Application of a novel reference material in an international round robin test on material emissions testing.

Emission testing of products is currently a rapidly increasing field of measurement activity. Labeling procedures for construction products are based on such emission test chamber measurements, and hence, measurement performance should be verified. One possible route is to conduct testing of one material in different laboratories within a round robin test (RRT), ideally using homogeneous reference materials, which can be used within interlaboratory studies or as part of the quality management system to ensure comparable results. The applicability of a lacquer system with nine added VOCs (hexanal, styrene, n-decane, limonene, 2-ethyl-1-hexanol, N-methyl-α-pyrrolidone, 2-ethylhexyl acrylate, dimethyl phthalate, and n-hexadecane) was evaluated in an international RRT with 55 participating laboratories. An intralaboratory quality check confirmed the homogeneity and reproducibility of the lacquer material for most of the compounds (RSD 5%-6%), which was confirmed in the RRT. However, emissions varied for the polar compound N-methyl-α-pyrrolidone and the higher boiling compounds 1,2-dimethyl phthalate, and n-hexadecane which could be traced back to analytical issues. In the RRT, the interlaboratory relative standard deviations (RSDs) ranged from 30% to 65% for all participants but for reference laboratories the range was between 20% and 45%.

Chronic maternal inflammation or high-fat-feeding programs offspring obesity in a sex-dependent manner.

BACKGROUND/OBJECTIVES: The current world-wide obesity epidemic partially results from a vicious circle whereby maternal obesity during pregnancy predisposes the offspring for accelerated weight gain and development of metabolic syndrome. Here we investigate whether low-grade inflammation, characteristic of the obese state, provides a causal role for this disastrous fetal programming in mice. METHODS: We exposed pregnant and lactating C57BL/6JBom female mice to either high-fat diet (HFD), or continuous infusion of lipopolysaccharide (LPS), a potent trigger of innate immunity, and studied offspring phenotypes. RESULTS: Both maternal LPS or HFD treatments rendered the offspring hyperphagic and inept of coping with a HFD challenge during adulthood, increasing their adiposity and weight gain. The metabolic effects were more pronounced in female offspring, while exposed male offspring mounted a larger inflammatory response to HFD at adulthood. CONCLUSIONS: This supports our hypothesis and highlights the programming potential of inflammation in obese pregnancies.

Is oral absorption of vigabatrin carrier-mediated?

The aim of the study was to investigate the intestinal transport mechanisms responsible for vigabatrin absorption in rats by developing a population pharmacokinetic (PK) model of vigabatrin oral absorption. The PK model was used to investigate whether vigabatrin absorption was carrier-mediated and if the proton-coupled amino acid transporter 1 (PAT1) was involved in the absorption processes. Vigabatrin (0.3-300mg/kg) was administered orally or intravenously to Sprague Dawley rats in the absence or presence of PAT1-ligands l-proline, l-tryptophan or sarcosine. The PK profiles of vigabatrin were described by mechanistic non-linear mixed effects modelling, evaluating PAT1-ligands as covariates on the PK parameters with a full covariate modelling approach. The oral absorption of vigabatrin was adequately described by a Michaelis-Menten type saturable absorption. Using a Michaelis constant of 32.8mM, the model estimated a maximal oral absorption rate (Vmax) of 64.6mmol/min and dose-dependent bioavailability with a maximum of 60.9%. Bioavailability was 58.5-60.8% at 0.3-30mg/kg doses, but decreased to 46.8% at 300mg/kg. Changes in oral vigabatrin PK after co-administration with PAT1-ligands was explained by significant increases in the apparent Michaelis constant. Based on the mechanistic model, a high capacity low affinity carrier is proposed to be involved in intestinal vigabatrin absorption. PAT1-ligands increased the Michaelis constant of vigabatrin after oral co-administration indicating that this carrier could be PAT1.

Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia.

G-protein-coupled receptor 41 (GPR41) also called free fatty acid receptor 3 (FFAR3) is a Gαi-coupled receptor activated by short-chain fatty acids (SCFAs) mainly produced from dietary complex carbohydrate fibers in the large intestine as products of fermentation by microbiota. FFAR3 is expressed in enteroendocrine cells, but has recently also been shown to be present in sympathetic neurons of the superior cervical ganglion. The aim of this study was to investigate whether the FFAR3 is present in other autonomic and sensory ganglia possibly influencing gut physiology. Cryostat sections were cut of autonomic and sensory ganglia of a transgenic reporter mouse expressing the monomeric red fluorescent protein (mRFP) gene under the control of the FFAR3 promoter. Control for specific expression was also done by immunohistochemistry with an antibody against the reporter protein. mRFP expression was as expected found not only in neurons of the superior cervical ganglion, but also in sympathetic ganglia of the thoracic and lumbar sympathetic trunk. Further, neurons in prevertebral ganglia expressed the mRFP reporter. FFAR3-mRFP-expressing neurons were also present in both autonomic and sensory ganglia such as the vagal ganglion, the spinal dorsal root ganglion and the trigeminal ganglion. No expression was observed in the brain or spinal cord. By use of radioactive-labeled antisense DNA probes, mRNA encoding the FFAR3 was found to be present in cells of the same ganglia. Further, the expression of the FFAR3 in the ganglia of the transgenic mice was confirmed by immunohistochemistry using an antibody directed against the receptor protein, and double labeling colocalized mRFP and the FFAR3-protein in the same neurons. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) on extracts from the ganglia supported the presence mRNA encoding the FFAR3 in most of the investigated tissues. These data indicate that FFAR3 is expressed on postganglionic sympathetic and sensory neurons in both the autonomic and somatic peripheral nervous system and that SCFAs act not only through the enteroendocrine system but also directly by modifying physiological reflexes integrating the peripheral nervous system and the gastro-intestinal tract.

Carotid-cavernous fistula. Demonstration of asymptomatic vascular "steal".

Abnormal distribution of cerebral vascular flow was studied in a patient who had a traumatic carotid-cavernous sinus fistula. Serial studies were performed using a method for determining relative cerebral vascular flow:99mtechnetium-diethylenetriamine pentaacetic acid (99mTc-DTPA) was injected intravenously and flow data were processed by a digital computer. Serial studies documented the occurrence of a vascular "steal" during temporary carotid occlusion; postoperative studies showed disappearance of the steal and obliteration of thiling arterial structures and capillary filling in the brain, and in demonstrating alteration in the cerebral circulation.

Primary aorto-enteric fistula: a practicable curable condition? Pathogenetic and clinical aspects.

Primary aorto-enteric fistulas is now being a rare occurrence because of an aggressive approach in terms of surgery of abdominal aortic aneurysms. Three cases is presented in an attempt to elucidate the ethiology, pathogenesis and diagnostic possibilities when dealing with primary aorto-enteric fistulas. The clinical presentation of the patients with primary aorto-enteric fistulas is inconstant, but a hightened index of suspicion should be present when a patient presents with gastrointestinal bleeding of obscure origin, abdominal or back pain and an abdominal mass. Endoscopy and diagnostic imaging may detect a fistula, but a high rate of false negative investigations are produced. The result of diagnostic workup is often laparotomy, which is the safest diagnostic method and may save the patients life.

Sertraline inhibits the transport of PAT1 substrates in vivo and in vitro.

BACKGROUND AND PURPOSE: Intestinal nutrient transporters may mediate the uptake of drugs. The aim of this study was to investigate whether sertraline interacts with the intestinal proton-coupled amino acid transporter 1 PAT1 (SLC36A1). EXPERIMENTAL APPROACH: In vitro investigations of interactions between sertraline and human (h)PAT1, hSGLT1 (sodium-glucose linked transporter 1) and hPepT1 (proton-coupled di-/tri-peptide transporter 1) were conducted in Caco-2 cells using radiolabelled substrates. In vivo pharmacokinetic investigations were conducted in male Sprague-Dawley rats using gaboxadol (10 mg·kg(-1), p.o.) as a PAT1 substrate and sertraline (0-30.6 mg·kg(-1)). Gaboxadol was quantified by hydrophilic interaction chromatography followed by MS/MS detection. KEY RESULTS: Sertraline inhibited hPAT1-mediated L-[(3)H]-Pro uptake in Caco-2 cells. This interaction between sertraline and PAT1 appeared to be non-competitive. The uptake of the hSGLT1 substrate [(14)C]-α-methyl-D-glycopyranoside and the hPepT1 substrate [(14)C]-Gly-Sar in Caco-2 cells was also decreased in the presence of 0.3 mM sertraline. In rats, the administration of sertraline (0.1-10 mM, corresponding to 0.3-30.6 mg·kg(-1), p.o.) significantly reduced the maximal gaboxadol plasma concentration and AUC after its administration p.o. CONCLUSIONS AND IMPLICATIONS: Sertraline is an apparent non-competitive inhibitor of hPAT1-mediated transport in vitro. This inhibitory effect of sertraline is not specific to hPAT1 as substrate transport via hPepT1 and hSGLT1 was also reduced in the presence of sertraline. In vivo, sertraline reduced the amount of gaboxadol absorbed, suggesting that the inhibitory effect of sertraline on PAT1 occurs both in vitro and in vivo. Hence, sertraline could alter the bioavailability of drugs absorbed via PAT1.

Electrical stimulation of sacral dermatomes in multiple sclerosis patients with neurogenic detrusor overactivity.

AIMS: Transcutaneous electrical stimulation of the dorsal penile/clitoral nerve (DPN) has been shown to suppress detrusor contractions in patients with neurogenic detrusor overactivity (NDO). However, the long-term use of surface electrodes in the genital region may not be well tolerated and may introduce hygienic challenges. The aim of this study was to assess whether electrical stimulation of the sacral dermatomes could suppress detrusor contractions in multiple sclerosis (MS) patients with NDO, hereby providing an alternative to DPN stimulation. MATERIALS AND METHODS: A total of 14 MS patients (8 M, 6 F) with low bladder capacity (<300 ml) and a recent urodynamic study showing detrusor overactivity incontinence participated in the study. Three successive slow fill cystometries (16 ml/min) were carried out in each patient. The first filling served as control filling where no stimulation was applied. In the second and third filling electrical stimulation of either the DPN or sacral dermatomes was applied automatically whenever the detrusor pressure exceeded 10 cmH2O. RESULTS: The control filling showed detrusor overactivity in 12 of the 14 patients. In 10 of the 12 patients one or more detrusor contractions could be suppressed with DPN stimulation. Electrical stimulation of the sacral dermatomes failed to suppress detrusor contractions in all patients. CONCLUSIONS: Although therapeutic effects may be present from stimulation of the sacral dermatomes, we were unable to demonstrate any acute effects during urodynamics. For this reason stimulation of the sacral dermatomes is not an option in a system that relies on the acute suppression of a detrusor contraction.

Treatment of neurogenic detrusor overactivity in spinal cord injured patients by conditional electrical stimulation.

PURPOSE: The feasibility of automatic event driven electrical stimulation of the dorsal penile/clitoral nerve in the treatment of neurogenic detrusor overactivity (NDO) was evaluated in individuals with spinal cord injury. MATERIALS AND METHODS: The study included 2 women and 14 men older than 18 years with NDO, bladder capacity below 500 ml and complete or incomplete suprasacral spinal cord injury. Detrusor pressure (Pdet) was recorded during ordinary, natural bladder filling. In a similar subsequent recording Pdet was used to trigger electrical stimulation when pressure exceeded 10 cm H2O. RESULTS: Of the 16 patients enrolled in this study 13 had increased bladder capacity together with a storage pressure decrease as a result of automatic, event driven electrical stimulation. In 2 patients stimulation could not inhibit the first undesired contraction, leakage occurred and finally 1 could not tolerate stimulation. During stimulated filling Pdet never exceeded 55 cm H2O. Thus, storage pressure was sufficiently low to prevent kidney damage. An average bladder capacity increase of 53% was achieved. CONCLUSIONS: This study demonstrates the feasibility of automatic, event driven electrical stimulation in the treatment of NDO. Although the setup in this experiment is not suitable in a clinical setting, the treatment modality is promising and it warrants further investigation.

Isolated necrotizing panarteritis of the gallbladder. Case report.

Two cases of isolated gallbladder involvement by necrotizing panarteritis histologically resembling classic polyarteritis nodosa are reported and the literature is reviewed. No reports suggest that isolated gallbladder involvement may evolve to systemic ('classic') polyarteritis nodosa. Finding of necrotizing panarteritis in the gallbladder without clinical evidence of systemic/multiorgan disease does not warrant extensive investigations.

Achilles tendon rupture in badminton.

The typical badminton player with an Achilles tendon rupture is 36 years old and, despite limbering up, is injured at the rear line in a sudden forward movement. He resumes work within three months and has a slight lack of dorsiflexion in the ankle as the main complication. Most patients resume badminton within one year, but some finish their sports career, mainly due to fear of a new injury. The investigation discusses predisposing factors and prophylactic measures.

Rapid growth and early rupture of a primary mycotic aneurysm of the abdominal aorta.

A case of a primary mycotic aneurysm of the abdominal aorta due to infection with Staphylococcus aureus is presented. The outcome was fatal because of rupture into the jejunum.

Prophylactic single-dose fosfomycin and metronidazole compared with neomycin, bacitracin, metronidazole and ampicillin in elective colorectal operations.

Two antibiotic regimens for the prophylaxis of infection after colorectal operations were compared in a prospective, double blind, randomised controlled trial in 244 patients. Ninety-five patients (39%) were either excluded before randomisation or withdrawn, leaving 149 for analysis. Group 1 (n = 72) received a single infusion of 8 g fosfomycin and 1 g metronidazole at the induction of anaesthesia. Group 2 (n = 77) received bacitracin 250 mg plus neomycin 250 mg (as four tablets on three occasions over two days), metronidazole 500 mg tablets three times a day for one day, and ampicillin 1 g intravenously at induction of anaesthesia. Nine patients in group 1 (13%), 95% confidence interval (CI) 6.9 to 22.4, developed infective complications, compared with 8 in group 2 (10%), 95% CI 4.6 to 19.4. The overall infection rate was 17 of 149 evaluable patients (11%), 95% CI 6.8 to 17.7. Seven patients died (five in group 1 and 2 in group 2), two of whom (one in each group) died as a direct result of infective complications. Long operations and obesity were the most important risk factors, and may indicate a need for longer prophylaxis. Fosfomycin, which is mainly active against aerobic bacteria, was both safe and useful when combined with metronidazole.

Technique for multi-view radionuclide angiography.

A new method utilizing computer subtraction allows 2 separate radionuclide angiograms to be performed during a single laboratory visit. Two separate intravenous injections of the radionuclide are given so that the patient's head can be imaged in 2 different projections. Background activity from the first injection is subtracted by the computer to allow good resolution of blood flow following the second injection. A static brain scan is performed after the second injection. Although single-view radionuclide angiography is widely used in the diagnostic evaluation of the brain, the addition of a second projection provides additonal important diagnostic information. The views obtained, however, must be determined individually for each patient on the basis of the clinical history and neurologic signs. The selection of appropriate views, the diagnostic quality of the studies, and the practical clinical application of this technique are illustrated by 2 case reports.