RESUMEN
The incidence of facial trauma is high. This study has the primary objective of documenting and cataloging maxillofacial fractures in polytrauma patients. From a total of 1229 multiple trauma cases treated at the Emergency Room of the Santo Antonio Hospital - Oporto Hospital Center, Portugal, between August 2001 and December 2007, 251 patients had facial wounds and 209 had maxillofacial fractures. Aged ranged form 13 to 86 years. The applied selective method was based on the presence of facial wound with Abbreviated Injury Scale ≥1. Men had a higher incidence of maxillofacial fractures among multiple trauma patients (86.6%) and road traffic accidents were the primary cause of injuries (69.38%). Nasoorbitoethmoid complex was the most affected region (67.46%) followed by the maxilla (57.42%). The pattern and presentation of maxillofacial fractures had been studied in many parts of the world with varying results. Severe multiple trauma patients had different patterns of maxillofacial injuries. The number of maxillofacial trauma is on the rise worldwide as well as the incidence of associated sequelae. Maxillofacial fractures on multiple trauma patients were more frequent among males and in road traffic crashes. Knowing such data is elementary. The society should have a key role in the awareness of individuals and in prevention of road traffic accidents.
É alta a incidência de traumas na face. Este estudo teve por objetivo documentar e catalogar as fraturas maxilofaciais em pacientes com politraumatismos. De um total de 1229 casos de politraumatizados tratados na Sala de Emergência do Hospital de Santo António - Centro Hospitalar do Porto, Portugal, entre Agosto de 2001 e Dezembro de 2007, 251 pacientes tiveram ferimentos na face e 209 apresentaram fraturas maxilofaciais. As idades variaram de 13 a 86 anos. O método de seleção baseou-se na presença de ferimentos na face com Abreviated Injury Scale ≥1. Os homens apresentaram maior incidência de fraturas maxilofaciais (86,6%) entre os pacientes com múltiplos traumatismos na face e os acidentes de trânsito foram a causa principal dos traumatismos (69,38%). A região mais afetada foi o complexo naso-órbito-etmoidal (67,46%), seguido pela maxila (57,42%). O padrão e a apresentação das fraturas maxilofaciais tem sido estudado em muitas regiões do mundo com resultados variados. Pacientes com politraumatizados graves apresentaram padrões diferentes de traumatismos maxilofaciais. O número de traumatismos maxilofaciais tem aumentado à escala mundial, assim como a incidência das sequelas associadas. Entre os pacientes com traumatismos múltiplos, a maioria pertencia ao sexo masculino, assim como a causa mais frequente foram os acidentes automobilísticos. É elementar o conhecimento destes dados. A sociedade tem um papel primordial nos cuidados individuais e na prevenção dos acidentes de trânsito.
Asunto(s)
Animales , Masculino , Ratones , Ratas , Reactivadores de la Colinesterasa , Colina/análogos & derivados , Diazinón/antagonistas & inhibidores , Neurotransmisores/farmacología , Fisostigmina/antagonistas & inhibidores , Pirrolidinas/antagonistas & inhibidores , Colina/metabolismo , Colina/farmacología , Inhibidores de la Colinesterasa/toxicidad , Diazinón/toxicidad , Ratones Endogámicos ICR , Fisostigmina/toxicidad , Pirrolidinas/toxicidad , Ratas Endogámicas , Receptores Colinérgicos/efectos de los fármacos , Receptores Colinérgicos/metabolismoRESUMEN
An activating mutation (V617F) in the pseudokinase domain of the Janus kinase (JAK)-2 tyrosine kinase has been described in 90% of patients with polycythemia vera (PV) and 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (MF). The discovery of JAK2V617F stirred the development of JAK2 inhibitors for treatment of patients with MF, ET and PV. Similar to other tyrosine kinase (TK) inhibitors in current use, JAK2 inhibitors target the adenosine triphosphate (ATP) binding site at the TK domain and not the pseudokinase domain, thus affecting both mutated and wild-type kinases. In fact, clinical trials of these compounds have demonstrated improvements in constitutional symptoms and splenomegaly in patients with both mutated and wild-type JAK2 MF. It is believed that these drugs may act not only through inhibition of neoplastic cell proliferation, but also by downregulating signaling through proinflammatory cytokine receptors. In this article, we review the current state of JAK2 inhibitors and discuss why these drugs could be a valuable addition to the treatment armamentarium for patients with and without the JAK2V617F mutation.
Asunto(s)
Janus Quinasa 2/antagonistas & inhibidores , Mutación Puntual , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/enzimología , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Benzamidas/uso terapéutico , Benzamidas/toxicidad , Citocinas/inmunología , Humanos , Imidazoles/uso terapéutico , Imidazoles/toxicidad , Janus Quinasa 2/química , Janus Quinasa 2/genética , Janus Quinasa 2/inmunología , Nitrilos , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/inmunología , Inhibidores de Proteínas Quinasas/toxicidad , Pirazoles/uso terapéutico , Pirazoles/toxicidad , Piridazinas/uso terapéutico , Piridazinas/toxicidad , Pirimidinas/uso terapéutico , Pirimidinas/toxicidad , Pirrolidinas/uso terapéutico , Pirrolidinas/toxicidad , Sulfonamidas/uso terapéutico , Sulfonamidas/toxicidadRESUMEN
The Caribbean encrusting and excavating sponge Cliona tenuis successfully competes for space with reef corals by undermining, killing, and displacing live coral tissue at rates of up to 20 cm per year. The crude extract from this sponge, along with the more polar partitions, kills coral tissue and lowers the photosynthetic potential of coral zooxanthellae. We used a bioassay-guided fractionation of the extract to identify the compound(s) responsible. The crude extract, the aqueous partition, and compound 1, herein named clionapyrrolidine A [(-)-(5S)-2-imino-1-methylpyrrolidine-5-carboxylic acid], when incorporated into gels at close to natural volumetric concentrations, killed coral tissue when brought into forced contact with live coral for periods of 1-4 days. This is the first report of a pure chemical produced by a sponge that kills coral tissue upon direct contact. The results are consistent with the localized coral death that occurs when C. tenuis-colonized coral fragments are thrown forcibly against live coral during storms. However, healed C. tenuis fragments placed directly onto live coral were killed readily by coral defenses, and fragments placed in close proximity to coral did not have any effect on the adjacent coral tissue. Solutions of clionapyrrolidine A in sea water were only slightly toxic against live coral. Hence, the coral death naturally brought about by C. tenuis when undermining live coral does not occur through external release of allelochemicals; below-polyp mechanisms must be explored further. N-acetylhomoagmatine (2), originally isolated from Cliona celata from the Northeastern Atlantic, was also assayed for comparison purposes because of its structural similarity to siphonodictidine, a toxic compound produced by a coral excavating sponge of the genus Aka. The lack of activity of N-acetylhomoagmatine at close to natural concentrations seems to indicate that the guanidine moiety, which is also present in siphonodictidine, is not a sufficiently strong structural motif for activity against corals.
Asunto(s)
Antozoos/citología , Antozoos/efectos de los fármacos , Poríferos/química , Poríferos/metabolismo , Pirrolidinas/metabolismo , Pirrolidinas/toxicidad , Animales , Bioensayo , Muerte Celular/efectos de los fármacos , Pirrolidinas/química , Pirrolidinas/aislamiento & purificaciónRESUMEN
This study investigated whether D,L-cis-2,3-Pyrrolidine dicarboxylate (D,L-cis-2,3-PDC), a new glutamate analogue, alters glutamate binding to cerebral plasma membranes and whether N-methyl-D-aspartate (NMDA) receptors are involved in the convulsant effect of this compound. D,L-cis-2,3-PDC reduced sodium-independent [3H]-L-glutamate binding to lysed membrane preparations from adult rat cortex and had no effect on sodium-dependent glutamate binding. Intracerebroventricular administration of D,L-cis-2,3-PDC (7.5-25 nmol/5 microl) induced generalized tonic-clonic convulsions in mice in a dose-dependent manner. The coadministration of MK-801 (7 nmol/2.5 microl), with D,L-cis-2,3-PDC (16.5 nmol/2.5 microl), fully protected the animals against D,L-cis-2,3-PDC-induced convulsions, while the coadministration of DNQX (10 nmol/2.5 microl) increased the latency to convulsions but did not alter the percentage of animals that had convulsions. These results suggest that D,L-cis-2,3-PDC-induced effects are mediated predominantly by NMDA receptors.
Asunto(s)
Convulsivantes , Ácidos Dicarboxílicos/farmacología , Ácidos Dicarboxílicos/toxicidad , Ácido Glutámico/metabolismo , Pirrolidinas/farmacología , Pirrolidinas/toxicidad , Convulsiones/inducido químicamente , Animales , Conducta Animal/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Ácidos Dicarboxílicos/antagonistas & inhibidores , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Masculino , Membranas/efectos de los fármacos , Membranas/metabolismo , Ratones , Fármacos Neuroprotectores/farmacología , Pirrolidinas/antagonistas & inhibidores , Quinoxalinas/farmacología , Ratas , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Faz-se uma revisäo clínico-farmacológica do cloridrato de buflomedil, importante molécula vasoativa, sobretudo ao nível da microcirculaçäo