Amelioration of intestinal disease severity in cystic fibrosis mice is associated with improved chloride secretory capacity

The variability in intestinal disease severity in patients with cystic fibrosis (CF) has been associated with the expression of secondary modifier genes. The locus containing these modifier genes in CF patients is syntenic with a modifier locus previously associated with survival in CF transmembrane conductance regulator-knockout mice. These previous studies showed that the proportion of CF mice that survive weaning (mildly affected mice) versus those that succumb to obstruction of the small intestine (severely affected) is related to their genetic background and the expression of modifier genes. In the present work, we show that the basal transepithelial chloride transport measured across jejuna obtained from mice of mixed genetic backgrounds segregates into two groups, some mice having low and others having high, near normal chloride transport. Further, we report that the segregation of mice with respect to intestinal chloride transport correlates with their predicted segregation on the basis of genotype at the "modifier locus." These findings support the hypothesis that intestinal disease modification in CF mice correlates with improved chloride transport through non-CF transmembrane conductance regulator chloride channels.     

Development of Immunosorbents for apoB-Containing Lipoproteins Apheresis

Abstract: Three types of sorbents were developed for the specific removal of atherogenic apoB-containing low-density lipoprotein (LDL) and lipoprotein LDL(a) (Lp[a])from human plasma. Two sorbents contained monospecific sheep polyclonal or mouse monoclonal antibodies against human apoprotein B-100. The third one was intended for specific removal of Lp(a) and contains sheep antibodies against human Lp(a). Thirty patients were treated for up to 9 years by LDL apheresis with anti-LDL immunosorbents. A pilot study of Lp(a) apheresis with 3 patients was conducted during 3 years. The results showed that extracorporeal immunosorption is safe and effective for lowering LDL and Lp(a). These procedures may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.     

Evaluation of the sensitivity of red blood cell markers to detect photodynamic membrane damage

BACKGROUND: Photodynamic dyes have been used to investigate pathogen reduction methods in RBC suspensions, but treatment with sensitizers and light can produce unwanted membrane damage during routine blood bank storage. This study compares the relative sensitivity of three assays for detecting RBC membrane damage. STUDY DESIGN AND METHODS: RBCs were treated with dimethylmethylene blue and red light-emitting diode light under four conditions differing in photodynamic stringency and subsequently stored under refrigerated conditions for up to 42 days. Hemolysis, potassium release, and the apoptosis marker annexin V binding were assayed immediately after phototreatment and following storage. RESULTS: In terms of increasing sensitivity for detecting photodynamic RBC membrane damage was enhanced ion leakage > hemolysis > annexin V binding. CONCLUSION: Although very stringent photodynamic treatment conditions generate annexin V-positive RBCs, the assay will not detect more subtle membrane damage that is readily detected by other well-established methods. In addition, many RBCs destined for photo-induced hemolysis later in storage are annexin V-negative throughout the storage period, suggesting that the two measures are not directly related.     

Self-Sustaining Status Epilepticus: A Condition Maintained by Potentiation of Glutamate Receptors and by Plastic Changes in Substance P and Other Peptide Neuromodulators

Summary: We describe a model of self-sustaining status epilepticus (SSSE) induced by stimulation of the perforant path in free-running rats. In this model, seizures can be transiently suppressed by intrahippocampal injection of a blocker of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate synapses but return in the absence of further stimulation when the drug ceases to act. However, seizures are irreversibly abolished by blockers of N -methyl- d -aspartate receptors given locally or systemically. SSSE is enhanced by substance P and its agonists and blocked by its antagonists. SSSE induces novel expression of substance P-like immunoreactivity in hippocampal principal cells. These changes and those in other limbic peptides may contribute to the maintenance of SSSE and to the modulation of hippocampal excitability during epileptic seizures.     

Inactivation of Leishmania donovani infantum and Trypanosoma cruzi in red cell suspensions with thiazole orange

BACKGROUND: Methods for pathogen inactivation are currently available in some European countries for treatment of plasma and platelet (PLT) components; no approved method for treatment of red cells (RBCs) or whole blood is ready for implementation. In a previous study, thiazole orange (TO), a dye commonly used to count reticulated RBCs and PLTs, exhibited potent photoactivity against human immunodeficiency virus-1 and several model viruses in RBC suspensions. The aim of this study is to further evaluate the ability of TO to inactivate pathogens by measuring its activity against the protozoa Leishmania donovani infantum and Trypanosoma cruzi. STUDY DESIGN AND METHODS: RBC suspensions were deliberately contaminated with L. donovani infantum promastigotes or T. cruzi trypomastigotes and either maintained as an untreated control, incubated with 80 mumol per L TO in the dark, or treated with TO and light. Control and treated samples were inoculated into medium and subsequently microscopically examined for growth. RESULTS: No growth was observed in samples treated with TO in the presence or absence of light, while matched control samples lacking TO and diluted up to 5 log consistently demonstrated Leishmania or T. cruzi growth (n = 3). CONCLUSION: TO inactivated Leishmania or T. cruzi to the limit of detection in RBC suspensions without intentional illumination.     

Epidemiology of small intestinal bacterial overgrowth

Small intestinal bacterial overgrowth(SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicat...