Morphological changes induced in erythrocyte by amyloid beta peptide and glucose depletion: A combined atomic force microscopy and biochemical study

Circulating red blood cells (RBCs) undergo aging, a fundamental physiological phenomenon that regulates their turnover. We show that treatment with beta amyloid peptide 1–42 (Aβ) accelerates the occurrence of morphological and biochemical aging markers in human RBCs and influences the cell metabolism leading to intracellular ATP depletion. The morphological pattern has been monitored using Atomic Force Microscopy (AFM) imaging and measuring the RBCs' plasma membrane roughness employed as a morphological parameter capable to provide information on the structure and integrity of the membrane-skeleton. Results evidence that Aβ boosts the development of crenatures and proto-spicules simultaneously to acceleration in the weakening of the cell-cytoskeleton contacts and to the induction of peculiar nanoscale features on the cell membrane. Incubation in the presence of glucose can remove all but the latter Aβ-induced effects.Biochemical data demonstrate that contemporaneously to morphological and structural alterations, Aβ and glucose depletion trigger a complex signaling pathway involving caspase 3, protein kinase C (PKC) and nitric oxide derived metabolites.As a whole, the collected data revealed that, the damaging path induced by Aβ in RBC provide a sequence of morphological and functional intermediates following one another along RBC life span, including: (i) an acceleration in the development of shape alteration typically observed along the RBC's aging; (ii) the development of characteristic membrane features on the plasma membrane and (iii) triggering a complex signaling pathway involving caspase 3, PKC and nitric oxide derived metabolites.     

New N-(phenoxydecyl)phthalimide derivatives displaying potent inhibition activity towards α-glucosidase

Several members of a new family of non-sugar-type α-glucosidase inhibitors, bearing a phthalimide moiety connected to a variously substituted phenoxy ring by an alkyl chain, were synthesized and their activities were investigated. The efficacy of the inhibition activity appeared to be governed by the chain length of the substrate. Substrates possessing 10 carbons afforded the highest levels of activity, which were one to two orders of magnitude more potent than the known inhibitor 1-deoxynojirimycin (dNM). Furthermore, structure–activity relationship studies indicated a critical role of electron-withdrawing substituents at the phenoxy group for the activity. Derivatives bearing a chlorine atom along with a strong electron-withdrawing group, such as a nitro group, were the most potent of the series.     

Structural and Functional Alterations of Subcutaneous Small Resistance Arteries in Severe Human Obesity

Obese persons are at increased cardiovascular risk and exhibit increased arterial stiffness and impaired endothelial function of large‐ and medium‐size arteries. We hypothesized that normotensive subjects suffering from severe obesity would also present remodeling and endothelial dysfunction of small resistance arteries. A total of 16 lean (age: 49.6 ± 2.9 years, BMI: 22.9 ± 0.3 kg/m², mean ± s.e.m.) and 17 age‐matched severely obese (BMI: 41.1 ± 2.3 kg/m²) normotensive subjects were investigated. None had glucose or lipid metabolic abnormalities except for insulin resistance. Resistance arteries, dissected from abdominal subcutaneous tissue, were assessed on a pressurized myograph. For superimposable blood pressure, the media thickness, media cross‐sectional area (CSA), and media‐to‐lumen ratio values of resistance arteries were markedly and significantly greater in obese compared to lean subjects (media thickness 26.3 ± 0.6 vs. 16.2 ± 0.6 µm, CSA 22,272 ± 1,339 vs. 15,183 ± 1,186 µm², and media‐to‐lumen ratio 0.113 ± 0.006 vs. 0.059 ± 0.001, respectively, P < 0.01). Acetylcholine‐induced relaxation was impaired in vessels from obese subjects compared to the lean individuals (?40.4 ± 1.3%, P < 0.01), whereas endothelium‐independent vasorelaxation was similar in all groups. Stiffness of small arteries as assessed by the stress/strain relationship was similar in lean and severely obese subjects. We conclude that severe human obesity is associated with profound alterations in structural and functional characteristics of small arteries, which may be responsible for the presence of elevated cardiovascular risk and increased incidence of coronary, cerebrovascular and renal events reported in obesity.     

Attenuation of induced bronchoconstriction in healthy subjects: effects of breathing depth.

The effects of breathing depth in attenuating induced bronchoconstriction were studied in 12 healthy subjects. On four separate, randomized occasions, the depth of a series of five breaths taken soon (approximately 1 min) after methacholine (MCh) inhalation was varied from spontaneous tidal volume to lung volumes terminating at approximately 80, approximately 90, and 100% of total lung capacity (TLC). Partial forced expiratory flow at 40% of control forced vital capacity (V(part)) and residual volume (RV) were measured at control and again at 2, 7, and 11 min after MCh. The decrease in V(part) and the increase in RV were significantly less when the depth of the five-breath series was progressively increased (P < 0.001), with a linear relationship. The attenuating effects of deep breaths of any amplitude were significantly greater on RV than V(part) (P < 0.01) and lasted as long as 11 min, despite a slight decrease with time when the end-inspiratory lung volume was 100% of TLC. In conclusion, in healthy subjects exposed to MCh, a series of breaths of different depth up to TLC caused a progressive and sustained attenuation of bronchoconstriction. The effects of the depth of the five-breath series were more evident on the RV than on V(part), likely due to the different mechanisms that regulate airway closure and expiratory flow limitation.     

Genetik des atopischen Ekzems

Atopic eczema (AE) is a chronic inflammatory skin disease characterized by severe pruritus, a defective skin barrier, and the formation of IgE antibodies against common environmental allergens. AE is a polygenic multifactorial disease; it is widely accepted that AE is caused by environmental factors acting on genetically predisposed individuals. However, because of multiple potential gene–gene and gene–environment interactions, the challenge remains to resolve the underlying pathomechanisms. Here we review the current state of knowledge, recent advances, and potential problems in the genetics of AE. In particular, the identification of genetic factors underlying the skin barrier defect has significantly improved our understanding of the disease and might lead to novel preventive and therapeutic strategies.     

Endothelial microvilli in the vessels of the rat gasserian ganglion and testis

Summary In the Gasserian ganglion and testis of the rat the endothelium of the small blood vessels has a singular appearance due to the presence of a high number of microvillous processes. These arise from the luminal surface, either individually, or in small groups. The significance of this structure is not known. It is pointed out that these vessels are particularly sensitive to cadmium intoxication.This investigation was performed during a tenure by Dr. Gabbiani of a fellowship of the Medical Research Council of Canada and was supported by the National Institutes of Health (Grant No. 5R01 HE-08794-04) and the Ministère de la Santé du Québec (projet 604-7-635).The authors wish to thank Dr. S. M. Shea for his advice in the measurement of the villi. The technical assistance of Miss Virginia Gilmore and of Mr. Eduardo Garriga is gratefully acknowledged.     

Variability at different spatial scales of a coralligenous assemblage at Giannutri Island (Tuscan Archipelago,northwest Mediterranean)

This study was carried out on the rocky cliffs of Giannutri Island (Tyrrhenian Sea, Italy) to test the hypothesis that coralligenous assemblages are consistent within the bathymetric range considered (25–35 m depth) over three different spatial scales (1000 m, 100 m and 10 m). A multi-factorial sampling design was used to assess patterns of vertical distribution in the studied area. Data on the percent cover of algae and invertebrates were collected at three depths (25, 30 and 35 m) using a photographic method, and percentage cover was obtained using a visual method. Analysis of the results using ANOVA indicated that the distribution and abundance of algae and some invertebrates of the sublittoral assemblages are clearly heterogeneous. Algae, sponges and bryozoans showed significant variability in distribution and abundance at different depths, but this variability was not consistent amongst transects. Ascidians did not show any variability, while the abundance of anthozoans differed significantly amongst transects. We concluded that heterogeneity in the distribution and abundance of the taxa analysed is related to the smallest spatial scale investigated (10's of m). Some of the possible causes of the observed variability are discussed.