Some bio-medical mechanisms in athletic prowess.

Variations in somato-genetic patterns in muscle-fibre biology, biochemical metabolic pathways and pulmonary physiology are hypothesized to have been concentrated by natural selection over the centuries in the Afrocentric peoples displaced from West Africa to the New World. These phenotypic and genotypic characteristics are attributed to provide the athletic prowess so well documented in African-Americans. Not the least of coincidence seems to be the influence of the compensatory mechanisms on oxygen transport and its availability to the tissues, in response to the sickle cell gene. The reduced availability coupled with reduced myoglobin in the preponderant fast-twitch muscle fibres which are adapted for rapid energy (ATP) regeneration, all give a NET outcome of muscle anatomical and biochemical advantages which support outstanding performances in athleticism.

Adjuvant effect of gamma-inulin is mediated by C3 fragments deposited on antigen-presenting cells.

The adjuvant effect of gamma-inulin, a strong activator of the alternative complement pathway, is well-known, but its exact mechanism is not revealed yet. Here, we show that macrophages, isolated from the peritoneal cavity of gamma-inulin-injected mice and used as antigen-presenting cells, enhance the proliferation of antigen-specific T-cells up to 2.5-fold when compared with macrophages of non-treated animals. This effect is abrogated by the presence of anti-C3 F(ab')2 fragments and by prior decomplementation of the donor animals with CVF. It is demonstrated that treatment of mice with the adjuvant results in deposition of C3-fragments onto the surface of peritoneal macrophages, as does in vitro incubation of the cells with gamma-inulin in the presence of fresh autologous serum. Prior incubation of macrophages with gamma-inulin plus serum in vitro enhances subsequent C3 production. Because it has been shown earlier that CR1/2 expressed on activated T-cells and interacting with covalently bound C3-fragments plays an important role in the augmentation of the adaptive response, our present results reveal a mechanism that contributes to the adjuvant effect of gamma-inulin and point to a further link between innate and adaptive immunity.

Anti-complementary action of polymorphic "solubility forms" of particulate inulin.

Inulin crystallizes in a series of polymorphic forms with different solubility rates, ranging from one instantly soluble at 23 degrees C (beta 0(23) inulin) through a form soluble at 37 degrees C with a half-time of 8 min (alpha 8(37) inulin) to a form virtually insoluble at 37 degrees C (gamma inulin). All forms are interconvertible, the more soluble and unstable progressing on standing to less soluble and more stable forms, only reversible by complete solution followed by recrystallization. The end product is the stable gamma inulin, only formed by polymers greater than 8000 mol. wt. A method is given for preparing pure "gamma inulin for injection", comprising insoluble ovoids of less than 1 micron diameter free of soluble inulin and endotoxin. An assay developed for complement action by the alternative pathway showed that gamma inulin was the most potent activator polymorph, more active than killed S. aureus and zymosan. Dissolved inulin and the more soluble polymorphs were inactive and in a mixture hindered alternative pathway activation by the gamma form.

The anti-melanoma activity of inulin in mice.

Finely divided, insoluble inulin (gamma polymorph), given intraperitoneally (i.p.) to C57BL mice 1-3 days after i.p. B16 melanoma cells, very significantly increased their mean survival time (MST) in low doses (less than or equal to 40 and less than or equal to 100 micrograms/mouse in 50 and 80% of tests, respectively). The gamma inulin was pure and free of endotoxin and soluble inulin, and was developed as a potent reagent specific for activating the alternative pathway of complement (APC). Its antitumour action paralleled its in vitro APC activation, namely, both activities were sharply dose-dependent up to a threshold dose above which they were dose-independent; dissolved inulin was inactive in vitro and in vivo, decreased the MST of the mice and in a mixture antagonized the in vitro and in vivo activities of gamma inulin; the more soluble (alpha) polymorphs were active in proportion to their gamma content but the effects were blocked at higher doses presumably by dissolved inulin. In addition, depletion of host APC with cobra venom factor or inulin before giving B16 cells increased their malignancy and abrogated the subsequent antitumour action of gamma inulin. The minimum i.p. dose of gamma inulin found to activate serum APC in vivo was 50 micrograms (2.5 mg/kg), i.e. close to the minimum antitumour dose. These close correlations and the specificity of the reagent indicate that activation in vivo of the APC (cellular or humoral) is an important first contact in stimulating host antitumour defences in this mouse model.

Acetylenics. 2. Synthesis and pharmacology of certain N,N-diakyl-3-phenylpropyn-2-amines. Some analogues with tryptamine-like behavioral effects in mice.

A number of N,N-dialkyl-3-phenylpropyn-2-amines 7 have been prepared and tested for their biological action. Certain analogues show tryptamine-like behavior effects in mice. The tryptamine-like activity of these compounds appears to be controlled by their lipophilicity. These compounds show only weak inhibition of rat liver monoamine oxidase. Although these compounds exhibit tryptamine-like action, experiments seem to indicate that there is no interaction with the tryptamine receptors.

Algammulin (gamma inulin/alum hybrid adjuvant) has greater adjuvanticity than alum for hepatitis B surface antigen in mice.

Algammulin is a new vaccine adjuvant comprising a stable suspension of 1-2 microns ovoids of the immune stimulant gamma inulin in which alum (Alhydrogel) is embedded as a protein carrier. Adjuvanticity tests in mice with Algammulin show that the presence of gamma inulin on the alum particles has synergistically enhanced their adjuvanticity for low doses of hepatitis B surface antigen. The primary-response titres of HBsAg-specific antibody from a given low dose of alum injected as Algammulin were 3- to 5.6-fold greater than those from the same alum dose injected as free alum. This corresponds closely with more extensive previous work using keyhole limpet haemocyanin as antigen.

The production of oxidants in Europa's surface.

The oxidants produced by radiolysis and photolysis in the icy surface of Europa may be necessary to sustain carbon-based biochemistry in Europa's putative subsurface ocean. Because the subduction of oxidants to the ocean presents considerable thermodynamic challenges, we examine the formation of oxygen and related species in Europa's surface ice with the goal of characterizing the chemical state of the irradiated material. Relevant spectral observations of Europa and the laboratory data on the production of oxygen and related species are first summarized. Since the laboratory data are incomplete, we examine the rate equations for formation of oxygen and its chemical precursors by radiolysis and photolysis. Measurements and simple rate equations are suggested that can be used to characterize the production of oxidants in Europa's surface material and the chemical environment produced by radiolysis. Possible precursor molecules and the role of radical trapping are examined. The possibility of oxygen reactions on grain surfaces in Europa's regolith is discussed, and the earlier estimates of the supply of O(2) to the atmosphere are increased.

Use of gamma-inulin/liposomes/Vitamin E adjuvant combination in contraceptive vaccines.

The adjuvanticity of two gamma inulin/liposomes/Vitamin E combinations was evaluated in the mouse, in contraceptive vaccines with sperm protein extracts or a synthetic HE2 peptide ("Human Epididymis gene product"; residues 15-28) as antigen. The HE2 peptide was not conjugated to a protein carrier, to ensure that the antibodies elicited were specific against the HE2 peptide. The adjuvant combinations were designed to increase adjuvanticity, as their components have complementary mechanisms, and their performance was compared to Freund's adjuvant. Antibody production against native sperm structures was determined in sera by ELISA immunoassay and immunohistology. Toxicity of adjuvants was determined by histopathological study and treated mice were monitored for signs of pain or distress. Our results show that the gamma inulin (1-2 microm particle size)/liposomes/Vitamin E combination, with sperm protein extracts, is better than Freund's adjuvant because it elicits good antibody titres without any toxicity. When the synthetic HE2 peptide is used as antigen, the gamma inulin (1-2 microm particle size)/liposomes/Vitamin E combination is less effective than Freund's adjuvant; nevertheless, the anti-HE2 antibodies elicited are highly specific and recognize native structures in sperm.

Distribution of sulfakinin-like peptides in the central and sympathetic nervous system of the American cockroach, Periplaneta americana (L.) and the field cricket, Teleogryllus commodus (Walker).

We describe the distribution of sulfakinin-like neuropeptides in the central and sympathetic nervous system of the American cockroach Periplaneta americana (L.) (Blattodea) and the field cricket Teleogryllus commodus (Walker) (Othoptera), using an antisulfakinin primary antibody and confocal laser scanning microscopy. We conclude that, in the cockroach, sulfakinin-like material is produced in ten pairs of anterior cells in the pars intercerebralis, as well as two pairs of medial and one major pair of lateral posterior brain cells. This contrasts with findings in other insects, including the cricket, where only the posterior cell groups express sulfakinin-immunoreactive material. Extensive arborization of dendrites containing sulfakinin-like peptides occurs within the neuropile of both species, suggesting a neurotransmitter/neuromodulator function. In the cockroach, there is clear evidence of direct distribution of sulfakinin-like peptides along axons to the foregut tissue, and a plexus of retrocerebral nerves is likely to serve as a neurohaemal release site. Neurohaemal release into the dorsal aorta is also postulated. Sulfakinin-immunoreactive axons do not innervate the hindgut in either cockroaches or crickets. Sulfakinin may function as a gut myotropin in the Blattodea, in addition to functioning as a neurotransmitter within the central nervous system. This latter function appears to be general across insect orders, while the neurohaemal distribution and myotropic activity are restricted to the Blattodea.

Helping people with alcohol problems.

Many nurses may feel reluctant to include questions on alcohol use in their general patient assessments but studies have shown that brief interventions on this subject can help people cut down on their drinking and improve their health.