Jejunal Creatine Absorption: What is the Role of the Basolateral Membrane?

The mechanism of the intestinal creatine absorption is not well understood. Previous studies have established the involvement of a CT1 carrier system in jejunal apical membrane. The current research was aimed at completing the picture of creatine absorption. To investigate the process supporting creatine exit from enterocyte, basolateral membrane vesicles isolated from rat jejunum were used. The presence of various symport and antiport mechanisms was searched and a NaCl-dependent electrogenic transport system for creatine was evidenced, which shares some functional and kinetic features with the apical CT1. However, Western blot and immunohistochemical experiments ruled out the presence of a CT1 transporter in the basolateral membrane. Further studies are required to identify the basolateral transport mechanism. However, in the in vivo conditions, the NaCl gradient is inwardly directed, therefore such a mechanism cannot energetically mediate the exit of creatine from the cell into the blood during the absorptive process, but rather it may drive creatine into the enterocyte. To shed more light on the creatine absorption process, a possible creatine movement through the paracellular pathway has been examined using the jejunal tract everted and incubated in vitro. A linear relationship between creatine transport and concentration was apparent both in the mucosa-to-serosa and serosa-to-mucosa directions and the difference between the two slopes suggests that paracellular creatine movement by solvent drag may account for transintestinal creatine absorption. As a matter of fact, when transepithelial water flux is reduced by means of a mucosal hypertonic solution, the opposite creatine fluxes tend to overlap. The findings of the present study suggest that paracellular creatine movement by solvent drag may account for transintestinal creatine absorption.     

What is the optimal vitamin D status for health?

The most objectively substantiated health-related reason for tanning is that it improves vitamin D status. The serum 25-hydroxyvitamin D concentration (25(OH)D) is the measure of vitamin D nutrition status. Human biology was probably optimized through natural selection for a sun-rich environment that maintained serum 25(OH)D higher than 100 nmol/L. These levels are now only prevalent in people who spend an above-average amount of time outdoors, with the sun high in the sky. The best-characterized criteria for vitamin D adequacy are based on randomized clinical trials that show fracture prevention and preservation of bone mineral density. Based upon these studies, 25(OH)D concentrations should exceed 75 nmol/L. This concentration is near the upper end of the 25(OH)D reference ("normal") range for populations living in temperate climates, or for people who practice sun-avoidance, or who wear head coverings. Officially mandated nutrition guidelines restrict vitamin D intake from fortified food and supplements to less than 25 mcg/day, a dose objectively shown to raise serum 25(OH)D in adults by about 25 nmol/L. The combined effect of current nutrition guidelines and current sun-avoidance advice is to ensure that adults who follow these recommendations will have 25(OH)D concentrations lower than 75 nmol/L. Therefore, advice to avoid UVB light should be accompanied by encouragement to supplement with vitamin D in an amount that will correct for the nutrient deficit that sun-avoidance will cause.     

Biodiversity and human health: evidence for causality?

The Millennium Ecosystem Assessment and other commentators have warned about the impacts that biodiversity decline will have on human health. There is no doubting that the natural world provides mankind with the majority of the resources required to sustain life and health. Many species provide food, fuel, medicines; with the potential for many more (as of yet) undiscovered uses for various species. Despite this, there have been very few attempts to actually investigate relationships between biodiversity (i.e. number of species, rather than the ability of specific species to provide health benefits) and human health. This paper reviews the available evidence and demonstrates that while the links between biodiversity and health seem intuitive, they are very difficult to prove. Socio-economics has a huge influence on health status and the exploitation of natural resources (leading to eventual biodiversity loss) tends to have a positive economic effects. More direct effects of biodiversity on health include the diversity of the internal microbiome, the effect of natural diversity on our mental health and well-being (although this has large social aspects with many people feeling fearful in very diverse environments). Still to be elucidated are the tipping points where the level of global biodiversity loss is such that human health can no longer be sustained.     

What is the evidence for the clinical value of SBRT in cancer of the cervix?

AimThe aim of this review is to describe and analyze indications and results of the use of SBRT in uterine cervix cancer, reviewing articles published from January 2010 up to August 2017, for any one of the four indications listed:

• 1Patient refusal or anatomic impediments to interstitial or intracavitary brachytherapy (BCT), i.e. SBRT as an “alternative” for BCT;
• 2Patients with voluminous tumors, or asymmetric tumors where BCT alone would not achieve curative doses, i.e. SBRT as a primary adjunct to BCT;
• 3Pelvic and para aortic adenopathy where SBRT could be used as a boost, i.e. SBRT as a primary adjunct to external beam pelvic radiotherapy;
• 4Small volume recurrences (postoperative or post radiotherapy), i.e. SBRT for salvage.

BackgroundCervix cancer standard treatment involves pelvic irradiation and chemotherapy, recent advances in irradiation techniques might offer new possible approaches.Material and methodsSystematic review of the English language literature about Cervix cancer, SBRT, published from January 2010 to January 2018 identified through a database search of PubMed, and Ovid MEDLINE, using pre-defined search phrases.ResultsThe results in the literature, in general, demonstrate rather weak efficacy of SBRT. In this review, we did not find strong evidence to recommend routine SBRT as a primary treatment for cervico-uterine cancers, i.e. as a replacement for BCT; in highly selected cases it might be considered useful as salvage therapy for relapsed cervix cancer.ConclusionThe existing data to not warrant recommending SBRT for the definitive treatment of cervix cancer, but may have some value in the recurrent/relapsed setting.     

Hormetic effects of curcumin: What is the evidence?

Curcumin (diferuloylmethane), a component of the yellow powder prepared from the roots of Curcuma longa or Zingiberaceae (known as turmeric) is not only widely used to color and flavor food but also used as a pharmaceutical agent. Curcumin demonstrates anti-inflammatory, anticarcinogenic, antiaging, and antioxidant activity, as well as efficacy in wound healing. Notably, curcumin is a hormetic agent (hormetin), as it is stimulatory at low doses and inhibitory at high doses. Hormesis by curcumin could be also a particular function at low doses (i.e., antioxidant behavior) and another function at high dose (i.e., induction of autophagy and cell death). Recent findings suggest that curcumin exhibits biphasic dose–responses on cells, with low doses having stronger effects than high doses; examples being activation of the mitogen-activated protein kinase signaling pathway or antioxidant activity. This indicates that many effects induced by curcumin are dependent on dose and some effects might be greater at lower doses, indicative of a hormetic response. Despite the consistent occurrence of hormetic responses of curcumin in a wide range of biomedical models, epidemiological and clinical trials are needed to assess the nature of curcumin’s dose–response in humans. Fortunately, more than one hundred clinical trials with curcumin and curcumin derivatives are ongoing. In this review, we provide the first comprehensive analysis supportive of the hormetic behavior of curcumin and curcumin derivatives.     

Cannabinoids for SARS-CoV-2 and is there evidence of their therapeutic efficacy?

To combat the coronaviruses and their novel variants, therapeutic drugs and the development of vaccines that are to be effective throughout human life are urgently needed. The endocannabinoid system (ECS) acts as a modulator in the activation of the microcirculation, immune system, and autonomic nervous system, along with controlling pharmacological functions such as emotional responses, homeostasis, motor functions, cognition, and motivation. The ECS contains endogenous cannabinoids, cannabinoid receptor (CBRs), and enzymes that regulate their biosynthesis, transport, and degradation. Moreover, phytocannabinoids and synthetic cannabinoids that mimic the action of endocannabinoids also play an essential role in the modulation of the ECS. Cannabinoids, the main constituents of cannabis (Cannabis sativa L.), are therapeutic compounds that have received international attention in the health field due to their therapeutic properties. Recently, they have been tested for the treatment of COVID-19 due to their antiviral properties. Indeed, cannabinoid-type compounds, and in particular cannabidiol (CBD), isolated from glandular trichomes found in the calyx of cannabis flowers with reported antiviral properties is hypothesized to be a therapeutic option in the ministration of SARS-CoV-2 consorted with COVID-19 disease. The relevant articles were determined from the database search published mainly in Web of Science, Google scholar, PubMed, Crossref, and ClinicalTrials.gov database during the pandemic period. The articles were evaluated for the therapeutic potentials, mechanisms of action of cannabinoids, the roles of the ECS in the immune system, impact of cannabinoids in SARS-CoV-2 septic, especially if they address the application of cannabinoids as drugs for the curability and management of SARS-CoV-2 and its novel variants. Although the evidence needed to be considered using cannabinoids in the control and treatment of viral diseases is currently in its infancy, they already offer an opportunity for clinicians due to their effects in relieving pain, improving appetite, and improving childhood epilepsy, especially in cancer and human immunodeficiency virus (HIV/AIDS) patients. In addition to these, the most recent scientific evidence emphasizes their use in the treatment of the coronavirus infected patients. In brief, all preclinic and clinic studies that have been reported show that, through the cannabinoid system, cannabinoids, particularly CBD, have many mechanisms that are effective in the treatment of patients infected by SARS-CoV-2. Thus, more extensive studies are necessary in this area to fully identify the effects of cannabinoids on SARS-CoV-2.     

What is river health?

1. Traditionally the assessment of river water quality has been based solely on the measurement of physical, chemical and some biological characteristics. While these measurements may be efficient for regulating effluent discharges and protecting humans, they are not very useful for large-scale management of catchments or for assessing whether river ecosystems are being protected. 2. Measurements of aquatic biota, to identify structural or functional integrity of ecosystems, have recently gained acceptance for river assessment. Empirical evidence from studies of river ecosystems under stress suggests that a small group of biological ecosystem-level indicators can assess river condition. However, physical and chemical features of the environment affect these indicators, the structure and function of which may be changed by human activities. 3. The term ‘river health’, applied to the assessment of river condition, is often seen as being analogous with human health, giving many a sense of understanding. Unfortunately, the meaning of ‘river health’ remains obscure. It is not clear what aspects of river health sets of ecosystem-level indicators actually identify, nor how physical, chemical and biological characteristics may be integrated into measures rather than just observations of cause and effect. 4. Increased examination of relationships between environmental variables that affect aquatic biota, such as habitat structure, flow regime, energy sources, water quality and biotic interactions and biological condition, are required in the study of river health.     

What is signal and what is noise in the brain?

The response of a cortical neuron to a stimulus can show a very large variability when repeatedly stimulated by exactly the same stimulus. This has been quantified in terms of inter-spike-interval (ISI) statistics by several researchers (e.g., [Softky, W., Koch, C., 1993. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J. Neurosci. 13(1), 334-350.]). The common view is that this variability reflects noisy information processing based on redundant representation in large neuron populations. This view has been challenged by the idea that the apparent noise inherent in brain activity that is not strictly related or temporally coupled to the experiment could be functionally significant. In this work we examine the ISI statistics and discuss these views in a recently published model of interacting cortical areas [Knoblauch, A., Palm, G., 2002. Scene segmentation by spike synchronization in reciprocally connected visual areas. I. Local effects of cortical feedback. Biol. Cybernet. 87(3), 151-167.]. From the results of further single neuron simulations we can isolate temporally modulated synaptic input as a main contributor for high ISI variability in our model and possibly in real neurons. In contrast to alternative mechanisms, our model suggests a function of the temporal modulations for short-term binding and segmentation of figures from background. Moreover, we show that temporally modulated inputs lead to ISI statistics which fit better to the neurophysiological data than alternative mechanisms.     

What is the best control strategy for multiple infectious disease outbreaks?

Effective control of infectious disease outbreaks is an important public health goal. In a number of recent studies, it has been shown how different intervention measures like travel restrictions, school closures, treatment and prophylaxis might allow us to control outbreaks of diseases, such as SARS, pandemic influenza and others. In these studies, control of a single outbreak is considered. It is, however, not clear how one should handle a situation where multiple outbreaks are likely to occur. Here, we identify the best control strategy for such a situation. We further discuss ways in which such a strategy can be implemented to achieve additional public health objectives.     

Misfolding of membrane proteins in health and disease: the lady or the tiger?

Protein misfolding is increasingly recognized as a factor in many diseases, including cystic fibrosis, Parkinson's, Alzheimer's and atherosclerosis. Many proteins involved in misfolding-based pathologies are membrane-associated, such that the bilayer may play roles in normal and aberrant folding. It can be argued that the in vivo partitioning of eukaryotic membrane proteins between folding and misfolding pathways is under kinetic control. Moreover, the balance between these pathways can be surprisingly delicate.     

Would selenium supplementation aid in therapy for Chagas disease?

Chagas disease, a neglected tropical disease discovered over 100 years ago, is caused by the intracellular parasite Trypanosoma cruzi and is most frequently associated with chronic cardiomyopathy and digestive disorders. Initial invasion of cells is followed by progressive inflammatory destruction of heart, muscles, nerves, and gastrointestinal (GI) tract tissue. Approximately 30% of patients progress to a chronic cardiomyopathy associated with increased morbidity and mortality. Seven to 10% of patients develop megasyndromes involving the GI tract, in particular, the esophagus and the colon. Results from several studies suggest that selenium (Se) deficiency could be an important factor in the pathogenesis of Chagas disease. In this opinion article, Se supplementation is proposed as an adjuvant therapy for treatment of chronic Chagas disease.