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Thomas R Pieber Eva Svehlikova Ines Mursic Tamara Esterl Manfred Wargenau Tina Sartorius Lioba Pauly Susann Schwejda-Guettes Annalena Neumann Valentin Faerber John Friedrich Stover Barbara Gaigg Angelika Kuchinka-Koch 《World journal of diabetes》2021,12(6):893-907
BACKGROUNDLactulose is approved for the symptomatic treatment of constipation, a gastrointestinal (GI) complication common in individuals with diabetes. Lactulose products contain carbohydrate impurities (e.g., lactose, fructose, galactose), which occur during the lactulose manufacturing process. These impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus (T2DM) using lactulose for the treatment of mild constipation. A previous study in healthy subjects revealed no increase in blood glucose levels after oral lactulose intake. However, it is still unclear whether the intake of lactulose increases blood glucose levels in individuals with diabetes.AIMTo evaluate the blood glucose profile after oral lactulose intake in mildly constipated, non-insulin-dependent subjects with T2DM in an outpatient setting.METHODSThis prospective, double-blind, randomized, controlled, single-center trial was conducted at the Clinical Research Center at the Medical University of Graz, Austria, in 24 adult Caucasian mildly constipated, non-insulin-dependent subjects with T2DM. Eligible subjects were randomized and assigned to one of six treatment sequences, each consisting of four treatments stratified by sex using an incomplete block design. Subjects received a single dose of 20 g or 30 g lactulose (crystal and liquid formulation), water as negative control or 30 g glucose as positive control. Capillary blood glucose concentrations were measured over a period of 180 min post dose. The primary endpoint was the baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period [AUCbaseline_c (0-180 min)]. Quantitative comparisons were performed for both lactulose doses and formulations vs water for the equal lactulose dose vs glucose, as well as for liquid lactulose vs crystal lactulose. Safety parameters included GI tolerability, which was assessed at 180 min and 24 h post dose, and adverse events occurring up to 24 h post dose.RESULTSIn 24 randomized and analyzed subjects blood glucose concentration-time curves after intake of 20 g and 30 g lactulose were almost identical to those after water intake for both lactulose formulations despite the different amounts of carbohydrate impurities (≤ 3.0% for crystals and approx. 30% for liquid). The primary endpoint [AUCbaseline_c (0-180 min)] was not significantly different between lactulose and water regardless of lactulose dose and formulation. Also with regard to all secondary endpoints lactulose formulations showed comparable results to water with one exception concerning maximum glucose level. A minor increase in maximum blood glucose was observed after the 30 g dose, liquid lactulose, in comparison to water with a mean treatment difference of 0.63 mmol/L (95% confidence intervals: 0.19, 1.07). Intake of 30 g glucose significantly increased all blood glucose endpoints vs 30 g liquid and crystal lactulose, respectively (all P < 0.0001). No differences in blood glucose response were observed between the different lactulose formulations. As expected, lactulose increased the number of bowel movements and was generally well tolerated. Subjects experienced only mild to moderate GI symptoms due to the laxative action of lactulose.CONCLUSIONBlood glucose AUCbaseline_c (0-180 min) levels in mildly constipated, non-insulin dependent subjects with T2DM are not affected by the carbohydrate impurities contained in 20 g and 30 g crystal or liquid lactulose formulations. 相似文献
23.
Clarissa von Haefen Marco Sifringer Stefanie Endesfelder Alexander Kalb Adrián González-López Annalena Tegethoff Nadine Paeschke Claudia D. Spies 《Journal of neuroimmune pharmacology》2018,13(3):383-395
Tissue damage and pathogen invasion during surgical trauma have been identified as contributing factors leading to neuroinflammation in the hippocampus, which can be protected by stimulation of the cholinergic anti-inflammatory pathway using the acetylcholinesterase inhibitor physostigmine. Macroautophagy, an intracellular degradation pathway used to recycle and eliminate damaged proteins and organelles by lysosomal digestion, seems to be important for cell survival under stress conditions. This study aimed to examine the role of autophagy in physostigmine-mediated hippocampal cell protection in a rat model of surgery stress. In the presence or absence of physostigmine, adult Wistar rats underwent surgery in combination with lipopolysaccharide (LPS). Activated microglia, apoptosis-, autophagy-, and anti-inflammatory-related genes and -proteins in the hippocampus were determined by Real-Time PCR, Western blot and fluorescence microscopy after 1 h, 24 h and 3 d. Surgery combined with LPS-treatment led to microglia activation after 1 h and 24 h which was accompanied by apoptotic cell death after 24 h in the hippocampus. Furthermore, it led to a decreased expression of ATG-3 after 24 h and an increased expression of p62/ SQSTM1 after 1 h and 24 h. Administration of physostigmine significantly increased autophagy related markers and restored the autophagic flux after surgery stress, detected by increased degradation of p62/ SQSTM1 in the hippocampus after 1 h and 24 h. Furthermore, physostigmine reduced activated microglia and apoptosis relevant proteins and elevated the increased expression of TGF-beta1 and MFG-E8 after surgery stress. In conclusion, activation of autophagy may be essential in physostigmine-induced neuroprotection against surgery stress. 相似文献
24.
Klaus W.W. Dörhage Jörg Wiltfang Vera von Grabe Annalena Sonntag Stephan T. Becker Benedicta E. Beck-Broichsitter 《Journal of cranio-maxillo-facial surgery》2018,46(6):953-957
Purpose
The positional non-synostotic plagiocephaly represents a cranial asymmetry affecting all 3 dimensions. The aim of this study was to evaluate volumetric indices to assess the efficiency in improving non-synostotic cranial asymmetries in treatment with head orthoses.Material and methods
A total of 96 infants were included in this observational retrospective study. The cohort was further divided into subgroups according to age of helmet supply (younger/older than 7.5 months) and duration of therapy (less/more than 150 days). With 3-dimensional photogrammetry data sets, the skull volume was separated into quadrants and set in relation to each other to create an Anterior Cranial Asymmetry Index (ACAI) and a Posterior Cranial Asymmetry Index (PCAI) as 3-dimensional parameters.Results
Treatment with head orthoses led to a significant reduction of ACAI (p < 0.0001) and PCAI (p = 0.001). Cranial asymmetry was more severe in the occipital region and significantly improved mainly during the first 75 days with a 40.08% decrease of PCAI value in the short-term therapy in the younger treatment subgroup (p = 0.003).Conclusions
The introduced parameters sufficiently reproduce the improvement of asymmetry during helmet therapy, following the trend of already established parameters. Asymmetry was significantly improved in the occiput region, and helmet therapy was highly effective in younger infants and in the early treatment period. 相似文献25.
Semantic abilities deteriorate early in patients with Alzheimer's disease (AD) and their residual language is characterised by strong lexical effects such as the age of acquisition of words and their typicality. The anatomical bases of this early semantic degradation have not been fully explored. To clarify which neural structures, when atrophic, alter lexical-semantic function in patients with very mild AD, this study correlated the lexical attributes of words produced in a semantic fluency task with grey matter density values from 3D MRI scans of mild AD patients. The voxel-based analyses showed a significant correlation between the lexical attributes characterising residual linguistic production in early AD patients and the integrity of regions of the medial temporal lobes, especially in areas of the perirhinal and parahippocampal cortex. This correlation was present in both hemispheres. There were no correlations within these structures with scores on neuropsychological tests not involving semantic or episodic memory. The results have implications for the role of medial temporal structures in episodic and semantic retrieval and argue against a unitary function of these structures in respect of episodic and semantic memory processes. This evidence suggests that specialised regions within the hippocampal complex engage in processes of encoding and retrieval for both semantic and episodic memories. 相似文献
26.
William Jonathan McGeown Michael Fraser Shanks Katrina Elaine Forbes-McKay Annalena Venneri 《Psychiatry Research: Neuroimaging》2009,173(3):218-227
In a study of the effects of normal and pathological aging on semantic-related brain activity, 29 patients with Alzheimer's disease (AD) and 19 controls subjects (10 young and 9 older controls) performed a version of the Pyramids and Palm Trees Test that had been adapted for use during functional magnetic resonance imaging (fMRI). Young and older controls activated the left inferior and middle frontal gyri, precuneus and superior parietal lobule. Right frontal and left temporal cortices were activated only in the young. The AD group activated only the left prefrontal and cingulate cortex. Separate analyses of high- and low-performing AD subgroups showed a similar pattern of activation in the left frontal lobe, although activiation was more widespread in low performers. High performers significantly deactivated anterior midline frontal structures, however, while low performers did not. When the older adult and AD groups were combined, there was a significant positive correlation between left frontal and parietal activation and Mini-Mental State Examination (MMSE) score (covarying for age), suggesting a disease effect. A significant negative correlation between activation in the left temporal cortex and age (covarying for MMSE score) reflected a possible age effect. These differential effects suggest that semantic activation paradigms might aid diagnosis in those cases for whom conventional assessments lack the necessary sensitivity to detect subtle changes. 相似文献
27.
28.
We examined the ultrastructural characteristics of the medullary steroidogenic cells in left and right female gonads of surgically bursectomized chick embryos killed on the 17th day of incubation. The steroidogenic cells of the bursectomized embryos have a more developed system of cisternae in the smooth endoplasmic reticulum than controls, and their mitochondria show some alterations in the density of the matrix and in the shape of the cristae. On the basis of these results, an enhancement of the steroidogenic activity in both gonads is suggested. 相似文献
29.
Annalena Civinini Valentina P. Gallo Stefania Petrucci 《Brain structure & function》1994,190(5):439-444
We examined the ultrastructural characteristics of the medullary steroidogenic cells in left and right female gonads of surgically bursectomized chick embryos killed on the 17th day of incubation. The steroidogenic cells of the bursectomized embryos have a more developed system of cisternae in the smooth endoplasmic reticulum than controls, and their mitochondria show some alterations in the density of the matrix and in the shape of the cristae. On the basis of these results, an enhancement of the steroidogenic activity in both gonads is suggested. 相似文献
30.
In this work we describe the adrenal homolog of the rainbow trout Oncorhynchus mykiss during development. At the histological level, the interrenal primordium is clearly evident in larvae 25 days after fertilization (dpf), and the immunohistochemical reactions for tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT), which mark the chromaffin cells, appear as early as 27 dpf. Both reactions are evident in cells localized in the head kidney and in some, probably migrating, cells close to the notochord. In 27-dpf larvae, the ultrastructural analysis shows the presence of the interrenal cells with mitochondria with tubulovesicular cristae, typical of steroidogenic cells, sometimes surrounded by smooth endoplasmic reticulum (SER) cisternae, indicating that in this stage the cells have the capacity for steroid synthesis and secretion. In the same stage the chromaffin cells are characterized by few and small membrane-bound granules containing cores of heterogeneous electron density. Both types of cells show large nuclei, numerous free or clumped ribosomes, developed rough endoplasmic reticulum (RER), and scarce SER. Rare nerve endings contacting chromaffin cells are present. In the subsequent developmental stages, a further differentiation of both types of cells is evidenced by modifications of cell organelles as mitochondria, chromaffin granules, RER, SER, and so on. A clear discrimination of the two types of catecholamine-containing cells, adrenaline and noradrenaline cells, is evident only 5 days after hatching. The presence of different interrenal cell types in larvae at 5 and 10 days after hatching probably indicates the activation of a physiological cellular cycle. The immunohistochemical and ultrastructural results are compared with those obtained by other authors in the same and other vertebrate species. 相似文献