Nogo‐B expression,in arterial intima,is impeded in the early stages of atherosclerosis in humans

Nogo‐B (Reticulon 4B) is considered to be a novel vascular marker, which may have a protective role in injury‐induced neointima formation and atherosclerosis. Nogo A/B is found to be crucial for monocyte/macrophage recruitment in acute inflammation and it is expressed in CD68 + macrophages. We hypothesize that macrophage infiltration in atherosclerosis is not dependent on Nogo‐B expression in arterial wall. We have assessed Nogo‐B expression and macrophage accumulation in the iliac arteries of healthy organ donors and organ donors with cardiovascular risk factors. Paraffin sections of 66 iliac arteries, from 44 deceased organ donors (17 women and 27 men), were studied. The healthy and cardiovascular risk (CVR) subgroups were created. With regard to staging of the atherosclerotic process, the thickness of arterial intima was measured in digitalized images of H+E stained tissue sections. Immunohistochemical reactions (Nogo‐B and CD68) were carried out in all arteries (66 samples). Western blotting (WB‐19 samples) and real‐time PCR (27 samples) were performed on selected arteries. Significantly higher Nogo‐B expression was demonstrated in the intima of the healthy subjects' subgroup, using immunohistochemistry. WB and real‐time PCR revealed a trend toward lower Nogo‐B expression in the adventitia of the CVR subgroup. Furthermore, the thickness of the intima was found to negatively correlate with the expression of Nogo‐B in the intima and media (r = ?0.32; p < 0.05; r = ?0.32; p < 0.05). Macrophage infiltrates were more prominent in intima of CVR subjects (0.65 vs 3.52 a.u.; p < 0.01). Macrophage density in intima increased with atherosclerosis progression (r = 0.37; p < 0.01). CD68 macrophages density in adventitia was lower in CVR arteries than in healthy arteries. The expression of Nogo‐B, in arterial intima, is impeded in the early stages of atherosclerosis. Accumulation of arterial intimal CD68 macrophages has been shown to progress; however, the overall macrophage density in the adventitia is reduced in arteries shown to have intimal thickening. Macrophage infiltration is not accompanied by Nogo‐B expression in atherosclerotic arteries.     

Evaluation of depression in patients with alzheimer's disease according to the location of medical care

The objective of the study was to assess the severity of depression and to assess the level of self-sufficiency of patients with Alzheimer's disease, with particular emphasis on the place of residence and level of education. The study covered 90 people diagnosed with Alzheimer's disease. All respondents were persons over 65?years of age and residents of cities with a population over one-hundred thousand. The research method based on this work is the author's own questionnaire, the Zung Self-Rating Depression Scale (ZSDS) about depression and the Karnofsky Performance Scale Index (KPSI) for assessment of a patient's self-sufficiency. Regardless of residence, patients with Alzheimer's disease displayed signs of mild or moderate depression (100% in social welfare homes and hospital patients and 60% in those with caregivers at home). Patients with Alzheimer's disease have an unsatisfactory salary in social-economic terms. In those with Alzheimer's disease, quality of life is best for those in family homes under the care of their immediate family. People with a vocational education were the largest group of people diagnosed with Alzheimer's. Patients at home and in the hospital had a higher level of physical activity, but most patients in the hospital needed regular medical care, as did patients in social welfare homes.     

Putative Biological Mechanisms of Efficiency of Substrate Reduction Therapies for Mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are inherited metabolic diseases caused by mutations in genes coding for lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Dysfunction of any of these enzymes results in the accumulation of GAGs, which leads to severe clinical symptoms and significantly shortened life span. Several kinds of therapies have been proposed to treat MPS, including bone marrow or stem cell transplantation, enzyme replacement therapy, and gene therapy. Another option is substrate reduction therapy (SRT), in which synthesis of GAGs is inhibited. Recent studies employing in vitro and animal models suggested that this therapy may be efficient in decreasing levels of GAGs in MPS cells, including those bearing two null alleles of the affected gene. Results of behavioral tests in animals as well as some preliminary clinical observations with pediatric patients corroborated the suggestions about possible efficacy of SRT in MPS treatment, including brain functions. Efficient reduction of GAG levels in MPS cells homozygous for null mutations may be intriguing in the commonly accepted scheme of SRT mode of action. In this paper, we propose an explanation of this phenomenon, based on already known facts. Thus, we suggest that SRT may lead to reduction of GAG levels in MPS cells due to inhibition of efficiency of GAG synthesis combined with (a) any readthrough of the stop codon, (b) dilution of already accumulated GAGs due to cell growth followed by cell divisions, and (c) action of endoglycosidases degrading GAGs, e.g., heparanase, in combination with functional GAG-specific hydrolases.     

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial

BackgroundNeuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.MethodsIn this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent “conventional” OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).ResultsThe incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).ConclusionsPerforming ANA significantly decreases the incidence of PD and ePOCD compared with “conventional” OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.     

Ocena skuteczności Lactobacillus rhamnosus ATC A07FA w zapobieganiu martwiczego zapalenia jelit wcześniaków z bardzo małą urodzeniową masą ciała: badanie z randomizacją (wstępne wyniki)

BackgroundEvidence suggests that probiotics, as a group, are reducing the risk of necrotizing enterocolitis (NEC). The efficacy of each probiotic strain needs to be evaluated separately.ObjectiveTo evaluate the efficacy of administering Lactobacillus rhamnosus ATC A07FA (L. rhamnosus) for the prevention of necrotizing enterocolitis (NEC) ≥2 by the criteria of Bell in very low-birth-weight preterm infants.MethodPreterm infants children fulfillingthe inclusion criteria (gestational age <32 weeks and birth weight <1500 g and partial orfull enteral feeding) were enrolled in a randomized, double-blind, placebo-controlled trial. They received L. rhamnosus (commercially available as Lakcid) at a dose of 1.2 × 10¹⁰ CFU or a placebo orally, twice daily, for the duration of the hospital stay. The primary outcome measures were NEC ≥2 by the criteria of Beli, sepsis and death.ResultsThe study was stopped prematurely because of slow recruitment. Data from 55 preterm infants were included in the fina? analysis. In the experimental group, compared with the placebo group, the risk of developing NEC ≥2 by the criteria of Beli was reduced, however the difference was not statistically significant (1/30; 3.3% versus A/25; 16%, RR 0.2, 95% Cl 0.02 do 1.75). L. rhamnosus did not significantly affect the risk of developing sepsis or death. There was also no difference between the probiotic and placebo groups for any of the other secondary outcomes. No adverse events were reported.ConclusionThe administration of L. rhamnosus ATC A07FA compared with placebo had no effect on the incidence of NEC. Further studies with sufficient sample size are warranted.     

Nawracające zapalenie opłucnej jako wiodący objaw rodzinnej gorączki śródziemnomorskiej

Familial Mediterranean Fever (FMF) is a disease with an autosomal recessive inheritance affecting inhabitants of the Mediterranean Sea basin area. It is the most prevalent fever-inflammatory syndrome manifested by fever episodes, serositis and rash. The symptoms regress spontaneously and between recurrent attacks of fever the child is healthy. Amyloidosis is the most serious complication. A case of a 8 year-old boy, a son of Armenian immigrants, with recurrent pleuritis is presented.     

Tapentadol – A representative of a new class of MOR-NRI analgesics

Tapentadol is a centrally acting analgesic with a dual mode of action as a μ-opioid receptor (MOR) agonist and a noradrenaline reuptake inhibitor (NRI). It was initially approved by the US Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients, and in August 2011, for chronic pain in an prolonged release form in the same population. Due to its limited protein binding capacity, the absence of active metabolites and significant microsomal enzyme induction or inhibition, tapentadol has a limited potential for drug–drug interactions. It appears to be well-tolerated and effective in the treatment of moderate-to severe acute and chronic pain. Owing to its dual mechanism of action, it is hypothesized to be good option in the treatment of both nociceptive and neuropathic pain.     

Orexins Protect Neuronal Cell Cultures Against Hypoxic Stress: an Involvement of Akt Signaling

Orexins A and B are peptides produced mainly by hypothalamic neurons that project to numerous brain structures. We have previously demonstrated that rat cortical neurons express both types of orexin receptors, and their activation by orexins initiates different intracellular signals. The present study aimed to determine the effect of orexins on the Akt kinase activation in the rat neuronal cultures and the significance of that response in neurons subjected to hypoxic stress. We report the first evidence that orexins A and B stimulated Akt in cortical neurons in a concentration- and time-dependent manner. Orexin B more potently than orexin A increased Akt phosphorylation, but the maximal effect of both peptides on the kinase activation was very similar. Next, cultured cortical neurons were challenged with cobalt chloride, an inducer of reactive oxygen species and hypoxia-mediated signaling pathways. Under conditions of chemical hypoxia, orexins potently increased neuronal viability and protected cortical neurons against oxidative stress. Our results also indicate that Akt kinase plays an important role in the pro-survival effects of orexins in neurons, which implies a possible mechanism of the orexin-induced neuroprotection.