Janice M. Zeller

Stimulation of human neutrophils, monocytes, and platelets by modified C-reactive protein (CRP) expressing a neoantigenic specificity

C-reactive protein (CRP) can be structurally modified by heat, acid, or urea-chelation to express a neoantigen designated by us as neo-CRP. This antigen is also expressed on the in vitro primary protein translation products of both human and rabbit CRP. Unmodified CRP and CRP complexed with pneumococcal C-poly-saccharide (CPS) do not express neo-CRP. Forms of CRP expressing neo-CRP but not native CRP antigenicity (even in the presence of CPS) consistently and in a dosedependent manner potentiated the respiratory burst response of human polymorphonuclear leukocytes and peripheral blood monocytes to heat-modified IgG. Forms of CRP expressing neo-CRP antigenicity also induced reactions of aggregation and secretion from isolated platelets and potentiated platelet activation stimulated by ADP in platelet-rich-plasma, while native CRP alone or complexed with CPS again did not. Unlike CRP-CPS complexes, forms of CRP expressing neo-CRP were not able to activate the complement system. These data emphasize the biologic potential inherent in this humoral acute-phase reactant, particularly in the activation of the formed elements of the blood important in the inflammatory response. Since these cell-activating properties are preferentially observed when CRP is structurally modified to express the neo-CRP antigen, such a molecular conversion may be central to the structure-function relationships of CRP at local sites of inflammation and tissue injury.

The influence of stress management training in HIV disease.

A pretest-posttest design (with a 6-week wait-list control and a 6-month comparison group) was used to compare the effectiveness of a 6-week stress management training program with standard outpatient care for 45 men with HIV disease. Outcomes included stress levels, coping patterns, quality of life, psychological distress, illness-related uncertainty, and CD4+ T-lymphocyte levels. At 6 weeks, intervention was associated with increases in the emotional well-being dimension of quality of life. After 6 months, the intervention group had a relative decline in HIV-related intrusive thinking, indicating that stress management training may have buffered illness-related psychological distress over time.

C-reactive protein selectively enhances the intracellular generation of reactive oxygen products by IgG-stimulated monocytes and neutrophils

The acute phase protein, C‐reactive protein (CRP), when heat‐aggiegated (Agg‐CRP), potentiates immunoglobulin G (IgG) Fc receptor‐mediated luminol‐ enhanced chemiluminescence (CL) in human monocytes and neutrophils. Luminol‐CL is a sensitive measure of phagocyte respiratory burst activity; however, the nature of oxidative products contributing to the light emission md their site of generation remain incompletely defined. To more precisely describe the oxidative burst of monocytes and neutrophils to Agg‐CRP, superoxide anion release was measured by cytochrome c reduction. In addition, the extracellular release of hydrogen peroxide was distinguished from hydrogen peroxide generation using a phenol red oxidation assay. Finally, a flow cytometric de‐;ermination of dichlorofluorescin (DCFH) oxidation was employed as an index of intracellular peroxide production. Although Agg‐CRP alone did not stimulate hydrogen peroxide generation by either monocytes or neutrophils, it significantly enhanced hydrogen peroxide generation in response to heat‐aggregated IgG (Agg‐IgG). In contrast, Agg‐CRP did not enhance the extracellular release of either hydrogen peroxide or superoxide anion from Agg‐IgG‐stimulated cells. The capacity of Agg‐CRP to enhance selectively intracellular oxidative product generation was confirmed when measuring DCFH oxidation in Agg‐IgG‐stimulated cells. To evaluate whether this selective enhancement of intracellular oxidative events could be attributed, at least in part, to a scavenging effect of Agg‐CRP, a cell‐free oxygen radical‐generating system was employed. Agg‐CRP did not significantly liminish the lucigenin‐amplified CL response induced by the xanthine/xanthine oxidase reaction. These results indicate that although Agg‐CRP enhances the intracellular generation of reactive oxygen intermediates by monocytes md neutrophils, extracellular release of those products is lot influenced by cell interaction with Agg‐CRP. It is tempting to speculate that CRP can selectively boost the microbicidal activities of monocytes and neutrophils within an inflammatory site by amplifying the intracellular generation of reactive oxygen products without increasing damage to surrounding normal tissues.

Enhancement of Human Peripheral Blood Monocyte Respiratory Burst Activity by Aggregated C-Reactive Protein

We had previously demonstrated that C‐reactive protein (CRP), an acute phase reactant, when aggregated or coupled to a ligand, interacts with monocytes and certain human peripheral blood lymphocytes. The purpose of the present study, after further characterizing the binding interaction of CRP with human monocytes, was to focus on the biological response of monocytes to CRP binding. Flow cytometric analysis of human mononuclear leukocytes, following incubation with fluoresceinated heat‐aggregated CRP (Agg‐CRP), revealed that while greater than 70% of monocytes bound Agg‐CRP, only 8% of lymphocytes demonstrated positive fluorescence. Furthermore, mean channel fluorescence values indicated that monocytes bound greater amounts of Agg‐CRP per cell than did lymphocytes. Luminol‐enhanced chemiluminescence (CL) was used as a measure of monocyte respiratory burst activity. Monocytes were stimulated only minimally by Agg‐CRP alone; however, Agg‐CRP substantially enhanced the CL response to heat‐aggregated IgG. This Agg‐CRP enhancing effect was selective for IgG‐initiated monocyte activation, as no augmentation in CL was observed following cell stimulation with phorbol myristate acetate or serum‐opsonized zymosan. These results demonstrate that aggregated CRP binds to the major proportion of human monocytes and selectively augments Fc receptor‐mediated stimulation of monocyte oxidative metabolism.

HIV Infection and Obesity: A Review of the Evidence

&NA; This article provides a review of recent evidence pertinent to the prevalence, morbidities, and predictive value of overweight and obesity in PLWH. Implications for clinical outcomes are discussed, and recommendations for patient management and future research are advanced.

Comparison of standard and immune-enhancing oral formulas in asymptomatic HIV-infected persons: a multicenter randomized controlled clinical trial

BACKGROUND Both standard and immune-enhancing oral formulas are widely used to forestall HIV wasting and to promote immune function. However, there is little scientific evidence to support the differential effects of these formulas in asymptomatic HIV disease. The aim of this study was to compare the effects of an immune-enhancing oral formula and a standard oral formula on nutrition and immune measures in asymptomatic HIV-infected persons. A secondary aim was to evaluate the feasibility of maintaining a diverse sample of outpatients on a long-term oral formula protocol. METHODS In this multicenter controlled nonblinded study, 90 asymptomatic HIV-infected persons with CD4 cell counts between 275 and 550 cells/mm3 were randomized to a control group; a standard oral formula group (Ensure Plus); or an immune-enhancing oral formula group (Advera). All groups received basic nutrition counseling. Participants were evaluated on nutrition, immune, and feasibility measures at 3-month intervals during the 12-month study period. Differences in nutrition and immune measures among the 3 groups were analyzed using the Kruskal-Wallis and Wilcoxon tests. Wilcoxon tests and correlation coefficients were used to analyze feasibility data. RESULTS Sixty-six outpatients completed the 12-month study protocol. Among the 3 groups, there were no significant differences with respect to body weight, bioelectrical impedance analysis (BIA)-derived body cell and fat mass, daily caloric intake, and serum albumin at any of the study visits. Moreover, absolute CD4+ T lymphocytes and percentages did not significantly differ at any time point among the 3 groups. Acceptability and tolerance of the formulas were high for both the standard and immune-enhancing oral formula groups. CONCLUSIONS Within the context and limitations of this study, standard and immune-enhancing oral formulas consumed daily for 1 year had no differential effects on nutrition or immune parameters in asymptomatic HIV-infected persons.

A pilot study of the safety and efficacy of cholestin in treating HIV-related dyslipidemia

OBJECTIVE We collected preliminary safety and efficacy data on the effects of Cholestin, a statin-containing dietary supplement, in individuals with dsylipidemia related to human immunodeficiency virus. METHODS Fourteen adults with dsylipidemia related to human immunodeficiency virus characterized by hypercholesterolemia, hypertriacylglycerolemia, or both participated in a randomized, double-blind, placebo-controlled pilot study in an infectious disease clinic based in an academic medical center. Participants were randomly assigned to receive 1.2 g of Cholestin twice daily (n = 7) or placebo (n = 7) for 8 wk. The main outcome measures were safety (hepatic function tests, plasma human immunodeficiency virus-1 RNA levels, CD4(+) cell counts, adverse effects) and efficacy (fasting serum cholesterol: total, high- and low-density lipoproteins, and fasting serum triacylglycerols). Safety and efficacy outcomes were evaluated at 2- and 8-wk intervals. RESULTS Twelve participants (n = 6 per group) completed the 8-wk treatment protocol. After 8 wk of treatment with Cholestin, there were significant declines from baseline in mean (+/- standard error of the mean) fasting total cholesterol (-30.8 +/- 8.8 versus 7.7 +/- 5.6; P = 0.01) and low-density lipoprotein cholesterol (-32.2 +/- 7.2 versus 26.3 +/- 14.2; P = 0.01) versus placebo. Moreover, the decline in fasting total cholesterol was significant (-40.2 +/- 4.8 versus 2.8 +/- 11.9; P = 0.006) after 2 wk of therapy, at which time the low-density lipoprotein cholesterol approached significance (-30.2 +/- 7.4 versus 4.4 +/- 15.2; P = 0.068). High-density lipoprotein cholesterol and triacylglycerol levels did not change at either time point. No adverse effects were seen with Cholestin. CONCLUSIONS Cholestin may safely lower total and low-density lipoprotein cholesterol in patients with dsylipidemia related to human immunodeficiency virus. Larger and longer-term trials of this approach are warranted.

Safety and Efficacy of Glucomannan for Weight Loss in Overweight and Moderately Obese Adults

Background. Few safe and effective dietary supplements are available to promote weight loss. We evaluated the safety and efficacy of glucomannan, a water-soluble fiber supplement, for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets. Methods. Participants were randomly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL (8 ounces) of water one hour before breakfast, lunch, and dinner for 8 weeks. The primary efficacy outcome was change in body weight after 8 weeks. Other efficacy outcomes were changes in body composition, hunger/fullness, and lipid and glucose concentrations. Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels. Results. A total of 53 participants (18–65 years of age; BMI 25–35 kg/m2) were enrolled and randomized. The two groups did not differ with respect to baseline characteristics and compliance with the study supplement. At 8 weeks, there was no significant difference between the glucomannan and placebo groups in amount of weight loss (−.40 ± .06 and −.43 ± .07, resp.) or other efficacy outcomes or in any of the safety outcomes. Conclusions. Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition, hunger/fullness, or lipid and glucose parameters. This trial is registered with NCT00613600.

Complementary and Alternative Therapies to Manage HIV-Related Symptoms

Persons with HIV infection report substantial use of complementary and alternative medical (CAM) therapies for symptom management. Anecdotal reports from patients indicate that CAM approaches are helpful; however, there is limited scientific information on the safety and efficacy of these therapies in the HIV population. The purpose of this review is to critically appraise the scientific evidence for selected CAM therapies that are used by HIV-infected persons to manage three common symptoms: nutritional alterations, pain, and depression.

Efficacy of a vibratory stimulus for the relief of HIV-associated neuropathic pain

Abstract Pain related to HIV disease is frequently debilitating. Of the many pain syndromes that occur in persons with HIV, distal symmetrical polyneuropathy (DSPN) is particularly devastating. Because DSPN often responds, at best, only partially to available pharmacologic interventions, non‐pharmacologic interventions need to be investigated. Vibration has been suggested to be effective for reducing pain in other populations with chronic pain. This randomized, sham‐controlled, double‐masked study tested the short‐term efficacy of a 45‐min vibration treatment for DSPN foot pain in persons infected with HIV. Vibration therapy was delivered using a portable platform foot vibrator that provided stimulation at a frequency of 60 Hz. For all patients, the control box for the vibrator emitted an audible hum and part of the control box lit up during treatment, but only patients randomized to active treatment received vibration. Pain intensity (0–10) was measured immediately prior to and after treatment. Subjects were also questioned regarding pain relief (0–100%) immediately after the treatment. The mean percentage pain relief was 61.0±33.1% (median 70.0; range 0–100) for all patients, 67.3±34.0% (median 80.0; range 0–100) for vibration patients, and 55.0±32.0% (median 60.0; range 0–100) for sham patients. No statistically significant differences were found between the vibration and sham groups with respect to percentage pain relief (Mann–Whitney test; P=0.19) or the pre‐ and post‐treatment current‐pain difference (Mann–Whitney test; P=0.92). These results underscore the necessity for control groups in studies of non‐pharmacologic therapies for pain.