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Ampholytes, Polyampholytes, pI and Zwitterion
Biochemistry

Ampholytes, Polyampholytes, pI and Zwitterion

Many substances in nature contain both acidic and basic groups as well as many different types of these groups in the same molecule. (e.g. proteins). These are called ampholytes (one acidic and one basic group) or polyampholytes (many acidic and basic groups). Proteins contains many different amino acids some of which contain ionizable side groups, both acidic and basic. Therefore, a useful term for dealing with the titration of ampholytes and polyampholytes (e.g. proteins) is the isoelectric point, pI. This is described as the pH at which the effective net charge on a molecule is zero.

For the case of a simple ampholyte like the amino acid glycine the pI, when calculated from the Henderson-Hasselbalch equation, is shown to be the average of the pK for the a-COOH group and the pK for the a-NH2 group:

pI = [pKa-(COOH) + pKa-(NH3+)]/2

For more complex molecules such as polyampholytes the pI is the average of the pKa values that represent the boundaries of the zwitterionic form of the molecule. The pI value, like that of pK, is very informative as to the nature of different molecules. A molecule with a low pI would contain a predominance of acidic groups, whereas a high pI indicates predominance of basic groups.

The Sliding Filament mechanism of muscle contraction
Physiology

The Sliding Filament mechanism of muscle contraction.

When a muscle contracts the light I bands disappear and the dark A bands move closer together. This is due to the sliding of the actin and myosin myofilaments against one another. The Z-lines pull together and the sarcomere shortens

 

The thick myosin bands are not single myosin proteins but are made of multiple myosin molecules. Each myosin molecule is composed of two parts: the globular "head" and the elongated "tail". They are arranged to form the thick bands.

It is the myosin heads which form crossbridges that attach to binding sites on the actin molecules and then swivel to bring the Z-lines together

 

Likewise the thin bands are not single actin molecules. Actin is composed of globular proteins (G actin units) arranged to form a double coil (double alpha helix) which produces the thin filament. Each thin myofilament is wrapped by a tropomyosin protein, which in turn is connected to the troponin complex. 

The tropomyosin-troponin combination blocks the active sites on the actin molecules preventing crossbridge formation. The troponin complex consists of three components: TnT, the part which attaches to tropomyosin, TnI, an inhibitory portion which attaches to actin, and TnC which binds calcium ions. When excess calcium ions are released they bind to the TnC causing the troponin-tropomyosin complex to move, releasing the blockage on the active sites. As soon as this happens the myosin heads bind to these active sites.

BONE
Anatomy

BONE

 A rigid form of CT, Consists of matrix and cells

 Matrix contains:

 organic component 35% collagen fibres

 inorganic salts 65% calcium phosphate (58,5%),  calcium carbonate (6,5%)

2 types of bone - spongy (concellous)

 compact (dense)

 Microscopic elements are the same

 Spongy bone consists of bars (trabeculae) which branch and unite to form a meshwork

 Spaces are filled with bone marrow

 Compact bone appears solid but has microscopic spaces

 In long bones the shaft is compact bone

 And the ends (epiphysis) consists of spongy bone covered with compact bone

Flat bones consists of 2 plates of compact bone with spongy bone in-between

 Periosteum covers the bone

 Endosteum lines marrow cavity and spaces

 These 2 layers play a role in the nutrition of bone tissue

 They constantly supply the bone with new osteoblasts for the repair and growth of bone

Microscopically

 The basic structural unit of bone is the Haversian system or osteon

 An osteon consists of a central Haversian canal

- In which lies vessels nerves and loose CT

- Around the central canal lies rings of lacunae

- A lacuna is a space in the matrix in which lies the osteocyte

- The lacunae are connected through canaliculi which radiate from the lacunae

- In the canaliculi are the processes of the osteocytes

- The canaliculi link up with one another and also with the Haversian canal

- The processes communicate with one another in the canaliculi through gap junctions

- Between two adjacent rows of lacunae lie the lamellae, 5-7µm thick

- In three dimensions the Haversian systems are cylindrical

- The collagen fibres lie in a spiral in the lamellae

- Perpendicular to the Haversian canals are the Volkman's canals

- They link up with the marrow cavity and the Haversian canals

- Some lamellae do not form part of a Haversian system

- They are the:

- Inner circumferential lamellae - around the marrow cavity

- Outer circumferential lamellae - underneath the outer surface of the bone

- Interstitial lamellae - between the osteons

Endosteum

Lines all cavities like marrow spaces, Haversian- and Volkman's canals

Consists of a single layer of squamous osteoprogenitor cells with a thin reticular CT layer underneath it

Continuous with the inner layer of periosteum

Covers the trabeculae of spongy bone

Cells differentiate into osteoblasts (like the cells of the periosteum)

Periosteum

 Formed by tough CT

 2 layers

Outer fibrous layer:  Thickest, Contains collagen fibres,

Some fibres enter the bone - called Sharpey's fibres

Contains blood vessels.

Also fibrocytes and the other cells found in common CT

Inner cellular layer

Flattened cells (continuous with the endosteum)

Can divide and differentiate into osteoprogenitor cells

spindle shaped

little amount of rough EPR

poorly developed Golgi complex

play a prominent role in bone growth and repair

Osteoblasts

Oval in shape, Have thin processes, Rough EPR in one part of the cell (basophilic)

On the other side is the nucleus, Golgi and the centrioles in the middle, Form matrix

Become trapped in the matrix

 

Osteocytes

Mature cells, Less basophilic than the osteoblasts, Lie trapped in the lacunae, Their processes lie in the canaliculi, Processes communicate with one another through gap junctions, Substances (nutrients, waste products) are passed on from cell to cell

Osteoclasts

 Very large,  Multinucleate (up to 50),  On inner and outer surface of bone,  Lie in depressions on the surface called Howships lacunae,  The cell surface facing the bone has short irregular processes

Acidophylic

 Has many lysosomes, polyribosomes and rough EPR

 Lysosomal enzymes are secreted to digest the bone

 Resorbs the organic part of bone

Histogenesis

Two types of bone development.

- intramembranous ossification

- endochondral ossification

In both these types of bone development temporary primary bone is deposited which is soon replaced by secondary bone. Primary bone has more osteocytes and the mineral content is lower.

 

Carisolv
Conservative Dentistry

CarisolvCarisolv is a dental caries removal system that offers a unique approach to
the treatment of carious dentin. It differs from traditional methods, such as
Caridex, by utilizing amino acids and a lower concentration of sodium
hypochlorite. Below is an overview of its components, mechanism of action,
application process, and advantages.

1. Components of Carisolv
A. Red Gel (Solution A)

Composition:
Amino Acids: Contains 0.1 M of three amino acids:
I-Glutamic Acid
I-Leucine
I-Lysine


Sodium Hydroxide (NaOH): Used to adjust pH.
Sodium Hypochlorite (NaOCl): Present at a lower
concentration compared to Caridex.
Erythrosine: A dye that provides color to the gel,
aiding in visualization during application.
Purified Water: Used as a solvent.



B. Clear Liquid (Solution B)

Composition:
Sodium Hypochlorite (NaOCl): Contains 0.5% NaOCl
w/v, which contributes to the antimicrobial properties of the solution.



C. Storage and Preparation

Temperature: The two separate gels are stored at 48°C
before use and are allowed to return to room temperature prior to
application.


2. Mechanism of Action

Softening Carious Dentin: Carisolv is designed to
soften carious dentin by chemically disrupting denatured collagen within the
affected tissue.
Collagen Disruption: The amino acids in the formulation
play a crucial role in breaking down the collagen matrix, making it easier
to remove the softened carious dentin.
Scraping Away: After the dentin is softened, it is
removed using specially designed hand instruments, allowing for precise and
effective caries removal.


3. pH and Application Time

Resultant pH: The pH of Carisolv is approximately 11,
which is alkaline and conducive to the softening process.
Application Time: The recommended application time for
Carisolv is between 30 to 60 seconds, allowing for quick
treatment of carious lesions.


4. Advantages

Minimally Invasive: Carisolv offers a minimally
invasive approach to caries removal, preserving healthy tooth structure
while effectively treating carious dentin.
Reduced Need for Rotary Instruments: The chemical
action of Carisolv reduces the reliance on traditional rotary instruments,
which can be beneficial for patients with anxiety or those requiring a
gentler approach.
Visualization: The presence of erythrosine allows for
better visualization of the treated area, helping clinicians ensure complete
removal of carious tissue.

Topical Anesthetics
Pharmacology

Topical Anesthetics

Benzocaine

Benzocaine is a derivative of procaine, an ester type local anesthetic, and is poorly soluble in water and is

available only as a topical anesthetic.

-  Localized allergic reactions are sometimes encountered    

-  Overdosing is unlikely as benzocaine is poorly absorbed into the blood, which decreases the likelihood of systemic toxicity.

- The onset of surface anesthesia is rapid requiring less than one minute.

Tetracaine

- Tetracaine is an ester type local anesthetic

-  Topically applied tetracaine as opposed to benzocaine has a prolonged duration of action.

Cocaine

- Cocaine is a ester type anesthetic that is used exclusively as a topical agent.

- Cocaine is unique among topical and injectable anesthetics in that it has vasoconstrictive as well as anesthetic properties. It is used sparingly because of its abuse potential but is still used when hemostasis of mucous membranes is essential.

- Cocaine is generally available in concentrations of 2-10 % solution.

Lidocaine

- Lidocaine is an amide local anesthetic that is available in injectable and topical formulations.

- It is available in gel, viscous solution, ointment and aerosol preparations in concentrations ranging from 2-10 %.

- The onset of anesthesia is slower relative to benzocaine but, the duration is about the same.

- Absorption into the bloodstream is greater than benzocaine providing a greater risk of systemic toxicity.

Recent Advances
Conservative Dentistry

Recent Advances in Restorative DentistryRestorative dentistry has seen significant advancements in materials and
techniques that enhance the effectiveness, efficiency, and aesthetic outcomes of
dental treatments. Below are some of the notable recent innovations in
restorative dentistry:

1. Teric Evoflow
A. Description

Type: Nano-optimized flow composite.
Characteristics:
Optimum Surface Affinity: Designed to adhere well
to tooth surfaces.
Penetration: Capable of penetrating into areas that
are difficult to reach, making it ideal for various restorative
applications.



B. Applications

Class V Restorations: Particularly suitable for Class V
cavities, which are often challenging due to their location and shape.
Extended Fissure Sealing: Effective for sealing deep
fissures in teeth to prevent caries.
Adhesive Cementation Techniques: Can be used as an
initial layer under medium-viscosity composites, enhancing the overall
bonding and restoration process.


2. GO
A. Description

Type: Super quick adhesive.
Characteristics:
Time Efficiency: Designed to save valuable chair
time during dental procedures.
Ease of Use: Fast application process, allowing for
quicker restorations without compromising quality.



B. Applications

Versatile Use: Suitable for various adhesive
applications in restorative dentistry, enhancing workflow efficiency.


3. New Optidisc
A. Description

Type: Finishing and polishing discs.
Characteristics:
Three-Grit System: Utilizes a three-grit system
instead of the traditional four, aimed at achieving a higher surface
gloss on restorations.
Extra Coarse Disc: An additional extra coarse disc
is available for gross removal of material before the finishing and
polishing stages.



B. Applications

Final Polish: Allows restorations to achieve a final
polish that closely resembles the natural dentition, improving aesthetic
outcomes and patient satisfaction.


4. Interval II Plus
A. Description

Type: Temporary filling material.
Composition: Made with glass ionomer and leachable
fluoride.
Packaging: Available in a convenient 5 gm syringe.

B. Characteristics

Dependable: A one-component, ready-mixed material that
simplifies the application process.
Safety: Safe to use on resin-based materials, as it
does not contain zinc oxide eugenol (ZOE), which can interfere with bonding.

C. Applications

Temporary Restorations: Ideal for use in temporary
fillings, providing a reliable and effective solution for managing carious
lesions until permanent restorations can be placed.

Thiamin: Vitamin B1
Biochemistry

Thiamin: Vitamin B1

Thiamin, or vitamin B1, helps to release energy from foods, promotes normal appetite, and is important in maintaining proper nervous system function.

RDA (Required Daily allowance) Males: 1.2 mg/day; Females: 1.1 mg/day

Thiamin Deficiency

Symptoms of thiamin deficiency include: mental confusion, muscle weakness, wasting, water retention (edema), impaired growth, and the disease known as beriberi.

Eosinopenia
General Pathology

Eosinopenia:
Causes

-Corticoid effect (Cushing's syndrome or therapy).
-Stress.



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