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Biomedical subjects

F Ferrari

Publications and source records attributed to F Ferrari.

At least 253 records · Page 14Linked to original sources
PubMedDate not supplied

Progesterone agonists and antagonists induce down- and up-regulation of estrogen receptors and estrogen inducible genes in human breast cancer cell lines.

The effects of the synthetic progestin R5020 and the antiprogestin RU486 on the cellular content of estrogen receptors (ER) and on cell responsiveness to estrogens, have been investigated in the sex hormone-sensitive human breast cancer cell lines MCF-7 and T47D. When T47D cells were treated with R5020 (Promegestone) (10(-8) M), ER was down-regulated to about 50% of the control level in a time-dependent manner. Maximum down-regulation was observed after 24 hours and remained at this level for the next 24 hours. Dihydrotestosterone (DHT) or dexamethasone (DEX) had no effect on ER sites. R5020 also down-regulated, although to a lesser extent, ER in the MCF-7 cells which contain fewer progesterone receptor (PR) sites. When MCF-7 cells were transfected with a progesterone receptor expression vector (tMCF-7) to increase the number of PR sites, R5020 down-regulated the ER to a level similar to that reached in T47D cells. In both cell lines ER down-regulation was completely inhibited by a 10-fold molar excess of the antiprogestin RU486 (Mifepristone) (10(-7) M). Surprisingly, when incubated with RU486 alone, T47D cells responded by up-regulating ER 2-4 fold. The functional relevance of inhibition and up-regulation of ER for the estrogen responsiveness of hormone-sensitive human breast cancer cells was tested by assaying the synthesis of an estrogen-regulated product, the PS2 protein. Estrogen induction of this protein was inhibited by at least 70% in T47D cells exposed to R5020 for 24 hours before estrogen administration and by about 25% in MCF-7 cells under the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
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Antinociceptive properties of morusin, a prenylflavonoid isolated from Morus nigra root bark.

The antinociceptive effects of morusin (1), the main prenylflavonoid present in the Morus nigra root barks have been investigated in classical models of pain in mice. The results showed that 1 exhibits a promising antinociceptive or analgesic profile by the intraperitoneal route, being more potent than some standard drugs used as reference. The mechanism by which the morusin exerts antinociceptive activity still remains undetermined, but our results strongly suggest that it involves the participation of the opioid system.

Analgesics↗
PubMedDate not supplied

Expression of bcl-2 in oral squamous cell carcinoma: an immunohistochemical study of 90 cases with clinico-pathological correlations.

Apoptosis is a genetically determined process playing an active role in tissue size regulation, morphogenesis and removing damaged cells that could be potentially dangerous for their host. Several agents involved in apoptosis regulation, such as the bcl-2 family components, act as oncogenes and are involved in oral carcinogenesis. Aim of this study is to explore bcl-2 immunoreactivity in oral cancers and to assess its potential clinico-pathological implications. Ninety oral squamous cell carcinoma and 10 normal mucosal formalin-fixed, paraffin-embedded samples were analysed for bcl-2 expression by immunohistochemistry. Normal oral mucosa showed a cytoplasmic pattern of bcl-2 immunoreactivity in the basal cell layers. Seventy-four cases of carcinoma (83%) showed no immunoreactivity, at variance with 16 cases (17%) manifesting consistent cytoplasmic positivity. Overall, the peripheral cells of differentiating epithelial tumour islands were intensely stained, with decreasing immunoreactivity toward the centre of the neoplastic nests. Fully keratinised tumour cells showed inconspicuous or absent bcl-2 immunoreactivity. No statistically significant correlations could be demonstrated between bcl-2 immunoreactivity and the sex of the patients, tumour size and with the occurrence of lymph node metastases. Though a direct correlation was found between bcl-2 immunoreactivity and increasing tumour stage, this did not reach statistical significance. Furthermore, G1 and G3 tumours displayed higher percentages of bcl-2-positive cells in comparison with G2 neoplasms and the different distribution of bcl-2 immunoreactivity in G2 and G3 was statistically significant (p<0.05). Finally, patients with absent or low (scores 0 and 1) bcl-2 immunoreactive tumours manifested poorer overall survival rates in comparison with patients with moderate or high (scores 2 and 3) bcl-2 immunoreactive tumours but the difference was not statistically significant. In normal oral mucosa bcl-2 protein is selectively present in the basal cell layers and possibly participates in the control of the terminal keratinocytes differentiation. The study of bcl-2 immunoreactivity possibly may be useful for better characterising and predicting the prognosis of oral SCC but cooperative studies are needed to assess its applications in the clinical practice.

Aged↗
PubMedDate not supplied

Cellular kinetics and expression of bcl-2 and p53 in ductal carcinoma of the breast.

In this study, the expression of p53 (wild-type and mutated form) and bcl-2 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) of the breast was evaluated by immunohistochemistry and PCR-SSCP and correlated with cellular kinetic parameters, i.e., mitotic index (MI) and apoptotic index (AI). The results showed a significant inverse correlation between p53 and bcl-2 expression in all cases of DCIS and IDC. In the DCIS group, two subgroups with different kinetic characteristics were identified. The first group was characterized by p53 positivity, bcl-2 negativity and high values of MI and AI; the other group was characterized by p53 negativity, bcl-2 positivity and low values of MI and AI. Conversely, in IDC some cases were p53 negative, bcl-2 positive and with high values of AI and MI, other cases were p53 positive, bcl-2 negative and with low AI and MI. Molecular biological analysis showed that p53 was wild-type in DCIS, while it was in the mutated form in IDC. These results suggest that in IDC mutated p53 contributes to a change in cellular kinetics and the selection of genetically aberrant cells, thereby favouring neoplastic progression. The coexistence of bcl-2 positivity and high AI could be explained by the presence of of apoptosis that work independently of bcl-2.

Adult↗
PubMedDate not supplied

Expression of the G2-M checkpoint regulators cyclin B1 and P34CDC2 in breast cancer: a correlation with cellular kinetics.

In this study, the expression of cyclin B1 and p34cdc2 in neoplastic and non-neoplastic breast lesions was evaluated by immunohistochemistry and quantitative analysis in relation to cellular kinetic parameters such as Mitotic Index (MI), Anatelophase Index (ATI), and Apoptotic Index (AI). The percentage of cyclin B1 and p34cdc2-positive cells was significantly higher in neoplastic glands than in their normal counterparts. This finding was paralleled by significantly higher values of MI, ATI, and AI in breast cancer than in normal glands. Furthermore, two groups with different cytokinetic characteristics were identified among infiltrating ductal carcinomas by an unsupervised learning technique of cluster analysis using the percentages of cyclin B1 and p34cdc2 positive cells and the cellular kinetic parameters (MI, ATI and AI) as variables. The final clusters, groups I and II, consisted of 42 and 13 cases respectively. The first cluster (group I) was characterized by a significantly linear correlation between the percentages of cyclin B1 and p34cdc2-positive cells. On the contrary, the second cluster (group II) revealed no correlation between these two proteins and was characterized by values of p34cdc2 largely exceeding those of cyclin B1. A positive correlation between the expression of these two proteins and the cellular kinetic parameters (MI, ATI and AI) was also found in group I but not in group II. These observations suggest that a disturbed nuclear translocation of Mitosis Promoting Factor (MPF) components is present in group II cases, resulting in a defective cellular division cycle. In fact, group I cases showed lymph node metastasis more frequently than group II cases. Our results suggest that the analysis of the cell cycle "machinery" components, such as the cyclins and their dependent kinases, can identify tumors with different levels of aggressiveness.

Adult↗
PubMedDate not supplied

[Coexistence of cystic fibrosis and celiac disease. Description of a clinical case and review of the literature].

A 14-month-old female infant with chronic diarrhea, recurrent respiratory infections and stunted growth was diagnosed as celiac disease with AGA detection and a positive intestinal biopsy. A gluten-free diet was introduced with a poor response. A sweat test was positive and heterozygosis for mutation of CFTR gene (both F508 and G542X) was found, demonstrating an association in the infant between cystic fibrosis and celiac disease. Fifteen cases of such association have been previously described in literature, but only three have been genetically studied. The co-existence of cystic fibrosis and celiac disease in the same subject has to be considered till now a casual finding, but are also discussed hypothesis of a non-casual linkage, formulated by some authors.

Celiac Disease↗
PubMedDate not supplied

Rheological and mechanical properties of pharmaceutical gels. Part I: Non-medicated systems.

Non-medicated gel systems based on polymers of different chemical nature and source have been characterized for rheological as well as for gel strength properties: a synthetic product, polyacrylic acid and a natural product, scleroglucan, both known to produce true gels, and two semi-synthetic materials, sodium carboxymethylcellulose and hydroxypropylmethylcellulose, both known to originate polymeric colloidal solutions, have been chosen. In particular, the rheological analysis involved the comparison of the different polymers on the basis either of viscosity (constant rate test) or of viscoelastic measurements (oscillation test). Subsequently the possible relationships between either viscosity or viscoelastic parameters (G', G", tg delta) and the gel strength parameter have been investigated. The mechanical resistance of the pharmaceutical gels examined didn't depend on the viscosity but rather on the viscoelasticity of the systems. In particular, low tg delta values were always accompanied by high gel strength values. A rank order correlation was found between the tg delta values obtained for the various samples at different frequency values and the relevant gel strength parameter: this suggests that mechanical resistance measurements, similarly to viscoelastic ones, give information on the structural properties of the samples and therefore represent a suitable tool in the optimization of gel formulations.

Elasticity↗
PubMedDate not supplied

Rheological and mechanical properties of pharmaceutical gels. Part II: Medicated systems: relevance to hydration properties and drug release.

Aim of this work was to evaluate the influence of rheological and mechanical properties of medicated gels containing two viscosity grades of either sodium carboxymethylcellulose or polyacrylic acid on hydration properties and drug release. The two polymers were chosen since they produce different semi-solid systems: polymeric colloidal solutions in the case of sodium carboxymethylcellulose and true gels in the case of polyacrylic acid. Salicylic acid and sodium salicylate were used as model drugs for sodium carboxymethylcellulose solutions, benzoic acid and sodium benzoate were employed for polyacrylic acid gels. The relationship previously found (Part I of this study) between the viscoelastic (tg delta) and the gel strength parameters in non-medicated gelified vehicles also exists in medicated gels: the higher the tg delta, the lower the gel strength. The results obtained on isoviscous samples (either colloidal solutions or true gels), containing two viscosity grades of the same polymer, demonstrate that an increase in tg delta and the concomitant decrease in the mechanical resistance of the sample always accompany an improvement in hydration properties. The different rheo-mechanical and hydration properties entrain different release profiles only when drugs are suspended in the vehicle (i.e. in the case of the free acids here considered). In these cases, the limiting step for drug release is likely the preliminary drug dissolution, which is in turn affected by the hydration propensity of the vehicle.

Excipients↗
PubMedDate not supplied

[Serial determinations of serum oxytocinase and ultrasonic biparietal cephalometry in normal and high-risk pregnancies].

The value of sonor biparietal cephalometry and serum oxytocinase that we have obtained with weekly simultaneous determinations in 14 females with normal pregnancy and in 5 with pathological pregnancy, from 24th to 39th week, show a statical positive relation. Serum oxitocinase determination against hormonal tests of the phetoplancental function (urinary oestriol, pregnandiol, serum HCS, ecc.) give advantages: it is the easyer, faster and less espandove determination. Therefore we think that it is helpful to determin togheter serial values of sonar biparietal cephalometry and serum oxytocinase to anticipate the endouterine fetal growth retardation.

Aminopeptidases↗
PubMedDate not supplied

Scatter factor receptor (c-Met) as possible prognostic factor in patients with oral squamous cell carcinoma.

This report was performed to study the biological role of c-Met in oral tumorigenesis by analyzing its expression in relation to clinicopathological features. Seventy-three cases of oral squamous cell carcinoma and 10 of normal mucosa were analysed for c-Met expression by immunohistochemistry. Normal oral squamous epithelium showed absent or low membranous positivity in the intermediate (malpighian-spinous) layer. Fifty-seven cases (78%) of carcinoma showed immunopositivity, with a prevalently membranous positivity and scattered areas also showing a cytoplasmic localization. Sixteen cases of carcinoma (22%) showed no positivity for c-Met. Among positive tumours, well-differentiated areas showed low or absent cytoplasmic positivity, while low-differentiated areas showed both membranous and cytoplasmic positivity. There was no statistically significant correlation between c-Met expression and sex, recurrence, staging or grading. The frequency of lymph node metastases was higher in c-Met-positive tumours (17/57, 29%) than in c-Met-negative ones (4/16, 25%). When analysed for prognostic significance, patients with negative/reduced c-Met expression had better survival rates than patients with high expression. The difference between survival rates was statistically significant (p<0.05). These data suggest that c-Met expression may be useful to identify cases of oral squamous cell carcinoma with a more aggressive and invasive phenotype.

Adult↗
PubMedDate not supplied

Maxillary post-traumatic outcome correction. Literature review and personal experience. Part III: loss of maxillary substance (free flaps-distraction osteogenesis).

Revascularised free flaps retain dual vascularisation, both periosteal and medullary, undoubtedly present optimal survival and minimal re-absorption in view of the prevalence of osteogenetic rather than osteoclastic phenomena. A revascularised free bone flap involves the transfer of a certain amount of bone tissue, whether or not associated with a muscular, skin and/or facial component, with the features of an axial flap, dissecting the vascular stalk of the donor site and re-anastomosing both the arterial and the venous components on to recipient vessels in the site of the primary defect. The vessels in question measure only about 2-4 mm, so that micro-surgery techniques must be applied. For bone defects less than 6 cm, with upkeep of the mandibular or maxillary cortical bone and preservation of the soft tissues, with residual bone of at least 8 mm in height and 4 mm in thickness, alveolar distraction may represent a valid alternative to bone grafts, at the same time as ensuring an increase of the alveolar bone and intraoral soft tissues involved in the distraction process.

Humans↗
PubMedDate not supplied

[Early kidney-pancreas transplantation in type 1 diabetics prevents hemodialysis].

BACKGROUND: The life-expectancy of type 1 diabetics (T1D) on dialysis is still shorter than that of non-diabetics. Pancreas transplantation (PT) in its different modalities should be considered as a life-saving procedure. METHODS: We analyzed our referral activity of T1D to PT from 1992. Since 2002, we have created a kidney and diabetes out-patient clinic devoted to the prevention of diabetic nephropathy and to the early referral of suitable T1D to combined kidney- pancreas transplantation (KPT) and isolated pancreas (PTA). RESULTS: In the last 14 yrs, 25 T1D underwent KP in our district (620000 inhabitants). At the beginning, KPT was performed abroad, but then the borders were closed. After stopping in the mid 1990s, KP activity restarted addressing preemptive KPT and PTA. Currently, only one patient is on dialysis while awaiting KPT. Four T1D were evaluated and excluded from the list on medical grounds; two patients are on the list and a further two patients are currently under evaluation. CONCLUSIONS: The implementation of a cooperative network among dialysis and transplant centers, supported by devoted out-patient clinics allowed the effective prevention of the dialysis requirement in T1D. Out-patient clinics devoted to diabetic nephropathy should play a pro-active role in preemptive KP, including the 'new' option of islet transplantation according to the Edmonton protocol.

Diabetes Mellitus, Type 1↗
PubMedDate not supplied

[Prophylaxis of group B streptococcal infections in the birth centers of Emilia Romagna].

OBJECTIVES: In the last decade several guidelines for prevention of neonatal group B streptococcal invasive disease have been published, mainly based on administration of intrapartum antibiotics. The spread of such recommendations yielded a reduction of the early-onset disease. The aim of the study was to investigate the practices for prophylaxis of neonatal infection in our region during the 2000 and to standardize them according to the new available evidence. METHODS: We conducted a multicenter study in Emilia Romagna, sending by mail a detailed questionnaire to the 28 birth centers of our region. RESULTS: Fifteen centers answered to the questionnaire. The practices were often differing from the recommendations of scientific societies. The most sensitive methods to identify colonized women were not widely used. Colonized infants were frequently treated with antibiotics and discharged later from the nursery. The incidence of neonatal invasive diseases was low, but most centers did not regularly collect a blood culture before antibiotic treatment is started. CONCLUSIONS: Repeated meetings among centers promoted the diffusion of information, the implementation of a shared protocol and the spread of the practices. The results of such meetings will be evalued in the next months.

Birthing Centers↗
PubMedDate not supplied

Hyperphagic effect of B-HT 920 in a modified X-maze test.

The influence on rat-feeding behavior of B-HT 920 (a selective agonist of D2DA receptors at low doses, but also a potent stimulant of alpha 2-adrenoceptors at high doses) was examined using a new experimental model. The apparatus adopted was an X-maze with alternate open and covered arms, each baited with two food-pellets. Individual rats were placed in the apparatus and observed for 5 min. Two essential aspects of rat behavior in the presence of food were considered: tasting and feeding. A number of parameters were recorded: latency to tasting and feeding; interval between tasting and feeding; total feeding time. We also took into account the type of arm in which the rats indulged in their first bout of tasting and feeding. In the first series of experiments, B-HT 920 was injected intraperitoneally (0.1, 1, 2 and 3 mg/kg) into fed and fasted rats; in the second series, the drug was injected intracerebroventricularly (10, 20 and 80 micrograms/rat) into fasted rats. In both experimental conditions, the drug significantly modified the animals' feeding behavior and affected their natural preference for the closed arms as places of choice in which to feed. Comparison of the results with those obtained using norepinephrine (20 micrograms/rat, intracerebroventricularly), a well-known hyperphagic agent, shows that B-HT 920 strongly stimulates feeding. Also, the results of the intracerebroventricular experiments confirm that the effect on feeding appears at doses that are active both on alpha 2-adrenoceptors and on D2DA receptors, as can be deduced from penile erection and stretching and yawning elicited in rats by the same D2DA stimulant doses. The involvement of the latter receptors in feeding has been investigated by means of a new series of experiments with rats treated with the D2DA antagonist sulpiride, before B-HT 920 at 100 micrograms/kg. The possible mechanisms underlying B-HT 920-hyperphagic effects and the value of the X-maze feeding test as a simple procedure indicative of changes in rat feeding and emotionality are discussed in the light of these latest findings.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

[Primary transitional-cell carcinoma of the male anterior urethra].

Primary carcinomas of the male anterior urethra account for less than 1% of all urological carcinoma. The majority of these neoplasias develop of the posterior part of the urethra (proximal portion). The most common histotype is the squamous-cellular carcinoma. We have only found 4 other published reports of primary transitional carcinoma of the male anterior urethra. The paper discusses the diagnostic and therapeutic procedures employed in these rare cases.

Aged↗
PubMedDate not supplied

B-HT 920 antagonizes rat neophobia in the X-maze test: a comparative study with other drugs active on adrenergic and dopaminergic receptors.

Since there is compelling evidence to suggest a significant participation of central noradrenergic (NA) and dopaminergic (DA) pathways in the modulation of anxiety disorders, the possible tranquillizing effect of B-HT 920, considered to be a selective agonist of central DA autoreceptors at low doses, but also a stimulant of central alpha 2-receptors at high doses, was investigated by means of the X-maze test. For comparison, other drugs active on alpha-adrenoceptors and DA receptor subtypes were similarly tested. B-HT 920 at high doses (1 and 2 mg/kg) significantly antagonized the animals' spontaneous avoidance of open spaces (a sign indicative of anxiety), despite the reported sedative effects of the drug; it should be pointed out, however, that the latter were observable in our tests only at 1 mg/kg, a more pronounced sedation was the sole effect of a low dose (100 micrograms/kg) of B-HT 920. In our experimental conditions, clonidine (50 micrograms/kg) and yohimbine (5, but not 1 and 2.5 mg/kg) exerted anxiolytic and anxiogenic effects, respectively, in line with theoretical expectations and with results already published. DPI (100 and 200 micrograms/kg) (reported to be a selective agonist at DA receptors mediating neuronal inhibition and also active on alpha-adrenoceptors) and B-HT 958 (1 and 10 mg/kg) (a stimulant of DA autoreceptors but a blocker of alpha 2-adrenoceptors) were unable to modify the natural preference of rats for closed arms. Hypomotility was obtained with both doses of B-HT 958 and with the higher dose of DPI.

Adrenergic alpha-Agonists↗