Current Resources for Evidence-Based Practice,July 2021

An extensive review of new resources to support the provision of evidence-based care for women and infants. The current column includes a discussion of how fetal monitoring may lead to overuse of birth-related interventions, commentaries on reviews focused on bedsharing, and women’s lifetime estrogen exposure and risk of cardiovascular mortality.     

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.     

Relationship of self-effecacy to cholesterol lowering and dietary change in hyperlipidemia

This study examined whether self-efficacy was associated with lipid lowering and dietary change among men undergoing dietary counseling to lower cholesterol levels. Twenty-five hyperlipidemic men (total cholesterol ≧220 mg/dL) participated in four weeks of dietary instruction. Plasma lipids were measured prior to treatment, at posttreatment, and at three- and twelvemonth follow-up. Dietary intake and self-efficacy as measured by the revised Eating Self-Efficacy Scale (ESES-R) were assessed at pretreatment, posttreatment, and three-month follow-up. Pre-treatment to posttreatment increases in self-efficacy in situations characterized by negative affect were related to extent of lipid lowering and dietary change. Although subjects showed significant reductions in cholesterol levels following treatment, by one year, lipid levels had returned to pretreatment values. Factors related to long-term maintenance of dietary change and lipid lowering among hyperlipidemics merit further research.     

Behaviorally conditioned suppression of a graft-versus-host response.

Cyclophosphamide (CY), previously used to condition suppression of humoral immune responses, was used to condition suppression of a graft-versus-host response (GvHR). Female (Lewis x Brown Norway) F1 rats were conditioned by pairing consumption of a saccharin solution with an intraperitoneal injection of CY at 50 mg/kg of body weight 48 days before immunization. On day 0, all animals were injected with a suspension of splenic leukocytes (2 x 10(7) cells per footpad) obtained from female Lewis donors. The regional GvHR was assessed on day 5 by weighing popliteal nodes. Conditioned animals given a single low-dose injection of CY and reexposed to conditioned stimuli had lymph node weights significantly lower than control groups and did not differ from animals given three injections of CY during the ongoing GvHR. The results suggest that conditioned immunosuppression, previously demonstrated in thymus-dependent and thymus-independent humoral immune responses, also affects the popliteal GvHR, a cellular immune response.     

Design,synthesis, tandem mass spectrometric sequencing and biological activity of NGF mimetics

Nine low molecular weight nerve growth factor (NGF)-like peptides have been designed to mimic the putative receptor-binding epitope of NGF defined by two β-hairpin loops. Eight different spacers were used as variable links between the β-loop amino acid residues, which from mutagenesis experiments were found to play an important role in the biological activity of NGF. These spacers were amino acids, natural or non-natural, differing in length (5–13 Å) and polarity. The peptides were synthesized via the Fmoc solid-phase peptide synthesis and purified by reversed-phase HPLC. Their primary sequences were analyzed by a combination of automated Edman degradation and mass spectrometry. The peptides were tested using two different biological assays, the fibre outgrowth from chick embryonic sympathetic ganglia and the PC 12 cell differentiation assay. Weak antagonistic effects could be observed for some peptides. © Munksgaard 1996.     

MALIGNANT HYPERTHERMIA IN BELGIAN LANDRACE PIGS RESTED OR EXCERCISED BEFORE EXPOSURE TO HALOTHANE

Thirteen of 31 Belgian Landrace pigs developed malignant hyperthermia(MH) after breathing halothane. A short period of exercise 1h before the administration of the triggering agent increasedthe incidence of the syndrome to 100% in eight similar pigs.Clinical symptoms were more marked and developed more rapidlyin the exercised pigs. All the reacting pigs became typicallyacidotic, developed rigor and died. Serum Na⁺, K+, Ca2⁺, c.p.k.,l.d.h. and protein concentrations were increased to a variableextent during the reaction and there was an increase in p.c.v.also. No hyper-glycaemia was detected in pigs which were restedbefore receiving halothane. Four of the eight exercised pigsbecame markedly hyperglycaemic and plasma noradrenaline increasedto higher values. Phosphocreatine and ATP decreased to low valuesand lactate increased in the muscles of all pigs which reacted.At the time of death, muscle glycogen had decreased significantlyin the rested, but not in the exercised, MH pigs. ^*Present address: ARC Meat Research Institute, Langford, BristolBS18 7DY.     

Metabolism of xylitol in dental plaque

Abstract – It has been reported previously that xylitol added to glucose used to challenge dental plaque in vivo caused a reduced acid formation. The aim of the present study was to approach the mechanism by which xylitol may affect glucose catabolism in plaque bacteria. Suspensions of freshly collected 4-day-old plaque bacteria were ineubated, one batch with labeled xylitol, one with labeled glucose, in vitro at 37°C. Samples of cells were taken out at time intervals, collected on paper discs and subjected to scintillation counting. It was observed that the plaque bacteria took up xylitol, the uptake increasing with incubation of more than 3–4 h, whereas the same cells took up glucose immediately. Cells which had taken up xylitol were extracted with boiling water, extracts concentrated and applied on thin-layer chromatography sheets. A radioactive component with mobility like xylitol-5-phosphate was isolated from the cell extracts, and also a component where labeled xylitol was associated with macromolecules. It is suggested that the accumulation of the metabolities within the cells inhibits glycolysis.     

Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63

Waanders E, Venselaar H, te Morsche RHM, de Koning DB, Kamath PS, Torres VE, Somlo S, Drenth JPH. Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63. Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein structure and function. We screened 464 subjects including 76 probands by direct sequencing or conformation‐sensitive capillary electrophoresis. We analyzed the effects of all known and novel mutations using a combination of splice site recognition, evolutionary conservation, secondary and tertiary structure predictions, Poly Phen , and p Mut and sift . We identified a total of 26 novel mutations in PRKCSH (n = 14) and SEC63 (n = 12), including four splice site mutations, eight insertions/ deletions, six non‐sense mutations, and eight missense mutations. Out of 48 PCLD mutations, 13 were predicted to affect splicing. Most mutations were located in highly conserved regions and homology modeling for two domains of Sec63p showed severe effects of the residue substitutions. In conclusion, we identified 26 novel mutations associated with PCLD and we provide in silico analysis in order to delineate the role of these mutations.