Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation.

BACKGROUND & AIMS: Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH. METHODS: We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B12 (B12) and folate (Fol) to reverse NASH features in mice and cell culture. RESULTS: Serum Hcy correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was downregulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to a block in autophagy. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B12/Fol, which promotes enzymatic conversion of Hcy to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated ß -oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH. CONCLUSIONS: HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B12/folate also may represent a novel first-line therapy for NASH. LAY SUMMARY: The incidence of non-alcoholic steatohepatitis, for which there are no approved pharmacological therapies, is increasing, posing a significant healthcare challenge. Herein, based on studies in mice, primates and humans, we found that dietary supplementation with vitamin B12 and folate could have therapeutic potential for the prevention or treatment of non-alcoholic steatohepatitis.

Eficacia del tratamiento tópico con Vimang® en pacientes con estomatitis subprótesis / Effectiveness of topical treatment with Vimang® in patients with denture stomatitis

Se efectuó un ensayo clínico terapéutico controlado de fase III en 120 pacientes con estomatitis subprótesis, atendidos en la Clínica Estomatológica Provincial Docente "Mártires del Moncada" de Santiago de Cuba, desde junio de 2010 hasta mayo de 2011, con vistas a evaluar la eficacia del tratamiento tópico con té de Vimang® en dichos pacientes. Se conformaron 2 grupos de 60 integrantes cada uno (de estudio y de control). Los primeros fueron tratados con enjuagatorios fríos de dicho té 4 veces al día y los segundos con el mismo tratamiento más vitaminas. Se utilizaron el porcentaje para variables cualitativas, así como la media aritmética y la desviación estándar para variables cuantitativas. Todos los integrantes del grupo de estudio se curaron y disminuyó el gasto de material, pero el costo-efectividad fue mayor por ser menor el tiempo de curación. El té de Vimang® resultó eficaz para eliminar las manifestaciones clínicas de esa lesión y no hubo reacciones adversas, de manera que se logró la curación de los afectados con ahorro de tiempo y recursos.

A stage III controlled therapeutic clinical trial was performed in 120 patients with denture stomatitis, attended in the Provincial School of Dentistry "Martires del Moncada" of Santiago de Cuba, from June 2010 to May 2011, in order to evaluate the effectiveness of topical treatment with Vimang® tea in these patients. Two groups (study and control) with 60 members each were divided. The first ones were treated with tea cold mouthwashes 4 times a day and the second ones with the same treatment and vitamins. The percentage for qualitative variables and the arithmetic mean and standard deviation for quantitative variables were used. All members of the study group were cured and material usage decreased but the cost-effectiveness was higher because of lower healing time. The Vimang® tea was effective in eliminating the clinical manifestations of that lesion and there were not adverse reactions, so that it was possible to cure those affected, saving time and resources.

A severe case of rat lungworm disease in Hawa'i.

A 23-year-old man living on the island of Hawa'i developed a life threatening case of eosinophilic meningitis caused by infection with Angiostrongylus cantonensis (rat lungworm disease: RLWD). He was comatose for 3 months, incurring brain and nerve damage sufficiently extensive that he was not expected to recover. The case was complicated by secondary infections of methicillin-resistant Staphylococcus aureus, Clostridium difficile, and pneumonia, which resulted in an empyema requiring a thoracoscopy and decortication. He was treated with prednisone, mebendozal, and pain medication for RLWD, and antibiotics and antifungal medications for the secondary infections. The administration of herbal supplements was requested by the family and approved, and these were administered through a gastric tube. Less than a month after being declared in a persistent vegetative state the man was able to talk, eat, and had regained some muscle functions. After release from the hospital he continued the use of supplements and received treatments of intravenous vitamin therapy. Four years after onset of the illness he is able to ride a bicycle, is a part time student, plays guitar, and is fluent in two foreign languages. RLWD is an emerging tropical disease of growing importance in Hawa'i.