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Glyceraldehyde 3-Phosphate Dehydrogenase Energy transformation: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate order viagra extra dosage 200mg line impotence with condoms. Glyceraldehyde 3-Phosphate Dehydrogenase Energy transformation: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate order 130 mg viagra extra dosage visa erectile dysfunction drugs singapore. Glyceraldehyde 3-Phosphate Dehydrogenase The enzyme-bound thioester intermediate reduces the activation energy for the second reaction: 24 1. Phosphoglycerate Mutase The next two reactions convert the remaining phosphate ester into a phosphate having a high phosphoryl transfer potential The first is an isomerization reaction 26 1. Enolase The next two reactions convert the remaining phosphate ester into a phosphate having a high phosphoryl transfer potential The second is a dehydration (lyase) reaction 27 1. Maintaining Redox Balance The solution to this problem lies in what happens to the pyruvate that is produced in glycolysis: Fermentation Pathways 32 1. Maintaining Redox Balance Lactic acid fermentation is use by bacteria and human muscles and produces lactate. Usually due to loss of uridyl transferase activity Symptoms include Failure to thrive infants Enlarged liver and jaundice, sometimes cirrhosis Cataracts Mental retardation 41 2. Control of Glycolysis In metabolic pathways, control is focused on those steps in the pathway that are irreversible. Control of Glycolysis The different levels of control have different response times: Level of Control Response Time Allosteric milleseconds Phosphorylation seconds Transcriptional hours 44 2. Fructose 2,6-bisphosphate A regulated bifunctional enzyme synthesizes and degrades fructose 2,6-bisphosphate: 49 2. The brain has a strong preference for glucose, while the red blood cells have and absolute requirement for glucose. Gluconeogenesis The three kinase reactions are the ones with the greatest positive free energies in the reverse directions 54 3. Gluconeogenesis The hexokinase and phosphofructokinase reactions can be reversed simply with a phosphatase 55 3. Formation of Phosphoenopyruvate The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate. Oxaloacetate Shuttle Oxaloacetate is synthesized in the mitochondria and is shuttled into the cytosol where it is converted into phosphoenolpyruvate 60 3. Regulation of Glycolysis and Gluconeogenesis Reciprocal regulation of glycolysis and gluconeogenesis in the liver 62 4. Evolution of Glycolysis and Gluconeogenesis Glycolysis and Gluconeogenesis are evolutionarily intertwined. Therapy for Anaphylactoid Reactions  Bronchosapsm  Minor-Uticaria, with or  Oxygen without Skin Itching  Mild- albuterol inhaler, 2 puffs  No therapy  Moderate-Epinephrine 0. Patients with prior evidence of an anaphylactoid reaction to contrast media should receive appropriate steroid and antihistamine prophylaxis prior to repeat contrast administration. In patients with prior history of allergic reactions to shellfish or seafood, anaphylactoid prophylaxis for contrast reaction is not beneficial. Patients undergoing cardiac catheterization with contrast media should receive adequate preparatory hydration. In patients with chronic kidney disease (creatinine clearance <60cc/min), the volume of contrast media should be minimized. Patient  Total Air Kerma at the Interventional Reference Point (K , a,r Dose Gy) is the x-ray energy delivered to air 15cm from for patient dose burden Assessment for deterministic skin effects. The Procedure/Patient  As patient size increases…  Image quality poor  Input dose of radiation increases exponentially  Scatter radiation more  As complexity increases. Procedure Related Issues to Minimize Exposure to Patient and Operator  Utilize radiation only when imaging is necessary  Minimize use of cine  Minimize use of steep angles of X-ray beam  Minimize use of magnification modes  Minimize frame rate of fluoroscopy and cine  Keep the image receptor close to the patient  Utilize collimation to the fullest extent possible  Monitor radiation dose in real time to assess patient risk/benefit during the procedure Tube Position and Scatter The scatter profile tilts as the x-ray tube is moved from the posterior to the anterior projection or when the tube is moved toward the cranial or caudal projections. Procedure Related Issues to Specifically Minimize Exposure to Operator  Use and maintain appropriate protective garments  Maximize distance of operator from X-ray source and patient  Keep above-table and below-table shields in optimal position at all times  Keep all body parts out of the field of view at all times Inverse Square Law 2 2 I / I = (d ) / (d ) 1 2 2 1 This relationship shows that doubling the distance from a radiation source will decrease the exposure rate to 1/4 the original. Staff Radiation Protection  Shielding  Lead>90%;Proper care of aprons  Thyroid shielding; <40 yo The Next Armani? Staff Exposure Limits  Whole Body 5 rem (50 mSv)/yr  Eyes 15 rem (150 mSv)/ yr  Pregnant Women 50 mrem (0.

Adverse effects: The drug appears to be well tolerated when administered in combination with zidovudine (with or without didanosine) buy viagra extra dosage 150 mg with mastercard what age can erectile dysfunction occur. The major toxicity associated with nevirapine to date is rash generic viagra extra dosage 200mg otc impotence icd 9, including severe or life-threatening rash. Fusion Inhibitors Enfuvirtide (T-20): Enfuvirtide is the first approved agent in fusion inhibitors. Both agents are effective in the prevention of influenza a virus infection in high-risk individuals. Additionally, both drugs can be used in the treatment of influenza A, effectively reducing the duration of symptoms when administered within 48 hours after their onset. The most common side effects are gastrointestinal intolerance and central nervous system effects (eg, nervousness, difficulty in concentrating, lightheadedness). Cancer cells manifest uncontrolled proliferation, loss of function due to loss of capacity to differentiate, invasiveness, and the ability to metastasize. Cancer arises as a result of genetic changes in the cell, the main genetic changes being; inactivation of tumor suppressor genes and activation of oncogenes. Chemotherapy Most anticancer drugs are antiproliferative, and hence affect rapidly growing dividing normal cells. Cytotoxic drugs are further classified into: • Alkylating agents and related compounds (e. Treatment of Malaria Four species of Plasmodium are responsible for human malaria: P. Although all may cause severe illness, P falciparum causes most of the serious complications and deaths. The effectiveness of antimalarial agents varies between parasite species and between stages in their life cycles. Parasite Life Cycle The mosquito becomes infected by taking human blood that contains parasites in the sexual form. The sporozoites that develop in the mosquito are then inoculated into humans at its next feeding. In the exoerythrocytic stage, the sporozoites multiply in the liver to form tissue schizonts. The merozoites invade red blood cells, multiply in them to form blood schizonts, and finally rupture the cells, releasing a new crop of merozoites. The gametocytes (the sexual stage) form and are released into the circulation, where they may be taken in by another mosquito. P falciparum and P malariae have only one cycle of liver cell invasion and multiplication, and liver infection ceases spontaneously in less than 4 weeks. So, treatment that eliminates these species from the red blood cells four or more weeks after inoculation of the sporozoites will cure these infections. In P vivax and P ovale infections, sporozoites also induce in hepatic cells the dormant stage (the hypnozoite) that causes subsequent recurrences (relapses) of the infection. Therefore, treatment that eradicates parasites from both the red cells and the liver is required to cure these infections. None of these drugs prevent infection except for pyrimethamine and proguanil which prevent maturation of P falciparum hepatic schizonts. It is rapidly and almost completely absorbed from the gastrointestinal tract, and is rapidly distributed to the tissues. Antimalarial Action: Chloroquine is a highly effective blood schizonticide and is most widely used in chemoprophylaxis and in treatment of attacks of vivax, ovale, malariae, or sensitive falciparum malaria. Chloroquine is not active against the preerythrocytic plasmodium and does not effect radical cure. Selective toxicity for malarial parasites depends on a chloroquine-concentrating mechanism in parasitized cells. Clinical uses: Acute Malaria Attacks (it clears the parasitemia of acute attacks of P vivax, P ovale, and P malariae and of malaria due to nonresistant strains of P falciparum), and chemoprophylaxis (It is the preferred drug for prophylaxis against all forms of malaria except in regions where P falciparum is resistant to 4-aminoquinolines). Adverse Effects: Gastrointestinal symptoms, mild headache, pruritus, anorexia, malaise, blurring of vision, and urticaria are uncommon. A total cumulative dose of 100 g (base) may, contribute to the development of irreversible retinopathy, ototoxicity, and myopathy. Contraindications: It is contraindicated in patients with a history of liver damage, alcoholism, or neurologic or hematologic disorders, psoriasis or porphyria, in whom it may precipitate acute attacks of these diseases.

Sulfonamides inhibit both gram-positive and gram-negative bacteria cheap viagra extra dosage 120mg amex erectile dysfunction treated by, Nocardia order viagra extra dosage 200 mg with visa erectile dysfunction statistics australia, Chlamydia trachomatis, and some protozoa. Some enteric bacteria, such as E coli, Klebsiella, Salmonella, Shigella, and Enterobacter, are inhibited. Pharmacokinetics: They are absorbed from the stomach and small intestine and distributed widely to tissues and body fluids, placenta, and fetus. Absorbed sulfonamides become bound to serum proteins to an extent varying from 20% to over 90%. Sulfonamides and inactivated metabolites are then excreted into the urine, mainly by glomerular filtration. Clinical Uses Oral Absorbable Agents: Sulfisoxazole and sulfamethoxazole are short- to medium-acting agents that are used to treat urinary tract infections, respiratory tract infections, sinusitis, bronchitis, pneumonia, otitis media, and dysentery. Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. Sulfadoxine, long- acting sulfonamide, in combination with pyrimethamine used as a second-line agent in treatment for malaria. Oral Nonabsorbable Agents: Sulfasalazine is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease. Sulfasalazine is split by intestinal microflora to yield sulfapyridine and 5-aminosalicylate. Salicylate released in the colon in high concentration is responsible for an antiinflammatory effect. Comparably high concentrations of salicylate cannot be achieved in the colon by oral intake of ordinary formulations of salicylates because of severe gastrointestinal toxicity. Silver sulfadiazine is a much less toxic topical sulfonamide and is preferred to mafenide for prevention of infection of burn wounds. Adverse Reactions: The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, and diarrhea. Stevens-Johnson syndrome, crystalluria, hematuria, hemolytic or aplastic anemia, granulocytopenia, and thrombocytopenia occur less frequently. Sulfonamides taken near the end of pregnancy increase the risk of kernicterus in newborns. It is absorbed well from the gut and distributed widely in body fluids and tissues, including cerebrospinal fluid. Trimethoprim concentrates in prostatic fluid and in vaginal fluid, which are more acid than plasma. Therefore, it has more antibacterial activity in prostatic and vaginal fluids than many other antimicrobial drugs. Trimethoprim can be given alone in acute urinary tract infections, because most community- acquired organisms tend to be susceptible to the high concentrations. Trimethoprim produces the predictable adverse effects of an antifolate drug, especially megaloblastic anemia, leukopenia, and granulocytopenia. This can be prevented by the simultaneous administration of folinic acid, 6-8 mg/d. Trimethoprim-Sulfamethoxazole( Cotrimoxazole) The half-life of trimethoprim and sulfamethoxazole is similar. Trimethoprim, given together with sulfamethoxazole, produces sequential blocking in this metabolic sequence, resulting in marked enhancement of the activity of both drugs. The combination often is bactericidal, compared to the bacteriostatic activity of a sulfonamide alone. Clinical uses: Trimethoprim-sulfamethoxazole is effective treatment for Pneumocystis carinii pneumonia, shigellosis, systemic Salmonella infections, urinary tract infections, and prostatitis. It is active against many respiratory tract pathogens; Pneumococcus, Haemophilus species, Moraxella catarrhalis, and Klebsiella pneumoniae. Mycobacteria are slowly growing organisms (can also be dormant) and thus completely resistant to many drugs, or killed only very slowly by the few drugs that are active. A substantial proportion of mycobacterial organisms are intracellular, residing within macrophages, and inaccessible to drugs that penetrate poorly. Finally, mycobacteria are notorious for their ability to develop resistance to any single drug.

Because of this buy 150mg viagra extra dosage free shipping wellbutrin xl impotence, levels of phenylalanine rise to toxic levels in the body buy viagra extra dosage 120 mg otc erectile dysfunction medication patents, which results in damage to the central nervous system and brain. Symptoms include delayed neurological development, hyperactivity, mental retardation, seizures, skin rash, tremors, and uncontrolled movements of the arms and legs. Babies exposed to excess phenylalanine in utero may present with heart defects, physical and/or mental retardation, and microcephaly. The person must closely follow a strict diet that is low in phenylalanine to avoid symptoms and damage. Some animal products and certain starches are also high in phenylalanine, and intake of these foods should be carefully monitored. Your body processes the food you eat both to use immediately and, importantly, to store as energy for later demands. If there were no method in place to store excess energy, you would need to eat constantly in order to meet energy demands. Distinct mechanisms are in place to facilitate energy storage, and to make stored energy available during times of fasting and starvation. The Absorptive State The absorptive state, or the fed state, occurs after a meal when your body is digesting the food and absorbing the nutrients (anabolism exceeds catabolism). Digestion begins the moment you put food into your mouth, as the food is broken down into its constituent parts to be absorbed through the intestine. The digestion of carbohydrates begins in the mouth, whereas the digestion of proteins and fats begins in the stomach and small intestine. The constituent parts of these carbohydrates, fats, and proteins are transported across the intestinal wall and enter the bloodstream (sugars and amino acids) or the lymphatic system (fats). From the intestines, these systems transport them to the liver, adipose tissue, or muscle cells that will process and use, or store, the energy. Depending on the amounts and types of nutrients ingested, the absorptive state can linger for up to 4 hours. The ingestion of food and the rise of glucose concentrations in the bloodstream stimulate pancreatic beta cells to release insulin into the bloodstream, where it initiates the absorption of blood glucose by liver hepatocytes, and by adipose and muscle cells. By doing this, a concentration gradient is established where glucose levels are higher in the blood than in the cells. Insulin also stimulates the storage of glucose as glycogen in the liver and muscle cells where it can be used for later energy needs of the body. If energy is exerted shortly after eating, the dietary fats and sugars that were just ingested will be processed and used immediately for energy. If not, the excess glucose is stored as glycogen in the liver and muscle cells, or as fat in adipose tissue; excess dietary fat is also stored as triglycerides in adipose tissues. The Postabsorptive State The postabsorptive state, or the fasting state, occurs when the food has been digested, absorbed, and stored. You commonly fast overnight, but skipping meals during the day puts your body in the postabsorptive state as well. However, due to the demands of the tissues and organs, blood glucose levels must be maintained in the normal range of 80–120 mg/ dL. In response to a drop in blood glucose concentration, the hormone glucagon is released from the alpha cells of the pancreas. Glucagon acts upon the liver cells, where it inhibits the synthesis of glycogen and stimulates the breakdown of This OpenStax book is available for free at http://cnx. Gluconeogenesis will also begin in the liver to replace the glucose that has been used by the peripheral tissues. After ingestion of food, fats and proteins are processed as described previously; however, the glucose processing changes a bit. The gluconeogenesis that has been ongoing in the liver will continue after fasting to replace the glycogen stores that were depleted in the liver. After these stores have been replenished, excess glucose that is absorbed by the liver will be converted into triglycerides and fatty acids for long-term storage.