ABSTRACT
Acute liver failure induces renal injury by triggering inflammation and oxidative stress. The heme oxygenase system has a preventive role against reperfusion injury, while garlic oil has antioxidants and anti-inflammatory effects. This study investigated the protective effects of garlic oil pretreatment on remote renal functions after liver ischemia/reperfusion (I/R), and clarifying gene expressions of heme oxygenase 1 (HO1), autophagy-related 7 (Atg7) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in renal tissues. Thirty six adult female Wistar rats were randomly divided into control, garlic oil-supplemented, liver I/R, and garlic oil-pretreated liver I/R groups. Liver ischemia was performed in anesthetized rats for 45 min, followed by reperfusion for 24 hours in metabolic cages. Serum samples were used for determination of liver enzymes and creatinine levels and total antioxidant capacity (TAC). Urine samples were assayed for albumin, volume and creatinine concentration. Right liver lobe and right kidney specimens were used for determination of oxidative stress markers (colorimeterically). Also, gene expressions of HO1, Atg7 and PGC1α were investigated in right kidney specimens using real time PCR. Left kidney specimens were used for histopathological studies. Liver I/R group exhibited higher liver enzymes and creatinine levels in serum, prominent oxidative stress in both liver and renal tissues, albuminuria, lowered GFR deranged renal structure, and upregulated HO1, Atg7 and PGC1α gene expressions in renal tissues. Garlic oil-pretreated I/R group restricted such detrimental changes in renal functions and structure, though it caused further upregulation of the studied gene expression in renal tissue to alleviate the oxidative stress. It is concluded that garlic oil exerted reno-protective effected against remote organ damage induced by liver I/R injury, through enhancing HO1, Atg7 and PGC1α gene expressions.
Subject(s)
Acute Kidney Injury/drug therapy , Allyl Compounds/pharmacology , Kidney/drug effects , Liver/metabolism , Sulfides/pharmacology , Acute Kidney Injury/metabolism , Animals , Antioxidants/metabolism , Creatinine/metabolism , Female , Heme Oxygenase-1/metabolism , Inflammation/metabolism , Kidney/metabolism , Oxidative Stress/drug effects , Rats , Rats, Wistar , Reperfusion Injury/metabolismABSTRACT
OBJECTIVES: Conventional neuroleptics ameliorate symptoms in children with autistic disorder; however, they are known to cause dyskinesias. Atypical neuroleptics, including olanzapine, may have less risk for dyskinesia, but their efficacy in autistic disorder is not established. This study was designed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a standard comparator treatment. METHOD: In a parallel groups design, 12 children with DSM-IV autistic disorder (mean age 7.8+/-2.1 years) were randomized to 6 weeks of open treatment with olanzapine or haloperidol. Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol. Outcome measures included the Clinical Global Impressions (CGI) and the Children's Psychiatric Rating Scale (CPRS). RESULTS: Both groups had symptom reduction. Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item. Subjects showed improvement on the CPRS Autism Factor (F1,9 = 24.4, p = .0008). Side effects included drowsiness and weight gain. CONCLUSIONS: The findings suggest that olanzapine is a promising treatment for children with autistic disorder. Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required.
Subject(s)
Antipsychotic Agents/therapeutic use , Autistic Disorder/drug therapy , Haloperidol/therapeutic use , Pirenzepine/therapeutic use , Benzodiazepines , Child , Child Development Disorders, Pervasive/drug therapy , Child, Preschool , Dose-Response Relationship, Drug , Female , Haloperidol/administration & dosage , Haloperidol/adverse effects , Humans , Male , Olanzapine , Pilot Projects , Pirenzepine/administration & dosage , Pirenzepine/adverse effects , Pirenzepine/analogs & derivatives , Treatment OutcomeABSTRACT
A preliminary clinical observation suggests the possibility of changes in valproate level when coadministered with guanfacine. Two pediatric inpatients (8 and 9 years of age) were treated with valproic acid and guanfacine concurrently. In one child, when guanfacine was tapered and discontinued, the plasma valproate concentration decreased by 41% from 128 microg/mL to 76 microg/mL. In the other case, studied in an ABA design, the child exhibited a rapid increase in plasma valproate levels while guanfacine was administered. It is proposed that guanfacine may affect the pharmacokinetics of valproic acid and lead to a significant increase in valproate plasma levels when used concurrently with this agent. The mechanism of this proposed interaction may involve drug-drug competition at the level of hepatic glucuronidation (conjugation), although shifts in protein binding cannot be ruled out.
Subject(s)
Adrenergic alpha-Agonists/adverse effects , Anticonvulsants/pharmacokinetics , Guanfacine/adverse effects , Valproic Acid/pharmacokinetics , Anticonvulsants/blood , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit and Disruptive Behavior Disorders/drug therapy , Attention Deficit and Disruptive Behavior Disorders/psychology , Child , Drug Interactions , Female , Humans , Male , Valproic Acid/bloodABSTRACT
To confirm the efficacy and tolerability of a new, low-dose, short-term triple therapy, 31 endoscopically diagnosed cases of peptic ulcer who were helicobacter pylori positive by brush cytology and urease test were inducted into the study. These patients were given lansoprazole 30 mg once a day, clarithromycin 250 mg twice a day and tinidazole 500 mg twice a day for one week only. Endoscopy, urease test and methylene blue test for helicobacter pylori were repeated four weeks after stopping the therapy. Ulcer healed in all the patients while helicobacter was eradicated in 90.3% of patients.
