Incidence,prevalence, mortality,disability-adjusted life years and risk factors of cancer in Australia and comparison with OECD countries, 1990–2015: findings from the Global Burden of Disease Study 2015

BackgroundComparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden – incidence, prevalence, mortality, disability-adjusted life years (DALYs) – and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD).MethodsThe general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors.ResultsIn 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908–217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061–49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2–29.8) of total deaths and 17.0% (95% UI: 15.0–19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1–37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24^th based on ASIR and ASDR, respectively.ConclusionThe incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge.     

Lipid peroxidation in purified plasma membrane fractions of rat liver in relation to the hepatoxicity of carbon tetrachloride

Preparations of rat liver sinusoidal plasma membrane have been tested for their ability to metabolize the hepatotoxin carbon tetrachloride (CCl4) to reactive free radicals in vitro and compared in this respect with standard preparations of rat liver microsomes. The sinusoidal plasma membranes were relatively free of endoplasmic reticulum-associated activities such as the enzymes of the cytochrome P450 system and glucose-6-phosphatase. CCl4 metabolism was measured as (i) covalent binding of [14C]-CCl4 to membrane protein, (ii) electron spin resonance spin-trapping of CCl3. radicals and (iii) CCl4-induced lipid peroxidation. By all of these tests, purified sinusoidal plasma membranes were found unable to metabolize CCl4. The fatty acid composition of the plasma membranes was almost identical to that of the microsomal preparation and both membrane fractions exhibited similar rates of the lipid peroxidation that was stimulated non-enzymically by gamma-radiation or incubation with ascorbate and iron. The absence of CCl4-induced lipid peroxidation in the plasma membranes seems to be due, therefore, to an absence of CCl4 activation rather than an inherent resistance to lipid peroxidation. We conclude that damage to the hepatocyte plasma membrane during CCl4 intoxication is not due to a significant local activation of CCl4 to CCl3. within that membrane.     

Does the VP1 gene of foot-and-mouth disease virus behave as a molecular clock?

Summary We have carried out a phylogenetic study of the evolution of the VP1 gene sequence from different serological types and subtypes of foot-and-mouth disease virus (FMDV). The maximum-likelihood method developed by Hasegawa and co-workers (Hasegawa et al. 1985) for the estimation of evolutionary parameters and branching dates has been used to decide between alternative models of evolution: constant versus variable rates. The results obtained indicate that a constant rate model, i.e., a molecular clock, seems to be the most plausible one. However, additional information suggests the possibility that the appearance of serotype CS has been accompanied by an episode of rapid evolution (Villaverde et al. 1991). We discuss the possibility that this evolution of RNA viruses was due to episodic positive Darwinian selection, which would have helped the new variant to escape the immunogenic pressure from the hosts. Offprint requests to: A. Moya     

Lipoxygenase- mediated cleavage of fatty acids in plant mitochondria

Incubation of cauliflower bud mitochondria in the presence of 5 mM CaCl2 results in a rapid hydrolysis of the main membrane phospholipsds. Under the action of phospholipase D, phosphatidic acid is produced and forms, within the membranes, a very labile complex with Ca2+ and HPO42-ions present in the incubation medium. With time, one observes a first step characterized by the formation of phosphatidic acid, followed by a second step linked to the breakdown of this phospholipid. The enzyme responsible for the disappearance of phosphalidic acid has been identified as lipoxygenase. In the presence of molecular oxygen, this enzyme acts on the polyun-saturated fatty acids of phosphatidic add (mainly C18:2 and C18:3) yielding small water-soluble molecules, one of them being identified as malondialdehyde (1, 3-propanedial). Experiments involving inhibitory conditions of the breakdown of phosphatidic acid indicate that lipoxygenase acts directly on membrane-bound phosphatidic acid without previous, involvement of a lipolytic acyl hydrolase activity. In addition, the lipoxygenase activity is fully sensitive to hydroxamate derivatives. It is proposed that the lipoxygenase activity may account for a part of the mitochondrial alternative electron pathway that is insensitive to cyanide.     

Development of a high-throughput screening assay for cytoprotective agents in rotenone-induced cell death

Parkinson’s disease (PD) is a neurodegenerative disease featured by selective loss of substantia nigra neurons. Rotenone administration in animals induces neurodegeneration accompanied by α-synuclein-positive Lewy body-like inclusions, recapturing typical histopathological features of PD. In an effort to screen for small-molecule agents to reverse rotenone-induced cytotoxicity, we developed and validated a sensitive and robust assay with neuroblastoma SK-N-SH cells. This assay was amenable to a high-throughput screening format with Z′ factor of 0.56. Robotic screening of a bioactive compound library led to the identification of carnosic acid that can effectively protect cells from rotenone treatment. Using a high-content image-based assay and Western blot analysis, we demonstrated that carnosic acid protects cells from rotenone stress by significant induction of HSP70 expression. Therefore, the assay reported here can be used to identify novel cytoprotective agents for clinical therapeutics of PD.     

Effects of glucocorticoids on the gene expression of nutrient transporters in different rabbit intestinal segments

Glucocorticoids (GCs) are counterregulatory hormones with broad effects on the digestion and absorption of dietary carbohydrates, lipids and proteins, but the underlying molecular mechanisms of these effects remain unclear. The present experiment was conducted to investigate the main expression sites of nutrient transporters and the effects of GCs on the gene expression of these transporters in the rabbit small intestine. The results showed that peptide transporter 1 (PepT1), facultative amino acid transporter (rBAT), neutral amino acid transporter (B⁰AT), excitatory amino acid transporter 3 (EAAT3), sodium-glucose transporter 1 (SGLT1) and glucose transporter 5 (GLUT5) were mainly expressed in the distal segment, glucose transporter 2 (GLUT2) and fatty-acid-binding protein 4 (FATP4) were mainly expressed in the proximal segment and cationic amino acid transporter 1 (CAT1) was mainly expressed in the middle segment of the rabbit small intestine. In addition, we analysed the effects of 3 h (short-term) or 7 days (long-term) dexamethasone (DEX) treatment on the gene expression of most nutrient transporters. The results showed that short-term DEX treatment significantly decreased PepT1, B⁰AT, EAAT3, rBAT and SGLT1 expressions in all small intestinal segments, while it significantly decreased GLUT2 in the duodenum and FATP4 in the duodenum and ileum (P < 0.05). Long-term DEX treatment also significantly decreased PepT1, CAT1, B⁰AT, EAAT3, rBAT and SGLT1 in all small intestinal segments and significantly decreased GLUT2 in the jejunum and FATP4 in the ileum (P < 0.05). In conclusion, DEX could decrease the gene expression of most nutrient transporters (except GLUT5) and affect the transport of intestinal amino acids, monosaccharides and fatty acids.     

Determination of trace levels of fatty acid metal salts by high-performance liquid chromatography with fluorescence prelabeling

A simple method is described for picomole determinations of fatty acid metal salts. Fatty acid salts are directly labeled with 4-bromomethyl-7-methoxycoumarin in the presence of excess ethylenediaminetetraacetic acid tripotassium salt without any solvent extractions. The fluorescence derivatives of fatty acids are separated by reverse-phase high-performance liquid chromatography followed by fluorometric detection. The response of each fatty acid (C8-C18) calcium salt is linear from 1 to 50 micrograms/ml of samples. The detection limit is about 7 pmol. Good recoveries are obtained for the calcium salts of myrystic acid and soap (C8-C18, C18:1,2). The new method is successfully applied to the study on biodegradation of fatty acids in river water.     

The involvement of parenchymal,Kupffer and endothelial liver cells in the hepatic uptake of intravenously injected liposomes effects of lanthanum and gadolinium salts

¹²⁵I-labeled albumin or poly(vinyl pyrrolidone) encapsulated in intermediate size multilamellar or unilamellar liposomes with 30–40% of cholesterol were injected intravenously into rats. In other experiments liposomes containing phosphatidyl[Me-¹⁴C]choline were injected. 1 h after injection parenchymal or non-parenchymal cells were isolated. Non-parenchymal cells were separated by elutriation centrifugation into a Kupffer cell fraction and an endothelial cell fraction. From the measurements of radioactivities in the various cell fractions it was concluded that the liposomes are almost exclusively taken up by the Kupffer cells. Endothelial cells did not contribute at all and hepatocytes only to a very low extent to total hepatic uptake of the ¹²⁵I-labels. Of the ¹⁴C-label, which orginates from the phosphatidylcholine moiety of the liposomes, much larger proportions were recovered in the hepatocytes. A time-dependence study suggested that besides the involvement of phosphatidylcholine exchange between liposomes and high density lipoprotein, a process of intercellular transfer of lipid label from Kupffer cells to the hepatocytes may be involved in this phenomenon. Lanthanum or gadolinium salts, which effectively block Kupffer cell activity, failed to accomplish an increase in the fraction of liposomal material recovered in the parenchymal cells. This is compatible with the notion that liposomes of the type used in these experiments have no, or at most very limited, access to the liver parenchyma following their intravenous administration to rats.