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Biomedical subjects

N Ramos

Publications and source records attributed to N Ramos.

7 recordsLinked to original sources
PubMed2001

Protamine inhibits tissue factor-initiated extrinsic coagulation.

The enhanced extrinsic coagulation in response to inflammation could contribute to disseminated intravascular coagulation, often manifesting cardiovascular complications. The complex mechanism remains unclear and effective management is not well established. The ability of protamine to offset bacterial endotoxin (LPS)-induced tissue factor (TF)-initiated extrinsic coagulation was demonstrated in human peripheral blood monocytes and cultured human leukaemia THP-1 monocytes, which was consistent with the inhibition of rabbit brain thromboplastin (rbTF) procoagulant activity in a cell-free in vitro model. Protamine significantly prolonged prothrombin time, further confirming the downregulation of the extrinsic pathway. However, thrombin time remained unaltered. Chromogenic assays were performed to dissect the extrinsic pathway, identifying inhibitory site(s). Protamine significantly inhibited factor VII (FVII) activation but not the dissected FX activation. The amidolytic activities of FVIIa and FXa were unaffected. The inhibited FVII activation in the presence of protamine was confirmed by the diminished FVIIa formation on Western blot analyses. Protamine preferentially inhibited TF-catalysed FVII activation, downregulating the extrinsic cascade. Protamine could be of anticoagulant significance in the management of the extrinsic hypercoagulation.

Anticoagulants↗
PubMed1999

Compound 48/80 suppresses monocytic tissue factor-initiated extrinsic blood coagulation induced by bacterial endotoxin.

BACKGROUND: Hypercoagulability is one of the commonly exhibited endotoxemia septic symptoms; it could contribute to the manifestation of disseminated intravascular coagulation presenting threats to cardiovascular functions. The underlying mechanism, however, remains largely complex and unknown. OBJECTIVES: We herein determine whether bacterial endotoxin (LPS) upregulates the activities of clotting factors in plasma, contributing to extrinsic hypercoagulation. Compound 48/80 (48/80) is also tested for its ability to suppress hypercoagulation. METHODS: In an in vitro infection model, we exposed whole blood to LPS (Escherichia coli 0111:B04; 100 ng/ml) for 2 h. Thrombin time (TT), prothrombin time (PT), and the activities of clotting factors ( FVII, FIX, FX ) in plasma contributing to the extrinsic coagulation were determined. Peripheral blood monocytes were isolated from Histoplaque 1077 gradient centrifugation, and the procoagulant activity was determined by a single-stage clotting assay on a Fibrometer. RESULTS: LPS drastically activated monocytic procoagulant activity which was defined as tissue factor (TF) activity, whereas LPS had no effect on TT, PT, and the activities of clotting factors in plasma. 48/80 not only instantaneously offset LPS-induced monocytic TF activation, but also significantly inhibited PT including the activities of clotting factors (FVII, FIX, and FX) in plasma, whereas TT remained unaffected. CONCLUSIONS: Monocytic TF activation was solely responsible for the extrinsic hypercoagulation in response to LPS. 48/80 effectively suppressed LPS-induced monocyticTF-initiated extrinsic coagulation at multiple sites, possibly presenting a new therapy for an instantaneous relief of hypercoagulation under septic conditions.

Blood Coagulation↗
PubMed1998

Paralytic shellfish poisoning: clinical and electrophysiological observations.

In paralytic shellfish poisoning a mollusc contaminated with a toxin (saxitoxin) causes a potentially lethal disease, clinically characterised by gastrointestinal and neurological symptoms, of which possible respiratory depression is the most serious. The toxin acts by blocking the sodium channels. We report 9 Portuguese patients with this disease. The mollusc was identified as Mytilus edulis, contaminated with the dinoflagellate Gymnodinium catenatum, and the toxin saxitoxin. Our patients had a benign clinical course with cerebellar ataxia as the most severe neurological impairment. Eight out of 9 patients had neurophysiological investigations, the largest number so far reported. Motor and sensory conduction velocities and amplitudes were normal. The proximal conduction times, as assessed by F waves, showed delayed conduction and decreased frequency, which returned to normal in few weeks. The somatosensory evoked potentials confirmed normal peripheral and central sensory conduction. The rich vascular supply at root level of the sodium channels of the proximal motor nerves may explain the greater vulnerability to toxin damage. The typically transient and quickly reversible nerve dysfunction caused by ion channel blockade is reported.

Adult↗