A comparative study of infections with rodent isolates of Giardia duodenalis in inbred strains of rats and mice and in hypothymic nude rats

Giardia isolated from mice and rats have been identified as Giardia duodenalis by morphological criteria. No differences in the electrophoretic mobilities of 28 enzymes were detected between the mouse and rat isolates or between these isolates and human and cat isolates. Infections with both rodent isolates have been studied in several strains of inbred rats. No significant differences were detected between the rat strains, with the mouse isolate producing a self-limiting infection and the rat isolate a chronic infection. After the primary infection was eradicated with metronidazole, all strains of rats were resistant to reinfection with the homologous isolate. Both isolates produced chronic infections in hypothymic nude rats. BALB/c mice were found to be relatively resistant to primary infection with either isolate but C3H mice became infected chronically with the mouse isolate and experienced a prolonged infection with the rat isolate. These findings resemble those observed with infections with G. muris in the same strains of mice (Roberts-Thomson & Mitchell 1978). It is suggested that infections with G. duodenalis in rats may offer a model for giardiasis that is based on organisms related closely to G. lamblia. Comparative studies using the two rodent isolates may lead to a better understanding of how the parasite establishes as a chronic infection and which antigens induce protective immune responses.     

Which model for propofol TCI in children

For several years, total intravenous anesthesia (TIVA) has demonstrated many advantages that allow consideration of propofol anesthesia as an interesting alternative in pediatric anesthesia. TIVA in children requires calculation and validation of pharmacokinetic (PK) models specifically adapted to the pediatric population. Several PK models based on a 3‐compartment approach have been proposed in children: all these models, which integrate only weight as covariable, show increased distribution volumes with a wide interindividual variability. However, as pharmacodynamic (PD) parameters are still debated in children, there is up to now, no PKPD model currently available for pediatric anesthesia. The particular importance to include physiological covariables, as size and age, to describe metabolic processes during growth and maturation in pediatric PKPD models is in agreement with recent allometric scaling works in children. The Schnider’s model, a model described in adults that includes numerous covariables, may be adapted and more efficient than the classical pediatric model to describe propofol–PKPD relationship in children over 5 years. Whatever is the model, a pharmacodynamic feed back such as the bispectral index may be useful to counteract the interindividual variability in the pediatric population.     

CHOLECYSTOKININ (PANCREOZYMIN)

The acetyl-derivative of the biologically active C-terminal 7-peptide portion of cholecystokinin (CCK), N-acetyl-O-sulfate-L-tyrosyl-L-methionyl-glycyl-L-tryptophyl-L-methionyl-L-aspanyl-L-phenylalanine amide was prepared by the condensation of 2-peptide segments with 1-isobutyloxycarbonyl-2-isobutyloxy-1,2-dihydroquinoline as coupling reagent. The N-terminal residue, tyrosine, was incorporated by the active ester method. The same 7-peptide was prepared also by stepwise chain-lengthening, starting with the C-terminal residue. The 9-fluorenylmethyloxycarbonyl group was applied for the protection of α-amino functions. In the release of amylase from acinar cells of the pancreas of guinea pigs, the acetyl-7-peptide amide was about 3 times more potent than CCK 27–33 and equal in potency to CCK 26–33. The new derivative strongly stimulated the contraction of the in situ guinea pig gall bladder.     

ADRENOCORTICOTROPHIN AND GLUCOCORTICOID RESPONSE TO EXCHANGE TRANSFUSION

Abstract. Plasma adrenocorticotrophin (ACTH) and glucocorticoid concentrations were measured during and for 3 hours after exchange transfusion in four groups of infants. Transfusions with ACD blood via the umbilical artery were performed on 10 infants of 35–40 weeks gestation and 11 infants of 27 to 33 weeks gestation. Ten transfusions via the umbilical vein were performed with ACD blood and 9 with heparin blood on infants of 32 to 41 weeks gestation. In all four types of transfusion there was a significant washing out of ACTH and glucocorticoids from the baby. An associated rise of plasma ACTH and glucocorticoid levels indicated increased secretion in the larger infants transfused with ACD blood via the umbilical artery. Equivocal results were obtained in the other groups. After all types of transfusion plasma glucocorticoid levels remained relatively constant for one hour and then doubled in the second and third hour. The results suggest that ( a ) exchange transfusion via the umbilical artery is more stressful than that via the umbilical vein, ( b ) the glucocorticoid response of premature infants to exchange transfusion is similar to that of mature infants, ( c ) an unspecified stimulus, which is not solely hypoglycaemia nor the metabolic reaction to a citrate load, results in a rise in plasma glucocorticoid levels 2–3 hours after all types of transfusion.     

Evaluation of emergence delirium in Asian children using the Pediatric Anesthesia Emergence Delirium Scale

Background: Emergence delirium (ED) is a common problem in children recovering from general anesthesia. ED causes disruption in the postanesthetic care unit, making nursing and monitoring more difficult, and is potentially dangerous to the child. The greatest hindrance to understanding ED was the lack of a standardized tool to assess it. The Pediatric Anesthesia Emergence Delirium (PAED) Scale was recently described to measure the degree of ED in children. In this prospective observational study, we sought to evaluate the incidence of ED by grading emergence behavior using the PAED Score in healthy Asian children undergoing outpatient surgery. Methods: Three hundred sixteen children aged 2–12 years undergoing general anesthesia for elective outpatient surgery were included. No premedication was administered. Induction behavior was graded using the induction compliance checklist, and the presence of any excitation on induction documented. Emergence behavior was recorded using the PAED Scale, and the children were separately assessed for clinical agitation. Results: One hundred and thirty‐six children (43%) had PAED Scores >0 and 33 (10.4%) had PAED Scores of ≥10. Only 28 children (8.9%) had clinical agitation consistent with ED, the rest were agitated for other reasons. A score of ≥10 on the PAED Scale was the best discriminator between presence and absence of clinical agitation. The area under the receiver operating characteristic curve for PAED Score of ≥10 was 0.98, with a true‐positive rate (sensitivity) of 0.85 and a false‐positive rate (1‐specificity) of 0.041. Four factors were found to be predictive of ED. These include young age, poor compliance at induction, lack of intraoperative fentanyl use and rapid time to awakening. Conclusions: The incidence of ED is approximately 10% in our population of healthy, unpremedicated Asian children undergoing day surgery. Young age, poor compliance at induction, lack of intraoperative fentanyl use and rapid time to awakening were predictive risk factors for ED in our population. A PAED Score of ≥10 was correlated with clinically significant ED and appeared to be the ideal cutoff score for ED.     

Plasma vitamin D metabolites in a patient with sporadic hypophosphataemic osteomalacia (adult-onset type)

Sporadic hypophosphataemic osteomalacia (adult-onset type) was demonstrated in a 40-year-old man on the basis of severe osteomalacia, hypophosphataemia, hyperphosphaturia and glycinuria. Plasma immunoreactive parathyroid hormone (iPTH) concentration was 9.3 ng prot./ml (normal range: 4-8 ng prot./ml). Plasma 25-hydroxy-vitamin D and 24,25-dihydroxy-vitamin D concentrations were 11 and 2.4 ng/ml respectively. Basal 1 alpha,25-dihydroxy-vitamin D concentrations were slightly elevated (116 and 96 pg/ml) and increased to 240 pg/ml after 3 days on a low-phosphorus diet. The patient was put on oral treatment with 25-hydroxycholecalciferol (100 microgram per day) and phosphorus (1500 mg per day). On the 4th month on treatment, a clinical improvement was apparent. Plasma 25(OH)D was 44 ng/ml, plasma 1,25(OH)2D was 256 pg/ml. However, plasma phosphorus remained low (0.77 mmol/l). On the 9th month of treatment a radiological improvement was evident despite a persistent hypophosphataemia (0.68 mmol/l). These facts suggest in our patient the existence of a vitamin D-independent renal phosphorus leak.     

THE KINETICS OF THE ADDITION OF GLUCOSE AND ACETALDEHYDE TO HISTONE PROTEINS

The time-course of the reaction of H1 and total histone withglucose, acetaldehyde or both has been studied using the NBTreduction test and fluorescence. With both methods, purifiedH1 histone gave higher absorbance with acetaldehyde than witha 1:1 combination of glucose and acetaldehyde. For total histone,the opposite was found; a 1:1 combination of the above two aldehydeshad the higher absorbance. As an explanation, the possibilityof different reactivity of the amino groups with glucose andacetaldehyde is proposed. A possible simultaneous interactionbetween glucose, acetaldehyde and serum protein, mainly albumin,may alter the results of the diagnostic protein glycation methods,e.g. of the fructosamine test; and, therefore, also the monitoringof diabetes.     

The Role of Free Radicals in the Pathogenesis of Amiodarone Toxicity

Free Radicals and Amiodarone Toxicity. Introduction: In vitro and in vivo studies were performed to elucidate the pathogenesis of amiodarone toxicity. Methods and Results: Rats were treated with amiodarone alone (500 mg/kg body weight per day) or together with antioxidants (silibinin or MTDQ-DA: 50 mg/kg body weight per day) or with either antioxidanl alone. They received amiodarone for 30 days and antioxidant for 33 days (3 days pretreatment) In vitro, amiodarone induced a dose-dependent chemiluminescence signal, which was inhibited by the two dihydroquinolin-type antioxidants (MTDQ-DA, CH 402). Chemiluminometric results from liver homogenate demonstrated that simultaneous treatment with silibinin partially prevented the liver homogenate superoxide anion radical scavenger capacity decreasing effect of amtodarone. Amiodarone treatment caused a significant increase of NADPH and Fe³⁺ induced lipid peroxidalion in the liver microsomal fraction, which antioxidants (silibinin, MTDQ-DA) were unable to prevent. Light microscopy of the lung tissue in amiodarone-treated rats showed accumulation of foamy macrophages with thickening of the interalveolar septa, pneumonitis, and variable interstitial tibrosis. Antioxidant treatment did not prevent these changes. Electron micrographs of lung from amiodarone-treated ruts showed lysosomal phospholipoidosis, intralysosomal electron dense deposits, and increased lysosome number and size. In contrast to rats treated with amiodarone alone, those treated with both amiodarone and silibinin had significantly fewer lysosomes (P < 0.01); the lysosome size, shape, and internal characteristics remained he same. Simultaneous treatment with silibinin and amiodarone decreased lysosomal phospholipoidosis compared to amiodarone treatment alone. Simultaneous treatment with MTDQ-DA and amiodarone did not show any beneficial effect. Pulse radiolysis and cobalt 60-gamma (⁶⁰Co-γ) radiolysis studies showed that the main free radical product in a reducing environment was a very reactive aryl radical formed after the partial deiodination of the amiodarone molecule. The radioseasitizing effect of amiodarone was also verified in rat liver microsomal preparations using in vivo amiodarone with or without MTDQ-DA pretreatment and ⁶⁰Co-γ irradiation with or without the in vitro addition of antioxidants (CH 402, MTDQ-DA). In vivo, the MTDQ-DA treatment also had a radiosensitizing effect; however, the in vitro addition of both antioxidants resulted in a radio-protective effect. The aryl radical also may emerge in vivo during the metabolism of amiodarone. Conclusion: These observations suggest that amiodarone in vitro and in vivo generates free radicals that may play a role in the pathogenesis of amiodarone toxicity beside other well-established mechanisms, and antioxidants may have a partial protective effect against amiodarone toxicity.     

Variant rs2200733 on Chromosome 4q25 Confers Increased Risk of Atrial Fibrillation: Evidence From a Meta‐Analysis

Variant rs2200733 on Chromosome 4q25 Confers Increased Risk . Introduction: Several genome‐wide association studies have identified rs2200733, a single‐nucleotide polymorphism (SNP) at 4q25 to be the most common chromosomal variant present in patients with atrial fibrillation (AF). We aimed to explore the association of rs2200733 with AF through a systematic review and meta‐analysis. Method: An extensive literature search was performed on PubMed, and other databases using the key words “genetics” and “AF.” Seven case‐control studies evaluating the association via multivariate analysis were identified including a total of 83,335 subjects (10,546 with AF, 72,789 referent individuals without AF). Meta‐analytic estimates were derived using random effects models. Potential sources of heterogeneity were examined in sensitivity analyses, and publication biases were estimated. Result: At pooled analysis, there was a strong independent association between the variant rs2200733 and the risk of AF (OR 1.89 [95% CI 1.62–2.16], P < 0.001). Minor allelic frequencies for SNP rs22000733 were significantly more prevalent in AF population than non‐AF. Metaregression results revealed that country of descent (logOR 0.38, P = 0.45) or site of study (logOR: ?0.16, P = 0.41) did not moderate the overall effect size. Conclusion: Variant rs2200733 on chromosome 4q25 independently confers increased risk of AF. This finding will aid in improving our understanding of AF pathophysiology, risk prediction, and stratification of treatment strategy. (J Cardiovasc Electrophysiol, Vol. 24, pp. 155‐161, February 2013)