Kidneys intrinsic factor

Pharmacokinetics The parietal cells of the stomach secrete intrinsic factor, which regulates the amount of vitamin B-12 absorbed in the terminal ileum. Bioavailability of oral preparations is approximately 25%. Vitamin B12 is primarily stored in the liver. Enterohepatic circulation plays a key role in recycling vitamin B-12 from mainly bile. If plasma-binding proteins are saturated, excess free vitamin B- 2 will be excreted in the kidney. 

Diuretics, by increasing kidney output, deplete calcium, magnesium, potassium, and zinc. This, in turn, depletes energy and lowers immune function. Over-the-counter antacids, as well as the peptic ulcer medication cimetidine, reduce iron and calcium assimilation, vitamin Bj , and intrinsic factor (without which Bi2 can t be absorbed). Drugs prescribed for heart disease reduce libido, and some of them render men impotent. 

Vitamin Bj2 may be found in liver, kidney, fish, and fortified milk and helps convert folic acid into its active form. Vitamin Bj2 is essential to synthesize DNA and promotes cellular division and is required for hematopoiesis (development of red blood cells in bone marrow) and to maintain the integrity of the nervous system. Vitamin Bj2 is absorbed in the intestine with the aid of an intrinsic factor produced by gastric parietal cells. Once absorbed, vitamin Bj2 binds to... 

The tridentate histidine ligand seemed convenient since it is a powerful ligand requiring only low concentrations. Vitamin B12 is sensitive to high temperatures, hence, the chelator should trap the c-[ Tc(CO)3] moiety at temperatures below 50 °C. The derivatives presented in Scheme 4.18 labeled quantitatively at 50 °C and a concentration between lO " M and 10 M within 30 min. No unspecific labeling was observed and the radiopharmaceutical is stable in serum. Both compounds are enzymatically active and bind to intrinsic factor IF. Preliminary in vivo mice studies showed good tumor uptake but also a high liver and/or kidney... 

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

A variation on the basic theme of receptor Tyr kinases is seen in receptors that have no intrinsic protein kinase activity but, when occupied by their ligand, bind a soluble Tyr kinase. One example is the system that regulates the formation of erythrocytes in mammals. The cytokine (developmental signal) for this system is erythropoietin (EPO), a 165 amino acid protein produced in the kidneys. When EPO binds to its plasma membrane receptor (Fig. 12-9), the receptor dimerizes and can now bind the soluble protein kinase JAK (Janus kinase). This binding activates JAK, which phosphory-lates several Tyr residues in the cytoplasmic domain of the EPO receptor. A family of transcription factors, collectively called STATs (signal transducers and activators of transcription), are also targets of the JAK kinase activity. An SH2 domain in STATS binds (P)-Tyr residues in the EPO receptor, positioning it for this phosphorylation by JAK. When STATS is phosphorylated in re-... 

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