Copper in disorders with neurological symptoms: Alzheimer`s, Menkes, and Wilson Diseases

Copper is an essential element for the activity of a number of physiologically important enzymes. Enzyme-related malfunctions may contribute to severe neurological symptoms and neurological diseases: copper is a component of cytochrome c oxidase, which catalyzes the reduction of oxygen to water, the essential step in cellular respiration. Copper is a cofactor of Cu/Zn-superoxide-dismutase which plays a key role in the cellular response to oxidative stress by scavenging reactive oxygen species. Furthermore, copper is a constituent of dopamine-β-hydroxylase, a critical enzyme in the catecholamine biosynthetic pathway. A detailed exploration of the biological importance and functional properties of proteins associated with neurological symptoms will have an important impact on understanding disease mechanisms and may accelerate development and testing of new therapeutic approaches. Copper binding proteins play important roles in the establishment and maintenance of metal-ion homeostasis, in deficiency disorders with neurological symptoms (Menkes disease, Wilson disease) and in neurodegenerative diseases (Alzheimer’s disease). The Menkes and Wilson proteins have been characterized as copper transporters and the amyloid precursor protein (APP) of Alzheimer’s disease has been proposed to work as a Cu(II) and/or Zn(II) transporter. Experimental, clinical and epidemiological observations in neurodegenerative disorders like Alzheimer’s disease and in the genetically inherited copper-dependent disorders Menkes and Wilson disease are summarized. This could provide a rationale for a link between severely dysregulated metal-ion homeostasis and the selective neuronal pathology.

Effectiveness of prevention programmes for obesity and chronic diseases amongst immigrants to developed countries - a systematic review

Objective: To determine whether interventions tailored specifically to  particular immigrant groups from developing to developed countries  decrease the risk of obesity and obesity-related diseases.

Design: Databases searched were MEDLINE (1966–September 2008), CINAHL (1982–September 2008) and PsychINFO (1960–September 2008), as well as Sociological Abstracts, PsychARTICLES, Science Direct, Web of Knowledge and Google Scholar. Studies were included if they were randomised control trials, ‘quasi-randomised’ trials or controlled before-and-after studies. Due to the heterogeneity of study characteristics only a narrative synthesis was undertaken, describing the target population, type and reported impact of the intervention and the effect size.

Results: Thirteen studies met the inclusion criteria. Ten out of thirteen (77 %) studies focused on diabetes, seven (70 %) of which showed significant improvement in addressing diabetes-related behaviours and glycaemic control. The effect on diabetes was greater in culturally tailored and facilitated interventions that encompassed multiple strategies. Six out of the thirteen studies (46 %) incorporated anthropometric data, physical activity and healthy eating as ways to minimise weight gain and diabetes-related outcomes. Of the six interventions that included anthropometric data, only two (33 %) reported improvement in BMI Z-scores, total skinfold thickness or proportion of body fat. Only one in three (33 %) of the studies that included cardiovascular risk factors reported improvement in diastolic blood pressure after adjusting for baseline characteristics. All studies, except four, were of poor quality (small sample size, poor internal consistency of scale, not controlling for baseline characteristics).

Conclusions: Due to the small number of studies included in the present review, the findings that culturally tailored and facilitated interventions produce better outcomes than generalised interventions, and that intervention content is more important than the duration or venue, require further investigation.

Applications of aptamers in nanodelivery systems in cancer, eye and inflammatory diseases

Aptamers are an interesting class of molecules that have potential in many facets of human health. They are characterized by high affinity and specificity to their targets, are small in size, have similar properties to antibodies, but are made synthetically. All of these properties, among others, give aptamers the potential to diagnose, image and treat like no other molecules. By combining the unique properties of aptamers with the ever expanding field of nanotechnology and all it has to offer, we are entering a very promising new area of targeted nanodelivery treatments. These treatments have found success in the complex disease processes of cancer, eye and inflammatory diseases.

Nano-lactoferrin in diagnostic, imaging and targeted delivery for cancer and infectious diseases

Lactoferrin (Lf) is a natural occurring iron binding protein present in many mammalian excretions and involved in various physiological processes. Lf is used in the transport of iron along with other molecules and ions from the digestive system. However its the modulatory functions exhibited by Lf in connection to immune response, disease regression and diagnosis that has made this protein an attractive therapeutic against chronic diseases. Further, the exciting potentials of employing nanotechnology in advancing drug delivery systems, active disease targeting and prognosis have also shown some encouraging outcomes. This review focuses on the role of Lf in diagnosing infection, cancer, neurological and inflammatory diseases and the recent nanotechnology based strategies.

What doesn’t kill you makes you fitter: A systematic review of high-intensity interval exercise for patients with cardiovascular and metabolic diseases

High-intensity interval exercise (HIIE) has gained popularity in recent years for patients with cardiovascular and metabolic diseases. Despite potential benefits, concerns remain about the safety of the acute response (during and/or within 24 hours postexercise) to a single session of HIIE for these cohorts. Therefore, the aim of this study was to perform a systematic review to evaluate the safety of acute HIIE for people with cardiometabolic diseases. Electronic databases were searched for studies published prior to January 2015, which reported the acute responses of patients with cardiometabolic diseases to HIIE (≥80% peak power output or ≥85% peak aerobic power, VO2peak). Eleven studies met the inclusion criteria (n = 156; clinically stable, aged 27-66 years), with 13 adverse responses reported (∼8% of individuals). The rate of adverse responses is somewhat higher compared to the previously reported risk during moderate-intensity exercise. Caution must be taken when prescribing HIIE to patients with cardiometabolic disease. Patients who wish to perform HIIE should be clinically stable, have had recent exposure to at least regular moderate-intensity exercise, and have appropriate supervision and monitoring during and after the exercise session.

Progressive adaptation in physical activity and neuromuscular performance during 520d confinement

To understand whether prolonged confinement results in reductions in physical activity and adaptation in the musculoskeletal system, six subjects were measured during 520 d isolation in the Mars500 study. We tested the hypothesis that physical activity reduces in prolonged confinement and that this would be associated with decrements of neuromuscular performance. Physical activity, as measured by average acceleration of the body's center of mass ("activity temperature") using the actibelt® device, decreased progressively over the course of isolation (p<0.00001). Concurrently, countermovement jump power and single-leg hop force decreased during isolation (p<0.001) whilst grip force did not change (p≥0.14). Similar to other models of inactivity, greater decrements of neuromuscular performance occurred in the lower-limb than in the upper-limb. Subject motivational state increased non-significantly (p = 0.20) during isolation, suggesting reductions in lower-limb neuromuscular performance were unrelated to motivation. Overall, we conclude that prolonged confinement is a form of physical inactivity and is associated with adaptation in the neuromuscular system.

Bone density and neuromuscular function in older competitive athletes depend on running distance

UNLABELLED: Individuals who are involved in explosive sport types, such as 100-m sprints and long jump, have greater bone density, leg muscle size, jumping height and grip strength than individuals involved in long-distance running. INTRODUCTION: The purpose of this study is to examine the relationship between different types of physical activity with bone, lean mass and neuromuscular performance in older individuals. METHODS: We examined short- (n = 50), middle- (n = 19) and long-distance (n = 109) athletes at the 15th European Masters Championships in Poznań, Poland. Dual X-ray absorptiometry was used to measure areal bone mineral density (aBMD) and lean tissue mass. Maximal countermovement jump, multiple one-leg hopping and maximal grip force tests were performed. RESULTS: Short-distance athletes showed significantly higher aBMD at the legs, hip, lumbar spine and trunk compared to long-distance athletes (p ≤ 0.0012). Countermovement jump performance, hop force, grip force, leg lean mass and arm lean mass were greater in short-distance athletes (p ≤ 0.027). A similar pattern was seen in middle-distance athletes who typically showed higher aBMD and better neuromuscular performance than long-distance athletes, but lower in magnitude than short-distance athletes. In all athletes, aBMD was the same or higher than the expected age-adjusted population mean at the lumbar spine, hip and whole body. This effect was greater in the short- and middle-distance athletes. CONCLUSIONS: The stepwise relation between short-, middle- and long-distance athletes on bone suggests that the higher-impact loading protocols in short-distance disciplines are more effective in promoting aBMD. The regional effect on bone, with the differences between the groups being most marked at load-bearing regions (legs, hip, spine and trunk) rather than non-load-bearing regions, is further evidence in support of the idea that bone adaptation to exercise is dependent upon the local loading environment, rather than as part of a systemic effect.

Creatine and the creatine transporter: a review

The cellular role of creatine (Cr) and Cr phosphate (CrP) has been studied extensively in neural, cardiac and skeletal muscle. Several studies have demonstrated that alterations in the cellular total Cr (Cr + CrP) concentration in these tissues can produce marked functional and/or structural change. The primary aim of this review was to critically evaluate the literature that has examined the regulation of cellular total Cr content. In particular, the review focuses on the regulation of the activity and gene expression of the Cr transporter (CreaT), which is primarily responsible for cellular Cr uptake. Two CreaT genes (CreaT1 and CreaT2) have been identified and their chromosomal location and DNA sequencing have been completed. From these data, putative structures of the CreaT proteins have been formulated. Transcription products of the CreaT2 gene are expressed exclusively in the testes, whereas CreaT1 transcripts are found in a variety of tissues. Recent research has measured the expression of the CreaT1 protein in several tissues including neural, cardiac and skeletal muscle. There is very little information available about the factors regulating CreaT gene expression. There is some evidence that suggests the intracellular Cr concentration may be involved in the regulatory process but there is much more to learn before this process is understood. The activity of the CreaT protein is controlled by many factors. These include substrate concentration, transmembrane Na+ gradients, cellular location, and various hormones. It is also likely that transporter activity is influenced by its phosphorylation state and by its interaction with other plasma membrane proteins. The extent of CreaT protein glycosylation may vary within cells, the functional significance of which remains unclear.

Older adults' neuromuscular adaptations to resistence training and effects on challenging gait tasks

Community locomotion is threatened when older individuals are required to negotiate obstacles, which place considerable stress on the musculoskeletal system. The vulnerability of older adults during challenging locomotor tasks is further compromised by age-related strength decline and muscle atrophy. The first study in this investigation determined the relationship between the major muscle groups of the lower body and challenging locomotor tasks commonly found in the community environment of older adults. Twenty-nine females and sixteen males aged between 62 and 88 years old (68.2 ±6.5) were tested for the maximal voluntary contraction (MVC) strength of the knee extensors and 1-RM for the hip extensors, flexors, adductors, abductors, knee extensors and flexors and ankle plantar flexors. Temporal measurements of an obstacle course comprising four gait tasks set at three challenging levels were taken. The relationship between strength and the obstacle course dependent measures was explored using linear regression models. Significant associations (p≤0.05) between all the strength measures and the gait performances were found. The correlation values between strength and obstructed gait (r = 0.356-0.554) and the percentage of the variance explained by strength (R2 = 13%-31%), increased as a function of the challenging levels, especially for the stepping over and on and off conditions. While the difficulty of community older adults to negotiate obstacles cannot be attributed to a single causal pathway, the findings of the first study showed that strength is a critical requirement. That the magnitude of the association increased as a function of the challenging levels, suggests that interventions aimed at improving strength would potentially be effective in helping community older adults to negotiate environmental gait challenges. In view of the findings of the first study, a second investigation determined the effectiveness of a progressive resistance-training program on obstructed gait tasks measured under specific laboratory conditions and on an obstacle course mimicking a number of environmental challenges. The time courses of strength gains and neuromuscular mechanisms underpinning the exercise-induced strength improvements in community-dwelling older adults were also investigated. The obstructed gait conditions included stepping over an obstacle, on and off a raised surface, across an obstacle and foot targeting. Forty-three community-living adults with a mean age of 68 years (control =14 and experimental=29) completed a 24-week progressive resistance training program designed to improve strength and induce hypertrophy in the major muscles of the lower body. Specific laboratory gait kinetics and kinematics and temporal measures taken on the obstacle course were measured. Lean tissue mass and muscle activation of the lower body muscle groups were assessed. The MVC strength of the knee extensors and 1-RM of the hip extension, hip flexion, knee extension, knee flexion and ankle plantar flexion were measured. A 25% increase on the MVC of the knee extensors (p≤0.05) was reported in the training group. Gains ranging between 197% and 285% were recorded for the 1-RM exercises in the trained subjects with significant improvements found throughout the study (p≤0.05). The exercise-induced strength gains were mediated by hypertrophic and neural factors as shown by 8.7% and 27.7% increases (p≤0.05) in lean tissue mass and integrated electromyographic activity, respectively. Strength gains were accompanied by increases in crossing velocity, stride length and reductions in stride duration, stance and swing time for all gait tasks except for the foot targeting condition. Specific kinematic variables associated with safe obstacle traverse such as vertical obstacle heel clearance, limb flexion, horizontal foot placements prior to and at post obstacle crossing and landing velocities resulted in an improved crossing strategy in the experimental subjects. Significant increases in the vertical and anterior-posterior ground reaction forces accompanied the changes in the gait variables. While further long-term prospective studies of falls rates would be needed to confirm the benefits of lower limb enhanced strength, the findings of the present study provide conclusive evidence of significant improvements to gait efficiency associated with a systematic resistance-training program. It appears, however, that enhanced lower body strength has limited effects on gait tasks involving a dynamic balance component. In addition, due to the larger strength-induced increases in voluntary activation of the leg muscle compared to relatively smaller gains in lean tissue mass, neural adaptations appear to play a greater contributing role in explaining strength gains during the current resistance training protocol.

MicroRNA in human cancer and chronic inflammatory diseases

MicroRNAs (miRNAs) are the non-coding RNAs that act as post-translational regulators to their complimentary messenger RNAs (mRNA). Due to their specific gene silencing property, miRNAs have been implicated in a number of cellular and developmental processes. Also, it has been proposed that a particular set of miRNA spectrum is expressed only in a particular type of tissue. Many interesting findings related to the differential expression of miRNAs in various human diseases including several types of cancers, neurodegenerative diseases and metabolic diseases have been reported. Deregulation of miRNA expression in different types of human diseases and the roles various miRNAs play as tumour suppressors as well as oncogenes, suggest their contribution to cancer and/or in other disease development. These findings have possible implications in the development of diagnostics and/or therapeutics in human malignancies. In this review, we discuss various miRNAs that are differentially expressed in human chronic inflammatory diseases, neurodegenerative diseases, cancer and the further prospective development of miRNA based diagnostics and therapeutics.