Pineal gland, the mystical third eye

Pineal gland 

It is a very small unpaired midline brain structure of endocrine gland, tiny as a rice grain size, situated laterally (anatomically asymmetrical) in the epithalamus, between two hemisphere, near the center of the brain, but devoid of blood-brain barrier (so having profuse blood flow, second only to kidney), well referred as pineal body, pineal word came as due its resemblance of a pine cone or pine apple shape.

Role of pineal gland

It has a role of maintaining circadian rhythm (are physical, mental, behavioral changes that follows a 24-hour cycle) and seasonal cycle in the body. When eyes are not stimulated with light (signals from retina of lightning environment), Serotonin neurotransmitter is converted to a hormone Melatonin to initiate sleep cycle by this tiny gland. That way Melatonin is called sleep hormone, whose secretion level is highest in the middle of the night.

Function

Due to it's resemblance of Parietal eye & the Photoreceptor cell in lower animal kingdom, it could phylogenetically regarded as vestigial remnant. 

Biomolecules Serotonin and Melatonin are structural analogies to DMT (dimethyltryptamine) released in REM phase, responsible for visualization of images and dreams, where a travel through time & space dimension occurs. DMT is most powerful hallucinogen found in naturally.

In the immediate state before death, large amount of DMT is produced.

As this endocrine gland/body, secreting Melatonin/DMT, works on similar pattern of our external eye being a photoreceptor in nature, seems an ancestral Parietal eye, vestigial to us, but still doing a powerful chemical production site which maintains circadian rhythm and a balance between wakefulness & sleep cycles. Many a time this has been referred as mythical Third eye, this is a door between our known to the unknown world. Due to the small size, it is most delayed discovered endocrine gland and still remains less understood, seems to many a mystical due to it's role in higher realm transcendental spiritual perception, perhaps due to triggering on of DMT production by controlled meditation or such willful activity by humans, as it receives the Sympathetic innervation from superior cervical ganglion.

Clinical aspects

Excessive calcification of Pineal gland disrupts its function. Aging is another reason of reduced Melatonin level causing disruptive sleep cycle.   

Happy chemicals of human body

Happiness is a very illusive term in human case as affecting variable are many. 

But for sure, happy people are more successful in multiple life domains.

• Physical, mental, emotional well-being is being governed or influenced by many external and internal factors, more often not in our control. 
• That's why this subject spans a lot many areas of external environmental factors and inner body chemistry. 
• Subjective well-being is all in the center of evaluation of happiness, positive and negative emotions are the end results.

Primary signaling chemicals of mood in humans are 4 (Neurotransmitter / Hormones) as below:

1. Serotonin, the mood stabilizer (neurotransmitter).
2. Oxytocin, the love hormone (hormone).
3. Dopamine, the rewarding chemical (neurotransmitter).
4. Endorphins, the pain killer (neurotransmitter).

Tips for living a happy life:

• Eat nourishing food, be in nature, exposure to sun shine, meditate for the feel good hormone (Serotonin).
• Keep company with good people, family, pet, love, laugh for the love hormone (Oxytocin).
• Do something meaningful each day with short and long term goal for the reward chemical (Dopamine).
• Get regular exercise, avoid news overdose, switch off bright screen - hours before bedtime, goodnight sleep of 6 to 8 hours every night for relaxing, pain killer (Endorphins).

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Interesting notes:

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Endorphins evolved in nature for survival. 

Injured animal run from predator or our ancestor's ran for help or to search for a source of water at any undisclosed distant places or a runner push through a race even in injury and likewise. 

Endorphin is produced in pain doesn't mean that one should inflict pain or harm oneself or over exercising beyond one's limit to feel good. Laughing out loud, meditation, working out in moderate, watching your favorite drama could help you to achieve this endorphin feel good effect.

Endorphins and dopamine: Endorphins relieve pain and dopamine motivates to push through challenges and provides a reward for doing so.

Opiates trigger the same receptor in the brain that triggers the release of endorphins. 

As endorphins binds pain signals and relieves, dopamine will motivate you to do same thing over and over again. So endorphins and dopamine actually work together. 

Out of more than 20 endorphins in our body, Beta endorphin is having stronger effect than morphine. That way the 'runner's high' exercise addiction and self harm could be understood. 

Sleep, neuronal activity and thrombotic events

Sleep stages & autonomic nervous system:

1. NREM sleep:

    1. Parasympathetic drive increases.

    2. Decline in Sympathetic drive, blood pressure, heart beat.

2. REM sleep:

    1. Profound Sympathetic nerve activity (increase).

Autonomic Nervous System, regulates involuntary physiologic processes like heart rate, blood pressure, respiration, digestion, sexual arousal etc. This is part of peripheral nervous system, comprising of Sympathetic, Parasympathetic and Enteric nervous system.

1. Sympathetic N.S.

    1. Afferent fibers -- Sensory input. 

                                                           } Central Nervous System

    2. Efferent fibers -- Motor output. }        ---->           motor pathway with 2 neuron series;

                                                                                       1. a Preganglionic neuron with a cell body in                                                                                                                         CNS.                                                                                                                                                                          

                                                                                       2. a Post ganglionic neuron with a cell body in 

                                                                                           the periphery that innervates target tissues. 

2. Parasympathetic N.S. 

    1. Afferent fibers -- Sensory input. 

                                                           } Central Nervous System

  2. Efferent fibers -- Motor output. }       ---->              1. S.N.S. activation, 

                                                                                           SNS innervates every every tissue in the body.

                                                                                           causes:

                                                                                           Elevated activity & attention.

                                                                                           "flight or fight" response,

                                                                                           b.p. & hear rate increases,

                                                                                           glycogenolysis ensues,

                                                                                           gastrointestinal peristalsis cease.

                                                                                        2. P.N.S. activation,

                                                                                            PNS innervates only the head, viscera,

                                                                                            external genitalia (smaller than SNS).

                                                                                            promotes: 

                                                                                            "rest & digest" response,

                                                                                            b.p. & heart rate lower,

                                                                                            gastrointestinal peristalsis/digestion restarts,

• Presynaptic neurons of both SNS and PNS utilize acetylcholine(ACh) as neurotransmitter.
• Postsynaptic Sympathetic neurons generally produce norepinephrine (NE) as their effector transmitter to act upon target tissue while Postsynaptic Parasympathetic neurons use ACh throughout.
• Enteric neurons use several neurotransmitters as ACh, Nitrous Oxide, Serotonin etc.

      Neurotransmitter, are chemical signals from one neuron to the next target cell, to quote a few:

• Acetylcholine is often used in Parasympathetic N.S. to have an inhibitory effect.
• Norepinephrine (Noradrenaline; neurotransmitter and a hormone as well) often works with Sympathetic N.S.to have a stimulating effect on the body.

Sexual arousals:

1  S.N.S. activation > increasing blood flow > decreasing food processing in the bowels > in turn would increase blood availability for genital engorgement.

2. P.N.S. activation > branches from Sacral plexus of Spinal nerves > arteries supplying erectile tissues. Nerves release Acetylcholine > Nitric Oxide from endothelial cells of trabecular arteries, eventually causes Nocturnal Penile tumescence. This NPT phenomena is of spinal regulation, brain or testosterone is not involved.

Sympathetic activity and REM sleep:

A research conclusion thankfully quoted here as, "REM sleep is associated with profound sympathetic activation in normal subjects, possibly linked to changes in muscle tone. The hemodynamic and sympathetic changes during REM sleep could play a part in triggering ischemic events in patients with vascular disease.

REM sleep is most manifest toward the end of sleep, before arousal. Sympathetic and hemodynamic alterations during REM sleep could conceivably initiate increased platelet aggregability, plaque rupture, or coronary vasospasm, thus acting as a triggering mechanism for thrombotic events that may present clinically only after arousal."

Brain waves, sleep stages and functional pathology

Brain waves are oscillating electrical voltage in the brain. Brain does not operate with any single frequency wave. Full spectrum of all brain wave frequencies are always there to be found. Only the dominant frequency determines our mental state.

EEG (Electroencephalogram) reveal their following types:

Frequency band    Frequency      Brain state              Notes

1. Gamma (γ)        35-44Hz    Concentration             High-level information processing is a 40 Hz

Problem solving,                                                          activity, 40 Hz deficiency creates learning

concentration.                                                               disability. Only a quiet mind access Gamma.

                                                                                      Gamma relates to expanded consciousness,                                                                                                                   spiritual emergence, higher virtues.

2. Beta (ß)              12-35 Hz     Anxiety dominant,    Normal dominant rhythm in alert, anxious, open

Busy,                                           active, external          eye, listening, thinking, judgment, processing  

active mind.                                attention, relaxed       information around us.

3.Alpha (α)            8-12 Hz          Very relaxed,          8-13 Hz, a bridge from external world to internal

Reflective,                                  passive attention        world, ability to shift states from external to 

restful.                                                                           internal and vice versa.

                                                                                     Our brain uses 13 Hz (high Alpha or low Beta)

                                                                                     for 'active' intelligence. Deficiency of 13 Hz

                                                                                     activity causes learning disability & attention
                                                                                     problem.

                                                                                      } Alpha-theta protocol, hypnogogic imagery.

4. Theta (θ)             4-8 Hz       Deeply relaxed,            

Drowsiness.                                 inward focused

4. Delta (δ)            0.5-4 Hz          Sleep                       Slowest wave

Sleep,

dreaming.

Sleep and brain waves:

1. During sleep stages, brain waves vary from alpha to theta to delta and again to alpha state to complete one cycle of 90 minutes.
2. 8-13 Hz frequency range of Alpha wave is a bridge from external world to the internal world, (A frequency range having ability to shift from external to internal world and vice versa).

• Sleep stages N1 to N3 of NREM are 'slow' waves.
• N1 and N2 mainly comprising Theta wave while N3 is deep Delta wave.
• REM sleep is of 'fast' Alpha rhythm.

Sleep stage and their frequency:

Sleep stage       Voltage and frequency     Physiology                    

1. REM sleep    Low amplitude (small),      Eye movement, dream,    

                          high frequency (fast),        arm/leg muscles               

                           Alpha rhythm.                  paralyzed, respiration &

                                                                    heart beat maximum.

2. NREM sleep   High amplitude (large),    Slow wave, Deep-/Delta

    (N1 to N3)       (i.e. high voltage),            sleep, No eye movement,

                            low frequency (slow),       respiration & heart beat 

                            (i.e. slow waves),              minimal.

                            waves & spindles.

                            Theta & Delta rhythm.

Alpha rhythm dominant effects; 'Creative', daydreaming, meditating, helps reduce stress and anxiety, relaxed state, mental readiness role in focus and attention.

 

Theta rhythm dominant effects; Deep relaxation, light sleep, improves mood and reduce stress level.

Delta rhythm dominant effects; Deep sleep, improves immune system and reduce stress level, state of 'physical healing', tissue repair and regeneration.

Brain waves, cranial nerves & functional pathology:

Apart from sleep and wakeful activity, some other very interesting phenomenon occurs:

"A brain wave extends through perineural system as far as injured part of the body. This is physiological justification for the placebo effect as tissue repair, internal recovery, powerful vector of homeostasis." 

Positive attitude of patient plays a vital role in healing. A significant role of nerve manipulation have been reported in recovery, rehabilitation and rebalancing.

Sleep architecture

Sleep:

    EEG shows, sleep is a dynamic behavior, not a passive activity.

    Neuroendocrinological structures and chemicals responsible for sleep regulation are:

• Sleep promoting neurons in anterior hypothalamus acts through cerebral cortex with neurotransmitters. 
• Sleep promoting hormone Melatonin produced in the pineal gland.

Sleep stages:

1. NREM sleep:

    No rapid eye movement.

    Restorative sleep, bodily recovery and growth

    Boosts immune system

    As you age, less NREM sleep

    N3 for insightful thinking and creativity.

2. REM sleep:

    Rapid eye movement.

    Essential to cognitive functions like memory, learning, creativity & vivid dreams.

    Deprived of REM sleep shortens life span.

    REM declines with growing age.

Sleep cycle:

    A hypnogram based on brain waves shows:

    1. 4-6 sleep cycles in a night.

    2. Each cycle last 90 minutes on average.

    3. Each cycle with 4 sleep stages;

Stage 1  NREM  N1       wake-sleep transition state                           1-5 mins          

Stage 2  NREM  N2       most of NREM sleep occurs in this stage   10-60 mins      

Stage 3  NREM  N3       slow wave-, delta-, deep sleep                     20-40 mins     

Stage 4   REM   REM    active sleep                                                    10-60 mins     

               N1, N2, N3 amounts 75%, while REM amounts 25% of all sleep.

Some other terms used, less often:

1. Core sleep: Slow wave sleep, mainly N2 and Deep sleep N3.
2. Optional sleep: rest of the sleep is grouped as Optional.

Monoclonal antibody treatment for Covid-19

Monoclonal antibody

They are the lab made protein, mimicking the natural immune system of the human body, to fight any infection like SARS-CoV-2. It is advised as to avoid hospitalization while being found with the positive Covid test.

Restrictions

It is restricted to people of 65 or more years in age. So fairly the Covid-19 patients are always asked to get tested quickly and then get advise for the treatment of monoclonal antibody infusion.

FDA has also now advised for the monoclonal antibody treatment for SARS-CoV-2 in a recent FDA news release. One can see the list of qualification for the Monoclonal antibody treatment on certain website of hospital.

More recommendations

"It's the best treatment we have to keep you out of the hospital. It keeps people out of the hospital 70 percent of the time," said Montgomery-area pulmonologist Dr. David Thrasher. "It's really a great treatment and everybody needs to ask for it."

The fifth nucleobase

Basic ingredient in genetic recipe

Four letter A,T,C,G of genetic alphabet forming three letter words (codon), specifying for 20 amino acids, makes the basic molecular foundation of all life forms. 

But some viruses show a fundamental genomic change, a modified novel fifth base in nucleotide.

Z genome with a noncanonical modified base

In a strategy to escape bacterial restriction enzyme, it was found in the genome of  200 phage virus like one as cyanophage S-2L, out of the four canonical Watson-Crick nucleobases A,T,C,G; A is replaced by the diaminopurine (Z) forming three hydrogen bonds with T, which makes it more stable and rigid from bacterial defenses than double bond A=T. It was first reported in 1977 by soviet researcher. Further study suggest that aminoadenine in place of adenine was included in the phylogeny of these bacteriophage since archaic.

Jordana Cepelewicz in her article further states that: 'Z and other modified DNA bases seem to have evolve to help viruses evade the defenses with which bacteria degrade foreign genetic material. The eternal arms race between bacteriophages and their host cells probably provides enough selection pressure to affect something as seemingly "sacrosanct" as DNA, according to Romesberg.'