The relative influence of arterial pressure versus intraoperative distention on lipid accumulation in primate vein bypass grafts

Atherosclerotic degeneration has been well documented to be the limiting factor for long-term function of aortacoronary vein bypass grafts. Injury, including that induced by pressure distention in preparation for grafting, is thought to play a role in this degeneration. Injury can be minimized by limiting the distending pressure, but vein grafts are chronically subjected to arterial pressures that far exceed native venous pressure. We evaluated the relative influence of arterial pressure and of higher pressure of distention on cholesterol and apolipoprotein-B accumulation by grafts in our established animal model of graft atherogenesis. Grafts were interposed in the femoral arteries of eight normolipemic stump-tailed macaque monkeys. Before insertion, each vein was distended at 125 mm Hg (arterial pressure) for 1 minute with autologous blood, followed by distention of one half of the vein at 350 mm Hg for 1 additional minute. Grafts and ungrafted control vein were removed 3 months later. Cholesterol concentration in grafts distended at 125 mm Hg was 213% (p less than 0.01) and apolipoprotein-B concentration was 430% (p less than 0.001) of that in ungrafted control veins, whereas in grafts distended at 350 mm Hg cholesterol was 250% (p less than 0.01) and apolipoprotein-B was 925% (p less than 0.001) of the control concentrations. Although morphologic differences between the two groups of grafts were less profound than biochemical differences, foam cells were observed more frequently in grafts distended at 350 mm Hg than in those distended at 125 mm Hg. These data demonstrate that chronic exposure to arterial pressure has a significant effect on graft cholesterol that is proportionally greater than that caused by intraoperative distention at moderate pressure. Nevertheless, the detrimental effects of excessive distending pressures should not be ignored.     

Effects of prostaglandin E1 and E2 analogues on mucosal injury-induced, and on bacterial translocation promoted by, experimental intestinal obstruction.

The aim of this experimental study was to investigate effects of prostaglandin E1 and E2 analogues on mucosal structure and bacterial translocation during small bowel obstruction. The study was carried out on 40 Wistar rats equally divided into four groups; group 1 = control, group 2 = intestinal obstruction by ligation of distal ileum, and groups 3 and 4 = obstruction and administration of PGE2 and PGE1, respectively. Intestinal bacterial content and translocation to mesenteric lymph nodes and to the blood were determined by microbiological analysis. Mucosal structural changes were assessed by histopathological examination and expressed as a structural damage score and as the thickness of the mucosal layer. Bacterial overgrowth was determined in all obstruction groups. Mucosal thickness was 39.7 microm in group 1 and 26.8 microm in group 2 (p <.001). The thickness was significantly preserved by administration of PGE1 and PGE2 (p <.001). Mean structural damage score was 0.4 in group 1 and 6.7 in group 2 (p <.001). The damage scores were significantly lower in groups treated with PGE1 and PGE2 than obstruction alone group (p <.001). Better scores were obtained in rats treated with PGE1 than rats treated with PGE2 (p =.0026). Translocation to the lymph nodes did not occur in group 1, but was 70% in group 2 (p =.0015); significantly lower rates of translocation to lymph nodes were observed in rats treated with PGE1 (p =.035), but not with PGE2. We conclude that mucosal structure is partly maintained by administration of PGE1 and PGE2 during intestinal obstruction; PGE1 is more effective than PGE2 for ameliorating mucosal injury. PGE1 prevents bacterial translocation by preserving structural integrity of the mucosa. PGE2 partially prevents mucosal damage but not bacterial translocation.     

Comparison of foveal optical coherence tomography angiography findings between premature children with ROP and non-premature healthy children

PurposeOur aim is to compare foveal microvascular structure, foveal retinal thickness, and best-corrected visual acuity (BCVA) in children with a history of premature retinopathy (ROP) and healthy children. It is also evaluated whether microvascular structural changes in the course of ROP had resulted from treatment modalities of ROP or the disease itself.MethodsThis is a cross-sectional observational comparative study. Seventy-one children were analyzed in four different groups: children treated with bevacizumab (18), or laser (19) for ROP; or spontaneously regressed disease (18) and non-premature healthy children (16). We analyzed foveal avascular zone (FAZ) and vessel densities (VDs) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at foveal and parafoveal region with optical coherence tomography angiography (OCT-A). Foveal thickness was measured by cross-sectional OCT. Correlations between FAZ area, foveal VD, central foveal thickness (CFT), BCVA, gestational age (GA), and birth weight (BW) were evaluated.ResultsAfter comparing of OCT-A parameters between all premature children (groups 1–3) and non-premature children (group 4), significant differences were found in VD-SCP (whole), VD-SCP (foveal), VD-SCP (parafoveal), CFT, and VD-DCP (foveal) (all p < 0.001). Significantly smaller FAZ area was also noted in ROP children. Higher foveal VD of SCP, DCP, and smaller FAZ area were significantly associated with lower GA and BW.ConclusionBy using OCT-A, significant foveal microvascular anomalies were identified in children with ROP irrespective of the treatment option or spontaneous regression. There has been a correlation between microvascular anomalies, CFT, and a lower BCVA.Subject terms: Retinal diseases, Diseases     

Magnesium modifies fentanyl-induced local antinociception and hyperalgesia

Fentanyl-induced hyperalgesia and antinociception after systemic administration has been shown in previous clinical and experimental studies. However, there is very little evidence regarding the local possible effects of fentanyl. The purpose of this study was to assess whether local (intraplantar) fentanyl administration can produce antinociception and hyperalgesia. In addition, we examined the effects of magnesium, N-methyl-D-aspartate receptor antagonist, on possible changes produced by fentanyl. The paw withdrawal latencies to radiant heat stimuli were measured to assess the thermal nociceptive actions. Intraplantar administration of fentanyl caused time and dose-dependent increase in the paw withdrawal latencies (antinociception). Coinjection of magnesium with fentanyl markedly enhanced the antinociception. However, fentanyl also markedly decreased paw withdrawal latencies 24 h after intraplantar administration (hyperalgesia). In the presence of magnesium, hyperalgesia after fentanyl administration was not observed. Consequently, following the fentanyl administration, local hyperalgesia after antinociception is a negative effect in pain treatment. Magnesium may not only prevent the hyperalgesia but also enhance antinociceptive effect of fentanyl.     

Molecular and geographical heterogeneity of hemoglobinopathy mutations in Azerbaijanian populations

With the carrier rate of 4%–8.6%, β-thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of β-thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. Α- and β-globin genes were evaluated in the carriers of mutations identified via hematological indices and hemoglobin fractions (n = 1,757). Genotyping of β-thalassemia carriers identified through population screening revealed 32 mutations, with codon 8 [–AA]–34.96%, IVS-II-1 [G > A]–16.35%, and IVS-I-110 [G > A]–10.12% leading the spectrum. Analysis of associations of β-thalassemia mutations with geographical regions of the country identified the strongest association between codon 8 [–AA] and Shaki-Zaqatala, and codon 5 [–CT] in Mountainous Shirvan regions (ri > 6.00; p < 0.05). HbS, HbD-Punjab, and HbE were the most prevalent among our variant hemoglobin cohort, commonly inherited in compounds with β-thalassemia than in the homozygous state. We identified nine α-thalassemia mutations, 20.5 kb and 3.7 kb deletions together accounting for 74% of the spectrum. Point mutations of α-thalassemia were less common among our observations and were mainly inherited in compounds with deletions. Our results allow a better understanding of the wide spectrum of mutations in Azerbaijan and highlights the high heterogeneity of hemoglobinopathies in the local population.