Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity.

We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in the modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of (60)Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants.

Potentiation of photodynamic therapy of cancer by complement: the effect of gamma-inulin.

Host response elicited by photodynamic therapy (PDT) of cancerous lesions is a critical contributor to the clinical outcome, and complement system has emerged as its important element. Amplification of complement action was shown to improve tumour PDT response. In search of a clinically relevant complement activator for use as a PDT adjuvant, this study focused on gamma-inulin and examined its effects on PDT response of mouse tumours. Intralesional gamma-inulin (0.1 mg mouse(-1)) delivered immediately after PDT rivaled zymosan (potent classical complement activator) in delaying the recurrence of B16BL6 melanomas. This effect of gamma-inulin was further enhanced by IFN-gamma pretreatment. Tumour C3 protein levels, already elevated after individual PDT or gamma-inulin treatments, increased much higher after their combination. With fibrosarcomas MCA205 and FsaR, adjuvant gamma-inulin proved highly effective in reducing recurrence rates following PDT using four different photosensitisers (BPD, ce6, Photofrin, and mTHPC). At 3 days after PDT plus gamma-inulin treatment, over 50% of cells found at the tumour site were CTLs engaged in killing specific targets via perforin-granzyme pathway. This study demonstrates that gamma-inulin is highly effective PDT adjuvant and suggests that by amplifying the activation of complement system, this agent potentiates the development of CTL-mediated immunity against PDT-treated tumours.

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.

Some bio-medical mechanisms in athletic prowess / Algunos de los mecanismos biomédicos de las proezas atléticas

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.

Existe la hipótesis de que los patrones somatogenéticos en la biología fibromuscular, las vías meta-bólicas bioquímicas, y la fisiología pulmonar, se han concentrado mediante selección natural a lo largo de siglos, en los pueblos afrocéntricos desplazados desde C1frica Occidental al Nuevo Mundo. A estas características fenotípicas y genotípicas se les atribuye las proezas atléticas, tan bien docu-mentadas en los afroamericanos. Tampoco parece ser coincidencia en lo más mínimo, la influencia de los me-canismos compensatorios de transporte de oxígeno, y su disponibilidad en los tejidos, en respuesta al gene de la célula falciforme. Esta disponibilidad reducida acoplada con la mioglobina reducida en las fibras musculares de contracción rápida preponderantes que están adaptadas para la rápida re-generación de energía (ATP), producen de conjunto un resultado neto en términos de ventajas musculares anatómicas y bioquímicas que constituyen la base de las actuaciones destacadas en el atletismo.

Production of oxygen by electronically induced dissociations in ice.

A solid-state chemical model is given for the production of O2 by electronic excitation of ice, a process that occurs on icy bodies in the outer solar system. Based on a review of the relevant available laboratory data, we propose that a trapped oxygen atom-water complex is the principal precursor for the formation of molecular oxygen in low-temperature ice at low fluences. Oxygen formation then occurs through direct excitation of this complex or by its reaction with a freshly produced, nonthermal O from an another excitation event. We describe a model for the latter process that includes competition with precursor destruction and the effect of sample structure. This allows us to put the ultraviolet photon, low-energy electron, and fast-ion experiments on a common footing for the first time. The formation of the trapped oxygen atom precursor is favored by the preferential loss of molecular hydrogen and is quenched by reactions with mobile H. The presence of impurity scavengers can limit the trapping of O, leading to the formation of oxygen-rich molecules in ice. Rate equations that include these reactions are given and integrated to obtain an analytic approximation for describing the experimental results on the production and loss of molecular oxygen from ice samples. In the proposed model, the loss rate varies, roughly, inversely with solid-state defect density at low temperatures, leading to a yield that increases with increasing temperature as observed. Cross sections obtained from fits of the model to laboratory data are evaluated in light of the proposed solid-state chemistry.

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.

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.

Increasing the specificity of the forensic luminol test for blood.

It is shown that the presumptive luminol chemiluminescence test for the presence of traces of blood can be made more determinative by measuring the peak emission wavelength of the luminol chemiluminescence. When sprayed onto a surface containing traces of human haemoglobin, a 1 g/L solution of aqueous luminol containing 7 g/L sodium perborate gives an emission peak at 455 +/- 2 nm, whereas the same mixture gives an emission peak at 430 +/- 3 nm when sprayed onto a surface containing traces of sodium hypochlorite (household bleach). This spectral difference can readily be determined using spectroscopic equipment that either scans the spectrum before significant luminescence decay occurs or corrects the spectrum for the effects of any decay. It was found that bovine haemoglobin and human haemoglobin showed no significant spectral differences.

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.

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.

Control of salt gland activity in the hatchling green sea turtle, Chelonia mydas.

We studied the control of salt gland secretion in hatchling Chelonia mydas. The threshold salt load to activate salt secretion was between 400 mumol NaCl 100 g bodymass (BM)-1 and 600 mumol NaCl 100 g BM-1, which caused an increase in plasma sodium concentration of 13% to 19%. Following a salt load of 2700 mumol NaCl 100 g BM-1, salt gland secretion commenced in 12 +/- 1.3 min and reached maximal secretory concentration within 2-7 min. Maximal secretory rate of a single gland averaged 415 mumol Na 100 g BM-1 h-1. Plasma sodium concentration and total osmotic concentration after salt loading were significantly higher than pretreatment values within 2 min. Adrenalin (25 micrograms kg BM-1) and the cholinergic agonist methacholine (1 mg kg BM-1) inhibited salt gland activity. Atropine (10 mg kg BM-1) reversed methacholine inhibition and stimulated salt gland secretion when administered with a subthreshold salt load. Arginine vasotocin produced a transient reduction in sodium secretion by the active gland, while atrial natriuretic factor, vasoactive intestinal peptide and neuropeptide Y had no measurable effect on any aspect of salt gland secretion. Our results demonstrated that secretion of the salt gland in C. mydas can be modified by neural and hormonal chemicals in vivo and that the cholinergic and adrenergic stimulation of an exocrine gland do not appear to have the typical, antagonist actions on the chelonian salt gland.

Oral motor feeding in the neonatal intensive care unit: exploring perceptions of parents and occupational therapists.

The purpose of this qualitative study was to explore the perceptions of three occupational therapists and three parents regarding occupational therapy services provided in the neonatal intensive care unit. Data were obtained through participant interviews. Role of the occupational therapist, parent training, and time spent with parents were themes that emerged from the therapist interviews. Themes from the parent interviews included occupational therapy intervention and treatment, time spent with occupational therapist, and perceptions. A cross-case analysis addressed two common themes: amount of time spent in parent training and perceptions of training provided. Implications for occupational therapy practice in the neonatal intensive care unit are discussed.

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.

The status of marketing in the health care industry: perspectives of marketing practitioners.

To assess the scope and status of the marketing function in the health care industry, a mail survey of marketing professionals in health care organizations in the Greater Baltimore region was undertaken. Questions were designed to identify important responsibilities, required skills, evaluation factors, and major problems in the practice of health care marketing. Analytic ability was the skill identified as being most necessary to perform their job while quality of service was factor most used to evaluate their performance. Planning, service and the development of products/services were indicated as being their most important responsibility. Inadequate budget and top management's lack of knowledge of marketing were cited as the most important hindrances to effectiveness in marketing jobs. Failure of marketing in the health care industry appears to be internal to the organizations themselves, that is, in terms of how it is interpreted and applied in practice. Solutions require greater understanding of and commitment to the varied roles of marketing professionals.

Vaccine adjuvants based on gamma inulin.

Algammulin and gamma-IN comprise a novel class of vaccine adjuvant. Their use in vaccines is to exploit the humoral defense known as the alternative pathway of complement. They use a "natural" mechanism and the biochemical basis of their action is well understood in general terms. They are fully researched up to the stage of specific commercial application. Inulin itself is registered for human use as a solution and is without physiological effect except for ACP activation as gamma-IN particles. The ACP comprises a relatively harmless part of the inflammatory response. Gamma inulin is nontoxic in several species including humans and is nonpyrogenic. The amount of systemic C3a produced from adjuvant-active doses of gamma-IN is expected to be very much less than that routinely tolerated without effect by human renal dialysis patients. Registration of gamma-IN should not be difficult. Gamma inulin in vivo is either dissolved and excreted unchanged or metabolized to simple foodstuffs. Its primary chemical structure is completely known, and it is inexpensive, readily available, and easy to handle and manufacture. It is completely stable under normal conditions of use and storage. Patent cover is either fully granted or accepted for granting in most developed countries. Alum is also registered for human use and its combination with gamma-IN known as Algammulin is equally nontoxic especially in the fine formulation, and is equally stable. The partial coating with inulin in Algammulin greatly reduces the undesirable effects of alum such as granuloma formation and IgE generation. Combinations of gamma-IN with immunogen carriers other than alum are feasible, either as hybrid particles or as simple mixtures of particles of similar size. Gamma inulin, and especially Algammulin, are potent enhancers of the Th1 immune response pathway, boosting seroconversion rates and immunological memory in protective Ab classes and enhancing cell-mediated immunity. The responses can equal those of CFA. They are also Th2 pathway enhancers, especially for IgA, and the emphasis on Th2 might be varied by altering the alum-to-inulin ratio in the final formulation. A dual response (balanced Th1 and Th2) may be desirable for several reasons. Their primary targets in vivo are probably lymphocytes rather than macrophages. Gamma inulin-based adjuvants therefore comprise new, safe, potent, and attractive candidates for enhancing responses to human and veterinary vaccines, especially those requiring cell-mediated defenses.

Consumer satisfaction and perceived quality of outpatient health services.

The authors examined factors related to consumer satisfaction and willingness to recommend the provider among 1,366 patients receiving examinations at a free-standing medical imaging facility. The nontechnical (nonmedical) characteristics of the service encounter were drawn from three conceptual domains--staff behavior, atmospherics, and information--and two subjective judgments regarding the medical service itself: examination comfort and perceived worth. The authors hypothesized that all of these factors are related to increased consumer satisfaction and willingness to recommend the provider. Data collection was based on a service script, and factor analysis was used to organize elements from each domain into a map of consumer perceptions. Multivariate logistic regression indicated that items from each domain were significantly related to patient satisfaction and willingness to recommend the provider.