RESUMEN
INTRODUCTION: One of the major concerns with post-acute sequelae of COVID-19 (PASC) is the development of pulmonary fibrosis, for which no approved pharmacological treatment exists. Therefore, the primary aim of this open-label study was to evaluate the safety and the potential clinical efficacy of a prolonged-release pirfenidone formulation (PR-PFD) in patients having PASC-pulmonary fibrosis. METHODS: Patients with PASC-pulmonary fibrosis received PR-PFD 1800 mg/day (1200 mg in the morning after breakfast and 600 mg in the evening after dinner) for three months. Blood samples were taken to confirm the pharmacokinetics of PR-PFD, and adverse events (AEs) were evaluated monthly using a short questionnaire. Symptoms, dyspnea, and pulmonary function tests (spirometry, diffusing capacity for carbon monoxide, plethysmography, and 6-min walk test [6MWT]) were evaluated at baseline, and one and three months after having started the PR-PFD treatment. RESULTS: Seventy subjects with mild to moderate lung restriction were included. The most common AEs were diarrhea (23%), heartburn (23%), and headache (16%), for which no modifications in the drug study were needed. Two patients died within the first 30 days of enrolment, and three opted not to continue the study, events which were not associate with PR-PFD. Pulmonary function testing, 6MWT, dyspnea, symptoms, and CT scan significantly improved after three months of treatment with PR-PFD. CONCLUSION: In patients with PASC pulmonary fibrosis, three months' treatment with PR-PFD was safe and showed therapeutic efficacy. Still, it remains to be seen whether the pulmonary fibrotic process remains stable, becomes progressive or will improve.
Asunto(s)
COVID-19 , Fibrosis Pulmonar Idiopática , Neumonía , Humanos , COVID-19/complicaciones , Progresión de la Enfermedad , Disnea/tratamiento farmacológico , Disnea/etiología , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/diagnóstico , Fenotipo , Neumonía/tratamiento farmacológico , Piridonas/efectos adversosRESUMEN
BACKGROUND: The most widely used treatment of portal-systemic encephalopathy (PSE) is the administration of oral, non-absorbable disaccharides. Theoretically, the inhibition of intestinal disaccharidases should induce malabsorption of disaccharides and increase delivery of undigested carbohydrates to the colon, thus stimulating the effects of lactulose and other non-absorbable disaccharides (that is, lactitol and lactose). AO-128 is an N-substituted derivative of valeolamine, an aminocyclitol that selectively inhibits intestinal disaccharidases. This study was performed to investigate whether AO-128 could be used as adjuvant therapy for the treatment of mild PSE in cirrhotic patients. METHODS: A double-blind, randomized, controlled trial was performed in 35 cirrhotic patients with PSE. Patients were given a 2-week treatment consisting of AO-128 (2 mg three times daily) or an identical placebo. The following features of PSE syndrome were assessed in a semiquantitative fashion before and after I and 2 weeks of therapy: mental state, asterixis, number connection test (NCT), venous blood ammonia concentration, electroencephalogram (EEG), and overall PSE index (PSEI). More patients receiving AO-128 than patients receiving placebo showed >40% improvement in the PSEI (83% versus 35%; P < 0.05). The mean stool pH decreased from 5.8+/-0.3 to 5.5+/-0.3 (P < 0.004) after AO-128 treatment, whereas no changes were observed in the placebo group. The EEG and nitrogen balance did not show significant changes in any of the two groups. A significant improvement was seen in the NCT performance after AO-128 (from grade 2.0+/-1.04 to grade 1.25+/-0.87; P < 0.05). Seven patients treated with AO-128 developed diarrhea, as compared with none in the placebo group (P < 0.05). CONCLUSION: These results suggest that AO-128 may be useful in the treatment of PSE, although further studies are required to establish the benefit of AO-128 and determine adequate individual doses.
Asunto(s)
Ciclohexanoles/uso terapéutico , Disacaridasas/antagonistas & inhibidores , Disacáridos/farmacocinética , Inhibidores Enzimáticos/uso terapéutico , Encefalopatía Hepática/tratamiento farmacológico , Ciclohexanoles/efectos adversos , Disacáridos/uso terapéutico , Método Doble Ciego , Inhibidores Enzimáticos/efectos adversos , Femenino , Encefalopatía Hepática/diagnóstico , Humanos , Absorción Intestinal/efectos de los fármacos , Masculino , Persona de Mediana EdadRESUMEN
Nonsteroidal anti-inflammatory drugs (NSAID) are widely used in current clinical practice. Several gastric lesions occur as a side effect. This review paper describes the spectrum of gastric lesions, its pathogenesis, prevalence and incidence as well as clinical data, common risk factors, treatment and the prophylaxis of NSAID gastric toxicity.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Gastritis/inducido químicamente , Adulto , Factores de Edad , Anciano , Algoritmos , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiulcerosos/uso terapéutico , Niño , Inhibidores de la Ciclooxigenasa/efectos adversos , Inhibidores de la Ciclooxigenasa/farmacología , Mucosa Gástrica/irrigación sanguínea , Mucosa Gástrica/efectos de los fármacos , Gastritis/epidemiología , Gastritis/patología , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/epidemiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Humanos , Incidencia , Persona de Mediana Edad , Neutrófilos/fisiología , Prevalencia , Ratas , Factores de Riesgo , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & controlRESUMEN
OBJECTIVES: 1) To evaluate the biochemical, renal, histological and splanchnic and systemic hemodynamic abnormalities induced by bile duct obstruction in rats, and 2) to study the temporal relationships between the start of portal hypertension, decrease of urinary sodium excretion and activation of the renin-angiotensin system. METHODS: Bile duct obstruction was induced in 127 male Wistar rats, and renal function, hemodynamic, biochemical and liver histology were evaluated at weeks 1, 2, 3 and 4 after complete bile duct obstruction; the data were compared to that in 30 control rats. RESULTS: Portal pressure significantly increased at week 1 (11.7 +/- 1.5. vs. 7.8 +/- 1.5 mmHg, p < 0.05) while the mean arterial pressure remained stable until week 4 when a slight decrease was observed (91.3 +/- 6.6 vs. 96.1 +/- 8.6 mmHg in control rats). A significant decrease in urinary sodium excretion was observed at week 1 (1.1 +/- 0.5 mEq/24 h) compared to control rats (2.3 +/- 0.6 mEq/24 h). In addition, hyperreninemia was observed at week 1 (5.1 +/- 0.2 vs. 2.4 +/- 1.3 ng Ang l/mL/h, p < 0.05) and hyperaldosteronism at week 2 (103 +/- 46 vs. 25.1 +/- 8.8 ng/24 h, p < 0.05) compared to control rats. CONCLUSION: A temporal relationship between the beginning of portal hypertension and a decrease of renal sodium excretion, hyperreninemia and hyperaldosteronism was observed in bile duct ligated rats. This experimental model could be used to evaluate the effects of new drugs to prevent biliary cirrhosis including the abnormalities in the renal handling of sodium.
Asunto(s)
Hipertensión Portal/fisiopatología , Cirrosis Hepática Biliar/fisiopatología , Sistema Renina-Angiotensina/fisiología , Sodio/orina , Animales , Hipertensión Portal/etiología , Hipertensión Portal/metabolismo , Riñón/fisiopatología , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/metabolismo , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
BACKGROUND: PBC progresses to cirrhosis and results in death due to liver failure or bleeding portal hypertension. Data of the clinical characteristics and survival of PBC patients allows the assessment of therapeutical alternatives as well as the establishment of inclusion criteria for liver transplantation. AIMS: One hundred and twenty patients with histological diagnosis of PBC, admitted from 1972 to 1992, were selected with the purpose of studying the clinical and biochemical characteristics and survival. METHODS: Patients who underwent liver transplant or those who had an incomplete follow-up were excluded. RESULTS: Therefore only 80 patients were included: these were seventy five women and five men, with mean age 46 +/- 11 years (X +/- SD) to whom demographic data, biochemical analysis, liver function (Child-Pugh) and liver damage (Ludwig) were recorded at the time of histological diagnosis, which was considered zero for calculating the survival (Kaplan Meier). The most common symptoms at diagnosis were pruritus in 63 patients, jaundice in 48, asthenia and adynamia in 55 patients. Eight cases were asymptomatic. According to Child-Pugh's classification, patients were grouped as follows: forty in stage A, 29 in B, and three in C; and according to liver damage (Ludwig), 8 in grade I, 28 in grade II, 22 in grade III and 14 in grade IV. The most frequent clinical associations were Sjögren's syndrome, in 30% of patients, although one case was associated to progressive muscular dystrophy and another one to multiple myeloma and hypothyroidism; in 58.7% of the cases, antimitochondrial antibodies were negative. One year survival was 75%, five years 44%, and seven years 13%. CONCLUSIONS: The most important characteristics of the studied patients were elevated percentage of negative antimitochondrial antibodies and short survival. it is important to impel the development of liver transplantation as the only mean to improve survival.
Asunto(s)
Cirrosis Hepática Biliar , Adulto , Anciano , Femenino , Humanos , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/mortalidad , Masculino , México/epidemiología , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To determine the diagnostic value of serum levels of copper, zinc and the Cu/Zn ratio in patients with hematological malignancies compared to gender- and age-matched control subjects. METHODS: A total of 44 patients with recently diagnosed and non-treated hematological malignancies were included: 17 lymphoma (11 non-Hodgkin), 15 acute leukemia (10 myeloblastic), and 12 with chronic leukemia (8 granulocytic); 95 healthy subjects were included. Copper and zinc serum levels were measured with a Perkin Elmer (model 2380) atomic absorption spectrophotometer. RESULTS: Serum copper levels (microgram/dL) were significantly lower in healthy subjects (54.4 +/- 8.9, p < 0.05) compared to patients with lymphoma (93.7 +/- 37.5), acute leukemia (80.6 +/- 44.6) or chronic leukemia (95.7 +/- 28.9) while serum zinc levels (microgram/dL) were significantly higher in healthy control subjects (100.4 +/- 14, p < 0.05) compared to patients with lymphoma (77.2 +/- 22.6), acute leukemia (66 +/- 15.6), or chronic leukemia (74.8 +/- 14.7). The Cu/Zn ratio was significantly lower in healthy subjects (0.54 +/- 0.13, p < 0.05) than in patients with lymphoma (1.21 +/- 0.5), acute leukemia (1.22 +/- 0.7), or chronic leukemia (1.28 +/- 0.4). Twenty three patients died during a mean follow-up period of 13 months and their serum zinc levels were significantly lower (68 +/- 21) than in the living patients (76 +/- 15, p < 0.05). CONCLUSION: Cu/Zn ratio is significantly higher in patients with lymphoma or acute and chronic leukemias compared to gender- and age-matched control subjects.
Asunto(s)
Cobre/sangre , Leucemia/sangre , Linfoma no Hodgkin/sangre , Zinc/sangre , Enfermedad Aguda , Adulto , Recuento de Células Sanguíneas , Proteínas Sanguíneas/análisis , Enfermedad Crónica , Femenino , Humanos , Leucemia/mortalidad , Linfoma no Hodgkin/mortalidad , Masculino , México/epidemiología , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Zinc/deficienciaRESUMEN
BACKGROUND AND METHODS: A possible association between hepatitis C virus infection (HCV) and membranoproliferative glomerulonephritis (MPGN) or membranous glomerulonephritis has recently been reported. The pathogenesis of this entity appears to be immunologically mediated. The purpose of this report is to describe the clinical, laboratory, and histopathological features of three patients with chronic HCV infection, without hepatitis B virus disease or autoimmune diseases, but with glomerular disease. RESULTS: All three patients had chronic hepatopathy stigmata, ascitis, peripheral edema, and normal blood pressure values. Laboratory results showed mild liver function abnormalities and normal levels of blood nitrogenous waste products. Microscopic hematuria, hypoalbuminemia, and variable proteinuria without hypercholesterolemia were found in all cases. All three had positive rheumatoid factor. Only one patient had positive antinuclear antibodies and antimitochondrial antibodies at low levels, and another displayed low C3 and C4 serum levels. Renal histology in the three cases showed type I membranoproliferative glomerulonephritis and hepatic cirrhosis in the liver biopsy. CONCLUSIONS: This report supports the association between chronic HCV infection and membranoproliferative glomerulonephritis. However, further studies are needed to establish more firmly the association as well as the mechanisms of pathogenesis and causality between them.
Asunto(s)
Glomerulonefritis Membranoproliferativa/complicaciones , Hepatitis C/complicaciones , Adulto , Femenino , Glomerulonefritis Membranoproliferativa/patología , Hepatitis C/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The aim of this study was to assess serum zinc levels in a cohort of healthy subjects and cirrhotic patients from Mexico City. A total of 153 healthy subjects and 100 cirrhotic patients, males and females aged 18-65, were studied. Inclusion criteria for healthy subjects were (1) Mexican-born with first and second generation relatives born in Mexico, and (2) somatometric (body mass index under 30) and clinical evaluation establishing that they had no underlying disease. Entry criteria for cirrhotic patients were (1) clinical and histological proven cirrhosis, (2) compensated liver disease (absence of coma, bleeding hemorrhage or refractory ascitis), and (3) cirrhosis of any cause. Zinc serum levels were measured with atomic absorption spectrophotometry. In healthy subjects, mean serum levels were 77.4 +/- 4.2 micrograms/dl (range 42.9-105.2 micrograms/dl). In cirrhotic patients zinc serum levels (58.9 +/- 16.1 micrograms/dl, range 22-88 micrograms/dl) were significantly lower than in healthy subjects (p < 0.05). A stepwise decline in serum zinc with worsening Child class (A, 73.4 +/- 13; B, 64.4 +/- 12; C, 55.8 +/- 15.6; p < 0.05 by ANOVA test) was found. In conclusion, this study confirms that zinc serum levels are significantly lower in cirrhotic patients and shows that zinc serum levels in a cohort of 153 healthy subjects from Mexico City were unexpectedly lower compared to those found in other countries. This last finding might be explained by different dietetic patterns and deserves further investigation.
Asunto(s)
Cirrosis Hepática/sangre , Zinc/sangre , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Estudios de Cohortes , Dieta , Femenino , Humanos , Cirrosis Hepática/clasificación , Cirrosis Hepática/virología , Cirrosis Hepática Alcohólica/sangre , Cirrosis Hepática Biliar/sangre , Masculino , México , Persona de Mediana Edad , Somatotipos , Espectrofotometría AtómicaRESUMEN
UNLABELLED: The mechanism of renal function abnormalities in experimental biliary cirrhosis can be partially explained by the absence of gastrointestinal bile flow, which predisposes to translocation of intestinal endotoxin, a potent renal vasoconstrictor. Since bile acids prevent the absorption of intestinal endotoxins, we aimed to evaluate the effects of ursodeoxycholic acid (UDCA) administration on renal function and hemodynamic abnormalities induced by 1 week of obstructive jaundice in rats. METHODS: Fifty-two rats were used; 30 had ligation of the common bile duct, 22 were sham operated. Bile duct ligated rats were randomly and blindly assigned to receive UDCA (25 mg/kg/day, n = 14) or placebo (n = 16) during 1 week. Sham rats received no treatment. Portal pressure (PP) as well as creatinine clearance (CrCl), urinary sodium (US), and plasma renin activity (PRA) were evaluated. Results are mean +/- SEM, with a significant value of p < 0.05. RESULTS: Portal pressure (10.4 +/- 1.1 vs. 12.1 +/- 0.8 mm Hg) was significantly lower in UDCA than in placebo-treated rats. ALT serum levels were also significantly lower in bile duct ligated rats receiving UDCA (77.3 +/- 28 IU/L) than in placebo-treated rats (162 +/- 65 IU/L). US (1.1 +/- 0.5 vs. 2.1 +/- 0.3 mEq/24 h) was significantly lower and PRA (6.0 +/- 2.6 vs. 1.9 +/- 1.0 ng Ang 1/mL/h) higher in bile duct ligated than in sham-operated rats. No differences were found between UDCA or placebo-treated bile duct ligated rats. CrCl was similar between sham (0.39 +/- 0.12 mL/min/100 g BW) and UDCA (0.32 +/- 0.16) but significantly lower in placebo-treated (0.28 +/- 0.07) than sham-operated rats (p < 0.05). CONCLUSION: UDCA administration had very mild effects on renal function abnormalities induced by experimental obstructive jaundice in rats. However, portal hypertension and biochemical abnormalities were partially improved.
Asunto(s)
Colestasis/tratamiento farmacológico , Riñón/efectos de los fármacos , Ácido Ursodesoxicólico/uso terapéutico , Análisis de Varianza , Animales , Colestasis/fisiopatología , Evaluación Preclínica de Medicamentos , Hemodinámica/efectos de los fármacos , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/fisiopatología , Riñón/fisiopatología , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Ácido Ursodesoxicólico/farmacologíaAsunto(s)
Trasplante de Hígado/patología , Adolescente , Adulto , Biopsia , Colestasis/patología , Femenino , Rechazo de Injerto/patología , Humanos , Isquemia/patología , Circulación Hepática , Pruebas de Función Hepática , Trasplante de Hígado/inmunología , Trasplante de Hígado/fisiología , Activación de Linfocitos , Masculino , Persona de Mediana EdadRESUMEN
Sodium benzoate is widely used in the Alimentary Industry at low doses for its antimicrobial action. It has also been used as a liver function test. The principle is to evaluate the liver capacity for conjugation of glycine to benzoic acid and to form hippuric acid which is excreted in the urine. In hyperammonemic syndromes, secondary to enzymatic deficiency of the urea cicle, sodium benzoate has the property to act as an alternative way of nitrogen excretion to urinary hippurate instead of urea. Recently, it has been proposed as a therapeutic alternative in cirrhotic patients with portal systemic encephalopathy. Historical, biochemical and clinical data which constitute the principles to validate its clinical application in Hepatology are reviewed in this manuscript.