RESUMEN
The response to wounds until healing requires the activity of many cell types coordinate in space and time, so that the types of cells in a wound and their localization may be of help to date lesions with respect to death, which would be useful in forensic pathology. Cells reacting to injury include dendritic cells; the early reaction of these cells to skin wounding has not yet been investigated in humans, which was the aim of this study. Samples of wounded and control skin were taken at autopsy and analyzed by affinity histochemistry. Both epidermal and dermal MHC-II+ cells increased transiently in number within the first hour after wounding, then decreased. In the epidermis the increase affected also CD1a+ cells, i.e. well differentiated Langherhans cells, which however increased less, earlier and for a shorter time period than MHC-II+ cells. Dermal MHC-II+ cells became part of a perivascular mononuclear cell infiltrate visible in the subpapillary dermis by 60 min after wounding, which contained also mast cells. The immediately perivascular MHC-II+ cells were DC-SIGN- and CD11c-, while MHC-II+, DC-SIGN+, CD11c+ dendritic cells were predominantly located at the periphery of infiltrates and some were near the epidermis. Mast cells underwent degranulation, besides increase in number, in the first hours after wounding. The results suggest that skin dendritic cells, including Langerhans cells, participate to the early response to wounding in concert with mast cells, and that subpapillary blood vessels are primary sites of cell infiltration during that response in humans. The results show that the ratio between CD1a positive and MHC-II positive cells in the epidermis, the degranulation index of mast cells and the relative volume of MHC-II positive cells in the dermis can be added to the tools useful to distinguish vital from post mortem lesions and, the first two of them, to estimate the interval between a lesion and death.
Asunto(s)
Células de Langerhans/citología , Células de Langerhans/metabolismo , Piel/citología , Piel/lesiones , Cicatrización de Heridas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD1/metabolismo , Recuento de Células , Niño , Preescolar , Femenino , Patologia Forense , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Inmunohistoquímica , Masculino , Mastocitos/citología , Persona de Mediana Edad , Cambios Post Mortem , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Among the pathogenic mechanisms of asthma, a role for oxidative/nitrosative stress has been well documented. Recent evidence suggests that histamine H4 receptors play a modulatory role in allergic inflammation. Here we report the effects of compound JNJ 7777120 (JNJ), a selective H4 receptor antagonist, on antigen-induced airway inflammation, paying special attention to its effects on lipocortin-1 (LC-1/annexin-A1), a 37 kDA anti-inflammatory protein that plays a key role in the production of inflammatory mediators. EXPERIMENTAL APPROACH: Ovalbumin (OA)-sensitized guinea pigs placed in a respiratory chamber were challenged with antigen. JNJ (5, 7.5 and 10 mg.kg⻹) was given i.p. for 4 days before antigen challenge. Respiratory parameters were recorded. Bronchoalveolar lavage (BAL) fluid was collected and lung specimens taken for further analyses 1 h after antigen challenge. In BAL fluid, levels of LC-1, PGD2 , LTB4 and TNF-α were measured. In lung tissue samples, myeloperoxidase, caspase-3 and Mn-superoxide dismutase activities and 8-hydroxy-2-deoxyguanosine levels were measured. KEY RESULTS: OA challenge decreased LC-1 levels in BAL fluid, induced cough, dyspnoea and bronchoconstriction and increased PGD2 , LTB4 and TNF-α levels in lung tissue. Treatment with JNJ dose-dependently increased levels of LC-1, reduced respiratory abnormalities and lowered levels of PGD2 , LTB4 and TNF-α in BAL fluid. CONCLUSIONS AND IMPLICATIONS: Antigen-induced asthma-like reactions in guinea pigs decreased levels of LC-1 and increased TNF-α and eicosanoid production. JNJ pretreatment reduced allergic asthmatic responses and airway inflammation, an effect associated with LC-1 up-regulation.
Asunto(s)
Anexina A1/metabolismo , Asma/prevención & control , Antagonistas de los Receptores Histamínicos/farmacología , Indoles/farmacología , Piperazinas/farmacología , Animales , Anexina A1/genética , Antígenos/inmunología , Asma/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Broncoconstricción/efectos de los fármacos , Broncoconstricción/inmunología , Tos/inmunología , Relación Dosis-Respuesta a Droga , Cobayas , Antagonistas de los Receptores Histamínicos/administración & dosificación , Indoles/administración & dosificación , Inflamación/inmunología , Inflamación/prevención & control , Pulmón/efectos de los fármacos , Pulmón/inmunología , Masculino , Ovalbúmina/inmunología , Piperazinas/administración & dosificación , Factor de Necrosis Tumoral alfa/inmunología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
AIM: While deproteinized bovine bone and bovine membranes have been well studied and can yield good results when used to treat bone defects and peri-implant dehiscences, enzymatically deantigenated equine bone and equine membranes have emerged as possible alternative biomaterials. The objective of this study was the clinical and histological assessment of such materials: equine bone granules, an equine collagen membrane and an equine pericardium membrane. METHODS: Enzymatically deantigenated equine bone and an equine collagen membrane were used to restore a bone defect caused by the removal of a bone cyst in the upper anterior maxilla. After 4.5 months, an implant was placed and a bone core sample was obtained from the grafted site. Implants threads, though, were exposed. This defect was grafted with a mixture of autogenous and equine bone and covered with an equine pericardium membrane. RESULTS: Four months after implant placement the peri-implant bone levels were maintained. A prosthesis was delivered three months later providing functional and esthetic rehabilitation. Also four-year follow-up controls showed implant success. Histological analysis of the bone core revealed that the graft material had undergone remodelling, and a fair amount of newly formed vital bone was present at the time of sample collection. CONCLUSION: The deantigenated equine bone is biocompatible and undergoes osteoclastic remodelling. Both the equine collagen and pericardium membrane acted as effective barriers for guided bone regeneration.
Asunto(s)
Trasplante Óseo , Quiste Radicular/cirugía , Animales , Femenino , Caballos , Humanos , Membranas/trasplante , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The hexahydric alcohol mannitol is widely used to shift fluids from the intracellular to the extracellular compartments, to increase diuresis and improve mucus clearance in the airways. In principle, because of its physicochemical properties, topical mannitol might also draw fluids out of epidermis or mucosa. Here, we report that topical mannitol applications on the hind paws of rats with adjuvant-induced arthritis reduced paw thickness and tissue edema without affecting the inflammatory infiltrates. Of note, the anti-edema effects of acute (4 h) mannitol application occurred earlier than those prompted by a similar treatment with classic anti-inflammatory drugs such as diclofenac or ketoprofen. Yet, the extent of edema reduction was higher with diclofenac or ketoprofen than with mannitol when the drugs were applied in a chronic (16 h) paradigm. Together, data demonstrate that topical application of mannitol exerts potent and fast anti-edema effects in a rat model of joint inflammation, suggesting a possible utilization in patients affected by osseo-arthritic disorders.
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Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Diclofenaco/uso terapéutico , Edema/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Manitol/uso terapéutico , Administración Cutánea , Animales , Antiinflamatorios/administración & dosificación , Artritis Experimental/complicaciones , Edema/inducido químicamente , Edema/complicaciones , Cetoprofeno/uso terapéutico , Masculino , Manitol/administración & dosificación , Ratas , Ratas WistarRESUMEN
BACKGROUND: Glucagon-like peptide 2 (GLP-2), a nutrient-responsive hormone, exerts various actions in the gastrointestinal tract that are mediated by a G-protein coupled receptor called GLP-2R. A little information is available on GLP-2R expression in enteric neurons and nothing on the interstitial cells of Cajal (ICC). METHODS: We investigated presence and distribution of the GLP-2R in the mouse duodenum by immunohistochemistry and the potential motor effects of GLP-2 on the spontaneous and neurally evoked mechanical activity. KEY RESULTS: The GLP-2R was expressed by the myenteric and submucosal neurons. Labelling was also present in nerve varicosities within the circular muscular layer and at the deep muscular plexus (DMP). No immunoreactive nerve fiber was seen within the longitudinal muscle layer. The GLP-2R-positive neurons were either excitatory (SP- and choline-acetyltransferase-positive) or inhibitory (vasoactive intestinal polypeptide and nNOS-positive). The ICC, both at the myenteric plexus and at the DMP, never expressed GLP-2R but, especially those at the DMP, were surrounded by GLP-2R-positive nerve varicosities co-expressing either excitatory or inhibitory neurotransmitters. Quantitative analysis demonstrated a consistent prevalence of GLP-2R on the excitatory pathways. In agreement, the functional results showed that the administration of GLP-2 in vitro caused decrease of the spontaneous contractions mediated by nitric oxide release and reduction of the evoked cholinergic contractions. CONCLUSIONS & INFERENCES: The present findings indicate that the GLP-2R is expressed by inhibitory and excitatory neurons, the GLP-2 inhibits the muscle contractility likely decreasing cholinergic neurotransmission and increasing nitric oxide production, and this effect is possibly mediated by the ICC-DMP recruitment.
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Duodeno/inervación , Duodeno/fisiología , Sistema Nervioso Entérico/citología , Contracción Muscular/fisiología , Músculo Liso/fisiología , Neuronas/fisiología , Receptores de Glucagón/metabolismo , Animales , Duodeno/citología , Péptido 2 Similar al Glucagón/metabolismo , Receptor del Péptido 2 Similar al Glucagón , Humanos , Inmunohistoquímica , Células Intersticiales de Cajal/citología , Células Intersticiales de Cajal/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Liso/inervación , Neurotransmisores/metabolismoRESUMEN
BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine-L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinal motility through vagal afferents and central nervous mechanisms; however, no data is available about a direct influence on the gastrointestinal wall. Our aim was to investigate the effects of GLP-1 on the spontaneous and evoked mechanical activity of mouse duodenum and colon and to identify the presence and distribution of GLP-1 receptors (GLP-1R) in the muscle coat. METHODS: Organ bath recording technique and immunohistochemistry were used. KEY RESULTS: Glucagon-like peptide-1 (up to the concentration of 1 mumol L(-1)) failed to affect spontaneous mechanical activity. It caused concentration-dependent reduction of the electrically evoked cholinergic contractions in circular smooth muscle of both intestinal segments, without affecting the longitudinal muscle responses. Glucagon-like peptide-1 inhibitory effect was significantly antagonized by exendin (9-39), an antagonist of GLP-1R. In both intestinal preparations, GLP-1 effect was not affected by guanethidine, a blocker of adrenergic neurotransmission, but it was significantly reduced by N(omega)-nitro-l-arginine methyl ester, inhibitor of nitric oxide (NO) synthase. Glucagon-like peptide-1 failed to affect the contractions evoked by exogenous carbachol. Immunohistochemistry demonstrated GLP-1R expression in the enteric neurons. Furthermore, 27% of GLP-1R immunoreactive (IR) neurons in the duodenum and 79% of GLP-1R-IR neurons in the colon, co-expressed nNOS. CONCLUSIONS & INFERENCES: The present results suggest that GLP-1 is able to act in the enteric nervous system by decreasing the excitatory cholinergic neurotransmission through presynaptic GLP-1Rs, which modulate NO release.
Asunto(s)
Sistema Nervioso Entérico/efectos de los fármacos , Péptido 1 Similar al Glucagón/farmacología , Neuronas Motoras/efectos de los fármacos , Neuronas/efectos de los fármacos , Sistema Nervioso Periférico/efectos de los fármacos , Receptores de Glucagón/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Animales , Sistema Nervioso Entérico/citología , Inhibidores Enzimáticos/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Péptido 1 Similar al Glucagón/antagonistas & inhibidores , Receptor del Péptido 1 Similar al Glucagón , Guanetidina/farmacología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo I/metabolismo , Nitroarginina/farmacología , Fragmentos de Péptidos/farmacología , Sistema Nervioso Periférico/citología , Simpaticolíticos/farmacologíaAsunto(s)
Antígenos/inmunología , Asma/inmunología , Hiperreactividad Bronquial , Antagonistas de los Receptores Histamínicos , Inflamación , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Mucosa Respiratoria , Animales , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/prevención & control , Tos/inducido químicamente , Tos/inmunología , Disnea/inducido químicamente , Disnea/inmunología , Cobayas , Antagonistas de los Receptores Histamínicos/farmacología , Antagonistas de los Receptores Histamínicos/uso terapéutico , Inflamación/inmunología , Inflamación/prevención & control , Masculino , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Receptores Acoplados a Proteínas G/inmunología , Receptores Histamínicos/inmunología , Receptores Histamínicos H4 , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunologíaAsunto(s)
Arritmias Cardíacas/fisiopatología , Mastocitos/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Relaxina/uso terapéutico , Animales , Modelos Animales de Enfermedad , Ventrículos Cardíacos/metabolismo , Histamina/metabolismo , Humanos , Masculino , Daño por Reperfusión/prevención & control , PorcinosRESUMEN
In this study we evaluated the effects of the CB1/CB2 cannabinoid receptor agonist CP55, 940 (CP) on antigen-induced asthma-like reaction in sensitized guinea pigs and we tested the ability of the specific CB2 receptor antagonist SR144528 (SR) and CB1 receptor antagonist AM251 (AM) to interfere with the effects of CP. Ovalbumin-sensitized guinea pigs placed in a respiratory chamber were challenged with the antigen given by aerosol. CP (0.4 mg/kg b.wt.) was given i.p. 3 hrs before ovalbumin challenge. Sixty minutes before CP administration, some animals were treated i.p. with either AM, or SR, or both (0.1 mg/kg b.wt.). Respiratory parameters were recorded and quantified. Lung tissue specimens were then taken for histopathological and morphometric analyses and for eosinophilic major basic protein immunohistochemistry. Moreover, myeloperoxidase activity, 8-hydroxy-2-deoxyguanosine, cyclic adenosine monophosphate (cAMP) and guanosine monophosphate (cGMP) levels, and CB1 and CB2 receptor protein expression by Western blotting were evaluated in lung tissue extracts. In the bronchoalveolar lavage fluid, the levels of prostaglandin D2 and tumour necrosis factor-alpha TNF-alpha were measured. Ovalbumin challenge caused marked abnormalities in the respiratory, morphological and biochemical parameters assayed. Treatment with CP significantly reduced these abnormalities. Pre-treatment with SR, AM or both reverted the protective effects of CP, indicating that both CB1 and CB2 receptors are involved in lung protection. The noted treatments did not change the expression of cannabinoid receptor proteins, as shown by Western blotting. These findings suggest that targeting cannabinoid receptors could be a novel preventative therapeutic strategy in asthmatic patients.