RESUMO
BACKGROUND: Benefits of recombinant human growth hormone (rhGH) alone or combined with glutamine in patients with intestinal failure because of short-bowel syndrome remain controversial. OBJECTIVE: We explored effects of rhGH on whole-body protein metabolism in patients with short-bowel syndrome with intestinal failure (SBS-IF) to gain insight into its mechanism of action. DESIGN: Eight stable hyperphagic patients with severe SBS-IF received, in a double-blind, randomized crossover study, low-dose rhGH (0.05 mg · kg⻹ · d⻹) and a placebo for two 3-wk periods. Leucine and glutamine kinetics under fasting and fed conditions, fat-free mass (FFM), and serum insulin were determined on the final day of each treatment. RESULTS: rhGH increased FFM and nonoxidative leucine disposal (NOLD; an index of protein synthesis) (P < 0.02), whereas FFM and NOLD were correlated in the fed state (r = 0.81, P = 0.015). With rhGH administration, leucine release from protein breakdown (an index of proteolysis) decreased in the fed compared with fasting states (P = 0.012), which was not observed with the placebo. However, the fast-to-fed difference in leucine release from protein breakdown was not significantly different between rhGH and placebo (P = 0.093). With rhGH, the intestinal absorption of leucine and glutamine increased (P = 0.036) and correlated with serum insulin (r = 0.91, P = 0.002). rhGH increased glutamine de novo synthesis (P < 0.02) and plasma concentrations (P < 0.03) in both fasting and fed states. CONCLUSIONS: In SBS-IF patients, feeding fails to decrease proteolysis in contrast to what is physiologically observed in healthy subjects. rhGH enhances FFM through the stimulation of protein synthesis and might decrease proteolysis in response to feeding. Improvements in de novo synthesis and intestinal absorption increase glutamine availability over the physiologic range, suggesting that beneficial effects of rhGH in hyperphagic patients might be achieved without glutamine supplementation.
Assuntos
Fármacos Gastrointestinais/uso terapêutico , Glutamina/biossíntese , Hormônio do Crescimento Humano/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Síndrome do Intestino Curto/tratamento farmacológico , Adulto , Composição Corporal/efeitos dos fármacos , Estudos de Coortes , Terapia Combinada , Estudos Cross-Over , Método Duplo-Cego , Feminino , Glutamina/sangue , Glutamina/metabolismo , Hormônio do Crescimento Humano/genética , Humanos , Hiperfagia/etiologia , Resistência à Insulina , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiopatologia , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral no Domicílio , Período Pós-Prandial , Biossíntese de Proteínas/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Proteínas Recombinantes/uso terapêutico , Índice de Gravidade de Doença , Síndrome do Intestino Curto/metabolismo , Síndrome do Intestino Curto/fisiopatologia , Síndrome do Intestino Curto/terapia , Aumento de Peso/efeitos dos fármacosRESUMO
AIM: To determine in a noninferiority study whether mesalamine foam is as effective as mesalamine liquid enema for inducing clinical remission in patients with active left-sided ulcerative colitis (UC). METHODS: In a multicenter investigator-blind trial, 375 patients with mild-to-moderate UC were randomized to receive mesalamine foam 1 g/80 mL/day or mesalamine liquid enema 1 g/100 mL/day for 4 wk (W). Inclusion criteria were: disease extension at least 5 cm from anorectal junction and not above splenic flexure and Clinical Activity Index (CAI) 1-4 > or = 4. Primary end point was clinical remission at W4 defined as a CAI 1-4 < or = 2. Noninferiority of the foam to liquid enema was declared if the lower limit of the 97.5% unilateral confidence interval (97.5% CI) of the difference in remission rates between foam and liquid enema groups was greater than -15% . RESULTS: Remission rates at W4 in foam versus liquid were 68.3%versus 73.6% in per protocol (PP) population (lower limit of 97.5% CI -15.1%) and 66.7%versus 70.5% in intention-to-treat (ITT) population (97.5% CI -13.4%). Remission rates at W2 were 48.1 %versus 50.6% in ITT (97.5% CI -12.8%) and 49.1%versus 52.1% in PP (97.5% CI -13.8%) in foam versus liquid, respectively. Both treatments were well tolerated. CONCLUSIONS: A 4-wk treatment of 1 g mesalamine foam induced a clinical remission in 68% patients versus 73% with 1 g mesalamine liquid enema. Although the noninferiority of mesalamine foam could not be strictly demonstrated at W4 in the PP analysis, it was achieved in the ITT population and at W2 in both populations. Mesalamine foam represents a therapeutic alternative to mesalamine liquid enema in patients with mild-to-moderate active proctitis and proctosigmoiditis.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Enema/métodos , Mesalamina/administração & dosagem , Proctite/tratamento farmacológico , Administração Retal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/complicações , Formas de Dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proctite/etiologia , Proctocolite/tratamento farmacológico , Proctocolite/etiologia , Método Simples-Cego , Resultado do Tratamento , Adulto JovemRESUMO
Intestinal bacteria play a key role in inflammatory bowel disease. Probiotics attempt to modify disease by favourably altering bacterial composition, immune status, and inflammation. Until recently, probiotic therapy was considered 'folk' medicine, but there now is emerging interest on the part of the general public and scientific communities in the use of probiotics in human disease. This practical, evidence-based review examines probiotics as therapy for inflammatory bowel disease in humans. There are very few such published randomized clinical trials, but some data exist that possibly show an efficacy of probiotics as maintenance therapy in chronic relapsing pouchitis. Obstacles to providing probiotic therapy include selection of appropriate strains, poorly regulated probiotic quality standardization, processing and human biologic factors which impair probiotic viability, difficulty in maintaining new bacterial populations in the gut, and local product unavailability. Studies have focused on specific inflammatory bowel disease subgroups, limiting general applicability for the practitioner. Basic research highlights the importance of bacteria in these conditions, and the possibility that probiotics will modify physiological parameters. Well-designed, randomized clinical studies are still required to define the role of probiotics as therapeutic agents in inflammatory bowel disease.