Biomedical subjects

C De Lorenzo

Publications and source records attributed to C De Lorenzo.

At least 19 recordsLinked to original sources

PubMed2005

Advanced strategies of short-term prophylaxis in menstrual migraine: state of the art and prospects.

Patients suffering from menstrual migraine (MM) may be ideal candidates for an intermittent prophylaxis, usually termed short-term or mini-prophylaxis. It covers the whole period of vulnerability, e. g., the perimenstrual period, starting some days before the expected onset of MM attack. Theoretically MM attacks are an optimal target for drugs specifically developed for acute head pain. Unfortunately, due to their particular tendency to be longer, more intense and less responsive to analgesics, symptomatic approaches alone are not often able to completely control pain and its correlates. Many drugs have been proposed for short-term prophylaxis of MM. In this paper we analyse only non-steroidal anti-inflammatory drugs, coxibs and triptans (especially those with longer half-life, naratriptan and frovatriptan). Moreover, MM can be prevented by a variety of hormonal manipulations, including oral contraceptives, which may be administered with an extended-dosing strategy; oestrogen replacement therapy; antioestrogen agents (danazol, tamoxifen); gonadotropin-releasing hormone agonists followed by oestrogen add-back therapy. Finally, the use of some products, such as magnesium and phytoestrogens, that probably meet the requirements of those patients that appreciate a more "natural" approach, is discussed.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent.

A new human, compact antibody was engineered by fusion of a human, antitumour ErbB2-directed scFv with a human IgG1 Fc domain. Overexpression of the ErbB2 receptor is related to tumour aggressiveness and poor prognosis. This new immunoagent meets all criteria for a potential anticancer drug: it is human, hence poorly or not immunogenic; it binds selectively and with high affinity to target cells, on which it exerts an effective and selective antiproliferative action, including both antibody-dependent and complement-dependent cytotoxicity; it effectively inhibits tumour growth in vivo. Its compact molecular size should provide for an efficient tissue penetration, yet suitable to a prolonged serum half-life.

Animals↗

PubMed2004

SPME analysis of volatile compounds from unfermented olives subjected to thermal treatment.

The effect of different types of thermal treatment, designed to increase the product's shelf-life, on the volatile composition of "Campo Real" unfermented table olives, has been studied by headspace solid-phase microextraction (HS-SPME) and GC-MS analysis. Different SPME fibres were evaluated to determine their selectivity for a mixture of the main components of the different spices used in "Campo Real" olive dressing. Of the different fibres investigated, the polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibre was selected for analysis of the olive brines, which contained nine main aroma components. The types of thermal treatment were sterilisation (121 degrees C, 15 min) and four pasteurisation conditions (60 degrees C or 80 degrees C each for 5 or 9 min). Pasteurisation did not lead to significant changes in the amounts of these nine volatile compounds; the 2-butanol signal was reduced by treatment at 80 degrees C. On the other hand, sterilisation of the brine resulted in an decrease in the signals from these compounds and the appearance of a new, high signal for benzaldehyde; the origin of this has not yet been determined. Results suggest that the selected pasteurisation conditions do not significantly modify the typical, and valued, aroma characteristics of "Campo Real".

Benzenesulfonates↗

PubMed2004

Oral contraceptives in women with migraine: balancing risks and benefits.

Oral contraceptives (OCs) are a safe and highly effective method of birth control, but can also be associated with some risks, mainly a potential thrombotic risk. OCs may condition the course of headache and sometimes start it, but their influence on the clinical evolution of migraine is not easily assessable. The last Classification of Headache Disorders of the International Headache Society clearly identifies an "exogenous hormone-induced headache" that could be triggered by intake of OCs. Old high-dose OCs could effectively worsen headache in a significant proportion of patients, but the newest formulations influence headache course to a lesser extent. In any case, while an increase in migraine frequency or intensity do not oblige the cessation of OCs, experiencing a migraine aura for the first time, or even a clear worsening of a preexistent aura suggest discontinuation of OCs. Even if both migraine and OCs intake are associated with an increased risk of ischaemic stroke, migraine per se is not a contraindication for OCs use; however, patients suffering from migraine with aura generally show a greater thrombotic risk than women with migraine without aura. Other risk factors (patient's age, tobacco use, hypertension, hyperlipidaemia, obesity and diabetes) must be carefully considered when prescribing OCs in migraine patients. Furthermore, all OCs, even those with low oestrogen content, are a major risk for venous thrombosis, particularly in women with hereditary thrombophilia. A thorough laboratory control of the genetics of prothrombotic factors and coagulative parameters should precede any decision of OCs prescription in migraine patients.

Contraceptives, Oral, Hormonal↗

PubMed2004

Picotamide in migraine aura prevention: a pilot study.

In an open, preliminary trial we evaluated the use of picotamide, an antiplatelet drug, in the prophylactic treatment of migraine aura (MA). Twenty-two women suffering from migraine with typical aura or MA without headache, diagnosed according to International Headache Society criteria, entered a nine-month study. They underwent a three-month run-in period free of prophylactic drugs, followed by a six-month treatment period (subdivided in two trimesters, TI and TII) with 300 mg of picotamide administered twice daily. A detailed diary reporting neurological symptoms, duration and frequency of MA was compiled by patients along the trial time. The number of MA significantly decreased during treatment (from 6.85+/-3.82 in the run-in trimester to 2.85+/-2.72 during TI and to 2.55+/-2.89 during TII). Also, MA duration was decreased significantly, being 36.75+/-20.28 min during run-in, 20.00+/-16.94 during TI and 17.75+/-16.26 during TII. In 25% of patients MA totally disappeared. The number and the features of aura neurological symptoms were also positively modified by the use of picotamide. No serious adverse event was provoked by picotamide administration. Picotamide is effective in reducing MA frequency, duration and symptomatology. The effect is clearly evident in the first trimester of treatment and is maintained with no further modifications during the second trimester.

Adolescent↗

PubMed2004

[Low-dose spiral CT of the lung in the follow-up of non-malignant lung disease].

PURPOSE: To assess image quality of chest CT with an 80 to 90 percent dose reduction in follow-up studies of patients with lung disease, dose and image quality of a low-dose protocol was investigated. MATERIALS AND METHODS: A follow-up low-dose CT (ND-CT, 120 kV, 10 mAs/slice, 3 mm slice thickness) was performed on 35 patients with non-malignant lung disease and compared with the initial standard dose CT (= SD-CT, 100 mAs/slice, 3 or 5 mm slice thickness). The dose was measured by thermo-luminescence in an Alderson phantom. Image quality was assessed by four independent radiologists in six perihilar, central and peripheral lung regions using a 4-point-scale ("very good", "good", "moderate", and "poor"). RESULTS: Effective dose was 0.5 mSv for ND-CT and 4.0 - 5.0 mSv for SD-CT. The ratings "very good"/"good" were given in the perihilar regions in ND-CT 97.5 % versus SD-CT 99.3 % (n. s.), in the central regions in ND-CT 96.4 % versus SD-CT 94.6 % (n. s.), and in the peripheral regions in ND-CT 70.0 % versus SD-CT 88.2 % (p < 0.01). CONCLUSION: Follow-up CT of pulmonary structures in patients with chronic lung disease can be performed with substantial dose reduction. A decrease of image quality may result in peripheral lung regions.

Adolescent↗

PubMed2003

Crystal structure of the dimeric unswapped form of bovine seminal ribonuclease.

Bovine seminal ribonuclease is a unique case of protein dimorphism, since it exists in two dimeric forms, with different biological and kinetic behavior, which interconvert into one another through three-dimensional swapping. Here we report the crystal structure, at 2.2 A resolution, of the unswapped form of bovine seminal ribonuclease. Besides completing the structural definition of bovine seminal ribonuclease conformational dimorphism, this study provides the structural basis to explain the dependence of the enzyme cooperative effects on its swapping state.

Animals↗

PubMed2003

Non-pharmacological approaches to chronic headaches: transcutaneous electrical nerve stimulation, lasertherapy and acupuncture in transformed migraine treatment.

In an open, randomized trial, we evaluated transcutaneous electrical nerve stimulation (TENS), infrared lasertherapy and acupuncture in the treatment of transformed migraine, over a 4-month period free of prophylactic drugs. Sixty women suffering from transformed migraine were assigned, after a one month run-in period, to three different treatments: TENS (Group T; n=20), infrared lasertherapy (Group L; n=20) or acupuncture (Group A; n=20). In each group the patients underwent ten sessions of treatment and monthly control visits. In Group T patients were treated for two weeks (5 days/week) simultaneously with three TENS units with different stimulation parameters (I: pulse rate = 80 Hz, pulse width = 120 micros; II: 120 Hz, 90 micros; III: 4 Hz, 200 micros). In Group L an infrared diode laser (27 mW, 904 nm) was applied every other day on tender scalp spots. In Group A acupuncture was carried out twice a week in the first two weeks and weekly in the next 6 weeks. A basic formula (LR3, SP6, LI4, GB20, GV20 and Ex-HN5) was always employed; additional points were selected according to each patient's symptomatology. The number of days with headache per month significantly decreased during treatment in all groups. The response in the groups differed over time, probably due to the different timing of applications of the three methods. TENS, lasertherapy and acupuncture proved to be effective in reducing the frequency of headache attacks. Acupuncture showed the best effectiveness over time.

Acupuncture Therapy↗

PubMed2003

[Migraine during pregnancy and lactation: treatment of the acute attack and non-pharmacological prophylactic strategies].

Migraine is a typical "women's disease": the fluctuations of sex hormones, in particular estrogens, during woman's reproductive life show a direct and major influence on migraine course. Even if during pregnancy a high percentage of migraineurs report an improvement of symptomatology, it is still controversial how to manage migraine crises occurring during pregnancy, considering that almost all drugs are partially or totally contraindicated during gestation. The most important drugs employed in acute attack management (triptans, non steroidal anti-inflammatory drugs, analgesics, antiemetics, ergot derivatives and combination products) are reviewed and the indications and contraindications of their use during the 3 trimesters of pregnancy and during lactation, taking into consideration the indications of the Food and Drug Administration and of the American Academy of Pediatrics, are analysed. Furthermore, the therapeutic effects of the 2 most important non pharmacological therapies used for migraine prophylaxis, biofeedback and acupuncture, are discussed. For this latter therapy, the personal preliminary positive experience using a predetermined formula of acupoints for the combined treatment of migraine and hyperemesis gravidarum is reported.

Abnormalities, Drug-Induced↗

PubMed2001

The RFG oligomerization domain mediates kinase activation and re-localization of the RET/PTC3 oncoprotein to the plasma membrane.

The RET/PTC3 oncogene arises from the fusion between the N-terminal encoding domain of the RFG gene and the tyrosine kinase encoding domain of RET receptor. RET/PTC3 is very frequent in papillary thyroid carcinomas, especially in children exposed to the Chernobyl accident. We have studied the functional consequences of the RFG-RET fusion. Here we show that the N-terminal coiled-coil domain of RGF mediates oligomerization and activation of the kinase and of the transforming capability of RET/PTC3. In addition, the RFG coiled-coil domain mediates a physical association between RET/PTC3 and RGF proteins, rendering RFG a bona fide substrate of RET/PTC3 kinase. Finally, we show that the coiled-coil domain of RGF is essential for the distribution of the RET/PTC3 protein at the membrane/particulate cell compartment level, where also most of the RFG protein is localized. We propose that fusion to the RFG coiled-coil domain provides RET kinase with a scaffold that mediates oligomerization and re-localization of the RET/PTC3 protein, a process that may be crucial for the signalling of this specific RET/PTC variant.

3T3 Cells↗

PubMed2000

Thermodynamic stability of the two isoforms of bovine seminal ribonuclease.

Bovine seminal ribonuclease (BS-RNase) is a dimeric protein with two identical subunits linked by two disulfide bridges, each subunit showing 80% of sequence identity with pancreatic RNase A. BS-RNase exists in two different quaternary conformations in solution: the MxM form, in which each subunit exchanges its alpha-helical N-terminal segment with its partner, and the M=M form with no exchange. By differential scanning microcalorimetry (DSC), the denaturation of the two dimeric forms of BS-RNase was found to be more complex than a simple two-state process. Monomeric derivatives of the dimeric protein follow instead a simple two-state mechanism, but are distinctly less stable than RNase A. The three-state N if I if D denaturation process of the two quaternary isoforms was interpreted by identifying in the dimers a central highly structured core, enclosing the covalently bonded subunit interface, which unfolds only after the periphery (mainly the N-terminal peptide) unfolds. Circular dichroism spectra of the two forms in the far-ultraviolet region show large differences between the secondary structure of the isoforms and that of the native BS-RNase mixture at equilibrium. This has been attributed to the presence in the equilibrium mixture of intermediate forms with displaced and disordered N-terminal alpha-helical segments.

Animals↗

PubMed2000

Trypsin sheds light on the singular case of seminal RNase, a dimer with two quaternary conformations.

Dimeric seminal RNase presents the singular case of a dimer with access at equilibrium to two conformations: one in which the subunits exchange, or swap, their NH(2)-terminal arms; the other with no exchange. Thus a continuous unfolding/refolding of structural elements into two alternative conformations takes place in the native protein at equilibrium. The phenomenon was investigated by kinetic and mass spectrometric analyses of the effects of trypsin on the native protein, on its isolated quaternary forms, as well as on a monomeric derivative of the protein and on homologous dimeric RNase A. The kinetics of tryptic action on the protein forms and on the protein derivatives, as well as the location of the tryptic cleavage sites, and their chronological sequence, led to the identification of relevant interconversion intermediates, to the description of a model for the interconversion process, and to a hypothesis for the unique phenomenon of the dual quaternary conformation of seminal RNase.

Animals↗

PubMed2000

Access to databases in complementary medicine.

Access to medical databases is a keystone for obtaining up-to-date and complete information for physicians. In the last few years, the rapid growth of the World Wide Web has given rise to an information revolution, enabling health care providers to gain access (often free) to an expanding volume of information that was previously inaccessible. Search engines and online databases assist the search for health information. In this article we examine the biomedical databases of primary interest in the field of alternative and complementary medicine, dividing them into Web accessible and nonaccessible databases and emphasizing the freely available ones. A further classification is major biomedical bibliographic databases specific to complementary medicine, and dedicated therapy or modality-specific databases.

Complementary Therapies↗

PubMed1999

A dimeric mutant of human pancreatic ribonuclease with selective cytotoxicity toward malignant cells.

Monomeric human pancreatic RNase, devoid of any biological activity other than its RNA degrading ability, was engineered into a dimeric protein with a cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on mouse and human normal cells. This dimeric variant of human pancreas RNase selectively sensitizes to apoptotic death cells derived from a human thyroid tumor. Because of its selectivity for tumor cells, and because of its human origin, this protein represents a potentially very attractive, novel tool for anticancer therapy.

3T3 Cells↗

PubMed1999

What is Drosophila telling us about cancer?

In Drosophila, genetic loss of the tumour suppressor protein Dlg (in dlg mutants) or p127 (in lgl mutants) leads to loss of epithelial structure and excess proliferation in the imaginal discs and brain of the developing larva. These phenotypes show most of the characteristic features of human neoplasia, so study of the gene products may contribute to our understanding of cancer. Both proteins occur in high molecular-mass complexes in the membrane-associated cytoskeleton, and they both appear to play dual roles as structural proteins and active partners in signal transduction. Dlg is a membrane-associated guanylate kinase homolog (MAGUK) found at septate junctions between epithelial cells, as well as at neuromuscular junctions. Specific domains of the protein are required for membrane targeting and for localisation injunctions, and for epithelial cell proliferation control; all of these functions are probably mediated through binding to other proteins. Loss of Dlg results in the absence of septate junctions, delocalisation of several proteins including Fasciclin III, Coracle, actin and tubulin, and loss of cell polarity. p127, although mostly associated with the plasma membrane, is in most cell types also present in the cytoplasm. It shows a dynamic subcellular distribution, and its cytosolic and membrane-associated forms play distinctive roles by interacting with different binding partners, in particular the non-muscle myosin II heavy chain. Defects associated with the lgl temperature-sensitive allele include loss of the columnar organisation of epithelial cells, indicating that p127 contributes to cell structure, presumably by stabilising the plasma membrane. In addition to their organising functions, both Dlg and p127 appear to be involved in signal transduction pathways. Study of these genes shows that some proteins play both structural and functional roles, and that cancer can involve changes in the organisation of signalling pathways in addition to changes in individual pathway components.

Animals↗

PubMed1999

Requirement of Drosophila I(2)gl function for survival of the germline cells and organization of the follicle cells in a columnar epithelium during oogenesis.

The lethal(2)giant larvae gene, or 1(2)gl, encodes a widely expressed cytoskeletal protein which acts in numerous biological processes during embryogenesis and oogenesis, including cell proliferation, and morphogenetic movements. Having identified the nucleotide change occurring in the l(2)gl(ts3) sequence, we produced by site-directed mutagenesis the identical change leading to the substitution of a serine by a phenylalanine at position 311 of p127l(2)gl and introduced the modified l(2)glF311 gene into l(2)gl flies. The transgene can fully rescue the development of l(2)gl flies raised at 22 degrees C but causes drastic effects on their development at 29 degrees C confirming the temperature sensitivity of the phenylalanine substitution at position 311. Fertility of females, albeit not of males, was strongly affected. Temperature-shift experiments and microscopic examination of ovaries showed that the mutation blocked egg chamber development at the onset of vitellogenesis (stages 8-9) with growth arrest of the oocyte, incomplete follicle cell migration over the oocyte associated with abnormal organization of the follicular epithelium, and apoptosis of the germline cells, as measured by TUNEL assays. By comparison to wildtype, we found that p127F311 is already reduced in amount at 22 degrees C and delocalized from the cytoskeletal matrix, albeit without affecting the apical localization of myosin II, a major partner of p127. At 29 degrees C, the level of p127F311 is even more reduced and the distribution of myosin-II becomes markedly altered at the apices of the follicle cells. These data indicate that during oogenesis p127 plays a critical function at the onset of vitellogenesis and regulates growth of the oocyte, follicle cell migration over the oocyte and their organization in a palisadic epithelium, as well as viability of the germline cells.

Animals↗

PubMed1998

Selective and asymmetric action of trypsin on the dimeric forms of seminal RNase.

Dimeric seminal RNase (BS-RNase) is an equilibrium mixture of conformationally different quaternary structures, one characterized by the interchange between subunits of their N-terminal ends (the MXM form); the other with no interchange (the M=M form). Controlled tryptic digestion of each isolated quaternary form generates, as limit digest products, folded and enzymatically active molecules, very resistant to further tryptic degradation. Electrospray mass spectrometric analyses and N-terminal sequence determinations indicate that trypsin can discriminate between the conformationally different quaternary structures of seminal RNase, and exerts a differential and asymmetric action on the two dimeric forms, depending on the original quaternary conformation of each form. The two digestion products from the MXM and the M=M dimeric forms have different structures, which are reminiscent of the original quaternary conformation of the dimers: one with interchange, the other with no interchange, of the N-terminal ends. The surprising resistance of these tryptic products to further tryptic action is explained by the persistence in each digestion product of the original intersubunit interface.

Animals↗

PubMed1997

Pathophysiological aspects of menstrual migraine.

We review the role of several biochemical and hormonal factors in menstrual migraine pathogenesis: ovarian hormones, aldosterone circadian rhythm, nocturnal urinary melatonin excretion, sympathetic autonomic system, prolactin levels and dopaminergic function, endogenous opioid tonus, platelet activity and arachidonic acid metabolites. In particular, we focus on certain aspects of platelet function and prostaglandin metabolism, taking into consideration the different behavior of platelet sensitivity to prostacyclin, intraplatelet 5HT, peripheral plasma concentrations of 6-keto-PGF1alpha and PGE2 in menstrual migraine sufferers and in control subjects during the menstrual cycle. A comprehensive view of the data suggests that a complex impairment of PG and 5HT metabolism, and of platelet function, may play a significant role in the pathogenesis of menstrual migraine. However, it is not yet clear whether these alterations are primary or secondary to neuroendocrine disorders.

Blood Platelets↗