Poverty and obesity: the role of energy density and energy costs.

Many health disparities in the United States are linked to inequalities in education and income. This review focuses on the relation between obesity and diet quality, dietary energy density, and energy costs. Evidence is provided to support the following points. First, the highest rates of obesity occur among population groups with the highest poverty rates and the least education. Second, there is an inverse relation between energy density (MJ/kg) and energy cost (US dollars/MJ), such that energy-dense foods composed of refined grains, added sugars, or fats may represent the lowest-cost option to the consumer. Third, the high energy density and palatability of sweets and fats are associated with higher energy intakes, at least in clinical and laboratory studies. Fourth, poverty and food insecurity are associated with lower food expenditures, low fruit and vegetable consumption, and lower-quality diets. A reduction in diet costs in linear programming models leads to high-fat, energy-dense diets that are similar in composition to those consumed by low-income groups. Such diets are more affordable than are prudent diets based on lean meats, fish, fresh vegetables, and fruit. The association between poverty and obesity may be mediated, in part, by the low cost of energy-dense foods and may be reinforced by the high palatability of sugar and fat. This economic framework provides an explanation for the observed links between socioeconomic variables and obesity when taste, dietary energy density, and diet costs are used as intervening variables. More and more Americans are becoming overweight and obese while consuming more added sugars and fats and spending a lower percentage of their disposable income on food.

Development of feline immunodeficiency virus ORF-A (tat) mutants: in vitro and in vivo characterization.

A functional ORF-A is essential for efficient feline immunodeficiency virus replication in lymphocytes. We have characterized a series of mutants of the Petaluma strain, derived from p34TF10 and having different combinations of stop codons and increasingly long deletions in ORF-A. Six clones proved fully replicative in fibroblastoid Crandell feline kidney cells and monocyte-derived macrophage cultures but failed to replicate in T cell lines and primary lymphoblasts. Cats inoculated with three selected mutants had considerably milder infections than controls given intact ORF-A virus. In vivo, the mutants maintained growth properties similar to those in vitro for at least 7 months, except that replication in lymphoid cells was strongly reduced but not ablated. One mutant underwent extensive ORF-A changes without, however, reverting to wild-type. Antiviral immune responses were feeble in all cats, suggesting that viral loads were too low to represent a sufficiently powerful antigenic stimulus.

Low prevalence of TT virus in the cerebrospinal fluid of viremic patients with central nervous system disorders.

TT virus (TTV) is a widespread infectious agent of humans identified in 1998. In infected individuals, TTV induces persistent viremia but its life cycle and pathogenic potential are still poorly understood. In the present study, the presence of TTV DNA in 32 consecutive paired serum and cerebrospinal fluid (CSF) samples from patients with neurological (mainly multiple sclerosis) disorders was investigated by means of a sensitive quantitative real-time PCR assay. Of the 24 patients who were found to carry TTV DNA in serum, 3 also had detectable TTV DNA in their CSF. Two TTV positive CSF samples had markers indicative of blood contamination or a disrupted blood-brain barrier and contained considerably lower TTV loads as compared with the corresponding serum samples, thus suggesting that the virus they contained was of plasma origin. These findings indicated that in general TTV does not permeate effectively an intact blood-brain barrier. Furthermore, the CNS does not represent a common site of TTV replication and persistence. However, at least one exception was observed: the third TTV positive CSF sample (obtained from a patient with subacute dementia of unknown origin) showed no markers suggestive of disrupted blood-brain barrier or blood contamination and had a TTV DNA concentration similar to that found in the patient's serum. In addition, the TTV isolates detected in the two body fluids were distinct genetically. The detection of TTV DNA in CSF is of considerable interest but the clinical significance remains unknown.

Immunogenicity of an anti-clade B feline immunodeficiency fixed-cell virus vaccine in field cats.

Attempts at vaccine development for feline immunodeficiency virus (FIV) have been extensive, both because this is a significant health problem for cats and because FIV may be a useful vaccine model for human immunodeficiency virus. To date, only modest success, producing only short-term protection, has been achieved for vaccine trials in controlled laboratory settings. It is unclear how relevant such experiments are to prevention of natural infection. The current study used a vaccine that employs cell-associated FIV-M2 strain fixed with paraformaldehyde. Subject cats were in a private shelter where FIV was endemic, a prevalence of 29 to 58% over an 8-year observation period. Cats roamed freely from the shelter through the surrounding countryside but returned for food and shelter. After ensuring that cats were FIV negative, they were immunized using six doses of vaccine over a 16-month period and observed for 28 months after the initiation of immunization. Twenty-six cats (12 immunized and 14 nonimmunized controls) were monitored for a minimum of 22 months. Immunized cats did not experience significant adverse effects from immunization and developed both antibodies and cellular immunity to FIV, although individual responses varied greatly. At the conclusion of the study, 0 of 12 immunized cats had evidence of FIV infection, while 5 of 14 control cats were infected. Thus, the vaccine was safe and immunogenic and did not transmit infection. Furthermore, vaccinated cats did not develop FIV infection in a limited clinical trial over an extended time period. Thus, the data suggest that a fixed, FIV-infected cell vaccine has potential for preventing natural FIV infection in free-roaming cats.

Prevention of coronary vascular disease by transplantation of T-cell-depleted bone marrow and hematopoietic stem cell preparation in autoimmune-prone w/BF(1) mice.

This project was designed to investigate the application of bone marrow transplantation to a progressive and ultimately fatal systemic autoimmune disease. Male (NZW x BXSB)F1 (W/BF1) mice develop acute systemic autoimmune disease characterized by degenerative coronary vascular disease (CVD) with myocardial infarctions, hypertension, thrombocytopenia, glomerulonephritis, and persistently elevated levels of circulating immune complexes. After preliminary studies established the onset of disease between 10 and 12 weeks of age, 6- to 8-week-old male W/BF1 mice were targeted for transplantation with either T-cell-depleted bone marrow or purified hematopoietic stem cells from haploidentical B6C3/F1 mice. Posttransplantation flow cytometric analysis of splenocytes demonstrated donor phenotypes in W/BF1 recipient mice that had received T-cell-depleted marrow or hematopoietic stem cell preparations (lineage negative, CD71 negative) from B6C3/F1 donors. Survival of W/BF1 mice transplanted with bone marrow from normal B6C3/F1 donors was very high, and assessment at 100 days after transplantation revealed reduction in onset and severity of disease. Autoantibodies to cardiolipin and double-stranded DNA were markedly reduced to levels present in normal mice. Immunohistochemistry of heart and kidney tissue revealed significant amelioration of degenerative CVD and glomerulonephritis in the majority of W/BF1 recipients of marrow transplants from B6C3/F1 donors. All engrafted W/BF1 mice displayed normal immunologic competence 100 days posttransplantation.

Alteration of cytokine levels in murine retrovirus infection: modulation by combination therapy.

Immunoregulatory cytokines may regulate the resistance or susceptibility of a host to retroviral infection. These cytokines may be therapeutically modulated to prevent or limit the progression of infection. The non-progression to AIDS of some HIV+ patients has been related to a strong type 1 cytokine response (IL-2, IL-12, and IFNgamma). For this reason, we investigated the ability of combination therapeutics to modulate cytokines in vivo towards a type 1 cytokine response in a murine retroviral infection using Friend leukemia virus (FLV). BALB/c mice were infected with FLV and treated with either 3'-azido-3'-deoxythymidine (AZT), the immunomodulator methionine enkephalin (MENK), or a combination of both AZT and MENK starting 3 d post infection. Splenocytes were harvested on days 1, 3, 7, 14, 21 and 28 post treatment initiation and cultured with 1 microg/ml concanavalin A (ConA) for 24 h. Supernatants were examined for IL-2, IL-4, IL-10, IL-12, and IFNgamma cytokine production using cytokine specific ELISAs. The levels of type 2 cytokines were not significantly changed by any treatment group over the course of the disease. However, although decreased in all infected animals, type 1 cytokines were partially maintained by the combination treatment through day 21. RT-PCR for cytokine specific mRNA confirmed these results, with expression of the type 1 cytokines, especially IFNgamma, being maintained through day 21. Establishment of a treatment regime that can maintain protective cytokine activities against disease progression may prove applicable to other retroviral infections.

Modulation of ex vivo cytokine production by splenocytes using in vitro combined therapeutics in murine retroviral model.

Altered levels of Type 1 and Type 2 cytokines are important in retrovirus-induced immunosuppression. The combination of immunostimulatory agents with antiviral drugs alters the course of murine retroviral infections. Previously, it was demonstrated that in vitro treatment of noninfected splenocytes and in vivo treatment of Friend leukemia virus (FLV)-infected mice with the combination of azidothymidine (AZT) and methionine enkephalin (MENK) significantly increases Type 1 cytokine levels and decreases Type 2 cytokines compared with treatment with only AZT. In order to study the effect of the time of initiation of immunomodulation on the course of retroviral infections, we examined the kinetics of cytokine production by isolated splenocytes from infected mice. BALB/c mice were infected with FLV, and spleen cells were removed at specified times postinfection (days 1, 3, 7, 10, and 14). Interleukin (IL)-2, interferon (IFN-gamma, IL-4, and IL-10 production by unstimulated or ConA-stimulated splenocytes treated in vitro with AZT, MENK, or AZT + MENK was determined after 48 h. The capacity of the isolated splenocytes to produce the Type 1 cytokines IL-2 and IFN-gamma in response to stimulation with ConA and combination therapy decreased over the course of infection. These results suggest that MENK treatment initiated later in the course of infection is unable to modulate the cytokine profile and would likely be ineffective in altering the course of FLV induced-disease. The results indicate the necessity to initiate antiretroviral therapy early in infection. Such information may be applicable in designing future regimens for HIV-1 infections in humans.

Morphine effects on HTLV-I infection in the presence or absence of concurrent HIV-1 infection.

Human T-cell leukemia virus type I (HTLV-I) infection is emerging as an important complication in HIV infection and AIDS in injecting drug users. HIV-1 and HTLV-I share a common host in CD4+ T lymphocytes. However, the result of HIV-1 infection is the decimation of this cell population, whereas a hallmark of HTLV-I infection is the inappropriate proliferation of infected cells. Combined epidemiologic data suggest that HTLV-I infection is enhanced during concurrent HIV-1/HTLV-I infection; however, there are currently no in vitro studies focusing on the effects of drugs of abuse on retrovirus coinfection. We have found that in an in vitro coinfection system (HIV-1 + HTLV-I), morphine treatment further enhanced the levels of HTLV-I p19. In addition, indicators of in vitro infection by cell-free HIV-1 were reduced by morphine treatment in both single and dual in vitro infection experiments. Interleukin 2 levels in the affected cultures were found to increase with combined HTLV-I infection and morphine treatment. These in vitro results indicate the need to further explore the activity of HTLV-I within opiate-treated cells, as this oncoretrovirus appears to be especially sensitive to morphine-induced alterations to its host cell environment.

[Additive effect of marihuana and retrovirus in the anergy of natural killer cells in mice]. / Marihuána és retrovírus additív hatása egerek természetes ölösejt-aktivitásának kimerülésében.

Among the immunosuppressive effects of marijuana, impairment of natural killer cell activity is significant. HIV also inhibits these cells. Friend leukemia virus complex and its helper component Rowson-Parr virus induce early immunosuppression in mice resembling human AIDS, and late leukemia, providing a small animal AIDS model. Leukemia susceptible BALB/c and resistant C57BL/6 mice were infected with these viruses. At different time points, their natural killer cells separated from spleens were treated with 0 to 10 micrograms/ml tetrahydrocannabinol, subsequently mixed with Yac-1 target cells for 4 and 18 h. The natural killer cell activity in both mouse strains infected by either virus complex or helper virus weakened on days 2 to 4 postinfection, normalized by day 8 and enhanced on days 11 to 14. Natural killer cell activity upon the effect of low concentration (1.0 to 2.5 micrograms/ml) of tetrahydrocannabinol slightly increased in BALB/c, was unaffected in C57BL/6, especially in 18 h assays. In the combined effects of marijuana and retrovirus, damages by marijuana dominated over those of retroviruses. Inhibition or reactive enhancement of natural killer cell activity on the effect of viruses are similar to those of infected but marijuana-free counterparts, but on the level of uninfected cells treated with marijuana. The effects of marijuana and retrovirus are additive resulting in anergy of natural killer cells.

Functional food science and behaviour and psychological functions.

The impact of ingesting various foods on psychological and behavioural functions is a topic of both interest and concern to the general public. In this article, the scientific literature concerning demonstrated cause-and-effect relationships is reviewed, beginning with methodological considerations specific to the quantification of particular behaviours and psychological events. The essential function of food is to satisfy hunger and the need for essential nutrients. The contributions of macronutrients to appetite and satiety are described, as well as their impact on metabolism and energy balance. Functional properties of macronutrient substitutes (high-intensity sweeteners, fat replacers) and flavour enhancers are examined in relation to their contribution to hunger, satiety, and energy balance. The effects of foods and individual nutrients on the performance of diverse psychomotor tasks are studied with consideration given to the various validated quantitative tools used to assess behaviour. The effects of food components on activation, sedation, and affective states such as dysphoria are also reviewed, with special attention given to brain function and neuroactive substances such as serotonin and the endorphins. The case of hyperactivity in children is given special emphasis with reference to the potential influence of sugar and food additives. Safety issues related to food constituents and additives are discussed. Finally, a set of criteria is proposed for the evaluation and elaboration of studies in the behavioural and psychological fields, along with suggestions for future research.

Inhibitory effect of biphalin and AZT on murine Friend leukemia virus infection in vitro.

Biphalin is a bivalent opioid analogue containing two tyrosine residues. We have examined the effect of biphalin's anti-retroviral potency in vitro using a murine model. Biphalin, in non-cytotoxic concentrations, suppressed in a dose-dependent fashion the replication of Friend leukemia virus (FLV) in Mus dunni cells as determined using a focus forming assay. FLV replication was substantially reduced by biphalin at 10(-4) M concentration. When biphalin was combined with 3'-azido-3'-deoxythymidine (AZT) the two acted synergistically in inhibiting FLV replication compared to either used alone. Using a reverse transcriptase (RT) assay, FLV RT levels also were noted to be reduced in the presence of biphalin. These observations indicate that biphalin possesses anti-retroviral activity in vitro, suggesting that this opioid peptide should be examined further in vivo to determine if it is a candidate for combined therapy with AZT and possibly other drugs for retrovirus infections including the human immunodeficiency virus (HIV).

Reducing ice cream energy density does not condition decreased acceptance or engender compensation following repeated exposure.

OBJECTIVES: The preferences for high-fat foods are believed to be based on their sensory attributes and energy density; however less is known about how such preferences might be weakened, other than in response to deterioration in flavor or textural quality. The aim of the present study was to see whether acceptability of reduced fat/energy foods would wane as the original post-ingestive nutritional benefits are reduced when palatability remains essentially constant. DESIGN: Repeated measures, within-subjects design conducted in two counterbalanced three week trials. SETTING/SUBJECTS: Sixteen normal-weight males (mean age 25.8 +/- 1.2 y) came to our laboratory at the Hôpital Hotel Dieu in Paris to eat an afternoon snack on 13 consecutive days (excluding weekends). INTERVENTION/OUTCOME MEASURES: Intake was recorded following repeated exposure to two flavors of standard (10% fat as a percentage of total solids weight), and low (3%) fat ice cream. One group received standard vanilla or low-fat strawberry ice cream on alternate days for two consecutive weeks; these flavor associations were reversed for a second group. The two flavors were rated as equipalatable at the beginning of the experiment at all energy levels. RESULTS: Subjects consumed the same quantity of ice cream throughout the experimental period, independent of energy density or flavor. Consequently, aggregate (summed) energy intake for subjects consuming low-fat ice cream was significantly lower (by 581 kJ (139 kcal), 15.4 g fat). Food intake records for the 24 h period immediately following the test sessions revealed no compensation for fat or energy. Despite the 28% reduction in energy density for the low-fat version, acceptance for the flavors associated with the reduced-energy versions had not declined by the end of the experimental period. CONCLUSIONS: The findings suggest that acceptance of reduced-fat foods may not be critically dependent on the post-ingestive metabolic effects when the reductions in energy density are small. Further tests with more severe reductions, and perhaps over more prolonged time periods, will be necessary to determine at what level of substitution acceptance might begin to deteriorate.

Combined in vitro effect of marijuana and retrovirus on the activity of mouse natural killer cells.

Both marijuana and retroviruses impair natural killer (NK) cell functions. No data on their simulataneous effects are available. Similarities to human AIDS induced early by Friend leukemia complex (FLC) and its replication competent helper Rowson-Parr virus (RPV) provides a mouse model to study drug-virus action. Leukemia susceptible BALB/c and resistant C57BL/6 mice were infected, then at time intervals their nylon wool-separated splenocytes were exposed to tetrahydrocannabinol (THC) for 3h. Natural killer (NK) cell activity against Yac-1 cells was assayed by 51Cr-release for 4 and 18h. Recovery of splenocytes was found to be suppressed by FLC, but in BALB/c only by RPV. After a transient enhancement in C57BL/6 by FLC, NK cell activity of both mice became suppressed early (2 to 4 days), normalized subsequently and enhanced late (11 to 14 days) postinfection. A moderate increase in BALB/c, no change in C57BL/6 were induced by low (1-2.5 microgram/ml) THC doses. NK cell activity of BALB/c became suppressed exponentially by higher (5-10 microgrtam/ ml) THC doses in 18h as compared to 4h assays, while its proportional and moderate impairment was seen in C57BL/6. The magnitude of NK cell activity of infected mice was determined by THC: enhancement or impairment followed those of untreated, infected counterparts, but on the level of THC-treated cells. Low doses hardly, high doses additively influenced NK cells of infected BALB/c. THC hardly affected very early and late enhancement in NK cell activiy of FLC infected C57BL/6, but augmented RPV induced suppression late in 18h assays. Genetic factors similar to endotoxin resistance, altered cytokine profile might determine these effects. Similar phenomena in humans might result in earlier manifestation of AIDS.

Opiate effects on in vitro human retroviral infection.

The transmission and progression of the human retroviruses HIV-1 and HTLV-1/2 can be most likely influenced by a variety of "lifestyle cofactors" which includes the use of certain injected pharmaceuticals. Some investigations have suggested that HIV-1 infected individuals who are injecting drug users (IDUs) may undergo an accelerated rate of progression to AIDS. It is known that opioid receptors exist on cells pertinent to immune function, and that the activation or inhibition of these receptors may enhance or down-regulate some cell activities. The mechanisms for these effects have not yet been elucidated, nor have the effects of opioids on retroviral infection models been fully determined. While some work has been performed on the effects of opiates on infection by HIV-1 and SIV virtually no work has been done on the potential effects of this class of drugs on HTLV-1 and 2 infection. The potential effects of opiates on these retroviruses are important because of the higher incidence of infection in IDUs. Because IDUs compose one of the emerging high risk populations for infection with HIV-1 and more recently HTLV it is relevant to analyze the direct and indirect effects of opioids on the progression of retroviral infections. Our preliminary results from in vitro syncytia formation studies suggest a modulation by opioid-selective receptor agonists of in vitro infection by both HIV-1 and HTLV-I. These initial results underscore the necessity for further studies to define and elucidate the role of opiate abuse in the infection by human retroviruses as well as the associated pathogenesis.

Marijuana, immunity and infection.

The influence of marijuana cannabinoids on immune function has been examined extensively over the last 25 yr. Various experimental models have been used employing drug-abusing human subjects, experimental animals exposed to marijuana smoke or injected with cannabinoids, and in vitro models employing immune cell cultures treated with various cannabinoids. For the most part, these studies suggest that cannabinoids modulate the function of T and B lymphocytes as well as NK cells and macrophages. In addition to studies examining cannabinoid effects on immune cell function, other reports have documented that these substances modulate host resistance to various infectious agents. Viruses such as herpes simplex virus and murine retrovirus have been studied as well as bacterial agents such as members of the genera Staphylococcus, Listeria, Treponema, and Legionella. These studies suggest that cannabinoids modulate host resistance, especially the secondary immune response. Finally, a third major area of host immunity and cannabinoids is that involving drug effects on the cytokine network. Employing in vivo and in vitro models, it has been determined that cannabinoids modulate the production and function of acute phase and immune cytokines as well as modulate the activity of network cells such as macrophages and T helper cells, Th1 and Th2. These results are intriguing and demonstrate that under certain conditions, cannabinoids can be immunomodulatory and enhance the disease process. However, more studies are needed to determine both the health risk of marijuana abuse and the role of the cannabinoid receptor/ligand system in immune regulation and homeostasis.