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Biomedical subjects

F Paoletti

Publications and source records attributed to F Paoletti.

At least 19 recordsLinked to original sources
PubMed2005

WEB-2086 and WEB-2170 trigger apoptosis in both ATRA-sensitive and -resistant promyelocytic leukemia cells and greatly enhance ATRA differentiation potential.

PAF-receptor antagonists WEB-2086 and WEB-2170 (WEBs) have been previously shown to induce differentiation in murine and human leukemia cells. The present study describes the apoptotic-differentiative effect of WEBs in all-trans-retinoic acid (ATRA)-sensitive (NB4) and -resistant (NB4-007-6 and NB4-MR4) acute promyelocytic leukemia (APL) cell lines as well as blasts from patients with t(15;17) APL. NB4 cells exposed to 0.5-1 mM WEBs underwent striking growth arrest and massive apoptosis without appreciable differentiation; IC50 values after 3-day treatment of NB4 were 0.4 and 0.25 mM for WEB-2086 and WEB-2170, respectively. WEBs induced apoptosis also in the two ATRA-resistant NB4-007-6 and NB4-MR4 cell lines and in blasts from patients with t(15;17) APL. Moreover, subapoptotic WEBs acted synergistically with low-dose (0.025-0.05 microM) ATRA; this allowed to increase ATRA differentiation potential up to 40-fold and to improve both number and intensity of NBT-positive NB4 cells at definitely higher levels than with 1 muM ATRA alone. The powerful antiproliferative-apoptotic activities of WEBs in vitro on ATRA-sensitive, ATRA-resistant APL cells and blasts from patients with APL as well as drug capabilities to enhance ATRA differentiation potential suggested that these agents also due to their recognized tolerability in vivo might improve, alone or in combination, clinical treatment of APL.

Antineoplastic Agents↗
PubMed2005

Central venous catheters. Observations on the implantation technique and its complications.

The growing utilization of central venous catheterism is linked to the necessity of treating with an always larger number of hospitalized and nonhospitalized patients. The technological development provided us with different devices and materials for specific indications. In the majority of cases the central venous catheter is positioned through direct puncture of a central vein using Seldinger method. The vessels used for the catheterism are: the internal jugular vein, the subclavian vein and femoral vein. The choice of the vein to use is influenced by the operator's experience and by factors depending on the patient. The internal jugular vein via posterior or median and the subclavian vein via subclavicular are the most used sites in the central venous catheterism. However, also the femoral vein can be considered a resource when the clinical conditions of the patient render problematic the positioning in the above mentioned sites. The positioning into the internal jugular vein is generally burdened with a very low risk of pneumothorax and other potentially dangerous complications for the patient. The femoral vein is generally burdened with a larger incidence of thrombosis and infections. The subclavian vein, even if it is the most used, is burdened with a larger incidence of immediate or retarded pneumothorax and accidental venous puncture. The most frequent immediate complications for catheterism are the arterial puncture, pneumothorax, arrhythmias and the wrong positioning. Among the late complications there are the catheter infections correlated, catheter and vessel thrombosis. The use of a proper technique, completed by the operator's experience and the right management of the device, lead to a decrease of the risk level related to the central venous catheterism.

Catheterization, Central Venous↗
PubMed2004

Modeling of a lower-hybrid current drive by including spectral broadening induced by parametric instability in tokamak plasmas.

By incorporating parametric instabilities of lower hybrid (LH) waves into a ray-tracing Fokker-Planck code, accurate simulations of the LH deposition profiles are provided, which are useful for interpreting the long-lasting internal transport barriers (ITBs) sustained by lower hybrid current drive (LHCD) on JET (Joint European Torus). Utilizing the new model, the simulation of the q-profile evolution results in agreement with that provided by the motional Stark effect reconstructed equilibria. Low magnetic shear (s approximately equal to 0) is produced by LHCD in a layer close to the ITB radial foot.

Journal Article↗
PubMed2004

Increased plasma levels of soluble CD40, together with the decrease of TGF beta 1, as possible differential markers of Alzheimer disease.

Alzheimer's disease (AD) is a progressive neurodegenerative illness and the most frequent cause of dementia in the elderly. The identification of activated microglia within neuritic plaques, coupled with the presence of numerous inflammatory proteins, suggests that inflammation is an integral part of the pathogenetic process in AD. In the present paper we have investigated the levels of circulating inflammatory mediators as potential AD biomarkers concentrating essentially on (a) soluble CD40 (sCD40), a member of the tumor necrosis factor receptor superfamily lacking the membrane-associated endodomain by alternative splicing, and (b) transforming growth factor (TGF)-beta 1, a cytokine deeply involved in AD and playing a protective role on CNS. Decrease of TGF-beta1 in AD patients could enhance the effects of pro-inflammatory cytokines produced by activated microglia as well as the expression of factors, such as the CD40/CD40 ligand complex, by microglia and astrocytes. Total venous blood samples were obtained from 33 patients with clinical diagnosis of possible late-onset AD, 40 healthy age-matched and 11 healthy young individuals. A significant increase of sCD40 levels plasma of AD patients versus healthy controls was measured, concomitantly with a decrease in TGF-beta1 concentration. These variations, however, showed no correlation with the expression of ApoE epsilon 4 allele, which was determined in order to assess the different frequency of this risk factor between AD and control groups. Since no comparable modifications were detected in patients affected by Parkinson's disease or non-AD-based dementia, we propose that sCD40 and TGF-beta1 plasma levels might represent possible differential biomarkers of AD, and be useful pre-mortem to support the clinical diagnosis of late-onset AD.

Adult↗
PubMed2004

Use of polylactic acid in face lipodystrophy in HIV positive patients undergoing treatment with antiretroviral drugs (HAART).

OBJECTIVES: The recent use of antiretroviral drugs in people with HIV infection produced a drastic reduction in mortality and a remarkable improvement in the quality of life for these patients. However the aesthetic and psychological consequences that come from the reorganization of the adipose tissue induced by these drugs (facial wasting, buffalo hump) may reduce this state of wellbeing. METHODS: Our group, in cooperation with the 3rd Division of Infective Diseases of the University of Rome "La Sapienza", decided to evaluate the efficacy of polylactic acid (PLA) in combating these problems in HIV positive patients undergoing treatment with antiretroviral drugs in an evaluating study of 4 cases. The evaluation of the obtained results was performed by follow-up at one, three, six and twelve months from the first infiltration and considering the clinical evaluation, the photographical documentation and the patient's judgement. RESULTS: In all cases we obtained an improvement of the local condition with the restoration of a more booming aspect. The change was noted both within the family and the work environment. In the first three cases the results were considered as optimal by both the operators and the patients. In the fourth case the result was evaluated as discreet (a remarkable loss of weight of the patient in the months following the treatment should be taken into consideration). CONCLUSIONS: We think a new study with ultrasonography of dermal thickness before, during and after the treatment is necesary. This study will give a more reliable evaluation of the product efficacy.

Adult↗
PubMed2002

Characteristics of the first H-mode discharges in the national spherical torus experiment.

We report observations of the first low-to-high ( L-H) confinement mode transitions in the National Spherical Torus Experiment. The H-mode energy confinement time increased over reference discharges transiently by 100-200%, as high as approximately 100 ms. This confinement time is approximately 2 times higher than predicted by a multimachine scaling. Thus the confinement time of spherical tori has been extended to a record high value, leading to an eventual revision of confinement scalings. Finally, the power threshold for H-mode access is >10x higher than predicted by an international scaling from conventional aspect-ratio tokamaks, which could lead to new understanding of H-mode transition dynamics.

Journal Article↗
PubMed2002

Adherence to HIV treatment: results from a 1-year follow-up study.

We evaluated adherence to HIV treatments every 4 months during one year in 63 HIV-infected subjects using combination therapies including a protease inhibitor. A total of 18 subjects reported a high level of adherence, 14 in two evaluations, and eight a low level of adherence in all the three evaluations. The remaining 23 subjects (36.5%) reported different levels of adherence to treatment in the three evaluations. These findings suggest that the level of adherence to treatment changes markedly for each patient over time.

Adolescent↗
PubMed2002

New antidepressants in the treatment of neuropathic pain. A review.

Before 1980s, tricyclics (TCAs) were considered, between antidepressants, the standard in the treatment of different kinds of neuropathic pain, for their action on noradrenergic and serotoninergic pathways, thought the high incidence of side effects. In 1980s a new class of antidepressants has been introduced, the selective serotonin reuptake inhibitors (SSRI). We reviewed some publications, including trials comparing SSRIs with TCAs in pain management. The available literature did not show an effective superiority of the former on the latter, though improved side-effect profile. Recently new antidepressants were introduced in the clinical use, with a significant reduction in side effects and equivalent efficacy on mood disorders. These new drugs may be classified in three categories: Serotonin and Noradrenergic Reuptake Inhibitors (SNaRI), like venlafaxine and nefazodone; Noradrenergic and Specific Serotoninergic Antidepressants (NaSSA), like mirtazapine, and Noradrenaline Reuptake Inhibitors (NaRI), like reboxetine. In this review we present the available publications of their application in the treatment of neuropathic pain. Venlafaxine (SNaRI), the most investigated of these new drugs, was shown to be effective in the treatment of different kinds of pain, with side-effects profile significantly better than TCAs. The other new antidepressants have been less extensively studied, thus only anecdotal therapeutic results and experimental works have been found and reported. Existing data are surely insufficient to conclude which of these new classes of drugs has the best clinical profile and can be more effective in the treatment of neuropathic pain, but the lower incidence of side effects should be considered. Further evidence-based research in the safety and efficacy of these promising agents in pain relief, is warranted.

Analgesics, Non-Narcotic↗
PubMed2002

Skin diseases as extrahepatic manifestations of HCV. Review of some clinical cases.

Among extra-hepatic manifestations of hepatitis C virus (HCV) infection particular interest is focused on some dermatological diseases such as: leukocytoclastic vasculitis, oral lichen planus, pruritus-urticaria, psoriasis. Aim of this paper is to analyze these typical dermatoses in a population of patients with HCV infection and describe the characteristic clinical pictures. These clinical pictures confirm the importance of liver examination in presence of skin diseases not related to other pathogenetic mechanisms.

Journal Article↗
PubMed2001

Accentuated response to phenylhydrazine and erythropoietin in mice genetically impaired for their GATA-1 expression (GATA-1(low) mice).

The response of mice genetically unable to up-regulate GATA-1 expression (GATA-1(low) mice) to acute (phenylhydrazine [PHZ]-induced anemia) and chronic (in vivo treatment for 5 days with 10 U erythropoietin [EPO] per mouse) erythroid stimuli was investigated. Adult GATA-1(low) mice are profoundly thrombocytopenic (platelet counts [x 10(9)/L] 82.0 +/- 28.0 vs 840 +/- 170.0 of their control littermates, P <.001) but have a normal hematocrit (Hct) (approximately.47 proportion of 1.0 [47%]). The spleens of these mutants are 2.5-fold larger than normal and contain 5-fold more megakaryocytic (4A5(+)), erythroid (TER-119(+)), and bipotent (erythroid/megakaryocytic, TER-119(+)/4A5(+)) precursor cells. Both the marrow and the spleen of these animals contain higher frequencies of burst-forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E)-derived colonies (2-fold and 6-fold, respectively) than their normal littermates. The GATA-1(low) mice recover 2 days faster from the PHZ-induced anemia than their normal littermates (P <.01). In response to EPO, the Hct of the GATA-1(low) mice raised to.68 proportion of 1.0 (68%) vs the.55 proportion of 1.0 (55%) reached by the controls (P <.01). Both the GATA-1(low) and the normal mice respond to PHZ and EPO with similar (2- to 3-fold) increases in size and cellularity of the spleen (increases are limited mostly to cells, both progenitor and precursor, of the erythroid lineage). However, in spite of the similar relative cellular increases, the increases of all these cell populations are significantly higher, in absolute cell numbers, in the mutant than in the wild-type mice. In conclusion, the GATA-1(low) mutation increases the magnitude of the response to erythroid stimuli as a consequence of the expansion of the erythroid progenitor cells in their spleen.

Anemia↗
PubMed2001

A cystatin-based affinity procedure for the isolation and analysis of papain-like cysteine proteinases from tissue extracts.

Cysteine-proteinases (CP) of the papain family can be affinity-adsorbed by egg white cystatin C coupled to Sepharose 4B, thus allowing their selective isolation from either tissue or cultured cell extracts as well as biolological fluids and culture media. CP complexed by immobilized cystatin are further analyzed by means of SDS-PAGE and Western blot followed by serial or parallel immunological detection. The single-step affinity adsorption of papain-like enzymes has the advantage, over immunoprecipitation techniques, of yielding the simultaneous and comprehensive picture of most CP, as both precursor and mature forms, in a given sample. Moreover, cell extraction in the presence of immobilized cystatin ensures a fast complexation of CP, avoiding artifacts, due to conversion, degradation, and, eventually, subtraction of constitutive enzymes from the sample because of their interactions with endogenous inhibitors. This will provide a pattern that might reflect more closely the real CP levels in intact cells. The method may be useful in the field of biochemistry, cell biology, and, possibly, clinical chemistry to perform rapid analyses of papain-like enzymes and to monitor changes in both cellular and extracellular CP profiles along with different physiopathological conditions.

Adsorption↗
PubMed2001

Reduced growth and skeletal changes in zinc-deficient growing rats are due to impaired growth plate activity and inanition.

We investigated the effects of dietary zinc deficiency on skeletal metabolism in an animal model. Thirty 21-d-old male Sprague-Dawley rats were fed for 28 d either a zinc-deficient (ZD) diet (1 mg zinc/kg) or a normal diet ad libitum (AL, 50 mg zinc/kg) or in the same quantity as the ZD (pair-fed, PF). Only in the ZD group were general physical signs of zinc deficiency observed. Compared with the AL and PF rats, ZD rats showed significantly lower mean values in ponderal growth rate, femur weight and length, circulating levels of insulin-like growth factor-I, bone mechanical properties and concentration of zinc and, on histomorphometry, a decrease in the thicknesses of the overall growth plate and hypertrophic cartilage. In contrast, although bone volume was significantly lower in the ZD and PF rats than in the AL rats, no difference was observed between the ZD and PF rats. Osteoclast surface/bone surface and osteoclast number/bone surface ratios were significantly greater in PF rats than in the other two groups and not different in ZD and AL rats. Collectively, these data indicate that zinc deficiency has profound effects on the skeletal system of growing rats. In particular, the effects of zinc deficiency on bone growth and mass are the result of the reduced activity of the growth plate, likely mediated by impairment in the insulin-like growth factor-I system. We did not demonstrate an effect on bone mass via increased bone resorption.

Animals↗
PubMed2000

Identification and characterization of a bipotent (erythroid and megakaryocytic) cell precursor from the spleen of phenylhydrazine-treated mice.

We have identified a cell population expressing erythroid (TER-119) and megakaryocyte (4A5) markers in the bone marrow of normal mice. This population is present at high frequency in the marrows and in the spleens involved in the erythroid expansion that occurs in mice recovering from phenylhydrazine (PHZ)-induced hemolytic anemia. TER-119(+)/4A5(+) cells were isolated from the spleen of PHZ-treated animals and were found to be blast-like benzidine-negative cells that generate erythroid and megakaryocytic cells within 24-48 hours of culture in the presence of erythropoietin (EPO) or thrombopoietin (TPO). TER-119(+)/4A5(+) cells represent a late bipotent erythroid and megakaryocytic cell precursors that may exert an important role in the recovery from PHZ-induced anemia. (Blood. 2000;95:2559-2568)

Animals↗
PubMed2000

Combined effect of sourdough lactic acid bacteria and additives on bread firmness and staling.

The effect of various sourdoughs and additives on bread firmness and staling was studied. Compared to the bread produced with Saccharomyces cerevisiae 141, the chemical acidification of dough fermented by S. cerevisiae 141 or the use of sourdoughs increased the volume of the breads. Only sourdough fermentation was effective in delaying starch retrogradation. The effect depended on the level of acidification and on the lactic acid bacteria strain. The effect of sourdough made of S. cerevisiae 141-Lactobacillus sanfranciscensis 57-Lactobacillus plantarum 13 was improved when fungal alpha-amylase or amylolytic strains such as L. amylovorus CNBL1008 or engineered L. sanfranciscensis CB1 Amy were added. When pentosans or pentosans, endoxylanase enzyme, and L. hilgardii S32 were added to the same sourdough, a greater delay of the bread firmness and staling was found. When pentosans were in part hydrolyzed by the endoxylanase enzyme, the bread also had the highest titratable acidity, due to the fermentation of pentoses by L. hilgardii S32. The addition of the bacterial protease to the sourdough increased the bread firmness and staling.

Bread↗