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Pubblicazioni - Colombo Dott.ssa Giulia
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Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology.
Brain Sci2020 Nov;10(12):. doi: E907.
Becchetti Andrea, Grandi Laura Clara, Colombo Giulia, Meneghini Simone, Amadeo Alida
Abstract
Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na-gated K channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have different roles in developing and mature brains. Under this respect, nicotinic receptors are paradigmatic, as different pathophysiological roles are exerted by distinct nAChR subunits in adult and developing brains. The widest evidence concerns ?4 and ?2 subunits. These participate in heteromeric nAChRs that are major modulators of excitability in mature neocortical circuits as well as regulate postnatal synaptogenesis. However, growing evidence implicates mutant ?2 subunits in ADSHE, which poses interpretive difficulties as very little is known about the function of ?2-containing (?2*) nAChRs in the human brain. Planning rational therapy must consider that pharmacological treatment could have different effects on synaptic maturation and adult excitability. We discuss recent attempts towards precision medicine in the mature brain and possible approaches to target developmental stages. These issues have general relevance in epilepsy treatment, as the pathogenesis of genetic epilepsies is increasingly recognized to involve developmental alterations.
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Clinical and pharmacological characteristics of elderly patients admitted for bleeding: impact on in-hospital mortality.
Ann Med2020 11;52(7):413-422. doi: 10.1080/07853890.2020.1808238.
Pani Arianna, Pastori Daniele, Senatore Michele, Romandini Alessandra, Colombo Giulia, Agnelli Francesca, Scaglione Francesco, Colombo Fabrizio
Abstract
INTRODUCTION:
Clinical and pharmacological characteristics of elderly patients hospitalized for bleeding and in-hospital mortality according to bleeding type are barely described.
METHODS:
Retrospective cohort study of 13,496 consecutive patients admitted to internal medicine wards. Clinical characteristics, comorbidities and pharmacological treatments were collected for each patient. Predictors of in-hospital mortality were investigated.
RESULTS:
Overall, 531 (3.9%) patients were admitted for bleeding: 189 clinically relevant non-major bleeding, 106 cerebral and 236 major non-cerebral (95.8% gastrointestinal (GI)). Among 106 cerebral bleedings, 28.3% and 24.5% were typical and atypical intracranial, respectively, and 47.2% were subdural haemorrhages. Most of patients with GI bleeding presented with anaemia (90.7%). A similar rate of GI bleeding was found in aspirin-treated patients taking or not proton pump inhibitors (PPI). In-hospital mortality was 9.98%. Age ?80 years (odds ratio (OR) 2.513, =.005), cerebral bleeding (OR 5.373, <.001), eGFR <30?ml/min/m (OR 2.388, =.035) and COPD (OR 2.362, =.024) were positively associated with mortality, while ACE inhibitors/ARBs use was negatively associated (OR 0.383, =.028).
CONCLUSIONS:
The most frequent type of major haemorrhage was GI bleeding, which was not modified by the use of PPI in patients taking aspirin. Cerebral bleeding increased all-cause death, which was lower in ACE inhibitors/ARBs users. KEY MESSAGE Gastrointestinal (GI) bleeding was the most common reason for hospital admission. The rate of GI bleeding was similar in patients on aspirin using or not PPI. Cerebral bleeding increased in-hospital mortality, which was lower in patients taking ACE inhibitors/ARBs.
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Adult-Onset Still Disease After Human Herpesvirus 6 Infection in an Elderly Patient: A Case Report.
J Clin Rheumatol2019 Nov;():. doi: 10.1097/RHU.0000000000001225.
Rossio Raffaella, Colombo Giulia, Piconi Stefania, Peyvandi Flora
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Y-chromosome and Surname Analyses for Reconstructing Past Population Structures: The Sardinian Population as a Test Case.
Int J Mol Sci2019 Nov;20(22):. doi: E5763.
Grugni Viola, Raveane Alessandro, Colombo Giulia, Nici Carmen, Crobu Francesca, Ongaro Linda, Battaglia Vincenza, Sanna Daria, Al-Zahery Nadia, Fiorani Ornella, Lisa Antonella, Ferretti Luca, Achilli Alessandro, Olivieri Anna, Francalacci Paolo, Piazza Alberto, Torroni Antonio, Semino Ornella
Abstract
Many anthropological, linguistic, genetic and genomic analyses have been carried out to evaluate the potential impact that evolutionary forces had in shaping the present-day Sardinian gene pool, the main outlier in the genetic landscape of Europe. However, due to the homogenizing effect of internal movements, which have intensified over the past fifty years, only partial information has been obtained about the main demographic events. To overcome this limitation, we analyzed the male-specific region of the Y chromosome in three population samples obtained by reallocating a large number of Sardinian subjects to the place of origin of their monophyletic surnames, which are paternally transmitted through generations in most of the populations, much like the Y chromosome. Three Y-chromosome founding lineages, G2-L91, I2-M26 and R1b-V88, were identified as strongly contributing to the definition of the outlying position of Sardinians in the European genetic context and marking a significant differentiation within the island. The present distribution of these lineages does not always mirror that detected in ancient DNAs. Our results show that the analysis of the Y-chromosome gene pool coupled with a sampling method based on the origin of the family name, is an efficient approach to unravelling past heterogeneity, often hidden by recent movements, in the gene pool of modern populations. Furthermore, the reconstruction and comparison of past genetic isolates represent a starting point to better assess the genetic information deriving from the increasing number of available ancient DNA samples.
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Combined leadless pacemaker and subcutaneous implantable cardioverter-defibrillator to manage recurrent transvenous system failures.
J Electrocardiol;54():43-46. doi: S0022-0736(18)30918-X.
Baroni Matteo, Colombo Giulia, Testoni Alessio, Arupi Michele, Lunati Maurizio, Cattafi Giuseppe
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and Nocturnal Frontal Lobe Epilepsy: Identification and Characterization of a Novel Loss of Function Mutation.
Front Mol Neurosci2019 ;12():17. doi: 10.3389/fnmol.2019.00017.
Villa Chiara, Colombo Giulia, Meneghini Simone, Gotti Cecilia, Moretti Milena, Ferini-Strambi Luigi, Chisci Elisa, Giovannoni Roberto, Becchetti Andrea, Combi Romina
Abstract
Mutations in genes coding for subunits of the neuronal nicotinic acetylcholine receptor (nAChR) have been involved in familial sleep-related hypermotor epilepsy (also named autosomal dominant nocturnal frontal lobe epilepsy, ADNFLE). Most of these mutations reside in and genes, coding for the ?4 and ?2 nAChR subunits, respectively. Two mutations with contrasting functional effects were also identified in the gene coding for the ?2 subunit. Here, we report the third mutation in the , found in a patient showing ADNFLE. The patient was examined by scalp EEG, contrast-enhanced brain magnetic resonance imaging (MRI), and nocturnal video-polysomnographic recording. All exons and the exon-intron boundaries of , , , , were amplified and Sanger sequenced. In the proband, we found a c.754T>C (p.Tyr252His) missense mutation located in the N-terminal ligand-binding domain and inherited from the mother. Functional studies were performed by transient co-expression of ?2 and ?2 , with either ?2 or ?4, in human embryonic kidney (HEK293) cells. Equimolar amounts of subunits expression were obtained by using F2A-based multi-cistronic constructs encoding for the genes relative to the nAChR subunits of interest and for the enhanced green fluorescent protein. The mutation reduced the maximal currents by approximately 80% in response to saturating concentrations of nicotine in homo- and heterozygous form, in both the ?2?4 and ?2?2 nAChR subtypes. The effect was accompanied by a strong right-shift of the concentration-response to nicotine. Similar effects were observed using ACh. Negligible effects were produced by ?2 on the current reversal potential. Moreover, binding of (±)-[H]Epibatidine revealed an approximately 10-fold decrease of both K and B (bound ligand in saturating conditions), in cells expressing ?2. The reduced B and whole-cell currents were not caused by a decrease in mutant receptor expression, as minor effects were produced by ?2 on the level of transcripts and the membrane expression of ?2?4 nAChR. Overall, these results suggest that ?2 strongly reduced the number of channels bound to the agonist, without significantly altering the overall channel expression. We conclude that mutations in are more commonly linked to ADNFLE than previously thought, and may cause a loss-of-function phenotype.
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Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas.
BMC Biol2019 01;17(1):3. doi: 10.1186/s12915-018-0622-4.
Grugni Viola, Raveane Alessandro, Ongaro Linda, Battaglia Vincenza, Trombetta Beniamino, Colombo Giulia, Capodiferro Marco Rosario, Olivieri Anna, Achilli Alessandro, Perego Ugo A, Motta Jorge, Tribaldos Maribel, Woodward Scott R, Ferretti Luca, Cruciani Fulvio, Torroni Antonio, Semino Ornella
Abstract
BACKGROUND:
Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America.
RESULTS:
Our analyses of 1.5?Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a "coastal and inland routes scenario" for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe.
CONCLUSIONS:
We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples.
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Use of oral anticoagulant drugs in older patients with atrial fibrillation in internal medicine wards.
Eur J Intern Med2018 06;52():e12-e14. doi: S0953-6205(18)30143-2.
Proietti Marco, Antoniazzi Stefania, Monzani Valter, Santalucia Paola, Franchi Carlotta, , Fenoglio Luigi M, Melchio Remo, Fabris Fabrizio, Sartori Maria Teresa, Manfredini Roberto, De Giorgi Alfredo, Fabbian Fabio, Biolo Gianni, Zanetti Michela, Altamura Nicola, Sabbà Carlo, Suppressa Patrizia, Bandiera Francesco, Usai Carlo, Murialdo Giovanni, Fezza Francesca, Marra Alessio, Castelli Francesca, Cattaneo Federico, Beccati Valentina, di Minno Giovanni, Tufano Antonella, Contaldi Paola, Lupattelli Graziana, Bianconi Vanessa, Cappellini Domenica, Hu Cinzia, Minonzio Francesca, Fargion Silvia, Burdick Larry, Francione Paolo, Peyvandi Flora, Rossio Raffaella, Colombo Giulia, Monzani Valter, Ceriani Giuliana, Lucchi Tiziano, Brignolo Barbara, Manfellotto Dario, Caridi Irene, Corazza Gino Roberto, Miceli Emanuela, Padula Donatella, Fraternale Giacomo, Guasti Luigina, Squizzato Alessandro, Maresca Andrea, Liberato Nicola Lucio, Tognin Tiziana, Rozzini Renzo, Bellucci Francesco Baffa, Muscaritoli Maurizio, Molfino Alessio, Petrillo Enrico, Dore Maurizio, Mete Francesca, Gino Miriam, Franceschi Francesco, Gabrielli Maurizio, Perticone Francesco, Perticone Maria, Bertolotti Marco, Mussi Chiara, Borghi Claudio, Strocchi Enrico, Durazzo Marilena, Fornengo Paolo, Dallegri Franco, Ottonello Luciano Carlo, Salam Kassem, Caserza Lara, Barbagallo Mario, Di Bella Giovanna, Annoni Giorgio, Bruni Adriana Antonella, Odetti Patrizio, Nencioni Alessio, Monacelli Fiammetta, Napolitano Armando, Brucato Antonio, Valenti Anna, Castellino Pietro, Zanoli Luca, Mazzeo Marco
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Determinants of carotid-femoral pulse wave velocity progression in hypertensive patients over a 3.7 years follow-up.
Blood Press2018 02;27(1):32-40. doi: 10.1080/08037051.2017.1378069.
Meani Paolo, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Giupponi Luca, Stucchi Miriam, Varrenti Marisa, Vallerio Paola, Facchetti Rita, Grassi Guido, Mancia Giuseppe, Giannattasio Cristina
Abstract
OBJECTIVE:
The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects.
MATERIALS AND METHODS:
We enrolled 333 consecutive hypertensive outpatients 18-80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75?±?0.53 years.
RESULTS:
At baseline the mean age was 54.5?±?12.6 years, SBP and DBP were 141.3?±?18.6 and 86.4?±?10.4?mmHg and PWV was 8.56?±?1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (?PWV 0.87?±?3.05 m/s). PWV and ?PWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ?PWV showed a greater increase as compared to patients with controlled BP (1.46?±?3.67 vs 0.62?±?2.61 m/s, p?
CONCLUSIONS:
the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies.
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K. pneumoniae liver abscess following deferoxamine subcutaneous self-injection.
Am J Hematol2017 May;92(5):480-481. doi: 10.1002/ajh.24675.
Furlan Ludovico, Graziadei Giovanna, Colombo Giulia, Forzenigo Laura Virginia, Solbiati Monica
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Arterial Stiffness in Aortic Stenosis: Relationship with Severity and Echocardiographic Procedures Response.
High Blood Press Cardiovasc Prev2017 Mar;24(1):19-27. doi: 10.1007/s40292-016-0176-x.
Bruschi Giuseppe, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Nava Stefano, Vallerio Paola, Casadei Francesca, Bruno Jolie, Moreo Antonella, Merlanti Bruno, Russo Claudio, Oliva Fabrizio, Klugmann Silvio, Giannattasio Cristina
Abstract
INTRODUCTION:
Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS.
AIM:
We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI).
METHODS:
30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated.
RESULTS:
On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: -42.9 ± 17.2 vs -27.9 ± 10.1, peak: -68.7 ± 29.2 vs -42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup.
CONCLUSIONS:
In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.
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Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease.
Open Heart;3(2):e000472.
Morici Nuccia, Farioli Laura, Losappio Laura Michelina, Colombo Giulia, Nichelatti Michele, Preziosi Donatella, Micarelli Gianluigi, Oliva Fabrizio, Giannattasio Cristina, Klugmann Silvio, Pastorello Elide Anna
Abstract
OBJECTIVE:
To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score).
METHODS:
We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2?years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score.
RESULTS:
Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7?ng/mL (sensitivity 46%, specificity 84%).
CONCLUSIONS:
In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2?years, demonstrating a possible long-term prognostic role of this biomarker.
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Mid-term survival after continuous-flow left ventricular assist device versus heart transplantation.
Heart Vessels2016 May;31(5):722-33. doi: 10.1007/s00380-015-0654-4.
Ammirati Enrico, Oliva Fabrizio G, Colombo Tiziano, Russo Claudio F, Cipriani Manlio G, Garascia Andrea, Guida Valentina, Colombo Giulia, Verde Alessandro, Perna Enrico, Cannata Aldo, Paino Roberto, Martinelli Luigi, Frigerio Maria
Abstract
There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.
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Ultrasonography versus computed tomography for suspected nephrolithiasis.
Intern Emerg Med2015 Jun;10(4):515-6. doi: 10.1007/s11739-015-1192-x.
Colombo Giulia, Solbiati Monica,
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Age-adjusted D-dimer cutoff levels and pulmonary embolism.
JAMA2014 Aug;312(5):557. doi: 10.1001/jama.2014.7604.
Colombo Giorgio, Furlan Ludovico, Colombo Giulia
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Blood pressure control in Italian essential hypertensives treated by general practitioners.
Am J Hypertens2012 Nov;25(11):1182-7. doi: 10.1038/ajh.2012.108.
Giannattasio Cristina, Cairo Matteo, Cesana Francesca, Alloni Marta, Sormani Paola, Colombo Giulia, Grassi Guido, Mancia Giuseppe
Abstract
BACKGROUND:
Adequate control of blood pressure (BP) is limited worldwide. This has serious consequences for public health because in hypertensive patients, uncontrolled BP is associated with a higher incidence of cardiovascular events, particularly stroke. The aim of this study was to investigate BP control in a cohort of treated patients with diagnosed hypertension, who were under general practitioner care in Italy.
METHODS:
Data were collected by 2,643 physicians on 8,572 individual Italian patients. Office BP was measured 5 min after seating each patient and then 3-5 min later. For each patient, data such as medical history of patients, physical examination data, antihypertensive drug usage, and self-BP measurement frequency were obtained.
RESULTS:
Male prevalence was 48.4%, and mean age was 64.3 ± 10.5 years. Based on the second measurement, BP control (<140/90 mm Hg) was observed in 33.5% of all patients (34.2% in men and 33.4% in women). BP control was much lower for systolic BP than for diastolic BP (35.9 vs. 61.3%, P < 0.0001); moreover, BP control was much more common in patients who were engaged in self-BP measurement (61.2 vs. 38.8%, P < 0.0001). A stricter BP control recommended by the guidelines of the European Society of Hypertension (ESH) and European Society of Cardiology (ESC) (<130/80 mm Hg) was observed in only 5.5% of diabetic patients.
CONCLUSIONS:
In treated Italian hypertensives effective BP control remains uncommon largely due to the failure to appropriately reduce the systolic BP. The stricter values recommended by the ESH/ESC guidelines for diabetic patients are achieved only by a small fraction of hypertensive diabetic population.
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Simvastatin reduces MMP1 expression in human smooth muscle cells cultured on polymerized collagen by inhibiting Rac1 activation.
Arterioscler Thromb Vasc Biol2007 May;27(5):1043-9.
Ferri Nicola, Colombo Giulia, Ferrandi Corrado, Raines Elaine W, Levkau Bodo, Corsini Alberto
Abstract
OBJECTIVE:
Activation of collagen receptors expressed by smooth muscle cells induces matrix metalloproteinase (MMP) expression. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to interfere with integrin signaling, but their effects on collagen receptor-mediated MMP expression have not been investigated.
METHODS AND RESULTS:
In the present study, we show that simvastatin (3 micromol/L) reduces MMP1 expression and secretion in human smooth muscle cells cultured on polymerized type I collagen by 39.9+/-11.2% and 36.0+/-2.3%, respectively. Reduced MMP1 protein levels correlate with a similar decrease in MMP1 promoter activity (-33.0+/-8.9%), MMP1 mRNA levels (-37.8+/-10.5%), and attenuation of smooth muscle cell collagen degradation (-34.2+/-6.1%). Mevalonate, and the isoprenoid derivative geranylgeraniol, precursors of geranylgeranylated proteins, completely prevent the inhibitory effect of simvastatin on MMP1. Moreover, the protein geranylgeranyltransferase inhibitor GGTI-286 significantly decreases MMP1 expression. Retroviral overexpression of dominant-negative mutants of geranylgeranylated Rac1 lead to a reduction of MMP1 protein (-50.4+/-5.4%) and mRNA levels (-97.9+/-1.0%), and knockdown of Rac1 by small interfering RNA downregulates MMP1 expression. Finally, simvastatin reduces GTP-bound Rac1 expression levels in smooth muscle cells cultured on polymerized collagen.
CONCLUSIONS:
These results demonstrate that simvastatin, by inhibiting Rac1 activity, reduces MMP1 expression and collagen degradation in human smooth muscle cells.
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FSH and LH together in ovarian stimulation.
Eur J Obstet Gynecol Reprod Biol2004 Jul;115 Suppl 1():S34-9.
Levi-Setti Paolo E, Cavagna Mario, Baggiani Annamaria, Zannoni Elena, Colombo Giulia V, Liprandi Valeria
Abstract
The authors review the physiology of the ovulatory cycle and the role of the gonadotrophins in ovulation induction in patients with anovulatory disorders and in multifollicular development for assisted reproductive technologies. The use of gonadotrophins with luteinizing hormone (LH) activity and the use of recombinant LH associated with follicle stimulating hormone (FSH) are discussed. The authors point out that administration of gonadotrophins with LH activity is essential in hypogonadotropic hypogonadal anovulation, and data available in the medical literature allow the conclusion that recombinant LH may be added to all ovarian stimulation protocols because it is difficult to determine which patients will benefit from LH administration and there is no evidence that LH affects adversely the outcome of ovarian stimulation. The use of recombinant LH in addition to recombinant FSH may be particularly useful when a GnRH antagonist is associated with the ovarian stimulation regimen, by preventing the fall in estradiol and diminishing FSH requirements.
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