RESUMO
Small intestinal bacterial overgrowth (SIBO) is common among patients with HIV-associated autonomic neuropathies (HIV-AN) and may be associated with increased bacterial translocation and elevated plasma inflammatory biomarkers. Pyridostigmine is an acetylcholinesterase inhibitor which has been used to augment autonomic signaling. We sought preliminary evidence as to whether pyridostigmine could improve proximal gastrointestinal motility, reduce SIBO, reduce plasma sCD14 (a marker of macrophage activation and indirect measure of translocation), and reduce the inflammatory cytokines IL-6 and TNFα in patients with HIV-AN. Fifteen participants with well-controlled HIV, HIV-AN, and SIBO were treated with 8 weeks of pyridostigmine (30 mg PO TID). Glucose breath testing for SIBO, gastric emptying studies (GES) to assess motility, plasma sCD14, IL-6, and TNFα, and gastrointestinal autonomic symptoms were compared before and after treatment. Thirteen participants (87%) experienced an improvement in SIBO following pyridostigmine treatment; with an average improvement of 50% (p = 0.016). There was no change in gastrointestinal motility; however, only two participants met GES criteria for gastroparesis at baseline. TNFα and sCD14 levels declined by 12% (p = 0.004) and 19% (p = 0.015), respectively; there was no significant change in IL-6 or gastrointestinal symptoms. Pyridostigmine may ameliorate SIBO and reduce levels of sCD14 and TNFα in patients with HIV-AN. Larger placebo-controlled studies are needed to definitively delineate how HIV-AN affects gastrointestinal motility, SIBO, and systemic inflammation in HIV, and whether treatment improves clinical outcomes.
Assuntos
Vias Autônomas/efeitos dos fármacos , Inibidores da Colinesterase/uso terapêutico , Infecções por HIV/tratamento farmacológico , Intestino Delgado/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Brometo de Piridostigmina/uso terapêutico , Vias Autônomas/imunologia , Vias Autônomas/microbiologia , Vias Autônomas/patologia , Translocação Bacteriana/efeitos dos fármacos , Translocação Bacteriana/imunologia , Esquema de Medicação , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Expressão Gênica , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Intestino Delgado/imunologia , Intestino Delgado/microbiologia , Intestino Delgado/patologia , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Recent electrophysiological studies on peripheral autonomic dysfunction in leprosy patients show a high prevalence of autonomic dysfunction as measured by abnormal vasomotor reflexes (VMR) and absent sympathetic skin response (SSR). Nothing is known about the reversibility of these autonomic parameters with treatment. Since there is evidence that small fiber function may be the most reversible component in neuropathies, we measured the effect of steroid treatment on autonomic parameters together with motor and sensory functions in leprosy patients with acute neuritis. Control subjects were investigated for repeatability testing of autonomic function. Due to a relatively high variability on repeat VMR testing in the controls, we defined a change in VMR testing as a change of > 30%. With this definition, the VMR of 14.8% of the patients improved, 75% remained unchanged, and 10.2% worsened. Absent SSR became positive in 16.6% and remained unchanged in 83.4%. Improvement in sensory motor functions was seen in 21.2% and 1.3% of the patients, respectively.
