[The syndrome of inappropriate diuretic hormone secretion (SIADH) ending lethal during the use of paliperidon and lamotrigine]. / Het syndroom van inadequate secretie van het antidiuretisch hormoon (SIADH) met letale afloop tijdens gebruik van paliperidon en lamotrigine.

Hyponatremia, as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), is well known with the use of nearly all antipsychotics and mood stabilizers. The first symptoms are atypical and are not always mentioned by the patient. However, not recognising the syndrome in due time can be lethal. We describe a 35-year-old woman who died due to lack of recognition of SIADH. The patient, who had a bipolar disorder and was for a long time on a paliperidone depot, developed complaints of nausea, vomiting and thirst after lamotrigine was prescribed. A few days after increasing the dose, she died; no evidence was found of suicide. The SIADH was probably triggered by the use of lamotrigine and paliperidone. Paying sufficient attention to the symptoms that may cause this syndrome, as well as their early recognition, could save lives.

[Pimavanserin: a new treatment for the Parkinson's disease psychosis]. / Pimavanserine: een nieuwe behandeling voor psychose bij de ziekte van Parkinson.

BACKGROUND: Clozapine is an effective drug for treating psychosis in Parkinson's disease (PDP) and is registered as such in the Netherlands. However, clozapine can have adverse effects, including agranulocytosis. The new drug pimavanserin was recently registered in the United States for the treatment of PDP.
AIM: To review the literature on pimavanserin and discuss the position it currently occupies in the Netherlands as a potential treatment for PDP.
METHOD: Systematic search of the literature.
RESULTS: We found reports on four randomised controlled trials (RCTs), one review and six articles about the pharmacokinetics and pharmacodynamics of pimavanserin. Pimavanserin is an effective treatment for PDP, and, like clozapine, it has very few negative effects on motor skills. However, all of the RCTs were funded by the manufacturer of pimavanserin and the trials were conducted in a very selective patient population. This means that results cannot be generalised. Long-term results are not yet available. In earlier trials clozapine was shown to have a greater and faster antipsychotic effect. Many clinicians and psychiatrists have a great deal of experience with this drug. Another important point is that no-one has yet conducted a trial comparing clozapine and pimavanserin.
CONCLUSION: Given that the current second drug of choice, namely quetiapine, has not been found to be effective for PDP, we are of the opinion that - if pimavanserin is registered in the Netherlands - pimavanserin could be used when the current drug of choice, clozapine, is not completely effective or is poorly tolerated. For patients who have cognitive impairments in addition to psychosis, we advise testing the patient's reaction to a cholinesterase inhibitor before starting the patient on a course of antipsychotics.

Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity.

In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function.

The fate of glycerol entering the rumen of dairy cows and sheep.

This study investigated the fate of glycerol entering the rumen, in particular whether glycerol could be absorbed across the rumen epithelium. Three non-lactating rumen-fistulated cows were used to calculate the overall disappearance rate of glycerol in vivo and evaluate the rate of ruminal glycerol absorption. Rumen epithelial tissues isolated from sheep were used to characterise glycerol transport properties. The rate of rumen microbial degradation of glycerol was then studied in an in vitro system under anaerobic and thermo-regulated conditions. The results showed that glycerol can be absorbed from the rumen in significant amounts. The fractional rate of absorption of glycerol was not affected by variations in glycerol concentration in the buffer solution in the in vivo study. The glycerol absorption apparently occurred largely by passive diffusion and was probably not facilitated by carriers. Glycerol also disappeared via microbial digestion and outflow from the rumen through the omasal orifice.

Effects of age and zinc supplementation on transport properties in the jejunum of piglets.

Zinc is effective in the prevention and treatment of post-weaning diarrhoea and in promoting piglet growth. Its effects on the absorption of nutrients and the secretory capacity of the intestinal epithelium are controversial. We investigated the effects of age, dietary pharmacological zinc supplementation and acute zinc exposure in vitro on small-intestinal transport properties of weaned piglets. We further examined whether the effect of zinc on secretory responses depended on the pathway by which chloride secretion is activated. A total of 96 piglets were weaned at 26 days of age and allocated to diets containing three different levels of zinc oxide (50, 150 and 2500 ppm). At the age of 32, 39, 46 and 53 days, piglets were killed, and isolated epithelia from the mid-jejunum were used for intestinal transport studies in conventional Ussing chambers, with 23 µm ZnSO4 being added to the serosal side for testing acute effects. Absorptive transport was stimulated by mucosal addition of d-glucose or l-glutamine. Secretion was activated by serosal addition of prostaglandin E2 , carbachol or by mucosal application of Escherichia coli heat-stable enterotoxin (Stp ). Jejunal transport properties showed significant age-dependent alterations (p < 0.03). Both absorptive and secretory responses were highest in the youngest piglets (32 d). The dietary zinc supplementation had no significant influence on jejunal absorptive and secretory responses. However, the pre-treatment of epithelia with ZnSO4 in vitro led to a small but significant decrease in both absorptive and secretory capacities (p < 0.05), with an exception for carbachol (p = 0.07). The results showed that, in piglets, chronic supplementation with zinc did not sustainably influence the jejunal transport properties in the post-weaning phase. Because transport properties are influenced by the addition of zinc in vitro, we suggest that possible epithelial effects of zinc depend on the acute presence of this ion.

Paludiculture can support biodiversity conservation in rewetted fen peatlands.

Paludiculture, the productive use of wet or rewetted peatlands, offers an option for continued land use by farmers after rewetting formerly drained peatlands, while reducing the greenhouse gas emissions from peat soils. Biodiversity conservation may benefit, but research on how biodiversity responds to paludiculture is scarce. We conducted a multi-taxon study investigating vegetation, breeding bird and arthropod diversity at six rewetted fen sites dominated by Carex or Typha species. Sites were either unharvested, low- or high-intensity managed, and were located in Mecklenburg-Vorpommern in northeastern Germany. Biodiversity was estimated across the range of Hill numbers using the iNEXT package, and species were checked for Red List status. Here we show that paludiculture sites can provide biodiversity value even while not reflecting historic fen conditions; managed sites had high plant diversity, as well as Red Listed arthropods and breeding birds. Our study demonstrates that paludiculture has the potential to provide valuable habitat for species even while productive management of the land continues.

Receptor for advanced glycation end products (RAGE) polymorphisms are associated with systemic lupus erythematosus and disease severity in lupus nephritis.

OBJECTIVE: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. METHODS: For this cross-sectional study DNA samples of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four RAGE polymorphisms: -429 T/C, -374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. RESULTS: The C allele of -429 T/C, the T allele of -374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE -429 T/C, the A allele of -374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. CONCLUSION: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN.

Caprine CSN1S1 haplotype effect on gene expression and milk composition measured by Fourier transform infrared spectroscopy.

The Norwegian dairy goat population has a high frequency of a CSN1S1 (alphaS1-casein) haplotype with negative effects on protein and fat content. It is characterized by a single point deletion in exon 12 of CSN1S1, leading to a truncated protein and hence a low content of alphaS1-casein in the milk. This haplotype together with another haplotype with a deletion in exon 9 are called "weak" haplotypes. "Strong" haplotypes, on the other hand, have positive effects on important milk production traits. We show that expression of CSN1S1 in the mammary gland of lactating goats is significantly lower in animals with 2 weak haplotypes. Moreover, the effects of defective alleles were not detected in animals having 1 strong and 1 weak haplotype. Expression levels of other genes in the casein cluster were not affected by the CSN1S1 haplotypes investigated. Milk samples from goats with 2 weak haplotypes could be distinguished from the other milk samples using Fourier transform infrared (FTIR) spectroscopy and partial least squares discriminant analysis (PLS-DA). The PLS-DA components were related to spectra of pure caseins and whey proteins, hence FTIR has a potential for identifying milk samples with low alphaS1-casein content and different protein composition. The results indicate that FTIR-based measurements can be incorporated into breeding plans, or for selection of milk samples with high casein content, which in turn may improve cheese-making properties of the milk.

[Rheumatoid arthritis: more than a joint disease]. / Reumatoïde artritis: meer dan een gewrichtsziekte.

Rheumatoid arthritis (RA), one of the most common autoimmune disorders, mostly manifests itself as polyarthritis. However, extra-articular organ manifestations can also occur, even though their incidence has decreased substantially due to effective treatment with disease-modifying anti-rheumatic drugs. In this article we describe three patient cases of extra-articular manifestations in RA in the absence of prominent arthritis. The diversity of symptoms in RA can be of interest to different medical specialties who will occasionally encounter them in daily practice.