By X. Kurt. Southeastern University. 2018.

Iron is inserted into protoporphyrin by the mitochondrial enzyme ferrochetalase to form the finished heme moiety buy generic antabuse 250 mg online. Globin synthesis Globin synthesis occurs in the cytoplasm of the 144 Hematology normoblast and reticulocyte generic antabuse 250mg amex. The polypeptide chains released from the ribosomes are folded into their three-dimensional configurations spontaneously cheap antabuse 500mg with mastercard. Determination of hemoglobin concentration Hemoglobin is measured to detect anemia and its severity and to monitor an anemic patient’s response to treatment purchase 250mg antabuse mastercard. The hemoglobin content a solution may be estimated by several methods: by measurement of its color cheap 250mg antabuse overnight delivery, its power of combining with oxygen or carbonmonoxide and by its iron content. In photometric techniques the absorbance of hemoglobin in a blood sample is measured electronically using a filter colorimeter or a direct read-out hemoglobin meter. When it is not possible to measure hemoglobin 146 Hematology accurately using a photometric technique a visual comparative technique can help to detect anemia and assess its severity. The technique is also used as a reference method against which all other color comparison methods should be calibrated. Principle of the test Whole blood is diluted 1 in 201 in a modified Drabkin’s solution which contains potassium ferricyanide and potassium cyanide. The red cells are hemolyzed and the hemoglobin is oxidized by the ferricyanide to methemoglobin (Hemiglobin, Hi). Hemoglobin values are obtained from tables prepared from a calibration graph or if using a direct read-out hemoglobin meter, for the digital display. Drabkin’s neutral diluting fluid: Potassium ferricyanide 200 mg Potassium cyanide 50 mg Potassium dihydrogen phosphate 140 mg Non-ionic detergent 1 ml (e. Take a sheet of graph paper and plot the absorbance of each standard (vertical axis) against its concentration in g/l (horizontal axis). Stopper the tube, mix, and leave the diluted blood at room temperature, protected from sunlight, for 4-5 minutes. Sources of error when measuring hemoglobin photometrically The following are the most important and commonest errors that can lead to unreliable test results when measuring hemoglobin photometrically: • Not measuring the correct volume of blood due to poor technique or using a wet or chipped pipette. When transferring a solution to a cuvette, allow the fluid to run down the inside wall of the cuvette. Carefully insert the cuvette in the colorimeter or hemoglobin meter (optical surfaces facing the light source). Ensure a solution is at room temperature before reading its absorbance other wise condensation will form on the outside of the cuvette which will give an incorrect reading. Turbidity can 153 Hematology be avoided by centrifuging the diluted sample or adding 5g/l NaCl to the reagent. HemoCue non-dilution photometric technique This method of measuring hemoglobin is both precise and accurate. It is one of the few photometric hemoglobin systems that does not require dilution or measuring of the blood A small drop (10µl) of blood is drawn by capillary attraction into a specially designed single used micro- cuvette of only 0. These lyze the blood and covert it to azidemethemoglobin, the absorption of which is read electronically in the HemoCue meter at wavelengths 565nm and 880nm (later reading compensates for any turbidity in the sample). A direct read-out of 154 Hematology hemoglobin (g/l or mmol/l) is obtained within 1 minute of inserting the cuvette in the meter. Sodium nitrite converts hemoglobin iron from the ferrous to the ferric state to form methemoglobin which then combines with azide to form azidemethemoglobin. Hold the microcuvette by two fingers in its rear end and bring the filling tip in contact with a freely-flowing blood that comes from a skin puncture. If air bubbles are seen in the optical eye of the cuvette due to inadequate filling of blood, the cuvette should be discarded and another cuvette be filled properly with the blood sample. After 30-50 seconds the photometer will find the steady state of the chemical reaction and the result will appear in the display. The display will show this result for 5 minutes provided the cuvette holder is left in its inner position. The optical eye of the cuvette should also be inspected for air bubbles, which if 157 Hematology present, can produce erroneously low reading. Oxyhemoglobin Method This is a reliable and inexpensive method of measuring hemoglobin but there is no stable oxyhemoglobin (HbO2) reference standard solution available for the direct calibration of the HbO2 technique.

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Nucleotidases (Phosphatases) These enzymes hydrolyse the nucleotides to the corresponding nucleosides and inorganic phosphate molecules buy 500 mg antabuse otc. Phosphatase Nucleotides Nucleoside + Phosphate Nucleosidases (Nucleoside phosphorylase) The nucleosides obtained above either absorbed or degraded into bases and sugars by nucleosidases buy discount antabuse 250mg on-line. Mechanism Transcription involves 3 stages i) Initiation ii) Elongation iii) Termination Three phases of transcription 1 antabuse 250mg generic. This complex enzyme buy antabuse 250mg mastercard, called the holoenzyme is needed to initiate transcription since the s factor is essential for recognition of the promoter discount antabuse 250mg amex. It is common for prokaryotes to have several s factors that recognize different types of promoter (in E. The holoenzyme binds to a promoter region about 40-60 bp in size and then initiates transcription a short distance downstream (i. With in the promoter lie two 6 bp sequences that are particularly important for promoter function and which are therefore highly conserved between species. Using the convention of calling the frst nucleotide of a transcribed sequence as +1, there 2 promoter elements 98 lie at position -10 and -35, that is about 10 and 35 bp respectively, downstream of where transcription will begin. The most common termination signal is a G ≡ C rich region is a palindrome, followed by an A = T rich sequence. Those that lack such a structure require an additional protein, called rho protein (r) to help recognize the termination site and stop transcription. The product of transcription in eukarryotes are called as primary transcripts and they undergo modifcation by a process called post transcriptional modifcation. Okasaki fragments are present in i) both the parental strands ii) both the daughter strands iii) leading strand iv) lagging strand c. G-C rich region followed by A-T rich region is a signal for i) initiation ii) elongation iii) termination iv) primer formation d. One among the following is not a modifed base i) pseudo uridine ii) isopentyl adenine iii) methyl guanosine iv) deoxy thymine e. The metabolism of our body comprises two major balanced activities: anabolism (synthesis) and catabolism (degradation). Whether the metabolic changes are exergonic or endergonic, most of them have to be catalysed by enzymes. If one particular enzyme is defcient or absent then that leads to a block in the pathway of biochemical reactions leading to metabolic abnormalities which are present throughout the life and handed over to the progeny. The absence or defciency of an enzyme will cause an abnormal accumulation of the intermediate products of metabolism in the body and increased excretion in urine as such or their degradation products. For example, in the following reaction a c b d R B C D P R is the reactant, B, C and D are intermediates and P is the product and a, b, c and d are enzymes catalyzing various steps of the reactions. In this reaction pathway, if any one of the enzyme is defcient or absent, the previous intermediate accumulates and produces toxicity. It also affects the amount of product (P) formation which may be essential biologically and there by leads to pathological diseases. Beadle and Tatum put forth their theory of one gene one enzyme hypothesis which states that one gene controls the synthesis of a single enzyme. Galactosemia, Von-Gierke’s disease, hemophilia, albinism, alkaptonuria and Tay-Sach’s disease are some of the important diseases due to inborn errors of metabolism. Due to the enzyme defect galactose accumulates in blood and is reduced by aldose reductase in the eye to the corresponding galactitol which causes cataract. The general condition is more severe if it is due to a defect in galactose 1 - phosphate uridyl tranferase, since galactose 1- phosphate accumulates and depletes the liver of inorganic phosphate. After 2 - 3 months of age the liver may show fatty infltration and lead to cirrhosis (non functioning of liver cells). Galactosemia at this age is associated with mental retardation due to accumulation of galactose and galactose 1 - phosphate in cerebral cortex. In this, the enzyme which is defcient is glucose 6-phosphatase that converts glycogen to glucose 6-phosphate and then to glucose. Massive enlargement of the liver, pronounced hypoglycemia in between meals, failure of blood glucose to rise on administration of glycogen and convulsion are seen in this condition. Since glucose 6- phosphate cannot leave liver cells, there is compensatory increase in glycolysis leading to increased levels of pyruvic acid and lactic acid. If any one or more of these factors are not synthesised adequately and properly that results in defect in blood clotting and thereby hemorrhage.

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If the diagnosis is unclear cheap 250 mg antabuse overnight delivery, a fluid challenge (maxi- A tachycardia may not be seen in the patient taking mum 5mL/kg) can be given and the response ob- beta blockers and up to 15% of the blood volume served buy generic antabuse 500 mg line; an improvement in the circulatory status may be lost without detectable signs in a fit order antabuse 500mg amex, young suggests hypovolaemia generic antabuse 500mg line. An arterial blood sample should be about the diagnosis buy antabuse 250 mg cheap, fluids can be restricted ini- analysed; a metabolic acidosis is usually found tially and a diuretic (e. As the • inotropes, antiarrhythmics, bronchodilators; legs are taken down from the lithotomy position, • antidepressants in overdose. The patient may be pyrexial and if the cardiac output Coronary artery flow is dependent on diastolic pressure is measured, it is usually elevated. Hypotension and tachycardia are therefore constriction ensues along with a fall in cardiac particularly dangerous. The diagnosis should be suspected in any patient who has had surgery associated with a sep- tic focus, for example free infection in the peri- Management toneal cavity or where there is infection in the Correction of the underlying problem will result in genitourinary tract. Spe- hours after the patient has left the recovery area, cific intervention is required if there is a significant often during the night following daytime surgery. If there is is corrected by the administration of fluids associated pyrexia, it may be an early indication of (crystalloid, colloid), the use of vasopressors (e. The combination of hypo- sists, then providing there is no contraindication a volaemia and vasodilatation will cause profound small dose of a beta blocker may be given intra- hypotension. Rarely, the quire early diagnosis, invasive monitoring and cir- development of an unexplained tachycardia after culatory support in a critical care area. Antibiotic anaesthesia may be the first sign of malignant therapy should be guided by a microbiologist. Has an effect at the 78 Postanaesthesia care Chapter 3 chemoreceptor trigger zone and increases gastric sue trauma), most patients start drinking within motility. Severe to 1400, who is still unable to take fluids by mouth side-effects, particularly dry mouth and blurred at 1800 will require: vision. This is The patient should be reviewed at 0800 with complemented by clinical evaluation of the pa- regard to further management. This is usually seen as thirst, a • any continued bleeding; dry mouth, cool peripheries with empty superficial • rewarming of cold peripheries causing veins, hypotension, tachycardia and a decrease vasodilatation. An The patient who has undergone major surgery will additional 1L of Hartmann’s solution per 24h may require close monitoring to ensure that sufficient need to be added to the above regimen to account volumes of the correct fluid are administered. A for such losses and adjusted according to the pa- standard postoperative regimen for the first 24h tient’s response. These losses may continue for up postoperatively might therefore consist of: to 48h after surgery and sufficient extra volumes of • 1. The of the day as described above to ensure that the effect of this is to increase water absorption by the volumes and type of fluid prescribed are adequate kidneys and reduce urine output. In addition: This results in sodium retention and increased uri- • The fluid balance of the previous 24h must be nary excretion of potassium. Modern surgical treatment re- into the tissues, which have the same effect as any stores function more rapidly, a process facilitated other form of fluid loss and are often referred to as by the elimination of postoperative pain. Such volumes are difficult to example is the internal fixation of fractures, fol- 80 Postanaesthesia care Chapter 3 lowed by potent analgesia allowing early mobiliza- what to expect postoperatively, what types of anal- tion. Ineffective treatment of postoperative pain gesia are available and also by allowing patients to not only delays this process, but also has other im- explore their concerns. Their nervous systems can be consid- pneumonia; ered to be sensitized to pain and will react more • muscle wasting, skin breakdown and cardio- strongly to noxious stimuli. Bad previous pain ex- vascular deconditioning; periences in hospital or anticipation of severe pain • thromboembolic disease—deep venous for another reason suggest that extra effort will be thrombosis and pulmonary embolus; required to control the pain. Prescribing should take these factors into • Economic costs: account rather than using them as an excuse for in- • prolonged hospital stay, increased medical adequate analgesia. There is no difference between complications; the pains suffered by the different sexes having the • increased time away from normal same operation. Pain following surgery on the • pain due to ischaemia from tissue swelling, body wall or periphery of limbs is less severe and haematoma formation restricting the circulation for a shorter duration. Regular measurement of pain means that it is more difficult to ignore and the efficacy of interventions Factors affecting the experience of pain can be assessed.

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Slow generic antabuse 250 mg amex, steady drug delivery how to get drugs to the right place order 250 mg antabuse free shipping, a task known directly to the bloodstream—without stopping as drug delivery cheap 250 mg antabuse free shipping. Unfortunately buy antabuse 500 mg with mastercard, this rarely happens with the typical Hormones such as testosterone generic antabuse 500 mg free shipping, progesterone, methods of delivering drugs: swallowing and and estrogen are available as skin patches. When swallowed, many medicines made forms of medicines enter the blood via a mesh­ of protein are never absorbed into the blood­ work of small arteries, veins, and capillaries in the stream because they are quickly chewed up by skin. Some of these If the drug does get to the blood from the intes­ include Duragesic® (a prescription-only pain tines, it falls prey to liver enzymes. For doctors medicine), Transderm Scop® (a motion-sickness prescribing such drugs, this first-pass effect (see drug), and Transderm Nitro® (a blood vessel- page 7) means that several doses of an oral drug widening drug used to treat chest pain associated are needed before enough makes it to the blood. Despite their advantages, Drug injections also cause problems, because they however, skin patches have a significant drawback. Both methods of administration also result in Inhaling drugs through the nose or mouth is fluctuating levels of the drug in the blood, which another way to rapidly deliver drugs and bypass is inefficient and can be dangerous. Pharmacologists can work around therapy for years, and doctors prescribe nasal the first-pass effect by delivering medicines via the steroid drugs for allergy and sinus problems. If can be inhaled by people with diabetes who rely clinical trials with inhaled insulin prove that it is on insulin to control their blood sugar daily. This safe and effective, then this therapy could make still-experimental technology stems from novel life much easier for people with diabetes. Cobb of the University of Texas the proteins a code, instructing the cell to do some­ Southwestern Medical Center at Dallas are studying thing, such as divide or grow. Medicines By Design I Molecules to Medicines 43 by learning how to hijack molecular transporters to shuttle drugs into cells. Gordon Amidon, a pharmaceutical chemist at the University of Michigan-Ann Arbor, has been studying one particular transporter in mucosal membranes lining the digestive tract. The challenge is a chemistry wants to extend this list by synthesizing hundreds problem—most drugs are water-soluble, but of different molecules and testing them for their membranes are oily. Membranes are genomics, and bioinformatics have sped the search usually constructed to permit the entry of only for molecules that Amidon and other researchers small nutrients and hormones, often through can test. Many pharmacologists are working hard to devise ways to work not against, but with nature, 44 National Institute of General Medical Sciences Scientists are also trying to slip molecules Act Like a Membrane through membranes by cloaking them in disguise. Researchers know that high concentrations of Steven Regen of Lehigh University in Bethlehem, chemotherapy drugs will kill every single cancer Pennsylvania, has manufactured miniature cell growing in a lab dish, but getting enough of chemical umbrellas that close around and shield these powerful drugs to a tumor in the body with­ a molecule when it encounters a fatty membrane out killing too many healthy cells along the way and then spread open in the watery environment has been exceedingly difficult. So far, Regen has only used test mole­ drugs can do more harm than good by severely cules, not actual drugs, but he has succeeded in sickening a patient during treatment. The ability to do this particles called liposomes to package and deliver in humans could be a crucial step in successfully drugs to tumors. Liposomes are oily, microscopic delivering therapeutic molecules to cells via capsules that can be filled with biological cargo, gene therapy. They are very, very small—only Anesthesia Dissected Scientists who study anesthetic medicines little physical resemblance to each other—can all have a daunting task—for the most part, produce anesthesia. Researchers do Sloan-Kettering Institute for Cancer Research in New know that anesthetics share one common York City clarified how certain types of these mys­ ingredient: Nearly all of them somehow terious medicines work. Veselis and his coworkers target membranes, the oily wrappings measured electrical activity in the brains of healthy surrounding cells. However, despite the volunteers receiving anesthetics while they listened fact that anesthesia is a routine part of to different sounds. To determine how sedated the surgery, exactly how anesthetic medicines people were, the researchers measured reaction work in the body has remained a mystery for more time to the sounds the people heard. It’s an important problem, since memory effects, they quizzed the volunteers at the anesthetics have multiple effects on key body func­ end of the study about word lists they had heard tions, including critical processes such as breathing. Veselis’ experiments Scientists define anesthesia as a state in which show that the anesthetics they studied affect sepa­ no movement occurs in response to what should rate brain areas to produce the two different effects be painful. The findings may help loses a pain response, the anesthesiologist can’t doctors give anesthetic medicines more effectively tell what is happening inside the person’s organs and safely and prevent reactions with other drugs and cells. Researchers have known about liposomes for many years, but getting them to the right place in the body hasn’t been easy. Once in the blood­ stream, these foreign particles are immediately shipped to the liver and spleen, where they are destroyed. Materials engineer David Needham of Duke University in Durham, North Carolina, is investi­ gating the physics and chemistry of liposomes to better understand how the liposomes and their cancer-fighting cargo can travel through the body. David Needham designed liposomes resembling tiny molecular “soccer Needham worked for 10 years to create a special balls” made from two different oils that wrap around a drug.

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