Antisickling activity of hydroxybenzoic acids in Cajanus cajan.

The amounts of phenylalanine and hydroxybenzoic acid in a Cajanus cajan methanolic extract were estimated. Results showed that the amount of phenylalanine and hydroxybenzoic acid per gram weight of bean was 4.92 mg +/- 0.13 mg and 21.0 mg +/- 3.0 micrograms, respectively. Sickling inhibition was observed to be efficient with the extract which contains a mixture of phenylalanine (0.69 mg/ml) and p-hydroxybenzoic acid (10.5 micrograms/ml), equivalent to those found in bean extract. The additive antisickling effect of both compounds can be therapeutically exploited for the treatment of sickle cell anemia.     

Change of residual strains in arteries due to hypertrophy caused by aortic constriction

The stress and strain that remain in an organ when the external load is removed are called residual stress and strain. They can be revealed by cutting up the organ in such a way as to reveal the zero-stress configuration. The function of the organ depends on the residual strain. For a blood vessel, the zero-stress configuration is very different from that of the no-load condition, and it changes over time when the physical stress acting on the vessel is changed. Data on rat aorta are presented. Physical changes were obtained by constricting the aorta at the celiac trunk level with a band of metal. Banding causes an increase of blood pressure and hypertrophy of the vessel in the upper body and a transient decrease of blood pressure in the lower body. If the aorta is cut transversely into rings and each ring is cut radially, it will open up into a noncircular arc, which may be characterized by its opening angle. It is shown that the opening angle varies systematically along the aorta and that it changes significantly together with changes of blood pressure and hypertrophy. In the ascending aorta, the opening angle increased from 171 degrees and to 214 degrees in 4 days after banding, then decreased gradually to an asymptotic value of 126 degrees in 40 days. At other sections, the swing of opening angle is smaller. The implications are discussed.     

Kidney transplantation under FK 506.

The experimental immunosuppressive drug FK 506 was given to 36 renal transplant recipients, many of whom were highly sensitized. Ten were undergoing kidney retransplantation, 10 also underwent liver transplantation at an earlier time (6 patients) or concomitantly (4 patients), and 2 patients received a third organ (heart or pancreas) in addition to a liver and kidney. With follow-ups of 4 to 13 months, all but 2 of the 36 patients are alive, 29 (81%) are dialysis free, and most have good renal function. Twenty of the 29 dialysis-free patients are receiving no or low-dose (2.5 to 5.0 mg/d) prednisone therapy. Only one kidney was lost to cellular rejection. However, patients who had antidonor cytotoxic antibodies in current or historical serum samples had a high rate (3 of 9) of irreversible humoral rejection. A low incidence of posttransplant hypertension was noteworthy. Hirsutism and gingival hyperplasia were not observed. Serum cholesterol levels in patients who took FK 506 were unexpectedly low, and the effect on the level of uric acid was minimal. The side effects of FK 506 therapy include nephrotoxicity, neurotoxicity, and potential induction of a diabetic state. These are similar to the side effects of cyclosporine use, but probably less severe. The seeming safety, efficacy, and relative freedom from side effects of FK 506 encourage further trials in kidney transplantation.     

Allospecificity of activated T cells grown from endomyocardial biopsies from heart transplant patients

Studies were conducted to determine the functional characteristics of lymphocytes infiltrating human heart allografts. We have developed methodologies to generate lymphocyte cultures from endomyocardial biopsies. Thirteen biopsies from four heart transplant recipients, obtained at different days during a posttransplant period of less than two months, were cultured in interleukin-2 (IL-2)-containing medium supplemented with irradiated autologous peripheral blood lymphocytes as feeder cells. Lymphocyte cultures were obtained from all 13 biopsies and they exhibited a proliferative response to IL-2, suggesting the presence of activated T cells that express IL-2 receptors. Several cultures consisted of Leu 3 (helper/inducer) T cells, whereas others were primarily Leu 2 (cytotoxic/suppressor) T cells or a mixture of both types of cells. Cultured lymphocytes were also shown to be able to undergo secondary proliferation to donor-specific leukocytes as measured by primed lymphocyte testing (PLT). The PLT specificity of these cells was frequently toward class II HLA antigens of the donor, but certain cultures had PLT specificity associated with class I HLA antigens. These results demonstrate the feasibility of growing functionally active T cells from heart transplant biopsies. An analysis of the phenotypes and allospecificity, as well as a functional characterization of these cells, should generate useful information about the types of T cells involved in cardiac transplant rejection.     

Effects of chronic nicotine pretreatment on (+)-amphetamine and nicotine-induced synthesis and release of [3H]dopamine from [3H]tyrosine in rat nucleus accumbens

The effects of chronic (14 day) administration of nicotine (1.5 mg kg-1 day-1) on the rat nucleus accumbens have been examined. Pretreatment of animals with nicotine increased the endogenous level of dopamine. The ability of (+)-amphetamine to stimulate formation and release of [3H]dopamine from [3H]tyrosine was greatly potentiated in tissue slices from the nucleus accumbens of rats pretreated with nicotine. Furthermore, nicotine was effective in stimulating the formation and release of from [3H]dopamine from [3H]tyrosine in tissue slices from chronic nicotine-treated animals.     

Differential hemodynamic effects and tolerance properties of nitroglycerin and an S-nitrosothiol in experimental heart failure

S-nitrosothiols are potent in vitro vasodilators, but little is known about their in vivo action. In this study, we compared the effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) on left ventricular (LV) hemodynamics in congestive heart failure rats. By using a twoday crossover design, stepwise i.v. infusions of SNAP or NTG at 3, 5 and 8 micrograms/min were administered for 30 min each, followed by a dose of 10 micrograms/min over the next 10 h. LV end-diastolic and peak-systolic pressures (LVEDP and LVPSP, respectively) were measured at selected intervals. SNAP and NTG produced maximal LVEDP reductions of 46 and 44%, respectively, at the highest infusion rate. However, at the lower doses, greater reductions of LVEDP were seen with SNAP. NTG had a smaller effect on LVPSP (maximum 6% reduction) than SNAP (maximum reduction of 15%). During the 10-h infusion of NTG, LVEDP gradually returned to base-line values, indicating the development of tolerance, despite relatively constant plasma levels of NTG over the infusion period. Tolerance in LVEDP effects was not observed during the 10-h infusion of SNAP. In the presence of NTG tolerance, rats were still responsive to SNAP (mean reduction of LVEDP 24%), suggesting the absence of cross-tolerance between these two nitrovasodilators. These results suggest that SNAP is a more potent in vivo vasodilator than NTG, has more arterial action than NTG and is less prone to produce LV hemodynamic tolerance.