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Biomedical subjects

I Franchini

Publications and source records attributed to I Franchini.

At least 37 records · Page 2Linked to original sources
PubMed1992

Nephropathies and exposure to perchloroethylene in dry-cleaners.

Even in specific risk groups, the relation between exposure to organic solvents and chronic renal diseases remains controversial. Thus, in a collaborative European study, we assessed the renal effects of occupational exposure to perchloroethylene (PCE) in dry-cleaners compared with matched controls who were simultaneously examined. Single high and low molecular weight proteins, kidney-derived antigens and enzymes, and prostanoids were measured in urine. beta 2-microglobulin, creatinine, laminin fragments, and anti-glomerular basement membrane antibodies were also measured in serum. A canonical function based on 23 such variables correctly classified 93% of individuals as either PCE-exposed or controls; with 13 markers, group membership was identified in 87% of subjects. Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p less than 0.0001) associated with tubular alterations. Changes were consistent with diffuse abnormalities along the nephron in workers exposed to low levels of PCE (median 15 parts per million). Generalised membrane disturbances might account for the increased release of laminin fragments, fibronectin, and glycosaminoglycans, for high molecular weight proteinuria, and for the increased shedding of epithelial membrane components from tubular cells with different location along the nephron (brush-border antigens and Tamm-Horsfall glycoprotein). These findings of early renal changes indicate that solvent-exposed subjects, especially dry-cleaners, need to be monitored for the possible development of chronic renal diseases.

Adolescent↗
PubMed1992

Reference values for early markers of renal damage.

In addition to the difficulties related to the definition of a reference population and hence of reference limits, special methodological problems have to be dealt with when early markers of renal damage are applied to monitor groups at risk. The urinary excretion of both high and low molecular weight proteins, as measured by sensitive immunoassays, is routinely applied in health surveillance programmes aimed at preventing the occurrence of adverse renal effects resulting from exposure to nephrotoxic chemicals, among which are several metals. Owing to the large intra-individual variability experimentally demonstrated for all indicators of renal impairment, carefully standardized sampling conditions must be adopted. At the individual level, repeated measurements should be performed before a diagnosis of renal disease or dysfunction is established. In fact, several physiological conditions may account for transient changes in renal function, leading to measured levels greatly exceeding reference limits.

Albuminuria↗
PubMed1992

Rat model of perchloroethylene-induced renal dysfunctions.

To investigate whether perchloroethylene (PCE) can induce renal disturbances and to compare morphological alterations with functional data, two groups of 12 male and female Fischer-344 mature rats were treated daily with PCE (500 mg/kg body wt in corn oil, p.o.) for 4 weeks. Sex- and age-matched control groups received corn oil only. Weekly, the urinary excretion of albumin (Alb), alpha 2 mu-globulin (alpha 2 mu) and retinol-binding protein (RBP) was measured in 24-hr urine samples using immunoassays specific for rat proteins. N-acetylglucosaminidase (NAG) activity was measured by a colorimetric assay. Electrophoretic analysis of proteinuria included SDS-PAGE and isoelectric-focusing of Alb purified from serum and urine. Weekly histopathology comprised light and electron microscopy. In the male rat, a trend toward progressive albuminuria (up to 15 times the pair-fed controls) was observed, together with transient increases in alpha 2 mu and NAG; RBP showed a twofold increase at the end of treatment. Histopathology failed to demonstrate glomerular changes, whereas it displayed alpha 2 mu accumulation and mild lesions in the S2 segment of proximal tubules. Thus, in the male rat, the selective damage to S2 was associated with "glomerular" proteinuria, the alpha 2 mu cortical content being closely correlated with albuminuria (n = 9, r = 0.92, P < 0.001). In the female rat, only minor, although statistically significant (P < 0.05), increases were recorded for Alb, whereas urinary alpha 2 mu reached up to four times the control values. As a whole, these findings suggest that PCE, like other hydrocarbons, selectively affects the tubular segment S2 in the rat. A competition with alpha 2 mu for tubular uptake could explain enhanced albuminuria. Owing to the species specificity of alpha 2 mu, caution should be exercised in extrapolating these findings to man.

Albuminuria↗
PubMed1992

Long-lasting impairment of neuroendocrine response to psychological stress in heroin addicts.

Performance in a vigilance task and the associated neuroendocrine changes during the performance in the task were examined in healthy subjects and in three groups of male heroin-addicts both before undergoing rehabilitation programmes and at various intervals from withdrawal (5 days, 1 to 2 mon, and 3 to 48 mon, respectively). Plasma levels of ACTH, beta-endorphin (EP) and prolactin (PRL) were measured every 10 min before and during performance. In drug addicts, simple reaction times never showed any significant difference as compared to control values. Despite similar baseline levels, ACTH exhibited a markedly depressed response to psychological testing in drug-addicts as compared to controls. Whereas a three-fold increase in ACTH was observed in 'normal' subjects during the performance (from 17 to 54 ng/l), mean values from drug-addicts remained unchanged. EP levels showed a wide scatter of individual values and inconsistent time courses over performance testing: after short-term abstinence, EP showed a three-fold increase over baseline control values but, contrary to what seen in 'normal' subjects, no changes over time were recorded. After long-term abstinence, basal EP was close to control values, but its increase during the testing period was still blunted. PRL levels decreased over the testing period both in controls and in heroin addicts. Thus, despite the lack of obvious signs of neurotoxicity, drug abusers show neuroendocrine changes consistent with a long-lasting selective impairment of the hypothalamic modulation of pituitary secretion.

Adrenocorticotropic Hormone↗
PubMed1992

Neurobehavioral and neuroendocrine effects of occupational exposure to perchloroethylene.

The hypothesis that long-term low-level exposure to perchloroethylene (PERC) may impair the dopaminergic control of prolactin (PRL) secretion and negatively affect neurobehavioral performance, was tested in a cross-sectional survey of dry-cleaners. Sixty female workers exposed to PERC in dry-cleaning shops and thirty controls recruited in a cleaning plant not using solvents were examined. PERC air concentration during four-hour random periods varied from 1 to 67 ppm (median 15 ppm). PERC blood levels ranged 12-864 mg/l (median 145 mg/l). A set of tests from a computer-based performance evaluation system was administered, including Finger Tapping with both dominant and non-dominant hands, Simple Reaction Times, Digit Symbol, and Shape Comparison in two different versions constructed to test Vigilance and the response to moderate stress, respectively. During the proliferative phase of the menstrual cycle, PERC-exposed workers showed increased serum PRL (12.1 +/- 6.7 ng/ml) as compared to their matched controls (7.4 +/- 3.1 ng/ml, p less than 0.001). Prolonged reaction times were also observed in all tests. However, neither the duration of exposure nor air and blood PERC concentrations were significantly correlated with performance. Nor were exposure variables associated with the increased PRL levels.

Adult↗
PubMed1990

Urinary excretion of brush-border antigen and plasma proteins in early stages of diabetic nephropathy.

In 109 patients with insulin-dependent diabetes mellitus (IDDM), we measured the urinary excretion of albumin, the low molecular weight proteins (LMWP) retinol-binding protein (RBP) and beta 2-microglobulin (beta 2m), and brush-border antigens (BBA) revealed by monoclonal antibodies. All such markers of kidney damage and/or dysfunction were higher in diabetic patients than in 44 controls. Increased urinary levels of BBA (p = 0.0001) were associated with higher values of albumin (p = 0.0002), RBP (p = 0.0005) and, to a lesser extent, of beta 2m (p = 0.1), different combinations of values above the reference limits being observed. Some 30 and 40% of patients with and without microalbuminuria, respectively, also exhibited signs of tubulopathy. Although under certain circumstances tubular defects may give rise to small increases in albuminuria, the most likely explanation for our findings is the coexistence of glomerular and tubular damage in some patients with IDDM. Neither the prognostic value nor the pathophysiological meaning of tubular damage and/or dysfunction can be assessed by the present study, owing to its cross-sectional design. Tubular markers thus deserve further studies to clarify whether in diabetic patients they indicate a more severe or diffuse kidney impairment.

Adolescent↗
PubMed1989

Endocrine effects of psychological stress associated with neurobehavioral performance testing.

Twenty-four healthy subjects were submitted to a computer-based performance evaluation system. The set of tests required sustained attention, and the last test was expressly designed to cause a moderate, acute psychological stress. Compared to baseline levels, both serum ACTH and beta-endorphins were increased after psychological testing in all subjects. Serum prolactin showed a slight and statistically nonsignificant decrease compared to baseline values. These results question the belief that psychological stress stimulates prolactin secretion, whereas it suggests that serum ACTH and beta-endorphins are reliable indicators of acute psychological stress.

Adrenocorticotropic Hormone↗
PubMed1989

[The nephrotoxicity of ionic and nonionic contrast media in urography. An evaluation with immunoenzyme technics and monoclonal antibodies].

The nephrotoxicity of ionic and nonionic contrast media (cm) was evaluated in 52 patients undergoing pyelography. The contrast media were i.v. injected in 30'. Urine samples were collected before, 2 and 48 hours after the injection. Urinary albumin (alb) and retinol binding protein (RBP) excretion was evaluated by immunoenzymatic methods; alb and RBP were considered as indicators of glomerular permeability and of tubular reabsorption, respectively. The urinary excretion of brush-border antigen of proximal tubule (BBA) was also measured, as an indicator of microtissue damage, by a sensitive double-antibody ELISA with monoclonal antibodies. The results demonstrate ionic cm to have greater functional effects than nonionic ones, as suggested by the increased urinary excretion of both alb and RBP. However, tubular damage seemed to be more severe with nonionic agents, as suggested by BBA excretion. Although toxic damage had little significance for the patients' health, long-term effects are not to be excluded.

Adult↗
PubMed1988

Selected toxicological aspects of chromium(VI) compounds.

Chromium(III) is thought to be an essential element in mammals, its toxicity being very low. On the contrary, chromium (VI) is highly toxic to man, even if its effects are generally local, involving the respiratory tract and the skin. Once absorbed, chromium(VI) is quickly reduced to the trivalent form which accounts for all of this element present in the blood stream or taken up by tissues. As a result, any differences in systemic toxicity can only be attributed to differential solubilities and absorption rates. The kidney should be regarded as the critical organ, although tubular damage following occupational exposure is mostly due to acute absorption and transient in nature. Sensitive immunochemical techniques for the measurement of specific proteins in the urine have been used for the early detection of kidney damage, a possible threshold having been indicated at exposure levels yielding 15 micrograms/g creatinine in urine. Such a threshold has been confirmed by using monoclonal antibodies to reveal antigens from the brush-border of proximal tubules. Two main features of kidney damage were, however, apparent. The first one is the lack of dose-effect/response relationships, i.e. the lack of any progression toward more severe impairments when the exposure intensity increases. The second one is that the recent absorption rate more than the cumulated dose is responsible for the observed nephrotoxic effects.

Albuminuria↗
PubMed1988

Brain dopamine as a target for solvent toxicity: effects of some monocyclic aromatic hydrocarbons.

Adult male rabbits were exposed to toluene, xylene, styrene, ethylbenzene, vinyltoluene or were dosed with hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tubero-infundibular dopamine. Such an effect was also caused by treatment with mandelic and phenylglyoxylic acids. These results indicate that dopamine is a target for some solvents of their metabolites, the presence of a lateral vinyl- or ethyl-chain which may be biotransformed into alpha-keto acids being crucial for the effect. Experiments in vitro suggest that dopamine condenses non-enzymatically with reactive carbonylic groups of such and other alpha-keto acids, thus becoming ineffective as neurotransmitter. This mechanism might account for the neurobehavioral and neuroendocrine changes which have been reported in workers occupationally exposed to styrene and to some solvent mixtures.

Animals↗
PubMed1987

A cross-sectional survey of kidney function in refinery employees.

We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

Adult↗
PubMed1987

Adrenal response in the pathogenesis of arterial hypertension in workers exposed to high noise levels.

Some neuroendocrine parameters known as stress indices were examined in two groups of healthy male workers in a glass factory: the first group (60 subjects) was exposed to high environmental noise levels [greater than 90 dB(A)]; the second group (52 subjects) was exposed to low noise levels [less than 78 dB(A)]. Subjects with histories of cardiovascular diseases or high arterial pressure were excluded from the study. In both groups serum catecholamines and cortisol, and urinary vanilmandelic and homovanillic acids were evaluated at the beginning and middle of morning and afternoon work-shifts, by high performance liquid chromatography with electrochemical detection. Norepinephrine, epinephrine and vanilmandelic acid were significantly increased (P less than 0.01) during work-shifts in the group exposed to 90 dB(A), compared with baseline levels and also with catecholamine levels in the group exposed to 78 dB(A). Serum dopamine, cortisol and homovanillic acid showed no significant differences. The increased stimulation of the sympatho-adrenal system in response to high and prolonged noise exposure might lead to an abnormal response of the cardiovascular system with increasing arterial pressure values.

Adrenal Glands↗
PubMed1986

Effects of some monocyclic aromatic solvents and their metabolites on brain dopamine in rabbits.

Adult male rabbits were exposed to high concentrations (750 ppm, 12 hours daily for 7 days) of toluene, xylenes, styrene, ethylbenzene, vinyltoluene (3-methylstyrene), and 7-methyl-styrene vapours or were dosed with 4 mM/kg/day i.p. of hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tuberoinfundibular dopamine. Such an effect was also caused by treatment with phenylglyoxylic and mandelic acids. Dopamine depletion was associated with an increase in homovanillic acid concentration in the same regions. These results indicate that dopamine metabolism is a target for the neurotoxic effects of some monocyclic aromatic hydrocarbons and their metabolites, a lateral vinyl- or ethyl-chain being crucial for the structure/activity relationship of such compounds.

Animals↗