Disease relevance of Human Experimentation

• IMPLICATIONS: Based on the recent observation of others that IL-10 has little toxicity when administered systemically to human volunteers and also on the findings of this study that it has antitumor and antimetastitic properties in mice, possible use of IL-10 in the treatment of human metastatic cancers deserves consideration [1].
• Pteroylglutamic acid, 10 microgram/ml, added to wines and given in doses of the beverages (4 ml/kg body weight that caused inebriation, was well absorbed by six normal human volunteers (mean maximal increment in serum folate concentration +/- SEM, 71 +/- 8 ng/ml) and by seven recently intoxicated chronic alcoholics (mean increment, 94 +/- 4 ng/ml) [2].
• After experimental endotoxemia in human volunteers, IL-1ra concentrations increase from a baseline concentration of 460 +/- 200 pg mL-1 to 14,870 +/- 290 pg mL-1 at 3 hours (P less than .05) [3].
• Seronegative human volunteers were immunized with a purified recombinant form of the HIV-1 envelope glycoprotein gp160 in a phase I vaccine trial [4].
• It has been reported that approximately one-third of human volunteers, smokers and nonsmokers, exhibit immediate cutaneous hypersensitivity to a glycoprotein antigen (TGP) purified from cured tobacco leaves and present in cigarette smoke [5].

Psychiatry related information on Human Experimentation

• The effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state [6].
• The effect of total sleep deprivation on plasma melatonin and cortisol in healthy human volunteers [7].
• Within a residential research ward, five human volunteers with histories of sedative drug abuse were exposed to progressive-ratio schedules of pentobarbital (200, 400, 600 mg) or placebo self-administration [8].
• Improved short-term spatial memory but impaired reversal learning following the dopamine D(2) agonist bromocriptine in human volunteers [9].
• The beta-carboline ZK 93,426, a benzodiazepine-antagonist with weak inverse agonist activity, was administered intravenously to human volunteers at a dose of 0.04 mg/kg when they initially reached slow-wave sleep during their night's sleep [10].

High impact information on Human Experimentation

• An attempt was made to isolate and identify the organisms capable of reducing digoxin from stool cultures obtained from human volunteers [11].
• Since the activity of testosterone reductases is rate limiting for testosterone metabolism in the liver, the effect of prolonged ethanol consumption by rats and human volunteers on the activities of these microsomal and cytosolic enzymes was studied [12].
• When charcoal-broiled beef was fed to human volunteers, who were then given phenacetin orally, the concentration of phenacetin in the plasma was lowered, but its half-life in the plasma was not changed [13].
• Physostigmine (an anticholinesterase agent that increases acetylcholine at the synapse), in a dose of 0.5 milligram, was given intravenously to seven normal human volunteers [14].
• In this issue of Immunity, Walther et al. have now shown that following experimental malaria infection of human volunteers, enhanced TGF-beta and T reg responses are associated with a faster parasite growth rate [15].

Chemical compound and disease context of Human Experimentation

• The extent to which topical and intradermal corticosteroids and topical indomethacin suppress sunburn erythema was investigated in human volunteers [16].
• The effect of the novel streptogramin antibiotic quinupristin/dalfopristin (synercid) on cytokine production in vitro was examined in monocytes obtained from healthy human volunteers and stimulated with either lipopolysaccharide or heat-killed Staphylococcus aureus (Pansorbin) [17].
• Serogroup Y and W135 Neisseria meningitidis capsular polysaccharide vaccines were tested as monovalent and divalent preparations in groups of 10 adult human volunteers at a dose of 50 (monovalent) or 100 micrograms (divalent) injected subcutaneously [18].
• The ability of leukotriene B4 to reproduce the inflammatory events of psoriasis, by topical application to the skin of normal human volunteers, was thus studied [19].
• Intestinal endogenous members of the family Enterobacteriaceae were eliminated in 12 human volunteers treated with 400 or 800 mg of oral norfloxacin per day for 5 days [20].

Biological context of Human Experimentation

• After experimental infection of human volunteers with a gonococcal variant incapable of inducing CD46 down-regulation, variants of this strain were reisolated that exhibited CD46 down-regulation [21].
• In eight healthy human volunteers, MSNA, RR interval, intra-arterial pressure, and respiration were measured during blood pressure reductions induced by nitroprusside and during blood pressure increases induced by phenylephrine [22].
• Platelet function and blood coagulation were studied in five human volunteers receiving penicillin-G in incremental doses of 1.2--48 million U/day, in six volunteers receiving ampicillin in incremental doses of 60--300 mg/kg/day (4--20 g/day), and in six volunteers receiving methicillin in incremental doses of 60--300 mg/kg/day [23].
• In humans, renin inhibition led to a larger increase in renal plasma flow in healthy human volunteers studied on a low salt diet to activate the renin system than did ACE inhibitors [24].
• The bioavailability of various formulations of digoxin was assessed after single and multiple doses in a series of crossover studies in human volunteers [25].

Anatomical context of Human Experimentation

• Skeletal muscle CoA and carnitine metabolism were investigated in six human volunteers at rest and after exhaustive exercise under normoxic and hypoxic conditions [26].
• In 6 human volunteers, both plasma secretin concentration and pancreatic bicarbonate output significantly increased when 2% 1-phenyl-1-hydroxy-N-pentane solution, 30 ml/30 min, was infused in the upper jejunum [27].
• In contrast to studies by other investigators, it was observed that epidermal cells isolated from flexor forearm skin of normal adult human volunteers are consistently superior to autologous peripheral blood mononuclear cells in triggering allogeneic lymphocytes to undergo blastogeneic transformation [28].
• In contrast to IL-1alpha and IL-1beta, immunoreactive IL-1ra was readily detected in the nasal washings of normal human volunteers [29].
• In healthy human volunteers, a single oral dose of enprostil (35 micrograms) inhibited basal gastric acid output by a mean of 71 percent, pentagastrin-stimulated output by 46 percent, sham-meal-stimulated output by 48 percent, and histamine-stimulated output by 16 percent [30].

Associations of Human Experimentation with chemical compounds

• In rats, long-term ethanol ingestion doubled microsomal 5alpha-testosterone reductase activity, a major pathway for testosterone metabolism, while in human volunteers the activity was increased two- to fivefold [12].
• These glucose anomers were dissolved rapidly and administered intravenously to human volunteers at a high dose (0.5 g/kg) over a 3-min period or a low dose (3.5 g) over a 20-s period [31].
• We studied the incorporation and metabolism of eicosapentanoic (EPA) and docosahexaenoic acid in six human volunteers who supplemented their normal Western diet for 5 mo daily with 10-40 ml of cod liver oil, rich in omega-3 polyunsaturated fatty acids [32].
• After infusion of G17 intravenously in normal human volunteers, COOH-terminal and NH2-terminal immunoreactive G17 fragments were generated [33].
• METHODS: Serum levels of the markers 7alpha-hydroxy-4-cholesten-3-one (C4) monitoring bile acid biosynthesis and lathosterol reflecting cholesterol synthesis were determined at 90-minute intervals in 8 human volunteers during standardized dietary conditions [34].

Gene context of Human Experimentation

• We investigated whether AMD3100, a selective CXCR4 antagonist, could mobilize hematopoietic progenitor cells from marrow to peripheral blood in healthy human volunteers [35].
• (111)In-Labeled diethylene-triamine-pentaacetate derivatives of minigastrin showed excellent targeting of CCK-B receptor-expressing tissues in animals and a normal human volunteer [36].
• The plasma hCRF-BP level was 0.9 +/- 0.08 nmol/L in normal human volunteers (10 men and 9 women; mean +/- SD age, 74.2 +/- 7.7 yr), decreased to 60% of basal levels 15 min after a bolus injection of 1 microgram/kg synthetic hCRF, and gradually returned to preinjection levels after 120 min [37].
• BACKGROUND: We have been studying the innate immune response of airways cells of healthy human volunteers to inhaled LPS, a Toll-like receptor 4 (TLR4) ligand, and have shown that macrophage phagocytic capacity is blunted [38].
• METHODS: The involvement of CYP2E1 was assessed through pretreatment of adult human volunteers with disulfiram to inhibit the enzyme and the role of CYP3A4 through its induction in a second cohort of adults with rifampin (INN, rifampicin) [39].

Analytical, diagnostic and therapeutic context of Human Experimentation

• The effect of the administration of the antibiotic neomycin sulfate on the absorption of digoxin was assessed in crossover studies in normal human volunteers [40].
• The plasma concentration of alpha 1-acid glycoprotein, a putative endogenous inhibitor of the site labeled by tritiated imipramine, was measured by a radial immunodiffusion assay in 36 normal human volunteers and 51 drug-free patients who fulfilled DSM-III criteria for major depression [41].
• A single oral administration of 240 mg ES-8891 to healthy human volunteers (n = 6) produced a significant inhibition of plasma renin activity (75% inhibition at 0.5 and 1 hour, 50% inhibition at 2 hours) with a good correlation of plasma levels of ES-8891 [42].
• In addition, healthy human volunteers drank grapefruit juice, and the ratio of cortisone to cortisol in their urine was measured by HPLC and used as an index of endogenous enzyme activity [43].
• Regional kinetic constants and cerebral metabolic rate for glucose in normal human volunteers determined by dynamic positron emission tomography of [18F]-2-fluoro-2-deoxy-D-glucose [44].

References