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1.
Oper Dent ; 48(1): 59-67, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36445958

RESUMO

OBJECTIVES: To compare the effects of particle abrasion medium and pressure on shear bond strength and biaxial flexural strength of three generations of zirconia (Lava Frame, Lava Plus, and Lava Esthetic) with the goal of optimizing the bond to zirconia. METHODS: 280 discs (14 mm diameter; 1 mm thickness) of each zirconia were milled and sintered. Specimens of each material were randomly distributed into 14 groups (n=20); half were tested for shear bond strength and half were tested for biaxial flexural strength. The specimens were particle abraded on one surface by 2 different media (50 µm alumina particles or 50 µm glass beads) for 10 seconds at three different pressures (15, 30, and 45 psi or 0.1, 0.2, 0.3 MPa). Untreated specimens served as positive control. A tube (1.50 mm diameter) filled with dual cured resin cement (Panavia SA) was placed onto the surface and light cured. Specimens were stored in water (37°C for 24 hours) and shear bond strength was measured in a universal testing machine (Instron). Biaxial flexural strength of each specimen was measured according to ISO 6872. Shear bond strength and biaxial flexural strength were compared individually with a 2-way analysis of variance (ANOVA) for factors surface treatment and zirconia composition. RESULTS: Significant differences were seen between surface treatments (p<0.01), zirconia composition (p<0.01) and their interaction (p<0.01) for both bond strength and flexural strength. With alumina particle abrasion, higher pressure produced higher bonds for Lava Frame and Lava Plus zirconia while the bond of Lava Esthetic declined with increased pressure. Higher pressure (>0.2 MPa or 30 psi) with alumina decreased biaxial flexural strength with Lava Esthetic zirconia. CONCLUSIONS: Particle abrasion with alumina produced a significantly better combination of bond strength while maintaining biaxial strength of three zirconia materials than particle abrasion with glass beads. The bond strength also depended upon the pressure of particle abrasion and the generation of zirconia used.


Assuntos
Colagem Dentária , Resistência à Flexão , Propriedades de Superfície , Teste de Materiais , Zircônio/química , Cimentos de Resina/química , Resistência ao Cisalhamento , Óxido de Alumínio , Análise do Estresse Dentário
2.
Horm Metab Res ; 47(10): 711-20, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26158397

RESUMO

Several key findings from the late 1960s to mid-1970s regarding thyroid hormone metabolism and circulating thyroglobulin composition converged with studies pertaining to the role of T lymphocytes in autoimmune thyroiditis. These studies cemented the foundation for subsequent investigations into the existence and antigenic specificity of thymus-derived natural regulatory T cells (nTregs). These nTregs prevented the development of autoimmune thyroiditis, despite the ever-present genetic predisposition, autoantigen (thyroglobulin), and thyroglobulin-reactive T cells. Guided by the hypothalamus-pituitary-thyroid axis as a fixed set-point regulator in thyroid hormone metabolism, we used a murine model and compared at key junctures the capacity of circulating thyroglobulin level (raised by thyroid-stimulating hormone or exogenous thyroglobulin administration) to strengthen self-tolerance and resist autoimmune thyroiditis. The findings clearly demonstrated an essential role for raised circulating thyroglobulin levels in maintaining the dominance of nTreg function and inhibiting thyroid autoimmunity. Subsequent identification of thyroglobulin-specific nTregs as CD4(+)CD25(+)Foxp3(+) in the early 2000s enabled the examination of probable mechanisms of nTreg function. We observed that whenever nTreg function was perturbed by immunotherapeutic measures, opportunistic autoimmune disorders invariably surfaced. This review highlights the step-wise progression of applying insights from endocrinologic and immunologic studies to advance our understanding of the clonal balance between natural regulatory and autoreactive T cells. Moreover, we focus on how tilting the balance in favor of maintaining peripheral tolerance could be achieved. Thus, murine autoimmune thyroiditis has served as a unique model capable of closely simulating natural physiologic conditions.


Assuntos
Linfócitos T Reguladores/imunologia , Tireoglobulina/sangue , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologia , Animais , Células Clonais , Meio Ambiente , Humanos , Tolerância Imunológica
3.
Transplant Proc ; 47(3): 763-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25891727

RESUMO

BACKGROUND: The proliferation rates of human T cells in vitro are affected by some factors such as initial T-cell number, dose of stimulating cells, and duration of culture. The transcription factor forkhead box P3 (FoxP3) has been used to identify regulatory T cells in humans and is thought to correlate with tolerance to allogeneic organ transplant. Thus, it is important to optimize conditions to expand FoxP3 cell proliferation to improve engraftment of allogeneic organ transplants. METHODS: We studied proliferative responses and FoxP3 expression in divided T cells with the use of flow cytometric analysis of Ki-67 in culture of different concentrations of responding cells (6 × 10(6), 4 × 10(6), 2 × 10(6), 1 × 10(6), and 0.5 × 10(6)cells/mL), different types of stimulating cells (lymphocytes and low density cells), and different numbers of HLA mismatches. RESULTS: The proportion of CD3(+) cells, CD4(+)CD25(+) cells, and CD4(+)CD25(+)FoxP3(+) cells among mononuclear cells were highest at initial cell concentration of 2 × 10(6) responder cells/mL with lymphocytes as stimulators at day-5 mixed lymphocyte reaction (MLR). They were highest at a concentration of 4 × 10(6) responder cells/mL with low density cells as stimulators. The recovery (%), proportion of CD3(+) cells, CD4(+)CD25(+) cells, and CD4(+)CD25(+)FoxP3(+) cells with 2 HLA-DR incompatibility were significantly higher than those of 1 HLA-DR incompatibility at day-5 MLR. CONCLUSIONS: Initial cell concentration and HLA-DR incompatibility can affect the generation of FoxP3+ T cells in human MLR. These factors could be considered for efficient generation of Tregs for clinical trials in the future.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Antígenos HLA-DR/imunologia , Linfócitos T Reguladores/imunologia , Biomarcadores/metabolismo , Contagem de Células , Proliferação de Células , Citometria de Fluxo , Humanos , Antígeno Ki-67/metabolismo , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Linfócitos T Reguladores/fisiologia
4.
Public Health ; 124(10): 559-64, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20832834

RESUMO

Injury results from the acute transfer of energy (or the acute lack of a vital element) from the environment to human tissue. It is thus, ipso facto, an 'environmental health' issue par excellence. This paper argues that injury consequently deserves consideration as a major strategic priority by environmental health professionals. Two international agreements concerning children's health and the environment have major implications for safety. The Children's Environmental Health Action Plan for Europe (CEHAPE) and the European Environmental Health Strategy make reference to the need for improved evidence and greater co-operation between the environmental and health sectors. CEHAPE is particularly relevant to safety as it focuses on four regional priority goals, the second of which refers to the prevention and reduction of health consequences from injuries by promoting safe, secure and supportive human settlements for all children. The natural strategic 'home' for injury prevention may therefore lie within environmental health, a domain from which it has generally been excluded. In support of this assertion, Scotland's recent policy initiative on the environment and human health 'Good Places, Better Health' is cited, where injury in children up to 8 years of age is one of four child health priorities being tackled during its initial implementation. An important test of the initiative may be its capacity to inform policy, practice and research in the field of injury prevention and safety promotion. If successful, it will help to validate the environmental health approach to a field that remains relatively neglected by public agencies, policy makers, practitioners and researchers.


Assuntos
Saúde Ambiental/organização & administração , Gestão da Segurança/organização & administração , Ferimentos e Lesões/prevenção & controle , Meio Ambiente , Disparidades nos Níveis de Saúde , Habitação , Humanos , Fatores Socioeconômicos
5.
Dig Dis Sci ; 52(8): 1861-6, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17415649

RESUMO

Studies on the pathophysiology of reflux esophagitis have focused on the associated motility and/or structural abnormalities, with relatively little attention directed to inflammatory mediators involved in the acid-induced mucosal injury. Mast cells line the subepithelial lamina propria in both humans and the opossum model, and are ideally positioned to respond to luminal agents that cross the mucosal barrier. To determine whether certain mast cell mediators are involved in acid-induced mucosal injury, epithelial injury scores following 60 min of luminal perfusion of the opossum esophagus with 100 mM HCl were compared in the presence and absence of two different mast cell stabilizers (disodium cromoglycate and doxantrazole) or the selective platelet-activating factor antagonist TCV-309. In control animals acid perfusion caused release of PAF and significant epithelial injury, characterized by epithelial sloughing and cleft formation. This injury was unaffected by pretreatment with disodium cromoglycate or doxantrazole but was completely prevented by TCV-309 (histology damage score, 2.40+/-0.28 in controls vs 0.50 +/- 0.14 in TCV-309-treated animals). These studies suggest that platelet-activating factor is an important mediator of acid-induced esophageal mucosal damage.


Assuntos
Esofagite Péptica/fisiopatologia , Refluxo Gastroesofágico/fisiopatologia , Fator de Ativação de Plaquetas/fisiologia , Animais , Cromolina Sódica/farmacologia , Mastócitos/efeitos dos fármacos , Gambás , Inibidores da Agregação Plaquetária/farmacologia , Compostos de Piridínio/farmacologia , Tetra-Hidroisoquinolinas/farmacologia , Tioxantenos/farmacologia , Xantonas/farmacologia
6.
Public Health ; 120(10): 889-903; discussion 903-7, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16965797

RESUMO

Historically, the physical environment has been a target for public health policy across the globe. This remains the case in developing countries where the enduring infectious and toxic challenge posed by the environment is tangible and its health impact is manifest. However, in Western societies, the relevance of the environment to health has become obscured. Even when this is not the case, the perspective is usually narrow, centering on specific toxic, infectious or allergenic agents in particular environmental compartments. It is rare for importance to be given to a health-determining role for the environment acting through broader psychosocial mechanisms. The result is that environmental manipulation is seen as a cornerstone of the public health response for comparatively few health concerns. This paper considers how public health policies and action on the physical environment may be pursued more optimally. The need for a more strategic approach, which employs a new conceptual model that recognizes the complexity and contextual issues affecting the relationship between the environment and health but retains sufficient flexibility and simplicity to have practical application, is identified. Building on recent work, a model is proposed and pointers are given for its use in a practical context.


Assuntos
Exposição Ambiental/efeitos adversos , Saúde Ambiental , Política de Saúde , Modelos Teóricos , Causalidade , Comportamentos Relacionados com a Saúde , Humanos , Internacionalidade , Escócia , Mudança Social , Justiça Social , Terminologia como Assunto , Organização Mundial da Saúde
7.
Can J Physiol Pharmacol ; 81(5): 451-8, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12774851

RESUMO

Acid-induced esophagitis is associated with sustained longitudinal smooth muscle (LSM) contraction and consequent esophageal shortening. In addition, LSM strips from opossums with esophagitis are hyper-responsive, while the circular smooth muscle (CSM) contractility is impaired. To determine the origin of these changes, studies were performed on esophageal smooth muscle cells isolated from opossum esophagi perfused intraluminally on 3 consecutive days with either saline (control; n = 8) or HCl (n = 9). CSM and LSM cells, obtained by enzymatic digestion, were exposed to various concentrations of carbachol (CCh) and fixed. CCh induced concentration-dependent contraction of both LSM and CSM cells. CCh-induced LSM cell contraction was not different between control and esophagitis animals; however, there was marked attenuation in the CCh-induced contraction of CSM cells from esophagitis animals. Morphological studies revealed significant hypertrophy of the CSM cells. These findings suggest that impaired CSM contractility can be attributed at least in part to alterations to the CSM cell itself. In contrast, hyper-contractility demonstrated in LSM strips is likely related to factors in the surrounding tissue.


Assuntos
Esofagite Péptica/induzido quimicamente , Esôfago , Músculo Liso , Animais , Carbacol/farmacologia , Separação Celular , Esofagite Péptica/patologia , Esofagite Péptica/fisiopatologia , Esôfago/patologia , Esôfago/fisiopatologia , Ácido Clorídrico , Hipertrofia , Técnicas In Vitro , Manometria , Contração Muscular/efeitos dos fármacos , Músculo Liso/patologia , Músculo Liso/fisiopatologia , Miócitos de Músculo Liso/patologia , Gambás
8.
Dig Dis Sci ; 46(6): 1194-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11414293

RESUMO

Increased esophageal blood flow may protect against damaging refluxed gastric juices. We have shown that mast cells, histamine, and nitric oxide increase esophageal blood flow in the opossum during acid perfusion. This study examined the roles of substance P and calcitonin gene-related peptide on acid-induced hyperemia and whether the effects of substance P are mediated by mast cells. The opossum distal esophagus was perfused with saline, acid, or capsaicin while blood flow and histamine release were determined. Neuropeptides and neurokinin antagonists were administered parenterally. Only acid or calcitonin gene-related peptide (not substance P or capsaicin) significantly increased blood flow, which was prevented by neurokinin or calcitonin-gene-related peptide antagonists. Acid, substance P, and capsaicin all increased histamine release. Pretreatment with neurokinin antagonists did not affect acid-induced histamine release. We conclude that calcitonin-gene-related peptide is an important mediator of acid-induced esophageal hyperemia, while substance P plays an indirect role.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/fisiologia , Esôfago/irrigação sanguínea , Substância P/fisiologia , Animais , Esôfago/efeitos dos fármacos , Feminino , Ácido Clorídrico/farmacologia , Masculino , Mastócitos/fisiologia , Gambás , Fluxo Sanguíneo Regional/efeitos dos fármacos
10.
Dig Dis Sci ; 46(4): 802-7, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11330416

RESUMO

Swallowing is an important defense mechanism against reflux esophagitis as it helps clear refluxed gastric contents from the esophagus, while bicarbonate in the saliva acts to neutralize acid. The purpose of the present study was to examine the effect of esophagitis on the deglutition reflex in anesthetized opossums. Animals perfused with either an acidified pepsin solution for 45 min or with 100 mM hydrochloric acid for 45 min on each of three consecutive days exhibited a significantly impaired deglutition reflex in comparison to baseline. Control animals perfused with 0.9% saline showed no impairment. Bilateral cervical vagotomy in animals perfused with acidified pepsin attenuated the impaired deglutition reflex. Taken together, these results suggest that esophagitis causes an impairment in the deglutition reflex that is mediated by vagal afferent pathways.


Assuntos
Deglutição , Esofagite/fisiopatologia , Reflexo Anormal , Animais , Esofagite/induzido quimicamente , Feminino , Ácido Clorídrico/administração & dosagem , Masculino , Mucosa/fisiopatologia , Gambás
11.
Am J Physiol Gastrointest Liver Physiol ; 280(3): G463-9, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11171629

RESUMO

Acute intraluminal acid perfusion induces esophageal shortening in humans and opossums. Lower esophageal sphincter (LES) hypotension and peristaltic dysfunction occur in patients and animal models of reflux esophagitis. This study examined whether similar shortening and motor dysfunction occur in anesthetized opossums after repeated esophageal acid exposure and whether this is associated with longitudinal muscle (LM) hyperresponsiveness. Manometry used before and after 3 consecutive days of 45-min perfusion with 100 mmol/l HCl or normal saline measured esophageal length and motor responses to induced swallows. LM electrical and mechanical responses were assessed using standard isometric tension and intracellular recording techniques. Compared with controls, repeated acid perfusion induced erosive esophagitis and significant esophageal shortening, associated with enhanced LM responses to carbachol, a significantly depolarized resting membrane potential, and abnormal spike patterns. LES resting pressure and swallow-induced peristalsis were unaffected. In this model of reflux esophagitis, marked persistent esophageal shortening and associated LM hyperresponsiveness occur before significant LES or peristaltic dysfunction, suggesting that esophageal shortening is the earliest motor disorder induced by acid injury.


Assuntos
Deglutição , Transtornos da Motilidade Esofágica/fisiopatologia , Esofagite Péptica/fisiopatologia , Músculo Liso/fisiopatologia , Animais , Modelos Animais de Doenças , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Transtornos da Motilidade Esofágica/etiologia , Transtornos da Motilidade Esofágica/patologia , Esofagite Péptica/induzido quimicamente , Esofagite Péptica/complicações , Esofagite Péptica/patologia , Esôfago/enzimologia , Esôfago/patologia , Esôfago/fisiopatologia , Feminino , Ácido Clorídrico , Técnicas In Vitro , Masculino , Manometria , Potenciais da Membrana , Músculo Liso/enzimologia , Gambás , Peristaltismo , Peroxidase/metabolismo
12.
Anaesth Intensive Care ; 28(3): 300-4, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10853213

RESUMO

The Australian Incident Monitoring Study (AIMS) database of the Australian Patient Safety Foundation (APSF) was reviewed from its inception in April 1987 to October 1997. A total of 5600 AIMS reports were lodged in that period. Reports in which fatigue was listed as a Factor Contributing to Incident were examined. This occurred in 152 reports, or 2.7% of all reports. Confidence interval analysis suggested that fatigue was associated with various concurrently reported factors. These included pharmacological incidents (especially syringe swaps) and time of day. Other factors significantly associated with fatigue reports were haste, distraction, inattention and failure to check equipment. Relieving anaesthetists and healthy patients were reported more often as factors minimizing incidents. Anaesthetists reporting fatigue more often reported incidents during induction. These data suggest that fatigue alleviation strategies and equipment checking routines, improved workplace design (including drug ampoule and syringe labelling protocols) and regulation of working hours will facilitate minimization of fatigue-related incidents. Definitive prospective studies might be most usefully targeted at these and related interventions.


Assuntos
Anestesiologia , Fadiga/complicações , Doenças Profissionais/complicações , Gestão de Riscos , Anestesiologia/instrumentação , Anestésicos Gerais/administração & dosagem , Atenção , Austrália , Intervalos de Confiança , Bases de Dados como Assunto , Rotulagem de Medicamentos , Segurança de Equipamentos , Arquitetura de Instituições de Saúde , Fadiga/prevenção & controle , Humanos , Erros de Medicação , Doenças Profissionais/prevenção & controle , Admissão e Escalonamento de Pessoal , Estudos Prospectivos , Gestão de Riscos/estatística & dados numéricos , Segurança , Seringas , Fatores de Tempo , Local de Trabalho
13.
Am J Physiol Gastrointest Liver Physiol ; 278(3): G477-85, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10712268

RESUMO

A novel in vitro model that combined functional and morphological techniques was employed to directly examine pathways regulating Brunner's gland secretion in isolation from epithelium. In vitro submucosal preparations were dissected from guinea pig duodenum. A videomicroscopy technique was used to measure changes in luminal diameter of glandular acini as an index of activation of secretion. Carbachol elicited concentration-dependent dilations of the lumen (EC(50) = 2 microM) by activating muscarinic receptors on acinar cells. Ultrastructural and histological analyses demonstrated that dilation was accompanied by single and compound exocytosis of mucin-containing granules and the accumulation of mucoid material within the lumen. Inflammatory mediators (histamine, PGE(1), PGE(2)) and intestinal hormones (CCK, gastrin, vasoactive intestinal polypeptide, secretin) also stimulated glandular secretion, whereas activation of submucosal secretomotor neurons by 5-hydroxytryptamine did not. This study directly demonstrates that multiple hormonal, inflammatory, and neurocrine agents activate Brunner's glands, whereas many have dissimilar effects on the epithelium. This suggests that Brunner's glands are regulated by pathways that act both in parallel to and in isolation from those controlling epithelial secretion.


Assuntos
Glândulas Duodenais/metabolismo , Duodeno/metabolismo , Animais , Glândulas Duodenais/efeitos dos fármacos , Glândulas Duodenais/ultraestrutura , Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , Duodeno/efeitos dos fármacos , Duodeno/ultraestrutura , Feminino , Cobaias , Hormônios/farmacologia , Técnicas In Vitro , Masculino , Comunicação Parácrina/fisiologia
14.
Paediatr Anaesth ; 10(1): 99-102, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10632919

RESUMO

A case of difficult intubation in a patient with Apert syndrome, who had recently undergone bilateral internal midface distraction, is described. The 14-year-old boy had no antecedent history of such difficulty, despite numerous previous anaesthetics. We suggest that trismus due to temporalis muscle fibrosis, and the altered relationships of the maxilla and mandible following midface advancement, were causal.


Assuntos
Acrocefalossindactilia/cirurgia , Intubação Intratraqueal , Acrocefalossindactilia/complicações , Adolescente , Ossos Faciais/cirurgia , Humanos , Masculino , Osteotomia , Síndromes da Apneia do Sono/etiologia , Trismo/complicações , Trismo/cirurgia
15.
Am J Physiol ; 275(5): G1063-72, 1998 11.
Artigo em Inglês | MEDLINE | ID: mdl-9815037

RESUMO

This study characterized mast cell- and capsaicin-sensitive sensory nerve vasodilator mechanisms regulating submucosal arterioles in the guinea pig ileum. The outside diameter of arterioles in in vitro submucosal preparations from milk-sensitized guinea pigs was monitored using videomicroscopy. Superfusion of the cow's milk protein, beta-lactoglobulin (beta-Lg; 5 microM), evoked large dilations, which became completely desensitized. beta-Lg-evoked dilations were blocked by pyrilamine or NG-monomethyl-L-arginine plus indomethacin but not by TTX. Electron microscopic studies revealed that mast cells, in preparations receiving beta-Lg, demonstrated significant reductions of the dispersed and intact granule areas compared with preparations not exposed to beta-Lg. Paired experiments were conducted to determine if capsaicin-sensitive, nerve-evoked responses involved mast cell degranulation. One preparation received capsaicin (200 nM) followed by beta-Lg (5 microM); the other preparation received the drugs in reverse order. Prior treatment with capsaicin or beta-Lg had no effect on subsequent dilations evoked by the alternate treatment. Electron microscopy showed that nerve-arteriole associations were 10 times closer than nerve-mast cell associations. Mast cell numbers were not increased by milk sensitization. These findings suggest that mast cell- and capsaicin-sensitive nerve-evoked vasodilator mechanisms act independently in a model in which mast cell numbers are not increased.


Assuntos
Arteríolas/fisiologia , Capsaicina/farmacologia , Íleo/irrigação sanguínea , Mastócitos/fisiologia , Vasodilatação/fisiologia , Alprostadil/farmacologia , Animais , Arteríolas/citologia , Arteríolas/efeitos dos fármacos , Bradicinina/farmacologia , Bovinos , Epoprostenol/farmacologia , Hipersensibilidade Alimentar , Cobaias , Íleo/inervação , Indometacina/farmacologia , Lactoglobulinas/farmacologia , Microscopia de Vídeo , Leite/imunologia , Músculo Liso/irrigação sanguínea , Músculo Liso/inervação , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Pirilamina/farmacologia , Serotonina/farmacologia , Vasodilatação/efeitos dos fármacos , ômega-N-Metilarginina/farmacologia
16.
Int J Food Microbiol ; 40(3): 211-43, 1998 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-9620129

RESUMO

Microbiological risk assessment aimed at devising measures of hazard management, should take into account all perceived hazards, including those not empirically identified. It should also recognise that safety cannot be "inspected into" a food. Rather hazard management should be the product of intervention strategies in accordance with the approach made mandatory in the EU Directive 93/43 and the USDA FSIS Pathogen Reduction HACCP system; Final Rule. It is essential too that the inherent variability of the biological attributes affecting food safety is recognised in any risk assessment. The above strategic principles may be conceptualised as a four-step sequence, involving (i) identification and quantification of hazards; (ii) design and codification of longitudinally integrated ("holistic") technological processes and procedures to eliminate, or control growth and metabolism of, pathogenic and toxinogenic organisms; (iii) elaboration of microbiological analytical standard operating procedures, permitting validation of "due diligence" or responsible care, i.e. adherence to adopted intervention strategies. This should be supported by empirically assessed reference ranges, particularly for marker organisms, while the term "zero tolerance" is refined throughout to tolerable safety limit; (iv) when called for, the need to address concerns arising from lay perceptions of risk which may lack scientific foundation. In relation to infectious and toxic hazards in the practical context the following general models for quantitative holistic risk assessment are presented: (i) the first order, basic lethality model; (ii) a second approximation taking into account the amount of food ingested in a given period of time; (iii) a further adjustment accounting for changes in colonization levels during storage and distribution of food commodities and the effects of these on proliferation of pathogens and toxin production by bacteria and moulds. Guidelines are provided to address: (i) unsubstantiated consumer concern over the wholesomeness of foods processed by an innovative procedure; and (ii) reluctance of small food businesses to adopt novel strategies in food safety. Progress here calls for close cooperation with behavioural scientists to ensure that investment in developing measures to contain risk deliver real benefit.


Assuntos
Qualidade de Produtos para o Consumidor , Manipulação de Alimentos/normas , Microbiologia de Alimentos , Indústria de Processamento de Alimentos/normas , Medição de Risco , Animais , Guias como Assunto , Humanos
17.
Int J Food Microbiol ; 39(1-2): 19-51, 1998 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-9562875

RESUMO

Microbiological risk assessment aimed at devising measures of hazard management, should take into account all perceived hazards, including those not empirically identified. It should also recognise that safety cannot be "inspected into" a food. Rather hazard management should be the product of intervention strategies in accordance with the approach made mandatory in the EU Directive 93/43 and the USDA FSIS Pathogen Reduction HACCP system; Final Rule. It is essential too that the inherent variability of the biological attributes affecting food safety is recognised in any risk assessment. The above strategic principles may be conceptualised as a four-step sequence, involving (i) identification and quantification of hazards; (ii) design and codification of longitudinally integrated ("holistic") technological processes and procedures to eliminate, or control growth and metabolism of, pathogenic and toxinogenic organisms; (iii) elaboration of microbiological analytical standard operating procedures, permitting validation of "due diligence" or responsible care, i.e. adherence to adopted intervention strategies. This should be supported by empirically assessed reference ranges, particularly for marker organisms, while the term "zero tolerance" is refined throughout to tolerable safety limit; (iv) when called for, the need to address concerns arising from lay perceptions of risk which may lack scientific foundation. In relation to infectious and toxic hazards in the practical context the following general models for quantitative holistic risk assessment are presented: (i) the first order, basic lethality model; (ii) a second approximation taking into account the amount of food ingested in a given period of time; (iii) a further adjustment accounting for changes in colonization levels during storage and distribution of food commodities and the effects of these on proliferation of pathogens and toxin production by bacteria and moulds. Guidelines are provided to address: (i) unsubstantiated consumer concern over the wholesomeness of foods processed by an innovative procedure; and (ii) reluctance of small food businesses to adopt novel strategies in food safety. Progress here calls for close cooperation with behavioural scientists to ensure that investment in developing measures to contain risk deliver real benefit.


Assuntos
Qualidade de Produtos para o Consumidor , Microbiologia de Alimentos , Medição de Risco , Defesa do Consumidor , Contaminação de Alimentos
18.
J Clin Gastroenterol ; 27 Suppl 1: S53-63, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9872499

RESUMO

We tested the hypothesis that rapidly developing gastric cytoprotection produced by topical application of exogenous compounds is a result of increased gastric mucosal fluid secretion. Ex vivo gastric chambers were prepared in rats which were subsequently exposed topically to one of the prostaglandin (PG) E1 analogues misoprostol or rioprostil, PGE2, nicotine, N-ethylmaleimide (NEM), 0.25 M HCl, or to their respective vehicles. All agents were added to empty chambers to avoid complications resulting from dilution by gastric contents. Effects of these agents on intraluminal volume changes, blood flow, juxtamucosal pH, histology, and on the mucosal damage resulting from necrotizing agents were studied. All six agents were cytoprotective and each increased net secretion of fluid by the chambered mucosae. Gastric blood flow was not significantly increased by NEM, by 0.25 M HCl, or by nicotine compared to controls, and the juxtamucosal pH was not significantly increased by any of the three agents for which this was studied. Vacuole formation in surface epithelial cells and subepithelial edema were seen after exposure to some agents, but none of the agents led to formation of a thick barrier of exfoliated cells and mucus. Ablation of primary afferent nerves with capsaicin abolished both protection by 0.25 M HCl and the net increase in fluid secretion by the mucosae. Capsaicin ablation did not alter either the protection afforded by NEM or the increase in volume of secretion. We conclude that increased mucosal fluid secretion is the common factor present with all six cytoprotective agents and hence may be the predominant mechanism of cytoprotection against topically applied necrotizing agents.


Assuntos
Antiulcerosos/farmacologia , Citoproteção , Dinoprostona/farmacologia , Etilmaleimida/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Ácido Clorídrico/farmacologia , Nicotina/farmacologia , Animais , Capsaicina , Citotoxinas , Feminino , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Misoprostol/farmacologia , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/efeitos dos fármacos , Rioprostila/farmacologia
19.
Can J Gastroenterol ; 11 Suppl B: 28B-36B, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9347175

RESUMO

Pre-epithelial defences include the coordinated actions of the lower esophageal sphincter and the esophageal muscles, which minimize reflux of gastric contents and promote clearance of refluxed material. The esophageal epithelium also possesses innate resistance to luminal damaging agents and may be protected luminally by a mucus or 'mucus bicarbonate' barrier and possibly a layer of hydrophobic surfactants. These components are derived from submucosal glands located in the submucosal connective tissue and from salivary secretions that may bind to the esophageal surface. Epithelial defences include the glycocalyx, permeability properties of the epithelial cell plasma membrane, junctional barriers to proton permeation through the paracellular pathway and ion transport processes for regulation of intracellular pH. Subepithelial defences involve mainly regulation of blood supply via responses of nerves, mast cells and blood vessels to influxing protons. Although the epithelium can withstand prolonged exposure to physiologically relevant concentrations of acid, the presence of pepsin or bile salts may overcome the permeability barrier, which probably resides in the superficial layers of epithelial cells. Focal destruction of these cells allows access of luminal acid and other aggressive agents to the vulnerable basolateral cell membranes and to the submucosa. The result is lesion production, although an efflux of alkaline plasma may protect the underlying submucosa and allow healing. Salivary-derived epidermal growth factor (EGF) is present in the luminal fluid, and lesion development may also provide access of EGF to receptors within the epithelium and in the underlying vasculature. Accelerated cell proliferation would then contribute to healing. Inflammation and healing should also be viewed as defensive responses, as can the development of Barrett's esophagus, in which the stratified squamous epithelium is replaced by a potentially acid-resistant columnar epithelium. Chronic inflammation and esophagitis only result when this multilayered set of defences is overcome. The challenge for research is to identify those components of the defensive repertoire that are defective in individuals who suffer from chronic esophagitis.


Assuntos
Esofagite Péptica/fisiopatologia , Animais , Esofagite Péptica/metabolismo , Esôfago/metabolismo , Esôfago/fisiopatologia , Humanos
20.
Gut ; 41(3): 381-9, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9378396

RESUMO

BACKGROUND: Colonic motor function has not been studied in the ambulatory setting over a prolonged period in the unprepared state. Furthermore, the disturbance of this function in patients with faecal incontinence is unknown. AIM: To study colonic function over two to three days in the ambulatory, unprepared state in health and in patients with idiopathic faecal incontinence. METHODS: Six healthy women and six women with faecal incontinence and a structurally intact anal sphincter ingested a dual radioisotope meal, and had a six sensor, solid state manometric probe colonoscopically inserted into the left colon. Scanning was performed until radioisotope left the gut and pressure was recorded for a median of 44 hours. RESULTS: Three of six patients showed abnormal gastric emptying. Patients showed no disturbance of colonic radioisotope transit. Controls had a median of 12, whereas patients had a median of 16, high amplitude propagated waves per 24 hours. In three patients urge incontinence was associated with high amplitude (up to 500 cm water) propagated waves which often reached the rectum. These high pressure waves were identical to those occurring in healthy subjects, the only difference being the lack of adequate sphincter response. Passive incontinence was not associated with colonic motor activity. Defaecation in all subjects was associated with identical propagated waves, and distal movement of 13% (median) of right colonic content and excretion of 32% from the left colon and rectum. The urge to defaecate was associated with either propagated waves (45%) or non-propagated contractions (55%). Rectal motor complexes were recorded in both groups of subjects, but similar rhythmic activity was also recorded in the sigmoid and descending colon. CONCLUSIONS: Normal colonic function consists of frequent high pressure propagated waves. Rhythmic activity occurs both proximal to and in the rectum. Defaecation is characterised by high pressure propagated waves associated with coordinated anal sphincter relaxation. Patients with faecal incontinence may have a widespread disturbance of gut function. Urge incontinence, an urge to defaecate, and defaecation can all be associated with identical high amplitude propagated pressure waves.


Assuntos
Colo/fisiopatologia , Incontinência Fecal/fisiopatologia , Trânsito Gastrointestinal , Monitorização Ambulatorial , Idoso , Colo/fisiologia , Defecação/fisiologia , Feminino , Motilidade Gastrointestinal , Humanos , Radioisótopos de Índio , Manometria , Pessoa de Meia-Idade , Reto/fisiologia , Reto/fisiopatologia
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