1,720,966 research outputs found
Peptides as potential therapeutics for Alzheimer\u27s disease
No full textIntracellular synthesis, folding, trafficking and degradation of proteins are controlled and integrated by proteostasis. The frequency of protein misfolding disorders in the human population, e.g., in Alzheimer\u27s disease (AD), is increasing due to the aging population. AD treatment options are limited to symptomatic interventions that at best slow-down disease progression. The key biochemical change in AD is the excessive accumulation of per-se non-toxic and soluble amyloid peptides (Aβ(1-37/44), in the intracellular and extracellular space, that alters proteostasis and triggers Aβ modification (e.g., by reactive oxygen species (ROS)) into toxic intermediate, misfolded soluble Aβ peptides, Aβ dimers and Aβ oligomers. The toxic intermediate Aβ products aggregate into progressively less toxic and less soluble protofibrils, fibrils and senile plaques. This review focuses on peptides that inhibit toxic Aβ oligomerization, Aβ aggregation into fibrils, or stabilize Aβ peptides in non-toxic oligomers, and discusses their potential for AD treatment
Changes in local capillarity of pure and hybrid MyHC muscle fiber types after nerve injury in rat extensor digitorum longus muscle (EDL)
Get PDFRecently, we evaluated capillary indices without discrimination by fiber type in rat extensor digitorum longus muscle (EDL) 4 weeks after nerve cut (NC), after double nerve crush (double NCR) and in two controls, from the start (CON-1) and the end (CON-2) of the experiment. In the present study, we determined the capillary indices related to specific myosin heavy chain (MyHC) fiber types. Fiber-type composition and local capillarity were assessed from a single, composite, multicolor image, where different MyHC-fiber types and capillaries were shown simultaneously. Applying local capillary indices [the number of capillaries around fiber (CAF) and the CAF scaled to fiber perimeter (CAF/FP)], to specific MyHC-fiber types, we found changes relevant to neuro-muscular studies. In the NC group, only type-2x fibers had a significantly lower CAF, and in the double NCR group, only type-2a fibers had a higher CAF in comparison with both controls. Both types of nerve injury elicited two responses: a coupled regulation of fiber size and capillarity in the oxidative, type 2a fibers and a capillarity independent regulation of fiber size in the glycolytic type-2b fibers. All subtypes of type-2 fibers had a better capillary supply (higher CAF/FP) in the NC and double NCR than in CON-2. The highest improvement was observed in type-2b fibersthis change was mirrored in an oxidative shift only in the double NCR group. Adopting fiber-type-specific capillary indices improves data analysis of rat EDL muscle samples
The Pharmacological Properties and Therapeutic Use of Apomorphine
No full textApomorphine <strong>(</strong>APO) is an aporphine derivative used in human and veterinary medicine. APO activates D<sub>1</sub>, D<sub>2S</sub>, D<sub>2L</sub>, D<sub>3</sub>, D<sub>4</sub>, and D<sub>5</sub> receptors (and is thus classified as a non-selective dopamine agonist), serotonin receptors (5HT<sub>1A</sub>, 5HT<sub>2A</sub>, 5HT<sub>2B</sub>, and 5HT<sub>2C</sub>), and α-adrenergic receptors (α<sub>1B</sub>, α<sub>1D</sub>, α<sub>2A</sub>, α<sub>2B</sub>, and α<sub>2C</sub>). In veterinary medicine, APO is used to induce vomiting in dogs, an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides). In human medicine, it has been used in a variety of treatments ranging from the treatment of addiction (<em>i.e.</em>, to heroin, alcohol or cigarettes), for treatment of erectile dysfunction in males and hypoactive sexual desire disorder in females to the treatment of patients with Parkinson's disease (PD). Currently, APO is used in patients with advanced PD, for the treatment of persistent and disabling motor fluctuations which do not respond to levodopa or other dopamine agonists, either on its own or in combination with deep brain stimulation. Recently, a new and potentially important therapeutic role for APO in the treatment of Alzheimer’s disease has been suggested; APO seems to stimulate Ab catabolism in an animal model and cell culture, thus reducing the rate of Ab oligomerisation and consequent neural cell death
Nanotechnology therapy for Alzheimer′s disease memory impairment attenuation
No full textCurrently, there is no cure for Alzheimer’s disease (AD) in humanstreatment is symptomatic only. Aging of the population, together with an unhealthy diet and lifestyle, contribute to the steady, global increase of AD patients. This increase creates significant health, societal and economical challenges even for the most developed countries. AD progresses from an asymptomatic stage to a progressively worsening cognitive impairment. The AD cognitive impairment is underpinned by progressive memory impairment, an increasing inability to recall recent events, to execute recently planned actions, and to learn. These changes prevent the AD patient from leading an independent and fulfilling life. Nanotechnology (NT) enables a new, alternative pathway for development of AD treatment interventions. At present, the NT treatments for attenuation of AD memory impairment are at the animal model stage. Over the past four years, there has been a steady increase in publications of AD animal models with a wide variety of original NT treatment interventions, able to attenuate memory impairment. NT therapy development, in animal models of AD, is faced with the twin challenges of the nature of AD, a chronic impairment, unique to human, of the tau protein and A β peptides that regulate several key physiological brain processes, and the incomplete understanding of AD′s aetiology. This paper reviews the state-of-the-art in NT based treatments for AD memory impairment in animal models and discusses the future work for translation to the successful treatment of AD cognitive impairment in human
Physical exercise, a potential non-pharmacological intervention for attenuating neuroinflammation and cognitive decline in Alzheimer’s disease patients
No full textThis narrative review summarises the evidence for considering physical exercise (PE) as a non-pharmacological intervention for delaying cognitive decline in patients with Alzheimer’s disease (AD) not only by improving cardiovascular fitness but also by attenuating neuroinflammation. Ageing is the most important risk factor for AD. A hallmark of the ageing process is a systemic low-grade chronic inflammation that also contributes to neuroinflammation. Neuroinflammation is associated with AD, Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders. Pharmacological treatment of AD is currently limited to mitigating the symptoms and attenuating progression of the disease. AD animal model studies and human studies on patients with a clinical diagnosis of different stages of AD have concluded that PE attenuates cognitive decline not only by improving cardiovascular fitness but possibly also by attenuating neuroinflammation. Therefore, low-grade chronic inflammation and neuroinflammation should be considered potential modifiable risk factors for AD that can be attenuated by PE. This opens the possibility for personalised attenuation of neuroinflammation that could also have important health benefits for patients with other inflammation associated brain disorders (i.e., Parkinson’s disease, late-onset epilepsy, amyotrophic lateral sclerosis and anxiety disorders). In summary, life-long, regular, structured PE should be considered as a supplemental intervention for attenuating the progression of AD in human. Further studies in human are necessary to develop optimal, personalised protocols, adapted to the progression of AD and the individual’s mental and physical limitations, to take full advantage of the beneficial effects of PE that include improved cardiovascular fitness, attenuated systemic inflammation and neuroinflammation, stimulated brain Aβ peptides brain catabolism and brain clearance
The Contribution of Type 2 Diabetes to Parkinson’s Disease Aetiology
No full textType 2 diabetes (T2D) and Parkinson’s disease (PD) are chronic disorders that have a significant health impact on a global scale. Epidemiological, preclinical, and clinical research underpins the assumption that insulin resistance and chronic inflammation contribute to the overlapping aetiologies of T2D and PD. This narrative review summarises the recent evidence on the contribution of T2D to the initiation and progression of PD brain pathology. It also briefly discusses the rationale and potential of alternative pharmacological interventions for PD treatment
Simultaneous visualization of myosin heavy chain isoforms in single muscle sections
No full textWe developed a staining protocol that enables simultaneous visualization of myosin heavy chain (MHC) pure and hybrid muscle fiber types in rat skeletal muscle. Up to eight differ-ent muscle fiber types can be visualized in a single section of the rat extensor digitorum longus muscle, which contains all four adult MHC isoforms and shows plasticity during the denervation-reinnervation process. Triple immunofluores-cent staining of MHC-1, MHC-2a and MHC-2b with primary antibodies BA-D5 (isotype IgG2b), SC-71 (isotype IgG1) and BF-F3 (isotype IgM) and with three fluorophore-labeled iso-type-specific secondary antibodies displays different mus-cle fiber types in a merged image of red, green and blue channels, each in its own color. Immunoperoxidase staining with primary antibody 6H1 directed against MHC-2x can be additionally applied on the same tissue section to facilitate the identification of muscle fibers containing MHC-2x. Triple staining can also be used in combination with other staining procedures to derive more information about the number of capillaries or the oxidative potential of muscle fiber types. Simultaneous visualization of multiple fiber types in a single merged image enables economical use of muscle samples and provides simple and rapid identification of all fiber types that are present in rat limb muscles
Changes in the capillarity of the rat extensor digitorum longus muscle 4 weeks after nerve injury studied by 2D measurement methods
No full textWe have previously shown by 3D study that 2 weeks after nerve injury there was no change in the length of capillaries per muscle fibre length in rat extensor digitorum longus muscle (EDL). The primary goal of the present 2D study was to determine the capillarity of rat EDL 4 weeks after various modes of nerve injury. Additionally, we wished to calculate the same capillary/fibre parameters that were used in our 3D stereological study. EDL muscles derived from denervated (4 weeks after nerve injury), re-innervated (4 weeks after two successive nerve crushes) and age-matched controls from the beginning (CON-1) and the end (CON-2) of the experiment were analysed in two ways. Global indices of capillarity, such as capillary density (CD) and capillary/fibre (C/F) ratio, were determined by automatic analysis, local indices as the number (CAF) and the length of capillaries around individual muscle fibres (Lcap) in relation to muscle fibre size were estimated manually by tracing the muscle fibre outlines and the transversally and longitudinally cut segments of capillaries seen in 5-%m-thin muscle cross sections. Four weeks after both types of nerve injury, CD increased in comparison to the CON-2 group (p < 0.001) due to atrophied muscle fibres in denervated muscles and probably proliferation of capillaries in re-innervated ones. Higher C/F, CAF (both p < 0.001) and Lcap (p < 0.01) in re-innervated than denervated EDL confirmed this assumption. Calculated capillary/fibre parameters were comparable to our previous 3D study, which strengthens the practical value to the adapted 2D method used in this study
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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