Immunohistochemical Profile of VEGF, PGE and TGF-β in Inflammatory Tenosynovitis of Carpal Tunnel Syndrome

Inflammatory tenosynovitis is an inflammation that involves the tendons and synovial sheaths caused by minor trauma repeated for a long period of time. This inflammatory disease may be involved in the onset of tunnel carpal syndrome (CTS), because of the thickening of the tendon sheath that may produce an increase in the carpal canal pressure and damage of the median nerve in the wrist. Recent studies suggest that in patients with CTS pathological changes occur in the subsynovial connective tissue, such as vascular proliferation and non-inflammatory synovial fibrosis. However, little is known about the pathological mechanism of tenosynovial thickening. The aim of this study is to evaluate the potential role of vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE 2 ) and trasforming growth factor-beta (TGF-β) in the modifications of connective synovial tissue of CTS specimens in order to determine whether these factors play a role in the development of this disease. Ten specimens from patients with CTS and four control tissues (cadavers) were analyzed by immunohistochemistry using specific antibodies against these growth factors. A temporary increase in the production of these molecules was found in cells within the vessels and synovial lining during the intermediate phase of the syndrome, when the histology of the tenosynovium changes from oedematous to fibrotic. Our data confirm a close correlation between the expression of PGE 2 and VEGF. Recent histological examinations have shown a marked increase in vascular proliferation and reduction of fibroblast density in specimens from CTS patients during the intermediate phase. Our study indicates that the expression of TGF-β in fibroblasts and vascular endothelial cells of synovial connective tissues of CTS patients was significantly higher than in those of controls. These findings suggest that angiogenesis appears to take place as a part of a regenerative reaction that results in fibrosis. We believe that VEGF, TGF-β and PGE 2 may be potential therapeutic targets in the treatment of this disease although proof of this evidence requires further studies

NEUROTROPHINS, THEIR RECEPTORS AND KI-67 IN HUMAN GH-SECRETING PITUITARY ADENOMAS: AN IMMUNOHISTOCHEMICAL ANALYSIS

Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM

Skin prick tests and specific IgE in 10-year-old children: Agreement and association with allergic diseases

BACKGROUND: Accurate assessment of atopic sensitization is pivotal to clinical practice and research. Skin prick test (SPT) and specific IgE (sIgE) are often used interchangeably. Some studies have suggested a disagreement between these two methods, and little is known about their association with allergic diseases. The aims of our study were to evaluate agreement between SPT and sIgE, and to compare their association with allergic diseases in 10-year-old children. METHODS: Skin prick test, sIgE measurements, and assessment of allergic diseases were performed in children aged 10 years in the Protection against Allergy: STUdy in Rural Environments (PASTURE) cohort. The agreement between SPT and sIgE was assessed by Cohen's kappa coefficient with different cutoff values. RESULTS: Skin prick tests and sIgE were performed in 529 children. The highest agreement (κ=.44) was found with a cutoff value of 3 and 5 mm for SPT, and 3.5 IU/mL for sIgE. The area under the curve (AUC) obtained with SPT was not significantly different from that obtained with sIgE. For asthma and hay fever, SPT (cutoff value at 3 mm) had a significantly higher specificity (P<.0001) than sIgE (cutoff value at 0.35 IU/mL) and the specificity was not different between both tests (P=.1088). CONCLUSION: Skin prick test and sIgE display moderate agreement, but have a similar AUC for allergic diseases. At the cutoff value of 3 mm for SPT and 0.35 IU/mL for sIgE, SPT has a higher specificity for asthma and hay fever than sIgE without difference for sensitivity

Endotoxin levels in cow's milk samples from farming and non-farming families - the PASTURE study

BACKGROUND: Children from farming families have less allergies than their peers. Consumption of farm milk or unpasteurized milk has been shown to explain (part of) the farming effect or protect against allergies independent of farming status. OBJECTIVES: We investigated whether the protective effect of farm milk consumption can be explained by higher levels of bacterial endotoxin in milk. METHODS: We measured endotoxin in approximately 400 farm milk and shop milk samples from farming and non-farming families, respectively, with the kinetic chromogenic Limulus Amebocyte Lysate test and compared endotoxin levels between groups defined by farming status and type of milk (farm milk/shop milk). RESULTS: Endotoxin levels were significantly higher in milk samples from non-farming families compared to farming families [adjusted geometric means ratio (95% confidence interval)=2.61 (1.53-4.43)]. No significant difference in endotoxin levels was found between shop milk and farm milk samples [adjusted geometric means ratio (95% confidence interval)=1.56 (0.94-2.58)]. The difference between farming and non-farming families could be explained completely for farm milk and partially for shop milk by storage conditions and temperature during transportation to the fieldworker's home. CONCLUSION: The farming effect and the effect of farm milk consumption cannot be explained by higher levels of endotoxin in milk from farmers and farm milk, respectively

Microbial diversity of French traditional cheeses: sensory and health benefits associated with food safety

International audienc

A switch in regulatory T cells through farm exposure during immune maturation in childhood

Background: Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm-milk exposure was partially mediated by regulatory T cells (Tregs). The aim of this study was to investigate the critical time window of the ‘asthma-protective’ farm effect via Tregs during childhood immune maturation. Methods: Tregs were assessed longitudinally at 4.5 and 6 years in 111 children (56 farm and 55 reference children) from the PASTURE/EFRAIM birth cohort (flow cytometry). Peripheral blood mononuclear cells were cultured unstimulated (U), with phorbol 12-myristate 13-acetate/ionomycin (PI) or lipopolysaccharide (LPS), and stained for Tregs (CD4+CD25highFOXP3upper20%). mRNA expression of Treg/Th1/Th2/Th17-associated cell markers was measured ex vivo. Suppressive capacity of Tregs on effector cells and cytokines was assessed. Detailed questionnaires assessing farm exposures and clinical phenotypes from birth until age 6 years were answered by the parents. Results: Treg percentage before and after stimulation and FOXP3mRNA expression ex vivo decreased from age 4.5 to 6 years (P(U,LPS) < 0.001; P(PI) = 0.051; P(FOXP3) < 0.001). High vs low farm-milk and animal-stable exposure was associated with decreased LPS-stimulated Treg percentage at age 6 years (P(LPS) = 0.045). Elevated LPS-stimulated-Treg percentage at age 6 was associated with increased risk of asthma (aOR = 11.29, CI: 0.96–132.28, P = 0.053). Tregs from asthmatics vs nonasthmatics suppressed IFN-γ (P = 0.015) and IL-9 (P = 0.023) less efficiently. mRNA expression of Th1/Th2/Th17-associated cell markers decreased between 4.5 and 6 years (P < 0.001). Conclusions: Tregs at the age of 6 years were decreased with farm exposure and increased within asthmatics, opposite to age 4.5 years. This immunological switch defines a critical ‘time window’ for Treg-mediated asthma protection via environmental exposure before age 6 years