Myricetin as a Promising Molecule for the Treatment of Post-Ischemic Brain Neurodegeneration

The available drug therapy for post-ischemic neurodegeneration of the brain is symptomatic. This review provides an evaluation of possible dietary therapy for post-ischemic neurodegeneration with myricetin. The purpose of this review was to provide a comprehensive overview of what scientists have done regarding the benefits of myricetin in post-ischemic neurodegeneration. The data in this article contribute to a better understanding of the potential benefits of myricetin in the treatment of post-ischemic brain neurodegeneration, and inform physicians, scientists and patients, as well as their caregivers, about treatment options. Due to the pleiotropic properties of myricetin, including anti-amyloid, anti-phosphorylation of tau protein, anti-inflammatory, anti-oxidant and autophagous, as well as increasing acetylcholine, myricetin is a promising candidate for treatment after ischemia brain neurodegeneration with full-blown dementia. In this way, it may gain interest as a potential substance for the prophylaxis of the development of post-ischemic brain neurodegeneration. It is a safe substance, commercially available, inexpensive and registered as a pro-health product in the US and Europe. Taken together, the evidence available in the review on the therapeutic potential of myricetin provides helpful insight into the potential clinical utility of myricetin in treating neurodegenerative disorders with full-blown dementia. Therefore, myricetin may be a promising complementary agent in the future against the development of post-ischemic brain neurodegeneration. Indeed, there is a scientific rationale for the use of myricetin in the prevention and treatment of brain neurodegeneration caused by ischemia.     

Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes.

AIMS: To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. METHODS: Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. RESULTS: PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P < 0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P < 0.001; anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication-free patients (P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427). CONCLUSIONS: In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.     

Ischemic tau protein gene induction as an additional key factor driving development of Alzheimer’s phenotype changes in CA1 area of hippocampus in an ischemic model of Alzheimer’s disease

Background

Tauopathies are a class of neurodegenerative illnesses associated with the aberrant accumulation of the tau protein in the brain. The best known out of these diseases is Alzheimer’s disease, a disorder where the microtubule associated tau protein becomes hyperphosphorylated (which lowers its binding affinity to microtubules) and accumulates inside neurons in the form of tangles. In this study, we attempt to find out whether brain ischemia may play an important role in tau protein gene alterations.

Breast cancer: Current and future endocrine therapies

Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones.     

Macular corneal dystrophy including histologic and ultrastructural changes

PURPOSE: The study reports the results of a histological and ultrastructural examination of the corneal button, obtained during penetrating keratoplasty from patient with clinically recognized macular corneal dystrophy. MATERIAL AND METHODS: 34-year-old male patient suffering from macular corneal dystrophy (MCD) has been treated on corneal epithelium defect and photophobia since his early childhood. Visual acuity was decreased on the Snellen test chart to 0.02. Slit-lamp examination, and ultrasonographical measurement of the cornea's thickness were performed. Removed during penetrating keratoplasty corneal button was divided into two pieces. One of them was prepared in standard procedure for histological examination in the light microscopy after having been stained with hematoxylin and eosin, alcian blue and paS-method. From the other part, slides for ultrastructural examination in the transmission electron microscopy were prepared with the use of standard method. The family history from the patient was also taken, and available relatives have undergone examination in search of typical MCD symptoms. RESULTS: Slit-lamp examination findings revealed diffuse, from limbus to limbus, stromal opacification. In measurement by pachymeter cornea's thickness was reduced. In the light microscopy, in typical stained slides, delaminations within stroma and deficit of endothelial cells were observed. After being stained with alcian blue, dark blue deposits in the places of delamination became visible. By transmission electron microscopic examination, intracellular and extracellular deposits were detected in the stroma, Descemet membrane and endothelium. Distended keratocytes with enormous vacuoles containing abnormal material were found. Pedigree was typical for autosomal recessive inherited disease. CONCLUSIONS: Histological and ultrastructural diagnosis is a basis of recognition of macular corneal dystrophy. Analysis of the pedigree as well as ultrasonographical measurement of the cornea's thickness is very helpful to establish the right diagnosis.     

Synaptosomal susceptibility on global ischaemia caused by cardiac arrest correlated with early and late times after recirculation in rats

The aim of the study was to assess the sensitivity of brain synaptosomes and their mitochondria to the effects of global cerebral ischaemia caused by temporary cardiac arrest and the early and late consequences. The effects of 10 min of global ischaemia were measured immediately and after 1 h, 24 h and 7 days post-resuscitation. Ischaemia caused a reduction in oxygen consumption by synaptosomes of about 20%, a drop in ATP/ADP ratio of about 40%, a decrease in CrP/Cr ratio at about 45% and a reduction of synaptic vesicles and disturbances in the mitochondrial structure in isolated synaptosomes and in nerve endings of brain specimens. Morphometric analysis showed that ischaemic conditions caused a decrease in synaptic vesicles by about 61% and an increase of mitochondrial damage to 58 and 50% after 1 and 24 h postreperfusion time, respectively. Seven days postresuscitation, all the observed changes returned to normal but small numbers (about 2%) of neurones which were destroyed neurons appeared at that time. It is concluded that global ischaemia with early resuscitation after cardiac arrest may lead to damage of synaptosomes and synaptic mitochondria. This, in turn, modifies substrate oxidation, synthesis of energy variables and affects neurotransmitter function. The observed disturbances return to normal later after resuscitation but the ischaemic events and reoxygenation caused selective morphological injury of certain neurones and this may form the basis for irreversible brain damage.     

Severe hepatic involvement in visceral larva migrans.

Because of its anatomical position, the liver may be involved in many protozoan and helminthic gastrointestinal infections. Visceral larva migrans caused by Toxocara canis is rarely taken into account in adult patients with cholestatic syndrome, especially when liver disease is not associated with hypereosinophilic reaction. We report on a 74-year-old immunocompetent woman who presented with fever, bronchospasm, erythema nodosum, weight loss and progressive jaundice. A liver biopsy showed caseating granulomatous hepatitis with secondary portal fibrosis and paucity of interlobular bile ducts. A step-by-step search for aetiological factors led us to a diagnosis of toxocariasis (positive enzyme-linked immunosorbent assay IgG test). An excellent clinical response to combined treatment with steroid and diethylcarbamazine, and a reduction in the antibody level against T. canis supported the diagnosis. Computed tomography and laparoscopy demonstrated multiple small mass lesions and fibrous perihepatitis. This report shows that visceral larva migrans may be a cause of prostrating chronic liver disease and should be suspected in every febrile patient with cryptogenic cholestatic hepatitis.     

Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain

BACKGROUND: Anesthetics, including isoflurane and nitrous oxide, an antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor, have been demonstrated to induce apoptotic neurodegeneration when administered during neurodevelopment. Xenon, also an N-methyl-D-aspartate antagonist, not only lacks the characteristic toxicity produced by other N-methyl-D-aspartate antagonists, but also attenuates the neurotoxicity produced by this class of agent. Therefore, the current study sought to investigate xenon's putative protective properties against anesthetic-induced neuronal apoptosis. METHOD: Separate cohorts (n = 5 or 6 per group) of 7-day-old rats were randomly assigned and exposed to eight gas mixtures: air, 75% nitrous oxide, 75% xenon, 0.75% isoflurane, 0.75% isoflurane plus 35% or 75% nitrous oxide, 0.75% isoflurane plus 30% or 60% xenon for 6 h. Rats were killed, and cortical and hippocampal apoptosis was assessed using caspase-3 immunostaining. In separate cohorts, cortices were isolated for immunoblotting of caspase 3, caspase 8, caspase 9, and cytochrome c. Organotypic hippocampal slices of postnatal mice pups were derived and cultured for 24 h before similar gas exposures, as above, and subsequently processed for caspase-3 immunostaining. RESULTS: In vivo administration of isoflurane enhances neuronal apoptosis. When combined with isoflurane, nitrous oxide significantly increases whereas xenon significantly reduces apoptosis to a value no different from that of controls. In vitro studies corroborate the ability of xenon to attenuate isoflurane-induced apoptosis. Isoflurane enhanced expression of indicators of the intrinsic and common apoptotic pathways; this enhancement was increased by nitrous oxide but attenuated by xenon. CONCLUSIONS: The current study demonstrates that xenon prevents isoflurane-induced neonatal neuronal apoptosis.