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5.
Ann Med Health Sci Res ; 4(4): 495-502, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25221693

RESUMO

Rollover crashes (ROCs) are responsible for almost a third of all highway vehicle occupant fatalities. Although ROCs are common and serious mechanism of injury, ROCs are under-reported. To analyze the causes, mechanism, impact and prevention of ROCs, we reviewed the literature between 1984 and 2013. By utilizing the search engines PubMed, MEDLINE and EMBASE by using key words "ROCs" "Ejection" and "vehicle" the initial search yielded 241 abstracts, of which 58 articles were relevant. Most of the articles were either retrospective or experimental studies funded by automobile companies. All vehicles are susceptible to rollovers to certain extents. Despite continuing innovation in vehicles' safety, human factor is pivotal in prevention of ROCs. Distracted driving, speeding and drinking escalate the chances of rollover crashes. Wearing a seatbelt greatly improves the chances of surviving a ROC.

8.
Eur J Trauma Emerg Surg ; 39(4): 397-403, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26815401

RESUMO

BACKGROUND: A quarter of trauma-related deaths are attributable to traumatic chest injury (TCI). OBJECTIVE: To outline the pattern and outcome of TCI in a rapidly developing country among different age groups. METHODS: We conducted a retrospective observational study for patients who sustained TCI and admitted between January 2008 and December 2010 to the Level I trauma center at Hamad General Hospital in Qatar. Patients were classified and analyzed in four age groups (group 1 ≤18, group 2 between 19-44, group 3 45-59, and group 4 >60 years). Multivariate regression analysis was performed for predictors of mortality. RESULTS: Of 5,118 cases admitted to the Section of Trauma Surgery, 1,355 (26.5 %) had TCI (12, 67, 16, and 5 % in groups 1-4, respectively), which was due to blunt trauma in 96 % of cases. The overall mean age was 33 ± 15 years and males comprised 94 % of cases. Children (≤18 years of age) had more traffic-related injury, intubation, high Injury Severity Score (ISS) (19 ± 12), and associated head and liver injuries in comparison to the other groups. The overall mortality rate was 13 % (24, 11, 12, and 16 % in groups 1-4, respectively). The death rate was higher in pedestrians, followed by motor vehicle crashes (MVCs) and fall-related injuries (24 vs. 13 vs. 7 %, respectively, p = 0.001). The highest mortality occurred within the first day (n = 115, 65 %). In comparison to old age, children were more likely to die early (on the first day) and the adult group died mostly within the first week of hospitalization. Independent predictors for mortality included associated head injury [odds ratio (OR) 2.3, 95 % confidence interval (CI) 1.48-3.62), ISS (OR 1.11, 95 % CI 1.09-1.13), and age (OR 0.37, 95 % CI 0.22-0.62). CONCLUSION: TCI is an alarming problem in Qatar, with a bimodal mortality curve. The highest mortality peak occurred in children, followed by old age. However, young males are the most exposed population. Regulatory efforts and strict enforcement of traffic laws would likely reduce morbidity and mortality.

9.
Eur J Trauma Emerg Surg ; 39(5): 507-10, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26815448

RESUMO

BACKGROUND: Percutaneous dilatational tracheostomy (PDT) is a routine surgical procedure for critically ill patients who require prolonged ventilatory support. METHODS: We conducted a retrospective cohort study of all PDTs performed at the adult Trauma Intensive Care Unit (TICU) of Hamad Medical Corporation in Doha, Qatar, from January 2009 through September 2012. For all adult patients, we analyzed the demographic characteristics, mean ventilator time before the procedure, injury severity score (ISS), complications, and outcomes. RESULTS: Of the 1,442 trauma patients admitted to the adult TICU during our study period, 124 (8.5 %) underwent PDT using the Ciaglia Blue Rhino technique. The vast majority were male (94.3 %). The mean age was 35 ± 15.6 years; mean ventilator time before the procedure, 12 ± 3 days; and mean ISS, 24.2 ± 9.3. More than half of patients had head injury (56 %), followed by chest and abdomen (26 %) and cervical spine injuries (18 %). Early complications included difficult tube placement (0.8 %), hypoxemia (0.8 %), minor bleeding (1.6 %), and hypotension (0.8 %), but the vast majority (93 %) of patients had no complications. The procedure-related mortality rate was 0 %. CONCLUSION: PDT is safe and can be performed with minimal complications even in a newly established trauma center.

10.
ACS Med Chem Lett ; 1(9): 488-92, 2010 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-24900236

RESUMO

In an effort to develop potent, orally bioavailable compounds for the treatment of neoplastic diseases, we developed a class of dual VEGFR-2 kinase and tubulin inhibitors. Targeting the VEGFR receptor kinase and tubulin structure allows for inhibition of both tumor cells and tumor vasculature. Previously, a combination of two compounds, a VEGF receptor tyrosine kinase inhibitor and tubulin agent, was demonstrated to produce an enhanced antitumor response in animal studies. We have reaffirmed their results, with the added benefit that both activities are found in one compound.

11.
Bioorg Med Chem Lett ; 16(5): 1191-6, 2006 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-16377187

RESUMO

Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 microM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC(50)=7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents.


Assuntos
Antimitóticos/síntese química , Antimitóticos/farmacologia , Oxidiazóis/química , Oxidiazóis/farmacologia , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Animais , Antimitóticos/química , Antimitóticos/classificação , Biopolímeros/química , Biopolímeros/metabolismo , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/classificação , Conformação Proteica/efeitos dos fármacos , Relação Estrutura-Atividade
12.
Bioorg Med Chem Lett ; 15(23): 5154-9, 2005 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-16198562

RESUMO

A novel triazole-containing chemical series was shown to inhibit tubulin polymerization and cause cell cycle arrest in A431 cancer cells with EC(50) values in the single digit nanomolar range. Binding experiments demonstrated that representative active compounds of this class compete with colchicine for its binding site on tubulin. The syntheses and structure-activity relationship studies for the triazole derivatives are described herein.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Triazóis/química , Triazóis/farmacologia , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia , Antineoplásicos/síntese química , Humanos , Microtúbulos/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/síntese química , Moduladores de Tubulina/síntese química , Células Tumorais Cultivadas
13.
Rev Neurol ; 35(9): 895-9, 2002.
Artigo em Espanhol | MEDLINE | ID: mdl-12436390

RESUMO

INTRODUCTION AND AIMS: The exploration of neurocognition in neurology departments has gone a long way from the traditional psychometric tests to the present day use of high technology methods in cognitive neurophysiology, as is the case of event related potentials. Given the increased sensitivity of these procedures, it has become absolutely essential to control the influence of environmental variables that may exert non controlled effects on the patient s response. Many neurocognitive laboratories have been set up in premises in which the spatial layout and the environmental characteristics have been determined beforehand and consequently technical staff has had to prepare these rooms in an empirical way. This gives rise to two types of drawbacks: interferences in the patient s concentration and low reproducibility of the results in other laboratories. METHOD: In this paper we present a proposed set of standardised conditions for a neurocognitive laboratory from an architectural perspective, and more specifically with regard to interior design. We outline the functional design of the premises, the conditions for workplaces where VDU computers (Video Display Units) are used and where psychometric evaluation is carried out. We also discuss the criteria to be followed when placing the laboratory within a hospital, lighting parameters, air conditioning and suggestions about psychological input. CONCLUSIONS: Although we do not seek to establish a rigid set of norms, these conditions will raise the quality of evaluations and facilitate the comparison of results because of the reduced variability from the environment.


Assuntos
Arquitetura , Planejamento Ambiental , Ambiente de Instituições de Saúde , Laboratórios , Neurofisiologia/métodos , Computadores , Humanos , Luz , Reprodutibilidade dos Testes , Enquadramento Psicológico , Local de Trabalho
14.
Rev. neurol. (Ed. impr.) ; 35(9): 895-899, 1 nov., 2002.
Artigo em Es | IBECS | ID: ibc-22313

RESUMO

Introducción y objetivo. La exploración de la neurocognición en los servicios de neurología se ha expandido desde las pruebas psicométricas clásicas hasta el empleo de métodos de alta tecnología en la neurofisiología cognitiva, como en el caso de los potenciales relacionados a eventos. Dado el aumento de la sensibilidad de estos procedimientos, se hace indispensable controlar la influencia de variables ambientales que pueden ejercer efectos no controlados en la respuesta del paciente. Muchos laboratorios de neurocognición se han instalado en locales en los que la distribución espacial y las características ambientales ya estaban previamente determinadas, y por ello el personal técnico ha acondicionado estas habitaciones de manera empírica. Esto provoca dos tipos de inconvenientes: las interferencias en la concentración del paciente y la poca reproductividad de los resultados en otros laboratorios. Desarrollo. Este trabajo presenta una propuesta de condiciones estandarizadas de un laboratorio de neurocognición desde el punto de vista arquitectónico, en particular de la especialidad de diseño de interiores. Se expone la organización funcional del local, las condiciones para los puestos de trabajo que utilizan ordenador VDU (Video Display Units) y para la evaluación psicométrica, los criterios para la localización del laboratorio dentro del hospital, los parámetros de iluminación, climatización y sugerencias sobre la adecuación psicológica. Conclusiones. Sin pretender establecer una norma rígida, estas condiciones elevarán la calidad de las evaluaciones y facilitarán la comparación de resultados al disminuir la variabilidad ambiental (AU)


Assuntos
Pessoa de Meia-Idade , Adulto , Idoso , Humanos , Arquitetura , Laboratórios , Planejamento Ambiental , Ambiente de Instituições de Saúde , Espanha , Enquadramento Psicológico , Reprodutibilidade dos Testes , Local de Trabalho , Neurofisiologia , Computadores , Luz , Glioma , Neoplasias Encefálicas
15.
J Cell Biol ; 156(5): 855-65, 2002 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-11864991

RESUMO

Many cellular components are transported using a combination of the actin- and microtubule-based transport systems. However, how these two systems work together to allow well-regulated transport is not clearly understood. We investigate this question in the Xenopus melanophore model system, where three motors, kinesin II, cytoplasmic dynein, and myosin V, drive aggregation or dispersion of pigment organelles called melanosomes. During dispersion, myosin V functions as a "molecular ratchet" to increase outward transport by selectively terminating dynein-driven minus end runs. We show that there is a continual tug-of-war between the actin and microtubule transport systems, but the microtubule motors kinesin II and dynein are likely coordinated. Finally, we find that the transition from dispersion to aggregation increases dynein-mediated motion, decreases myosin V--mediated motion, and does not change kinesin II--dependent motion. Down-regulation of myosin V contributes to aggregation by impairing its ability to effectively compete with movement along microtubules.


Assuntos
Citoesqueleto de Actina/metabolismo , Melanóforos/metabolismo , Microtúbulos/metabolismo , Proteínas Motores Moleculares/metabolismo , Transporte Proteico/fisiologia , Xenopus laevis/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Transformada , Dineínas/metabolismo , Cinesinas , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Proteínas Musculares/metabolismo , Miosina Tipo V/metabolismo , Feniltioureia/farmacologia , Pigmentos Biológicos/metabolismo , Proteínas de Xenopus
16.
Int Rev Cytol ; 204: 179-238, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11243595

RESUMO

Motor proteins in the kinesin, dynein, and myosin superfamilies are tightly regulated to perform multiple functions in the cell requiring force generation. Although motor proteins within families are diverse in sequence and structure, there are general mechanisms by which they are regulated. We first discuss the regulation of the subset of kinesin family members for which such information exists, and then address general mechanisms of kinesin family regulation. We review what is known about the regulation of axonemal and cytoplasmic dyneins. Recent work on cytoplasmic dynein has revealed the existence of multiple isoforms for each dynein chain, making the study of dynein regulation more complicated than previously realized. Finally, we discuss the regulation of myosins known to be involved in membrane trafficking. Myosins and kinesins may be evolutionarily related, and there are common themes of regulation between these two classes of motors.


Assuntos
Dineínas/metabolismo , Cinesinas/metabolismo , Proteínas Motores Moleculares/metabolismo , Miosinas/metabolismo , Animais , Transporte Biológico , Dineínas/genética , Dineínas/fisiologia , Humanos , Cinesinas/genética , Cinesinas/fisiologia , Miosinas/genética , Miosinas/fisiologia , Organelas/metabolismo
18.
Pigment Cell Res ; 12(5): 283-94, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10541038

RESUMO

We present an overview of the research on intracellular transport in pigment cells, with emphasis on the most recent discoveries. Pigment cells of lower vertebrates have been traditionally used as a model for studies of intracellular transport mechanisms, because these cells transport pigment organelles to the center or to the periphery of the cell in a highly co-ordinated fashion. It is now well established that both aggregation and dispersion of pigment in melanophores require two elements of the cytoskeleton: microtubules and actin filaments. Melanosomes are moved along these cytoskeletal tracks by motor proteins. Recent studies have identified the motors responsible for pigment dispersion and aggregation in melanophores. We propose a model for the possible roles of the two cytoskeletal transport systems and how they might interact. We also discuss the putative mechanisms of regulation of pigment transport, especially phosphorylation. Last, we suggest areas of research that will receive attention in the future in order to elucidate the mechanisms of organelle transport.


Assuntos
Melanóforos/metabolismo , Miosina Tipo V , Organelas/metabolismo , Pigmentos Biológicos/metabolismo , Actinas/metabolismo , Animais , Transporte Biológico , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Citoplasma/metabolismo , Citoesqueleto/metabolismo , Dineínas/metabolismo , Peixes , Cinesinas , Microtúbulos/metabolismo , Proteínas Musculares/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fosforilação , Xenopus , Proteínas de Xenopus
19.
J Cell Biol ; 143(6): 1547-58, 1998 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-9852150

RESUMO

Melanophores move pigment organelles (melanosomes) from the cell center to the periphery and vice-versa. These bidirectional movements require cytoplasmic microtubules and microfilaments and depend on the function of microtubule motors and a myosin. Earlier we found that melanosomes purified from Xenopus melanophores contain the plus end microtubule motor kinesin II, indicating that it may be involved in dispersion (Rogers, S.L., I.S. Tint, P.C. Fanapour, and V.I. Gelfand. 1997. Proc. Natl. Acad. Sci. USA. 94: 3720-3725). Here, we generated a dominant-negative construct encoding green fluorescent protein fused to the stalk-tail region of Xenopus kinesin-like protein 3 (Xklp3), the 95-kD motor subunit of Xenopus kinesin II, and introduced it into melanophores. Overexpression of the fusion protein inhibited pigment dispersion but had no effect on aggregation. To control for the specificity of this effect, we studied the kinesin-dependent movement of lysosomes. Neither dispersion of lysosomes in acidic conditions nor their clustering under alkaline conditions was affected by the mutant Xklp3. Furthermore, microinjection of melanophores with SUK4, a function-blocking kinesin antibody, inhibited dispersion of lysosomes but had no effect on melanosome transport. We conclude that melanosome dispersion is powered by kinesin II and not by conventional kinesin. This paper demonstrates that kinesin II moves membrane-bound organelles.


Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Cinesinas/fisiologia , Melanóforos/fisiologia , Melanossomas/fisiologia , Proteínas Musculares/fisiologia , Pigmentos Biológicos/metabolismo , Animais , Anticorpos/farmacologia , Proteínas de Ligação ao Cálcio/química , Agregação Celular , Eletroporação , Proteínas de Fluorescência Verde , Cinesinas/química , Proteínas Luminescentes/metabolismo , Lisossomos/fisiologia , Lisossomos/ultraestrutura , Substâncias Macromoleculares , Melanóforos/ultraestrutura , Melanossomas/ultraestrutura , Microscopia de Vídeo , Movimento , Proteínas Musculares/química , Pinocitose , Proteínas Recombinantes de Fusão/metabolismo , Transfecção , Xenopus , Proteínas de Xenopus
20.
Pigment Cell Res ; 8(4): 215-20, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8610073

RESUMO

Herein we report the effects of microtubule- and actin-like filament disrupting drugs, as well as the microtubule stabilizer taxol, on PCH-induced pigment granule aggregation within erythrophores of the freshwater crustacean Macrobrachium potiuna. Dose-response curves (DRCs) to the pigment-concentrating hormone PCH were determined under control and experimental conditions to evaluate the effects elicited by the cytoskeleton-affecting drugs. Colchicine, at temperatures 22 degrees C and 4 degrees C, and vinblastine significantly inhibited the aggregating response to PCH and affected the dynamics of the process, as shown by the change in the slope of the regression curve calculated from the DRCs. Lumicolchicine, a colchicine analogue with no affinity for tubulin, also inhibited pigment migration, though no change in the slope of the regression curve was observed. The inhibitory effects of lumicolchicine demonstrate that changes in sites other than cytoskeleton, such as membrane permeability, may also cause a decrease in the PCH-induced aggregating responses and that the colchicine effects may result from its action on cellular sites additional to the cytoskeleton. Taxol, a microtubule stabilizer, did not affect the DRC to PCH, and DMSO improved the PCH-evoked responses, pointing out to the maintenance of tubulin in the polymerized state as the appropriate condition for aggregation. Cytochalasin B, an actin-like filament disrupter, diminished the aggregating responses to the hormone, with no change in the slope of the regression curve, indicating that these elements take part in the process and that cytosolic calcium rise, sol/gel transformations and endoplasmic reticulum motility may well play an important role in granule migration. It is suggested that microtubules are steadily polymerized as a requirement for pigment aggregation and that process is biphasic, the initial phase being dependent on the microtubule integrity.


Assuntos
Cromatóforos/efeitos dos fármacos , Citoesqueleto/fisiologia , Hormônios de Invertebrado/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Cromatóforos/metabolismo , Colchicina/farmacologia , Citocalasina B/farmacologia , Citoesqueleto/efeitos dos fármacos , Dimetil Sulfóxido , Relação Dose-Resposta a Droga , Supressores da Gota/farmacologia , Lumicolchicinas/farmacologia , Paclitaxel/farmacologia , Palaemonidae/citologia , Pigmentos Biológicos/metabolismo , Análise de Regressão , Temperatura , Vimblastina/farmacologia
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