Calcium phosphate nanoparticle adjuvant.

Vaccination to protect against human infectious diseases may be enhanced by using adjuvants that can selectively stimulate immunoregulatory responses. In a murine model, a novel nanoparticulate adjuvant composed of calcium phosphate (CAP) was compared with the commonly used aluminum (alum) adjuvants for its ability to induce immunity to herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) infections. Results indicated that CAP was more potent as an adjuvant than alum, elicited little or no inflammation at the site of administration, induced high titers of immunoglobulin G2a (IgG2a) antibody and neutralizing antibody, and facilitated a high percentage of protection against HSV-2 infection. Additional benefits of CAP include (i) an insignificant IgE response, which is an important advantage over injection of alum compounds, and (ii) the fact that CAP is a natural constituent of the human body. Thus, CAP is very well tolerated and absorbed. These studies were performed with animal models. By virtue of the potency of this CAP adjuvant and the relative absence of side effects, we believe that this new CAP formulation has great potential for use as an adjuvant in humans.

Whey protein concentrates with and without immunoglobulins: a review.

ABSTRACT Whey protein, a high-biological-value protein from milk, is available with and without immunoglobulins. The possibility of providing passive immunization through food is unique to mammals, who receive it through colostrum at birth. Colostrum contains both immunostimulatory and immunosuppressive immunoglobulins. Later, the mammals are able to make their own immunoglobulins, but in time of illness that ability may become impaired. Some of the whey proteins contain bovine immunoglobulins, which are similar to human immunoglobulins. This type of whey may be of clinical importance to patients who are immunocompromised. However, all whey proteins are rich in cysteine and glutamate. These serve as precursors of glutathione, a potent antioxidant, which is needed in greater quantities during stress. In this review, the benefits of consuming whey protein with and without immunoglobulins are examined. Characteristics of these products are discussed, and an account is given of supportive studies using the whey containing immunoglobulins in the clinical setting. Patients with acquired immunodeficiency syndrome and cancer are used as examples. Finally, a guide on use of whey protein is provided.

A role for Th2 T-memory cells in early airway obstruction.

The role of T-cell memory in late-phase allergic lung inflammation is not well defined. To evaluate the role of systemic T-cell memory in allergic late-phase lung inflammation, BALB/c mice were injected intraperitoneally with ovalbumin (OVA) or ragweed (RW) allergens (Test I and Test II groups) or saline (control groups C I and C IV) and then challenged intratracheally with the allergen. Late-phase allergic lung inflammation was defined by: (i) recruitment of eosinophils to airways, (ii) IL-5 mRNA upregulation in BAL fluid cells, and (iii) detection of a Th2 cell cytokine profile in BAL fluids. The number of eosinophils recruited in allergic mice following intratracheal challenge with allergen was at least 300-fold higher P < or = 0.01) in mice with allergen-specific T-memory cells in BAL fluid (Test I and Test II) than in control mice without allergen-specific T-memory cells (C I and C IV). Further, the number of eosinophils recruited in Test I and II correlated with the magnitude of in vitro T-cell memory responses (r = 0.93, P < or = 0.04). Moreover, IL-5 mRNA upregulation in BAL cells and Th2 cytokine production in BAL fluids were observed only in Test I and Test II, and not in any of the control groups. Further, results from pulmonary function tests performed on the same allergic animals indicated that only animals from Test I and Test II groups had impaired lung function after allergen challenge. Taken together, these data strongly suggest that allergen-specific Th2-type T-cell memory is required for the development of allergic asthma. That is, without T-cell memory responses, no eosinophil recruitment and release of EPO (which is known to induce bronchoconstriction) occurred in the airways, and no Th2 cytokine profile was detected in the BAL fluid. Furthermore, if the Th2 cytokine profile was absent, then pulmonary functions remained normal.

Dietary fish oil and cytokine and eicosanoid production during human immunodeficiency virus infection.

BACKGROUND: Dietary fish oil (FO) has been shown to modulate the immune system. The purpose of this study was to explore the effects of FO supplementation on the production of dienoic eicosanoids and cytokines in patients with human immunodeficiency virus (HIV) infection. METHODS: This was a randomized, prospective, double-blind study that included homosexual males with HIV infection. Patients were asked to consume voluntarily five food bars daily containing FO (n = 10) or safflower oil (SO) (n = 9) for 6 weeks. At baseline and week 6, plasma was obtained to measure incorporation of omega-3 fatty acids. At baseline, week 3, and week 6, measurements were made of changes in dienoic eicosanoids and cytokines from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) or spontaneously releasing cells. RESULTS: In the FO group but not the SO group, there was increased incorporation of the omega-3 fatty acid docosahexaenoic acid (DHA) into the phospholipids of the fatty acids of the plasma. In the FO group, there was a significant decrease (p = .01) in 6-keto prostaglandin (PG) F1 alpha released from PBMC. There was a significant increase (p = .01) in interleukin (IL)-6 released from the PBMC in the FO group between baseline and week 3 and between week 3 and week 6. At week 6, there was significantly more IL-6 (p = .01) released from the PBMC in the FO group compared with the SO group. There was no change in CD4 cell counts by analysis of variance. CONCLUSIONS: The FO-containing food bars were well tolerated and allowed incorporation of omega-3 fatty acids to occur. Despite evidence of significant metabolic effects on eicosanoid and cytokine production, widespread clinical use of FO for HIV-infected patients is not warranted without further study, particularly given the trend toward a decline in CD4 cell numbers at this dose and with this type of fish oil.

Nutrition support and the human immunodeficiency virus (HIV).

Nutritional support of patients with HIV or acquired immune deficiency syndrome (AIDS) has many similarities to other disease states in that the same nutritional products and techniques are used. Some patients with HIV, and many with AIDS without secondary infection, experience a metabolic milieu similar to patients with cancer cachexia. In providing dietary counselling to the HIV patient, we encounter many of the obstacles that must be overcome to improve nutrition in cancer: anorexia, gastrointestinal discomfort, lethargy, and poor nutrient utilization, which limit the ability for nutritional repletion. When a secondary infection is superimposed on HIV, patients resemble more highly catabolic trauma patients or patients in the intensive care unit (ICU), where, despite aggressive efforts to feed, there is usually a net nitrogen wasting leading to the more rapid development of cachexia. However, even in this setting, feeding will limit substantially net catabolism when compared to total starvation. Because the nutritional needs of HIV patients vary greatly, individual strategies have to be designed as the patient moves through the stages of disease. Patients are generally able to consume adequate nutrition either as regular food or dietary supplements during the latency period of viral replication. Once secondary infections become prevalent, artificial diets administered by tube or by vein may be required during the period of active secondary infections, with dietary supplements often helpful during more quiescent periods. Patients with HIV are among the most challenging for clinicians providing nutritional support. Knowledge from treatment of patients with other diseases may be useful, but more data must be gathered on the unique aspects of aetiology and treatment of the anorexia, malabsorption, and ultimate wasting associated with AIDS.

Glutamine content of whole proteins: implications for enteral formulas.

In two recent clinical trials in surgical patients, supplementation of total parenteral nutrition with daily doses of 12 or 20 g of glutamine resulted in a diminished loss of free glutamine in skeletal muscle tissue. Studies in animals exploring the use of both enteral and parenteral glutamine supplementation suggest that glutamine may be an essential nutrient in the maintenance of gut structure and function during critical illness. These findings have led to heightened interest in the glutamine content of enteral formulas. This article describes a method for estimating the glutamine content of whole-protein enteral formulas. The average amount of glutamine in selected, whole-protein formulas ranges from a minimum of 3.55 g/4200 kJ to a maximum of 5.15 g/4200 kJ. Although it is still too early to define the safest and most effective dose of glutamine, there are two points regarding glutamine supplementation that clearly merit further investigation: no clinical trials have been conducted to assess the potential benefits of glutamine supplementation of an enteral diet or to assess the effects of using diets containing protein-bound glutamine rather than free glutamine.

Dietary modification of chyle composition in chylothorax.

Nutrition support has played a major role in the treatment of chylothorax, both to prevent malnutrition and to minimize chyle production and flow. This report evaluates chyle composition in a patient with chylothorax who was placed on a low-fat diet, medium-chain triglyceride diet, and total parenteral nutrition in sequence. Both triglyceride content and volume of chyle declined, but drainage persisted, ultimately requiring thoracic duct ligation. The chyle triglyceride while on total parenteral nutrition, which presumably originates from both the intestine and plasma, contained more long-chain unsaturated fatty acids than the circulating serum triglyceride. Of particular interest was the detection of an appreciable amount of medium-chain fatty acids in the chyle triglyceride, constituting 20% of the triglyceride fatty acids when an enteral formulation with medium-chain triglyceride as a sole fat source was administered. The finding of almost threefold more decanoic acid (C10:0) than octanoic acid (C8:0), despite the presence of considerably more octanoic acid in the original diet, suggests that trioctanoin may be a preferable medium-chain triglyceride substrate for the nonsurgical treatment of chylothorax.

Modular enteral diets: cost and nutritional value comparisons.

For selected patients, especially those with hepatic or renal failure, it may be necessary to restrict fluid, protein, electrolytes, and/or other micronutrients. The provision of enteral formulas with fixed percentages of nutrients that need to be restricted often results in the patient's receiving inadequate amounts of many that do not need to be restricted. One means of avoiding this problem is to use a micronutrient-free commercial solution, thus allowing the controlled addition of specific micronutrient "modules" needed to meet nutritional goals. There are only two formulas of this type available; however, they are more costly than any other product in our formulary and contain specific amino acid patterns developed for a specific disorder. We have designed, from macronutrient and micronutrient modules, modular tube feeding diets that can vary according to patient needs. We report on five patients treated. The protein quality (chemical score) provided by the modular diet is better than that provided by the nonmodular diet. The average daily cost to the hospital for a modular diet, including labor, is approximately one-third the cost of the nonmodular commercial diet, including labor ($7.72 vs $28.93). One anticipated difficulty is the high level of nutrition knowledge required by the prescribing individual.