Dithiocarbamates and iron chelators were recently considered for the treatment of AIDS and neurodegenerative diseases. In this study, we show that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes. Using cell cultures, the pyrrolidine derivative of dithiocarbamate (PDTC) was investigated in detail. Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit I kappa B from the latent cytoplasmic form of NF-kappa B in cells treated with phorbol ester, interleukin 1, and tumor necrosis factor alpha. Other DNA binding activities and the induction of AP-1 by phorbol ester were not affected. The antioxidant PDTC also blocked the activation of NF-kappa B by bacterial lipopolysaccharide (LPS), suggesting a role of oxygen radicals in the intracellular signaling of LPS. This idea was supported by demonstrating that treatment of pre-B and B cells with LPS induced the production of O2- and H2O2. PDTC prevented specifically the kappa B-dependent transactivation of reporter genes under the control of the HIV-1 long terminal repeat and simian virus 40 enhancer. The results from this study lend further support to the idea that oxygen radicals play an important role in the activation of NF-kappa B and HIV-1.

Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells.

Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: An animal model of HLA-B27-associated human disorders

https://zenodo.org/record/1258307/files/article.pdf

Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?

Context.—Medical evidence may be biased over time if completion and publication
of randomized efficacy trials are delayed when results are not statistically
significant.Objective.—To evaluate whether the time to completion and the time to publication
of randomized phase 2 and phase 3 trials are affected by the statistical significance
of results and to describe the natural history of such trials.Design.—Prospective cohort of randomized efficacy trials conducted by 2 trialist
groups from 1986 to 1996.Setting.—Multicenter trial groups in human immunodeficiency virus infection sponsored
by the National Institutes of Health.Patients.—A total of 109 efficacy trials (total enrollment, 43708 patients).Main Outcome Measures.—Time from start of enrollment to completion of follow-up and time from
completion of follow-up to peer-reviewed publication assessed with survival
analysis.Results.—The median time from start of enrollment to publication was 5.5 years
and was substantially longer for negative trials than for results favoring
an experimental arm (6.5 vs 4.3 years, respectively; P<.001;
hazard ratio for time to publication for positive vs negative trials, 3.7;
95% confidence interval [CI], 1.8-7.7). This difference was mostly attributable
to differences in the time from completion to publication (median, 3.0 vs
1.7 years for negative vs positive trials; P<.001).
On average, trials with significant results favoring any arm completed follow-up
slightly earlier than trials with nonsignificant results (median, 2.3 vs 2.5
years; P=.045), but long-protracted trials often
had low event rates and failed to reach statistical significance, while trials
that were terminated early had significant results. Positive trials were submitted
for publication significantly more rapidly after completion than were negative
trials (median, 1.0 vs 1.6 years; P=.001) and were
published more rapidly after submission (median, 0.8 vs 1.1 years; P=.04).Conclusion.—Among randomized efficacy trials, there is a time lag in the publication
of negative findings that occurs mostly after the completion of the trial
follow-up.

/pdf/effect-of-the-statistical-significance-of-results-on-the-2kobdtadoc.pdf

Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials.

Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.

• Human immunodeficiency virus (HIV) causes a spectrum of immunodysfunction, the most severe of which is the acquired immunodeficiency syndrome (AIDS). We have followed the course of psoriasis in 13 patients over 2 ½ years in a population of more than 1000 HIV-positive individuals. Four patients had a history of mild psoriasis that became severe and uncontrollable as symptoms of immunodeficiency developed. Psoriasis and HIV positivity, AIDS-related complex, or AIDS simultaneously developed in nine patients. In addition to psoriasis, Reiter's syndrome (arthritis, urethritis, and conjunctivitis) developed in one patient in the first group and three patients in the second group. Opportunistic infections, especially candidiasis andStaphylococcus, drugs, and an altered immune system may contribute to the development or flare of psoriasis in these patients. The appearance of severe psoriasis (especially in a patient with other risk factors for HIV) should prompt evaluation for HIV, and may be a poor prognostic indicator in HIV-positive patients, since nine of our 13 patients have died. Immunosuppressive therapy with methotrexate is contraindicated in this group of patients. Newer forms of drug therapy including etretinate show promising results for the management of AIDS-associated psoriasis. (Arch Dermatol1987;123:1622-1632)

Acquired Immunodeficiency Syndrome— Associated Psoriasis and Reiter's Syndrome

We randomized 389 symptomatic patients with human immunodeficiency virus (HIV) infection to ditiocarb sodium (400 mg/m 2 orally for 24 weeks) or a placebo. Patients were well balanced according to Centers for Disease Control (CDC) group, CD4 + cell number, and duration of disease prior to entry. Ten new acquired immunodeficiency syndrome (AIDS)—defining opportunistic infections occurred in the treated patients and 21 in the controls. Reduction of new opportunistic infections in the ditiocarb group was significant in all patients (relative risk [RR], 0.44) and in patients with AIDS (CDC groups IV-C1 and IV-D) (RR, 0.12). The size of the effect of ditiocarb was maintained when data were reanalyzed after exclusion of a patient who progressed to Pneumocystis carinii pneumonia who was not strictly CDC-defined (RR, 0.46), or when considering as new opportunistic infections three events, which were clinically active at entry, but for which the definitive diagnosis was made during study (RR, 0.49). The administration of ditiocarb did not induce any major adverse clinical or biological reactions. We conclude that, in this study, ditiocarb was safe and reduced the incidence of opportunistic infections in patients with symptomatic HIV infection. ( JAMA . 1991;265:1538-1544)

https://jamanetwork.com/journals/jama/articlepdf/385434/jama_265_12_035.pdf

Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS. A randomized, double-blind, placebo-controlled, multicenter study.

Brewton Gary W

Papers

Acquired Immunodeficiency Syndrome— Associated Psoriasis and Reiter's Syndrome

Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS. A randomized, double-blind, placebo-controlled, multicenter study.

Remission of AIDS-associated psoriasis with zidovudine

Remission of AIDS-associated psoriasis with zidovudine.

Genetic Susceptibility to AIDS: Absence of an Association with Group-Specific Component (Gc)