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Biomedical subjects

A Gandolfi

Publications and source records attributed to A Gandolfi.

At least 19 recordsLinked to original sources
PubMed2006

Cell resensitization after delivery of a cycle-specific anticancer drug and effect of dose splitting: learning from tumour cords.

After a single dose of an anticancer agent, changes due to cell death are expected to occur in the distribution of cells between proliferating and quiescent compartment as well as in the oxygenation and nutritional state of surviving cells. These changes are transient because tumour regrowth tends to restore the pretreatment status. The reoxygenation due to the decrease of oxygen consumption is expected to induce cell recruitment from quiescence into proliferation, and consequently to increase the sensitivity of the cell population to a successive treatment by a cycle-specific drug. In previous papers we proposed a model of the response of tumour cords (cylindrical arrangements of tumour cells growing around a blood vessel of the tumour) to single-dose treatments. The model included the motion of cells and oxygen diffusion and consumption. On the basis of that model suitably extended to better account for the action of anticancer drugs, we study the time course of the oxygenation and of the redistribution of cells between the proliferating and quiescent compartments. By means of simulations of the response to a dose delivered as two spaced equal fractions, we investigate the dependence of tumour response on the spacing between the fractions and on the main parameters of the system. A time window may be found in which the delivery of two fractions is more effective than the delivery of the undivided dose.

Antineoplastic Agents↗
PubMed2005

A model with 'growth retardation' for the kinetic heterogeneity of tumour cell populations.

In the present paper we propose a continuous cell population model based on Shackney's idea of growth retardation. Cells are characterized by two state variables: the cell maturity x, 0 < or = x < or = 1, and a state variable T that identifies the rate of maturation along cell cycle. During their life span, cells can change T at random by jump transitions to T values corresponding to slower maturation rates, while at each jump the maturity x is conserved. Both the time evolution of the population and the exponential stationary solution are numerically computed. The distribution of the cell cycle transit time in asynchronous exponential growth is investigated by Monte Carlo simulation. An approximated formula for the distribution of cell cycle time is also provided.

Algorithms↗
PubMed2001

Intraindividual and intraspecies variability of ITS1 sequences in the ancient asexual Darwinula stevensoni (Crustacea: Ostracoda).

The lack of variability in ITS regions within individuals and within species has been explained as the result of concerted evolution. In fact, many examples of intraindividual variation in the ITS regions have been reported. Here we report evidence of within-individual variation of the ITS1 region in the obligate parthenogenetic species Darwinula stevensoni. We analysed 46 clones obtained from 12 individuals of D. stevensoni, from three Italian sites and one site in Luxembourg. Seven nucleotides out of 366 were variable. Most variability (80%) was found among clones within individuals, and the remainder of the variability was observed among individuals. No difference was found among populations or between habitats. The low intraspecific variability and the observation of recombinant molecules are evaluated in light of the relevant literature. The high percentage of variation within individuals and the occurrence of recombination without meiosis are discussed by considering the ancient asexual "status" of the species.

Analysis of Variance↗
PubMed2001

[Acute cholestatic hepatitis caused by propafenone. Report of a case and review of the literature].

A case of acute cholestatic hepatitis associated with use of propafenone is reported. Hepatitis developed 3 weeks after the beginning of administration of this drug. The close time relationship between the administration of the antiarrhythmic drug and the acute onset of the liver damage, the exclusion of hepatobiliary disease and the rapid normalisation of biochemical parameters following withdrawal of the drug strongly suggest that propafenone was involved in the pathogenesis of this syndrome. Meticulous taking of patient history and clinical assessment are mandatory for the early identification of drug-induced hepatotoxicity and avoidance of more severe types of reactions, such as liver failure.

Acute Disease↗
PubMed2001

[Long-term audition results in patients with chronic endolymphatic hydrops after selective vestibular neurotomy and endolymphatic sac surgery].

The purpose of the present study was to evaluate the long-term auditory results in the ears of patients suffering from unilateral Ménière's disease (Md) who had undergone retrolabyrinthine vestibular neurotomy (RVN) associated with endolymphatic sac (ES) surgery. Retrospective evaluation was performed on 45 patients with unilateral Md who had undergone RVN between 1982-1997. All patients had previously been treated with medical therapy for at least 6 months without showing any response. The forms of ES surgery performed were as follows: simple ES decompression (ESD) in 15 patients, chronic endolymphatic mastoid shunt (EMS) using a sylastic sheet in 15 ears and ES exclusion (ESE) of the proximal section in the remaining 15 patients. Evaluation of the results was performed using the parameters indicated by the "Committee on Hearing and Equilibrium"--AAO-HNS 1995. Comparison of the average post-operative and preoperative PTAs revealed a worsening of 9.2 dB (sd: +/- 17.1) in the ESE group. This variation was statistically significant (p < 0.05). When the individual patients were evaluated, the PTA remained unchanged in 10 cases (67%) in the ESD group, in 13 (87%) in the EMS group and in 10 (67%) in the ESE group. In no case did hearing improve. Statistical analysis did not reveal any significant difference between the three groups of patients. Tinnitus, present prior to surgery in all patients, disappeared or improved in 6 patients (40%) in the ESD group, in 6 (40%) of the EMS group and in 5 (33%) of the ESE group. The differences between groups were not significant. The sensation of plugged ears, present prior to surgery in 11 patients in the ESD and EMS groups and in 13 patients in the ESE group disappeared or improved respectively in 9 (82%), 10 (91) and 11 (85%) of the patients. The 10 remaining patients who did not have the sensation of plugged ears prior to surgery did not refer its appearance after surgery. Again for this symptom the difference between groups was not significant. The results of this research would appear to indicate that in patients with Md, evolution of the hearing symptoms observed after RVN can be improved by applying an EMS. This finding must be validated in a larger sampling.

Adult↗
PubMed2001

[Acoustic neuroma: clinical-functional finding, results and surgical complication].

The present work provides clinical-functional findings, results and surgical complications observed in a consecutive series of 100 subjects with acoustic neuroma (AN). Analysis of the data has made it possible to draw some important conclusions. Compromised hearing is found in 90% of the ears affected by AN. Indeed the percentage of normal hearing in such cases does not exceed 5%. There is, however, no clear correlation between degree of hearing and tumor size. The symptoms of AN do not always present unilateral or asymmetrical hearing loss, unilateral tinnitus and/or dizziness. At times AN presents atypical symptoms and can even be asymptomatic. Sudden onset of unilateral hearing loss, acute vertigo, persistent monolateral tinnitus and even isolated symptoms of the V or VI cranial nerve should lead one to suspect AN. Only by applying the diagnosis of suspected AN in a large number of cases is it possible to lower the time gap between the onset of symptoms and the definitive diagnosis of AN, increasing the number of cases diagnosed while the AN is still small. Auditory brainstem responses (ABR) are still the means of choice for screening and following up subjects where AN is suspected. Reduced ABR sensitivity reported in the literature for intracanal ANs must induce further testing with magnetic resonance imaging with gadolinium in all subjects where an AN is suspected, even when the ABR is normal. Recording of transient evoked otoacoustic emissions in the presence and in the absence of contralateral white noise has proved to be a simple, inexpensive, non-invasive test for the diagnosis of suspected retrocochlear pathologies. A deficit in vestibular function is most frequently encountered when the AN is already quite large and an alteration in the smooth pursuit test is only found when the AN involves the brainstem. These data have led us to conclude that vestibular reflex studies do not play any role in early diagnosis of AN. Surgical exeresis is the treatment of choice in those cases where "watch and scan" (only hearing ear in the absence of neurological complications; AN < 0.5 cm in the ponto-cerebellar angle, particularly in elderly patients) is not indicated. The enlarged translabyrinthine approach is indicated in all cases of AN, no matter what the tumor size and extent of pre-operative hearing. Promptly and correctly treating intra and postoperative complications, most frequently encountered in patients with AN > 2 cm, reduces the mortality and morbidity to a minimum. Modern otological microsurgery and monitoring techniques make it possible to preserve the VIIth facial nerve in more than 90% of the ears, consequently preserving or nearly preserving normal VIIth nerve function 1 year after surgery in at least three out of four patients. No matter what approach is used, hearing can be preserved measurably in approximately 50% of the ears undergoing surgery and to a socially useful or nearly useful level in a significantly lower proportion of patients. In this regard the most satisfactory results are obtained when preoperative hearing is normal and the AN is < 2 cm.

Adolescent↗
PubMed2000

Cell kinetics in a tumour cord.

In some tumours, the viable cells grow around blood vessels forming cylindrical structures called tumour cords, which are surrounded by regions of necrosis. In the present paper, we propose a mathematical model for the cell kinetics in a tumour cord at the stationary state. Both proliferating cells and quiescent cells are considered, and the proliferating cell population is structured by age. Cell migration towards cord periphery is accounted for from a continuum viewpoint. The age distribution of proliferating cells, the fraction of cells in S phase, the growth fraction and the velocity along the cord radius are computed. The predictions of the model are compared with literature data obtained from two experimental rat hepatomas. The model was used to compute the profile of the oxygen tension within the cord. Possible modifications and extensions are also presented.

Animals↗
PubMed2000

Persistence of asexuality through mixed reproduction in Eucypris virens (Crustacea, Ostracoda).

The ostracod species Eucypris virens exhibits geographical parthenogenesis, with rare sexual populations in southern Europe and widespread asexual populations elsewhere. DNA sequence data from the nuclear ITS1 and mitochondrial COI regions have been used to estimate genetic variabilities and reconstruct phylogenies. The observed divergence was exceptionally high, with intraspecific maxima of 10.3% (ITS1) and 20.9% (COI) among European lineages, levels reported for interspecific comparisons of other taxa. Phylogenetic reconstructions reveal multiple origins of asexual clones from sexual populations. However, we argue that such data can only provide a lower limit on the number of origins of asexual reproduction, and an upper limit on the age of asexual lineages. Congruence between gene trees for different loci can provide support for the inference of long-term apomictic reproduction. Nuclear and mitochondrial data differ in their placement of some asexual clones, possibly indicating that genetic exchange has taken place between sexual and asexual lineages. Such intraspecific hybridization is one route to combine the benefits of both reproductive modes, and it might explain how asexuality managed to persist in E. virens even in long, evolutionary terms.

Animals↗
PubMed2000

Paradoxical effects of contralateral white noise on evoked otoacoustic emissions in ears with acoustic neuroma.

A contralateral suppression effect on evoked otoacoustic emissions (EOAEs) is usually present in normally hearing subjects and in patients with sensorineural hearing loss, while it is absent or reduced in ears to which the vestibular nerve has been cut and in ears with acoustic neuroma (AN). To date, a paradoxical effect, that is an increase in EOAE amplitude during contralateral stimulation, has been described in one ear with sensorineural hearing loss of unknown aetiology and in three ears with AN (two in the present paper). Evidence has been provided that the contralateral suppression effect on EOAEs is accomplished largely, if not entirely, via the medial olivocochlear bundle (OCB). According to clinical data the absence or the reduced amount of contralateral suppression effect on EAOEs may be attributed to a totally, or partially, damaged or malfunctioning medial OCB. The way in which a contralateral noise may increase EOAE amplitude is more difficult to explain. One attractive hypothesis is that this paradoxical effect is a result of some pathological adaptive process in the medial OCB.

Acoustic Stimulation↗
PubMed2000

Disposition of dodecanedioic acid in humans.

The disposition of dodecanedioic acid (C12) was investigated in six overnight-fasting healthy male volunteers, who received a 165-min i. v. infusion of 42.45 mmol of C12 added to 150 microCi of [1-12-(14)C]C12. Blood samples were collected up to 360 min after the start of infusion, and concentration of serum labeled C12 was determined. Expired radioactivity (microCi/min) was measured up to 600 min and at 24 h. The 24-h C12 urinary excretion was around 5% of the administered amount. The percentage of C12 oxidized was 81.7 +/- 9.5% (mean +/- S.D.) of administered amount as estimated from the area under the curve of measured (14)CO(2) expiration rate. C12 kinetics was described by assuming a single compartment. A saturable rate of C12 tissue uptake (model A) and a linear rate of tissue uptake (model B) were considered. The kinetics of CO(2) produced by C12 oxidation was described by a fast pathway acting in parallel to a slow pathway modeled by first order kinetics. Parameters of model B were estimated for each subject, whereas model A was identified by fitting the pooled data of all subjects. On the basis of estimates obtained from model B, an average calorie delivery of 500 kcal/day was predicted in the plateau phase for the infusion rate of our experiments. When estimated from model A, the maximal rate of tissue uptake was 0.38 +/- 0.08 mmol/min, with a maximal calorie delivery of 750 kcal/day. These results appear promising for C12 utilization in parenteral nutrition, because C12 elimination with urine is low, whereas tissue uptake and oxidation are rather efficient.

Adult↗
PubMed2000

Subclinical hepatic encephalopathy: role of tryptophan binding to albumin and the competition with indole-3-acetic acid.

BACKGROUND: The role of tryptophan (TRY) and its metabolites in the pathogenesis of hepatic encephalopathy is conflicting. The aim of the present study is to investigate in posthepatitis cirrhotic patients with encephalopathy the serum levels of TRY and those of its metabolite indole-3-acetic acid, as well as TRY binding curve to serum albumin and the competition with indole-3-acetic acid. The presence of a relationship between encephalopathy severity and circulating free TRY was also investigated. METHODS: Serum TRY and indole-3-acetic acid were analyzed by HPLC; binding of TRY to serum albumin and the competition with indole-3-acetic acid was studied by equilibrium dialysis. RESULTS: Serum-free TRY was significantly higher in cirrhotic patients (43.33 +/- 14.70 vs 28.87 +/- 8.77 mumol/L, P = 0.02). The binding capacity of albumin was reduced in cirrhotics and further decreased by the addition of indole-3-acetic (K = 6.63 +/- 0.97 x 10(3) mol/L-1, gamma = 1.16 +/- 0.45 x 10(2) mol/L-1 in normal sera vs K = 1.04 +/- 0.20 x 10(3) mol/L-1, gamma = 1.91 +/- 0.92 10(2) mol/L-1 in cirrhotic sera). A multivariate analysis showed that among the psychometric tests the only independent predictor of serum levels of free TRY was the Block Design (R2 = 0.94, B = 0.16 +/- 0.01, beta = 0.97; P < 0.0001). CONCLUSIONS: A high percent ratio of free/total TRY and indoleacetic acid (IAA) was found in cirrhotic patients with hepatic encephalopathy. The concentrations of serum-free IAA and TRY correlated with the degree of subclinical encephalopathy, suggesting a role of these compounds in the development of mental derangement in liver cirrhosis.

Adult↗
PubMed1997

Binding of indole-3-acetic acid to human serum albumin and competition with L-tryptophan.

Indole-3-acetic acid (IAA) is a product of tryptophan (Trp) metabolism and is found to be markedly increased in uremic sera. IAA binding to defatted human serum albumin at 37 degrees C and pH 5, 7.4, and 8.5 was studied by equilibrium dialysis, and data were analyzed assuming two independent high affinity binding sites plus a class of low affinity sites. The estimated values of the association constant of dominant site were: 7.96 x 10(3) M-1 at pH 5, 11.57 x 10(3) M-1 at pH 7.4, and 6.30 x 10(3) M-1 at pH 8.5. The competition between IAA and Trp for albumin binding at pH 7.4 was investigated. The results suggest that one specific albumin site is common for IAA and Trp, but the data were not adequately predicted by a purely competitive scheme. A better prediction was achieved assuming that the binding of IAA to a site different from the common site inhibits Trp binding.

Binding Sites↗
PubMed1997

Cell loss and the concept of potential doubling time.

The in vivo infusion of Bromodeoxyuridine (BrdUrd), followed by delayed biopsy and bivariate DNA-BrdUrd flow cytometry, allows the potential doubling time (Tpot) of human tumors to be estimated. According to Steel, the mathematical definition of Tpot is Tpot = ln 2/Kp, where Kp is the rate constant of cell production. All the operative formulas which allow the estimation of Tpot from flow cytometric data derive from this definition. Most authors, however, identify the potential doubling time as the doubling time that the same cell population would exhibit if cell loss were removed. We denote here as T(d)noloss this quantity. Although these two definitions are equivalent in the case of uniform random cell loss, we show, in the framework of Steel's theory of growing cell populations, that Tpot and T(d)noloss become distinct kinetic quantities when cell loss is not uniform, i.e., when loss differently affects the quiescent and the proliferative compartment. We discuss the validity of the two formulas currently used for the calculation of Tpot, one based on LI and the other on the v-function, in conditions of non-uniform cell loss. Moreover, we propose two formulas for the estimation of the cycle time T(C), which require, in addition to T(S) and LI, that a measure of the growth fraction be available.

Antimetabolites, Antineoplastic↗
PubMed1997

Steel's potential doubling time and its estimation in cell populations affected by nonuniform cell loss.

The in vivo infusion of the thymidine analogue bromodeoxyuridine (BrdUrd). followed by delayed biopsy and bivariate DNA-BrdUrd flow cytometry, makes it possible to estimate Steel's potential doubling time (Tpot) of human tumors. In the present paper, the expression of Steel's Tpot for a rather general cell population model, in which the distribution of cell loss is assumed to be nonuniform, is derived in terms of the model parameters. We show that Steel's Tpot of a population can be markedly different for the doubling time that would be exhibited by the population in the absence of cell loss. These doubling times, on the contrary, are equal when loss is uniform. Moreover, we studied the influence of modes of cell loss different from the uniform random loss on the estimation of Tpot by using the labeling index or the nu-function, quantities that can be determined from the bivariate DNA-BrdUrd distribution.

Bromodeoxyuridine↗
PubMed1997

Serum uremic toxins from patients with chronic renal failure displace the binding of L-tryptophan to human serum albumin.

The level of free tryptophan (Trp) and its metabolites in serum appears to be related to some pathologic states, such as chronic renal failure and neuropsychiatric disorders, so that a precise characterization of tryptophan binding to serum albumin is of interest. In the present paper, the binding of L-tryptophan to defatted human serum albumin at 37 degrees C and at pH 7.4 was studied by means of equilibrium dialysis. The competition between L-tryptophan and serum solutes extracted from uremic patients undergoing hemodialysis, before dialysis treatment, was also investigated. Solutes were extracted from uremic pools of sera using two different deproteinization methods: serum ultrafiltration and heat denaturation of serum proteins followed by ultrafiltration. We found 1.10 +/- 0.03 binding sites for Trp to defatted albumin with an association constant 11.37 +/- 1.03 x 10(3) M-1. The competition experiments suggested that the number of Trp binding sites were not significantly modified by the addition of solutes obtained with the method of ultrafiltration with respect to the binding of L-tryptophan to albumin in the absence of competitors, while their affinity constant was markedly reduced (2.66 +/- 0.18 x 10(3) M-1). Moreover, a significant reduction of the affinity constant was observed when competitors for Trp were obtained using heat deproteinization associated with ultrafiltration (1.91 +/- 0.15 x 10(3) M-1 vs. 2.66 +/- 0.18 x 10(3) M-1; P < 0.005). These results might be ascribed to the fact that the last procedure has a higher yield with a more complete liberation of uremic toxins from serum proteins, so that they became probably totally free thus competing at higher extent with L-tryptophan for albumin binding sites.

Binding Sites↗
PubMed1997

Kinetics of dodecanedioic acid and effect of its administration on glucose kinetics in rats.

Dodecanedioic acid (C12), a saturated aliphatic dicarboxylic acid with twelve C atoms, was given as an intraperitoneal bolus to male Wistar rats, with the aim of evaluating C12 suitability as an energy substrate for parenteral nutrition. The 24 h urinary excretion of C12 was 3.9% of the administered dose. C12 kinetics were investigated by a one-compartment model with saturable tissue uptake and reversible binding to plasma albumin. The analysis of plasma concentration and urinary excretion data from different animals yielded the population means of the kinetic parameters: renal clearance was 0.72 ml/min per kg body weight (BW) (much smaller than inulin clearance in the rat), and maximal tissue uptake was 17.8 mumol/min per kg BW corresponding to 123.7 J/min per kg BW. These results encourage the consideration of C12 as a possible substrate for parenteral nutrition. To investigate the effect of C12 administration on glucose kinetics, two other groups of rats, one treated with an intraperitoneal bolus of C12 and the other with saline, were subsequently given an intravenous injection of D[-U-14C]glucose in a tracer amount. Radioactivity data of both control and C12-treated rats were analysed by means of a two-compartment kinetic model which takes into account glucose recycling. The estimates of glucose pool size (2.3 mmol/kg BW) and total-body rate of disappearance (82.1 mumol/min per kg BW) in control rats agreed with published values. In C12-treated rats, the rate of disappearance appeared to be reduced to 36.7 mumol/min per kg BW and the extent of recycling appeared to be negligible.

Animal Nutritional Physiological Phenomena↗