RESUMO
The objective of this review was to outline current implementation of biosecurity, the impact of biosecurity on the industry, and producers' and veterinarians' perceptions of biosecurity, with a focus on the Canadian dairy industry. Biosecurity has an important role in farm safety by reducing the spread of pathogens and contaminants, improving animal health and production, and maintaining human safety. Implementation of biosecurity practices varies among farms and countries. Because Canada's supply management system is different than other countries, different barriers and perceptions of biosecurity may exist. Producers may have negative perspectives on biosecurity, such as it being expensive or time consuming. Producers are motivated or deterred from biosecurity implementation for many reasons, including perceived value, disease risk, and financial incentives or deterrents. In addition, because veterinarians are a trusted source of information, their approaches to discussions on biosecurity implementation are important to understand. Veterinarians and producers appear to have differing opinions on the importance of biosecurity and approaches to discussing biosecurity. Improving biosecurity implementation requires a multifactorial approach, such as individualized education and awareness for producers, further research into efficacy of and barriers to biosecurity, and development of strategies for effective communication between veterinarians and producers.
Assuntos
Indústria de Laticínios , Canadá , Animais , Humanos , Bovinos , Médicos Veterinários/psicologia , PercepçãoRESUMO
Implementing biosecurity protocols is necessary to reduce the spread of disease on dairy farms. In Ontario biosecurity implementation is variable among farms, and the barriers to implementing biosecurity are unknown. Thirty-five semistructured interviews were conducted between July 2022 and January 2023 with dairy producers (n = 17) and veterinarians (n = 18). Participants also completed a demographic survey. Thematic analysis was performed with constructivist and grounded theory paradigms. Thematic coding was done inductively using NVivo software. Dairy producers' understanding of the definition of biosecurity varied, with all understanding that it was to prevent the spread of disease. Furthermore, the most common perception was that biosecurity prevented the spread of disease onto the farm. Both veterinarians and producers stated that closed herds were one of the most important biosecurity protocols. Barriers to biosecurity implementation included a lack of resources, internal and external business influencers, individual perceptions of biosecurity, and a lack of industry initiative. Understanding the barriers producers face provides veterinarians with the chance to tailor their communication to ensure barriers are reduced or for other industry members to reduce the barriers.
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Indústria de Laticínios , Médicos Veterinários , Médicos Veterinários/psicologia , Ontário , Animais , Bovinos , Fazendeiros/psicologia , Inquéritos e Questionários , Fazendas , Humanos , Doenças dos Bovinos/prevenção & controleRESUMO
In November 2017, eight confirmed measles cases were reported to Public Health England from a hospital in the West Midlands. A multidisciplinary Incident Management Team (IMT) was established to determine the extent of the problem and coordinate an outbreak response. Between 1 November 2017 and 4 June 2018, a total of 116 confirmed and 21 likely measles cases were linked to this outbreak; just under half (43%) were aged over 15 years of age. Fifty-five of the confirmed cases were hospitalised (48%) and no deaths were reported. At the start of the outbreak, cases were mostly individuals of Romanian origin; the outbreak subsequently spread to the wider population. Over the 8-month response, the IMT conducted the following control measures: extensive contact tracing, immediate provision of post-exposure prophylaxis, community engagement amongst specific high-risk groups, MMR awareness raising including catch-up campaigns and enhanced vaccination services at selected GP surgeries. Key challenges to the effective control measures included language difficulties limiting community engagement; delays in diagnosis, notification and appropriate isolation of cases; limited resources for contact tracing across multiple high-risk settings (including GPs and hospitals) and lack of timely data on vaccine coverage in sub-groups of the population to guide public health action.
Assuntos
Surtos de Doenças/prevenção & controle , Sarampo/epidemiologia , Sarampo/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , Busca de Comunicante , Inglaterra/epidemiologia , Feminino , Comunicação em Saúde , Humanos , Programas de Imunização , Lactente , Masculino , Sarampo/transmissão , Vírus do Sarampo , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Profilaxia Pós-Exposição , Adulto JovemRESUMO
Despite the impact of problem gambling on affected family members (AFMs), there are limited large-scale population level studies identifying the negative mental health (NMH) and positive mental health (PMH) characteristics of AFMs. Furthermore, no study has explored whether PMH characteristics are protective in the relationships between AFM status and NMH characteristics. This study involved secondary data analysis from the Third Social and Economic Impact Study of Gambling in Tasmania. Using a subsample of 1,869 adults (48.30 % male; meanage = 48.48; 4.67 % AFMs), this study aimed to explore whether: (1) AFM status is associated with NMH (depression, anxiety, panic, post-traumatic stress disorder, social anxiety, binge drinking, tobacco use, and drug use symptoms) and PMH (quality of life [QOL], personal growth/autonomy, interpersonal/social skills, coping skills) characteristics after separately controlling for sociodemographic, problem gambling severity, and other NMH characteristics; (2) PMH characteristics moderate (buffer) the relationships between AFM status and NMH characteristics; and (3) gender influences these relationships. AFM status, defined as exposure to family member gambling problems, significantly positively predicted NMH characteristics (depression, anxiety, panic, PTSD, and tobacco use symptoms) and negatively predicted QOL (physical, social) and planning coping. The strength of these relationships generally attenuated after controlling for various covariates. Gender did not moderate these relationships. Religious coping exacerbated the relationship between AFM status and panic disorder symptoms. These findings can inform the development of intervention initiatives for family members exposed to gambling problems. Future population-representative research is required using a range of affected other types, longitudinal study designs, and more comprehensive measures.
Assuntos
Família , Jogo de Azar , Humanos , Masculino , Feminino , Jogo de Azar/psicologia , Jogo de Azar/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Família/psicologia , Qualidade de Vida/psicologia , Tasmânia/epidemiologia , Adaptação Psicológica , Austrália/epidemiologia , Saúde MentalRESUMO
PURPOSE: Ventral hernia repairs (VHR) are among the most commonly performed operations by general surgeons. Despite advances in technology there remains high complication and readmission rates. Preoperative anemia has been linked to poor outcomes and readmission across several surgical procedures, however the link to ventral hernia repair outcomes is limited. METHODS: Utilizing the American College of Surgeons National Safety and Quality Improvement Project (NSQIP) database for years 2016-2018, a total of 115,000 patients met inclusion criteria. Using propensity matching we matched two groups of patients who underwent VHR: (1) those with preoperative anemia and (2) those with normal hemoglobin levels. Anemia criteria was set forth by the World Health Organization (WHO). RESULTS: Univariate analysis did demonstrate statistical significance in post-operative outcomes percentage of serious surgical site infection, poor renal outcomes, transfusion, and unplanned remission in those with preoperative anemia who underwent VHR. In a multivariate analysis, patients who underwent ventral hernia repair with pre-operative anemia had significantly greater odds of unplanned readmission (odds ratio 1.35, 95% confidence interval 1.16-1.57) and serious surgical site infection (odds ratio 1.35, 95% confidence interval 1.04-1.74) independent of known risk factors such as smoking, diabetes and obesity. CONCLUSIONS: Preoperative anemia is a risk factor for poor postoperative outcomes in those undergoing ventral hernia repair and should be considered when evaluating a patient for repair.
Assuntos
Anemia , Hérnia Ventral , Humanos , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/cirurgia , Hérnia Ventral/complicações , Hérnia Ventral/cirurgia , Fatores de Risco , Anemia/complicações , Anemia/cirurgiaRESUMO
We examined the influence of insect cadaver desiccation on the virulence and production of entomopathogenic nematodes (EPNs), common natural enemies of many soil-dwelling insects. EPNs are often used in biological control, and we investigated the feasibility of applying EPNs within desiccated insect cadavers. Desiccation studies were conducted using the factitious host, Galleria mellonella (Lepidoptera: Pyralidae, wax moth larvae) and three EPN species (Heterorhabditis bacteriophora 'HB1', Steinernema carpocapsae 'All', and Steinernema riobrave). Weights of individual insect cadavers were tracked daily during the desiccation process, and cohorts were placed into emergence traps when average mass losses reached 50%, 60%, and 70% levels. We tracked the proportion of insect cadavers producing infective juveniles (IJs), the number and virulence of IJs produced from desiccated insect cadavers, and the influence of soil water potentials on IJ production of desiccated insect cadavers. We observed apparent differences in the desiccation rate of the insect cadavers among the three species, as well as apparent differences among the three species in both the proportion of insect cadavers producing IJs and IJ production per insect cadaver. Exposure of desiccated insect cadavers to water potentials greater than -2.75 kPa stimulated IJ emergence. Among the nematode species examined, H. bacteriophora exhibited lower proportions of desiccated insect cadavers producing IJs than the other two species. Desiccation significantly reduced the number of IJs produced from insect cadavers. At the 60% mass loss level, however, desiccated insect cadavers from each of the three species successfully produced IJs when exposed to moist sand, suggesting that insect cadaver desiccation may be a useful approach for biological control of soil insect pests.
Assuntos
Dessecação , Hidratação , Lepidópteros/parasitologia , Rabditídios/patogenicidade , Solo , Água , Animais , Cadáver , Controle Biológico de Vetores , Reprodução/fisiologia , Rabditídios/fisiologia , Virulência/fisiologiaRESUMO
Having a sick infant in the NICU can be quite stressful and overwhelming to parents. They require support and may have varied needs. A systematic review of qualitative and quantitative studies from 5 electronic databases (Ovid Medline, EMBASE, PsycINFO, CINAHL and Sociological Abstracts), covering January 2001 - March 2016 identified the needs and stressors of parents of term or near-term Infants in the NICU. Six articles addressed the needs and 14 identified the stressors of parents. Parents' most important need was for accurate and honest information. Needs focused around sensitive infant care and involvement in decision-making. The greatest stressor for parents was alteration to the parental role, followed by infant appearance. Fathers and parents of infants undergoing surgery are an under-researched population. Based on the evidence, enhancing staff-parent communication would better meet parental needs and reduce stressors. Our key recommendations highlight the need for family-centred and individualised care practices in the NICU.
Assuntos
Unidades de Terapia Intensiva Neonatal , Pais/psicologia , Adulto , Pai , Feminino , Humanos , Recém-Nascido , Masculino , Assistência Centrada no Paciente , Grupo Associado , Guias de Prática Clínica como Assunto , Nascimento Prematuro/psicologiaRESUMO
OBJECTIVE: To measure the intrapharyngeal pressure (IPP) generated by high-flow nasal cannula (HFNC) at varying flow rates up to 5 l min(-1). STUDY DESIGN: We studied 14 infants on HFNC or NCPAP using IPP manometry to measure the IPP generated at flows of 1, 2, 3, 4 and 5 l min(-1). RESULT: On average flow rates of 1, 2, 3, 4 and 5 l min(-1) generated an IPP (cm of H(2)O) of 1.70+/-0.34, 1.75+/-0.2, 2.62+/-0.28, 3.78+/-0.44 and 4.84+/-0.51 respectively. CONCLUSION: HFNC delivers significant IPP and is potentially a well-tolerated and viable option to provide CPAP at flows of > or = 3 min(-1) in infants with respiratory distress.
Assuntos
Cateterismo , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Feminino , Humanos , Recém-Nascido , Masculino , Cavidade NasalRESUMO
OBJECTIVE: Given interventions implemented in recent years to reduce maternal deaths, we sought to determine the incidence and causes of maternal deaths for 1998-2003. METHOD: Records of public hospitals and state pathologists were reviewed to identify pregnancy-related deaths within 12 months of delivery and determine their underlying causes. RESULTS: Maternal mortality declined (p=0.023) since surveillance began in 1981-83. The fall in direct mortality (p=0.0003) included 24% fewer hypertension deaths (introduction of clinical guidelines, reorganization of antenatal services) and 36% fewer hemorrhage deaths (introduction of plasma expanders). These improvements were tempered by growing indirect mortality (p=0.057), moving to 31% of maternal deaths from 17% in 1993-95. INTERPRETATION: Declines in direct mortality may be associated with surveillance and related improvements in obstetric care. Increased indirect deaths from HIV/AIDS, cardiac disease, sickle cell disease and asthma suggests the need to improve collaboration with medical teams to implement guidelines to care for pregnant women with chronic diseases.
Assuntos
Causas de Morte , Mortalidade Materna/tendências , Feminino , Hemorragia/mortalidade , Hospitais Públicos , Humanos , Hipertensão Induzida pela Gravidez/mortalidade , Jamaica/epidemiologia , Serviços de Saúde Materna , Complicações do Trabalho de Parto/mortalidade , Vigilância da População , Guias de Prática Clínica como Assunto , Gravidez , Complicações na Gravidez/mortalidade , Resultado da GravidezRESUMO
Ultra-High-Molecular-Weight-Polyethylene (UHMWPE) is the material of choice for one of the articulating surfaces in many total joint replacements, notably hip and knee prostheses. The various methods used by the orthopaedic biomaterials industry to sterilize and anneal UHMWPE components, and the resulting oxidation and crosslinking, affect the mechanical wear resistance properties in ways still unknown at the microscopic and molecular levels. Transmission electron microscopy and chemical pyrolysis were used to quantify crosslinking induced by gamma irradiation and annealing in air. Changes in lamellar stacking and the amount of crosslinking suggest two types of crosslinking: relatively unstable crosslinks in the amorphous region initially resulting from gamma irradiation which are later replaced by more thermally stable crosslinks resulting from rearrangements at the annealing temperature. Lamellar mobility, the ability of crystalline lamellae to flow in the material, is enhanced during the transition from one type of bond to the other, and this appears to optimize near eight hours of annealing time. Results from decomposition and percent crystallinity measurements provide further support for this theory.
Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/efeitos da radiação , Polietilenos/química , Polietilenos/efeitos da radiação , Ar , Reagentes de Ligações Cruzadas/química , Raios gama , Dureza , Temperatura Alta , Teste de Materiais , Conformação MolecularRESUMO
A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T4). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T3) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1-6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging (123I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement. LEARNING POINTS: Free tri-iodothyronine (T3) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.Medicines and supplements sourced online for weight loss may contain thyroxine (T4) or T3 and should be considered as a cause of unexplained exogenous hyperthyroidism.
RESUMO
BACKGROUND: Parents of infants admitted to the Neonatal Intensive Care Unit (NICU) are at risk of psychological distress and NICU-related stress. However, parents of infants admitted to NICU for cardiac surgery are an under-researched population. AIMS: Identify levels of NICU-related stress, and levels of psychological distress, reported by parents of infants admitted to the NICU for cardiac surgery. STUDY DESIGN: Observational study. SUBJECTS: 69 parents of infants admitted to the NICU for cardiac surgery (cardiac group) and 142 parents of healthy infants (control group). OUTCOME MEASURES: Questionnaire packs provided to parents prior to discharge (time-point 1), and at six and 12months corrected age included: Hospital Anxiety and Depression Scale, Coping Inventory for Stressful Situations, and Family Support Scale. The Parental Stressor Scale:NICU was administered to the cardiac group at time-point 1. RESULTS: The cardiac group reported (i) that parental role alteration was the most stressful aspect of the NICU and (ii) higher scores for anxiety and depression than the control group at all three time-points, with the highest levels reported during the NICU stay. Correlation analyses indicated (i) stress associated with the sights and sounds of the NICU, and the appearance and behaviour of the infant in the NICU, had a significant positive association with anxiety and depression, and (ii) a significant negative relationship between anxiety and task-focused coping. CONCLUSIONS: An individualised parent-targeted intervention aimed at reducing stress associated with the NICU and enhancing task-focused coping style may help to reduce levels of anxiety and depression within this group of parents.
Assuntos
Procedimentos Cirúrgicos Cardiovasculares/psicologia , Cardiopatias Congênitas/cirurgia , Pais/psicologia , Estresse Psicológico/etiologia , Adulto , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Terapia Intensiva Neonatal/psicologia , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/epidemiologiaRESUMO
PURPOSE: A clonogenic assay was used to determine the effects of the growth factors TGFbeta1 and TGFbeta3 on the radiation responses of a normal rat epithelial cell line (IEC6) and a human colonic carcinoma epithelial cell line (Widr). METHODS AND MATERIALS: The radiation sensitivity and ability to recover from potentially lethal damage (PLD), of preconfluent monolayer cultures, was assessed in the presence of the growth factors for 24 h prior to, during, and after irradiation. RESULTS: The surviving fractions of both cell lines assessed immediately following irradiation were unaffected by TGFbeta1 or TGFbeta3. However, TGFbeta3 (but not TGFbeta1) significantly reduced the amount of PLD recovery in the Widr cells (but not in the IEC6 cells). This was associated with a reduction in the shoulder region of the survival curve, rather than a change in slope. A comparative analysis of the effects of TGFbetas 1 and 3 on cell cycle events in the two cell lines demonstrated significantly more Widr cells in the S phase, in the presence of TGFbeta3 only, compared to the controls. This remained constant both before and immediately following irradiation. In the IEC6 cell line TGFbeta3 produced an increase in the numbers of G1 phase cells, characteristic of a G1 arrest. CONCLUSION: It seems likely that TGFbeta3-induced radiosensitisation in Widr cells, 6 h after a single dose of irradiation, is related to its effects on cell cycle events such that the failure of these cells to arrest in G1, either before or after irradiation, results in significantly reduced recovery from DNA damage. This, however, may not be the only mechanism by which this growth factor produces this effect. Indeed, it will also be necessary to investigate these effects in in vivo models and to determine the response to fractionated irradiation before the potential therapeutic benefit of both the differential effects observed between the two TGFbeta isoforms and also between the malignant and normal cell lines can be fully assessed.
Assuntos
Ciclo Celular/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Animais , Ciclo Celular/efeitos da radiação , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Linhagem Celular/efeitos dos fármacos , Linhagem Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Tolerância a Radiação , Ratos , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/efeitos da radiação , Ensaio Tumoral de Célula-TroncoRESUMO
Immune Tolerance Therapy for Haemophilia A Patients with Acquired Factor VIII Alloantibodies: Comprehensive Analysis of Experience at a Single Institution Eleven children with severe haemophilia A associated with the IVS 22 inversion and acquired high titre neutralising antibodies to factor VIII underwent immune tolerance induction. HLA class I and high resolution class II type is detailed for each patient. A three phase approach to immune tolerance induction was used. During phase 1, which lasted a median of six weeks, patients received factor VIII 100 IU/kg twice daily. Phase 2 comprised a factor VIII dose reduction to 100 IU/kg once daily, and continued for a median duration of 14 weeks. Subsequently 10 of the 11 patients satisfied the criteria of absent factor VIII neutralising activity by the Bethesda method, and a factor VIII elimination half life of greater than 5 h, allowing progression to phase 3, a further factor VIII dose reduction to 50 IU/kg three times weekly. A model for dose reduction as factor VIII tolerance evolves, based on pharmacokinetic analysis, is described.
Assuntos
Fator VIII/administração & dosagem , Fator VIII/imunologia , Hemofilia A/tratamento farmacológico , Hemofilia A/imunologia , Tolerância Imunológica , Pré-Escolar , Feminino , Hemofilia A/sangue , Humanos , Imunoterapia , Lactente , Isoanticorpos/imunologia , MasculinoRESUMO
1. Standard whole cell patch clamp recording techniques were used to study the pharmacological characteristics and site of econazole-mediated inhibition of calcium release-activated calcium current (Icrac) in the human leukaemic T cell line, Jurkat. 2. Extracellularly applied econazole blocked Icrac in a concentration-dependent manner (IC50 approximately 14 microM). Block developed over a relatively slow timecourse of 30-60 s (10 microM), and only partially reversed over minutes. 3. Econazole dialysed from the pipette into the cytosol at concentrations ranging from 0.1 to 30 microM did not reduce Icrac, or quantitatively affect Icrac block by extracellularly applied econazole. 4. A less lipophilic quaternary iodide derivative of econazole was synthesized to retard absorption through the cell membrane. When applied extracellularly, this compound blocked Icrac in a concentration-dependent manner with onset kinetics comparable to econazole. 5. Results with intracellularly dialysed econazole and the quaternary econazole derivative provide convergent evidence that econazole blocks Icrac via an extracellular interaction. 6. The inability of intracellularly applied econazole to inhibit Icrac argues against the notion that econazole inhibits capacitative Ca2+ entry pathways secondary to its known inhibitory effects on cytochrome P-450.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Econazol/farmacologia , Linfócitos T/efeitos dos fármacos , Econazol/análogos & derivados , Humanos , Células Jurkat , Microdiálise , Linfócitos T/metabolismoRESUMO
Voltage-dependent calcium (Ca2+) channel currents in freshly dissociated adult guinea-pig jugular ganglion neurons were examined and characterized using the whole-cell patch-clamp technique. Electrophysiological analysis demonstrated a high-threshold current, but no low-threshold or T-type current. A fraction of the total Ca2+ current was inhibited by omega (omega)-conotoxin GVIA (Cg (inTX; 10 microM); the dihydropyridine antagonist nifedipine (NIF; 10 microM), inhibited a large fraction of the CgTX-insensitive current. The remaining CgTX/NIF-insensitive current was completely inhibited by omega-agatoxin IVA (AgIVA; 100 nM). These results demonstrated that the whole-cell Ca2+ channel current consisted only of N-, L- P-type components. Of these currents, only the L-type was partially inhibited by both histamine and carbachol (0.01-100 microM).
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Canais de Cálcio/metabolismo , Gânglios Parassimpáticos/citologia , Neurônios Aferentes/metabolismo , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Eletrofisiologia , Gânglios Parassimpáticos/efeitos dos fármacos , Gânglios Parassimpáticos/metabolismo , Cobaias , Histamina/farmacologia , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Parassimpatomiméticos/farmacologiaRESUMO
Certain synthetic and endogenous steroids are known to modulate neuronal responses to gamma-aminobutyric acid (GABA) and also change the firing frequency of certain neurons. However, there is nothing known of the effect(s) of steroids on voltage-gated calcium currents in mammalian neurons. We show here that the steroids (0.1-100 microM) allotetrahydrocorticosterone (THCC), dehydroepiandrosterone sulfate (DHEAS) and pregnanolone can rapidly and reversibly depress voltage-gated calcium currents in freshly isolated adult hippocampal CA1 pyramidal neurons. This blocking action occurs in the presence of picrotoxin (10 microM). Tail current analysis shows that THCC appears to be a ligand that selectively and reversibly depresses the omega-conotoxin (fraction GVIA) sensitive portion of the calcium current. These results demonstrate that certain steroid metabolites have a direct membrane site of action which may influence brain excitability.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Hipocampo/metabolismo , Sistema Nervoso/química , Neurônios/metabolismo , Esteroides/farmacologia , Animais , Desidroepiandrosterona/farmacologia , Cobaias , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Neurônios/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Picrotoxina/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Esteroides/isolamento & purificação , Testosterona/análogos & derivados , Testosterona/farmacologia , ômega-Conotoxina GVIARESUMO
Ca(2+) release-activated Ca(2+) current (I(crac)) has been previously characterized biophysically in Jurkat lymphocytes and other non-excitable cells, but pharmacology remains poorly developed. The present objective was to delineate with whole cell recording details of the interaction of the chloride channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), with I(crac) in Jurkat cells. NPPB reversibly inhibited I(crac) in a concentration-dependent manner (IC(50)=5 microM). Kinetics for block and unblock of I(crac) by NPPB indicated a bimolecular interaction. Michaelis-Menten analysis indicated that NPPB interacts competitively with extracellular Ca(2+) permeating the I(crac) pathway. Finally, analysis of the pH dependence of I(crac) block by NPPB revealed a reduction in the apparent affinity during extracellular alkalinization that based on the pK(a) for NPPB, suggested that the neutral form of NPPB blocks the Ca(2+) release-activated Ca(2+) (CRAC) channel. Taken together, our results suggest a direct interaction between NPPB and the CRAC channel, and should help guide insights for developing novel and more selective analogues.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Nitrobenzoatos/farmacologia , Canais de Cloreto/antagonistas & inibidores , Estimulação Elétrica , Eletrofisiologia , Humanos , Concentração de Íons de Hidrogênio , Células Jurkat , Cinética , Técnicas de Patch-ClampRESUMO
The neurosteroids pregnenolone (PE) and pregnenolone-sulfate (PS) have been shown to interact with the GABAA receptor in the central nervous system. In contrast, nothing is known of any possible modulation of voltage-gated calcium channels (VGCC). We have examined the interaction of PE, PS and progesterone on VGCC in acutely isolated adult guinea-pig hippocampal CA1 neurons using the whole-cell patch clamp technique. PE and PS depressed the calcium current at low micromolar concentrations (0.001-100 microM). The time to peak of the calcium current was slowed by PE and PS. The blocking action of PE and PS occurs in the presence of 10 microM picrotoxin. In contrast, progesterone had no effect on the Ca2+ current, indicating specificity for PE and PS. These results demonstrate a direct and novel membrane site of action for PE and PS, suggesting a possible role influencing brain excitability.
Assuntos
Canais de Cálcio/efeitos dos fármacos , Hipocampo/citologia , Neurônios/efeitos dos fármacos , Pregnenolona/farmacologia , Progesterona/farmacologia , Animais , Cálcio/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Cobaias , Cinética , Potenciais da Membrana/efeitos dos fármacos , Picrotoxina/farmacologiaRESUMO
One hundred and forty-four solitary bone cysts were treated by curettage and packing with freeze-dried crushed cortical-bone allograft. One hundred and eight healed primarily. There was a higher rate of recurrence in young patients (less than ten years old), in active cysts, in females, and in incompletely packed cysts. However, of the cysts that were completely packed, 88 per cent healed. These data show that freeze-dried allogeneic crushed cortical bone is superior to similiarly processed cancellous bone and gives results similar to those achieved with fresh autogenous cancellous bone. Orthopaedic surgeons should therefore consider the use of freeze-dried allogeneic crushed cortical bone instead of autogenous grafts to avoid the morbidity and increased risk of complications associated with the procedure to obtain the autogenous bone.