RANKL Triggers Treg-Mediated Immunoregulation in Inflammatory Osteolysis.

The chronic inflammatory immune response triggered by the infection of the tooth root canal system results in the local upregulation of RANKL, resulting in periapical bone loss. While RANKL has a well-characterized role in the control of bone homeostasis/pathology, it can play important roles in the regulation of the immune system, although its possible immunoregulatory role in infectious inflammatory osteolytic conditions remains largely unknown. Here, we used a mouse model of infectious inflammatory periapical lesions subjected to continuous or transitory anti-RANKL inhibition, followed by the analysis of lesion outcome and multiple host response parameters. Anti-RANKL administration resulted in arrest of bone loss but interfered in the natural immunoregulation of the lesions observed in the untreated group. RANKL inhibition resulted in an unremitting proinflammatory response, persistent high proinflammatory and effector CD4 response, decreased regulatory T-cell (Treg) migration, and lower levels of Treg-related cytokines IL-10 and TGFb. Anti-RANKL blockade impaired the immunoregulatory process only in early disease stages, while the late administration of anti-RANKL did not interfere with the stablished immunoregulation. The impaired immunoregulation due to RANKL inhibition is characterized by increased delayed-type hypersensitivity in vivo and T-cell proliferation in vitro to the infecting bacteria, which mimic the effects of Treg inhibition, reinforcing a possible influence of RANKL on Treg-mediated suppressive response. The adoptive transfer of CD4+FOXp3+ Tregs to mice receiving anti-RANKL therapy restored the immunoregulatory capacity, attenuating the inflammatory response in the lesions, reestablishing normal T-cell response in vivo and in vitro, and preventing lesion relapse upon anti-RANKL therapy cessation. Therefore, while RANKL inhibition efficiently limited the periapical bone loss, it promoted an unremitting host inflammatory response by interfering with Treg activity, suggesting that this classic osteoclastogenic mediator plays a role in immunoregulation.

[Practical aspects for minimizing errors in the cross-cultural adaptation and validation of quality of life questionnaires]. / Cómo minimizar errores al realizar la adaptación transcultural y la validación de los cuestionarios sobre calidad de vida: aspectos prácticos.

BACKGROUND: The development and validation of questionnaires for evaluating quality of life (QoL) has become an important area of research. However, there is a proliferation of non-validated measuring instruments in the health setting that do not contribute to advances in scientific knowledge. AIMS: To present, through the analysis of available validated questionnaires, a checklist of the practical aspects of how to carry out the cross-cultural adaptation of QoL questionnaires (generic, or disease-specific) so that no step is overlooked in the evaluation process, and thus help prevent the elaboration of insufficient or incomplete validations. METHODS: We have consulted basic textbooks and Pubmed databases using the following keywords quality of life, questionnaires, and gastroenterology, confined to «validation studies¼ in English, Spanish, and Portuguese, and with no time limit, for the purpose of analyzing the translation and validation of the questionnaires available through the Mapi Institute and PROQOLID websites. RESULTS: A checklist is presented to aid in the planning and carrying out of the cross-cultural adaptation of QoL questionnaires, in conjunction with a glossary of key terms in the area of knowledge. The acronym DSTAC was used, which refers to each of the 5 stages involved in the recommended procedure. In addition, we provide a table of the QoL instruments that have been validated into Spanish. CONCLUSIONS: This article provides information on how to adapt QoL questionnaires from a cross-cultural perspective, as well as to minimize common errors.

The role of liver transplantation in patients with Caroli's disease.

Caroli's disease, characterized by segmental or diffuse dilation of the intrahepatic biliary ducts, is a rare disease which is difficult to treat. The course of the disorder is characterized by recurrent episodes of cholangitis and hospital stays, with a consequent loss of quality-of-life and productive capacity, often ending in death due to uncontrolled infection. Endoscopic drainage of the bile duct, percutaneously or surgically, is palliative, and presents bad results in the follow-up of these patients. Orthotopic liver transplantation appears to be an effective curative option for the treatment of patients with Caroli's disease associated to complications. The authors present the course of two cases of this disease, associated with congenital fibrosis of the liver worsened by repeated episodes of cholangitis, submitted to orthotopic liver transplantation.

Acute hepatitis C complicated by pancreatitis: another extrahepatic manifestation of hepatitis C virus?

In hepatitis C virus (HCV) infection a number of extrahepatic manifestations have been described, generally caused by immune phenomena. Here we report a case of acute pancreatitis, detected during an acute hepatitis C infection, in an elderly female patient.

Motor activity of the gallbladder in systemic sclerosis.

OBJECTIVE: We sought to measure gallbladder emptying in scleroderma patients, when stimulated by exogenous cholecystokinin. METHODS: Twenty-eight consecutive scleroderma patients were evaluated. Ten were excluded for the presence of gallstones. Gallbladder motor function was studied in 18 patients and 18 controls, using specific parameters for the quantification of gallbladder emptying dynamics. Resting gallbladder volumes were compared using the Dodds method with real-time ultrasound. Cholecystokinin (CCK)-stimulated gallbladder function (0.02 microg/kg CCK intravenous infusion/30 min) was assessed by a scintigraphic technique using 99mTc-DISIDA. Five patients presented with CREST syndrome, 13 with the diffuse form of scleroderma. Four were men, 14 women (average age = 46.6+/-15.4 yr). Patients and controls were paired by gender, age, and weight. RESULTS: Resting gallbladder volumes were larger in the four men with scleroderma than in the women with this disease (p < 0.03, Mann-Whitney). The mean gallbladder resting volume in scleroderma patients was not different from the mean volume detected among controls (p = 0.25), even when controlling for gender (p = 0.78 for women, p = 0.08 for men), scleroderma disease subtype (p = 0.50), or disease duration (p = 0.48). Latency period, ejection period, ejection rate, or ejection fraction as measured during cholecystokinin-stimulated scintigraphic studies were not significantly different between patients and controls. A trend was detected for reduction of the ejection period in scleroderma women (p = 0.70) when compared with scleroderma men. More than 35% of the scleroderma patients presented biliary lithiasis. CONCLUSIONS: There was no significant difference in gallbladder dynamics measured by a scintigraphic technique in scleroderma patients, compared with controls, when gallbladder motor function was evaluated by intravenous CCK.

Percutaneous transluminal angioplasty of the hepatic veins for treatment of Budd-Chiari syndrome.

The authors report a case of Budd-Chiari syndrome caused by occlusion of all of the hepatic veins which was treated by percutaneous transluminal angioplasty. There were two recurrences requiring redilatation. Two years later, the patient was asymptomatic and off medication.