RESUMEN
Healthcare workers (HCWs) have increased exposure and subsequent risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This case-control study was conducted to investigate the contemporaneous risks associated with confirmed SARS-CoV-2 infection amongst HCWs following in-work exposure to a confirmed coronavirus disease-2019 (COVID-19) case. We assessed the influence of demographic (age, sex, nationality, high risk co-morbidities and vaccination status) and work-related factors (job role, exposure location, contact type, personal protective equipment (PPE) use) on infection risk following nosocomial SARS-CoV-2 exposure. All contact tracing records within the hospital site during waves 1-3 of the COVID-19 pandemic in Ireland were screened to identify exposure events, cases and controls. In total, 285 cases and 1526 controls were enrolled, as a result of 1811 in-work exposure events with 745 index cases. We demonstrate that male sex, Eastern European nationality, exposure location, PPE use and vaccination status all impact the likelihood of SARS-CoV-2 infection following nosocomial SARS-CoV-2 exposure. The findings draw attention to the need for continuing emphasis on PPE use and its persisting benefit in the era of COVID-19 vaccinations. We suggest that non-work-related factors may influence infection risk seen in certain ethnic groups and that infection risk in high-risk HCW roles (e.g. nursing) may be the result of repeated exposures rather than risks inherent to a single event.
Asunto(s)
COVID-19 , Infección Hospitalaria , Masculino , Humanos , Pandemias , COVID-19/epidemiología , SARS-CoV-2 , Estudios de Casos y Controles , Irlanda/epidemiología , Infección Hospitalaria/epidemiología , Personal de Salud , Factores de Riesgo , HospitalesRESUMEN
AIMS: To establish what practical and emotional means of support are required on initiation of insulin pump therapy and how needs change over time, using GENIE, a social network intervention. METHODS: The study's longitudinal design used semi-structured interviews, surveys (PAID, CLARKE) and HbA1c values at time of pump initiation, and at 3 and 6 months. Interviews used GENIE to capture participants' expectations and experiences of pump therapy and associated support and resources. Thematic analysis was used with sequential, time-ordered matrices. RESULTS: A total of 16 adults undertook 47 interviews. A total of 94 services, resources and activities were acquired, while tally, frequency and value of network members increased over time. The novelty of pump therapy impacted on participants' self-management needs. Key themes included: 1) the independent nature of managing diabetes; 2) overcoming the challenges and illness burden associated with pump use; 3) the need for responsive and tailored emotional and practical support; and 4) useful resources when incorporating pump therapy. GENIE was thought to be novel and beneficial. CONCLUSIONS: A social network approach determined what resources and support people with diabetes require when incorporating a new health technology. Visualisation of support networks using concentric circles enabled people to consider and mobilise support and engage in new activities as their needs changed. The novelty of pump therapy creates new illness-related work, but mobilisation of personally valued flexible, tailored support can improve the process of adaptation.
Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Sistemas de Infusión de Insulina , Automanejo , Análisis de Redes Sociales , Apoyo Social , Adulto , Anciano , Diabetes Mellitus/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Insulina/administración & dosificación , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Adulto JovenRESUMEN
Color image analysis was used to assess proliferative changes in smooth muscle cells from cultured segments of rabbit aortas. Proliferating cells were labeled with bromodeoxyuridine (BrdU) and visualized by immunohistochemical staining of histologic sections. A Macintosh IIfx computer with a Data Translation digitizer board, Javelin color camera and a color-enhanced version of National Institutes of Health Image 1.31 image analysis software (ColorImage 1.31) was used to acquire red, green and blue (RGB)-filtered grayscale images from microscopic slides of control and treated aortas. The BrdU-labeled (brown) and nonlabeled, hematoxylin (blue)-stained nuclei were identified on the RGB gray-scale images using a thresholding technique and sampled for nuclear number and area. An increase in the number of BrdU-labeled nuclei in the region of experimental perturbation was demonstrated by this semiautomated method. Thus, this Macintosh-based color image analysis method proved to be effective in rapidly quantitating immunohistochemically defined smooth muscle proliferation in microscopic tissues.
Asunto(s)
Recuento de Células/métodos , Desarrollo de Músculos , Músculo Liso Vascular/crecimiento & desarrollo , Animales , Aorta , Bromodesoxiuridina , División Celular , Interpretación de Imagen Asistida por Computador , Inmunohistoquímica , Músculo Liso Vascular/citología , Músculo Liso Vascular/ultraestructura , Técnicas de Cultivo de Órganos , Conejos , Programas Informáticos , Túnica Íntima/crecimiento & desarrollo , Túnica Media/crecimiento & desarrolloRESUMEN
1,1,1,2-Tetrafluoroethane (R-134a), a nonozone-depleting alternative air-conditioning refrigerant and propellant for pharmaceutical preparations, is oxidatively defluorinated by rat hepatic microsomes. In this report we show that induction of cytochrome P-450IIE1 in rats, by pyridine administration, resulted in an 8-fold increase in the rate of R-134a metabolism by hepatic microsomes (Vmax 47 vs. 6 nmol F-/mg microsomal protein/15 min). Furthermore, when data were normalized for P-450 content, a 4-fold increase in R-134a metabolism was noted for IIE1-enriched microsome preparations. In contrast, phenobarbital and Aroclor 1254 decreased the specific activity of hepatic microsomes for this function. The microsomal content of P-450IIE1, as evaluated by Western blot, was elevated significantly only in microsomes from pyridine-treated rats. p-Nitrophenol and aniline, which are metabolized at high rates by rat P-450IIE1, decreased the rate of R-134a defluorination by hepatic microsomes; Dixon plot analysis indicated competitive inhibition with a Ki of 36 microM p-nitrophenol or 115 microM aniline. Pyridine also potently induced defluorination of R-134a catalyzed by rabbit liver microsomes. Studies with individual P-450 isozymes purified from rabbit liver showed that the phenobarbital- and polycyclic hydrocarbon-induced isozymes (IIB1 and IA2) defluorinated R-134a at negligible rates (1.9 and 0.4 nmol F-/nmol P-450/60 min, respectively). In contrast, P-450IIE1 catalyzed defluorination of R-134a at a relatively high rate (16.2 nmol F-/nmol P-450/60 min); isozyme IA1, which also is induced by nitrogen-containing heterocycles such as pyridine, was somewhat active (5.3 nmol F-/nmol P-450/60 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Hidrocarburos Fluorados/metabolismo , Microsomas Hepáticos/enzimología , Oxidorreductasas N-Desmetilantes/metabolismo , Compuestos de Anilina/metabolismo , Animales , Biotransformación , Western Blotting , Citocromo P-450 CYP2E1 , Sistema Enzimático del Citocromo P-450/análisis , Sistema Enzimático del Citocromo P-450/inmunología , Electroforesis en Gel de Poliacrilamida , Fluoruros/análisis , Fluoruros/metabolismo , Técnicas In Vitro , Isoenzimas/metabolismo , Masculino , Nitrofenoles/metabolismo , Oxidación-Reducción , Oxidorreductasas N-Desmetilantes/análisis , Oxidorreductasas N-Desmetilantes/inmunología , Piridinas/farmacología , Ratas , Ratas Endogámicas F344RESUMEN
1,1,1,2-Tetrafluoroethane (R-134a) is a non-ozone-depleting alternative to dichlorodifluoromethane for use as an air-conditioning refrigerant and as a propellant in anti-asthmatic and other pharmaceutical preparations. Hepatic microsomes, supplemented with NADPH, catalyzed the release of F- from R-134a; metabolite production was positively correlated with both duration of incubation and gas phase [R-134a]. Defluorination of R-134a was inhibited by CO, lack of NADPH, or heat denaturation of microsomes. Release of F- from R- 134a biotransformation as shown by the near-total lack of dehalogenation during anaerobic incubations. R-134a did not produce a difference spectrum (360 to 500 nm) with either oxidized or dithionite-reduced microsomes. Microsomes from phenobarbital- or Aroclor 1254-treated rats produced greater amounts of F- per mg protein from high concentrations of R-134a than did microsomes from untreated rats, but when normalized for microsomal cytochrome P-450 content both phenobarbital and Aroclor treatment decreased the specific activity (nmol F-/nmol cytochrome P-450) of R-134a metabolism. Furthermore, while defluorination of R-134a by microsomes from livers of untreated rats was substrate-saturable (Vmax, 11 nmol of F-/nmol cytochrome P-450/15 min; KM, 8% R-134a), R-134a dehalogenation by microsomes from Aroclor-treated rats was nonsaturable with [R-134a] as high as 69%. Microsomes from phenobarbital-treated rats retained the saturable, low KM activity, but also exhibited the apparently nonsaturable kinetic component when [R-134a] was greater than 24%.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Fluoruros/metabolismo , Hidrocarburos Fluorados/metabolismo , Microsomas Hepáticos/metabolismo , Animales , Arocloros/farmacología , Azidas/farmacología , Biotransformación , Fluoruros/análisis , Formiatos/farmacología , Halotano/metabolismo , Técnicas In Vitro , Cinética , Masculino , Oxidación-Reducción , Fenobarbital/farmacología , Potenciometría , Ratas , Ratas Endogámicas F344 , EspectrofotometríaRESUMEN
The thermodynamic behavior and lack of ozone-depleting potential of 1,1,1,2-tetrafluoroethane (R-134a) suggest it as a likely replacement for dichlorodifluoromethane (R-12), now used as the refrigerant in many air-conditioning systems. To further the presently incomplete toxicological analysis of R-134a, the effects of R-134a on cell viability and functional competence of glucose metabolism were evaluated in suspension cultures of hepatocytes derived from fed or fasted rats. R-134a concentrations up to and including 75% (750,000 ppm) in the gas phase of sealed culture flasks did not produce evidence of cytolethality (LDH leakage) following 2 hr of exposure; in contrast, halothane (1,1,1-trifluoro-2-bromo-2-chloroethane) caused cell death at a gas phase concentration of only 1250 ppm. In hepatocytes isolated from fed rats. R-134a at concentrations of 12.5 to 75% increased glycolysis (production of lactate + pyruvate) in a concentration-dependent manner; no effect was observed at 5%. At 25%, R-12 and 1,1,2,2-tetrafluoro-1,2-dichloroethane (R-114) were of equal potency to R-134a in stimulating glycolysis: 1,1,1,2,2-pentafluoro-2-chloroethane (R-115) depressed glycolysis slightly. Halothane, at concentrations as low as 300 ppm, markedly increased rates of glycolysis. Glucose production by hepatocytes of fed rats was decreased by R-134, R-12, and R-114 only at concentrations of 25% or more. On the other hand, halothane (greater than or equal to 300 ppm) potently decreased glucose production by hepatocytes. In cells isolated from livers of fasted rats, R-134a exposure inhibited gluconeogenesis in a concentration-dependent manner although this effect was not significant until R-134a concentrations reached 12.5%. Comparative potency studies showed that R-134a, R-12, or R-114 (25% gas phase) inhibited gluconeogenesis about equally while as little as 300 ppm halothane was effective and R-115 (25%) was without effect. Considering that the threshold for alteration of the rate of glucose metabolism in this in vitro paradigm is about 12.5% R-134a, we conclude that toxicologically significant alteration of glucose-linked bioenergetics is unlikely at the levels of R-134a exposure anticipated in workplace or environment.
Asunto(s)
Glucosa/metabolismo , Hidrocarburos Fluorados/toxicidad , Hígado/metabolismo , Animales , Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromatografía de Gases , Medios de Cultivo/análisis , Femenino , Gluconeogénesis/efectos de los fármacos , Glucólisis/efectos de los fármacos , Halotano/toxicidad , Hidrocarburos Fluorados/análisis , Hidrocarburos Halogenados/toxicidad , Técnicas In Vitro , Cinética , Hígado/citología , Ratas , Ratas Endogámicas F344RESUMEN
alpha 2u-Globulin (alpha G), the major urinary protein of sexually mature male rats, is a key determinant of susceptibility to hyaline droplet nephropathy (HDN) induced by a variety of hydrocarbons in male rats. Arguments against extrapolating renal toxicity and carcinogenicity data for HDN-inducing toxicants from male rats to risk assessment for humans rely on the observation that humans do not express alpha G. Yet, human serum and urine are known to contain proteins coded for by the same gene family that also controls alpha G synthesis in the rat. Therefore, to understand some of the quantitative and qualitative differences between proteins of human and male rat urine which confer apparent resistance to HDN in humans, urinary proteins of male F344 rats (ca. 3 months old) and normal human males were compared by cation exchange, gel filtration, SDS-PAGE, and partially identified by Western blotting. We observed that (1) the protein content of human urine is only 1% that of male rat urine; (2) human urinary proteins, recovered by (NH4)2SO4 precipitation followed by dialysis, are primarily of high (greater than or equal to 75 kDa) molecular weight (MW) with minor components of 12-66 kDa; (3) male rat urine has little high-MW protein, but is rich in alpha G (18.5 kDa); (4) at pH 5, the most cationic fraction of human urinary protein constituted only about 4% of the total while the analogous fraction of rat urine, containing alpha G, contained 26% of total urinary protein; and (5) cationic (at pH 5.0) human urinary proteins included small amounts of proteins, e.g., alpha 1-acid glycoprotein, and alpha 1-microglobulin, which are products of the gene family coding for alpha G in rat. Thus, although humans excrete trace amounts of proteins similar to alpha G, the very low protein content of human urine, the relatively small proportion of cationic to total proteins, and the high MW of the most abundant human urinary proteins form a biological basis for suggesting that humans are not at risk for the type of fuel and solvent hydrocarbon-induced nephropathy, and the sequelae of such nephropathy, observed in male rats.
Asunto(s)
Hialina/metabolismo , Enfermedades Renales/inducido químicamente , Lisosomas/metabolismo , Proteinuria/inducido químicamente , Adulto , Animales , Cromatografía en Gel , Cromatografía por Intercambio Iónico , Electroforesis en Gel de Poliacrilamida , Humanos , Enfermedades Renales/orina , Masculino , Peso Molecular , Proteinuria/orina , RatasRESUMEN
As part of its toxicological evaluation we assessed the in vitro metabolism of 1,1,1,2-tetrafluoroethane (R-134a), a non-ozone-depleting chemical likely to replace dichlorodifluoromethane (R-12) as an air-conditioning refrigerant. Hepatocyte suspensions in sealed flasks produced increasing quantities of F- (detected in the liquid media) as the headspace concentration of R-134a increased from 1% to 50% (balance of atmosphere 95% O2-5% CO2); the kinetics of defluorination suggested substrate-saturation. Little F- was detected in cultures without R-134a or in cell suspensions heated prior to addition of R-134a. Halothane (1,1,1-trichloro-2-bromo-2-chloro-ethane), although not defluorinated by hepatocytes maintained with 95% O2, inhibited defluorination of R-134a. Hepatocytes from phenobarbital-treated rats dehalogenated high (greater than or equal to 25%) concentrations of R-134a at greater rates than cells from untreated rats. These findings are consistent with the hypothesis that oxidative metabolism of R-134a by cytochrome P-450 can occur in vivo.
Asunto(s)
Hidrocarburos Fluorados/metabolismo , Hígado/metabolismo , Animales , Biotransformación , Células Cultivadas , Halotano/metabolismo , Halotano/farmacología , Cinética , Hígado/efectos de los fármacos , Masculino , Oxidación-Reducción , Fenobarbital/farmacología , Potenciometría , Ratas , Ratas Endogámicas F344RESUMEN
We evaluated the contractility of bovine retinal microvascular pericytes in culture by permeabilizing the cells with 0.1% Triton X-100 and measuring their response to MgATP. Sequential photographs of the cells were taken over 20 min and their surface areas were measured. Our study directly demonstrates that pericytes are contractile cells, which respond to MgATP in a dose-dependent fashion over a relatively short time course (minutes). Pericytes did not contract in response to GTP, pyrophosphate or beta, gamma-methylene ATP. Immunofluorescence study showed the presence of muscle actin in Triton X-100-treated cells before and after contraction, indicating preservation of this cytoskeletal protein even after treatment with the detergent. Similar experiments on human umbilical vein endothelial cells, bovine lens epithelial cells and human retinal pigment epithelial cells showed that these cells were significantly less contractile than retinal pericytes. That pericytes show substantial contraction over a short time course indicates that these cells may play a major role in regulating blood flow in the microcirculation.