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By S. Basir. North Georgia College and State University, the Military College of Georgia. 2019.

An easy way to remember this is by like vector analysis: when T4 and T3 uptake both are high generic alli 60 mg free shipping, the patient really is hyperthyroid; when they both are low best purchase for alli, the patient is hypothyroid cheap alli 60mg with amex. However buy discount alli 60mg line, when they vary in opposite directions, for example, high T4 with low T3 uptake, they “cancel each other out,” that is, it is a protein-binding abnormality as described above. Patients may be asymptomatic or report the vague and subtle symptoms of hypothyroidism, such as fatigue. Thyroid hormone replacement can be prescribed in an attempt to relieve symptoms or possibly to reduce cardiovascular risk. The overwhelming majority of patients with hypothyroidism can be treated with once-daily dosing of synthetic levothyroxine, which is biochem- ically identical to the natural hormone. Levothyroxine is relatively inexpen- sive, has a long half-life (6-7 days), allowing once-daily dosing, and gives a predictable response. Older thyroid preparations, such as desiccated thyroid extract, are available but are not favored because they have a high content of T3, which is rapidly absorbed and can produce tachyarrhythmias, and the T4 content is less predictable. In older patients and in those with known car- diovascular disease, dosing should start at a low level, such as 25 to 50 μg/d, and increased at similar increments once every 4 to 6 weeks to an average dose of 1. Overly rapid replacement with the sud- den increase in metabolic rate can overwhelm the coronary or cardiac reserve. Depending on the cause of hypothyroidism and the amount of residual gland function, individual patient needs will vary widely. She denies excess dieting, although she does work out with her team 3 hours daily. She has been reading about her diagnosis on the Internet and wants to try desiccated thyroid extract instead of the medicine you gave her. On examination, she weighs 175 lb, her heart rate is 64 bpm at rest, and her blood pres- sure is normal. Tell her that this delay in resolution of symptoms is normal and schedule a follow-up visit with her in 2 months. Hashimoto thyroiditis is the most common cause of hypothy- roidism with goiter in the United States. It is most commonly found in middle-aged women, although it can be seen in all age groups. Patients can present with a rubbery, nontender goiter that may have “scalloped” borders. Iodine deficiency is exceedingly uncommon in the United States because of iodized salt. Patients with thyroid cancer usually are euthyroid and have a history of head and neck irradiation. Several different autoantibodies directed toward components of the thyroid gland will be present in the patient’s serum; however, of these, antithyroperoxidase antibody almost always is detectable (also called antimicrosomal antibody). On thyroid biopsy, lymphocytic infiltra- tion and fibrosis of the gland are pathognomonic. The presence of these autoantibodies predicts progressive gland failure and the need for hormone replacement. In a young woman with oligomenorrhea, pregnancy should always be the first diagnosis considered. Urine pregnancy tests are easily per- formed in the office and are highly sensitive. In this patient, the next most likely diagnosis is hypothalamic hypogonadism, secondary to her strenuous exercise regimen. These young women are at risk for osteo- porosis and should be counseled on adequate nutrition and offered combined oral contraceptives if the amenorrhea persists. The amount of hormone batch to batch and the patient dose response are believed to be more predictable than with other forms of hormone replacement, such as thyroid extract, which is made from desiccated beef or pork thyroid glands. There is no evidence that the natural hormone replacement is superior to the synthetic form. Other medications, especially iron- containing vitamins, should be taken at different times than levothy- roxine because they may interfere with absorption. Clinical Pearls ➤ The most common causes of oligomenorrhea are disorders of the hypo- thalamic-pituitary-gonadal axis, such as polycystic ovarian syndrome and hypothyroidism. Both hypothyroidism and hyperprolactinemia may cause hypothalamic dysfunction, leading to menstrual irregularities. This page intentionally left blank Case 13 A 49-year-old woman presents to the emergency room complaining of a 4-week history of progressive abdominal swelling and discomfort. She has no other gastrointestinal symptoms, and she has a normal appetite and normal bowel habits. Her medical history is significant only for three pregnancies, one of which was complicated by excessive blood loss, requiring a blood transfusion. She is happily married for 20 years, exercises, does not smoke, and drinks only occasionally. On pointed questioning, however, she does admit that she was “wild” in her youth, and she had snorted cocaine once or twice at parties many years ago. She is thin, her complexion is sallow, her sclerae are icteric, her chest is clear, and her heart rhythm is regular with no murmur. Her abdomen is distended, with mild diffuse tenderness, hypoactive bowel sounds, shifting dullness to percussion, and a fluid wave. Her history reveals a blood transfusion with postpartum hemorrhage and cocaine use. Her abdomen is dis- tended, with mild diffuse tenderness, shifting dullness to percussion, and a fluid wave, consistent with ascites. Learn the complications of chronic hepatitis, such as cirrhosis and portal hypertension. Considerations This 49-year-old woman had been in good health until recently, when she noted increasing abdominal swelling and discomfort, indicative of ascites. The physical examination is consistent with ascites with the fluid wave and shift- ing dullness. Her laboratory studies are significant for hypoalbuminemia and coagulopathy (prolonged prothrombin time), indicating probable impaired hepatic synthetic function and advanced liver disease. She does have prior exposures, most notably a blood transfusion, which put her at risk for hepatitis viruses, espe- cially hepatitis C. Currently, she also has a low-grade fever and mild abdomi- nal tenderness, both signs of infection. Bacterial infection of the ascitic fluid must be considered, because untreated cases have a high mortality. Thus, paracentesis using a needle introduced through the skin into the peritoneal cavity can be used to assess for infection as well as to seek an etiology of the ascites. The most common causes of chronic hepatitis are viral infections, such as hepatitis B and C, alcohol use, chronic exposure to other drugs or toxins, and autoimmune hepatitis. Less common causes are inherited meta- bolic disorders, such as hemochromatosis, Wilson disease, or α1-antitrypsin deficiency. Hepatitis C infection is most commonly acquired through percutaneous exposure to blood. It also can be transmitted through exposure to other body fluids, although this method is less effective. Risk factors for acquisition of hepatitis C include intravenous drug use, sharing of straws to snort cocaine, hemodialysis, blood transfusion, tattooing, and piercing. Most patients diagnosed with hepatitis C are asymptomatic, and report no prior history of acute hepatitis. The clinician must have a high index of suspi- cion and offer screening to those individuals with risk factors for infection. Approximately 70% to 80% of all patients infected with hepatitis C will develop chronic hepatitis in the 10 years following infection. Among those with cirrhosis, 1% to 4% annually may develop hepatocellular carcinoma. Therapy is directed toward reducing the viral load to prevent the sequelae of end-stage cirrhosis, liver failure, and hepatocellular car- cinoma. Currently, the treatment of choice for chronic hepatitis C is combi- nation therapy with pegylated alpha-interferon and ribavirin. However, the therapy has many side effects, such as influenzalike symptoms and depression with interferon, and hemolysis with ribavirin.

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In the inherited condition of Wilson’s disease discount alli 60mg free shipping, the secretion of copper into bile is abnormal order alli cheap, resulting in a low blood level of the copper-binding protein ceruloplasmin generic alli 60mg mastercard. Glycogen is mainly stored in the liver and muscle cells buy alli without prescription, but the kidneys and intestines also store some limited amounts of glycogen (Table 6. The inability to degrade glycogen may cause cells to become pathologically engorged, lead- ing to a functional loss of glycogen as an energy source and a blood glucose buffer. For example, the enzyme glucose-6-phosphatase is localised on the cisternal (inner) surface of the endoplasmic reticulum, and glucose-6-phosphate must be transported (translocated) across the endoplasmic reticulum to gain access to the enzyme. Mutation of either the phosphatase or the translocase will lead to symptoms characteristic of von Gierke’s disease. Hepatocytes secrete bile into canaliculi, then into bile ducts, where it is modified by addition of a bicarbonate-rich secretion from ductal epithelial cells. Further modification occurs in the gall bladder, where it is concentrated up to fivefold, through absorption of water and electrolytes. Only relatively small quantities of bile acids are lost from the body; approximately 95% of bile acids delivered to the duodenum are absorbed back into blood within the ileum. Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver (enterohepatic circulation). Hepatocytes extract bile acids very efficiently from sinusoidal blood; they are re-secreted into canaliculi. The net result of enterohepatic recirculation is that each bile salt molecule may be reused up to 20 times, and often 2 or 3 times during a single digestive phase (Figure 6. Liver disease, and damage to the canalicular system, can result in escape of bile acids into the systemic circulation. Assay of systemic levels of bile acids is used clinically as a sensitive indicator of hepatic disease. Bile acids are steroids, characterised by a carbon skeleton with four fused rings, generally arranged in a 6-6-6-5 fashion. Within the intestines, bacteria convert primary bile acids to secondary bile acids, for example deoxycholate (from cholate) and lithocholate (from chenodeoxycholate). Both primary and secondary bile acids are re-absorbed by the intestines and delivered back to the liver via the portal circulation. They facilitate the digestion of dietary triacylglycerols by acting as emulsifying agents; emulsification increases the surface area of fat, making it available for digestion by lipases. They facilitate the intestinal absorption of fat-soluble vitamins (vitamin A, retinol; vitamin D, cholecalciferol; vitamin E, tocopherol; and vitamin K). Their synthesis and subsequent excretion in the faeces represents the only significant mech- anism for the elimination of excess cholesterol. In humans, roughly 500 mg of cholesterol is converted to bile acids and eliminated in bile every day. Bile acids and phospholipids solubilise cholesterol in the bile, thereby preventing the pre- cipitation of cholesterol in the gall bladder. When chyme from an ingested meal enters the small intestine, acid and partially digested fats and proteins stimulate secretion of the enteric hormones cholecystokinin and secretin. Its effect on the biliary system is similar to that on the pancreas; it simulates biliary duct cells to secrete bicarbonate and water, expanding the volume of bile and increasing the flow rate into the intestine. The processes of gall bladder filling and emptying can be visualised using an imaging technique called scintography. This procedure is utilised as a diagnostic aid in certain types of hepatobiliary disease. Scintography is the process of obtaining a photographic recording of the distribution of an internally administered radiopharmaceutical with the use of a gamma camera. As surfactants (detergents), bile acids are potentially toxic to cells and so their levels are tightly regulated. In this way a negative-feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are already high. Bile acid sequestrants bind bile acids in the gut, preventing their re-absorption. In so doing, more endogenous cholesterol is directed to the production of bile acids, thereby lowering cholesterol levels. Cholesterol synthesis occurs in the cytoplasm and microsomes (smooth endoplasmic reticulum) (Figure 6. A relatively constant level of cholesterol in the body (150–200 mg/dl) is maintained primarily by controlling the level of de novo synthesis. The level of cholesterol synthesis is regulated in part by the dietary intake of cholesterol. Cholesterol from both diet and synthesis is utilised in the formation of membranes and in the synthesis of the steroid hormones and bile acids. The cellular supply of cholesterol is maintained at a steady level by three distinct mechanisms: 1. Synthesis begins with the transport of acetyl-CoA from the mitochondrion to the cytosol. The phosphorylation reactions are required to solubilise the isoprenoid intermediates in the pathway. Intermediates in the pathway are used for the synthesis of prenylated proteins, dolichol, coenzyme Q and the side chain of haem a. In the liver, drugs may undergo first-pass metabolism, a process in which they are modified, activated or inactivated, before they enter the systemic circulation; alternatively, they may be left unchanged. An oral drug that is absorbed and metabolised in the liver is said to show the ‘first-pass effect’. Medications that are metabolised by the liver must be used with caution in patients with hep- atic disease; such patients may need lower doses of the drug. Alcohol is primarily metabolised by the liver, and accumulation of its products can lead to cell injury and death. The rate of this metabolism is an important determinant of the duration and intensity of the pharmacological action of drugs. While both do occur, the major metabolites of most drugs are detoxication products. Drug hepatotoxicity is a common cause of acute liver failure, with an incidence of 1 in 10 000–100 000. Phase I reactions (also termed non-synthetic reactions) may occur by oxidation, reduction, hydrolysis, cyclisation and decyclisation reactions. If the metabolites of phase I reactions are sufficiently polar, they may be readily excreted at this point. However, many phase I products are not elim- inated rapidly and undergo a subsequent reaction in which an endogenous substrate combines with the newly incorporated functional group to form a highly polar conjugate. Quantitatively, the smooth endoplasmic reticulum of the hepatocyte is the principal organelle of drug metabolism. Other sites of drug metabolism include epithelial cells of the gastrointestinal tract, the lungs, the kidneys and the skin. Primarily membrane- associated proteins, they are located in the inner membrane of mitochondria and the endoplasmic reticulum of cells, and metabolise thousands of endogenous and exogenous compounds. Most of these enzymes can metabolise multiple substrates, and many can catalyse multiple reactions. Most alcohol consumed is metabolised in the liver, while the small quantity that remains unmetabolised permits alcohol concentration to be measured in breath and urine. This presents two potential problems: first, the porphyrin haem ring is hydrophobic and must be solubilised to be excreted, and second, iron must be conserved for new haem synthesis. At the sinusoidal surface of the liver, unconjugated bilirubin detaches from albumin and is transported through the hepatocyte membrane by facilitated diffusion. Within the hepatocyte, bilirubin is bound to two major intracellular proteins, cytosolic Y protein (ligandin or glutathione S-transferase B) and cytosolic Z protein (also known as fatty acid-binding protein). The binding of bilirubin to these proteins decreases the efflux of bilirubin back into the plasma, and therefore increases net bilirubin uptake. It is poorly soluble in water at physiologic pH, and conversion to a water-soluble form is essential for elimination by the liver and kidney. This is achieved by hepatic glucuronic acid conjugation of the propionic acid side chains of bilirubin; bilirubin glucuronides are water-soluble and readily excreted in bile. Other compounds, such as xylose and glucose, may also undergo esterification with bilirubin.

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Subjects were injected with 3cc volume duction of neuropathic pain has been demonstrated in a patient fol- of 0 buy alli once a day. The patient was signif- amcinolone buy alli mastercard, and 10 patients were injected with 3 cc volume of 0 discount 60mg alli overnight delivery. Of crucial duration order alli discount, current pain medication, last shoulder injection, passive importance, however, was that the patient over an almost complete range of motion, terminal arc pain. Rotator cuff lesion was examined cessation of pain syndrome reported (pain scale 0–1). Ultrasound-guided sub- good to move passively and in the meantime could be started with a acromial-subdeltoid bursa injection was done by same physiatrist. Conclusion: Subacromial-subdeltoid bursa in- 1Ludhiana, India jection of the same total volume of lidocaine with different amount J Rehabil Med Suppl 55 Poster Abstracts 73 of steroid has signifcantly different therapeutic effect. The patient was diagnosed histopathologically as diffuse large to inject appropriate dose of triamcinolone as required. However, scintigraphy is valuable in staging, it can detect multifocal involvement which alters therapy. Conclusion: As mentioned above all imaging methods who developed diffuse anterior thigh edema as a result of an injury have different properties complementig each other that should be while attempting a jump-over during pentathlon training described benefted from for diagnosis and handled in manipulation of am- here. Material and Methods: A 37-year-old man with pain on his biguous lesions ran into on classical imaging techniques. He had a history of injury to his left lower extremity 7 months ago while jumping 237 over during a penthatlon training. Arslan 1Gülhane Military Medical Academy, Nuclear Medicine, Ankara, pulses were normal bilaterally. Firstly, he had been treated with Turkey, 2Gülhane Military Medical Academy, Physical Medicine ice, elevation, immobilization and some nonsteroidal anti-infam- matory drugs. He had taken some analgesics and myorelaxant and Rehabilitation, Ankara, Turkey drugs with the diagnosis of myalgia but his symptoms were not Introduction/Background: Chronic recurrent multifocal osteomy- relieved through 7 months. Patients may complain of pain, tenderness, swelling and of edema anterior compartment of the thigh. It is characterized by noninfectious bone lesions at ed the presence of extensive edema in the anterior compartment of multiple sites. Involvement of metaphysis adjacent to the growth the left thigh from groin level to suprapatellar area. The patient was consulted with male was complaining of joint stiffness at mornings and backache an orthopedic surgeon and non-surgical treatments were suggested. Pelvic X-ray graphy showed sclerosis and contour Conservative treatments are going on and symptoms are decreased irregularity at right sacroiliac joint. Spondyloar- with high-energy injuries but it may be also occurred with lower- thropathy was suspected by the clinician initially and a Tc99m- energy injuries and this severe condition should not be overlooked. There were increased activ- ity in right sacroiliac joint, right trochanter major of femur, 5th and 236 7th thoracic vertebrae, frst lumbar vertebrae (L1) on bone scintig- raphy. A multidiscipli- Turkey, 2Gülhane Military Medical Academy, Oncology, Ankara, nary investigation is necessary. Radiologic evaluation begins with Turkey, 3Gülhane Military Medical Academy, Physical Medicine a plain radiograph of the symptomatic site. Osteolytic or sclerotic and Rehabilitation, Ankara, Turkey lesions may be seen on X-ray graphy. The patient having de- generative changes on lumbosacral x-ray graphy was considered to be affected by sacroiliitis and a whole-body bone scintigraphy 238 was requested. The chronic pain was correlated with both disease-related and the likely causes are hormonal changes and edema. Common factors such as rigidity and daily living activities and also general treatment options are activity modifcation, splinting, steroid injec- factors such as gender and depression. Symptoms were worse at night and she also complained of sleep disturbance because of pain. Motor and sensory examination of both Umay 1Ministry of Health Ankara Diskapi Yildirim Beyazit Education and upper limbs was normal. Results: Signifcant reduc- partment of Physical Therapy and Rehabilitation, Ankara, Turkey tion in pain and recovery of sleep disturbances noted and it was continiued from the day after the frst session to delivery. Conclu- Introduction/Background: Although musculoskeletal problems are sion: In recent years kinesio-taping has become popular in muscu- common, there have been few reports that describe the prevalence loskeletal problems. This technique also relieves pressure and irritation lence of musculoskeletal pain and its impact on activities of daily of the neurosensory receptors that can create pain. Leblebici1 and motor complications, comorbid conditions, and health-related 1Baskent University, Physical Medicine and Rehabilitation, Adana, quality of life were evaluated and recorded. Pain lasting longer than Turkey three months was defned as ‘chronic pain’ and participants were questioned relative to the characteristics of the chronic pain. Results: There was no statistically signifcant cor- J Rehabil Med Suppl 55 Poster Abstracts 75 relation between age and the risk of fall. Also, it was not determined infammatory arthritis and as an evaluation of the temperomandibu- the signifcant correlation between the values of latency and ampli- lary joint, it is however a new method for objective pain evaluation. Material and Methods: In inten- may be not alone signifcant factor for the risk of fall. Thir- measurements may not be provide a signifcant contribution to evalu- teen (n=9. Our participants can be considered as pain of the retinaculum patellae and were included in this study. It is thought to work by underlining that there may be a 90 degrees and 45 degrees. Results: The temperature differences risk of falling more than expected in the community. To our knowledge, this is the frst 1 2 3 report of an objective assessment of pain of the retinaculum patel- M. Our fndings could help making it Shiraz University of Medical Sciences, Physical Medicine and Re- possible to localize and assess pain more precisely. We suppose distal crease of the ance obtained from the electrode applied to the hand was measured, wrist as a point of no. The patients with omalgia and the low back pain in para- tween each two points, and each segments between each 2points lyzed side were done the hyperthermia of hot pack and the xylocaine are called 1to7 from proximal to distal. Results: Mean age of par- intramuscular injection, and visual analogue scale was compared ticipants was 45. Results: For of distal sensory latency (both antidromic and orthodromic) with the patients with omalgia and the low back pain, the difference was inching method are greater in patients than control group (p-value admitted in the individual value that was able to be put in the resting <0. Conclusion: We reveal signifcant difference of antidro- the improvement of the pain sensation was, the smaller increases of mic sensory latency between two adjacent points belonged to ffth impedance when the low back pain was improved by the effect of and sixth segments. Conclusion: The pain is a subjective phenomenon, latency between points was greater in patients than control group and it is changeable. The objective evaluation is diffcult because but only sixth segment had statistically signifcant difference. Kimura, and electromyography was bell’s type facial nerve palsies were compared in 5 years interval performed with monopolar needle electrode 1 inch and a half in The presence or absences of spontaneous activities in orbicularis the muscle bellies. In each patient the perception of pain was as- oculi or frontals muscles were considered. Results: The results showed the following: volved sites and normal sites in each patient calculated. Finally the The perception of pain was much higher during the nerve conduc- data of two groups were compared statistically. Results: Only in 25% of patients Conclusion: Nevertheless, the pain perceived in both tests was with Bell’s palsy the spontaneous activities were recorded while high, considering this kind of tests as painful and invasive tests it was recordable in all trauma patients at p=0. Material and Methods: 3 month retrospective study of inpatients 1Ahvaz Jundishapur Univeristy of Medical Scineces - Ahvaz - Iran, from Apr–Jun 2015 (n=25). The study end point was either pa- Physical Medicine and Rehabilitation, Ahvaz, Iran, 2Ahvaz Jundis- tient discharge or optimised analgesia. We captured demographic hapur Univeristy of Medical Scineces - Ahvaz - Iran, Neurology, data, injuries/treatments nature, and pain scores at admission and Ahvaz, Iran, 3Ahvaz Jundishapur Univeristy of Medical Sciences discharge/end points. Data displayed as median (range) unless - Ahvaz - Iran, Health Research Center- Diabetes Research Center- otherwise stated. Pain scores tend to improve and Introduction/Background: Most of the post stroke patients suffer analgesia use tended to decrease over time. Discussion: We described the with the method of including stretching exercises in addition to dis- profle, pain prevalence, and use of analgesia in rehabilitation pa- port injection in the affected muscles.

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It inhibits gastric acid secretion and stimulates the production of mucus and bicarbonate discount 60mg alli mastercard. Its use is mainly restricted because of its potential side effects; it is also used to induce abortion or labour order alli cheap. Of these actions 60 mg alli otc, mucin syn- 3 thesis and secretion are of particular importance in view of mucosal surface protection generic alli 60mg free shipping. However, the risk of peptic ulceration with these drugs still remains, as well as a number of other side effects. Binding of histamine, and therefore initiation of this response, is prevented by the H2 antagonist, cimetidine. This would explain the observation that misoprostol directly inhibits gastric acid production. Fatty acid synthesis occurs in the cytosol (fatty acid oxidation occurs in the mitochondria; compartmentalisation of the two pathways allows for distinct regulation of each). Oxidation or synthesis of fats utilises an activated two-carbon intermediate, acetyl- CoA, but the acetyl-CoA in fat synthesis exists temporarily bound to the enzyme complex as malonyl-CoA. Synthesis of malonyl-CoA is the first committed step of fatty acid synthesis (Figure 5. This conformational change is enhanced by citrate and inhibited by long-chain fatty acids (Figure 5. Both isoenzymes are allosteri- cally activated by citrate and inhibited by palmitoyl-CoA and other short- and long-chain fatty acyl-CoAs. Continued condensation of malonyl-CoA with acetyl-CoA units is catalysed by fatty acid synthase, eventually leading to the 16-carbon palmitic acid (Figure 5. Insulin is known to stimulate synthesis of both enzymes, whereas starvation leads to decreased synthesis. It was first identified as a glucose-responsive transcription factor (it is required for the glucose-induced expression of the hepatic isoenzyme of glycolysis, pyruvate kinase). Fatty acids are stored as triacylglycerol in all cells, but primarily in adipocytes of adipose tissue. This means that adipocytes must have glucose to oxidise in order to store fatty acids in the form of triacylglycerols. This release is controlled by a complex series of interrelated cascades that result in the activation of hormone-sensitive lipase. In adipocytes this stimulus can come from glucagon, adrenaline (epinephrine) or β-corticotropin. Hormone-sensitive lipase hydrolyses fatty acids from carbon atoms 1 or 3 of triacylglycerols. The resulting diacylglycerols are substrates for either hormone-sensitive lipase or the non- inducible enzyme diacylglycerol lipase. Free fatty acids diffuse from adipose cells, combine with albumin in the blood and are thereby transported to other tissues. The mobilisation of adipose lipid stores is inhibited by numerous stimuli, the most signifi- cant being insulin (through the inhibition of adenyl cyclase activity). In a well-fed individual, insulin release prevents the inappropriate mobilisation of stored lipid; instead any excess fat and carbohydrate are incorporated into the triacylglycerol pool within adipose tissue. Phospholipids are degraded at the 2 position by pancreatic phospholipase A2 releasing a free fatty acid and the lysophospholipid. These products may diffuse into the intestinal epithelial cells, where the re-synthesis of triacylglycerols occurs. Both dietary triacylglycerols and cholesterol are packaged into chylomicrons; these enter the blood (left subclavian vein) via the lymph system. They are metabolically very active; their stored triacylglycerol is constantly hydrolysed and re-synthesised. Free fatty acids may be absorbed directly by tissues, or bound to albumin for transport; human serum albumin possesses multiple fatty acid binding sites of various affinities. Glycerol is returned via the blood to the liver (and kidneys), where it is converted to the glycolytic intermediate dihydroxyacetone phosphate (glycerol is an important source of glucose in gluco- neogenesis). These proteins are thought to facilitate the transfer of fatty acids between extra- and intracellular membranes. Studies in aP2-deficient mice have shown that this lipid chaperone has a significant role in several aspects of the metabolic syndrome, including type 2 diabetes and atherosclerosis. Chylomicron remnants, containing primarily cholesterol, apo-E and apo-B-48, are then taken up by the liver through interaction with the chylomicron remnant receptor (this recognition requires apo-E). Chylomicrons therefore function to: • deliver dietary triacylglycerols to adipose tissue and muscle • deliver dietary cholesterol to the liver. The endocytosed membrane vesicles (endosomes) fuse with lysosomes, in which the apoproteins are degraded and the cholesterol esters are hydrolysed to yield free cholesterol. The precise mechanism for these effects is unclear, but it may be mediated through the regulation of apo-B degradation. This process has the effect of lowering the level of intracellular cholesterol, since the cholesterol stored within cells as cholesteryl esters will be mobilised to replace the cholesterol removed from the plasma membrane. Lysosomal enzymes degrade the apoproteins and release free fatty acids and cholesterol. This can lead to excess circulating levels of cholesterol and cholesteryl esters when the dietary intake of fat and cholesterol is excessive. Excess cholesterol tends to be deposited in the skin and tendons and within the arteries, which can lead to atherosclerosis. Individuals suffering from diabetes mellitus, hypothyroidism or kidney disease often exhibit abnormal lipoprotein metabolism as a result of secondary effects of their disorders. The resultant hypercholesterolaemia leads to premature coronary artery disease and atherosclerotic plaque formation. Familial hypercholesterolaemia was the first inherited disorder recognised as being a cause of myocardial infarction (heart attack). Caucasians and Japanese with the apo-E-ε4 isoform have between 10 and 30 times the risk of developing Alzheimer’s by 75 years of age. While the exact mechanism is unknown, evidence suggests an interaction with amyloid. Alzheimer’s disease is characterised by plaques consisting of the peptide beta-amyloid. However, the isoform apo-E-ε4 is much less effective, which might result in an increased vulnerability to Alzheimer’s in individuals with that gene variation. Drug therapy is considered as an option only if non-pharmacologic interventions (altered diet and exercise) have failed to lower plasma lipids. These are compounds that bind bile acids; the drop in hepatic reabsorption of bile acids releases a feedback inhibition, resulting in a greater amount of cholesterol being converted to bile acids to maintain a steady level in the circulation. Focus on: atherosclerosis ‘Arteriosclerosis’ is a general term describing any hardening or loss of elasticity of medium or large arteries, and refers to the formation of an atheromatous plaque. Lipoprotein-associated phospholipase A2 is an emerging cardiovascular risk marker. Monocytes enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and may play a role in the development of atherosclerosis and rheumatoid arthritis. There is also smooth- muscle proliferation and migration from tunica media to intima, responding to cytokines secreted by damaged endothelial cells. They are thought to participate in the removal of many foreign substances and waste materials in the body. It is characterised by a remodelling of arteries involving the concomitant accumulation of fatty substances called plaques. As the plaques grow, artery wall thickening occurs without any narrowing of the artery lumen; stenosis, the narrowing of the artery opening, is a late event, which may or may not occur, and is likely the result of repeated plaque rupture and healing responses. Most commonly a plaque will rupture, forming a thrombus, which can rapidly slow or stop blood flow, leading to death of the tissues fed by the artery: an infarction. There is some evidence that atherosclerosis may be caused by an infection of the vascular smooth-muscle cells. Chickens, for example, develop atherosclerosis when infected with the Marek’s disease herpesvirus. Herpesvirus infection of arterial smooth-muscle cells has been shown to cause cholesteryl ester accumulation, which is associated with atherosclerosis.

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