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Biomedical subjects

L Giuliani

Publications and source records attributed to L Giuliani.

At least 37 records · Page 2Linked to original sources
PubMed2000

Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques.

Prolonged antiretroviral therapy (ART) is not likely to eradicate human immunodeficiency virus type I (HIV-I) infection. Here we explore the effect of therapeutic immunization in the context of ART during primary infection using the simian immunodeficiency virus (SIV251) macaque model. Vaccination of rhesus macaques with the highly attenuated poxvirus-based NYVAC-SIV vaccine expressing structural genes elicited vigorous virus-specific CD4 + and CD8+ T cell responses in macaques that responded effectively to ART. Following discontinuation of a six-month ART regimen, viral rebound occurred in most animals, but was transient in six of eight vaccinated animals. Viral rebound was also transient in four of seven mock-vaccinated control animals. These data establish the importance of antiretroviral treatment during primary infection and demonstrate that virus-specific immune responses in the infected host can be expanded by therapeutic immunization.

Animals↗
PubMed1999

Detection of basic fibroblast growth factor mRNA in urinary bladder cancer: correlation with local relapses.

Natural history of bladder cancer is characterized by high risk of disease progression even for patients with a clinical diagnosis of superficial disease; in these tumors, the occurrence of local relapse is known to be dependent on the angiogenesis rate. Basic fibroblast growth factor (bFGF), has been described to be elevated in urine and serum of patients with bladder cancer. We investigated the expression of bFGF at mRNA level in a panel of 32 transitional cell tumors of the urinary bladder and in normal bladder tissues used as controls. Expression of bFGF was found elevated in most tumors of high stage, where its presence was found correlated with the occurrence of early local relapses. Furthermore, bFGF was found highly expressed in the majority of tumors showing a high bcl-2 expression rate. Our data suggest that bFGF expression could contribute to the progression of disease; it may provide a prognostic indicator in the identification of patients with high risk for occurrence of local relapses.

Adult↗
PubMed1998

Prevalence of papillomavirus, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus type 2 in urinary bladder cancer.

Recent epidemiological studies suggest that the risk for urological malignancies may be related to the exposure to infectious agents. Human Papillomaviruses type 16 and 18 (HPV 16, HPV 18), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and herpes simplex virus type 2 (HSV-2) have been suggested previously as cofactors in the pathogenesis of some malignancies in humans. The present paper, the presence of HPV 16, HPV 18, EBV, CMV and HSV-2 genomes was investigated in a panel of 35 biopsies from urinary bladder carcinomas using the polymerase chain reaction (PCR). Sequences of EBV, HPV, CMV and HSV-2 genomes were detected in 34%, 31%, 11% and 9% of tissue samples respectively, while in 20% of patients we found more than one viral infection. Absence of viral genomes was found in normal bladder. To our knowledge, this is the first report concerning the association of EBV, CMV and HSV-2 with bladder cancer. This finding may raise the question whether such viral infection may contribute to development and progression of some types of urological malignancies in humans.

Adult↗
PubMed1997

Experience with hair testing in the clinical biochemistry laboratory of Ca' Granda Niguarda Hospital, Milan, Italy.

In our laboratory, analysis of human hair for drugs of abuse detection was first performed in 1980. In the last 10 years we have processed about 2000 subjects/year ('living subjects' only). In the last 3 years we have also introduced hair analysis of cocaine: at first only in clinical applications, but for the last 2 years this analysis is now routine. Our application of hair analysis includes: clinical toxicology, medico-legal and administrative agencies. Requests come for example from several Committees for Driving Licenses, Addiction Treatment Centers and Legal Authorities. Hair samples are currently collected from the occipital area at the back of the head, which appears to show less variability in hair growth rate. At present we perform hair analysis using highly sensitive radioimmunoassay screening methods for the detection of parent drug and/or metabolites. All positive cases of cocaine and opiates abuse are confirmed by gas chromatography-mass spectrometry in electron impact or chemical ionization mode. Positive cases for opiates are also analysed using a specific morphine radioimmunoassay kit. Data show that, when the opiates/morphine ratio is higher than 6, we are dealing with consumption of codeine and/or dihydrocodeine. In our routine work last year there were 177 (263 samples) positive opiates subjects out of 2244 patients; positive cocaine subjects were 290 (362 samples) out of 2001 patients. Guidelines for hair analysis in Lombardia have been established based on the experience of our laboratory. Furthermore it will be possible to apply a unique protocol for all Committees for Driving Licenses, involving hair testing in addition to urine assay.

Biomarkers↗
PubMed1997

Sulphation of the heterocyclic amine 1,2,3,4-tetrahydroisoquinoline in the human liver and intestinal mucosa: interindividual variability.

The sulphation rate of 1,2,3,4-tetrahydroisoquinoline (TIQ) was measured in the human liver and in the intestinal mucosa isolated from the transverse colon, ileum and duodenum. The rate (mean +/- SD) of hepatic TIQ sulphation was 500 +/- 174 pmol/min per mg in women (n = 61) and 591 +/- 201 in men (n = 39; P = 0.0087), varying over one order of magnitude in men and women. The sulphation rate of testosterone showed the same sex-dependent pattern and was correlated (r = 0.6055; P < 0.001) with that of TIQ. The frequency distribution of TIQ sulphation rate in human liver was bimodal: 70% of the population fell into the low-activity subgroup and the remaining 30% feel into the high-activity subgroup. In the colon (n = 56), the rate of TIQ sulphation was 30.4 +/- 15.6 pmol/min per mg and the values were similar in men and women (29.8 and 30.9 pmol/min per mg, respectively) but, varied over one order of magnitude and correlated (r = 0.7231; P < 0.001) with that of 4-nitrophenol. The rate of TIQ sulphation changed along the human bowel and mean (+/-SD) estimates for duodenum, ileum and transverse colon were 444 +/- 25, 182 +/- 87 and 30.4 +/- 15.6 pmol/ min per mg, respectively. The present results are consistent with the view that the heterocyclic amine TIQ is sulphated in the human liver and intestinal mucosa. TIQ-sulphotransferase activity varies among subjects and is mostly associated with the liver and duodenum.

Adult↗
PubMed1997

(-)-salbutamol sulphation in the human liver and duodenal mucosa: interindividual variability.

1. Salbutamol as a beta 2-adrenergic agonist used in the treatment of lung obstructive disease and premature labour. It has a bioavailability of 50% and sulphation is the main route of its metabolism. (-)-Salbutamol retains most of the beta 2-adrenergic activity and, thereby, we describe the interindividual variability in the sulphation rate of (-)-salbutamol in 100 specimens of human liver and duodenal mucosa. 2. The mean rate (pmol/min/mg of salbutamol sulphation was 498 in the duodenum and 141 in the liver with 4-fold variation within +/-2 SD units in both tissues. 3. A modelling approach based on the comparison of the best fittings obtained using a gaussian and the sum of two gaussian curves revealed the presence of two subgroups in the hepatic rate of salbutamol sulphation and their means were 69.5 and 105 pmol/min/mg (p < 0.05). In the duodenum, the rate of salbutamol sulphation approached normality. 4. The rates of salbutamol and 4-nitrophenol sulphation correlated highly (r = 0.853; p < 0.001) in the liver whereas in duodenum the rates of salbutamol and dopamine correlated highly (r = 0.914; p < 0.001), 4-Nitrophenol and dopamine are the diagnostic substrates of phenol- and catechol-sulphotransferases respectively. These findings are consistent with the view that the rate of salbutamol sulphation is higher in the gut than in liver and it varies considerably in both tissues.

Adrenergic beta-Agonists↗
PubMed1997

Radiofrequency exposure near high-voltage lines.

Many epidemiologic studies suggest a relationship between incidence of diseases like cancer and leukemia and exposure to 50/60 Hz magnetic fields. Some studies suggest a relationship between leukemia incidence in populations residing near high-voltage lines and the distance to these lines. Other epidemiologic studies suggest a relationship between leukemia incidence and exposure to 50/60 Hz magnetic fields (measured or estimated) and distance from the main system (220 or 120 V). The present work does not question these results but is intended to draw attention to a possible concurrent cause that might also increase the incidence of this disease; the presence on an electric grid of radiofrequency currents used for communications and remote control. These currents have been detected on high- and medium-voltage lines. In some cases they are even used on the main system for remote reading of electric meters. This implies that radiofrequency (RF) magnetic fields are present near the electric network in addition to the 50/60 Hz fields. This intensity of these RF fields is low but the intensity of currents induced in the human body by exposure to magnetic fields increases with frequency. Because scientific research has not yet clarified whether the risk is related to the value of magnetic induction or to the currents this kind of exposure produces in the human body, it is reasonable to suggest that the presence of the RF magnetic fields must be considered in the context of epidemiologic studies.

Electrophysiology↗
PubMed1996

Zidovudine glucuronidation in human liver: interindividual variability.

Zidovudine 3'-azido-3'-deoxythymidine is the drug chosen for the treatment of patients suffering from AIDS; zidovudine being a potent inhibitor of HIV replication. The drug is extensively metabolized by conjugation with glucuronic acid into an inactive compound, and 30-40% of the dose is eliminated presystemically. We studied the variability and characterized the frequency distribution of the activity of zidovudine glucuronosyl transferase in 93 specimens of human liver. A rapid and reproducible radiometric assay for the glucuronidation of 14C-zidovudine is reported. The method is based on the extraction of the unreacted zidovudine into organic solvents and the radioactivity of the unextractable zidovudine glucuronide was measured in the aqueous phase residue. The rate of zidovudine glucuronidation was neither sex- nor age-dependent, ranged over 1 order of magnitude, and was positively skewed. The possibility that endogenous bilirubin should interact with glucuronidation of zidovudine was explored and the endogenous concentration of bilirubin was measured in the microsomal preparations of 59 liver samples. The final concentration of bilirubin in the assay mixture for zidovudine glucuronidation ranged between 2.2 and 13.2 microM and did not interact with the rate of zidovudine glucuronidation. The kinetics of glucuronosyl transferase towards zidovudine was studied in 20 livers, Michaelis-Menten kinetics were observed and the K(m) estimate ranged over 2-fold with an average of 2.89 mM. These in vitro results are consistent with the view that the rate of glucuronidation varies over 1 order of magnitude in the human liver and its distribution is positively skewed. This variability may modulate the patient's exposition to zidovudine and thereby the efficacy of therapy.

Adult↗
PubMed1995

[Colorectal carcinoma in the elderly. Assessment of prognostic factors].

Between 1976 and December 1992 a total of 80 patients aged 80 or over underwent surgery for colorectal cancer at the Surgical Clinic of Pisa University. Twelve patients died, 18 presented non-lethal complications and 48 had a normal postoperative recovery. The type of surgery did not appear to be correlated with mortality. Urgency, associated with the advanced stage of cancer (according to Duke's classification modified by Aster-Coller), was the factor which most severely influenced mortality. A marked prognostic improvement can be obtained by an early diagnosis and careful evaluation of the patient's overall conditions.

Age Factors↗
PubMed1995

Glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB): interindividual variability in human liver, lung, kidney and intestine.

The rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) was measured in specimens of human liver (n = 93), sigmoid colon (n = 56), renal cortex (n = 67) and lung (n = 68). In the liver there was a weak but significant (r = - 0.247 p = 0.017) negative correlation between the activity of glutathione transferase and the liver donor's age. Such a correlation was not found in the renal cortex, lung and colon. In the renal cortex and in lung the rate of glutathione conjugation with CDNB was a little but significantly (p < 0.05) higher in women than men, whereas no sex-dependent difference was observed in the liver and colon. The distribution of glutathione transferase activity was polymorphic in the mucosa of colon and renal cortex of men but not in that of women. Smoking seems not to affect the glutathione conjugation rate with CDNB in lung. The activity of glutathione transferase was 2-, 6-, and 7-fold greater in liver than in the renal cortex, lung and colon, respectively. There was a large interindividual variability of the hepatic glutathione transferase activity, and because this variability, 15% of the population studied catalyzed the glutathione conjugation with CDNB at a rate similar to those of the renal cortex and duodenum. The subjects with low expression of the hepatic glutathione transferase should be more exposed to the effects of toxic and carcinogenic compounds.

Adult↗
PubMed1994

Stereoselective inhibition by chloroquine of histamine N-methyltransferase in the human liver and brain.

This study was designed to determine whether both enantiomers of chloroquine inhibit histamine N-methyltransferase. The mean estimates of IC50 for the d- and l-enantiomers of chloroquine were 4.9 and 17.8 microM (liver), respectively and 6.9 and 21.6 microM (brain), respectively. Ki estimates were significantly lower with d- than with l-chloroquine; hence, d-chloroquine interacts with the enzyme more effectively than l-chloroquine. If the adverse effects of chloroquine are due to the inhibition of histamine N-methyltransferase, therapy with the l-enantiomer might have lower toxicity. The residual activity of histamine N-methyltransferase should reflect both the degree of inhibition by chloroquine and the level of enzyme expression. The rate of histamine methylation was measured in 100 human liver samples and its range and fold of variation were 29% and threefold, respectively. Susceptibility to chloroquine should be greater in subjects with limited expression of histamine N-methyltransferase

Adult↗
PubMed1994

Human liver budesonide sulphotransferase is inhibited by testosterone and correlates with by testosterone sulphotransferase.

Budesonide, a corticosteroid used in the treatment of asthma and allergic reactions, is almost entirely cleared by metabolism in man. We describe the sulphation of budesonide in human liver and lung and provide evidences that the sulphation of budesonide is catalysed by testosterone sulphotransferase. A rapid and reproducible radiometric assay for budesonide sulphotransferase is described. Liver specimens were obtained from 35 men and 65 women and lung specimens from 2 women and 17 men. The average hepatic budesonide sulphation rate was significantly higher in men (41.1 pmol.min-1.ml-1) than women (28.2 pmol.min-1.mg-1). In the lung, the mean budesonide sulphation rate was 5.0 pmol.min-1.mg-1. Testosterone strongly inhibited the hepatic sulphation of budesonide, whereas p-nitrophenol and dopamine were poor inhibitors; the IC50 was 7.0 uM (testosterone), 320 uM (p-nitrophenol) and 510 uM (dopamine). The hepatic rates of testosterone, p-nitrophenol and dopamine sulphation were measured in the same samples assayed for budesonide sulphotransferase. There was a correlation between the hepatic rates of budesonide and testosterone sulphation (P < 0.001; r = 0.810). The activity of testosterone sulphotransferase was significantly greater in men than women (22.0 vs. 17.2 pmol.min-1.mg-1), whereas those of dopamine and p-nitrophenol sulphotransferase were not sex dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Interindividual variability of the human hepatic sulphotransferases.

The variability among subjects of the hepatic activities of O-sulphotransferase towards dopamine, p-nitrophenol, testosterone and ethinyloestradiol and of N-sulphotransferase with 1,2,3,4-tetrahydroisoquinoline (TIQ) as substrate is described. The rates of testosterone and TIQ sulphation were higher in men than women whereas those of ethinyloestradiol, dopamine and p-nitrophenol were similar in both sexes. The sulphotransferase activities towards p-nitrophenol and dopamine were positively skewed whereas those towards ethinyloestradiol approached normality. The coefficients of variations for the sulphotransferase activities ranged between 34% and 62% indicating a considerable variability among subjects. The rates of dopamine-, TIQ- and p-nitrophenol-sulphation were measured in the mucosa of the human intestine, and the duodenum/liver ratios were 10, 0.9 and 0.1, respectively. Thus the contribution of the intestine in the sulphation of xenobiotics is substrate dependent.

Adult↗
PubMed1993

Tumor targeting potential and metabolism of 5-[125I]iodo-2'-deoxyuridine injected intratumorally in patients with breast cancer.

We have previously demonstrated the high tumor targeting potential of the thymidine analogue 125IUdR in experimental animal models following direct intratumoral or locoregional (intracavitary) administration. The aim of the present work was to evaluate the metabolism and selectivity (based on differential cell proliferation kinetics) of 125IUdR incorporation in patients with breast cancer following a similar approach. 125IUdR (4-8 MBq) was injected intratumorally by ultrasound-guided percutaneous injection in 7 patients with breast cancer 24 hours before ablative surgery. Blood and urine samples were collected up to 72 hours after injection and analyzed by HPLC using a C18 reversed-phase column and methanol:water (20:80) as the mobile phase. Following resection, the radioactivity of the tumor and the surrounding tissues was measured in a gamma counter, and microautoradiography was performed on semithin tissue sections to determine the site of tracer incorporation at the cellular level. Activity in plasma peaked at 0.5 to 1 hour after 125IUdR injection (4.96 +/- 1.08% of injected dose/liter), declining thereafter with a mean T1/2 of 11.24 +/- 2.78 hours. By HPLC analysis, undegraded 125IUdR was about 15-30% of total plasma activity, with a biphasic pattern peaking at both 1-3 hours and approximately 12 hours. In addition to free 125I-, about 10% of early plasma activity was constituted by a labeled metabolite (tentatively identified as radio-iodouracil), rising to about 50-60% at later time points. About 70-90% of urinary radioactivity was 125I-, and 5-20% was undegraded 125IUdR in the first 24-hour samples, while the remainder was iodouracil. High tumor/nontumor ratios were obtained (mean 147.4 +/- 125.2, range 27-397) with average tumor/blood ratios at the time of surgery equal to 32.7 +/- 18.6 (range 5-56). An average 0.0244 +/- 0.0189% of the injected dose was present per gram of tumor (range 0.001-0.061% ID/g). Microautoradiography confirmed the high values of tumor/nontumor incorporation ratios and demonstrated the specificity of 125IUdR incorporation mostly in the tumor cell nuclei, with only occasional incorporation by normal-appearing tubular cells. These results suggest the potential of radiolabeled IUdR for tumor targeting in humans, to be used whenever a satisfactory route of locoregional administration allowing for homogeneous tracer distribution within the tumor mass is accessible and in the presence of favorable tumor cell proliferations kinetics.

Aged↗
PubMed1993

Minoxidil sulphation in human liver and platelets. A study of interindividual variability.

Minoxidil requires to be sulphated to exert its hypotensive effect. We report on interindividual variability in the rate of minoxidil sulphation in 118 specimens of human liver and in platelets obtained from 100 healthy subjects and 100 newborns. The frequency distribution histogram of the hepatic activity of minoxidil sulphotransferase was positively skewed; the mean was 631 pmol.min-1 x mg-1. After logarithmic transformation of the enzyme activity, the frequency distribution histogram became symmetrical and did not significantly deviate from normality. The rate of minoxidil sulphation was not different in platelets from adults (0.74 pmol.min-1 x mg-1) and newborns (1.16 pmol.min-1 x mg-1). The frequency distribution histograms were positively skewed and the results of normal equivalent deviation analysis was compatible with the presence of at least two subgroups of sulphotransferase in liver and platelets. Thus, two phenotypes of sulphotransferase exist in human liver and platelets, and the "extensive sulphator" phenotype contributes to skewing the frequency distribution. In platelets, the percentage of subjects that fall in the two subgroups is different at birth and in adulthood. This can explain the different shape of the frequency distribution in newborn and adult platelets and suggests that platelet minoxidil sulphotransferase undergoes modification after birth.

Adult↗
PubMed1993

Sulphation and glucuronidation of ritodrine in human foetal and adult tissues.

Ritodrine is a beta 2-adrenoceptor agonist used for the management of preterm labour. It is inactivated by conjugation with sulphate and glucuronic acid. There is more ritodrine sulphate than ritodrine glucuronide in urine from the newborn whereas equal amounts of ritodrine glucuronide and sulphate are excreted in maternal urine [Clin. Pharmacol. Ther 44, 634-641, 1988]. We show that, in the mid-gestational human fetal liver, ritodrine sulphotransferase is well expressed, whereas the glucuronidation of ritodrine is little developed compared to the adult liver. The average sulphotransferase activity was 308 pmol.min-1 per mg protein in fetal (N = 48) and 145 pmol.min-1 per mg protein in adult (N = 32) liver. The rates of ritodrine sulphation in fetal gut, lung and kidney were higher than in the corresponding adult tissues. The development and tissue distribution patterns of ritodrine sulphotransferase are consistent with those of dopamine sulphotransferase. Ritodrine and dopamine are sulphated by thermolabile enzymes. The activity of glucuronyl transferase was measurable in only 5 of the 48 foetal livers assayed, and in those in which could be assayed, the average activity was 44.6 pmol.min-1 per mg protein, one-tenth of that in adult livers (524 pmol.min-1 per mg protein).

Adult↗
PubMed1993

(+) and (-) terbutaline are sulphated at a higher rate in human intestine than in liver.

The sulphation of (+) and (-) terbutaline was investigated in specimens of human intestinal mucosa isolated from the duodenum, ileum, ascending colon and sigmoid colon and in specimens of liver and lung. The lung specimens came from 8 current smokers and 11 ex-smokers, the latter having stopped at least 3 months before surgery. The rates (pmol.min-1.mg protein-1) of (+) and (-) terbutaline sulphation were 1195 and 948 (duodenum), 415 and 317 (ileum), 268 and 166 (ascending colon), 263 and 193 (sigmoid colon) and 45 and 34 (liver), respectively. Terbutaline sulphotransferase was more active in the small and large intestine than in the liver. In the lung, the rate of (+) terbutaline sulphation was 118 (ex-smokers) and 82 (smokers), and for (-) terbutaline it was 82 (ex-smokers) and 56 (smokers). In the gut, the activity of catechol sulphotransferase was significantly correlated with that of (+)- and (-)- terbutaline sulphotransferase whereas no correlation was found with phenol sulphotransferase. This correlation, the finding of the higher activity of terbutaline sulphotransferase in gut than in liver, and the pronounced thermal inactivation of the enzyme, are all consistent with the view that catechol sulphotransferase has a role in the sulphation of terbutaline.

Adult↗