Essential Oils for deep sleep

Essential oil is a concentrated hydrophobic liquid extracted from plants. It contains volatile chemical compounds which healing effects are ascribed to. Researchers have investigated a variety of health benefits attributed to these compounds and shown their big therapeutic implications.

Essential oils are among the undeniable natural remedies that help you to sleep thanks to their relaxing and soothing properties. They act in a holistic way and make it possible to restore our balance, which is essential for restorative rest and therefore our health.
If you are one of the 25% of Americans who experience acute insomnia, restless sleep, difficulty falling asleep, try a drug-free sleep solution, try essential oils.

Essential oils and sleep: which essential oil to choose?

Essential oils promote relaxation, and improve the quality of sleep. Our selection below will allow you to find the essential oil(s) that is adapted to your needs:

Noble camomile Essential oil (Roman camomile): soothing action, antispasmodic

Lemon Essential oil (Citrus Limonum): nervous calming
Geranium essential oil (Pelargonium asperum): balancing, relaxing, soothing

Fine lavender Essential oil (Lavandula angustifolia): muscle relaxant, anti-depressive, calming, rebalancing

Mandarin Essential oil (Citrus reticulata): relaxing action, sedative

Marjoram Essential oil (Origanum majorana): antispasmodic, rebalancing of the nervous system, sedative, used in particular against anxiety and hypertension

St. John’s wort Essential oil (Hypericum perforatum): calming, reduces tension

Neroli essential oilOrange blossoms (Citrus aurantium): sedative, antidepressant, soothing action, restores vitality and self-confidence, helps to fight stress and insomnia.

Orange essential oil (Citrus sinensis): sedative, nervous system rebalancing, spasmolytic, cardiac regulator, used in particular against insomnia and depression

Petit grain bigaradier essential oil (Citrus aurantium) calming, balancing, sedative, helps to fight against anxiety and anxiety, restless sleep, night awakening

Valerian Essential oil (Valeriana officinalis): calming, reduces tension, promotes sleep

How to use essential oils to sleep better

Diffusion: put 20 to 25 drops of essential oil into an electric diffuser and turn it On for 5 minutes before going to bed

Pillow mist: spray once or twice on your pillow before going to bed

Massage oil: put 4 to 10 drops of essential oil into a vegetable oil such as sweet almond, macadamia oil or St. John’s wort macerate. Simply massage the solar plexus before going to bed. If you have the possibility to have your feet, back, legs and stomach massaged.

Bath (adult): mix 5 to 10 drops of essential oil with a solvent (Solub HE, Neutral Base) or on Epsom salts (one glass) before adding them to the bath water just before going to sleep. Stay in the bath for 15 minutes and go to bed right away. For children’s baths, limit essential oils to 5 drops.

A soft piece of fabric with essential oils: Take a piece of cloth and soak it with 10 drops of essential oil. Then slide the fabric into your pillow cover before going to sleep.

Synergies of essential oils to sleep like a baby

You can make the following essential oil blends and use them for the above applications:

lavender essential oil (5 drops) + Marjoram essential oil (5 drops)
essential oil lavender (5 drops) + essential oil Camomile (5 drops)
lavender essential oil (5 drops) + Orange essential oil (5 drops)
lavender essential oil (5 drops) + Petitgrain essential oil (5 drops)

Children’s sleep – their favourite essential oils

Not sure which essential oil to choose for your child’s sleep? Let him choose! Let him smell 3 or 4 essential oils and use the one he has chosen. He will naturally choose the one he needs. Generally children like the following essential oils:

Fine lavender Essential oil (Lavandula angustifolia): muscle relaxant, anti-depressive, calming, rebalancing,

Mandarin Essential oil (Citrus reticulata): muscle relaxant, sedative

Neroli essential oil – Orange blossom (Citrus aurantium): sedative, anti-depressant, soothing action, restores vitality and self-confidence, helps to fight stress and insomnia.

Orange essential oil (Citrus sinensis): sedative, nervous system rebalancing, spasmolytic, cardiac regulator, used in particular against insomnia and depression
essential oil Petitgrain bigaradier (Citrus aurantium) with calming, balancing, sedative action helps to fight anxiety, restless sleep, night awakening

Organic Relaxing Massage Oil

Relaxing massage oil will help to relieve your tension and make it easier to fall asleep. This composition contains a synergy of essential oils that provide immediate psychological relief and help to rebalance the nervous system. Relaxing massage oil can also be used against children’s sleep disorders (restless sleep, nightmares).




Best Essential Oils and Their Health Benefits

An Essential oil is a concentrated hydrophobic liquid containing volatile – at normal temperatures – chemical compounds from plants. The term ‘essential‘ does not mean ‘necessary‘ or as with the terms essential amino acid or essential fatty acid which are so-called since they are nutritionally required by a given living in contrast to fatty oils.

Before the discovery of distillation, all essential oils were extracted directly from biomass (the bark, flowers, fruits etc.). They have been used therapeutically for thousands of years by Greeks Romans and Egyptians to remedy everything from skin conditions and injuries to fever and so many other diseases.

Extraction

Egyptians and Phoenicians Jews and Arabs, Indians and Chinese greeks and Romans and even Mayas and Aztecs all possessed innovative extraction processes, maceration, alembic distillation, etc. Hydrodistillation of fresh plant material is the most used technique to isolate essential oils.

Hydrodistillation

Hydrodistillation is an ancient technique for the extraction of essential oils, it is still being applied in several sectors such as food cosmetics and pharmaceutical industry.

Raw plant material such as flowers leaves wood bark roots seeds and peels are extracted by water distillation whilst soaked and boiled with water in a distillation apparatus for hydrodistillation. The mixture is heated and volatile materials are carried away. Most oils are distilled in a single process. One exception is ylang-ylang (Cananga odorata) which requires a purification step through fractional distillation.

The recondensed water (plant water essence) may be sold as another fragrant product.

Other techniques

Other methods have been developed and introduced to extract Essential Oils :

Mechanical/Cold expression

Solvent extraction

Ethanol is the most common bio-solvent obtained by the fermentation of sugar-rich materials such as sugar beet and. Its outstanding feature is the easy manipulation of the dielectric constant value of water that can be made to vary over a wide range just by changing the temperature and pressure. Ethanol is used to extract fragrant compounds from dry plant materials as well as from impure oils or concretes that have been produced firstly by organic solvent extraction expression or enfleurage. For instance, the extraction yield of essential oils from Japanese citrus was increased by 44% compared to the traditional extraction methods <fn>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154587/</fn>. Problems of the traditional extraction techniques such as steam distillation lie in the huge quantities of plant material which are required to extract essential oils on a commercial scale.

Florasols extraction

Essential Oils production

According to various economic analyses, growth will continue and by the 2020s production is expected to reach 370,000 tonnes annually and be valued at more than $10 Billion USD (current dollars) <fn>https://www.intechopen.com/books/potential-of-essential-oils/essential-oils-market-and-legislation</fn>

World production of essential oils (000 t; 000,000 USD). Source: EFEO, ISMEA.
World production of essential oils (000 t; 000,000 USD). Source: EFEO, ISMEA.

Best essential oils and their health benefits

Whichever oils you choose to use ensure that when purchasing said oils, you get the ones that are organically produced and that they don’t include chemicals obtained during processing. Here’s a list of 10 popular essential oils whose benefits are mostly centered on disease prevention. <fn>Web site: https://draxe.com/essential-oil-uses-benefits/</fn>

  • Peppermint: Used to boost energy and help with digestion.
  • Lavender: Used for stress relief.
  • Sandalwood: Used to calm nerves and help with focus.
  • Bergamot: Used to reduce stress and improve skin conditions like eczema.
  • Rose: Used to improve mood and reduce anxiety.
  • Chamomile: Used for improving mood and relaxation.
  • Ylang-Ylang: Used to treat headaches, nausea and skin conditions.
  • Tea Tree: Used to fight infections and boost immunity.
  • Jasmine: Used to help with depression, childbirth, and libido.
  • Lemon: Used to aid digestion, mood, headaches and more.



Dried plant material used as home fragrance

Create your own natural and safe (non-toxic) home fragrance

To make your own home fragrance, you don’t need to be an apothecary or chemist. All you have to do is find the right products and choose the smell you prefer. Here are 3 recipes of dried plants that are 100% natural and safe for your health.

The best way to do this is to get away from the commercial home fragrances and use a homemade essential oil diffuser.

1. Alcohol + Essential oil + Water

Alcohol evaporates faster than water, making it a good choice for diffusing the aroma in large spaces. Combustion will not produce a slightly greasy smoke, unlike methods that use vegetable oil (as below).

  • Put 60 milliliters of hot water into a jar or vial.
  • Add 60 milliliters of alcohol.
  • Add 25 drops of the essential oil of your choice.
    Mixup.

2. Vegetable oil + essential oil

The proportion to be respected is 30% essential oil and 70% vegetable oil. You can try almond oil or safflower oil which have a very discreet scent. Add the essential oil of your choice and mix up.

Avoid mineral oils because they are made with petroleum.

3. Vegetable oil + essential oil + alcohol

In this case, use 60 milliliters of vegetable oil (almond or safflower) with 2 or 3 teaspoons of alcohol and a generous shave of essential oil, again respecting the 30/70% proportion.

Whatever mixture you choose, put your perfume into a pretty glass or ceramic recipient. Add diffusers or another dry vegetable tip that will help to raise the liquid upwards. Soak the tip for two or three hours and then turn it over. Every few days, you can add more essential oil to compensate after evaporation.

Which essential oil to choose?

Here are some suggestions:

  • Lemon, lemongrass, thyme (cleansing action).
  • Lavender, mint, cedar, jasmine, orange to give a positive atmosphere, and fight depression.
  • Eucalyptus and lavender to lower blood pressure.




Easy ways to improve Gut Health Naturally

The gastrointestinal tract is important to human health and key to this is the trillions of bacteria that live in our gut, it carries food from the mouth to the stomach, converts it into small digestible parts easily and properly absorbed in the body. Gastroenterologists can test for specific conditions associated with the Microbiome like an overgrowth of certain bacteria in the gut which can potentially negatively impact our metabolic health. How to improve our Gut Health naturally?

Signs of an unhealthy gut

Signs that something in the gut isn’t working as it should be:

  • Frequent stomach disturbances like gas, bloating, constipation, diarrhea
  • A high-sugar diet can decrease the number of bacteria in the gut, cause increased inflammation in the body
  • Atypical weight changes which can occur when the gut is not working well
  • Chronic high levels of stress, sleep disturbance have also been linked to an unhealthy gut
  • Skin Irritations
  • Food intolerances, autoimmune conditions

How to improve your Gut Health Naturally

Change your diet

Focus on cutting out foods that are known as aggravator factors of bowels and other gut discomforts. The idea is to follow a low-sugar diet and drink plenty of water then once the trial is over, re-introduce foods and watch for symptoms of gastrointestinal distress.

Eat slowly

Chewing slowly helps promote full digestion and absorption of nutrients.

Stay hydrated

Drinking water abundantly has significant benefits on the mucosal lining of the intestines, it promotes the maintenance of a balance of good bacteria fighting on your behalf: fermenting unused energy substrates, regulating the development of the gut, and producing vitamins.

Maintaining good hydration can be key to having a healthy digestive system.

Check for food intolerances

Unlike a food allergy that involves the organisms immune system, food intolerance is an incapacity to digest the food. It is also essential to bear in mind, however, that food intolerances can be tough to diagnose and therefore require special medical attention.

stress levels

A recent systematic review of all the human studies suggests that the majority do not show any response to probiotics on mood stress or symptoms of mental illness. This study suggests that a strong link may exist between stress and gut good bacteria, therefore it might be necessary to keep up daily habits and physical activity that help prevent anxiety and reduce stress. Read more on how to reduce your stress.




At-Home Anemia Test (60 seconds)

Anemia is usually defined as a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood.

It can also be defined as a lowered ability of the blood to carry oxygen. Iron-deficiency anemia, also spelled iron-deficiency anaemia, is anemia caused by a lack of iron.

Accurate Diagnosis Within 60 Seconds, At Low Cost

When anemia comes on slowly, the symptoms are often vague and may include feeling tired, weakness, shortness of breath or a poor ability to exercise. Anemia that comes on quickly often has greater symptoms, which may include confusion, feeling like one is going to pass out, loss of consciousness, or increased thirst. Anemia must be significant before a person becomes noticeably pale. Additional symptoms may occur depending on the underlying cause.

At-Home Anemia Test Produces Accurate Diagnosis Within 60 Seconds, At Low Cost.

A device that uses a single drop of blood can quickly diagnose anemia and allow inexpensive at-home monitoring.

“Our goal is to get this device into patients’ hands so they can diagnose and monitor anemia themselves,” said Dr. Wilbur Lam, a physician and professor in the department of pediatrics at Emory University School of Medicine, in a statement.

The basic test produces results in about 60 seconds and requires no electrical power. Because of its simplicity and ability to deliver results without electricity, the device could also be used in resource-poor nations. A companion smartphone application can automatically correlate the visual results to specific blood hemoglobin levels.

The disposable self-testing device uses a chemical reagent that produces visible color changes corresponding to different levels of anemia.

As for the new diagnostic device, researchers concede they still need to earn FDA approval before the product can reach consumers. Lam and several of his colleagues have teamed up to launch a startup, called Sanguina, to commercialize the test under the brand name AnemoCheck. They anticipate the product reaching shelves by 2016.

Source: Tyburski E, Gillespie S, Stoy W, et al. Disposable platform provides visual and color-based point-of-care anemia self-testing. The Journal of Clinical Investigation. 2014.




NuWhite Glutathione, Intense Skin Whitening

NuWhite Advanced Whitening contains L-Glutathione, Collagen and Placenta. All NuWhite components are approved by U.S FDA.

NuWhite is a Japan formulated supplement that has undergone thorough research and clinical studies. Its ingredients are carefully processed and formulated through Japan’s Technology to preserve purity and stability of its potency ensuring product’s effectivity.

100% HandMade Whitening Glutathione Soap with Honey Kojic Smell at 9,99€ ONLY – STOCK LIMITED!

PACKAGING

It is available in a sealed pink recipient that contains 1600 mg of l-glutathione, collagen, placenta, Vitamin C and CoQ10.

NUWHITE GLUTATHIONE INGREDIENTS

6 Powerful Extracts working together to give INTENSE SKIN WHITENING:
  1. Glutathione 700mg
  2. Placenta 300mg
  3. Collagen 250mg
  4. Vitamin C 200mg
  5. CoQ10 100mg
  6. Pomegranate Ellagic Acid 50mg
  • S-Glutathione 700 mg  – for pores and skin whitening, it is also a strong anti-oxidant.

S-Glutathione is a Powerful antioxidant that helps fight free radicals. It whitens skin by controlling skin pigmentation.
–Keeps skin healthy and glowing.

  • Collagen 250 mg – Collagen fights and reverses skin-aging process, reduces wrinkles, fine lines and other unsightly sign of skin aging. It also maintains healthy and glowing skin.
  • Placenta 350 mg– Clinically proven effective in skin whitening and skin nourishing an ingredient with cell renewing. Rich source of natural and potent amino acids that are essential for the production of beautiful and healthy skin.  Maintains skin healthy and glowing.
  • Vitamin H 200 mg– Aids in pores and skin whitening, boosts immune system, and in addition builds collagen.
  • CoQ10 100mg – Powerful antioxidant that can withstand and reverse skin damage. Preserve collagen and elastin within cells to make skin younger.
  • Pomegrenate Ellagic Acid 50mg  – Protects skin against photoaging, supports skin cell regeneration, promotes healing and prevents cancerous changes due to UV exposure. Clinically proven to reduce fine lines and wrinkles. Effectively lighten and brighten skin.
  • Ascorbic Acid: Aids in skin whitening. Protects skin from free radicals that causes skin damage. Boost immune system. With anti-aging properties.

NuWhite Glutathione Review

  • It’s a concentrated of whitening supplement. Nuwhite is a softgel capsule easy to swallow, readily dissolve in the gastric juice, enhances bioavailability of the active ingredients thus ensuring effective absorption of the skin enhancing ingredients.
  • Combination of the 6 powerful extracts will avoid you taking lots of beauty supplements. Nuwhite provides skin whitening, anti-aging, skin renewal and moisturizing. Gives you beautiful skin in just one step.

After taking NuWhite Glutathione for a month, according to customers reviews, a clear improvement in the skin color, which becomes clearly lighter, brighter and softer.

Pros:
  • NuWhite Glutathione contains L- Glutathione, Collagen, Placenta Extract, CoQ10, Pomegranate Ellagic Acid known as anti-aging supplements. So once you pop a pill, you’re not only whitening your skin but also adding a boost in anti-aging department.
  • No discomforts like vomiting, headache, nausea, breakouts, or whatsoever while taking this supplement
  • Made the skin glowing.
  • The packaging- it is color pink! It is tightly sealed and contains a leaflet that has information about the product.
  • The scent- unscented.
  • It’s in a softgel capsule that made it faster in absorption.
  • This supplement gave me a good night sleep.
  • I’m already fair to begin with but it made my skin pinkish/rosy white in tone.
  • t lessened cystic pimples popping around my chin which I experience every month.
  • It also maintained my skin color despite the hot humid weather. I’m always outside doing errands in the afternoon.
  • I also noticed that my my wounds heal faster. I have thin skin and I easily get a scratch from sharp objects,
  • Batch, manufacturing and expiry date printed on the package.
Cons:
  • Not easily accessible, you have to purchase it online.
  • Because of the softgel’s size, some may find it hard to swallow.
  • The price can be steep to budget conscious individuals.

 

 




Probiotics for Chronic Constipation

There are approximately 3.8·1013 single-celled microorganisms for every single “reference man”  weighing 140 pounds, and their total mass is about 200 grams (ncbi.nlm.nih.gov).

Intestinal microbiota aids in the breakdown of food products into absorbable nutrients, stimulates the host immune system, suppress inflammation [source], prevents the expansion of pathogenic bacteria and produces a substantial variety of biologically major compounds such as short-chain fatty acids that nourish the gut.

Gut Bacteria
Gut Bacteria

The concept behind probiotics was introduced in the early 19th century when Nobel laureate Elie Metchnikoff (1845–1916), known as the father of probiotics <fn>Front Public Health. 2013; 1: 52. Published online 2013 Nov 13. Prepublished online 2013 May 30. doi: 10.3389/fpubh.2013.00052 </fn>.

Elie Metchnikoff (1845–1916)
Elie Metchnikoff (1845–1916)

Probiotics are given or attenuated microorganisms defined as, when administered in adequate amounts, being able to confer health benefits on their host when they are given in.

Lactobacillus acidophilus, for example, lives in our digestive, urinary and genital systems and can be found in some fermented foods like yogurt. It may help reduce cholesterol, prevent Diarrhea, prevent Vaginal Infections, promote Weight Loss and improve symptoms of irritable bowel.

Lactobacillus acidophilus
Lactobacillus acidophilus

Studies suggest that taking probiotic supplements may shift the balance of gut bacteria in a way that increases your body’s defenses against allergies, infections, and cancer.

Probiotics and constipation

Chronic constipation is a symptom-based gastrointestinal disorder most common among the elderly, it is characterized by bowel movements that occur more frequently than normal. Constipation is most likely multifactorial. According to Harvard Medical School, it is more frequent than diarrhea and affects approximatively 14% of adults each year.

Researchers have shown an increased interest in the potential therapeutic applications of Probiotics to prevent or treat a variety of health problems including constipation and diarrhea. They also found a favorable effect in stool consistency and relief in abdominal discomfort making them increasingly used as alternative treatment options.

Although Probiotics have still been widely used nowadays for the treatment of constipation, the industry still has serious concerns about the long-term safety of probiotics which remain still partly unclear.

Mechanism of action

Several mechanisms have been proposed by which probiotics may benefit chronic constipation. Probiotics may modify the altered intestinal microbiota, and may eventually influence gut sensory-motor functions (Kawabata et al.). A healthy gut can benefit the regularity of your digestion as well as cognitive function like mood. One in vitro study (Bar et al.) suggested that Escherichia coli Nissle 1917 Supernatants (clear liquid overlying material deposited by settling, precipitation, or centrifugation) (Mutaflor®) could effectively enhance colonic contractility by direct stimulation of smooth muscle cells.

A recent study reported that methane and carbon dioxide, which are principal end products of bacterial fermentation could increase stool bulk and promote colonic transit (Lopez).

Which probiotic strains are best for constipation?

Proven probiotics available for constipation and bloating in adults are:

  • Lactobacillus casei Shirota (or L. Casei), which has effects on constipation and stool hardness, but not necessarily on flatulence and bloating
  • Lactobacillus plantarum LP01 (or L. Plantarum), which would facilitate stool evacuation
  • Bifidobacterium breve BR03 (or B. Patent), which would also improve the consistency of stool, helping to expel it
  • Bifidobacterium lactis DN-173 010 (or B. Lactis)
  • Bifidobacterium lactis B94 
  • Bifidobacterium lactis HN019
  • Bifidobacterium longum W11 (or B. Longum) 
  • Escherichia coli Nissle 1917 (or E. Coli), which allowed treated patients to go from 2 to 6 trips to the toilet per week

Proven probiotics available for constipation and bloating in children are:

  • Lactobacillus reuteri (or L. Reuteri), which has been shown to have an effect on chronic constipation in infants
  • Lactobacillus Casei rhamnosus Lcr35 or L, Casei), which relieves constipation while reducing abdominal pain



Tips to reduce the stress of a completing project

How to reduce the stress of a completing project that you have to execute efficiently and productively.

According to the Canadian Mental Health Association, work demands can cause physical and emotional stress with short- and long-term repercussions on a person’s well-being. For example, long-distance driving, layoffs, accidents, tight deadlines, setbacks, punctual customers, absent teams, and budget cuts can make the workplace an increasingly stressful environment.

The ability to manage stress is a talent that is acquired through direct experience, in the immediate context of daily living, by learning about triggers and ways to deal with stressful situations, you can focus on the task at hand without feeling overwhelmed or compromising your health.

Here are some warning signs to watch for and some effective ways to combat stress at work.

Signs and symptoms of excessive work stress

  • Anxiety, irritability, depression
  • Apathy, loss of interest in work
  • Sleep disorders
  • Fatigue
  • Difficulty concentrating
  • Muscle tension, headaches
  • Gastric problems
  • Social withdrawal
  • Loss of sexual desire
  • Alcohol or drug abuse

What strategies should be adopted to limit stress related to a work project?

Task planning

Involve stakeholders before the project is launched, take their comments and opinions to understand their personal and professional constraints beforehand. Therefore, define a schedule/calendar accordingly in order to start your project management perfectly.

Communication

As we will keep reminding you over and over again, communication within a team is essential. Regular communication is essential. The project manager needs to know what his team is doing, and the teams need to understand what everyone is doing. Communicate at a good pace.

Roles defined for a manageable workload

Stress is often generated because of confusion about the roles and responsibilities that have not been clearly defined. Before the project is launched, clearly define the roles and responsibilities of each team member and limit everyone’s workload according to their abilities and skills. It is very important to remember that stress management is equal to the workload required.

Breaks between colleagues

Humour and jokes are a great way to dissipate tensions and build relationships between colleagues. A coffee break, off-site discussions lead to a pleasant atmosphere and create teams more motivated to achieve their objectives. As a result, these small intermittent breaks are not a waste of time, on the contrary, they improve the performance of the current project.

Individual meetings

Individual meetings are also very important in project management. They allow each team member to express their concerns and needs regarding the project. An excellent way for the project manager to clear up misunderstandings, understand everyone’s expectations and increase the positive growth of the project. Feeling listened to will encourage your teams to be motivated in their tasks.

In project management, it is important that your teams do not feel overworked, less stress for more productivity. Today, well-being at work is very beneficial for everyone, so maintain it!




Hydroxychloroquine: Mechanism of Action

Introduction

Hydroxychloroquine (HCQ), is an aminoquinoline used for the prevention and treatment of uncomplicated malaria (caused by P. falciparum, P. malariae, P. ovale, or P. vivax) in areas where malaria is vulnerable to chloroquine. Other applications may include the treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda. It is taken by mouth. HCQ is being investigated for the prevention and diagnosis of coronavirus disease 2019 (COVID‐19) High-quality epidemiological care (Stein, et al., 2000).

The FDA approval for emergency use of hydroxychloroquine and chloroquine in COVID-19 treatment was revoked on 15 June 2020 (FDA.gov, 2020).

Hydroxychloroquine obtained approval from the FDA on 18 April 1955 (FDA.gov, 1955).

A recent research recorded a COVID-19.10 fatality in the hydroxychloroquine treated population (Chary, et al., 2020).

Figure 1. Structure of HCQ
Figure 1. Structure of HCQ

Pharmacodynamics

Hydroxychloroquine affects both lysosomes function and plasmodia in humans. Changing the pH of the lysosomes decreases the low-affinity self-antigen presentation in autoimmune diseases and interferes with plasmodia’s ability to proteolyze hemoglobin for its energy needs. Hydroxychloroquine has a long duration of action, as for some indications it might be taken weekly. Hydroxychloroquine can lead to serious hypoglycemia and thus it is recommended that diabetic patients control their blood glucose levels. Hydroxychloroquine in areas where chloroquine resistance has been identified, is not effective against malaria (Wolpin, et al., 2014).

Pharmacokinetics

Absorption

Hydroxychloroquine is bioavailable in 67-74 percent. Bioavailability of the enantiomers R and S did not vary significantly. Following an oral dose of 200 mg, hydroxychloroquine reached a Cmax of 129.6ng / mL with a blood Tmax of 3.26h and a plasma Tmax of 50.3ng / mL with a plasma Tmax of 3.74h. Following intravenous doses of 155 mg and 310 mg, blood Cmax ranged from 1161-2436ng / mL with an average of 1918ng / mL.

Volume of distribution

55,22 L (blood) and 44,257 L (plasma)

Protein binding

In general, hydroxychloroquine is protein-bound in plasma by 50 percent. The hydroxychloroquine S enantiomer is 64 percent plasma bound protein. It is bound to serum albumin by 50 percent and alpha-1-acid glycoprotein by 29 percent. The R enantiomer is plasma-bound protein by 37 percent. It is linked to serum albumin by 29 percent and alpha-1-acid glycoprotein by 41 percent.

Metabolism

Hydroxychloroquine is N-dealkylated by CYP3A4 to the active metabolite called desethylhydroxychloroquine and to the inactive metabolites desethylchloroquine and bidesethylchloroquine. The main metabolite is desethylhydroxychloroquine.

Figure 2. HCQ metabolites. Source (drugbank.ca)
Figure 2. HCQ metabolites. Source (drugbank.ca)

Route of elimination

40-50 percent of hydroxychloroquine is excreted by the kidney, while only 16-21 percent of the dose is excreted in the urine as an unchanged drug. 5 percent of the dose is sloughed off in the skin and 24-25 percent is eliminated in the feces.

Half-life

Oral hydroxychloroquine has a half-life of 3-4 hours of absorption. A 200 mg oral hydroxychloroquine dose has a half-life of 22.4 days in blood, and 123.5 days in the plasma. A 155 mg dose intravenous (iv) has a half-life of 40 days.

Clearance

96mL/min

Mechanism of Action

The precise mechanism of action of HCQ is unknown. Hydroxychloroquine has been shown to accumulate in malaria parasite lysosomes, elevating the pH of the vacuole. This behavior interferes with the ability of the parasite to proteolyze hemoglobin, preventing its normal growth and replication. Hydroxychloroquine may also interfere with the action of parasitic heme polymerase, causing the toxic substance beta-hematin to accumulate.

Hydroxychloroquine concentration in human organelles often raises their pH, which inhibits the processing of antigens, prevents dimerization of the alpha and beta chains of the major histocompatibility complex ( MHC) class II, inhibits the cell’s antigen presentation and decreases the inflammatory response. High pH in the vesicles may alter the recycling of MHC complexes to present only the high-affinity complexes on the surface of the cells. Self-peptides bind to low-affinity MHC complexes and therefore are less likely to be exposed to autoimmune T cells. Hydroxychloroquine also lowers cytokine releases, such as interleukin-1 and tumor necrosis factor, probably by Toll-like receptor inhibition.

The elevated pH in endosomes prohibits the use of virus particles (such as SARS-CoV and SARS-CoV-2) for fusion and cell entry.

Hydroxychloroquine also blocks the terminal glycosylation of ACE2, the receptor that targets SARS-CoV and SARS-CoV-2 for cell entry. ACE2 which is not in the glycosylated state may interact less efficiently with the spike protein SARS-CoV-2, further inhibiting viral entry.

References

Chary, M. et al., 2020. COVID-19: Therapeutics and Their Toxicities. J Med Toxicol.

FDA.gov, 1955. [email protected]: FDA-Approved Drugs. [Online]
Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=reportsSearch.process&rptName=1&reportSelectMonth=4&reportSelectYear=1955&nav
[Accessed 2020].

FDA.gov, 2020. Coronavirus (COVID-19) Update: Daily Roundup June 15, 2020. [Online]
Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-june-15-2020
[Accessed 2020].

Stein, M., Bell, M. J. & Ang, L.-C., 2000. Hydroxychloroquine neuromyotoxicity. The Journal of rheumatology, 27(12), p. 2927.

Wolpin, B. M. et al., 2014. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma.. The oncologist, 19(6), p. 637.




5 Tips to help you reduce Stress

Stress is defined as a situation of excessive nervous tension, psychologically, a state of disruption caused by an attack.

Initially, stress was defined as a physiological response of the body to an exhausting, dangerous or distressing situation. The body then produces specific hormones. This notion was later extended to any state of disruption caused by a confrontation with danger, a physical or psychological threat, a difficult environment.

Here 5 tips to help you reduce your stress… in less than 5 minutes!

1. Analyse an image

Get a nice-looking image with several small details, which you can hang near your desk, for example. When you face a stressful situation, take 5 minutes to fix the image by spending several minutes contemplating the details it in an extremely precise way.

2. Guided relaxation (meditation)

Guided relaxation plays an important role to help you relax and relieve stress. For example, I recommend Gabrielle Bernstein guided meditation which offers a variety of small relaxation exercises of only 3 or 4 minutes.

3. Breathing

Breathing really influences stress and reduces its symptoms. By simply taking a few moments for a deep breath, you will be able to calm down quickly. Make sure that you are in a quiet place, place one hand on your stomach and inhale deeply through your nose, slowly counting to four. Then exhale through your mouth, always counting to four. Feel the air entering your lungs, focus on the breath in your mouth.

4. Walking

Go out for 5 minutes to get some air. However, the exercise doesn’t stop there: you will have to walk quietly, paying attention to all the sensations that stimulate your senses, such as the heaviness of your steps, the wind on your face, the fabric of your gloves on your hands, the singing of birds or the small rocks on the sidewalk.

5. Visualization

Visualization can be used in all situations. In this case, you will most likely be able to reduce your stress level by visualizing a place, real or imaginary, in which you feel totally comfortable. The important thing is not necessarily to see images in your head, but rather to try to feel the sensation of relief and well-being that this place gives you. Do this visualization regularly, for 5 minutes, even in quiet moments. This will help the effects to be done more quickly when you feel the need.

Above all, don’t despair: it is really possible to overcome stress, by taking the time, changing certain habits and using the right tools, and being patient.

Read more: Tips to reduce the stress of a completing project