Morphine-6-glucuronide is responsible for the analgesic effect after morphine administration: a quantitative review of morphine, morphine-6-glucuronide, and morphine-3-glucuronide.

BACKGROUND: Morphine-6-glucuronide (M6G) is a strong µ-receptor agonist with higher affinity than morphine itself. It has been suggested that M6G contributes to the analgesic effect after administration of morphine, but the extent of its contribution remains unclear. METHODS: In order to elucidate the relative contribution of both drugs to the overall analgesic effect mediated by the µ-receptor, published data on µ-receptor binding, plasma protein binding, concentrations [preferably area under the concentration-time curve (AUC)] of morphine and M6G in blood or cerebrospinal fluid (CSF), or concentration ratios were used to calculate free CSF concentration corrected for receptor binding for each compound. To compare different routes of administration, free CSF concentrations of M and M6G corrected for potency were added and compared with oral administration. RESULTS: Based on AUC data, there is a major contribution of M6G to the overall analgesic effect; the mean contributions being estimated as 96.6%, 85.6%, 85.4%, and 91.3% after oral, s.c., i.v., and rectal administration of morphine, respectively. In patients with renal insufficiency, 97.6% of the analgesic effect is caused by M6G when morphine is given orally. Owing to accumulation of M6G over time in these patients, morphine may be regarded as a prodrug. CONCLUSIONS: When administering morphine to patients, the analgesic effect is mainly caused by M6G instead of morphine itself, irrespective of the route of administration. Therefore, the patient's kidney function plays a key role in determining the optimal daily dose of morphine.

[An orientational examination of the effects of extracts from mixtures of herbal drugs on selected renal functions]. / Orientacní sledování vlivu výluhu ze smesí rostlinných drog na vybrané funkce ledvin.

The paper aimed to determine the effects of mixtures of selected medicinal plants on some physiological renal functions, i.e. excretion of urine and electrolytes and changes in the quantity of prostaglandins E2 (PGE2) and kallikrein-kinins in rat blood plasma after water and salt load. The following medicinal plants were selected for the examination: downy birch (Betula pubescens EHRH.), everlasting flower (Helichrysum arenarium L. MOENCH.), hawthorn (Crataegus oxyacantha L.), woodland strawberry (Fragaria vesca L.), sweet corn (Zea mays L.), German chamomile (Matricaria recutita L.), and field horsetail (Equisetum arvense L.). Herbal drugs were used to compose 6 mixtures. Extracts from these mixtures were administered to Wistar strain males and their effects were compared with the effects of an administered suspension of hydrochlorothiazide, an extract from field horsetail herb alone, and a control group of animals which was not administered any preparation. The greatest diuretic effect was found in a mixture composed of birch leaves (Betulae folium), hawthorn berries (Crataegi fructus), strawberry leaves (Fragariae folium), corn silk (Maydis stigmata), chamomile flowers (Matricariae flos), and horsetail herb (Equiseti herba). Its effect was greater by 47% and 34% than the effect of a horsetail herb extract and a hydrochlorothiazide suspension (p < 0.05), respectively. The extract from this mixture also increased the quantity of prostaglandins E2 and kallikrein-kinins in rat blood plasma in water and salt load.

Neutrophil adherence-augmenting and chemotactic plasma activities in acute myocardial infarction: effect of fibrinolytic treatment.

Polymorphonuclear neutrophils (PMNs) participate in the development of myocardial reperfusion injury during fibrynolytic treatment. In 40 patients with acute myocardial infarction, we evaluated the effect of streptokinase treatment on plasma activity augmenting PMN adherence and chemotactic plasma activity in peripheral venous blood with the use of neutrophils obtained from healthy donors. In all patients we observed the appearance of marked plasma chemotactic activity and plasma activity augmenting PMN adherence. Peak values of both plasma activities in the conventionally treated group were reached on the third day following the onset of symptoms. In streptokinase treated patients both plasma activities reached a peak on the second day after the onset of symptoms. Furthermore, streptokinase in vitro induced adherence of control PMNs in a dose-dependent manner, as well as increasing both chemotaxis and random migration of control cells. Thus, both chemotactic plasma activity and neutrophil adherence augmenting plasma activity may be used for monitoring the inflammatory response to myocardial infarction. However, during fibrynolytic treatment the presence of chemotactic stimuli in peripheral blood may be affected by streptokinase per se.

Polymorphonuclear neutrophils function in splenectomized patients.

Some essential functions of polymorphonuclear neutrophils (PMN) were evaluated in 30 patients splenectomized because of rupture of the spleen. These cells revealed normal random migration, adherence, unstimulated O2- and H2O2 production. Phagocytosis of viable staphylococci was higher than in controls, whereas chemotaxis, bactericidal capacity, aggregation and stimulated O2- and H2O2 production were significantly impaired. PMN from splenectomized patients manifested also the decreased intracellular myeloperoxidase activity. The percentage of cells with receptor for Fc IgG in peripheral blood was markedly decreased. Plasma of these patients induced increased adherence of autologous as well as control neutrophils. The possible mechanisms leading to the observed events are discussed.

The influence of increasing glucose concentrations on selected functions of polymorphonuclear neutrophils.

The influence of increasing glucose concentrations on some essential functions in polymorphonuclear neutrophils (PMN) was evaluated in vitro in 20 healthy persons. PMN chemotaxis, adherence, phagocytosis and bactericidal capacity were estimated. Higher than physiologic glucose concentrations were found to diminish chemotaxis, phagocytosis and bactericidal capacity. The results obtained may indicate another possible mechanism that accounts for the increased susceptibility to infection observed in diabetic patients. However, PMN adherence rose parallel with increasing glucose concentrations reaching maximum values at 300 mg/dl (16.6 mmol/l). The changes of PMN adherence may suggest the participation of these cells in the development of microangiopathic injuries.

Polymorphonuclear neutrophils function in untreated patients with chronic myeloid leukemia.

Morphologically mature polymorphonuclear neutrophils (PMN) isolated from the peripheral blood of 30 patients were examined. These cells manifested the diminution of phagocytosis, random migration, chemotaxis, thermotaxis and bactericidal capacity. The surface charge of circulating PMN and the percent representation of cells with receptor for Fc IgG were significantly decreased. Stimulated as well as unstimulated oxygen consumption, production of O2- and H2O2 were significantly decreased, whereas the hexose monophosphate shunt activity was similar to that noticed in controls. The aggregation of leukemic PMN was practically normal, however their adherence was significantly higher. The possible mechanisms responsible for the observed PMN defects are discussed.

Evidence of polymorphonuclear neutrophils (PMN) activation in patients with insulin-dependent diabetes mellitus.

Polymorphonuclear neutrophils' chemotaxis, surface charge, superoxide anions generation, NBT (nitro blue tetrazolium) reduction and intracellular lysozyme, and beta-glucuronidase content were estimated in patients with type I diabetes mellitus in a similar state of metabolic control. The chemotaxis of diabetic cells toward bacterial chemotactic factors was similar to controls, whereas migration toward complement-derived chemoattractants was significantly reduced. Polymorphonuclear neutrophils isolated from diabetic patients, when unstimulated, produced significantly greater amounts of superoxide anions and reduced NBT more efficiently. They also revealed reduced surface charge and lower intracellular content of lysozyme, whereas beta-glucuronidase content was similar to controls. The results obtained seem to indicate that neutrophils in patients with insulin-dependent diabetes manifest signs of being in the activated state. The possible mechanisms of such stimulation are discussed.

A new micromethod for the evaluation of Fc receptor expression on polymorphonuclear neutrophils.

A simple method for the evaluation of rosetting polymorphonuclear neutrophils is described. It uses small (200 microliter) quantities of heparinized whole blood and is simpler than the micromethod proposed by Buescher and Gallin. The high concentration of neutrophils and paucity of lymphocytes considerably simplify the evaluation of specimens and make the technique particularly useful in granulopenic states. There was a close correlation between results obtained using this technique and those from a standard method requiring the isolation of polymorphonuclear neutrophils.

Prostatic calculi: a review.

Prostatic calculi are rare in children, infrequent below age 40, and common in males over 50. They may be solitary but usually occur in clusters and are associated with some other disease process (nodular hyperplasia, prostatic carcinoma, metabolic abnormalities). They are most often asymptomatic; however, symptoms that may be attributable to prostatic calculi include reduction of the urinary stream, prostatism, and intense lower back and leg pain. Treatment may be accomplished by transurethral resection, but prostatectomy is the best means to insure complete removal. Prostatic calculi may form by two related mechanisms with obstruction and stasis of prostatic fluid as central entities in both. These mechanisms are calcification of corpora amylacea and simple precipitation of prostatic secretion. They may arise spontaneously, initiating an inflammatory reaction that contributes to their growth, or they may arise as the consequence of another pathologic situation producing acinar obstruction. It appears that infection probably occurs secondary to stone formation.

[Possibility of using the larvae of anuran amphibians as a test model for the quantitative determination of hypophyseal hormones]. / O vozmozhnosti primeneniia lichinok beskhvostykh amfibii v kachestve test-modeli dlia kolichestvennogo opredeleniia nekotorykh gipofizarnykh gormonov.

A possibility to use the larvae of ecaudate amphibia as a test model for the quantitative determination of certain hypophyseal hormones has been shown. The physiological reactions of the pigmentary cells in tadpoles of Rana temporaria can be used for a quick and exact testing of the adrenocorticotropic hormone preparations (ACTH): corticotropin and Zn-corticotropin. Evidently the method elaborated for the biological testing of hypophyseal hormones may be used in the production of the endocrinous preparations as a quick assessment of melanocyte-stimulating hormones in integral raw and sublimated hypophyses.

Radioimmune assays and molecular studies that place Anopheles B and Turlock serogroup viruses in the Bunyavirus genus (Bunyaviridae).

Molecular analyses indicate that Turlock virus (TUR, Turlock serogroup) and Boraceia virus (BOR, Anopheles B serogroup) have virion RNA species and polypeptides comparable in size to those of members of the Bunyavirus genus and unlike those of members of the newly defined Phlebovirus, Nairovirus, or Uukuvirus genera (Bunyaviridae). The 11 terminal 3' end nucleotides of the three virion RNA species of both BOR and TUR viruses (HOUCAUCACAUG...) are identical in sequence to the 3' end sequences of the viral RNA species of snowshoe hare (SSH) and La Crosse bunyaviruses (LAC, California serogroup, Bunyavirus genus). Competition radioimmune assays (RIA), using iodinated LAC nucleocapsid polypeptide (N), or LAC glycoproteins (G1, G2), and LAC rabbit hyperimmune antisera, or iodinated Oriboca (ORI, Group C, Bunyavirus genus) N, or G1 and G2 polypeptides and LAC antisera, or iodinated Bunyamwera (BUN, Bunyamwera serogroup, Bunyavirus genus) N, or G1 and G2 polypeptides and BUN or LAC antisera, have indicated that the virion polypeptides of BOR virus share antigenic determinants with these other bunyaviruses. Competition RIA analyses also have shown that TUR virus shares antigenic determinants with LAC virus. The competition RIA analyses have confirmed the antigenic relationships of LAC, SSH, trivittatus, Bwamba, Aino, Simbu, Mermet, Guaroa, Lumbo, Tahyna, ORI, Anopheles A, BUN, Capim, Guama and Shark river viruses (Bunyavirus genus members), and lack of antigenic relationships between Karimabad, or Chagres, or sandfly fever, Sicilian, Viruses (Phlebovirus genus members), and the bunyaviruses, LAC, ORI, or BUN.

Genotypic varieties of La Crosse virus isolated from different geographic regions of the continental United States and evidence for a naturally occurring intertypic recombinant La Crosse virus.

The tripartite ribonucleic acid (RNA) genomes of 23 alternate isolates of La Crosse virus have been analyzed by the procedure of oligonucleotide fingerprinting. By comparison with the fingerprints of the three viral RNA species (large, medium and small) of prototype La Crosse virus, the viruses have been categorized in terms of the degree of their RNA sequence relatedness. The A type La Crosse viruses, which have been recovered from Wisconsin, Minnesota, Indiana and Ohio, have viral RNA sequences that are closely related to those of prototype La Crosse virus. The B type La Crosse viruses, which have been recovered from Minnesota, Wisconsin and Illinois, have RNA sequences which, although related, are easily distinguished from those of type A viruses. A La Crosse virus isolate obtained from Rochester, Minnesota, appears to be an intertypic type A/B recombinant, it has a small size RNA segment like those of the B type La Crosse virus isolates, but medium- and large-sized RNA species like those of the A type La Crosse virus isolates. The C type La Crosse viruses have viral RNA sequences that neither closely resemble the A or B type La Crosse viruses. They have been recovered from eastern Ohio, New York State, Texas, Georgia and North Carolina.

Characterization of the viral ribonucleic acids and structural polypeptides of Anopheles A, Bunyamwera, Group C, California, Capim, Guama, Patois, and Simbu bunyaviruses.

Analyses of the viral ribonucleic acids and structural polypeptides of 17-22 of the 119 accepted or proposed members of the Bunyavirus genus of arboviruses (family Bunyaviridae), have shown that from the standpoint of their structural components these viruses are highly comparable to each other. The average molecular weights for the three viral RNA species (L, large, M, medium, S, small) of 17 bunyaviruses were 2.93 X 10(6) (L, range 2.7-3.1 X 10(6)), 2.0 X 10(6) (M, range 1.8-2.3 X 10(6)), and 0.435 X 10(6) (Sm range 0.28-0.50 X 10(6)). The average molecular weights of the three major virion polypeptides (glycoproteins G1 and G2, and nucleocapsid protein, N) of 22 bunyaviruses were 115 X 10(3) (G1, range 108-120 X 10(3)), 37 X 10(3) (G2, range 20-41 X 10(3)) and 22 X 10(3) (N, range 19-25 X 10(3)). These results indicate that the structural components of bunyaviruses are different from those reported for Phlebotomus fever, Uukuniemi, and Crimean-Congo hemorrhagic fever, and other members of the Bunyaviridae family that are not currently assigned to a genus.

A comparison of La Crosse virus isolated obtained from different ecological niches and an analysis of the structural components of California encephalitis serogroup viruses and other bunyaviruses.

Analyses of the oligonucleotide fingerprints of the three genome ribonucleic acid (RNA) species of 11 isolates of La Crosse (LAC) virus, obtained from various ecological niches in the northern United States and compared to those of prototype LAC virus, showed that in each place from which these isolates were obtained LAC variants and varieties were present with related, but distinguishable, nucleotide sequences for their large, medium, or small RNA species. The RNA genomes of prototypes trivittatus (TVT), snowshoe hare (SSH), Tahyna (TAH), and Lumbo (a variety of TAH) viruses of the California encephalitis (CE) serogroup, and Guaroa of the Bunyamwera serogroup also consist of three RNA species, each with unique and distinguishable nucleotide sequences which bear little resemblance to those of the LAC virus isolates. The virions of CE group viruses (CE, Jamestown Canyon, Keystone, LAC, Melao, SSH, TVT, TAH viruses and South River, an unregistered virus) have three major viral polypeptides, designated G1, G2, and N.

La Crosse virus soluble cell culture antigen.

A virus-free soluble antigen, obtained by ammonium sulfate precipitation of the supernatant fluids of La Crosse virus-infected BHK-21 cell cultures, was more reactive and more specific than infected suckling mouse brain antigen when compared by immunodiffusion and counterelectrophoresis tests. By complement fixation tests, the antigen was cross-reactive with heterologous California group arbovirus hyperimmune mouse ascitic fluids, but to a lesser degree than was the standard sucrose-acetone-extracted infected suckling mouse brain antigen. The major virion nucleocapsid protein of La Crosse virus was found by polyacrylamide gel electrophoresis to be the soluble antigen protein responsible for precipitation in immunodiffusion and counterelectrophoresis tests.