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Sulfasalazine is a drug that is chemically related to aspirin and used in the treatment of ulcerative colitis. Oral sulfasalazine is broken down into two metabolites in the lower digestive tract. Of these, 5-aminosalicylic acid (5-ASA) is the therapeutically active product. Since the discovery that 5-ASA (which by itself is not orally active) is the active molecule, a variety of drug delivery strategies have been developed to chemically link 5-ASA with other molecules, and coated capsules and slow-release formulations have been designed to get the 5-ASA into the large intestine where it acts on the luminal side of the colon (inside the digestive tract). Intestinal absorption of 5-ASA occurs, but increased blood levels of the drug do not confer any additional therapeutic benefit and may, in fact, be toxic to the kidney. Fourteen patients with ulcerative colitis in remission took part in a study to evaluate the ability of several different formulations of 5-ASA-containing preparations to increase colonic concentrations of the drug. Each subject received a novel formulation (olsalazine; disodium azodisalicylate), both as coated tablets and gel capsules, and three other commercially available mesalazine formulations (Asacol, Pentasa, or Salofalk). Colonic and blood levels, as well as urinary excretion, of 5-ASA were determined after five days of each treatment. Olsalazine treatment doubled the colonic concentration of 5-ASA compared with Pentasa and Salofalk but not with Asacol; blood levels and urinary excretion of 5-ASA were decreased compared with the mesalazines. This indicates that olsalazine is one of the best vehicles for delivering 5-ASA to its site of action, while reducing the systemic concentrations of the drug that may be harmful to the kidney. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background and purpose: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. Methods: A total of 21 patients with polysomnography‐confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11C‐donepezil PET) and nigrostriatal dopaminergic function (18F‐DOPA PET). Clinical examination included the Movement Disorder Society–Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. Results: The 11C‐donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11C‐donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. Conclusion: Reduced neocortical 11C‐donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients. [ABSTRACT FROM AUTHOR]

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The costs and medical benefits of an early, routine laxative screening test in patients with diarrhoea of uncertain origin was evaluated. During a two year period 200 consecutive, unselected patients complaining of diarrhoea were considered for the study in whom a three day faecal collection was undertaken. Fifty four patients denying laxative consumption had diarrhoea (mean daily stool weight greater than 200 g) of uncertain origin at their initial visit of whom 47 were screened to detect ingestion of anthraquinones, bisacodyl, phenolphthalein, and magnesium salts. Seven patients had positive tests. No single clinical feature could have predicted the outcome of the test. The possible cost savings of the programme were estimated by not releasing the results of the test to the clinicians until the patient's investigations were complete. The seven patients with laxative abuse spent a total of 35 days in hospital and were seen on 29 occasions in the outpatient clinic after the laxative screening test was positive. The cost of the screening programme was cheaper than the costs of the diagnostic procedures in patients with laxative abuse. We recommend the use of a comprehensive, early laxative screening programme in all patients with diarrhoea of uncertain origin as a cost effective procedure. [ABSTRACT FROM PUBLISHER]

Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had 11 C-PK11195 and 18 F-DOPA PET to assess microglial activation and striatal dopamine system integrity, respectively. Comparisons were made with healthy controls. Five LRRK2-NMCs had subclinical reductions of putaminal 18 F-DOPA uptake. Three of them had significantly raised nigral 11 C-PK11195 binding bilaterally. These findings indicate that nigrostriatal dysfunction and neuroinflammation occur in LRRK2-NMCs. Studies in larger cohorts with appropriate follow-up are needed to elucidate the significance of neuroinflammation in the premotor phase of LRRK2-PD.

Objective: Although not typical of Parkinson's disease (PD), caudate dopaminergic dysfunction can occur in early stages of the disease. However, its frequency and longitudinal implications in large cohorts of recently diagnosed patients remain to be established. We investigated the occurrence of caudate dopaminergic dysfunction in the very early phases of PD (<2 years from diagnosis) using 123 I-FP-CIT single photon emission CT and determined whether it was associated with the presence or subsequent development of cognitive impairment, depression, sleep and gait problems., Methods: Patients with PD and healthy controls were identified from the Parkinson's Progression Markers Initiative (PPMI) database. We defined a clinically significant caudate dysfunction as 123 I-FP-CIT binding <-2 SDs compared with the controls' mean and categorised three groups accordingly (no reduction, unilateral reduction, bilateral reduction). All statistical analyses were adjusted for mean putamen binding., Results: At baseline, 51.6% of 397 patients had normal caudate dopamine transporter binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate.Compared with those with a baseline normal caudate function, at the4-year follow-up patients with a baseline bilateral caudate involvement showed a higher frequency of cognitive impairment (p<0.001) and depression (p<0.001), and worse cognitive (p<0.001), depression (<0.05) and gait (<0.001) ratings. Significant caudate involvement was observed in 83.9% of the population after 4 years (unilateral 22.5%, bilateral 61.4%)., Conclusions: Early significant caudate dopaminergic denervation was found in half of the cases in the PPMI series. Baseline bilateral caudate involvement was associated with increased risk of developing cognitive impairment, depression and gait problems over the next 4 years., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The technology of electrically adjustable optical interfaces has found applications in, e.g., camera lenses, where an adjustable focal length provides automatic focusing for the camera. In this paper, we will investigate a liquid lens, where both the focal length and the tilt of this lens can be adjusted electrically. Specifically, the tilting ability of this lens will be tested by combining the liquid lens with a projector in order to scan lines across a three-dimensional (3D) object. The linearity, reproducibility, hysteresis, and time response of its tilting functionality will be tested. Further, crosstalk between the two functionalities of the liquid lens is tested for the specific case, where the focal length is set to infinity. Finally, the liquid lens and the projector in combination with four stereo cameras will be demonstrated as a 3D imaging setup.

Many metabolic processes in plants are regulated by manganese (Mn) but limited information is available on the molecular mechanisms controlling cellular Mn homeostasis. In this study, a yeast assay was used to isolate and characterize two genes, MTP8.1 and MTP8.2, which encode membrane-bound proteins belonging to the cation diffusion facilitator (CDF) family in the cereal species barley (Hordeum vulgare). Transient expression in onion epidermal cells showed that MTP8.1 and MTP8.2 proteins fused to the green fluorescent protein (GFP) are localized to Golgi. When heterologously expressed in yeast, MTP8.1 and MTP8.2 were found to be Mn transporters catalysing Mn efflux in a similar manner as the Golgi localized endogenous yeast protein Pmr1p. The level of MTP8.1 transcripts in barley roots increased with external Mn supply ranging from deficiency to toxicity, while MTP8.2 transcripts decreased under the same conditions, indicating non-overlapping functions for the two genes. In barley leaves, the expression of both MTP8 genes declined in response to toxic Mn additions to the roots suggesting a role in ensuring proper delivery of Mn to Golgi. Based on the above we suggest that barley MTP8 proteins are involved in Mn loading to the Golgi apparatus and play a role in Mn homeostasis by delivering Mn to Mn-dependent enzymes and/or by facilitating Mn efflux via secretory vesicles. This study highlights the importance of MTP transporters in Mn homeostasis and is the first report of Golgi localized Mn2+ transport proteins in a monocot plant species.

Mononuclear leucocyte zinc was determined together with serum zinc, albumin and serum alkaline phosphatase activity before and after zinc supplementation (2 x 50 mg of zinc-gluconate daily during 3 months) in patients with alcoholic liver cirrhosis (n = 10), alcoholic chronic pancreatitis (n = 10) and Crohn's disease (n = 10). Initial mononuclear leucocyte zinc concentrations did not differ between the patient groups and the reference group (n = 10), whereas initial serum zinc values were lower in the patients with alcoholic liver cirrhosis and Crohn's disease. This difference disappeared, however, when serum zinc concentrations were corrected for albumin levels, which were lower in all the patient groups. Higher initial activity of serum alkaline phosphatase was found in the alcoholic patients. In all the patient groups serum zinc concentrations increased significantly after zinc supplementation. Only in patients with Crohn's disease was there also an increase in serum alkaline phosphatase and albumin. Mononuclear leucocyte zinc did not respond to zinc supplementation in any of the patient groups. The results of our study indicate that mononuclear leucocyte zinc is not a sensitive indicator of marginal zinc deficiency.