Functional cortical mapping and structural subcortical anatomy predicts intra-operative speech arrest: a nTMS-tractography study.

Objective: Cortical speech mapping using navigated Transcranial Magnetic Stimulation (nTMS) has a variable positive predictive value (PPV) when compared with intraoperative direct electrical stimulation.

Methods: This is a single centre prospective study of all patients undergoing pre-operative nTMS and tractography (frontal aslant tract (FAT) and arcuate fasciculus (AF)) for awake surgery between October 2018 and November 2023. We reviewed operative notes for speech arrest, collected data on demographics, histopathology and pre-/post-operative language assessment.

Impaired Mineral Ion Metabolism in a Mouse Model of Targeted Calcium-Sensing Receptor (CaSR) Deletion from Vascular Smooth Muscle Cells.

Background: Impaired mineral ion metabolism is a hallmark of CKD-metabolic bone disorder. It can lead to pathologic vascular calcification and is associated with an increased risk of cardiovascular mortality. Loss of calcium-sensing receptor (CaSR) expression in vascular smooth muscle cells exacerbates vascular calcification Conversely, vascular calcification can be reduced by calcimimetics, which function as allosteric activators of CaSR.

Claudin-2 Expression Levels in Ulcerative Colitis: Development and Validation of an In-Situ Hybridisation Assay for Therapeutic Studies.

Ulcerative colitis is a chronic inflammatory disease affecting the colon and is characterized by epithelial damage and barrier dysfunction. Upregulation of the tight junction protein claudin-2 by cytokines is hypothesized to contribute to the dysregulation of the epithelial barrier. New therapeutic agents which block the action of cytokines are being investigated in patients with ulcerative colitis.

Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor.

Epidemiological studies suggest an inverse correlation between dietary calcium (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In the colon, CaSR has been suggested to regulate proliferation of colonocytes.

An integrated characterization of serological, pathological, and functional events in doxorubicin-induced cardiotoxicity.

Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1.

Significant attenuation of stimulated cortisol in early Graves disease without adrenal autoimmunity.

Objective: To investigate cortisol responses to adrenocorticotropic hormone during thyrotoxic (G1) and euthyroid (G2) phases in patients with Graves disease (GD) who were without adrenal autoimmunity.

Methods: Fifteen patients with GD, who were thyrotropin receptor antibody positive and 21-hydroxylase antibody negative, were recruited to this prospective pilot study. A modified short Synacthen test (SST) was performed, in which cortisol was measured every 30 minutes for 2 hours during G1 and G2.

Evaluation of novel urinary renal biomarkers: biological variation and reference change values.

A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We used two multiplex assays for these novel biomarkers to quantify biomarker concentration in serial urine collections from rats of both sexes administered varying concentrations of cisplatin. From these data, we calculate inter-individual variation and reference ranges from predose animals and intra-individual variation and reference change values from undosed control animals.

Application of Dolichos biflorus in immunoassay detection of kidney collecting duct biomarkers.

Currently there are no biomarkers for detecting collecting duct damage in man. Antibodies to several collecting duct-specific antigens exist but sandwich assays have been difficult to establish due to the need for two different antibodies to the same protein. We hypothesized that a collecting duct-specific lectin could be used in combination with a collecting duct-specific antibody to negate the need for two different antibodies.

Expression and localization of rat aldo-keto reductases and induction of the 1B13 and 1D2 isoforms by phenolic antioxidants.

The aldo-keto reductase (AKR) phase I drug metabolism enzyme superfamily is implicated in detoxification or bioactivation of a wide variety of carbonyl-bearing compounds. In this study, we have used antibodies raised against purified recombinant rat AKR isoforms 1A3, 1B4, 1C9, 1D2, and 7A1 to characterize the expression profile of these superfamily members in the rat and define their localization by immunohistochemistry. Western blotting showed that AKR1A3, AKR1B4, and AKR1C9 are ubiquitously expressed, whereas AKR1D2 and AKR7A1 are present in liver, adrenal gland, and kidney, with the latter also present in testis, spleen, and stomach.

Expression of hexokinase isoforms in the dorsal root ganglion of the adult rat and effect of experimental diabetes.

The effect of streptozotocin (STZ)-induced diabetes on expression and activity of hexokinase, the first enzyme and rate-limiting step in glycolysis, was studied in sensory neurons of lumbar dorsal root ganglia (DRG). The DRG and sciatic nerve of adult rats expressed the hexokinase I isoform only. Immunofluorescent staining of lumbar DRG demonstrated that small-medium neurons and satellite cells exhibited high levels of expression of hexokinase I.

Thioredoxin interacting protein is increased in sensory neurons in experimental diabetes.

Diabetic neuropathy is a major complication of diabetes and has multifactoral aetiology. The exact cause of damage is unknown although high glucose and oxidative stress are known to contribute significantly. In order to identify molecular targets of the disease and possibly new therapeutic targets, we previously examined the effect of diabetes on dorsal root ganglia (DRG) neurons using Affymetrix gene chip arrays.

Identification of changes in gene expression in dorsal root ganglia in diabetic neuropathy: correlation with functional deficits.

This study aimed to correlate the onset of functional deficits in diabetic neuropathy with changes in gene expression in rat dorsal root ganglia (DRG). After 1, 4, or 8 weeks of streptozotocin-induced diabetes, sensory and motor nerve conduction velocities (NCV) were measured as an indicator of neuropathy and changes in gene expression were measured using Affymetrix oligonucleotide microarrays. No significant changes in NCV were found after 1 week of diabetes, but after 4 and 8 weeks, there was a significant reduction in both sensory and motor NCV.

Gene transfer of an engineered transcription factor promoting expression of VEGF-A protects against experimental diabetic neuropathy.

Peripheral neuropathy is a common, irreversible complication of diabetes. We investigated whether gene transfer of an engineered zinc finger protein transcription factor (ZFP-TF) designed to upregulate expression of the endogenous vascular endothelial growth factor (VEGF)-A gene could protect against experimental diabetic neuropathy. ZFP-TF-driven activation of the endogenous gene results in expression of all of the VEGF-A isoforms, a fact that may be of significance for recapitulation of the proper biological responses stimulated by this potent neuroprotective growth factor.

Mitogen-activated protein kinase p38 mediates reduced nerve conduction velocity in experimental diabetic neuropathy: interactions with aldose reductase.

This study examined the role of p38 mitogen-activated protein (MAP) kinase in transducing high glucose into deficits in nerve conduction velocity (NCV) that are characteristic of diabetic neuropathy. p38 activation and NCV were measured in streptozocin-induced diabetic rats treated with a p38 inhibitor, an aldose reductase inhibitor, and insulin. Dorsal root ganglia (DRG) from diabetic animals showed marked activation of p38 at 12 weeks of diabetes.

Activation of JNK in sensory neurons protects against sensory neuron cell death in diabetes and on exposure to glucose/oxidative stress in vitro.

Diabetes activates all three groups of MAP kinases in sensory ganglia. Inhibition of this activation for the ERK and p38 groups prevents nerve damage, and agents that improve neuronal function in diabetic rats-antioxidants and aldose reductase inhibitors-also inhibit activation of ERK and p38 in dorsal root ganglia (DRG). However, these same treatments consistently increase activation of JNK.

Insulin prevents depolarization of the mitochondrial inner membrane in sensory neurons of type 1 diabetic rats in the presence of sustained hyperglycemia.

Mitochondrial dysfunction has been proposed as a mediator of neurodegeneration in diabetes complications. The aim of this study was to determine whether deficits in insulin-dependent neurotrophic support contributed to depolarization of the mitochondrial membrane in sensory neurons of streptozocin (STZ)-induced diabetic rats. Whole cell fluorescent video imaging using rhodamine 123 (R123) was used to monitor mitochondrial inner membrane potential (deltapsi(m)).