Therapeutic targeting of autophagy in myocardial infarction and heart failure

Introduction: Myocardial infarction (MI) is the leading cause of death. When MI is not lethal, heart failure (HF) is a major consequence with high prevalence and poor prognosis. The targeting of autophagy represents a potentially therapeutic approach for the treatment of both pathologies.

Areas covered: PubMed searches were performed to discuss the current state of the art regarding the role of autophagy in MI and HF. We review available and potential approaches to modulate autophagy from a pharmacological and genetic perspective. We also discuss the targeting of autophagy in myocardial regeneration.

Expert commentary: The targeting of autophagy has potential for the treatment of MI and HF. Autophagy is a process that takes place in virtually all cells of the body and thus, in order to evaluate this therapeutic approach in clinical trials, strategies that specifically target this process in the myocardium is required to avoid unwanted effects in other organs.     

Nursing management of the pregnant hemodialysis patient

Pregnancy is an uncommon occurrence in the end stage renal disease (ESRD) patient population and more so in the patient on chronic hemodialysis therapy. The management of the pregnant hemodialysis patient covers a wide spectrum of concerns. Many resources must be used to deliver safe, quality care to the patient. The knowledge gained from our experience in caring for a pregnant hemodialysis patient will benefit the nephrology nursing community. With the advent of erythropoietin, the number of pregnant ESRD patients may grow, and the demand for knowledge on how to care for these patients will also become increasingly evident.     

Evolving in thin air--lessons from the llama fetus in the altiplano

Compared with lowland species, fetal life for mammalian species whose mothers live in high altitude is demanding. For instance, fetal llamas have to cope with the low fetal arterial PO2 of all species, but also the likely superimposition of hypoxia as a result of the decreased oxygen environment in which the mother lives in the Andean altiplano. When subjected to acute hypoxia the llama fetus responds with an intense peripheral vasoconstriction mediated by alpha-adrenergic mechanisms plus high plasma concentrations of catecholamines and neuropeptide Y (NPY). Endothelial factors such as NO and endothelin-1 also play a role in the regulation of local blood flows. Unlike fetuses of lowland species such as the sheep, the llama fetus shows a profound cerebral hypometabolic response to hypoxia, decreasing cerebral oxygen consumption, Na-K-ATPase activity and temperature, and resulting in an absence of seizures and apoptosis in neural cells. These strategies may have evolved to prevent hypoxic injury to the brain or other organs in the face of the persistent hypobaric hypoxia of life in the Andean altiplano.     

Review: Placental syncytiotrophoblast membranes--domains, subdomains and microdomains

Human placental syncytiotrophoblast (STB) is an epithelium responsible for materno-fetal exchange. Ions play multiple roles in STB, as in other transport epithelia. We have been interested in the character and functional expression of ion channels in STB membrane fractions. Characterization of ion channels and their relationship with different domains, subdomains and microdomains of STB membranes is important to explain the intracellular mechanisms operating in the placental barrier. The aim of this paper is to summarize our work on this subject. We isolated and purified basal membrane (BM) and two fractions from the apical membrane, a classical fraction (MVM) and a light fraction (LMVM). They were used either for reconstitution into giant liposomes or for transplantation into Xenopus oocyte membranes followed by electrophysiological recordings to characterize chloride and cationic channels in STB from term human placenta. In addition, Western blot analysis, using ion channel antibodies, was performed on purified apical and basal membrane fractions. We also reported the presence of two functional microdomains (lipid rafts) in LMVM and MVM, using detergent resistant membranes (DRMs) and cholesterol-sensitive depletion. Moreover we found evidence of cytoskeletal participation in lipid rafts of different composition. Our results contribute to knowledge of the ion channels present in STB membranes and their participation in the physiology of this epithelium in normal and pathological pregnancies.     

Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous peritonitis: a meta-analysis

BACKGROUND AND GOALS: Adenosine deaminase (ADA) levels are used for diagnosing tuberculosis in several locations and although many studies have evaluated ADA levels in ascitic fluid. These studies have defined arbitrary cut-off points creating difficulties in the clinical application of the results. The goals of this study are: to determine the usefulness of ADA levels in ascitic fluid as a diagnostic test for peritoneal tuberculosis (PTB) and define the best cut-off point. STUDY: A systematic review was done on the basis of 2 independent searches. We selected prospective studies that included consecutive patients. Diagnosis of PTB had to be confirmed by bacteriologic or histologic methods and ADA levels determined by the Giusti method. Inclusion/exclusion criteria were applied by 2 independent reviewers. A receiver operating characteristic curve was constructed to establish the optimal cut-off point and the likelihood ratios (LRs) estimated using fixed-effect pooled method. RESULTS: Twelve prospective studies were found. Four of them met the inclusion criteria and were thus included in the meta-analysis. They included 264 patients, of which 50 (18.9%) had PTB. ADA levels showed high sensitivity (100%) and specificity (97%) using cut-off values from 36 to 40 IU/L. The included studies were homogeneous. Optimal cut-off point was determined at 39 IU/L, and LRs were 26.8 and 0.038 for values above and below this cut-off. CONCLUSIONS: This study supports the proposition that ADA determination is a fast and discriminating test for diagnosing PTB with an optimal cut-off value of 39 IU/L.     

Diverse calcium channel types are present in the human placental syncytiotrophoblast basal membrane

The functional expression of calcium channels has been scarcely studied in human placental syncytiotrophoblast. We have presently sought to characterize Ca(2+) currents of the healthy syncytiotrophoblast basal membrane using purified basal membranes reconstituted in giant liposomes subjected to patch-clamp recordings. We detected presence of channels with high permeability to Ca(2+) (relative PCa/PK up to 99.5) using K(+) solutions in symmetric conditions. Recordings performed in Ba(2+) gradients showed Ba(2+)-conducting channels in 100% of experiments. Ba(2+) total patch currents were consistently blocked by addition of NiCl(2), Nifedipine (L-type voltage-gated calcium channel blocker) or Ruthenium Red (TRPV5-TRPV6 channel blocker); Nifedipine and Ruthenium Red exerted a synergic blocking effect on Ba(2+) total patch currents. Immunohistochemistry of placental villi sections evidenced presence of alpha(1) subunit of voltage-gated calcium channels and TRPV5-TRPV6 channels in basal and apical syncytiotrophoblast plasma membranes; these three calcium channels were also detected in purified basal and apical fractions using Western blot. These results show the presence of three types of calcium channels in the syncytiotrophoblast basal membrane by both functional and molecular means. These basal membrane calcium channels would not be directly involved in mother-to-fetus Ca(2+) transport, but could participate in other relevant trophoblast processes, such as exocytosis and Ca(2+) transport regulation.