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PubMed2000

Contemporary activation of different endothelial receptors accounts for a reserve mechanism of nitric oxide-mediated relaxation.

The aim of this study was to investigate whether the inhibition of one of the endothelial receptor sites in the rat pulmonary artery (muscarinic, histaminergic, purinergic, alpha2-adrenergic) affects the NO-mediated relaxation induced by the activation of the other type of receptors. Acetylcholine (ACh)-, histamine (Hist)-, adenosine (Ade)-, and clonidine (Clon)-induced endothelium-dependent relaxations were reduced by the administration of specific antagonists of muscarinic, H1-histaminergic, purinergic or alpha2-adrenergic receptors, respectively. The inhibition of H1-histaminergic receptors by chlorphenyramine did not prevent ACh-induced relaxation. Similarly, the inhibition of muscarinic receptors by atropine did not prevent the relaxations to histamine, adenosine and clonidine. On the other hand, the relaxations induced by acetylcholine, histamine, adenosine or clonidine were regularly reduced by NO-synthase inhibitor N(G)-nitro-L-arginine methyl ester (10(-4) mol/l). These results suggest that the inhibition of NO-synthase abolished arterial relaxations induced by all agonists. After inhibition of one type of the endothelial receptors, the NO-dependent relaxation could still be evoked by activation of one of the others.

Acetylcholine↗

PubMed2000

Walmsley's Web watch.

The ADEE site serves as a portal to other educational sites around the world. The address can be book-marked and used as a focus to explore and use the Web in a constructive way without becoming overwhelmed with the large amount of information that is present. There are, of course, many other sites that act as a resource and contain links to other web pages. This site is simple to use, contains links to web pages that are of high quality and will prove useful to people wishing to update their current knowledge.

Dentistry↗

PubMed2001

[Access to care, access to rights, and health education: stakes of the global management fo patients].

Together with primary care physicians, the public health clinic of the Max Fourestier Hospital (Nanterre, France) initiated a pilot experience within the framework of its access to health care network (ADES). In addition to full access to traditional health care, patients who agree to participate in this unique network benefit from a medical and social risk screening and prevention program. This program is proposed to all patients who, by definition, have one or more medical or social risk factors. At each visit, targeted history taking and the physical exam can lead to individualized propositions for a global approach to screening and prevention, whatever the initial reason for consulting. In addition, patients who require permanent care benefit from the dose link between the medical care and social care teams. Over the last year, this experience has involved 3430 consultations in a polyvalent clinic that has provided global care including health education and screening for health risks. Our analysis of the medical and ethical issues involved points out the importance of a global approach to health care.

Ethics, Medical↗

PubMedDate not supplied

Drug misadventuring in neonatal nephrology.

Drug-related problems are associated with significant morbidity and mortality. Numerous factors contribute to the development of drug-related problems. These factors may be patient-dependent, such as the patient's degree of organ function and/or dysfunction, and underlying disease states. On the contrary the factors may depend on the specific drug and its pharmacokinetic parameters. Recently it has been also demonstrated the importance of genetic factors. Drug-related problems include a wide range of situations including the so-called drug misadventuring: adverse drug reaction (ADR), adverse drug event (ADE), drug-induced disorder (DID), adverse drug experience (ADEexp). Certain drug classes are commonly associated with drug-induced disorders. Antibiotics and chemotherapeutic agents are responsible for approximately 30 percent of all adverse reactions. By an epidemiologic point of view between 3% and 11% of hospital admissions could be attributed to drug-related problems. Drug-induced disorders have historically been classified as predictable (Type A) or unpredictable (Type B) toxicity. Thus, a substantial portion of drug-induced disorders are predictable and potentially avoidable The kidney is vulnerable to drugs because of its high blood flow and large capillary surface area, its role as the excretory route for many drugs and its detoxifying action. Drug-induced acute renal failure accounts for 20% of total cases of acute renal failure in adult patients. Little is known about epidemiology of drug-induced disorders, especially in the pediatric kidney. Systematic epidemiological data on the incidence of drug-induced acute renal failure in newborn are not available. However, an increase in the last 10 years, in the involvement of drugs in acute renal failure has been observed in newborns. In the past it was suggested that drug-induced kidney damage (especially tht caused by aminoglycosides or glycopeptides) is less frequent and severe in newborns than in adults. However, this subject is controversial. Furthermore, it has recently been confirmed that low birth weights contribute to early onset of end stage renal disease. In view of the extremely widespread use of drugs in neonatology and the multiplicity of potential nephrotoxic factors, it is important to prevent iatrogenic effects. Ten rules for prevention of drug-induced nephrotoxicity are presented.

Drug-Related Side Effects and Adverse Reactions↗

PubMed1975

[UV-mutagenesis in Bacillus subtilis. IV. Analysis of revertants to methionine prototrophy].

UV light induces in Bacillus subtilis met5 ade6 two classes of revertants to prototrophy to methionine which can be easily distinguished by their phenotype: double (Met+Ade+) and solitary (Met+) revertants. Crosses of revertants with the wild type, carried out in transformational experiments, showed that original (direct) mutation met5 is presented in chromosome of double revertants. Consequently they are extragenic suppressor revertants. In the chromosome of solitary revertants Met+ an extragenic suppressor was not detected; reversions Met+ seem to be of an intragenic nature. It is possible to use reversions to prototrophy to methionine as a model to study UV-mutagenesis in suppressor and non-suppressor genes.

Methionine↗

PubMed2002

Symbiotic characterization of isoleucine+valine and leucine auxotrophs of Sinorhizobium meliloti.

Ten isoleucine+valine and three leucine auxotrophs of Sinorhizobium meliloti Rmd201 were obtained by random mutagenesis with transposon Tn5 followed by screening of Tn5 derivatives on minimal medium supplemented with modified Holliday pools. Based on intermediate feeding, intermediate accumulation and cross-feeding studies, isoleucine+valine and leucine auxotrophs were designated as ilvB/ilvG, ilvC and ilvD, and leuC/leuD and leuB mutants, respectively. Symbiotic properties of all ilvD mutants with alfalfa plants were similar to those of the parental strain. The ilvB/ilvG and ilvC mutants were Nod-. Inoculation of alfalfa plants with ilvB/ilvG mutant did not result in root hair curling and infection thread formation. The ilvC mutants were capable of curling root hairs but did not induce infection thread formation. All leucine auxotrophs were Nod+ Fix-. Supplementation of leucine to the plant nutrient medium did not restore symbiotic effectiveness to the auxotrophs. Histological studies revealed that the nodules induced by the leucine auxotrophs did not develop fully like those induced by the parental strain. The nodules induced by leuB mutants were structurally more advanced than the leuC/leuD mutant induced nodules. These results indicate that ilvB/ilvG, ilvC and one or two leu genes of S. meliloti may have a role in symbiosis. The position of ilv genes on the chromosomal map of S. meliloti was found to be near ade-15 marker.

DNA Transposable Elements↗

PubMed1976

[Coffee pulp and hulls. XI. Chemical characteristics of silaged coffee pulp with Napier grass (Pennisetum purpurem) and corn plant (Zea mays)].

Various physical and chemical changes that occur during the process of preparation of coffee pulp silage with the addition of molasses and forage, were identified and measured quantitatively. Three types of silage were prepared in duplicate in laboratory concrete silos, 45 cm wide and 50 cm high. The silages contained the following components: coffee pulp (EPC), pulp and Napier grass (EPCN), and pulp with corn fodder (EPCM). On a fresh basis, the last two contained equal proportions of coffee pulp and forage. Around 16% molasses were aded to all silages. Time of ensiling was 132 to 141 days. In order to determine the physical changes, the silage was weighed at the start and end of the ensiling period; the pH was determined at the end of same, and the drained liquids were measured during the experimental period. To determine the chemical changes, analyses were carried out on the various components used and on the mixtures ensiled at the start and at the end of the experimental period. The pH of the silage was 4.5, 4.3, and 3.8, and the losses of dry matter 10.6, 25.2, and 33.3% for the three types of silages, respectively. These percentages suggest that a better fermentation took place in those silages containing forages. The better fermentation of EPCN over EPC was due to the Napier grass which provided greater amounts of chemical components susceptible of fermentation than those found in coffee pulp. The quality of EPCM was superior due not only to the presence of corn fodder, which produced an effect similar to that of Napier grass, but also due to the fact that the coffee pulp used in this case contained the greater concentrations of soluble carbohydrates and lower levels of lignin than the coffee pulp used alone or with Napier grass. As a result of the fermentation process, in all three types of silage a decrease in dry matter content, of cellular contents and soluble carbohydrates was observed, as well as an increase in cellular walls and its components, and of protein. The magnitude of these changes was found to be directly related to the losses in dry matter. From the results of this research, it was concluded that the addition of forage improves the chemical characteristics of silage prepared from coffee pulp.

Animal Feed↗

PubMed2003

Experimental transmission of Chikungunya virus by Anopheles stephensi mosquitoes.

The Ades aegypti mosquito has been considered the principal vector of Chikungunya (CHIK) virus. As CHIK epidemics usually occur in urban regions and Anopheles stephensi is another highly endophilic and anthropophilic mosquito, there is a very high probability of this mosquito to feed on CHIK virus-infected patients, to pick up and transmit the virus. Therefore the present study was conducted to test the CHIK virus transmission capability for the A. stephensi mosquito. The obtained results showed that this mosquito species is capable of transmitting CHIK virus. It is surmised that during any epidemic of febrile illness CHIK virus isolation attempts should also be made from this mosquito species.

Alphavirus Infections↗

PubMedDate not supplied

[UV spectra of adenine methyl and glycosyl derivatives and their transformation induced by amino acid carboxylic groups].

UV absorption spectra of adenine, adenosine and their methyl derivatives were studied in dimethylsuloxide (DMSO). Considerable changes in UV spectra of adenine under methylation at the 1 and 3 positions, and adenosine under methylation at the 1 position attested the essential structural reconstruction of adenine purine ring. Ade and m6Ade were shown to form complexes with deprotonated carboxylic group of amino acids (carboxylate-ion) through two H-bonds involving amino group and N7H imino group, tautomeric transition N9H-->N7H being initiated namely by interaction with carboxylate-ion. Considerable changes in UV spectra of m1Ade, m1A, and m3Ade under interaction with neutral carboxylic group of amino acids were interpreted as a result of proton transfer from amino acid to the base.

Adenine↗

PubMed2003

Screening of augmenter of liver regeneration-binding proteins by yeast-two hybrid technique.

OBJECTIVE: To investigate the biological function of augmenter of liver regeneration (ALR), we used yeast-two hybrid technique to detect proteins in hepatocytes interacting with ALR. METHODS: ALR bait plasmid was constructed by using yeast-two hybrid system 3, then transformed into yeast AH109. The transformed yeast was mated with yeast Y187 containing liver cDNA library plasmid in a 2XYPDA medium. Diploid yeast was plated on a synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) containing x-alpha-gal for selection and screening. After extracting and sequencing of the plasmid from blue colonies. Analysis was performed by bioinformatics. RESULTS: Of 36 colonies sequenced, 14 are metallothionein, 12 albumin, and 3 selenoprotein P. One colony is a new gene with unknown function. CONCLUSION: The successful cloning of gene of ALR interacting protein has paved the way for studying the physiological function of ALR and associated proteins.

Animals↗

PubMed2003

[Hemorheological changes at reconstructive operations on the aorta].

Fifteen patients who had undergone aortic reconstructions were examined. Hemorheologic studies were performed at the following stagest initial anesthesia, the end of operation, the early postoperative period, and the 2nd-3rd days after operation. A study was made of blood viscosity at a shift rate 5-300 s(-1), of suspension stability, caisson viscosity (CV), and the yield stress (YS). The back light diffusion intensity was recorded on the erythroaggregometer ADE=5 (Russia) to evaluate the time of linear aggregate formation (T(1)), the time of three-dimensional aggregate formation (T(2)), characteristics of the end size of the aggregates (Ampl), total hydrodynamic strength of the aggregates (Beta), strength index of especially large aggregates (Ia((2,5))). The index of erythrocyte aggregation (IEA) and the index of erythrocyte deformation (IED) were also computed. Initially, the normal blood viscosity values were marked. However, in the early postoperative period, their values returned to the preoperative level. In patients with complications, blood viscosity appreciably rose, exceeding the preoperative parameters. At the end of operation there was a decrease in erythrocyte aggregation, especially due to the TT(1) and Ampl rise, while beta dropped. In the postoperative period, patients without complications demonstrated the growth of erythrocyte aggregation but Ampl of cell aggregation diminished. In the postoperative period, patients with complications showed a considerable intensification of erythrocyte aggregation due to the rise of Ampl, Beta and Ia((2,5)). Toward the end of operation a decrease of plasma viscosity was revealed in the presence of GV rise. In the postoperative period, patients with complications demonstrated the growth of plasma viscosity concurrently with CV lowering. Toward the end of operation the YS increased. However, in patients with the uncomplicated postoperative period, the magnitude of this parameter dropped and reached permissible values in the given patient group whereas in patients with complications, the YS remained significantly high.

Aortic Aneurysm, Abdominal↗

PubMed2003

Enterprise-wide drug-drug interaction alerting system.

According to the Institute of Medicine's (IOM) 1999 report To Err is Human: Building a safer Health System, "medical errors kill some 44,000-98,0001 people in U.S. hospitals each year. Partners HealthCare System (PHS) is a large integrated delivery network in Boston, MA, which has as a goal improving patient care by preventing adverse drug events (ADE) and reducing medication errors enterprise-wide. PHS has developed a drug-drug Interaction (DDI) detection feature, for the suite of clinical applications currently used by its two major teaching institutions, Brigham & Women's Hospital (BWH) and Mass General Hospital (MGH). The following clinical applications will be using this drug-drug interaction feature: NICU Order Entry (OE) at BWH, MGH OE for pediatrics and adults, the Partners outpatient medical record, The LMR, and BICS OE at BWH.

Algorithms↗

PubMed2003

Intelligent intravenous infusion pumps to improve medication administration safety.

Intravenous (IV) medications are vital in the management of hospitalized patients. Inpatients frequently receive several IV medications concurrently, and these are commonly delivered with infusion pump systems. In particular, critically ill patients receive potent "high-alert" IV drugs, many with narrow safety margins requiring careful nursing titration. However, while intravenous medications have important benefits, errors associated with IV medication administration can result in severe or life-threatening adverse drug events (ADEs). Although errors in prescribing are often intercepted, administration errors do not get caught with most current systems While several safety improvements in IV infusion pump design have reduced mechanical complications, errors with IV drug administration such as incorrect programming persist. Intelligent IV infusion pumps have integrated software to provide point of care decision support (DS). This software includes drug library profiles configured for specific patient care units and includes programming of safety limits for drug/dose calculations.

Decision Making, Computer-Assisted↗

PubMed1992

Development of genetic engineering in Bacillus megaterium.

The opportunities for industrial genetic engineering in several species of Bacillus other than B. subtilis and B. thuringiensis are now becoming a reality. Many species have advantages for certain industrial applications, such as the lack of alkaline proteases, stable plasmid maintenance, and production of thermostable enzymes. It is now possible to increase production levels in many Bacillus strains that are already high producers of amylases, proteases, penicillinases, and penicillin amidases, by the introduction of such genes on high-copy-number plasmids. Possible problems in gene regulation, expression, limits on protein production, and secretion will be encountered, but recent reports on comparisons of expression of bacterial and eukaryotic genes in B. subtilis and B. megaterium (Shivakumar et al. 1989; Donovan et al. 1989a, 1989c; Ginsburgh et al. 1989) suggest that some species may prove to be better expression hosts for specific genes than others. What is needed is extensive comparative studies in promising species to better understand the parameters affecting cloning, gene expression, and protein secretion in the bacilli. In this chapter we have emphasized the development of genetic analysis and rDNA methods in B. megaterium. While the chromosomal map is still not a complete circle, many gene loci have been mapped, some with three-factor crosses, and have been characterized by enzyme assays (leu, trp, hem, cob, cbl) as well as complementation with B. subtilis genes (trp, dnaK, pur, met, ssp) E. coli genes (ATPase), hybridization (spoVG, abrB, sigK, ssp), and by growth on intermediates (trp, leu, thy, gua, ade, pur, pyr, his, arg). A mapping kit of 12 strains is available, and can facilitate the mapping of new mutations rapidly. This is of great advantage in strain construction since genes can be transferred at will by cotransduction. A partial physical map generated by pulse gel electrophoresis is also available (Muse 1990). It remains to be determined whether gene conversion occurs in B. megaterium as it does in B. subtilis. This is a powerful tool for rescuing genes and mutations of interest from the chromosome. There are now over 600 mutants available in our laboratory, over 100 in the laboratory of J.C. Vary, and several more that have been characterized in various laboratories throughout the world. Many of these are available in stock culture collections, although this source needs to be expanded. Mutants that should be useful for genetic engineering include recombination negative, protease negative, and plasmidless wild type, as well as Lac negative and several auxotrophs in the plasmidless background, and many sporulation negative mutants.

Bacillus megaterium↗

PubMed1992

Genes for directing vacuolar morphogenesis in Saccharomyces cerevisiae. II. VAM7, a gene for regulating morphogenic assembly of the vacuoles.

VAM7 gene function has shown to be required for proper morphogenesis of the vacuole in yeast. The DNA fragments that complemented the defective vacuolar morphology of the vam7-1 mutation were isolated from a yeast genomic library. An overlapping 2.5-kilobase BglII-HindIII region was found to be sufficient for complementation of the vam7-1 phenotype. This fragment was integrated at the chromosomal VAM7 locus, indicating that it contained an authentic VAM7 gene. On nucleotide sequencing of the VAM7 gene, an open reading frame of 948 base pairs, coding for a hydrophilic polypeptide of 316 amino acid residues, was identified. The deduced amino acid sequence of the carboxyl-terminal region of the VAM7 gene product has heptad repeats and shows potential ability to form a coiled-coil structure. Disruption of VAM7 was not lethal; cells with a disrupted VAM7 gene did not, however, have a prominent large vacuoles but rather numerous small compartments that accumulated the histochemical marker molecule of the vacuolar compartment. They contained mature forms of the vacuolar marker proteins carboxypeptidase Y and vacuolar glycoprotein vgp72. A mutant with both vam7 and vam5 null mutations was constructed and shown to have neither vacuolar structures stained with ade-related fluorochrome nor mature forms of vacuolar marker proteins. These findings suggested that the VAM7 gene product functions in the process of morphogenic assembly of the vacuolar compartment but is not involved in the protein sorting and delivery to the vacuole.

Amino Acid Sequence↗

PubMed2004

[Identification of proteins interacting with androgen receptor- associated coregulator 267-alpha (ARA267-alpha) with the yeast two-hybrid system].

OBJECTIVE: To search for proteins interacting with ARA267-alpha with the yeast two-hybrid system in order to further investigate the function of ARA267-alpha. METHODS: We screened a pretransformed human brain cDNA library with the pGBKT7-PHD-SET recombinant plasmid as a bait which express four PHD(plant homeodomain) and one SET[Su(var)3-9, Enhancer-of-zeste, Trithorax] conserved domains in ARA267-alpha. The plasmids in positive yeast clones were selectively identified by restriction analysis and DNA sequencing. The interactions were retested by yeast two-hybrid assay. RESULTS: There were about six hundreds positive yeast clones on SD/-Ade/-His/-Leu/-Trp/2.5 mmol/L 3-AT/ X-alpha-Gal high-stringency selection plates. The pACT2-cDNA plasmids in sixty-five yeast clones were isolated and thirty-five cDNA inserts were sequenced. Sixteen different genes, including DR6(death receptor-6), PIAS3 (protein inhibitor of activated STAT3)and RanBPM(Ran-binding protein in the microtubule-organizing center), were identified after BLAST in GenBank. The yeast two-hybrid retest showed that all but RanBPM were true interactors of ARA267-alpha-PHD-SET. CONCLUSION: The ARA267-alpha-PHD-SET can interact with several distinct proteins. This suggests that ARA267-alpha is a protein having multiple functions. RanBPM might be a transcriptional factor.

Carrier Proteins↗

PubMed2004

[Proteinases inhibitors in sera of diabetic patients with non-proliferative retinopathy].

Diabetes is associated with a hypercoagulable state. Eighty percent of patients with diabetes mellitus die due to various thrombotic vascular complications. Disorder of coagulation and fibrynolysis is associated with diabetic retinopathy and nephropathy. Angiogenesis requires degradation of vascular basement membrane prior to migration and proliferation of endothelial cells. Various serine proteases play important role in this process. The homeostatic system is also the source of endogenous inhibitors of angiogenesis. Human serum contains various factors able to induce or suppress formation of new blood vessels. The aim of the present study was to evaluate the activity of some angiogenesis inhibitors, anti-proteases, anti-thrombin III, a1 anti-trypsin and a2 anti-plasmin in sera of patients with diabetes mellitus type 1 and 2 and non-proliferative retinopathy, and to correlate this activity to total angiogenic potential of these sera, measured by mice cutaneous test. Sera of 22 persons with DM1, aged 33-70 years, 35 persons with DM2, aged 37-79 years, and 51 healthy people, aged 22-80 years (as control group) were studied. Direct serum-induced cutaneous angiogenesis test in mice (SIA) was applied. Berichrom (ade Behring) tests and immunoturbidimetric method were used for evaluation of anti-proteases activity. Angiogenic activity of DM1 patients sera was statistically lower than this parameter in DM2 patients and in control group. Levels of anti-proteases were similar in DM1, DM2 and control group, with one exception: anti-thrombin level was lower in DM2 patients' sera than this in the control group. Analysis of correlation revealed important difference in behaviour of DM1 sera, as compared to other groups. Significant negative correlation was observed between angiogenic activity and anti-thrombin, as well as anti-trypsin level of DM1 patients' sera. On the other hand, correlation analysis performed for the sera of control group revealed significant positive correlation between their angiogenic activity and anti-thrombin level. No other correlations were found.

Adult↗

PubMed1992

Adenosine receptor-mediated alterations in prostacyclin production and cardiac function in the isolated rabbit heart.

The subtype of adenosine receptor linked to cardiac prostacyclin (PGI2) synthesis, measured as immunoreactive 6-keto-PGF1 alpha, was investigated in the rabbit heart perfused with Krebs' buffer at 20 ml/min. Adenosine (6.4-50 nmol) decreased 6-keto-PGF1 alpha synthesis, coronary perfusion pressure (PP) and myocardial contractility (dp/dt max), whereas higher doses (200 nmol) increased 6-keto-PGF1 alpha output and decreased PP, heart rate (HR) and dp/dt max. Injections (3.2-50 nmol) or infusion (0.6 microM) of A1 receptor agonist 1-deaza,2-chloro,N6 cyclopentyladenosine increased 6-keto-PGF1 alpha production and decreased HR and PP without affecting dp/dt max. 1-Deaza,2-chloro,N6 cyclopentyladenosine 100 to 200 nmol produced similar effects as lower doses except that it decreased transiently PP and reduced dp/dt max. 1,3-Dipropyl,8-cyclopentylxanthine (0.06 microM) prevented the effects of 1-deaza,2-chloro,N6 cyclopentyladenosine (50 mumol) and adenosine (10 microM) to increase 6-keto-PGF1 alpha output and decrease HR and minimized the decrease in dp/dt max. A2 receptor agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido-ade nos ine (1.6-12.5 nmol) or 0.6 microM decreased 6-keto-PGF1 alpha output, PP and dp/dt max without changes in HR. 3,7-Dimethyl-1-propargylxanthine prevented 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine-induced decrease in 6-keto-PGF1 alpha output, PP and dp/dt max; HR was not altered by this agent. These data suggest that stimulation of A2 receptors reduce cardiac PGI2 synthesis and PP, but activation of A1 adenosine receptors increased PGI2 synthesis, produced vasoconstriction and decreased HR.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗