A furostanol saponin from fruits of Balanites aegyptiaca

A new furostanol saponin was isolated from the mesocarp of Balanites aegyptiaca fruits and identified as 26-O-beta-D-glucopyranosyl-(25R)-furost-5-ene-3,22,26-triol 3-O-[[alpha-L-rhamnopyranosyl-(1-->2)]-[beta-D-xylopyranosyl-(1-->2)]-be ta- D-xylopyranosyl-(1-->2)]-beta-D-xylopyranoside (balanitesin).     

Dieldrin in fish and shellfish from the Mersey Estuary and Liverpool Bay

OBJECT: The authors studied the reliability of a new method for noninvasive assessment of cerebral perfusion pressure (CPP) in head-injured patients in which mean arterial blood pressure (ABP) and transcranial Doppler middle cerebral artery mean and diastolic flow velocities are measured. METHODS: Cerebral perfusion pressure was estimated (eCPP) over periods of continuous monitoring (20 minutes-2 hours, 421 daily examinations) in 96 head-injured patients (Glasgow Coma Scale score < 13) who were admitted to the intensive care unit. All patients were sedated, paralyzed, and ventilated. The eCPP and the measured CPP (ABP minus intracranial pressure, measured using an intraparenchymal microsensor) were compared. The correlation between eCPP and measured CPP was r=0.73; p < 10(-6). In 71% of the examinations, the estimation error was less than 10 mm Hg and in 84% of the examinations, the error was less than 15 mm Hg. The method had a high positive predictive power (94%) for detecting low CPP (< 60 mm Hg). The eCPP also accurately reflected changes in measured CPP over time (r > 0.8; p < 0.001) in situations such as plateau and B waves of intracranial pressure, arterial hypotension, and refractory intracranial hypertension. A good correlation was found between the average measured CPP and eCPP when day-by-day variability was assessed in a group of 41 patients (r=0.71). CONCLUSIONS: Noninvasive estimation of CPP by using transcranial Doppler ultrasonography may be of value in situations in which monitoring relative changes in CPP is required without invasive measurement of intracranial pressure.     

Accuracy of portable chest radiography in the critical care setting. Diagnosis of pneumonia based on quantitative cultures obtained from protected brush catheter

Sixty-six supine portable chest radiographs done on the day of bronchoscopy in 62 critical care unit patients suspected of having pneumonia were examined in a blinded fashion by two radiologists. Quantitative culture results obtained from protected brush catheter (PBC) specimens were compared with chest radiograph scores. For one observer, the sensitivity of the chest radiograph for predicting the presence of positive culture results was 0.60, specificity was 0.29, overall agreement was 0.41, positive predictive value was 0.34, and negative predictive value was 0.55. For the second observer, the values were as follows: sensitivity, 0.64; specificity, 0.27; overall agreement, 0.41; positive predictive value, 0.35; and negative predictive value, 0.55. The kappa statistic was calculated at 0.27 indicating marginal interobserver reproducibility. We conclude the portable chest radiograph in the critical care setting is not accurate in predicting the presence of pneumonia when the diagnosis is based on quantitative cultures obtained from protected brush catheter specimens.     

Cleavage of Müllerian inhibiting substance activates antiproliferative effects in vivo

Müllerian inhibiting substance (MIS), an inhibitor of growth and development of the female reproductive ducts in male fetuses, requires precise proteolytic cleavage to yield its biologically active species. Human plasmin is now used to cleave and, thereby, activate immunoaffinity-purified recombinant human MIS at its monobasic arginine-serine site at residues 427-428. To avoid the need for exogenous enzymatic cleavage and to simplify purification, we created an arginine-arginine dibasic cleavage site (MIS RR) using site-directed mutagenesis to change the serine at position 428 (AGC) to an arginine (cGC). The mutant cDNA was then stably transfected into a MIS-responsive ocular melanoma cell line, OM431, followed by cloning for amplified expression to test its biological activity in vitro and in vivo. Media from each clone were assayed for production of MIS RR by a sensitive ELISA for holo-MIS, and high- and low-producing clones were selected for further study. Media from the highest MIS RR producer caused Müllerian duct regression in an organ culture bioassay. Other transfections were done with an empty vector (pcDNAI Neo) or a construct lacking the leader sequence and thus failing to secrete MIS, to serve as controls. The OM431 clones containing the MIS RR mutant were growth inhibited in monolayer culture. The high- and low-producing MIS RR OM431 clones, along with transfected OM431 controls, were injected into the tail veins of immunosuppressed severe combined immunodeficiency mice for in vivo analyses. Four to 6 weeks later, pulmonary metastases were counted in uniformly inflated lungs. OM431 clones containing the more easily cleaved MIS RR displayed a significant dose-dependent reduction in pulmonary metastases when compared to the lungs of animals given injections of OM431 clones containing empty vector, leaderless MIS, or wild-type MIS that requires activation by plasmin cleavage. Since the purification protocol of MIS RR is less complicated than that for wild-type MIS, which requires subsequent enzymatic activation, MIS RR can be used for scale-up production with increased yields for further therapeutic trials against MIS-sensitive tumors.     

The effect of Pseudomonas aeruginosa infection on clinical parameters in steady-state bronchiectasis

STUDY OBJECTIVE: To investigate the effect of Pseudomonas aeruginosa infection on clinical parameters in Chinese patients with noncystic fibrosis and steady-state bronchiectasis. DESIGN: Prospective, cross-sectional clinicomicrobiological study with informed consent. SETTING: Consecutive outpatient recruitment from a specialist bronchiectasis respiratory clinic. PATIENTS: Outpatients (n = 100; 62 women; 55.1+/-16.7 years old; FEV1/FVC 1.4+/-0.7/2.1+/-0.9 L), who had stable respiratory symptoms for more than 3 weeks. MEASUREMENTS AND RESULTS: Respiratory pathogens isolated from the sputum were: Pseudomonas aeruginosa (33), Haemophilus influenzae (10), Moraxella catarrhalis (2), other Gram-negative bacilli (5), Streptococcus pneumoniae (6), Staphylococcus aureus (5), mycobacteria (3), and yeast (1). Clinical parameters in patients with positive isolation of P aeruginosa were compared with those without the organism in the sputum culture (non-P aeruginosa). In the P aeruginosa group, the FEV1/FVC ratio and sputum volume were lower (p < 0.005) and higher (p < 0.0001), respectively, than those of the non-P aeruginosa group. The FEV1/FVC ratio (< 60%) and sputum volume (grading > 5) were independently associated with a positive sputum isolation of P aeruginosa with odds ratios of 3.1 (confidence interval [CI] 1.2 to 8.4; p < 0.01) and 4.7 (CI 1.6 to 13.3; p < 0.001), respectively. CONCLUSIONS: P aeruginosa is the predominant respiratory pathogen isolated in the sputum of Chinese patients with steady-state bronchiectasis, and its isolation is associated with high sputum output (> or = 75th quartile) and moderately severe airflow obstruction (FEV1/FVC < 60%).     

Injections of D-amphetamine into the ventral pallidum increase locomotor activity and responding for conditioned reward: a comparison with injections into the nucleus accumbens

The nucleus accumbens and ventral pallidum receive dopamine (DA) projections from the mesencephalon. Although DA inputs to the nucleus accumbens are implicated in both locomotion and reward processes, little is known of the behavioural significance of DA in the ventral pallidum. These studies examined the effects of D-amphetamine injected into the nucleus accumbens or ventral pallidum on locomotor activity and responding for a conditioned reward (CR). In the nucleus accumbens D-amphetamine dose dependently (1, 3 and 10 microg) increased locomotion within 5-10 min of injection. Intra-ventral pallidum microinjections of D-amphetamine also increased activity in this dose range, but the effect occurred with a longer latency (5-20 min). The magnitude of the response evoked by ventral pallidum injections was lower than that evoked by nucleus accumbens injections. The GABAA antagonist picrotoxin (0.1 microg) stimulated activity when injected into the ventral pallidum but not the nucleus accumbens, providing a pharmacological dissociation between the two injection sites. In the CR studies, D-amphetamine injected into both sites potentiated responding for a CR previously paired with food delivery, without altering responding on an inactive lever. Picrotoxin injected into the ventral pallidum reduced responding and abolished the selectivity of responding for CR. The results show that DA release in the ventral pallidum enhances locomotion and responding for a CR, providing evidence that DA in the ventral pallidum plays a significant role in the mediation of the effects of D-amphetamine. The failure of picrotoxin to elevate responding for CR despite increasing locomotor activity indicates that pharmacologically-induced blockade of GABAA receptors in the ventral pallidum disrupts goal-directed responding.     

The anaerobic oxidation of hydrazine: a novel reaction in microbial nitrogen metabolism

PURPOSE: Pulmonary involvement (PI) is common in leptospiral infection, usually characterized by hemoptysis and diffuse bilateral infiltrates on chest radiographs. Alveolar haemorrhage (AH) has already been proved by autopsy and some case-reports with fiberoptic bronchoscopy (FB) and bronchoalveolar lavage (BAL). The purpose of this study was 1/to evaluate the incidence of AH in leptospirosis 2/to define the impact of BAL on the early diagnosis of the infection. PATIENTS AND METHODS: FB with BAL were performed in 23 consecutive patients with leptospirosis (13 patients with patent signs of PI: group 1, 10 patients without: group 2). AH was defined by a percentage of siderophages > or = 20% and/or a Golde score > 100 and/or an haemorrhagic aspect of BAL fluid. Culture tests were performed on specific medium. RESULTS: We diagnosed AH in all patients of group 1 and in 7 patients of group 2. Filaments were seen in 6 specimens of BAL fluid, initially thought to be leptospires, but culture tests were negative. CONCLUSION: AH is identified in all cases of leptospirosis with PI. Occult AH often occurs to patients without any respiratory symptom. Physicians should consider leptospiral infection in the differential diagnosis of AH. Culture-tests for leptospirosis in BAL do no help in diagnosing leptospirosis.