thromboxane-b2 and Headache

This multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessed renal function during dosing with etoricoxib 90 mg daily, celecoxib 200 mg twice daily, and naproxen 500 mg twice daily. Male and female subjects 60 to 81 years old (n = 85), in sodium balance on a controlled, normal sodium diet, were treated for 15 days. There were no clinically meaningful between-treatment differences in urinary sodium excretion, creatinine clearance, body weight, or serum electrolytes during the 2 weeks of treatment. Etoricoxib and celecoxib had no effect on the urinary thromboxane metabolite, 11-dehydrothromboxane B(2), while significantly decreasing the urinary prostacyclin metabolite, 2,3-dinor-6-keto PGF(1alpha). Decreases were greater for both metabolites following naproxen. Ambulatory systolic blood pressures were significantly higher than placebo for all treatments, with moderately greater increases for etoricoxib relative to other active treatments on day 14. Ambulatory diastolic blood pressures were significantly higher than placebo for etoricoxib and naproxen but not for celecoxib.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Celecoxib; Constipation; Creatinine; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Electrolytes; Etoricoxib; Female; Headache; Humans; Male; Middle Aged; Naproxen; Potassium; Prostaglandins; Pyrazoles; Pyridines; Sodium; Sulfonamides; Sulfones; Thromboxane B2

D-003 is a mixture of very high molecular weight aliphatic acids purified from sugar cane wax showing cholesterol-lowering and antiplatelet effects proven in experimental and clinical studies. Experimental evidence indicates that inhibition of platelet aggregation induced by D-003 is associated with a reduction of thromboxane B2 (TxB2) and an increase of prostacyclin (Pgl2) serum levels. This double-blinded, randomized, placebo-controlled study was undertaken to investigate whether D-003 (20 mg/day) modifies serum levels of TxB2 and Pgl2 and inhibits platelet aggregation in human healthy volunteers. Thirty-one subjects were randomized to placebo or D-003 at 20 mg/day for 14 days. Serum levels of TxB2 and Pgl2 and platelet aggregation to arachidonic acid (AA) (1.75 mM) and collagen (1 microg/ml) were assessed. D-003 (20 mg/day) significantly reduced (p < 0.001) TxB2by 36.4% and increased Pgl2 serum levels by 31% compared with baseline, and these changes were different from placebo. As expected, D-003 significantly inhibited (p < 0.001) platelet aggregation to AA (81.9-65.6%) and to collagen (75.3-62.3%). No subject withdrew from the study. No drug-related disturbances were observed. We conclude that D-003 at 20 mg/day for 14 days significantly inhibited platelet aggregation to AA and collagen and reduced TxB2 and increased Pgl2 serum levels. These results are consistent with those observed in experimental models, indicating that the antiplatelet effect of D-003 is associated with the observed changes on the levels of AA metabolites. Further studies, however, should explore the mechanism involved in this action in greater depth.

Topics: Adult; Arachidonic Acids; Asthenia; Collagen Type I; Double-Blind Method; Drug Administration Schedule; Epoprostenol; Fatty Acids; Female; Headache; Humans; Male; Middle Aged; Plant Extracts; Platelet Aggregation; Saccharum; Tablets; Thromboxane B2; Time Factors; Waxes

A clinical study was conducted to determine the effect of IVIG infusion rates on adverse experiences (AE) and on serum levels of cytokines and vasoactive substances.. Forty-two healthy volunteers were randomized into 3 groups with maximum IVIG infusion rates of 0.04, 0.06, and 0.08 ml/kg/min, and a final dose of 0.5 g IgG/kg body weight.. Adverse reactions were noted only at the highest infusion rate of 0.08 ml/kg/min, except in 1 subject infused at 0.06 ml/kg/min. There were significant increases in IL-6 (p = 0.011) and thromboxane B2 (p = 0.007) in AE subjects as compared to non-AE subjects.. IVIG-induced adverse reactions occur more often with rapid infusion rates and may be mediated by elevated levels of inflammatory cytokines and vasoactive substances.

Topics: Adult; Chymases; Cytokines; Dizziness; Headache; Histamine; Humans; Immunoglobulins, Intravenous; Inflammation Mediators; Interleukin-1; Interleukin-6; Kininogen, High-Molecular-Weight; Leukocyte Count; Lymphocytes; Male; Neutrophils; Serine Endopeptidases; Thromboxane B2; Time Factors; Tryptases; Tumor Necrosis Factor-alpha; Vasomotor System

We encountered a 10-year-old girl with fluctuating sensorineural hearing loss, episodic headache, and white matter stroke. Strenuous exercise, febrile illness, and general anesthesia all temporarily worsened hearing. Audiologic findings were asymmetric: left-sided retrocochlear dysfunction consistent with auditory neuropathy contrasted with cochlear hearing loss in the right ear. Platelets obtained during a headache-free period showed excessive responsiveness to collagen in vitro, while episodic elevations of thromboxane B(2) and thrombin-antithrombin III complex were noted in blood sampled during headache. Treatment of hyperaggregability of platelets with aspirin and antioxidant vitamins relieved headache, while adenosine triphosphate administration improved hearing thresholds. In this patient, hearing impairment and white matter strokes appeared to respectively related to impaired blood flow to the cochlea and white matter caused by platelet dysfunction triggered by physiologic stresses.

Topics: Adenosine Triphosphate; Antithrombin III; Audiometry; Blood Platelets; Child; Collagen; Evoked Potentials, Auditory, Brain Stem; Female; Functional Laterality; Headache; Hearing Loss, Sensorineural; Humans; Magnetic Resonance Imaging; Peptide Hydrolases; Platelet Aggregation; Stroke; Thromboxane B2