Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson`s Disease

Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson`s disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In this study, most of the impairments presented by C57BL/6 mice infused with a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril) were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and memory deficits with no major motor impairments. Such infusion decreased the levels of the enzyme tyrosine hydroxylase in the olfactory bulb, striatum, and substantia nigra by means of apoptotic mechanisms, reducing dopamine concentration in different brain structures such as olfactory bulb, striatum, and prefrontal cortex, but not in the hippocampus. These findings reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. These results also provide new insights in experimental models of PD, indicating that the i.n. administration of MPTP represents a valuable mouse model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Low Intensity Laser Therapy in Temporomandibular Disorder: a Phase II Double-Blind Study

The purpose of this study was to evaluate the analgesic effect of Low Intensity Laser Therapy (LILT) and its influence on masticatory efficiency in patients with temporomandibular dysfunction (TMD). This study was performed using a random, placebo-controlled, and double-blind research design. Fourteen patients were selected and divided into two groups (active and placebo). Infrared laser (780 nm, 70 mw, 60s, 105J/cm(2)) was applied precisely and continuously into five points of the temporomandibular joint (TMJ) area: lateral point (LP), superior point (SP), anterior point (AP), posterior point (PP), and posterior-inferior point (PIP) of the condylar position. This was performed twice per week, for a total of eight sessions, To ensure a double-blind study, two identical probes supplied by the manufacturer were used: one for the active laser and one for the inactive placebo laser. They were marked with different letters (A and B) by a clinician who did not perform the applications. A Visual Analogue Scale (VAS) and a colorimetric capsule method were employed. Data were obtained three times: before treatment (Ev1), shortly after the eighth session (Ev2), and 30 days after the first application (Ev3). Statistical tests revealed significant differences at one percent (1%) likelihood, which implies that superiority of the active group offered considerable TMJ pain improvement. Both groups presented similar masticatory behavior, and no statistical differences were found. With regard to the evaluation session, Ev2 presented the lowest symptoms and highest masticatory efficiency throughout therapy. Therefore, low intensity laser application is effective in reducing TMD symptoms, and has influence over masticatory efficiency [Ev2 (0.2423) and Ev3 (0.2043), observed in the interaction Evaluations x Probes for effective dosage].

Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental wernicke's encephalopathy

Although earlier studies on thiamine deficiency have reported increases in extracellular glutamate concentration in the thalamus, a vulnerable region of the brain in this disorder, the mechanism by which this occurs has remained unresolved. Treatment with pyrithiamine, a central thiamine antagonist, resulted in a 71 and 55% decrease in protein levels of the astrocyte glutamate transporters GLT-1 and GLAST, respectively, by immunoblotting in the medial thalamus of day 14 symptomatic rats at loss of righting reflexes. These changes occurred prior to the onset of convulsions and pannecrosis. Loss of both GLT-1 and GLAST transporter sites was also confirmed in this region of the thalamus at the symptomatic stage using immunohistochemical methods. In contrast, no change in either transporter protein was detected in the non-vulnerable frontal parietal cortex. These effects are selective; protein levels of the astrocyte GABA transporter GAT-3 were unaffected in the medial thalamus. In addition, astrocyte-specific glial fibrillary acidic protein (GFAP) content was unchanged in this brain region, suggesting that astrocytes are spared in this disorder. Loss of GLT-1 or GLAST protein was not observed on day 12 of treatment, indicating that down-regulation of these transporters occurs within 48 h prior to loss of righting reflexes. Finally, GLT-1 content was positively correlated with levels of the neurofilament protein alpha -internexin, suggesting that early neuronal drop-out may contribute to the down-regulation of this glutamate transporter and subsequent pannecrosis. A selective, focal loss of GLT-1 and GLAST transporter proteins provides a rational explanation for the increase in interstitial glutamate levels, and may play a major role in the selective vulnerability of thalamic structures to thiamine deficiency-induced cell death.

Syndromes with salivary dysfunction predispose to tooth wear: case reports of congenital dysfunction of major salivary glands, Prader-Willi, congenital rubella, and Sjogren's syndromes.

Four cases-of congenital dysfunction of the major salivary glands as well as of Prader-Willi, congenital rubella, and Sjogren's syndromes-were identified in a series of 500 patients referred for excessive tooth wear. Although there was evidence of consumption of highly acidic drinks, some occlusal parafunction, and unacceptable toothbrushing habits, salivary dysfunction was the salient factor predisposing a patient to tooth wear in these syndromal cases. The 500 subjects have been characterized either as having medical conditions and medications that predispose them to xerostomia or lifestyles in which workplace- and sports-related dehydration lead to reduced salivary flow. Normal salivation, by buffering capacity, clearance by swallowing, pellicle formation, and capacity for remineralization of demineralized enamel, protects the teeth from extrinsic and intrinsic acids that initiate dental erosion. Thus, the syndromes, unrelated in many respects, underline the importance of normal salivation in the protection of teeth against tooth wear by erosion, attrition, and abrasion.

Cognitive behaviour therapy for the management of obsessive-compulsive disorder

Current research reflects conflict regarding best practice in the treatment of obsessive-compulsive disorder (OCD). The. present study reports on the psychological treatment of a 54-year-old woman diagnosed with OCD, and follows the implementation of pharmacological treatment. The study utilises both exposure and response prevention (ERP) and cognitive therapy (CT), although there was no attempt to compare these approaches in an experimental design. Measures of avoiding and neutralising behaviours were taken on three occasions across treatment. Measures were also taken of intrusive thoughts, appraisal of responsibility, and effective challenging, both across treatment and at follow-up. The results indicate that gains were made in addition to those reported following the implementation of medication. The results also suggest that the addition of CT to exposure and response prevention facilitates the extinction of neutralising behaviours.

Auditing complications of laparoscopy in a major tertiary hospital in Australia

Objective To review complications in both diagnostic and operative laparoscopic procedures at a university-affiliated major teaching hospital and to assess possible risk factors for complications. Design and setting A retrospective review of all laparoscopic procedures at the Royal Women's Hospital Brisbane, Australia, from 1990 to 1997 inclusive. A non-medical or nursing independent assessor reviewed charts. Data were collected on a standard form. Incomplete charts were excluded from analysis. Results There was a total of 1505 procedures. Analysis was based on 1435 complete data records. The overall complication rate was 2.86% with infection (1.3%) being the most common. The rate of gastrointestinal injury was 0.14%. Compared with women who had diagnostic laparoscopies, a higher rate of complication was found in women who had undergone operative laparoscopic procedures. However, this difference did not reach statistical significance. The complication rate was unrelated to seniority of the surgeon. Conclusion Complications can occur in any laparoscopic procedure. Regular reviews, especially in teaching hospitals, will provide feedback to clinicians to improve quality of care.

Articulatory dysfunction in multiple sclerosis: An electropalatographic study

Dysfunction of the articulatory subsystem (i.c.. the lips, tongue, and jaw) has bccn identified as a major contributor to the reduction in speech intelligibility experienced by a high proportion of people with multiple sclerosis (MS). In particular. consonant imprecision has been reported to be the articulatory deficit that contributes most to variations in overall intelligibility of MS speakers. Electropalatography(EPG) IS an instrurncntal technique that visually documents the location and timing of tongue-topalatc contacts during speech. Although such a technique would be valuablc in objectively assessing the articulatory disturbances exhibited by individuals with dysarthria ia motor speech disorder) associated with MS, to-date no such study ha< been reported. The aim of the present study was to use EPG to assess tongue-to-palate contact patterns and articulatory timing in patients with dysarthria associated with MS. A dysarthric participant with a diagnosis of definite MS was fitted with an acrylic EPG palate (Reading EPG.?) and asked to read aloud a list of single syllable words which contained lingual consonants in the word-initial position and in consonant clusters. Each mord was repeated five times. The EPG palate was specifically moulded to tit the participant's hard palate and contained 62 electrodes that detected the tongue contacts. A non-neurologically impaired participant matched for age and sex servcd as a control. The results of the study revealed that the tongue-to-palate contacts produced by the participant with MS varied from those produced by the control in a number of ways in regard to spatial configurations and timing characteristics exhibited. The rcsults arc discussed in relation to the neuropathophysiological effects of MS on speech production. The potcntial use of EPG in programs for treating speech disorders associated with MS will be highlightcd.

Power of the joint segregation analysis method for testing mixed major-gene and polygene inheritance models of quantitative traits

Understanding the genetic architecture of quantitative traits can greatly assist the design of strategies for their manipulation in plant-breeding programs. For a number of traits, genetic variation can be the result of segregation of a few major genes and many polygenes (minor genes). The joint segregation analysis (JSA) is a maximum-likelihood approach for fitting segregation models through the simultaneous use of phenotypic information from multiple generations. Our objective in this paper was to use computer simulation to quantify the power of the JSA method for testing the mixed-inheritance model for quantitative traits when it was applied to the six basic generations: both parents (P-1 and P-2), F-1, F-2, and both backcross generations (B-1 and B-2) derived from crossing the F-1 to each parent. A total of 1968 genetic model-experiment scenarios were considered in the simulation study to quantify the power of the method. Factors that interacted to influence the power of the JSA method to correctly detect genetic models were: (1) whether there were one or two major genes in combination with polygenes, (2) the heritability of the major genes and polygenes, (3) the level of dispersion of the major genes and polygenes between the two parents, and (4) the number of individuals examined in each generation (population size). The greatest levels of power were observed for the genetic models defined with simple inheritance; e.g., the power was greater than 90% for the one major gene model, regardless of the population size and major-gene heritability. Lower levels of power were observed for the genetic models with complex inheritance (major genes and polygenes), low heritability, small population sizes and a large dispersion of favourable genes among the two parents; e.g., the power was less than 5% for the two major-gene model with a heritability value of 0.3 and population sizes of 100 individuals. The JSA methodology was then applied to a previously studied sorghum data-set to investigate the genetic control of the putative drought resistance-trait osmotic adjustment in three crosses. The previous study concluded that there were two major genes segregating for osmotic adjustment in the three crosses. Application of the JSA method resulted in a change in the proposed genetic model. The presence of the two major genes was confirmed with the addition of an unspecified number of polygenes.

Major colour patterns of reef-building corals are due to a family of GFP-like proteins

Reef-building corals are renowned for their brilliant colours yet the biochemical basis for the pigmentation of corals is unknown. Here, we show that these colours are due to a family of GFP-like proteins that fluoresce under ultraviolet (UV) or visible light. Pigments from ten coral species were almost identical to pocilloporin (Dove et al. 1995) being dimers or trimers with approximately 28-kDa subunits. Degenerative primers made to common N-terminal sequences yielded a complete sequence from reef-building coral cDNA, which had 19.6% amino acid identity with green fluorescent protein (GFP). Molecular modelling revealed a 'beta -can' structure, like GFP, with 11 beta -strands and a completely solvent-inaccessible fluorophore composed of the modified residues Gln-61, Tyr-62 and Gly-63. The molecular properties of pocilloporins indicate a range of functions from the conversion of high-intensity UV radiation into photosynthetically active radiation (PAR) that can be regulated by the dinoflagellate peridinin-chlorophyll-protein (PCP) complex, to the shielding of the Soret and Q(x) bands of chlorophyll a and c from scattered high-intensity light. These properties of pocilloporin support its potential role in protecting the photosynthetic machinery of the symbiotic dinoflagellates of corals under high light conditions and in enhancing the availability of photosynthetic light under shade conditions.

An investigation of symptom-specific muscle hyperreactivity in upper extremity cumulative trauma disorder

Objective: The study examined symptom-specific muscle hyperreactivity in patients with chronic pain with upper limb cumulative trauma disorder (CTD). Design: Four tasks were presented in counterbalanced order and included neutral, general stressor, personal stressor, and pain stressor tasks. Ratings of stressfulness and recordings of skin conductance level confirmed the effectiveness of the experimental manipulations in inducing stress experiences for all subject groups. Setting: The study was conducted in a university research center. Patients: Thirty patients with CTD were matched as closely as possible for age and gender to control groups of chronic low back pain, arthritis, and pain-Free subjects Outcome Measures: Surface electromyograph recordings were taken from the frontalis, forearm flexors, trapezius, and lower back during baseline and tasks. Results: The study found no evidence of greater muscle tension increases or extended duration of return to baseline for the CTD or low back pain patients at any of the muscle sites for any of the tasks in comparison to control groups. Conclusions: The results indicate that symptom-specific psychophysiological responses may be limited to certain subgroups rather than being characteristic of chronic musculoskeletal pain patients in general.

Advances in the diagnosis of primary immunodeficiency disorders in childhood

Primary immunodeficiency disorders in childhood usually present as unusual, recurrent or severe infections, symptomatic infections with organisms of low pathogenicity, or as recognizable syndromes which are known to have associated immunological abnormalities. In many of the primary immunodeficiency disorders, there are known patterns of inheritance, and other family members may be affected. Some primary immunodeficiency disorders are relatively common, such as selective IgA deficiency, and often do not lead to major morbidity. Others, such as the severe combined immune deficiency syndromes, are relatively rare, and are fatal in early life if not recognized and treated early. Diagnosis of a primary immunodeficiency disorder depends on appropriate use of laboratory investigations. Often there will be abnormalities detected on a complete blood film and measurement of immunoglobulin isotypes. More complex investigations should be undertaken in conjunction with a paediatric immunology service. In recent years, many of the clinically defined primary immunodeficiency disorders have been shown to have associated specific gene defects. For some, this has led to the identification and characterization of defective or absent gene products. The consequences of this new knowledge are more accurate diagnosis, early diagnosis including antenatal diagnosis, detection of undiagnosed disease in other family members, and the potential for new therapies including gene or gene product therapy.