Subcellular localization of hydrogen peroxide production in human polymorphonuclear leukocytes stimulated with lectins, phorbol myristate acetate, and digitonin: an electron microscopic study using CeCl3

The ultrastructural H2O2-producing site in human polymorphonuclear leukocytes (PMN) stimulated with soluble stimuli was studied using a CeCl3-technique. CeLlular aggregation and formation of small vacuoles were observed when PMN were stimulated with 100 microgram/ml concanavalin-A, 1 mg/ml phytohemagglutinin, or 100 microgram/ml wheat germ agglutinin for 10 min at 37 degrees C. Electron-dense deposits formed from the reaction of H2O2 and CeCl3 were observed on the contact surface of the plasma membrane of aggregated PMN stimulated with lectins. Treatment with 5 microgram/ml cytochalasin-B before lectin- stimulation induced an enhanced formation of vacuoles, degranuLation, rounding of the contour, cellular aggregation, and enhancement of the deposits. Phorbol myristate acetate (PMA; 100 ng/ml) induced strong leukocyte aggregation, the formation of multiple huge vacuoles, degranulation, and H2O2 production at almost all of the contact surface between adjoining PMN and between PMN and erythrocytes, mononuclear cells, or thrombocytes. In PMN stimulated with digitonin (B microgram/ml), vacuolar formation, degranulation, multiple projections on the surface, and H2O2 production on the whole surface membrane were demonstrated. It is shown that cellular aggregation and cell-to-cell contact have an important role in the induction of O2- production induced by lectins or PMA and that O2- production induced by the detergent is not dependent on leukocyte aggregation.     

Utilization of traditional healers for treatment of malaria among female residents in Makurdi city and its environs

ObjectiveTo ascertain the role of traditional healers in malaria treatment and its impact on control of the disease.MethodsThe study was cross-sectional in nature. Test-run structured and semi-structured questionnaires were either interviewer or self administered to adult women aged 18 years old and above. House holds were selected using systematic random sampling methods. Information such as age, educational level, marital status, occupation and methods of malaria treatment were obtained. Focused group discussions about beliefs and perceptions on utilization of traditional healers and in depth discussions on treatment and control of malaria were also carried out.ResultsOf the 2 075 respondents studied, 49.7% (n=1 031) utilized traditional healers for treatment of malaria, including 16.7% (n=172) utilizing traditional healers strictly while 83.3% (n=859) combining it with other treatment methods such as hospital/clinic, pharmacy/chemist shop, herbs or spiritual healing. The major contributors to utilization of traditional healers were: illiteracy and ignorance, poverty, unemployment/underemployment and slow pace of the comprehensive package implementation of the “roll back malaria” (RBM) programme initiate in the community.ConclusionsHealth education should be intensified while adequate facilities put in place to commence home management of malaria and probable free distribution of the artemisinin-based combination therapy (ACT).     

Mitochondrial disease in mouse results in increased oxidative stress

It has been hypothesized that a major factor in the progression of mitochondrial disease resulting from defects in oxidative phosphorylation (OXPHOS) is the stimulation of the mitochondrial production of reactive oxygen species (ROS) and the resulting damage to the mtDNA. To test this hypothesis, we examined the mitochondria from mice lacking the heart/muscle isoform of the adenine nucleotide translocator (Ant1), designated Ant1(tm2Mgr) (-/-) mice. The absence of Ant1 blocks the exchange of ADP and ATP across the mitochondrial inner membrane, thus inhibiting OXPHOS. Consistent with Ant1 expression, mitochondria isolated from skeletal muscle, heart, and brain of the Ant1-deficient mice produced markedly increased amounts of the ROS hydrogen peroxide, whereas liver mitochondria, which express a different Ant isoform, produced normally low levels of hydrogen peroxide. The increased production of ROS by the skeletal muscle and heart was associated with a dramatic increase in the ROS detoxification enzyme manganese superoxide dismutase (Sod2, also known as MnSod) in muscle tissue and muscle mitochondria, a modest increase in Sod2 in heart tissue, and no increase in heart mitochondria. The level of glutathione peroxidase-1 (Gpx1), a second ROS detoxifying enzyme, was increased moderately in the mitochondria of both tissues. Consistent with the lower antioxidant defenses in heart, the heart mtDNAs of the Ant1-deficient mice showed a striking increase in the accumulation of mtDNA rearrangements, whereas skeletal muscle, with higher antioxidant defenses, had fewer mtDNA rearrangements. Hence, inhibition of OXPHOS does increase mitochondrial ROS production, eliciting antioxidant defenses. If the antioxidant defenses are insufficient to detoxify the ROS, then an increased mtDNA mutation rate can result.     

Aminostigmine — A new anticholinesterase drug

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 25, No. 1, pp. 87–88, January, 1991.     

Instructions to authors

We investigated the effect of glucose and glucose polymer ingestion on plasma arginine vasopressin (pAVP) levels, on plasma osmolality (p-osm), and on performance during two prolonged endurance events. The study subjects were 37 Finnish elite endurance athletes, of whom 18 were orienteers and 19 cross-country skiers. Plasma AVP increased in both combined glucose and glucose polymer groups, but the increase in the glucose polymer group was significantly smaller (P 0.001) than that in the glucose group. A significant change in p-osm caused a significant change in pAVP and vice versa. Both the orienteers and the skiers on glucose polymer tended to have more success in the competition; the orienteers on glucose polymer ran the last third of the competition significantly faster than those on glucose (P 0.05). It is suggested, in the light of the smaller pAVP response, that after glucose polymer ingestion the physical stress in prolonged endurance exercise is smaller than after ingestion of glucose.     

Reduction of lymphocytic β-adrenoceptor level in chronic alcoholics and rapid reversal after ethanol withdrawal

Plasma catecholamine levels, lymphocytic beta-adrenoceptor densities and lymphocytic cAMP production were studied in 10 male subjects attending a withdrawal clinic after prolonged alcohol abuse. On admission the mean beta-adrenoceptor density was 29 +/- 9 fmol mg-1 protein (about 60% of the mean level of healthy control subjects, P less than 0.002). The following day a significant elevation of the beta-adrenoceptor level up to 46 +/- 19 fmol mg-1 protein (P less than 0.05) took place. This was accompanied by a parallel activation of the beta-adrenoceptor-mediated cAMP production of the lymphocytes. No major changes in beta-adrenoceptor levels or cAMP production took place during the next 7 days. Plasma catecholamine levels were elevated at arrival and decreased steadily during the withdrawal period. In conclusion, chronic alcoholism is associated with a reduction of lymphocytic beta-adrenoceptor density and functioning, which is followed by a rapid reversal during abrupt ethanol withdrawal. Thus an accelerated responsiveness to catecholamines may occur during the first ethanol-free day of chronic alcoholics.     

Effect of benzonal on the liver mono-oxygenase system of laboratory animals

The data are provided on benzonal as having the properties of the monoxygenase system inducer, evidenced by the shortening of hexenal sleep, increase of the intensity of the epr-signal of cytochrome P-450, activation of lipid peroxidation, carboxylesterase and arylesterase in the liver. The properties of benzonal described can be made use of for increasing the body resistance to the toxic action of xenobiotics.     

Immunoelectron microscopic findings in oral mucosa of patients with dermatitis herpetiformis and linear IgA disease

Abstract – Two patients with dermatitis herpetiformis and one with linear IgA disease were examined. Two of the patients had oral lesions and all three showed IgA deposits detected by direct immunofluorescence in apparently normal buccal mucosa. To localize the target structures for IgA deposition, biopsy specimens were taken from normal appearing buccal mucosa for immunoelectron microscopy. The patients with dermatitis herpetiformis had distinct IgA deposits in the upper connective tissue. These were often associated with elastic fibers and occasionally also with capillary walls. In contrast, the patient with linear IgA disease had IgA deposition at the subbasal lamina. Though the clinical expressions may be similar the present immunoelectron microscopic fmdings in oral mucosa clearly differentiate dermatitis herpetiformis from linear IgA disease.