Biomedical subjects

A Bianco

Publications and source records attributed to A Bianco.

At least 37 records · Page 2Linked to original sources

PubMed2001

Synthesis of a carbocyclic sialic acid analogue for the inhibition of influenza virus neuraminidase.

The influenza virus neuraminidase (NA) is essential for viral infection and offers a potential target for antiviral drug development. We prepared a carbocyclic sialic acid analogue, potentially able to inhibit NA. Its structure is an analogue of the transition-state of the reaction catalysed by NA. As starting material, quinic acid was selected owing to its ready availability and its stereochemical feature suitable for the target structure. The quinic acid was first converted in the shikimic acid; then two of the three hydroxyl functions of this product were selectively functionalised to obtain the target molecule (3R,4S,5R)-4-acetamido-3-guanidino-5-hydroxycyclohex-1-ene-1-carboxylic acid.

Acetamides↗

PubMed2001

A structural characterization of the interactions between titin Z-repeats and the alpha-actinin C-terminal domain.

Titin and alpha-actinin, two modular muscle proteins, are with actin the major components of the Z-band in vertebrate striated muscles where they serve to organize the antiparallel actin filament arrays in adjacent sarcomeres and to transmit tension between sarcomeres during activation. Interactions between titin and alpha-actinin have been mainly localized in a 45-amino acid multiple motif (Z-repeat) in the N-terminal region of titin and the C-terminal region of alpha-actinin. In this study, we provide the first quantitative characterization of alpha-actinin-Z-repeat recognition and dissect the interaction to its minimal units. Different complementary techniques, such as circular dichroism, calorimetry, and nuclear magnetic spectroscopy, were used. Two overlapping alpha-actinin constructs (Act-EF34 and Act-EF1234) containing two and four EF-hand motifs, respectively, were produced, and their folding properties were examined. Complex formation of Act-EF34 and Act-EF1234 with single- and double-Z-repeat constructs was studied. Act-EF34 was shown quantitatively to be necessary and sufficient for binding to Z-repeats, excluding the presence of additional high-affinity binding sites in the remaining part of the domain. The binding affinities of the different Z-repeats for Act-EF34 range from micromolar to millimolar values. The strongest of these interactions are comparable to those observed in troponin C-troponin I complexes. The binding affinities for Act-EF34 are maximal for Zr1 and Zr7, the two highly homologous sequences present in all muscle isoforms. No cooperative or additional contributions to the interaction were observed for Z-repeat double constructs. These findings have direct relevance for evaluating current models of Z-disk assembly.

Actinin↗

PubMed2001

Fullerene-based amino acids and peptides.

Recent advances in the chemistry of fullerene have allowed the synthesis of many classes of novel fullerene derivatives. Among these classes, fullerene-based amino acids and peptides are particularly interesting, both for structural studies and biological applications. In this review, we will discuss our own achievements in this rapidly growing field. In particular, the application of fulleroproline (Fpr) amino acids and peptides to medicinal chemistry and material science will be highlighted.

Amino Acids↗

PubMed2001

Aromatic sialic acid analogues as potential inhibitors of influenza virus neuraminidase.

The influenza virus neuraminidase (NA) is an enzyme essential for viral infection and offers a potential target for antiviral drug development. We aimed our research at the synthesis of non-carbohydrate molecules able to inhibit NA as transition-state analogues. Aromatic sialic acid analogues (compound 5 and compound 10) were synthesised in good yields starting from commercially available benzoic acids using a suitable synthetic strategy.

Antiviral Agents↗

PubMed2001

Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer. A Southern Italy Cooperative Oncology Group (SICOG) phase III trial.

OBJECTIVE: This phase III study was aimed at evaluating whether the addition of gemcitabine (G) to vinorelbine (V) could improve the survival and quality of life (QoL) of elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, aged >or=70 years, were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1200 mg/m(2) plus V 30 mg/m(2) on days 1 and 8 every 3 weeks. Survival was the main end point of the study. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned on the first 60 patients per arm. RESULTS: In May 1999, an interim analysis was performed with the survival data of the first 120 eligible patients (V(arm)=60, G+V(arm)=60). Forty-nine patients had stage IIIB disease and 71 patients stage IV disease, median potential follow-up of 14 months (range; 3-22), 93 patients had died (G+V(arm)=41, V(arm)=52). Median survival time (MST) was 29 weeks and projected 1-year survival was 30% in the G+V(arm); these values were 18 weeks and 13% in the V(arm). At multivariate Cox analysis, the risk of death in the G+V(arm) compared with V(arm) was 0.48 (95% C1=0.29-0.79; P<0.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The ORR was 22 and 15% in the G+V and V(arms), respectively. Toxicity was not irrelevant in both arms. CONCLUSIONS: G+V treatment is associated with a significantly better survival than V alone in elderly NSCLC patients. The magnitude of the difference justifies the early closure of the study. The G+V regimen is now the SICOG reference regimen in this type of patients.

Aged↗

PubMed2001

Non-alcoholic steatohepatitis induced by carbamazepine and variegate porphyria.

A 42-year-old woman presented with acute bullous skin lesions and angio-oedema that had developed 3 months after initiation of treatment with carbamazepine for epilepsy. Chromatographic analysis of urinary porphyrins was compatible with variegate porphyria. This was manifested initially by neurological symptoms that were mistaken for epilepsy and later by cutaneous symptoms also. Histological findings excluded hepatic porphyria, but revealed severe fatty changes thought to be caused by idiosyncratic metabolism of carbamazepine. While the porphyrinogenicity of carbamazepine is well known, the presence of variegate porphyria has not been reported. The toxic hepatic effects of the drug on hepatic cytochrome P-450, which is involved in haem metabolism, could have aggravated the pre-existent porphyria, provoking the onset of skin lesions.

Adult↗

PubMed2001

[Extracorporeal shock wave lithotripsy in the therapy of salivary calculi: efficacy, risks and limits. Review of the literature. Note 1].

The authors carry out a review of the international literature on an alternative methodology to surgical therapy of lithiasis of the salivary glands, indicating information, limitations and possible complications. More than fifty papers by international authors were analysed regarding their experience on the use of electro-magnetic waves in the treatment of salivary gland lithiasis. It was observed that extracorporeal lithotripsy is an alternative and valid method to surgery, considering that the complications are negligible. Considering the expectations and the relationship between cost and advantage, extracorporeal lithotripsy can be considered as first treatment with surgery as second therapeutic choice.

Equipment Design↗

PubMed2001

[Extracorporeal shock wave lithotripsy in the treatment of salivary calculi. Our experience. Note 2].

In this study the authors, making use of a non-surgical therapeutic method like extracorporeal shock wave lithotripsy, aim to show the advantages of this method compared with surgery, in the therapy of lithiasis of the salivary glands. Seven patients suffering from calculi of the salivary glands were treated. The authors obtained the best result in each patient and in 5 of these obtained the complete disappearance of sialolithiasis. The authors, considering that there is an ever higher number of requests for this treatment, put extracorporeal lithotripsy in the foreground in the therapy of sialolithiasis.

Adult↗

PubMed2001

[Indications for the surgical treatment of abdominal aortic aneurysms].

BACKGROUND: On the basis of a literature review and of personal experience, the authors analyze the main indications and the best strategy for elective surgical repair of infrarenal abdominal aortic aneurysm (AAA). METHODS: Personal experience concerning elective surgical treatment of 110 patients with infrarenal AAA, is presented. RESULTS: No operative deaths have been observed and the postoperative recovery was regular in 108 patients. Two early complications (colon ischemia) and ten late postoperative complications (5 pseudoaneurysms, 5 sexual dysfunctions) occurred. CONCLUSIONS: The main therapeutic guidelines concerning the management of AAA should follow specific indications (aneurysm dimensions and growth rates). Indications for operative repair of aneurysms obviously should be judged in relation to the presence or absence of associated risk factors or concomitant medical conditions. In most cases, aneurysm repair can be performed safely, despite associated medical risks, by careful preoperative evaluation and preparation.

Adult↗

PubMed2001

[Adrenal synchronous metastasis from non small cell lung carcinoma (NSCLC): combined surgical treatment? Case report and review of the literature].

The adrenal gland is a frequent site for metastases from non small cell lung carcinoma (NSCLC). Surgical strategy in patients with operable NSCLC with adrenal synchronous metastases is yet unclear. On the basis of a literature survey and of a personal case report, the authors analyze the main indications and the best strategy for solitary synchronous metastases in the adrenal gland from NSCLC.

Adrenal Gland Neoplasms↗

PubMed2000

Vena cava injury. A serious complication during laparoscopic right adrenalectomy.

We report our experience with a case of vena cava injury during laparoscopic right adrenalectomy. A laparoscopic right adrenalectomy was performed in a 22-year-old woman who suffered from a right surrenalian adenoma. Four trocars were used for the transperitoneal laparoscopic approach with the patient in the lateral decubitus position. After isolation of the medial margin of the gland and clipping and sectioning of the main adrenal vein, the right side of the vena cava was injured during dissection of the right upper pole, due to the use of monopolar scissors. The hemorrhage was managed immediately with the aid of fenestrated atraumatic forceps and an aspiration probe. A fifth trocar was inserted to evaluate the size of the lesion, which was then sutured laparoscopically with croised 5/0 nonresorbable stitches. No transfusion was needed. Operating time was 210 min. The post-operative course was uneventful. Hospital stay was 7 days. At 10-month follow-up, the patient had no problems related to the intraoperative complication. Our preliminary experience shows that the laparoscopic approach enables safer management of lesions involving large abdominal vessels. We believe that the transperitoneal approach is the preferential route for laparoscopic adrenalectomies. Monopolar coagulation can be dangerous and must be avoided when dissecting large vessels.

Adrenalectomy↗

PubMed2000

Solid-phase synthesis and structural characterization of highly substituted hydroxyproline-based 2,5-diketopiperazines

Two general solid-phase methods for the synthesis of a new class of 2,5-diketopiperazines (DKPs) containing the trans-4-hydroxy-L-proline amino acid residue (Hyp) have been developed. An N-protected hydroxyproline methyl ester was linked through the hydroxyl function to the Ellman resin. The synthesis procedures were conceived to enable a sequence of Hyp alkylation, Hyp N-acylation, cyclization, and amide bond alkylation. Up to three different centers of molecular diversity were introduced around the DKP scaffold. Highly functionalized bicyclic compounds were obtained in good yield and purity. The alkylation of hydroxyproline alpha CH was performed without control of the diastereoselectivity. During the final alkylation of the backbone, amide bond epimerization at the alpha-carbon atoms of the two amino acid residues was observed. The structures of representative DKPs were elucidated with multidimensional NMR experiments. The described reaction pathways can be applied to the identification of heterocyclic molecule inhibitors to diverse enzyme targets.

Journal Article↗

PubMed2000

The HB-19 pseudopeptide 5[Kpsi(CH2N)PR]-TASP inhibits attachment of T lymophocyte- and macrophage-tropic HIV to permissive cells.

The HB-19 pseudopeptide 5[Kpsi(CH2N)PR]-TASP[psi(CH2N) indicating a reduced peptide bond], which binds the cell surface-expressed nucleolin, is a potent inhibitor of HIV infection. Here, by using primary T lymphocyte cultures and an experimental cell model to monitor HIV entry, we show that HB-19 inhibits in a dose-dependent manner both T lymphocyte- and macrophage-tropic HIV isolates. Similar positively charged control pseudopeptides have no effect on HIV infection even at high concentrations. These observations, and the fact that HB-19 has no effect on SIV-mac and HIV-1 pseudotyped with VSV envelope glycoproteins, confirm the specific nature of this inhibitor against the entry process mediated by the HIV envelope glycoproteins. Finally, association of low doses of HB-19 with beta-chemokines or AZT results in an increased inhibitory effect on HIV infection. HB-19 has no inhibitory effect when added to cells a few hours after HIV entry. On the other hand, in HB-19-pretreated cells, the inhibitory effect persists for several hours, even after washing cells to remove away the unbound pseudopeptide. Under such conditions, the attachment of HIV particles to cells is inhibited as efficiently as by neutralizing monoclonal antibodies directed against the V3 loop. In view of its specific mode of action on various HIV isolates, HB-19 represents a potential anti-HIV drug.

Anti-HIV Agents↗

PubMed2000

Gastric MALT lymphomas: the value of an endoscopic follow-up evaluation.

BACKGROUND: Findings have demonstrated the close association between primary gastric B-cell lymphomas originating from mucosa-associated lymphoid tissue (MALT) and Helicobacter pylori (HP) infection, with their regression after an HP eradication therapy in up to 70% of the cases. Endoscopic-biopsy diagnosis and endoscopic ultrasound are of major importance as decisive prognostic factors and therapeutic determinants. OBJECTIVES: We report 3 years of experience and follow-up evaluation in the management of MALT lymphomas. We also describe the guidelines strategy therapy used in our institution. METHODS: Since July 1996, nine patients with a histologic diagnosis of low-grade, HP-positive MALT gastric lymphomas, have been followed up. All patients had stage IE lymphomas (according to Musshoff classification). Eradication of HP was performed with triple therapy amoxycillin, clarithromycin, and omeprazole using over a 14-day period. The patients were seen for endoscopic follow-up assessment after 3, 6, 9, and 15 months, then twice a year. The actual median follow-up time was 30.4 months (range, 16-38 months). RESULTS: All the patients are now free of disease and asymptomatic. We have registered two cases of HP relapse (both after 1-year follow-up evaluation), positively treated with the same triple therapy, and three cases of disease relapse treated with single-dose chemotherapy (plus radiotherapy in one patient). CONCLUSIONS: In our experience the eradication of HP appears to be effective, and we consider it the first therapeutic option in patients with stage IE gastric low-grade MALT lymphoma, although long-term results are still needed. Prolonged follow-up evaluation (particularly by endoscopy) is necessary (and feasible in our experience) to determine whether these remissions are long-lasting. We recommend that HP be eradicated in these lymphomas before referral to other standard treatment.

Aged↗

PubMed2000

Polymorphisms at the glutathione S-transferase, GSTP1 locus: a novel mechanism for susceptibility and development of atopic airway inflammation.

A common feature of environmental irritants is their ability to cause local inflammation which could alter airway function. The principal targets of such injury are the epithelial cells lining the airway passages and the lower respiratory gas-exchange areas. While host atopy is a recognized risk factor for airway inflammation, atopy alone cannot cause asthma. We hypothesize that susceptibility to persistent airway inflammation in atopic individuals is characterized by an inherited deficiency in the effectiveness of detoxification of inhaled irritants and products of oxidative stress such as reactive oxygen species (ROS). Our case-control studies show that polymorphisms at the glutathione S-transferase, GSTP1, locus on chromosome 11q13 may account for variation in host response to oxidative stress, a key component of airway inflammation. Frequency of the GSTP1 Val/Val genotype is reduced in atopic subjects compared with nonatopic subjects. Trend analysis also shows a significant decrease of GSTP1 Val/Val (with parallel increase of GSTP1 Ile/Ile) genotype frequency with increasing severity of airflow obstruction/bronchial hyperresponsiveness. The implication of specific polymorphisms at the GSTP1 locus in airway inflammation is entirely novel: however, GST are recognized as a supergene family of enzymes critical in 1) cell protection from the toxic products of ROS-mediated reactions, 2) modulation of eicosanoid synthesis.

Bronchial Hyperreactivity↗

PubMed2000

Respiratory infections and asthma.

Clinical and experimental evidence suggests an important role for respiratory infections in the development of asthma attacks. Viral upper respiratory infections have been associated with 80% of asthma exacerbations in children and 50% of all asthma episodes in adults. Human rhinovirus has been implicated as the principal virus associated with asthma episodes. Separate studies indicate that atypical bacteria such as Chlamydia pneumoniae and Mycoplasma pneumoniae may precipitate asthma symptoms. Although not completely clarified, the intricate pathogenetic mechanisms by which viral infections promote asthma attacks have been extensively investigated in recent years. By contrast, it has not yet been established whether atypical bacterial infections are an epiphenomenon or a pathogenic event in asthma.

Asthma↗

PubMed2000

Th1/Th2 lymphocyte polarization in asthma.

Asthma is a complex inflammatory disease of the lung characterized by variable airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Inflammation in asthma consists of airway infiltration by mast cells, lymphocytes, and eosinophils. There is accumulating evidence that CD4+ lymphocytes with a Th2-cytokine pattern play a pivotal role in the pathogenesis of asthma. These cells orchestrate the recruitment and activation of the primary effector cells of the allergic response (mast cells and eosinophils), through the release of cytokines such as IL-4, IL-5, and IL-13. Allergic inflammation is also implicated in airway epithelium changes, although the mechanisms by which inflammatory cells and, in particular, T cells interact with the epithelium are not completely clarified. This paper explores the role of T cells in the allergic inflammation of asthma.

Asthma↗

PubMed2000

The -403 G-->A promoter polymorphism in the RANTES gene is associated with atopy and asthma.

Asthma is a complex inflammatory condition often associated with bronchial hyperreactivity and atopy. Genetic and environmental factors are implicated and several candidate genes have been implicated. Of these, the chemokine RANTES is responsible for the recruitment of inflammatory cells such as eosinophils and T-lymphocytes. We have recently identified a polymorphism within the RANTES promoter (-403 G-->A) and have examined its role, using a PCR-RFLP assay, in the development of atopy and asthma in 201 Caucasian subjects. Atopic status was determined using skin prick testing and serum IgE levels. Severity of airway dysfunction was assessed using spirometric measurement (FEV1) and methacholine challenge (PC20). The -403 A allele was associated with an increased susceptibility to both atopy and asthma. Thus, the proportion of subjects carrying this allele was higher in each of atopic non-asthmatics, non-atopic asthmatics and atopic asthmatics compared with non-atopic, non-asthmatic controls. In particular, this allele was associated with skin test positivity but not IgE level. Homozygosity for the -403 A allele conferred a 6.5-fold increased risk of moderate/severe airway obstruction (FEV1 < or = 80% predicted), a marker for established asthma. Our data, whilst preliminary, indicate that the association of RANTES genotype with both atopy and asthma reflect independent effects, suggesting different mechanisms for the role of this chemokine in atopy and development of airway obstruction.

Adenine↗