Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis

Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of the TLR4 gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies

Thyroid Ultrasound in IDDM

Insulin dependent diabetes mellitus (IDMM) is often associated with autoimmune thryroiditis (AIT) and a high prevalence of thyroid antibodies (TA). Ultrasound imaging of the thyroid may contribute to the evaluation of patients with AIT. We therefore investigated ultrasound findings of the thyroid in 83 IDDM patients (44F, 39M) with an age range of 2.3-22.3 yrs (median 11.1). Thyroid volume (ml) determined by ultrasound ranged between 1.3 and 17.9 (median 5.7). Thyroid volumes of 75 healthy children (32F, 43M) with an age range of 2.0 to 11.8 yrs (median 7.6) ranged between 1.6 and 13.2 ml (median 4.8) and did not show a significant difference from the IDDM group from age 4 to 12. TA were positive in 18.8% of the IDDM group. Thyroid volume was higher in TA (+) diabetics (p=0.05), a finding which may be attributed to a higher percentage of cases with elevated TSH in the TA (+) group. Two diabetic patients showed non-homogeneous hypoechogenecity in the ultrasound compatible with AIT which was later confirmed in one of these cases by aspiration biopsy. Ultrasound imaging of the thyroid may contribute to the evaluation of patients with AIT in IDDM