Correction of ultrastructural paclitaxel-induced spinal cord motoneurons lesions

Background. Paclitaxel-induced peripheral neuropathy (PIPN) is a major side effect of paclitaxel in patients with cancer with no fully known mechanisms. The aim of the study was to investigate the fine sub-microscopic structure of the spinal cord anterior horn neurons in PIPN combined with 2-ethyl-6-methyl-3-hydroxypyridine succinate administration. Methods. The experiment was performed on 80 white rats, which were administered intraperitoneally with Paclitaxel (Actavis, Romania), pre-dissolved in an isotonic saline at a dose of 2 mg / kg body weight four times a day to achieve a dose of 8 mg / kg. Then 48 of these animals were injected intraperitoneally 2-ethyl-6-methyl-3-hydroxypyridine succinate at a dose of 10 mg / kg (32 rats received intraperitoneally water for injection). Observation periods were 1, 7, 14, 21, 28 days. Results. We found that 2-ethyl-6-methyl-3-hydroxypyridine corrects the morpho-functional state of the motor neurons of the spinal cord and revealed a positive metabolic effect on them. Conclusion. This was manifested by the improvement of the electron microscopic picture of the neuronal structures responsible for their protein-synthetic (granular endoplasmic reticulum, ribosomes and polysomes), respiratory (mitochondria), and protective (lysosomes) functions.

Dentate nucleus deep brain stimulation: Technical note of a novel methodology assisted by tractography

Background: The cerebellum has emerged as an attractive and promising target for neuromodulation in movement disorders due to its vast connection with important cortical and subcortical areas. Here, we describe a novel technique of deep brain stimulation (DBS) of the dentate nucleus (DN) aided by tractography. Methods: Since 2015, patients with movement disorders including dystonia, ataxia, and tremor have been treated with DN DBS. The cerebellar target was initially localized using coordinates measured from the fastigial point. The target was adjusted with direct visualization of the DN in the susceptibility-weighted imaging and T2 sequences of the MRI and finally refined based on the reconstruction of the dentatorubrothalamic tract (DRTT). Results: Three patients were treated with this technique. The final target was located in the anterior portion of DN in close proximity to the DRTT, with the tip of the lead on the white matter and the remaining contacts on the DN. Clinical outcomes were variable and overall positive, with no major side effect. Conclusion: Targeting the DN based on tractography of the DRTT seems to be feasible and safe. Larger studies will be necessary to support our preliminary findings.

Exercise Inhibits Doxorubicin-Induced Damage to Cardiac Vessels and Activation of Hippo/YAP-Mediated Apoptosis

Dose-related cardiomyopathy is a major side effect following doxorubicin (Dox). To investigate whether exercise (Ex)-induced vasculogenesis plays a role in reducing Dox-induced cardiotoxicity, GFP+ bone marrow (BM) cells from GFP transgenic mice were transplanted into wild-type mice. Transplanted mice were treated with Dox, Ex, Dox+Ex, or control. We found Dox therapy resulted in decreased systolic and diastolic blood flow, decreased ejection fraction and fractional shortening, and decreased vascular endothelial cells and pericytes. These abnormalities were not seen in Dox+Ex hearts. Heart tissues from control-, Ex-, or Dox-treated mice showed a small number of GFP+ cells. By contrast, the Dox+Ex-treated hearts had a significant increase in GFP+ cells. Further analyses demonstrated these GFP+ BM cells had differentiated into vascular endothelial cells (GFP+CD31+) and pericytes (GFP+NG2+). Decreased cardiomyocytes were also seen in Dox-treated but not Dox+Ex-treated hearts. Ex induced an increase in GFP+c-Kit+ cells. However, these c-Kit+ BM stem cells had not differentiated into cardiomyocytes. Dox therapy induced phosphorylation of MST1/2, LATS1, and YAP; a decrease in total YAP; and cleavage of caspase-3 and PARP in the heart tissues. Dox+Ex prevented these effects. Our data demonstrated Dox-induced cardiotoxicity is mediated by vascular damage resulting in decreased cardiac blood flow and through activation of Hippo-YAP signaling resulting in cardiomyocyte apoptosis. Furthermore, Ex inhibited these effects by promoting migration of BM stem cells into the heart to repair the cardiac vessels damaged by Dox and through inhibiting Dox-induced Hippo-YAP signaling-mediated apoptosis. These data support the concept of using exercise as an intervention to decrease Dox-induced cardiotoxicity.

Statin-induced rhabdomyolysis: a cautionary tale for high-dose rosuvastatin

Statins are a widely prescribed lipid-lowering agent for preventing adverse cardiovascular events. However, a major side effect is rhabdomyolysis, a breakdown of muscle tissue, which can cause acute kidney injury and death. We present a case of a 77-year-old Chinese woman who was started on 40 mg rosuvastatin post-percutaneous coronary intervention and ultimately developed rhabdomyolysis and acute kidney injury one month later. This case highlights the need to consider patient risk factors for developing statin-induced rhabdomyolysis when choosing the right dose of statin to prescribe.

Should Couch Potatoes Be Encouraged to Use Transcranial Direct Current Stimulation?

A very high percentage of the world population doesn’t exercise enough and, as a consequence, is at high risk of developing serious health conditions. Physical inactivity paired with a poor diet is the second cause of death in high income countries. In this paper, I suggest that transcranial direct stimulation (tDCS) holds promise for “couch potatoes” because it could be used to make them more active, without causing any major side-effect. I also argue that other, less safe, tools could be used to achieve the goal of decreasing physical inactivity, insofar as they have overall fewer side-effects than physical inactivity.

Chronic exposure of ErbB TKIs inhibits DRA expression and activity through an ERK/Elk-1/CREB/AP-1 dependent pathway

Diarrhea is the major side effect of first- and second-generation ErbB tyrosine kinase inhibitors (TKI), the mechanism of which remains incompletely understood. The current studies were carried out over the time frame that ErbB TKIs usually initiate diarrhea. We report in Caco-2/bbe cells that exposure of ErbB TKIs, but not non-ErbB TKIs for six days at clinically-relevant concentrations significantly reduced the expression of DRA and inhibited apical Cl-/HCO3-exchange activity. The ErbB TKIs decreased DRA expression through an ERK/Elk-1/CREB/AP-1 dependent pathway. The blockade of ERK phosphorylation by ErbB TKIs decreased the phosphorylation of Elk-1 and the amount of total and p-CREB, and reduced the expression of C-Fos, which is part of the AP-1 complex that maintain DRA expression. Altogether, our studies demonstrate that ErbB TKIs decrease expression and activity of DRA, which occurs over the time frame that these drugs clinically cause diarrhea, and since DRA is part of the intestinal neutral NaCl absorptive process, the reduced absorption is likely to represent a major contributor to the ErbB TKI-associated diarrhea.

Thyroid hormone (T3) plus dual-specificity phosphatase-5 siRNA therapy regenerates the myocardium lost as a result of doxorubicin cardiotoxicity

Doxorubicin is a widely used antineoplastic drug. However, its major side effect, cardiotoxicity, results from cardiomyocyte loss that causes left ventricle (LV) wall thinning, chronic LV dysfunction and heart failure. Here, we show that transient therapy with thyroid hormone (triiodothyronine, T3) and dual-specificity phosphatase-5 (DUSP5) siRNA results in cardiomyocyte proliferation. siRNA-directed depletion of DUSP5, a nuclear localized p-ERK1/2-specific phosphatase, sensitizes cardiomyocytes to the proliferative effects of T3 by potentiating p-ERK1/2 accumulation resulting from the activation of T3-mediated insulin-like growth factor-1 (IGF-1) signaling. In mice with chronic doxorubicin cardiotoxicity, this therapy regenerates the LV myocardium by cardiomyocyte proliferation, reverses LV dysfunction and prevents progressive chamber dilatation, providing a strategy for addressing a currently untreatable condition.

Role of nano-collagen particles dressing in the management of chronic ulcer: a prospective non-randomized trial on 100 cases

Background: Collagen has unique property of adhere to the ulcer floor thus reduces plasma oozing, bacterial colonization, pain and ulcer size which boost the process of granulation and epithelialization thus healing.Methods: In this prospective, non-randomized study 100 patients of different age and sex having chronic ulcer situated on various parts of the body were taken. Nano collagen particles preparation “collofibre” of TNC health care was used.Results: Most of the patients fall in their most productive life (3rd and 4th decade), restricted mobility due to pain. Thus anaemia, diabetes, old age, debility, bed ridden situations, other associated injuries and certain medical conditions contribute to delay in ulcer healing and hospital stay. Bacterial contamination, presence of necrotic tissue and slough delay the healing process. 73% of patients complain of itching and burning sensation after application otherwise no major side effect detected.Conclusions: Use of nano collagen particles dressing accelerate the healing process in chronic ulcers.

Surgery for Patients with Radiation-Induced Constrictive Pericarditis

Radiation-induced heart disease (RIHD) is a major side effect of chest radiation therapy (RT). Most changes of pericardium will occur within a few weeks after receiving chest RT, while most of them will take decades or more to become constrictive pericarditis. Pericardiectomy is an effective treatment method. Here, we report 2 cases of radiation pericarditis after chest RT at our center.

Contrast Induced Nephropathy After Brain and Cervical CT Angiography in Stroke Patients: A Prospective Study

Background: Contrast-induced nephropathy (CIN) is a major side effect of intravenous iodinated contrast and causes both short- and long-term adverse effects. While diagnostic and interventional procedures of brain ischemia are recently advanced, it is necessary to be cautious about its major side effect. Objectives: To evaluate CIN and its risk factors in neurology patients after brain and cervical CT angiography. Materials & Methods: This prospective cross-sectional study was conducted on all patients who were admitted in stroke department of Nemazee hospital, affiliated to Shiraz University of Medical Sciences, Fars, Iran, and had undergone brain and cervical CT angiography from September 2014 to September 2016. Blood urea nitrogen (BUN) and creatinine (Cr) before contrast (BUN1, Cr1), 3 days after contrast (BUN2, Cr2), and 30 days after contrast (BUN3, Cr3) were recorded. t-test, paired t-test, Chi-squared test, repeated measurement-test and also SPSS V. 21 are used for statistical analysis. Results: 5(2.7%) patients developed CIN after receiving contrast. However, repeated measurement of glomerular filtration rate (GFR) and Cr at the end of one month showed no significant changes between Cr3 and GFR3 in 2 groups of non-CIN and CIN patients, and all patients showed normal renal function at that time. Multiivariate logistic regression analysis demonstrated that hemoglobin (Hb) level is related to CIN (OR:0.5, CI: 0.28-0.90). Conclusion: Our data showed that the rate of CIN in neurovascular evaluation was insignificant, but it is related to Hb level.