A truncation in the RYR1 gene associated with central core lesions in skeletal muscle fibres

A novel single-nucleotide deletion in exon 100 of the RYR1 gene, corresponding to deletion of nucleotide 14,510 in the human RyR1 mRNA (c14510delA), was identified in a man with malignant hyperthermia and in his two daughters who were normal for malignant hyperthermia. This deletion results in a RyR1 protein lacking the last 202 amino acid residues. All three subjects heterozygotic for the mutated allele presented with a prevalence of type 1 fibres with central cores, although none experienced clinical signs of myopathy. Expression of the truncated protein resulted in non-functional RYR1 calcium release channels. Expression of wild-type and RyR1(R4836fsX4838) proteins resulted in heterozygotic release channels with overall functional properties similar to those of wild-type RyR1 channels. Nevertheless, small differences in sensitivity to calcium and caffeine were observed in heterotetrameric channels, which also presented an altered assembly/stability in sucrose-gradient centrifugation analysis. Altogether, these data suggest that altered RYR1 tetramer assembly/stability coupled with subtle chronic changes in Ca2+ homoeostasis over the long term may contribute to the development of core lesions and incomplete malignant hyperthermia susceptibility penetrance in individuals carrying this novel RYR1 mutation.     

Dibucaine in Ionic-Gradient Liposomes: Biophysical,Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.     

Effectiveness of foot orthoses in patients with rheumatoid arthritis related to disability and pain: a systematic review and meta-analysis

Background

Epidemiological studies consistently report a 90% prevalence of foot pain. Mechanical and other non-pharmacological interventions such as orthoses and footwear can play an important role in managing foot pathology in patients whose systemic disease is controlled. The effectiveness of treatment with insoles has been examined in various randomised controlled trials, which have reported immediate clinical improvements, with reduced foot pain and disability and enhanced functionality. The aim of this systematic review is to determine the effectiveness of foot orthoses in patients with rheumatoid arthritis (RA), in comparison with other treatments, in terms of enhanced disability and reduced pain.

Methods

A systematic review and meta-analysis was conducted of a number of randomised controlled trials focusing on patients with RA. The search was conducted in Cochrane, CINAHL, PubMed, EMBASE, SCOPUS and Cuiden, by means of an independent peer review. The Mesh terms and fields used were foot, ankle, joint, RA, foot, orthosis, insole and foot orthosis.

Results

Of the initial 118 studies considered, 5 were included in the final systematic review and meta-analysis. These five studies had enrolled a total of 301 participants, with follow-up periods ranging from 4 to 36 months. Although the use of orthoses seems to alleviate foot pain, our meta-analysis did not reveal statistically significant differences between control and intervention groups regarding long- and short-term pain relief and/or reduced disability.

Conclusions

Foot orthoses can relieve pain and disability and enhance patients, but no significant differences were found between control and intervention groups.

     

Management of pregnancies complicated by anti-Fy(a) alloimmunization

BACKGROUND: The objective was to evaluate the management and outcome of patients with anti-Fy(a) at the Ohio State University. STUDY DESIGN AND METHODS: A database search for patients with pregnancies complicated only by anti-Fy(a) from 1959 to 2004. Collected information included maternal testing, fetal therapy, and neonatal outcomes. RESULTS: The final data set included 18 pregnancies in 15 women where anti-Fy(a) was the only maternal alloantibody present and the fetus was Fy(a) antigen-positive. Maternal antibody titers of at least 32 and optical density at 450 nm values in modified Liley Zone IIB or III identified all fetuses or neonates with significant hemolytic disease (2/18, 11%). No fetuses had hydrops, and there were no deaths attributed to hemolytic disease of the fetus and newborn. CONCLUSION: Anti-Fy(a) has the potential to lead to significant fetal hemolysis. Management guidelines developed for D sensitization are appropriate for pregnancies complicated by anti-Fy(a) alloimmunization.     

Oral paracoccidioidomycosis: a case without lung manifestations

AIM: The aim of this article is to present a case of Paracoccidioidomycosis with involvement of the oral cavity but without pulmonary manifestations. BACKGROUND: Paracoccidioidomycosis is a fungal infection caused by Paracoccidioides brasiliensis. It is an endemic disease representing a serious health problem for Latin American countries, especially Brazil. This infection primarily affects the lungs of adult men and is acquired through inhalation or accidental inoculation of the fungus. It can spread to other organs and tissues, mainly the oral cavity. Administration of antifungal medication always resolves the disease. REPORT: A 58-year-old black male presented with three painless, ulcerated, mulberry-like granulomatous lesions located in the floor of the mouth, on the superior alveolar ridge, and on the hard palate, which had evolved over a period of two years. Facial asymmetry was observed due to edema in the lower lip and lymphadenopathy. He had smoked for more than six years but showed no evidence of lung alterations, productive cough, or fever. Panoramic radiography showed no signs of a bone lesion in the jaws. Both a radiograph and a CT scan of the thorax showed no areas of nodular infiltration. Fibrobronchoscopic examination of the entire respiratory tract was normal. Biopsies of the oral lesions were performed, and tissue sections exhibited oral mucosa coated with non-keratinized stratified squamous epithelium with acanthosis and focal areas of exocytosis. The underlying connective tissue showed an intense lymphocytic and polymorphonuclear infiltrate in addition to multinuclear giant cells and coagulation necrosis. A special stain used for fungus (the Grocott-Gomori method) was positive. Pulmonary biopsy exhibited aerial spaces containing macrophages, dark granular hemossiderin, and absence of fungus. This was considered normal. In agreement with the recommendation of pneumologists 400 mg/day of ketoconazole was prescribed for the patient. After two months of treatment, even though the oral lesions had resolved completely, the therapy was maintained for six months more. One year after following treatment the patient was in good health and free of any signs of a recurrent infection. SUMMARY: Based on clinical, radiographic, and histologic findings the differential diagnosis included paracoccidioidomycosis and squamous cell carcinoma. Following clinical and biopsy examinations of the oral lesions and the lungs a final diagnosis of paracoccidioidomycosis was made. This is a prime example of oral manifestations of a systemic disease in which the dentist is the initial health care professional to evaluate the patient due to the location of the lesions.     

POLARIZATION OF DENTAL CARIES AMONG INDIVIDUALS AGED 15 TO 18 YEARS

Objective:

To evaluate the role of socioeconomic variables and self-perceived oral health in the polarization of caries among adolescents in Santa Bárbara D''Oeste, Brazil.

Material and Methods:

Cross-sectional study. Sampling was randomized and sample size was defined according to WHO criteria. Two hundred and seventy seven adolescents (15 to 18 year-old) were examined by five trained examiners that assessed DMFT index according to WHO criteria. Self-perceived oral health, access to dental services and socio-demographic variables were self-reported. Student''s t tests, chi-square tests, and multivariate logistic regression (with significant caries index (SiC) as the outcome), were performed.

Results:

Mean DMFT was 5.48 (±4.22) and the proportion of "caries free" subjects was 15.5%. Mean DMFT (9.71±2.85) and mean D (1.67±2.18) of SiC positive subjects were significantly higher than mean DMFT (2.88±2.17) and mean D (0.45±0.87) of SiC negative subjects (p<0.0001). Mean D of white (0.76±1.51) was significantly smaller than mean D of non-white subjects (1.32±2.01). The only variable independently associated with the "SiC positive" outcome was "report of toothache within six months prior to the study" [OR=1.83 (95%CI 1.08 to 3.12)], p<0.001.

Conclusion:

SiC was associated with "report of toothache" but not with sociodemographic variables in the studied population.     

Effect of enamel matrix proteins on the treatment of intrabony defects: a split-mouth randomized controlled trial study

The objective of this split-mouth, double-blind, randomized controlled trial was to compare the clinical effect of treatment of 2- or 3-wall intrabony defects with open flap debridement (OFD) combined or not with enamel matrix proteins (EMP). Thirteen volunteers were selected with one pair of or more intrabony defects and probing pocket depth (PPD) > or = 5 mm. All individuals received instructions regarding oral hygiene and were submitted to scaling and root planing. Each participant received the two treatment modalities: test sites were treated with OFD and EMP, and control sites received only OFD. After 6 months, a significant reduction was observed in PPD for the EMP group (from 6.42 +/- 1.08 mm to 2.67 +/- 1.15 mm) and for the OFD group (from 6.08 +/- 1.00 mm to 2.00 +/- 0.95 mm) (p < 0.0001), but with no significant difference between groups (p = 0.13). A significant gain in relative attachment level (RAL) was observed in both groups (EMP: from 13.42 +/- 1.88 mm to 10.75 +/- 2.26 mm, p < 0.001; OFD: from 12.42 +/- 1.98 mm to 10.58 +/- 2.23 mm, p = 0.013), but with no significant difference between groups (p = 0.85). Gingival recession (GR) was higher in the EMP group (from 1.08 +/- 1.50 mm to 2.33 +/- 1.43 mm; p = 0.0009) than in the OFD group (from 0.66 +/- 1.15 mm to 1.16 +/- 1.33 mm; p = 0.16), but this difference was not significant (p = 0.06). In conclusion, the results showed that OFD combined with EMP was not able to improve treatment of intrabony defects compared to OFD alone.