RESUMO
Data from our present studies demonstrate the capability of a 105,000 X g pellet from rat normal bone marrow, turpentine-induced hyperplastic bone marrow, and chloroma tumor to transform precursor arachidonic acid into prostaglandins. The activity of the prostaglandin synthetase systems in these tissues is inhibited by the known nonsteroid antiinflammatory drug indomethacin and by two unsaturated fatty acids previously demonstrated in other tissues. Although the overall biosynthesis of prostaglandin E2 (PGE2) was higher in the hyperplastic bone marrow than in the chloroma tumor, the PGF2alpha:PGE2 ratio was markedly higher (8-fold) in the chloroma tissue. This latter increase was probably due to the increased transformation of PGE2 into PGF2alpha by the NADPH-dependent PGE2 9-ketoreductase (an enzyme that catalyzes the transformation of PGE2 and PGF2alpha). These results indicate the greater capability of the malignant chloroma tissue to form PGF2alpha than of nonmalignant hyperplastic bone marrow. Although the role of PGF2alpha in the malignant myelogenous leukemic tumor is presently unclear, its increased formation in this tissue suggests that this substance may play a role in the hyperproliferative process.
Assuntos
Leucemia Experimental/metabolismo , Prostaglandinas E/biossíntese , Prostaglandinas F/biossíntese , Animais , Ácidos Araquidônicos/metabolismo , Medula Óssea/metabolismo , Ácidos Graxos Insaturados/farmacologia , Hidroxiprostaglandina Desidrogenases/metabolismo , Hiperplasia/metabolismo , Técnicas In Vitro , Indometacina/farmacologia , Cinética , Leucemia Experimental/patologia , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patologia , RatosRESUMO
Human skin membranes bind prostaglandin E2 (PGE2) with high affinity (with an apparent dissociation constant, Kd, of 3.14 X 10(-9) M) and specificity. This binding is inhibited by trypsin or heat treatment suggesting that PGE2 receptors have protein components. Exposure of the membranes to ultraviolet irradiation (UVB) resulted in the loss of the membrane binding capacity for PGE2. This UVB-ihibitory effect could be prevented by 5,5'-dithiobis-(2-nitrobenzoic acid), a known protein sulfhydryl-oxidizing agent and alpha-tocopherol, a known lipid anti-oxidant. These results suggest that UVB-irradiation possibly initiate the reduction of critical protein disulfide groups and the peroxication of lipids in the membranes, which are essential for the receptor-PGE2 interaction.
Assuntos
Prostaglandinas E/metabolismo , Pele/metabolismo , Antioxidantes/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/efeitos da radiação , Feminino , Temperatura Alta , Humanos , Oxirredução , Receptores de Prostaglandina/efeitos dos fármacos , Receptores de Prostaglandina/efeitos da radiação , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Tripsina , Raios UltravioletaRESUMO
Specific binding of [3H]prostaglandin E2 ([3H]PGE2) and [3H]prostaglandin F2 alpha ([3H]PGF2 alpha) to plasma membrane and smooth endoplasmic reticulum fractions prepared from rat skin was demonstrated by the Millipore filter assay system. Specific binding was greater in the smooth endoplasmic reticulum fraction. Maximum binding was attained in the presence of Ca++ (0.5 x 10(-3) M), pH 7.2, and at a temperature of 37 C. Unlabeled PGE2 at a concentration of approximately 700 x 10(-9) M inhibited binding to the smooth endoplasmic reticulum fraction by approximately 90%. Other unlabeled prostaglandins, PGE1, PGF2 alpha, and a PGE2 analog, 7-0-13-prostynoic acid, at the same concentration inhibited binding by 40%, 25%, and 30%, respectively. A variety of unlabeled fatty acids (palmitic, oleic, linoleic, eicosatrienoic, and eicosatetraenoic acids), at the higher concentration of approximately 1700 x 10(-9) M, inhibited binding less than 30%, suggesting the presence of specific receptors for PGE2 in the smooth endoplasmic reticulum. Similar results were obtained for the competitive binding studies with [3H]PGF2 alpha. Proteolytic digestion of the membrane fraction by trypsin and pronase, or boiling for 15 min caused marked inhibition of binding, suggesting that the receptors for PGE2 and PGF2 alpha have a protein component. The Scatchard plot analysis of the equilibrium-binding data of [3H]PGE2 and [3H]PGF2 alpha to normal smooth endoplasmic reticulum fractions revealed an apparent dissociation constant (Kd) of 1.1 x 10(-9) M with a binding site concentration of 75 x 10(-12) M for [3H]PGE2, and a Kd of 1,0 x 10(-9) M with a binding site concentration of 35 x 10(-12) M for [3H]PGF2 alpha. These data indicate a greater concentration of binding sites for PGE2 than PGF2 alpha in the normal skin smooth endoplasmic reticulum. On the other hand, analysis of smooth endoplasmic reticulum from skin of essential fatty acid-deficient rats revealed a Kd of 1.2 x 10(-9) M with a binding site concentration of 75 x 10(-12) M for [3H]PGE2, and a Kd of 2.2 x 10(-9) M with a binding site concentration of 175 x 10(-12) M for [3H]PGF2 alpha. The concentration of binding sites for PGF2 alpha in the smooth endoplasmic reticulum of the skin of these rats is increased 5-fold when compared to normal values, whereas that of PGE2 was not altered. These results suggest a possible alteration of PGF2 alpha specific binding to skin endoplasmic reticulum during the pathophysiological abnormalities that accompany essential fatty acid-deficiency syndrome.
Assuntos
Membrana Celular/metabolismo , Prostaglandinas E/metabolismo , Prostaglandinas F/metabolismo , Pele/metabolismo , Animais , Sítios de Ligação , Cátions Bivalentes , Endopeptidases/farmacologia , Retículo Endoplasmático/metabolismo , Ácidos Graxos Essenciais/deficiência , Membranas Intracelulares/metabolismo , Cinética , RatosRESUMO
An effective risk-management program focuses attention on and minimizes events that ideally should not occur. In the laboratory, risk-management issues can be divided along two major lines: (1) patient-care-related issues and (2) employee-related issues (safety). The Joint Commission on Accreditation of Healthcare Organizations, Chicago, Ill, has established formal requirements for risk-management programs for hospitals and clinical departments. These requirements include patient-care-related activities and management functions related to the safety-management functions. The concept of a formal risk-management program may be new to pathologists and laboratory professionals; the components of the program are traditional elements of laboratory policies and procedures. Key items identified as building blocks for risk management are these: (1) risk prevention, (2) risk identification, (3) risk assessment, (4) corrective actions, and (5) loss control. Through the systematic implementation of a comprehensive risk-management program, laboratories have the opportunity to reduce liability exposure and improve the quality of care and services.
Assuntos
Laboratórios , Patologia Clínica , Gestão de Riscos , HumanosRESUMO
During the course of dockside ship maintenance, a compartment was partially flooded with tricholotrifluoroethane gas. One sailor entered the compartment, collapsed, and was then rescued by two other men. All three victims then climbed a 11-m (36-ft) ladder and collapsed. They all experienced a rapid development of cardiac arrest. We report on the pathologic, toxicologic, and pathophysiologic aspects of the incident.
Assuntos
Acidentes de Trabalho , Ar Condicionado/instrumentação , Clorofluorcarbonetos de Metano/intoxicação , Navios , Etano Clorofluorcarbonos , Clorofluorcarbonetos de Metano/sangue , Parada Cardíaca/induzido quimicamente , Humanos , Pulmão/metabolismo , MasculinoRESUMO
In the last issue of Healthcare Executive, we introduced the first in a two-part series on quality in healthcare. The series, which is predicated on a five-hour roundtable discussion among eight healthcare leaders, was moderated by Thomas C. Dolan, Ph.D., FACHE, CAE, ACHE's president and chief executive officer, and jointly sponsored by ACHE and the Bayer Quality Network, an educational forum for sharing innovative and effective continuous quality improvement methods with healthcare executives. In Part I, participants spoke about current issues as they relate to quality. They discussed the reliability of existing quality data and expressed a need for more practical indicators and measurement systems. The consumer mindset was discussed, as leaders debated the value of customer satisfaction surveys and ways to create more realistic consumer expectations. In terms of employers and third parties, participants suggested tailoring quality information and presenting it in a simplified fashion. Finally, leaders emphasized the need for better performance information, as well as the use of outcomes data for both educational and quality improvement purposes. In Part II, the dialogue remains compelling. Participants cover new ground as they talk about the role of accreditors in regulating quality, of governance teams and senior management in creating an organizational culture to support quality, and of physicians in attracting both business partners and patients based on quality. Following is the second in our two-part series.
Assuntos
Garantia da Qualidade dos Cuidados de Saúde , Acreditação , Conselho Diretor , Humanos , Liderança , Cultura Organizacional , Objetivos Organizacionais , Satisfação do Paciente , Diretores Médicos , Estados UnidosRESUMO
When executives at Anne Arundel Medical Center committed the organization to a strategic focus on measuring and improving performance, they didn't simply tinker with the margins of clinical activity; they dispatched teams of clinicians and patients to redesign care. In developing clinical pathways, the teams achieved dramatic reductions in length of stay--and increased satisfaction all around. Jonathan T. Lord, M.D., previously senior vice president for medical staff affairs at the Annapolis, MD, facility, spoke recently with senior editor Kevin Lumsdon about the intricacies of the initiative--and how he's taking that experience into his current position as executive vice president for clinical services at the SunHealth Alliance, Charlotte, NC.
Assuntos
Administração Hospitalar/normas , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Relações Comunidade-Instituição/normas , Participação nas Decisões , Maryland , North CarolinaRESUMO
What is the health care organization's responsibility to maintaining a healthy community, and how does the board fit into that role? Has the field's understandable fixation on costs and the penetration of managed care into most markets affected that role? Leaders of both for-profit and not-for-profit organizations often believe that they are fulfilling their community obligations as long as they provide uncompensated care to the indigent and the uninsured. But is that really being accountable to the community? And if it's not, then what is community accountability? The American Hospital Association's Division of Trustee Leadership and Trustee magazine posed these questions to 13 health care and community leaders last December. Their different perspectives provide for some surprising answers.
Assuntos
Planejamento em Saúde Comunitária/organização & administração , Relações Comunidade-Instituição , Responsabilidade Social , American Hospital Association , Diretores de Hospitais , Liderança , Pessoas sem Cobertura de Seguro de Saúde , Objetivos Organizacionais , Curadores , Cuidados de Saúde não Remunerados , Estados UnidosAssuntos
Gestão da Qualidade Total , Atitude do Pessoal de Saúde , Participação da Comunidade , Procedimentos Clínicos , Administradores Hospitalares , Programas de Assistência Gerenciada/organização & administração , Programas de Assistência Gerenciada/estatística & dados numéricos , Inovação Organizacional , Avaliação de Resultados em Cuidados de Saúde , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
The distribution of the hydrolysis of 1-acyl-2-[1-14C]arachidonoyl-sn-glycero-3-phosphocholine and the simultaneous biosynthesis of prostaglandins by subcellular fractions from human and rat skin membrane preparations were determined. The phospholipase A2 activity was distributed among the subcellular particulate preparations with the highest specific activity in the 105000g particulate fraction. The activity was optimal at pH 7.5 in the presence of 1.0 mM-CaCl2 and was inhibited by EDTA. The hydrolysis of phosphatidylcholine by the skin 105000g particulate fraction was inhibited by cortisol and triamcinolone acetonide and it was stimulated by histamine, bradykinin, retinoic acid and cholera enterotoxin (freeze-dried Vibrio cholerae). Furthermore hydrolysis of phosphatidylcholine by the skin phospholipase A was also enhanced by low concentrations of prostaglandin E2 and prostaglandin F2 alpha. These last results suggest that the amplication of the hydrolysis of phosphatidylcholine by prostaglandin E2 and prostaglandin F2 alpha, with the consequent release of arachidonic acid (the substrate of prostaglandin synthesis) is likely a positive-feedback regulation of the arachidonic acid-prostaglandin cascade.
Assuntos
Ácidos Araquidônicos/metabolismo , Fosfatidilcolinas/metabolismo , Fosfolipases A/metabolismo , Fosfolipases/metabolismo , Pele/enzimologia , Animais , Anti-Inflamatórios/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Técnicas In Vitro , Fosfolipases A2 , Prostaglandinas/biossíntese , Prostaglandinas E/farmacologia , Prostaglandinas F/farmacologia , Ratos , Pele/efeitos dos fármacos , Pele/metabolismo , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismoRESUMO
The activity of an NADPH-dependent PGE2-9-ketoreductase has been demonstrated in rat and human skin. This activity is localized in the high speed supernatant fraction, indicating the presence of an active PGE2-9-ketoreductase associated with the cytoplasmic fraction of the skin. Transformation of PGE2 into PGF2alpha is enhanced by skin specimens from psoriatic plaques and EFA-deficient rats, both characterized by excessive cellular proliferation and increased NADPH production. Incubations of the 105,000 g supernatant fractions from normal and EFA-deficient rats demonstrated that the activity of the PGE2-9-ketoreductase was elevated in high speed preparations from EFA-deficient rats. Results from these studies suggest that the increased activity of PGE2-9-ketoreductase observed in skin from human psoriatic plaques and EFA-deficient rats may be due in part to the increased generation of NADPH by these tissues and in part to alteration of the PGE2-9-ketoreductase by the excessive proliferation of the tissues.
Assuntos
Oxirredutases do Álcool/metabolismo , Ácidos Graxos Essenciais/deficiência , Hidroxiprostaglandina Desidrogenases/metabolismo , Pele/enzimologia , Animais , Divisão Celular , Glicólise , Humanos , Cinética , NAD , NADP , Prostaglandinas E/metabolismo , Prostaglandinas F/biossíntese , Psoríase/enzimologia , Ratos , Pele/metabolismo , Especificidade da EspécieRESUMO
[3H]PGE2 and [3H]PGF2alpha bound to PM and ER prepared from rat skin with high affinity and specificity. Maximum binding was achieved in the presence of Ca2+ (5.0 x 10(-4) M). Unlabeled PGE2 and PGF2alpha inhibited [3H] PGE2alpha binding to ER in a dose-dependent manner with approximately 90% inhibition at a concentration of 1.5 x 10(-10) M. PGF2alpha inhibited approximately 40% of the same concentration. A variety of fatty acids inhibited binding less than 30% at 3.0 x 10(-10) M. The [3H]PGE2 binding was inactivated by pronase, trypsin, and heat treatment. Decreased specific binding of [3H]PGE2 to membrane fractions of EFA-deficient rats was demonstrated in our experiments, whereas binding of [3H]PGF2alpha was elevated. These results indicate that the abnormality of skin under EFA deficiency alters the ability of the membrane preparations to bind prostaglandins.
Assuntos
Membranas/metabolismo , Prostaglandinas E/metabolismo , Prostaglandinas F/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Prostaglandina/metabolismo , Pele/metabolismo , Animais , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Ácidos Graxos Essenciais/deficiência , Cinética , Proteínas de Membrana/metabolismo , RatosRESUMO
We have described a patient with sickle cell trait who, after severe exertion, had rhabdomyolysis, acute renal failure, and disseminated intravascular coagulation secondary to sickling. Autopsy showed the characteristic histopathology of sickle cell crisis and not terminal sicklemia.
Assuntos
Injúria Renal Aguda/patologia , Anemia Falciforme/patologia , Coagulação Intravascular Disseminada/patologia , Rabdomiólise/patologia , Traço Falciforme/patologia , Adolescente , Capilares/patologia , Humanos , Masculino , Músculos/patologia , Esforço Físico , Baço/patologiaRESUMO
Inhibition of the activity of sheep vesicular gland prostaglandin synthetase (a rare limiting enzyme in the biosynthesis of prostaglandins) was demonstrated in the presence of homogenates prepared from skin lesions characterized histologically by epidermal disruption. These inhibitory effects were not observed in homogenates of skin lesions characterized by a lack of epidermal disruption.
Assuntos
Oxigenases de Função Mista/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/biossíntese , Dermatopatias/metabolismo , Pele/enzimologia , Animais , Ovinos , Dermatopatias/enzimologia , Úlcera Cutânea/enzimologiaRESUMO
Prostaglandin biosynthesis from arachidonic acid by skin microsomal fraction preparation was enhanced by UV-irradiation at wavelengths of 254 and 360 nm. In the presence of 8-methoxy psoralen (8 MOP) and coal tar, prostaglandin biosynthesis was further enhanced approximately 2-fold by UV-irradiation at 254 nm. Stimulation was less by UV-irradiation at 360 nm. 8-MOP enhanced the conversion of PGE2 into PGF2-9-ketoreductase prepared from skin high speed supernatant fractions. UV-irradiation at 254 nm and 360 nm with or without the photosensitizers had no effect on the activity of the PGE2-9-ketoreductase. These data therefore indicate that the action of UV-irradiation, 8-methoxy psoralen and coal tar on the skin may in part be due to their regulation of the biosynthesis and metabolism of prostaglandins in this tissue.
Assuntos
Microssomos/efeitos da radiação , Prostaglandinas/biossíntese , Pele/efeitos da radiação , Animais , Ácidos Araquidônicos/metabolismo , Bovinos , Alcatrão/farmacologia , Técnicas In Vitro , Metoxaleno/farmacologia , Microssomos/efeitos dos fármacos , Microssomos/metabolismo , Ácido Micofenólico/farmacologia , Prostaglandinas E/biossíntese , Prostaglandinas F/biossíntese , Ratos , Pele/efeitos dos fármacos , Pele/metabolismo , Raios UltravioletaRESUMO
The evolving vesicular patch test reaction served as a human model for immunologically induced epidermal damage. We observed that inhibitory factor(s) were detectable in the homogenates only after epidermal disruption had appeared. Maximum inhibition correlated with acute changes seen histologically in the evolving patch test reaction. During resolution of the patch test reaction, the presence of inhibitory factor(s) in the skin homogenates became undetectable. A white ring similar to the Woronoff ring described after ultraviolet light and coal tar therapy of psoriatic plaques was reproduced surrounding the vesicular patch test reaction, suggesting that the inhibitory substance(s) detected following epidermal trauma of various types (physical, immunologic, inflammatory, etc.) functioned in vivo in a similar fashion. Our results suggest that Woronoff's ring is a nonspecific phenomenon that can be formed following various types of trauma to the skin rather than a specific occurrence associated only with the treatment of psoriatic plaques.