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NEET MDS Synopsis

Thiazide diuretics
Pharmacology

Thiazide diuretics

Chlorothiazide, Hydrochlorothiazide

Mechanism(s) of Action

1.    Block facilitated Na/Cl co-transport in the early distal tubule. This is a relatively minor Na absorption mechanism and the result is modest diuresis 

2.    Potassium wasting effect 

a.    Blood volume reduction leads to increased production of aldosterone 
b.    Increased distal Na load secondary to diuretic effect 
c.    a + b = increase Na (to blood) for K (to urine) exchange which produces indirect K wasting

3.    Increase distal Ca re-absorption (direct effect) 

o    causes an increase in plasma calcium.This is unimportant NORMALLY but makes thiazides VERY inappropriate choice for hypercalcemic patients.

4.    Anti-diuretic effect in nephrogenic diabetes insipidus patients secondary to depletion of Na and Water. 

Toxicity
 
•    Electrolyte imbalance (particularly hypokalemia) ,Agranulocytosis , Allergic reactions 
•    Hyperuricemia , Thrombocytopenia 
 

COMPOSITE RESINS
Dental Materials

COMPOSITE RESINS

Applications / Use


Anterior restorations for aesthetics (class III, IV, V, cervical erosion abrasion lesions)
Low-stress posterior restorations (small class I, II)
Veneers
Cores for cast restorations
Cements for porcelain restorations
Cements for acid-etched Maryland bridges
Repair systems for composites or porcelains


Polymerization--reaction of small molecules (monomers) into very large molecules (polymers)

Cross-linking-tying together of polymer molecules by chemical reaction between the molecules to produce a continuous three-dimensional network

Connective Tissue
Anatomy

Connective Tissue

Functions of Connective tissue:

→ joins together other tissues

→ supporting framework for the body (bone)

→ fat stores energy

→ blood transports substances

 

Connective tissue is usually characterized by large amounts of extracellular materials that separate cells from each other, whereas epithelial tissue is mostly cells with very little extracellular material. The extracellular substance of connective tissue consists of protein fibers which are embedded in ground substance containing tissue fluid.

Fibers in connective tissue can be divided into three types:

→ Collagen fibers are the most abundant protein fibers in the body.

→ Elastic fibers are made of elastin and have the ability to recoil to original shape.

→ Reticular fibers are very fine collagen fibers that join connective tissues to other tissues.

Connective tissue cells are named according to their functions:

 → Blast cells produce the matrix of connective tissues

→ Cyte cells maintains the matrix of connective tissues

→ Clast cells breaks down the matrix for remodeling (found in bone)

Osteogenesis in Oral Surgery
Oral and Maxillofacial Surgery

Osteogenesis in Oral Surgery
Osteogenesis refers to the process of bone formation, which
is crucial in various aspects of oral and maxillofacial surgery. This process is
particularly important in procedures such as dental implant placement, bone
grafting, and the treatment of bone defects or deformities.
Mechanisms of Osteogenesis
Osteogenesis occurs through two primary processes:


Intramembranous Ossification:

This process involves the direct formation of bone from mesenchymal
tissue without a cartilage intermediate. It is primarily responsible for
the formation of flat bones, such as the bones of the skull and the
mandible.
Steps:
Mesenchymal cells differentiate into osteoblasts (bone-forming
cells).
Osteoblasts secrete osteoid, which is the unmineralized bone
matrix.
The osteoid becomes mineralized, leading to the formation of
bone.
As osteoblasts become trapped in the matrix, they differentiate
into osteocytes (mature bone cells).





Endochondral Ossification:

This process involves the formation of bone from a cartilage model.
It is responsible for the development of long bones and the growth of
bones in length.
Steps:
Mesenchymal cells differentiate into chondrocytes (cartilage
cells) to form a cartilage model.
The cartilage model undergoes hypertrophy and calcification.
Blood vessels invade the calcified cartilage, bringing
osteoblasts that replace the cartilage with bone.
This process continues until the cartilage is fully replaced by
bone.





Types of Osteogenesis in Oral Surgery
In the context of oral surgery, osteogenesis can be classified into several
types based on the source of the bone and the method of bone formation:


Autogenous Osteogenesis:

Definition: Bone formation that occurs from the
patient’s own bone grafts.
Source: Bone is harvested from a donor site in the
same patient (e.g., the iliac crest, chin, or ramus of the mandible).
Advantages:
High biocompatibility and low risk of rejection.
Contains living cells and growth factors that promote healing
and bone formation.


Applications: Commonly used in bone grafting
procedures, such as sinus lifts, ridge augmentation, and implant
placement.



Allogeneic Osteogenesis:

Definition: Bone formation that occurs from bone
grafts taken from a different individual (cadaveric bone).
Source: Bone is obtained from a bone bank, where it
is processed and sterilized.
Advantages:
Reduces the need for a second surgical site for harvesting bone.
Can provide a larger volume of bone compared to autogenous
grafts.


Applications: Used in cases where significant bone
volume is required, such as large defects or reconstructions.



Xenogeneic Osteogenesis:

Definition: Bone formation that occurs from bone
grafts taken from a different species (e.g., bovine or porcine bone).
Source: Processed animal bone is used as a graft
material.
Advantages:
Readily available and can provide a scaffold for new bone
formation.
Often used in combination with autogenous bone to enhance
healing.


Applications: Commonly used in dental implant
procedures and bone augmentation.



Synthetic Osteogenesis:

Definition: Bone formation that occurs from
synthetic materials designed to mimic natural bone.
Source: Materials such as hydroxyapatite, calcium
phosphate, or bioactive glass.
Advantages:
No risk of disease transmission or rejection.
Can be engineered to have specific properties that promote bone
growth.


Applications: Used in various bone grafting
procedures, particularly in cases where autogenous or allogeneic grafts
are not feasible.



Factors Influencing Osteogenesis
Several factors can influence the process of osteogenesis in oral surgery:


Biological Factors:

Growth Factors: Proteins such as bone morphogenetic
proteins (BMPs) play a crucial role in promoting osteogenesis.
Cellular Activity: The presence of osteoblasts,
osteoclasts, and mesenchymal stem cells is essential for bone formation
and remodeling.



Mechanical Factors:

Stability: The stability of the graft site is
critical for successful osteogenesis. Rigid fixation can enhance bone
healing.
Loading: Mechanical loading can stimulate bone
formation and remodeling.



Environmental Factors:

Oxygen Supply: Adequate blood supply is essential
for delivering nutrients and oxygen to the bone healing site.
pH and Temperature: The local environment can
affect cellular activity and the healing process.



CHEMICAL AGENTS
General Microbiology

CHEMICAL AGENTS

Chlorine and iodine are most useful disinfectant Iodine as a skin disinfectant and chlorine as a water disinfectant have given consistently magnificent results. Their activity is almost exclusively bactericidal and they are effective against sporulating organisms also. 
Mixtures of various surface acting agents with iodine are known as iodophores and these are used for the sterilization of dairy products.

Apart from chlorine, hypochlorite, inorganic chioramines are all good disinfectants but they act by liberating chlorine. 

Hydrogen peroxide in a 3% solution is a harmless but very weak disinfectant whose primary use is in the cleansing of the wound.
 
Potassium permanganate is another oxidising agent which is used in the treatment of urethntzs. 

Formaldehyde — is one of the least selective agent acting on proteins. It is a gas that is usually employed as its 37% solution, formalin. 

When used in sufficiently high concentration it destroys the bacteria and their spores.


Classification of chemical sterilizing agents

Chemical disinfectant

Interfere with membrane functions

•    Surface acting agents : Quaternary ammonium, Compounds, Soaps and fatty acids

•    Phenols : Phenol, cresol, Hexylresorcinol

•    Organic solvent : Chloroform, Alcohol

Denatures proteins

•    Acids and alkalies : Organic acids, Hydrochloric acid , Sulphuric acid

Destroy functional groups of proteins

•    Heavy metals :  Copper, silver , Mercury

•    Oxidizing agents: Iodine, chlorine, Hydrogen peroxide

•    Dyes : Acridine orange, Acriflavine

•    Alkylating agents : Formaldehyde, Ethylene oxide

Applications and in-use dilution of chemical disinfectants

Alcohols : Skin antiseptic Surface disinfectant, Dilution used 70%

Mercurials : Skin antiseptic Surface disinfectant Dilution Used 0.1 %

Silver nitrate : Antiseptic (eyes and burns)  Dilution Used 1 %

Phenolic compound : Antiseptic skin washes  Dilution Used .5 -5 %

Iodine : Disinfects inanimate object, Skin antiseptic Dilution used  2%

Chlorine compounds  : Water treatment Disinfect inanimate objects , Dillution used 5 %

Quaternary ammonium Compounds : Skin antiseptic , Disinfects inanimate object, Dilution Used < 1 %

Glutaraldehyde: Heat sensitve instruments, Dilution used 1-2 %

Cold sterilization can be achieved by dipping the precleaned instrument in 2% solution of gluteraldehyde for 15-20 minutes. This time is sufficient to kill the vegetative form as well as spores ofthe organisms that are commonly encountered in the dentistry.

Ethylene oxide is an a agent extensively used in gaseous sterilization. It is active against all kinds of bacteria and their spores. but its greatest utility is in sterilizing those objects which are damaged by heat (e.g. heart lung machine). It is also used to sterlise fragile, heat sensitive equipment, powders as well as components of space crafts.


Evaluation of Disinfectants

Two methods which are widely employed are:

 Phenol coefficient test, Kelsey -Sykes test
 
These tests determine the capacity of disinfectant as well as their ability to retain their activity.
 

Pharmacology NEET MDS MCQ Discussion Part 1
NEET MDS

Rheumatoid Arthritis
Orthopaedics

- The hallmark feature of rheumatoid arthritis is persistent symmetric polyarthritis (synovitis) of hands and feet.
- The spontaneous onset of excruciating pain, edema, and inflammation in the metatarsalphalangeal joint of the great toe (podagra) is highly suggestive of acute crystal-induced arthritis.
- Podagra is the initial joint manifestation in 50% of gout cases and is eventually involved in 90%.

- RA is a chronic autoimmune multisystem disease having inflammatory arthritis and systemic manifestation.
 
Pathogenesis –
1.    Women (30 to 50 years) are more commonly affected
2.    HLA-DR 4 Q is a risk factor for RA.
3.    Initial site of disease is synovial membrane
Initiation phase – It is due to non – specific inflammation
 
Amplification phase – Due to T cell activation
 
Chronic inflammatory phase – Due to cytokines IL – 1, TNF- alpha (AIPG 2009) and IL – 6
 
Diagnostic criteria
Four of seven criteria are required
1.    Morning stiffness – lasting 1 hour before maximal improvement
2.    Arthritis of 3 or more joint areas – 14 possible joint areas are right or left PIP MCP, wrist, elbow, knee, ankle and MTP joints
3.    Arthritis of hand joints.
4.    Symmetrical arthritis.
5.    Rheumatoid nodules.
6.    Positive Serum rheumatoid factor
7.    Radiographic changes – including erosions or unequivocal bong decalcification localized in or most marked adjacent to the involved joint.

Rickets and Osteomalacia 
General Pathology

Rickets and Osteomalacia 

Rickets in growing children and osteomalacia in adults are skeletal diseases with worldwide distribution. They may result from
1. Diets deficient in calcium and vitamin D
2. Limited exposure to sunlight (in heavily veiled women, and inhabitants of northern climates with scant sunlight)
3. Renal disorders causing decreased synthesis of 1,25 (OH)2-D or phosphate depletion 
4. Malabsorption disorders.

Although rickets and osteomalacia rarely occur outside high-risk groups, milder forms of vitamin D deficiency (also called vitamin D insufficiency) leading to bone loss and hip fractures are quite common in the elderly.

Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia. When hypocalcemia occurs, PTH production is increased, that ultimately leads to restoration of the serum level of calcium to near normal levels (through mobilization of Ca from bone & decrease in its tubular reabsorption) with persistent hypophosphatemia (through increase renal exretion of phosphate); so mineralization of bone is impaired or there is high bone turnover.

The basic derangement in both rickets and osteomalacia is an excess of unmineralized matrix. This complicated in rickets by derangement of endochondral bone growth.

The following sequence ensues in rickets:
1. Overgrowth of epiphyseal cartilage with distorted, irregular masses of cartilage
2. Deposition of osteoid matrix on inadequately mineralized cartilage
3. Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondral junction
4. Microfractures and stresses of the inadequately mineralized, weak, poorly formed bone
5. Deformation of the skeleton due to the loss of structural rigidity of the developing bones 


Gross features
• The gross skeletal changes depend on the severity of the disease; its duration, & the stresses to which individual bones are subjected.
• During the nonambulatory stage of infancy, the head and chest sustain the greatest stresses. The softened occipital bones may become flattened. An excess of osteoid produces frontal bossing. Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the "rachitic rosary." The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward, creating anterior protrusion of the sternum (pigeon breast deformity). The pelvis may become deformed.
• When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing, most notably, lumbar lordosis and bowing of the legs .
• In adults the lack of vitamin D deranges the normal bone remodeling that occurs throughout life. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, thus producing the excess of persistent osteoid that is characteristic of osteomalacia. Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks.

Microscopic features

• The unmineralized osteoid can be visualized as a thickened layer of matrix (which stains pink in hematoxylin and eosin preparations) arranged about the more basophilic, normally mineralized trabeculae.

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