Behaviour changes in a transgenic model of Huntington's disease

Huntington's disease is an autosomal dominant inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin with unknown function. Transgenic mice expressing the N-terminal of huntingtin, containing 82 glutamines, exhibit a progressive disorder, which resembles to the human disease. In this study, we tested the longitudinal behaviour changes in this transgenic line in open-field and elevated-plus-maze tests. The motor performance deteriorated at 12 weeks of age and the disease progressed as indicated by the decreased total distance covered, the decreased mean velocity and the decreased exploratory behaviour. The level of anxiety was unchanged in transgenic mice as compared with their littermate controls. The motor deterioration was similar to that in other Huntington's disease models, while the level of anxiety was different. These tests are suitable means of following the progression of the disease and useful for studies of the effects of therapeutic interventions.     

Bilateral sagittal split osteotomy and temporomandibular disorders: rigid fixation versus wire fixation

OBJECTIVE: The effects of orthognathic surgery on temporomandibular disorders may be related to the surgical method that is used. Specifically, it has been suggested that the choice of stabilization technique may play a major role in the functional outcome of mandibular advancement surgery. The purpose of this study was to prospectively compare long-term (2 years) signs and symptoms of temporomandibular disorders after orthognathic surgery with bilateral sagittal split osteotomy in 127 patients randomized to receive rigid or wire fixation. STUDY DESIGN: Signs and symptoms of temporomandibular disorders were evaluated before and 2 years after surgery by means of the overall craniomandibular index (CMI), dysfunction index (DI), and muscle index (MI). Patients also reported subjective symptoms of temporomandibular disorders by marking areas of pain on a standard drawing of the head and rating the pain in each area on a scale ranging from 1 (very mild) to 7 (very extreme). Subjective pain was also assessed through use of the Oral Health Status Questionnaire and by a rating of the difficulty in opening the mouth because of pain. RESULTS: There were no statistically significant differences in the CMI, MI, or DI change scores between the wire and rigid fixation groups (mean CMI(wire) = 0.05, mean CMI(rigid) = 0.04; mean DI(wire) = 0.02, mean DI(rigid) = 0. 01; mean MI(wire) = 0.08, mean MI(rigid) = 0.08) 2 years after surgery. Temporomandibular joint sounds also demonstrated no significant differences between the two fixation methods. Subjective pain reports were consistent with the clinical examinations. On average, both wire and rigid scores decreased slightly, but the change scores were not significantly different between groups. CONCLUSIONS: These findings suggest that the long-term (2 years) effects of wire and rigid internal fixation methods on the signs and symptoms of temporomandibular disorders do not differ. Earlier concerns about increased risk for temporomandibular disorders with rigid fixation were not supported by these results.     

Assessment of the dentin-pulp complex response to caries by ADC mapping

The prognostic potential of apparent diffusion coefficient (ADC) mapping was studied as complemented by high-resolution 3D T(1)-weighted MRI in the assessment of dentin-pulp complex response to caries. Twenty-six extracted human teeth, with or without caries lesions of different grades in accord with the International Caries Detection and Assessment System (ICDAS), were analyzed by high-resolution MRI at 2.35 T. A signal rise in demineralized hard dental tissues in high-resolution T(1)-weighted MR images enabled assessment of the demineralization depth over the whole range of ICDAS scores. ADC maps of the teeth were calculated from corresponding diffusion-weighted images of four different b values: 0, 132, 317, 635 s/mm(2). These maps enabled reliable differentiation between intact (ADC > 1.0·10(-9) m(2)/s) and affected (ADC < 1.0·10(-9) m(2)/s) regions of dental pulp. Linear regression analyses of demineralization depth in relation to ICDAS score and then also to average ADC of dental pulp showed that a demineralization depth increase of one millimeter corresponds to an ICDAS score increase of 1.2 and an average ADC decrease of 0.07·10(-9) m(2)/s. Results of the study indicate that the average ADC value of dental pulp could be used as a potential marker to assess tissue response to caries comparable to that of ICDAS scoring.     

Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial

Sialorrhea (drooling) is a common symptom of Parkinson's disease (PD) that can significantly impair a patient's health and quality of life. Fifty-four PD subjects with troublesome sialorrhea were enrolled using a multicenter, randomized, double-blind, sequential-dose escalation design in which subjects received a single intraglandular treatment with botulinum toxin type B (doses of 1,500 Units [0.3 mL]; 2,500 Units [0.5 ml]; or 3,500 Units [0.7 ml]) or placebo. Postinjection, subjects were followed acutely for 4 weeks and long-term for up to 20 weeks. Safety/tolerability, as assessed by adverse events, was the primary outcome measure. Efficacy, as assessed by the Drooling Frequency and Severity Scale and unstimulated salivary flow rate, was secondary. Gastrointestinal-related adverse events occurred more frequently in the active groups versus placebo group (31% vs 7%), with dry mouth being most common (15%). There were no serious adverse events attributed to botulinum toxin type B or discontinuations due to adverse events from treatment. At 4 weeks postinjection, Drooling Frequency and Severity Scale scores significantly improved versus placebo (-1.3 ± 1.3) in a dose-related manner (-2.1 ± 1.2, P = 0.0191; -3.3 ± 1.4, P < 0.0001; -3.5 ± 1.1, P < 0.0001, respectively) and unstimulated salivary flow rates significantly decreased in all active groups versus placebo (P ≤ 0.0009). Furthermore, treated subjects appeared to have more sustained improvement in sialorrhea than placebo subjects. We conclude that intraglandular injection of botulinum toxin type B was safe, tolerable, and efficacious in treating sialorrhea in PD patients. Additional studies are warranted to further confirm the drug's robust efficacy, as well as evaluate its effect with repeated dosing.     

Correlation Between Oocyte Number and Follicular Fluid Concentration of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Women After Superovulation Treatment

Follicular growth, ovulation, and luteinization are influenced by interactions of peptide and steroid hormone-signaling cascades in the ovary. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the regulation of several endocrine processes and is present in ovarian follicular fluid (FF). However, little is known about PACAP in FF with regard to maturation, ovulation, fertilization, and successful pregnancy. The aim of this pilot study was to investigate whether there is a correlation between PACAP concentration in FF and ovarian response to superovulation treatment in infertile women, performed in volunteers (n?=?132; aged between 20 and 35). After treatment, the number of harvested oocytes was recorded and PACAP immunoreactivity in FF was measured by radioimmunoassay. All the corresponding PACAP concentrations were below 290?fmol/ml in cases when the number of harvested oocytes exceeded 14 per patient, while in all cases above 290?fmol/ml, the number of oocytes was below 14. Using these cutoff values, we determined three study groups: high-PACAP concentration, high-oocyte number, and low-PACAP concentration-low-oocyte number groups. Median values of PACAP concentration in these groups were 411.2, 106.5, and 101.0?fmol/ml, respectively, while the median values of harvested oocytes were 5.5, 19.0, and 5.0, respectively. Differences were significant, indicating a correlation between concentration of PACAP in FF and the number of recruited oocytes. Higher concentrations of PACAP in FF might be associated with lower number of developing oocytes, while low concentrations of PACAP might correlate with a markedly higher number of ova retrieved, thus predicting a higher chance for ovarian hyperstimulation. Our present study is among the first few human clinical studies with direct conclusions drawn for possible clinical impact of PACAP.     

Comparative Examination of Inner Ear in Wild Type and Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)-Deficient Mice

Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide with well-known neuroprotective and neurotrophic effects. The involvement of PACAP in sensory processing has also been documented, but little is known about its effects in the auditory system. PACAP and its specific receptor (PAC1) are present in the cochlea and in brain structures involved in auditory pathways. Recently, we have shown that PACAP protects cochlear cells against oxidative stress-induced apoptosis. The endolymphatic Ca(2+) concentration controlled by Ca(2+) buffers of the hair cells is essential for the normal hearing processes. In this study we examined the localization of PAC1 receptor and Ca(2+) buffering proteins (parvalbumin, calretinin, calbindin) in the inner ear of 5-day-old PACAP-deficient mice compared with wild-type mice in order to get a closer insight into the effect of endogenous PACAP in the cochlear function. We did not find differences in the distribution pattern of PAC1 receptors between the two groups, but wild-type animals showed significantly higher PAC1 receptor expression. In contrast, inner and outer hair cells of PACAP-deficient mice showed more pronounced parvalbumin, calbindin, and calretinin immunopositivity compared with wild-type mice. Elevated endolymphatic Ca(2+) is deleterious for cochlear function, while the high concentration of Ca(2+) buffers in hair cells may offer protection. The increased immunoreactivity of Ca(2+) binding proteins in the absence of PACAP provide further evidence the important role of PACAP in the hearing processes.