ABSTRACT
Cerebral cavernous malformations (CCMs) are congenital abnormalities of the cerebral vessels. The de novo development of new lesions in this disease has been reported. However, the underlying mechanism of progressive CCMs in such patients remains unclear. This report documents two cases of multiple probable CCMs that showed a progressive behaviour. The plasma levels of vascular endothelial growth factor (VEGF), and transforming growth factor-beta1 (TGF-beta1) were measured using an enzyme-linked immunosorbent assay (ELISA). The concentration of both VEGF and TGF-beta1 in plasma was increased in these patients. A relationship was observed between high concentrations of growth factors and progressive CCMs. Even though a causal linkage between these conditions cannot be confirmed, a continuous high VEGF level in plasma could be a possible clinical indicator for subsequent intracerebral haemorrhages in the CCM patients.
Subject(s)
Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/etiology , Hemangioma, Cavernous, Central Nervous System/blood , Hemangioma, Cavernous, Central Nervous System/complications , Vascular Endothelial Growth Factor A/blood , Biomarkers/analysis , Biomarkers/blood , Causality , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/metabolism , Cerebral Arteries/pathology , Cerebral Hemorrhage/prevention & control , Cerebral Veins/diagnostic imaging , Cerebral Veins/metabolism , Cerebral Veins/pathology , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Hemangioma, Cavernous, Central Nervous System/physiopathology , Humans , Male , Middle Aged , Predictive Value of Tests , Radiography , Transforming Growth Factor beta1/analysis , Transforming Growth Factor beta1/blood , Up-Regulation/physiology , Vascular Endothelial Growth Factor A/analysisABSTRACT
A 14-year-old girl presented with seizures. Radiological examinations revealed an arachnoid cyst in left middle fossa and a cystic mass in the interpeduncular cistern. The cyst was opened and the wall of the cyst and a mass were biopsied. The histological findings were characteristic of an arachnoid cyst and hamartoma, respectively. A hypothalamic hamartoma associated with an arachnoid cyst is comparatively rare; however, such a case may help clarify the genesis of this malformation.
Subject(s)
Arachnoid Cysts/diagnosis , Brain Diseases/diagnosis , Hamartoma/diagnosis , Hypothalamus , Seizures/etiology , Adolescent , Arachnoid Cysts/complications , Arachnoid Cysts/pathology , Brain Diseases/complications , Brain Diseases/pathology , Diagnosis, Differential , Female , Hamartoma/complications , Hamartoma/pathology , HumansABSTRACT
Cellular damage of various organs by ischemia following reperfusion is assumed to be at least in part due to lipid peroxidation in biomembranes, and oxygen-derived free radicals play a major role. The level of lipid peroxides in liver tissue increased during 90-min ischemia. When reflow of hepatic blood was allowed, a greater increase in the lipid peroxides was observed. Similar increases were obtained in several serum markers (GOT, GPT and LDH) during the period of ischemia or ischemia-reperfusion. In addition, levels of cytochrome p-450 and NADPH cyt. c reductase activity decreased in proportion to the decrease in microsomal proteins during ischemia or ischemia-reperfusion. On the other hand, superoxide dismutase in blood was significantly increased by ischemia-reperfusion. Rats died within 2 days after liver ischemia of 90 min, while all animals subjected to 30-min ischemia survived. Histopathological examinations indicated that extensive coagulation with erythrocytes occurred and the extent was dependent on the time of ischemia. The liver injury by ischemia-reperfusion could be a useful experimental model for studying liver injury induced by free radicals, for developing hepatoprotective drugs, or for investigating liver transplantation.
Subject(s)
Lipid Peroxidation , Liver Diseases/pathology , Reperfusion Injury/pathology , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Cytochrome P-450 Enzyme System/metabolism , Disease Models, Animal , Free Radicals , L-Lactate Dehydrogenase/metabolism , Lipid Peroxides/metabolism , Liver Diseases/metabolism , Male , NADPH-Ferrihemoprotein Reductase/metabolism , Rats , Rats, Inbred Strains , Reperfusion Injury/metabolism , Superoxide Dismutase/blood , Time FactorsABSTRACT
The effects of bifemelane hydrochloride (BF) upon various cholinergic markers, muscarinic receptors, acetylcholinesterase (AChE) and choline acetyltransferase (CAT), in the aged rat brain were examined. Marked reduction of the density of muscarinic receptors (Bmax) as well as AChE and CAT activity concomitant with aging was observed. Administration of BF in daily doses of 10 mg/kg for 4 weeks to aged rats significantly decreased the apparent dissociation constant (Kd) for QNB in muscarinic receptors in the forebrain, but did not affect the value of Bmax. CAT activity also increased significantly compared with that of control aged rats, but administration of BF did not alter AChE activity. These results indicate that long-term treatment with BF enhances the affinity of muscarinic receptors for QNB as well as CAT activity and that BF may have therapeutic application in the treatment of CNS cholinergic dysfunctions.
Subject(s)
Aging/physiology , Antidepressive Agents/pharmacology , Benzhydryl Compounds/pharmacology , Brain/drug effects , Cerebral Cortex/drug effects , Parasympathetic Nervous System/drug effects , Acetylcholinesterase/metabolism , Animals , Brain/enzymology , Cerebral Cortex/enzymology , Choline O-Acetyltransferase/antagonists & inhibitors , Cholinesterase Inhibitors/pharmacology , Kinetics , Male , Nerve Tissue Proteins/metabolism , Rats , Rats, Inbred Strains , Receptors, Muscarinic/drug effectsABSTRACT
We examined neurochemically the effects of bifemelane (BF) on muscarinic ACh (mACh-R) and beta-adrenergic receptors (beta-AdR) and imipramine binding sites and the activities of acetylcholinesterase (AChE), choline acetyltransferase (CAT) and monoamine oxidase (MAO) in the P2 fractions of rat brain, ex vivo and in vitro. Male rats were given daily injections of 10, 30 mg/kg BF, p.o., for a period of 4 weeks. The Kd and Bmax values for mACh-R in the rat forebrain by administration of 10, 30 mg/kg BF decreased significantly compared with that of the control, although the Kd and Bmax values for beta-AdR and imipramine binding sites were almost identical. The Km and Vmax values of A- and B-form MAO decreased in rats that had been administered 30 mg/kg BF for 4 weeks. The binding of 3H-QNB (quinuclidinyl benzilate) on mACh-R, 125I-CYP (iodocyanopindolol) on beta-AdR and 3H-imipramine on imipramine binding sites decreased by 60, 20 and 70% in the presence of 1 microM BF, respectively, while the addition of 1 microM BF inhibited MAO activity by about 50%. However, CAT and AChE activities were not inhibited by BF.
Subject(s)
Antidepressive Agents/pharmacology , Benzhydryl Compounds/pharmacology , Brain/metabolism , Receptors, Adrenergic, beta/metabolism , Receptors, Cholinergic/metabolism , Acetylcholinesterase/metabolism , Animals , Choline O-Acetyltransferase/metabolism , Male , Monoamine Oxidase/metabolism , Rats , Rats, Inbred StrainsABSTRACT
The extraction and partial purification of endogenous "monoamine oxidase (MAO) inhibitor-like" material from the monkey brain are described. The endogenous material (F-1 and F-2) obtained after Bio-Gel P-2 gel filtration and silica column chromatography inhibited MAO in the monkey brain mitochondria toward 5-hydroxytryptamine (5-HT), beta-phenylethylamine (beta-PEA), tyramine and dopamine as substrates. The inhibitory effects of F-1 and F-2 were non-linear concentration dependent, and F-1 non-competitively inhibited A-form MAO, while F-2 inhibited A-form MAO competitively and inhibited B-form MAO non-competitively. These substances were more potent inhibitors of A-form than of B-form MAO. F-2 was heat stable but liable to the treatment with pepsin and trypsin. F-1 was not inactivated by heat treatment and digestion with pepsin and trypsin. F-1 may be a low molecular weight (less than 1350) compound, including certain monoamines or their metabolites or other unidentified compounds, while F-2 was a low molecular weight (about 2500) peptide.
