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1.
Child Abuse Negl ; : 106335, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37400323

RESUMO

BACKGROUND: War and violence have a serious negative impact on the wellbeing and mental health of many children. Caregivers play an important role in mitigating or exacerbating this impact. OBJECTIVE: This study evaluates the impact of the nine session Caregiver Support Intervention on improving children's wellbeing and examines putative mediators of changes in children's psychosocial wellbeing. PARTICIPANTS AND SETTING: 240 female caregivers were randomly allocated (1:1) to the CSI or a waitlist control comparison condition. The study was implemented in Lebanon, in an area characterized by high levels of poverty and a high number of the Syrian refugees. METHODS: A parallel group Randomized Controlled Trial reporting on caregiver-reported child-level wellbeing. We used a combination of the Kid- and Kiddy-KINDL (parent version) for index children ages three to 12. Putative mediators of the CSI on children's psychosocial wellbeing included harsh parenting, caregiver psychological distress, caregiver wellbeing. Measurements were conducted at baseline, post-intervention and 3-months follow-up. RESULTS: We demonstrated a statistically significant change in caregiver reported children's psychosocial wellbeing at post-intervention (Mdiff =4.39, 95 % CI = 1.12, 7.65, p < 0.01, d = 0.28) but not at follow-up (Mdiff = -0.97, 95 % CI = -4.27, 2.32, p > 0.05). The proportion of the total effect of the CSI intervention on child psychosocial wellbeing mediated by caregiver distress, caregiver wellbeing and harsh parenting was 77 %. CONCLUSION: The CSI holds potential for down-stream short-term effect on improving children's psychosocial wellbeing, beyond the previously reported positive caregiver outcomes. This effect was not sustained three months post intervention. The study confirms caregiver wellbeing and parenting support as dual pathways mediating child psychosocial wellbeing. Prospective trial registration: ISRCTN22321773.

2.
Epidemiol Psychiatr Sci ; 30: e5, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33413736

RESUMO

AIMS: When the Interagency Standing Committee (IASC) adopted the composite term mental health and psychosocial support (MHPSS) and published its guidelines for MHPSS in emergency settings in 2007, it aimed to build consensus and strengthen coordination among relevant humanitarian actors. The term MHPSS offered an inclusive tent by welcoming the different terminologies, explanatory models and intervention methods of diverse actors across several humanitarian sectors (e.g., health, protection, education, nutrition). Since its introduction, the term has become well-established within the global humanitarian system. However, it has also been critiqued for papering over substantive differences in the intervention priorities and conceptual frameworks that inform the wide range of interventions described as MHPSS. Our aims are to clarify those conceptual frameworks, to argue for their essential complementarity and to illustrate the perils of failing to adequately consider the causal models and theories of change that underlie our interventions. METHODS: We describe the historical backdrop against which the term MHPSS and the IASC guidelines were developed, as well as their impact on improving relations and coordination among different aid sectors. We consider the conceptual fuzziness in the field of MHPSS and the lack of clear articulation of the different conceptual frameworks that guide interventions. We describe the explanatory models and intervention approaches of two primary frameworks within MHPSS, which we label clinical and social-environmental. Using the examples of intimate partner violence and compromised parenting in humanitarian settings, we illustrate the complementarity of these two frameworks, as well as the challenges that can arise when either framework is inappropriately applied. RESULTS: Clinical interventions prioritise the role of intrapersonal variables, biological and/or psychological, as mediators of change in the treatment of distress. Social-environmental interventions emphasise the role of social determinants of distress and target factors in the social and material environments in order to lower distress and increase resilience in the face of adversity. Both approaches play a critical role in humanitarian settings; however, the rationale for adopting one or the other approach is commonly insufficiently articulated and should be based on a thorough assessment of causal processes at multiple levels of the social ecology. CONCLUSIONS: Greater attention to the 'why' of our intervention choices and more explicit articulation of the causal models and theories of change that underlie those decisions (i.e., the 'how'), may strengthen intervention effects and minimise the risk of applying the inappropriate framework and actions to a particular problem.


Assuntos
Altruísmo , Conflitos Armados , Saúde Mental , Sistemas de Apoio Psicossocial , Meio Social , Humanos , Refugiados
3.
J Cell Biol ; 133(6): 1355-66, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8682870

RESUMO

A question of broad importance in cellular neurobiology has been, how is microtubule cytoskeleton of the axon organized? It is of particular interest because of the history of conflicting results concerning the form in which tubulin is transported in the axon. While many studies indicate a stationary nature of axonal microtubules, a recent series of experiments reports that microtubules are recruited into axons of neurons grown in the presence of a microtubule-inhibitor, vinblastine (Baas, P.W., and F.J. Ahmad. 1993.J. Cell Biol. 120:1427-1437: Ahmad F.J., and P.W. Baas. 1995. J. Cell Sci, 108:2761-2769; Sharp, D.J., W. Yu, and P.W. Baas. 1995. J. Cell Biol, 130:93-103; Yu, W., and P.W. Baas. 1995. J. Neurosci. 15:6827-6833.). Since vinblastine stabilizes bulk microtubule-dynamics in vitro, it was concluded that preformed microtubules moved into newly grown axons. By visualizing the polymerization of injected fluorescent tubulin, we show that substantial microtubule polymerization occurs in neurons grown at reported vinblastine concentrations. Vinblastine inhibits, in a concentration-dependent manner, both neurite outgrowth and microtubule assembly. More importantly, the neuron growth conditions of low vinblastine concentration allowed us to visualize the footprints of the tubulin wave as it polymerized and depolymerized during its slow axonal transport. In contrast, depolymerization resistant fluorescent microtubules did not move when injected in neurons. We show that tubulin subunits, not microtubules, are the primary form of tubulin transport in neurons.


Assuntos
Transporte Axonal , Axônios/metabolismo , Tubulina (Proteína)/análise , Tubulina (Proteína)/metabolismo , Animais , Axônios/ultraestrutura , Células Cultivadas , Corantes Fluorescentes , Microinjeções , Microtúbulos/metabolismo , Neuritos/efeitos dos fármacos , Polímeros , Ratos , Rodaminas , Succinimidas , Tubulina (Proteína)/química , Vimblastina/farmacologia
4.
Neurogastroenterol Motil ; : e13333, 2018 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-29575442

RESUMO

BACKGROUND: Gastric emptying is a complex physiological process regulating the division of a meal into smaller partitions for the small intestine. Disrupted gastric emptying contributes to digestive disease, yet current measures may not reflect different mechanisms by which the process can be altered. METHODS: We have developed high temporal resolution solid and liquid gastric emptying breath tests in mice using [13 C]-octanoic acid and off axis- integrated cavity output spectroscopy (OA-ICOS). Stretched gamma variate and 2-component stretched gamma variate models fit measured breath excretion data. KEY RESULTS: These assays detect acceleration and delay using pharmacological (7.5 mg/kg atropine) or physiological (nutrients, cold exposure stress, diabetes) manipulations and remain stable over time. High temporal resolution resolved complex excretion curves with 2 components, which was more prevalent in mice with delayed gastric emptying following streptozotocin-induced diabetes. There were differences in the gastric emptying of Balb/c vs C57Bl6 mice, with slower gastric emptying and a greater occurrence of two-phase gastric emptying curves in the latter strain. Gastric emptying of C57Bl6 could be accelerated by halving the meal size, but with no effect on the occurrence of two-phase gastric emptying curves. A greater proportion of two-phase gastric emptying was induced in Balb/c mice with the administration of PYY (8-80 nmol) 60 min following meal ingestion. CONCLUSIONS AND INFERENCES: Collectively, these results demonstrate the utility of high temporal resolution gastric emptying assays. Two-phase gastric emptying is more prevalent than previously reported, likely involves intestinal feedback, but contributes little to the overall rate of gastric emptying.

5.
Science ; 362(6410)2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30287634

RESUMO

The Pioneer and Voyager spacecraft made close-up measurements of Saturn's ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical interaction between the rings and atmosphere. Exploring this interaction provides information on ring composition and the influence on Saturn's atmosphere from infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the region between the D ring and Saturn during the spacecraft's Grand Finale phase. We used these measurements to characterize the atmospheric structure and material influx from the rings. The atmospheric He/H2 ratio is 10 to 16%. Volatile compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as well as larger organic-bearing grains, are flowing inward at a rate of 4800 to 45,000 kilograms per second.

6.
Epidemiol Psychiatr Sci ; 26(2): 129-138, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27040595

RESUMO

Early research on the mental health of civilians displaced by armed conflict focused primarily on the direct effects of exposure to war-related violence and loss. Largely overlooked in this war exposure model were the powerful effects of ongoing stressors related to the experience of displacement itself. An ecological model of refugee distress is proposed, drawing on research demonstrating that mental health among refugees and asylum seekers stems not only from prior war exposure, but also from a host of ongoing stressors in their social ecology, or displacement-related stressors. Implications of this model for addressing the mental health and psychosocial needs of refugees and other displaced populations are considered.


Assuntos
Conflitos Armados/psicologia , Saúde Mental , Refugiados/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/psicologia , Violência/psicologia , Guerra , Adaptação Psicológica , Adulto , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Meio Social , Exposição à Guerra
7.
Comput Mech ; 59(3): 523-537, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28603326

RESUMO

Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena-both in isolation and in interaction-to explore emergent cellular-level features under physiological and pathological conditions.

8.
Neuroscience ; 136(3): 895-905, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16344159

RESUMO

Information processing in the inferior colliculus depends on interactions between ascending pathways and intrinsic circuitry, both of which exist within a functional tonotopic organization. To determine how local projections of neurons in the inferior colliculus are related to tonotopy, we placed a small iontophoretic injection of biodextran amine at a physiologically characterized location in the inferior colliculus. We then used electrophysiological recording to place a grid of small deposits of Chicago Sky Blue throughout the same frequency range to specify an isofrequency contour. Using three-dimensional computer reconstructions, we analyzed patterns of transport relative to the physiologically determined isofrequency contour to quantify the extent of the intrinsic connection lamina in all three dimensions. We also performed a quantitative analysis of the numbers of cells in different regions relative to the biodextran amine injection. Biodextran amine-labeled fibers were mainly located dorsomedial to the injection site, confined within the isofrequency contour, but biodextran amine-labeled cells were mainly located ventrolateral to the injection site. When we counted numbers of labeled cells classified by morphological type, we found that both elongate and multipolar cells were labeled within the isofrequency contour. Because the dendrites of multipolar cells typically extend outside the isofrequency lamina, it is likely that they receive input from other isofrequency contours and relay it to more dorsomedial portions of their specific isofrequency contour, along with the frequency-specific projections of the elongate cells. Within a given isofrequency contour, there is a consistent organization in which intrinsic connections ascend from the ventrolateral portion to more dorsomedial points along the contour, forming a cascaded system of intrinsic feedforward connections that seem ideally suited to provide the delay lines necessary to produce several forms of selectivity for temporal patterns in inferior colliculus neurons.


Assuntos
Vias Auditivas/anatomia & histologia , Vias Auditivas/fisiologia , Colículos Inferiores/citologia , Colículos Inferiores/fisiologia , Neurônios/fisiologia , Estimulação Acústica/métodos , Animais , Compostos Azo , Biotina/análogos & derivados , Mapeamento Encefálico , Contagem de Células , Quirópteros/anatomia & histologia , Quirópteros/fisiologia , Dextranos , Relação Dose-Resposta à Radiação , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Auditivos/efeitos da radiação , Imageamento Tridimensional/métodos , Neurônios/classificação , Azul Tripano
9.
Neurotox Res ; 7(4): 251-63, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16179262

RESUMO

A number of studies have implicated the interactions of the excitatory amino acid L-glutamate (Glu) with its ionotropic and metabotropic receptors as important components of the mechanism underlying the dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium [MPP(+)]. Furthermore, microdialysis experiments have demonstrated that perfusion of relatively high concentrations of MPP(+) into the rat striatum evoke a delayed, massive release of Glu. Interestingly, perfusion of MPP(+) also mediates a similar release of glutathione (GSH). Together, these observations raise the possibility that the rise of extracellular Glu mediated by MPP(+) may be the result of hydrolysis of released GSH by gamma-glutamyl transpeptidase (gamma-GT). In the present investigation it is demonstrated that perfusions of solutions of 0.7 and 1.3 mM MPP(+) dissolved in artificial cerebrospinal fluid into the rat striatum evoke neurotoxic damage to dopaminergic terminals, assessed by both a two-day test/challenge procedure and tyrosine hydroxylase immunoreactivity, but without the release of Glu. Perfusions of 2.5 mM MPP(+) cause more extensive dopaminergic neurotoxicity and a dose-dependent release of Glu. However, neither this release of Glu nor MPP(+)-induced dopaminergic neurotoxicity are blocked by the irreversible gamma-GT inhibitor acivicin. Together, these observations indicate that a rise of extracellular levels of Glu is not essential for the dopaminergic neurotoxicity of MPP(+). Furthermore, the rise of extracellular Glu caused by perfusion of 2.5 mM MPP(+) is not the result of the gamma-GT-mediated hydrolysis of released GSH. It is possible that the rise of extracellular levels of Glu, L-aspartate, L-glycine and L-taurine evoked by perfusions of 2.5 mM MPP(+) into the rat striatum may reflect, at least in part, the release of these amino acids from astrocytes.


Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Dopaminérgicos/toxicidade , Espaço Extracelular/metabolismo , Ácido Glutâmico/metabolismo , Glutationa/metabolismo , Neostriado/metabolismo , Síndromes Neurotóxicas/metabolismo , Aminoácidos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Dopamina/metabolismo , Eletroquímica , Inibidores Enzimáticos/farmacologia , Espaço Extracelular/efeitos dos fármacos , Imuno-Histoquímica , Isoxazóis/farmacologia , Masculino , Microdiálise , Neostriado/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , gama-Glutamiltransferase/antagonistas & inibidores , gama-Glutamiltransferase/metabolismo
10.
J Geophys Res Planets ; 120(3): 495-514, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26690960

RESUMO

The Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration, and long-term preservation. This will guide the future search for biosignatures. Here we report the definitive identification of chlorobenzene (150-300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS) and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs, and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of Martian chlorine and organic carbon derived from Martian sources (e.g., igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets, or interplanetary dust particles. KEY POINTS: First in situ evidence of nonterrestrial organics in Martian surface sediments Chlorinated hydrocarbons identified in the Sheepbed mudstone by SAM Organics preserved in sample exposed to ionizing radiation and oxidative condition.

11.
J Comp Neurol ; 255(2): 293-304, 1987 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-2880879

RESUMO

This study compared the distribution of methionine enkephalin-, dynorphin A 1-8-, and neurotensin-immunoreactive (IR) perikarya in laminae I and IV-VII of selected segments of lumbar spinal cord of cat(L5) and rat(4). Immunoreactive neurons for each peptide were found throughout the dorsal horn and dorsal lamina VII but were quantified only within laminae I and IV-VII. In lamina I, both large (greater than 20 micron) and small (less than 20 micron) IR neurons were identified. Large IR neurons for each peptide in both species resembled Waldeyer neurons studied by Golgi stain and were outnumbered by small IR neurons. Comparison among the laminae of the distribution of met-enkephalin IR neurons showed a similar pattern in the two species with the majority of IR neurons (greater than 65%) in laminae V and VI. Differences in laminar distribution occurred between species for the other peptides. Dynorphin IR neurons were greatest in number in lamina V in rat but greatest in number in laminae I and V in cat. Neurotensin IR neurons occurred predominantly in cat lamina I but were nearly equal in density in rat laminae I and VI. The topographic distribution of each peptide in laminae V and VI was similar between the two species with IR neurons occurring laterally in lamina V and more medially in lamina VI. Comparisons between species of the numbers of IR neurons/segment indicated distinct relationships for each peptide. The number of met-enkephalin IR neurons in laminae of cat L5 was generally two times greater than the number of IR neurons in the same laminae of rat L4, except in laminae I and IV, where the numbers were nearly equal. In contrast, the number of dynorphin IR neurons in cat laminae was generally one-half the number in rat, except in lamina I, where the number in cat was two times greater than rat. A high degree of variability occurred in laminar comparisons of neurotensin IR neurons. Neurotensin IR neurons in lamina I of cat outnumbered those of rat 2:1, but in laminae IV-VII, the ratio of cat to rat IR neurons varied from 1:1 to 1:20. The met-enkephalin, dynorphin, and neurotensin IR neurons quantified in this study may be interneurons or may serve as projection neurons to brainstem and/or thalamic nuclei. The observed differences in distribution may be relevant to differences in spinal cord physiology in the two species.


Assuntos
Dinorfinas/metabolismo , Encefalina Metionina/metabolismo , Neurotensina/metabolismo , Medula Espinal/metabolismo , Animais , Gatos , Técnicas Imunoenzimáticas , Interneurônios/metabolismo , Vias Neurais/metabolismo , Ratos , Especificidade da Espécie
12.
J Comp Neurol ; 279(4): 619-28, 1989 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-2563738

RESUMO

This study examined the number of met-enkephalin, dynorphin A 1-8, and neurotensin immunoreactive (IR) neurons in the marginal zone (lamina I) at one thoracic (T8:cat,T9:rat), one midlumbar (L5:cat,L4:rat), and one lower lumbar or sacral (S1:cat,L6:rat) spinal cord segment in the cat and rat. Marginal zone IR neurons ranged 10-70 microns in diameter in cats and 10-50 microns in rats and were flattened, pyramidal, fusiform, or polygonal in morphology. Immunoreactive neurons for each peptide in both species were found in the marginal zone at all spinal levels, but with a differential segmental distribution. The average number of IR neurons per 50-microns section generally was lowest in thoracic cord and greatest in lower lumbar/sacral cord for all peptides. For enkephalin and dynorphin, the estimated total number of IR neurons per segment and number of IR neurons per volume (mm3) generally were lowest in the midlumbar segments and highest in the thoracic and lower lumbar/sacral cord. For neurotensin, the estimated total number of neurons per segment remained lowest in the thoracic and largest in the lower lumbar/sacral cord. The number of neurotensin IR neurons per volume was equal in the thoracic and midlumbar cord, but remained highest at lower lumbar/sacral levels. The IR neurons quantified in this study may be interneurons or may serve as supraspinal projection neurons. The large number of IR neurons observed in segments receiving a relatively large visceral afferent input suggests that some of these neurons may be involved in visceral sensory processing. In addition, the segmental distribution of the IR neurons indicates that physiological and pharmacological studies on the effects of opioid and/or neurotensin peptides should be interpreted in light of the spinal segment(s) investigated.


Assuntos
Dinorfinas/metabolismo , Encefalina Metionina/metabolismo , Neurotensina/metabolismo , Medula Espinal/metabolismo , Animais , Gatos , Imuno-Histoquímica , Masculino , Ratos , Ratos Endogâmicos , Especificidade da Espécie , Medula Espinal/citologia
13.
J Comp Neurol ; 284(1): 36-47, 1989 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-2474001

RESUMO

The purpose of the present study was to quantify the extent to which several peptides and serotonin coexist with substance P or somatostatin in selected lumbar dorsal root ganglia of the cat. The technique for the simultaneous visualization of two antigens by immunofluorescence was used to investigate the coexistence of neuropeptides in the lumbar dorsal root ganglia of colchicine-treated cats. Perikarya immunoreactive for calcitonin gene-related peptide, galanin, leu-enkephalin, somatostatin, and substance P were visualized in both the lumbar 5 and 6 dorsal root ganglia. In contrast, no immunoreactivity was observed for adipokinetic hormone, bombesin, dynorphin A, met-enkephalin, oxytocin, tyrosine hydroxylase, thyrotropin-releasing hormone, vasopressin, vasoactive intestinal peptide, or serotonin in either ganglion examined. Substance P coexisted with calcitonin-gene-related peptide, somatostatin, and leu-enkephalin. Somatostatin was colocalized with calcitonin gene-related peptide, leu-enkephalin, and substance P but coexisted with galanin minimally. The cell area of immunoreactive perikarya was also examined. Data concerning the cross-sectional area of immunoreactive cells indicated that somatostatin-immunoreactive perikarya were generally the largest population observed (up to approximately 6,000 microns2). Somatostatin and calcitonin gene-related peptide, as well as substance P and calcitonin gene-related peptide, coexisted in populations of cell bodies that had a smaller size (less than 2,000 microns2). These results suggest that certain peptides which coexist in the dorsal root ganglia may provide histochemical markers for functional groups of primary afferent neurons.


Assuntos
Gatos/metabolismo , Gânglios Espinais/metabolismo , Neurônios Aferentes/metabolismo , Neuropeptídeos/metabolismo , Somatostatina/metabolismo , Substância P/metabolismo , Vias Aferentes/metabolismo , Animais , Contagem de Células , Gânglios Espinais/citologia , Imuno-Histoquímica , Masculino , Neurônios Aferentes/citologia , Serotonina/metabolismo
14.
J Med Chem ; 28(2): 204-9, 1985 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3844034

RESUMO

Several amino acid derived azolides (I) have been synthesized and investigated for their inhibitory activity toward human leukocyte elastase and porcine pancreatic elastase. The inhibitory activity was found to be dependent on the nature of the precursor amino acid ester. Thus, compounds derived from L-valine methyl ester 3, L-norvaline methyl ester 5, DL-norleucine methyl ester 9, and L-methionine methyl ester 10 were found to inhibit irreversibly both enzymes. Compound 10 was found to be a specific and selective inhibitor of human leukocyte elastase. In contrast to these, inhibitors derived from glycine methyl ester 1, D-valine methyl ester 4, and D-norvaline methyl ester 6 were found to be inactive. The results of the present study show that latent isocyanates derived from appropriate amino acids can serve as selective inhibitors of serine proteases and are of potential pharmacological value.


Assuntos
Aminoácidos , Cianatos/farmacologia , Leucócitos/enzimologia , Pâncreas/enzimologia , Elastase Pancreática/antagonistas & inibidores , Animais , Matemática , Suínos
15.
Neuroscience ; 22(3): 1057-66, 1987 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3683846

RESUMO

The central gray region (lamina X) of the lumbar spinal cord in cat was examined by electron microscopy. This region consisted of three morphological zones. Medially, the first zone was comprised of ependyma which surrounded the central canal. The ependyma in the cat spinal cord was similar to most vertebrate spinal ependyma. Secondly, a subependymal zone consisted of glial processes arranged parallel to the long axis of the spinal cord. This glial zone was widest lateral to the central canal and extended approximately 75 microns. The lateral edge of the glial zone intermingled with a neuropil zone, the third zone. The components of the neuropil zone consisted of dendrites, myelinated and unmyelinated axons, synaptic terminals, astrocytes and neurons. The dendrites and neurons generally were oriented parallel with the long axis of the spinal cord. Three synaptic terminal types were categorized according to vesicular morphology, i.e. small round vesicles, flattened vesicles and dense core vesicles. The central gray region has been implicated in nociception and has been shown to receive both primary afferent and supraspinal input. The results from this study are consistent with the central gray region being an area of multiple synaptic inputs which may form the morphological basis of nociceptive processing that ascends to brainstem nuclei.


Assuntos
Medula Espinal/ultraestrutura , Animais , Gatos , Epêndima/ultraestrutura , Microscopia Eletrônica , Neuroglia/ultraestrutura
16.
Neuroscience ; 85(3): 837-46, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9639277

RESUMO

The descending serotonergic system provides a powerful inhibitory input to the dorsal horn of the spinal cord. Little is known about the chemical identity of the spinal neurons that the serotonergic system innervates, although spinal enkephalinergic neurons are likely candidates. This study investigated the apposition of serotonin-immunoreactive varicosities onto enkephalin- and neurotensin-immunoreactive neurons in the rat lumbosacral spinal cord. Using a double immunofluorescence technique, serotonin-immunoreactive varicosities were observed to abut the soma or proximal dendrites of [Met]enkephalin- and neurotensin-immunoreactive neurons. Nearly 75% of all [Met]enkephalin- and neurotensin-immunoreactive neurons were apposed by serotonin-immunoreactive varicosities in the marginal zone and dorsal gray commissure. In substantia gelatinosa, approximately half of the [Met]enkephalin- and neurotensin-immunoreactive neurons were juxtaposed by serotonin-immunoreactive varicosities. [Met]enkephalin-immunoreactive neurons also were bordered by serotonin-immunoreactive varicosities in the nucleus proprius (65%) and sacral parasympathetic nucleus (75%). The results of this study suggest that the descending serotonergic system mediates nociception via probable contacts with intrinsic enkephalin and neurotensin spinal systems. The mode of action of spinal serotonin on enkephalin and neurotensin neurons may be through "volume" transmission vs synaptic or "wiring" transmission.


Assuntos
Encefalinas/análise , Neurônios Aferentes/química , Neurotensina/análise , Serotonina/análise , Medula Espinal/química , Animais , Anticorpos , Contagem de Células , Encefalinas/imunologia , Imunofluorescência , Masculino , Neurônios Aferentes/citologia , Neurotensina/imunologia , Nociceptores/fisiologia , Dor/fisiopatologia , Sistema Nervoso Parassimpático/fisiologia , Núcleos da Rafe/citologia , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/fisiologia , Serotonina/imunologia , Medula Espinal/citologia , Sinapses/química
17.
Neuroscience ; 79(4): 1153-63, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9219974

RESUMO

The presence of estrogen receptor protein and estrogen receptor messenger RNA was revealed in peripheral ganglionic neurons of the rat. The pelvic parasympathetic autonomic ganglion and lumbosacral dorsal root sensory ganglia were examined for estrogen receptor-containing neurons because they have known projections to the uterus and uterine cervix. The vagal nodose ganglia were studied for estrogen receptor-containing neurons because they are suspected sources of influence on the uterus. Immunohistochemistry. in situ hybridization histochemistry and retrograde tracing were utilized. Immunoreactivity for estrogen receptors was evident in the nuclei of a subpopulation of neurons in the pelvic ganglia, sixth lumbar and first sacral dorsal root ganglia and nodose ganglia. Some estrogen receptor-positive neurons also contained the retrograde tracer FluoroGold that previously had been injected into the uterus and uterine cervix. Estrogen receptor messenger RNA was also evident in a subpopulation of ganglionic neurons. These data suggest that a certain population of neurons in autonomic and sensory ganglia are capable of synthesizing estrogen receptors and these receptors can serve as binding sites for estrogen. Thus, certain aspects of the structure, function and neurochemistry of some autonomic and sensory neurons may be influenced by the sex steroid estrogen.


Assuntos
Sistema Nervoso Autônomo/metabolismo , Neurônios Aferentes/metabolismo , Receptores de Estrogênio/ultraestrutura , Animais , Sistema Nervoso Autônomo/ultraestrutura , Feminino , Imuno-Histoquímica , Hibridização In Situ , Neurônios Aferentes/ultraestrutura , Proteínas/ultraestrutura , RNA Mensageiro/ultraestrutura , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/metabolismo
18.
Neuroscience ; 84(3): 935-52, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9579795

RESUMO

Retrograde, transneuronal tracing with Bartha's strain of pseudorabies virus was used in rats to identify spinal cord, brainstem and hypothalamic loci of uterine-related neurons that could function in the regulation of uterine activity. Based on the premise that estrogen might influence such uterine-related neurons, the existence of estrogen receptors in neurons in these same loci was examined. Viral injections were made into the uterine cervix, body and cervical end of the uterine horns, and the rats allowed to survive for four to six days. After four days, mainly the spinal cord, medulla and pons contained virus-infected neurons. After longer survival times, progressively higher levels of the neuraxis contained viral-labeled neurons, so that by six days hypothalamic uterine-related neurons were identified. First-order virus-infected neurons were visualized by immunohistochemistry in the pelvic paracervical parasympathetic ganglia and in inferior mesenteric sympathetic ganglia. Preganglionic and putative interneurons were labeled in the lumbosacral spinal cord and thoracic spinal cord mainly in the lateral horn area (sacral parasympathetic nucleus and intermediolateral nucleus), lateral aspect of the dorsal horn, intermediate gray, lamina X and dorsal gray commissural area. In the brainstem, labeling was most evident and consistent in the nucleus tractus solitarius, ventrolateral medulla, raphe magnus and pallidus nuclei, parapyramidal area, A5 cell group, Barrington's nucleus of the pons and periaqueductal gray of the midbrain. In the hypothalamus, virus-infected neurons were most marked in the paraventricular nucleus, with fewer in the medial preoptic area and ventromedial hypothalamic nucleus. Estrogen receptor-immunoreactive neurons were most often present among the virus-labeled uterine-related neurons of the spinal cord, nucleus tractus solitarius, ventrolateral medulla, periaqueductal gray, medial preoptic area and ventromedial hypothalamic nucleus. These results identify a multisynaptic pathway of neurons whose eventual output is involved in uterine functions, whose distribution is similar to that revealed by pseudorabies virus tracing from other visceral organs, and which are often mixed among estrogen-responsive neurons.


Assuntos
Sistema Nervoso Central/citologia , Herpesvirus Suídeo 1 , Receptores de Estrogênio/metabolismo , Sinapses/fisiologia , Útero/inervação , Vias Aferentes/citologia , Vias Aferentes/fisiologia , Animais , Vias Eferentes/citologia , Vias Eferentes/fisiologia , Feminino , Imuno-Histoquímica , Fenótipo , Ratos , Ratos Sprague-Dawley
19.
J Nucl Med ; 17(7): 620-2, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1271108

RESUMO

A case of occult pelvic osteomyelitis is presented. The involved portions of the left pubis and left ischium presented as "cold" areas on the original bone scan with 99mTc-diphosphonate. The presumed mechanism for this unusual finding in osteomyelitis is compression of the microcirculation to bone by subperiosteal and intraosseous pus.


Assuntos
Osteomielite/diagnóstico , Ossos Pélvicos , Cintilografia , Criança , Humanos , Masculino , Compostos Organofosforados , Tecnécio
20.
Brain Res ; 624(1-2): 304-8, 1993 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-8252406

RESUMO

Retrograde transport of the fluorescent tracer Fluorogold was used in combination with immunohistochemical staining for the enzyme glutaminase to identify putative glutamatergic neurons belonging to the rat spinomesencephalic tract. Glutaminase-like staining in spinal projection neurons suggests that the relay of nociceptive information from the spinal cord to midbrain may involve the excitatory amino acid glutamate.


Assuntos
Glutaminase/metabolismo , Mesencéfalo/metabolismo , Medula Espinal/metabolismo , Estilbamidinas , Animais , Corantes Fluorescentes , Imuno-Histoquímica , Mesencéfalo/citologia , Vias Neurais/citologia , Vias Neurais/metabolismo , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Transmissão Sináptica
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