Safe use of perampanel in a carrier of variegate porphyria

Objectives. Treatment of chronic epilepsy in acute porphyrias may be difficult because many antiepileptic drugs can cause activation of clinically-latent conditions. Methods. A 44 year-old lady with drug-resistant chronic epilepsy and a previous genetic diagnosis of variegate porphyria was referred to our epilepsy centre. We started her on perampanel, a structurally novel selective non-competitive AMPA receptor antagonist recently approved for the treatment of partial and secondarily generalized seizures in humans. There are no previous reports about the outcome of exposure to perampanel of carriers of acute porphyria. Results. Perampanel was assessed in silico to be probably not porphyrogenic. Administration of the drug up to 4 mg/day did not lead to elevation of urinary porphobilinogen excretion, nor to any symptoms of acute porphyria after more than 23 months of treatment. Conclusions. Perampanel up to 4 mg/day was tolerated in long-term therapy in this carrier of protoporphyrinogen oxidase deficiency. However, since perampanel is a weak inducer of cytochrome P450 enzymes, vigilance should be maintained for clinical and biochemical signs of activation of acute porphyria when used in a carrier of acute porphyria

A study of the TEX86 paleothermometer in the water column and sediments of the Santa Barbara Basin, California

Particulate organic matter collected during a 2-year period, as part of an ongoing sediment trap study, and a high-resolution sediment record from 1850 to 1987 A.D. from the Santa Barbara Basin were analyzed for TEX86, a temperature proxy based on marine crenarchaeotal membrane lipids. Highest fluxes of crenarchaeotal lipids in the water column were found in May-June 1996 and from October 1996 to January 1997 and, in general, showed a good correlation with mass fluxes. TEX86 reconstructed temperatures from the sediment trap series ranged from 8 to 11°C and were usually substantially lower than sea surface temperatures (SST), indicating that unlike in previous studies, the TEX86 corresponds to subsurface temperatures, likely between 100 and 150 m. TEX86 temperature variations observed in trap samples were not coupled to changes in SST or deep-water temperatures and only to some degree with crenarchaeotal lipid fluxes. This suggests that a complex combination of different depth origins and seasonal growth periods of Crenarchaeota contributed to the variations in TEX86 signal during the annual cycle. TEX86 temperatures in the two sediment cores studied (8-13°C) were also substantially lower than those of instrumental SST records (14-17.5°C) confirming that TEX86 records a subsurface temperature signal in the Santa Barbara Basin. This result highlights the importance of performing calibration studies using sediment traps and core tops before applying the TEX86 temperature proxy in a given study area

Western Arctic Ocean temperature variability during the last 8000 years

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 38 (2011): L24602, doi:10.1029/2011GL049714.We reconstructed subsurface (∼200–400 m) ocean temperature and sea-ice cover in the Canada Basin, western Arctic Ocean from foraminiferal δ18O, ostracode Mg/Ca ratios, and dinocyst assemblages from two sediment core records covering the last 8000 years. Results show mean temperature varied from −1 to 0.5°C and −0.5 to 1.5°C at 203 and 369 m water depths, respectively. Centennial-scale warm periods in subsurface temperature records correspond to reductions in summer sea-ice cover inferred from dinocyst assemblages around 6.5 ka, 3.5 ka, 1.8 ka and during the 15th century Common Era. These changes may reflect centennial changes in the temperature and/or strength of inflowing Atlantic Layer water originating in the eastern Arctic Ocean. By comparison, the 0.5 to 0.7°C warm temperature anomaly identified in oceanographic records from the Atlantic Layer of the Canada Basin exceeded reconstructed Atlantic Layer temperatures for the last 1200 years by about 0.5°C.J.R.F., T.M.C., and R.C.T. thank support by USGS Global Change Program, G.S.D. thanks support from the USGS Global Change Program and the NSF Office of Polar Programs, A.d.V. thanks support by Fond québécois de la recherché sur la nature et les technologies (FQRNT) and the Ministere du Développement économique, innovation et exportation (MDEIE) of Quebec.2012-06-1

Renal Failure Affects the Enzymatic Activities of the Three First Steps in Hepatic Heme Biosynthesis in the Acute Intermittent Porphyria Mouse

Chronic kidney disease is a long-term complication in acute intermittent porphyria (AIP). The pathophysiological significance of hepatic overproduction of the porphyrin precursors aminolevulinate acid (ALA) and porphobilinogen (PBG) in chronic kidney disease is unclear. We have investigated the effect of repetitive acute attacks on renal function and the effect of total or five-sixth nephrectomy causing renal insufficiency on hepatic heme synthesis in the porphobilinogen deaminase (PBGD)-deficient (AIP) mouse. Phenobarbital challenge in the AIP-mice increased urinary porphyrin precursor excretion. Successive attacks throughout 14 weeks led to minor renal lesions with no impact on renal function. In the liver of wild type and AIP mice, 5/6 nephrectomy enhanced transcription of the first and rate-limiting ALA synthase. As a consequence, urinary PBG excretion increased in AIP mice. The PBG/ALA ratio increased from 1 in sham operated AIP animals to over 5 (males) and over 13 (females) in the 5/6 nephrectomized mice. Total nephrectomy caused a rapid decrease in PBGD activity without changes in enzyme protein level in the AIP mice but not in the wild type animals. In conclusion, high concentration of porphyrin precursors had little impact on renal function. However, progressive renal insufficiency aggravates porphyria attacks and increases the PBG/ALA ratio, which should be considered a warning sign for potentially life-threatening impairment in AIP patients with signs of renal failure

The Atlantic Ocean at the last glacial maximum: 1. Objective mapping of the GLAMAP sea-surface conditions

Recent efforts of the German paleoceanographic community have resulted in a unique data set of reconstructed sea-surface temperature for the Atlantic Ocean during the Last Glacial Maximum, plus estimates for the extents of glacial sea ice. Unlike prior attempts, the contributing research groups based their data on a common definition of the Last Glacial Maximum chronozone and used the same modern reference data for calibrating the different transfer techniques. Furthermore, the number of processed sediment cores was vastly increased. Thus the new data is a significant advance not only with respect to quality, but also to quantity. We integrate these new data and provide monthly data sets of global sea-surface temperature and ice cover, objectively interpolated onto a regular 1°x1° grid, suitable for forcing or validating numerical ocean and atmosphere models. This set is compared to an existing subjective interpolation of the same base data, in part by employing an ocean circulation model. For the latter purpose, we reconstruct sea surface salinity from the new temperature data and the available oxygen isotope measurements

Silica burial enhanced by iron limitation in oceanic upwelling margins

In large swaths of the ocean, primary production by diatoms may be limited by the availability of silica, which in turn limits the biological uptake of carbon dioxide. The burial of biogenic silica in the form of opal is the main sink of marine silicon. Opal burial occurs in equal parts in iron-limited open-ocean provinces and upwelling margins, especially the eastern Pacific upwelling zone. However, it is unclear why opal burial is so efficient in this margin. Here we measure fluxes of biogenic material, concentrations of diatom-bound iron and silicon isotope ratios using sediment traps and a sediment core from the Gulf of California upwelling margin. In the sediment trap material, we find that periods of intense upwelling are associated with transient iron limitation that results in a high export of silica relative to organic carbon. A similar correlation between enhanced silica burial and iron limitation is evident in the sediment core, which spans the past 26,000 years. A global compilation also indicates that hotspots of silicon burial in the ocean are all characterized by high silica to organic carbon export ratios, a diagnostic trait for diatoms growing under iron stress. We therefore propose that prevailing conditions of silica limitation in the ocean are largely caused by iron deficiency imposing an indirect constraint on oceanic carbon uptake

Silicic acid biogeochemistry in the Gulf of California: Insights from sedimentary Si isotopes

Iron is considered to play a large role in the cycling of Si in Fe-limited regions of the ocean, but little is known about its role in Si biogeochemistry outside these areas. Here, we present published sediment trap data, new nutrient profiles and high resolution sedimentary records (Si isotopes, Biogenic silica%, N% and C%) from the Gulf of California, a non-Fe-limited region, to investigate the history of Si cycling in this highly productive basin. Modern nutrient profiles show that silicic acid in subsurface waters is in excess relative to nitrate and is therefore incompletely utilized during moderate winter upwelling events. Modern data, however, suggest that during intense upwelling episodes, silicic acid is preferentially utilized relative to nitrate by the biota, which we suggest reflects transient iron limitation. Our new delta Si-30 record from the Guaymas Basin shows dramatic variations at millennial timescales. Low delta Si-30 values synchronous with Heinrich events are interpreted as resulting from the decline in Si(OH)(4) utilization at times of decreased upwelling strength, while nearly complete Si(OH)(4) utilization was observed at times of invigorated upwelling and increased opal burial during the Holocene, the Bolling-Allerod and the last glacial period. We attribute the complete utilization of Si(OH)(4) to the occurrence of transient Fe limitation at these times. Our study highlights the importance of Fe limitation on Si and C cycling in coastal upwelling regions and suggests that upwelling dynamics, in combination with Fe availability, have the potential to modulate marine Si distribution and opal burial even at short timescales.KEYWORDS: North Pacific, Coastal upwelling regimes, Climate change, Marine diatoms, Biogenic silica, Guaymas basin, Equatorial Pacific, Iron, Late quaternary, Southern ocea

A review of nitrogen isotopic alteration in marine sediments

Key Points: Use of sedimentary nitrogen isotopes is examined; On average, sediment 15N/14N increases approx. 2 per mil during early burial; Isotopic alteration scales with water depth Abstract: Nitrogen isotopes are an important tool for evaluating past biogeochemical cycling from the paleoceanographic record. However, bulk sedimentary nitrogen isotope ratios, which can be determined routinely and at minimal cost, may be altered during burial and early sedimentary diagenesis, particularly outside of continental margin settings. The causes and detailed mechanisms of isotopic alteration are still under investigation. Case studies of the Mediterranean and South China Seas underscore the complexities of investigating isotopic alteration. In an effort to evaluate the evidence for alteration of the sedimentary N isotopic signal and try to quantify the net effect, we have compiled and compared data demonstrating alteration from the published literature. A >100 point comparison of sediment trap and surface sedimentary nitrogen isotope values demonstrates that, at sites located off of the continental margins, an increase in sediment 15N/14N occurs during early burial, likely at the seafloor. The extent of isotopic alteration appears to be a function of water depth. Depth-related differences in oxygen exposure time at the seafloor are likely the dominant control on the extent of N isotopic alteration. Moreover, the compiled data suggest that the degree of alteration is likely to be uniform through time at most sites so that bulk sedimentary isotope records likely provide a good means for evaluating relative changes in the global N cycle

Body Shape and Life Style of the Extinct Balearic Dormouse Hypnomys (Rodentia, Gliridae): New Evidence from the Study of Associated Skeletons

Hypnomys is a genus of Gliridae (Rodentia) that occurred in the Balearic Islands until Late Holocene. Recent finding of a complete skeleton of the chronospecies H. morpheus (Late Pleistocene-Early Holocene) and two articulated skeletons of H. cf. onicensis (Late Pliocene) allowed the inference of body size and the calculation of several postcranial indexes. We also performed a Factorial Discriminant Analysis (FDA) in order to evaluate locomotory behaviour and body shape of the taxa. Using allometric models based on skull and tooth measurements, we calculated a body weight between 173 and 284 g for H. morpheus, and direct measurements of articulated skeletons yielded a Head and Body Length (HBL) of 179 mm and a Total Body Length of 295 mm for this species. In addition to the generally higher robustness of postcranial bones already recorded by previous authors, H. morpheus, similar to Canariomys tamarani, another extinct island species, displayed elongated zygopodium bones of the limbs and a wider distal humerus and femur than in an extant related taxon, Eliomys quercinus. Indexes indicated that Hypnomys was more terrestrial and had greater fossorial abilities than E. quercinus. This was also corroborated by a Discriminant Analysis, although no clear additional inference of locomotory abilities could be calculated

Multidecadal variations in the early Holocene outflow of Red Sea Water into the Arabian Sea

We present Holocene stable oxygen isotope data from the deep Arabian Sea off Somalia at a decadal time resolution as a proxy for the history of intermediate/upper deep water. These data show an overall δ18O reduction by 0.5‰ between 10 and ~6.5 kyr B.P. superimposed upon short-term δ18O variations at a decadal-centennial timescale. The amplitude of the decadal variations is 0.3‰ prior, and up to 0.6‰ subsequent, to ~8.1 kyr B.P. We conclude from modeling experiments that the short-term δ18O variations between 10 and ~6.5 kyr B.P. most likely document changes in the evaporation-precipitation balance in the central Red Sea. Changes in water temperature and salinity cause the outflowing Red Sea Water to settle roughly 800 m deeper than today