Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models.

Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs due to reorganization of translation of mRNA in nociceptors.

"Of mice and men": the relevance of Cometin and Erythropoietin origin for its effects on murine spiral ganglion neuron survival and neurite outgrowth .

Neurotrophic factors (NTF) play key roles in the survival of neurons, making them promising candidates for therapy of neurodegenerative diseases. In the case of the inner ear, sensorineural hearing loss (SNHL) is characterized over time by a degeneration of the primary auditory neurons, the spiral ganglion neurons (SGN). It is well known that selected NTF can protect SGN from degeneration, which positively influences the outcome of cochlear implants, the treatment of choice for patients with profound to severe SNHL.

Meteorin Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Mice.

Chemotherapy-induced peripheral neuropathy is a challenging condition to treat, and arises due to severe, dose-limiting toxicity of chemotherapeutic drugs such as paclitaxel. This often results in debilitating sensory and motor deficits that are not effectively prevented or alleviated by existing therapeutic interventions. Recent studies have demonstrated the therapeutic effects of Meteorin, a neurotrophic factor, in reversing neuropathic pain in rodent models of peripheral nerve injury induced by physical trauma.

Antihyperalgesic effects of Meteorin in the rat chronic constriction injury model: a replication study.

Data from preclinical research have been suggested to suffer from a lack of inherent reproducibility across laboratories. The goal of our study was to replicate findings from a previous report that demonstrated positive effects of Meteorin, a novel neurotrophic factor, in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Notably, 5 to 6 intermittent subcutaneous (s.

Automated sequential chromogenic IHC double staining with two HRP substrates.

Automated IHC double staining using diaminobenzidine and HRP Magenta is illustrated utilizing a new acidic block with sulfuric acid to prevent cross-reactivity. Residual cross-reactivity in double staining is determined to arise from chromogenic-bound antibodies and amplification system during the first part of the double staining.

A novel quantitative immunohistochemistry method for precise protein measurements directly in formalin-fixed, paraffin-embedded specimens: analytical performance measuring HER2.

In clinical routine pathology today, detection of protein in intact formalin-fixed, paraffin-embedded tissue is limited to immunohistochemistry, which is semi-quantitative. This study presents a new and reliable quantitative immunohistochemistry method, qIHC, based on a novel amplification system that enables quantification of protein directly in formalin-fixed, paraffin-embedded tissue by counting of dots. The qIHC technology can be combined with standard immunohistochemistry, and assessed using standard bright-field microscopy or image analysis.

Improved catalyzed reporter deposition, iCARD.

Novel reporters have been synthesized with extended hydrophilic linkers that in combination with polymerizing cross-linkers result in very efficient reporter deposition. By utilizing antibodies to stain HER2 proteins in a cell line model it is demonstrated that the method is highly specific and sensitive with virtually no background. The detection of HER2 proteins in tissue was used to visualize individual antigens as small dots visible in a microscope.

Novel horseradish peroxidase substrates for use in immunohistochemistry.

New chromogens expand the colour palette for horseradish peroxidase chromogens used in immunohistochemistry. Tissue staining of cytokeratin with three new cyanine-based chromogens is described. Their use as fluorescent reporters is demonstrated.

CGRP-receptor antagonism in migraine treatment.

Primary headaches are among the most prevalent neurological disorders, afflicting up to 16% of the adult population. Associated pain originates from intracranial blood vessels that are innervated by sensory nerves storing several neurotransmitters. In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP) but not with other neuronal messengers.

The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers.

PACAP38 is an endogenous peptide located in trigeminal perivascular nerve fibers in the brain. It reduces neuronal loss and infarct size in animal stroke models and has been proposed a candidate substance for human clinical studies of stroke. The effect on systemic hemodynamics and regional cerebral blood flow (rCBF) is not well understood.

Phase I safety, tolerability, and pharmacokinetic study of recombinant human mannan-binding lectin.

Mannan-binding lectin (MBL), a human plasma protein, plays an important role in the innate immune defence. MBL recognizes microorganisms through surface carbohydrate structures. Due to genetic polymorphisms, MBL plasma concentrations range from 5 to 10,000 ng/mL.

The in vivo effect of adrenomedullin on rat dural and pial arteries.

Adrenomedullin is related to the calcitonin gene-related peptide (CGRP) family and is present in cerebral blood vessels. It may be involved in migraine mechanisms. We measured the change in dural and pial artery diameter, mean arterial blood pressure and local cerebral blood flow flux (LCBF(Flux)) after intravenous (i.

Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up.

Background: The duration of protection afforded by hepatitis B vaccination is unknown.

Objective: To determine antibody persistence and protection from hepatitis B virus (HBV) infection.

Design: Prospective cohort study.

BIBN4096BS antagonizes human alpha-calcitonin gene related peptide-induced headache and extracerebral artery dilatation.

Background And Objective: Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine pathogenesis. BIBN4096BS is the first CGRP receptor antagonist available for human studies, and its efficacy in the acute treatment of migraine has been demonstrated. We investigated the ability of BIBN4096BS to inhibit human alphaCGRP (h-alphaCGRP)-induced headache and cerebral hemodynamic changes in healthy volunteers.

SNP genotyping using microsphere-linked PNA and flow cytometric detection.

Background: Single nucleotide polymorphisms (SNPs) represent the most frequent form of genetic variations. Some of the most sensitive methods for SNP genotyping employ synthetic oligonucleotides, such as the peptide nucleic acid (PNA). We introduce a new method combining allele-specific hybridization, PNA technology, and flow cytometric detection.

The phosphodiesterase 3 inhibitor cilostazol dilates large cerebral arteries in humans without affecting regional cerebral blood flow.

Cilostazol, an inhibitor of phosphodiesterase (PDE) type 3, is used clinically in peripheral artery disease. PDE3 inhibitors may be clinically useful in the treatment of delayed cerebral vasospasm after subarachnoid hemorrhage. The authors present the first results on the effect of cilostazol on cerebral hemodynamics in normal participants.

Inhibitory effect of BIBN4096BS on cephalic vasodilatation induced by CGRP or transcranial electrical stimulation in the rat.

Calcitonin gene-related peptide (CGRP) is believed to play a pivotal role in the pathogenesis of migraine via activation of CGRP receptors in the trigeminovascular system. The CGRP receptor antagonist, BIBN4096BS, has proven efficacy in the acute treatment of migraine attacks and represents a new therapeutic principle. We used an improved closed cranial window model to measure changes of the middle meningeal artery (MMA) and cortical pial artery/arteriole diameter (PA) and changes in local cortical cerebral blood flow (LCBF(Flux)) in anaesthetised artificially ventilated rats.

Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth.

Background: The duration of protection after hepatitis B vaccination of infants is unknown.

Methods: We determined antibody to hepatitis B surface antigen (anti-HBs) at 4-13 years of age in 363 low risk children who had been vaccinated starting at birth with hepatitis B vaccine. Those with nonprotective titers (<10 mIU/mL) received a booster dose.

Short PNA molecular beacons for real-time PCR allelic discrimination of single nucleotide polymorphisms.

The typing of a single nucleotide polymorphism with DNA probes is sometimes problematic because of the limited discriminating power of long DNA probes. As an alternative to existing assays, we have developed a real-time PCR assay for the genotyping of single nucleotide polymorphisms using short peptide nucleic acid (PNA) molecular beacons. A single nucleotide polymorphism in exon 6 of the XPD gene was chosen as the model system.

A qualitative study of the importance and etiology of chronic respiratory disease in Alaska native children.

Objectives: To generate new hypotheses about factors that may contribute to chronic respiratory disease in Alaska Native children in rural Alaska.

Methods: Qualitative formative research with interviews of community members, village healthcare providers, and referral providers in the Yukon-Kuskokwim Delta Region of Alaska.

Results: The respondents identified chronic and acute respiratory illnesses as the most important serious child health problems of the region.

Detection of gamma-globin mRNA in fetal nucleated red blood cells by PNA fluorescence in situ hybridization.

Objectives: Fetal nucleated red blood cells (NRBC) that enter the peripheral blood of the mother are suitable for non-invasive prenatal diagnosis. The application of peptide nucleic acid (PNA) probes for tyramide amplified flow fluorescence in situ hybridization (FISH) detection of gamma-globin mRNA in fixed fetal NRBC is investigated.

Methods: Hemin-induced K562 cells or nucleated blood cells (NBC) from male cord blood were mixed with NBC from non-pregnant women and analysed using both slide and flow FISH protocols.

Changes in antibiotic-prescribing practices and carriage of penicillin-resistant Streptococcus pneumoniae: A controlled intervention trial in rural Alaska.

From 1998 to 2000, 13 rural Alaskan villages (population, 3326) were surveyed annually by nasopharyngeal cultures for Streptococcus pneumoniae carriage. Data regarding antibiotic use for the entire population was abstracted from clinic records. In 1999, education of medical providers and the community about appropriate antibiotic use began in 4 villages; this program was expanded to include all villages in 2000.