Search results for " hypoxia"

Metabolic effects of hypoxia and sleep at high altitude(5050)

2010

A minireview on NHE1 inhibitors. A rediscovered hope in oncohematology.

2015

Background: Na+/H+ exchanger-1 (NHE-1) is involved in pH regulation and is up-regulated in different malignancies. Activation of NHE-1 is one way for allowing cells to avoid intracellular acidification and protect them against apoptosis. Inhibitors of NHE-1 are able to decrease intracellular pH and induce apoptosis. Some statins can also act by partial inhibition of NHE-1. This review presents progress in understanding the mechanisms of action of these inhibitors, connections with certain genetic mutations and acquired treatment resistance, as well as new patents on them. Methods: A MEDLINE search for original and review articles using key terms, Na+/H+ exchanger, leukemia, cariporide, and …

Data from: Proactive avoidance behaviour and pace-of-life syndrome in Atlantic salmon

2019

Individuals in a fish population differ in key life history traits such as growth rate and body size. This raises the question of whether such traits cluster along a fast-slow growth continuum according to a pace-of-life syndrome (POLS). Fish species like salmonids may develop a bimodal size distribution, providing an opportunity to study the relationships between individual growth and behavioural responsiveness. Here we test whether proactive characteristics (bold behaviour coupled with low post-stress cortisol production) are related to fast growth and developmental rate in Atlantic salmon, Salmo salar. Boldness was tested in a highly controlled two-tank hypoxia test were oxygen levels we…

Development and biological investigations of hypoxia-sensitive prodrugs of the tyrosine kinase inhibitor crizotinib

2019

Despite the huge success of tyrosine kinase inhibitors as anticancer agents, severe side effects are a major problem. In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed. The 2-aminopyridine functionality of crizotinib (essential for target kinase binding) was considered as ideal position for prodrug derivatization. Consequently, two different prodrugs were synthesized with the nitroimidazole unit attached to crizotinib either via carbamoylation (A) or alkylation (B) of the 2-aminopyridine moiety. The successful prodrug design could be proven by docking studies and a dr…

Adipose Tissue in Sleep Apnea

2015

Obesity is increasingly recognized as a very complex metabolic state. Besides visceral obesity and white adipose tissue (WAT) function, the most recent studies point to a major metabolic role of brown adipose tissue (BAT) in energy metabolism. Visceral obesity is associated with hypoxia of adipose tissue and inflammation, both these features being also present in patients with obstructive sleep apnea (OSA). Obesity and OSA may share some common pathogenetic mechanisms, since hypoxia and inflammation are major features of OSA as well. However, the unique pattern of intermittent hypoxia occurring in OSA patients during sleep may modify the response of WAT and BAT in both lean and obese subjec…

Tumor Oxygenation Under Normobaric and Hyperbaric Hyperoxia

1997

Tumor hypoxia is an important factor limiting the efficiency of sparsely ionizing ra-diation and O2-dependent chemotherapy. Since the tumor pO2 is the result of a dynamic steady state between oxygen supply and O2 consumption of the tumor tissue, hypoxia could be reduced either by increasing the O2-supply or by reducing the O2 demand of the tumor cells. The O2 supply can be improved for instance by (i) increasing the arterial oxy-gen partial pressure, (ii) improving (and homogenizing) the tumor perfusion, or (iii) en-hancing the O2 release from blood into the tissue by right-shifting the HbO2 dissociation curve. Theoretically, it should also be possible to improve tumor oxygenation by a rela…

TH-302 + Gemcitabine (G + T) vs Gemcitabine (G) in Patients with Previously Untreated advanced Pancreatic Cancer (PAC)

2012

ABSTRACT Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G…

Muscle Oxygen Delivery in the Forearm and in the Vastus Lateralis Muscles in Response to Resistance Exercise: A Comparison Between Nepalese Porters a…

2020

Altitude ascending represents an intriguing experimental model reproducing physiological and pathophysiological conditions sharing hypoxemia as the denominator. The aim of the present study was to investigate fractional oxygen extraction and blood dynamics in response to hypobaric hypoxia and to acute resistance exercises, taking into account several factors including different ethnic origin and muscle groups. As part of the “Kanchenjunga Exploration & Physiology” project, six Italian trekkers and six Nepalese porters took part in a high altitude trek in the Himalayas. The measurements were carried out at low (1,450 m) and high altitude (HA; 4,780 m). Near-infrared spectroscopy (NIRS)-d…

Chronic Intermittent Hypoxia is associated with Liver Damage and Atherosclerosis in Patients with Non-alcoholic Fatty Liver Disease

2015

P1013 : Chronic intermittent hypoxia is associated with liver damage and atherosclerosis in patients with non-alcoholic fatty liver disease

2015

all the steatosis grades, except S2 vs S3. The diagnostic performances of CAP in quantifying each steatosis grade was: for S ≥1 AUC=0.813 (cutoff 260dB/m, Se = 64.84%, Sp =87.27%, PPV=80.8%, NPV=75%, +LR =5.09, −LR =0.40, DA=76.11%); for S ≥2 AUC=0.822 (cutoff 285dB/m, Se = 69.70%, Sp =85.12%, PPV=47.9%, NPV=93.5%, +LR =4.68, −LR =0.36, DA=82.08%); for S ≥3 AUC=0.838 (cutoff 294dB/m, Se =83.33%, Sp =82.54%, PPV=23.3%, NPV=98.7%, +LR =4.77, −LR =0.20, DA=81.59%). AUCs calculated between two steatosis grades only were: 0.772 (for S0 vs S1), 0.874 (S0 vs S2), 0.904 (S0 vs S3), 0.659 (S1 vs S2), 0.777 (S1 vs S3), and 0.665 (S2 vs S3) respectively. Conclusions: Maximal diagnostic accuracy could …