Influence of dietary supplementation of short-chain fatty acid sodium propionate in people living with HIV (PLHIV).

BACKGROUND: Non-AIDS-associated chronic diseases in HIV+ patients have been on the rise since the advent of antiretroviral therapy. Especially cardiovascular diseases and disruption in the gastrointestinal tract have limited health-related quality of life (QoL). Several of those complications have been associated with chronic systemic inflammation. Short-chain fatty acids (SCFA), with propionate as one of the major compounds, have been described as an important link between gut microbiota and the immune system, defining the pro- and the anti-inflammatory milieu through direct and indirect regulation of T-cell homeostasis. The effects of dietary supplementation of sodium propionate (SP) in people living with HIV (PLHIV) have not yet been investigated prior to this study. OBJECTIVES: To investigate the impact of SP uptake among PLHIV and its relevance to improve QoL, the study aimed to investigate metabolic, immunological, microbiome and patient-reported QoL-related changes post-SP supplementation with follow-up. METHODS: A prospective, non-randomized, controlled, monocentric interventional study was conducted in WIR, Center for Sexual Health and Medicine, in Bochum, Germany. 32 HIV+ patients with unaltered ART-regimen in the last three months were included. Participants were given SP for a duration of 12 weeks in the form of daily oral supplementation and were additionally followed-up for another 12 weeks. RESULTS: The supplementation of SP was well tolerated. We found an improvement in lipid profiles and long-term blood glucose levels. A decrease in pro-inflammatory cytokines and a depletion of effector T cells was observed. Regulatory T cells and IL-10 decreased. Furthermore, changes in taxonomic composition of the microbiome during follow-up were observed and improvement of items of self-reported life-quality assessment. CONCLUSION: Taken together, the beneficial impact of SP in PLHIV reflects its potential in improving metabolic parameters and modulating pro-inflammatory immune responses. Thus, possibly reducing the risk of cardiovascular disorders and facilitating long-term improvement of the gut flora.

Epidemiological composition, clinical and treatment characteristics of the patient cohort of the German Competence Network for HIV/AIDS.

OBJECTIVE: As its central basis for research, the Competence Network for HIV/AIDS (KompNet) established a nationwide cohort study on HIV-positive patients being in medical care in Germany. In this paper, we describe the epidemiological composition, and clinical as well as treatment characteristics of the KompNet cohort over time. METHODS: The KompNet cohort is an open, retrospective and prospective, multi-center, disease-specific and nationwide cohort study that started gathering data in June 2004. Semiannually, follow up visits of the patients are documented, covering a wide range of clinical and sociodemographic data. At enrollment and three years afterwards, an EDTA-sample is taken; a serum-sample is taken at every follow up. RESULTS: As of 20.10.2008, a total of 15,541 patients were enrolled by 44 documenting sites. In September 2007, the cohort size was reduced to ten outpatient clinics and fifteen private practitioners, covering a total of 9,410 patients. The documentation of these patients comprised 24,117 years of follow up-time since enrollment (mean: 2.6 years), 62,862 person years inclusive data documented retrospectively on course of HIV-infection and antiretroviral therapy (ART, mean: 6.7 years). Due to the short period of recruitment till now, rates of death (0.3%-0.8%) and losses to follow up (1.1%-5.5%) were low. 84.9% of patients were men. Main risk of transmission was sex between men (MSM: 62.9%). Mean age was 45 years. About two third of patients were classified as CDC-stage B or C. Therapy regimens of currently treated patients complied with recent guidelines. Trends of mean CD4 cell count/microl regarding the initial therapy and concerning the population under treatment reflected the developments and the changing standards of antiretroviral therapy over time. CONCLUSION: The KompNet cohort covers about a quarter of all patients estimated as being under treatment in Germany. Its composition can be accounted approximately representative for the situation of clinical care and treatment in the scope of HIV/AIDS in Germany. Therefore, it is an important instrument for measuring the course of HIV/AIDS, the reality of use of antiretroviral therapy and its clinical and psychosocial outcomes in Germany.

Mononuclear cells in atopic dermatitis in vivo: immunomodulation of the cutaneous infiltrate by medium-dose UVA1 phototherapy.

INTRODUCTION: Recently, medium-dose UVA1 phototherapy (50 J/cm2) has achieved great therapeutic success within the treatment of severe atopic dermatitis (AD). Histologically, AD is recognised by a pathological perivascular dermal infiltrate including T lymphocytes, eosinophils and Langerhans cells. The purpose of our study was to investigate the extent to which UVA1 irradiation is able to modulate the mononuclear dermal inflammatory infiltrate using different monoclonal antibodies. PATIENTS AND METHODS: Biopsy specimens before and after treatment with medium-dose UVA1 irradiation (cumulative dose: 750 J/cm2) from 15 patients suffering from severe AD were analysed immunohistochemically concerning the presence of CD4+ and CD8+ T lymphocytes, CD1a+ Langerhans cells and EG2+ activated eosinophils. RESULTS: Compared to lesional skin of patients with AD before UVA1 irradiation, the relative number of CD4+ cells, CD1a+ dendritic cells and activated EG2+ eosinophils within the dermal infiltrate could be decreased significantly after treatment. In contrast, medium-dose UVA1 phototherapy led to a significant increase of the percentage of dermal CD8+ cells. These alterations were closely linked to a decrease of the absolute skin-infiltrating cells and a substantial clinical improvement of the skin. CONCLUSIONS: In summary, our findings demonstrate that medium-dose UVA1 irradiation leads to a remarkable modulation of the dermal mononuclear infiltrate in patients with severe atopic dermatitis referring to a decrease of dermal Langerhans cells, activated eosinophils and CD4 cell count as well as to a relative increase of CD8+ lymphocytes. The immunomodulation of the cutaneous infiltrate is associated with a depletion of cytotoxic agents, the defective IgE overproduction and the aberrant presence of T lymphocytes combined with the pathological cytokine pattern.

Effects of antipsoriatic therapies on hepatic microsomal enzyme activity in patients with psoriasis.

OBJECTIVE: The influence of several antipsoriatic therapies on microsomal enzyme activity was assessed by comparing measurements of antipyrine kinetics prior to and two weeks after initiation of therapy. METHODS: Serum and urine analysis was carried out by means of high performance liquid chromatography (HPLC). Each form of therapy was examined separately. 10 patients were treated with etretinate. The groups treated with 8-methoxypsoralene (8-MOP) in combination with UVA irradiation (PUVA), etretinate in combination with PUVA (RePUVA), anthralin, or combined UVA and UVB irradiation (SUP) consisted of 7 patients each. RESULTS: Neither anthralin nor SUP therapy led to any significant changes in antipyrine kinetics. Antipyrine clearance under the other regimens was, however, reduced. It was 23% lower in PUVA-treated patients, 20% lower in those receiving retinoids and 28% lower in those under RePUVA (p<0.05 - 0. 01). CONCLUSIONS: PUVA, etretinate and RePUVA inhibit microsomal enzyme activity in the liver. Possible drug interactions with other P subset450 inducing or inhibiting agents should be considered in the therapy of psoriatic patients.

Oligosymptomatic neurosyphilis with false negative CSF-VDRL in HIV-infected individuals?

The true prevalence of neurosyphilis in HIV-infection is unknown, since a sufficiently sensitive and specific test is lacking. In a prospective study we found reactive serum TPHA and FTA-ABS IgG tests in 95 (31%) of 307 HIV-infected patients. Three of 11 patients with latent syphilis revealed reactive CSF-VDRL tests, six others only demonstrated CSF abnormalities. Resolution of CSF abnormalities during a six month follow up after high dose antibiotic therapy led to the diagnosis of oligosymptomatic or asymptomatic neurosyphilis in all nine patients. Thus, the specificity of the CSF-VDRL was 100%, but the sensitivity was only 33%. The overall prevalence of neurosyphilis was 2.9%, increasing to 9.5% in patients with a reactive serum TPHA. Our study emphasizes the importance of antibiotic therapy for presumptive neurosyphilis in HIV-infected patients with latent syphilis and CSF abnormalities but nonreactive CSF-VDRL tests, even if they are neurologically asymptomatic or present with complaints inconclusive of neurosyphilis.

Cimetidine and the immuno-response in healthy volunteers.

We compared the immunologic measurements from treatment of 12 healthy volunteers (six male, six female) with 800 and 1,600 mg cimetidine. In the first trial 800 mg cimetidine was administered daily to the volunteers over a period of 7 d; after an interruption of 2 months, 1,600 mg of cimetidine was applied daily for 21 d. The most striking result of our study was an increased mitogen-induced lymphocyte proliferation. This conclusion can be drawn from the fact that phytohaemagglutinin (PHA) (0.4 microgram/well) and pokeweed mitogen (PWM) (0.4 microgram/well) induced lymphocyte proliferation were found to be significantly increased in comparison to pretreatment values on day 7 in both cimetidine regimens (800 mg; PHA: mean proliferation 66,500 before treatment to 166,00 cpm, PWM: mean proliferation 8,800 before treatment to 34,000 cpm; 1,600 mg; PHA; mean proliferation 48,700 before treatment to 81,600 cpm; PWM: mean proliferation 6,300 before treatment to 16,200 cpm). Increased mitogen-induced proliferation following cimetidine intake is of special interest because the mechanisms of this activation process are incompletely known. Lymphocyte proliferation response is dependent on the availability of extracellular calcium. The function of the other bivalent cations is unknown. We found that the extent of mitogen-induced lymphocyte proliferation correlates with cellular intralymphocytic zinc and magnesium amounts (coefficients of correlation [r]) (800 mg: PHA/Mg r = 0.84; PHA/Zn r = 0.86; PWM/Mg r = 0.88; PWM/Zn r = 0.87). Though the application of both cimetidine doses causes enhanced mitogen-induced lymphocyte proliferation on day 7, T lymphocytes with different phenotypic properties appear to be influenced by cimetidine. In the first dose regimen (800 mg) the number of the CD8 lymphocytes decreased significantly from 16.1% (365 cell/microliters blood) to 12.7% (264 cells/microliters blood) after 7 d of cimetidine intake. After the period of high-dose (1,600 mg) cimetidine administration (at day 21) numbers of CD4 lymphocytes were significantly increased from 41.5% (860 cells/microliters blood) to 56.3% (1,210 cells/microliters blood). Our results show that although different cimetidine doses obviously influence different cell types of healthy volunteers, the cellular mechanisms are the same, namely, a proliferation and an increased incorporation of magnesium and zinc in lymphocytes.