On the Action of Cyclosporine A, Rapamycin and Tacrolimus on M. avium Including Subspecies paratuberculosis

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) may be zoonotic. Recently the "immuno-modulators" methotrexate, azathioprine and 6-MP and the "anti-inflammatory" 5-ASA have been shown to inhibit MAP growth in vitro. We concluded that their most plausible mechanism of action is as antiMAP antibiotics. The "immunosuppressants" Cyclosporine A, Rapamycin and Tacrolimus (FK 506) treat a variety of "autoimmune" and "inflammatory" diseases. Rapamycin and Tacrolimus are macrolides. We hypothesized that their mode of action may simply be to inhibit MAP growth. METHODOLOGY: The effect on radiometric MAP (14)CO(2) growth kinetics of Cyclosporine A, Rapamycin and Tacrolimus on MAP cultured from humans (Dominic & UCF 4) or ruminants (ATCC 19698 & 303) and M. avium subspecies avium (ATCC 25291 & 101) are presented as "percent decrease in cumulative GI" (%-DeltacGI.) PRINCIPAL FINDINGS: The positive control clofazimine has 99%-DeltacGI at 0.5 microg/ml (Dominic). Phthalimide, a negative control has no dose dependent inhibition on any strain. Against MAP there is dose dependent inhibition by the immunosuppressants. Cyclosporine has 97%-DeltacGI by 32 microg/ml (Dominic), Rapamycin has 74%-DeltacGI by 64 microg/ml (UCF 4) and Tacrolimus 43%-DeltacGI by 64 microg/ml (UCF 4) CONCLUSIONS: We show heretofore-undescribed inhibition of MAP growth in vitro by "immunosuppressants;" the cyclic undecapeptide Cyclosporine A, and the macrolides Rapamycin and Tacrolimus. These data are compatible with our thesis that, unknowingly, the medical profession has been treating MAP infections since 1942 when 5-ASA and subsequently azathioprine, 6-MP and methotrexate were introduced in the therapy of some "autoimmune" and "inflammatory" diseases

HIV, syphilis, and hepatitis B and C prevalence among patients with mental illness: a review of the literature Prevalência de infecção por HIV, sífilis e hepatite B e C entre portadores de doenças mentais crônicas

A limited number of studies worldwide have investigated the prevalence of HIV, syphilis, and hepatitis B and C infection among psychiatric patients. However, prevalence of these infections in the population with chronic mental illness has not been clearly established. Most of the published papers are from developed countries and have derived from relatively small and non-representative samples. We performed a systematic review of the published literature to identify studies on these infectious diseases within psychiatric populations in Brazil and other developing countries. Overall, prevalence rates varied from 0% to 29% for HIV; 1.6% to 66% for HBV; 0.4% to 38% for HCV; and 1.1% to 7.6% for syphilis. Several risk factors were identified and discussed, although sampling limitations restrict the generalization of study findings. This review highlights the lack of information on the prevalence of sexually transmitted diseases and their associated factors among persons with chronic mental illness and identifies gaps in the knowledge base in both developing and developed countries.<br>Os portadores de doenças mentais crônicas encontram-se em risco para a infecção pelo HIV e outras infecções sexualmente transmissíveis. Entretanto, a prevalência dessas infecções entre portadores de doença mental crônica ainda não está claramente estabelecida nesta população. A maioria dos trabalhos sobre o tema foi conduzida em países desenvolvidos, com amostras relativamente pequenas e não representativas. Foi realizada uma revisão sistemática da literatura para identificar estudos sobre a prevalência do HIV, sífilis, hepatite B e C entre pacientes com doença mental crônica no Brasil e no mundo. De um modo geral, as prevalências variaram de 0% a 29%, 3 a 66%, 0,4 a 38% e 3,3% a 7,6% para HIV, hepatite B, hepatite C e sífilis, respectivamente. Vários fatores de risco foram identificados e discutidos, embora a literatura atual não demonstre achados significativos gerados por estudos representativos. Tal revisão destaca a escassez de informação sobre a prevalência de infecções sexualmente transmitidas e seus fatores associados entre portadores de doenças mentais crônicas e identifica lacunas no conhecimento atual em países desenvolvidos bem como nos em desenvolvimento