A pilot observational study on magnesium and calcium imbalance in elderly patients with acute aortic dissection

Vianello, Elena; Dozio, Elena; Barassi, Alessandra; Sammarco, G.; Tacchini, Lorenza; Marrocco-Trischitta, Massimiliano M.; Trimarchi, Santi; Romanelli, Massimiliano Marco Corsi

doi:10.1186/s12979-016-0083-y

Cited by 16 publications

(17 citation statements)

References 28 publications

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“…Functional enrichment analysis suggests that PPIA is, in addition, related to viral responses. In this regard, PPIA is necessary for the replication and reactivation of several virus, including human Cytomegalovirus (CMV) ( 61 ), proposed to be a general cause of immunosenescence ( 62 , 63 ) and more specifically of immunosenescence after SCI ( 64 ). Whether anti-PPIA AAb levels could be an underlying mechanism of immunosenescence/immunodepression after SCI is worth of further studies.…”

Section: Discussionmentioning

confidence: 99%

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

et al. 2018

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Spinal cord injury (SCI) results in long-term neurological and systemic consequences, including antibody-mediated autoimmunity, which has been related to impaired functional recovery. Here we show that autoantibodies that increase at the subacute phase of human SCI, 1 month after lesion, are already present in healthy subjects and directed against non-native proteins rarely present in the normal spinal cord. The increase of these autoantibodies is a fast phenomenon–their levels are already elevated before 5 days after lesion–characteristic of secondary immune responses, further supporting their origin as natural antibodies. By proteomics studies we have identified that the increased autoantibodies are directed against 16 different nervous system and systemic self-antigens related to changes known to occur after SCI, including alterations in neural cell cytoskeleton, metabolism and bone remodeling. Overall, in the context of previous studies, our results offer an explanation to why autoimmunity develops after SCI and identify novel targets involved in SCI pathology that warrant further investigation.

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Section: Discussionmentioning

confidence: 99%

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

et al. 2018

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“…As outlined in the introduction, there is a current interest in repurposing of MTK for the treatment of patients with neurodegenerative diseases such as dementia patients [ 10 , 13 , 14 , 15 ], which show dysphagia, and, therefore, a mucoadhesive film might have certain advantages. Especially for repurposing of MTK in neurodegenerative diseases, preclinical evidence of efficacy in rodent models is typically required.…”

Section: Resultsmentioning

confidence: 99%

“…As evidence arises from animal experiments and from case reports that MTK might be a valuable therapeutic in the field of neurodegenerative diseases [ 13 , 14 , 15 , 23 , 24 ], we found it relevant to investigate whether MTK can be detected in human CSF, as a proof of concept that MTK can pass the blood–brain barrier in humans. After a single dose treatment with MTK mucoadhesive film, we detected MTK in the CSF of healthy subjects in a pharmacological relevant dose in the range of the IC50 (MTK IC50 < 5nM [ 25 ]).…”

Section: Discussionmentioning

confidence: 99%

“…Leukotriene production is elevated in the AD brain [ 11 , 12 ]; leukotrienes are involved in various aspects of AD pathologies, in particular, neuroinflammation and neuronal cell death, and genetic and pharmacological blockage of leukotrienes in animal models of neurodegenerative diseases, including AD, have demonstrated efficacy in reducing pathology and promoting cognitive functions (reviewed in [ 10 ]). Finally, MTK is associated with a reduced risk of dementia, and a recent case report suggested that MTK might improve cognitive function in patients with dementia [ 13 , 14 , 15 ]. Oral mucoadhesive application has several advantages, such as the relatively easy and convenient accessibility of the oral cavity, the limiting of first-pass effects and degradation during the gastro-intestinal transit and the rapid drug absorption due to high blood circulation in the mucosa (as reviewed in [ 16 , 17 ]).…”

Section: Introductionmentioning

confidence: 99%

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Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice

Michael

Sousa

Conway³

et al. 2020

Pharmaceutics

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The leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low- and non-responders in the population. Besides that, tablets are suboptimal formulations for patients suffering from dysphagia, for example, seen in patients with neurodegenerative diseases such as Alzheimer’s disease, a disease with increasing interest in repurposing of MTK. This, and the need for an improved bioavailability, triggered us to reformulate MTK. Our aim was to develop a mucoadhesive MTK film with good safety and improved pharmacological features, i.e., an improved bioavailability profile in humans as well as in a mouse model of Alzheimer’s disease. We tested dissolution of the MTK mucoadhesive film and assessed pharmacoexposure and kinetics after acute and chronic oral application in mice. Furthermore, we performed a Phase I analysis in humans, which included a comparison with the marketed tablet form as well as a quantitative analysis of the MTK levels in the cerebrospinal fluid. The novel MTK film demonstrated significantly improved bioavailability compared to the marketed tablet in the clinical Phase 1a study. Furthermore, there were measurable amounts of MTK present in the cerebrospinal fluid (CSF). In mice, MTK was detected in serum and CSF after acute and chronic exposure in a dose-dependent manner. The mucoadhesive film of MTK represents a promising alternative for the tablet delivery. The oral film might lower the non-responder rate in patients with asthma and might be an interesting product for repurposing of MTK in other diseases. As we demonstrate Blood-Brain-Barrier (BBB) penetrance in a preclinical model, as well as in a clinical study, the oral film of MTK might find its use as a therapeutic for acute and chronic neurodegenerative diseases such as dementias and stroke.

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“…Studies have suggested that there is a close relationship between Mg and vascular diseases and that it has a protective effect against vascular diseases. Such as endothelin-1, this effect has been associated with suppressor effect against many factors showing agonistic effect in the development of vasoconstriction (17)(18)(19). In the case of endothelial damage, it also blocks abnormal coagulation by binding specific coagulation factors such as Ca (20).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Serum Magnesium Levels in Patients with Erectile Dysfunction and Healthy Peers

Benli̇¹,

Çırakoğlu²,

Ayyıldız³

2018

JAREM

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Objective: Erectile dysfunction (ED) is a very common health problem among men that disrupts the quality of life. The aim of this study was to investigate whether serum magnesium levels in patients with ED are different from those in healthy individuals. Methods:The study accessed the data of 344 patients who applied to the urology clinic from 2014 to 2016. Patients were divided into two groups: patients with ED, Group 1 (n=155) and those without ED, Group 2 (control; n=189). Characteristics such as patients' age, additional diseases, and smoking habits were recorded and compared between the two groups along with laboratory parameters such as levels of serum magnesium, calcium, and inflammatory markers. Sexual situation was assessed with the SHIM-5 form.Results: Patients aged 63.15±8.90 years were included in Group 1 and those aged 61.63±8.01 years were included in Group 2 (p=0.101). There were no differences between the groups in terms of BMI and waist circumference (p>0.05). Serum magnesium levels were 1.94±0.20 and 2.00±0.17 mg/dl in groups 1 and 2, respectively (p=0.008). WBC value for inflammatory makers were 6.94±1.74 and 6.58±1.43 in groups 1 and 2, respectively (p=0.04).Conclusion: Our study found that serum magnesium values were reduced in ED patients than in the control group. Therefore, it may be beneficial to determine serum magnesium values in ED patients. Additionally, serum magnesium values may be used as markers for the early identification of patients at risk.

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A pilot observational study on magnesium and calcium imbalance in elderly patients with acute aortic dissection

Cited by 16 publications

References 28 publications

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies

Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice

Comparison of Serum Magnesium Levels in Patients with Erectile Dysfunction and Healthy Peers

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