Antepartum pelvic floor muscle training (PFMT) plus perineal massage vs. postpartum PFMT alone: analysis of pelvic floor disorders, Quality of Life and sexual function.

Background: The aim of this study was to analyze how antepartum pelvic floor muscle training (PFMT) plus perineal massage associated with postpartum PFMT have a significant impact on pelvic floor health during pregnancy and after delivery.

Methods: One thousand two hundred thirty-three women were enrolled from January 2019 to December 2021. They were divided into two groups: 786 women underwent postpartum PFMT only, 447 women experienced both prepartum perineal massage and PFMT and postpartum PFMT.

Combined treatment with vaginal native tissue repair plus mid-urethral sling or pelvic floor muscle training in patients with anterior defect and occult stress urinary incontinence: quality of life and sexual function analysis.

Background: The aim of this study was to compare the efficacy of vaginal native tissue repair (VNTR) combined with tension-free transobturator tape (TVT-O) or pelvic floor muscle training (PFMT) in terms of quality of life (QoL) and sexual function (SF) in women affected by anterior defect and occult stress urinary incontinence (OSUI).

Methods: One hundred forty-seven patients with symptomatic anterior defect with OSUI underwent VNTR. In 71 patients TVT-O was inserted and 76 underwent PFMT after surgery.

TOT in combination with solifenacin or intravaginal prasterone in postmenopausal women with mixed urinary incontinence: A retrospective analysis in 112 patients.

Objectives: The aim of this study was to compare the efficacy of the transobturator tape (TOT) procedure combined with solifenacin (TOT-S) or prasterone (TOT-P) in postmenopausal women affected by mixed urinary incontinence (MUI) with a predominant stress urinary incontinence component.

Methods: This is a retrospective analysis including 112 patients: 60 patients of the TOT-S group and 52 patients of the TOT-P group. Physical examination, 3-day voiding diary, urodynamic tests, and Vaginal Health Index (VHI) were compared at the beginning of the analysis and after 12 weeks of follow-up (FU).

The Pros and the Cons for the Use of Silybin-Rich Oral Formulations in Treatment of Liver Damage (NAFLD in Particular).

The increasing prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) worldwide is becoming a challenge for the modern global care system. The lipotoxic process is characterized by an oxidative stress followed by a burst of the inflammatory response, prompting the wound healing process (fibrosis), which can ultimately lead to the development of cirrhosis and the subsequent complications. There is no consensus concerning an effective pharmacological treatment.

Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment.

Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of immunosuppression. We hypothesized that this assumption may be false.

MiR-143/145 deficiency attenuates the progression of atherosclerosis in Ldlr-/-mice.

The miR-143/145 cluster regulates VSMC specific gene expression, thus controlling differentiation, plasticity and contractile function, and promoting the VSMC phenotypic switch from a contractile/non-proliferative to a migrating/proliferative state. More recently increased miR-145 expression was observed in human carotid atherosclerotic plaques from symptomatic patients. The goal of this study was to investigate the contribution of miR-143/145 during atherogenesis by generating mice lacking miR-143/145 on an Ldlr-deficient background.

Quantification of trabectedin in human plasma: validation of a high-performance liquid chromatography-mass spectrometry method and its application in a clinical pharmacokinetic study.

A rapid, sensitive and specific HPLC-MS/MS method was developed and validated for the quantification of trabectedin in human plasma after using deuterated trabectedin as Internal Standard (IS). After the addition of ammonium sulphate, the analyte was extracted from human plasma with acidified methanol (0.1 M HCl).

Molecular regulation of cholesterol metabolism: HDL-based intervention through drugs and diet.

The overloading of cholesterol in the arteries remains the principal cause of cardiovascular diseases. Since available anticholesterolemic drugs are not completely effective and have several severe adverse effects, the aim of this review is to analyze current research focused on the emerging, innovative therapeutic strategies based on both pharmacological and nutritional interventions to control cholesterol metabolism. Pharmacological interventions mainly involve the use of molecules capable of interfering with high-density lipoprotien (HDL) metabolism and the reverse cholesterol transport (RCT) through genetic control of apolipoprotein A-I (ApoA-I), agonism at liver X-receptor alpha (LXRalpha), or inhibition of cholesteryl ester transport protein (CETP), scavenger receptor BI(SR-BI), and ecto F0F1ATPase/synthase.

Development and validation of two liquid chromatography-tandem mass spectrometry methods for the determination of silibinin and silibinin hemisuccinate in human plasma.

To investigate the pharmacokinetics of silibinin and silibinin hemisuccinate in human plasma, two high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods were developed and validated. The methods require a small volume of sample (100μL), and the recovery of the analytes was complete with a good reproducibility (CV% 1.7-9.

Pharmacokinetics and antineoplastic activity of galectin-1-targeting OTX008 in combination with sunitinib.

Purpose: OTX008 is a galectin-1-targeting compound, currently undergoing a phase I clinical trial. This study aimed at investigating OTX008 pharmacokinetics (PK) and antineoplastic activity.

Methods: Pharmacokinetics and activity of OTX008 were analyzed in the human ovarian carcinoma A2780-1A9 and glioblastoma U87MG xenografted in nude mice.

Silibinin hemisuccinate binding to proteins in plasma and blood cell/plasma partitioning in mouse, rat, dog and man in vitro.

Background: The determination of plasma protein binding and blood cell/plasma partitioning is important when prescribing silibinin hemisuccinate to patients concomitantly receiving other drugs and to estimate the safety margins of exposure at the no observed adverse events levels determined from toxicity studies conducted in rats and dogs.

Methods: Protein binding of [3'-14C]silibinin hemisuccinate (1, 10, 100, 1000 and 4000 μM) was evaluated in human, dog, rat and mouse plasma by ultrafiltration. Blood cell/plasma partitioning in all these species was also determined.

High density lipoproteins and atherosclerosis: emerging aspects.

High density lipoproteins (HDL) promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. This ability is responsible for the most relevant anti-atherogenic effect of HDL. The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes.

MicroRNAs and lipoproteins: a connection beyond atherosclerosis?

MicroRNAs (miRNAs) are short non-coding RNAs involved in the regulation of gene expression at the post-transcriptional level that have been involved in the pathogenesis of a number of cardiovascular diseases. Several miRNAs have been described to finely regulate lipid metabolism and the progression and regression of atherosclerosis including, miR-33, miR-122. Of note miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR-33 approaches are under intensive investigation.

A first in human phase I study of the proteasome inhibitor CEP-18770 in patients with advanced solid tumours and multiple myeloma.

Background: The safety, pharmacokinetics (PK) and pharmacodynamics of CEP-18770, a new peptide boronic acid proteasome inhibitor, have been investigated after intravenous administration on days 1, 4, 8 and 11 of every 21d cycle in patients with solid tumours and multiple myeloma (MM).

Patients And Methods: Thirty-eight patients were treated with CEP-18770 at escalating doses from 0.1 to 1.

Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of the novel inhibitor of angiogenesis E-3810 in human plasma and its application in a clinical pharmacokinetic study.

E-3810, 6-[[7-[(1-aminocyclopropyl)methoxy]-6-methoxy-4-quinolyl]oxy]-N-methyl-naphthalene-1-carboxamide, is a novel, potent, dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors with antiangiogenic properties, now under early clinical evaluation as an anticancer agent. To investigate its clinical pharmacokinetics, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to measure the drug in human plasma on the basis of simple protein precipitation with methanol after addition of deuterated E-3810 as internal standard. The method requires a small volume of sample (100 µl) and is rapid and selective, allowing good resolution of peaks in 5 min.

Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of the novel proteasome inhibitor CEP-18770 in human plasma and its application in a clinical pharmacokinetic study.

CEP-18770, [(1R)-1-{[(2S,3R)-3-hydroxy-2-{[(6-phenyl-2-pyridinyl)carbonyl]amino}butanoyl]amino}-3-methylbutyl]boronic acid, is a novel proteasome inhibitor, now under early clinical evaluation as an anticancer agent. To investigate its clinical pharmacokinetics, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to measure the drug in human plasma, based on simple protein precipitation with acetonitrile after the addition of irbesartan as internal standard. The method requires a small volume of sample (100 µl) and is rapid and selective, allowing good resolution of peaks in 5 min.

Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer.

Introduction: Although some studies have suggested that gemcitabine delivered as a fixed dose rate (FDR) infusion of 10 mg/m(2)/min could be more effective than when administered as the standard 30-min infusion, the available pharmacokinetic data are still too limited to draw definitive conclusions. This study is aimed to investigate the plasmatic and intracellular pharmacokinetics of gemcitabine given as FDR at doses of 600 and 1,200 mg/m(2) in combination with 75 mg/m(2) of cisplatin in advanced non-small-cell lung cancer (NSCLC) patients.

Patients And Method: The patients were divided into two groups receiving different initial doses of the drug: 4 patients received 600 mg/m(2) gemcitabine 60-min i.

Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of ST1926, a novel oral antitumor agent, adamantyl retinoid derivative, in plasma of patients in a Phase I study.

E-3-(4'-Hydroxy-3'-adamantylbiphenyl-4-yl) acrylic acid (ST1926) is a novel oral synthetic adamantyl retinoid derivative, now under early clinical investigation in patients with ovarian cancer. To investigate the pharmacokinetics of this new antitumor agent in human plasma, we developed and validated a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method based on the addition of ST2222 as internal standard and simple protein precipitation with methanol. The method requires a small volume of sample (100microL); it is rapid and selective, allowing a good resolution of peaks from the plasma matrix in 9min.

Simultaneous determination of gemcitabine and its main metabolite, dFdU, in plasma of patients with advanced non-small-cell lung cancer by high-performance liquid chromatography-tandem mass spectrometry.

Gemcitabine, 2',2'-difluoro-2'-deoxycytidine (dFdC) is a pyrimidine antimetabolite employed against several human malignancies. It undergoes intracellular activation to the pharmacologically active triphosphate form (dFdCTP) and metabolic inactivation to the metabolite 2',2'-difluorodeoxyuridine (dFdU). In order to investigate the human plasma pharmacokinetics of dFdC and dFdU, we developed and validated an HPLC-MS/MS method, adding 2'-deoxycytidine as internal standard and simply precipitating the protein with acetonitrile.