tetracycline and Cerebral-Hemorrhage

Hemorrhagic transformation (HT) associated with recombinant tissue plasminogen activator (rt-PA) complicates and limits its use in stroke. Here, we provide a focused review on the involvement of matrix metalloproteinase 9 (MMP-9) in rt-PA-associated HT in cerebral ischemia, and we review emerging evidence that the selective inhibitor of the sulfonylurea receptor 1 (Sur1), glibenclamide (U.S. adopted name, glyburide), may provide protection against rt-PA-associated HT in cerebral ischemia. Glyburide inhibits activation of MMP-9, ameliorates edema formation, swelling, and symptomatic hemorrhagic transformation, and improves preclinical outcomes in several clinically relevant models of stroke, both without and with rt-PA treatment. A retrospective clinical study comparing outcomes in diabetic patients with stroke treated with rt-PA showed that those who were previously on and were maintained on a sulfonylurea fared significantly better than those whose diabetes was managed without sulfonylureas. Inhibition of Sur1 with injectable glyburide holds promise for ameliorating rt-PA-associated HT in stroke.

Topics: Animals; Antioxidants; Aspirin; ATP-Binding Cassette Transporters; Brain Ischemia; Cells, Cultured; Cerebral Hemorrhage; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Synergism; Endothelial Cells; Glyburide; Heparin; Humans; Hypoglycemic Agents; Matrix Metalloproteinase 9; Mice; Mice, Knockout; Potassium Channels, Inwardly Rectifying; Prospective Studies; Receptors, Drug; Recombinant Proteins; Retrospective Studies; Risk; Sulfonylurea Receptors; Tetracycline; Tissue Plasminogen Activator; Treatment Outcome

Topics: Age Factors; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Blood Coagulation; Cerebral Hemorrhage; Child; Chloramphenicol; Drug Hypersensitivity; Erythromycin; Female; Fetus; Fusidic Acid; Humans; Kidney; Lincomycin; Liver; Maternal-Fetal Exchange; Penicillins; Polymyxins; Pregnancy; Tetracycline

Acinetobacter baumannii is considered an important nosocomial pathogen worldwide owing to its increasing antibiotic resistance. This study aimed to determine the complete genome sequence of A. baumannii strain A1296 and to perform a comparative analysis among A. baumannii.. The complete genome sequence of A. baumannii A1296 was sequenced on two SMRT cells using P6C4 chemistry on a PacBio Single Molecule, Real-Time (SMRT) RS II instrument. The A1296 genome sequence was annotated using Prokaryotic Genome Automatic Annotation Pipeline (PGAAP), and the sequence type and resistance genes of the strain were analysed.. Here we present the complete genome sequence of A. baumannii strain A1296, belonging to a novel sequence type (ST1469) and isolated from patient in China, that was sensitive to multiple antibiotics. The genome of A. baumannii A1296 was 3810701bp in length, including one circular chromosome and two plasmids. The tet(39) resistance gene was located on the small plasmid in this A. baumannii strain.. The genome sequence of A. baumannii strain A1296 can be used as a reference sequence for comparative analysis aimed at elucidating the acquisition, dissemination and mobilisation of resistance genes among A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Cerebral Hemorrhage; China; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Sequence Annotation; Plasmids; Sequence Analysis, DNA; Tetracycline

Intracranial hemorrhage in preterm neonates may result in neonatal mortality and functional disabilities, but its pathogenic mechanisms are poorly defined and better therapies are needed. We used a tetracycline-regulated transgenic system to test whether the induction of vascular endothelial growth factor (VEGF) in the germinal matrix leads to intracranial hemorrhage. This genetic strategy initially induced a dense network of loosely adjoined endothelial cells and pericytes near lateral ventricles, similar to the immature vascular rete in human fetal brains. Yet, this rich vascular network transformed into low-vasculature patches correlated with hemorrhage and caspase-3 activation near birth. Gene expression and biochemical analyses suggested that downstream mediators of VEGF in this network include transcriptional factors ETS1 and HIF2α (hypoxia-inducible factor 2α), components of the PDGFβ (platelet-derived growth factor β) and TGFβ (transforming growth factor-β) receptor signaling pathways, matrix metalloproteinase-9 (MMP-9), and cathepsins. Prenatal administration of glucocorticoids markedly reduced mortality and cerebral hemorrhage in mutant animals, as in human neonates. This protective effect was not due to blocking vasculogenesis, but was instead associated with inhibition of neurovascular proteases, notably MMP-9, cathepsin B, and caspase-3. Collectively, these results support a causative role of VEGF in perinatal cerebral hemorrhage and implicate its downstream proteases as potential therapeutic targets.

Topics: Animals; Animals, Newborn; Betamethasone; Caspase 3; Cathepsin B; Cerebral Hemorrhage; Disease Models, Animal; Embryo, Mammalian; Enzyme Activation; Enzyme Induction; Gene Expression Profiling; Glucocorticoids; Humans; Matrix Metalloproteinase 9; Mice; Neovascularization, Pathologic; Peptide Hydrolases; Phenotype; Prosencephalon; Protease Inhibitors; Tetracycline; Vascular Endothelial Growth Factor A

Three cases of probable neurobrucellosis are reported. The diagnosis was made on the basis of immunological tests. Two patients with a clinical picture of meningomyelitis showed a definitive clinical improvement under tetracycline and streptomycin therapy. The immunological reactions found in the record case were even more positive in the spinal fluid than in the blood. In the case 3 with a clinical presentation of cerebral hemorrhage the histopathological studies demonstrated non specific chronic leptomeningitis and local hemorrhages in the caudate nucleus bilaterally. The diagnose and treatment of neurobrucellosis are discussed, stressing the importance of an early therapy.

Topics: Adolescent; Adult; Brucella; Brucellosis; Cerebral Hemorrhage; Female; Humans; Male; Meningitis; Myelitis; Peripheral Nervous System Diseases; Serologic Tests; Tetracycline

Topics: Adolescent; Brain; Brain Diseases; Brain Edema; Cerebral Hemorrhage; Child; Craniocerebral Trauma; Diagnosis, Differential; Encephalitis; Encephalocele; Humans; Hydrocephalus; Infant; Intracranial Pressure; Meningitis; Papilledema; Pseudotumor Cerebri; Spinal Puncture; Tetracycline; Tomography, X-Ray Computed; Vitamin A

Topics: Anti-Bacterial Agents; Bronchopneumonia; Candidiasis; Cerebral Hemorrhage; Chlortetracycline; Encephalitis; Erythromycin; Humans; Influenza, Human; Intracranial Embolism; Intracranial Embolism and Thrombosis; Neuritis; Pathology; Penicillins; Streptomycin; Tetracycline; Thrombophlebitis