Peritoneal carcinomatosis following laparoscopic resection of an adrenocortical tumor causing primary hyperaldosteronism

A clinical syndrome combining hypertension and hypokalemic alkalosis led to the diagnosis of primary hyperaldosteronism, caused by a right-sided, 2 cm large, apparently benign aldosterone-producing adenoma. The adrenal tumor was completely resected by laparoscopic adrenalectomy. Six months after surgery, the patient exhibited a severe relapse of hyperaldosteronism. Extensive peritoneal metastases of a mixed aldosterone- and cortisol-secreting adrenocortical carcinoma were found at abdominal laparotomy. In the light of this case report, we discuss the possibility that laparoscopic resection of adrenocortical tumors might contribute to their subsequent peritoneal dissemination.     

The Arabidopsis GNOM ARF-GEF mediates endosomal recycling,auxin transport,and auxin-dependent plant growth

Exchange factors for ARF GTPases (ARF-GEFs) regulate vesicle trafficking in a variety of organisms. The Arabidopsis protein GNOM is a brefeldin A (BFA) sensitive ARF-GEF that is required for the proper polar localization of PIN1, a candidate transporter of the plant hormone auxin. Mutations in GNOM lead to developmental defects that resemble those caused by interfering with auxin transport. Both PIN1 localization and auxin transport are also sensitive to BFA. In this paper, we show that GNOM localizes to endosomes and is required for their structural integrity. We engineered a BFA-resistant version of GNOM. In plants harboring this fully functional GNOM variant, PIN1 localization and auxin transport are no longer sensitive to BFA, while trafficking of other proteins is still affected by the drug. Our results demonstrate that GNOM is required for the recycling of auxin transport components and suggest that ARF-GEFs regulate specific endosomal trafficking pathways.     

Receptor profiling and endocrine interactions of tibolone

The receptor profiles and in vivo activity of tibolone, and its primary metabolites, Delta(4)-isomer, and 3alpha- and 3beta-hydroxytibolone, were studied and compared to those of structurally related compounds. The Delta(4)-isomer was the strongest binder and activator of the progesterone receptor (PR); tibolone was 10 times weaker in binding and half as potent in transactivation of PR; 3alpha- and 3beta-hydroxytibolone did not bind or activate PR. In rabbits oral tibolone produced a minor progestagenic effect in the endometrium, whereas co-administration of tibolone and the anti-estrogen ICI 164,384 unmasked tibolone's progestagenic effect. 3-Hydroxytibolones were the strongest binders and activators of the estrogen receptors (ERs), with greater affinity for ERalpha than for ERbeta. Tibolone showed weaker binding and activation of both ERs and the Delta(4)-isomer has a binding and activation activity of less than 0.1% of E2 for ERalpha or ERbeta. Tamoxifen and 4-hydroxytamoxifen showed partial ERalpha agonistic effects with a maximal response of 12% and raloxifene of 3-5%. Oral administration of 1mg tibolone to ovariectomized rats induced an estrogenic effect on vaginal epithelium. The Delta(4)-isomer was a stronger binder and activator of the androgen receptor (AR) than tibolone; both 3-hydroxytibolones did not bind or activate AR. Introducing a 7alpha-methyl group decreased progestagenic and increased androgenic activity. We conclude that the progestagenic and androgenic activities of tibolone are mediated by the Delta(4)-isomer, and the estrogenic activity, by the 3-hydroxytibolones. The estrogenic activity of the 3-hydroxytibolones masked the progestagenic activity of tibolone in rabbit endometrium. Full estrogenic response was observed in rat vaginal tissue after oral administration of tibolone.     

Hydrological connectivity, and the exchange of organic matter and nutrients in a dynamic river–floodplain system (Danube, Austria)

1. The relationship between hydrological connectivity, and the exchange processes of suspended sediments, organic matter and nutrients (NO₃-N) was investigated in a dynamically connected river–floodplain segment of the Danube over a 15-month period in 1995 and 1996 in the Alluvial Zone National Park, Austria. 2. Based on water level dynamics and water retention times, three phases of river–floodplain connectivity were identified: disconnection (phase I), seepage inflow (phase II) and upstream surface connection (phase III). The frequency of occurrence of these phases was 67.5%, 29.3% and 3.2%, respectively, during the study period. 3. A conceptual model is presented linking hydrological connectivity with ecological processes. Generally, the floodplain shifts from a closed and mainly biologically controlled ecosystem during phase I to an increasingly open and more hydrologically controlled system during phases II and III. Phase I, with internal processes dominating, is designated the ‘biotic interaction phase’. 4. Phase II, with massive nutrient inputs to the floodplain yet relatively high residence times, and therefore, high algal biomass, is classified as the ‘primary production phase’. This demonstrates that water level fluctuations well below bankfull may considerably enhance floodplain productivity. 5. Finally, since transport of particulate matter is mainly restricted to short flood pulses above bankfull level, phase III has been defined as the ‘transport phase’. 6. The floodplain served as a major sink for suspended sediments (250 mt ha^??1 year^??1), FPOM (96 mt ha^??1 year^??1), particulate organic carbon (POC; 2.9 mt ha^??1 year^??1) and nitrate-nitrogen (0.96 mt ha^??1 year^??1), but was a source for dissolved organic carbon (DOC; 240 kg ha^??1 year^??1), algal biomass (chlorophyll-a; 0.5 kg ha^??1 year^??1) and CPOM (21 kg ha^??1 year^??1). Considerable quantities of DOC and algal biomass were exported to the river channel during phase II, whereas particulate matter transport was largely restricted to the short floods of phase III. 7. The Danube Restoration Project will create a more gradual change between the individual phases by increasing hydrological connectivity between the river channel and the floodplain, and is predicted to enhance productivity by maintaining a balance between retention and export of nutrients and organic matter.     

ORG 33201: A new highly selective orally active aromatase inhibitor

Org 33201 has been selected as a very potent aromatase inhibitor. The compound is an enantiomer of a SC₂H₅ substituted imidazoylethylphenalene. Org 33201 inhibited human aromatase activity for 50% at a concentration of 2.2 × 10⁹ mol/l. More than 200-fold higher concentrations were needed for the inhibition of other cytochrome P-450 enzymes. In vivo the compound was active in rats (ED₅₀ = 0.035 mg/kg) and dogs (1 mg/kg gave 70% inhibition) after oral administration. It can be concluded that Org 33201 is a potent and highly selective orally active aromatase inhibitor.     

Contrasting levels of β-diversity and underlying phylogenetic trends indicate different paths to chemical diversity in highland and lowland willow species

Diverse specialised metabolites contributed to the success of vascular plants in colonising most terrestrial habitats. Understanding how distinct aspects of chemical diversity arise through heterogeneous environmental pressures can help us understand the effects of abiotic and biotic stress on plant evolution and community assembly. We examined highland and lowland willow species within a phylogenetic framework to test for trends in their chemical α-diversity (richness) and β-diversity (variation among species sympatric in elevation). We show that differences in chemistry among willows growing at different elevations occur mainly through shifts in chemical β-diversity and due to convergence or divergence among species sharing their elevation level. We also detect contrasting phylogenetic trends in concentration and α-diversity of metabolites in highland and lowland willow species. The resulting elevational patterns contribute to the chemical diversity of willows and suggest that variable selective pressure across ecological gradients may, more generally, underpin complex changes in plant chemistry.     

Phospholipid transfer protein is present in human tear fluid

The human tear fluid film consists of a superficial lipid layer, an aqueous middle layer, and a hydrated mucin layer located next to the corneal epithelium. The superficial lipid layer protects the eye from drying and is composed of polar and neutral lipids provided by the meibomian glands. Excess accumulation of lipids in the tear film may lead to drying of the corneal epithelium. In the circulation, phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) mediate lipid transfers. To gain insight into the formation of tear film, we investigated whether PLTP and CETP are present in human tear fluid. Tear fluid samples were collected with microcapillaries. The presence of PLTP and CETP was studied in tear fluid by Western blotting, and the PLTP concentration was determined by ELISA. The activities of the enzymes were determined by specific lipid transfer assays. Size-exclusion and heparin-affinity chromatography assessed the molecular form of PLTP. PLTP is present in tear fluid, whereas CETP is not. Quantitative assessment of PLTP by ELISA indicated that the PLTP concentration in tear fluid, 10.9 +/- 2.4 microg/mL, is about 2-fold higher than that in human plasma. PLTP-facilitated phospholipid transfer activity in tears, 15.1 +/- 1.8 micromol mL(-)(1) h(-)(1), was also significantly higher than that measured in plasma. Inactivation of PLTP by heat treatment (+58 degrees C, 60 min) or immunoinhibition abolished the phospholipid transfer activity in tear fluid. Size-exclusion chromatography of tear fluid indicated that PLTP eluted in a position corresponding to a size of 160-170 kDa. Tear fluid PLTP was quantitatively bound to Heparin-Sepharose and could be eluted as a single peak by 0.5 M NaCl. These data indicate that human tear fluid contains catalytically active PLTP protein, which resembles the active form of PLTP present in plasma. The results suggest that PLTP may play a role in the formation of the tear film by supporting phospholipid transfer.     

Why current UK legislation on embryo research is immoral. How the argument from lack of qualities and the argument from potentiality have been applied and why they should be rejected

On 22 January 2001, the UK became the first country to approve of embryonic stem cell research by passing the Human Fertilisation (Research Purposes) Regulations 2001, which legislated new research purposes for which early embryos can be used, in addition to those approved by the Human Fertilisation and Embryology Act 1990. Legal advisory committees, most notably the Chief Medical Officer's Expert Group and the House of Lords' Select Committee, have offered various reasons, which can also be found in the ethics literature, to justify this change. Those examined here are the views that: 1. Early embryos lack relevant qualities (or 'the argument from lack of qualities') and 2. Early embryos only have a potentiality to become humans with moral status (or 'the argument from potentiality'). The validity of these arguments is questioned and a case is made for egalitarian speciesism. Embryos have moral status (used here in the restricted sense of the status possessed by all members of the class of beings which deserve the greatest moral significance in equal measure). They have more value than the value that should be assigned to non-human beings from the start of fertilisation. Current UK legislation on embryo research is immoral.