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)

Pharmacokinetics and clinical effects of ceftizoxime (CZX), a new cephalosporin antibiotic, were investigated and following results were obtained. 1) Ceftizoxime was given by intravenous injection or drip infusion for 1 hour at a single dose of 30 mg/kg. After intravenous injection, the mean peak serum level of 3 children was 95.9 mcg/ml at 15 minutes and half-life time was 1.18 hours. After 1 hour drip infusion, the mean peak serum level of 3 children was 79.5 mcg/ml at the end of infusion and half-life time was 1.20 hours. The urinary level was high and the mean urinary recovery rate was 69.6% and 63.4% up to 6 hours after intravenous injection and 1 hour drip infusion, respectively. 2) CZX was administered in dose of 39--76 mg/kg to 7 pediatric patients (4 cases of purulent meningitis, 2 of septicemia with purulent meningitis, and 1 of aseptic meningitis) by a single intravenous injection. In patients with purulent meningitis, passage into the cerebrospinal fluid was relatively as good as 30% of serum level at the same time in the presence of remarkable signs of inflammation, but poor in cases of mild inflammation or aseptic meningitis. 3) Cerebral puncture fluid level in 1 patient with cerebral abscess was as good as 65.5% of serum level at the same time. 4) CZX was given to 28 cases of respiratory tract infection, 1 of tonsillitis with otitis media, 6 of scarlet fever, 1 each of maxillary sinusitis and bacterial endocarditis, 6 of purulent meningitis, 2 of septicemia, 5 of septicemia suspected, 2 of septicemia with purulent meningitis, 1 each of osteomyelitis, typhoid fever, peritonitis and biliary tract infection, 16 of urinary tract infection, 14 of skin and soft tissue infection, and 1 of external otitis, totaling 87 cases. The mean daily dose of 101.6 mg/kg was administered for an average of 10 days mainly by intravenous injection 4 times daily. Clinical results obtained were excellent in 34 cases, and good in 46. Bacteriological effectiveness rate was 100%. As for side effects, fever, fever with rash, fever with cough and diarrhea appeared in 1 each case out of 182 cases including 95 drop out cases. As for laboratory findings, eosinophilia, thrombocytopenia, elevation of GOT, that of GOT with GPT, and that of GOT with LDH appeared in 10, 2, 2, 3 and 1 cases, respectively.
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PMID:[Pharmacokinetics and clinical effects of ceftizoxime in pediatric field (author's transl)]. 627 4

Trimethoprim-sulfamethoxazole (TMP-SMZ) is one of the most commonly used antibiotics. Although many of its adverse effects are well recognized, TMP-SMZ related hepatotoxicity is considered rare and is usually characterized by cholestasis or mixed hepatocellular-holestatic reactions. In this study, we describe the case of a previously healthy young man with acute fulminant liver failure caused by TMP-SMZ. The patient presented with complaints of 'flu-like' symptoms with myalgia and fever after taking TMP-SMZ for 7 d for otitis externa. The patient subsequently developed fever, worsening jaundice, and a rash on his neck and chest. Liver enzymes peaked on day 3 with alanine aminotransferase (ALT) 11,549, aspartate aminotransferase (AST) 23,289, alkaline phosphatase 245, and total bilirubin 10.3 mg/dL, with a conjugated bilirubin of 8.3 mg/dL, prothrombin time (PT) 60.5 s, partial normalized ratio (PTT) 49 s, and international normalized ratio (INR) 7.5. Of note, acetaminophen level on admission was undetectable. Serology for hepatitis A, B, C, cytomegalovirus, HIV, toxoplasmosis, and blood cultures were all negative. The patient developed hepatic encephalopathy with hallucination on day 4. Laboratory tests revealed a serum ammonia level of 190 U, serum creatinine kinase (CK) 10,466 (42 on admission), serum creatinine 8.2 mg/dL (1.2 on admission), and significant metabolic acidosis. Renal ultrasound was unremarkable. The patient was started on hemodialysis for acute renal failure. Meanwhile, liver transplantation assessment was also initiated. On day 8 post-admission (15 d after taking TMP-SMZ), the patient received a successful orthotopic liver transplant.
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PMID:Successful orthotopic liver transplantation after trimethoprim-sulfamethoxazole associated fulminant liver failure. 1470 31

To clarify whether ototopical glucocorticoid treatment is associated with impaired hypothalamic-pituitary-adrenal axis (HPA) activity and altered hepatic metabolism, one commercially available dexamethasone-containing ointment was tested. At present, very little is known about the effects of ototopical glucocorticoid treatment on HPA and liver function. Ten beagle dogs received two daily therapeutic doses of dexamethasone (0.6 mg/ear) in the outer auditory canal for 21 d in a single-blind, placebo-controlled study. Resting cortisol concentrations were assessed before, during, and after treatment using an RIA system. Adrenal function and HPA feedback sensitivity were measured by a standard dose (250 microg) ACTH stimulation test. Serum biochemical and hematological parameters were measured, whether ototopical glucocorticoids affect hepatic function was studied, and blood cell counts were made. Ototopical dexamethasone treatment induced a marked suppression (to about 100%) of resting plasma cortisol concentrations below the placebo effect (P < 0.0001) within the first 11 d, and these remained reduced during the entire treatment period up to d 19. As well, an ACTH stimulation test found a markedly reduced rise in plasma cortisol concentrations (P = 0.0004). Concomitantly, significant increases in serum activities of alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase were detected. Moreover, we found a significant reduction in differential leukocyte counts of eosinophils and lymphocytes, whereas neutrophils increased. Although cortisol levels and hematological parameters returned to baseline 7 d after treatment cessation, liver enzyme activities remained elevated. In conclusion, these findings suggest that after ototopical application, dexamethasone is sufficiently absorbed from the auditory canal to suppress HPA function as well as to alter metabolic and hemopoietic profiles. Thus, in long-term treatment of otitis externa or media, the systemic adverse suppression of HPA has to be considered in relation to stress exposure, whereas changes in serum enzyme activities may not be interpreted as hepathopathy.
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PMID:Evidence for ototopical glucocorticoid-induced decrease in hypothalamic-pituitary-adrenal axis response and liver function. 1580 95