RESUMEN
WHAT IS KNOWN ON THE SUBJECT?: Frailty and multimorbidity are common in later life. A higher level of frailty is associated with a higher risk of adverse physical and psychological health situations. Older adults with pain have been reported to be lonelier and more depressed, as well as less happy and less satisfied with their life as compared to those without pain. In view of the high prevalence of pain among older adults and the reversibility of frailty, it is important to explore the relationship between pain, frailty and psychological parameters in order to devise patient-centred interventions. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Frailty index is positively correlated with the presence of pain, and associated with gender, functional mobility and loneliness. Among these significant variables, loneliness was the factor that contributed the most to the frailty index. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: It is essential to put the focus of healthcare on both the physical and psychological aspects of well-being. All nurses are advised to improve the management of pain in older people in order to lower the levels of pain, frailty and psychological distress among this population. Nursing care should address the loneliness level especially the problem of social loneliness among older adults particularly those living in nursing homes. ABSTRACT: Introduction In view of the high prevalence of pain among older adults and the reversibility of frailty, it is important to explore the relationship between pain, frailty and psychological parameters in order to devise patient-centred interventions. Aim To examine the levels of frailty, pain and psychological parameters among older adults living in Hong Kong nursing homes, and the cross-sectional relationships among these items. Methods A cross-sectional study was conducted among 178 residents from six nursing homes. Frailty, pain, mobility, happiness, loneliness and life satisfaction of participants were assessed using validated questionnaires. Results A multiple linear regression (R(2) = 0.338, P < 0.05) showed that the frailty index was associated with loneliness, functional mobility and gender. Among these significant variables, loneliness was the factor that contributed the most to the frailty index. Discussion It is essential to put the focus of healthcare on both the physical and psychological aspects of well-being. Findings suggest that apart from improving mobility and reducing pain, loneliness could be a target of psychosocial interventions to reduce frailty and improve quality of life. Implications for practice It is advised that nursing care should address loneliness, especially the problem of social loneliness among older adults particularly those living in nursing homes.
Asunto(s)
Comorbilidad , Anciano Frágil/psicología , Hogares para Ancianos , Soledad/psicología , Casas de Salud , Dolor/psicología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Hong Kong , Humanos , MasculinoRESUMEN
BACKGROUND: The quality of life of nursing home residents has increasingly become an important dimension when evaluating care in a nursing home. Not a lot is known about the quality of life of nursing home residents in Hong Kong. AIM: To investigate factors associated with the quality of life of nursing home residents to inform care management policies and service delivery. METHODS: This study reports data from 125 nursing home residents. The Hong Kong Chinese version of the World Health Organization's Quality of Life-Brief version was used. Other measures used include the Mini-Mental State Examination, the Mini-Nutritional Assessment, the Geriatric Depression Scale, the Modified STRATIFY Falls Prediction Tool and the Modified Barthel Index. A univariate analysis and a multiple regression analysis were then performed to identify the influencing factors. RESULTS: The participants reported a moderate level of quality of life, with the exception in the domain of social relationships. A univariate analysis found some associations between demographic and clinical characteristics and quality of life. A multiple regression analysis indicated that pain, being younger (65-74 years), having son(s) or daughter(s), and cognitive impairment were negatively associated factors. LIMITATIONS: The smallness of the sample from a single study site limits the generalizability of the findings. CONCLUSION: This study provides information that has hitherto been lacking on the quality of life and associated factors among local nursing home residents in Hong Kong. The preliminary findings can help healthcare staff to identify those at risk of suffering from a low quality of life and to design appropriate care interventions to improve the quality of life of such residents. IMPLICATIONS: Adequate pain relief, family connectedness and special attention to the needs of those with cognitive impairment are important considerations in ensuring a better quality of life for older people in long-term residential care.
Asunto(s)
Actividades Cotidianas/psicología , Envejecimiento/psicología , Hogares para Ancianos/organización & administración , Casas de Salud/organización & administración , Satisfacción del Paciente/estadística & datos numéricos , Calidad de la Atención de Salud/organización & administración , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Relaciones Familiares , Femenino , Hong Kong , Humanos , Masculino , Persona de Mediana Edad , Manejo del DolorRESUMEN
The microwave assisted extraction (MAE) technique has been evaluated for the extraction of active pharmaceutical ingredients (API) from various solid dosage forms. Using immediate release tablets of Compound A as a model, optimization of the extraction method with regards to extraction solvent composition, extraction time and temperature was briefly discussed. Complete recovery of Compound A was achieved when samples were extracted using acetonitrile as the extraction solvent under microwave heating at a constant cell temperature of 50 degrees C for 5 min. The optimized MAE method was applied for content uniformity (single tablet extraction) and potency (multiple tablets extraction) assays of release and stability samples of two products of Compound A (5 and 25mg dose strength) stored at various conditions. To further demonstrate the applicability of MAE, the instrumental extraction conditions (50 degrees C for 5 min) were adopted for the extraction of montelukast sodium (Singulair) from various solid dosage forms using methanol-water (75:25, v/v) as the extraction solvent. The MAE procedure demonstrated an extraction efficiency of 97.4-101.9% label claim with the greatest RSD at 1.4%. The results compare favorably with 97.6-102.3% label claim with the greatest RSD at 2.9% obtained with validated mechanical extraction procedures. The system is affordable, user-friendly and simple to operate and troubleshoot. Rapid extraction process (7 min/run) along with high throughput capacity (up to 23 samples simultaneously) would lead to reduced cycle time and thus increased productivity.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Formas de Dosificación , Microondas , Preparaciones Farmacéuticas/análisis , Éteres/análisis , Éteres/aislamiento & purificación , Hidrocarburos Fluorados/análisis , Hidrocarburos Fluorados/aislamiento & purificación , TemperaturaRESUMEN
The objectives of this study were to determine if lipid transfer protein I (LTP I)-facilitated phospholipid (PC) transfer activity regulates the plasma lipoprotein distribution of cyclosporine (CSA) and if the association of CSA with high-density lipoproteins (HDL) is due to the high protein and/or alterations in coat lipid content of HDL. To assess if LTP I-facilitated PC transfer activity regulates the plasma lipoprotein distribution of CSA, (14)C-PC- or (3)H-CSA-enriched HDL or low-density lipoproteins (LDL) were incubated in T150 buffer [pH 7.4, containing a (14)C-PC- or (3)H-CSA-free lipoprotein counterpart +/- exogenous LTP I (1.0 microg protein/mL)] or in delipidated human plasma that contained 1.0 microg protein/mL of endogenous LTP I in the presence or absence of a monoclonal antibody TP1 (30 microg protein/mL) directed against LTP I for 90 min at 37 degrees C. To assess the influence of HDL subfraction lipid composition and structure on the plasma distribution of CSA, CSA at 1000 ng of drug/mL of plasma was incubated in human plasma pretreated for 24 h with a lecithin:cholesterol acyltransferase (LCAT) inhibitor, dithionitrobenzoate (DTNB; 3 mM). To assess the binding of CSA to apolipoproteins AI, AII, and B, increasing concentrations of CSA were added to a constant concentration of either apolipoprotein AI, AII, or B. Equilibrium dialysis was used to determine free and bound fractions and Scatchard plot analysis was used to determine binding coefficients. To assess the influence of hydrophobic core lipid volume on the plasma distribution of CSA, CSA was incubated in plasma from patients with well-characterized dyslipidemias. The hydrophobic core lipid volume (CE + TG) within each lipoprotein subfraction was correlated to the amount of CSA recovered in each plasma sample from the different human subjects. The percent transfer of PC from LDL to HDL was different than the percent transfer of CSA in T150 buffer or human plasma source. In the presence of TP1, only PC transfer from LDL to HDL decreased. For plasma incubated with CSA and separated into HDL(2) and HDL(3), 35-50% of drug originally incubated was recovered in the HDL(3) fraction, with the remaining drug being found within the other fractions. When CSA was incubated in plasma pretreated with DTNB, the percentage of CSA recovered in the HDL(3) and HDL(2) fractions was not significantly different compared with that in the HDL(3) and HDL(2) fractions from untreated control plasma. CSA distribution into HDL inversely correlated with the hydrophobic core lipid volume of HDL, whereas distribution into LDL and triglyceride-rich lipoproteins directly correlated with their respective hydrophobic core lipid volumes. We further observed that CSA has high binding affinity and multiple binding sites with apolipoproteins AI (k(d) = 188.9 nM; n = 2), AII (k(d) = 184.7 nM; n = 2), and B (k(d) = 191 nM; n = 3). These findings suggest that the transfer of CSA between different lipoprotein particles is not influenced by LTP I-facilitated PC transfer activity probably because of the high affinity of CSA for the protein components of HDL and LDL.
Asunto(s)
Proteínas Portadoras/metabolismo , Ciclosporina/metabolismo , Glicoproteínas , Inmunosupresores/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Fosfolípidos/metabolismo , Proteínas Portadoras/farmacología , Proteínas de Transferencia de Ésteres de Colesterol , Ciclosporina/análisis , Humanos , Inmunosupresores/análisis , Proteínas/química , Proteínas/metabolismoRESUMEN
PURPOSE: Mild heat treatment of Fungizone (FZ, an amphotericin B:deoxycholate preparation) leads to a new self-associated form (HFZ) that demonstrates improved therapeutic index in vivo. The origin of the improvement may lie in the differential stability in the presence of serum proteins. The purpose of this study is to assess the effect of human serum albumin (HSA) on the structure and stability and in vitro channel forming ability of these two preparations against model fungal and mammalian membrane vesicles. METHODS: Kinetic absorption and CD spectroscopy were used to assess the kinetic and equilibrium stability of the characteristic amphotericin B complexes in the presence of HSA. Kinetic fluorescence spectroscopy of pyranine entrapped in model fungal and mammalian membrane vesicles was used to measure the cation-selective channel forming ability of HZ and HFZ delivered from HSA. RESULTS: It is shown that FZ is rapidly converted from its aggregated form to a protein-bound monomer in the presence of HSA, whereas HFZ demonstrates greater stability by persisting as a stable inactive aggregate. Fluorescence measurements of ion currents show that HSA attenuates the membrane-activity of both preparations. However, the activity of both HFZ and FZ remains significant against ergosterol-containing membranes. This is the first direct measurement of the intrinsic channel forming abilities of these amphotericin B preparations in the presence of serum proteins. CONCLUSION: These data provide a mechanistic rationale for the similar efficacy and lower toxicity of HFZ.
Asunto(s)
Anfotericina B/química , Antifúngicos/química , Canales Iónicos/química , Albúmina Sérica/química , Dicroismo Circular , Concentración de Iones de Hidrógeno , Indicadores y Reactivos , Cinética , Membranas Artificiales , Espectrometría de Fluorescencia , Espectrofotometría UltravioletaRESUMEN
Epidemiological studies suggest that nonsteroidal anti-inflammatory agents decrease the risk of colorectal cancer. This is believed to be mediated, at least in part, by inhibition of cyclooxygenase (COX) activity. There are two COX isoenzymes, namely the constitutively expressed COX-1 and the inducible COX-2. COX-2 is overexpressed in adenomas and colorectal cancers, and COX-2-specific inhibitors have been shown to inhibit intestinal polyps in Apc(Delta716) mice more effectively than dual COX-1/COX-2 inhibitors such as sulindac. Various Apc knockout mice, including the multiple intestinal neoplasia (Min) mouse and the Apc(Delta716) mouse, are limited by their lack of large numbers of colonic adenomas and aberrant crypt foci, the putative precursors of large-bowel polyps and cancers. Our DNA mismatch-repair-deficient Min mouse model (Apc+/-Msh2-/-) has genetic features of both familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, and most importantly, rapidly develops numerous small- and large-bowel adenomas, as well as colonic aberrant crypt foci. The purpose of this study was to determine the effects of COX inhibitors on intestinal adenomas and colonic aberrant crypt foci in this accelerated polyposis, mismatch-repair-deficient Min mouse model, in addition to a standard Min mouse model. Weanling Apc+/-Msh2-/- and Min mice were fed diets containing no drug, sulindac, or a specific COX-2 inhibitor (MF-tricyclic). Apc+/-Msh2-/- and Min mice were sacrificed after 4 weeks and 5 months on diet, respectively. Apc+/-Msh2-/- mice treated with MF-tricyclic had significantly fewer small-bowel polyps (mean +/- SD, 178 +/- 29) compared with mice on sulindac (278 +/- 80), or control diet (341 +/- 43; P < 0.001). There was no difference in numbers of large-bowel polyps or aberrant crypt foci in mice in the three groups. MF-tricyclic was also effective in reducing both small- and large-bowel polyps in Min mice. Western analysis demonstrated COX-2 expression in both large- and small-bowel polyps from mice of both genotypes. This study demonstrates that a specific COX-2 inhibitor is effective in preventing small-bowel polyps in mismatch-repair-deficient Min mice and both small- and large-bowel polyps in standard Min mice. Therefore, specific COX-2 inhibitors may be useful as chemopreventive and therapeutic agents in humans at risk for colorectal neoplasia.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa/farmacología , Proteínas de Unión al ADN , Pólipos Intestinales/tratamiento farmacológico , Isoenzimas/antagonistas & inhibidores , Lesiones Precancerosas/tratamiento farmacológico , Proteínas Proto-Oncogénicas/fisiología , Adenoma/tratamiento farmacológico , Adenoma/enzimología , Adenoma/genética , Animales , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/genética , Cruzamientos Genéticos , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/sangre , Reparación del ADN/genética , Femenino , Furanos/farmacología , Genes APC/genética , Pólipos Intestinales/enzimología , Pólipos Intestinales/genética , Masculino , Proteínas de la Membrana , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína 2 Homóloga a MutS , Lesiones Precancerosas/enzimología , Lesiones Precancerosas/genética , Prostaglandina-Endoperóxido Sintasas , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , Especificidad por Sustrato , Sulindac/sangre , Sulindac/farmacologíaRESUMEN
The intestinal permeability of hexarelin and EP 51389, two growth hormone releasing hexa- and tri- peptide analogues, was assessed in vitro with side-by-side diffusion chambers in the apical-to-basolateral (AP-to-BL) and in the basolateral-to-apical (BL-to-AP) direction using excised rat jejunal segments. The effect of EP 51389 on P-glycoprotein (P-gp) was evaluated by rhodamine 123 accumulation on monolayers of CH(R)C5 cells with increasing concentrations of EP 51389. Hexarelin and EP 51389 permeability were found to be < 1%. Permeability coefficients (P(app)) were 18.87 +/- 2.86 (x10(-7) cm/s) and 5.87 +/- 0.45 (x10(-7) cm/s) for hexarelin and EP 51389, respectively. Bidirectional studies revealed that hexarelin transport was similar in both directions. EDTA did not influence hexarelin permeability. Permeability was predominantly secretory for EP 51389 as P(app) in the BL-to-AP direction [32.56 +/- 6.11 (x10(-7) cm/s)] was greater than AP-to-BL. Confirming involvement of a secretory transport system, chlorpromazine inhibited EP 51389 transport across the jejunum. EP 51389 inhibited P-gp in a dose dependent manner resulting in the intracellular accumulation of rhodamine in CH(R)C5 cells. These results suggest that: 1) the intestinal permeability of hexarelin and EP 51389 is poor; 2) the passage of hexarelin is mainly via a transcellular passive pathway since the contribution of paracellular permeability to the overall permeability is rather low; 3) P-gp may act as a potential barrier for the intestinal absorption of EP 51389.
Asunto(s)
Hormona del Crecimiento/farmacología , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Oligopéptidos/metabolismo , Oligopéptidos/farmacología , Péptidos/química , Animales , Western Blotting , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Clorpromazina/farmacología , Densitometría , Relación Dosis-Respuesta a Droga , Resistencia a Múltiples Medicamentos , Ácido Edético/farmacología , Masculino , Modelos Teóricos , Ratas , Ratas Sprague-Dawley , Rodamina 123/farmacología , Factores de TiempoRESUMEN
The purpose of this investigation was to determine the serum pharmacokinetics, tissue distribution, and renal toxicity of amphotericin B (AmpB) following administration of a single intravenous dose (1 mg/kg of body weight) of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to New Zealand White female rabbits. FZ solutions were heated at 70 degrees C for 20 min to produce HFZ. Blood samples were obtained before drug administration and serially thereafter. After collection of the 48-h blood sample, each rabbit was humanely sacrificed and the right kidney, spleen, lungs, liver, and heart were harvested for AmpB analysis. Serum creatinine levels were measured before and 10 h after drug administration. AmpB concentrations in the serum and tissues were analyzed using high-performance liquid chromatography. FZ administration to rabbits resulted in a greater-than-50% increase in serum creatinine concentrations compared to baseline. However, HFZ administration resulted in no difference in serum creatinine concentrations compared to baseline. The AmpB area under the concentration-time curve (AUC) after HFZ administration was significantly lower than the AmpB AUC in rabbits administered FZ. However, AmpB systemic total body clearance was significantly greater in rabbits administered HFZ than in rabbits administered FZ without any differences in volume of distribution at steady state. Kidney tissue AmpB concentrations, although not significantly different, were greater in rabbits administered FZ than in rabbits administered HFZ. Likewise, lung and spleen AmpB concentrations, although not significantly different, were greater in rabbits administered FZ than in rabbits administered HFZ. However, liver AmpB concentrations were significantly lower in rabbits administered FZ than in rabbits administered HFZ. No significant differences in heart AmpB concentration between rabbits administered FZ and those given HFZ were found. These findings suggest that the pharmacokinetics, tissue distribution, and renal toxicity of AmpB are modified following administration of HFZ. HFZ could be an improved low-cost AmpB drug delivery system that has a potentially higher therapeutic index than FZ.
Asunto(s)
Anfotericina B/sangre , Antifúngicos/sangre , Riñón/efectos de los fármacos , Anfotericina B/efectos adversos , Anfotericina B/farmacocinética , Animales , Antifúngicos/efectos adversos , Antifúngicos/farmacocinética , Área Bajo la Curva , Femenino , Inyecciones Intravenosas , Riñón/metabolismo , Conejos , Distribución TisularRESUMEN
Mutations in the human adenomatous polyposis (APC) gene are causative for familial adenomatous polyposis (FAP), a rare condition in which numerous colonic polyps arise during puberty and, if left untreated, lead to colon cancer. The APC gene is a tumor suppressor that has been termed the "gatekeeper gene" for colon cancer. In addition to the 100% mutation rate in FAP patients, the APC gene is mutated in >80% of sporadic colon and intestinal cancers. The Apc gene in mice has been mutated either by chemical carcinogenesis, resulting in the Min mouse Apcdelta850, or by heterologous recombination, resulting in the Apcdelta716 or Apedelta1368 mice (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). Although homozygote Apc-/- mice are embryonically lethal, the heterozygotes are viable but develop numerous intestinal polyps with loss of Apc heterozygosity within the polyps (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). The proinflammatory, prooncogenic protein cyclooxygenase (COX)-2 has been shown to be markedly induced in the Apcdelta716 polyps at an early stage of polyp development (M. Oshima et al., Cell, 87: 803-809, 1996). We demonstrate here that treatment with the specific COX-2 inhibitor rofecoxib results in a dose-dependent reduction in the number and size of intestinal and colonic polyps in the Apcdelta716 mouse. The plasma concentration of rofecoxib that resulted in a 55% inhibition of polyp number and an 80% inhibition of polyps > 1 mm in size is comparable with the human clinical steady-state concentration of 25 mg rofecoxib (Vioxx) taken once daily (A. Porras et al., Clin. Pharm. Ther., 67: 137, 2000). Polyps from both untreated and rofecoxib- or sulindac-treated Apcdelta716 mice expressed COX-1 and -2, whereas normal epithelium from all mice expressed COX-1 but minimal amounts of COX-2. Polyps from either rofecoxib- or sulindac-treated mice had lower rates of DNA replication, expressed less proangiogenic vascular endothelial-derived growth factor and more membrane-bound beta-catenin, but showed unchanged nuclear localization of this transcription factor. This study showing the inhibition of polyposis in the Apcdelta716 mouse suggests that the specific COX-2 inhibitor rofecoxib (Vioxx) has potential as a chemopreventive agent in human intestinal and colon cancer.
Asunto(s)
Anticarcinógenos/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Genes APC/genética , Neoplasias Intestinales/prevención & control , Pólipos Intestinales/prevención & control , Isoenzimas/antagonistas & inhibidores , Lactonas/farmacología , Transactivadores , Animales , Anticarcinógenos/farmacocinética , Núcleo Celular/metabolismo , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/farmacocinética , Proteínas del Citoesqueleto/metabolismo , Replicación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Neoplasias Intestinales/enzimología , Neoplasias Intestinales/genética , Pólipos Intestinales/enzimología , Pólipos Intestinales/genética , Isoenzimas/biosíntesis , Lactonas/farmacocinética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Sulfonas , Sulindac/análogos & derivados , Sulindac/farmacocinética , Sulindac/farmacología , beta CateninaRESUMEN
The purpose of the present study was to examine the influence of heat-induced superaggregation of Amphotericin B (AmB) in the Fungizone (FZ) formulation on its interaction with human serum components and relate this to reduced toxicity. Whole serum distribution studies showed that a significantly lower percentage of AmB from HFZ was recovered in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) fractions and a greater percentage recovered in the lipoprotein-deficient plasma (LPDP), though the majority of both preparations were recovered in LPDP. Circular dichroism (CD) and difference absorption spectroscopy were used to determine the stability of FZ and heat-treated FZ (HFZ) in the presence of HDL, LDL, serum, and albumin. The CD studies indicate that the "core" aggregate of HFZ is more stable in the presence of HDL and LDL, whereas the FZ is less stable and more dynamic with the core aggregate dissociating to a greater extent in the presence of either purified lipoprotein. Absorption studies with whole serum and purified albumin suggest that FZ aggregates are far less stable in the presence of albumin than HFZ and that interaction with serum albumin is a dominant feature for both drug preparations. HFZ also has a different effect on the cytokine response in vitro. Studies using THP-1 human monocytes show that HFZ provokes a smaller release of tumor necrosis factor (TNF)-alpha than FZ. This cytokine may be associated with the unpleasant side effects of AmB. These findings suggest that heat-induced superaggregation of AmB alters its interaction with HDL, LDL, serum proteins, and monocytes, and these findings may be important in explaining the reduced toxicity of the superaggregated form of AmB.
Asunto(s)
Anfotericina B/química , Anfotericina B/metabolismo , Antifúngicos/química , Antifúngicos/metabolismo , Proteínas Sanguíneas/metabolismo , Lipoproteínas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Dicroismo Circular , Calor , HumanosRESUMEN
Hong Kong government policy encourages and facilitates families to care for their older members as long as possible by providing families and their older relatives with community support services. Residential care for the elderly is viewed as a last resort. Due to the inadequate supply of community support services, the long period of care required, and the gradual breakdown of values of filial support, families may increasingly give up their caring roles and seek residential care for their dependent elderly relatives. A shortfall in subsidized residential care may lead to needy elderly persons' being cared for in private residential facilities. The demand for private residential care is projected to increase, despite criticism about the standard of care provided. Although an Ordinance, a Regulation, and a Code of Practice for residential care homes are in place to control, monitor, and upgrade private residential care in Hong Kong, problems remain that put the elderly at risk of receiving substandard services. These include the existence of substandard private aged care homes operating either with or without a license; the provision of substandard "places" to the elderly under the government's "bought place" scheme and "enhanced bought place" scheme; ineffective inspection; a lack of grading to indicate the quality of private aged care homes; and a general neglect of the quality of care. We provide recommendations to address these concerns. This requires paying attention to both the quality of care, as well as to the physical environment of homes.
Asunto(s)
Política Pública , Instituciones Residenciales , Anciano , Anciano de 80 o más Años , Hogares para Ancianos , Hong Kong , Humanos , Sector PrivadoRESUMEN
In this study, fluorescence-conjugated ligands were employed to label dopaminergic D1-like and D2-like receptors, respectively, in neurons derived from the frontal cortex of embryonic rats. The receptor binding sites were visualized and analyzed using confocal microscopy. Our results showed that fluorescently labeled receptors tended to form clusters with a diameter of about one micrometer and were distributed on both somata and dendrites. Chronic treatment with tetrodotoxin reduced the number of fluorescent clusters of both D1-like and D2-like receptors, while chronic treatment with a high concentration of potassium increased the number of fluorescent clusters of both D1-like and D2-like receptors. Further, chronic treatment with SCH23390 up-regulated the number of D1-like receptor clusters, whereas chronic treatment with bromocriptine down-regulated the number of D2-like receptor clusters. In addition, chronic treatment with spiperone down-regulated the number of D1-like receptor clusters. These results suggest that both neuronal activity and dopaminergic receptor occupancy are important factors that determine dopaminergic receptor clustering which is an essential step toward synaptogenesis during neuronal maturation process.
Asunto(s)
Agregación de Receptores/fisiología , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Benzazepinas/farmacología , Sitios de Unión , Bromocriptina/farmacología , Agonistas de Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Microscopía Confocal , Ratas , Ratas Long-Evans , Espiperona/farmacologíaRESUMEN
Surgical correction of unilateral coronal synostosis offers a unique opportunity to examine the molecular differences between an abnormal and a normal cranial suture. We isolated and identified a cDNA fragment whose expression was up-regulated in the premature fusing and fused coronal sutures, as compared with normal coronal sutures. The nucleotide sequence of the full-length cDNA of this gene, human NELL-1, has approximately 61% homology with the chicken Nel gene. Both chicken Nel and human NELL-1 are comprised of six epidermal growth factor-like repeats. The human NELL-1 messages were localized primarily in the mesenchymal cells and osteoblasts at the osteogenic front, along the parasutural bone margins, and within the condensing mesenchymal cells of newly formed bone in sites of premature sutural fusion. Human multiorgan tissue mRNA blot showed that NELL-1 was specifically expressed in fetal brain but not in fetal kidney, liver, or lung. We also showed that Nell-1 was expressed in rat calvarial osteoprogenitor cells and was largely absent in rat tibiae and fibroblast cell cultures. In conclusion, our data suggest that the NELL-1 gene is preferentially expressed in cranial intramembranous bone and neural tissue (both of neural crest cell origin) and is up-regulated during unilateral premature closure of the coronal suture. The precise role of this gene is unknown.
Asunto(s)
Suturas Craneales/metabolismo , Craneosinostosis/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas del Tejido Nervioso/genética , Secuencia de Aminoácidos , Animales , Proteínas de Unión al Calcio , Células Cultivadas , Embrión de Pollo , Clonación Molecular , Lateralidad Funcional/fisiología , Humanos , Hibridación in Situ , Datos de Secuencia Molecular , Osteoblastos/citología , Ratas , Regulación hacia ArribaRESUMEN
OBJECTIVES: To study the efficacy of karaoke singing and its implications in the rehabilitation of mental patients in Hong Kong Chinese. METHODS: A double blind controlled trial was conducted over six weeks in a small sample of chronic schizophrenic patients matched in age, sex and duration of illness. The index group practised karaoke and the controlled group practised simple singing. Subjects were assessed in changes in mood and social interaction. RESULTS: No significant difference was detectable within the 2 groups. However, significant differences of anxiety and social interaction at the end of the third and sixth weeks respectively, were detectable between the 2 groups. CONCLUSION: Karaoke therapy may be more effective than simple singing in improving social interaction. There is preliminary evidence that it may be anxiety-provoking for unstable schizophrenic patients. More research is required for further elucidation of the characteristics of favourable candidates, optimal schedule and active components of the therapy.
Asunto(s)
Musicoterapia , Esquizofrenia/rehabilitación , Adolescente , Adulto , Afecto , Antipsicóticos/uso terapéutico , Ansiedad/psicología , Estudios de Casos y Controles , China/etnología , Clorpromazina/uso terapéutico , Método Doble Ciego , Hong Kong , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Esquizofrenia/tratamiento farmacológico , Psicología del Esquizofrénico , AutoimagenRESUMEN
Dioxabicyclooctanyl naphthalenenitriles have been reported as a class of potent and nonredox 5-lipoxygenase (5-LO) inhibitors. These bicyclo derivatives were shown to be metabolically more stable than their tetrahydropyranyl counterparts but were not well orally absorbed. Replacement of the phenyl ring in the naphthalenenitrile 1 by a pyridine ring leads to the potent and orally absorbed inhibitor 3g (L-739,010, 2-cyano-4-(3-furyl)-7-[[6-[3-(3-hydroxy-6,8-dioxabicyclo[3.2.1] octanyl)]-2-pyridyl]methoxy]naphthalene). Compound 3g inhibits 5-HPETE production by human 5-LO and LTB4 biosynthesis by human PMN leukocytes and human whole blood (IC50S of 20, 1.6, and 42 nM, respectively). Derivative 3g is orally active in the rat pleurisy model (inhibition of LTB4, ED50 = 0.3 mg/kg) and in the anesthetized dog model (inhibition of ex vivo whole blood LTB4 and urinary LTE4, ED50 = 0.45 and 0.23 microgram/kg/min, respectively, i.v. infusion). In addition, 3g shows excellent functional activity against ovalbumin-induced dyspnea in rats (60% inhibition at 0.5 mg/kg, 4 h pretreatment) and Ascaris-induced bronchoconstriction in conscious sheep (50% and > 85% inhibition in early and late phases, respectively at 2.5 micrograms/kg/min, i.v. infusion) and, more particularly in the conscious antigen sensitive squirrel monkey model (53% inhibition of the increase in RL and 76% in the decrease of Cdyn, at 0.1 mg/kg, po). In rats and dogs, 3g presents excellent pharmacokinetics (estimated half-lives of 5 and 16 h, respectively) and bioavailabilities (26% and 73% when dosed as its hydrochloride salt at doses of 20 and 10 mg/kg, respectively, in methocel suspension). Based on its overall biological profile, compound 3g has been selected for preclinical animal toxicity studies.
Asunto(s)
Broncodilatadores/farmacología , Inhibidores de la Lipooxigenasa , Inhibidores de la Lipooxigenasa/síntesis química , Naftalenos/síntesis química , Animales , Ascaris , Disponibilidad Biológica , Broncodilatadores/síntesis química , Broncodilatadores/química , Perros , Disnea/tratamiento farmacológico , Humanos , Inflamación , Inhibidores de la Lipooxigenasa/farmacocinética , Inhibidores de la Lipooxigenasa/farmacología , Espectroscopía de Resonancia Magnética , Masculino , Conformación Molecular , Estructura Molecular , Naftalenos/farmacocinética , Naftalenos/farmacología , Infecciones por Nematodos/fisiopatología , Piridinas , Ratas , Proteínas Recombinantes/antagonistas & inhibidores , Saimiri , Ovinos , Spodoptera , TransfecciónRESUMEN
Two cyclooxygenase isozymes catalyze conversion of arachidonic acid to prostaglandin H2: constitutive COX-1 and inducible COX-2. To assess the role of COX-2 in colorectal tumorigenisis, we determined the effects of COX-2 gene (Ptgs2) knockouts and a novel COX-2 inhibitor on Apc delta716 knockout mice, a model of human familial adenomatous polyposis. A Ptgs2 null mutation reduced the number and size of the intestinal polyps dramatically. Furthermore, treating Apc delta716 mice with a novel COX-2 inhibitor reduced the polyp number more significantly than with sulindac, which inhibits both isoenzymes. These results provide direct genetic evidence that COX-2 plays a key role in tumorigenesis and indicate that COX-2-selective inhibitors can be a novel class of therapeutic agents for colorectal polyposis and cancer.
Asunto(s)
Poliposis Adenomatosa del Colon/enzimología , Proteínas del Citoesqueleto/genética , Furanos/farmacología , Genes APC/fisiología , Isoenzimas/genética , Prostaglandina-Endoperóxido Sintasas/genética , Poliposis Adenomatosa del Colon/tratamiento farmacológico , Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon , Animales , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Espacio Extracelular/fisiología , Femenino , Dosificación de Gen , Regulación Enzimológica de la Expresión Génica/fisiología , Regulación Neoplásica de la Expresión Génica/fisiología , Mucosa Intestinal/enzimología , Mucosa Intestinal/patología , Isoenzimas/efectos de los fármacos , Isoenzimas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutagénesis/fisiología , Prostaglandina-Endoperóxido Sintasas/efectos de los fármacos , Prostaglandina-Endoperóxido Sintasas/metabolismo , Sulindac/farmacología , Factores de TiempoRESUMEN
BACKGROUND: The open complex formed at the initiation site of transcription within the active site of RNA polymerase is unique to actively transcribing genes and is thus an ideal target for the design of transcription inhibitors. Many redoxactive tetrahedral cuprous chelates of 1,10-phenanthroline (OP) or derivatives cleave the single-stranded template, principally at sequence positions -7 to -3, whereas the redox-inactive tetrahedral cuprous chelate of 2, 9-dimethyl-OP (neocuproine) blocks transcription, but does not cleave. The octahedral (OP)3-Fe2+ chelate has no effect. Different promoters can give different cleavage patterns. We therefore searched for structural determinants of the open complex that are important in the cleavage reaction. RESULTS: Using site-directed mutagenesis, we systematically altered the nucleotides at the cleavage sites of the Escherichia coli lac UV-5-RNA polymerase open complex (positions -6 to -4), which are highly variable in E. coli promoters. Surprisingly, these changes had little effect on catalytic activity, on transcription inhibition by the cuprous complex of neocuproine and on the cleavage patterns generated by the cuprous chelates of OP derivatives. The scission pattern of a lac UV-5 promoter mutant in which the cleavage sites have the sequence of the trp EDCBA promoter is that of the lac UV-5 promoter, not the trp EDCBA promoter. CONCLUSIONS: Nucleotide-specific interactions are not responsible for the observed cleavage patterns. The recognition of the tetrahedral OP chelate must be due to a specific structure of the single-stranded regions, determined by RNA polymerase-DNA interactions in the upstream regulatory region.
Asunto(s)
Cobre/metabolismo , Fenantrolinas/metabolismo , Regiones Promotoras Genéticas/genética , Transcripción Genética/genética , Quelantes/metabolismo , Cobre/farmacología , Daño del ADN/efectos de los fármacos , Huella de ADN , ADN de Cadena Simple/efectos de los fármacos , ADN de Cadena Simple/metabolismo , ARN Polimerasas Dirigidas por ADN/metabolismo , Electroforesis en Gel de Poliacrilamida , Escherichia coli/enzimología , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Quelantes del Hierro/farmacología , Operón Lac/genética , Mutagénesis Sitio-Dirigida/genética , Oxidación-Reducción , Fenantrolinas/farmacología , Transcripción Genética/efectos de los fármacosRESUMEN
The variability in plasma and urine equine procaine measurement between three independent laboratories using current methods led to the development of a sensitive, reliable, and reproducible high-performance liquid chromatographic method. Standardbred mares were administered either a penicillin G procaine preparation intramuscularly or procaine hydrochloride subcutaneously, and blood and urine were collected at defined time intervals. By HPLC the detection limits for procaine in plasma and urine were 1 and 10 ng/mL, respectively. In contrast procaine in plasma could not be detected by GC-NPD, while the urinary detection limit was 50 ng/mL. The concentration of fluoride in the collection tubes and repetitive freeze-thawing modified plasma procaine measurement. Urinary pH was a factor in estimation of urine procaine levels with greater recovery and reproducibility of results at pH 5 as compared to pH 7. This HPLC method provides a simple, sensitive, and reliable quantitation of procaine in equine plasma and urine.