Medical hypotheses
-
Alzheimer's disease (AD) is the most common cause of dementia in developed countries. AD is characterized pathologically by the presence of senile plaques and neurofibrillary tangles (NFTs), the major constituents of which are amyloid beta protein (A beta) and tau protein, respectively. Based on the disease pathology, numerous blood and cerebrospinal fluid (CSF) tests have been proposed for early detection of AD. ⋯ In human AD brains, AGEs are distributed in the cytosol of neurons in the hippocampus and para-hippocampal gyrus. In this paper, we discuss the pathophysiological role for toxic AGEs (TAGE) in AD. We further review here the possibility that serum or cerebrospinal fluid levels of TAGE could become a promising biomarker for early detection of AD.
-
Voltage-dependent calcium channels (VDCCs) are heteromultimeric complexes that mediate calcium influx into cells in response to changes in membrane potential. The alpha1A subunit, encoded by the CACNA1A gene, is the pore-forming subunit specific to the neuronal P/Q-type VDCCs. These are implicated in fast excitatory and inhibitory neurotransmission. ⋯ These drugs improve ataxia in cases of CCA, olivopontocerebellar atrophy and ataxia-telangiectasia. On the basis of the neuropathological identity of SCA 6 with CCA, and given the capacity of gabapentin and pregabalin to decrease P/Q-type VDCCs inactivation, in this paper the authors put forward the hypothesis that the administration of gabapentin and pregabalin might prove beneficial in SCA 6 as the ataxia caused by this disease would be expected to improve. The authors hope that researchers working with this illness will be inspired and encouraged to undertake the appropriate clinical and experimental work.
-
Oxidative stress underlies postoperative atrial fibrillation and electrophysiological remodelling associated with rapid atrial pacing. An increasing body of evidence indicates that the formation of reactive oxygen species (ROS) released following extracorporeal circulation are involved in the structural and functional myocardial impairment derived from the ischemia-reperfusion cycle. ROS behave as intracellular messengers mediating pathological processes, such as inflammation, apoptosis and necrosis, thereby participating in the pathophysiology of atrial fibrillation. ⋯ In turn, experimental studies have revealed that non-enzymatic antioxidants produce a significant functional amelioration in cardiomyocytes subjected to an oxidative challenge. Moreover, clinical studies with patients scheduled for primary coronary artery bypass graft surgery had a reduced incidence of postoperative atrial fibrillation. We present the hypothesis of non-hypoxic preconditioning based on the association of pretreatment with n-3 polyunsaturated fatty acids followed by ascorbate plus alpha-tocoferol supplementation diminishes the incidence of postoperative atrial fibrillation in patients subjected to cardiac surgery with extracorporeal circulation.
-
Amniotic fluid embolism, a rare, sudden and often fatal illness of pregnancy may not be a true embolic event resulting from the physical obstruction of the pulmonary vasculature. The high degree of variability in symptoms, the lack of characteristic findings on radiological exam, the absence of a dose-response effect on symptoms, and the occasional occurrence of coagulopathies are not entirely consistent with a physical block to the circulation as the main mechanism of disease. Alternatively, it might be the result of complement activation initiated by fetal antigen leaking into the maternal circulation. ⋯ Direct measurement of serum complement as well as serum tryptase and urinary histamine are readily obtained tests in community hospitals as well as tertiary care hospitals. If the hypothesis proves true, this investigation may be of profound importance to understanding immune tolerance. Rather, than asking why one pregnant woman in 20,000 develops a violent immune reaction to the fetus, a better question is why do not all pregnant women reject the fetus which is a large collection of foreign antigens?
-
Hematopoietic stem cells transplantation has been wildly used in clinical settings and has shown exciting results in treating a wide variety of diseases. However, the relative small number of hematopoietic stem cells in bone marrow, even lower in peripheral or umbilical cord blood limits its clinical utility. There are several protocols, which have been developed to expand hematopoietic stem cells to reach clinical goal. ⋯ And the recombinant fusion proteins could be used in expanding hematopoietic stem cells. Meanwhile, Cdx4 fusion proteins would be more efficient than other methods that had been developed for it can up-regulate a cocktail of hox genes, which has been proved to be capable of amplifying hematopoietic stem cells. It would provide us an alternative protocol to amplify hematopoietic stem cells if the hypothesis proved to be practical.