Symptomatic and neuroprotective effects following activation of nigral group III metabotropic glutamate receptors in rodent models of Parkinson's disease

Background and purpose:

Increased glutamatergic innervation of the substantia nigra pars reticulata (SNpr) and pars compacta (SNpc) may contribute to the motor deficits and neurodegeneration, respectively, in Parkinson''s disease (PD). This study aimed to establish whether activation of pre-synaptic group III metabotropic glutamate (mGlu) receptors reduced glutamate release in the SN, and provided symptomatic or neuroprotective relief in animal models of PD.

Experimental approach:

Broad-spectrum group III mGlu receptor agonists, O-phospho-l-serine (l-SOP) and l-2-amino-4-phosphonobutyrate (l-AP4), were assessed for their ability to inhibit KCl-evoked [³H]-d-aspartate release in rat nigral prisms or inhibit KCl-evoked endogenous glutamate release in the SNpr in vivo using microdialysis. Reversal of akinesia in reserpine-treated rats was assessed following intranigral injection of l-SOP and l-AP4. Finally, the neuroprotective effect of 7 days'' supra-nigral treatment with l-AP4 was examined in 6-hydroxydopamine (6-OHDA)-lesioned rats.

Key results:

l-SOP and l-AP4 inhibited [³H]-d-aspartate release by 33 and 44% respectively. These effects were blocked by the selective group III mGlu antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG). l-SOP also reduced glutamate release in the SNpr in vivo by 48%. Injection of l-SOP and l-AP4 into the SNpr reversed reserpine-induced akinesia. Following administration above the SNpc, l-AP4 provided neurochemical, histological and functional protection against 6-OHDA lesion of the nigrostriatal tract. Pretreatment with CPPG inhibited these effects.

Conclusions and implications:

These findings highlight group III mGlu receptors in the SN as potential targets for providing both symptomatic and neuroprotective relief in PD, and indicate that inhibition of glutamate release in the SN may underlie these effects.     

A systematic review of musculoskeletal disorders among dental professionals

Abstract:  Musculoskeletal problems have become a significant issue for the profession of dentistry and dental hygiene. This review provides a detailed examination and discussion regarding the prevalence of musculoskeletal disorders (MSD) in dental personnel and possible causative factors. All research studies or literature reviews, which have reported on the prevalence of musculoskeletal symptoms and/or potential risk factors for this problem in dentists, dental hygienists and dental students, were selected for inclusion. Our literature suggests that the prevalence of general musculoskeletal pain ranges between 64% and 93%. The most prevalent regions for pain in dentists have been shown to be the back (36.3–60.1%) and neck (19.8–85%), while the hand and wrist regions were the most prevalent regions for dental hygienists (60–69.5%). Interestingly, we found that studies on MSDs among dental and dental hygiene students are quite limited. Many risk factors have been identified, including static and awkward posture and work practices. Overall, the review suggests that musculoskeletal problems represent a significant burden for the dental profession. More research in the form of larger studies is urgently required, to help more clearly elucidate the development of this important issue for dental hygienists and dental hygiene students.     

Role of previous hospitalization in clinically-significant MRSA infection among HIV-infected inpatients: results of a case-control study

Background  

HIV-infected subjects have high incidence rates of Staphylococcus aureus infections, with both methicillin-susceptible and methicillin-resistant (MRSA) strains. Possible explanations could include the high burden of colonization, the behavioral risk factors, and the frequent exposures to health care facilities of HIV-infected patients. The purpose of the study was to assess the risk factors for clinically- significant methicillin-resistant Staphylococcus aureus (CS-MRSA) infections in HIV-infected patients admitted to Infectious Diseases Units.     

Development of a parent-report computer-adaptive test to assess physical functioning in children with cerebral palsy II: upper-extremity skills

The specific aims of this study were to (1) examine the psychometric properties (unidimensionality, differential item functioning, scale coverage) of an item bank of upper-extremity skills for children and adolescents with cerebral palsy (CP); (2) evaluate a simulated computer-adaptive test (CAT) using this item bank; (3) examine the concurrent validity of the CAT with the Pediatric Outcomes Data Collection Instrument (PODCI) upper-extremity core scale; and (4) determine the discriminant validity of the simulated CAT with Manual Ability Classification System (MACS) levels and CP type (i.e. diplegia, hemiplegia, or quadriplegia). Parents ( n =180) of children and adolescents with CP (spastic diplegia 49%, hemiplegia 22%, or quadriplegia 28%) consisting of 102 males and 78 females with a mean age of 10 years 6 months (SD 4y 1mo, range 2–21y), and MACS levels I through V participated in calibration of an item pool and completed the PODCI. Confirmatory factor analyses supported a unidimensional model using 49 of the 53 upper-extremity items. Simulated CATs of 5, 10, and 15 items demonstrated excellent accuracy (intraclass correlation coefficient [ICCs] >0.93) with the full item bank, had high correlations with the PODCI upper-extremity core scale score (ICC 0.79), and discriminated among MACS levels. The simulated CATs demonstrated excellent overall content coverage over a wide age span and severity of upper-extremity involvement. The future development and refinement of CATs for parent report of physical function in children and adolescents with CP is supported by our work.     

A One-Stop Carpal Tunnel Clinic

INTRODUCTION

By December 2008, 90% of referrals requiring hospital admission will need to be seen and treated within the 18-week patient pathway. Previously, patients within our trust with suspected carpal tunnel syndrome had to wait 3 months to see a specialist in clinic and, once assessed, would have to wait up to a further 6 months for an open carpal tunnel decompression under local anaesthetic (OCTD/LA). We set up a one-stop clinic, where patients would have their out-patient consultation and surgery on the same day. We evaluated the clinic in order to assess whether it led to reduced waiting times whilst maintaining good clinical outcome and patient satisfaction.

PATIENTS AND METHODS

Patients were selected on the basis of the standard referral letter alone. Those selected were then assessed by a single surgeon in the clinic. The patients deemed appropriate underwent an OCTD/LA and were discharged the same day. Patients were followed up with a patient satisfaction and Boston questionnaire.

RESULTS

Forty-six patients underwent 63 OCTD/LA, waiting an average of 2.2 months (9 weeks) from referral. There was high patient satisfaction and improvement in symptoms following treatment in the clinic.

CONCLUSIONS

We believe a one-stop carpal tunnel clinic can be an efficient and cost-effective way of treating this common condition.     

Functional abnormalities of human neutrophils collected by continuous flow filtration leukopheresis.

Continuous flow filtration leukopheresis (FL) is a relatively simple, inexpensive, and efficient technique of harvesting blood neutrophils from normal donors for transfusion into neutropenic recipients. There has been concern, however, that neutrophils may be functionally altered druing this leukopheresis procedure. Human neutrophils obtained by various FL techniques were studied for in vitro chemotaxis by a 51Cr-radiolabel method and for in vitro killing and phagocytosis of Staphylococcus aureus. We compared their function with neutrophils obtained by the NCI-IBM cell separator and by dextran sedimentation from whole blood. FL neutrophils eluted from nylon filters after 3-hr collection periods were functionally abnormal by all parameters tested, while neutrophils obtained by cell separator after similar collection times were not significantly different from control cells. However, neutrophils from 3-hr FL collections were found to include both normal and abnormal populations of cells. Loosely adherent cells, eluted after tapping the filters, were functionally normal; more adherent cells, eluted after tapping the filters and representing the bulk of cells collected, were progressively more abnormal the less readily they were eluted. Shortened FL collection times (1-2 hr) were found to decrease the functional defects. Also, administration of dexamethasone to donors prior to filtration leukopheresis diminished the functional defects of FL neutrophils perhaps by altering adherence characteristics of the cells. These studies show that neutrophils obtained by filtration leukopheresis are functionally abnormal in relation to the time and extent of adherence to nylon filters.     

甘草锌对顺铂毒性及抗癌效果的影响

本文观察了甘草锌对顺铂毒性及抗癌作用的影响。结果表明甘草锌对顺铂引起的肾脏、血液、生殖系统损害及致死毒性均有一定保护作用。经金属硫蛋白(MT)测定结果显示小鼠心、肝、肾组织中MT的含量均有明显增加,但其肿瘤组织中MT浓度较对照组无明显差别。经体内、外抑瘤实验表明甘草锌对顺铂的抗癌效果无明显影响。因此提示甘草锌可通过诱导MT降低顺铂毒性,有望作为抗癌药物的减毒剂应用于临床。     

Poor Immune Responses of Newborn Rhesus Macaques to Measles Virus DNA Vaccines Expressing the Hemagglutinin and Fusion Glycoproteins

A vaccine that would protect young infants against measles could facilitate elimination efforts and decrease morbidity and mortality in developing countries. However, immaturity of the immune system is an important obstacle to the development of such a vaccine. In this study, DNA vaccines expressing the measles virus (MeV) hemagglutinin (H) protein or H and fusion (F) proteins, previously shown to protect juvenile macaques, were used to immunize groups of 4 newborn rhesus macaques. Monkeys were inoculated intradermally with 200 μg of each DNA at birth and at 10 months of age. As controls, 2 newborn macaques were similarly vaccinated with DNA encoding the influenza virus H5, and 4 received one dose of the current live attenuated MeV vaccine (LAV) intramuscularly. All monkeys were monitored for development of MeV-specific neutralizing and binding IgG antibody and cytotoxic T lymphocyte (CTL) responses. These responses were poor compared to the responses induced by LAV. At 18 months of age, all monkeys were challenged intratracheally with a wild-type strain of MeV. Monkeys that received the DNA vaccine encoding H and F, but not H alone, were primed for an MeV-specific CD8⁺ CTL response but not for production of antibody. LAV-vaccinated monkeys were protected from rash and viremia, while DNA-vaccinated monkeys developed rashes, similar to control monkeys, but had 10-fold lower levels of viremia. We conclude that vaccination of infant macaques with DNA encoding MeV H and F provided only partial protection from MeV infection.