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Activated protein kinases initiate a phosphorylation cascade generic 100mg phenytoin otc, in which multiple protein kinases phosphorylate (add a phosphate group to) numerous and various cellular proteins generic phenytoin 100mg online, including other enzymes (Step 6) discount phenytoin 100mg line. The phosphorylation of cellular proteins can trigger a wide variety of effects, from nutrient metabolism to the synthesis of different hormones and other products. The effects vary according to the type of target cell, the G proteins and kinases involved, and the phosphorylation of proteins. The calcium ions then act as second messengers in two ways: they can influence enzymatic and other cellular activities directly, or they can bind to calcium-binding proteins, the most common of which is calmodulin. For example, the presence of a significant level of a hormone circulating in the bloodstream can cause its target cells to decrease their number of receptors for that hormone. This process is called downregulation, and it allows cells to become less reactive to the excessive hormone levels. When the level of a hormone is chronically reduced, target cells engage in upregulation to increase their number of receptors. The three most common types of interaction are as follows: • The permissive effect, in which the presence of one hormone enables another hormone to act. For example, thyroid hormones have complex permissive relationships with certain reproductive hormones. A dietary deficiency of iodine, a component of thyroid hormones, can therefore affect reproductive system development and functioning. Insulin increases the liver’s storage of glucose as glycogen, decreasing blood glucose, whereas glucagon stimulates the breakdown of glycogen stores, increasing blood glucose. Regulation of Hormone Secretion To prevent abnormal hormone levels and a potential disease state, hormone levels must be tightly controlled. Feedback loops govern the initiation and maintenance of most hormone secretion in response to various stimuli. Role of Feedback Loops The contribution of feedback loops to homeostasis will only be briefly reviewed here. Positive feedback loops are characterized by the release of additional hormone in response to an original hormone release. The initial release of oxytocin begins to signal the uterine muscles to contract, which pushes the fetus toward the cervix, causing it to stretch. This, in turn, signals the pituitary gland to release more oxytocin, causing labor contractions to intensify. Negative feedback is characterized by the inhibition of further secretion of a hormone in response to adequate levels of that hormone. An example of a negative feedback loop is the release of glucocorticoid hormones from the adrenal glands, as directed by the hypothalamus and pituitary gland. As glucocorticoid concentrations in the blood rise, the hypothalamus and pituitary gland reduce their signaling to the adrenal glands to prevent additional glucocorticoid secretion (Figure 17. This signaling is inhibited when glucocorticoid levels become elevated by causing negative signals to the pituitary gland and hypothalamus. Role of Endocrine Gland Stimuli Reflexes triggered by both chemical and neural stimuli control endocrine activity. These reflexes may be simple, involving only one hormone response, or they may be more complex and involve many hormones, as is the case with the hypothalamic control of various anterior pituitary–controlled hormones. Humoral stimuli are changes in blood levels of non-hormone chemicals, such as nutrients or ions, which cause the release or inhibition of a hormone to, in turn, maintain homeostasis. For example, osmoreceptors in the hypothalamus detect changes in blood osmolarity (the concentration of solutes in the blood plasma). This reabsorption causes a reduction of the osmolarity of the blood, diluting the blood to the appropriate level. High blood glucose levels cause the release of insulin from the pancreas, which increases glucose uptake by cells and liver storage of glucose as glycogen. An endocrine gland may also secrete a hormone in response to the presence of another hormone produced by a different endocrine gland. Such hormonal stimuli often involve the hypothalamus, which produces releasing and inhibiting hormones that control the secretion of a variety of pituitary hormones. A common example of neural stimuli is the activation of the fight-or-flight response by the sympathetic nervous system. When an individual perceives danger, sympathetic neurons signal the adrenal glands to secrete norepinephrine and epinephrine. These responses boost the body’s transport of oxygen to the brain and muscles, thereby improving the body’s ability to fight or flee. Foods and liquids should not be microwave-heated in any form of plastic: use paper, glass, or ceramics instead. This complex secretes several hormones that directly produce responses in target tissues, as well as hormones that regulate the synthesis and secretion of hormones of other glands. In addition, the hypothalamus–pituitary complex coordinates the messages of the endocrine and nervous systems. In many cases, a stimulus received by the nervous system must pass through the hypothalamus–pituitary complex to be translated into hormones that can initiate a response. The hypothalamus is a structure of the diencephalon of the brain located anterior and inferior to the thalamus (Figure 17.

To more completely detect diabetes mellitus purchase 100mg phenytoin free shipping, stressing the system with a defined glucose load tests carbohydrate metabolic capacity order phenytoin 100 mg overnight delivery. To do this discount phenytoin 100 mg on line, a high- carbohydrate drink or meal is given to the patient, blood is collected 2 hours after ingestion, and the glucose concentration is determined. In the fasting state the arterial (capillary) blood glucose concentration is 5 mg/dl higher than the venous concentration. Preparation and preservation Samples for glucose determination The following factors which affects the stability of glucose in body fluid must be take in to account, such as: • Those glycolytic enzymes found particularly in the red cells, which under goes glycolysis at an average rate of approximately 10 mg/dl/hr in whole blood or 5 mg/dl/hr in sufficiently centrifuged plasma which still contain leukocytes Keeping these considerations in mind, there are several ways to prevent or retard glycolysis in specimen to be analyzed. For example: • Sample for glucose analysis should be delivered to the laboratory as soon as possible after being drowned from the patient. Note When certain enzymatic glucose methods are used, fluoride anticoagulated blood should not be used, as the fluoride might inhibit the enzyme. Use of serum separator gel tubes, processed as quickly as possible with in thirty minutes if possible- is preformed for these methods. For non pregnant adults, the fasting serum or plasma glucose concentration should normally be less than 110 mg/dl and the serum or plasma glucose taken 2 hours 140 mg/dl. Including in the new criteria from the expert committee on the diagnosis and classification of Diabetes Mellitus. A random blood glucose (blood drawn with out considering time since the last meal) equal to or greater than 200 mg/dl, along with symptoms of diabetes (polyuria, polydipsia, and un explained weight loss), 3. A 2- hour post load glucose level equal to or greater than 200 mg/dl during an oral glucose tolerance test. The various methods for the quantitative determination of glucose can be divided in to three general categories. Of these, enzymatic methods using hexokinase or glucose oxidase methodology are most commonly used 76 7. The use of enzymes is a means of achieving absolute specificity in the determination of glucose concentration. The two most widely used automated enzyme glucose methods are based on the enzymes hexokinase and glucose oxidase. In the presence of peroxidase enzyme the released H2O2 reacts with oxygen acceptors like aminophenazene and phenol forming a rose colored quinone rose derivative. The intensity of color is directly proportional to the amount of glucose present in the sample and the absorbance is read at 546nm. Urine sample cannot be used directly as urine may contain electrolysis those inhibit enzyme activity N. H2O2+ aminophenazene + phenol peroxidase quinone imine (rose) Glucose oxidase is specific to β,D- glucose so mutase is present to convert α ,D- glucose to β – configuration 7. Some of these non glucose reducing substances are other sugars and metabolic compounds and materials such as uric acid, creatinine, ascorbic acid, certain amino acids, creatine, and phenol. The oxidation- reduction methods for determining blood glucose differ primarily in the way they handle the non-glucose reduction substances. When the non-glucose reducing substances are removed as part of a glucose determination, the resulting value is called the true glucose value. The decrease in yellow color is directly proportional to the concentration of glucose present in the sample and the absorbance is taken at 420 nm. On the addition of phosphomolybdic acid (arsenomolybdic acid) to the reaction mixture the cuprous ions quantitatively reduces molybdic acid to lower oxides of molybdium which is blue in color. The intensity of blue color is directly proportional to the concentration of glucose present in the sample and the absorbance of the solution is read at 680 nm. In this specific method glucose reacts with O-toludine in hot acetic acid and in the presence of thiourea, forming a green colored derivative, which is called shiff- base (glucosylamine). Both stock and working glucose standards 0 should be stored (kept) at 4-10 C Procedure B St T Distilled water (ml) 0. The relation ship between Absorbance (A) and concentration (C) In the detection and treatment of diabetes it is sometimes necessary to have more information than can be obtained from only testing the fasting specimen for glucose. To conduct oral glucose tolerance test on a subject, first blood and urine samples are taken in fasting state, and. If blood glucose level is normal and urine sample is negative the individual will be loaded with 75 gm glucose dissolved in 300 ml of water. The blood sample are analyzed for glucose concentration and the urine samples are qualitatively tested for glucose. Most probably slight elevation may be observed after 3 hours then falls down below the normal range with in one or one half hours b. Intravenous Glucose Tolerance Test: this method is less commonly used, although it eliminates the variable factors involved in the rate of intestinal absorption in different individuals. Glucose is given per kg body weight by infusing 20gm% W/V glucose solution and the infusion will be completed with in half an hour. In normal individuals the blood glucose concentration does not rise to more than 250 mg% at the end of infusion and falls below the fasting level with in 2 hours. Endocrine: Insulin increases carbohydrate tolerance while all other hormones considered earlier tend to decrease its tolerance. Self- Monitoring of glucose Many patients (especially those with type 1(insulin- dependent diabetes mellitus)) now regularly monitor their own blood glucose concentrations on the advice of their health care provider, using reagent test strips and reflectance meter.

Principle Casein is the main protein found in milk and is present at a concentration of about 30-40 gms/lit purchase phenytoin 100 mg on line. Casein is insoluble in ethanol and ether and this property is used to remove unwanted fat materials from the preparation 100mg phenytoin free shipping. The amount of casein weighted = X gms The amount of casein present in 100 ml of milk= X gms The percentage yeild = 100 x X/100 = Y gms Result The amount of casein present in 100 ml of milk = Y gms 3 phenytoin 100 mg mastercard. Since all proteins contain peptide bond, this method is fairly specifc and there is little interference with other compounds. Stock standard solution 1g of protein (egg albumin) is weighed and made upto 100ml with distilled water. Concentration = l0mg / ml Working standard solution 10ml of the stock is diluted to 100ml using distilled water. From the values obtained, a standard graph is drawn using concentration of protein in X - axis and optical density in the Y - axis. Principle A solution of orthotoluidine in glacial acetic acid when treated with glucose produces a blue coloured product with an absorption maximum at about 640nm. A blank is also prepared simultaneously comprising 1ml of distilled water and 4 ml of orthotoluidine reagent. The amount of glucose present in the given blood sample is then calculated 169 Protocol for glucose estimation Blank Standard Plasma S. Optical density at 640 nm Graph Y axis T & T1 2 A Optical density at 640nm X axis 0 B Concentration of glucose in mg Calculation For T1 &T2 The optical density A of T1 & T2 corresponds to B mg of glucose 1. Sulphuric acid (1N) 171 Procedure Standardisation of Potassium permanganate 10ml of oxalic acid is pipetted out into a clean conical fask and 10ml of dilute sulphuric acid is added and heated to 60 ° C. Precipitation of calcium oxalate 2ml of serum is taken in a centrifuge tube and 2ml of distilled water is added followed by 1ml of 4 % ammonium oxalate. Tabular Column Titration I Standardisation of Potassium permanganate Standard Oxalic acid Vs Potassium permanganate S. No Volume Burette Volume of Indicator of Oxalic acid Initial Final Potassium (ml) permanganate (ml) (ml) (ml) 1. No of Oxalic acid Indicator permanganate (ml) Initial Final (ml) (ml) (ml) Test solution oxalic acid liberated 1. Alcohol 173 Procedure The middle fnger of the individual to be tested for blood group is cleaned with alcohol and the excess of alcohol is wiped out with sterile cotton. A small drop of anti A is added in the portion A, anti B in the portion B and anti D in the portion D. A small prick is made on the cleaned fnger, the frst drop of blood coming out is wiped off and second drop of blood is collected directly on the region marked as A, B andD. Immediately, blood is mixed with the corresponding anti antibody by using the sterile stick and observed for any agglutination in the form of clump formation. If the clump is observed in the region marked as A, the blood group is A and the formation of clump in B shows presence of B blood group. The formation of clump in the D region shows presence of Rh positive blood group and if there is no clump formation it shows the presence of Rh negative blood group. Clump formation in the regions A and D shows the presence of A+ blood group and clump formation in the regions B and D shows the presence of B+ blood group. If the clump formation is observed immediately in A blood group type it can be denoted as A type, if it is not immediate then the blood group is of A. Cardiac Anatomy ▪ 2 upper chambers ▪ Right and left atria ▪ 2 lower chambers ▪ Right and left ventricle ▪ 2 Atrioventricular valves (Mitral & Tricuspid) ▪ Open with ventricular diastole ▪ Close with ventricular systole ▪ 2 Semilunar Valves (Aortic & Pulmonic) ▪ Open with ventricular systole ▪ Open with ventricular diastole The Cardiovascular System ▪ Pulmonary Circulation ▪ Unoxygenated – right side of the heart ▪ Systemic Circulation ▪ Oxygenated – left side of the heart Anatomy Coronary Arteries How The Heart Works Anatomy Coronary Arteries ▪ 2 major vessels of the coronary circulation ▪ Left main coronary artery ▪ Left anterior descending and circumflex branches ▪ Right main coronary artery ▪ The left and right coronary arteries originate at the base of the aorta from openings called the coronary ostia behind the aortic valve leaflets. Sinus bradycardia is often seen as a normal variation in athletes, during sleep, or in response to a vagal maneuver. Sinus Arrest or Pause A sinus pause or arrest is defined as the transient absence of sinus P waves that last from 2 seconds to several minutes. The ventricles do not receive regular impulses and contract out of rhythm, and the heartbeat becomes uncontrolled and irregular. Frequently is seen as the last-ordered semblance of a heart rhythm when resuscitation efforts are unsuccessful. Torsades usually terminates spontaneously but frequently recurs and may degenerate into ventricular fibrillation. Rhythm Identification ▪ This rhythm strip is from an 86-year-old woman who experienced a cardiopulmonary arrest. Rhythm Identification ▪ This rhythm strip is from a 69-year-old man complaining of shortness of breath. Rhythm Identification ▪ This rhythm strip is from a 52-year-old man found unresponsive, apneic, and pulseless. Rhythm Identification ▪ These rhythm strips are from a 78-year-old man complaining of shortness of breath.

The use of the correct tech- nique for obtaining the gastric lavage is important because of the scarcity of bacilli in children compared to adults generic 100 mg phenytoin otc. The technique requires a nasogastric tube inserted in an inpatient setting cheap phenytoin 100mg amex, because the sensitivity of outpatient gastric lavages has not been evaluated phenytoin 100 mg online. Early morning samples, optimally from three consecutive days, should be obtained before the child has had a chance to eat or move, as these ac- tivities dilute the bronchial secretions accumulated during the night. Initially, the stomach contents should be aspirated, and then a small amount of sterile water injected through the nasogastric tube. Since gastric acidity is poorly tolerated by the tubercle bacilli, neutrali- zation of the specimen with 10 % sodium carbonate or 40 % anhydrous sodium phosphate should be performed immediately. Even under the best technical condi- tions, tubercle bacilli can be only recovered in 70 % of infants and in 30 % to 40 % of ill children. Clear instructions for collecting the sputum sample must be given in order to avoid ob- taining nasopharyngeal secretions and saliva, which are not acceptable for analysis. Another technique to obtain bronchial secretions is by stimulating cough using an aerosol solution of propylene glycol in 10 % sodium chloride, or by bronchoalveolar la- vage. The bronchoalveolar lavage (instilling a total of 180 mL of saline solution and obtaining the sample by aspiration of the bronchial contents) is an invasive technique and requires the use of anesthesia, so its use in children must be well justified. Diagnosis 539 Bronchoscopy may be useful in determining endobronchial involvement and also in distinguishing M. Renal disease is a rare event in children, but when it is suspected, overnight urine specimens must be collected in the early morning and immediately sent for analy- sis, as the tubercle bacilli poorly tolerate the acid pH of urine. Enhancement of the yield may be possible by staining any typical clot (bride veil) formed in cerebrospinal fluid specimens. Nevertheless, in children in whom bacilli in the respiratory secretions are sparse, results may be negative. In these cases, a single organism on a slide is highly suggestive and warrants further inves- tigation. Conventional cultures on Löwenstein-Jensen solid medium are commonly used in low-income countries, while automated culture methods are widely employed in high-income countries for the rapid detection and recovery of mycobacteria (Caminero 2003) (see Chapters 12 and 14). Specimens from body sites naturally contaminated, such as sputum and urine, re- quire a decontamination process prior to culture in order to allow the growth of mycobacteria in the culture media, without overgrowth of the commensal flora. According to several reports, the sensitivity and specificity of the nucleic acid amplification methods in smear-positive cases may exceed 95 %, but the sen- sitivity in smear-negative cases, which includes most of the pediatric cases, varies from 40 % to 70 % (Eisenach 1990, Morcillo 2001, Saltini 1998). Speci- ficity is even more controversial, and false positive results have been observed in up to 20 % of controls (Smith 1996). The size of induration and not erythema must be measured by placing the ruler transversally to the long axis of the forearm (ruler-based reading). Multiple puncture techniques should no longer be used because of its intrinsic limitations and inaccuracy (Arnadottir 1996, International Union Against Tuberculosis and Lung Disease 1991, World Health Organization 1963). For other high-risk groups, such as children with increased environmental exposure, or those younger than four years old, a reaction equal or greater than 10 mm is a positive result. False- negative results may be caused by recent vaccination with live-attenuated virus, anergy, immunosuppression, immune deficiency, or malnutrition (Flament 1994). Tuberculin skin test: cutoff size of reactive area for positive tuberculin reaction Cut off area (mm) ≥ 5 mm ≥ 10 mm ≥ 15 mm Contact to infectious cases with Children from high prevalence Children ≥ 5 years or without symptoms. Cost-benefit analyses have shown that universal school-based skin testing programs are not effective in finding ill children, and the targeted screening of high risk children is more efficient and less costly than screening all students. Bacteriological diagno- sis and drug susceptibility testing of the mycobacterium causing the disease in the index case is extremely important. It is often impossible to obtain a sputum from young children, so analyzing the strain isolated from the index adult case may be the only way to determine the appropriate treatment for the child (Chadna 2003, Comstock 1974, International Union Against Tuberculosis and Lung Disease 1991, Jacobs 1993). Nevertheless, the hilar region may be difficult to evalu- ate by a posteroanterior radiograph view, so the systematic inclusion of a lateral view radiograph is necessary. When one or several granulomas or calcifications are detected in the lung parenchyma or hilar/mediastinal lymph nodes (primary bipolar complex), these could just be evidence of a past infection with M. However, the absence of calcification in the lesions lends support to the possibility of active primary disease. A fan-shaped lesion on the radiograph is a manifestation of bronchial obstruction, leading to segmental disease characterized by atelectasis and consolidation of the involved area. Other chest radiographic observations include linear, interstitial and nodular densities, cavities with consolidation, empyema, bronchiectasis or focal masses. Computed tomography imaging can reveal basal cistern inflammation, hydrocephalus and meningeal enhancement, as well as focal parenchymal abnormalities, such as tuberculomas and infarction. In adults, tuberculous osteomyelitis usually originates in the epiphysis of long bones with spread into the adjacent joint space. However, computed tomography scans and magnetic resonance imaging are super- fluous when chest radiograph findings are diagnostic. There are several aspects of treatment that are markedly different in children and require special consideration, such as the availability of pediatric for- mulations, dosing, side effects, and follow-up (Correa 1997, Blumberg 2004). Treatment of asymptomatic tuberculosis infection The purpose of treating asymptomatic infection is to prevent the development of active disease in the future.