Elastase in hyperpnea-induced guinea pig airway constriction

Aerosolized elastase has been shown to produce airway constriction in guinea pigs. In this study, we examined whether endogenous elastase plays a role in isocapnic hyperpnea-induced airway constriction using an elastase inhibitor, eglin-c. The study was divided into three experiments. In the first experiment, we used an elastase inhibitor, eglin-c, to suppress hyperpnea-induced bronchoconstriction. Twenty-two young male Hartley guinea pigs were divided into three groups: control (n=8), eglin-c(1) (a lower dose of eglin-c, n=7), and eglin-c(2) (a higher dose of eglin-c, n=7). In the second experiment, we tested whether eglin-c affects pulmonary function following 15 min of normal air ventilation in two groups of animals: control (n=8) and eglin-c (n=8). In the third experiment, animals were divided into two groups: control (n=7) and compound 48/80 (a mast cell degranulating agent, n=7). Airway function was examined in the anesthetized-paralyzed animal. In the first and third experiments, 15 min of isocapnic hyperpnea caused marked decreases in dynamic respiratory compliance, forced expiratory flow at 0.1 s and maximal expiratory flow at 50% total lung capacity, demonstrating hyperpnea-induced airway constriction. This bronchoconstriction was significantly attenuated by eglin-c and by pretreatment with compound 48/80. In the second experiment, eglin-c did not significantly affect bronchial function following normal air ventilation. These data suggest that elastase released from mast cells directly or indirectly induces hyperpnea-induced bronchoconstriction.     

Four new sesquiterpenes from Petasites formosanus

Four new eremophilane-type sesquiterpenes, petasones A (1) and B (2), S-petasitin (3), and petasinol (4), were isolated from the aerial parts of Petasites formosanus. Their structures were elucidated by spectroscopic and chemical methods as 3alpha-[(Z)-3-methylsulfinylacryloxy]eremophila-7(11), 9-dien-8-one; 3alpha-[(E)-3-methylsulfinylacryloxy]eremophila-7(11), 9-dien-8-one; 3alpha-[(Z)-3-methylthioacryloxy]-11-hydroxyeremophila -6, 9-dien-8-one; and 3alpha-[(E)-3-methylsulfinylacryloxy]-8beta-hydroxy eremophila-9, 11-diene, respectively.     

Conformation of native, reduced and [5-55]Ala bovine pancreatic trypsin inhibitor in the gas phase

BACKGROUND: The effect of high levels of linear acceleration (G) on the cochlea has never been studied prospectively. HYPOTHESIS: Linear acceleration at high levels has no effect on the human cochlea as demonstrated by a comparison of pre- and post-exposure measurements. METHODS: There were 22 healthy volunteers who underwent exposure to up to 9 G in a military aviation training centrifuge. Prior to exposure they were screened for cochleovestibular disorders and underwent tympanometry, audiometry and distortion product otoacoustic emissions testing (DPOAE). Immediately after exposure, they underwent serial testing of each of these parameters until they returned to baseline. RESULTS: There was no significant change in tympanometry in any subject. Audiometry revealed a temporary threshold shift of 30 db at 6 kHz in one ear of a single subject. This was accompanied by a complete loss of DPOAE at the same frequency. DPOAE did not return to baseline at 2 weeks even though the audiogram had reverted to baseline by 8 d. Four other ears displayed significant losses of emissions at single frequencies without an accompanying change on the audiogram. CONCLUSIONS: This study demonstrates that accelerative stress may cause transient injury to the cochlea. The mechanism of injury due to acceleration is probably ischemia, although a purely mechanical effect on the outer hair cells cannot be precluded. These data also reinforce a growing body of evidence that demonstrates the greater sensitivity of DPOAE over psychoacoustic testing in detecting early or subclinical cochlear damage.     

Low dietary protein impairs blood coagulation in BHE/cdb rats

The influence of dietary protein on blood coagulation tests was evaluated in BHE/cdb rats. Three experiments were conducted in order to compare effects of diets with low (8 g/100 g diet) or high (38 g/100 g diet) protein, to establish values for coagulation tests at intermediate (12-30 g/100 g diet) concentrations of dietary protein, and to compare feeding identical quantities of diets with 8 g protein/100 g diet vs. 18 g protein/100 g diet. After 4 wk of feeding the semipurified diets, bleeding time exceeded 15 min in the groups fed low protein diets, compared to a range of 3-6 min for the groups fed high protein diets. Several in vitro tests of coagulation were abnormal in the rats fed low protein diets. For example, prothrombin time averaged 27 +/- 8 s in rats fed 8 g protein/100 g diet plus beef tallow, but 17 +/- 1 s in rats fed 38 g protein/100 g diet plus tallow. The coagulation deficit in rats fed low protein was not affected by fat source (tallow vs. menhaden oil), but fibrinogen was elevated in rats fed diets with menhaden oil. Conversely, no differences in coagulation tests were observed among rats fed 12-30 g protein/100 g diet. Bleeding times ranged from 7 to 9 min, and prothrombin time was 17-18 s. Significant differences in plasma fibrinogen concentration and prothrombin time were observed in rats fed 8 vs. 18 g protein/100 g diet at a fixed rate of 6 g/100 g body weight. Platelet and blood cell numbers were unaffected by dietary protein. The evidence for multiple deficits in the coagulation system suggests that hepatic function in BHE/cdb rats may become impaired when the rats are fed low protein diets of the composition used here.     

Electrophysiological features in the management of meralgia paraesthetica

Meralgia paraesthetica is a condition which presents with pain and paresthesia over the anterolateral thigh, due to entrapment of the lateral femoral cutaneous nerve. Our local experience of 12 cases highlights the usefulness of antidromic sensory nerve conductions in the diagnostic and prognostic aspects of this condition. Follow-up studies suggest that patients with initial reduction rather than absent sensory amplitudes on the affected side more likely to experience symptomatic improvement over an 8 to 24 month period.     

Taxol induces concomitant hyperphosphorylation and reorganization of vimentin intermediate filaments in 9L rat brain tumor cells

Taxol, a microtubule stabilizing agent, has been extensively investigated for its antitumor activity. The cytotoxic effect of taxol is generally attributed to its antimicrotubule activity and is believed to be cell cycle dependent. Herein, we report that taxol induces hyperphosphorylation and reorganization of the vimentin intermediate filament in 9L rat brain tumor cells, in concentration- and time-dependent manner. Phosphorylation of vimentin was maximum at 10(-6) M of taxol treatment for 8 h and diminished at higher (10(-5) M) concentration. Enhanced phosphorylation of vimentin was detectable at 2 h treatment with 10(-6) M taxol and was maximum after 12 h of treatment. Taxol-induced phosphorylation of vimentin was largely abolished in cells pretreated with staurosporine and bisindolymaleimide but was unaffected by H-89, KT-5926, SB203580, genistein, and olomoucine. Thus, protein kinase C may be involved in this process. Hyperphosphorylation of vimentin was accompanied by rounding up of cells as revealed by scanning electron microscopy. Moreover, there was a concomitant reorganization of the vimentin intermediate filament in the taxol-treated cells, whereas the microtubules and the actin microfilaments were less affected. Taken together, our data demonstrate that taxol induces hyperphosphorylation of vimentin with concomitant reorganization of the vimentin intermediate filament and that this process may be mediated via a protein kinase C signaling pathway.