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Biomedical subjects

R H Carpenter

Publications and source records attributed to R H Carpenter.

At least 37 records · Page 2Linked to original sources

Co-variability of smooth and saccadic latencies in oculomotor pursuit.

Latencies of smooth pursuit and saccadic eye movement responses to a horizontal ramp target show considerable random variation from trial to trial, which is uncorrelated between the two types of response. This implies that the functional pathways that are responsible for most of the delay in each case are essentially independent.

Eye Movements↗

Beyond the Darrow-Yannet diagram: an enhanced plot for body fluid spaces and osmolality.

The C-plot is a new method of plotting the volumes and osmolality of extracellular and intracellular body fluids, which in many circumstances is an improvement on the classical Darrow-Yannet diagram. The C-plot allows natural perturbations to be seen easily, and enables the relation between threats to fluid homoeostasis and the physiological mechanisms that counter those threats to be appreciated. The course of such events can also be shown in a single diagram.

Body Fluid Compartments↗

Distribution of quick-phase intervals in optokinetic nystagmus.

The distribution of the intervals between quick phases in optokinetic nystagmus shows the same general characteristics as saccadic latency to visual targets and as congenital nystagmus. In each case, for intervals of 150 ms and above, the distribution of reciprocal latency is normal; at shorter intervals, there may be a second component equivalent to 'express' saccades.

Humans↗

Subchronic oral administration of acemannan in the rat and dog.

Acemannan is the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed O-acetyl groups, with a mannose monomer/acetyl ratio of approximately 1:1. This complex polysaccharide is extracted from Aloe vera (barbadensis Miller); the technical material contains approximately 78% acemannan. Technical grade acemannan was administered po to rats for 14 d at 5% of the diet and for 6 mo at up to 2,000 mg/kg/d, and to beagle dogs for 90 d at up to 1,500 mg/kg/d without significant effect on any parameter measured in either species.

Administration, Oral↗

Toxicologic evaluation of injectable acemannan in the mouse, rat and dog.

Acemannan, the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed 0-acetyl groups with a mannose monomer/acetyl ratio of approximately 1:1 and extracted from Aloe vera (barbadensis Miller), was administered as a 1.0 mg/ml solution to mice, rats and dogs, either as single dose or repeated at 4-d intervals for 8 doses by iv or ip routes. No significant signs of intoxication and no deaths occurred in animals treated with the single injection of acemannan at dosages of 80 mg/kg iv or 200 mg/kg ip in mice, 15 mg/kg iv or 50 mg/kg ip in rats, and 10 mg/kg iv or 50 mg/kg ip in dogs. On repeated injections systemic toxicity was limited to obvious transient discomfort that appeared dose related. There was accumulation of macrophages and monocytes without subsequent inflammatory reaction in lungs of the iv-treated animals, and in liver and spleen and on peritoneal surfaces of ip-treated animals. The effects were not considered adverse, but were consistent with the known immune stimulating activity of acemannan. A few deaths occurred in mice and rats that were suggestive of resulting from improper injection or sequella of necrosis of the injection site. The NOAELs for acemannan determined from these repeated injection studies were 20 mg/kg iv or ip in the mouse, 4.0 mg/kg iv and 50 mg/kg ip in the rat, and 1.0 mg/kg iv in dogs; 5.0 mg acemannan/kg ip in the dog was considered to be LOAEL, based on the emesis and abdominal discomfort induced.

Animals↗

In vitro evaluation of the synergistic antiviral effects of acemannan in combination with azidothymidine and acyclovir.

The antiviral effects of selected combinations between acemannan (ACE-M), a long-chained, polydispersed, beta-(1,4)-acetylated mannan, were tested in combination with azidothymidine (AZT) and acyclovir (ACY) in vitro. The rationale for such combinations was based on the antiviral and immunomodulatory properties exhibited by ACE-M. In addition, the observed antiviral effects of ACE-M against human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses appear to be related to modification of the glycosylation of viral glycoproteins. Therefore, the inhibitory effect of ACE-M does not overlap with that of AZT or ACY. The studies presented herein show that ACE-M combined with suboptimal noncytotoxic concentrations of AZT or ACY act synergistically to inhibit the replication of HIV-1 and herpes simplex virus type 1 (HSV-1), respectively. The median effect method was not applicable for analysis because the test compounds show mutually nonexclusive drug effects. For a meaningful evaluation and interpretation of the effects of drug combinations, the biological significance of combinations must be considered, that is, the protective effect of the combination, the noncytotoxicity of the combination, the mechanism(s) of action of the individual compounds comprising the combination, and so forth. With respect to effects on U1 cells latently infected with HIV-1, treatment with combinations of AZT and ACE-M does not potentiate virus replication.

Acyclovir↗

Inhibition of AIDS virus replication by acemannan in vitro.

Acemannan (ACE-M), a beta-(1,4)-linked acetylated mannan, was evaluated for in vitro activity against human immunodeficiency virus type 1 (HIV-1). Castanospermine (CAS), deoxymannojirimycin (DMN), swainsonine (SWS), azidothymidine (AZT), and dideoxythymidine (DDC) were tested in parallel as control compounds. In vitro antiviral efficacy of ACE-M was evaluated in a variety of cell lines including human peripheral mononuclear, CEM-SS1 and MT-2(2) cells. The virus strain, number of infectious units per cell, and target cell line were important factors in determining the degree of inhibition of viral cytopathic effect in the presence of ACE-M and other control compounds tested. Maximum inhibitory effect was observed in CEM-SS cells infected with the RFII strain of HIV-1. This inhibitory effect was determined to be concentration-dependent. Assay design included primary screening to measure cell viabilities of infected target cells in the presence and absence of test compounds. When tested on HIV-1/RFII-infected CEM-SS cells, the 50% inhibitory effect of CAS (IC50 = 28), an inhibitor of alpha-glucosidase I, was determined to be similar to that observed for ACE-M (IC50 = 45). However, DMN and SWS, inhibitors of mannosidase I and II, tested in parallel to CAS and ACE-M, exhibited no IC50 values. Antiviral potential of ACE-M as an inhibitor of syncytia formation was also explored using CEM-SS cells. Suppression of syncytia formation was observed at an ACE-M concentration of 31.25 micrograms/ml, and complete inhibition was observed at 62.5 micrograms/ml. In addition, HIV-1 RNA levels were studied to establish the antiviral potential of ACE-M in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiviral Agents↗

The biological activities of mannans and related complex carbohydrates.

Complex polymers containing mannose (mannans) possess significant biological activity when administered to mammals. When given orally, they inhibit cholesterol absorption and induce hypocholesterolemia. If administered by other routes, they bind to mannose-binding proteins and induce macrophage activation and interleukin-1 release, inhibit viral replication, stimulate bone marrow activity, promote wound healing and inhibit tumor growth. This range of activities makes the mannans, potentially important biological-response modifiers and therapeutic agents.

Animals↗

Automated and manual quantitative assays of choriogonadotropin in serum compared.

We found the analytical performance of a rapid, automated assay of human choriogonadotropin (hCG) in serum, the Stratus hCG Fluorometric Enzyme Immunoassay, superior to a widely used manual assay for hCG (Hybritech Tandem-E hCG). The two assays were comparable in sensitivity; recovery; cross reactivity with lutropin, follitropin, and thyrotropin; and freedom from interference from hemoglobin and bilirubin. Patient-correlation studies indicated good quantitative agreement [Stratus hCG = (1.08 X Tandem hCG) - 4.3 int. units/L]. However, intra- and interassay precision was substantially better with the Stratus hCG assay, and this may allow earlier confirmation of pregnancy.

Antibodies, Monoclonal↗

Response of anestrous ewes to norgestomet and PMSG.

A 10-day treatment regime with a subcutaneous ear implant containing 3 mg of norgestomet, accompanied by an intramuscular injection of 1.5 mg norgestomet and 0.5 mg estradiol valerate (EV) on day 1 and 750 I. U. pregnant mares serum gonadotropin (PMSG) given intravenously on day 10, proved effective in eliciting estrus in 72% of 110 anestrous ewes within 5 days of treatment. Ewes which were treated in months closer in proximity to the normal breeding scason responded with significatly increased induction of estrus, with 71, 37, 59, 74, and 97% in estrus for ewes which were treated in February through June, respectively. Comparable estrous response in nontreated, control ewes was 0, 13, 0, 10, and 24% during February through June, respectively. (Treated vs controls, P<.01). Pregnancy rate to first service of ewes in estruc was 51% in treated and 30% in control ewes (P>.10). Overall pregnancy rate for all ewes in both groups was 36% in treated and 3% in control ewes during 5 or 16 days of breeding, respectively (P<.01).

Journal Article↗

Estrus and pregnancy rates following synchronization with chronolone intravaginal sponge or norgestomet ear implant in cycling ewes.

Two experiments were conducted to evaluate the efficacy of a 3-mg ear implant of norgestomet, left in situ for 10 days, in conjunction with a single injection of 1.5 mg norgestomet and 0.5 mg estradiol valerate (EV) for controlling fertile estrus in the ewe. This treatment regime was compared with a 20-mg cronolone impregnated, intravaginal sponge left in situ for 14 days (Experiment 1) and a modification of the cronolone-sponge-treatment to include a single injection of 1.5 mg norgestomet and 0.5 mg EV (Experiment 2). The percentage of ewes synchronized was not significantly affected by progestin treatment (Experiment 1-cronolone pessary alone, 96%; norgestomet implant and injection of norgestomet and EV, 92%; Experiment 2-cronolone pessary + injection of norgestomet and EV, 84%; Norgestomet implant + injection of norgestomet and EV, 96%). In Experiment 1, the first service pregnancy rate (pregnant of ewes mated) of 80% for cronolone-treated ewes was significantly higher than the 59% observed in norgestomet-treated ewes (P<.05). In Experiment 2, no significant differences were observed in pregnancy rates between the two treatment groups (Cronolone, 57%; Norgestomet, 65%).

Journal Article↗

Synchronized breeding of cycling ewes to produce fetuses of known gestational age.

A treatment regime involving a subcutaneous ear implant containing 3 mg of 17 alpha-acetoxy-11 beta-methyl-19-nor-preg-4-ene-3,20,dione (norgestomet) accompanied by an intramuscular injection of 1.5 mg norgestomet and 0.5 mg estradiol valerate proved effective for synchronizing estrus in the cycling ewe. Pregnancy rates were equivalent to those of control ewes mated concurrently. Sixty-two percent of all treated ewes became pregnant at the synchronized estrus. The initiation of the treatment regime was scheduled to allow delivery of fetuses of a specified age on the date requested by the investigator.

Animals↗