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Biomedical subjects

A Miglietta

Publications and source records attributed to A Miglietta.

At least 19 recordsLinked to original sources
PubMed2001

Estradiol increases IRS-1 gene expression and insulin signaling in breast cancer cells.

This study demonstrates how the potentiating effects of E2 on insulin signaling in ER-positive breast cancer cells are consequent to an enhanced IRS-1 expression [corrected]. It induces an increase of both PI-3K/AKT and ERK1/2 activities. A direct action of E2 in the regulating mouse IRS-1 gene is also investigated in both Chinese hamster ovary and MCF-7 cells that are transfected with mouse IRS-1 regulatory sequences. The authors have reported, for the first time, how E2 induction of IRS-1 mRNA was correlated with a direct positive regulatory role of E2 on the IRS-1 promoter. This effect seems to be not strictly related to the cell type.

Analysis of Variance↗
PubMed2001

Cytoskeleton-interacting activity of geiparvarin, diethylstilbestrol and conjugates.

Geiparvarin, a natural compound isolated from the leaves of Geijera parviflora, inhibits the growth of various tumor cell lines with a mode of action which may be attributed to its anti-microtubular activity. Our previous findings indicated that geiparvarin is able to inhibit the in vitro polymerization of tubulin and to derange the microtubular network in fibroblasts more effectively in the presence of paclitaxel. To further explore its biological activity here we have studied the effects exerted on the other components of the cytoskeleton by geiparvarin and two derivatives obtained by conjugating the 3(2H)-furanone ring of geiparvarin with diethylstilbestrol (DES). Firstly, observations by electron microscopy confirmed anti-microtubular properties, a near-total absence of microtubules is detected when tubulin is incubated with drugs in the presence of paclitaxel, whereas microtubule formation is not inhibited by drugs when assembly is induced by guanosine 5'-triphosphate (GTP). Immunofluorescence assays demonstrated that geiparvarin and DES act in a vinblastine-like fashion, causing a marked depletion of intermediate filaments while the network of microfilaments is not affected. Both the conjugates alter the 'stress fibers' organization of actin and disrupt the vimentin pattern; generally they derange cytoskeleton more markedly than the parent compounds. The cell growth inhibiting effects of geiparvarin and derivatives are dose-dependent; they vary according to the cell line used, when compounds were administered either alone or simultaneously with paclitaxel. Unlike other anti-microtubule agents, they do not exhibit cell-cycle compartment specificity and do not influence thymidine uptake in the cell.

3T3 Cells↗
PubMed2001

Lumbar disc excision in children and adolescents.

STUDY DESIGN: The authors examined a case series of patients under the age of 18 years treated for lumbar intervertebral disc herniation. OBJECTIVES: To evaluate postoperative and long-term results of surgery in patients younger than 18 years. SUMMARY OF BACKGROUND DATA: There are only a few series, with controversial results, available on the surgical treatment of disc herniation in growing patients. METHODS: Between 1975 and 1991, a consecutive series of 129 patients 9-18 years of age (average age, 16.2 years) underwent surgery for lumbar intervertebral disc herniation. Low back pain associated with leg pain was the main clinical symptom in 106 subjects (82%), back pain in 17 (13%), and leg pain in 6 (5%). RESULTS: Short-term results were excellent or good for 123 cases (95%), with complete pain relief in 97 (75%) and moderate but incomplete relief in 26 (20%). A total of 98 (76%) long-term responses obtained at a mean follow-up of 12.4 years revealed excellent outcomes in 40% of the cases, good in 47%, and poor in 13%. Ten patients (10%) underwent reintervention after 9 years on average (2 fusions and 8 re-explorations for herniated disc). CONCLUSIONS: Results have confirmed a tendency for outcomes to deteriorate between the short-term and long-term follow-up in young patients treated by discectomy: this tendency and the rate of reintervention (10%) confirmed the need for long-term follow-up of children and adolescents treated for disc herniation.

Adolescent↗
PubMed2001

Antimicrotubular and cytotoxic activity of geiparvarin analogues, alone and in combination with paclitaxel.

Geiparvarin is an antiproliferative compound isolated from the leaves of Geijera parviflora, and may represent a new drug which targets tubulin. To better explore the potential use of this agent, we investigated the antimicrotubular and cytotoxic effects of new synthetic aromatic derivatives of geiparvarin. These drugs inhibited polymerization of microtubular protein, particularly when the assembly was induced by paclitaxel. The microtubular network organization of fibroblasts was altered more effectively by some drugs. Normal microtubule architecture completely disappeared when the cells were treated simultaneously with drugs and paclitaxel: microtubules depolymerized or were reorganized into bundles, in a similar but more disarrayed fashion than that observed after treatment with paclitaxel alone. Cytotoxicity studies showed a dose-dependent effect, whereas combined administration of drugs and paclitaxel increased cytotoxicity, more effectively in paclitaxel versus derivatives administration alone.

3T3 Cells↗
PubMed2001

[Scombroid syndrome with severe and prolonged cardiovascular involvement].

Scombroid poisoning is a form of ichthyosarcotoxism caused by eating spoiled fish, mainly of the scombroid family. Inappropriate storage of these fish can lead to the decarboxylation of histidine in the flesh to histamine by enterobacteria. The symptoms of histamine poisoning mimic those of an IgE-mediated food allergy, as well as flushing, headache, diarrhea and palpitations. However, in some cases, the scombroid poisoning can be characterized by very serious symptoms, as well as cardiovascular compromission. We describe two cases of scombroid poisoning with severe hypotension requiring continuous intravenous dopamine with resolution of symptoms only several hours later.

Adult↗
PubMed2000

Cellular uptake and cytotoxicity of solid lipid nanospheres (SLN) incorporating doxorubicin or paclitaxel.

Solid Lipid Nanospheres (SLN) are colloidal therapeutic systems proposed for several administration routes and obtained by dispersing warm microemulsions in cold water. SLN as carriers of doxorubicin and paclitaxel have been previously studied. In this study, the cellular uptake of SLN and the cytotoxicity of doxorubicin and paclitaxel incorporated into SLN were investigated on two cell-lines, human promyelocytic leukemia (HL60) and human breast carcinoma (MCF-7). Cellular uptake of SLN was determined by incorporating 6-coumarin as fluorescent marker. The cellular uptake of fluorescent SLN was clearly evidenced by fluorescence microscopy. The cytotoxicity of doxorubicin incorporated in SLN was higher compared to the conventional doxorubicin solution, even at the lower concentrations. Paclitaxel in SLN was about 100-fold more effective than free paclitaxel on MCF-7 cells, while on HL60 cells a lower sensitivity was achieved with paclitaxel in SLN. Unloaded SLN had no cytotoxic effect on HL60 and MCF-7 cells.

Antibiotics, Antineoplastic↗
PubMed2000

Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine.

BACKGROUND/AIMS: Interferon alpha provides benefit in only a limited number of patients with chronic anti-HBe-positive hepatitis B. The aim of this study was to verify the long-term efficacy of lamivudine treatment of these patients and the incidence of lamivudine-resistant hepatitis B virus mutants. METHODS: Fifteen consecutive patients with chronic anti-HBe-positive hepatitis B were treated with lamivudine 100 mg once daily for 52 weeks. Levels of alanine aminotransferase, HBV DNA, hepatitis B surface antigen, and IgM antibodies to hepatitis B core antigen were monitored during therapy and 12-month follow up. The polymerase gene was amplified by polymerase chain reaction and the region coding for YMDD amino acid motif was directly sequenced. RESULTS: Only 2/15 patients (13%) had a sustained virological and biochemical response and improved histologically. Eleven out of 15 (74%) showed inhibition of viral replication and normalization of alanine aminotransferase levels during lamivudine treatment but relapsed 1-12 months after terminating therapy. In the two remaining patients (13%), HBV DNA initially became negative but reappeared in the serum after 24 weeks, and in both patients the emergence of YMDD mutants was demonstrated. CONCLUSIONS: Our data confirm the antiviral efficacy of lamivudine in anti-HBe-positive patients, but response to a 1-year course was only transient as the majority of patients relapsed after therapy withdrawal. The lack of a sustained effect and the emergence of lamivudine-resistant mutants suggest that therapy for chronic hepatitis B should be based on a combination of several therapeutic agents.

Adult↗
PubMed2000

[Pancytopenia caused by ticlopidine treated with filgrastim. Description of a case].

Ticlopidine is an antiplatelet agent that is used to reduce the occurrence of atherothrombotic arterial events, but it can sometime cause severe haematological side-effects. We describe the case of a 79-year old woman suffering from ischaemic cardiopathy and chronic cerebral vasculopathy treated with ticlopidine, who developed a rare pancytopenia on the 26th day of ticlopidine treatment. The patient was successful treated with intravenous antibiotics and with filgrastim, with complete reversion of the pancytopenia.

Aged↗
PubMed1997

Von Willebrand factor abnormalities in IgA nephropathy.

BACKGROUND: Plasma concentration of von Willebrand factor (vWF) has been used as an index of endothelial dysfunction. Increased release of vWF from endothelial cells has been reported in several conditions, and there is also evidence that dysfunctioning endothelial cells synthesize defective molecules. In fact, unusually large vWF multimers have been described and related to the pathogenesis of some microangiopathic diseases. Abnormal levels of vWF have been reported in primary glomerulitis, but this was no referred to histological diagnosis. Furthermore, no qualitative vWF analysis was performed in these glomerulopathies. Therefore the aim of our study was to analyse quantitatively and qualitatively vWF in patients with IgA (IgAN) and non-IgA mesangial proliferative glomerulonephritis (PGN). METHODS: Fourteen IgAN patients, eight PGN patients, seven subjects with different glomerulonephritides, and 10 healthy controls formed the basis of this study. On peripheral venous blood collected in the presence of protease inhibitors, vWF parameters were investigated. vWF antigenic activity (vWF:Ag) was measured by electroimmunodiffusion. vWF subunits mobility was studied by crossed immunoelectrophoresis (CIE) and in some patients vWF multimeric analysis was performed by SDS-agarose gel electrophoresis. RESULTS: Mean vWF:Ag was significantly higher in PGN patients as compared to controls, while there was no significant difference between PGN and IgAN patients and between IgAN and controls. CIE revealed a pre-peak in 12 of 14 IgAN patients and a migration index which did not differ between controls, IgAN, and PGN subjects. No pre-peak was observed in PGN and in other glomerulonephritides. Analysis of plasma vWF multimeric pattern by SDS-agarose gel electrophoresis disclosed in four IgAN patients abnormally large vWF multimers that were not documented in PGN subjects. CONCLUSIONS: This study, by showing the presence of a pre-peak and of large vWF multimers in IgAN patients, suggests an altered postsecretory handling of the vWF in IgAN and possibly a different role of the vWF in IgAN in respect to PGN.

Adult↗
PubMed1997

Geiparvarin and derivatives in combination with taxol: effect on microtubular organization in 3T3 fibroblasts.

Geiparvarin, a natural product that exhibits antiproliferative activity, inhibits the growth of various tumour cell lines with a mechanism of action so far unknown. Our preliminary findings showed that geiparvarin and some derivatives obtained from its conjugation with diethylstilboestrol and meso-hexestrol significantly inhibit taxol-induced in vitro polymerization of both tubulin and microtubular protein. In this study we investigated the effect of geiparvarin and of the oestrogen-combined derivatives on the cellular microtubular network of fibroblasts. Geiparvarin altered the microtubular organization of fibroblasts and strengthened the derangement of the microtubular pattern in cells exposed simultaneously to taxol. However, the microtubular network remained quite well organized in fibroblasts exposed to geiparvarin and preincubated with taxol, which in this case prevented the deranging effect of the former. The antimicrotubular activity of the oestrogen-combined derivatives was more similar to that of geiparvarin than to that of the oestrogens, and often this activity was stronger than that of each reference drug alone; the cytotoxic activity examined in the same experimental conditions generally confirmed the microscopic analysis.

3T3 Cells↗
PubMed1996

Interaction of geiparvarin and related compounds with purified microtubular protein.

Geiparvarin is an antiproliferative compound whose mechanism of action has not yet been identified. We have investigated the biochemical action on purified microtubular protein, as well as on tubulin, of geiparvarin and of some derivatives resulting from its conjugation with two synthetic oestrogens, diethylstilboestrol and meso-hexoestrol, in comparison with the antimicrotubular action of the reference oestrogens. Geiparvarin and derivatives did not inhibit colchicine binding to tubulin nor did they significantly influence GTP-induced polymerization. On the contrary, they effectively counteracted the stimulating effect of taxol on microtubule formation, both in the presence and in the absence of microtubule-associated proteins. A competitive inhibition mechanism at the taxol binding site of tubulin may thus be proposed to explain the antimicrotubular action of geiparvarin.

Animals↗
PubMed1995

Antimicrotubular effect of calvatic acid and of some related compounds.

A structure-activity relationship has been established between calvatic acid and some related synthetic compounds, and their ability to inhibit GTP-induced microtubular protein polymerization in vitro. These compounds were effective in a dose- and a time-dependent manner. The most active drug was the p-chloro substituted compound, which showed its inhibitory activity without any preincubation period, which the others needed. Since if cysteine was present, polymerization was no longer affected, an involvement of titratable -SH groups of tubulin could be suggested. In contrast, taxol-induced polymerization was only slightly inhibited by these compounds, and colchicine-binding activity was not generally impaired.

Animals↗
PubMed1994

Mild balanoposthitis.

AIM: To identify and study cases of mild balanoposthitis (MBP) with penile pathology among patients observed at a dermatology clinic over an 18-month period. MATERIALS: The study included 321 patients with penile pathology. The term MBP was used to describe balanoposthitis of a localised, inflammatory nature with few, non-specific symptoms and a tendency to become chronic or recur. Two hundred and seventy had diseases clearly identifiable by clinical examination or laboratory tests; 51 cases were diagnosed as MBP and these patients had blood tests (to evaluate immune status) and microbiological examination; when these proved negative, a series of patch tests was also used. RESULTS: Of the 51 patients diagnosed as having MBP, the cause was ascertained in 34 cases (infection, mechanical trauma, contact irritation, contact allergy, etc.), whereas no specific aetiological factor was detected to explain the symptoms in the remaining 17 cases.

Adolescent↗
PubMed1993

Cytoskeletal modifications induced by 4-hydroxynonenal.

The antiproliferative action of 4-hydroxynonenal (HNE) could be related to an interaction with cytoskeletal structures. In this paper the effects exerted by HNE on microtubules and on microfilaments are examined by immunofluorescence. HNE alters cell morphology causing both the depolymerization of the microtubular structures and the dissolution of the stress-fibres. Taxol protects microtubules, preventing the depolymerizing effect of the aldehyde. The action of HNE could be attributed to its affinity for sulphydryl groups, which are essential in maintaining tubulin and actin both in the polymerized form.

3T3 Cells↗
PubMed1992

Aldehyde-induced modifications of the microtubular system in 3T3 fibroblasts.

The molecular structure of aldehydes is closely related to their antimicrotubular effect. Morphological modifications of the microtubular system in living cells after incubation with certain aldehydes are consistent with biochemical alterations detected in previous research. The microtubular arrangement was visualized by an immunofluorescence technique with antitubulin antibodies, while the content of tubulin in the cells was evaluated by a colchicine binding assay. 2-Nonenal behaved similarly to 4-hydroxynonenal, a lipid peroxidation product, disorganizing microtubular network in 3T3 fibroblasts and decreasing the amounts of tubulin able to bind labelled colchicine. Nonanal did not significantly impair the tubulin characteristics in the cells, despite the fact that it has been shown to be active on the purified microtubular system; benzaldehyde was ineffective. This would appear to explain the mechanisms of interaction of aliphatic aldehydes which might be suitable for use as antimicrotubular drugs.

3T3 Cells↗
PubMed1992

Familial idiopathic hyperphosphatasia (FIH): response to long-term treatment with pamidronate (APD).

A 5-year-old child suffering from familial idiopathic hyperphosphatasia (FIH) was treated by: (1) intravenous infusion of pamidronate (APD) (3 h) (0.75 mg/kg/day) for 5 days; and (2) oral administration of APD (8 mg/kg/day) for 1 year, in association with calcium (1 g/day) as calcium gluconate. A decrease of both serum calcium and phosphate, and a slight PTH increase were observed immediately after the IV treatment; serum alkaline phosphatase did not change, but a marked and rapid decline in the hydroxyprolinuria was observed: basal 659 +/- 207 during IV treatment 169 +/- 59 (mean +/- SD mg/24 h, P < 0.005). At the end of one year of oral APD treatment clinical and radiological findings showed a remarkable improvement. Serum calcium, phosphate and PTH returned to the initial values. Plasma alkaline phosphatase levels showed a 70% decrease: basal 1370 IU/l, 1 year 410 IU/l whereas the hydroxyprolinuria values were similar to those determined at the end of the intravenous treatment (212 +/- 13 mg/24 h), but still significantly lower than the basal levels (P < 0.01). No side-effects were observed. APD appears to be a promising treatment for patients with FIH.

Administration, Oral↗