Biomedical subjects
Publications and source records attributed to S Sophasan.
Two new 2-substituted furans, 1-(2-furyl)pentacosa-16,18-diyne and 23-(2-furyl)tricosa-5,7-diynoic acid, have been isolated from stems of Polyalthia suberosa. The structures were assigned by spectroscopic methods. The two compounds together with the previously reported kalasinamide, N-trans-feruloyltyramine and N-trans-coumaroyltyramine showed anti-HIV activities.
1. Alterations in skeletal muscle function of chronically K(+)-depleted male and female rats were investigated in isolated soleus muscles. 2. By 16 weeks K+ deficiency, plasma K+ concentrations in both male and female rats were reduced to approximately 2 mEq/L, which was accompanied by an approximate 50% reduction in muscle K+ content and a marked increase in muscle Na+ content. These changes were similar in both males and females. 3. Plasma creatine phosphokinase activity progressively increased with time in K(+)-depleted male rats, whereas only a slight increase was observed in female rats. 4. Maximum isometric twitch tension (Pt) and tetanic tension (Po) of K(+)-depleted soleus muscles from male rats was markedly suppressed; this was not seen for soleus muscles obtained from female rats. 5. After exposure to insulin in low-K+ solution, the contractile tension of soleus from the K(+)-depleted male rats was suppressed to a greater extent. 6. All alterations in muscle function during chronic K+ depletion were restored to normal after 2 weeks K+ repletion. 7. The results suggest that there is a preponderance for male over female rats in developing alterations in skeletal muscle function during chronic K+ deficiency. The changes may be associated with abnormalities of muscle membrane permeability and cellular function.
Organic anion transporter 1 (OAT1) is the para-aminohippurate (PAH) transporter in the basolateral membrane of the proximal tubule. The present study investigated whether or not nonsteroidal anti-inflammatory drugs (NSAIDs) are transported by OAT1. All of the NSAIDs tested inhibited [14C]PAH uptake via OAT1 expressed in Xenopus laevis oocytes. Ibuprofen, indomethacin, salicylurate, and naproxen showed the strongest potency to inhibit [14C]PAH uptake (Ki approximately 2-10 microM); acetylsalicylate, salicylate, and phenacetin exhibited moderate potency (Ki approximately 300-400 microM), and acetaminophen (paracetamol) exhibited the weakest inhibitory potency (Ki approximately 2 mM). Radiolabeled acetylsalicylate, salicylate, and indomethacin were taken up by OAT1 and the uptake rate of these three NSAIDs was enhanced by the outwardly directed dicarboxylate gradient. The efflux of the preloaded [14C]PAH from the oocytes via OAT1 was trans-stimulated by PAH and glutarate added to the media. The addition of salicylate, acetylsalicylate, or salicylurate into the media also trans-stimulated the efflux of PAH, whereas indomethacin did not. The present study indicates that OAT1 is responsible for the renal uptake and secretion of NSAIDs.
In the present study, we investigated the interactions between antibiotics, especially beta-lactam antibiotics, and rat renal organic anion transporter 1 (OAT1). [(14)C]p-Aminohippurate (PAH) uptake via OAT1 expressed in Xenopus laevis oocytes was inhibited by all of the penicillins and cephalosporins tested. Penicillin G, carbenicillin, cephaloridine, cephalothin, cefazolin, and cephalexin inhibited [(14)C]PAH uptake via OAT1 in a competitive manner (K(i) = 0.29-2.33 mM). Cinoxacin, a quinolone gyrase inhibitor, also inhibited PAH uptake via OAT1. Other antibiotics, such as gentamicin, streptomycin, and vancomycin, which do not contain anionic moieties, did not interact with OAT1. [(3)H]Penicillin G and [(14)C]cephaloridine were demonstrated to be transported via OAT1. Using the cells that stably expressed OAT1, we analyzed the cytotoxicity of several beta-lactam antibiotics. Cells expressing OAT1 showed higher susceptibility to cephaloridine (a potentially nephrotoxic beta-lactam antibiotic) toxicity than did control cells. The present study suggests that OAT1 is the major organic anion transporter in the kidney that is responsible for the renal secretion of antibiotics, especially that of beta-lactam antibiotics. Furthermore, the culture cell system expressing OAT1 was revealed to be useful for the prediction of the nephrotoxicity of beta-lactam antibiotics.
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The temporal relationship between changes in cytosolic free calcium and proximal tubular function was examined in rats following 24 h of unilateral and bilateral ureteral obstruction. Immediately after release of unilateral ureteral obstruction, proximal tubular functions were found to be normal. Cytosolic free calcium in isolated proximal tubules of the ureteral obstructed and contralateral kidneys were 160 +/- 8 and 172 +/- 15 nM, respectively. On the 7th day after release, cytosolic free calcium was not different from the sham control value (135 +/- 6 vs. 149 +/- 7 nM). In contrast, immediately after release of bilateral ureteral obstruction, cytosolic free calcium was increased significantly to 219 +/- 6 from 139 +/- 9 nM in sham-operated controls. Subsequent declines in cytosolic free calcium to 196 +/- 15 and 148 +/- 7 nM were observed at 3 and 7 days after release of bilateral ureteral obstruction, respectively. Over this period, renal tubular functions gradually returned to normal. Changes in cytosolic free calcium correlate well with the reported improvement in renal tubular function after release of bilateral ureteral obstruction. Therefore, one possible mechanism for the impairment of tubular function observed in bilateral ureteral obstruction may be an increase in cytosolic free calcium.
A possible role of dopamine in the diuretic and natriuretic action of atrial natriuretic peptide (ANP) was evaluated in the rat. ANP was infused into the left renal artery of anesthetized rats whose kidneys were denervated. ANP both at 12 and 1.2 pmol/h caused immediate ipsilateral increases in urine volume (V), urine Na excretion (UNaV), and fractional excretion of Na (FENa). Ipsilateral glomerular filtration rate (GFR) and renal plasma flow (RPF) increased with 12 pmol/h ANP but not with 1.2 pmol/h ANP. Intravenous infusion of haloperidol, Sch-23390, or carbidopa markedly attenuated the increase in V, UNaV, and FENa with 12 pmol/h ANP and completely abolished the increases in GFR and RPF. Haloperidol, Sch-23390, and carbidopa also completely abolished the renal effects of 1.2 pmol/h ANP. In the presence of carbidopa, a small dose of dopamine infused into the systemic circulation, which by itself has no effects on blood pressure, V, GFR, RPF, and UNaV, restored the diuretic and natriuretic effects of ANP. In addition, an increase in urinary guanosine 3',5'-cyclic monophosphate by ANP was not affected by either haloperidol or carbidopa. These data indicate that dopamine may be necessary, as a permissive agent, for the renal effects of ANP to manifest and that the effects of dopamine may be independent of ANP-stimulated guanylate cyclase activation.
1 day after bilateral ureteral occlusion (BUO), the extracellular fluid (ECF) volume of rats was increased by 2.8 ml/100 g body weight above those values observed after either a sham operation or after 1 day of unilateral ureteral occlusion (UUO). The plasma urea concentration of BUO rats averaged about five times the values of either sham or UUO groups. The release of BUO of 1-day duration resulted in post-obstructive diuresis and natriuresis, whereas oliguria was observed after the release of UUO of 1-day duration. Contralateral nephrectomy of the normal kidney after the release of UUO 1-day duration (UUO-RN) resulted in an improvement of the damaged kidney functions, possibly due to an elevation of renal blood flow. Polyfructosan clearance of the UUO kidney was increased to a level significantly above the corresponding BUO value, 147 +/- 34 as compared to 101 +/- 8 microliters/min/100 g body weight. However, post-obstructive diuresis was not observed. When the ECF volume of UUO-RN rats was elevated, towards those values observed in BUO rats by saline infusion, the rate of urine formation was insignificantly elevated above the nontreatment group, even though the sodium excretion rate was increased about three times the values of both the UUO-RN and BUO groups. When the plasma urea concentration of the UUO-RN group was elevated towards the BUO value, moderate diuresis was observed. But when both the ECF volume and plasma urea concentration of UUO-RN rats were increased towards the level of the BUO rats, post-obstructive natriuresis and diuresis were evident.(ABSTRACT TRUNCATED AT 250 WORDS)
In situ glucose absorption in the mouse was significantly inhibited by cytochalasin E. Cytochalasin E (5 micrograms/ml) also inhibited glucose absorption up to 55.5% in mouse jejunum in vitro. During its inhibition transmural potential difference (PD) was increased from -7.4 to -0.4 mV, together with a decrease in glucose accumulation in the intestinal tissues. Furthermore, it was also found that cytochalasin E induced an alteration in Km value from 2.9 X 10(-3) to 4.0 X 10(-2) M and a constant Vmax value of 55.5 mumol/100 mg wet wt tissue/min. It is postulated that cytochalasin E is a possible competitive inhibitor of glucose at the receptor sites of carriers on the microvillar membrane of the intestinal absorptive cells.
Kidney function was studied in rats after the release of 24 hours of bilateral ureteral ligation (BUL). After deligation, natriuresis was observed for 1 day while diuresis persisted up to 4 days. The possible defective collecting tubule to reabsorb sodium may improve within 1 day, since the urinary sodium concentration was well below the sham value. During the early phase of deligation, the glomerular filtration rate (GFR) averaged only 15 per cent of the sham value. Heterogeneity of the surface nephrons was apparent. About 17 per cent of the observed surface nephrons had no tubular fluid flow, suggesting possibly that these nephrons may not contribute to the kidney GFR. In the other 83 per cent of the nephrons, the stop-flow pressure, 29.0 mm. Hg, was lower than the sham value, 33.6 mm. Hg, whereas the proximal tubular pressure of 15.1 mm. Hg was significantly above the sham value of 13.2 mm. Hg. Both these factors may have induced a reduction in the effective filtration pressure, from 20.1 to 13.9 mm. Hg, and may have contributed to the reduction in GFR in those functioning nephrons. Four days later, a similar proportion of the surface nephrons still showed a marked reduction in function, whereas others had improved significantly. The proximal tubular pressure, the stop-flow and the effective filtration pressures approached the sham values. These improvements may be associated with an increase in GFR to 42 per cent of the sham value. It is suggested that the prolong suppression of the kidney GFR may not be due to the drastic change in the glomerular capillary pressure of the surface nephrons, at this latter period.
The dose-response effects of dopamine on kidney function were studied in rats. Th arterial blood pressure was increased only transiently, after continuous intravenous infusion of dopamine for 2 hr, while heart rate was elevated throughout. Drastic diuresis was usually observed during the early phase of infusion especially when the dose of dopamine was greater than 46 micrograms/min-kg BW. Natriuresis was also found to be dose-dependent but its duration was much more prolonged than diuresis. Both, the increase in glomerular filtration rate (GFR) and reduction in tubular salt reabsorption may be responsible for this elevation in the rate of sodium excretion. Dopamine, at low dose, insignificantly increased the GFR but at a higher dose (90 micrograms/min-kg BW), a 16% increment was observed. This elevation in GFR may not be due to a concomitant increase in the renal blood flow, since phenoxybenzamine, an alpha-adrenergic blocking agent, which would further reduce the renal vascular resistance, abolished the effects of dopamine on GFR, diuresis and natriuresis. It was suggested that the increase in GFR may be due to the differences in the responsiveness of the afferent and the efferent arterioles to dopamine, in the presence of normal alpha-adrenergic receptors. Dopaminergic receptors in the kidney of rat, if present, may not play a significant role in determining the renal function.
The excretion rate of Tamm Horsfall mucoprotein was determined in normal and endemic boys. This latter group of boys showed presumptive signs of bladder stone, which include oxalate crystalluria, and difficult and sometimes painful voiding. At least 2 distinct forms of this mucoprotein are present in the urine. Semiquantitatively, there was no apparent difference in the excretion rate of this mucoprotein between the 2 groups of boys. The kidney function of these 2 groups was comparable and within the normal range. Furthermore, the presence of 5 mg. per cent of this mucoprotein in the solution of calcium and oxalate did not increase the ability of the solution to form more calcium oxalate precipitate nor did it induce precipitation of calcium oxalate from the dilute solution. We conclude that Tamm Horsfall mucoprotein may not have a role in the formation of oxalate crystalluria or bladder stone.
The effect of various cytochalasins on intestinal glucose absorption in several animals species was investigated in vitro. Glucose absorption in mouse jejunum was highly inhibited (68.1%) by cytochalasin E (25.0 micrograms/ml) within 30-min incubation and less extent in rat (48.9%), hamster (34.1%), frog (28.1%), guinea pig (27.5%), rabbit (24.3%) and turtle jejunum (22.7%). Among cytochalasins A, B, C, D and E, cytochalasin E was a most potent derivative that could inhibit glucose absorption by up to 55.5% at a concentration of only 5.0 micrograms/ml in mouse jejunum and its effect may possibly be related to the formation of mini villi and the intracellular vacuoles in the intestinal absorptive cells.
Renal blood flow (RBF) in rat was measured by using a noncannulating electromagnetic flowmeter. In the sham control rats, anesthetized with Inactin, RBF averaged 7 ml/min/g KW when arterial blood pressure was above 110 mm Hg. Autoregulation of RBF was observed when the arterial blood pressure was in the range of 110-150 mm Hg. Glomerular filtration rate (GFR), measured by polyfructosan clearance, averaged 1.08 ml/min/g KW. In experimental rats with 24 h of bilateral ureteral ligation (BUL), RBF averaged 38% of control value. During 1/2-3 h following release of the left ureteral occlusion, RBF increased to 60% of control value. The autoregulatory ability of the damaged kidney was reduced during BUL and did not improve after releasing occlusion. During the post-obstructive period arterial blood pressure remained stable. Thus, a high total renal vascular resistance was responsible for the depressed RBF. GRF in these rats averaged only 9% of control value. The reduction in RBF alone does not explain the drastic reduction in GFR in this model of renal failure.
Acute kidney failure was produced in the anesthetized rat by 1 h of complete renal artery occlusion. Kidney function was studied either immediately after release of the occlusion or 1 day later using clearance, micropuncture, histological, and nephron dissection techniques. Polyfructosan clearance was decreased to 5% of normal after temporary occlusion. Proximal tubular pressure (PTP) averaged 13-14 mmHg in normal kidneys, 39 mmHg immediately after release of unilateral occlusion, 19 mmHg 1 day after unilateral occlusion, and 25 mmHg 1 day after bilateral occlusion. The increased PTP reduces the glomerular filtration rate (GFR). Glomerular capillary pressure, estimated from the sum of the stop-flow and arterial plasma colloid osmotic pressures, was not decreased after temporary ischemia. Single-nephron GFR, measured without intratubular pressure control, was only slightly below normal 1 day after bilateral occlusion. Most distal tubules from ischemia-damaged kidneys contained hyaline casts. Tubular obstruction is a major factor in this model of acute kidney failure.
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