We investigated a newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) to determine its suitability to evaluate enteric bacteria. This compound, PABA-UDCA, is deconjugated by cholylglycine hydrolase to release free PABA whereas it is completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriological experiments, almost all of the microorganisms which split glycocholic acid deconjugated this compound. In animal experiments, urinary excretions of PABA were measured for 6 hours following oral administration of 10 mg PABA-UDCA. Ten control rats excreted 338.5 +/- 43.8 micrograms (mean +/- SD) of PABA; 10 rats with intestinal bacterial overgrowth due to enteric stagnant loops excreted more (673.6 +/- 222.1 micrograms; p less than 0.01), whereas 10 rats in each of 8 groups with intestinal antisepsis by oral administration of various antibiotics excreted significantly less (p less than 0.001) (ampicillin + doxycycline + fradiomycin: 18.3 +/- 16.7, polymixin B + tinidazole: 14.0 +/- 8.0, polymixin B: 224.9 +/- 74.3, tinidazole: 42.7 +/- 27.3, kanamycin: 50.3 +/- 18.2, clindamycin: 57.4 +/- 23.3, vancomycin: 70.4 +/- 27.0, and paromomycin: 160.4 +/- 51.9 micrograms). These observations indicate that this compound is likely to offer a simple and rapid method for evaluation of intestinal microorganisms without the use of radioisotopes or expensive, special apparatus.

4-Aminobenzoic Acid↗

PubMedDate not supplied

Biological and clinical roles of adrenomedullin in circulation control and cardiovascular diseases.

1. Adrenomedullin (AM) is found ubiquitously in tissues and organs, especially in cardiovascular tissues and in the kidney, lung and endocrine glands. It has multifunctional biological properties, of which, its effects on the control of circulation and body fluid volume regulation seem to be the most outstanding and characteristic. 2. Acute administration of a high dose of AM induces a vasodilator depressor response, cardiac inotropic effects, diuresis and suppression of aldosterone secretion in experimental animals. 3. Long-term continuous administration of a very low dose of AM causes vasodilation in sheep (0.5 microgram/kg per h) and hypotension in rats (0.8 microgram/kg per h). 4. The plasma concentration of AM increases under pathological conditions such as congestive heart failure, myocardial infarction and hypertensive and renal diseases. Under these disease conditions, AM may be produced in vascular endothelial and smooth muscle cells and in cardiac myocytes in response to volume expansion, hypertension and activated humoral factors, such as catecholamine and the renin-angiotensin system. 5. Increased AM in the circulating blood and cardiovascular tissues may counteract pathological deviation in the system that controls circulation and body fluid volume, acting against cardiovascular damage and disease. 6. Because of these beneficial properties in the cardiovascular system, AM and its pharmaceutical ligands should prove useful in the treatment of cardiovascular diseases.

Adrenomedullin↗

PubMedDate not supplied

Long-term survivors after hepatectomy for hepatocellular carcinoma.

Sixteen long-term (more than 5 years) survivors after hepatic resection performed for hepatocellular carcinoma (HCC) from 1970 to 1988, were reviewed. The mean age of the patients was 51 years. There were 11 males and 5 females. HBs antigen was positive in 9 patients. Liver cirrhosis was associated with 11 patients but its severity was designated as Child's A in all patients except one. The mean tumour diameter was 2.8 cm and was relatively small. At the first operation, limited procedures (i.e. partial hepatectomy and subsegmentectomy) were employed in 87.5% of patients. A large percentage of tumours were located in S5 and S6 segments. A recurrence of HCC occurred in 9 patients after the first resection. A second resection was carried out in 7 patients, in 2 of which a third resection was done. Transcatheter arterial embolization (TAE) was performed on 4 patients. These results show that, in addition to detection of small tumours and early resection, repeated operation or TAE for treatment of recurrent HCC was important in achieving long-term survival after HCC resection.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Antihypertensive effect of transplant of rat kidney or its unclipping. Hemodynamic effects and control mechanisms.

The acute transplantation of a normal kidney into a recipient rat with Goldblatt one-kidney, one clip hypertension (1K1C) results in a blood pressure (BP) fall toward but not below normal levels within 1 hour. Removal of the clip in a 1K1C hypertensive rat also normalizes the BP rapidly. These changes are not mediated by external fluid loss and occur after indomethacin pretreatment, but are associated with a fall in cardiac output. The mechanism of release of a depressor secretion from the kidney transplant appears to be under barostatic control. Thus, transplanting a kidney into a hypertensive recipient caused a prompt BP decline, whereas transplanting an SHR kidney into a hypertensive recipient did not lower the BP. The prompt BP fall seen after unclipping also indicates that abrupt exposure of the kidney to a high perfusion pressure initiates the release of some depressor agent. When the recipient rat was made hypertensive by injecting renin, the kidney transplant did not lower the BP. When angiotensin in subpressor dose was infused into the renal artery of the kidney transplant, the BP of the recipient did not fall, whereas infusion of norepinephrine in equiconstrictor doses did not prevent the depressor response. These experiments suggest that, in addition to a barostatic stimulus for depressor release, angiotensin acts as a specific inhibitor.

Acute Disease↗

PubMedDate not supplied

Thyrotoxic periodic paralysis complicated with primary aldosteronism.

A 35-year-old man presented with acute onset of bilateral lower extremity weakness after ingesting a large amount of carbohydrates. Laboratory investigation revealed severe hypokalemia (1.9 mEq/l) and hyperthyroidism. The patient also exhibited primary aldosteronism due to a left adrenal adenoma. As a diagnostic tool, paralysis with hypokalemia (2.8 mEq/l) was induced with a glucose infusion. After treatment with methimazole, there were no further episodes of paralysis and subsequent induction of paralysis with glucose was impossible, though primary aldosteronism persisted. These findings indicate that hyperthyroidism played a major role in the development of periodic paralysis, while primary aldosteronism apparently increased the patient's vulnerability to paralytic attacks.

Adenoma↗