RESUMEN
AIMS: Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively. METHODS: Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects. RESULTS: Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred. CONCLUSIONS: In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule.
Asunto(s)
Aspirina/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Inhibidores de la Ciclooxigenasa/administración & dosificación , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/prevención & control , Cardiomiopatías Diabéticas/prevención & control , Inhibidores de Agregación Plaquetaria/administración & dosificación , Adulto , Aspirina/efectos adversos , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Estudios Cruzados , Inhibidores de la Ciclooxigenasa/efectos adversos , Inhibidores de la Ciclooxigenasa/uso terapéutico , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/epidemiología , Cardiomiopatías Diabéticas/epidemiología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Resistencia a Medicamentos , Inglaterra/epidemiología , Femenino , Hemorragia/inducido químicamente , Hemorragia/complicaciones , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Riesgo , Medición de RiesgoRESUMEN
BACKGROUND: The UK military runs a comprehensive mental health service ordinarily accessed via primary care referrals. AIMS: To evaluate the feasibility of self-referral to mental health services within a military environment. METHODS: Three pilot sites were identified; one from each service (Royal Navy, Army, Air Force). Socio-demographic information included age, rank, service and career duration. Clinical data included prior contact with general practitioner (GP), provisional diagnosis and assessment outcome. RESULTS: Of the 57 self-referrals, 69% (n = 39) had not previously accessed primary care for their current difficulties. After their mental health assessment, 47 (82%) were found to have a formal mental health problem and 41 (72%) were offered a further mental health clinician appointment. The data compared favourably with a large military mental health department that reported 87% of primary care referrals had a formal mental health condition. CONCLUSIONS: The majority of self-referrals had formal mental health conditions for which they had not previously sought help from primary care; most were offered further clinical input. This supports the view that self-referral may be a useful option to encourage military personnel to seek professional care over and above the usual route of accessing care through their GP.
Asunto(s)
Servicios de Salud Mental/estadística & datos numéricos , Personal Militar/psicología , Autoinforme , Adolescente , Adulto , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Personal Militar/estadística & datos numéricos , Proyectos Piloto , Reino UnidoRESUMEN
OBJECTIVES: The aim of the study was to examine whether UK HIV testing guidelines which recommend the expansion of HIV testing in high HIV prevalence areas have been implemented in England. METHODS: An online survey tool was used to conduct an audit of sexual health commissioners in 40 high HIV prevalence areas (diagnosed prevalence > 2 per 1000) between May and June 2012. Responders were asked to provide details of expanded HIV testing programmes that they had commissioned in nontraditional settings and perceived barriers and facilitators involved in introducing expanded testing. RESULTS: The response rate was 88% (35 of 40). Against the key audit standards, 31% (11 of 35) of areas had commissioned routine testing of new registrants in general practice, and 14% (five of 35) routine testing of general medical admissions. The majority of responders (80%; 28 of 35) had commissioned some form of expanded testing, often targeted at risk groups. The most common setting for commissioning of testing was the community (51%; 18 of 35), followed by general practice (49%; 17 of 35) and hospital departments (36%; 13 of 35). A minority (11%; four of 35) of responders had commissioned testing in all three settings. Where testing in general practice took place this was typically in a minority of practices (median 10-20%). Most (77%; 27 of 35) expected the rate of HIV testing to increase over the next year, but lack of resources was cited as a barrier to testing by 94% (33 of 35) of responders. CONCLUSIONS: Not all high HIV prevalence areas in England have fully implemented testing guidelines. Scale-up of existing programmes and continued expansion of testing into new settings will be necessary to achieve this.
Asunto(s)
Infecciones por VIH/epidemiología , Tamizaje Masivo , Auditoría Clínica , Recolección de Datos , Inglaterra/epidemiología , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
Background: Diabetes is one of the fastest-growing health emergencies of the 21st century, placing a severe economic burden on many countries. Current management approaches have improved diabetic care, but several limitations still exist, such as decreased efficacy, adverse effects, and the high cost of treatment, particularly for developing nations. There is, therefore, a need for more cost-effective therapies for diabetes management. The evidence-based application of phytochemicals from plants in the management of diseases is gaining traction. Methodology: Various plants and plant parts have been investigated as antidiabetic agents. This review sought to collate and discuss published data on the cellular and molecular effects of medicinal plants and phytochemicals on insulin signaling pathways to better understand the current trend in using plant products in the management of diabetes. Furthermore, we explored available information on medicinal plants that consistently produced hypoglycemic effects from isolated cells to animal studies and clinical trials. Results: There is substantial literature describing the effects of a range of plant extracts on insulin action and insulin signaling, revealing a depth in knowledge of molecular detail. Our exploration also reveals effective antidiabetic actions in animal studies, and clear translational potential evidenced by clinical trials. Conclusion: We suggest that this area of research should be further exploited in the search for novel therapeutics for diabetes.
Asunto(s)
Diabetes Mellitus , Plantas Medicinales , Animales , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/farmacología , Insulina/uso terapéutico , Fitoterapia , Plantas Medicinales/química , HumanosRESUMEN
Aspergillus flavus and Aspergillus parasiticus cause perennial infection of agriculturally important crops in tropical and subtropical areas. Invasion of crops by these fungi may result in contamination of food and feed by potent carcinogenic aflatoxins. Consumption of aflatoxin contaminated foods is a recognised risk factor for human hepatocellular carcinoma (HCC) and may contribute to the high incidence of HCC in Southeast Asia. This study conducted a survey of Vietnamese crops (peanuts and corn) and soil for the presence of aflatoxigenic fungi and used microsatellite markers to investigate the genetic diversity of Vietnamese Aspergillus strains. From a total of 85 samples comprising peanut (25), corn (45) and soil (15), 106 strains were isolated. Identification of strains by colony morphology and aflatoxin production found all Vietnamese strains to be A. flavus with no A. parasiticus isolated. A. flavus was present in 36.0% of peanut samples, 31.1% of corn samples, 27.3% of farmed soil samples and was not found in virgin soil samples. Twenty-five per cent of the strains produced aflatoxins. Microsatellite analysis revealed a high level of genetic diversity in the Vietnamese A. flavus population. Clustering, based on microsatellite genotype, was unrelated to aflatoxin production, geographic origin or substrate origin.
Asunto(s)
Arachis/microbiología , Aspergillus flavus/aislamiento & purificación , Aspergillus flavus/metabolismo , Aspergillus/metabolismo , Productos Agrícolas/microbiología , Zea mays/microbiología , Aflatoxinas/biosíntesis , Aspergillus/clasificación , Aspergillus/genética , Aspergillus/aislamiento & purificación , Aspergillus flavus/clasificación , Aspergillus flavus/genética , Variación Genética , Geografía , Repeticiones de Microsatélite , Filogenia , Microbiología del Suelo , VietnamRESUMEN
This study investigated the protective effects of carvedilol alone and coadministered with prednisolone and diltiazem on doxorubicin (DOX) and 5-fluorouracil (5-FU)-induced toxicity. Each of 2 pools of 70 female rats were randomly allotted into 10 groups of 7 animals each and treated as follows: Group 1: normal saline (10 mL/kg); Group 2: normal saline and DOX (40 mg/kg)/5-FU (20 mg/kg) alone; Group 3: gallic acid (200 mg/kg) and DOX/5-FU; Group 4: carvedilol (0.075 mg/kg) and DOX/5-FU; Group 5: carvedilol (0.15 mg/kg) and DOX/5-FU; Group 6: carvedilol (0.30 mg/kg) and DOX/5-FU; Group 7: diltiazem (3.43 mg/kg) and DOX/5-FU; Group 8: diltiazem (3.43 mg/kg), carvedilol (0.15 mg/kg), and DOX/5-FU; Group 9: prednisolone (0.57 mg/kg) and DOX/5-FU; and Group 10: prednisolone (0.57 mg/kg), carvedilol (0.15 mg/kg), and DOX/5-FU. Treatments were done p.o. for 16/14 days for the DOX/5-FU models. DOX/5-FU was administered i.p. to the rats in Groups 2-10 on day 14/10-14. On day 17/15 (DOX/5-FU), blood samples were collected, and liver and kidneys of rats were harvested for antioxidant and histopathological assessments. Carvedilol alone and coadministered with prednisolone significantly (P < .05) decreased alanine aminotransferase level compared with administration of DOX alone. Carvedilol alone and coadministered with diltiazem significantly (P < .05) decreased creatinine level compared with administration of DOX/5-FU alone. Carvedilol alone and coadministered with diltiazem and prednisolone significantly (P < .05) increased the level of hepatic superoxide dismutase and catalase, and decreased malondialdehyde compared with DOX administration alone. Histopathological observations correlated with results of biochemical and antioxidant analyses. Carvedilol administered alone and coadministered with diltiazem and prednisolone reduced the effect of DOX/5-FU-induced hepatic and renal toxicities due to enhanced in vivo antioxidant activity. The protective effect was more prominent in the doxorubicin model compared with the 5-fluorouracil test. Coadministration of carvedilol with either diltiazem or prednisolone did not show better protection relative to carvedilol alone.
Asunto(s)
Lesión Renal Aguda/prevención & control , Antibióticos Antineoplásicos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Sustancias Protectoras/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Carbazoles/farmacología , Carbazoles/uso terapéutico , Carvedilol , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Diltiazem/farmacología , Diltiazem/uso terapéutico , Modelos Animales de Enfermedad , Doxorrubicina/toxicidad , Quimioterapia Combinada/métodos , Femenino , Fluorouracilo/toxicidad , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Prednisolona/farmacología , Prednisolona/uso terapéutico , Propanolaminas/farmacología , Propanolaminas/uso terapéutico , Sustancias Protectoras/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Wistar , Resultado del TratamientoAsunto(s)
Neuropatías Amiloides Familiares/diagnóstico , Amiloide/química , Mutación Missense , Mutación Puntual , Prealbúmina/análisis , Trastornos de la Visión/diagnóstico , Cuerpo Vítreo/química , Sustitución de Aminoácidos , Neuropatías Amiloides Familiares/complicaciones , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/cirugía , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Prealbúmina/genética , Análisis de Secuencia de ADN , Trastornos de la Visión/etiología , Trastornos de la Visión/cirugía , Agudeza Visual , Vitrectomía , Cuerpo Vítreo/cirugíaRESUMEN
Tuberculosis therapy utilizes drugs that while effective cause treatment-related toxicity. Modulation of antitubercular drugs-induced toxicity by methionine and vitamin B-complex in patients was evaluated. 285 treatment-naïve tuberculosis patients at the Chest Clinics of Infectious Diseases Hospital, Yaba and General Hospital, Lagos in Lagos, Nigeria was prospectively recruited and allotted into test (antitubercular medicines, methionine and vitamin B-complex) and control groups (antitubercular medicines). Data on adverse drug reactions and blood samples were collected at initiation, 2 months and 6 months, and then analyzed. Red blood cells and packed cell volume were significantly higher (P < 0.05) in the test group compared to control at 6 months of therapy. At the end of 2 months, results showed a significant decrease (P < 0.001) in aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, urea, creatinine and total bilirubin in the test group compared to control. Reduced glutathione and superoxide dismutase were significantly increased (P < 0.001) and malondialdehyde significantly decreased (P < 0.001) in the test versus control groups at the end of 2 and 6 months. Adverse drug reactions were significantly lower (P < 0.001) in the test group (32.4%) compared to control group (56.2%), with 1 death. Hepatotoxicity was significantly higher (P = 0.026) in control (6.9%), compared to test group (0%). Alcohol and cigarette smoking were significantly (P = 0.019 and P = 0.027) associated with the occurrence of adverse drug reactions. Methionine and vitamin B-complex modulated hepatic, renal, hematological, antioxidant indices and adverse effects in patients administered antitubercular medicines. Such interventions can enhance compliance and better treatment outcomes in tuberculosis patients.
Asunto(s)
Antituberculosos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Metionina/administración & dosificación , Tuberculosis/tratamiento farmacológico , Complejo Vitamínico B/administración & dosificación , Adulto , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Antituberculosos/farmacología , Aspartato Aminotransferasas/sangre , Quimioterapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/metabolismo , Femenino , Humanos , Masculino , Metionina/farmacología , Persona de Mediana Edad , Nigeria , Estudios Prospectivos , Tuberculosis/sangre , Tuberculosis/metabolismo , Complejo Vitamínico B/farmacología , Adulto JovenRESUMEN
We have demonstrated the use of an optical indium tin oxide (ITO) (quartz) waveguide as a new platform for immunosensors with fluorescent europium(III) chelate nanoparticle labels (Seradyn) in a competitive atrazine immunoassay. ITO as a solid surface facilitated the successful use of particulate labels in a competitive assay format. The limit of detection in the new nanoparticle assay was similar to a conventional ELISA. The effect of particle size on bioconjugate binding kinetics was studied using three sizes of bioconjugated particle labels (107, 304, and 396nm) and a rabbit IgG/anti-IgG system in a 96-well plate. A decrease in particle size resulted in faster binding but did not increase the assay sensitivity. Flux calculations based on the particle diffusivity prove that faster binding of the small particles in this study was primarily due to diffusion kinetics and not necessarily to a higher density of antibodies on the particle surface. The results suggest that ITO could make a good platform for an optical immunosensor using fluorescent nanoparticle labels in a competitive assay format for small molecule detection. However, when used in combination with fluorescent particulate labels, a highly sensitive excitation/detection system needs to be developed to fully utilize the kinetic advantage from small particle size. Different regeneration methods tested in this study showed that repeated washings with 0.1 M glycine-HCl facilitated the reuse of the ITO waveguide.
Asunto(s)
Atrazina/análisis , Técnicas Biosensibles/métodos , Europio/química , Fluoroinmunoensayo/métodos , Herbicidas/análisis , Nanotubos/química , Compuestos de Estaño/química , Atrazina/química , Técnicas Biosensibles/instrumentación , Quelantes/química , Materiales Biocompatibles Revestidos/química , Colorantes Fluorescentes/química , Fluoroinmunoensayo/instrumentación , Herbicidas/química , Tamaño de la PartículaRESUMEN
The possible activation of ras sequences in papillomavirus-associated carcinomas of the upper alimentary canal of cattle was investigated by restriction enzyme and hybridization analysis, and by DNA-mediated transformation of NIH3T3 cells. In three cancers, a squamous cell carcinoma of the palate, a squamous cell carcinoma of the rumen, and a transitional cell carcinoma of the urinary bladder, repetitive DNA sequences present in the Ha-ras 1 locus showed anomalous restriction patterns, indicating rearrangements and, in the case of the palate cancer, amplification. Genomic DNA from several cancers was capable of inducing focus formation in the NIH3T3 transformation test. DNA from primary, secondary and tertiary transformants was analysed by hybridization to bovine ras probes and by nucleotide sequencing of polymerase chain reaction products. Bovine Ha-ras 1 sequences were found in all transformants, but no nucleotide differences were detected in exon 1 or exon 2 between normal, cancer and transformed cells. It is concluded that the Ha-ras 1 gene is activated in alimentary canal carcinomas, although the activating mutation has not yet been mapped. The possible relationship between papillomavirus infection and activation of the ras gene is considered.
Asunto(s)
Carcinoma de Células Escamosas/veterinaria , Enfermedades de los Bovinos/genética , Neoplasias del Sistema Digestivo/veterinaria , Genes ras , Papillomaviridae/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/microbiología , Bovinos , Enfermedades de los Bovinos/microbiología , Células Cultivadas , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , ADN Viral/genética , ADN Viral/aislamiento & purificación , Neoplasias del Sistema Digestivo/genética , Neoplasias del Sistema Digestivo/microbiología , Exones , Regulación Neoplásica de la Expresión Génica , Regulación Viral de la Expresión Génica , Datos de Secuencia Molecular , Metástasis de la Neoplasia , Sondas de Oligonucleótidos , Papillomaviridae/patogenicidad , Reacción en Cadena de la Polimerasa , TransfecciónRESUMEN
Three different Harvey-ras (Ha-ras) genes have been identified in the bovine genome by screening a lambda phage-bovine DNA library with the ras gene of the Harvey murine sarcoma virus. The genes have been characterized by hybridization and heteroduplex analysis with both the viral and human Ha-ras genes. Based on heteroduplex mapping, the putative direction of transcription and the approximate position of the coding regions of the bovine genes were established. Two genes, bovine Ha-ras 1 and 2, both show an arrangement of exons and introns typical of c-Ha-ras genes. However, they are distinct entities as they have different nucleotide sequences and physical maps, and heteroduplexes between them contain a region of non-homology upstream of exon 1. The third gene, c-Ha-ras 3, does not contain introns and is a pseudogene, analogous to human c-Ha-ras 2. The nucleotide sequence of both Ha-ras 1 and Ha-ras 2 has been determined and shows that Ha-ras 1 encodes a bona fide ras protein, whereas Ha-ras 2 has diverged considerably from a recognizably functional sequence.
Asunto(s)
Genes ras , Biblioteca Genómica , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bovinos , Clonación Molecular/métodos , Humanos , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Mapeo Restrictivo , Homología de Secuencia de Ácido NucleicoRESUMEN
The soluble nitrate reductase of Rhizobium japonicum bacteroids has been purified and its properties compared to those of aerobically grown cells. The enzymes from both sources are similar with molecular weights of about 70 000 suggesting no close relationship with the molybdo-protein component of nitrogenase. Nitrite, the product of nitrate reductase, strongly inhibited the nitrogenase activity from bacteroids, at concentrations less than 100 muM. Thus, an interference in the rate of nitrogen fixation is possible as a result of nitrate reductase activity. A study of the distribution of nitrate reductase in bacteroids indicates that a proportion of the total activity is membrane-bound but that this activity is similar to that in the soluble fraction. Purified nitrate reductase required reduced viologen dyes for activity. Neither NADPH or NADH or FAD could substitute as electron donors. Dithionite is a strong inhibitor and inactivated nitrate reductase from all sources examined. This inactivation is prevented by methyl viologen. Purified nitrate reductase from bacteroids and bacteria Rhizobium japonicum is practically unaffected by exposure to oxygen.
Asunto(s)
Nitrato Reductasas/metabolismo , Rhizobium/enzimología , Cromatografía en Gel , Ditionita/farmacología , Activación Enzimática , Membranas/enzimología , Peso Molecular , Nitrato Reductasas/antagonistas & inhibidores , Nitrato Reductasas/aislamiento & purificación , Nitritos/farmacología , Nitrogenasa/antagonistas & inhibidores , Nitrogenasa/metabolismo , Solubilidad , Glycine max , Viológenos/farmacologíaRESUMEN
PURPOSE: To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. RESULTS: A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P <.001), nausea or vomiting (P =.003), and fever without documented infection (P =.007), and less hospitalization for febrile neutropenia than did CMFP (P =.001). Alopecia, peripheral neuropathy, and myalgia or arthralgia were more severe with paclitaxel (all P <.0001). Overall, quality of life was similar for both treatments (P > = .07). CONCLUSION: Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Paclitaxel/uso terapéutico , Adulto , Anciano , Análisis de Varianza , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/secundario , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Prednisona/administración & dosificación , Prednisona/efectos adversos , Calidad de VidaRESUMEN
PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.
Asunto(s)
Antineoplásicos/uso terapéutico , Enfermedades Óseas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/uso terapéutico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Óseas/complicaciones , Enfermedades Óseas/patología , Neoplasias de la Mama/complicaciones , Quimioterapia Adyuvante , Difosfonatos/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Hipercalcemia/complicaciones , Megestrol/administración & dosificación , Persona de Mediana Edad , Metástasis de la Neoplasia , Pamidronato , Tamoxifeno/administración & dosificaciónRESUMEN
BACKGROUND: National Agency for Food and Drugs Administration and Control (NAFDAC), which is responsible for pharmacovigilance activity in Nigeria, recently withdrew injection gentamicin 280 mg, used in the management of life-threatening and multidrug-resistant infections from circulation, due to reported toxicity. Thus, this study aimed to investigate the toxicity profile of the commonly used strengths (80 mg and 280 mg) of gentamicin on kidney using animal models. METHODS: Animals were divided into five groups of 16 rats each. For rats of groups 1 and 2, gentamicin (1.14 mg/kg each group) was administered intramuscularly twice daily for 7 and 14 days, respectively, after which eight of them were sacrificed by cervical dislocation. Blood was collected via cardiac puncture and the kidneys were carefully removed and weighed immediately. The remaining eight animals were kept for reversibility study for another 7 and 14 days, respectively. For groups 3 and 4, gentamicin (4 mg/kg each group) was administered as a single daily dose for 7 and 14 days, respectively, and eight animals from the groups were subjected to reversibility study for 7 and 14 days, respectively. Group 5, the control group animals, were given 10 ml/kg distilled water for 14 days. Histopathology of the kidneys, serum creatinine levels, and antioxidant enzyme activities were investigated. RESULTS: Significant increase (p ≤ 0.001) in the level of creatinine of rats administered 4.0 mg/kg for 14 days was observed compared with all other groups. Significant (p ≤ 0.001) elevations in the lipid peroxidation in all gentamicin-administered animals and acute tubular necrosis in most of the gentamicin-administered animals were observed. CONCLUSION: Toxicity profile of gentamicin on the kidneys is dependent on both dose and duration of administration. The findings justify the decision made by NAFDAC to ban the use of high-dose inj. gentamicin 280 mg in Nigeria.
Asunto(s)
Antibacterianos/farmacología , Antioxidantes/uso terapéutico , Gentamicinas/farmacología , Riñón/efectos de los fármacos , Farmacovigilancia , Animales , Creatinina/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , RatasRESUMEN
Genetic complementation of a spontaneous mutant, impaired in flocculation, Congo red binding, and colonization of root surface, led to the identification of a new regulatory gene in Azospirillum brasilense Sp7, designated flcA. The deduced amino acid sequence of flcA shared high similarity with a family of transcriptional activators of the LuxR-UphA family. The most significant match was with the AgmR protein, an activator for glycerol metabolism in Pseudomonas aeruginosa. Derivatives of Sp7 resulting from site-directed Tn5 mutagenesis in the flcA coding sequence were constructed by marker exchange. Characterization of the resulting mutant strains showed that flcA controls the production of capsular polysaccharides, the flocculation process in culture, and the colonization of the root surface of wheat. This study provides new information on the genetic control of the mechanism of plant root colonization by Azospirillum.
Asunto(s)
Azospirillum brasilense/fisiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Triticum/microbiología , Secuencia de Aminoácidos , Azospirillum brasilense/genética , Azospirillum brasilense/ultraestructura , Proteínas Bacterianas/química , Proteínas de Unión al ADN/química , Genes Fúngicos , Genes Reguladores , Prueba de Complementación Genética , Genotipo , Datos de Secuencia Molecular , Familia de Multigenes , Mutación , Fenotipo , Raíces de Plantas , Proteínas Represoras/química , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Transactivadores/química , Factores de Transcripción/químicaRESUMEN
When HeLa cells or BHK cells were subjected to heat shock at 42 degrees C (for 2 h) or 45 degrees C (for 10 min) there was extensive dephosphorylation of ribosomal protein S6. Concomitantly ribosomal protein L14, which is not significantly phosphorylated in normal cells, became phosphorylated, as did a non-structural protein of Mr = 27000, associated with the ribosomes. The latter effects were not prevented by cycloheximide or actinomycin D. When cells shocked at 45 degrees C for 10 min were returned to 37 degrees C for 2 h there was rephosphorylation of ribosomal protein S6 and dephosphorylation of the 27 kDa protein, but not of ribosomal protein L14.
Asunto(s)
Calor , Proteínas Ribosómicas/metabolismo , Animales , Cricetinae , Cicloheximida/farmacología , Dactinomicina/farmacología , Electroforesis en Gel de Poliacrilamida , Células HeLa/metabolismo , Humanos , Riñón/metabolismo , Peso Molecular , Fosforilación , Proteína S6 RibosómicaRESUMEN
When administered as a single agent to previously treated patients with advanced breast cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has good activity. This trial was undertaken to compare paclitaxel with standard chemotherapy as front-line treatment for this disease. Patients with measurable or evaluable metastatic breast cancer, no prior chemotherapy for metastatic disease, and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomized to receive either paclitaxel 200 mg/m2 intravenously over 3 hours for eight cycles over 24 weeks or standard treatment with oral cyclophosphamide 100 mg/m2/d days 1 to 14, intravenous methotrexate 40 mg/m2 days 1 and 8, intravenous 5-fluorouracil 600 mg/m2 days 1 and 8, and oral prednisone 40 mg/m2 daily days 1 to 14 (CMFP) for six cycles over 24 weeks. Patients whose disease progressed or relapsed were recommended for second-line therapy with epirubicin. Accrual has been completed with 209 patients randomized, and an interim analysis of the first 100 patients is reported here. Analysis of quality of life, assessed by the linear analogue scale and overall quality of life indices, is ongoing. Objective response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and 35% (confidence interval, 22% to 51%) with CMFP, with stable disease in an additional 33% and 29%, respectively. Median time to progression was 5.5 months with paclitaxel and 6.4 months with CMFP, with a median survival of 17.3 months for patients treated with paclitaxel and 11.3 months for those given CMFP. Grades 3 and 4 neutropenia occurred in 64% of patients with paclitaxel and 63% with CMFP. However, febrile neutropenia was the primary reason for hospitalization in 1% of paclitaxel courses, compared with 8% with CMFP. Major infections (World Health Organization grade 4) were seen in 7% of patients treated with CMFP, but in none of those given paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel and 27% of CMFP patients. Alopecia and peripheral neuropathy were more common with paclitaxel. Quality of life assessments in the first 100 patients suggest better overall results for those treated with paclitaxel compared with CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated and provides control of metastatic cancer comparable to that of CMFP combination therapy when used as front-line therapy in an outpatient setting.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/uso terapéutico , Ciclofosfamida/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Metotrexato/administración & dosificación , Metástasis de la Neoplasia , Prednisona/administración & dosificación , Análisis de SupervivenciaRESUMEN
Clinical organ transplantation has evolved through advances in patient care in parallel with investigations in associated biologies. It has developed from a cottage industry to an important medical specialty driven increasingly by the availability of newer and more effective immunosuppressive drugs, and dependent on consistently close collaborations between university-based clinical scientists and the pharmaceutical industry. Particularly during the past decade, however, this industry has undergone striking changes, consolidating into huge multi-national corporations, each competing for patients, their doctors, and for support of the allied hospitals. Because of the growth of "Big Pharma," the relationship between academia and industry has changed. There have been many advantages to such mutually dependent interactions. A combination of university-based expertise and the specialized knowledge and resources of industry have produced important scientific gains in drug development. Commercial sponsorship of applied research has been crucial. The orchestration of multicenter controlled clinical drug trials has provided invaluable information about the effectiveness of newer agents. But there are also disadvantages of increasing concern. Indeed, the power of "Big Pharma" in many medical fields including transplantation is such that presentation of data can be delayed, adverse results withheld, and individual investigations hampered. Clinical trials may be protracted to stifle competition. Monetary considerations may transcend common sense. Several measures to enhance the clinical relationship between the pharmaceutical industry and those involved with organ transplantation are suggested, particularly the use of third party advisors in the production of clinical trials, support for more basic research and in the dissemination of results. In this way, the increasingly problematic phenomenon of commercialization of the field of transplantation can be tempered and controlled.
Asunto(s)
Industria Farmacéutica/tendencias , Trasplante de Órganos/tendencias , Humanos , Apoyo a la Investigación como AsuntoRESUMEN
1 The effects of 12 prostaglandins on guinea-pig isolated trachea have been examined in the presence of indomethacin. Two series of experiments were carried out, the first on preparations without tone ('zero tone'), and the second on preparations with tone induced with acetylcholine ('high tone'). 2 The compounds tested fell into two groups. The first, comprising prostaglandins F1 alpha, F2 alpha, F2 alpha acetal, I2 and Wy 17186, contracted both zero and high tone preparations. The second, comprising prostaglandins A1, A2, B1, B2, E1, E2 and F2 beta, contracted zero, but relaxed high tone preparations. Responses to the second group of compounds are probably the resultant of their contractile and relaxant actions. 3 The order of potency for contracting zero tone preparations was prostaglandin E (PGE) greater than F = 1 = Wy 17186 greater than B greater than A, 2-series compounds being 5 to 18 times more potent than 1-series compounds. 4 The order of potency for relaxing high tone preparations was PGE greater than F beta greater than B greater than A greater than Wy 17186 greater than F alpha = I = 0. There was little difference between the potency of 1- and 2-series compounds. 5 The possible relevance of these results to the interpretation of the effects of prostaglandins on human airways is discussed.