Treatment of metabolic diseases

Martin has used this strategy for the preparation of (3-(l,6) and P,(3-(l,l) hnked C-disaccha-rides, as shown in Scheme 7.7.73 Such C-disaccharides are a class of nonhydrolyzable mimics of disaccharide and potential glycosidase inhibitors in the treatment of metabolic diseases (Scheme 7.7). 

Dexamethasone (Eig. 8.3) is used for treatment of metabolic diseases in ruminants and for inflammatory diseases in a number of animal species. It is... 

A company s business developer needs to be aware of direct and indirect competition as actors and factors in terms of the market as well as in specific product challenges. It may be that the market opportunity can be treated by different modalities such as in the treatment of metabolic diseases like type II diabetes. Modifying someone s diet so that they lose weight can be... 

H. Satoh, US Patent 6,706,763 (March 16, 2004) Assignee Kyorin Pharmaceutical Company Utility Treatment of Metabolic Diseases... 

Finally, the similar computational strategy discussed in this chapter in combination with appropriate wet experiments may also be useful in rational redesign of many other metabolic enzymes for the therapeutic treatments of metabolic diseases. 

ACC is the rate-limiting enzyme in fatty acid synthesis and fatty acid oxidation, and its inhibition is attractive for treatment of metabolic diseases.9 10 Indeed, ACC2 knockout mice are resistant to diet-induced obesity and type 2... 

Peroxisome proliferator-activated receptors are ligand-activated receptors which regulate a number of genes involved in nutrient metabolism and energy homeostasis, and thus have served as drug targets for the treatment of metabolic diseases. Anne Reifel Miller and Alan M. Warshawsky review peroxisome proliferator-activated receptor y modulation for the treatment of type 2 diabetes. 

Engineering commensal bacteria for the treatment of metabolic diseases... 

Engineered commensal bacteria can also be nsed in the treatment of metabolic diseases. Examples of these metabolic diseases are obesity, high blood pressure, diabetes and hyperlipidemia that arises from unhealthy lifestyles and diet, and that needs to be treated nsing pills and injections in specified doses at particular time-points (Heng et al., 2015), thns reducing a patient s qnaUty of life. 

This electrolyte plays a vital role in the acid-base balance of the body. Bicarbonate may be given IV as sodium bicarbonate (NaHC03) in the treatment of metabolic acidosis, a state of imbalance that may be seen in diseases or situations such as severe shock, diabetic acidosis, severe diarrhea, extracorporeal circulation of blood, severe renal disease, and cardiac arrest. Oral sodium bicarbonate is used as a gastric and urinary alkalinizer. It may be used as a single drug or may be found as one of the ingredients in some antacid preparations. It is also useful in treating severe diarrhea accompanied by bicarbonate loss. 

Studies have demonstrated that reversal of metabolic acidosis can improve bone disease associated with CKD.38 Serum bicarbonate levels should be maintained at 22 mEq/L (22 mmol/L) in patients with bone disease associated with CKD.39 The treatment of metabolic acidosis is described below. 

Hofbauer LC, Heufelder AE (2000) Clinical review 114 hot topic. The role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases. J Clin Endocrinol Metab 85 2355-2363... 

The inhalation route for administering drugs into the pulmonary system for treatment of respiratory diseases eliminates many bioavailability problems such as plasma binding and first-pass metabolism, which are encountered in parenteral or oral administration. Consequently, a small inhalation dose is adequate for achieving... 

No attempt will be made to give an overview of the main pathways of the several dozen neurotransmitters, neuromodulators and co-transmitters which are possibly involved in the aetiology of mental illness. Instead a summary is given of the relevant pathways involved in the synthesis and metabolism of those transmitters which have conventionally been considered to be involved in the major psychiatric and neurological diseases and through which the psychotropic drugs used in the treatment of such diseases are believed to operate. 

Alkaloids play a very important role in organism metabolism and functional activity. They are metabolic products in plants, animals and micro-organisms. They occur in both vertebrates and invertebrates as endogenous and exogenous compounds. Many of them have a distributing effect on the nervous systems of animals. Alkaloids are the oldest successfully used drugs throughout the historical treatment of many diseases ... 

Aspirin (acetylsalicylic acid, Figure 7.9) is a derivative of salicyclic acid, which was first used in 1875 as an antipyretic and antirheumatic. The usual dose for mild pain is 300-600 mg orally. In the treatment of rheumatic diseases, larger doses, 5-8 g daily, are often required. Aspirin is rapidly hydrolysed in the plasma, liver and eiythrocytes to salicylate, which is responsible for some, but not all, of the analgesic activity. Both aspirin and salicylate are excreted in the urine. Excretion is facilitated by alkalinisation of the urine. Metabolism is normally very rapid, but the liver enzymes responsible for metabolism are easily saturated and after multiple doses the terminal half-life may increase from the normal 2-3 h to 10 h. A soluble salt, lysine acetylsalicylic acid, with similar pharmacological properties to aspirin, has been used by parenteral administration for postoperative pain. Aspirin in low doses (80-160 mg daily) is widely used in patients with cardiovascular disease to reduce the incidence of myocardial infarction and strokes. The prophylaxis against thromboembolic disease by low-dose aspirin is due to inhibition of COX-1-generated thromboxane A2 production. Because platelets do not form new enzymes, and COX-1 is irreversibly inhibited by aspirin, inhibition of platelet function lasts for the lifetime of a platelet (8-10 days). 

Azathioprine is a cytotoxic inhibitor of purine synthesis effective for the control of tissue rejection in organ transplantation. It is also used in the treatment of autoimmune diseases. Its biologically active metabolite, mercaptopurine, is an inhibitor of DNA synthesis. Mercaptopurine undergoes further metabolism to the active antitumour and immunosuppressive thioinosinic acid. This inhibits the conversion of purines to the corresponding phosphoribosyl-5 phosphates and hypoxanthine to inosinic acid, leading to inhibition of cell division and this is the mechanism of the immunosuppression by azathioprine and mercaptopurine. Humans are more sensitive than other species to the toxic effects of the thiopurines, in particular those involving the haematopoietic system. The major limiting toxicity of the thiopurines is bone marrow suppression, with leucopenia and thrombocytopenia. Liver toxicity is another common toxic effect. 

---