scholarly journals The effect of pamidronate delivery in bisphosphonate-naïve patients on neutrophil chemotaxis and oxidative burst

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeffrey W. Chadwick ◽  
Howard C. Tenenbaum ◽  
Chun-Xiang Sun ◽  
Robert E. Wood ◽  
Michael Glogauer

Abstract The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ), a morbid condition associated with bisphosphonate administration, has not been fully elucidated. Recent research utilizing a murine model has revealed that the neutrophil becomes dysfunctional following exposure to bisphosphonates. Accordingly, the impairment of neutrophil function could play an important role in the pathogenesis of MRONJ via an infectious mechanism mediated by the suppression of the innate immune system. Currently, the existing human data are insufficient to substantiate this theory. To investigate, we isolated neutrophils from blood and oral rinse samples from bisphosphonate-naïve patients who were recently diagnosed with multiple myeloma both prior to and one month following their initial infusion of pamidronate, an intravenous bisphosphonate agent. Stimulated blood and oral neutrophil superoxide production and chemotactic capabilities were found to be impaired relative to baseline values. These results suggest that impaired neutrophil function may partially contribute to the aetiology underlying the pathophysiological processes linked to the development of MRONJ. Further, as the functional status of circulating neutrophils was reflected in the oral cavity where sampling can be accomplished in a non-invasive fashion, it is conceivable that neutrophil function could serve as a potential biomarker for MRONJ prognostication.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumin Li ◽  
Jia Liu ◽  
Yukun Cao ◽  
Xiaoyu Han ◽  
Guozhu Shao ◽  
...  

AbstractMyocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiac-specific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. The LGE-positive patients had significant higher serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels and lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group. The LGE% was independently associated with the Nt-proBNP levels, GCS, LV end-diastolic maximum wall thickness (MWT) and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP ≥ 108.00 pg/mL and MWT ≥ 17.30 mm had good diagnostic performance for LGE, with a specificity of 81.25% and sensitivity of 70.00%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.


Author(s):  
Seung-Hun Lee ◽  
So-Young Choi ◽  
Min-Su Bae ◽  
Tae-Geon Kwon

Abstract Purpose This retrospective study was aimed to evaluate the clinical characteristics and treatment outcomes in patients with osteonecrosis of the jaw who were receiving oral versus intravenous (IV) bisphosphonate (BP). Materials and methods This retrospective study enrolled subjects who had been diagnosed with medication-related osteonecrosis of the jaw (MRONJ) during the period from July 2010 to June 2014. Information regarding the following demographic and clinical characteristics was collected: demographic data, administration route and type of BP, duration of BP medication, primary disease, number of involved sites, location of the lesion, number of surgeries, outcome of treatments, and laboratory test. All the patients were divided into oral and IV BP groups; and the between-group differences were compared. Results Total 278 patients were divided into two groups as per the route of BP administration. The proportion of oral BP-related MRONJ group were more dominant over IV BP group (oral BP, n = 251; IV BP, n = 27). In the IV BP group, the average dosing duration (31.4 months) was significantly shorter than that in the oral BP group (53.1 months) (P < 0.001). The average number of involved sites in the oral BP group (1.21 ± 0.48) was smaller than that in the IV BP group (1.63 ± 0.84) (P < 0.001). The average number of surgeries was higher in the IV BP group (1.65 ± 0.95) as compared to that in the oral BP group (0.98 ± 0.73) (P < 0.001). Outcome after the surgery for MRONJ after IV BP was poor than oral BP group. Conclusion IV administration of BP causes greater inhibition of bone remodeling and could lead more severe inflammation. Therefore, even if the duration of IV administration of BP is shorter than that of oral BP, the extent of the lesion could be more extensive. Therefore, the result suggests that the MRONJ after IV BP for cancer patients needs to be considered as different characteristics to oral BP group for osteoporosis patents.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Peter P. Ricci ◽  
Otto J. Gregory

AbstractThe presence of ammonia within the body has long been linked to complications stemming from the liver, kidneys, and stomach. These complications can be the result of serious conditions such as chronic kidney disease (CKD), peptic ulcers, and recently COVID-19. Limited liver and kidney function leads to increased blood urea nitrogen (BUN) within the body resulting in elevated levels of ammonia in the mouth, nose, and skin. Similarly, peptic ulcers, commonly from H. pylori, result in ammonia production from urea within the stomach. The presence of these biomarkers enables a potential screening protocol to be considered for frequent, non-invasive monitoring of these conditions. Unfortunately, detection of ammonia in these mediums is rather challenging due to relatively small concentrations and an abundance of interferents. Currently, there are no options available for non-invasive screening of these conditions continuously and in real-time. Here we demonstrate the selective detection of ammonia using a vapor phase thermodynamic sensing platform capable of being employed as part of a health screening protocol. The results show that our detection system has the remarkable ability to selectively detect trace levels of ammonia in the vapor phase using a single catalyst. Additionally, detection was demonstrated in the presence of interferents such as carbon dioxide (CO2) and acetone common in human breath. These results show that our thermodynamic sensors are well suited to selectively detect ammonia at levels that could potentially be useful for health screening applications.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aidan Kenny ◽  
Eva M. Jiménez-Mateos ◽  
María Ascensión Zea-Sevilla ◽  
Alberto Rábano ◽  
Pablo Gili-Manzanaro ◽  
...  

Abstract Alzheimer’s disease (AD) is characterized by a progressive loss of neurons and cognitive functions. Therefore, early diagnosis of AD is critical. The development of practical and non-invasive diagnostic tests for AD remains, however, an unmet need. In the present proof-of-concept study we investigated tear fluid as a novel source of disease-specific protein and microRNA-based biomarkers for AD development using samples from patients with mild cognitive impairment (MCI) and AD. Tear protein content was evaluated via liquid chromatography-mass spectrometry and microRNA content was profiled using a genome-wide high-throughput PCR-based platform. These complementary approaches identified enrichment of specific proteins and microRNAs in tear fluid of AD patients. In particular, we identified elongation initiation factor 4E (eIF4E) as a unique protein present only in AD samples. Total microRNA abundance was found to be higher in tears from AD patients. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD with elevated levels present in AD tear fluid samples compared to controls. Our study suggests that tears may be a useful novel source of biomarkers for AD and that the identification and verification of biomarkers within tears may allow for the development of a non-invasive and cost-effective diagnostic test for AD.


2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Scott M. Langevin ◽  
Melissa Eliot ◽  
Rondi A. Butler ◽  
Agnes Cheong ◽  
Xiang Zhang ◽  
...  

2020 ◽  
Author(s):  
Yumin Li ◽  
Jia Liu ◽  
Yukun Cao ◽  
Xiaoyu Han ◽  
Guozhu Shao ◽  
...  

Abstract Myocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiacspecific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. Serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels were elevated in LGE-positive patients compared with LGE-negative patients. The LGE-positive patients had lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group and the healthy controls. The LGE% was independently associated with the Nt-proBNP levels, GCS, MWT and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP≥108 pg/mL and MWT≥17.3 mm had good diagnostic performance for LGE, with a specificity of 81.3% and sensitivity of 70.0%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.


Oral Oncology ◽  
2012 ◽  
Vol 48 (5) ◽  
pp. 469-474 ◽  
Author(s):  
Marco Mozzati ◽  
Giorgia Gallesio ◽  
Valentina Arata ◽  
Renato Pol ◽  
Matteo Scoletta

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xavier Hadoux ◽  
Flora Hui ◽  
Jeremiah K. H. Lim ◽  
Colin L. Masters ◽  
Alice Pébay ◽  
...  

Abstract Studies of rodent models of Alzheimer’s disease (AD) and of human tissues suggest that the retinal changes that occur in AD, including the accumulation of amyloid beta (Aβ), may serve as surrogate markers of brain Aβ levels. As Aβ has a wavelength-dependent effect on light scatter, we investigate the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Aβ. Significant differences in the retinal reflectance spectra are found between individuals with high Aβ burden on brain PET imaging and mild cognitive impairment (n = 15), and age-matched PET-negative controls (n = 20). Retinal imaging scores are correlated with brain Aβ loads. The findings are validated in an independent cohort, using a second hyperspectral camera. A similar spectral difference is found between control and 5xFAD transgenic mice that accumulate Aβ in the brain and retina. These findings indicate that retinal hyperspectral imaging may predict brain Aβ load.


2020 ◽  
Vol 9 (3) ◽  
pp. 872
Author(s):  
Till van Gemmeren ◽  
Ramona Schuppner ◽  
Gerrit M. Grosse ◽  
Jessica Fering ◽  
Maria M. Gabriel ◽  
...  

To investigate whether neutrophil granulocytes’ function relates to post-stroke infections and clinical outcome after stroke, we prospectively recruited 95 patients after ischemic stroke and tested them for their microbiocidal neutrophil functions in this exploratory study. Additionally, 24 age-adjusted controls were examined regarding neutrophil function. Phagocytic capacity and the ability of the neutrophil granulocytes to produce reactive oxygen species (ROS) as well as CD11b and CD16 receptor expression profile were measured by flow cytometry at days 1, 3, 7, and 90 after symptom onset. Primary outcome was the development of an infection within the first week after stroke. Results of neutrophil functional measurements were compared between patients with and without infection as well as between all stroke patients and controls. Further risk factors for the development of infections were summarized in an infection-risk score for the purpose of multivariate statistical analysis. The ROS production in neutrophils after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) was reduced at baseline in patients with post-stroke infections compared to those without (p = 0.013). This difference proved to be independent from the infection-risk score in the binary logistic regression (p = 0.011). Phagocytosis and oxidative bursts were not significantly reduced in the whole stroke patient group compared to controls. Dysfunction of neutrophil granulocytes seems to play a significant role in the development of post-stroke infections. Further studies are warranted to investigate neutrophil granulocytes´ function as a potential biomarker of post-stroke infections.


Author(s):  
Sophie Hardy ◽  
Andrea Schneider ◽  
Marion Frankenberger ◽  
Andrea Koch ◽  
Katrin Milger ◽  
...  

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