Changes in the respiratory system of patients with rheumatoid arthritis--personal observations

13 patients with RA admitted to our Institute with symptoms of respiratory involvement were described. Taking under consideration pulmonary function tests, radiological findings and histological examinations, we recognised 7 cases with interstitial lung disease, 3 cases with recurrent respiratory infection with bronchiectasis, 1 case with pleuritis, 1 with Caplan's syndrome and 1 with alveolar haemorrhage. The role of RF, and treatment with gold in the development of interstitial lung disease, as well as character of physiologic abnormalities concerning the small airways and its potential connection with bronchiolitis were discussed.     

External and internal calibration of the MHC class I-specific receptor Ly49A on murine natural killer cells

Expression of the H-2Dd-specific inhibitory receptor Ly49A on murine NK cells is subject to MHC class I-dependent modulation in vivo. As a result, NK cells in H-2Dd-transgenic mice express low cell surface levels of Ly49A, whereas NK cells from nontransgenic C57BL/6 (B6) mice express high levels. The purpose of this study was to assess the role of MHC class I molecules on the NK cell itself vs those on surrounding cells in this calibration and to test whether the Ly49A levels are subject to regulation in mature NK cells also. Analysis of transgenic mice with mosaic expression of an H-2Dd/Ld transgene showed that MHC class I molecules on surrounding cells (external ligands) and on the NK cell itself (internal ligands) played distinct roles in the determination of Ly49A levels. External ligands were involved in down-regulation of Ly49A levels in vivo, whereas internal ligands kept the down-regulated levels of Ly49A low upon NK cell activation in vitro. Furthermore, in an experimental system based on adoptive transfer of spleen cells, receptor down-regulation of Ly49A occurred as a rapid adaptation process in mature NK cells after interaction with the H-2Dd ligand in vivo. This suggests that Ly49 levels are not fixed but can be changed in mature NK cells when they are exposed to a changed MHC class I environment.     

Gas chromatography in express diagnosis of candidiasis and monitoring of antifungal therapy efficacy by D-arabinitol and mannose levels in pediatric patients]

Methods for preventing and treating Ebola virus hemorrhagic fever are not still available despite the fact that this virus have been studied for 20 years. Methods of immunization of the animals (sheep, goats) non-susceptible to Ebola virus with live virus preparations were developed to obtain the hyperimmune anti-Ebola virus sera required to have highly immune antivirus gamma-globulins. These methods made it possible to obtain the immune sera having high virus-neutralizing antibodies. Caprine immunoglobulins were obtained from sera by fractionation of immune sera by Kohn's method. The neutralization indices of the immunoglobulins obtained were at least Ig. When administered in the first hours of infection, the protective effect of these preparations was shown on guinea pigs infected with LD50 of the strain pathogenic to the animals. Preclinical trials of these immunoglobulins on laboratory animals and clinical trials on volunteers were performed. The preparation was used as a preventive agent when accidents took place at the laboratory working with Ebola virus. The similar preparation from equine sera having high neutralizing and protective properties was elaborated at the Virological Center, Microbiological Institute, Russian Ministry of Defense. Its prophylactic efficiency was also shown in infected gamadrias.     

Fluoride exposure in cervids inhabiting areas adjacent to aluminum smelters in Norway. I. Residue levels

Mandibular fluorine concentrations were determined in 1,425 red deer (Cervus elaphus), 240 moose (Alces alces), and 424 roe deer (Capreolus capreolus) collected in Norway from 1990 to 1993 in seven municipalities in which aluminum smelters are located, in eight neighboring municipalities, and in eight reference areas representing background levels. Background fluorine concentration was significantly correlated with age in all three species. Roe deer had the highest mean background fluorine level in each age group, followed by red deer. Due to differences in fluoride exposure, large variations in bone fluorine residues were evident between locations. In Ardal, the district most severely exposed to fluoride contamination, nine of ten cervids had fluorine concentrations exceeding background levels. The proportions of red deer with fluorine residues exceeding background levels also were high in neighboring municipalities to Ardal. We propose that roe deer are a better biomonitor of local fluoride exposure than red deer and moose, due to their more sedentary behavior.     

Gastric antrectomy with selective gastric vagotomy does not influence gallbladder motility during interdigestive and postprandial periods

Fasting gastrointestinal motility and gallbladder motility during the interdigestive state and in the postprandial period was studied in eight patients who were operated for ulcer disease with an antrectomy and selective gastric vagotomy. Nocturnal motility recording revealed all three phases of the migrating motor complex (MMC) in all but one patient, where no phase III activity was recorded. In the rest of the patients 3-10 events with phase III activity were recorded. At scintigraphy ([75Se]HCAT) a cyclic gallbladder filling and emptying in relation to the MMC cycle was found. Episodes with emptying were confined to phase II and a total of 13 episodes with a median duration of 25 min (range 10-70 min) were observed. A median of 10.7% (6.1-17.7%) of the gallbladder contents was emptied. In a control group of eight healthy young men the values were 13.5 min (9-36 min) and 6.9% (3.7-31.1%), respectively. These differences were not significant. During the postprandial period, a lag period in gallbladder emptying of median 15 min (5-20 min) was observed when food ingestion took place during phase I of the MMC. Thereafter a gradual emptying occurred with a rate of 0.95% min (0.71-1.15%/min). In a control group of healthy young males, the lag period was 13.5 min (9-22.5 min) and the emptying rate 0.61%/min (0.08-0.77%/min). When food ingestion occurred during phase II of the MMC, the lag period of gallbladder emptying in the patient group was median 0 min (0-5 min) and the emptying rate was 0.77%/min (0.33-0.86%/min). The values in the control group were 0 min (-9 to 13.5 min) and 0.76%/min (0.54-2.25%/min), respectively. These differences between the patients and controls were not significant. In conclusion, antrectomy and selective gastric vagotomy do not influence fasting gastrointestinal motility or gallbladder motility during the interdigestive state or in the postprandial period.     

Auxiliary agents for the peroral administration of peptide and protein drugs: synthesis and evaluation of novel pepstatin analogues

The peroral administration of (poly)peptide drugs requires the development of delivery systems, which provide a protective effect toward a gastrointestinal enzymatic attack. A promising strategy for such systems represents polymer-enzyme inhibitor conjugates in which the embedded therapeutic agent is protected. However, the practical use of polymer-inhibitor conjugates has so far been limited by high production costs of these auxiliary agents. To solve this problem for delivery systems shielding from pepsinic degradation, structurally simplified analogues of the pepsin inhibitor pepstatin A have been synthesized. The synthesis of tripeptide analogues, described by McConnell et al., led us to pursue further modifications varying the C-terminus. Our target to attach a spacer moiety-enabling the free access of pepsin to the inhibitor-should be combined with an attractive synthetic approach providing low production costs in large-scale preparation. Structure modifications comprised either the side chain of the third amino acid which served as starting compound designing the C-terminus (L-leucine, L-isoleucine, L-norvaline) as the length of the spacer link, simulated by a linear alkyl group (n-butyl, n-hexyl, and n-octyl). The inhibitory activities which have been evaluated by an enzyme assay were significantly dependent on the nature of the side chain, whereas the length of the spacer had no influence on the inhibitory effect. Analogues bearing the isobutyl or n-propyl moiety as side chain displayed a strong inhibitory effect which was comparable to that pepstatin A. These congeners represent promising auxiliary agents for the peroral administration of (poly)peptide drugs.     

Breast cancer and benign breast disease patients evaluated in relation to oxidative stress

The 'WHO Analgesic Ladder' is a well validated approach for the selection of appropriate analgesic therapy for cancer pain as well as pain in AIDS. The mainstay of analgesic intervention for cancer and AIDS pain of moderate to severe intensity continues to be the appropriate use of opioid analgesics. There is, however, a growing appreciation for the role of adjuvant analgesics, such as antidepressants and other psychotropic medications, at each step of the WHO Analgesic Ladder, particularly in the treatment of neuropathic pain. Knowledge of the indications and usefulness of psychotropic analgesic drugs in cancer and AIDS pain populations will be most important to clinicians practicing in psycho-oncology/AIDS settings, particularly since these drugs are useful not only in the treatment of psychiatric complications of cancer and AIDS, but also as adjuvant analgesic agents in the management of pain. This paper reviews the literature on the use of antidepressants, psychostimulants, neuroleptics, anticonvulsants and other psychotropic analgesics in the management of cancer and AIDS pain. Mechanisms of analgesia, drug selection, and recommendations for clinical usage are discussed. The appropriate and timely use of psychotropic adjuvant analgesic drugs represents an opportunity for active psychiatric contribution to the multidisciplinary management of cancer and AIDS pain.     

Separation of the enantiomers of ibuprofen and its major phase I metabolites in urine using capillary electrophoresis

This report describes a simple, rapid, automated microassay for measuring in vitro changes of oxidative burst of phagocytes following challenge with metals for orthopedic devices. The production of reactive oxygen species (ROS) by polymorphonuclear leukocytes (PMNs) was measured using 2',7'-dichlorofluorescin-diacetate (DCFH-DA) as fluorescent probe. DCFH-DA enters the cells and is oxidized by ROS to fluorescent DCF. The DCF generated was directly proportional to ROS produced intracellularly: The fluorescence intensity was read and converted to an index of ROS production by cells. In our experimental system, granulocytes (PMNs) were isolated from normal human blood and seeded in microplates. To verify if metals could influence ROS production, chromium, cobalt, nickel, molybdenum, titanium, aluminum, and vanadium prepared as aqueous extracts in phosphate-buffered saline were tested onto PMNs using phorbolmyristate acetate (PMA) as positive control. Molybdenum, aluminum, and vanadium increased ROS generation by PMNs, while signals not different from unstimulated PMNs were recorded for chromium, cobalt, nickel, and titanium. The DCFH-DA microplate-based assay provides an in vitro tool for the detection of oxygen-reactive species generated by PMNs as a response to metals.     

Differential time course of angiotensin-induced AP-1 and Krox proteins in the rat lamina terminalis and hypothalamus

Binding to olfactory receptors is the first step in odorant and pheromonal recognition and discrimination. These receptors constitute one of the most important, although poorly known, families of neuronal receptors. In this study we used degenerated oligonucleotides and a RT-PCR approach to selectively amplify olfactory receptors in the nasal epithelium of the domestic pig Sus scrofa. Several combinations of oligonucleotide were tested and allowed the isolation of eleven different partial sequences belonging to the seven transmembrane olfactory receptor family. These receptors formed a separate family within the seven transmembrane receptor superfamily in pigs. Using the criteria of Ben Arie et al. [Ben-Arie N., Lancet D., Taylor C., Khen M., Walker N., Ledbetter DH., Carrozzo R., Patel K., Sheer D., Lehrah H. and North M., Hum. Mol. Genet., 3 (1994) 229-235], the 11 receptors described here can be classified into three known families and seven subfamilies (one known and six new).     

Hyperpolarization induces a rise in intracellular sodium concentration in dopamine cells of the substantia nigra pars compacta

We investigated the effect of changes in membrane-voltage on intracellular sodium concentration ([Na+]i) of dopamine-sensitive neurons of the substantia nigra pars compacta in a slice preparation of rat mesencephalon. Whole-cell patch-clamp techniques were combined with microfluorometric measurements of [Na+]i using the Na+-sensitive probe, sodium-binding benzofuran isophthalate (SBFI). Hyperpolarization of spontaneously active dopamine neurons (recorded in current-clamp mode) caused the cessation of action potential firing accompanied by an elevation in [Na+]i. In dopamine neurons voltage-clamped at a holding potential of -60 mV elevations of [Na+]i were induced by long-lasting (45-60 s) voltage jumps to more negative membrane potentials (-90 to -120 mV) but not by corresponding voltage jumps to -30 mV. These hyperpolarization-induced elevations of [Na+]i were depressed during inhibition of I(h), a hyperpolarization-activated inward current, by Cs+. Hyperpolarization-induced elevations in [Na+]i might occur also in other cell types which express a powerful I(h) and might signal lack of postsynaptic activity.