An Improved Spectrophotometric Method for Determination of Total 3-Methoxy-4-Hydroxyphenylglycol in Urine

Abstract A clinically useful spectrophotometric method for the determination of 3-methoxy-4-hydroxyphenylglycol (MHPG) is presented. After treatment with barium chloride, the urine is hydrolyzed with Glusulase (β-glucuronidase and sulfatase).† The hydrolysate is passed through a column of Amberlite CG-4B‡ to remove any 3-methoxy-4-hydroxymandelic acid (MHMA) and the pH is adjusted to neutral. The MHPG is extracted with ethyl acetate and returned into potassium carbonate solution. Conversion of the MHPG to vanillin is accomplished with periodate and the vanillin is subsequently extracted with toluene and then potassium carbonate solution. The vanillin concentration is determined at 360 nm and 380 nm. The mean recovery of added MHPG standard was 54.9%. The mean daily excretion of MHPG in 23 samples from 10 normal subjects was 1.87 ± 0.6 mg (range 0.81-3.64). In 3 subjects with pheochromocytoma the excretion of MHPG was markedly elevated. There was an excellent correlation of the MHMA and MHPG excretion.</jats:p

Climate variability over the last 35,000 years recorded in marine and terrestrial archives in the Australian region: An OZ-INTIMATE compilation

The Australian region spans some 60° of latitude and 50° of longitude and displays considerable regional climate variability both today and during the Late Quaternary. A synthesis of marine and terrestrial climate records, combining findings from the Southern Ocean, temperate, tropical and arid zones, identifies a complex response of climate proxies to a background of changing boundary conditions over the last 35,000 years. Climate drivers include the seasonal timing of insolation, greenhouse gas content of the atmosphere, sea level rise and ocean and atmospheric circulation changes. Our compilation finds few climatic events that could be used to construct a climate event stratigraphy for the entire region, limiting the usefulness of this approach. Instead we have taken a spatial approach, looking to discern the patterns of change across the continent. The data identify the clearest and most synchronous climatic response at the time of the Last Glacial Maximum (LGM) (21 ± 3 ka), with unambiguous cooling recorded in the ocean, and evidence of glaciation in the highlands of tropical New Guinea, southeast Australia and Tasmania. Many terrestrial records suggest drier conditions, but with the timing of inferred snowmelt, and changes to the rainfall/runoff relationships, driving higher river discharge at the LGM. In contrast, the deglaciation is a time of considerable south-east to north-west variation across the region. Warming was underway in all regions by 17 ka. Post-glacial sea level rise and its associated regional impacts have played an important role in determining the magnitude and timing of climate response in the north-west of the continent in contrast to the southern latitudes. No evidence for cooling during the Younger Dryas chronozone is evident in the region, but the Antarctic cold reversal clearly occurs south of Australia. The Holocene period is a time of considerable climate variability associated with an intense monsoon in the tropics early in the Holocene, giving way to a weakened monsoon and an increasingly El Niño-dominated ENSO to the present. The influence of ENSO is evident throughout the southeast of Australia, but not the southwest. This climate history provides a template from which to assess the regionality of climate events across Australia and make comparisons beyond our region.14 page(s

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10 -11 to 5.0 × 10 -21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10 -6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation