ABSTRACT
The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects on the body, especially on the cardiac system and gastrointestinal tract. ACE II is responsible for converting Ang II into the active peptide Ang-(1-7), which in turn binds to a metabotropic receptor, the Mas receptor (MasR). Recent studies have demonstrated that Diminazene Aceturate (DIZE), a trypanosomicide used in animals, activates the ACE II pathway. In this study, we aimed to evaluate the antidiarrheal effects promoted by the administration of DIZE to activate the ACE II/Ang-(1-7)/MasR axis in induced diarrhea mice models. The results show that activation of the ACE II pathway exerts antidiarrheal effects that reduce total diarrheal stools and enteropooling. In addition, it increases Na+/K+-ATPase activity and reduces gastrointestinal transit and thus inhibits contractions of intestinal smooth muscle; decreases transepithelial electrical resistance, epithelial permeability, PGE2-induced diarrhea, and proinflammatory cytokines; and increases anti-inflammatory cytokines. Enzyme-linked immunosorbent assay (ELISA) demonstrated that DIZE, when activating the ACE II/Ang-(1-7)/MasR axis, can still interact with GM1 receptors, which reduces cholera toxin-induced diarrhea. Therefore, activation of the ACE II/Ang-(1-7)/MasR axis can be an important pharmacological target for the treatment of diarrheal diseases.
Subject(s)
Angiotensin II/metabolism , Angiotensin I/metabolism , Antidiarrheals/therapeutic use , Diarrhea/metabolism , Diminazene/analogs & derivatives , Peptide Fragments/metabolism , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Animals , Antidiarrheals/pharmacology , Castor Oil/toxicity , Diarrhea/chemically induced , Diarrhea/drug therapy , Diminazene/pharmacology , Diminazene/therapeutic use , Dose-Response Relationship, Drug , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Male , Mice , Proto-Oncogene Mas , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiologyABSTRACT
Arthur de Carvalho Drops® (ACD) is a traditional Brazilian herbal medicine used to treat functional gastrointestinal disorders (FGIDs). ACD is a formulation of herbal extracts from Matricaria recutita (chamomile), Foeniculum vulgare (fennel) and Gentiana lutea L. (gentian). Considering the popular use for FGIDs, the aim of this work was to investigate the ACD effect on gastric and intestinal parameters with emphasis in a mechanistic approach using isolated duodenal preparations of rodents. Analytical method was developed and validated for quantify three actives principles/markers (Apigenin-7-glucoside, gentiopicroside and anethole) in ACD. The treatment with ACD significantly reduced the emetogenic stimuli induced by cisplatin in rats, showed a laxative effect, reduced the bethanechol-enhanced gastrointestinal transit and completely reversed the contraction induced by carbachol in rat duodenum. However, ACD did not alter the secretory gastric volume or total gastric acidity. The ACD affect the contractions of duodenal smooth muscle mediated by Ca2+ channels and it is also able to inhibit the contractile response mediated by the release from its intracellular store. Furthermore, the relaxant effects of ACD appear independent of the nitric oxide pathway in rat duodenum. These results suggest that ACD could be beneficial for the treatment of disorders of the gastrointestinal tract.
ABSTRACT
Bone involvement is a common finding in many types of lymphoma (Clin Oncol 9(3): 195-196, 1997). However, cranial vault affliction has been regarded as an exceedingly rare presentation, particularly in the case of primary lymphoma (J Neurosurg 108(5): 1018-1020, 2008). Our objective is to describe a series of five immunocompetent patients with histologically confirmed cranial vault lymphoma (CVL), and to conduct a systematic review of the current literature. Our review points out identical imaging patterns in most of the lesions for all reported CVL cases, despite their different histological subtypes. This typical pattern can be seen on computed tomography (CT) scans and magnetic resonance imaging (MRI) as an expansive tumor that affects all three compartments of the cranial vault, including the scalp, skull bone, and pachymeninges, even in the absence of osteolysis. We argue that the absence of osteolysis might enhance diagnostic capability. In the appropriate clinical setting, these features represent important disease characteristics that may help with an earlier diagnosis. Large B-cell lymphoma was the most common subtype of primary CVL.
Subject(s)
Dura Mater/pathology , Lymphoma/diagnosis , Skull/pathology , Adolescent , Adult , Aged , Female , Humans , Immunocompetence , Lymphoma/pathology , Magnetic Resonance Imaging , Male , Middle Aged , PubMed/statistics & numerical data , Scalp/pathology , Scalp/physiopathology , Tomography, X-Ray ComputedABSTRACT
O linfoma de zona marginal é um linfoma de baixo grau com curso clínico indolente e potencial de recidiva.1,2 Apresentamos um caso de recidiva tardia após 25 anos de aparente remissão completa, levantando a possibilidade de recidiva de doença preexistente ou desenvolvimento de novo clone neoplásico.
Marginal zone lymphoma is a low grade lymphoma with an indolent course and chance to relapse. We present a case of a patient who suffered relapse after 25 years of apparently complete remission of a low-grade non-Hodgkin lymphoma.
