25-HCC

Metabolites of vitamin D, eg, cholecalciferol (CC), are essential in maintaining the appropriate blood level of Ca ". The active metabolite, 1,25-dihydroxycholecalciferol (1,25-DHCC), is synthesized in two steps. In the fiver, CC is hydroxylated to 25-hydroxycholecalciferol (25-HCC) which, in combination with a globulin carrier, is transported to the kidney where it is converted to 1,25-DHCC. This step, which requites 1-hydroxylase formation, induced by PTH, may be the controlling step in regulating Ca " concentration. The sites of action of 1,25-DHCC are the bones and the intestine. Formation of 1,25-DHCC is limited by an inactivation process, ie, conversion of 25-HCC to 24,25-DHCC, catalyzed by 24-hydroxylase. 

Vitamin D3, whether of dietary or skin origin, is hydroxylated in the liver to 25-hydroxycholecalciferol (25-HCC). This undergoes another hydroxylation in the kidneys to the very active compound 1,25-dihydroxycholecalciferol (1,25-DHCC). This reaction is catalyzed by la-hydroxylase, a mitochondrial cytochrome P-450 mixed-function oxidase normally found in the kidneys, although some pathological tissues such as sarcoid granulomas may also possess the enzyme (H12). 

Vitamin D is the sunshine vitamin . It was originally discovered as a crude mixture called vitamin Dj (no longer available as a supplement). Ergosterol, the plant equivalent of cholesterol, is converted to vitamin D2 by ultraviolet light. Vitamin D3 (cholecalciferol) is formed in the skin from 7-dehydrocholesterol (an intermediate in the cholesterol biosynthesis pathway) in the presence of ultraviolet light, which opens the B-ring of the steroid nucleus (Fig. 51.3). Cholecalciferol is successively hydroxylated first in the liver forming 25-hydroxycholecalciferol (25-HCC) and then in the kidney to form the most active form 1,25-dihydroxy cholecalciferol (1,25-DHCC), also known as calcitriol. 

The kidney cells are adaptable in that they can hydroxylate 25-HCC in alternative positions according to the need of the body for calcium. When the plasma calcium concentration tends to be low, the highly active 1,25-DHCC is formed but in normal and hypetcalcaemic conditions the isomer 21,25-DHCC is produced instead. The latter is less active in promoting absorption of calcium but acts on the kidney to increase calcium excretion. 

A practical outcome of these discoveries concerns the treatment of patients suffering from vitamin D-resistant rickets, who respond only to huge doses of the vitamin. This condition can result from chronic renal failure or from an inherited metabolic defect affecting the enzyme responsible for hydroxylating 25-HCC at the 1-position. Consequently the kidney cells are... 

In the kidney, the effect of PTH in promoting phosphate excretion does not depend on the presence of vitamin D. The vitamin itself, however, promotes retention of phosphate by reabsorption. High levels of vitamin D therefore enhance the blood levels of both calcium and phosphorus on account of the action of the vitamin on osteoclasts and kidney cells, respectively. Recent work suggests that the enzyme system which converts 25-HCC to 1,25-DHCC in the kidney is regulated by PTH rather than being controlled directly by the blood calcium level. It has been suggested that the formation of 1,25-DHCC may also be affected by the phosphate concentration in the kidney cells. 

Vitamin D. One of the most important factors affecting calcium absorption is an adequate supply of vitamin D, whether from the diet or exposure to ultraviolet radiation of the sun. Vitamin D or its derivative (metabolite), 25-hydroxyc-holecalciferol (25-HCC), increases calcium absorption by inducing synthesis of a calcium-binding protein that facilitates transport of the calcium through the intestinal walls. 

Phase analysis and texture of the metal particles. Iron powders are constituted of the a-Fe phase with a body-centered cubic (bcc) lattice, whereas Fe-Co powders appear as a mixture of three phases that are quite similar to those of pure metals (bcc for a-Fe and a mixture of hep and fee for cobalt) (6). In the Fe.Nil(m system, a single fee phase is observed over the whole available composition range U s 25) with a linear dependence of the lattice parameter versus z, which shows the existence of a fee solid solution as already evidenced for the Co.rNiu)o-. system (33). The XRD patterns of the Fe [CovNi(1()o -,v)] i - powders depend on the composition An fee phase is always observed either as a single phase or as the main phase a second hep phase with weak and broad lines appears for a cobalt content x > 35 a third body-centered cubic (hcc) phase can be evidenced when x > 80. 

Approximately 350 million people worldwide are chronic carriers of HBV, with the majority living in Asia and Africa. In the United States approximately one million people have chronic HBV infection. Although chronically infected, individuals may remain asymptomatic for long periods. Spontaneous loss of HBeAg occurs in 7% to 20% of patients each year, but spontaneous loss of HBsAg occurs in only 1% to 2% per year [14]. Health experts estimate that 2% of patients with chronic HBV infection develop cirrhosis each year, and that 15% to 25% of patients with chronic HBV infection will die prematurely from cirrhosis or hepatocellular carcinoma (HCC). 

The other program involves systemic administration of the gene-laden adenovirus via a hepatic artery catheter to treat hepatocellular carcinoma (HCC). The hepatic artery supplies the normal liver with 25% of its blood supply. However, it is the sole blood supply for the carcinoma. Preclinical results demonstrated efficacy in a rat HCC model. In a small, open-label clinical trial of patients positive for HCC, but also having post-hepatitis cirrhosis, patient response was marginal [22]. 

The down-regulated proteins in HCC tissues have been identified. Park et al. identified aldehyde dehydrogenase 2 (25) and ferritin light chain (32). Kim et al. identified HSP 27, cathepsin D, and others (26). Lim et al. identified cytochrome B5, liver car-boxyesterase, and others (27). Li et al. identified SOD 1, aldolase B, and others (28). Fujii et al. identified galectin-1 (29). Kim et al. identified argininosuccinate synthase, carbamoyl-phosphate s mthase, and others (31). Table 1 shows the summary of the proteins whose expression was different between HCC cancer tissues and non-cancerous tissues. 

The hyperfine coupling tensor (A) describes the interaction between the electronic spin density and the nuclear magnetic momentum, and can be split into two terms. The first term, usually referred to as Fermi contact interaction, is an isotropic contribution also known as hyperfine coupling constant (HCC), and is related to the spin density at the corresponding nucleus n by [25]... 

For the HCCH and HCC segments, which are of particular interest to polyaromatic compounds, high relative sensitivity (0.5 and 0.25) was also predicted for the DEPT2-INADEQUATE pulse sequence (Figure 8 C). The main reason why this pulse sequence performs so well is that it incorporates refocusing of AP proton-carbon coherences prior to the creation of DQ carbon coherences. Its performance is also boosted by a smaller number of pulses (6 H and 7 C vs. 11 H and 10 C) and delays compared to those of the COS-INADEQUATE pulse sequence. 

From Table 1.6, we read the value of H, for carbon dioxide at 25°C Hcc>2 = 1640 atm/mol. The mole fraction of carbon dioxide in air is about 0.000314. Therefore, the partial pressure of carbon dioxide is... 

HCC. In the studied group, 75 % of patients were correctly classified into the HCC group using AFP marker, whereas healthy volunteers were negatively diagnosed with HCC. The results of the study using the AFP markers show that AFP is not suitable as a universal marker, because 25 % of patients known to suffer from liver cancer did not show positive results. The average sensitivity and specificity of this marker are 40-65 % and 76-96 %, respectively. 

Complications such as variceal bleeding, hepatic encephalopathy, ascites and infections as well as reduced renal function also influence the mortality rate of liver cirrhosis (in Germany some 25,000/year). The main causes of death are hepatic coma or liver failure (25-40%), bleeding (20-30%), infections (about 10%) and HCC (about 5%). Spontaneous bacterial peritonitis is fatal in 50-70%, and with liver dysfunction even in 90% of cases. Occurrence of the hepatorenal syndrome is almost invariably fatal. 

Spontaneous regression As far as I know, it was E.B. Gottfried et al. (1982) who first reported spontaneous regression of HCC. In the meantime, further (> 25) unusual observations of this kind have been published. However, recurrence after such regression has also been reported. (52, 62, 69, 76, 104, 112, 119, 162, 166)... 

At present, merely 5% of patients suffering from HCC have any chance of being cured. Some 25-30% of inoperable patients were rendered operable by means of preoperative selective irradiation with yttrium microparticles (intra-arterially) or by several cycles of cisplatin + IFN-a2b + doxorubicin + 5-fluorouracil. The results could be further improved by postoperative treatment with lipiodol-J k In this context, the overall chance of recovery is reported to be 15%. 

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