in human foetal lung cells infected with human cytomegalovirus (HCMV) or herpes simplex virus type 1 (HSV-1).

Study of the adjuvant activity of new MDP derivatives and purified saponins and their influence on HIV-1 replication in vitro.

Muramyl dipeptide (MDP), eight new lipophilic MDP derivatives (MDPs) and three purified saponins were evaluated for their ability to induce immune responses in mice immunized with HIV-1 envelope protein rgp160 and for their ability to influence the HIV-1 replication in vitro. Three of nine new synthetic MDP derivatives (beta-butyl-MDP, MTPO-26 and beta-cholesteryl-MDP) and one saponin (Taurosid I) have been shown to induce strong humoral immune responses to HIV-1 envelope glycoproteins rgp160 and rgp120. Three substances (beta-butyl-MDP, MDP-cholyl and beta-G27-MDP) induced high levels of T-cell stimulation to HIV-1 rgp160.

Pharmacokinetics and extracellular distribution to blood, brain, and muscle of alovudine (3'-fluorothymidine) and zidovudine in the rat studied by microdialysis.

Microdialysis was applied to sample the free drug concentration in the extracellular fluid in brain, muscle, and blood of rats given alovudine (n = 6) (3'-fluorothymidine) or zidovudine (n = 5) (25 mg/kg s.c.).

Effect of resistance on combination chemotherapy for human immunodeficiency virus infection.

The effect of 3 drug combinations (AZT/FLT, AZT/ddI and FLT/ddI) upon the replication of AZT-sensitive and -resistant human immunodeficiency virus (HIV) was studied. The 3 combinations synergistically inhibited drug sensitive virus. However, AZT resistant virus showed an altered response to the combinations containing AZT: synergy was replaced by addition or antagonism.

Penetration of zidovudine and 3'-fluoro-3'-deoxythymidine into the brain, muscle tissue, and veins in cynomolgus monkeys: relation to antiviral action.

Cynomolgus monkeys had microdialysis probes implanted under ketamine anesthesia into peripheral veins, thigh muscles, and the brain in order to sample the extracellular fluid for the concentrations of unbound nucleoside analogs. A dose of 25 mg of zidovudine or 3'-fluoro-3'-deoxythymidine (FLT) per kg was administered subcutaneously to each of three animals. Relatively high antiviral concentrations of FLT and zidovudine were present in peripheral tissues and in the brain.

Early appearance of simian immunodeficiency virus (SIV) antigen and antibodies as variables in evaluating antiviral drugs in macaques.

SIV infection in macaques has become an important animal model for HIV-1 infection in humans. An antibody assay was therefore developed and compared to a commercially available antigen assay with respect to their usefulness to monitor the course of simian immunodeficiency virus (SIV) infection in cynomolgus monkeys. A peptide, JB6T, consisting of 21 amino acids with the sequence NSWGCAFRQVCHTTVPWVNDS corresponding to a segment in the env protein of human immunodeficiency virus (HIV) type 2 was used as antigen in an enzyme-linked immunosorbent assay (ELISA).

Antiviral effects of 3'-fluorothymidine and 3'-azidothymidine in cynomolgus monkeys infected with simian immunodeficiency virus.

An acute infection with simian immunodeficiency virus (SIVSM) in cynomolgus monkeys was used to evaluate the antiviral effects of 3'-fluorothymidine (FLT) and 3'-azidothymidine [zidovudine (ZDV)]. Neither compound prevented the infection despite dosing prior to virus inoculation. FLT was about ten times more potent than ZDV in delaying the appearance of SIVSM antigen in the monkeys.

Search for epitopic sites of antibodies to germ cell alkaline phosphatase.

This study comprises a search for epitopic sites of the germ cell alkaline phosphatase by the use of polyclonal and monoclonal antibodies. The aim of this study was to define epitopes of the germ cell alkaline phosphatase molecule by synthetic peptides representing the known sequence of the molecule. The amino acid sequences of the epitopes to which antisera react were not known.

Isoenzymes of alkaline phosphatases in seminomas. An immunohistochemical and biochemical study.

Placental alkaline phosphatase (the PLAP-like isoenzyme) and liver alkaline phosphatase (LAP) were demonstrated immunohistochemically by use of monoclonal antibodies in the tumor cells of twelve seminomas and one seminoma metastasis. Intestinal alkaline phosphatase (IAP) was not found. The PLAP-like and LAP enzymes showed high catalytic activities compared to normal testis.

Significance of alkaline phosphatase isozymes in the monitoring of patients with colorectal carcinoma.

The clinical course of colorectal carcinoma may be monitored by tumor markers such as carcinoembryonic antigen (CEA), carcinoma antigen (CA) 19-9 and CA-50. Alkaline phosphatase isozymes were previously used to study the clinical course of testicular and gynecologic tumors. In this study we investigated 8 patients with advanced colorectal carcinoma.

Patterns of seminoma tissue markers and deletions.

Seminomas and control tissues were analyzed for several tumor markers. Very high levels of placental alkaline phosphatase (PLAP)-like enzyme levels were found in all 18 seminomas studied. The majority of the seminomas were of phenotype I, thus differing from palcental PLAP.

Improved radioimmunolocalization of carcinomas using Fab fragments with anti-CEA specificity.

A model system with human colonic grafts containing carcinoembryonic antigen (CEA) in nude mice was used to improve specificity and sensitivity of the radioimmunolocalization method. Monoclonal antibody MAb I-38S1 and monkey anti-CEA appeared to have high in vitro and in vivo specificity. Fab fragments of MAb I-38S1 improved localization ratios.