The Ca2+-dependent protease Calpain A regulates Cactus/I kappaB levels during Drosophila development in response to maternal Dpp signals.

Regulation of NF kappaB activity is central to many processes during development and disease. Activation of NF kappaB family members depends on degradation of inhibitory I kappaB proteins. In Drosophila, a nuclear gradient of the NF kappaB/c-rel protein Dorsal subdivides the embryonic dorsal-ventral axis, defining the extent and location of mesodermal and ectodermal territories. Activation of the Toll pathway directs Dorsal nuclear translocation by inducing proteosomal degradation of the I kappaB homologue Cactus. Another mechanism that impacts on Dorsal activation involves the Toll-independent pathway, which regulates constitutive Cactus degradation. We have shown that the BMP protein Decapentaplegic (Dpp) inhibits Cactus degradation independent of Toll. Here we report on a novel element of this pathway: the calcium-dependent protease Calpain A. Calpain A knockdowns increase Cactus levels, shifting the Dorsal gradient and dorsal-ventral patterning. As shown for mammalian I kappaB, this effect requires PEST sequences in the Cactus C-terminus, implying a conserved role for calpains. Alteration of Calpain A or dpp results in similar effects on Dorsal target genes. Epistatic analysis confirms Calpain A activity is regulated by Dpp, indicating that Dpp signals increase Cactus levels through Calpain A inhibition, thereby interfering with Dorsal activation. This mechanism may allow coordination of Toll, BMP and Ca(2+) signals, conferring precision to Dorsal-target expression domains.

Graded maternal short gastrulation protein contributes to embryonic dorsal-ventral patterning by delayed induction.

Establishment of the dorsal-ventral (DV) axis of the Drosophila embryo depends on ventral activation of the maternal Toll pathway, which creates a gradient of the NFkB/c-rel-related transcription factor dorsal. Signaling through the maternal BMP pathway also alters the dorsal gradient, probably by regulating degradation of the IkB homologue Cactus. The BMP4 homologue decapentaplegic (dpp) and the BMP antagonist short gastrulation (sog) are expressed by follicle cells during mid-oogenesis, but it is unknown how they affect embryonic patterning following fertilization. Here, we provide evidence that maternal Sog and Dpp proteins are secreted into the perivitelline space where they remain until early embryogenesis to modulate Cactus degradation, enabling their dual function in patterning the eggshell and embryo. We find that metalloproteases encoded by tolloid (tld) and tolkin (tok), which cleave Sog, are expressed by follicle cells and are required to generate DV asymmetry in the Dpp signal. Expression of tld and tok is ventrally restricted by the TGF-alpha ligand encoded by gurken, suggesting that signaling via the EGF receptor pathway may regulate embryonic patterning through two independent mechanisms: by restricting the expression of pipe and thereby activation of Toll signaling and by spatially regulating BMP activity.

Fisiopatologia da dermatite atópica: novos conhecimentos / Physiopathology of atopic dermatitis: new knowledge

Fatores ambientais e de origem genética, imunológica e bioquímica säo elementos interdependentes que criam o "ambiente atópico", responsável pelo início, manutençäo, agravamento e desaparecimento do processo. O linfócito CD4+, as células apresentadoras de antígeno e os monócitos säo geneticamente determinados para responder ao antígeno atópico com produçäo de interleucina-4 indispensável para "viragem" IgE, característica da doença. Por seu turno, os monócitos do atópico secretam anormalmente grande quantidade de prostaglandina E2, imunologicamente depressora do interferon gama e bioquimicamente relacionada com os leucotrienos da membrana celular e com os ácidos linoléioco e linolênico, deficientes na pele desses enfermos. As moléculas de adesäo endoteliais (ELAM-1) e as intercelulares (ICAM-1) säo receptores de superfície que dirigem o linfócito memória do gânglio para a pele inflamada.

A double-blind, placebo-controlled comparison of sodium cromoglycate and ketotifen in the treatment of childhood asthma.

We compared three treatments: sodium cromoglycate 5 mg aerosol and placebo syrup (39 patients), placebo aerosol and ketotifen syrup (39 patients), and placebo aerosol and syrup (36 patients). The patients (mean age 11.7 years) had mostly allergic, moderately severe asthma. Treatments were added to current therapy (mostly bronchodilators only) for 3 months. Aerosols were taken four times daily and syrups twice daily. The following results were significant at a level of 5%. At the final clinic visit, the changes from baseline in lung function favored sodium cromoglycate over the other treatments. During month 3, sodium cromoglycate was superior to ketotifen for night symptoms, morning tightness, daytime symptoms, and cough. Bronchodilator use decreased more with sodium cromoglycate than ketotifen. Patients' and clinicians' overall opinions of treatment effectiveness favored sodium cromoglycate over ketotifen and placebo. In these patients, sodium cromoglycate was both effective and superior to ketotifen.

Arborizaçäo urbana como influência na epidemiologia da polinose na cidade de Caxias do Sul, RS, Brasil / Urban arborization as influence in epidemiology of pollinosis in the city of Caxias do Sul, RS, Brazil

A incidência de polinose no Brasil näo é conhecida, porém existe um aumento recente na regiäo Sul. A cidade de Caxias do Sul, possui uma incidência de 4,8% entre a populaçäo, é considerada regiäo de polinose endêmica. O Ligustrum sp é uma árvore ornamental amplamente distribuída na zona central da cidade. O total de 157 pacientes com "hay fever" foi pesquisado para a presença de sensibilidade cutânea a alergenos. Houve 50,3% de testes cutâneos positivos para o extrato político de Ligustrum. As árvores com pólen alergênico, e, especialmente o Ligustrum lucidum deve ser poribido o plantio nas cidades

Epidemiologia da polinose na populaçäo de algumas cidades do Estado do Rio Grande do Sul / Epidemiology of pollinosis in the population of some cities from the state of Rio Grande do Sul

A incidência de sensibilizaçäo a pólens tem aumentado recentemente na Regiäo Sul do Brasil. Através de entrevistas dirigidas, foi estudada uma populaçäo de 4.207 indivíduos em diferentes cidades do Estado do Rio Grande do Sul. A periodicidade anual da doença, associada aos sintomas característicos, permitiu diagnosticar neste grupo 62 (1,4%) pessoas com provável polinose. A cidade de Caxias do Sul, com uma incidência de 4,8%, somada a pesquisas paralelas nas áreas médica e botânica, constitui regiäo de polinose endêmica, asim como a cidade de Passo Fundo, que apresenta uma incidência média de 2,3%

A multicentre double-blind group comparative trial of two dose levels of nedocromil sodium and placebo in the management of perennial extrinsic asthma.

The efficacy of nedocromil sodium 4 mg or 2 mg q.i.d. in the management of perennial extrinsic asthma was evaluated in a double-blind, placebo-controlled, multicentre trial. Nedocromil sodium, especially at the dose of 4 mg q.i.d., was consistently rated higher than placebo on clinical assessment and diary card measurement. Compared with placebo, there were significant improvements for nedocromil sodium (4 X 4 mg) in asthma severity scores (p less than 0.05 after 1 and 2 weeks of treatment) and clinician's opinion of treatment (p less than 0.001). The results suggest that nedocromil sodium is effective in the maintenance treatment of patients with perennial extrinsic asthma and further studies with longer-term treatment periods are suggested.