Destabilisation and subsequent lysis of human erythrocytes induced by Plasmodium falciparum haem products

In falciparum malaria, both infected and uninfected red cells have structural and functional alterations. To investigate the mechanisms of these modifications, we studied the effects of two Plasmodium falciparum haem products (haematin and malaria pigment in the synthetic form beta-haematin) on isolated human red blood cells (RBCs) and purified RBC ghosts. A dose- and time-dependent incorporation of haematin into RBC ghosts and intact cells was observed, which was in proportion to the extent of haematin- induced haemolysis. RBCs pre-incubated with haematin were more sensitive to haemolysis induced by hypotonic shock, low pH, H2O2 or haematin itself. Haemolysis was not related to membrane lipid peroxidation and only partially to oxidation of protein sulphydryl groups and it could not be prevented by scavengers of lipid peroxidation or hydroperoxide groups. N-acetylcysteine partly protected the oxidation of SH groups and significantly reduced haemolysis. In contrast, beta-haematin was neither haemolytic nor oxidative towards protein sulphydryl groups. Beta-haematin did destabilise the RBC membrane, but to a lesser extent than haematin, inducing increased susceptibility to lysis caused by hypotonic medium, H2O2 or haematin. This study suggests that the destabilising effect of haematin and, to a much less extent, beta-haematin on the RBC membrane does not result from oxidative damage of membrane lipids but from direct binding or incorporation which may affect the reciprocal interactions between the membrane and cytoskeleton proteins. These changes could contribute to the reduced red cell deformability associated with severe malaria.     

Laparoscopic gastric banding and body composition in morbid obesity

BACKGROUND AND AIM: Gastric banding induced considerable and rapid weight loss in morbid obesity. Nevertheless data on changes in body composition following gastric banding are scanty. In this study, we evaluated the 2-year changes in body composition in a small group of morbidly obese women treated by laparoscopic adjustable gastric banding (LAGB) associated with a well balanced low-calorie diet. METHODS AND RESULTS: We studied 20 premenopausal morbid obese women with BMI ranging from 35 to 57 (kg/m2) before, and 6, 12 and 24 months after laparoscopic adjustable gastric banding (LAGB). A well balanced 5.4 MJ/day hypocaloric diet was prescribed after surgery. Total body water (TBW), fat-free mass (FFM) and fat mass (FM) were investigated using conventional bioelectrical impedance analysis (BIA). Tissue hydration was also assessed by impedance vector analysis and the RXc graph method. The subjects showed a total weight loss of 28% of baseline body weight. In the first 6 months after surgery, patients lost 18.5+/-5.9 kg of body weight (17.6+/-6.2 kg of FM and 0.7+/-1.4 kg of FFM). From 6 to 12 months, a further 12.5+/-7.5 kg of body weight was lost (10.5+/-8.2 kg of FM and 2.2+/-3.8 kg of FFM). During the last 12 months, weight loss was 3.0+/-2.3 kg (1.9+/-3.7 kg of FM and 1.1+/-2.9 kg of FFM). The weight loss observed after LAGB was mainly due to a decrease in FM, whereas TBW, FFM and BCM were only slightly and non-significantly reduced. No changes in body hydration status were observed after surgery. CONCLUSIONS: LAGB associated with a well balanced low-calorie diet achieved a satisfactory 2-year weight loss, while sparing FFM and not causing body fluid alterations.     

Effects of malaria heme products on red blood cell deformability

In falciparum malaria, the deformability of the entire erythrocyte population is reduced in proportion to disease severity, and this compromises microcirculatory blood flow through vessels partially obstructed by cytoadherent parasitized erythrocytes. The cause of rigidity of uninfected erythrocytes in not known but could be mediated by malaria heme products. In this study, we show that red blood cell deformability (RBC-D), measured by laser-assisted optical rotational cell analyzer, decreased in a dose-dependent manner after incubation with hemin and hydrogen peroxide but not with hemoglobin or beta-hematin. Hemin also reduced mean red cell volume. Albumin decreased and N-acetylcysteine (NAC) both prevented and reversed rigidity induced by hemin. Hemin-induced oxidative damage of the membrane seems to be a more important contributor to pathology than cell shrinkage because the antioxidant NAC restored RBC-D but not red blood cell volume. The findings suggest novel approaches to the treatment of potentially lethal malaria.     

Spinal glioneuronal tumor with neuropil‐like islands and meningeal dissemination: histopathological and radiological study of a pediatric case

Cerebral and spinal location of glioneuronal tumors have been recently described as a novel type of primary CNS neoplasia. A distinctive rare form of glioneuronal tumors with neuropil‐like islands (GTNI) have been reported to occur in the adult cerebrum, whereas spinal GTNI localization is extremely rare. In the present report we describe a case of a 15‐month‐old child with a spinal GTNI of the cervical region and meningeal dissemination. Histologically the tumor was composed of round, small neurocytic‐like cells arranged around eosinophilic neuropil cores and embedded in a diffuse fibrillar glial component forming prominent “rosetted” neuropil islands displaying strong immunoreactivity for neuronal markers. Cerebral GTNI shows abundant glial components not rarely exhibiting anaplastic features that justify their inclusion within the group of diffuse astrocytomas. In contrast, including our case, spinal GTNI do not show histological evidence of anaplastic features and exhibits a significant neuronal component that may imply considering these lesions in a separate group. Nevertheless, due to their exceptional rarity, the natural history of these lesions is not yet fully understood, but spinal GTNI seems to have an unfavorable clinical course despite their benign histopathological features, which must be taken into account for appropriate treatment and follow‐up of the patient.     

Blood inflammatory markers and risk of dementia: The Conselice Study of Brain Aging

Incidence studies of blood inflammatory markers as predictors of dementia in older age are few and did not take into account hyperhomocysteinemia, although this condition is associated with both inflammation and increased risk of dementia. We investigated the relationships of baseline serum C-reactive protein (CRP), serum interleukin 6 (IL6), plasma alpha-1-antichymotrypsin, and hyperhomocysteinemia (defined as plasma total homocysteine > 15 μmol/L) with risk of incident Alzheimer's disease (AD) and vascular dementia (VaD) in a dementia-free Italian population-based elderly cohort (n = 804, 53.2% women, mean age 74 years) with 4 years of follow-up. No inflammatory marker, alone or in combination, predicted AD risk whereas the combination of high CRP and high IL6 was associated with risk of VaD (HR, 2.56; 95%CI, 1.21–5.50) independently of socio-demographic confounders, traditional risk factors and hyperhomocysteinemia. By contrast, in the same model, hyperhomocysteinemia was independently associated with AD (HR, 1.91; 95%CI, 1.02–3.56) but not VaD risk. Blood inflammatory markers are associated with increased VaD risk but do not predict AD, which seems selectively associated with hyperhomocysteinemia.