PRMT1 inhibition perturbs RNA metabolism and induces DNA damage in clear cell renal cell carcinoma.

In addition to the ubiquitous loss of the VHL gene in clear cell renal cell carcinoma (ccRCC), co-deletions of chromatin-regulating genes are common drivers of tumorigenesis, suggesting potential vulnerability to epigenetic manipulation. A library of chemical probes targeting a spectrum of epigenetic regulators is screened using a panel of ccRCC models. MS023, a type I protein arginine methyltransferase (PRMT) inhibitor, is identified as an antitumorigenic agent.

Prothrombotic activity of cytokine-activated endothelial cells and shear-activated platelets in the setting of ventricular assist device support.

Background: We systematically analyzed the synergistic effect of: (i) cytokine-mediated inflammatory activation of endothelial cells (ECs) with and (ii) shear-mediated platelet activation (SMPA) as a potential contributory mechanism to intraventricular thrombus formation in the setting of left ventricular assist device (LVAD) support.

Methods: Intact and shear-activated human platelets were exposed to non-activated and cytokine-activated ECs. To modulate the level of LVAD-related shear activation, platelets were exposed to shear stress patterns of varying magnitude (30, 50, and 70 dynes/cm, 10 minutes) via a hemodynamic shearing device.

Trigger-oriented HIV testing at Internal Medicine hospital Departments in Northern Italy: an observational study (Fo.C.S. Study).

Background: Early detection of undiagnosed HIV infected patients is of paramount importance. The attitude of Italian hospital-based Internal Medicine physicians to prescribe HIV testing following the detection of HIV-associated signs, symptoms and behaviours (triggers) has been reported to be poor. The aim of the study is to quantify the extent of the missed opportunities for early HIV diagnosis in Internal Medicine Departments (IMD).

Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine.

Background: Patients with clear cell renal cell carcinoma (ccRCC) have few therapeutic options, as ccRCC is unresponsive to chemotherapy and is highly resistant to radiation. Recently targeted therapies have extended progression-free survival, but responses are variable and no significant overall survival benefit has been achieved. Commercial ccRCC cell lines are often used as model systems to develop novel therapeutic approaches, but these do not accurately recapitulate primary ccRCC tumors at the genomic and transcriptional levels.

Clonal evolution and tumor-initiating cells: New dimensions in cancer patient treatment.

Human cancer is not a uniform disease but a plethora of disparate tumor types and subtypes. The differences that exist between individual tumors (intertumoral heterogeneity) present a significant roadblock to the eradication of cancer. It has also become increasingly clear that variations across individual tumors (intratumoral heterogeneity) have important implications to cancer progression and treatment efficacy.

Opposing roles for mammary epithelial-specific PPARγ signaling and activation during breast tumour progression.

Background: Among women worldwide, breast cancer is the most commonly diagnosed cancer, and the second leading cause of cancer-related deaths. Improved understanding of breast tumourigenesis may facilitate the development of more effective therapies. Peroxisome proliferator-activated receptor (PPAR)γ is a transcription factor that regulates genes involved in insulin sensitivity and adipogenesis.

Evaluation of use of antibiotics without prescription among young adults in Albania case study: Tirana and Fier District.

Background: Self-medication is defined as the utilization of drugs to treat self-diagnosed disorders or symptoms, or the irregular or continuous use of a prescribed drug for chronic or repeated diseases or symptoms. The main problem with self-medication with antimicrobials is the emergence of pathogenic resistance. Antimicrobial resistance is an existing problem world-wide, mainly in developing countries.

Loss of PPARγ expression in mammary secretory epithelial cells creates a pro-breast tumorigenic environment.

Breast cancer is the leading cause of new cancer diagnoses among women. Using peroxisome proliferator-activated receptor (PPAR)γ((+/-)) mice, we showed normal expression of PPARγ was critical to stop 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast tumorigenesis. PPARγ is expressed in many breast cell types including mammary secretory epithelial (MSE) cells.

Contact investigation based on serial interferon-gamma release assays (IGRA) in children from the hematology-oncology ward after exposure to a patient with pulmonary tuberculosis.

Background: Interferon-gamma release assays (IGRAs) have high specificity and sensitivity for the diagnosis of tuberculosis (TB) infection. However, their role as a screening tool in children with immunodeficiency disorders is still unclear. In the present study, we performed a contact investigation using serial IGRAs on children with immunodeficiency conditions exposed to a contagious TB patient.

The inhibin B response to a motilin receptor agonist in male rats.

Background: In a repeat oral dose toxicity study, all of 16 male rats given 100 mg/kg/day GSK1322888 sustained testicular injury after 4 weeks of treatment; the findings were not reversible after 12 weeks off-dose. The current study was conducted to further characterize testicular toxicity and to explore the possible relationship between onset of lesions, and changes in circulating hormone levels.

Methods: Male Sprague Dawley rats were orally administered 30 or 100 mg/kg/day GSK1322888 for 2 weeks with a 4-week off-dose period.

PPAR Medicines and Human Disease: The ABCs of It All.

ATP-dependent binding cassette (ABC) transporters are a family of transmembrane proteins that pump a variety of hydrophobic compounds across cellular and subcellular barriers and are implicated in human diseases such as cancer and atherosclerosis. Inhibition of ABC transporter activity showed promise in early preclinical studies; however, the outcomes in clinical trials with these agents have not been as encouraging. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate genes involved in fat and glucose metabolism, and inflammation.

Lopinavir pharmacokinetic profiles in HIV-infected patients during rifabutin-based anti-mycobacterial therapy.

Objectives: To evaluate the pharmacokinetic profile of ritonavir-boosted lopinavir in HIV-infected patients during rifabutin-based anti-mycobacterial therapy.

Patients And Methods: A longitudinal, cross-over pharmacokinetic evaluation of lopinavir with and without rifabutin in HIV-infected subjects with mycobacterial disease was done. All received lopinavir/ritonavir (400/100 mg twice a day) + an adjusted rifabutin dose of 150 mg every other day.

Stromal adipocyte PPARγ protects against breast tumorigenesis.

Peroxisome proliferator-activated receptor (PPAR)γ regulates the expression of genes essential for fat storage, primarily through its activity in adipocytes. It also has a role in carcinogenesis. PPARγ normally stops the in vivo progression of 7,12-dimethylbenz[a]anthracene (DMBA)-mediated breast tumours as revealed with PPARγ haploinsufficient mice.

The potential role for corticosterone in the induction of cleft palate in mice after treatment with a selective NK-1 receptor antagonist, casopitant (GW679769B).

Background: Casopitant is a potent and selective NK-1 receptor antagonist that has shown clinical efficacy in the prevention of chemotherapy-induced and postoperative-induced nausea and vomiting.

Methods: In an embryo-fetal development study, pregnant mice were given vehicle (sterile water) or doses of 30, 100, or 300 mg/kg/day casopitant on Gestation Day (GD) 6 to 15. Fetuses were evaluated for external, visceral, and skeletal abnormalities on GD 18.

[Tubercular disease: clinical aspects and drug resistance].

The emergence of multidrug-resistant TB (MDR-TB), and, more recently of extensively drug-resistant TB (XDR-TB) is a real threat to achieve TB control and elimination. Over 500.000 new cases of MDR TB occurred in 2008 worldwide, of whom 50.

[Pain and basic functional activites in a group of patients with cutaneous wounds under V.A.C therapy in hospital setting].

Introduction: Topical Negative Pressure Wound Therapy (NPWT), in Italy known as V.A.C.

Two-year outcome of a prospective, controlled study of a disease management programme for elderly patients with heart failure.

Objective: Elderly heart failure patients are at high risk of events. Available studies and systematic reviews suggest that elderly patients benefit from disease management programmes (DMPs). However, important questions remain open, including the optimal follow-up intensity and duration and whether such interventions are cost-effective during long-term follow-up and in different healthcare systems.

[Two years of randomized and controlled clinical studies on pressure ulcers: does it change anything in the A.H.C.P.R. guidelines?].

The problem of the pressure ulcers is today one of the critical and controversial appearance of nursing. To use A.H.