Residents and interns in the 3 university hospitals: their knowledge of and attitudes to drug allergy.

BACKGROUND: Previous studies revealed there are many gaps in the awareness and knowledge regarding the diagnosis and management of drug allergy (DA) among various health-care professionals. OBJECTIVE: To assess the knowledge, attitudes, and practices towards DA among residents and interns of 3 university hospitals in the region of Trakya (Thrace), Turkey. METHODS: A cross-sectional survey was conducted at university hospitals of 3 cities in the Trakya region: 1. Trakya University Medical Faculty, Edirne (n = 405), 2. Namik Kemal University Medical Faculty, Tekirdag (n = 114), and 3. Canakkale 18 Mart University Medical Faculty, Canakkale (n = 111). A Turkish questionnaire was developed based on previous published studies. RESULTS: The majority of participants (67%) had not received education on DA as a separate subject during their medical education. Less than a third (28.3%) of all respondents were satisfied with their knowledge concerning patients with clinical signs of DA. Of the 6 knowledge questions on DA, the average score for the study was 3.51 out of 6 (58.5%). Residents had a higher knowledge score (3.93 ± 1.1) compared with interns (3.05 ± 1.2) (p < 0.001). The lowest percentage of correct answers were in response to questions on laboratory confirmation of drug-related anaphylaxis (14.5%) and the possibility of penicillin toleration in patients with a history of penicillin allergy (11.8%). The majority of participants (92%) believe that medical doctors should be educated in DA. There were no significant correlations between taking DA histories and the frequency during daily practice of encountering patients. CONCLUSION: Our study revealed that DA knowledge and attitudes are not at satisfactory level among respondents, and we concluded the importance and necessity of reinforcement of DA education in pre- and postgraduate education of medical doctors.

Sprouty proteins inhibit receptor-mediated activation of phosphatidylinositol-specific phospholipase C.

Sprouty (Spry) proteins are negative regulators of receptor tyrosine kinase signaling; however, their exact mechanism of action remains incompletely understood. We identified phosphatidylinositol-specific phospholipase C (PLC)-γ as a partner of the Spry1 and Spry2 proteins. Spry-PLCγ interaction was dependent on the Src homology 2 domain of PLCγ and a conserved N-terminal tyrosine residue in Spry1 and Spry2. Overexpression of Spry1 and Spry2 was associated with decreased PLCγ phosphorylation and decreased PLCγ activity as measured by production of inositol (1,4,5)-triphosphate (IP(3)) and diacylglycerol, whereas cells deficient for Spry1 or Spry1, -2, and -4 showed increased production of IP(3) at baseline and further increased in response to growth factor signals. Overexpression of Spry 1 or Spry2 or small-interfering RNA-mediated knockdown of PLCγ1 or PLCγ2 abrogated the activity of a calcium-dependent reporter gene, suggesting that Spry inhibited calcium-mediated signaling downstream of PLCγ. Furthermore, Spry overexpression in T-cells, which are highly dependent on PLCγ activity and calcium signaling, blocked T-cell receptor-mediated calcium release. Accordingly, cultured T-cells from Spry1 gene knockout mice showed increased proliferation in response to T-cell receptor stimulation. These data highlight an important action of Spry, which may allow these proteins to influence signaling through multiple receptors.

Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1.

Branching of ureteric bud-derived epithelial tubes is a key morphogenetic process that shapes development of the kidney. Glial cell line-derived neurotrophic factor (GDNF) initiates ureteric bud formation and promotes subsequent branching morphogenesis. Exactly how GDNF coordinates branching morphogenesis is unclear. Here we show that the absence of the receptor tyrosine kinase antagonist Sprouty1 (Spry1) results in irregular branching morphogenesis characterized by both increased number and size of ureteric bud tips. Deletion of Spry1 specifically in the epithelium is associated with increased epithelial Wnt11 expression as well as increased mesenchymal Gdnf expression. We propose that Spry1 regulates a Gdnf/Ret/Wnt11-positive feedback loop that coordinates mesenchymal-epithelial dialogue during branching morphogenesis. Genetic experiments indicate that the positive (GDNF) and inhibitory (Sprouty1) signals have to be finely balanced throughout renal development to prevent hypoplasia or cystic hyperplasia. Epithelial cysts develop in Spry1-deficient kidneys that share several molecular characteristics with those observed in human disease, suggesting that Spry1 null mice may be useful animal models for cystic hyperplasia.

Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction.

Intercellular signaling molecules and their receptors, whose expression must be tightly regulated in time and space, coordinate organogenesis. Regulators of intracellular signaling pathways provide an additional level of control. Here we report that loss of the receptor tyrosine kinase (RTK) antagonist, Sprouty1 (Spry1), causes defects in kidney development in mice. Spry1(-/-) embryos have supernumerary ureteric buds, resulting in the development of multiple ureters and multiplex kidneys. These defects are due to increased sensitivity of the Wolffian duct to GDNF/RET signaling, and reducing Gdnf gene dosage correspondingly rescues the Spry1 null phenotype. We conclude that the function of Spry1 is to modulate GDNF/RET signaling in the Wolffian duct, ensuring that kidney induction is restricted to a single site. These results demonstrate the importance of negative feedback regulation of RTK signaling during kidney induction and suggest that failures in feedback control may underlie some human congenital kidney malformations.