无所事事，就看了朋友们的status，
哇，个个都变了，
而我却仿佛困在一个小筐筐里，走不出来。
我大部分时间都在考试读书，好像都跟外面的世界脱离了关系。
我在想，有必要吗？

时常让自己读读读，真的有用？
对自己要求那么高，是怕输？是怕达不到别人对我的期望？还是不能面对失败？

也许每个都有。。
可是我累了，真得好累了，
我只想放下身段，轻轻松松做我自己，
与我爱的家人朋友一起度过快乐时间。：）

Introduction of Botox

The medicine Botox® is actually botulinum toxin released by Clostridium botulinum. Clostridium botulinum produces seven serotypes of the toxin that is botulinum toxin A±G but the commonly used Botox in the treatment of wrinkle is botulinum toxin A.(BT-A). Besides, it is a neurotoxin that is made up of a light chain and heavy chain linked by a single disulphide bond.  (Image Adapted from Centerr for Cellular Molecular Biology in Hyderabad )                                                                                                    

The botulinum toxin initial uses were for strabismus(crossed eye), blepharospasm (uncontrollable blinking), and cervical dystonia (wry neck). (Tortora G.J, Derrickson.B. 2010.) In the year of 2002, it was approved to be used cosmetically to treat facial lines and wrinkles. Follow by then, in the year 2004, FDA approved Botox for treating excessive underarm sweating. 

The presence of high doses of botulinum toxin in food causes food poisoning and could be fatal. They can enter the body easily and interfere with the transmission of nerve impulses, causing disturbances in sensory and also paralysis of the respiratory muscles, leading to suffocation. However, the Botox used for injections is diluted with saline or other liquid. Thus, the dose given is so small that it does not cause significant harmful effect. (eMedicineHealth. 2010.) 

Figure 2: Botox Available in Market
 (Image Adapted from BotoxTreatment.com)

How Wrinkles Formed?

There are three types of wrinkles: dynamic wrinkles, static wrinkles, and wrinkle folds with each formed by different factors. The articles will be explaining more on dynamic wrinkles as botox works well in it.

Figure 1: Release of Acetylcholine into synaptic cleft
(Image adopted from Rugged Elegance)

The dynamic wrinkles are formed by repeated contraction of muscle through facial expression. When impulse arrives at axon terminal, neurotransmitter acetylcholine is exocytosised into the synaptic cleft to attach to the receptors on the postsynaptic membrane. This generate muscle action potential and trigger muscle contraction.(Tortora G.J, Derrickson.B. 2010.) The shortening of sarcomeres and fiber during muscle contraction will then causes the skin to becomes bunch together, forming lines between the muscles. 

 

Click on the video to show how muscle contract(Adopted from youtube.com)

 

Besides, frequent muscle contraction causes the skin elastic tissue network deteriorates by deformation of the dermis and the hypodermis layers. The skin will becomes looser, loses the ability to snap back to its original state after being deformed and thus wrinkles are formed. Furthermore, as skin cells regenerate themselves at slower rate and tend to favor a specific orientation with age, frequent facial expression with muscle contraction causes wrinkles to become permanent and more pronounced.In addition, the height of the bulging of the wrinkles depends on the amplitude of the muscle contraction.(Dr. Jonathan Hoenig. 2002-2004.)

The second type static wrinkles occur from the loss of elasticity of the skin due to lifestyle and age while wrinkle folds, is caused by the loss of subcutaneous facial fat and sagging of the underlying facial structures.Folds appear when skin is deformed but disappear after removal of the deformation. Repetition of skin folding on the same site would progressively give rise to permanent wrinkles.(Nadia M.T, Prem.K,Jean L. n.d.)

The Mechanism of Botox in Wrinkles Reduction

Generally, the Botox or BT-A works by weakens or paralyzes muscles by inhibiting the release of acetylcholine. Soon after the Botox is injected,

Figure 1:Binding of BT-A with receptors on plasma membrane

1.0 The heavy chain of the BT-A bind irreversible with specific receptors called sialoglycoproteins in the plasma membrane of motor nerve.

1.1 The binding  allows efficient uptake of Botox by the motor nerve and facilitates selective targeted treatment at the injection site.

 

Figure 2:Endocytosis of BT-A into motor nerve cytoplasm

2.0 The binding induces receptor-mediated endocytosis of the toxin where the Botox molecule passes through the cell membrane of the motor nerve and into its cytoplasm.

2.1 The light chain of BT-A that is responsible for the toxicity is activated and split off in the cell.
(This is due to the fact that the subunit of BT-A are linked together by only single disulphide bond, the BT-A is therefore unstable and can break down into inactive subunits as a result of minimal mechanical and thermal stresses. )

Figure3: Inactivation of SNAP 25

3.0 Light chain of Botox cleaves apart a synapse-specific protein,  synaptosomal-associated protein of 25kDa( SNAP25) that enable neurotransmitter acetylcholine storing vesicles to attach to cell membrane. 

3.1 SNAP-25 is inactivated from a fusion complex of three proteins.

All the images above adopted from:

Allergan Incorporation. 2010. Mechanism of Action.

4. Cleaving SNAP25 prevents acetylcholine storing vesicles from fusing with the membrane and prevents the release of acetylcholine into the neuromuscular junction (the space between the motor nerve and the muscle).

As Acetylcholine act as chemical trigger of ion channel, inhibiting the release of acetylcholine causes blockage in transmission of the nerve impulses to neuromuscularjunction and myoneural (muscle-nerve) junctions. Thus, muscle cannot contract and the muscle activity decreases.  (P. Becker-Wegerich, L. Rauch and T. Ruzicka. 2001.)

Figure 4: Difference in the neuromuscular junction after botox injection. Notice that the acetylcholine is no longer released into end plate region after injection. (Image adopted from emedicine.com)

Click on the video below to view how botox inhibit muscle contraction.


 (Video adopted from youtube.com)

The Effectiveness of Botox in Wrinkle Reduction

It is well known that the Botox can treat the dynamic wrinkles that normally appear on forehead. The picture below shows  forehead of  patients before and after injected with botox.

Figure 1: Picture of patient before and after treatment of Botox

                                                        (Image adopted from: Billinkoff Aesthetic Incorporation)

There are also others area injected with Botox. The others commonly area injected with botox are shown in the picture below:

Figure 2: Others commonly injected area

                                                                                            (Image adopted from: Hana Dental Center)

However, the effect of Botox is just temporaly and normally can last for few to several months depending on area of muscle injected and individual patient. The functional recovery is due to the formation of new neural sprouts and this process takes at least 2-3 months in striated muscles but probably takes much longer in smooth muscles. This is because longer clinical effects have been described when injections of Botox are given in a smooth muscle such as the detrusor.(Allergan Incorporation. 2010) The diagram below showing the recovery of muscle contraction.

A)Figure 1:  Nerve Sprouting: 

1. New nerve endings sprout and connect to the muscle after the original nerve ending is blocked.


2. The ability of the nerve to cause muscle contractions is renew . 






Figure 2:  Reestablishment of Nerve Connection:

1. Eventually, the new nerve sprouts retract.

2. The original nerve ending regains its function,acetylcholine released. 

Figure 1&2 adopted from: Allergan Incorporation. 2010. Mechanism of Action


Click on the video below to view how Botox is injected and it's effectiveness. (Adopted from Youtube.com)

  Adverse Effect of Botox

1. Droopy eye lid:

Any Botox administered around the eye has the potential to affect the muscle that opens then upper eyelid. As Botox can spread from an injection site approximately 1 inch or 2.5cm and is a paralyzing toxin, the muscle that opens then lid is technically also paralyzed, which may make it difficult to open then eyelid carefully. Poor location of the injection and excessive doses of Botox are the culprits of eyelid drooping.  (R.W. Westreich, 2008)

2. More wrinkles:

This happens because the paralyzed facial muscles force other muscles to move in an effort to recreate the facial expressions that Botox has blocked.

For example, when injected, Botox temporarily paralyzes the muscles there and its freezing effects prevent people from frowning. Since there is no muscle contraction, no wrinkles are formed. However, muscles in the upper nose, middle eyebrow and eyelid may try to recreate the expression of a scowl. Repetitions of this cause new wrinkles. (Sharon Bell, 2007)

3 Limit emotion experience:

Due to the paralysis of muscles causes by the injection of botox, facial muscles that have been injected will have less movement therefore less feedback to the brain on facial expressivity.

For example, reading negative emotional words causes contraction of the corrugator supercilii, which pulls the eyebrows down towards the centre of the face to produce vertical frown lines at the top of the nose, whereas reading positive emotional words activates the zygomaticus, which raises the corners of the mouth to produce a smile. These findings provide evidence that involuntary facial expressions can evoke emotions, and suggest that the brain mechanisms involved in experiencing emotions are also used in understanding the emotional content of language. (Mo, 2010)

4 Botox may leak into brain:

Botox might migrate from its injection site into other parts of the nervous system. In the current study, researchers injected botulinum toxin into one side of the hippocampus into the brains of rats and observed it to migrate to the other side of the brain. When the toxin was injected into the brain’s superior colliculus, which is involved in vision, it migrated into the animals’ eyes. (David Gutierrez, 2009)

5. Botox induced muscle paralysis rapidly degrades bone:

A study conducted by Department of Orthopaedics and Sports Medicine, University of Washington show that Botox can actually degrades some of the bones in body. (Sarah E.W,a David A.S, Blair A. B, Steven D, Sundar S and Ted S. G. 2006.)For more information, click here.

                 Others Uses of Botox

1. Cure migraines :

Patients suffering from migraines and severe tension headaches are now turning to Botox for treatment. Botox injections block brain receptors from registering Migraine pain. Muscles begin to relax, reducing tension. (Jeffrey Raval, 2010)

 2. Cure excessive underarm sweating :

Those with a condition known as hyperhidrosis or excessive perspiration is also finding some relief with Botox. Hyperhidrosis is the result of overactive sweat glands. Botox injection can inhibit nerves in body that control the sweat glands. (Keion Moradi, 2007)

3. Cure overactive bladder :

Symptoms of overactive bladder include urinary frequency, urgency or urge incontinence. Botox toxin paralyzes the nerves that release chemicals that cause the muscle to become stimulated. Without the stimulation, the muscle weakens and reduces the spasticity that patients have. The toxin is delivered through a cytoscope, a small telescope that is inserted through the urethra and into the bladder. This means no incisions have to be made in the skin. ( John Tyler, 2003)

4. Enlarged prostate:

Botox causes the muscles around the prostate relax, alleviating pressure on the urethra. Botox treatment for an enlarged prostate report less pain during urination. (Keion Moradi, 2007)

Alternatives Other Than Botox

1. Hexapeptide:

Hexapeptide is said to be alternative to Botox as it is less risky compared to Botox. It works by blocking the Specific Site Kinase, thus preventing the clustering of acetylcholine which is neccessary to activate action potential. (Inyline. N.d) For more information about hexapeptide and related product, click here.

2. Collagen:

Collagen is another well known anti-wrinkle product and it can be injected into muscle as well. It helps to regenerate cell and thus preventing the deformation of dermis due to muscle contraction.( OxynergyParis. N.d.)

3. Hyaluronic Acid:

It support structural protein collagen and elastin, and give the skin elasticity and softness. This is due to its capability to bind large amount of water, which plumpness up the skin. It also helps in building up the cell framework and cell differentiation. ( OxynergyParis. N.d.)