While resveratrol protects organisms from the deleterious effects of oxidative stress, its multifarious mechanism of action limits its potential as a selective medicinal agent. To address this shortcoming, we have designed a molecular scaffold that we have termed a resveramorph. The structure of this compound class possesses much of the functional group characteristics of resveratrol but in a non-planar molecular arrangement and, in the present work, we probe the neuroprotective activities of two resveramorph analogs. These novel compounds were found to protect neurotransmission from hydrogen peroxide-induced oxidative stress. Our findings demonstrate that, at a subnanomolar level, one analog, resveramorph 1, protects synaptic transmission from acute oxidative stress at the Drosophila neuromuscular junction. These results position resveramorphs as potential lead compounds in the development of new drugs for neurodegenerative diseases.
Objective: To highlight the association of early donor chimerism status at 2nd month with various survival outcomes.
Method: The retrospective study was conducted at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, and comprised patient data from January 2011 to July 2016. Data related to participants who underwent human leukocyte antigen-matched transplants for bone marrow failure syndrome and beta thalassemia major. Short tandem repeat-based polymerase chain reaction was used to assess donor chimerism status. Overall survival, disease-free survival, relapse-free survival, and graft versus host disease-free survival rates were noted. Data was analysed using SPSS 23.
Results: Of the 106, 64(60.4%) had bone marrow failure syndrome and 42(39.6%) had beta thalassemia major. The overall median follow-up was 13.53 months (range: 1.81-62.73 months). Early donor chimerism status was associated with overall survival (p=0.02) and disease-free survival (p=0.01). Mixed donor chimerism was less hazardous in terms of overall survival (p=0.04) and disease-free survival (p=0.02).
Conclusion: Early mixed donor chimerism contributed to optimal survival in nonmalignant disease.
Key Words: Hematopoietic stem cell transplantation, Nonmalignant diseases, Survival outcome, Conditioning regimen.
(2018) BK channels and a cGMP-dependent protein kinase (PKG) function through independent mechanisms to regulate the tolerance of synaptic transmission to acute oxidative stress at the Drosophila larval neuromuscular junction,
Introduction
A proatlantal intersegmental artery (PIA) is an exceedingly rare primitive anastomosis between the carotid and vertebrobasilar circulations. PIA’s may be accompanied by ipsilateral or bilateral vertebral artery (VA) agenesis and can originate from the cervical internal carotid artery (ICA, type I) or external carotid artery (ECA, type II) before eventually joining the vertebrobasilar system. Several authors have described this anomaly in different clinical scenarios, but to our knowledge, there are no studies documenting intracranial vertebral artery angioplasty through a type II PIA in the setting of a vertebrobasilar stroke.
Methods
Single case study
Results
A 62‐year‐old male presented to the ED with slurred speech that began one hour prior to arrival. Computer tomography (CT) of the head revealed a small right posterior acute parietal subdural hematoma, and CT perfusion scan revealed ischemia of the cerebellar hemispheres bilaterally with small areas of core infarction and a moderate‐to‐large surrounding penumbra. Magnetic resonance imaging (MRI) of the brain was positive for bilateral acute ischemic strokes of the cerebellar and pontine arteries. CT angiogram of the head and neck revealed high grade stenosis of the right intracranial VA and narrowing of the left V1, V2, and V3 segments. The proximal left V4 segment was occluded with distal reconstitution. Catheter angiogram of the ICAs and ECAs showed that the patient’s right VA did not originate from the right subclavian artery but instead from the right ECA. The patient was subsequently determined to have a type II PIA with critical stenosis. We proceeded with right VA submaximal angioplasty via the type II PIA. The procedure went without complications and resulted in restoration of vertebrobasilar blood flow, with only moderate stenosis following the submaximal angioplasty. On day 5 postoperatively, the patient reported resolution of his symptoms and was subsequently discharged.
Conclusions
We presented a case of vertebrobasilar stroke in which the right VA did not originate from the right subclavian artery but instead from the ECA, with a subsequent diagnosis of a type II PIA. The only option for management was to perform the right VA angioplasty via the PIA, which we believe to be the first documented case of intracranial vertebral angioplasty through a type II PIA. This case serves as a reminder of the very rare cases of persistent fetal circulation and the importance of performing a catheter angiogram of both the ICA and ECA. Evaluation of the ECA and subsequent observation of a PIA can completely change both the management and outcomes of the patient. This case underscores the complexity of the intracranial atherosclerotic disease, the beneficial role of endovascular intervention, and the necessity of future studies to identify the optimal treatment methods for vertebrobasilar stroke.
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