In Japan the incidence of atypical mycobacteriosis has steadily increased, with Mycobacterium avium-intracellulare complex (MAC) the most common infecting organism. A standard chemotherapy regimen for MAC infection has not been established because of significant resistance to anti-mycobacterial drugs. Sparfloxacin has good antimicrobial activity against several acid-fast bacteria and is expected to be an effective drug for treating mycobacteriosis. We examined the effects of adding sparfloxacin to anti-tuberculotic combination therapy in six patients with MAC pulmonary disease. Drug susceptibility was also assessed using the agar dilution method. The minimum inhibitory concentrations (MICs) for sparfloxacin, levofloxacin, isoniazid, rifampicin, streptomycin, ethambutol and clarithromycin was measured in clinical isolates from all patients; sparfloxacin showed the lowest MIC. Bacteriological and clinical improvements were observed in the four patients who completed the study. Dosing was discontinued in two patients because of pruritic skin eruptions. Sparfloxacin shows promise as an anti-mycobacterial agent for treating MAC pulmonary disease.

Aged↗

PubMedDate not supplied

Usefulness of sparfloxacin against Chlamydia pneumoniae infection in patients with bronchial asthma.

The efficacy of sparfloxacin (SPFX) for the control of bronchial asthma was evaluated in 26 patients with suspected Chlamydia pneumoniae infection. Patients were randomly allocated to receive SPFX 200 mg/day (n = 14) or control treatment (n = 12) for 21 days. Significant improvements in serum C-reactive protein levels, and significant decreases in peripheral eosinophil counts, serum eosinophil cationic protein (ECP) and sputum ECP were observed in the SPFX-treated group at day 21. SPFX-treated patients also had a significantly reduced frequency of asthma symptoms, reduced inhalant beta2-stimulant use, and significant increases in morning peak expiratory flow. At the end of the study, C. pneumoniae was undetectable in two SPFX-treated patients who underwent polymerase chain reaction testing, but one control patient who was tested still had detectable levels of C. pneumoniae. These results suggest that SPFX could be used to control bronchial asthma in patients with suspected persistent C. pneumoniae infection.

Administration, Inhalation↗

PubMedDate not supplied

Shear stress induces not only platelet aggregation but also platelet-tumor cell interaction.

To investigate the interaction between platelets and tumor cells under well-defined flow conditions, the effect of tumor cells on platelet aggregation induced by shear stress was studied using a cone and plate viscometer adapted for measuring transmitted light intensity. Aggregation was markedly enhanced by HMV-1 cells in a cell number-dependent fashion under shear stress of 12 dyne/cm2. Enhancement was not observed at a high shear stress of 108 dyne/cm2. A monoclonal antibody against GPIIb/IIIa, 7E3 completely abolished enhancement of aggregation by HMV-1. Apyrase had similar inhibitory effects. Scanning electronmicroscopy showed that direct contacts of platelets with HMV-1 cells could be demonstrated when platelet-platelet interaction was inhibited by 7E3 or apyrase. These results may indicate that, at a shear stress of 12 dyne/cm2, direct contacts of platelets and HMV-1 cells may trigger enhancement of platelet aggregation.

Blood Flow Velocity↗

PubMedDate not supplied

Change in intracellular calcium ions during shear induced platelet aggregation.

The authors have developed a method to measure intracellular calcium ion concentration ([Ca2+]i) during shear-induced platelet aggregation. A cone and plate viscometer was adapted for continuous recording of both light transmission and fluorescence intensity. Citrated platelet rich plasma was incubated with Indo-1AM at a concentration of 10 microns for 30 min at 37 degrees C, then applied to the albumin density gradient to prepare washed platelets. To Indo-1AM loaded washed platelets, fibrinogen, and von Willebrand factor (vWf) were added, with 1 mM CaCl2. Platelets were then exposed to changing shear stress (6-108 dynes/cm2) for simultaneous measurement of aggregation and [Ca2+]i. [Ca2+]i in resting platelets was estimated as approximately 100 nM. At low shear stress (10-20 dynes/cm2), [Ca2+]i did not change. In contrast, a marked increase in [Ca2+]i was observed concurrent with aggregation at high shear stress (100-108 dynes/cm2). However, no increase was seen in the presence of 1 mM EGTA. The increase was prevented by monoclonal antibodies against GPIb or vWf, which inhibited vWf binding to GPIb. A monoclonal anti-vWf antibody, which inhibited vWf binding to the GPIIb/IIIa complex, did not affect [Ca2+]i increase during high shear induced platelet aggregation. These results suggest that binding of vWf to GPIb may trigger Ca2+ influx.

Blood Flow Velocity↗

PubMedDate not supplied

Dexamethasone hypertension in rats: role of prostaglandins and pressor sensitivity to norepinephrine.

Glucocorticoid hypertension was induced by oral administration of dexamethasone (DX) in male Wistar rats. The mechanism of hypertension was studied by observing the changes in plasma renin activity, urinary excretion of prostaglandin E2 (PGE2), and the pressor response to norepinephrine. Following administration of DX (0.1 mg/day), the blood pressure began to rise within 3 days and reached a plateau on the 5th day (from 108 +/- 2 to 162 +/- 7 mm Hg, mean +/- SE). On the other hand, urine volume and urinary excretion of sodium were increased. In spite of the marked natriuresis and diuresis, the administration of DX resulted in a marked decrease in the urinary excretion of PGE2. This decrease in PGE2 excretion appeared before the blood pressure rose and continued throughout the experiment. Plasma renin activity did not change. The pressor response to norepinephrine was enhanced on the 2nd day of DX treatment, at which time the blood pressure was not yet elevated, and it was further augumented on the 6th day. In the DX-treated rats, the pressor response to norepinephrine was not enhanced by administration of indomethacin, whereas the pressor response was significantly potentiated by indomethacin in control rats. These results suggest that DX-induced hypertension in rats is associated with inhibition of prostaglandin synthesis leading to increased sensitivity in the vascular response to norepinephrine.

Animals↗