Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia

Although principally produced by the pancreas to degrade dietary proteins in the intestine, trypsins are also expressed in the nervous system and in epithelial tissues, where they have diverse actions that could be mediated by protease-activated receptors (PARs). We examined the biological actions of human trypsin IV (or mesotrypsin) and rat p23, inhibitor-resistant forms of trypsin. The zymogens trypsinogen IV and pro-p23 were expressed in Escherichia coli and purified to apparent homogeneity. Enteropeptidase cleaved both zymogens, liberating active trypsin IV and p23, which were resistant to soybean trypsin inhibitor and aprotinin. Trypsin IV cleaved N-terminal fragments of PAR(1), PAR(2), and PAR(4) at sites that would expose the tethered ligand (PAR(1) = PAR(4) > PAR(2)). Trypsin IV increased [Ca(2+)](i) in transfected cells expressing human PAR(1) and PAR(2) with similar potencies (PAR(1), 0.5 microm; PAR(2), 0.6 microm). p23 also cleaved fragments of PAR(1) and PAR(2) and signaled to cells expressing these receptors. Trypsin IV and p23 increased [Ca(2+)](i) in rat dorsal root ganglion neurons that responded to capsaicin and which thus mediate neurogenic inflammation and nociception. Intraplantar injection of trypsin IV and p23 in mice induced edema and granulocyte infiltration, which were not observed in PAR (-/-)(1)(trypsin IV) and PAR (-/-)(2) (trypsin IV and p23) mice. Trypsin IV and p23 caused thermal hyperalgesia and mechanical allodynia and hyperalgesia in mice, and these effects were absent in PAR (-/-)(2) mice but maintained in PAR (-/-)(1) mice. Thus, trypsin IV and p23 are inhibitor-resistant trypsins that can cleave and activate PARs, causing PAR(1)- and PAR(2)-dependent inflammation and PAR(2)-dependent hyperalgesia.

Novel probiotics and prebiotics : road to the market

Novel probiotics and prebiotics designed to manipulate the gut microbiota for improving health outcomes are in demand as the importance of the gut microbiota in human health is revealed. The regulations governing introduction of novel probiotics and prebiotics vary by geographical region. Novel foods and foods with health claims fall under specific regulations in several countries. The paper reviews the main requirements of the regulations in the EU, USA, Canada and Japan. We propose a number of areas that need to be addressed in any safety assessment of novel probiotics and prebiotics. These include publication of the genomic sequence, antibiotic resistance profiling, selection of appropriate in vivo model, toxicological studies (including toxin production) and definition of target population.

Oral myofunctional and electromyographic evaluation of the anterior suprahyoid muscles and tongue thrust in patients with class II/1 malocclusion submitted to first premolar extraction

Objective: The aim of this study was to assess the existence of myofunctional alterations before and after first premolar extraction in Class II/1 malocclusion patients that could endanger the long-term dental arch stability. Materials and Methods: The study was performed by means of morphological, functional and electromyographic analyses in 17 Class II/1 malocclusion patients (group T) and 17 Class I malocclusion patients (group C), both groups with 12-30-year age range (mean age: 20.93 ± 4.94 years). Results: Data analyzed statistically by Student's t-test showed a significant decrease in the maxillary and mandibular dental arch perimeters after orthodontic treatment (p<0.05). The Kruskal-Wallis test analyzed data from tongue posture at rest and during swallowing, not showing significant differences after treatment (groups Tb and Ta) (p>0.05). However, group T differed significantly from group C (p<0.05). The electromyographic data showed that the anterior right and left suprahyoid muscles acted synergistically in both groups, while having a lower myoelectric activity in group T during swallowing. Conclusions: Myofunctional alterations observed after the orthodontic treatment in Class II/1 malocclusion seemed to jeopardize the long-term orthodontic stability, making recurrence possible. Further research should be conducted to compare electromyographic data before and after orthodontic treatment in order to corroborate the results of the present investigation.

The Mexican road to change

Discurso pronunciado por el Secretario de Programación y Presupuesto de México el día 10 de mayo.

Activities of the ECLAC Secretariat to support the integration of a gender perspective into the economic and social development of Latin America and the Caribbean (1 January 2000 to 31 December 2003)

Includes bibliography

Activities of the ECLAC Secretariat relating to the mainstreaming of a gender perspective in the economic and social development of Latin America and the Caribbean: 1 July 2001 to 31 March 2003

Includes bibliography

Actividades de la Secretaría de la CEPAL relacionadas con la integración de la mujer en el desarrollo económico y social de América Latina y el Caribe desde el 1o de junio de 1991 hasta el 31 de mayo de 1994 = Activities of the ECLAC Secretariat from 1 June 1991 to 31 May 1994 relating to the integration of women into the economic and social development of Latin America and the Caribbean

Incluye Bibliografía

Actividades de la Secretaría de la CEPAL relacionadas con las mujeres de América Latina y el Caribe, 1o de junio de 1994-30 de abril de 1996 = Activities of the ECLAC Secretariat relating to the women of Latin America and the Caribbean for the period from 1 June 1994 to 30 April 1996

Incluye Bibliografía

Actividades de la Secretaría de la CEPAL relacionadas con la integración de la mujer en el desarrollo económico y social de América Latina y el Caribe desde el 1o de junio de 1994 hasta el 30 de agosto de 1997 = Activities of the ECLAC Secretariat relating to the integration of women into the economic and social development of Latin America and the Caribbean from 1 June 1994 to 30 August 1997

Incluye Bibliografía

Activities of the ECLAC Secretariat relating to the integration of women into the economic and social development of Latin America and the Caribbean from 1 September 1997 to 30 August 1999

Includes bibliography