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1.
Br J Anaesth ; 120(2): 353-360, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29406183

RESUMO

BACKGROUND: Significant cardiorespiratory events are frequent in patients undergoing gastrointestinal endoscopy. Central to the occurrence of respiratory events is an unsecured airway. This study sought to determine the efficacy of a new laryngeal mask airway, the LMA®GastroTM Airway (Teleflex Medical, Athlone, Ireland), in patients undergoing upper gastrointestinal endoscopy. New design features include a dedicated channel for oesophageal intubation and separate channel with terminal cuff for lung ventilation. METHODS: In a prospective, open label, observational study, 292 ASA physical status classification 1 and 2 patients at low risk of pulmonary aspiration undergoing upper gastrointestinal endoscopy received i.v. propofol anaesthesia and standardized insertion of the LMA®GastroTM Airway. Endoscopy outcomes included insertion success, first attempt success, and ease of endoscope insertion. LMA®GastroTM Airway outcomes included insertion success, first attempt success, ease of insertion, lowest oxygen saturation, airway compromise, laryngospasm, bloodstained device, and sore throat. RESULTS: Per protocol analysis (n=290), the endoscopy success rate amongst the cohort with successful LMA®GastroTM Airway insertion was 99% [95% confidence interval (CI): 98, 100]. LMA®GastroTM Airway insertion success rate (n=292) was 99% (95% CI: 98, 100). For endoscopy and LMA®GastroTM Airway insertion success, the lower limit of the 95% CIs was at least 98%, indicating LMA®GastroTM Airway efficacy. Median (inter-quartile range) lowest intraoperative oxygen saturation was 98% (98, 99). Only one serious adverse event occurred (re-admission for sore throat and inability to tolerate fluids) and was reported to the Tasmanian Health and Medical Human Research Ethics Committee. CONCLUSIONS: The LMA®GastroTM Airway appears effective for clinical use in upper gastrointestinal endoscopy. CLINICAL TRIAL REGISTRATION: ACTRN12616001464459.


Assuntos
Endoscopia Gastrointestinal/métodos , Máscaras Laríngeas , Adulto , Idoso , Idoso de 80 Anos ou mais , Manuseio das Vias Aéreas , Anestesiologia/educação , Anestésicos Intravenosos , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Humanos , Máscaras Laríngeas/efeitos adversos , Laringismo/epidemiologia , Laringismo/etiologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Faringite/epidemiologia , Faringite/etiologia , Propofol , Estudos Prospectivos , Adulto Jovem
2.
Hum Mol Genet ; 22(11): 2129-40, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23396536

RESUMO

Parkinson's disease (PD) is associated with loss of dopaminergic signalling, and affects not just movement, but also vision. As both mammalian and fly visual systems contain dopaminergic neurons, we investigated the effect of LRRK2 mutations (the most common cause of inherited PD) on Drosophila electroretinograms (ERGs). We reveal progressive loss of photoreceptor function in flies expressing LRRK2-G2019S in dopaminergic neurons. The photoreceptors showed elevated autophagy, apoptosis and mitochondrial disorganization. Head sections confirmed extensive neurodegeneration throughout the visual system, including regions not directly innervated by dopaminergic neurons. Other PD-related mutations did not affect photoreceptor function, and no loss of vision was seen with kinase-dead transgenics. Manipulations of the level of Drosophila dLRRK suggest G2019S is acting as a gain-of-function, rather than dominant negative mutation. Increasing activity of the visual system, or of just the dopaminergic neurons, accelerated the G2019S-induced deterioration of vision. The fly visual system provides an excellent, tractable model of a non-autonomous deficit reminiscent of that seen in PD, and suggests that increased energy demand may contribute to the mechanism by which LRRK2-G2019S causes neurodegeneration.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Proteínas de Drosophila/genética , Expressão Gênica , Doença de Parkinson/genética , Doença de Parkinson/patologia , Proteínas Serina-Treonina Quinases/genética , Degeneração Retiniana/genética , Animais , Apoptose/genética , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Eletrorretinografia , Feminino , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Mutação , Células Fotorreceptoras/metabolismo , Células Fotorreceptoras/patologia , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia
3.
Hum Mol Genet ; 21(8): 1760-9, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22215442

RESUMO

Parkinson's disease (PD) is characterized by movement disorders, including bradykinesia. Analysis of inherited, juvenile PD, identified several genes linked via a common pathway to mitochondrial dysfunction. In this study, we demonstrate that the larva of the Drosophila parkin mutant faithfully models the locomotory and metabolic defects of PD and is an excellent system for investigating their inter-relationship. parkin larvae displayed a marked bradykinesia that was caused by a reduction in both the frequency of peristalsis and speed of muscle contractions. Rescue experiments confirmed that this phenotype was due to a defect in the nervous system and not in the muscle. Furthermore, recordings of motoneuron activity in parkin larvae revealed reduced bursting and a striking reduction in evoked and miniature excitatory junction potentials, suggesting a neuronal deficit. This was supported by our observations in parkin larvae that the resting potential was depolarized, oxygen consumption and ATP concentration were drastically reduced while lactate was increased. These findings suggest that neuronal mitochondrial respiration is severely compromised and there is a compensatory switch to glycolysis for energy production. parkin mutants also possessed overgrown neuromuscular synapses, indicative of oxidative stress, which could be rescued by overexpression of parkin or scavengers of reactive oxygen species (ROS). Surprisingly, scavengers of ROS did not rescue the resting membrane potential and locomotory phenotypes. We therefore propose that mitochondrial dysfunction in parkin mutants induces Parkinsonian bradykinesia via a neuronal energy deficit and resulting synaptic failure, rather than as a consequence of downstream oxidative stress.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiologia , Drosophila/fisiologia , Metabolismo Energético , Neurônios/fisiologia , Estresse Oxidativo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Catalase/metabolismo , Drosophila/genética , Drosophila/metabolismo , Glicólise , Larva/fisiologia , Locomoção , Potenciais da Membrana , Mitocôndrias/metabolismo , Contração Muscular , Neurônios/metabolismo , Consumo de Oxigênio , Terminações Pré-Sinápticas/fisiologia , Terminações Pré-Sinápticas/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Potenciais Sinápticos
4.
Oecologia ; 175(2): 493-500, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24619199

RESUMO

The environment mothers are exposed to has resonating effects on offspring performance. In iteroparous species, maternal exposure to stressors generally results in offspring ill-equipped for survival. Still, opportunities for future fecundity can offset low quality offspring. Little is known, however, as to how intergenerational effects of stress manifest in semelparous species with only a single breeding episode. Such mothers would suffer a total loss of fitness if offspring cannot survive past multiple life stages. We evaluated whether chronic exposure of female sockeye salmon (Oncorhynchus nerka) to a chase stressor impaired offspring performance traits. Egg size and early offspring survival were not influenced by maternal exposure to the repeated acute stressor. Later in development, fry reared from stressed mothers swam for shorter periods of time but possessed a superior capacity to re-initiate bouts of burst swimming. In contrast to iteroparous species, the mechanisms driving the observed effects do not appear to be related to cortisol, as egg hormone concentrations did not vary between stressed and undisturbed mothers. Sockeye salmon appear to possess buffering strategies that protect offspring from deleterious effects of maternal stress that would otherwise compromise progeny during highly vulnerable stages of development. Whether stressed sockeye salmon mothers endow offspring with traits that are matched or mismatched for survival in the unpredictable environment they encountered is discussed. This study highlights the importance of examining intergenerational effects among species-specific reproductive strategies, and across offspring life history to fully determine the scope of impact of maternal stress.


Assuntos
Exposição Materna , Salmão/fisiologia , Especificidade da Espécie , Estresse Fisiológico , Animais , Cruzamento , Meio Ambiente , Feminino , Estágios do Ciclo de Vida , Mães , Óvulo , Reprodução/genética , Natação
5.
J Neonatal Perinatal Med ; 16(1): 119-128, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36565070

RESUMO

OBJECTIVE: We sought to determine the clinical and histopathological factors associated with intestinal hemorrhage and its correlation with clinical outcomes in neonates with surgical necrotizing enterocolitis (NEC). METHODS: A retrospective study compared clinical and histopathology information in neonates following surgical NEC with severe hemorrhage and those with mild/moderate hemorrhagic lesions seen on resected intestine pathology. RESULTS: The infants with severe hemorrhage (Grade 3-4, 81/148, 54.7%) had significantly lower exposure to antenatal steroids (52.5 % vs 76.9 %; p = 0.004), had higher gestational age (28.5 weeks [7.14] vs. 26.58 [2.90]; p = 0.034), lost more bowel length (p = 0.045), had higher CRP levels at 2 weeks (p = 0.035), and had less intestinal failure ([30.3 % vs 52.5 %]; p = 0.014) than mild/moderate (Grade 0-2, 67/148, 45.2%) hemorrhage group. Those with severe hemorrhage had significantly higher mean inflammation score (2.67 [0.94] vs. 1.63 [0.92]; p = <0.001), higher necrosis scores (1.95 [1.28] vs. 1.49 [1.35]; p = 0.037), higher neovascularization (p = 0.01), higher fibroblasts (p = 0.023) and higher lymphocyte percentages up to 48 hours (p < 0.05) following NEC than mild/ moderate hemorrhage group.On multivariable regression, less exposure to antenatal steroids (OR 0.18 [95% CI 0.05-0.58]; p = 0.005), higher inflammation (OR 3.7 [95% CI 2.09-7.32]; p = 0.001), and lymphocyte count on the day of onset/24 hours following NEC (OR 1.06 [95% CI 1.02-1.11]; p = 0.005) were independently associated with a higher odd of severe intestinal hemorrhage. CONCLUSION: The surgical NEC infants with intestinal hemorrhage were less likely to have antenatal steroid exposure but had higher inflammation grade and lymphocyte counts following NEC onset on multivariable regression modeling.


Assuntos
Enterocolite Necrosante , Doenças Fetais , Doenças do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Recém-Nascido Prematuro , Estudos Retrospectivos , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/cirurgia , Intestinos , Hemorragia , Inflamação/complicações
6.
Opt Express ; 20(24): 26292-8, 2012 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-23187483

RESUMO

We report our experimental results for linear analog optical links that use phase or frequency modulation and optical discrimination. The discriminators are based on two architectures: a cascaded MZI FIR lattice filter and a ring assisted MZI (RAMZI) IIR filter. For both types of discriminators, we demonstrate > 6 dB improvement in the link's third-order output intercept point (OIP3) over a MZM link. We show that the links have low second-order distortion when using balanced detection. Using high optical power, we demonstrate an OIP3 of 39.2 dBm. We also demonstrate 4.3dB improvement in signal compression.


Assuntos
Amplificadores Eletrônicos , Desenho Assistido por Computador , Modelos Teóricos , Dispositivos Ópticos , Oscilometria/instrumentação , Fótons , Processamento de Sinais Assistido por Computador , Simulação por Computador , Desenho de Equipamento , Humanos
7.
R Soc Open Sci ; 8(9): 210916, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34527276

RESUMO

A new decomposition algorithm based on QR factorization is introduced for processing and comparing irregularly shaped stress and deformation datasets found in structural analysis. The algorithm improves the comparison of two-dimensional data fields from the surface of components where data is missing from the field of view due to obstructed measurement systems or component geometry that results in areas where no data is present. The technique enables the comparison of these irregularly shaped datasets without the need for interpolation or warping of the data necessary in some other decomposition techniques, for example, Chebyshev or Zernike decomposition. This ensures comparisons are only made between the available data in each dataset and thus similarity metrics are not biased by missing data. The decomposition and comparison technique has been applied during an impact experiment, a modal analysis, and a fatigue study, with the stress and displacement data obtained from finite-element analysis, digital image correlation and thermoelastic stress analysis. The results demonstrate that the technique can be used to process data from a range of sources and suggests the technique has the potential for use in a wide variety of applications.

8.
J Parkinsons Dis ; 11(4): 1805-1820, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34250948

RESUMO

BACKGROUND: Inherited mutations in the LRRK2 protein are common causes of Parkinson's disease, but the mechanisms by which increased kinase activity of mutant LRRK2 leads to pathological events remain to be determined. In vitro assays (heterologous cell culture, phospho-protein mass spectrometry) suggest that several Rab proteins might be directly phosphorylated by LRRK2-G2019S. An in vivo screen of Rab expression in dopaminergic neurons in young adult Drosophila demonstrated a strong genetic interaction between LRRK2-G2019S and Rab10. OBJECTIVE: To determine if Rab10 is necessary for LRRK2-induced pathophysiological responses in the neurons that control movement, vision, circadian activity, and memory. These four systems were chosen because they are modulated by dopaminergic neurons in both humans and flies. METHODS: LRRK2-G2019S was expressed in Drosophila dopaminergic neurons and the effects of Rab10 depletion on Proboscis Extension, retinal neurophysiology, circadian activity pattern ('sleep'), and courtship memory determined in aged flies. RESULTS: Rab10 loss-of-function rescued LRRK2-G2019S induced bradykinesia and retinal signaling deficits. Rab10 knock-down, however, did not rescue the marked sleep phenotype which results from dopaminergic LRRK2-G2019S. Courtship memory is not affected by LRRK2, but is markedly improved by Rab10 depletion. Anatomically, both LRRK2-G2019S and Rab10 are seen in the cytoplasm and at the synaptic endings of dopaminergic neurons. CONCLUSION: We conclude that, in Drosophila dopaminergic neurons, Rab10 is involved in some, but not all, LRRK2-induced behavioral deficits. Therefore, variations in Rab expression may contribute to susceptibility of different dopaminergic nuclei to neurodegeneration seen in people with Parkinson's disease.


Assuntos
Neurônios Dopaminérgicos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Proteínas rab de Ligação ao GTP , Animais , Neurônios Dopaminérgicos/metabolismo , Drosophila/metabolismo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Mutação/genética , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
9.
R Soc Open Sci ; 7(12): 200823, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33489256

RESUMO

Thermoelastic stress analysis using arrays of small, low-cost detectors has the potential to be used in structural health monitoring. However, evaluation of the collected data is challenging using traditional methods, due to the lower resolution of these sensors, and the complex loading conditions experienced. An alternative method has been developed, using image decomposition to generate feature vectors which characterize the uncalibrated map of the magnitude of the thermoelastic effect. Thermal data have been collected using a state-of-the-art photovoltaic effect detector and lower cost, lower thermal resolution microbolometer detectors, during crack propagation induced by both constant amplitude and frequency loading, and by idealized flight cycles. The Euclidean distance calculated between the feature vectors of the initial and current state can be used to indicate the presence of damage. Cracks of the order of 1 mm in length can be detected and tracked, with an increase in the rate of change of the Euclidean distance indicating the onset of critical crack propagation. The differential feature vector method therefore represents a substantial advance in technology for monitoring the initiation and propagation of cracks in structures, both in structural testing and in-service using low-cost sensors.

10.
G3 (Bethesda) ; 10(6): 1903-1914, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32321836

RESUMO

LRRK2 mutations cause Parkinson's, but the molecular link from increased kinase activity to pathological neurodegeneration remains undetermined. Previous in vitro assays indicate that LRRK2 substrates include at least 8 Rab GTPases. We have now examined this hypothesis in vivo in a functional, electroretinogram screen, expressing each Rab with/without LRRK2-G2019S in selected Drosophila dopaminergic neurons. Our screen discriminated Rab10 from Rab3. The strongest Rab/LRRK2-G2019S interaction is with Rab10; the weakest with Rab3. Rab10 is expressed in a different set of dopaminergic neurons from Rab3. Thus, anatomical and physiological patterns of Rab10 are related. We conclude that Rab10 is a valid substrate of LRRK2 in dopaminergic neurons in vivo We propose that variations in Rab expression contribute to differences in the rate of neurodegeneration recorded in different dopaminergic nuclei in Parkinson's.


Assuntos
Drosophila , Doença de Parkinson , Animais , Neurônios Dopaminérgicos/metabolismo , Drosophila/genética , Drosophila/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Mutação , Doença de Parkinson/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
11.
Stress ; 11(5): 398-410, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18609307

RESUMO

Gestational cocaine treatment results in significantly increased maternal aggression towards an intruder by postpartum day six, while acute postpartum treatment dose dependently decreases maternal aggressive (MA) behavior. Both increased and decreased aggression in the cocaine-treated dams are correlated with either decreased or increased levels of oxytocin in the amygdala, respectively. The current study was an effort to determine whether the effect of gestational cocaine on maternal aggression is transient or would continue into the postpartum period; whether an intermittent cocaine treatment regimen, which incorporates gestational and postpartum intermittent cocaine treatment, would differ from chronic daily gestational treatment; and finally, whether next generation female offspring of cocaine-treated or control dams would have altered MA behavior and oxytocin system changes attributable to either prenatal drug exposure, rearing condition or both. We now report no increase in maternal aggression following chronic gestational treatment and significantly lower levels of aggression in intermittently treated dams on postpartum day eight, with no significant effects in either group on postpartum day 12. Young adult female offspring of the cocaine-treated and control dams, who reared their own natural litters and were tested on postpartum day eight for maternal aggression, had higher levels of maternal aggression towards an intruder attributable to both prenatal cocaine exposure and rearing condition. Higher aggression in cocaine-reared next generation dams was associated with lower levels of oxytocin in the amygdala. Intergenerational effects of cocaine were apparent with respect to aggression and oxytocin system changes.


Assuntos
Agressão/efeitos dos fármacos , Cocaína/farmacologia , Comportamento Materno/efeitos dos fármacos , Período Pós-Parto , Efeitos Tardios da Exposição Pré-Natal , Animais , Química Encefálica , Cocaína/administração & dosagem , Feminino , Masculino , Ocitocina/fisiologia , Gravidez , Ratos , Ratos Sprague-Dawley
12.
Invert Neurosci ; 8(2): 63-70, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18443837

RESUMO

How do deficits in neuronal growth, aging or synaptic function affect the final, mechanical output of a single muscle twitch? We address this in vivo (indeed in situ) with a novel ergometer that records the output of a large specialised muscle, the Drosophila jump muscle. Here, we describe in detail the ergometer, its construction and use. We evaluated the ergometer by showing that adult fly jump muscle output varies little between 3 h and 7 days; but newly eclosed flies produce only 65%. In a mutant with little octopamine (Tbetah), jump muscle performance is reduced by 28%. The initial responses of synaptic growth mutants (highwire and spinster) do not differ from wild type, as expected on the homeostatic hypothesis. However, responses in highwire mutations gradually decline following repeated stimuli, suggesting physiological as well as anatomical abnormalities. We conclude that the assay is robust, sensitive and reliable with a good throughput.


Assuntos
Drosophila/fisiologia , Ergometria , Músculos/fisiologia , Mutação , Junção Neuromuscular/fisiologia , Animais , Comportamento Animal , Drosophila/genética , Ergometria/instrumentação , Ergometria/métodos , Octopamina/genética
13.
J Biomed Mater Res A ; 83(4): 1032-1038, 2007 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17584893

RESUMO

Long term success of percutaneous implants is dependent on soft tissue attachment to prevent infection and epithelial downgrowth, which leads to failure of the implant. Fibronectin coatings are known to enhance fibroblast attachment in vitro, but are subject to desorption from serum protein competition in vivo. This paper quantifies the binding of fibronectin to titanium alloy by silanization and the durability of this attachment when soaked in protein-rich fluid compared with adsorbed fibronectin. The biological activity of fibronectin bound to silanized titanium alloy was confirmed by analyzing cell area, morphology, immunolocalization of focal contacts, and metabolism of dermal fibroblasts. This was compared with both adsorbed fibronectin and uncoated titanium alloy. Silanized titanium alloy bound over twice the amount of fibronectin compared to untreated titanium alloy. On soaking in fetal calf serum there was no significant loss of fibronectin (p = 0.589) from the silanized surface but a significant 44% loss (p = 0.002) from untreated surfaces. Fibroblasts on silanized fibronectin had significantly larger cell areas and more vinculin focal contact markers when compared to untreated surfaces (p < 0.005). The results confirm the durability of silanized fibronectin from protein competition and bioactive effect on fibroblasts.


Assuntos
Adesão Celular/efeitos dos fármacos , Fibroblastos/metabolismo , Fibronectinas/química , Titânio/química , Ligas , Fibronectinas/farmacologia , Humanos , Técnicas In Vitro , Titânio/farmacologia
15.
BMC Biol ; 4: 17, 2006 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-16768790

RESUMO

BACKGROUND: The processes by which eggs develop in the insect ovary are well characterized. Despite a large number of Drosophila mutants that cannot lay eggs, the way that the egg is moved along the reproductive tract from ovary to uterus is less well understood. We remedy this with an integrative study on the reproductive tract muscles (anatomy, innervation, contractions, aminergic modulation) in female flies. RESULTS: Each ovary, consisting of 15-20 ovarioles, is surrounded by a contractile meshwork, the peritoneal sheath. Individual ovarioles are contained within a contractile epithelial sheath. Both sheaths contain striated muscle fibres. The oviduct and uterine walls contain a circular striated muscle layer. No longitudinal muscle fibres are seen. Neurons that innervate the peritoneal sheath and lateral oviduct have many varicosities and terminate in swellings just outside the muscles of the peritoneal sheath. They all express tyrosine decarboxylase (required for tyramine and octopamine synthesis) and Drosophila vesicular monoamine transporter (DVMAT). No fibres innervate the ovarioles. The common oviduct and uterus are innervated by two classes of neurons, one with similar morphology to those of the peritoneal sheath and another with repeated branches and axon endings similar to type I neuromuscular junctions. In isolated genital tracts from 3- and 7-day old flies, each ovariole contracts irregularly (12.5 +/- 6.4 contractions/minute; mean +/- 95% confidence interval). Peritoneal sheath contractions (5.7 +/- 1.6 contractions/minute) move over the ovary, from tip to base or vice versa, propagating down the oviduct. Rhythmical spermathecal rotations (1.5 +/- 0.29 contractions/minute) also occur. Each genital tract organ exhibits its own endogenous myogenic rhythm. The amplitude of contractions of the peritoneal sheath increase in octopamine (100 nM, 81% P < 0.02) but 1 microM tyramine has no effect. Neither affects the frequency of peritoneal sheath contractions. CONCLUSION: The muscle fibres of the reproductive tract are circular and have complex bursting myogenic rhythms under octopaminergic neuromodulation. We propose a new model of tissue-specific actions of octopamine, in which strengthening of peritoneal sheath contractions, coupled with relaxation of the oviduct, eases ovulation. This model accounts for reduced ovulation in flies with mutations in the octopaminergic system.


Assuntos
Drosophila/fisiologia , Junção Neuromuscular/anatomia & histologia , Octopamina/fisiologia , Oviposição/fisiologia , Tiramina/fisiologia , Animais , Drosophila/anatomia & histologia , Feminino , Contração Muscular , Músculos/anatomia & histologia , Músculos/inervação , Junção Neuromuscular/fisiologia , Ovário/anatomia & histologia , Ovário/inervação
16.
NPJ Parkinsons Dis ; 3: 34, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29214211

RESUMO

In a number of Drosophila models of genetic Parkinson's disease (PD) flies climb more slowly than wild-type controls. However, this assay does not distinguish effects of PD-related genes on gravity sensation, "arousal", central pattern generation of leg movements, or muscle. To address this problem, we have developed an assay for the fly proboscis extension response (PER). This is attractive because the PER has a simple, well-identified reflex neural circuit, in which sucrose sensing neurons activate a pair of "command interneurons", and thence motoneurons whose activity contracts the proboscis muscle. This circuit is modulated by a single dopaminergic neuron (TH-VUM). We find that expressing either the G2019S or I2020T (but not R1441C, or kinase dead) forms of human LRRK2 in dopaminergic neurons reduces the percentage of flies that initially respond to sucrose stimulation. This is rescued fully by feeding l-DOPA and partially by feeding kinase inhibitors, targeted to LRRK2 (LRRK2-IN-1 and BMPPB-32). High-speed video shows that G2019S expression in dopaminergic neurons slows the speed of proboscis extension, makes its duration more variable, and increases the tremor. Testing subsets of dopaminergic neurons suggests that the single TH-VUM neuron is likely most important in this phenotype. We conclude the Drosophila PER provides an excellent model of LRRK2 motor deficits showing bradykinesia, akinesia, hypokinesia, and increased tremor, with the possibility to localize changes in neural signaling.

17.
Prosthet Orthot Int ; 30(3): 279-85, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17162518

RESUMO

Stump ulcers are common problems in amputees. Temporary discontinuation of prosthetic limb use is frequently employed to facilitate healing. Inevitably, this limits activity and may, for instance, prevent an amputee from going to work. A survey of clinical practice was carried out based on the premise that controlled continued prosthetic limb use in patients with stump ulcers will not adversely affect the ulcer nor prevent healing. The survey would also form a basis for developing future guidelines in the management of stump ulcers. All consecutive patients attending the Chapel Allerton Hospital prosthetic clinic between January 2003 and May 2004 with stump ulcers were recruited into the study. Primary outcome measures were changes in the surface area of the ulcers and in clinical photographs taken on 2 occasions 6 weeks apart. Some 102 patients with a mean age 60 years (range 18 - 88 years) were recruited. Eight patients who were established prosthetic limb users did not complete the study and were excluded from the analysis. Of the patients 52 were newly referred patients with delayed surgical wound healing while 42 were established prosthetic limb users for at least 1 year. Continued prosthetic limb was associated with a significant reduction in ulcer size (p < 0.05). Mean sizes of the ulcers at first and second observations were 3.30 cm2 (range 0.06 - 81) and 0.70 cm2 (range 0.00 - 13.00) respectively. The ulcers improved in 83 cases while two were unchanged. Deterioration was observed in nine cases. The current clinical practice is to allow most of the patients to commence or continue prosthetic limb wearing despite the presence of stump ulceration. This observational study found that, despite prosthetic use, 60 (64%) cases healed completely within the six-week study period and 23 (25%) ulcers reduced in size. The ulcers were unchanged in 2% of the cases. Deterioration was observed in nine (9%) cases. This survey suggests that the current practice of allowing patients to use their prostheses is safe. A clinical trial is now needed to establish whether this practice alters healing rate or has any other disadvantages for new or established amputees.


Assuntos
Cotos de Amputação/fisiopatologia , Amputados/reabilitação , Membros Artificiais/efeitos adversos , Úlcera por Pressão/etiologia , Cicatrização/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cotos de Amputação/patologia , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera por Pressão/fisiopatologia , Ajuste de Prótese , Estresse Mecânico , Fatores de Tempo , Resultado do Tratamento
18.
Pharmacol Biochem Behav ; 81(4): 769-85, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15996723

RESUMO

Studies using dopaminergic and serotonergic agonists or antagonists implicate involvement of these systems in various aspects of early maternal behavior and postpartum aggression towards an intruder in rats, both of which are associated with the presence of oxytocin in specific brain regions. It is unclear however, if or how long-term uptake inhibition of either neurotransmitter system alone or in combination, affects oxytocin system dynamics or maternal behavior/aggression. Pregnant women frequently take drugs (antidepressants, cocaine) that induce long-term reuptake inhibition of dopamine and/or serotonin, thus it is important to understand these effects on behavior and biochemistry. Rat dams were treated throughout gestation with amfonelic acid, fluoxetine, or a combination of both, to investigate effects of reuptake inhibition of dopamine and serotonin systems respectively, on maternal behavior, aggression and oxytocin. The more appetitive aspects of maternal behavior (nesting, licking, touching) and activity were increased by the low dose of amfonelic acid, high dose of fluoxetine, or the high dose combination more than other treatments. Aggression was decreased by amfonelic acid and somewhat increased by fluoxetine. Dopamine uptake inhibition appears to have a strong effect on hippocampal oxytocin levels, while receptor dynamics may be more strongly affected by serotonin uptake inhibition.


Assuntos
Agressão/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Comportamento Materno/efeitos dos fármacos , Ocitocina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Fluoxetina/farmacologia , Masculino , Ácido Nalidíxico/análogos & derivados , Naftiridinas/farmacologia , Período Pós-Parto , Gravidez , Ratos , Ratos Sprague-Dawley
19.
Clin Infect Dis ; 33(11): 1834-41, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11692294

RESUMO

Leptospirosis is frequently misdiagnosed as a result of its protean and nonspecific presentation. Leptospirosis, a zoonosis with global distribution, commonly occurs in tropical and subtropical regions; most reported cases in the United States occur in Hawaii. All laboratory-confirmed leptospirosis cases in the State of Hawaii from 1974 through 1998 (n=353) were clinically evaluated. The most common presentation involved nonspecific signs or symptoms, including fever, myalgia, and headache. Jaundice occurred in 39% of cases; conjunctival suffusion was described in 28% of these cases. Initiation of antibiotics before the seventh day of symptoms was associated with a significantly shortened duration of illness. Because early recognition and initiation of antibiotic therapy are important, clinicians should familiarize themselves with the clinical presentation of leptospirosis, and when evaluating a patient with a febrile illness, they should obtain exposure and travel histories and entertain the possibility of leptospirosis in the differential diagnosis.


Assuntos
Leptospirose/diagnóstico , Leptospirose/tratamento farmacológico , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Feminino , Havaí , Humanos , Lactente , Leptospira/isolamento & purificação , Leptospirose/microbiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
FEBS Lett ; 481(2): 189-92, 2000 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10996321

RESUMO

Diacylglycerol acyltransferase has a universal role in catalyzing the acyl-CoA-dependent formation of triacylglycerol in microorganisms, animals and plants. Acylation stimulating protein, from human blood, is known to enhance diacylglycerol acyltransferase activity and triacylglycerol biosynthesis in human adipocytes. In the current study, acylation stimulating protein was also shown to enhance diacylglycerol acyltransferase activity in microsomes from cell suspension cultures of oilseed rape. Enzyme stimulation occurred over the pH range of 6-9 but the degree of stimulation decreased with increasing ionic strength at pH 7.4. Varying acyl-CoA concentration did not affect the degree of stimulation. Membranes from triacylglycerol producing cells in plants and humans may have similar binding sites for acylation stimulating protein which have been preserved during molecular evolution. The results suggest that human acylation stimulating protein may be useful in modifying lipid biosynthesis in plants.


Assuntos
Aciltransferases/metabolismo , Proteínas Sanguíneas/farmacologia , Brassica/citologia , Complemento C3a/análogos & derivados , Microssomos/efeitos dos fármacos , Triglicerídeos/biossíntese , Acil Coenzima A/metabolismo , Acil Coenzima A/farmacologia , Brassica/efeitos dos fármacos , Brassica/enzimologia , Catálise/efeitos dos fármacos , Técnicas de Cultura de Células/métodos , Células Cultivadas , Diacilglicerol O-Aciltransferase , Relação Dose-Resposta a Droga , Evolução Molecular , Humanos , Concentração de Íons de Hidrogênio , Cinética , Microssomos/enzimologia , Microssomos/metabolismo , Concentração Osmolar , Cloreto de Potássio/farmacologia
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