BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

               Malaria disease and Anti-malarial drugs WHO recommended second malaria vaccine: Please click   https://www.nature.com/articles/d41586-023-03115-1 Malaria: - Estimated 300-500 million human infections per year throughout the world - Transmitted to humans through the bite of female Anopheles mosquitoes - The parasite Plasmodium spp  cause infections in humans that is transmitted by the vector (mosquito).   Four major species are identified namely P falciparum, P vivax, P ovale, P malariae Antimalarial Drugs Overview Table: Category Drug Examples Target Stage Mechanism of Action Notable Side Effects Resistance Issues 4-Aminoquinolines Chloroquine, Amodiaquine Blood schizonts Inhibits heme detoxification (toxic buildup) Retinopathy, pruritus Widespread in P. falciparum 8-Aminoquinolines Primaquine, Tafenoquine Liver hypnozoites, gametocytes Produces reactive oxygen species Hemolysis (G6PD deficiency), GI upset Resistance...

           Notes on Salmonella - Enteric or Typhoid fever, the diagnosis, treatment, and prevention               of  Typhoid        Salmonella:  Salmonella bacteria typically live in the intestines of animals and humans and are usually transmitted to humans through contaminated food or water. Main types of Salmonella associated with human infections are Salmonella enterica serotype Typhi (S. Typhi)   and Salmonella serotypes Paratyphi A, B, or C typhi  that cause typhoid fever and paratyphoid fever respectively. Salmonella are found as a gut flora / normal flora in many vertebrate species.  The bacteria are often associated with contaminated food, particularly undercooked or raw eggs, poultry, meat, and unpasteurized dairy products.  Common symptoms of a Salmonella infection include diarrhea, abdominal cramps, fever, nausea, and vomiting. These symptoms c...

Similar to most metabolic pathways, glucose synthesis and breakdown is regulated by three different mechanisms : a) Allosteric regulators b) Covalent modification c) Changes in gene expression Regulation of glycolytic pathway: As described on the previous page and in figure 1, glycolysis is regulated by three irreversible enzymes namely : Hexokinase / glucokinase, Phosphofructokinase, and Pyruvate kinase. Figure 1: Allosteric Regulators of Glycolysis and Gluconeogenesis  Hexokinase / glucokinase: Hexokinase is a ubiquitously expressed enzyme that sets the pace of glycolysis. Hexokinase has a high affinity for glucose and transfers a negatively charged phosphate group to a glucose molecule. This step traps the glucose inside the cells and funnels it into various metabolic pathways. The high concentration of glucose-6-phosphate signals that the cell no longer requires energy or other biosynthetic pathways, and inhibits enzyme hexokinase. Glucokinase is expres...

  Glycogen synthesis and Breakdown Pathway Introduction Glycogen is a polysaccharide that consists of glucose molecules linked together by glycosidic linkage. In animals and humans; glucose is stored in the form of glycogen in the liver (~10%) and muscles (~2%). These stored glycogen molecules can readily be degraded into glucose molecules and enter into the glycolytic pathway for energy. Liver glycogen can also contribute to the maintenance of normal blood glucose.  The glycogen synthesis and breakdown pathway are highly regulated and, the synthesis and breakdown do not occur at the same time.  Glycogenesis F igure 1: Overview of Glycogen synthesis (Glycogenesis) Synthesis of Glycogen The addition of glucose to form glycogen requires a primer molecule where the glucose can be added to the non-reducing ends. During  de novo  synthesis, glucose molecules are added to tyrosine residues of primer protein glycogen. The enzyme Glycogen synthase ...

PBL case objective a)Differential Diagnosis of Jaundice b)Biochemical basis for the diagnosis of acute liver disease c) Biochemical basis for the diagnosis of obstructive jaundice Clinical case 1:  A 52-year-old male patient arrived at the medical facility with complaints of nausea, vomiting, abdominal pain, and yellowing of the skin (icteric jaundice) that had persisted for one week. Upon conducting a physical examination, the patient was found to have stable vital signs, and there were no signs of hepatic encephalopathy (a condition affecting brain function due to liver disease). The patient exhibited yellowing of the sclera (the white part of the eyes) and tenderness in the right upper quadrant of the abdomen when touched. The laboratory investigation results are presented below. Total serum Bilirubin - 15.4 mg/dL Direct bilirubun-11.5 mg/dl Aspartate transaminase- 720 U/L Alanine transaminase - 1625 U/L Alkaline Phosphatase- 211 U/L Total Protein- 7.3 g/dl...

PBL Case Objective a) Describe how alcohol is metabolized in the body. b) Discuss the cause of hematological abnormalities if any. c) Discuss how biochemical results correlate with the provisional diagnosis. d) Discuss any test recommendations. e) Discuss the provisional diagnosis. Clinical Presentation A 40 years old man was admitted to the hospital with hematemesis, loss of consciousness, and swelling of lower limbs. The patient had a history of alcoholism with daily consumption of approximately 1 to 2 L of beer every day for the past ten years. the physical examination showed hepatomegaly and mild ascites. The hematological and biochemical results are presented below. Discussions Alcohol Metabolism occurs in the liver. The liver is the major tissue for alcohol metabolism in the body. Before alcohol reaches the liver, the alcohol dehydrogenase isoform present in the stomach metabolizes a minor quantity of alcohol.  The quantity of alcohol metabolized in ...

Overview of the Topics Anticoagulant Drugs (Click Here) Thrombolytic Drugs (Click Here) Antiplatelet Drugs (Click Here) Multiple Choice Practice Questions (Click Here) Antiplatelet drugs - Platelet aggregation occurs in response to vascular injury - The aggregation of platelets  in the coronary artery can lead to the development of atherosclerotic plaque - It may precipitate coronary vasospasm, myocardial infarction, and stroke Clinical Indication - Prophylaxis of arterial thrombosis - Therapeutic management of myocardial infarction and stroke - Should be infused within 2 hours of myocardial infarction or stroke for significant benefit Clinically Important Antiplatelet Agents - Thromboxane A2 pathway, ADP pathway & GPIIb/IIIa receptors are the therapeutic targets to prevent platelet activation and aggregation. The drugs include - Aspirin - Clopidogrel - Abciximab Aspirin - Aspirin inhibits platelet aggregation and prolongs bleeding time  - Aspirin irreversib...

Case objective a) Discuss an overview of bilirubin metabolism b) Discuss neonatal physiological jaundice c) Discuss inborn errors of bilirubin metabolism d) Discuss biochemical/molecular diagnosis Case Presentation : A 48-year-old woman had a history of jaundice for decades, with no related symptoms. A laparoscopic evaluation showed a smooth liver with normal consistency and morphologic features but with a grossly black appearance. A biopsy specimen revealed coarse, deep-brown, pigmented granules on periodic acid–Schiff staining primarily at the canalicular pole of the hepatocytes and especially in the pericentral zones.  The laboratory investigation results are given below: Serum Total bilirubin - 4.6 mg/dL Direct-reacting bilirubin - 2.4 mg/dL Aspartate transaminase - 38 U/L Alanine transaminase - 25 U/L Alkaline phosphatase - 45 U/L Serum Albumin- 4.2 gm/dL Prothrombin time- 12 seconds Expression of the multidrug resistance associated protein 2 (MRP2) was ab...

                  Pathogenesis, Diagnosis, and treatment of Malaria Malaria : -  A mosquito-borne infectious disease caused by the bite of a mosquito that carries the parasitic protozoa called Plasmodium species - The disease can be fatal and life-threatening for humans, transmitted to humans through the bite of infected female Anopheles mosquitoes. - Plasmodium species comes under the parasite group called "Sporozoa" - Malaria is one of the major zoonotic diseases that cause millions of human deaths each year - It is a major public health concern, especially in tropical and subtropical regions. More than 75% of deaths occur in the African region of the world, over a million people mostly children die from malaria each year worldwide Plasmodium species: - Malaria is a vector-borne infection that is spread through the bite of the mosquito, thus the term given for this type of infection is a 'zoonotic disease'. The infected...