Hormonal changes during a 20-week confinement

BACKGROUND: When the European Space Agency planned the EUROMIR'95 long-duration flight with a European astronaut on board the Russian orbital MIR station, it organized simultaneously a ground simulation, called the Human Behaviour Study, of this manned space mission. The ground simulation was a confinement experiment, and this paper describes the changes in volume-regulating hormones that occurred during and after 20 weeks of confinement. METHODS: In a normobaric diving chamber, 3 subjects were confined for 135 d. Arterial pressure, plasma concentrations of blood volume-regulating hormones (active renin and arginine-vasopressin), and urinary variables (aldosterone, arginine-vasopressin, and metabolites of catecholamines) were measured before, during, and after confinement. RESULTS: Arterial pressure was increased from week 1 until week 15 of confinement, while heart rate was elevated from week 6 until the end of the simulation. Plasma active renin was elevated throughout the confinement (after week 6). Urine volume increased transitively on the first 2 d of confinement. CONCLUSIONS: The results obtained during this long-term confinement experiment have major importance regarding concerns about spaceflight and bed rest data, because we observed hormonal changes during the experiment that normally are assigned to the fluid shift that occurs in weightlessness or in the head-down tilt position (i.e., an increase of renin, an increase of urinary volume during the first two days, and a decreased urinary cyclic guanosine monophosphate.     

Potent and selective bicyclic lactam inhibitors of thrombin: Part 2: P1 modifications

The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors is described. We have explored the SAR with modifications to the P1 site. The introduction of arginine mimetics at the P1 site led to potent and selective thrombin inhibitors.     

Gd-DPTA enhanced MRI in Bell's palsy and herpes zoster oticus: an overview and implications for future studies

Magnetic resonance imaging (MRI) is a new and important tool for use in diagnosing and investigating diseases affecting the facial nerve. In recent gadolinium-DTPA enhanced MRI (Gd-MRI) studies it has unequivocally been demonstrated that ipsilateral facial nerve contrast enhancement, predominantly in the meatal portion, is present in both Bell's palsy and herpes zoster oticus. In this overview, the results of MRI studies performed on patients with acute peripheral facial palsy, especially Bell's palsy and herpes zoster oticus, are discussed. The Gd-MRI pattern in Bell's palsy is very similar to that seen in herpes zoster oticus, and the findings reported so far support the theory that an inflammation may be the cause of the nerve injury in both cases. So far, however, Gd-MRI has not been helpful in evaluating the severity and/or prognosis of the facial palsy. Further studies employing improved techniques, including three-dimensional fast (or turbo) spin echo (3DFSE) MRI with heavily T2-weighted sections and high resolution three-dimensional Fourier transform (3DFT) MRI, need to be conducted in order to determine whether it is possible to follow the course of the disease and whether MRI and/or Gd-MRI are useful prognostic tools in the early stages of palsy.     

Isolation of the factor VIII-von Willebrand factor complex directly from plasma by gel filtration

A high capacity gel filtration system was developed with the purpose of isolating factor VIII (FVIII) and von Willebrand factor (vWF) directly from plasma in significantly higher yields than obtained by cryoprecipitation, the technique most commonly used to recover FVIII-vWF from human plasma. After laboratory-scale gel filtration of plasma, a FVIII-containing fraction was collected containing about 90% of FVIII in the applied plasma and with almost tenfold higher purity than that obtained by cryoprecipitation. The gel filtration step has been scaled up for use as the initial step in the manufacturing process for a FVIII preparation (Nordiate).     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Physiologo-biochemical characteristics if Gluconobacter oxydans and prospects for its use in biotechnology and biosensor systems (review)

Gluconobacter oxydans possesses a unique organization of metabolic systems, which are characterized by reduction of major dissimilation pathways, surface localization of main oxidative enzymes responsible for partial oxidation of carbon substrates, high performance of electron-transport chains, and accumulation of partially oxidized metabolites in the medium. These features allow us to use the cells of these microorganisms in biotechnology for production of several food products and medicines. The use of G. oxydans in biosensors for estimation of concentrations of sugars, aldoses and polyalcohols is promising. Physiological and biochemical features of these microorganisms enabling their use in biotechnology and receptor elements of biosensors are reviewed.     

Identification and characterization of human metabolites of CAI [5-amino-1-1(4''-chlorobenzoyl-3,5-dichlorobenzyl)-1,2,3-triazole- 4-carboxamide)

BACKGROUND: Bronchoscopic bronchoalveolar lavage in children to investigate bronchial disorders such as asthma has both ethical and procedural difficulties. OBJECTIVE: The aim of this study was to establish a standardized non-bronchoscopic method to perform bronchoalveolar lavage in children attending for elective surgery to obtain normal cellular data. METHODS: Bronchoalveolar lavage was performed on normal children (n = 55) by infusing saline (20 mL) through an 8 FG suction catheter passed after endotracheal intubation. Oxygen saturation, heart and respiratory rate were monitored during the bronchoalveolar lavage procedure. Cellular analysis and total protein estimation of the lavage fluid were performed. Epithelial lining fluid volume was calculated (n = 15) using the urea dilution method. RESULTS: The procedure was well tolerated by all children. Total cell count and differential cell count for children (macrophages 70.8 +/- 2.3%, lymphocytes 3.8 +/- 0.6%, neutrophils 5.7 +/- 1.0%, eosinophils 0.14 +/- 0.03%, epithelial cells 19.6 +/- 2.1%, mast cells 0.21 +/- 0.02%) were similar to those reported for adults. Age and sex comparisons revealed no differences between groups. The mean total protein recovered in the cell free supernatant was 49.72 +/- 4.29 mg/L and epithelial lining fluid volume was 0.82 +/- 0.11% of return lavageate. CONCLUSION: This method allows bronchoalveolar lavage to be performed safely and quickly on children attending for routine elective surgery. Using this method and taking the 'window of opportunity' of elective surgery, the presence or absence of airway inflammation could be studied in children with various patterns of asthma during relatively asymptomatic periods.