Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This was a phase II, randomised, open-label, multi-centre study to assess the safety, tolerability, and efficacy of sitafloxacin (DU-6859a, 400 mg once daily) compared with imipenem (imipenem/cilastatin, 500 mg three times daily) in the treatment of hospitalised patients with pneumonia. Patients (n=69) were entered into the study in the intent-to-treat group, 35 in the sitafloxacin and 34 in the imipenem group. Patients (n=65) were included in the clinically evaluable population and 42 in the bacteriologically evaluable population. Baseline demographic data and clinical characteristics were similar for both treatment groups and across all patient populations. The incidence, severity and type of adverse events were similar in both treatment groups. The frequency of adverse events, which were considered to be related to the study of drugs was low and generally similar between the two groups. Mild transient increases in alanine aminotransferase and alkaline phosphatase occurred in the sitafloxacin treatment group, but there were no apparent trends in the other serum enzyme levels. The clinical response at the first and second follow-up assessments indicated that 94-97% of patients in the clinically evaluable population and 91% of patients in the intent-to-treat population were classified as cured in both treatment groups. The bacteriological response was classified as satisfactory for all patients (100%) in the bacteriologically evaluable population in the imipenem treatment group and satisfactory for 90 and 95% of cases at the first and second follow-up assessments in the bacteriologically evaluable population in the sitafloxacin treatment group, respectively. In conclusion, for the treatment of pneumonia, sitafloxacin was considered as safe and as tolerable as imipenem and preliminary data from this study suggest that it may have similar efficacy.
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PMID:An open, randomised, multi-centre study comparing the safety and efficacy of sitafloxacin and imipenem/cilastatin in the intravenous treatment of hospitalised patients with pneumonia. 1128 62

A chemiluminescent sandwich ELISA test has been developed for the detection and quantitation of pneumolysin. The test is based on a mouse monoclonal as the capture antibody and on rabbit polyclonal IgGs as detection antibodies, in combination with an anti-rabbit IgG alkaline phosphatase conjugate. The estimated detection limit of the purified recombinant toxin in phosphate-buffered saline with 0.05% Triton X-100 is around 5 pg ml(-1), with averaged intra- and inter-assay variation coefficients of 7% and 13.5%, respectively. The assay has been applied to the quantitation of pneumolysin in pneumococcal isolates, providing, for the first time, a direct measurement of the amount of the toxin produced by different strains, a variation has been found in their pneumolysin content. The test is highly specific as no other purified toxins or human pneumonia- or meningitis-associated bacteria yielded false-positive results. This specific and highly sensitive method could help in the diagnosis of human infections.
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PMID:A specific and ultrasensitive chemiluminescent sandwich ELISA test for the detection and quantitation of pneumolysin. 1148 15

The strategy in the choice of antipsychotic agent must take into account the hepatic tolerance according to non-negligible incidence of liver disorders among psychiatric population (presence of risk factors like alcoholism, drugs of abuse intake, polymedication including potentially hepatotoxic drugs.). More than 1 000 drugs have been listed as being responsible of hepatic side effects; 16% of these agents were neuropsychiatric drugs. Antidepressive drugs (tricyclic agents or SSRI), mood stabilizing agents and neuroleptic drugs have been implicated in biological or/and clinical hepatotoxicity. For these reasons, some psychotropic agents have been withdrawn of the pharmaceutical market like alpidem or medifoxamine. Atrium*, sometimes used to correct tremor induced by neuroleptic drugs, has been withdrawn recently, as well. Isolated elevations of hepatic enzymes occur frequently with phenothiazines drugs (frequency evaluated to 20%) but also with other classes of neuroleptic agents, as well. On the contrary, clinical hepatitis have been more rarely described with neuroleptic drugs like phenothiazine agents (0,1-1%) or with haloperidol (0,002%). The definition of hepatotoxicity is based on biological parameters (elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT) or on clinical abnormalities (hepatitis, jaundice.). Clinical hepatitis could be either cytolytic or cholestatic. Clinical diagnosis and the research of its origin may include many investigations like abdominal ultrasonogram and percutaneous liver biopsy. The present article describes the cases of hepatic disorders reported with AAD (Atypical Antipsychotic Drugs), which are available in France (amisulpride, clozapine, olanzapine, risperidone). This new pharmacological class of antipsychotic drugs has showed great interest to improve negative symptoms of schizophrenia and to reduce disabling side effects like dystonia. According to the bibliographic data available, the following points and information must be clinically taken into account. Frequency of hepatic troubles: according to the bibliographic data, AAD appeared generally well tolerated in most cases. The frequency of hepatic troubles remains in general very low or rare. The cases published were observed with clozapine, olanzapine and risperidone. Nevertheless, some authors have observed higher frequency of hepatic enzymes elevation with some AAD. In an investigation comparing hepatic tolerance of clozapine (n=167) versus haloperidol (n=71), 37,3% of clozapine treated patients showed a relevant SGPT increase versus 16,6% with haloperidol. Nature of the hepatic troubles: among the clinical observations, asymptomatic biological disorders of the hepatic function are generally described but cytolytic or cholestatic hepatitis were reported, as well. Symptomatic hepatic dysfunctions were, sometimes, associated with other disorders like convulsions, pneumonia or malignant syndrome. Thus, hepatic check-up may be relevant in case of significant side-effect outcome. Delay time before the hepatic episode: hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. These delay times are very similar to those observed with other psychotropic drugs. Reversibility of the hepatic troubles and rechallenge of the responsible agent: all cases were reversible after the AAD withdrawal except with one patient (39 years old) treated by clozapine (350 mg/day) who developed a fulminant and irreversible hepatitis after 8 weeks of monotherapy. In most cases, the AAD was withdrawn after the hepatic episode according to the significant risk of irreversible alteration. Nevertheless, normalization of hepatic enzymes has been described despite AAD maintenance at the same dosage or after dosage reduction. Rechallenge of clozapine after a first episode was performed for three patients, only one redeveloped a new hepatic disorder. According to different authors, special care is required if maintenance or rechallenge of the agent is indispensable after a first episode of isolated hepatic enzyme elevation (i.e resistance or intolerance to other treatments). In this case, biological and clinical supervision has to be carefully scheduled, which demands a satisfactory compliance from the patient. On the contrary, in case of clinical hepatotoxicity, rechallenge or maintenance is absolutely inadvisable. Mechanism of the hepatic troubles: precise mechanisms of the hepatotoxicity remain unclear. Contrary to phenothiazine drugs, no information is available on the respective rule of the agents and their metabolites. Hypersensitivity syndrome or eosinophilia has been reported, suggesting a possible immuno-allergic mechanism. Presence of risk factors: risk factors have been retrieved, in some observations, like high daily dosage, high plasmatic concentration, age, alcoholism, obesity or antecedent of hepatic disorders like Gilbert syndrome. Special care is advisable with these patients. As hepatotoxicity has been observed after surdosage (or suicide attempt), a hepatic check-up has to be performed in these clinical situations. Co-medication with hepatotoxic drugs may increase the risk as it has been suggested. In many observations, co-medication made difficult the incrimination of the AAD in the hepatic disorders outcome. Monotherapy has the great advantage to make easier the withdrawal of the responsible agent and its substitution. As drugs of abuse like cocaine or ecstasy are notoriously responsible of hepatotoxicity, they represent a probable factor of risk. Moreover, their detection is fundamental during the clinical investigation. Conclusion - Diagnosis of toxic hepatitis is mainly based on the chronology between agent introduction and hepatic disorder onset but other causes must be excluded. Bibliographic data analysis greatly contributes to confirm toxic hepatitis diagnosis. Nevertheless, this article emphasized the limits of bibliographic review to compare drugs towards tolerance. Most of the bibliographic data were case-reports for which it was sometimes difficult to provide absolute evidence of the responsibility of the agent. Moreover, spontaneous notification to health national administration is rarely systematic, in particular with isolated elevation of hepatic enzymes, and even more rarely published in international reviews. Nevertheless, according to the present data available in the literature, systematic and regular hepatic survey does not seem necessary in absence of risk factors. As for other side effects, which may occur more or less rapidly, great advantages may be obtained from psycho-education programs associating the patients in order to detect the first symptoms. Because little long-term hepatic follow-up comparing AAD is available, controlled studies should be carried out to precise the frequency and the risk factors (covariables) to prevent hepatitis outcome.
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PMID:[Hepatic tolerance of atypical antipsychotic drugs]. 1250 67

Mast cells play an important role in tissue inflammation, fibrosis and remodelling. They are found in bronchoalveolar lavage fluid (BAL) of healthy persons only in small numbers. We investigated the number of mast cells in interstitial lung diseases and analysed our data for correlations with clinical parameters, cellular and non-cellular parameters of BAL. We found following counts of mast cells in % of total BAL cells: Sarcoidosis (n = 123); 0.22 +/- 0,04 %, idiopathic pulmonary fibrosis (IPF) (n = 35); 0.39 +/- 0.47 %, cryptogenic organising pneumonia (COP) (n = 27); 2.05 +/- 2.19 %, hypersensitivity pneumonitis (HP) (n = 24); 1.02 +/- 1.05 %, rheumatoid lung (n = 20); 0.21 +/- 0.21 %, respiratory bronchiolitis-associated interstitial lung disease (RBILD) (n = 11); 0.16 +/- 0.29 %) and control group (n = 16); 0.06 +/- 0.16 %. Compared to controls mast cells were increased in COP (p < 0.001) and HP (p < 0,01). Correlation analysis showed that an increased mast cell count correlated with: Higher age (sarcoidosis (p = 0.03); smaller vital capacity (sarcoidosis (p = 0.01)), smaller FEV 1 (sarcoidosis (p = 0.04), RBILD (p = 0.04)); higher alkaline phosphatase in BAL (sarcoidosis (p = 0.004), HP (p = 0.02), COP (p = 0.04); higher albumin level in BAL (sarcoidosis (p = 0.000), IPF (p = 0.003); higher cell counts in BAL (sarcoidosis (p = 0.013), COP (p = 0.04)); lower portion of macrophages in BAL cells (sarcoidosis (p = 0.001), HP (p = 0.02), COP (p = 0.02)); higher portion of lymphocytes in BAL cells (sarcoidosis (p = 0.03)); higher portion of neutrophils in BAL cells (sarcoidosis (p = 0.007)); higher portion of eosinophils in BAL cells (sarcoidosis (p = 0.001), HP (p = 0.006)). Correlations to smoking history in pack years and to lymphocyte surface markers CD3, CD4, CD8 were not found. In conclusion comparing different interstitial lung diseases we found significantly increased mast cell counts in COP and HP. Moreover there were correlations of increased mast cell counts with more intensive alveolitis and exudation.
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PMID:[Mast cells in bronchoalveolar lavage fluid of patients with interstitial lung diseases]. 1269 May 58

A 77-year-old man with pneumonia associated with acute myeloid leukemia was introduced to the hepatology unit at our hospital for hyperbilirubinemia. He had been suffering from a high fever because of pneumonia. He was icteric and his serum concentrations of total and direct bilirubin were 13.1 and 7.9 mg/dl, respectively. However, the other standard biochemical examinations for hepatic function, such as serum concentrations of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase were normal except for lactate dehydrogenase. Lactate dehydrogenase isoenzyme analysis revealed that the high concentration was derived from leukemia cells. Ultrasonography of the abdomen revealed no abnormality in the liver or biliary tract. Administration of antibiotics for pneumonia decreased the serum bilirubin concentration, however, he died because of respiratory failure caused by the progression of pneumonia at 33 days after the admission. It was suggested that a disturbance in the bilirubin metabolism without hepatocyte necrosis or mechanical cholestasis might be involved in the pathogenesis of hyperbilirubinemia in patients with infectious diseases.
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PMID:Unusual hyperbilirubinemia associated with bacterial pneumonia and acute myeloid leukemia. 1280 38

Histoplasma capsulatum (Hc) is a facultative intracellular fungal pathogen that causes acute and chronic pneumonia. In this study, we investigated the role of the pulmonary collectins, surfactant proteins (SP) A and D, in the clearance of Hc yeast from the lung. Exposure of yeast to either collectin induced a dose-dependent decrease in [3H]leucine incorporation by several strains of Hc. This decrement was attributed to killing of the collectin-exposed yeast since it failed to grow on agar medium. Exposure to SP-A or -D resulted in increased yeast permeability based on a leak of protein from the organism and enhanced access of an impermeant substrate to intracellular alkaline phosphatase. Inbred and outbred SP-A null (-/-) mice were modestly more susceptible to pulmonary infection with Hc than strain and age-matched SP-A (+/+) control mice. The increase in susceptibility was associated with a decrement in the number of CD8+ cells in the lungs of SP-A-/- mice. Neither SP-A nor SP-D inhibited the growth of macrophage-internalized Hc. We conclude that the SP-A and SP-D are antimicrobial proteins that directly inhibit the growth of Hc by increasing permeability of the organism and that Hc gains asylum from collectin-mediated killing by rapid entry into pulmonary macrophages.
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PMID:Macrophage-independent fungicidal action of the pulmonary collectins. 1285 53

The degree of metabolic rehabilitation of the bronchopulmonary system was evaluated in non-specific pulmonary diseases, like pneumonia or chronic obstructive bronchitis, by using the data of biochemical testing of the exhaled-air vapor condensate. Nine parameters were investigated, i.e. enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase, alkaline phosphatase (AP), gamma-glutamate amino-transpeptidase (GGT) as well as parameters of protein metabolism--common protein, seromucoid (SC), C-reactive protein and urea. AST, ALT, AP, GGT, SC and urea were acknowledged as the most informative parameters. The results are indicative of that the recovery of metabolic processes in the bronchopulmonary system was not completed.
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PMID:[Vapor condensate of exhaled air in evaluating the impaired metabolism of the bronchopulmanory system in nonspecific lung diseases]. 1523 Jan 10

BACKGROUND: The pattern of liver function tests (LFTs) in community-acquired pneumonia has not been investigated in detail. Although abnormal tests are thought to be more frequent in patients with atypical pneumonia, the prognostic value of LFTs have not been clearly established. METHODS: We assessed 96 consecutive patients admitted to one hospital with a chest infection over a period of 6 weeks. The infection was classified as bronchitis or lobar pneumonia on clinical and radiological criteria. The site and severity of the infection were assessed and correlated with LFTs and standard British Thoracic Society prognostic criteria. Mortality and length of stay in survivors were used as major outcome measures. RESULTS: There were 17 deaths (18%) overall and patients with abnormal LFTs were significantly more likely to die than those with normal tests (25% vs. 5%; p=0.026). Length of stay was significantly longer in survivors with abnormal liver function than in those with normal tests (9.7 vs. 5.8 days; p=0.006). A low albumin was the most useful predictor of poor outcome and carried a relative risk of dying of 1.8, comparable to the predictive value of tachypnoea. ALT was increased threefold in those succumbing to their disease, but alkaline phosphatase levels were not predictive of outcome and an increase in gamma GT appeared to be protective. CONCLUSIONS: Abnormal LFTs are common in community-acquired pneumonia and are of prognostic value. Patients with a low albumin or raised ALT are significantly more likely to die from their disease or to stay in hospital for a prolonged period. However, other LFTs are of less value in predicting prognosis.
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PMID:The pattern and significance of abnormal liver function tests in community-acquired pneumonia. 1558 47

A 12 y old girl was admitted 24 days after start a WHO multidrug therapy scheme for multibacillary leprosy (dapsone, clofazimine and rifampicin) with intense jaundice, generalized lymphadenopathy, hepatoesplenomegaly, oral erosions, conjunctivitis, morbiliform rash and edema of face, ankles and hands. The main laboratory data on admission included: hemoglobin, 8.4 g/dL; WBC, 15,710 cells/mm3; platelet count, 100,000 cells/mm3; INR = 1.49; increased serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, direct and indirect bilirubin. Following, the clinical conditions had deteriorated, developing exfoliative dermatitis, shock, generalized edema, acute renal and hepatic failure, pancytopenia, intestinal bleeding, pneumonia, urinary tract infection and bacteremia, needing adrenergic drugs, replacement of fluids and blood product components, and antibiotics. Ten days after admission she started to improve, and was discharged to home at day 39th, after start new supervised treatment for leprosy with clofazimine and rifampicin, without adverse effects. This presentation fulfils the criteria for the diagnosis of dapsone hypersensitivity syndrome (fever, generalized lymphadenopathy, exfoliative rash, anemia and liver involvement with mixed hepatocellular and cholestatic features). Physicians, mainly in geographical areas with high prevalence rates of leprosy, should be aware to this severe, and probably not so rare, hypersensitivity reaction to dapsone.
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PMID:Dapsone hypersensitivity syndrome in an adolescent during treatment during of leprosy. 1565 79

Chlamydophila pneumoniae is an obligate intracellular bacterium that causes bronchitis, pharyngitis, and pneumonia and may be involved in atherogenesis and Alzheimer's disease. Genome sequencing has identified three eukaryote-type serine/threonine protein kinases, Pkn1, Pkn5, and PknD, that may be important signaling molecules in Chlamydia. Full-length PknD was cloned and expressed as a histidine-tagged protein in Escherichia coli. Differential centrifugation followed by sodium carbonate treatment of E. coli membranes demonstrated that His-PknD is an integral membrane protein. Fusions of overlapping PknD fragments to alkaline phosphatase revealed that PknD contains a single transmembrane domain and that the kinase domain is in the cytoplasm. To facilitate solubility, the kinase domain was cloned and expressed as a glutathione S-transferase (GST) fusion protein in E. coli. Purified GST-PknD kinase domain autophosphorylated, and catalytic mutants (K33G, D156G, and K33G-D156G mutants) and activation loop mutants (T185A and T193A) were inactive. PknD phosphorylated recombinant Cpn0712, a type III secretion YscD homolog that has two forkhead-associated domains. Thin-layer chromatography revealed that the PknD kinase domain autophosphorylated on threonine and tyrosine and phosphorylated the FHA-2 domain of Cpn0712 on serine and tyrosine. To our knowledge, this is the first demonstration of a bacterial protein kinase with amino acid specificity for both serine/threonine and tyrosine residues and this is the first study to show phosphorylation of a predicted type III secretion structural protein.
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PMID:Chlamydophila pneumoniae PknD exhibits dual amino acid specificity and phosphorylates Cpn0712, a putative type III secretion YscD homolog. 1776 19


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