Vitamin D and cardiovascular disease prevention

Vitamin D is a precursor of the steroid hormone calcitriol that is crucial for bone and mineral metabolism. Both the high prevalence of vitamin D deficiency in the general population and the identification of the vitamin D receptor in the heart and blood vessels raised interest in the potential cardiovascular effects of vitamin D. Experimental studies have demonstrated various cardiovascular protective actions of vitamin D, but vitamin D intoxication in animals is known to induce vascular calcification. In meta-analyses of epidemiological studies, vitamin D deficiency is associated with an increased cardiovascular risk. Findings from Mendelian randomization studies and randomized, controlled trials (RCTs) do not indicate significant effects of a general vitamin D supplementation on cardiovascular outcomes. Previous RCTs, however, were not adequately designed to address extra skeletal events, and did not focus on vitamin D-deficient individuals. Therefore, currently available evidence does not support cardiovascular benefits or harms of vitamin D supplementation with the commonly used doses, and whether vitamin D has cardiovascular effects in individuals with overt vitamin D deficiency remains to be evaluated. Here, we provide an update on clinical studies on vitamin D and cardiovascular risk, discuss ongoing vitamin D research, and consider the management of vitamin D deficiency from a cardiovascular health perspective.

Key points

• The vitamin D receptor (VDR) and enzymes for vitamin D metabolism are expressed throughout the cardiovascular system
• VDR and 1α-hydroxylase knockout mice have hypertension with myocardial hypertrophy and increased activity of the renin–angiotensin–aldosterone system
• The molecular effects of VDR activation indicate various anti-atherosclerotic and protective effects on the heart and on common cardiovascular risk factors
• Observational studies have shown that low 25-hydroxyvitamin D levels are associated with an adverse cardiovascular risk profile and significantly increased risk of cardiovascular events
• Mendelian randomization studies and randomized clinical trials have not shown significant effects of vitamin D on cardiovascular events, but these trials were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals
• Vitamin D supplementation is currently not indicated for the purpose of cardiovascular disease prevention, but treatment of vitamin D deficiency is critical for skeletal health

Introduction

The critical involvement of vitamin D in bone and mineral metabolism is historically known. The identification of the vitamin D receptor (VDR) in almost all human organs including the heart and the blood vessels, and observations that individuals deficient in vitamin D are at increased risk of various extraskeletal diseases, stimulated research on the role of vitamin D for overall and cardiovascular health. In this Review, we summarize the existing knowledge on the effects of vitamin D on cardiovascular diseases and associated risk factors, with a particular focus on meta-analyses of large, epidemiological studies and randomized, controlled trials (RCTs). First, we provide a short summary of vitamin D metabolism and current vitamin D guidelines, a historical perspective on vitamin D and cardiovascular diseases, and a brief overview on the mechanistic effects of VDR activation on cardiovascular risk factors, the blood vessels, and the heart. The principal aspect of this Review is an update on observational studies, Mendelian randomization studies, and RCTs on vitamin D and cardiovascular risk. Finally, we outline and discuss ongoing vitamin D research, including large RCTs, and present our conclusions on how to deal with the management of vitamin D deficiency from a public health and cardiovascular health perspective.

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Figure 1: Human metabolism of vitamin D.

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Source: NatureReviewsCardiology

Vitamin D and cardiovascular disease prevention

Gallstones: Epidemiology, Pathophysiology and Management.

Gallstones grow inside the gallbladder or biliary tract. These stones can be asymptomatic or symptomatic; only gallstones with symptoms or complications are defined as gallstone disease. Based on their composition, gallstones are classified into cholesterol gallstones, which represent the predominant entity, and bilirubin (‘pigment’) stones. Black pigment stones can be caused by chronic hemolysis; brown pigment stones typically develop in obstructed and infected bile ducts. For treatment, localization of the gallstones in the biliary tract is more relevant than composition. Overall, up to 20% of adults develop gallstones and >20% of those develop symptoms or complications. Risk factors for gallstones are female sex, age, pregnancy, physical inactivity, obesity and over nutrition. Factors involved in metabolic syndrome increase the risk of developing gallstones and form the basis of primary prevention by lifestyle changes. Common mutations in the hepatic cholesterol transporter ABCG8 confer most of the genetic risk of developing gallstones, which accounts for ∼25% of the total risk. Diagnosis is mainly based on clinical symptoms, abdominal ultrasonography and liver biochemistry tests. Symptoms often precede the onset of the three common and potentially life-threatening complications of gallstones (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge on the genetics and pathophysiology of gallstones has expanded recently, current treatment algorithms remain predominantly invasive and are based on surgery. Hence, our future efforts should focus on novel preventive strategies to overcome the onset of gallstones in at-risk patients in particular, but also in the population in general.

Introduction

Gallstones (cholelithiasis) are masses in the gallbladder or biliary tract that are caused by abnormally high levels of either cholesterol or bilirubin (a breakdown product of heme) in bile (Fig. 1). Gallstones are common (∼10–20% of the global adult population), and >20% of people with gallstones will develop symptoms in their lifetime (including biliary colic or infections), usually in adulthood. Gallstone disease is defined by the occurrence of symptoms or complications caused by gallstones in the gallbladder and/or the bile ducts. From a clinical perspective and in treatment algorithms, those with asymptomatic stones are not generally classified as having gallstone disease. Gallstone disease is among the gastrointestinal conditions associated with the highest socioeconomic costs.

Read more: Gallstones: Epidemiology, Pathophysiology and Management.

Figure 1: Classification of gallstones.

PrimeView Poster:

Gallstones are masses in the gallbladder or biliary tract. 10–20% of adults will develop gallstones in their lifetime, and >20% of those will develop symptoms or complications. This Primer by Lammert et al. focuses on the formation of gallstones, summarizes the current principles of treatment of the stones and their potential complications and envisions future approaches for this widespread disease. And this PrimeView focuses on the most common risk factors, which include genetics, ethnicity, sex, age, drugs, parasites, over nutrition and pregnancy.

Frank Lammert, Kurinchi Gurusamy, Cynthia W. Ko,Juan-Francisco Miquel, Nahum Méndez-Sánchez, Piero Portincasa, Karel J. van Erpecum, Cees J. van Laarhoven& David Q.-H. Wang

View poster: Gallstone Poster (high-resolution PDF (1.30 MB))

Source: NatureReviewsDiseasePrimers

Breast milk hormones found to impact bacterial development in infants' guts

Intestinal microbiome of children born to obese mothers significantly different from those born to mothers of healthy weight

A new study finds that hormones in breast milk may impact the development of healthy bacteria in infants' guts, potentially protecting them from intestinal inflammation, obesity and other diseases later in life.

The study, published Monday in the American Journal of Clinical Nutrition, examines the role of human milk hormones in the development of infants' microbiome, a bacterial ecosystem in the digestive system that contributes to multiple facets of health.

"This is the first study of its kind to suggest that hormones in human milk may play an important role in shaping a healthy infant microbiome," said Bridget Young, co-first author and assistant professor of pediatric nutrition at CU Anschutz. "We've known for a long time that breast milk contributes to infant intestinal maturation and healthy growth. This study suggests that hormones in milk may be partly responsible for this positive impact through interactions with the infant's developing microbiome."

Researchers found that levels of insulin and leptin in the breast milk were positively associated with greater microbial diversity and families of bacteria in the infants' stool.

Read more: Breast milk hormones found to impact bacterial development in infants' guts

A new study examined the role of human milk hormones in the development of infants' microbiome

Source: ricardoferrando/Fotolia

Bipolar, autism, and schizophrenia might share genetic origin

A new, in-depth genetic study, published in JAMA Psychiatry, finds a potential link between bipolar disorder, schizophrenia, and autism. Although the findings are tentative, they open the door to new avenues of investigation.

Bipolar disorder, previously called manic depression, causes dramatic shifts in mood, along with swings in activity and energy levels.

Thought to affect almost 1 to 3 percent of Americans, bipolar disorder can be an incredibly disruptive condition.

Bipolar disorder is thought to share a common genetic origin with a number of other psychiatric conditions. Although evidence of this connection is growing, the search is still in its infancy.

New research, led by Dr. James Potash, puts another gene-shaped piece in the jigsaw. The study was a joint venture, conducted at the University of Iowa Carver College of Medicine, Johns Hopkins School of Medicine in Baltimore, MD, and Cold Spring Harbor Laboratory, NY.

Read more: Bipolar, autism, and schizophrenia might share genetic origin

The genetics behind psychiatric disorders are slowly revealed.

Source: medicalnewstoday

Human Embryo Implantation Model in Lab Dish

Scientists based at The Rockefeller University have created an experimental system that models the implantation of a human embryo. The new system, an adaptation of one used to recapitulate the implantation of a mouse embryo, provides an attachment substrate, surrounds the blastocyst with just the right chemical environment, and provides scaffolding that accommodates the morphological movements that are particular to human embryos. For example, a human blastocyst undergoing implantation assumes a disk-like shape, whereas the mouse blastocyst is oblong.

The in vitro system has been used to show molecular and cellular processes in human development that occur up to day 14 after fertilization. The system, which has experimentally replicated implantation outside of the uterus for the first time, promises to expand scientists’ ability to answer basic questions about our own development, as well as to understand early pregnancy loss.

Details of the work appeared May 4 in the journal Nature, in an article entitled, “Self-Organization of theIn Vitro Attached Human Embryo.” The article paid particular attention to postimplantation development of the human embryo, a process that remains mysterious.

Read more: Human Embryo Implantation Model in Lab Dish

Source: genengnews

The mechanisms and functions of spontaneous neurotransmitter release

Fast synaptic communication in the brain requires synchronous vesicle fusion that is evoked by action potential-induced Ca2+ influx. However, synaptic terminals also release neurotransmitters by spontaneous vesicle fusion, which is independent of presynaptic action potentials. A functional role for spontaneous neurotransmitter release events in the regulation of synaptic plasticity and homeostasis, as well as the regulation of certain behaviours, has been reported. In addition, there is evidence that the presynaptic mechanisms underlying spontaneous release of neurotransmitters and their postsynaptic targets are segregated from those of evoked neurotransmission. These findings challenge current assumptions about neuronal signalling and neurotransmission, as they indicate that spontaneous neurotransmission has an autonomous role in interneuronal communication that is distinct from that of evoked release.

Key points

• Synaptic terminals can release neurotransmitter by spontaneous vesicle fusion that is independent of presynaptic action potentials.
• The traditional view of spontaneous neurotransmitter release suggests that spontaneous events occur randomly in the absence of stimuli owing to low-probability conformational changes in the vesicle fusion machinery.
• Recent studies have identified key distinctions between the synaptic vesicle fusion machineries that perform spontaneous versus evoked neurotransmitter release.
• In mammalian hippocampal synapses and at the Drosophila melanogaster neuromuscular junction, spontaneous and evoked neurotransmitter release events show some spatial segregation and activate distinct populations of postsynaptic receptors.
• Segregation of spontaneous neurotransmission enables selective neuromodulation that is independent of evoked release.
• In mammalian hippocampal synapses and at the D. melanogaster neuromuscular junction, spontaneous release events activate specific postsynaptic signal transduction cascades that maintain synaptic efficacy or regulate structural plasticity and synaptic development.
• Novel strategies that selectively target spontaneous release events are needed to address whether spontaneous release can signal independently during ongoing activity in intact neuronal circuits.
• Introduction

Introduction

Our current insights into the mechanisms underlying synaptic transmission originate from experiments that were conducted in the 1950s by Bernard Katz and colleagues. A key aspect of these studies was the discovery of spontaneous neurotransmitter release events, which seemed to occur in discrete 'quantal' packets. This fundamental observation enabled the complex and seemingly intractable nature of action potential-evoked neurotransmission to be analyzed and understood on the basis of its unitary components. Although the original work solely relied on electrophysiological analysis, later studies that used electron microscopy provided visual validation of the hypothesis that neurotransmission occurs through fusion of discrete synaptic vesicles that contain neurotransmitters with the presynaptic plasma membrane.

Read more: The mechanisms and functions of spontaneous neurotransmitter release

Figure 3: Segregation of spontaneous and evoked neurotransmission.

Source: Nature Reviews Neuroscience

Vitamin D Could Repair Nerve Damage in Multiple Sclerosis

A protein activated by vitamin D could be involved in repairing damage to myelin in people with multiple sclerosis (MS), according to new research from the University of Cambridge. The study, published today in the Journal of Cell Biology, offers significant evidence that vitamin D could be a possible treatment for MS in the future.

Researchers, from the MS Society Cambridge Centre for Myelin Repair, identified that the ‘vitamin D receptor’ protein pairs with an existing protein, called the RXR gamma receptor, already known to be involved in the repair of myelin, the protective sheath surrounding nerve fibres.

By adding vitamin D to brain stem cells where the proteins were present, they found the production rate of oligodendrocytes (myelin making cells) increased by 80%. When they blocked the vitamin D receptor to stop it from working, the RXR gamma protein alone was unable to stimulate the production of oligodendrocytes.

Read more: Vitamin D Could Repair Nerve Damage in Multiple Sclerosis

Neuron with oligodendrocyte and myelin sheath (edited)

Source: scitechconnect/Andrew c

Neurodegenerative disease damage reversed in fruit flies

Alzheimer's and Parkinson's symptoms have been reversed in fruit flies following treatment with a drug-like chemical, says research published in the Proceedings of the National Academy of Sciences.

The discovery, which centers around the protection of brain cells, could be a turning point in the fight against neurodegenerative disease, say the authors.

Neurodegenerative diseases occur when groups of nerve cells in the brain die, making it difficult for a person to move and to think.

According to Claire Bale, of Parkinson's UK, the symptoms of Parkinson's tend not to appear until 70 percent of nerve cells in the brain have already been lost.

Unfortunately, current treatments are only able to tackle the symptoms of the condition - they cannot slow or stop the degeneration of these cells.

Read more: Neurodegenerative disease damage reversed in fruit flies

Scientists are making progressing in techniques to protect nerve cells.

Source: medicalnewstoday

New gene testing method can identify mutations, prioritize variants in breast and ovarian cancer genes

A research team led by an award-winning genomicist at Western University has developed a new method for identifying mutations and prioritizing variants in breast and ovarian cancer genes, which will not only reduce the number of possible variants for doctors to investigate, but also increase the number of patients that are properly diagnosed.

These potentially game-changing technologies, developed by Peter Rogan, PhD, students and his collaborators from Western's Schulich School of Medicine & Dentistry, reveal gene variants that were missed by conventional genetic testing.

Their method, described in BMC Medical Genomics, was first applied to 102 individuals at risk or with a diagnosis of inherited breast cancer. The team also studied 287 women with no known mutations for an article published in Human Mutation.

Rogan, Canada Research Chair in Genome Bioinformatics, says that 16 to 20 per cent of women in southwestern Ontario, who have their BRCA genes tested for breast and/or ovarian cancer risk, carry disease-causing gene variants that are well-understood by clinicians and genetic counselors. If a patient tests positive for an abnormal BRCA1 or BRCA2 gene and have never had breast cancer, there is a much higher-than-average risk of developing the deadly disease.

Read more: New gene testing method can identify mutations, prioritize variants in breast and ovarian cancer genes

Source: azonano

A novel device claims to be an 'off switch' for painful menstruation.

It’s estimated that nine out of 10 women suffer from period pain each month, and an unfortunate 10 percent of those will get it so bad, they could be incapacitated for up to three days. 

Other than using contraceptives to skip their period altogether (just like astronauts do), menstruating women have precious few options to beat this thing and get on with their lives. Some over-the-counter pain-killers and a strategically placed hot water bottle is about it.

But there’s another option behind secret door #3, and early reports are saying this thing actually works. Dubbed Livia, this new medical device claims to be an"off switch for menstrual pain".

Okay, so first thing’s first: how does this supposed 'miracle cure' actually work? 

As the Livia website explains, the device comes with two electrodes, which you need to place on the painful areas on your abdomen. Switch the device on, and these electrodes will start delivering imperceptible electric pulses to your nerves, which will settle the pain.

Read more: A novel device claims to be an 'off switch' for painful menstruation.

Source: sciencealert