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Biomedical subjects

P Sartorelli

Publications and source records attributed to P Sartorelli.

At least 19 recordsLinked to original sources

Seasonal changes in serum metabolites in free-ranging alpine marmots (Marmota marmota).

Circannual changes in serum parameters and body mass were studied in free-ranging Marmota marmota that had been shot in Switzerland (Grisons) for management reasons in May, July, and September of 1995, 1996, and 1997; and in April 1996. Markers of lipid (triglycerides, cholesterol), protein (total protein, urea-nitrogen) and mineral (calcium, inorganic phosphate) metabolism were evaluated in 111 haemolysis-free serum samples; the effects of sex, age, reproductive status, season and year were tested. Mean body mass was higher in adult males than in adult females in July and September, and serum cholesterol concentrations were lower in adult males in May. Pregnant females had lower concentrations of total protein than non-pregnant females, and triglyceride concentrations were negatively correlated with the number of uterine ampullae. Inorganic phosphate decreased and total protein increased with age. In adults, triglycerides, cholesterol and urea-nitrogen increased mainly from May to July and decreased between September and May. Total protein, calcium and phosphate did not change throughout the year. This suggests that, during the active season, ingested lipids and amino acids were utilised for metabolic needs or lipid storage, while in winter, lipids were catabolised and protein was spared. Quantitative differences between years, observed for triglycerides and total protein during the active season, were probably due to different climatic conditions in each year.

Age Factors↗

In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study.

To obtain better insight into the robustness of in vitro percutaneous absorption methodology, the intra- and inter-laboratory variation in this type of study was investigated in 10 European laboratories. To this purpose, the in vitro absorption of three compounds through human skin (9 laboratories) and rat skin (1 laboratory) was determined. The test materials were benzoic acid, caffeine, and testosterone, representing a range of different physico-chemical properties. All laboratories performed their studies according to a detailed protocol in which all experimental details were described and each laboratory performed at least three independent experiments for each test chemical. All laboratories assigned the absorption of benzoic acid through human skin, the highest ranking of the three compounds (overall mean flux of 16.54+/-11.87 microg/cm(2)/h). The absorption of caffeine and testosterone through human skin was similar, having overall mean maximum absorption rates of 2.24+/-1.43 microg/cm(2)/h and 1.63+/-1.94 microg/cm(2)/h, respectively. In 7 out of 9 laboratories, the maximum absorption rates of caffeine were ranked higher than testosterone. No differences were observed between the mean absorption through human skin and the one rat study for benzoic acid and testosterone. For caffeine the maximum absorption rate and the total penetration through rat skin were clearly higher than the mean value for human skin. When evaluating all data, it appeared that no consistent relation existed between the diffusion cell type and the absorption of the test compounds. Skin thickness only slightly influenced the absorption of benzoic acid and caffeine. In contrast, the maximum absorption rate of testosterone was clearly higher in the laboratories using thin, dermatomed skin membranes. Testosterone is the most lipophilic compound and showed also a higher presence in the skin membrane after 24 h than the two other compounds. The results of this study indicate that the in vitro methodology for assessing skin absorption is relatively robust. A major effort was made to standardize the study performance, but, unlike in a formal validation study, not all variables were controlled. The variation observed may be largely attributed to human variability in dermal absorption and the skin source. For the most lipophilic compound, testosterone, skin thickness proved to be a critical variable.

Adolescent↗

Some aspects of erythrocyte metabolism in insulin-treated diabetic dogs.

Insulin-dependent diabetes mellitus (IDDM) is a common metabolic disease often complicated by a number of pathological conditions among which are haematological changes and alterations in blood cell function. Human and feline diabetes mellitus patients have been reported to be associated with oxidative stress that can lead to membrane alterations and to reduced erythrocyte life-span. Erythrocyte function in dogs affected by IDDM has been investigated during insulin therapy, paying attention to antioxidant status, membrane resistance, enzyme activities and 2,3-diphosphoglycerate (2,3DPG) concentration. Thirteen diabetic and 36 healthy dogs were bled and haematology and blood chemistry assays were performed to evaluate the degree of compensation. Osmotic fragility, the activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD) and pyruvate-kinase (PK) and the concentrations of reduced glutathione (GSH) and 2,3DPG were evaluated in the erythrocytes. Diabetic dogs did not differ from controls in terms of haematological parameters, except for higher numbers of platelets. Higher values of fructosamine, glucose, protein, plasma potassium and calculated osmolality were detected in the plasma from diabetic dogs. No differences were detected in osmotic fragility, GSH concentration and PK activity between the two groups but 2,3DPG concentration and G6PD activity were statistically significantly higher in the diabetic group. The results indicate minimal alterations in erythrocyte functions occur in insulin-treated diabetic dogs. This contrasts with what has been reported for IDDM humans and cats.

2,3-Diphosphoglycerate↗

Dermal exposure assessment in occupational medicine.

The importance of dermal exposure has increased during the last few years, mainly because of the reduction of respiratory exposure to toxicants. Pesticides, aromatic amines and polycyclic aromatic hydrocarbons are considered to be the chemicals at highest dermal risk. In the occupational exposure limit lists of the American Conference of Governmental Industrial Hygienists (ACGIH) and of many countries, compounds that can be absorbed through the skin are identified by a skin notation. However, a generally accepted criterion for assigning skin notation does not exist. The recent attempts to develop health-based dermal occupational exposure limits (DOELs) have not been accepted, thus in practice their use has remained limited. To predict the systemic risk associated with dermal exposure and to enable agencies to set safety standards, penetration data are needed. Moreover, there is a need for a practical risk assessment model, particularly for small and medium-sized enterprises.

Environmental Monitoring↗

Evaluation in vitro of canine neutrophil function.

Polymorphonuclear granulocyte (PMN) phagocytosis may be affected by many pathological changes. A panel of tests requiring relatively small volumes of blood was applied to 16 healthy dogs in order to obtain normal values and to standardize techniques. PMNs were isolated by discontinuous Percoll gradients; chemotaxis was tested in a modified Boyden chamber using the leading front method; fluorescinated yeast uptake was evaluated on a slide and superoxide (SO) production and adherence was carried out on a microtitre plate. The different aspects of phagocytosis showed no correlation with one another. Better results were obtained using a 60 min incubation period using interleukin-8 (25 ng/mL) as an activator for chemotaxis, and incubating plates for 30 min with phorbol myristate acetate (10(-6)mol/L) to assess SO production.

Animals↗

Essential oils from Piper cernuum and Piper regnellii: antimicrobial activities and analysis by GC/MS and 13C-NMR.

The essential oils of Piper cernuum and Piper regnellii leaves were analyzed by gas chromatography-mass spectrometry (GC-MS) and the results were compared to that obtained by means of a program designed to analyse (13)C-NMR data of complex mixtures. Bicyclogermacrene (21.88 %)/beta-caryophyllene (20.69 %) and myrcene (52.60 %)/linalool (15.89 %) were the major constituents in essential oil from leaves of P. cernuum and P. regnellii, respectively. Both essential oils presented growth inhibitory activities against Staphylococcus aureus and Candida albicans.

Anti-Bacterial Agents↗

Asbestos exposure assessment by mineralogical analysis of bronchoalveolar lavage fluid.

Mineralogical analysis of bronchoalveolar lavage fluid (BALF) by electron microscopy can represent the most suitable method for assessing asbestos exposure. However, it has been claimed that no standardized or systematic approach to the subject of mineralogical analysis exists. This study aimed to evaluate BALF mineralogical analysis by transmission electron microscopy as biomarker of asbestos fiber load. BALF was examined in 108 exposed workers and 57 patients who underwent diagnostic fiberoptic bronchoscopy for various clinical purposes. Asbestos bodies in BALF were counted with a phase-contrast microscope. Fibers were counted and analyzed by transmission electron microscopy, which showed a significant difference between the two populations and positive results for all exposed subjects. Only 82.2% of the exposed population tested positive for asbestos bodies. Subjects with long-term exposure had higher concentrations of fibers than did those with more recent exposure, probably because of the higher workplace exposure levels in the past. The results of the study confirm that fiber concentration in BALF can be considered as a reliable biomarker of past asbestos exposure, even many years after the end of exposure.

Adult↗

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from coal dust.

To understand the dermal uptake of chemicals bound to soil and dust, information on the neat substance is helpful but does not seem sufficient. Because of its content of polycyclic aromatic hydrocarbons (PAHs) coal is suspected to be carcinogenic. However, experimental carcinogenity studies on coal dust never succeeded in demonstrating a higher incidence of cancer in treated animals. The aim of the study was to assess dermal penetration through human skin of PAHs from coal dust. A sample of coal dust was grinded and sieved, using the particle size of < 30 microm. An in vitro static diffusion cell system validated by in vitrolin vivo comparison has been used to study dermal penetration through human skin of PAHs from coal dust compared with their percutaneous absorption as pure compounds. No percutaneous penetration of PAHs was observed in the cells where coal dust was applied, while dermal penetration was demonstrated for PAHs applied in an acetone solution. Results agree with the literature that PAHs are poorly absorbed through the skin from solids. Dermal risk assessment of PAHs should take into account not only the degree and the extent of skin contamination, but also their bioavailability, which is heavily influenced by the physico-chemical characteristics of the matrix.

Administration, Cutaneous↗

Percutaneous penetration studies for risk assessment.

During the last few years the general interest in the percutaneous absorption of chemicals has increased. It is generally accepted that there is very few reliable quantitative and qualitative data on dermal exposure to chemicals in the general population and in occupationally exposed workers. In order to predict the systemic risk of dermally absorbed chemicals and to enable agencies to set safety standards, data is needed on the rates of percutaneous penetration of important chemicals. Standardization of in vitro tests and comparison of their results with the in vivo data could produce internationally accepted penetration rates and/or absorption percentages very useful for regulatory toxicology. The work of the Percutaneous Penetration Subgroup of EC Dermal Exposure Network has been focussed on the standardization and validation of in vitro experiments, necessary to obtain internationally accepted penetration rates for regulatory purposes. The members of the Subgroup analyzed the guidelines on percutaneous penetration in vitro studies presented by various organizations and suggested a standardization of in vitro models for percutaneous penetration taking into account their individual experiences, literature data and guidelines already in existence. During the meetings of Percutaneous Penetration Subgroup they presented a number of short papers of up to date information on the key issues. The objective was to focus the existing knowledge and the gaps in the knowledge in the field of percutaneous penetration. This paper is an outcome of the meetings of the Percutaneous Penetration Subgroup and reports the presentations on the key issues identified throughout the 3-year duration of the Dermal Exposure Network (1997-1999).

Journal Article↗

Phenylpropanoid derivatives and biflavones at different stages of differentiation and development of Araucaria angustifolia.

Chemical investigations carried out with tissues at different developmental stages of Araucaria angustifolia established the presence of E and Z isomers of octadecyl p-coumarate and octadecyl ferulate in undifferentiated callus; in the seedling stems, the source of explants, three biflavones of the amentoflavone-type were isolated, whereas the diterpene, trans-communic acid, was obtained from the seedling roots. Adult stems accumulated the benzaldehydes, vanillin, p-hydroxybenzaldehyde and coniferaldehyde; the lignans, pinoresinol, eudesmin and lariciresinol; and the isoflavones, cabreuvine and irisolidone.

Cell Differentiation↗

Phenylpropanoids and tetrahydrofuran lignans from Piper solmsianum.

A tetrahydrofuran lignan as well as the known tetrahydrofuran lignan, (-)-grandisin, and five phenylpropanoid derivatives were isolated from Piper solmsianum. Their structures were determined by means of spectral analyses, including 2D NMR techniques such as NOE-DIFF and HMBC 3J(C-H).

Anthracenes↗

Non-specific immunity and ketone bodies. II: In vitro studies on adherence and superoxide anion production in ovine neutrophils.

The effects of the ketone bodies beta-OH-butyrate and acetoacetate (2.4 or 4.8 mmol/l), administered singly or simultaneously in vitro, on adherence and superoxide anion (SO) production in ovine neutrophils were investigated by simultaneous assay in 96-well microplates. Because the acetoacetate used was a lithium salt, the effect of 2.4 and 4.8 mmol/l lithium chloride was also tested. Neutrophils from eight non-lactating, non-pregnant ewes were used. SO release from neutrophils was found to be very low in basal conditions and was apparently not stimulated by contact with plastic. Administration of 10(-7) mol/l phorbol myristate acetate (PMA) caused a rapid increase and release of SO production, but smaller than that induced by co-stimulation with plastic and 10(-7) mol/l PMA. LiCl (2.4 and 4.8 mmol/l) significantly increased PMA-stimulated release, but inhibited plastic and PMA co-stimulated SO release. Administration of 2.4 mmol/l ketone bodies inhibited plastic and PMA-costimulated SO release, but the effect of acetoacetate could be due to the lithium component. Administration of 4.8 mmol/l ketone bodies had no effect. Adherence was significantly increased by contact with plastic, and moreover by 10(-7) mol/l PMA. The effect was similar when PMA was acting alone or with plastic. Neither basal nor stimulated adherence were affected by 2.4 or 4.8 mmol/l ketone bodies. LiCl at a concentration of 4.8 mmol/l increased PMA and plastic co-stimulated adherence. The results suggest that, in sheep, only the ketone body beta-OH butyrate at concentrations seen in mild ketosis, could decrease bactericidal activity, while adherence is not affected. In addition to other factors that could impair the efficiency of the immune system in ketotic ruminants, the reduced bactericidal activity may contribute to the higher occurrence of infectious disease in these animals.

3-Hydroxybutyric Acid↗

Characteristics of the response of ovine granulocytes (PMNs) to zymosan-activated serum (ZAS) and to recombinant human interleukin-8 (IL-8).

The chemotactic activity of zymosan-activated serum (ZAS) and of two concentrations of recombinant human IL-8 (IL-8(25), 25 ng/ml; IL-8(50), 50 ng/ml) for ovine polymorphonuclear granulocytes (PMNs) was tested in a modified Boyden chamber. Thick cellulose acetate filters and the leading front method were used to quantify the movements of the cells. Both ZAS and IL-8(25) exerted a chemotactic effect on ovine PMNs (P < 0.01): IL-8(50) induced a more homogeneous response (P < 0.001). To verify the characteristics of the responsiveness to the chemokines after short-term (st) or long-term (lt) repeated samplings, chemotaxis was investigated 1 (T1st), 2 (T2st), 24 (T3st) and 48 h (T4st) after the basal sampling (T0st) and 15 days (T1lt) after the basal sampling (T0lt). No differences in chemotaxis were found in long-term repeated samplings. In contrast an increase in the responsiveness to IL-8(25) and to IL-8(50) (P < 0.05) was detected at T2st in comparison with T0st. Furthermore, the significance of the distance run by activated PMNs compared with the controls, increased from T0st to T2st, as a sign of a more homogeneous response to the chemokines. In the absence of evident changes in circulating leucocyte numbers and in serum cortisol concentrations, these findings could be interpreted as a consequence of a different expression of chemoattractant receptors on the membrane of PMNs collected at different times.

Animals↗

Multiroute exposure assessment and excretion of urinary metabolites of fenitrothion during manual operations on treated ornamental plants in greenhouses.

The results of environmental and biological (five subjects) monitoring of exposure to fenitrothion during manual operations on treated ornamental plants in greenhouses are reported. Urinary excretion [GM (GSD)] of alkylphosphates [dimethylphosphate (DMP) + dimethylthiophosphate (DMTP)] (nmol/g creat) was 244.8 (1.8), 174.0 (2.0), and 354.4 (1.6) respectively, on the first (Monday), third (Wednesday), and fifth (Friday) days of work. These levels were not significantly higher than those recorded in a control group (21 subjects) in which urinary excretion [GM (GSD)] of DMP + DMTP was 102.8 (4.2) nmol/g creat. Air concentrations of fenitrothion (nmol/m3) ranged from 45.5 to 81.2 on Monday, 17.3 to 27.1 on Wednesday, and 9.7 to 19.1 on Friday. Dose estimates showed that the respiratory-absorbed doses of fenitrothion accounted, on the average (GM), for 94.7%, 93.1%, and 91.5% of the total absorbed dose on Monday, Wednesday, and Friday, respectively. Multiple regression analysis showed a significant correlation (r2 = 0.595) between urinary excretion of DMP + DMTP, respiratory-absorbed dose, and skin-absorbed dose, estimated on Monday and Wednesday. Total estimated absorbed doses did not exceed the acceptable daily intake for fenitrothion. Serum and erythrocyte cholinesterase activities were not significantly different before and after exposure.

Adult↗

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from lubricating oil.

OBJECTIVES: Percutaneous penetration of polycyclic aromatic hydrocarbons (PAHs) is affected by various factors connected to exposure conditions. The nature of the matrix, such as that of oil, can strongly affect their percutaneous penetration. Risk assessment should consider these effects. We examined the effect of matrix on percutaneous penetration of PAHs, particularly that of lubricating oil. METHODS: The test apparatus consisted of an in vitro static diffusion cell system using full-thickness monkey (Cercopithecus aetiops) skin as the membrane and saline solution with gentamycin sulfate and 4% bovine serum albumin as receptor fluid. Chemical analysis of PAHs in the samples obtained from cells was carried out by inverse-phase HPCL, and the results were read by spectrofluorimetry. RESULTS: Comparing the penetration of 13 PAHs from a lubricating oil and from acetone solution with artificial sweat resulted in a significantly slower passage from the oil matrix for acenaphthene, anthracene, phenanthrene, fluoranthene, naphthalene, pyrene, fluorene (Mann-Whitney U test, P < 0.05). No significant differences in the passage were found for chrysene because, in the test with oil, its concentration was very often below the detection limit. For benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene it was possible to demonstrate a passage through the skin only when compounds were applied in acetone solution with artificial sweat. CONCLUSIONS: The results of the study suggest the necessity of dermal penetration data relevant for risk assessment, obtained under experimental conditions similar to the real exposure conditions.

Acetone↗