- Do not fear the Framingham: Practical application to properly evaluate and modify cardiovascular risk in commercial divers. [Journal Article]
- UHUndersea Hyperb Med 2018 Jan-Feb; 45(1):75-82
- In April 2016 the Association of Diving Contractors International (ADCI) consensus guidelines began recommending annual cardiovascular risk stratification of commercial divers using the Framingham Ri...
In April 2016 the Association of Diving Contractors International (ADCI) consensus guidelines began recommending annual cardiovascular risk stratification of commercial divers using the Framingham Risk Score (FRS). For those at elevated risk, further testing is recommended. This approach has raised concerns about potential operational and financial impacts. However, the prevalence of elevated cardiovascular risk and need for additional testing among commercial divers is not known.
- Impact of hyperbaric oxygenation on oxidative stress in diabetic patients. [Journal Article]
- UHUndersea Hyperb Med 2018 Jan-Feb; 45(1):9-17
- Taking into consideration that a high concentration of oxygen can express toxic effects due to production of reactive oxygen species (ROS), the aim of our investigation was to establish the influence...
Taking into consideration that a high concentration of oxygen can express toxic effects due to production of reactive oxygen species (ROS), the aim of our investigation was to establish the influence of hyperbaric oxygenation on oxidative stress parameters and antioxidant enzymes in patients with diabetes mellitus (DM) type 2. Investigation included 50 patients with DM type 2 divided into two groups. The first group consisted of 25 patients, mean age 70 years, mean duration of illness 12 years and without manifest peripheral vascular complications (Wagner 0). The second group consisted of 25 patients, mean age 74 years, mean duration of illness 17 years and with manifest peripheral vascular complications (Wagner 1-5). All patients underwent the same therapeutic protocol, which included 10 hyperbaric oxygenation therapies, once a day for a duration of 60 minutes, with an average partial oxygen pressure of 1.7 atmospheres absolute (ATA). In blood samples the following parameters of redox balance were determined: levels of nitrites (NO₂-), index of lipid peroxidation (TBARS), superoxide anion radical (O₂-), hydrogen peroxide (H₂O₂) and antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Our results clearly show that hyperbaric oxygen (HBO₂) therapy does not have a pro-oxidative effect. Additionally, it seems that this procedure strongly mobilized the antioxidant enzyme system, thus improving defense from oxidative damage. All significant data are marked as P ⟨0.05. Our results have shown that in terms of ROS production, HBO₂ can be safe to use in patients suffering from DM type 2 with or without vascular complications.
- Simultaneous monitoring of pazopanib and its metabolites by UPLC-MS/MS. [Journal Article]
- JPJ Pharm Biomed Anal 2018 Mar 09; 154:373-383
- Pazopanib is a multi-targeted tyrosine kinase inhibitor (TKI) approved as first-line treatment for patients with advanced renal cell carcinoma (RCC) and as second-line treatment for patients with adv...
Pazopanib is a multi-targeted tyrosine kinase inhibitor (TKI) approved as first-line treatment for patients with advanced renal cell carcinoma (RCC) and as second-line treatment for patients with advanced soft tissue sarcoma (STS) previously treated with chemotherapy. The most common adverse events, observed during the RCC and STS trials, were gastrointestinal disorders, hypertension, fatigue, elevated ALAT and ASAT, but the molecular mechanisms explaining pazopanib toxicity remain unclear. Therapeutic activity is considered to be mainly dependent on pazopanib exposure as the primary metabolites are inactive or display low plasma concentrations, but metabolites may be involved in toxicity as relationships between metabolite profiles and toxicity have not been evaluated. We report here, for the first time, the validation of a method for the simultaneous quantification of pazopanib and semi-quantification of its metabolites (relative determination). As there are no standards available, pazopanib metabolites were generated with human liver microsomes (HLM) to provide controls in the development of an UPLC-MS/MS method for monitoring both pazopanib and metabolites. The optimised method was validated for specificity, linearity, sensitivity, precision, accuracy, matrix effect and stability. The coefficient of variation (CV%) for intra-day and inter-day precision varied from 2.1% to 7.9% and 5.6% to 13.1% respectively. The biases varied from -12% to 2.3% (intra-day) and 3.8% to 13.1% (inter-day) for accuracy evaluation. Intra-day and inter-day precision CV were respectively 20.1% and 19.6% and accuracy biases were between 20.7% (intra-day) and 3.8% (inter-day) at the limit of quantification. The recoveries from matrix samples spiked with pazopanib were respectively 102.6 ± 12.9% and 102.5 ± 1.2% at low and high levels of calibration range. No matrix effect was evidenced as demonstrated by the normalised matrix factor values: 1.3 ± 0.1 and 1.2 ± 0.2 respectively measured at low and high part of calibration range. A good stability of pazopanib was observed during short term, long term and in process storage conditions and after three freeze/thaw cycles. The method was applied to clinical samples from three patients treated with pazopanib to establish the metabolite profiles (semi-quantitative data) during treatment. The assessment of metabolite profiles could be useful to improve our understanding of the occurrence of adverse events and to improve pazopanib pharmacokinetic-pharmacodynamic relationships.
- Increase of lifetime cadmium intake dose-dependently increased all cause of mortality in female inhabitants of the cadmium-polluted Jinzu River basin, Toyama, Japan. [Journal Article]
- EREnviron Res 2018 Mar 20; 164:379-384
- CONCLUSIONS: The present study documents that individual LCd dose-dependently decreased life prognosis over long-term observation in women. LCd was significantly related to the increased mortality for renal disease and toxic effect of Cd in women. The result provides clear evidence that life prognosis was adversely affected by Cd-exposure, especially in women.
- Linalyl acetate prevents olmesartan-induced intestinal hypermotility mediated by interference of the sympathetic inhibitory pathway in hypertensive rat. [Journal Article]
- BPBiomed Pharmacother 2018 Mar 20; 102:362-368
- Olmesartan-associated enteropathy (OAE) is a life-threatening pathological condition, but its underlying mechanisms have not been elucidated. Although intestinal hypermotility is frequently accompani...
Olmesartan-associated enteropathy (OAE) is a life-threatening pathological condition, but its underlying mechanisms have not been elucidated. Although intestinal hypermotility is frequently accompanied by chronic diarrhea, there have been no studies of olmesartan-induced hypermotility. Intestinal motility should be well regulated by the enteric nervous system, but degeneration of enteric neurons has been reported in patients with chronic diarrheal diseases, such as irritable bowel syndrome, suggesting a connection between OAE and intestinal hypermotility. In this study, interference with this inhibitory pathway was analyzed in a model of olmesartan-induced intestinal hypermotility (OIH) in rats with nicotine-induced hypertension exposed to chronic immobilizing stress. The effects of the potent inhibitory neurotransmitters norepinephrine (NE) and sodium nitroprusside (SNP), which act via different pathways, were assessed ex vivo, with only NE-modulated frequency and amplitude of spontaneous contractions found to be elevated in OIH rat jejunum. Clinical symptoms frequent in OAE, including atrophy of the intestinal epithelium and weight loss, were observed in these rats. Interestingly, olmesartan significantly elevated heart rate while lowering blood pressure in OIH rats. These abnormal conditions were prevented by adding linalyl acetate (LA), while the blood pressure-lowering effects of olmesartan were maintained. These findings suggest that olmesartan induces intestinal hypermotility by interfering with the sympathetic inhibitory pathway, and reduces epithelial cell size or body weight in hypertensive rats. As LA prevented these effects, combination treatment with olmesartan plus LA may provide better antihypertensive efficacy without inducing OAE.
- Enhanced lipoxygenase/LTD4 signaling accounts for the exaggerated hypertensive and nephrotoxic effects of cyclosporine plus indomethacin in rats. [Journal Article]
- BPBiomed Pharmacother 2018 Mar 20; 102:309-316
- The combined use of cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) causes exaggerated rises in systolic blood pressure (SBP) and nephrotoxicity. We examined whether these influen...
The combined use of cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) causes exaggerated rises in systolic blood pressure (SBP) and nephrotoxicity. We examined whether these influences relate to the arachidonate/5-lipoxygenase (LOX) pathway. Rats were treated with CSA (20 mg kg-1 day-1), indomethacin (5 mg kg-1 day-1), or their combination for 10 days. Changes in SBP and renal biochemical/histopathological characteristics along with leukotriene levels were determined in rats treated with or without LT receptor antagonists. CSA or indomethacin caused: (i) renal tubular atrophy and interstitial fibrosis, (ii) increases in serum creatinine, blood urea nitrogen (BUN), and renal LTD4, LTB4, TNF-α, TGF-β1, and caspase-3, and (iii) decreases in renal PGE2 and total antioxidant capacity (TAC). SBP measured by tail-cuff plethysmography was increased by CSA but not indomethacin. These effects were mostly intensified in rats treated with CSA plus indomethacin. The co-treatment with montelukast (cysteinyl LT receptor blocker), but not ONO-4057 (LTB4 receptor blocker), ameliorated CSA/indomethacin-evoked hypertension, renal structural/biochemical deterioration, and LTD4 levels. Moreover, montelukast exhibited a greater capacity in reversing inflammatory, oxidative, apoptotic, and fibrotic abnormalities induced by CSA/indomethacin. Overall, lipoxygenase/LTD4 upregulation contributes to the exaggerated hypertension and nephrotoxicity caused by CSA/indomethacin. The therapeutic potential of cysteinyl LT receptor antagonism in rectifying CSA/NSAIDs-evoked anomalies is warranted.
- Frailty and Comorbidities Among Survivors of Adolescent and Young Adult Cancer: A Cross-Sectional Examination of a Hospital-Based Survivorship Cohort. [Journal Article]
- JAJ Adolesc Young Adult Oncol 2018 Mar 23
- CONCLUSIONS: The prevalence of frailty and comorbidities is high among AYA cancer survivors suggestive of accelerated aging.
- AMPK Phosphorylation of ACE2 in Endothelium Mitigates Pulmonary Hypertension. [Journal Article]
- AJAm J Respir Crit Care Med 2018 Mar 23
- CONCLUSIONS: Impaired phosphorylation of ACE2 Ser-680 by AMPK in pulmonary endothelium leads to a labile ACE2 and hence is associated with the pathogenesis of PH. Thus, AMPK regulation of the vasoprotective ACE2 would be a potential target for PH treatment.
- Real life practices of chronic thromboembolic pulmonary hypertension screening. Results from the REMOTEV observational study. [Letter]
- CRClin Respir J 2018 Mar 23
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- The non-biphenyl-tetrazole AT1 receptor blocker eprosartan is a unique and robust inverse agonist of the active state of AT1 receptor. [Journal Article]
- BJBr J Pharmacol 2018 Mar 23
- CONCLUSIONS: These findings suggest that eprosartan may be a better therapeutic option than other ARBs, and that comparative studies investigating eprosartan and other ARBs for the treatment of diseases caused by chronic agonist-independent AT1R activation are warranted.