ABSTRACT
BACKGROUND AND PURPOSE: Kinins are pro-inflammatory peptides that are released during tissue injury, including that caused by inflammatory bowel disease. Herein, we assessed the role and underlying mechanisms through which the absence of kinin B(1) receptors exacerbates the development of dextran sulfate sodium (DSS)-induced colitis in mice. EXPERIMENTAL APPROACH: B(1) and B(2) receptor antagonists and B(1) receptor knockout mice (B1(-/-) ) were used to assess the involvement of B(1) and B(2) receptor signalling in a DSS-colitis. B(1) receptor, B(2) receptor, occludin and claudin-4 expression, cytokine levels and cell permeability were evaluated in colon from wild-type (WT) and B1(-/-) mice. KEY RESULTS: DSS-induced colitis was significantly exacerbated in B1(-/-) compared with WT mice. IL-1ß, IFN-γ, keratinocyte-derived chemokine and macrophage inflammatory protein-2 were markedly increased in the colon from DSS-treated B1(-/-) compared with DSS-treated WT mice. Treatment of WT mice with a selective B(1) receptor antagonist, DALBK or SSR240612, had no effect on DSS-induced colitis. Of note, B(2) receptor mRNA expression was significantly up-regulated in colonic tissue from the B1(-/-) mice after DSS administration. Moreover, treatment with a selective B(2) receptor antagonist prevented the exacerbation of colitis in B1(-/-) mice following DSS administration. The water- or DSS-treated B1(-/-) mice showed a decrease in occludin gene expression, which was partially prevented by the B(2) receptor antagonist. CONCLUSIONS AND IMPLICATIONS: A loss of B(1) receptors markedly exacerbates the severity of DSS-induced colitis in mice. The increased susceptibility of B1(-/-) may be associated with compensatory overexpression of B(2) receptors, which, in turn, modulates tight junction expression.
Subject(s)
Colitis/metabolism , Receptor, Bradykinin B1/metabolism , Receptor, Bradykinin B2/metabolism , Animals , Bradykinin/analogs & derivatives , Bradykinin/pharmacology , Bradykinin B1 Receptor Antagonists , Bradykinin B2 Receptor Antagonists , Colitis/chemically induced , Colitis/pathology , Cytokines/metabolism , Dextran Sulfate , Dioxoles/pharmacology , Homeostasis , Intestinal Mucosa/metabolism , Intestines/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Peroxidase/metabolism , Receptor, Bradykinin B1/genetics , Sulfonamides/pharmacology , Tight Junctions/metabolism , Up-RegulationABSTRACT
Homer1a regulates expression of group I metabotropic glutamate receptors type I (mGluR1 and mGluR5) and is involved in neuronal plasticity. It has been reported that Homer1a expression is upregulated in the kindling model and hypothesized to act as an anticonvulsant. In the present work, we investigated whether pilocarpine-induced status epilepticus (SE) would alter Homer1a and mGluR5 expression in hippocampus. Adult rats were subjected to pilocarpine-model and analyzed at 2h, 8h, 24h and 7 d following SE. mRNA analysis showed the highest expression of Homer1a at 8h after SE onset, while immunohistochemistry demonstrated that Homer1a protein expression was significantly increased in hippocampus, amygdala and piriform and entorhinal cortices at 24h after SE onset when compared to control animals. The increased Homer1a expression coincided with a significant decrease of mGluR5 protein expression in amygdala and piriform and entorhinal cortices. The data suggest that during the critical periods of epileptogenesis, overexpression of Homer1a occurs to counteract hyperexcitability and thus Homer1a may be a molecular target in the treatment of epilepsy.
Subject(s)
Carrier Proteins/metabolism , Pilocarpine/toxicity , Receptors, Metabotropic Glutamate/metabolism , Status Epilepticus/metabolism , Animals , Carrier Proteins/genetics , Homer Scaffolding Proteins , Male , Rats , Rats, Wistar , Receptor, Metabotropic Glutamate 5 , Receptors, Metabotropic Glutamate/genetics , Seizures/chemically induced , Seizures/metabolism , Status Epilepticus/chemically induced , Status Epilepticus/geneticsABSTRACT
Stiff skin syndrome is a rare cutaneous disease, scleroderma-like disorder that presents in infancy or early childhood with rock-hard skin, limited joint mobility, and mild hypertrichosis. Normally, it occurs in the absence of visceral or muscle involvement. Patients do not present immunologic abnormalities or vascular hyperactivity. We describe two adults who initially were diagnosed suffering from scleroderma but fit criteria for stiff skin syndrome. A review of the clinical range of this disorder and discussion of the differential diagnosis with scleroderma is presented.
Subject(s)
Dermis/pathology , Fascia/pathology , Scleroderma, Diffuse/pathology , Adult , Diagnosis, Differential , Disease Progression , Female , Humans , Joint Diseases/pathology , MaleABSTRACT
We describe eight cases of pediatric patients whose neuroimages performed after seizures revealed abnormalities that were compatible with edema surrounding calcified lesions and which disappeared in subsequent examinations.
Subject(s)
Brain Diseases/parasitology , Brain Edema/parasitology , Calcinosis/parasitology , Epilepsy/parasitology , Neurocysticercosis/diagnosis , Adolescent , Brain Edema/pathology , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Male , Neurocysticercosis/pathology , Remission, Spontaneous , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
Five years old, female, who started with tonic-clonic seizures on the right side of the body, with vomits and unconsciousness. The patient had been hospitalized for eight times in the last sixty days because of seizures. At physical exam, she had a severe arterial hypertension (270/140 mmHg). The computerized tomographic scan and magnetic resonance imaging revealed hypodense areas, mainly on the right parietal-temporal region, suggesting presence of edema. The angiography showed stenosis of the right renal artery, that was the cause of arterial hypertension. After the control of arterial hypertension by nephrectomy, the patient had a complete remission of the symptoms, as well as the images anomalies.
