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 effects of postmenopausal hormone therapy on social activity, partner relationship, and sexual life – experience from the EPHT trial

<p>Abstract</p> <p>Background</p> <p>With the exception of sexual functioning and weight, social and behavioural effects of postmenopausal hormone therapy (HT) have not been reported from trials. This paper reports such results from the EPHT-trial in Estonia.</p> <p>Methods</p> <p>A randomized trial, with a blind and non-blind sub-trial in Estonia. From 1999–2001, 1778 women were recruited. The mean follow-up was 3.6 years. Women's experiences were asked in the first and final study year by mailed questionnaires (74 and 81% response rates). Comparisons of the groups were made by cross-tabulation and logistic regression, adjusting for age.</p> <p>Results</p> <p>There were no differences between the HT and non-HT groups in regard to being employed, the extent of social involvement or marital status or opinions on aging. There was no difference in the frequency of free-time exercise, or overweight. Some of the indicators suggested less sexual inactivity, but the differences were small.</p> <p>Conclusion</p> <p>In a trial setting, postmenopausal hormone therapy did not influence work or social involvement or health behaviour.</p> <p>Trial registration</p> <p>ISRCTN35338757</p

Knowledge, Perceptions and Information about Hormone Therapy (HT) among Menopausal Women: A Systematic Review and Meta-Synthesis

BACKGROUND: The use of hormone therapy (HT) by menopausal women has declined since the Women's Health Initiative randomized trial (WHI) in 2002 demonstrated important harms associated with long-term use. However, how this information has influenced women's knowledge and attitudes is uncertain. We aimed to evaluate the attitudes and perceptions towards HT use, as well as specific concerns and information sources on HT since the WHI trial. METHOD/RESULTS: We did a systematic review to assess the attitudes and knowledge towards HT in women, and estimate the magnitude of the issue by pooling across the studies. Using meta-synthesis methods, we reviewed qualitative studies and surveys and performed content analysis on the study reports. We pooled quantitative studies using a random-effects meta-analysis. We analyzed 11 qualitative studies (n = 566) and 27 quantitative studies (n = 39251). Positive views on HT included climacteric symptom control, prevention of osteoporosis and a perceived improvement in quality of life. Negative factors reported included concerns about potential harmful effects, particularly cancer risks. Sources of information included health providers, media, and social contact. By applying a meta-synthesis approach we demonstrate that these findings are broadly applicable across large groups of patients. CONCLUSIONS: Although there are clear hazards associated with long-term HT use, many women view HT favorably for climacteric symptom relief. Media, as a source of information, is often valued as equivalent to health providers

Seasonal variations in the nitrogen isotopic composition of settling particles at station K2 in the western subarctic North Pacific

Intensive observations using hydrographical cruises and moored sediment trap deployments during 2010 and 2012 at station K2 in the North Pacific western subarctic gyre (WSG) revealed seasonal changes in δ15N of both suspended and settling particles. Suspended particles (SUS) were collected from depths between the surface and 200 m; settling particles by drifting traps (DST; 100-200 m) and moored traps (MST; 200 and 500 m). All particles showed higher δ15N values in winter and lower in summer, contrary to the expected by isotopic fractionation during phytoplankton nitrate consumption. We suggest that these observed isotopic patterns are due to ammonium consumption via light-controlled nitrification, which could induce variations in δ15N(SUS) of 0.4-3.1 ‰ in the euphotic zone (EZ). The δ15N(SUS) signature was reflected by δ15 N(DST) despite modifications during biogenic transformation from suspended particles in the EZ. δ15 N enrichment (average: 3.6 ‰) and the increase in C:N ratio (by 1.6) in settling particles suggests year-round contributions of metabolites from herbivorous zooplankton as well as TEPs produced by diatoms. Accordingly, seasonal δ15 N(DST) variations of 2.4-7.0 ‰ showed a significant correlation with primary productivity (PP) at K2. By applying the observed δ15 N(DST) vs. PP regression to δ15 N(MST) of 1.9-8.0 ‰, we constructed the first annual time-series of PP changes in the WSG. Moreover, the monthly export ratio at 500 m was calculated using both estimated PP and measured organic carbon fluxes. Results suggest a 1.6 to 1.8 times more efficient transport of photosynthetically-fixed carbon to the intermediate layers occurs in summer/autumn rather than winter/spring

Southward displacement of the North Atlantic Subtropical Gyre circulation system during North Atlantic cold spells

Key Points: - Rapid subsurface oceanographic change in the tropical W Atlantic reflect shifting Subtropical Gyre - Subsurface warming responds to deglacial AMOC perturbations (Heinrich Stadials 2, 1, and the Younger Dryas) - Southward propagation of Salinity Maximum Water during Northern Hemisphere cold spells shift the mixing zone of tropical and subtropical waters During times of deglacial Atlantic Meridional Overturning Circulation (AMOC) perturbations, the tropical Atlantic experienced considerable warming at subsurface levels. Coupled ocean‐atmosphere simulations corroborate the tight teleconnection between the tropical Atlantic and climate change at high northern latitudes, but still underestimate the relevance of the subsurface N Atlantic Subtropical Gyre (STG) for heat and salt storage and its sensitivity to rapid climatic change. We here reconstruct vertical and lateral temperature and salinity gradients in the tropical W Atlantic and the Caribbean over the last 30 kyrs, based on planktic deep and shallow dwelling foraminiferal Mg/Ca and δ18O‐records. The rapid and large amplitude subsurface changes illustrate a dynamic STG associated with abrupt shifts of North Atlantic hydrographic and atmospheric regimes. During full glacial conditions, the STG has been shifted southward while intensified Ekman‐downwelling associated to strengthened trade winds fostered the formation of warm and saline Salinity Maximum Water (SMW). The southward propagation of SMW was facilitated by the glacially eastward deflected North Brazil Current. During periods of significant AMOC perturbations (Heinrich Stadials 1, and the Younger Dryas), extreme subsurface warming by ~6°C led to diminished lateral subsurface temperature gradients. Coevally, a deep thermocline suggests that SMW fully occupied the subsurface tropical W Atlantic and that the STG reached its southernmost position. During the Holocene, modern‐like conditions gradually developed with the northward retreat of SMW and the development of a strong thermocline ridge between the Subtropical Gyre and the tropical W Atlantic

Variable Growth and Acid Production by Lactococci in Whole Milk Concentrated by Ultrafiltration and Diafiltration

Growth and acid production of several commercial strains of Lactococcus lactis ssp. were followed in whole milk, and whole milk retentate containing 32% solids, diafiltered to reduce lactose content. Generation times of some strains were longer in retentate than in whole milk. Because of the importance of acid production rates in cheese making, increased buffer capacity of UF retentate, and the potential for bacteriophage infection, starter growth and acid production in retentate should be considered before starter blends are used to make UF cheese. Growth rates of each strain in retentate should be considered when starter blends to be grown in UF retentate are formulated. Equal inocula of two unmatched strains can result in domination by one strain by as much as 96:4 after bulk starter has been grown to high cell density. To avoid serious problems with starters in UF retentate, blends should be formulated using strains with similar growth characteristics in UF retentate, or strain ratios should be adjusted to provide viable final numbers of all strains in a given blend

The Oxygen Isotope Composition of Planktonic Foraminifera from the Cariaco Basin, Venezuela: Seasonal and Interannual Variations

Material collected during a three-year sediment trapping experiment in the Cariaco Basin, Venezuela (January 1997 to December 1999) is used to examine both temporal and inter-species variability in the oxygen isotope composition of planktonic foraminifera. Specifically, this study compares the oxygen isotope composition of six species of planktonic foraminifera (Globigerinoides ruber (pink), Globigerina bulloides, Neogloboquadrina dutertrei, Orbulina universa, Globorotalia menardii and Globorotalia crassaformis) with the climatology and hydrography of the region, and evaluates the application of each species for use in paleoceanographic reconstructions. The isotope results are consistent with known depth habitats for all six species. The lowest δ18O values (- 1 to - 2‰) were measured on G. ruber (pink) and G. bulloides, two species that live in the surface mixed layer. Values for deeper-dwelling species such as N. dutertrei, G. menardii and G. crassaformis are higher, predominantly ranging from 0 to - 0.5‰. Temperature estimates derived using species-specific paleotemperature equations indicate that G. ruber (pink) accurately estimates sea surface temperatures (SSTs) throughout the year, while G. bulloides temperature estimates are similar to measured surface temperatures only during the upwelling season (January-April). For the remainder of the year, the δ18O-derived temperatures for G. bulloides typically are lower than the measured SST. Although the maximum flux of all species occurs during upwelling, the flux-weighted annual mean isotopic composition of the six species indicates that only G. bulloides is biased towards this season. Therefore, we conclude that the sediment δ18O record of G. ruber (pink) is most suitable for estimating past values of mean annual SST, while G. bulloides provides information on conditions during spring upwelling. The depth of calcification of N. dutertrei varies seasonally in response to changes in the depths of the thermocline and chlorophyll maximum. As a result, the δ18O difference between G. ruber (pink) and N. dutertrei provides an estimate of the annual surface to thermocline temperature gradient in the basin

Oceanographic Controls on the Carbon Isotopic Compositions of Sinking Particles from the Cariaco Basin

This study examined the relationship between carbon isotopic composition of sinking organic matter (OM) and the biological, physical and chemical properties of the surface ocean in the Cariaco Basin. The 13C/ 12C ratio of OM (δ 13C org) in sinking particles was determined on sediment trap samples from four depths collected from 1996 to 1999 as part of the CArbon Retention In A Colored Ocean time series. Water column properties, including temperature, productivity, chlorophyll and concentration of dissolved CO 2, were concurrently measured on monthly cruises. The δ 13C org varied from a high of -17.7‰ to a low of -22.6‰ during the study period. The variation of the δ 13C org throughout seasonal cycles was directly proportional to the strength of upwelling and was negatively correlated with temperature (r 2=0.64). During the 1996-1997 upwelling event, the strongest during the study period, the δ 13C org increased by ∼4.4‰ whereas during the 1998-1999 upwelling event, the weakest during the study period, the δ 13C org only increased by ∼3.3‰. Contrary to most previous studies, we observed a negative relationship (r 2=0.53) between [CO 2 aq] and the estimated isotopic fractionation factor (ε p). However, there was no correlation between ε p and the calculated growth rates indicating that there was non-diffusive uptake of carbon into phytoplankton cells. It thus appears that [CO 2 aq] does not control the δ 13C org in the water column of the study site. The best explanation for the isotopic enrichment observed is a carbon concentrating mechanism (CCM) in phytoplankton. The existence of a CCM in phytoplankton has major implications for the interpretation of the δ 13C org in the Cariaco Basin