Biomedical subjects
Publications and source records attributed to F Ali.
Classically, the "rim sign" has been described throughout the hepatobiliary scan. The authors present a case of a late rim sign visualized at 25 minutes postinjection that proved to be acute upon chronic acalculous cholecystitis without gangrene.
The development of potent antithrombotic agents from the fibrinogen platelet receptor binding sequences Fg-alpha 572-575 -Arg-Gly-Asp-Ser- and Fg-gamma 400-411 -HHLGGAKQAGDV, believed to be a cryptic RGD-type sequence, is described. The tetrapeptide Ac-RGDS-NH2 itself is capable of inhibiting platelet aggregation in vitro at high concentrations, IC50 91.3 +/- 0.1 microM [in vitro antiaggregatory activity employing dog platelet rich plasma (PRP)/ADP], due to low platelet fibrinogen receptor affinity, Ki 2.9 +/- 1.9 microM (purified, reconstituted human platelet GPIIb/IIIa), relative to fibrinogen, Ki 38.0 +/- 6.0 nM. The peptide is also unstable to plasma, suffering total loss of in vitro activity upon incubation in PRP for 3 h (T1/2 90 min). Only modest improvements in potency were achieved with linear analogues of Ac-RGDS-NH2, while dramatic results were achieved with cyclic analogues, culminating in the cyclic disulfide Ac-cyclo-S,S-[Cys-(N alpha-Me)Arg-Gly-Asp-Pen]-NH2 (SK&F 106760) with improved plasma stability (100% activity after 3 h), affinity (Ki 58 +/- 20 nM purified human receptor), and potency (IC50 0.36 +/- 0.4 microM dog PRP/ADP). The affinity of this peptide is 2 orders of magnitude greater than that of Ac-RGDS-NH2. The affinity of the analogue is also comparable to fibrinogen. This peptide constitutes a first potent small peptide entry into the class of novel antithrombotic agents called fibrinogen receptor antagonists.
Because pleural pressure (Ppl) has important effects on venous return and left ventricular function, it is possible that the magnitude of respiratory fluctuations in Ppl importantly influences cardiac output (pulmonary blood flow, QL) during exercise. To examine this question, we increased (+15 cmH2O) and decreased (-11 cmH2O) the amplitude of fluctuations in Ppl by elastic loading and unloading, respectively, during steady-state exercise (50 W) and estimated the corresponding changes in QL from measurement of breath-by-breath alveolar O2 consumption [(Vo2)A] by a modification of the technique of Beaver et al. (J. Appl. Physiol. 51: 1662-1675, 1981). Load changes were applied for three breaths. Using oscilloscopic volume feedback, subjects maintained constant breathing pattern and end-expiratory volume during control and experimental breaths. This procedure minimized errors in computing (Vo2)A. Furthermore, because over the brief period of load change (especially the first 1 or 2 breaths) mixed venous and arterial O2 contents were not likely to have changed, changes in (Vo2)A reflected changes in QL according to the Fick principle. In six normal subjects, neither loading nor unloading had any effect on (Vo2)A in the first, second, or third breath (P greater than 0.5). Additional studies at rest produced equally negative results. We conclude that the magnitude of respiratory fluctuations in Ppl has no short-term effect on pulmonary blood flow at rest or during mild exercise.
A novel method to measure specific gravity (SG) of tissues, pycnometry (PYC), is described. This method utilizes a 2ml glass pycnometer filled with distilled H2O to determine the displacement volume of a tissue sample and an equation to compute SG from the sample's weight and the pycnometer's weight before and after adding the sample. The PYC method was validated using glass SG standards over the range 1.02-1.26, and against the column density gradient (DG) method using brain tissue from 250-300 g male rats. Factors which affect PYC accuracy, i.e. sample size, were also evaluated. Our results indicate that PYC SG values are highly correlated with the glass SG standards (slope = 1.0107, r = 0.9955, p less than 0.001), and highly correlated with DG when approximately 0.120 ml tissue samples are used in the pycnometer. The DG method was preferable to the PYC method, however, when small tissue samples, i.e. 0.60 ml or less, were used.
U-78517G belongs to a novel group of compounds-aminosteroids (AS) which are potent inhibitors of central nervous system tissue lipid peroxidation and are devoid of classical glucocorticoid and mineralocorticoid activities. The AS have been found to possess cerebral protective properties against ischaemia, ischaemic oedema, trauma to the cerebrum and spinal cord and in sub-arachnoid hemorrhage. The possible efficacy of U-78517G in attenuating peritumoural oedema was examined in rats harbouring cerebral 9L gliosarcomas. 19 Sprague-Dawley rats were implanted intracranially with 9L gliosarcoma cells. On day 14 post implantation rats were randomized to control (no treatment n = 10) and AS treated animals (n = 9). On day 20 animals were sacrificed and six brain samples per rat were examined for the percentage of water content. Oedema was assessed with the wet/dry weight technique. The AS treated animals were found to have a significant increase in peritumoural oedema (+1.38%, P less than 0.001) possibly related to an increase in cerebral blood flow associated with AS treatment. Further studies are, however, underway to precisely clarify this unexpected observation.
This study compared the anti-platelet effect of Ac-RGDS-NH2 which is a peptide fragment from fibrinogen to Ac-RGES-NH2 in which the aspartic acid (D) of Ac-RGDS-NH2 has been replaced by glutamic acid (E). When Ac-RGDS-NH2 was infused intracoronary at concentrations of 100-400 mM, acute platelet-dependent thrombus formation in the dog coronary artery was inhibited. However, infusion of Ac-RGES-NH2 intracoronary at similar concentrations to Ac-RGDS-NH2 failed to inhibit platelet-dependent thrombus formation in the dog. Ac-RGDS-NH2 and Ac-RGES-NH2 were also tested for their ability to inhibit collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 elicited concentration-dependent inhibition of collagen-induced aggregation with no effect of Ac-RGES-NH2 on collagen-induced platelet aggregation. Thus, Ac-RGDS-NH2 is an effective antiplatelet agent after intracoronary administration in the dog and also inhibits collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 is a specific inhibitor of platelet aggregation as replacement of the aspartic acid in Ac-RGDS-NH2 with glutamic acid results in complete loss of biological activity.
In order to find out whether the sympatho-adrenal system is activated in relation to heat stroke, plasma levels of norepinephrine (NE) and epinephrine (E) were measured using high pressure liquid chromatography in seven patients with heat stroke. The mean NE +/- SD levels on admission and six hours afterwards were 1397 +/- 317 and 717 +/- 239 pg/ml, respectively. The corresponding values for E were 257 +/- 55 and 32 +/- 15 pg/ml. The levels of both NE and E on admission were considerably higher than those of the controls: 328 +/- 62 and 88 +/- 16 pg/ml (12 normal subjects). This increase in both NE and E indicates activation of the sympatho-adrenal system in patients with heat stroke. The alpha-mediated effect of catecholamines may be important in impairing heat dissipation and thus may contribute to the pathogenesis of heat stroke.
Pregnant rats were treated from day 9 through 12 of gestation with 12.5% ethanol, 25% ethanol, 1% acetaldehyde, cyanamide (an inhibitor of the enzyme aldehyde dehydrogenase), or a combination of cyanamide and ethanol. Embryos were recovered on gestational day 12 and were quantitatively assessed on the basis of 16 recognizable developmental endpoints (morphological scores). The head and the crown-rump lengths of the embryos were also measured. Total resorption occurred in two animals treated with cyanamide and two treated with cyanamide and ethanol. Acetaldehyde and ethanol (at both concentrations) were found to reduce the head length of the embryos but had no significant effects on morphological scores and crown-rump length. The combination of ethanol with cyanamide caused a greater reduction in head length and also significantly reduced crown-rump length, as well as the morphological scores. The results suggest that the deleterious effects of ethanol could be attributed to acetaldehyde, its primary metabolite, although other underlying factors cannot be ruled out.
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To evaluate the role of catecholamines (CA) in uremia, we used "high performance" liquid chromatographic technique with electrodetection to determine plasma and brain concentration of dopamine (DA), norepinephrine (NE) and epinephrine (E) in rats with acute and chronic uremia. The results revealed a steady elevation in plasma CA (p less than 0.05) in both acutely and chronically uremic rats when compared to the level of these neurotransmitters in controls. The highest changes were observed in DA and the least in NE (16.8 +/- 3.2 vs. 0.5 +/- 0.2 ng/ml and 93.2 +/- 11.1 vs. 68.1 +/- 16.3 ng/ml). There was a positive correlation between plasma CA and the duration of uremia (r = 0.97; p less than 0.05). The elevations were more pronounced in acutely uremic rats than in chronically uremic rats. This was followed by a concomitant depletion in the concentration of DA, NE and E in the brain. The defects in catecholaminergic neurotransmission as evidence of dysfunction in the autonomic nervous system may contribute to the development of neuropathy.
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