Renal system structure

An analogous mechanism in the mammalian cell may explain the high toxicity of these peptide antibiotics. Their specific nephrotoxicity may be due either to a difference of the structure between renal cell membranes and those in other cells or it may be due to the high concentration of the antibiotics in the renal system. 

Carbonic anhydrase (CA) exists in three known soluble forms in humans. All three isozymes (CA I, CA II, and CA III) are monomeric, zinc metalloenzymes with a molecular weight of approximately 29,000. The enzymes catalyze the reaction for the reversible hydration of C02. The CA I deficiency is known to cause renal tubular acidosis and nerve deafness. Deficiency of CA II produces osteopetrosis, renal tubular acidosis, and cerebral calcification. More than 40 CA II-defi-cient patients with a wide variety of ethnic origins have been reported. Both syndromes are autosomal recessive disorders. Enzymatic confirmation can be made by quantitating the CA I and CA II levels in red blood cells. Normally, CA I and CAII each contribute about 50% of the total activity, and the CAI activity is completely abolished by the addition of sodium iodide in the assay system (S22). The cDNA and genomic DNA for human CA I and II have been isolated and sequenced (B34, M33, V9). Structural gene mutations, such as missense mutation, nonsense... 

Oral bioavailability of a drug is primarily dependent upon its rate and extent of drug absorption and systemic clearance. Systemic clearance is primarily composed of hepatic, renal and biliary clearance. The PK properties are in turn directly impacted by the drug s physical properties, such as, log P, log D and pKa. The physical properties are in turn a function of the compound s structure, molecular weight, number of hydrogen bond donors and acceptors, and number of rotatable bonds. Oral bioavailability is the outcome from the dynamic interplay of these factors in the biological system. 

The metabolic encephalopathies comprise a series of neurological disorders not caused by primary structural abnormalities rather, they result from systemic illness, such as diabetes, liver disease and renal failure. Metabolic encephalopathies usually develop acutely or subacutely and are reversible if the systemic disorder is treated. If left... 

The alkylglycoside vector is a kidney-specific delivery system that has recently been established [23-25].This vector is efficiently taken up from the basal side of the renal epithelium in a blood flow-limited manner and it can be used with several types of therapeutic molecules. The following sections summarize and discuss, first, how the novel kidney-specific alkylglycoside vector was identified, second, its structural and size requirements and third, the potential limitations of delivery to the kidney and the characterization of its binding sites on kidney cell membranes. 

Proton pump inhibitors undergo rapid first-pass and systemic hepatic metabolism and have negligible renal clearance. Dose reduction is not needed for patients with renal insufficiency or mild to moderate liver disease but should be considered in patients with severe liver impairment. Although other proton pumps exist in the body, the H+,K+ ATPase appears to exist only in the parietal cell and is distinct structurally and functionally from other H+ -transporting enzymes. 

A topographical model has been proposed to explain why (E)-2-(3,4-dihydroxyphenyl)cyclopropylamine, 1, and alpha-methyldopamine (AMDA) are inactive in the renal vascular dopamine (DA) receptor system. In this model a steric protrusion (S2) resides approximately lX above the generalized plane of the receptor and acts to impede interaction with molecules such as 1 and AMDA which possess additional bulk in this region. Recent developments in DA structure-activity relationships offer further support for the existence of the S2 site. 

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