Fluidity state of lymphocyte plasma membrane in malignant hyperthermia susceptible pigs and humans

Recent studies suggest that abnormalities occur at the lipid level in malignant hyperthermia susceptible humans and pigs. To test this hypothesis, we first investigated the physical state of plasma membranes of lymphocytes isolated from normal and malignant hyperthermia susceptible swine. In halothane-challenged pigs, malignant hyperthermia susceptibility was also assessed by ryanodine binding assay on purified sarcoplasmic reticulum membranes. The results clearly show that plasma membrane of lymphocytes from malignant hyperthermic pigs are significantly more fluid than controls. We then attempted to apply the same methodology to lymphocytes prepared from human patients previously diagnosed by the halothane and caffeine contracture test. In that case, there was no clear relationship between malignant hyperthermia susceptibility and the fluidity state of lymphocyte plasma membranes.     

INDUCTION OF ALCOHOL DEHYDROGENASE IN LIVER AND GASTRO-INTESTINAL TRACT

Experiments were designed to determine whether the increased rate of ethanol clearance previously demonstrated in alcoholics, in normal humans and in rats following prolonged alcohol ingestion is due to an increase in activity of enzymes involved in its metabolism. Alcohol was given in various doses to 56 rats, and alcohol dehydrogenase (ADH) and lactic dehydrogenase (LDH) assayed in liver, bile, colon, stomach and small intestine. Results were compared with 13 controls and rats given either actinomycin D or cycloheximide. Results of our experiments clearly show that the activity of ADH and LDH in liver, stomach and small intestine significantly increases with administration of single and repeated doses of alcohol, and the effect persists for a significant time. The effect of alcohol appears to be specific, as increased activity in enzymes not involved in its metabolism was not found. Increased ADH activity could be blocked by actinomycin and cycloheximide which suggests that alcohol induced de novo synthesis of this enzyme protein. The increase in activity of the rate-limiting enzyme, ADH, by its substrate ethanol, provides a plausible explanation for the observed tolerance in both rats and man conditioned by prior administration of alcohol. The increase in LDH, a terminal enzyme involved in ethanol metabolism, provides further indirect evidence that ethanol can be metabolized at a faster rate through the normal pathway. The finding of both ADH and LDH in significant amounts in stomach and small intestine in both normal and alcohol-fed rats suggests that ethanol can be metabolized to a significant extent in extrahepatic sites. This is contrary to the current view that alcohol is metabolized entirely by the liver, and that the multiple metabolic derangements in the alcoholic are the consequence of its obligatory metabolism in that organ.     

Methylparaben concentration in commercial Brazilian local anesthetics solutions

Objective

To detect the presence and concentration of methylparaben in cartridges of commercial Brazilian local anesthetics.

Material and methods

Twelve commercial brands (4 in glass and 8 in plastic cartridges) of local anesthetic solutions for use in dentistry were purchased from the Brazilian market and analyzed. Different lots of the commercial brands were obtained in different Brazilian cities (Piracicaba, Campinas and São Paulo). Separation was performed using high performance liquid chromatography (HPLC) with UV-Vis detector. The mobile phase used was acetonitrile:water (75:25 - v/v), pH 4.5, adjusted with acetic acid at a flow rate of 1.0 ml.min^-1.

Results

When detected in the solutions, the methylparaben concentration ranged from 0.01% (m/v) to 0.16% (m/v). One glass and all plastic cartridges presented methylparaben.

Conclusion

1. Methylparaben concentration varied among solutions from different manufacturers, and it was not indicated in the drug package inserts; 2. Since the presence of methylparaben in dental anesthetics is not regulated by the Brazilian National Health Surveillance Agency (ANVISA) and this substance could cause allergic reactions, it is important to alert dentists about its possible presence.     

Molar incisor hypomineralization: prevalence,severity and clinical consequences in Brazilian children

International Journal of Paediatric Dentistry 2010; 20: 426–434 Background. The prevalence of molar incisor hypomineralization (MIH) varies considerably around the world; however, few studies have examined MIH in South American countries. Objective. To evaluate the prevalence, severity, and clinical consequences of MIH in Brazilian children residing in rural and urban areas of the municipality of Botelhos, Minas Gerais, Brazil. Methods. Children aged 6 to 12 years (n = 918) with all four‐first permanent molars erupted had these teeth evaluated according to the European Academy of Paediatric Dentistry (EAPD) criteria. The examinations were conducted by two previously trained examiners, and the dental impact caused by MIH was evaluated with the Decayed, Missing and Filled Teeth (DMFT) index (WHO). Results. Molar incisor hypomineralization was present in 19.8% of the 918 children, with a higher prevalence in rural areas. The majority of the defects presented were demarcated opacities without post‐eruptive structural loss, which has been considered as mild defects. Children with MIH had higher DMFT values. Conclusion. Despite the high prevalence of MIH, the severity of the defects was mild. The results indicate a positive association between MIH and the presence of dental caries.     

Malignancy: Changes in Circulating Immature and Mature Dendritic Cells During IL-2 Cancer Immunotherapy and Their Relation with Lymphocyte Increase and Clinical Response

Lymphocytosis is the main biomarker predicting the efficacy of subcutaneous IL-2 anticancer immunotherapy. In addition, it has been demonstrated the fundamental role of dendritic cells (DC) in the generation of an effective anticancer immunity. However, the relation between IL-2 and DC system needs to be further understood. This preliminary study was performed in an attempt to analyze changes in circulating DC during IL-2 cancer immunotherapy in relation to lymphocyte variations and clinical efficacy of treatment. The study included 20 metastatic renal cell cancer patients, who underwent subcutaneous low-dose IL-2 immunotherapy (6.000.000 IU/day for 6 days/week for 4 weeks). To evaluate DC, venous blood samples were collected before and after 2 weeks of IL-2 injections, corresponding to the period of maximum lymphocytosis. Immature (CD123(+) ) and mature (CD11c(+) ) DC were measured by FACS and monoclonal antibodies. IL-2 induced a significant increase in the mean number of circulating mature DC, whereas no substantial change occurred in immature DC mean number. The increase in mature DC was associated with a control of disease, whereas no rise was observed in patients who had progressed on IL-2 immunotherapy. Moreover, the increase in mature DC mean number was significantly higher in patients showing evident lymphocytosis, with lymphocyte enhancement greater than 1000 cells/mmc, than in patients with less pronounced lymphocytosis, even though no significant correlation was seen in between mature DC and lymphocyte increase. This preliminary study would suggest that IL-2 may stimulate DC system and that the clinical anticancer efficacy of IL-2 is associated with the increase in circulating mature DC, which could be considered as a new favourable biomarker during IL-2 immunotherapy.     

Diagnostic accuracy of blood qualitative nucleic acid testing for polyomavirus-associated nephropathy in kidney recipients

Aim:   Polyomavirus-associated nephropathy (PVAN) is an important cause of graft loss following kidney transplantation and may only be diagnosed with kidney transplant biopsy. Early detection may improve outcomes by enabling early intervention. Serum polyomavirus polymerase chain reaction (PVPCR) has been used to identify patients at risk of PVAN, but prior studies have not assessed all patients with negative PVPCR with transplant biopsy, potentially overestimating test performance.
Methods:   We assessed the diagnostic accuracy of qualitative PVPCR for detection of PVAN in a population undergoing protocol biopsies. We included all patients receiving kidney or kidney-pancreas transplants and followed at Westmead Hospital, Sydney, Australia, between May 2002 and March 2007, excluding those with graft loss prior to 1 month post transplant or without PVPCR testing in the first 12 months. We compared PVPCR to contemporaneous transplant biopsies assessed with light microscopy and immunohistochemistry.
Results:   Of the 257 included patients, 246 (96%) underwent biopsy within 30 days of PVPCR. Eight of 36 patients with positive PVPCR had PVAN and one of 210 patients with negative PVPCR had PVAN. The point prevalence of PVAN was therefore 3.7%, with PVPCR sensitivity 89% (95% CI 57% to 99%) and specificity 88% (95% CI 83% to 92%). The negative predictive value is 99.5% (95% CI 97.3% to 100.0%).
Conclusion:   Qualitative PVPCR on serum is a reliable triage test for excluding the presence of PVAN. Screening for PVAN need not include biopsy in patients with negative PVPCR.     

The quality and management of written information presented to women undergoing hysterectomy

• ? A study of a random sample of hospitals in England that provide information leaflets for women undergoing hysterectomy indicates a large variation in quality.
• ? In general, the findings reveal that written information for patients is given a relatively low priority.
• ? Production and dissemination of information for hysterectomy patients is somewhat ad hoc.
• ? It is not clear that any evaluation of the leaflets has been conducted to prove the efficacy of the available literature.
• ? While the majority of leaflets include information deemed essential by past hysterectomy patients, the presentation of the recovery process often implies no control for the patient, and conceives normality with a narrow perspective about what healthy behaviour means for women. The provision of a specific timetable for resumption of housework duties in 65% of the leaflets is a case in point.
• ? On the basis of the results of the survey, recommendations are made concerning the improvement of the standard of patient information leaflets.