Effect of coating of aluminum carboxymethylcellulose beads on the release and bioavailability of diclofenac sodium

Menière's disease and fluctuating hearing loss are related to labyrinthine fluid pressure variations. The development of a new indirect method of analysis of the tympanic membrane displacement during the stapedial reflex, using the Marchbanks Measurements System (MMS 10), allows us to study inner ear fluid pressure during these pathological conditions. In this study, measurements with this method were made in four groups of patients: a control group with normal hearing (n=7), stable sensorineural hearing loss (n=9), fluctuating hearing loss (n=8), and Menière's disease (n=25). Results show, first, a good relationship between the recording of negative curves, suggesting a high pressure, and the acute episodes of fluctuating hearing loss; and, secondly, in the case of Menière's disease two types of situation: positive and negative curves suggesting normal and high pressures, respectively.     

Colocalization of muscarinic acetylcholine receptors and protein kinase C gamma in rat parietal cortex

The present investigation analyzes the cellular distribution of muscarinic acetylcholine receptors (mAChRs) and the gamma isoform of protein kinase C (PKC) in the rat parietal cortex employing the monoclonal antibodies M35 and 36G9, respectively. Muscarinic cholinoceptive neurons were most present in layers 2, 3 and 5, whereas most PKC gamma-positive cells were found in layers 2, 5 and 6. Under normal, non-stimulated conditions, approximately 58% of all muscarinic cholinoceptive neurons were immunoreactive for PKC gamma. Conversely, nearly all PKC gamma-positive neurons were M35-immunoreactive. Although both pyramidal and nonpyramidal neurons express the two types of protein, the pyramidal cell type represents the vast majority. Of all cortical neurons, the large (15-25 microns in diameter) muscarinic cholinoceptive pyramidal neurons in layer 5 express the gamma isoform of PKC most abundantly and most frequently. Approximately 96% of these cells are immunoreactive for PKC gamma. Stimulation of mAChRs by the cholinergic agonist carbachol resulted in a pronounced increase in the intensity of 36G9 immunoreactivity, which may suggest that the mAChRs are functionally linked to the colocalized PKC gamma. No change was found in the number of 36G9-immunoreactive neurons. In contrast, the number of immunocytochemically detectable muscarinic cholinoceptive neurons increased by approximately 38% after carbachol stimulation. The high degree of codistribution in cortical neurons of both transduction proteins suggests a considerable cholinergic impact upon the regulation of PKC gamma, a candidate key enzyme in cortical learning and memory mechanisms.     

The current problems in protecting the health of the population in the oil- and gas-producing regions of Tyumen Province

A socioeconomic and medicodemographic analysis of modern problems related to population health protection in the oil and gas extraction regions of Tyumen Province has been carried out under conditions of radical reconstruction of the national economy. Changes in the parameters of natural migration of the population for each year over a period of 1991 to 1995 are followed up, and specific features of the migration processes, effects of socioeconomic and medical factors on the health status of individual population groups, rates of increment in the number of disabled subjects, and population mortality from various causes analyzed. The authors discuss the status of public health services and offer measures for improving their efficacy in the above regions.     

The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina

BACKGROUND: In a previous study, we did follow-up on 418 patients who were exposed to tryptophan in 1989, of whom 47 (11%) had definite and 63 (9%) possible eosinophilia-myalgia syndrome (EMS). METHODS: We assessed mortality and clinical spectrum of illness since 1989 for 242 (58%) of the 418 tryptophan-exposed patients from the original study. To assess outcomes, we used hospital and death records, interviewer-administered questionnaires, physical examinations, and laboratory tests. RESULTS: During the follow-up interval, mortality from all causes was 19% in those with definite EMS, 7% in possible EMS, and 3% in those who were not ill. The age- and sex-adjusted mortality in those with definite EMS was more than 3 times that of the general population or of tryptophan users in the practice who were not ill. Six deaths (66%) among the definite EMS case patients occurred during the 18 months immediately after symptom onset. Compared with the tryptophan users who were not ill, survivors with definite EMS continued to report excess morbidity for 6 major EMS symptoms (myalgia, arthralgia, weakness, rash, alopecia, and sclerodermiform skin changes), but they also reported that the symptom number and severity diminished with time. None of the tryptophan users who were not ill in 1989 developed a symptom complex suggesting new EMS during the follow-up interval. CONCLUSIONS: This study assessing a tryptophan-exposed population found those persons who developed EMS during the 1989 epidemic were at increased risk for death, particularly early after disease onset. Survivors reported improvement or resolution of major symptoms, suggesting that the severity of EMS diminishes with time. We found no evidence of delayed onset of EMS in tryptophan users who were not ill in 1989, regardless of the brand used.     

Ionic conductivity, transference numbers, composition and mobility of ions in cross-linked lysozyme crystals

Basic fibroblast growth factor (bFGF) gene expression as well as its immunoreactivity were studied after partial unilateral hemitransection of the rat brain during a time course of 24 h, 72 h, 7 and 14 days. The mechanical injury resulted in a global increase of bFGF gene expression at the 24-h time interval. This global increase was seen at the ipsilateral site at the level of the lesion as well as rostral to the lesion in the ipsilateral hemisphere. The upregulation in bFGF gene expression was in most of the areas investigated due to an upregulation in glial cells as seen by means of nonradioactive in situ hybridization compared with immunocytochemistry for glial fibrillary acidic protein (GFAP). Basic FGF immunoreactivity (IR) was increased around the lesion in glial cell nuclei 7 days after the injury. This increase was also detected in GFAP positive glial cells surrounding small vessels in the lesioned area. Moreover, in the present paper we demonstrate increased tenascin immunoreactivity in the lesioned area 7 days after injury. The tenascin IR was increased at the edges of the lesion as well as in vessel like structures. The tenascin IR was partially codistributed with GFAP IR in the lesioned area. The lesion was also characterized by an increase in vimentin IR as well as in laminin IR. It is suggested that the observed changes in the expression of bFGF, matrix proteins (laminin, tenascin) and intermediate filaments (vimentin) are involved in (a) tissue repair, (b) protection of neuronal cells from excitotoxic influences and (c) formation of new vessels in the lesioned area.     

The utilisation of creatine and its analogues by cytosolic and mitochondrial creatine kinase

We have investigated the utilisation of four analogues of creatine by cytosolic Creatine Kinase (CK), using 31P-NMR in the porcine carotid artery, and by mitochondrial CK (Mt-CK), using oxygen consumption studies in isolated heart mitochondria and skinned fibers. Porcine carotid arteries were superfused for 12 h with Krebs-Henseleit buffer at 22 degrees C, containing 11 mM glucose as substrate, and supplemented with either 20 mM beta-guanidinopropionic acid (beta-GPA), methyl-guanidinopropionic acid (m-GPA), guanidinoacetic acid (GA) or cyclocreatine (cCr). All four analogues entered the tissue and became phosphorylated by CK as seen by 31 P-NMR, Inhibition of oxidative metabolism by 1 mM cyanide after accumulation of the phosphorylated analogue resulted in the utilisation of PCr, beta-GPA-P, GA-P and GA-P over a similar time course (approximately 2 h), despite very different kinetic properties of these analogues in vitro. cCr-P was utilised at a significantly slower rate, but was rapidly dephosphorylated in the presence of both 1 mM iodoacetate and cyanide (to inhibit both glycolysis and oxidative metabolism respectively). The technique of creatine stimulated respiration was used to investigate the phosphorylation of the analogues by Mt-CK, Isolated mitochondria were subjected to increasing [ATP], whereas skinned fibres received a similar protocol with increasing [ADP]. There was a significant stimulation of respiration by creatine and cCr in isolated mitochondria (decreased K(m) and increased Vmax vs control), but none by GA, mGPA or beta-GPA (also in skinned fibres), indicating that these latter analogues were not utilised by Mt-CK. These results demonstrate differences in the phosphorylation and dephosphorylation of creatine and its analogues by cytosolic CK and Mt-CK in vivo and in vitro.