Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies on antimicrobial activity, absorption and excretion and clinical use of cefoxitin in pediatric field were performed. 1. MIC of cefoxitin was compared with that of cefazolin and/or ampicillin for clinical isolates of Staphylococcus aureus (36 strains), Escherichia coli (35 strains), Klebsiella pneumoniae (34 strains) and Haemophilus influenzae (80 strains). MIC of cefoxitin against S. aureus was approximately 1-2 tubes higher than that of cefazolin. Many strains of E. coli and K. pneumoniae that showed high MIC to cefazolin were sensitive to cefoxitin. It is presumed that the results are due to the strong resistance of cefoxitin to beta-lactamase degradation. MIC of cefoxitin against H. influenzae was approximately 1-2 tubes lower than that of cefazolin, but approximately 4 tubes higher than that of ampicillin. 2. Serum level and urinary recovery rate of cefoxitin after one shot i.v. injection of 25 mg/kg were examined. The serum mean levels were 33.8 microgram/ml at 1/2 hour, 7.0 microgram/ml at 1 hour and 2.9 microgram/ml at 2 hours after the injection, respectively, and the drug was not detected in serum at 4 and 6 hours after the injection. The mean half-life of serum level was 27.1 minutes. The mean urinary recovery rate within 6 hours after injection was 96.0% and most of the drug were excreted into urine within 2 hours after the injection. 3. In order to evaluate clinical response, bacteriological response and side effects, cefoxitin was applied to 19 cases, i.e., 12 cases of either acute lobar pneumonia or acute bronchopneumonia, 2 cases of acute pyelitis, 1 case each of acute bronchitis, acute purulent tonsillitis, acute purulent arthritis, acute orbital phlegmon and acute buccal abscess. As for clinical response, the overall efficacy rate (the percentage of cases showed excellent and good efficacy) was 88.9%. As for bacteriological response, among the 13 strains which were determined or supposed to be causative organisms, i.e., 6 strains of Streptococcus pneumoniae, 2 strains of H. influenzae and 1 strain each of streptococcus pyogenes, alpha-Streptococcus, Enterococcus, E. coli and Neisseria sp., all strains were disappeared except for Enterococcus which was reduced by the treatment with cefoxitin. No side effect was observed in any case. Abnormalities of laboratory findings were observed in 3 cases, i.e., 1 case each of reduction of RBC and Hb, elevation of GOT and GPT and elevation of GPT, but all of them returned to normal following completion of the dosage term.
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PMID:[Laboratory and clinical studies on cefoxitin in pediatric field (author's transl)]. 728 22

Both bacteriological and clinical studies of the effectiveness of cefoxitin (CFX) in the treatment of infections associated with abdominal surgery have been carried out at Tokyo Metropolitan Toshima Hospital from September 1979 through August 1980. The results of these studies are summarized in the following: 1. The clinical isolates from the 29 surgical patients were studied and anaerobes were found in 16 patients (55% of the patients). B. fragilis was found in 11 of the 16 patients (69%) from whom anaerobes were isolated. In all of these patients, aerobes were also isolated--most frequently E. coli or K. pneumoniae. 2. The in vitro antibacterial activity of cefoxitin (CFX) against 83 clinical isolates was compared to that of cephalothin (CET), cefazolin (CEZ) and carbenicillin (CBPC). The activity of CFX against Gram-positive bacteria was generally slightly inferior to that of the other 3 antibiotics. Among the Gram-negative aerobic organisms, CEZ was the most active against E. coli and CFX and CEZ against K. pneumoniae. However, CFX, with MIC's of 0.78-12.5 micrograms/ml, showed the greatest activity against B. fragilis, followed by CBPC, CEZ and CET, in order of decreasing activity. 3. CFX was administered in a 1-hour drip infusion to 3 patients following abdominal surgery, and concentrations of CFX in the serum and the exudate were measured. Peak serum concentrations were obtained at the end of the infusion, with a mean peak level of 97.93 micrograms/ml. Peak concentrations in the exudate were observed 30 to 60 minutes later and varied from 21.10 to 56.25 micrograms/ml. 4. Of the 20 patients administered of CFX, complete clinical and bacteriological data of anaerobic infections were available in 8 patients. The clinical evaluation was 'good' in 7 patients and 'fair' in 1. The bacteriological evaluation was 'eradicated' in 5 patients and 'decreased' in 3. As for side effects, elevations of S-GOT and S-GPT were observed in 4 of the 20 patients received CFX, but these abnormalities might also be attributable to other factors such as underlying disease, surgical intervention etc. No other side effects were found in these patients.
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PMID:[Bacteriological and clinical studies of cefoxitin with special reference to anaerobic infections in the patients of abdominal surgery (author's transl)]. 732 55

Macrolide and tetracycline antibiotics, which are protein synthesis inhibitors, are effective in the treatment of mycoplasma pneumonia. We evaluated the clinical efficacy and safety of roxithromycin, a new macrolide antibiotic, in the treatment of mycoplasma pneumonia. Roxithromycin was administered orally to patients who had been definitely diagnosed through Mycoplasma pneumoniae isolation or serum antibody titer as having mycoplasma pneumonia. The efficacy assessment was based on clinical signs and symptoms of infection as well as bacterial culture from clinical samples. Clinical efficacy was excellent in 6 cases, good in 6 cases and fair in 1 case, with an efficacy rate of 92.3%. The bacteriological effect was evaluated in 6 patients: the organism was eradicated in 4 cases and unchanged in 2 cases. In this study, the MIC of roxithromycin against M. pneumoniae fell in the range 0.0156-0.00625 mg/l. No adverse reaction was observed. As for abnormal laboratory findings, two cases showed elevated serum glutamic-pyruvic transaminase (S-GPT), one elevated serum glutamic-oxaloacetic transaminase and S-GPT, and one reduced neutrophil counts. From our results, we consider that roxithromycin is useful in the treatment of mycoplasma pneumonia.
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PMID:Efficacy of roxithromycin in the treatment of mycoplasma pneumonia. 775 59

Blood and urine levels of cefozopran (CZOP) were determined, and its efficacy and safety profile was evaluated in the field of pediatrics. The results of this study are summarized as follows. 1. Blood levels of CZOP peaked in 30 minutes to 1 hour (initial blood collection) after intravenous administration at a dose of 20 or 40 mg/kg. Its blood levels at 6 hours after intravenous administration were 1.6 micrograms/ml (HPLC) or 1.9 micrograms/ml (bioassay) at a dose of 20 mg/kg and 2.9 to 9.1 micrograms/ml (HPLC) or 2.9 to 8.4 micrograms/ml (bioassay) at a dose of 40 mg/kg. The half-lives were 1.58 to 2.27 hours (HPLC) and 1.53 to 1.85 hours (bioassay), respectively. The rate of recovery of CZOP in the urine in the first 8 hours after intravenous administration at a dose of 20 mg/kg was 61.5% (HPLC) or 54.6% (bioassay), and urine levels of CZOP at 6 to 8 hours after administration were 157.3 micrograms/ml (HPLC) and 129.7 micrograms/ml (bioassay). 2. When CZOP was administered to 16 patients with respiratory tract infections, 2 patients with urinary tract infections, 2 patients with acute enteritis, 1 patient with skin soft tissue infection, and 1 patient with purulent lymphadenitis, the responses were excellent in 68% of patients and good in 32% with an overall efficacy rate of 100%. 3. Bacteriological effect of CZOP was excellent and the rate of bacterial eradication was 100% (9/9). 4. MICs of CZOP against clinical isolates (Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Streptococcus pneumoniae, Escherichia coli, Moraxella (Branhamella) catarrhalis) were compared to those of other injectable cephems ceftazidime (CAZ), cefuzonam (CZON), flomoxef (FMOX), cefmetazole (CMZ). The MICs of cefozopran (CZOP) against Gram-positive organisms, S. aureus, MRSA, and S. pneumoniae, were nearly as low as those of CZON and were clearly lower than those of CAZ. MICs of CZOP against Gram-negative organisms were examined and the MIC against E. coli was as low as those of other antibiotics but the MIC of CZOP against M. (B.) catarrhalis was higher, at 1.56 micrograms/ml, than those of CAZ, FMOX, and CMZ. 5. Diarrhea was experienced by 1 of 22 patients as a side effect from CZOP, and abnormal laboratory tests including increases of eosinophil counts in 2 patients (9.1%), a decrease of neutrophil counts in 1 patient (4.5%), thrombocytosis in 1 patient (4.5%), and an elevation of GPT in 3 patients (13.6%).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pharmacokinetic and clinical studies on cefozopran in the field of pediatrics]. 785 87

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluations. 1. Antibacterial activities. MIC profile of AZM was as follows: 0.78 approximately 1.56 micrograms/ml against Staphylococcus aureus, < or = 0.025 approximately 0.10 microgram/ml against Streptococcus pyogenes, 0.10 approximately 0.39 and 6.25 micrograms/ml against Streptococcus pneumoniae, < or = 0.025 approximately 0.39 microgram/ml against Moraxella(Branhamella) catarrhalis, 0.39 approximately 3.13 micrograms/ml against Haemophilus influenzae, and 0.20 approximately 6.25 micrograms/ml against Haemophilus parainfluenzae. 2. Absorption and excretion. The elimination half-life of AZM after its administration at 10 mg/kg/day for three days was 28.1 approximately 46.1 hours. The cumulative urinary excretion rate in the first 120 hours after start of treatment was 4.01 approximately 8.47%. 3. Clinical evaluation. AZM was given to 76 pediatric patients to treat following infections: pharyngitis in seven, tonsillitis in 11, bronchitis in 11, pneumonia in 19, Mycoplasma pneumonia in eight, scarlet fever in 13, infective enteritis in one, SSTI in four, and otitis media in two. Effectiveness of AZM was assessed in 75 patients and the drug was rated "excellent" or "good" in 71 resulting in an efficacy rate of 94.7%, 87.0% of the 46 cases indicated that AZM had eradicated bacteria identified before the treatment. One patient complained of moderate diarrhea which disappeared after treatment of anti-diarrheic. Abnormal laboratory changes were reported in 12 patients in the following: decreased leukocytes in eight, increased eosinophils in two, increased platelet count in one, and increased GPT in one. All cases of abnormality was deemed mild in severity and clinically insignificant.
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PMID:[Pharmacokinetic and clinical evaluation of azithromycin using fine granules or capsules in the pediatric patients]. 898 10

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.
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PMID:[Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics]. 963 60

A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was conducted with stock strains and clinical isolates. The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases. The results were as follows: 1. In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three clinically isolated species from patients, Staphylococcus aureus (S. aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the others were treated with the same drugs except for DMPPC. The MICs were measured for these bacterial strains inoculated at the concentration of 10(6) CFU/ml. The MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S. pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram-negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella pertussis (B. pertussis) were 0.10 microgram/ml and similar to those of PIPC. The MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae) were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non beta-lactamase producing strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1 micrograms/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H. influenzae did not produce beta-lactamase and 1 strain was a high producer. The MICs of TAZ/PIPC against beta-lactamase nonproducing strains were < or = 0.025 microgram/ml in 5 strains and 0.39 microgram/ml in 1 strain, and the values were similar to those of PIPC and SBT/CPZ. While the MIC of TAZ/PIPC against the high beta-lactamase producing strain was 0.78 microgram/ml; similar to that of SBT/CPZ and smaller than that of PIPC. 2. The results of clinical effects on 7 diseases in 33 cases were as follows: TAZ/PIPC was clinically judged "excellent" in 17 (51.5%); good in 14 (42.4%); fair in 2 (6.1%). No case with no response was seen in this study, and the total efficacy rate of "excellent" and "good" was 93.9%. 3. Bacteriological effects were evaluated in 17 strains of 4 species, and all of them were eradicated. 4. Adverse reactions were judged in 35, which consisted of 33 in which the clinical effects were evaluated and 2 dropped from this study. Of these cases, diarrhea was observed in 4 (11.4%). 5. Laboratory tests revealed an increase in platelets in 1 of 32 cases (3.1%), and eosinophilia in 2 of 29 cases (6.9%). Biochemical profile showed an increase in GPT alone and abnormal increases in both GOT and GPT in 1 each out of 21 cases.
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PMID:[Basic and clinical studies on tazobactam/piperacillin in pediatric field]. 975 31

A randomized, single-center, open-label study of posaconazole (POS) was performed to determine the concentration of POS in the skin of 30 healthy adult human subjects receiving 400 mg POS oral suspension twice daily for 8 days with a high-fat meal. Blood samples for plasma POS level determination were collected at prespecified times on day 1 and day 8. From each subject, two 4-mm skin punch biopsy samples were obtained, one immediately before or after both the first and last doses of POS. A MIC(90) value of 250 ng/ml, which encompasses the majority of common dermatophytes, was used to calculate the time above the MIC(90) in plasma and skin. On days 1 and 8, POS attained peak plasma concentrations at median times of 8 and 5 h, respectively. On days 1 and 8, POS peak skin concentrations were attained at 12 and 3 h, respectively; peak skin concentrations were produced from a single composite profile. On day 8, POS concentrations in skin and plasma for the entire dosing interval were severalfold higher than the MIC(90). POS dosed at 400 mg twice daily per os was well tolerated in healthy subjects. Two subjects reported increased alanine aminotransferase (ALT) levels. The findings of this study demonstrate adequate skin penetration and have certain implications for the treatment of dermatophytic skin and nail infections.
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PMID:Skin concentrations and pharmacokinetics of posaconazole after oral administration. 2019 2

Shedding of the human NKG2D ligand MIC (MHC class I-chain-related molecule) from tumor cell surfaces correlates with progression of many epithelial cancers. Shedding-derived soluble MIC (sMIC) enables tumor immune escape through multiple immune suppressive mechanisms, such as disturbing natural killer (NK) cell homeostatic maintenance, impairing NKG2D expression on NK cells and effector T cells, and facilitating the expansion of arginase I+ myeloid suppressor cells. Our recent study has demonstrated that sMIC is an effective cancer therapeutic target. Whether targeting tumor-derived sMIC would enhance current active immunotherapy is not known. Here, we determined the in vivo therapeutic effect of an antibody co-targeting sMIC with the immunostimulatory IL-15 superagonist complex, ALT-803, using genetically engineered transplantable syngeneic sMIC+ tumor models. We demonstrate that combined therapy of a nonblocking antibody neutralizing sMIC and ALT-803 improved the survival of animals bearing sMIC+ tumors in comparison to monotherapy. We further demonstrate that the enhanced therapeutic effect with combined therapy is through concurrent augmentation of NK and CD8 T cell anti-tumor responses. In particular, expression of activation-induced surface molecules and increased functional potential by cytokine secretion are improved greatly by the administration of combined therapy. Depletion of NK cells abolished the cooperative therapeutic effect. Our findings suggest that administration of the sMIC-neutralizing antibody can enhance the anti-tumor effects of ALT-803. With ALT-803 currently in clinical trials to treat progressive solid tumors, the majority of which are sMIC+, our findings provide a rationale for co-targeting sMIC to enhance the therapeutic efficacy of ALT-803 or other IL-15 agonists.
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PMID:Cooperative therapeutic anti-tumor effect of IL-15 agonist ALT-803 and co-targeting soluble NKG2D ligand sMIC. 2662 16

Azithromycin is extensively used in children with community-acquired pneumonia (CAP). Currently, the intravenous azithromycin is used off-label in children partly due to lacking of pharmacokinetic data. Our objective was to evaluate the population pharmacokinetics (PPK) and optimize dose strategy in order to improve treatment in this distinctive population. This was a prospective, multicenter, open-labeled pharmacokinetic study. Blood samples were collected from hospitalized pediatric patients and concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PPK analysis was conducted using NONMEM software. The pharmacokinetic data from 95 pediatric patients (age range, 2.1 to 11.7 years) were available for analysis. The PPK was best fitted by a two-compartment model with linear elimination. Covariate analysis verified that body weight and alanine aminotransferase (ALT) had significant effects on azithromycin pharmacokinetics, yielding a 24% decrease of clearance in patients with ALT of >40. Monte Carlo simulation showed that for children with normal liver function, a loading-dose strategy (a loading dose of 15 mg/kg of body weight followed by maintenance doses of 10 mg/kg) would achieve the ratio of the area under free drug plasma concentration-time curve over 24 h (fAUC) to MIC90 (fAUC/MIC) target of 3 h in 53.2% of hypothetical patients, using a normative MIC susceptibility breakpoint of 2 mg/liter. For children with ALT of >40, the proposed dose needed to decrease by 15% to achieve comparable exposure. The corresponding risk of overdose for the recommended dosing regimen was less than 5.8%. In conclusion, the PPK of azithromycin was evaluated in children with CAP and an optimal dosing regimen was constructed based on developmental pharmacokinetic-pharmacodynamic modeling and simulation.
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PMID:Population Pharmacokinetics and Dosing Optimization of Azithromycin in Children with Community-Acquired Pneumonia. 2994 52


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