Effectiveness of the flash glucose monitoring system in preventing severe hypoglycemic episodes and in improving glucose metrics and quality of life in subjects with type 1 diabetes at high risk of acute diabetes complications.

Aims: To assess the effectiveness of the intermittent-scanned continuous glucose monitoring (isCGM) system in preventing severe hypoglycemic episodes and in improving glucose parameters and quality of life.

Methods: Four hundred T1D individuals were enrolled in a prospective real-word study with an intermittently scanned continuous glucose monitoring device during the 12-months follow-up. The primary endpoint was the incidence of severe hypoglycemic events.

Suppression of Kynurenine 3-Monooxygenase as a Treatment for Triple-negative Breast Carcinoma.

Kynurenine 3-monooxygenase (KMO), a key enzyme within the kynurenine (KYN) pathway of tryptophan (TRY) metabolism, enables the excess production of toxic metabolites (such as 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid and quinolinic acid), and modulates the balance between these toxic molecules and the protective metabolite, kynurenic acid (KYNA). Despite its importance, KMO suppression as a treatment for cancer has not been fully explored. Instead, researchers have focused on prevention of KYN pathway activity by inhibition of enzymes indoleamine 2,3-dioxygenase (IDO1 and IDO2) or tryptophan 2,3-dioxygenase (TDO, also known as TDO2).

Relationship between the in vitro efficacy, pharmacokinetics and in vivo efficacy of curcumin.

Considerable interest continues to be focused on the development of curcumin either as an effective stand-alone therapeutic or as an adjunct therapy to established therapies. Curcumin (1, 7-bis (4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5- dione; also called diferuloylmethane) is a polyphenolic phytochemical extracted from the root of curcuma longa, commonly called turmeric. Despite evidence from in vitro (cell culture) and preclinical studies in animals, clinical studies have not provided strong evidence for a therapeutic effect of curcumin.

The complex lipid, SPPCT-800, reduces lung damage, improves pulmonary function and decreases pro-inflammatory cytokines in the murine LPS-induced acute respiratory distress syndrome (ARDS) model.

Context: Acute respiratory distress syndrome (ARDS) is a highly fatal, inflammatory condition of lungs with multiple causes. There is no adequate treatment.

Objective: Using the murine LPS-induced ARDS model, we investigate SPPCT-800 (a complex lipid) as treatment for ARDS.

Study protocol of a phase 1 clinical trial establishing the safety of intrapleural administration of liposomal curcumin: curcumin as a palliative treatment for malignant pleural effusion (IPAL-MPE).

Introduction: This is a phase 1, open-label, single-centre, uncontrolled, dose-escalation study to evaluate the feasibility, tolerability and pharmacokinetic profiles of a single dose of liposomal curcumin, administered via an existing tunnelled indwelling pleural catheter (TIPC) directly to the tumour site in individuals with diagnoses of malignant pleural effusion. Primarily, we aim to determine a maximum tolerated dose of liposomal curcumin administered via this method.

Methods And Analysis: We will use a 3+3 expanded cohort for predefined dose-escalation levels or until a predefined number of dose-limiting toxicities are reached.

The Mystery of Chemotherapy Brain: Kynurenines, Tubulin and Biophoton Release.

The majority of patients receiving chemotherapy experience post-chemotherapy cognitive impairment, sometimes referred to as "chemo brain" or "chemo fog." The cognitive impairment associated with this syndrome can be severe, and can sometimes last for many years after therapy discontinuation. Despite extensive investigations, its etiology is unknown.

The Safety and Exploration of the Pharmacokinetics of Intrapleural Liposomal Curcumin.

Background: Malignant pleural effusion (MPE) is the accumulation of fluid in the pleural cavity as a result of malignancies affecting the lung, pleura and mediastinal lymph nodes. Curcumin, a compound found in turmeric, has anti-cancer properties that could not only treat MPE accumulation but also reduce cancer burden. To our knowledge, direct administration of curcumin into the pleural cavity has never been reported, neither in animals nor in humans.

Intense Uptake of Liposomal Curcumin by Multiple Myeloma Cell Lines: Comparison to Normal Lymphocytes, Red Blood Cells and Chronic Lymphocytic Leukemia Cells.

Background/aim: Curcumin is being widely investigated for its anticancer properties and several studies in the literature suggest that curcumin is distributed to a higher degree in cancer cells compared to normal cells. The goal of this study was to investigate the disposition of curcumin in the form of Lipocurc™ in multiple myeloma (MM)-causing plasma cell lines and B-lymphocytes from healthy individuals and compare the uptake to previously published data for red blood cells (RBCs), peripheral blood mononuclear cells (PBMCs) from healthy individuals and PBMCs from patients with chronic lymphocytic leukemia (CLL-cells).

Materials And Methods: Two MM-producing cell lines were studied: RPMI-8266, an IgG lambda cell line, and NCL-H929, an IgA kappa line.

A 58-Year-Old Woman With Pneumonia and Gram-Negative Diplococci.

A 58-year-old woman with COPD, cor pulmonale, diabetes, and hypertension had a productive cough of greenish and purulent sputum, low-grade fever, and shortness of breath. Medications were metformin, losartan, cholecalciferol, folic acid, a multivitamin, fluticasone by inhalation, and, as needed, ipratropium by inhalation. She lived alone and worked as a physician, had received that year's seasonal influenza vaccine, was a heavy smoker, did not drink alcohol or use illicit drugs, and had no personal or family history of allergy and autoimmunity.

The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma.

The failure of chemotherapy and radiation therapy to achieve long-term remission or cure in patients with glioblastoma (GBM) is, in a large part, due to the suppression of the immune system induced by the tumors themselves. These tumors adapt to treatment with chemotherapy or radiation therapy by stimulating secretion of molecules that cause tryptophan metabolism to be disrupted. Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are produced, accelerating metabolism along the kynurenine pathway and resulting in excess levels of quinolinic acid, 3-hydroxyanthranilic acid and other neurotoxic molecules.

Short wavelength infrared optical windows for evaluation of benign and malignant tissues.

There are three short wavelength infrared (SWIR) optical windows outside the conventionally used first near-infrared (NIR) window (650 to 950 nm). They occur in the 1000- to 2500-nm range and may be considered second, third, and fourth NIR windows. The second (1100 to 1350 nm) and third windows (1600 to 1870 nm) are now being explored through label-free linear and multiphoton imaging.

Vulnerable atherosclerotic plaque detection by resonance Raman spectroscopy.

A clear correlation has been observed between the resonance Raman (RR) spectra of plaques in the aortic tunica intimal wall of a human corpse and three states of plaque evolution: fibrolipid plaques, calcified and ossified plaques, and vulnerable atherosclerotic plaques (VPs). These three states of atherosclerotic plaque lesions demonstrated unique RR molecular fingerprints from key molecules, rendering their spectra unique with respect to one another. The vibrational modes of lipids, cholesterol, carotenoids, tryptophan and heme proteins, the amide I, II, III bands, and methyl/methylene groups from the intrinsic atherosclerotic VPs in tissues were studied.

Clinical predictors and microbiology of ventilator-associated pneumonia in the intensive care unit: a retrospective analysis in six Italian hospitals.

The purpose of this study was to assess the main clinical predictors and microbiological features of ventilator-associated pneumonia (VAP) in the Intensive Care Unit (ICU) environment. This work is a retrospective analysis over one year from September 2010 to September 2011. Patients' risk factors, causes of admission, comorbidities and respiratory specimens collected in six Italian ICUs were reviewed.

Bifunctional role of pro-inflammatory cytokines after traumatic brain injury.

Background: Pro-inflammatory cytokines play an essential role in maintenance of normal brain function as well as in repair after traumatic brain injuries (TBI). However, massive and uncontrolled release of these cytokines, particularly interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, can also result in a great deal of additional brain damage. Levels of these cytokines may increase in the brain thousands of times more than do the corresponding levels in serum.

Sphingosine Kinase Inhibitors as Maintenance Therapy of Glioblastoma After Ceramide-Induced Response.

Ceramide and sphingosine 1-phosphate (S1P) are sphingolipid metabolites with important signaling functions. Ceramides promote apoptosis, whereas S1P favors proliferation, angiogenesis and cell survival. The balance between these opposing signaling functions is referred to as the sphingolipid rheostat.

Curcumin for the Treatment of Glioblastoma.

Glioblastoma multiforme is a highly aggressive primary cancer of the brain associated with a poor prognosis. Modest increases in survival can sometimes be achieved with the use of temozolomide and radiation therapy after surgery, but second-line therapy after recurrence has a limited efficacy. Curcumin has demonstrated promising results against this form of cancer in experimental models.

Review: The Prolonged QT Interval: Role of Pro-inflammatory Cytokines, Reactive Oxygen Species and the Ceramide and Sphingosine-1 Phosphate Pathways.

Patients with QT prolongation have delayed cardiac repolarization and may suffer fatal ventricular arrhythmias. To determine the role of cytokines in causing this syndrome, we reviewed reports on patients with rheumatoid arthritis, psoriasis and other inflammatory conditions. These patients frequently have prolonged QT, which correlates with increases in tumor necrosis factor alpha, and interleukin-1β and 6.

Microbiologic characteristics and predictors of mortality in bloodstream infections in intensive care unit patients: A 1-year, large, prospective surveillance study in 5 Italian hospitals.

Background: Bloodstream infections (BSIs) from multidrug-resistant (MDR) bacteria cause morbidity and mortality in intensive care unit (ICU) patients worldwide. This study investigated the incidence of BSIs in 5 adult general ICUs in Rome, Italy, and evaluated the mortality rate and risk factors associated with these infections.

Methods: Over a 12-month period, 1,318 patients were enrolled.

Curcumin and cancer stem cells: curcumin has asymmetrical effects on cancer and normal stem cells.

Curcumin has been shown to have numerous cytotoxic effects on cancer stem cells (CSCs). This is due to its suppression of the release of cytokines, particularly interleukin (IL)-6, IL-8 and IL-1, which stimulate CSCs, and also to its effects at multiple sites along CSC pathways, such as Wnt, Notch, Hedgehog and FAK. In spite of its multiple actions targeting CSCs, curcumin has little toxicity against normal stem cells (NSCs).

Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

Background: The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system.

Materials And Methods: The actions of curcumin in suppressing cytokine release and cytokine storm are discussed.

Results: Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α.

Differences in fluorescence profiles from breast cancer tissues due to changes in relative tryptophan content via energy transfer: tryptophan content correlates with histologic grade and tumor size but not with lymph node metastases.

The correlation between histologic grade, an increasingly important measure of prognosis for patients with breast cancer, and tryptophan levels from tissues of 15 breast carcinoma patients was investigated. Changes in the relative content of key native organic biomolecule tryptophan were seen from the fluorescence spectra of cancerous and paired normal tissues with excitation wavelengths of 280 and 300 nm. Due to a large spectral overlap and matching excitation–emission spectra, fluorescence resonance energy transfer from tryptophan-donor to reduced nicotinamide adenine dinucleotides-acceptor was noted.