ORAL LESIONS: TOPICAL MEDICATIONS, a CLINICO-PHARMACOLOGICAL STUDY” Dr.Anil K.Sahni MS, FICS, Advanced DHA

International Journal of Scientific & Engineering Research Volume 4, Issue 1, January-2013 1 ISSN 2229-5518

“ORAL LESIONS: TOPICAL MEDICATIONS, A CLINICO-PHARMACOLOGICAL STUDY” Dr.Anil K.Sahni MS, FICS, Advanced DHA

Abstract-Clinical Practice & Hence Medical Education & Clinical Research, Witnessed Recent Considerable Increase, In Oro-Pharyngeal Diseases,With Substantial Statistically Increased Emergence Of Smoke, SmokeLess Tissue Reactions Clinical Entities E.g Various Stomatitis, Oral Mucositis, Frictional Hyperkeratosis & Sub-Mucous Fibrosis Etc.,Comprising Variety Of Clinico-Morpho-Pathological Combinations And Differing PreMalignant / Malignant Transformations. Present Study Includes More Than (2) Decades Of, Thousands Of Patients Mangement, Manifesting Different Stages Of Distinctly Variables / Mixed Clinical Presentations,Of Oral Cavity Diseases, Due To Traditional Betel, Tobacco Chewing Habits & More Recently Available Preparations Like PanMasalas & Others. Conducted Mostly, In The Eastern Parts Of India, As One Of The Maximum Incidence In The World Or Elsewhere. One Of The Most Important Clinical Applicabilities Of Basics Of Clinico-Pathological Oncology Involving Severity, Chronicity & Transformations Of Oral Lesions, Because Of Constant Exposure To Aetiological Variants, While Management Of Initial Stages Of Oral Pathologies, By Implying ‘Drug Delivery System(DDS)’ Aspects Of Pharmaco-Therapeutics, Evolved The Situation Circumstance Of Using Available Systemic, Regional Relevant Medicines Together Safely, As A ‘Local Application Preparation’,To Achieve Significant Improvement In A Large Percentage Of Population,With Variety Oral Lesions Manifestations To Significantly High ProportionsClosed Surveillance For Availability Of More Sophisticated Effective ,Safe Alternative Pharmacological Substances,To Be Replacedly Included , As Basic Constituents Of Discussed ‘Oral Preparation’, Was Maintained To Maximize Patient Benefit. Under Honest Discrete Supervision,Closely Monitored Observations Based Clinical Evaluations & Assessments, In Thousands Of Patients, Have Statistical & Logistic Support Of UseFulness, As Definitive Treatment Or Symptomatic Relief & Or As An Adjunt To Latest Modalities Of Management.Evidently Demonstrable Drastic Improvements In Associated Co-Existing ‘Oral Lesion’ Variables, Specially Of Recently More Common Infective, Inflammatory, Metabolic, Auto-Immune, Post Radiation, Chemotherapy & Other Similar Clinical Entities, Added Considerably To ‘Oral Preparaton’ UseFulness.

Keywords- 1. Smoke & Smokeless Tobacco Tissue Reactions 2. Oral Reactive Lesions Variables, Oral Pre-Malignant Lesions (OPL I & II) 3. Local Chemoprophylaxis: Clinical Efficacy & Drug Delivery System(DDS) 4. SupportiveMeasures:Chemoprevention, Nicotine Dependence Treatments, Cancer Diagnostics, Surgical & Physiotherapy Interventions WHO Classification Categorized Diseases, In 1970s & 1980s Onwards.1,2,3,Reactive Allergic 1.INTRODUCTION Clinical Scenario Hypersensitivity Reactions,Exhibit Different During Last (25) Years, Is Overwhelmed With Severity, Recurrence, Relapse And Chronicity Gradual Statistically Considerable, Increased Variants, Have Variable Premalignant (±) Evidence Of Clinical Entities Like Nicotine Malignant Transformation Potentials & Stomatitis, Oral Mucositis Of Varying Status Gradation As ‘Risk Factors’. Aetiopathogenesis, Oral Mucosal Frictional Hyperkeratosis, Oral Lichen Planus, The Attributing Aetiological Factors Include Candidiasis And Other Recently More Oral Hygiene, Tobacco Smoke & Smokeless Common Infective, Inflammatory, Nutritional, Tissue Reactions, Different Methods Of Intra- Metabolic, Auto-Immune, Post-Radiation, Oral Tobacco Applications, Available By Chemotherapy Diseases Oral Affections, Different Names, Swedish Stuff Etc. Used in Besides Established Oral Pre-Malignant lesions United States, Scandinavia & South Asia (OPL I & II) and Oral Carcinoma. Including India And Other Parts Of Globe. ------Presence Of Nonhomogeneous Group Of Author’s Correspondence Address: Compounds & Other Toxic Contents E.g. Dr.Anil K.Sahni Aldehydes, Polycyclic Hydrocarbons, A-1 / F-1 Block-A Dilshad Garden Delhi-110095 Nitrosamines, Heavy Metals & Other India. Chemicals Are Believed To Be Responsible E-Mail:[email protected] Causative Factors. [email protected] Mobile:09873083100 In The Discussed Clinico-Pharmacological Study,The Aetio-Pathogenesis Based

Scientific Pharmacological Help To These Other Indications For UseFul Applications, Lesions Had Been Achieved By A Included Different Stages Of Radiation Combination Of Different Groups Of ChemoTherapy Induced Mucositis, Oral Available Systemic Medications,, Belonging To Manifestations Of HIV/AIDS, Different Pharmacological Category.. The KidneyTransplant Patients, Other Various Different Ingredients Have Been Immunosuppressive Conditions And Constantly Replaced By Recent More Therapies Etc. Efficacious ,, Gradually Available Drug Molecules,,With Consideration Of The Local Application Ingredients Included, ‘Drug Delivery Pharmaco-Therapeutics,, To Local Antiseptics, Local Anaerobs, Achieve Maximal Available Medical Therapy Antimicrobials, Local Antifungals, Local Support,, As Curetive & Or Palliative Steroids ± Chemoprophylaxis Agents In Management Or As Adjjunct To Latest Suitable Soothing Emollient Base. Treatment Modalities.. Clinico-Pathological Oncology The Use Of ‘Oral Preparation’, Aspects Of The Study,, Comprised OverAll As Definitive Curetive Management, Control Of Severity,, Chronicity & Symptomatic, Palliative Therapy, As An Transformations Of Oral Lesions,, Because Of Adjunt To Latest Modalities Of Constant Exposure To Aetiological Variants,, PhysioTherapy; Oral Mouth Dilatation Devices By Management Of Initial Stages Of Oral Etc., Surgical Interventions; Submucosal Pathologies,, Minimizing The OverAll Injections, CryoSurgery, Low Level Laser Mortality & Morbidity Of Significantly Therapy40, Skin Grafting Etc. And Other Prevalent Disease Processes.. Latest Modalities Of Oral Disease Manifestations Management Was Done 2.MATERIALS AND METHODS Under Expert Supervision..

The Study Includes More Than (21/2) Decades Referring The Needy Patients For Specific Of,Mangement Of Thousands Of Patients, In Specialized ManageMent,, Depending Upon Different Stages Of Distinctly Variable Available Resources Circumstances.. Diseases / Mixed Clinical Pictures Of Oral OverAll Prognosis Explained Treatment Risk Cavity Manifestations.Largely Conducted In Consent Had Been Judiciously Retained The Eastern Parts Of India, As One Of The With Proper AwareNess To Patients.. Maximum Incidence In The World Or Elsewhere, Due To Traditional Betel , Tobacco Chewing Habits & More Recently Available Preparations Like PanMasalas, Supportive Measures: By Causative Factors Guthkas etc. Besides Other Conventional Abstinence,Nicotine Dependence Treatments TobaccoUse Methods. Etc., Along With Cancer Diagnostics (Oncosurgery Histopathology, Biomarkers & The Study Also Included SubjectsDifferent Imaging Etc.) For Premalignant And Regions Of India, Europe, Africa, Middle Malignant Transformations,Under Discrete East, South East Asia Clinical Expertise Supervision,Were & Other Parts Of The World. Incorporated As Available.

International Journal of Scientific & Engineering Research Volume 4, Issue 1, January-2013 3 ISSN 2229-5518

As Evident By Initial Phases Of Study, ‘Recorded Prescription During 1980s’

PHOTOGRAPH-1

Ingredients Included Basic Essential The Comparative Therapeutic Constituents In Those Forms, Assessment & Evaluation Of Various As Were Available About (25)Years Ingredients Of Local Application; With Before, Replacedly Better AvailAble With An Inquest For More Sophisticated Alternatives, Having Comparable Effective Alternative Pharmacological Mucosal Absorption, Minimal Side- Substances. Recently Availables Effects & Better Therapeutic Efficay Conveniently Effective Pharamacological Results Had Been Timely Done. Agents Were Replacedly IncludedTo Maximize Patient Benefits. VARIOUS INGREDIENTS LOCAL ADMINISTRATION Supplementary Treatment: AVAILABILITIES IncludedOralHygieneMaintenance • Local Antiseptics: Betadine, Povidone By Repeated Rinsing, Iodine, cetrimide, chlorhexidine, & Or Use Of Available Mouth Washes, benzydamines, glycols, thymols, menthols, Fortified B. Complex Lactobacillus KMNO4 Etc. Preparations. & Other Available Minerals • Local Anaerobic Antiseptics: Recent & Nutrients. Availables; metronidazole Preparations Etc.

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• Local Antifungals: Several Recent As Primary/Adjuvant Chemo-Therapy Preparations Including Antifungal Systemic & Chemoprevention Medications Lozenges, nystatin, clotriamzole, Troches,  Antioxidants, Anticholinergics & Coating fuconazole Preparations. Agents • Local Steroids: hydrocortisone,  Antiinflammatory agents beclomethasone, triamcinolone Etc.  Aminoacids (Especially L-Glutamine with • Local Anti-Allergic & Anaesthetic: Enhanced Delivery Systems) diphenhydramine and lidocaine Ointment  Growth Factors: GM-CSF (Granulocyte Preparations Macrophage Colony Stimulating Factor), • Spirulina Fusiformis Therapy G-CSF (Granulocyte Colony Stimulating Factor), Topical & or Systemic • Antimicrobials: HSV – Antiviral Therapy, Administrations. Most Effective Available • calcium phosphate Rinse (Caphosol), e.g. Palifermin fluoride Gel, magnesium hydroxide,  Protease Inhibitors, e.g. Bowman & Birk aluminium Hydroxide, silver Nitrate Inhibitor Concentrate (BBIC) etc. Solution, chamonile Mouth Wash, Coating  Bleomycin 5 FU Based Chemotherapy Agents (sucralfate), Effervescent mucomelt; (Edatrexate etc.) n-acetyl cysteine (600 Mgm.),  High Dose Melphalan glutathione Replenishers39 Etc.  Tea and Tea Components, Especially • Traumeel S (Homeopathy) Green Tea (Polyphenolic Compounds Called AS Catechins Most Abundant The Above Mentioned Gradually Epigallocatechin, -3 Gallate (EGCG). Available ‘Better Alternatives’, Recent Availabilities Include:- For ‘Basic Ingredients Of Local AmlexanoxOralPaste,100MgmPaste Preparation’, Were Assessed Evaluated Contains (5)Mgm Amlexananox(Anti- For Safety Profiles,Convenience, Clinical Ulcer Agent) -Rebamipide, Efficacy,Costs Etc. , And Were Replacedly Anti-UlcerDrug,(100)MgmsTablet, 34,35 Incorporated Into ‘Oral Preparation’ . TDS Orally

6 ROLE OF OTHER MEDICATIONS SCAR MANAGEMENT MEDICATIONS • Vitamin ‘A’, Retinol Etc. Retinoids, - • Centella Asiatica, Wheat Germ Carotene, 13-Cis-Retinoids (Topical)13,14, Oil, Lavandus, Aloe Vera, Tea N-4-Hydroxy-Carbophenyl-Retinamide Tree Oil & Honey Cream Etc. (4hcr), Feneretinide.  Other Herbal Preparations • Vitamin ‘E’: -Tocopherol, Gelenium  Chinese Medications • Lycopene  Choline Salicylates, Tannic Acids, Tannins • Lactoferrin Etc. • Cyproxanthin  Recent Scarolytic Ointment; Contractubex • Transforming Growth Factor Beta 1 Etc.

International Journal of Scientific & Engineering Research Volume 4, Issue 1, January-2013 5 ISSN 2229-5518

Chronic Stomatitis Type III With A Granular Mucosa Dorsum Of Tongue, Stomatitis With Erosions

Nicotine Stomatitis Partial Erosions Caused By Smoking

Chronic Candidiasis Chronic Nodular Candidiasis

International Journal of Scientific & Engineering Research Volume 4, Issue 1, January-2013 6 ISSN 2229-5518

ACUTE(±) CHRONIC Statistical Reports Of Prevalence, In (4 / 1,000) ORAL PATHOLOGIES Adults In Rural India And As Many As (5) SUBMUCUS FIBROSIS Million Young Indians Sufferers. Schwartz(1952) Formulated The Term, Known Causative Agents Include: Areca Nut, ‘Atrophica Idiopathica Mucosa Oris’ to Betel Quid Chewing, describe an oral fibrosing disease, While The Ingredients And Nomenclature Of Betel Joshi(1953),Used‘Oral Sub-Mucous Fibrosis Quid Vary By Region, (OSF)’, All Though Basic Constituents In Different To Describe Diseases Characterizied By, Combinations Are: • Fibrous Tissue reaction Beneath Oral Areca Nut (Fruit Of The Areca Catechu Palm Mucosa, Due To Variable Aetiological Tree, Erroneously Termed Betel Nut): Variants Attributing Constant Prolonged Arecoline, An Alkaloid Found In The Areca Friction ; Irritation, ? Chemical, Repeated Nut, Promotes Salivation, Stains Saliva Red, Trauma, Nutritional, Recurrent Infections And Is A Stimulant. & Inflammations Of Different Causes. Betel Leaf (From The Piper Betel, A Pepper • Leading To Allergic Hypersenstivity Shrub), Tobacco, Reactions ; Increased Fibrogenesis Slaked Lime (Calcium Hydroxide): Maintains Beneath Oral Mucosal Layer. The Active Ingredients In Its Freebase Or This Hypersensitivity Reaction May Alkaline Form, Thus Facilitating Their Often Results. Entrance Into The Bloodstream In A Juxta-Epithelial Inflammation That Via Sublingual Absorption Leads To Increased Fibroblastic Catechu (Extract Of The Acacia Catechu Tree): Activity Resulting In Formation Of Stains Saliva Red. Collagen Fibrein Lamina Propria. The Habit Practiced Predominately In These Collagen Fibers Are Non Degradable Southeast Asia And India, From Thousands And The Phagocytic Of Years.Similar To Tobacco Chewing In Activity Is Minimized. Westernized Societies.

• "Oral Submucous Fibrosis--A Chronic Disseminated Intravascular The Increased Popularity Of The Habit Of Coagulation Syndrome Chewing Pan Masala( Mixture Of Spices With Local Coagulopathy.", Including, Betel Nuts, Catechu, Menthol, Reports Are Available In Literature. Cardamom, Lime And Others), With Mild Prevalence & Aeiology;The Clinical Entity Stimulating Effect ,Often Eaten At The End Of Being Well Recognized For Its Malignant The Meal To Help Digest Food And Potential As A Mouth Freshner.

Submucous Fibrosis Leading To Restricted Mouth Opening Ability, Buccal Mucosa Has Marbling Appearance

International Journal of Scientific & Engineering Research Volume 4, Issue 1, January-2013 7 ISSN 2229-5518

Submucous Fibrosis Tongue: Submucous Fibrosis Tongue With Atrophy, Erosions Squamous Cell Carcinoma Development The Present Study Includes Available Wrinkles, White Leathery Lesion11, Ulcer (±), Statistical Evidence Of, Hyper Keratinization, Acanthosis, Epithelial Relation Between Differential Uses Of Variety Fibrosis + Atrophy & Hyper-Plasia, Overlying Of Tobacco Products, Epithelium, Epithelial Dysplasia, Epithelial Especially Recent Availabilities Of Different Vacuolations, Gingival Reactions (±) PanMasalas,Gutkhas, Containing Increased Concentrations Of Including Progressive Difficulty In Opening Various Chemicals ? Synthetic Mouth Of Variable Extents, Difuse , Localized Substances ? Adulterations , Fibrous Bands, Adhesions Formation At Cheap Alternatives Etc. Various Folds & Sulcii Of Oral Cavity, With With Localized & Or Generalized Nature Of Differing PreMalignant & Or Malignant Oral Manifestations, Transformations. & Different Clinical Histories Of Severity, Chronicity, Previous Episodes, Recurrences , PINDORG J.J: (3) Clinical Stages Relapses Etc. o Stage 1: Stomatitis Aetiopathogenesis; o Stage 2: Fibrosis  Dose Dependence Between Areca Quid A- Early Lesions, Blanching Of Chewing Habit & SMF The Oral Mucosa  Areca Nut:Alkaloids;Arecoline(Most Imp.) B- Older Lesions, Vertical And • Modulation Metal Protienases,Lysal Circular Palpable Fibrous Bands Oxidases & Collagenases In And Around The Mouth Effect Collagen Metabolism: Increased Or Lips, Resulting In A Mottled, Fibrosis Marble-Like Appearance Of • During  Fibrosis : Water Retaining The Buccal Mucosa ProteoGlycans o Stage 3: OSF Sequelae Increased Collagen Type 1 Production A- Leukoplakia Genetic Predisposition: Aetiological B- Speech And Hearing Deficits Importance • Gene PolyMorphism: Coding For Treatment; Depends On The Degree Of Tumor Necrosis Factor- (TNF-) : Clinical Involvement. Fibroblast Stimulation Fibrosis o Early Disease Detection, Cessation Of The Habit Is Sufficient. • Other Cytokinins Aberrations o Most Patients Present With Moderate- Transforming Growth Factor-Beta & Interferon- To-Severe Disease. Moderate-To-Severe OSF Is  Collagen Production &  Degradation Irreversible. • Genetic Predisposition o Medical Treatment;Symptomatic, Human Leukocyte Antigen Molecules: Predominantly Preventive & Aimed At HLA-A10,-B7 & DR-3 Clinical Manifestations; Mouth Movements Improvements.

International Journal of Scientific & Engineering Research Volume 4, Issue 1, January-2013 8 ISSN 2229-5518

Pentoxifylline (Trental), A Methylxanthine Excision Of Bands & Adhesions Etc. Derivative With Vasodilator Properties,

Increases Mucosal Vascularity, Stem Cell Therapy: Autologous BoneMarrow Recommended As An Adjunct Therapy In Stem Cells Intralesional Injection, Is A Safe The Routine Management And Effective Treatment Modality . o Submucosal injections: Induces Angiogenesis In The Area Of Lesion -Hylase7 Decreasing The Disease Extent(Fibrosis), -Hydrocortisone Leading To Significant Increase In Mouth -Human Chorionic Opening. 8,9,10 Gonadotrophins (Placentrax) 2-3 ml per sitting twice or thrice in a week MUCOSITIS for three to four weeks. (MUCOSAL INFLAMMATION) Aim To Achieve Similar Results By Using ‘Steroidal Constituent ’ Of Aetio-Pathogenesis: Besides Various The ‘Oral Lotion’, Had Been Practiced For Etiological Variants Of Vivid Clinical Disease Years, With Differentially Sucessful Result Entities Including Metabolic, Outcomes.The Latest Availability Of Nutritional,ImmunoCompromised ‘Topical Steroid’ States,Tranplant Patients Chemotherapy E.g triamcinolone Etc. ,The Clinical (Standard & Or Marrow Ablative), Radiation Efficacy, Safety Profile , Local & Systemic Therapy, Drugs, Chemicals Induced Are SideEffects Are Comparatively Important. Convincingly Acceptable. o Surgical Treatment:Indicated In Clinical Manifestations: Progressive Fibrosis, Beside Other Presentations, When Inter-Incisor Distance Becomes Less ‘Dysgeusia’ Or An Alteration In Taste Than 2 Centimetres (0.79 In). Perception Or "Taste Blindness," Multiple Release Incisions Deep To Mucosa, Temporary Condition, Because Of Effects On Submucosa And Fibrotic Tissue And Suturing Taste Buds. The Gap Or Dehiscence By Mucosal Graft Obtained From Tongue And Z-Plasty Multiple Deep Z-Shaped Incisions Are Made And Then Sutured In A Straighter Fashion To Gain Length.

Aspirin Burn Antibiotic Induced Stomatitis

International Journal of Scientific & Engineering Research Volume 4, Issue 1, January-2013 9 ISSN 2229-5518

“CHEMICAL / CONTACT ORAL INFLAMMATORY LESIONS”

Agricultural Compounds Contact Stomatitis, Erosions

MUCOSAL INJURY PATHOPHYSIOLOGY (3) Additional Signaling & Amplification Phase: Enhancement Synergism Of Previous Mucosal Injury & Subsequent Healing Process Pathways Leading To Generation Of Involves All Mucosal Layers Including Additional ProInflammatory Cytokines. Extracellular Matrix Besides Epithelium Only. Upto This Stage Mucosal Anatomy Being Intact. (5) Stages Process Involve Complex Molecular, Cellular & Histopathological (4) Symptomatic, Ulceration Phase: Clinical Events Manifestations Including Ulcerations, Pain, Bleeding, Complicated By Microbial (1)Initiation Phase: Oxidative Stress Due To SuperInfections & Decreased Salivary Different Mechanisms Being Basic Causative Function Leads To Enhance Mucosal Injury Factor. (5) Healing Phase: Process Depends Upon (2) Upregulation Of Transcription Factors & Angiogenesis And Increased Biological Messenger Signals Generation Phase: Activity Of Extracellular Matrix. NK- beta (Central vital role) In Myeloblastic Conditions Healing Phase May Not Begin Until Leucocyte Recovery.

Subsequent Upregulation Of All (5) Phases Does Not Necessarily Follow Upgradation Of Cycloxygenase-2 Linear Progression, Regulators  Upregulation But May Occur Simultaneously At Different Multiple Matrix Locations. ProInflammatory Metalloproteinase Cytokines, e.g. System TNF-, IL-1, Mucositis Assessment Evaluators: Scales IL-b Commonly Used, Combined Information From Both Patient’s Signs And Symptom In Addition Sphyringomyelinase & Ceramide Scores, With Patient’s Functional Status & Pathways, Fibronectin Break-Up And Ability To Eat. Macrophagic Activities (Complex Events) Lead To, Further Mucosal Injury & Apoptosis.

NICOTINE DEPENDENCE TREATMENTS

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(A) Non-Pharmacologic Treatments Overall NRT Efficacy In Various Subgroups Including Different Smoking 1) Self Help, Intervention & Counseling Characteristics Varying Mild, Moderate, Etc. By Print, Live & Various Electronics High Dependence Levels, Body Weights, Media Aids Including Telephone Based Ethnic, Racial Groups & Genders, By Cessation Counseling & Others. Various NRT Preparations, Studies Are Available & In Process. 2) Behavioural Therapies Include Guidance And Instructions On Elements Of Nicotine 2) FDA-ApprovedNon-Nicotine Fading Quit Date Contracting, Pharmacologic Treatments: Management Of Smoking Triggers, (i) Bupropion SR (Zyban) – An Anti- Relaxation Techniques Strategies, Trigger Depressant, Exact Action Mechanism Not Management & Relapse Prevention Fully Known, Efficacy Mediated By In Various ‘Cognitive-Behavioural Reduction Dopamine & Norepinephrine Smoking Cessation Programme’ & Uptake & Or Nicotine Receptor ‘Educational Control Condition’, Schedules. Antagonist Effects. The Second Mechanism May Involve Drug Ability To Prevent / Diminish Post Cessation (B) Pharmacologic Treatments3 Negative Effects & Weight Gain, Cited As Causes Of Relapse Among Smokers. 1) FDA (Food & Drug Administration)- (ii) Varenicline (Chantix) – Is An 42 Approved Neuronal Nicotinic Acetylcholine Nicotine-Replacement Therapies: Receptor (nAchR) Partial Agonist, By US-FDA Approved (5) Nicotine Activation Of These Receptors Widely Replacement Therapies (NRTs): Expressed On Dopamine & GABA (i) Transdermal Patch, (ii) Gum, (iii) Nasal Neurons In The Ventral Tegmental Area, Spray, (iv) Inhaler, (v)Lozenge, Varenicline Has Attenuation Effect On While 6th NRT (vi) The Sublingual Tablet Dopamine Release While Maintaining Is Used Only In Europe. Dopaminergic Tone, Thus Minimizing Nicotine Craving & NRTs Are Tolerable, Safe With Results Withdrawal By Agonist Function, Achieved By: While Antagonist Properties May (i) Ameliorating Withdrawal Symptoms Attenuate Reinforcing Nicotine Effects, Due To Initial Physical & Leading To Reduced Smoking Satisfaction Psychological Reactions To Cessation, And Relapse Likelihood. E.g. Irritability, Restlessness, Tobacco Dependence Treatment & Depressed Mood & Poor Clinical Oncology,Have Different Concentrations Versatile Aspects. If Tobacco Is The Choice, Chewing May Be (ii) Reducing Nicotine Craving Preferred Over Smoking, Experience & Limiting Possible With Assured Oral Hygeine Maintainence. Weight Gain (For Gum & Patch) Overall Assessment And Management Of Generalized Body Affections Of Tobacco (iii) Providing Safer Way To Experience 4Including Atherosclerosis, Peripheral Neurobiological&Psychophysiologic Vascular Diseases Etc, Effects Of Nicotine. Being Important Constituent Of For Quit Rates Relapse Intervals, Rapid Nicotine Dependence Management. Release Formulations Have Better Efficacy DIAGNOSTIC AIDS15 For Post Cessation Cravings. Include: (A) Surgical Pathology 32

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 FNAC, Histopathology: Excisional, Incisional (C) Imaging Biopsy, Exfoliated Cell Sampling25,26,27 For Size And Other Details Of Lesion, (1) Global Obtained by Mouth Rinse, Stage Migration By Plain X-Ray Films, CT, Swabs Etc., Angiography, USG, MRI & MR (2) Specific, e.g. Scrapes of Leucoplakia Spectroscopy Nuclear Medicine And Or Other Lesions. Positron Emission Tomography (PET)  Immuno-Histochemistry (IHC) Especially FDG (Radiolabelling)-PET.  For Deciding Type, Nature Of Lesions, Tissue Of Origin, (±) Metastasis, Including Dysplasia Presence With Severity Degree, HEAD & NECK CARCINOMA28 Loss Of Heterozygosity (LOH), RISK FACTORS: Allelic Imbalance (AI), CIS Being  Alcohol , Tobacco, Areca Nut / Quids Important Predictive Parameters. / Pan Masalas,Various Other Chewing  For Confirming Various Benign Lesions, Tobacco Preparations,Snuffs Etc. Premalignant (OPL I & II), Malignant Alone Or Concurrent Use. Lesions & Course Of Disease Process. Precipitated By Poor Dento-Oral (B) Molecular Diagnostics 19,20 Hygeine,Sumps,Sore Circulating Tumor Markers Teeth,Susceptibility,Leucoplakia Etc. 26,27,28 Detection ,Tumor NDA, Circulating  Human Papilloma Virus & Tumor Related Antibodies, Mutant P53 Other Viral Infections Human Gene Sequences, Viral DNA - ELISA Test Simplex Virus-1 (HSV-1), For Serum IgA Response To EBV-related EBV, IG-18, E6 PRO,+P3Tumor diseases, Anti-TK (Thymidine kinase) Suppressor Gene P53, Leading to P53 Antibodies, Fluorescence Degradation Tumorigenesis, P53 Spectroscopy,Mid-InfraRed Fibreoptic Tumor Suppressants, Spectroscopy Attenuated Total Plummer-Vinson & Reflectance Spectroscopy, Being Important Paterson Kelly Syndrome Tool For Differentiating Between Benign  Poor Nutrition, Carcinogen Exposure, & Malignant Oral Mucosa21,22,23,24 Genetics.

Sanguinaria-Associated Oral Leukoplakia

Homogenous Leukoplakia Buccal Mucosa MALIGNANT TRANSFORMATIONS 29,30

(A) (B) (C) Medium Risk Low Risk/ High Risk IJSER © 2013 Lesions Lesionshttp://www.ijser.org Equivocal Risk • Speckled • Syphlitic Glossitis Lesions Erythroplakia • Oral Submucous • Discoid Lupus • Erythroplakia Fibrosis Erythematosis • Sideropenic • Oral Lichen International Journal of Scientific & Engineering Research Volume 4, Issue 1, January-2013 12 ISSN 2229-5518

POTENT

POTENTIALS FOR MALIGNANT CHANGE

o ↑ With ↑ Age Of Pt. o ↑ With ↑ Age Of Lesion o ↑ In Smokers o ↑ In Alcohol Consumption o Anatomical Site Dependence -Floor Of The Mouth ↑ With Leucoplakia12 -Ventral Surface Of Tongue Esp. Younger ♀ Even Without Associated Risk Factors

LOCAL MEDICATIONS: OTHER INDICATIONS Leuko-Erythematous Lesions

With The Use Of Discussed Preparation; Ulcerative Lesion Reasonably Good Results Achieved, In Following Conditions:

(1)HIV AIDS Oral Manifestations (2) Other Immunosuppressive Conditions (3) Immunosuppressive Therapies (4)KIDNEY TRANSPLANT PATIENTS

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(8) Difficult Endo-Tracheal Intubation Conditions, ? (Decraesed Mouth Opening) Oral SMF Extending To Oro-Naso- Pharyngeal Regions Re-Assessment during Pre-Anaesthetic Checkup Or Otherwise Important Cause

“RESULTS”

 The Discussed Clinico-Pharmacological Study Involves, Successful Overall Management Of Thousands Of Patients, >(2500) Uremic Stomatitis, Cases,Comprising Large Variety Of ‘Oral Lesions’ Variables, Gray-Pseudomembranous Lesion Clinical Distinct & Or Mixed Clinical Manifestations, Hyperkeratotic (White) Lesion Differing In Regards To Cure, Definitive, Symptomatic Management, Of Varying Disease Severity & Chronicity, Recurrence, Relapse & Or Progression To Pre-Malignant & Or Malignant Lesions.

 Gradually Better Available Pharmacological Substance Alternatives, For The Basic Constituents Of The ‘Oral Necrotic Pseudomembrane Preparation’, Were Replacedly Administered,During >2 Covered Ulceration Decades (20-25 Years) Continuing Study Duration. UREMIC MANIFESTATIONS  Augmentation Support By; Newer Efficacious Systemic & Or Local (5) Radiation Mucositis Of Different Medications, 38 Aetiopathogenesis , Chemoprevention Measures, 34,35,36,37 Chemotherapy Induced Abstinence Control Management

Regulations Of Various Causative

(6) Drug Reaction Manifestations, Metal Factors, E.g Nicotine Poisonings Etc. Dependence/Replacement Treatments Etc. Gradually Available In Due Course Of

(7) Dentition And Denture Related These Many Years, Lesions Were Appropriately Incorporated.

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 Retaining Discrete Expert Clinical While The Sucessful Use Applicabilities Also Assessment Increased Several Folds For Oral Lesions As The Basic Diagnostic And Accompanying Recently More Prevalent Therapeutic Tool Infective, Inflammatory Conditions,Immuno- In Regards To Treatment Efficacy End Compromised Situations,Renal Transplant Points, Patients, & Several OthersClinical Entities. Various Surgical, Histo-Pathologies, Molecular Diagnostics (Different Bio- The Fundamental Need To Have All The Markers) & Imaging Techniques, Necessary Basic Ingredients Assessments32,33 (Anti-Septic, Anti-Microbial Specially For Were Colloborated,In The Disease Anaerobs Flora, Anti-Fungal & Tropical Management Plan As And Where So-Ever Steroid In A Suitable Welcoming Use Needed And Practically Available In Flavour Base), Consideration Of Resources. Constituted For Efficient Delivery Convenient Preparation Module,  After Properly Conveyed Needed Demands Intensive Pharmaco-Therapeutics ‘AwareNess’, Research To Provide ‘Prognosis Explained Treatment Safe, Efficient Medications Effective By Consent’, Local/Tropical/Regional Route Of Was Seeked, From Allmost Every Patient, Administration , With Maximally Effective Especially In The Situations Of Mucosal Barrier Absorption & Minimal Local Clinically Evident Suspicion. & Or Systemic Side-Effects.

 Repeated Referral Advise, The Convincing Rendered Help By With AwareNess Of Expert Management Combining Age-Old Herbal & Resources, Or Other School Of Medicines Effective Well Before, Within Time, Preparations, Especially In Peripheries Were Being An Important Part Of The OverAll Emphasized, Management Module, In Demanding Situations. For Oral Disease Manifestations. While The Safe Oral Application Use Of “DISCUSSION” Classical Scarolytics Applications, Available Topical Steroids, Retaining The Very Basic Aim Of The Study, To More Recent Applications With Similar Initiated More Than (25) Years Ago, Pharmaco-Kinetics To Definititively Treat & Or Provide Like Contractubex ,Amlexanox, Maximal Relief In The Usually Mixed Along With Advent Of SuccessFul Intra-Oral Combinations Of ‘Oral Lesions’ & Or Solitary Appliances For Variables, Cryo-Surgery & Laser Applications & Under Closed Obsevation Clinical Expertise Physio-Therapy, Supervision,With The Then Available At Appropriate Time,Stage Of Disease Process, Constituent Ingredients & Supplementary May Offer Necessary Remedial Solution For Therapy. Contolling Basic Underlying Witnessed Gradually Available Efficacious Patho-Genesis Of Ac./ Sub-Ac./ Chronic Medication Alternatives, Inflammatory Changes, Conversion Processes Supportive Chemo-Preventive Therapies, Of Cicatrization Involving Fibrin, Collagen & Surgical & Physiotherpy Procedural Supports, Other Similar Simulating Tissue Reactions.

ACUTE (±) CHRONIC ORAL LESIONS

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Hyper Senstivity (Trauma, Infective, Inflammatory, Chemical, Chr. Irritation, Frictional) Tissue Reactions

‘THERAPY’

Tropical Steroid, Healing By Cicatrization Tropical Antifungal, (COLLAGEN  FIBROUS TISSUE REACTIONS Antiseptics, Keratolytics, Etc.) Other Medications (Chemo-

Prevention Etc.)

“AIMED AT”

PRE-MALIGNANT & OR MALIGNANT TRASFORMATIONS

“DEFINITIVE SUPPORT BY ABSTINENCE FROM CAUSATIVE FACTORS, NICOTINE DEPENDENCE MANAGEMENTS (NRTs) Etc., & AVAILABLE CANCER DIAGNOSTICS”.

‘Oral Lesions: Clinico-AetioPathogenesis & Pharmaco-Kinetics Aspects’

“TABLE”

“SUMMARY”

As Discussed The Study, Incorporating Replacedly Better Available Safe Being One Of The Most Needed, Pharmacological Agents, Important, Clinical Research, For Various Constituent Ingredients Of The Of Present Times, ‘Oral Topical Application’, With An Aim To Control (Minimize), With Efficacious Oral Mucosal Absorption, Considerably Prevalent Oral Disease Entities, Clinically Justifiable Result Outcome, More Disabling Due To Non-AwareNess, & Minimal Side-Effects(Local/Systemic Etc.) ‘No’ & Or Unproper Treatment, ManageMent GuideLines, Recurrence, Relapse, Chronicity, With Or Without Pre-Malignant & Or Malignant Transformations.

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Supported By Various Gradually Available Systemic & Or Local Therapies. Surgical & Physiotherapy Interventions Etc. Prevention And Or Regulation Management Of Basic Aetiological Factors, E.g Nicotine Dependence/Replacement Managements Etc. Judiciously, Expert Regular Clinical Assessments,In Colloboration With Various Histopathologies (Invasive, Minimal/ Non-Invasive …), Tumor “ACKNOWLEDGEMENTS” Markers, Biological Assays, Imaging, And Various Diagnostic & Or Sincere Gratitudes For The Medical Teachers, Therapeutic Tools. Experts & Pioneers, Clinical Practicioners With Excellence, The Fundamental Management Guidelines Of, In The Parts Of The Globe, Proper Awareness & ‘Prognosis Explained Having Predominant Prevalence Of These Treatment Risk Consent’, Diseases, With Timely Emphasized No-Delay, For Wisdom To Foresee Extents & Magnitudes Referral Of The Cases For Expertise Of These ‘Mixed Variety Of Oral Lesions’ , Management, As Needed, Especially In View Of Initiation Of Newer Minimizing The Morbidity & Mortality In A Tobacco Products, Large Group of Population, Side-Effects Of Recent Treatment Modalities With Significant Disease Prevalence. & Diseases, In Conjunction With ‘World Health OverAll Control Of Severity,, Chronicity & Organization(WHO)’ Reports Transformations Of Oral Lesions31,, Because Of During 1970s & 1980s OnWards. Constant Exposure To Aetiological Variants,, By Management Of Initial Stages Of Oral Pathologies,, Minimizing The OverAll Mortality & Morbidity Of Significantly Prevalent Disease Processes.. The Pharmacological Aspects Of The Study Demands, Needed Appropriate Medications, Satisfying Parametres Of Therapeutics, FUNDING /SUPPORT; No Financial Based Upon The Principles Of ‘Drug Delivery Assistance WhatSo Ever Received System’, During Discussed Work. Research Of Modern Pharmaceuticals, Supported By Causative Factors Abstinence Regulations & Other Recent Management Modalities For Prevalent Versatile ‘Oral Disease Manifestations’ Of Vivid Aetio-Pathogenesis.

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