RESUMO
Enterococcal spondylitis (ES) is a disease of commercial broiler chickens, with a worldwide distribution. Symmetrical hind limb paralysis typical of ES results from infection of the free thoracic vertebra (FTV) by pathogenic strains of Enterococcus cecorum . To determine the pathogenesis of ES, birds with natural and experimental ES were studied over time. In natural disease, case birds (n = 150) from an affected farm and control birds (n = 100) from an unaffected farm were evaluated at weeks 1-6. In control birds, intestinal colonization by E. cecorum began at week 3. In case birds, E. cecorum was detected in intestine and spleen at week 1, followed by infection of the FTV beginning at week 3. E. cecorum isolates recovered from intestine, spleen, and FTV of case birds had matching genotypes, confirming that intestinal colonization with pathogenic strains precedes bacteremia and infection of the FTV. Clinical intestinal disease was not required for E. cecorum bacteremia. In 1- to 3-week-old case birds, pathogenic E. cecorum was observed within osteochondrosis dissecans (OCD) lesions in the FTV. To determine whether OCD of the FTV was a risk factor for ES, 214 birds were orally infected with E. cecorum, and the FTV was evaluated histologically at weeks 1-7. Birds without cartilage clefts of OCD in the FTV did not develop ES; while birds with OCD scores ≥3 were susceptible to lesion development. These findings suggest that intestinal colonization, bacteremia, and OCD of the FTV in early life are crucial to the pathogenesis of ES.
Assuntos
Enterococcus , Infecções por Bactérias Gram-Positivas/veterinária , Doenças das Aves Domésticas/microbiologia , Espondilite/veterinária , Animais , Galinhas/microbiologia , Enterococcus/genética , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/microbiologia , Intestinos/microbiologia , Paralisia/etiologia , Paralisia/microbiologia , Paralisia/veterinária , Filogenia , Doenças das Aves Domésticas/etiologia , Doenças das Aves Domésticas/mortalidade , Baço/microbiologia , Espondilite/microbiologia , Vértebras Torácicas/microbiologiaRESUMO
OBJECTIVE: Evaluate physiological and behavioral pain responses of premature infants following instillation of mydriatic eyedrops for retinopathy of prematurity (ROP) examinations. While burning and stinging occurs in older patients, the infant pain response is not well characterized. STUDY DESIGN: Vital sign and video monitor recorded infant responses before, during and after mydriatic (tropicamide 1%, phenylephrine 2.5%) administration upon first ROP exam. Two masked observers graded Premature Infant Pain Profile (PIPP) scores immediately before and following eyedrop administration. Scores <7 indicate no/minimal pain, 7 to 12 slight/moderate, >12 severe. RESULT: Twenty infants had mean premydriatic PIPP score 3.6 (s.d. 1.6), mean postmydriatic score 5.7 (s.d. 3.4), mean change 2.1 (s.d. 3.4) (P=0.01). One (5%) had premydriatic PIPP score ≥7, seven (35%) post scores ≥7 (P=0.07) with one >12. CONCLUSION: Mydriatic drops cause a clinically significant pain response in one-third of infants. Non-pharmacological supportive measures are recommended for all infants until predictive factors are defined.
Assuntos
Midriáticos/efeitos adversos , Medição da Dor/métodos , Fenilefrina/administração & dosagem , Fenilefrina/efeitos adversos , Retinopatia da Prematuridade/diagnóstico , Tropicamida/efeitos adversos , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Soluções Oftálmicas , Philadelphia , Estudos Prospectivos , Retinopatia da Prematuridade/fisiopatologiaRESUMO
OBJECTIVE: The purpose of this pilot trial was to determine whether rates of contact dermatitis following cutaneous antisepsis for central catheter placement were similar among neonates treated with chlorhexidine gluconate and povidone-iodine. Chlorhexidine gluconate absorption was also evaluated. STUDY DESIGN: Infants weighing > or =1500 g and > or =7 days of age were randomized to a 10% povidone-iodine or 2% chlorhexidine gluconate site scrub before catheter placement. Primary outcomes evaluated included dermatitis, catheter colonization and chlorhexidine gluconate absorption. RESULT: A total of 48 neonates were enrolled. Colonization rates were similar among treatment groups (P<0.6). Dermatitis did not occur at chlorhexidine gluconate (central catheters, n=24; peripheral catheters, n=29) sites. Seven neonates had measurable chlorhexidine gluconate concentrations (range 13 to 100 ng ml(-1)) during catheterization. CONCLUSION: In this small trial chlorhexidine gluconate antisepsis was tolerated by study neonates. Chlorhexidine gluconate was cutaneously absorbed. Larger trials are needed to determine efficacy and tolerance of chlorhexidine gluconate in neonates.
Assuntos
Anti-Infecciosos Locais/efeitos adversos , Cateterismo Venoso Central/efeitos adversos , Clorexidina/análogos & derivados , Dermatite de Contato/etiologia , Povidona-Iodo/efeitos adversos , Anti-Infecciosos Locais/farmacocinética , Cateteres de Demora/microbiologia , Clorexidina/efeitos adversos , Clorexidina/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Projetos Piloto , Absorção CutâneaRESUMO
OBJECTIVE: To report ophthalmic findings in the Screech owl (Megascops asio). Sample population Twenty-three, apparently healthy adult captive Screech owls in Maryland. PROCEDURES: OU of all owls underwent complete ophthalmic examination. One randomly assigned eye of each bird was measured by phenol red thread tear test (PRT), and the other eye by Schirmer tear test (STT). TonoVet rebound tonometry and TonoPen-XL applanation tonometry were performed in each eye to measure IOP. Conjunctival swabs were cultured from one eye of 10 birds, corneal diameter was measured in OU of eight birds, and streak retinoscopy was performed on OU of seven birds. Ten birds were anesthetized, and A-scan ultrasonography using a 15-MHz probe was performed to obtain axial intraocular measurements. RESULTS: Ophthalmic abnormalities were noted in 24/46 (52%) of eyes. Median STT result was < or = 2 mm/min, ranging < or = 2-6 mm/min, and mean +/- SD PRT was 15 +/- 4.3 mm/15 s. Mean +/- SD IOP were 9 +/- 1.8 mmHg TonoVet-P, 14 +/- 2.4 mmHg TonoVet-D, and 11 +/- 1.9 mmHg TonoPen-XL. Coagulase negative staphylococcal organisms were cultured from all conjunctival swabs. Mean +/- SD corneal dimensions were 14.5 +/- 0.5 mm vertically and 15.25 +/- 0.5 mm horizontally. All refracted birds were within one diopter of emmetropia. Mean +/- SD axial distance from the cornea to the anterior lens capsule was 4.03 +/- 0.3 mm, from cornea to the posterior lens capsule was 10.8 +/- 0.5 mm, and from cornea to sclera was 20.33 +/- 0.6 mm. CONCLUSIONS: This study reports ophthalmic examination findings in Screech owls, and provide means and ranges for various ocular measurements. This is the first report of rebound tonometry and PRT in owls.
Assuntos
Anormalidades do Olho/veterinária , Oftalmopatias/veterinária , Fenômenos Fisiológicos Oculares , Estrigiformes/fisiologia , Animais , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/patologia , Oftalmopatias/diagnóstico , Oftalmopatias/patologia , Feminino , Pressão Intraocular , Masculino , Valores de Referência , Lágrimas/metabolismo , Tonometria Ocular/métodos , Tonometria Ocular/veterináriaRESUMO
Biventricular hypertrophy was noted at 24 weeks' gestation in a fetus with isolated cytochrome-c oxidase (COX) deficiency. Shock, caused by hypertrophic cardiomyopathy and severe pulmonary hypertension, led to the patient's death on day 6. His phenotype defines a new lethal variant of COX deficiency characterized by prenatal-onset cardiopulmonary pathophysiology.
Assuntos
Cardiomiopatias/congênito , Cardiomiopatias/genética , Deficiência de Citocromo-c Oxidase/genética , Hipertensão Pulmonar/congênito , Hipertensão Pulmonar/genética , Acidose/genética , Adulto , Cardiomegalia/congênito , Cardiomegalia/genética , Citrato (si)-Sintase/deficiência , Citrato (si)-Sintase/genética , Ecocardiografia , Transporte de Elétrons/genética , Feminino , Doenças Fetais/genética , Humanos , Recém-Nascido , Lactatos/metabolismo , Masculino , Músculo Esquelético/patologia , Fenótipo , Gravidez , Ultrassonografia Pré-NatalRESUMO
The nicotinic receptor drug candidate, 3-(2,4-dimethoxybenzylidene)-anabaseine (also known as GTS-21; DMXBA), its hydroxy metabolites, and some related analogs were evaluated with the two-electrode voltage-clamp technique in mouse 5-hydroxytryptamine (5-HT)(3A) receptors expressed in Xenopus oocytes. Although DMXBA lacked partial agonist activity, its hydroxy-benzylidene metabolites and related analogs were partial agonists, displaying the following rank order of potency (EC(50)) and apparent efficacy: 5-HT, 0.9 +/- 0.06 microM (100% efficacy) > 3-(2-hydroxy,4-methoxybenzylidene)-anabaseine (2-OH-MBA), 2.0 +/- 0.3 microM (63% efficacy) > 3-(2,4-dihydroxybenzylidene)-anabaseine, 2.6 +/- 0.3 microM (63% efficacy) > 3-(2-methoxy,4-hydroxybenzylidene)-anabaseine, 17.2 +/- 1.0 microM (30% efficacy). To examine the influence of a benzylidene ring hydroxy substituent, the agonist actions of the three possible monohydroxy isomers were examined. The rank order of potency, based on EC(50) determinations, and apparent efficacy was: 3-(2-hydroxybenzylidene)-anabaseine, 20.3 +/- 2.6 microM (63% efficacy) > 3-(4-hydroxybenzylidene)-anabaseine, 32.3 +/- 5.9 microM (14% efficacy) > 3-(3-hydroxybenzylidene)-anabaseine (3-OH-BA) (no agonist activity). Both DMXBA and 3-OH-BA antagonized 5-HT-mediated currents, with IC(50) values of 15.7 +/- 0.9 and 27.5 +/- 4.7 microM, respectively. DMXBA demonstrated both competitive and noncompetitive forms of antagonism over the range of concentrations tested. These results suggest that a hydroxy substituent at the 2' position of the benzene ring is necessary and sufficient for partial agonist activity; substitution at the 4' position with a hydroxy or methoxy group further enhances agonist potency. Because 2-OH-MBA is a primary metabolite of DMXBA, it may contribute to the physiological, biochemical, and behavioral effects of the parent compound when administered in vivo.
Assuntos
Anabasina/análogos & derivados , Anabasina/farmacologia , Compostos de Benzilideno/farmacologia , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Sítios de Ligação , Eletrofisiologia , Agonistas Nicotínicos/farmacologia , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Piridinas/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Receptores 5-HT3 de Serotonina , Xenopus laevisRESUMO
In utero surgery may provide benefit to a compromised fetus. The possibility of fetal surgery in a twin pregnancy extends the risk-benefit calculus beyond that of the fetus and mother to include the companion fetus and raises the issue of when, if ever, may fetus B be placed at substantial risk to benefit fetus A. Insight into the ethical dimensions of this issue is provided by the norms that govern the use of children in nontherapeutic research and the justifications used in twin-to-twin transplant cases.
Assuntos
Doenças em Gêmeos , Procedimentos Cirúrgicos Eletivos , Ética Médica , Feto/cirurgia , Feminino , Humanos , Gravidez , Gêmeos , Estados UnidosRESUMO
Despite major improvements in infant intensive care, neonatal meningitis remains a devastating disease. Survivors of bacterial meningitis are at high-risk for life-long neurological handicaps, and despite a reduction in mortality, the morbidity of neonatal meningitis has not changed substantially over the last thirty years. A substantial improvement in outcome is unlikely to result from further refinements in ICU technology or new antibiotics. However, recent advancements in our understanding of the pathogenesis of meningitis and the pathophysiology of brain injury in meningitis may provide the opportunity to interrupt the mechanisms that allow bacteria to enter the central nervous system and initiate the inflammatory response. Strategies aimed at modulating the inflammatory response must be chosen carefully, so as not to disrupt normal host responses needed for the infant to recover from the infectious episode.
Assuntos
Lesões Encefálicas/prevenção & controle , Doenças do Recém-Nascido/prevenção & controle , Meningites Bacterianas/prevenção & controle , Complicações na Gravidez , Antibacterianos/uso terapêutico , Lesões Encefálicas/etiologia , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/etiologia , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/complicações , Meningites Bacterianas/microbiologia , GravidezRESUMO
UNLABELLED: Neonates who require a central venous catheter (CVC) for prolonged vascular access experience high rates of catheter-related bloodstream infection (CRBSI). PURPOSE: A multicenter randomized clinical trial was undertaken to ascertain the efficacy of a novel chlorhexidine-impregnated dressing (Biopatch Antimicrobial Dressing) on the CVC sites of neonates for the prevention of catheter tip colonization, CRBSI, and bloodstream infection (BSI) without a source. Setting. Six level III neonatal intensive care units. Patients Studied. Neonates admitted to study units who would require a CVC for at least 48 hours. METHODS: Eligible infants were randomized before catheter placement to 1 of the 2 catheter site antisepsis regimens: 1) 10% povidone-iodine (PI) skin scrub, or 2) a 70% alcohol scrub followed by placement of a chlorhexidine-impregnated disk over the catheter insertion site. A transparent polyurethane dressing (Bioclusive Transparent Dressing) was used to cover the insertion site in both study groups. Primary study outcomes evaluated were catheter tip colonization, CRBSI, and BSI without an identified source. RESULTS: Seven hundred five neonates were enrolled in the trial, 335 randomized to receive the chlorhexidine dressing and 370 to skin disinfection with PI (controls). Neonates randomized to the antimicrobial dressing group were less likely to have colonized CVC tips than control neonates (15.0% vs 24.0%, relative risk [RR]: 0.6 95% confidence interval [CI]: 0.5-0.9). Rates of CRBSI (3.8% vs 3.2%, RR: 1.2, CI: 0.5-2.7) and BSI without a source (15.2% vs 14.3%, RR: 1.1, CI: 0.8-1.5) did not differ between the 2 groups. Localized contact dermatitis from the antimicrobial dressing, requiring crossover into the PI treatment group, occurred in 15 (15.3%) of 98 exposed neonates weighing =1000 g. No neonates in the PI group developed contact dermatitis. CONCLUSION: The novel chlorhexidine-impregnated dressing, replaced weekly, was as effective as cutaneous disinfection with 10% PI and redressing the site every 3 to 7 days for preventing CRBSI and BSI without a source in critically ill neonates requiring prolonged central venous access. The risk of local contact dermatitis under the chlorhexidine dressing limits its use in low birth weight infants who require prolonged central access during the first 2 weeks of life.
Assuntos
Infecções Bacterianas/prevenção & controle , Bandagens , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Clorexidina/administração & dosagem , Contaminação de Equipamentos/prevenção & controle , Povidona-Iodo/administração & dosagem , Administração Cutânea , Administração Tópica , Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Infecções Bacterianas/microbiologia , Cateteres de Demora/microbiologia , Clorexidina/uso terapêutico , Desinfecção/métodos , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Povidona-Iodo/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: In recent years, the increased prevalence of breastfeeding in conjunction with early discharge practices has increased the risk for marked hyperbilirubinemia in neonates. This has resulted in the potential for bilirubin brain injury in affected infants. The purpose of this study was to identify all infants >/=36 weeks' gestational age with bilirubin levels >25 mg/dL and evaluate them for early and late evidence of bilirubin brain injury. METHODS: We reviewed the charts of all infants (from 1993-1996) >/=36 weeks' gestational age who were readmitted to the hospital during the first week of life with bilirubin levels >25 mg/dL. Readmission records were reviewed for early signs of bilirubin encephalopathy. Magnetic resonance imaging (MRIs) and Brainstem auditory-evoked responses (BAERs) were reviewed for evidence of bilirubin toxicity. At follow-up, study infants had a complete neurodevelopmental examination, repeat MRIs, and behavioral hearing evaluations. RESULTS: From 1993 to 1996, we identified 6 term and near-term infants readmitted to the hospital within the first week of life with peak bilirubin values ranging from 26.4 mg/dL (451 micromol/L) to 36.9 mg/dL (631 micromol/L). Five of 6 infants had bilirubin values >30 mg/dL (513 micromol/L). All were exclusively breastfed or fed a combination of breast and bottle feedings. Five of 6 infants presented with abnormal neurologic signs. Four infants had initial MRIs, 3 of whom had increased signal intensity in the basal ganglia consistent with kernicterus. Two infants had abnormal BAERs; both also had abnormal MRIs. Five of 6 infants received exchange transfusions and all were treated with phototherapy and intravenous fluids. Follow-up examinations between 3 months and 2 years showed resolution of clinical signs in all but 1 infant. Four infants had a subsequent normal MRI and 1 had residual hearing impairment. One infant demonstrated severely abnormal developmental evaluations, as well as both an abnormal initial MRI and BAERs. Follow-up MRI showed evidence of encephalomalacia with changes not characteristic of kernicterus. CONCLUSIONS: We observed transient neurologic abnormalities in 5 of 6 infants readmitted to the hospital during the first week of life with marked hyperbilirubinemia. The abnormalities resolved following aggressive management using hydration, phototherapy, and exchange transfusion and may not correlate with long-term prognosis. Less aggressive therapy may be associated with residual neurologic abnormalities. We speculate that inadequate establishment of breastfeeding coupled with early discharge practices may play a role in the development of marked hyperbilirubinemia in these infants.
Assuntos
Aleitamento Materno , Deficiências do Desenvolvimento/etiologia , Icterícia Neonatal/complicações , Kernicterus/complicações , Desenvolvimento Infantil , Deficiências do Desenvolvimento/diagnóstico , Potenciais Evocados Auditivos do Tronco Encefálico , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Icterícia Neonatal/diagnóstico , Kernicterus/diagnóstico , Imageamento por Ressonância Magnética , Exame NeurológicoRESUMO
In mammals that use the ventilatory system as the principal means of increasing heat loss, raising body temperature causes the adoption of a specialised breathing pattern known as panting and this is mediated by the thermoregulatory system in the preoptic area of the hypothalamus. In these species an additional respiratory drive is also present at raised body temperature, since breathing can reappear at low Pa,CO2 levels, when stimulation of chemoreceptors is minimal. It is not known whether the preoptic area is also the source of this additional drive. Rats do not pant but do possess this additional respiratory drive at raised body temperatures. We have therefore tested whether the preoptic area of the hypothalamus is the source of this additional respiratory drive in rats. Urethane anaesthesia and hyperoxia were used in eleven rats to minimise behavioural and chemical drives to breathe. The presence of the additional respiratory drive was indicated if rhythmic diaphragmatic EMG activity reappeared during hypocapnia (a mean Pa,CO2 level of 21+/-2 mm Hg, n = 11), induced by mechanical ventilation. The additional respiratory drive was absent at normal body temperature (37¿C). When the temperature of the whole body was raised using an external source of radiant heat, the additional respiratory drive appeared at 40.6+/-0.5 degrees C (n = 3). In two further rats this drive was induced at normal body temperature by localised warming in the preoptic area of the intact hypothalamus. The additional respiratory drive appeared at similar temperatures to those in control rats in three rats following isolation of the hypothalamus from more rostral areas of the brain. In contrast, the additional respiratory drive failed to appear at these temperatures in three rats after isolating the hypothalamus from the caudal brainstem, by sectioning pathways medial to the medial forebrain bundle. Since the preoptic area is known to contain thermoreceptors and to receive afferents from peripheral thermoreceptors, the results show that this area is also the source of the additional respiratory drive at raised body temperature in anaesthetised rats.
Assuntos
Anestesia Intravenosa , Temperatura Corporal , Área Pré-Óptica/fisiologia , Respiração , Animais , Apneia/fisiopatologia , Pressão Sanguínea , Regulação da Temperatura Corporal , Diafragma/fisiologia , Eletromiografia , Frequência Cardíaca , Histocitoquímica , Temperatura Alta , Hipertermia Induzida , Hipocapnia/fisiopatologia , Área Pré-Óptica/patologia , Ratos , Ratos Sprague-Dawley , Uretana , Ventiladores MecânicosRESUMO
The "one-pot" synthesis of triarylamines from an aniline and two different aryl halides is described. A catalytic system composed of Pd2(dba)3/P(t-Bu)2-o-biphenyl (1) is used to prepare a variety of triarylamines in a single flask by the coupling of an aniline with an aryl bromide and aryl chloride. The synthesis of triarylamines containing a heterocyclic aryl group is also described by employing a one-flask, two-step method. These methods can be used to synthesize both discrete triarylamines and a triarylamine library.
Assuntos
Aminas/síntese química , Compostos de Anilina/química , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância MagnéticaAssuntos
Artrite Infecciosa/microbiologia , Candida albicans/isolamento & purificação , Candidíase/complicações , Articulação do Quadril/microbiologia , Articulação do Joelho/microbiologia , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Doenças em Gêmeos , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/tratamento farmacológico , Masculino , Osteomielite/microbiologia , Fatores de RiscoRESUMO
Mammals that use the ventilatory system as the principal means of increasing heat loss, i.e. that pant, show two fundamental changes in the control of breathing at raised temperatures. First, alveolar ventilation increases by more than, rather than in proportion to, the increase in CO2 production. Second, hypocapnia no longer causes apnoea. Rats do not use the ventilatory system as the principal means of increasing heat loss, so we have investigated whether rats also show these two changes at raised temperatures. Breathing was detected from diaphragmatic electromyogram (EMG) activity. Anaesthesia and hyperoxia were used to minimise behavioural and hypoxic drives to ventilation and arterial PCO2 (Pa,CO2) was controlled using mechanical ventilation. At 36.6 +/- 0.1 >C, breathing was absent as long as Pa,CO2 was held below a threshold level of 32.9 +/- 0.7 mm Hg (n = 14) under steady-state conditions. When body temperature in rats was raised above 37 >C, both fundamental changes in the control of breathing became apparent. First, at 39 >C the mean Pa,CO2 level during spontaneous breathing (39.6 +/- 5.4 mm Hg, n = 4) fell by 3.9 +/- 1.4 mm Hg (P < 0.05, Student's paired t test). Second, at 39.9 +/- 0.1 >C breathing was present when mean Pa,CO2 levels were only 18.2 +/- 1.5 mm Hg (n = 14), the lowest mean Pa,CO2 level we could achieve with mechanical ventilation. We calculate, however, that at 39.9 >C, the drive to breathe from the increased CO2 production alone would not sustain breathing below a Pa,CO2 level of 27.8 +/- 1.4 mm Hg (n = 13). In rats at raised body temperatures therefore a respiratory drive exists that is in addition to that related to the increase in CO2 production.
Assuntos
Temperatura Corporal/fisiologia , Dióxido de Carbono/metabolismo , Mecânica Respiratória/fisiologia , Animais , Apneia/fisiopatologia , Gasometria , Pressão Sanguínea/fisiologia , Diafragma/fisiologia , Eletromiografia , Frequência Cardíaca/fisiologia , Hipocapnia/sangue , Hipocapnia/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Ventiladores MecânicosRESUMO
[equation--see text] The N-arylation of indoles, including a variety of substituted ones, has been carried out using bulky, electron-rich phosphines as the supporting ligand in combination with Pd(2)(dba)(3). Using this catalyst system, the efficient coupling of indole and a variety of substituted indoles with aryl iodides, bromides, chlorides, and triflates can be achieved.
Assuntos
Indóis/química , Paládio , Brometos , Catálise , Cloretos , Desenho de Fármacos , Iodetos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Preterm infants have an increased incidence of infection, which is principally due to deficiencies in neonatal host defense mechanisms. Monocyte adherence is important in localizing cells at sites of infection and is associated with enhanced antimicrobial functions. We isolated cord blood monocytes from preterm and full-term infants to study their adhesion and immune functions, including superoxide (O2-) generation, degranulation, and cytokine secretion and their adhesion receptors. O2- production and degranulation were significantly diminished, by 28 and 37%, respectively, in adherent monocytes from preterm infants compared to full-term infants (P < 0. 05); however, these differences were not seen in freshly isolated cells. We also observed a significant decrease of 35% in tumor necrosis factor alpha secretion by lipopolysaccharide-stimulated adherent monocytes from preterm infants compared to full-term infants (P < 0.05); however, this difference was not observed in interleukin-1beta or interleukin-6 production by the monocytes. The cell surface expression of the CD11b/CD18 adhesion receptor subunits was significantly decreased (by 60 and 52%, respectively) in monocytes from preterm infants compared to full-term infants (P < 0. 01). The cascade of the immune response to infection involves monocyte upregulation and adherence via CD11b/CD18 receptors followed by cell activation and the release of cytokines and bactericidal products. We speculate that monocyte adherence factors may be important in the modulation of immune responses in preterm infants.
Assuntos
Antígenos CD11/biossíntese , Antígenos CD18/biossíntese , Recém-Nascido Prematuro/sangue , Leucócitos Mononucleares/química , Leucócitos Mononucleares/citologia , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Peso ao Nascer , Adesão Celular/fisiologia , Degranulação Celular/efeitos dos fármacos , Sangue Fetal/citologia , Idade Gestacional , Humanos , Recém-Nascido , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/farmacologiaRESUMO
Experiments were performed to measure the apneic threshold for CO2 and its fundamental properties in anesthetized rats under steady-state conditions. Breathing was detected from diaphragmatic electromyogram activity. Mechanical hyperventilation resulted in apnea once arterial PCO2 (PaCO2) had fallen far enough. Apnea was not a reflex response to lung inflation because it did not occur immediately, was not prevented by vagotomy, and was reversed by raising PaCO2 without changing mechanical hyperventilation. The apneic threshold was measured by hyperventilating rats mechanically with O2 until apnea had occurred and then raising PaCO2 at constant hyperventilation until breathing reappeared. The mean PaCO2 level of the apneic threshold in 42 rats was 32.8 +/- 0.4 Torr. The level of the threshold did not depend on the volume at which the lungs were inflated. The level of the threshold, under steady-state conditions, was the same when approached from hypocapnia as from eupnea. The level of the threshold could be raised by 9 Torr by chronic elevation of the eupneic PaCO2 level by 18 Torr.
Assuntos
Apneia/fisiopatologia , Dióxido de Carbono/fisiologia , Anestesia , Animais , Dióxido de Carbono/sangue , Eletromiografia , Masculino , Ratos , Ratos Sprague-Dawley , Mecânica Respiratória/fisiologia , VagotomiaRESUMO
In urethane-anaesthetized rats, stimulation of carotid body chemoreceptors desynchronizes the cortical electroencephalogram and increases the sensitivity of thalamic and cortical somatosensory neurones to peripheral sensory nerve stimulation. Peripheral chemoreceptors were stimulated by injecting a bolus (30 ml) or infusing 100 ml of 0.18 M NaCl solution equilibrated with 100% CO2 into an internal carotid artery, the cortical electroencephalogram and ventilation were monitored routinely. This stimulus induced hyperventilation and desynchronization of the cortical electroencephalogram. Anaesthetized rats also showed spontaneous periodic increases in ventilation rate accompanied by changes of the cortical electroencephalogram from high-voltage low frequency to low-voltage high frequency which seemed to be identical with those evoked by stimulating chemoreceptors. The activity of identified somatosensory neurons in the thalamic ventrobasal complex, layer IV of the somatosensory cortex, or the cuneate nucleus was recorded extracellularly during and following chemoreceptor activation. Neurones in the ventrobasal thalamus and somatosensory cortex showed a decrease in latency and an increase in probability of discharge to supramaximal electrical stimulation of the forepaw which was more pronounced following infusion stimulation of the carotid body than following bolus stimulation. In contrast, neurons within the cuneate nucleus showed a slight increase in latency to onset and a decrease in the probability of firing following the same stimulus. The results indicate that stimulation of the carotid body chemoreceptors leads to an enhancement of the response of somatosensory neurons to their normal physiological input.
Assuntos
Encéfalo/fisiologia , Corpo Carotídeo/fisiologia , Células Quimiorreceptoras/fisiologia , Neurônios/fisiologia , Córtex Somatossensorial/fisiologia , Tálamo/fisiologia , Anestésicos Intravenosos , Animais , Dióxido de Carbono/sangue , Dióxido de Carbono/farmacologia , Artéria Carótida Interna , Córtex Cerebral/fisiologia , Células Quimiorreceptoras/efeitos dos fármacos , Estimulação Elétrica , Eletroencefalografia/efeitos dos fármacos , Feminino , Membro Anterior , Ratos , Ratos Endogâmicos , Respiração/efeitos dos fármacos , Respiração/fisiologia , Pele/inervação , UretanaRESUMO
Immaturity of local innate defenses has been suggested as a factor involved in the pathophysiology of necrotizing enterocolitis (NEC). The mRNA of enteric human defensins 5 (HD5) and 6 (HD6), antibiotic peptides expressed in Paneth cells of the small intestine, have significantly lower levels of expression in fetal life compared with the term newborn and adult. In the current study, intracellular HD5 was demonstrated by immunohistochemistry at 24 wk of gestation, but at low levels, consistent with findings at the mRNA level. These data suggest that the low level enteric defensin expression, characteristic of normal intestinal development, may contribute to the immaturity of local defense, which predisposes the premature infant to NEC. To test if levels of defensin expression are altered in NEC, specimens from six cases of patients with NEC and five control subjects (four patients with atresia and one with meconium ileus) were analyzed to determine HD5 and HD6 mRNA levels by in situ hybridization. Compared with the control group, the level of enteric defensin expression per Paneth cell assessed by image analysis was increased 3-fold in cases of NEC (p = 0.02, analysis of variance and covariance). In addition, the number of Paneth cells was increased 2-fold in the small intestinal crypts of NEC specimens compared with those of control subjects (p < 0.01, covariance analysis). In healthy tissue, peptide levels within Paneth cells paralleled mRNA levels through development. In tissue from infants with NEC, the steady state level of intracellular peptide was not increased in conjunction with the observed rise in defensin mRNA. A straightforward interpretation of this finding is that HD5 is actively secreted in this setting and the Paneth cells maintain a constant steady state level of intracellular peptide, but the possibility of translational regulation of peptide expression is also consistent with these data. The associations between NEC and enteric defensin expression reported here offer support for future studies to address the role of these endogenous host defense factors in the pathophysiology of this disease.
Assuntos
Proteínas Sanguíneas/genética , Enterocolite Pseudomembranosa/fisiopatologia , Celulas de Paneth/metabolismo , Adulto , Análise de Variância , Atividade Bactericida do Sangue , Proteínas Sanguíneas/biossíntese , Defensinas , Enterocolite Pseudomembranosa/cirurgia , Feto , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Humanos , Hibridização In Situ , Lactente , Recém-Nascido , Intestino Delgado/crescimento & desenvolvimento , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Celulas de Paneth/patologia , RNA Mensageiro/biossíntese , Valores de Referência , Transcrição GênicaRESUMO
To gain an understanding of the prevalence, utilization patterns, and practice implications of the use of Native American healers together with the use of physicians, we conducted semistructured interviews at an urban Indian Health Service clinic in Milwaukee, Wisc, of a convenience sample of 150 patients at least 18 years old. The mean age of patients was 40 years, and the sex distribution was 68.7% women and 31.3% men. Thirty tribal affiliations were represented, the largest groups being Ojibwa (20.7%), Oneida (20.0%), Chippewa (11.3%), and Menominee (8.0%). We measured the number of patients seeing healers and gathered information on the types of healers, the ceremonies used for healing, the reasons for seeing healers, and whether patients discuss with their physicians their use of healers. We found that 38.0% of the patients see a healer, and of those who do not, 86.0% would consider seeing one in the future. Most patients report seeing a healer for spiritual reasons. The most frequently visited healers were herbalists, spiritual healers, and medicine men. Sweat lodge ceremonies, spiritual healing, and herbal remedies were the most common treatments. More than a third of the patients seeing healers received different advice from their physicians and healers. The patients rate their healer's advice higher than their physician's advice 61.4% of the time. Only 14.8% of the patients seeing healers tell their physician about their use. We conclude that physicians should be aware that their Native American patients may be using alternative forms of treatment, and they should open a respectful and culturally sensitive dialogue about this use with their patients.