Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 1: eradication of Helicobacter in the cachexia of idiopathic parkinsonism

BACKGROUND: Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate. AIM: To consider the candidature of Helicobacter in parkinsonism with cachexia. METHODS: We explore the relationship between being underweight and inflammatory products in 124 subjects with idiopathic parkinsonism and 195 controls, and present the first case-series evidence of efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of cachexia. RESULTS: Association of a low body mass index with circulating interleukin-6 was specific to parkinsonism (p = .002), unlike that with antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated gene product (p < .04). Marked reversibility in both cachexia and disability of idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case, Helicobacter pylori eradication in another, follow-up being > or = 3.5 years. The latter presented with postprandial bloating, and persistent nausea: following eradication, radioisotope gastric-emptying returned towards normal, and upper abdominal symptoms regressed. Reversibility of their cachexia/disability contrasts with the outcome of anti-Helicobacter therapy where eradication repeatedly failed (one case), and in non-Helicobacter gastritis (three cases). Anti-parkinsonian medication remained constant. Intestinal absorption and barrier function were normal in all. CONCLUSION: Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism.     

Metabolic Changes in Cerebral Cortex, Hippocampus, and Cerebellum During Sustained Bicuculline-Induced Seizures

Abstract— The objective of the present experiments was to study metabolic correlates to the localization of neuronal lesions during sustained seizures. To that end, status epilepticus was induced by i.v. administration of bicuculline in immobilized and artificially ventilated rats, since this model is known to cause neuronal cell damage in cerebral cortex and hippocampus but not in the cerebellum. After 20 or 120 min of continuous seizure activity, brain tissue was frozen in situ through the skull bone, and samples of cerebral cortex, hippocampus, and cerebellum were collected for analysis of glycolytic metabolites, phosphocreatine (PCr), ATP, ADP, AMP, and cyclic nucleotides. After 20 min of seizure activity, the two “vulnerable” structures (cerebral cortex and hippocampus) and the “resistant” one (cerebellum) showed similar changes in cerebral metabolic state, characterized by decreased tissue concentrations of PCr, ATP, and glycogen, and increased lactate concentrations and lactate/ pyruvate ratios. In all structures, though, the adenylate energy charge remained close to control. At the end of a 2-h period of status epilepticus, a clear deterioration of the energy state was observed in the cerebral cortex and the hippocampus, but not in the cerebellum. The reduction in adenylate energy charge in the cortex and hippocampus was associated with a seemingly paradoxical decrease in tissue lactate levels and with failure of glycogen resynthesis (cerebral cortex). Experiments with infusion of glucose during the second hour of a 2-h period of status epilepticus verified that the deterioration of tissue energy state was partly due to reduced substrate supply; however, even in animals with adequate tissue glucose concentrations, the energy charge of the two structures was significantly lowered. The cyclic nucleotides (cAMP and cGMP) behaved differently. Thus, whereas cAMP concentrations were either close to control (hippocampus and cerebellum) or moderately increased (cerebral cortex), the cGMP concentrations remained markedly elevated throughout the seizure period, the largest change being observed in the cerebellum. It is concluded that although the localization of neuronal damage and perturbation of cerebral energy state seem to correlate, the results cannot be taken as. evidence that cellular energy failure is the cause of the damage. Thus, it appears equally probable that the pathologically enhanced neuronal activity (and metabolic rate) underlies both the cell damage and the perturbed metabolic state. The observed changes in cyclic nucleotides do not appear to bear a causal relationship to the mechanisms of damage.     

Lack of Adjustment Latitude at Work as a Trigger of Taking Sick Leave—A Swedish Case-Crossover Study

Objectives

Research has shown that individuals reporting a low level of adjustment latitude, defined as having few possibilities to temporarily adjust work demands to illness, have a higher risk of sick leave. To what extent lack of adjustment latitude influences the individual when making the decision to take sick leave is unknown. We hypothesize that ill individuals are more likely to take sick leave on days when they experience a lack of adjustment latitude at work than on days with access to adjustment latitude.

Methods

A case-crossover design was applied to 546 sick-leave spells, extracted from a cohort of 1 430 employees at six Swedish workplaces, with a 3–12 month follow-up of all new sick-leave spells. Exposure to lack of adjustment latitude on the first sick-leave day was compared with exposure during several types of control periods sampled from the previous two months for the same individual.

Results

Only 35% of the respondents reported variations in access to adjustment latitude, and 19% reported a constant lack of adjustment latitude during the two weeks prior to the sick-leave spell. Among those that did report variation, the risk of sick leave was lower on days with lack of adjustment latitude, than on days with access (Odds Ratio 0.36, 95% Confidence Interval 0.25–0.52).

Conclusions

This is the first study to show the influence of adjustment latitude on the decision to take sick leave. Among those with variations in exposure, lack of adjustment latitude was a deterrent of sick leave, which is contrary to the à priori hypothesis. These results indicate that adjustment latitude may not only capture long-lasting effects of a flexible working environment, but also temporary possibilities to adjust work to being absent. Further studies are needed to disentangle the causal mechanisms of adjustment latitude on sick-leave.     

Lycodes adolfi Nielsen and Foss?, 1993 (Teleostei: Zoarcidae) found in the Arctic Ocean

Adolf’s eelpout, Lycodes adolfi, was found at five bottom trawl stations in 2007–2009, on the slope towards the Sofia Deep north of Spitsbergen, at depths of 970–1,220 m and water temperatures below 0°C. Previously, the species has been known from cold and deep waters south of 74°N to both sides of Greenland and in the Norwegian Sea. The present material represents the first records from the Arctic Ocean and may indicate a wider arctic distribution of this species.     

Analysing the outer membrane subproteome of Methylococcus capsulatus (Bath) using proteomics and novel biocomputing tools

High-resolution two-dimensional gel electrophoresis and mass spectrometry has been used to identify the outer membrane (OM) subproteome of the Gram-negative bacterium Methylococcus capsulatus (Bath). Twenty-eight unique polypeptide sequences were identified from protein samples enriched in OMs. Only six of these polypeptides had previously been identified. The predictions from novel bioinformatic methods predicting β-barrel outer membrane proteins (OMPs) and OM lipoproteins were compared to proteins identified experimentally. BOMP () predicted 43 β-barrel OMPs (1.45%) from the 2,959 annotated open reading frames. This was a lower percentage than predicted from other Gram-negative proteomes (1.8–3%). More than half of the predicted BOMPs in M. capsulatus were annotated as (conserved) hypothetical proteins with significant similarity to very few sequences in Swiss-Prot or TrEMBL. The experimental data and the computer predictions indicated that the protein composition of the M. capsulatus OM subproteome was different from that of other Gram-negative bacteria studied in a similar manner. A new program, Lipo, was developed that can analyse entire predicted proteomes and give a list of recognised lipoproteins categorised according to their lipo-box similarity to known Gram-negative lipoproteins (). This report is the first using a proteomics and bioinformatics approach to identify the OM subproteome of an obligate methanotroph.     

A five-year prospective study of fatigue in primary Sjögren's syndrome

Introduction  

Fatigue is prevalent in primary Sj?gren's syndrome (pSS), and contributes to the considerably reduced health related quality of life in this disease. The symptom is included in proposed disease activity and outcome measures for pSS. Several studies indicate that there is an inflammatory component of fatigue in pSS and other chronic inflammatory rheumatic diseases. The purpose of this study was to investigate fatigue change in pSS in a longitudinal study, and explore whether any clinical or laboratory variables at baseline, including serum cytokines, were associated with a change in fatigue scores over time.     

Specific SCAR markers and multiplex real-time PCR for quantification of two <Emphasis Type="Italic">Trichoderma</Emphasis> biocontrol strains in environmental samples

Several strains from the genus Trichoderma (Ascomycetes, Hypocreales) are commercially used as biocontrol agents, e.g. in formulations containing the two Trichoderma strains IMI206039 (Hypocrea parapilulifera B.S. Lu, Druzhinina & Samuels) and IMI206040 (T. atroviride P. Karst). To quantify the presence of the two isolates after application, we developed primers for SCAR markers (Sequence-Characterised Amplified Region). In order to quantify both fungal strains simultaneously, we also designed fluorophore-labelled probes distinguishing the two strains, to be used in combination with the SCAR primers. In incubations of two different soils, artificially inoculated and maintained under controlled conditions, the quantification through amplification with the SCAR markers in qPCR and through colony-forming units from plate counting correlated well. Further tests of the markers on samples taken from a golf green treated with a product containing both strains indicated that the two biocontrol strains did not establish, either on the golf green or in the surrounding area.     

Influence of dolomitic lime on DOC and DON leaching in a forest soil

The influence of liming on leaching and distribution of dissolved organic carbon (DOC) and nitrogen (DON) in mineral soil was investigated in a leaching experiment with soil columns. Soil samples from separate horizons (O, A and B horizons) were collected from control and limed plots in a field liming experiment in a spruce forest in southern Sweden. The field liming (0.88 kg m^-2) had been carried out 8 years before sampling. To minimize the variation among replicates, soil profiles were reconstructed in the laboratory so that the dry weight was the same for each individual soil horizon regardless of treatment. Two soil column types were used with either the O+A horizons or the O+A+B horizons. One Norway spruce seedling (Picea abies (L.) Karst) was planted in each soil column. Average pH in the leachate water was greater in the limed treatment than in the control treatment (5.0 versus 4.0 for O+A columns and 4.3 versus 3.8 for O+A+B columns). After reaching an approximate steady state, the leaching of DOC was 3--4 times greater from the limed O+A and O+A+B columns than from the corresponding control columns but the leaching of DON increased (3.5 times) only in the limed O+A columns. There was a significant correlation between DOC and DON in the leachates from all columns except for the control O+A+B columns, which indicated a decoupling of DOC and DON retention in the B horizon in the control treatment. This might be explained by a selective adsorption of nitrogen poor hydrophobic compounds (C/N ratio: 32--77) while there was a lower retention of nitrogen rich hydrophilic compounds (C/N ratio: 14--20). Proportionally more hydrophobic compounds were leached from the limed soil compared to the unlimed soil. These hydrophobic compounds also became more enriched in nitrogen after liming so in the limed treatment nitrogen might be adsorbed at nearly the same proportion as carbon, which might explain the fact that there was no decoupling of leached DOC and DON from the B horizon after liming.