Familial clustering of non-nuclear autoantibodies and C3 and C4 complement components in systemic lupus erythematosus

OBJECTIVE: To determine whether key features of systemic lupus erythematosus (SLE), namely, production of non-nuclear antibodies (anti-C1q and anticardiolipin antibodies [aCL]) and depletion of complement components C3 and C4, aggregate in families. In addition, we examined relationships between anti-C1q and C3 and C4 levels. METHODS: The study cohort comprised 1,037 predominantly white (82%) nuclear families in which at least 1 member had SLE. Associations of antibody measurements between probands and their unaffected siblings were examined using parametric and nonparametric analyses, along with associations between unaffected siblings and their parents. The heritability of anti-C1q, C3, and C4 was estimated, and interdependencies between these factors were examined in a regression model accounting for the family structure of the data set. RESULTS: We demonstrated associations between siblings for anti-C1q (odds ratio [OR] 3.74, 95% confidence interval [95% CI] 2.65, 5.28) and IgG and IgM aCL (OR 4.08, 95% CI 1.83, 5.13 and OR 2.06, 95% CI 1.46, 2.91, respectively) and, for anti-C1q, association between unaffected parents and their unaffected offspring (OR 4.34, 95% CI 2.16, 8.72). We also demonstrated significant heritability of anti-C1q, C3, and C4 (approximately 45%). Anti-C1q was negatively associated with C3 and C4 in SLE probands but not in their healthy relatives. CONCLUSION: Non-nuclear antibodies and C3 and C4 cluster within the families of SLE probands, suggesting that specific autoantibody formation is partly genetically determined, even if the total genetic effect in unaffected relatives is insufficient to cause disease. Anti-C1q antibodies accelerate C3 and C4 depletion in patients with SLE but have no effect in the absence of disease.     

Thai herbal antipyretic 22 formula (APF22) inhibits UVA‐mediated melanogenesis through activation of Nrf2‐regulated antioxidant defense

Thai herbal antipyretic 22 formula (APF22), a polyherbal formula, has been traditionally used to treat dermatologic problems including hyperpigmentation. Exposure of the skin to ultraviolet A (UVA) causes abnormal melanin production induced by photooxidative stress. This study thus aimed to investigate the protective effects of APF22 extracts and phenolic compounds, ferulic acid (FA), and gallic acid (GA; used as positive control and reference compounds), on melanogenesis through modulation of nuclear factor E2‐related factor 2 (Nrf2) signaling and antioxidant defenses in mouse melanoma (B16F10) cells exposed to UVA. Our results revealed that the APF22 extracts, FA, and GA reduced melanin synthesis as well as activity and protein levels of tyrosinase in UVA‐irradiated B16F10 cells. Moreover, APF22 extracts and both FA and GA were able to activate Nrf2‐antioxidant response element signaling and promote antioxidant defenses including glutathione, catalase, glutathione peroxidase, and the glutathione‐S‐transferase at both mRNA and enzyme activity levels in irradiated cells. In conclusion, APF22 extracts suppressed UVA‐mediated melanogenesis in B16F10 cells possibly via redox mechanisms involving activation of Nrf2 signaling and upregulation of antioxidant defenses. Moreover, pharmacological action of the APF22 extracts may be attributed to the phenolic compounds, FA, and GA, probably serving as the APF22's active compounds.     

Reproductive health and quality of life of young Burmese refugees in Thailand

Background  

Of the 140 000 Burmese* refugees living in camps in Thailand, 30% are youths aged 15-24. Health services in these camps do not specifically target young people and their problems and needs are poorly understood. This study aimed to assess their reproductive health issues and quality of life, and identifies appropriate service needs.     

Effect of biting speed and jaw separation on force used to incise food

Biting food too quickly might affect the control of jaw-closing muscles and the estimation of bite force. The objectives of this study were to compare the incisal bite forces used to cut food and the activity of masseter (MA) and anterior temporalis (AT) muscles between slow, habitual and fast biting speeds and also between small and large jaw openings. Twenty subjects were asked to use their incisors to cut through a 5 mm thick of chewing gum. In the first experiment, subjects bit at 10-mm incisal separation with slow, habitual and fast biting speeds, and in the second experiment, subjects bit with their habitual speed at 10- and 30-mm incisal separations. The activities in the MA and AT muscles were assessed with surface electromyography, and the bite force was recorded by a force sensor placed beneath the chewing gum. Peak bite forces and associated MA amplitudes were increased significantly as biting speed was increased (P's < .05). Anterior temporalis amplitude was significantly increased during fast biting compared to slow and habitual biting (P's < .001). At 30-mm incisal separation, both peak bite force and AT amplitude were significantly increased, whereas MA amplitude was significantly decreased, compared to those at 10-mm separation (P's < .05). Biting off food quickly with incisor teeth results in larger activities in both MA and AT muscles. In addition, biting a large piece of food resulted in increased activity of AT muscle. Both conditions could be injury stimulator for jaw muscles.     

Genotypic profile of Streptococcus suis serotype 2 and clinical features of infection in humans, Thailand

To examine associations between clinical features of Streptococcus suis serotype 2 infections in humans in Thailand and genotypic profiles of isolates, we conducted a retrospective study during 2006-2008. Of 165 patients for whom bacterial cultures of blood, cerebrospinal fluid, or both were positive for S. suis serotype 2, the major multilocus sequence types (STs) found were ST1 (62.4%) and ST104 (25.5%); the latter is unique to Thailand. Clinical features were examined for 158 patients. Infections were sporadic; case-fatality rate for adults was 9.5%, primarily in northern Thailand. Disease incidence peaked during the rainy season. Disease was classified as meningitis (58.9%) or nonmeningitis (41.1%, and included sepsis [35.4%] and others [5.7%]). Although ST1 strains were significantly associated with the meningitis category (p<0.0001), ST104 strains were significantly associated with the nonmeningitis category (p<0.0001). The ST1 and ST104 strains are capable of causing sepsis, but only the ST1 strains commonly cause meningitis.     

Premalignant lesions of cholangiocarcinoma: characteristics on ultrasonography and MRI

Background and objective

Cholangiocarcinoma (CCA) is an aggressive malignancy with high prevalence rate in Asia. The CCA premalignant lesions, including Biliary intraepithelial neoplasia (Bil-IN) and Intraductal papillary neoplasm of biliary tract (IPNB), share a common carcinogenesis; however, on imaging, patterns of presentation are different. Patterns and imaging characteristics on ultrasonography (US) and Magnetic resonance imaging (MRI) of both Bil-IN and IPNB are reported herein.

Methods

In this retrospective study of imaging findings in premalignant CCA, pathology-proven cases of Bil-IN and IPNB at Chulabhorn Hospital were analyzed. Demographics, locations of lesions, imaging characteristics of both Bil-IN and IPNB were assessed, compared, and described.

Results

Twenty-one premalignant lesions, 13 Bil-INs and 8 IPNBs, from 18 patients were included. Both Bil-IN and IPNB lesions were found more commonly at the right than left intrahepatic ducts (66.7% vs. 33.3%), and had more peripheral than central locations (85.7% vs. 14.3%). On US, Bil-IN commonly presented as focal bile duct dilatation (76.9%), whereas IPNB was more variable with hyperechoic nodules (37.5%), focal bile duct dilatation (37.5%), and diffuse bile duct dilatation with intraductal nodules (25%). On MRI, focal bile duct dilatation and nonfunctioning bile excretion are the most sensitive findings with sensitivities in the range of 84.6% to 100%. The presence of intraductal nodules and connection to the biliary system are findings that were significantly different between IPNB and Bil-IN, 62.5% versus 7.7% (p = 0.014) and 75% versus 15.4% (p = 0.018), respectively.

Conclusions

Premalignant lesions of CCA, including Bil-IN and IPNB, have different imaging presentations. Knowledge of imaging presentations may improve early detection and increase confidence in diagnosis.