Alcohol consumption and burden of disease in the Americas in 2012: implications for alcohol policy / El consumo de alcohol y la carga de morbilidad en la región de las Américas en el 2012: implicaciones para las políticas relacionadas con el consumo de alcohol

OBJECTIVE:To describe the volume and patterns of alcohol consumption up to and including 2012, and to estimate the burden of disease attributable to alcohol consumption as measured in deaths and disability-adjusted life years (DALYs) lost in the Americas in 2012. METHODS: Measures of alcohol consumption were obtained from the World Health Organization (WHO) Global Information System on Alcohol and Health (GISAH). The burden of alcohol consumption was estimated in both deaths and DALYs lost based on mortality data obtained from WHO, using alcohol-attributable fractions. Regional groupings for the Americas were based on the WHO classifications for 2004 (according to child and adult mortality). RESULTS: Regional variations were observed in the overall volume of alcohol consumed, the proportion of the alcohol market attributable to unrecorded alcohol consumption, drinking patterns, prevalence of drinking, and prevalence of heavy episodic drinking, with inhabitants of the Americas consuming more alcohol (8.4 L of pure alcohol per adult in 2012) compared to the world average. The Americas also experienced a high burden of disease attributable to alcohol consumption (4.7% of all deaths and 6.7% of all DALYs lost), especially in terms of injuries attributable to alcohol consumption. CONCLUSIONS: Alcohol is consumed in a harmful manner in the Americas, leading to a high burden of disease, especially in terms of injuries. New cost-effective alcohol policies, such as increasing alcohol taxation, increasing the minimum legal age to purchase alcohol, and decreasing the maximum legal blood alcohol content while driving, should be implemented to decrease the harmful consumption of alcohol and the resulting burden of disease.

OBJETIVO:Describir el volumen y los modelos de consumo de alcohol hasta el año 2012 incluido, y calcular la carga de morbilidad atribuible al consumo de alcohol medida según el número de defunciones y los años de vida ajustados en función de la discapacidad (AVAD) perdidos en la Región de las Américas en el 2012. MÉTODOS: Los datos sobre el consumo de alcohol se obtuvieron a partir del Sistema Mundial de Información sobre el Alcohol y la Salud (GISAH, por sus siglas en inglés) de la Organización Mundial de la Salud (OMS). La carga del consumo de alcohol se calculó según la mortalidad y según los AVAD perdidos con base en los datos de mortalidad obtenidos de la OMS, tomando en consideración las fracciones atribuibles al alcohol. La división en subregiones se basó en las clasificaciones de la OMS del año 2004 (según la mortalidad en niños y adultos). RESULTADOS: Se observaron variaciones regionales en el volumen total de alcohol consumido, la proporción del mercado del alcohol atribuible al consumo de alcohol no registrado, los hábitos de consumo, la prevalencia del consumo y la prevalencia de los episodios de consumo excesivo de alcohol. Los habitantes de la Región de las Américas consumieron más alcohol (8,4 litros de alcohol puro por adulto en el 2012) en comparación con el promedio mundial. La Región también experimentó una alta carga de morbilidad atribuible al consumo de alcohol (4,7% de las defunciones y 6,7% de los AVAD perdidos), especialmente en forma de lesiones atribuibles al consumo de alcohol. CONCLUSIONES: El alcohol se consume de una manera perjudicial en la Región de las Américas y ello comporta una alta carga de morbilidad, especialmente en forma de lesiones. Con objeto de disminuir el consumo perjudicial de bebidas alcohólicas y la carga de morbilidad resultante, es preciso introducir nuevas políticas en materia de consumo de alcohol que sean eficaces en función de los costos, tales como el incremento de los impuestos sobre el alcohol, el aumento de la edad mínima legal para adquirir alcohol, y la disminución de la concentración máxima legal de alcohol en sangre mientras se conduce.

Development of a novel method to evaluate sialylation of glycoproteins and analysis of gp96 sialylation in Hela, SW1990 and A549 cell lines

BACKGROUND: Glycoproteins play a critical role in the cellular activities of eukaryotes. Sialic acid is typically the outermost monosaccharide of glycolipids and glycoproteins, and is necessary for normal development. RESULTS: A strategy based on avidin-biotin affinity was established to enrich sialylated glycoproteins from HeLa cervical carcinoma, SW1990 pancreatic adenocarcinoma, and A549 lung adenocarcinoma cells. Using HPLC-MS/MS, western blot, real-time PCR, and enzyme-linked immunosorbent assay, gp96 was identified in all three cell lines. No significant difference in the protein expression of gp96 was detected at the whole cell level, but the amount of bioti-nylated gp96 in SW1990 cells was 30-40 % lower than that in A549 and HeLa cells, and the amount of sialylated gp96 in SW1990 cells was 30 % lower than that in A549 and HeLa cells. Immunoblotting results showed that the expression of sialyltransferase proteins in the total cell lysates from HeLa and A549 cells were higher than that in SW1990 cells. CONCLUSIONS: We established a new method for investigating the expression and sialylation of glycoproteins using metabolic labeling, click chemistry, and avidin-biotin affinity. We successfully used this method to purify sialylated glycoproteins from cancer cell lines. Our results showed that the levels of gp96 sialylation varied across different cancer cell lines, and this may be because of differences in sialyltransferase expression.

The Genetically Modified Polysialylated Form of Neural Cell Adhesion Molecule-Positive Cells for Potential Treatment of X-Linked Adrenoleukodystrophy

PURPOSE: Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. MATERIALS AND METHODS: PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. RESULTS: Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. CONCLUSION: These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.

Increasing the alpha 2, 6 Sialylation of Glycoproteins May Contribute to Metastatic Spread and Therapeutic Resistance in Colorectal Cancer

Abnormal glycosylation due to dysregulated glycosyltransferases and glycosidases is a key phenomenon of many malignancies, including colorectal cancer (CRC). In particular, increased ST6 Gal I (beta-galactoside alpha 2, 6 sialyltransferase) and subsequently elevated levels of cell-surface alpha 2, 6-linked sialic acids have been associated with metastasis and therapeutic failure in CRC. As many CRC patients experience metastasis to the liver or lung and fail to respond to curative therapies, intensive research efforts have sought to identify the molecular changes underlying CRC metastasis. ST6 Gal I has been shown to facilitate CRC metastasis, and we believe that additional investigations into the involvement of ST6 Gal I in CRC could facilitate the development of new diagnostic and therapeutic targets. This review summarizes how ST6 Gal I has been implicated in the altered expression of sialylated glycoproteins, which have been linked to CRC metastasis, radioresistance, and chemoresistance.

Expression patterns of influenza virus receptors in the respiratory tracts of four species of poultry

The primary determinant of influenza virus infectivity is the type of linkage between sialic acid and oligosaccharides on the host cells. Hemagglutinin of avian influenza viruses preferentially binds to sialic acids linked to galactose by an alpha-2,3 linkage whereas hemagglutinin of human influenza viruses binds to sialic acids with an alpha-2,6 linkage. The distribution patterns of influenza receptors in the avian respiratory tracts are of particular interest because these are important for initial viral attachment, replication, and transmission to other species. In this study, we examined the distribution patterns of influenza receptors in the respiratory tract of chickens, ducks, pheasants, and quails because these species have been known to act as intermediate hosts in interspecies transmission. Lectin histochemistry was performed to detect receptor-bearing cells. Cell-specific distribution of the receptors was determined and expression densities were compared. We observed species-, site-, and cell-specific variations in receptor expression. In general, receptor expression was the highest in quails and lowest in ducks. Pheasants and quails had abundant expression of both types of receptors throughout the respiratory tract. These results indicate that pheasants and quails may play important roles as intermediate hosts for the generation of influenza viruses with pandemic potential.

Comparative analysis of differential expression of sialic acids and adhesion molecules on mononuclear cells of bone marrow and peripheral blood in childhood acute lymphoblastic leukaemia at diagnosis and clinical remission.

Childhood acute lymphoblastic leukaemia (ALL) is characterized by the neoplasm of immature haematopoietic precursor cells (HPCs). We report significant differences between the expression of sialoglycoproteins and adhesion molecules on mononuclear cells (MNCs) of bone marrow (BM) and peripheral blood (PB) from individual children at diagnosis of the disease. Lymphoblasts in PB predominantly expressed 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs), sialic acid, alpha2-3 linked sialic acid, L- and P-selectins and vascular cell adhesion molecule -1 (VCAM-1) on their surface compared to BM, as determined with selective lectins and monoclonal antibodies (mAbs) by flow cytometric analysis. CD34+CD38+ cells present either in diagnostic PB or BM always showed enhanced expression of both alpha2-3 and alpha2-6 linked sialic acids, Neu5,9Ac2-GPs, L- and P-selectins and VCAM-1, compared to CD34+CD38- population, as confirmed by higher mean fluorescence intensity (MFI). Expression of ICAM-1 was reverse. However, MFI of Neu5,9Ac2-GPs was always higher both in CD34+CD38+ and CD34+CD38- population in PB compared to BM. Diverse trend of these cell surface macromolecules was observed during clinical remission. This is the first comparative study between PB and BM, where significant differential distribution of sialylated macromolecules and adhesion molecules was observed. Hence, supervising these cell surface macromolecules at various stages of treatment might help in minimal residual disease detection, identifying mobilization factor(s) and in isolation of normal HPCs for autologous BM transplantation.

Effect of catecholamines on bursa of fabricius in chicken.

Effect of catecholamines are studied on the bursa of fabricius of chicken. It is found that in epinephrine (E) treated chicken, the lymph follicles are slightly decreased in size. Some amount of nuclear pycnosis is visible in E and norepinephrine (NE) treated chicken. There is no change in the bursa weight and histology in NE treated groups. No deviation is observed in the level of DNA, RNA, total protein and sialic acid content of catecholamine treated birds.

O-acetyl sialic acid binding lectin as a probe for detection of subtle change on cell surface induced during acute lymphoblastic leukemia (ALL) and its clinical application.

A novel probe, a 9-O-acetylated sialic acid binding lectin, namely achatininH (ATNH) has been used for the detection of changes on the cell surface during acute lymphoblastic leukemia (ALL). ATNH does not agglutinate normal human erythrocytes, however it is capable of agglutinating erythrocytes and peripheral blood mononuclear cells (PBMC) of patients suffering from ALL. The differential expression of a key receptor, 9-O-acetylated sialo glyco conjugate (9-O-AcSG), on PBMC was observed using a simple lymphoproliferative assay (LA). The extent of expression of 9-O-AcSG was used as an index to distinguish ALL patients of different clinical stages and assess the probability of relapse. The amount of ATNH needed for maximum stimulation served as a tool to indirectly measure the extent of expression of 9-O-AcSG on PBMC surface. The acetylated sialo glycoconjugate was expressed at a very high concentration during acute phase of the disease. Subsequently it decreased during treatment persisted during maintenance therapy and reappeared with relapse. PBMC of normal human donors required 80 times more ATNH in comparison to the untreated acute phase ALL patients. No cross reactivity was found in non Hodgkin's lymphoma, chronic myelogenous leukemia and thalassaemia patients.

Use of isotopically radiolabelled GM3 ganglioside to study metabolic alterations in Salla disease.

We report the preparation of radioactive GM3 ganglioside and its use in the study of sialic acid storage disorders. For the first time GM3 was isotopically radiolabeled in three positions of the molecule: at the sialic acid acetyl group, [3H-Neu5Ac]GM3, at the C1 of the fatty acid moiety, [14C-Stearoyl]GM3, and at C3 of sphingosine, [3H-Sph]GM3. The radioactive GM3 administered to cultured human fibroblasts from a patient suffering from Salla disease was taken up by the cells and metabolized. An analysis of the distribution of radioactivity within the ganglioside metabolic derivatives showed an accumulation of free sialic acid and ceramide in the pathological cells.

Cell free ascitic fluid prevents loss of cell surface sialic acid from Zajdela Ascitic Hepatoma cells in culture.

In the Zajdela Ascitic Hepatoma (ZAH), a rat tumor, high levels of cell surface sialic acid residues are present which masked the immunogenicity of the cells. We have shown here that cell surface sialic acid level goes down rapidly when ZAH cells are put in culture. The reduction in surface sialic acid levels is due to a decrease in sialic acid residues on the major sialylated glycoprotein, gp 120, as well as a decrease in gp 120 polypeptide. The loss of sialic acid from the cultured cells is reduced if the cells are cultured in the presence of cell free ascitic fluid from ZAH tumor.

Peanut agglutinin binding by gastric mucosal epithelial cells in Helicobacter pylori associated gastritis.

Gastric biopsies (42) from patients with peptic ulcer disease were classified into Helicobacter pylori positive (32) and negative (10) groups, based on the results of tissue urease test and microscopic demonstration of spiral bacteria. A statistically significant difference in peanut agglutinin (PNA) binding between the two groups was observed, attributable to exposure of sialic acid residues on gastric epithelium in the H. pylori positive group. That the negative binding was due to sialic acid, was further confirmed by application of sialidase digestion technique. These results support the existing biochemical evidence for exposure of sialic acid residues on H. pylori colonized epithelium.

Changes in glycosylation of microvillus membranes in Giardia lamblia infected mice intestine.

Giardia lamblia infection has been shown to modify the glycosylation process of microvillus membranes in mice intestine. Sialic acid content of the membranes was enhanced 3-fold but there was no change in fucose content of infected animals compared to the controls. The binding of 125I-wheat germ agglutinin was augmented and that of Ulex Europeus agglutinin was unaltered to infected membranes. The binding of 125I-peanut agglutinin to brush borders was however, significantly reduced in Giardia infected mice. Kinetic analysis revealed that the observed binding of peanut agglutinin to the membrane was associated with reduced number of the lectin reactive sites (control = 649 and infected 380 nmole/protein) with no change in the affinity constant (Ka = 95.7 nmole/ml) in Giardia infected mice intestine.

Dosagem de ácido siálico urinário em crianças normais e sua aplicaçäo para a determinaçäo de sialidoses e sialúrias / Urinary sialic acid measurement in normal childrens and it application in sialidosis and sialuria determination

A determinaçäo do ácido siálico urina é um método útil para a detecçäo de diversas doenças genéticas nas quais há um distúrbio no metabolismo desse composto, denominadas "sialidoses" (incluindo sialidose e galactosialidose) "sialúrias" (incluindo doenças de Salla e doença infantil de acúmulo de ácido siálico). Neste trabalho foram determinadas as concentraçöes urinárias de ácido siálico em 43 crianças normais, cujas idades variaram de 6 meses a 8 anos e meio. Foram estabelecidos os níveis normais para a concentraçäo urinária de ácido siálico livre e total, os quais declinaram sensivelmente com o aumento da idade. A medida da fraçäo livre é recomendada uma vez que seu aumento ocorre nas sialúrias, enquanto que nas sialidoses o que ocorre é um aumento da fraçäo ligada. Os dados apresentados säo importantes para a interpretaçäo dos resultados da dosagem de ácido siálico urinário em crianças, tendo sua utilidade sido comprovada pela avaliaçäo de dois casos de sialidose previamente diagnosticados

Effect of adrenalectomy and administration of prednisolone on gastric ulcer formation in forestomachectomized Shay albino rats.

The gastric ulcerogenic effect of the glucocorticoid, prednisolone, was studied in albino rats. Shay operation in forestomachectomized rats with intact adrenals induced acute gastric ulcers in the corpus, whereas adrenalectomy prevented the development of gastric ulcers in another group of forestomachectomized Shay rats. Only superficial erosion of gastric epithelium was noticed in 66.67% of these rats. Administration of prednisolone to another group of similarly operated rats increased the number and severity of gastric ulceration, whether the adrenals were ablated or otherwise. From the observation of acid and mucous content of the stomach, it is postulated that the reduced mucous secretion may be an important predisposing factor in gastric ulcerogenic effect of steroids.