Modulation of host cell growth during FIV infection in vitro.
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Biomedical subjects
Publications and source records attributed to A Corradi.
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IL-1 receptor antagonist (IL-1ra) is a newly described member of the IL-1 family, isolated from supernatants of Ig stimulated monocytes, that binds competitively to IL-1 receptors without stimulating target cells. Also epithelial cells produce IL-1ra in a form which lacks a secretory signal sequence. Here we have compared the biosynthesis and secretion of IL-1ra in monocytes and keratinocytes. Our data show that monocytes produce two molecular forms of IL-1ra, of 18 Kd and 23 Kd respectively, which differ in the degree of glycosylation. Both forms are secreted via the "classical" endoplasmic reticulum (ER)-Golgi secretory pathway. By contrast keratinocytes produce IL-1ra in a molecular form of 20 Kd, which is not N-glycosylated: 20 Kd IL-1ra is detectable in supernatants of keratinocytes, although in small amounts. The presence of IL-1ra in keratinocytes cultures fluids is not inhibited by Brefeldin A (BFA), suggesting a possible secretion through the leaderless secretory pathway.
The present study was undertaken in order to establish whether oxytocin (OT) affects the dopaminergic control of PRL secretion in normal women during follicular, periovulatory and luteal phase of their menstrual cycle. For this purpose, 22 normal women were tested with a lower (1 mg) or higher (10 mg) dose of the dopaminergic antagonist metoclopramide (MCP) with or without the concurrent treatment with OT (2 IU injected plus 0.033 IU/min infused for 2 h). Since OT was found unable to modify the effect of either 1 or 10 mg MCP, in additional experiments the same doses of MCP and OT were administered after dopamine (0.04 micrograms/kg/min for 2 h) infusion. Also in these experimental conditions OT failed to modify the PRL response to MCP. These data argue against a role of OT in modulation of the dopaminergic control of PRL secretion in normal women.
In order to establish whether the age-related reduced growth hormone (GH) responsiveness to GH-releasing hormone (GHRH) could be improved by treatment with low amounts of theophylline, a drug mainly acting through cyclic adenosine 3', 5'-monophosphate (cAMP), and calcium-mediated mechanisms, eight adult subjects (aged 20-37) and eight elderly men (aged 64-79) were tested with GHRH (50 micrograms in an iv bolus), theophylline (1.67 mg/min for 3 h), or the combination of both drugs. The GH response to GHRH was significantly lower in the older than in the younger group (mean peaks were 4.5 and 7.5 times higher than baseline, respectively). Theophylline did not change basal GH levels in any subjects and GHRH-induced GH rise in the younger group, whereas it restored normal GH responses to GHRH in the older subjects (mean peak responses were eight times higher than baseline in both groups). These data show that in elderly subjects the mechanism underlying the GHRH-induced GH secretion may be fully activated by GHRH during treatment with low amounts of theophylline.
The pharmacokinetics of iopamidol 370 (Iopamiro), a non-ionic water soluble organic iodine compound, were studied in adults with different degrees of chronic renal failure and in healthy volunteers. After 50 ml were administered i.v., plasma and urine levels were determined. The main pharmacokinetic parameters were calculated on the basis of bi-compartimental open model. There were significant differences from healthy volunteers in t1/2 beta, which increased with the degree of renal failure as the clearance values decreased. t1/2 beta was equal to 1.67 h in healthy volunteers, 4.24 h in patients with mild renal failure and 10.03 h in patients with severe renal failure. The clearance decreased as follows: 0.11 (l/h kg) in healthy volunteers, 0.06 (l/h kg) in patients with mild renal failure and 0.02 (l/h kg) in patients with severe renal failure. No significant differences were found in distribution volume values nor in t1/2 alpha.
The prevention of fractures in the elderly population has become a primary objective of public health because of the costs involved, in both economic and social terms. The present effective method for measuring bone mass has called attention to the relationship between osteoporosis and the risk of fracture. A reduction in bone mass is a determining factor, but not in itself sufficient for an overall understanding of the problem. This study collates anatomical, physiological, biomechanical and epidemiological data, which makes it possible to evaluate the different factors involved in predicting fractures in subjects affected with osteoporosis.
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Experiments were conducted on euvolemic rats to characterize renal hemodynamic responses to a unilateral increase in renal venous pressure. Ipsilateral renal blood flow (RBF, electromagnetic flow probe) was measured in four groups to determine the roles of the renal nerves and endogenous prostaglandins. In control rats, elevation of venous pressure (3 to 22 mmHg) produced vasoconstriction and a 16% increase in renal vascular resistance (RVR) at 130 mmHg arterial pressure (P less than 0.001). In acutely denervated kidneys, a 19-mmHg increase in venous pressure reduced RBF but did not alter RVR (5% decrease), since there were proportional decreases in RBF and the arteriovenous pressure gradient. Indomethacin-treated rats with innervated kidneys responded to a similar increase in venous pressure with pronounced constriction; RVR increased by 50% (P less than 0.005). Venous compression elicited a 24% increase in RVR (P less than 0.05) in indomethacin-treated rats with denervated kidneys. The opposing effects of denervation and indomethacin treatment were significant and noninteractive. The findings indicate 1) activation of an ipsilateral renorenal neural reflex mediated a significant portion of the vasoconstriction; and 2) enhanced synthesis of prostaglandins produced net dilatory effects that attenuated the neurally mediated constriction. The opposing actions of the renal nerves and prostaglandins on the RVR responses to increased venous pressure were directly related to arterial pressure between 70 and 130 mmHg. In response to decrements in arterial pressure, the general pattern of vasodilation was not impaired by denervation of indomethacin when venous pressure was normal or elevated. These observations indicate that the origin of the pressure change, i.e., arterial vs. venous, engages different vasoactive factors that are responsible for varying circulatory responses in the rat kidney.
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The effects of unilateral partial renal venous ligation on whole kidney and single nephron function were determined in anesthetized euvolemic Munich-Wistar rats using clearance, blood flow, and micropuncture techniques. Increased venous pressure (4-22 mmHg) reduced glomerular filtration rate (GFR) and renal plasma flow (RPF) to 60% of control values; filtration fraction (FF) was constant. Similar responses occurred in the superficial cortex, as evidenced by a 40% fall in SNGFR determined while intratubular pressure was maintained at the elevated precollection level. Fractional reabsorption by the proximal convoluted tubule remained constant, indicating maintenance of glomerulotubular balance. The contralateral kidney exhibit a diuresis and natriuresis while GFR and RPF were stable. In the experimental kidney single nephron glomerular plasma flow decreased by 35% due to increments in preglomerular and efferent arteriolar resistance. The transcapillary hydrostatic pressure gradient was unchanged since there were similar 7- to 8-mmHg increases in glomerular capillary and Bowman's space pressures. Filtration pressure disequilibrium was observed in control and experimental periods. Mean effective ultrafiltration pressure was similar in both periods. Specific values for the ultrafiltration coefficient (Kf) fell from 0.023 to 0.015 nl . s-1. mmHg-1. Accordingly, partial renal venous ligation produces ipsilateral vasoconstriction and a fall in GFR that is primarily due to a proportional decline in Kf.
The renal extraction of insulin and glucagon was studied in dogs subjected to temporary interruption of vascular perfusion of the liver. This was performed using hepatic artery occlusion after functional end-to-side portacaval anastomosis. The renal extraction of immunoreactive insulin and glucagon was studied by means of renal arterial-venous concentration differences with concurrent estimates of renal plasma flow and glomerular filtration rate. The degree of liver damage was reflected by dramatic increases of liver enzymes in the plasma after ischaemia and by hypoglycemia which developed in all the animals. Ninety minute occlusion of hepatic blood flow resulted in a dramatic reduction of renal plasma flow and glomerular filtration rate. Portacaval shunt alone had little effect on these parameters. Because hypoglycemia developed after hepatic insult, some animals were made hyperglycemic by intravenous infusion of glucose. In both (hypo- and hyperglycemic) groups of animals the percentage extraction of hormones by the kidney fell dramatically 60 minutes after the end of the hepatic ischaemia and this reduction persisted 180 min later. These data suggest that the impaired renal function may contribute to the increased plasma levels of islet hormones observed during acute hepatic failure.
Glomerular hemodynamics were studied, by micropuncture, in Munich-Wistar rats submitted to 24-hour bilateral ureteral ligation (BUL). Glomerular capillary pressure (PG), intratubular pressure (PT), and pressure in the first order peritubular capillaries (EAP) were measured with a servonulling device. Single nephron filtration fraction (SNFF) was calculated from arterial and peritubular blood protein concentrations. Single nephron glomerular filtration rate (SNGFR) was both measured by conventional micropuncture techniques and calculated from efferent arteriole blood flow and SNFF. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent (Re) arteriole were calculated. Measurements were repeated in the left kidney after releasing the ureter. Sham operated rats were used as control. BUL caused a fall in SNGFR (from 101.8 +/- 9.7 to 40.7 +/- [SEM] 6.0 nl/min/kg body wt), accounted for by a rise in PT (from 14.1 +/- 0.7 to 28.9 +/- 3.1 mm Hg), glomerular hemodynamics (particularly PG and AABF) being unchanged. A marked increase in Ra (from 6.6 +/- 0.7 to 10.8 +/- 1.5 dynes. sec. cm-5) occurred after releasing the ureter, lessening both PG and AABF. Therefore, a low SNGFR was maintained despite the concomitant normalization of PT.
Glomerular hemodynamics were studied, by micropuncture, in Munich-Wistar rats submitted to 24-hour unilateral ureteral ligation (UUL). Glomerular capillary pressure (PG), intratubular pressure (PT) and pressure in the first-order peritubular capillaries (EAP) were measured with a servonulling device. Single nephron filtration fraction (SNIFF) was calculated fmom arterial and peritubular blood protein concentration. SNGFR was both measured by conventional micropuncture techniques and calculated from efferent arteriole blood flow (EABF) and SNFF. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent (Re) arterioles were calculated. Measurements were repeated 1 to 2 hours after the release of the ureter. Sham-operated rats were used as control. UUL caused a marked increase in Ra (from 4.9 +/- [SD] 2.4 to 12.7 +/- 5.1 dynes/sec/cm-5). The fall in SNGFR (from 111.9 +/- [SD] 23.9 to 34.4 +/- 23.1 nl/min/kg body wt) was secondary to a decrease in both PG and AABF. A further increase in Ra (16.0 +/- 6.7 dynes.sec.cm-5) occurred after releasing the ureter. SNGFR, however, was unaltered (33.7 +/- 16.6 nl/min/kg body wt) since PG decreased parallel to PT, but AABF did not significantly change. Conclusion. Ureteral obstruction determines, in 24 hours, a marked cortical ischemia that is not promptly reversed by ureteral release.
Observations conducted on a group of workers exposed to chromium (who showed a rapid urinary excretion of the metal and progressive increase of clearance with cumulative years of exposure), induced the authors to evaluate the nephrotoxic action of chromium in rats exposed to acute and chronic intoxication. The progressive Cr accumulation in the renal cortex during the course of testing explains the increase of the excreted fraction of filtered Cr, and therefore, the clearance, of the metal through the reduction of the tubular lumen-epithelium gradient. Paralleling the anatomical lesions (demonstrated only at the level of the proximal tubular cells), are the increasing modifications of the cellular lesion or altered reabsorption registered by several urinary indicators. Similar changes were found in subjects chronically exposed to the metal; their reversibility is linked to the possibility of repairing the epithelial damage by stopping exposure.
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In order to study the effects of acute ureteral obstruction on glomerular hemodynamics, glomerular hydrostatic capillary pressure (PG), pressure in the first-order peritubular capillaries (EAP), and intratubular pressure (PT) were directly measured in superficial nephrons on Munich-Wistar rats by micropuncture with a servo-nulling device, in control conditions and one to two hours after ureteral ligation. Single nephron filtration fraction (SNFF) was calculated from arterial and peritubular blood protein concentration. SNGFR was measured by conventional micropuncture techniques in control conditions and was calculated from efferent arteriole blood flow (EABF) and SNFF during ureteral obstruction. EABF was obtained by timed complete collection of blood from superficial efferent arterioles. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent arterioles (Re) were calculated from conventional equations. Ureteral obstruction markedly increased PT from 12.9 +/- 1.4 to 36.8 +/- 6.1 (SD) mm Hg. The fall in SNGFR (from 23.3 +/- 6.4 to 17.9 +/- 5.2 [SD] nl/min) was blunted by the rise in PG (from 45.5 +/- 3.6 to 59.3 +/- 4.0 [SD] mm Hg) and AABF (from 130.0 +/- 59.1 to 144.2 +/- 69.0 [SD] nl/min), secondary to a fall in Ra. These results demonstrate that SNGFR is maintained early after complete ureteral obstruction because of afferent arteriole dilatation.
Hemodynamic pressure in glomerular capillaries (GCP) and in first order peritubular capillaries (EAP) in superficial nephrons of mutant Wistar rats with surface glomeruli was measured by micropuncture with a servo-nulling device in the following conditions: 1) control;2) norepinephrine infusion (NE); 3) epinephrine infusion (E): 4) dopamine infusion (D); 5) hemorrhagic hypotension (HH); 6) HH + NE; 7) HH + E; 8) HH + D; 9) acute hypertension secondary to bilateral cervical vagotomy and occlusion of both common carotid arteries. BP was also recorded. Both GCP/BP and EAP/GCP ratios averaged 0.40 in control conditions, but only the EAP/GCP ratio remained constant in all conditions under study, indicating that approximately 60% of the hydrostatic pressure in glomerular capillaries is constantly dissipated by the efferent arteriole. When all values of EAP were plotted against the respective values of GCP, a liner relationship was detected (r=0.843). These results indicate that changes of pressure in the first order peritubular capillaries of superficial nephrons are merely secondary to changes in glomerular capillary pressure.
In haemorrhagic rats norepinephrine normalises BP but maintains renal cortical pressures at low levels. Dopamine, however, can normalise both BP and renal cortical pressures. Dopamine is therefore useful in treating haemorrhagic hypotension in addition to or while awaiting blood transfusion. The efferent arteriole in superficial nephrons is a passive resistance in glomerular haemodynamics.