RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, …



SYNOPSIS

Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.

“SERUM PROTEIN PATTERN, C-REACTIVE PROTEIN AND CERULOPLASMIN LEVELS IN ALCOHOL-DEPENDENT MALES”

Name of the candidate : Dr. ANITHA MARIA THOMAS THATTIL

Guide : Dr. SHIVASHANKARA AR MSc, PhD

Course and Subject : M.D. BIOCHEMISTRY

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DEPARTMENT OF BIOCHEMISTRY

FR. MULLER MEDICAL COLLEGE HOSPITAL,

KANKANADY, MANGALORE – 575 002

2010

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE.

ANNEXURE – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

|1. |Name of the candidate |DR ANITHA MARIA THOMAS THATTIL |

| |And address |POSTGRADUATE RESIDENT (MD) |

| |(in block letters) |DEPARTMENT OF BIOCHEMISTRY |

| | |FATHER MULLER MEDICAL COLLEGE |

| | |MANGALORE. |

|2 |Name of the Institution |FATHER MULLER’S MEDICAL COLLEGE |

|3 |Course of study and |MD BIOCHEMISTRY |

| |Subject | |

|4 |Date of admission to course |30-04-10 |

|5 |Title of the Topic |

| |“SERUM PROTEIN PATTERN, C-REACTIVE PROTEIN AND CERULOPLASMIN LEVELS IN ALCOHOL-DEPENDENT MALES” |

| | |

|6 |BRIEF RESUME OF THE INTENDED WORK: |

| |6.1 Need for the study |

| |Alcohol-dependence is a disabling addictive disorder, characterized by compulsive and uncontrolled consumption of alcohol despite |

| |its negative effects on the drinker's health, relationships, and social standing.1 High alcohol consumptions are correlated with an|

| |increased risk of developing cardiovascular disease, malabsorption, chronic pancreatitis, alcoholic liver disease, cancer, and |

| |damage to the central nervous system and peripheral nervous system . The most common cause of illness and death from liver disease |

| |is long-term alcohol consumption. Liver is the primary site of alcohol metabolism. Injury to the liver comes not only from ethanol, |

| |but its dangerous products of metabolism like acetaldehyde and free radicals.1,2 Many molecular and metabolic phenomena have been |

| |implicated in the pathogenesis of alcohol-related diseases. Alcohol promotes the formation of free radicals and interferes with |

| |antioxidant defense mechanisms of the body. Toxic compounds like acetaldehyde generated during alcohol metabolism, form adducts with|

| |DNA and proteins. 1,2 |

| | |

| |Changes in plasma protein levels and status of acute phase protein pattern are keenly studied by researchers worldwide. Serum total |

| |proteins can be affected in heavy drinkers. A common feature of chronic alcoholic liver disease is progressive hypoalbuminaemia.2 |

| |C-reactive protein (CRP) has been found to be an accurate marker of alcoholic hepatitis. It is also considered a marker of future |

| |cardiovascular death.2 Studies have shown conflicting results about the serum copper and ceruloplasmin levels in alcoholics. 3 |

| | |

| |There are still some gaps in our knowledge about serum protein patterns, the role of C-reactive protein and ceruloplasmin in the |

| |pathophysiology of alcohol-related disorders. This study has been undertaken to throw more light on the relevance and importance of |

| |these biochemical parameters in alcohol-dependent patients. |

| | |

| |6.2 Review of Literature |

| |Alcohol-dependence syndrome, according to ICD-10 is diagnosed if three or more of the six criteria are met for at least a period of |

| |one month during last 12 months. These criteria are craving for alcohol, impaired capacity to control alcohol taking behaviour, |

| |physiological withdrawal state, tolerance, preoccupation with alcohol use and persistent alcohol use despite clear evidence of |

| |harmful consequences. A number of self-report screening tests have been developed to identify alcoholics as well as persons at risk.|

| |One of the most widely used alcohol screening test is CAGE (C-cut down, A-annoyed, G-guilty, E-eye opener), which contains only four|

| |questions. Reliability and validity studies of this test have been conducted in diverse samples with generally acceptable levels of |

| |sensitivity. The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item screening instrument that may be used for recording |

| |comprehensive and sequential alcohol use. It has been shown to be sensitive and specific in discriminating alcoholics from |

| |nonalcoholics. The AUDIT total score increases with the severity of alcohol-dependence and related problems.4 |

| | |

| |Acute as well chronic ethanol consumption has been shown to inhibit hepatic protein synthesis and secretion. Studies have found |

| |progressive hypoalbuminemia in patients with chronic alcoholic liver disease. In spite of a rise in mRNA level of albumin in liver |

| |in response to alcohol intoxication, the decrease in serum albumin level is attributed to nutritional status of the subjects. |

| |Albumin is a potential subject of formation of adduct by acetaldehyde, an alcohol metabolite. This albumin or other protein adducts |

| |can stimulate the formation of immunoglobulins, thus causing a rise in serum globulin level.1,2,5 The appearance of |

| |carbohydrate-deficient isoforms of glycoproteins such as transferrin has been proved as a marker of chronic alcohol consumption. 2 |

| | |

| |Majority of the plasma glycoproteins are acute phase proteins. It has been reported that chronic alcohol consumption stimulates the |

| |hepatic synthesis of acute phase proteins. Prominent among the acute phase proteins is CRP. Moderate alcohol intake is associated |

| |with decreased CRP and leukocyte count, but there is an inverse association with heavy drinking.6 CRP has also been found to be an |

| |accurate marker of alcoholic hepatitis. |

| | |

| |Altered serum levels of copper and ceruloplasmin have been reported by previous studies but, there are contradicting findings with |

| |some studies reporting lower levels while others reporting higher levels in alcoholics.3 |

| |6.3 Objectives of the study |

| |To estimate the serum levels of total proteins, albumin, C-reactive protein and serum ceruloplasmin in alcohol-dependent males in |

| |comparison to healthy controls. |

| |To study the serum protein electrophoresis pattern in alcohol- dependent males in comparison to healthy controls. |

|7. |Material and methods: |

| |7.1 Source of data |

| |Subjects will be Alcohol–dependent male patients admitted to the de-addiction centre of Father Muller Medical College Hospital. |

| |Healthy male volunteers will be the controls. |

| |Data are collected through questionnaires and assays of serum proteins and protein pattern. |

| |7.2 Method of collection of data ( including sampling procedure, if any) |

| |Type of study |

| |Cross sectional, case control study |

| |Method of collection of data |

| |30 alcohol-dependent male in-patients will be recruited randomly for the study over a period of 1 year. Psychiatric diagnosis, |

| |medical history, relevant clinical findings and other investigations will be obtained from the clinical case files. Sociodemographic|

| |data will be collected using a proforma designed for the study. Alcohol consumption related data will be obtained by using AUDIT |

| |which is a screening questionnaire for detailed alcohol use history. |

| |Controls include thirty age-matched normal, apparently healthy males. CAGE questionnaire will be administered to volunteers to |

| |exclude those with problem drinking. |

| |Inclusion criteria for cases: |

| |1. Age: 18-65 years. |

| |2. Alcohol dependence syndrome - diagnosed by a psychiatrist. |

| | |

| |Exclusion criteria: |

| |1. Patients in delirium |

| |2. Patients with systemic illnesses |

| |3. Patients with other substance abuse/dependence including nicotine. |

| |Methods : |

| |About 5 ml venous blood will be collected and in serum under aseptic precautions and following assays will be done : |

| |Total proteins: estimated by biuret method, 7 |

| |Albumin : estimated by bromocresol green dye binding method, 7 |

| |C-reactive protein (CRP): estimated by turbidometric method, 8 |

| |Ceruloplasmin: Assayed using p-phenylene diamine dihydrochloride as the substrate.9 |

| |Serum protein electrophoresis: carried out using agarose gel and horizontal gel electrophoresis equipment.7 |

| |Plan for data analysis |

| |Collected data will be analysed by |

| |- unpaired t test |

| |- Karl Pearson correlation co efficient |

| | |

| | |

| | |

| | |

| |7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please|

| |describe briefly. |

| |Yes. With aseptic precautions, about 5ml of venous blood will be collected from inpatients with alcoholic-dependence syndrome and |

| |controls after taking written informed consent. |

| | |

| |7.4 Has ethical clearance been obtained from your institution in case of 7.3 |

| |Yes. |

|8 |LIST OF REFERENCES |

| |Zakhari S. Overview: How is alcohol metabolized in the body? Alcohol Res Health. 2006; 29:245-255. |

| |Das SK, Dhanya L, Vasudevan DM. Biomarkers of alcoholism: an updated review. Scand J Clin Lab Invest. 2008; 68: 81-92. |

| |Wu CT, Lee JN, Shen WW, Lee SL. Serum zinc, copper and ceruloplasmin levels in male alcoholics. Biol Psychiatry. 1984; 19:1333-1338. |

| |World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic |

| |Guidelines. Geneva: World Health Organization;1992. |

| |Annoni G, Weiner FR , Colombo M , Czaja MJ and Zern MA. Albumin and collagen gene regulation in alcohol and virus-induced human liver|

| |disease. Gastroenterology. 1990; 98: 197-202. |

| |Vanbiervliet G, Breton FL, Allieri MR et al. Serum C-reactive protein: A non-invasive marker of alcoholic hepatitis. Scandinavian |

| |Journal of Gastroenterology. 2006 ; 41: 1473 – 1479. |

| |Varley H, Gowenlock AH, Bell M. Varley’s Practical Clinical Biochemistry; 5th edition.London:William Heinemann Medical Books |

| |Limited ;1980: 538-595. |

| |Otsuji S, Shibata H, Umeda M. Turbidimetric immunoassay of serum C-reactive protein. Clin Chem. 1982; 28: 2121–2124. |

| |Sunderman FW, Nomoto S, Measurement of human serum ceruloplasmin by p-phenylenediamine oxidase activity. Clinical chemistry.1970; |

| |16:903-909. |

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| | |

| | |

|9 |Signature of candidate | |

|10 |Remarks of the guide | |

|11 |Name & Designation of | |

| |(in block letters) | |

| |11.1 Guide |Dr. SHIVASHANKARA AR MSc, PhD |

| | |ASSOCIATE PROFESSOR |

| | |FATHER MULLER MEDICAL COLLEGE, |

| | |KANKANADY, MANGALORE |

| | | |

| |11.2 Signature | |

| |11.5 Head of Department |Dr. MALATHI M M.B.B.S, MD., |

| | |PROFESSOR AND HOD |

| | |FATHER MULLER MEDICAL COLLEGE, |

| | |KANKANADY, MANGALORE |

| | | |

| | | |

| |11.6 Signature | |

|12 |12.1 Remarks of the |

| |Chairman and Principal |

| | |

| | |

| |12.2 Signature |

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