Multi-system neurological disease is common in patients with OPA1 mutations

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal `dominant optic atrophy plus` variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra study)

Aims: To compare the amount of intraoperative intraocular bleeding in patients with diabetes with macula-involving tractional retinal detachment (TRD) undergoing pars plana vitrectomy (PPV) with and without preoperative intravitreal bevacizumab (IVB) injection. Methods: An institutional study was carried out with consecutive patients with diabetic retinopathy and macula-involving TRD of recent (3 months) onset who were randomly assigned to PPV only (PPV group) or PPV combined with one IVB (1.5 mg/0.06 ml) injection 2 weeks prior to surgery (bevacizumab (BEV)/PPV group). All patients underwent 23-gauge PPV 3 weeks after baseline. The main outcome measure was erythrocyte count in the fluid retrieved from the vitrectomy cassette using a Neubauer counting chamber. Results: The study included 20 patients. The mean erythrocyte count was 14865x10(3) (SD 19332x10(3); median 4500x10(3)) cells in the BEV/PPV group, and 176240x10(3) (SD 108375x10(3); median 166600x10(3)) cells in the PPV group. The mean erythrocyte count was significantly lower in the BEV/PPV group than in the PPV group (p < 0.0001). No major adverse events were identified. Conclusion: Preoperative IVB injection was associated with reduced intraocular bleeding during 23-gauge PPV for diabetic macula-involving TRD. Further studies are needed to confirm our preliminary findings.

Inflammatory mediators involved in the nociceptive and oedematogenic responses induced by Tityus serrulatus scorpion venom injected into rat paws.

The present study investigated the role of kinins, prostaglandins (PGs) and nitric oxide (NO) in mechanical hypernociception, Spontaneous nociception and paw oedema after intraplantar (ipl) injection of Tityus serrulatus venom (Tsv) in male Wistar rats. Tsv was ipl-injected in doses of 0.01-10 mu g/paw. Pre-treatment (30 min prior) with DALBK (100 nmol/paw) and icatibant (10 nmol/paw), B1 and B2 selective kinin receptor antagonists, L-NAME (50 mg/kg, i.p., a non-selective nitric oxide synthase inhibitor) or celecoxib, selective COX-2 inhibitor, was given 1 h prior per os (5 mg/kg, p.o.), significantly reduced the hypernociceptive response (Von Frey method), the spontaneous nociception (determined by counting the number of flinches) and paw oedema (plethysmometer method) induced by Tsv at doses of 1.0 and 10 mu g/paw for both nociceptive and oedematogenic responses, respectively. Nevertheless, indomethacin (5 mg/kg, i.p.. 30 min prior) was ineffective in altering all of these events. The results of the present study show that Tsv, injected ipl into the rat paw, causes a dose-dependent paw oedema, mechanical hypernociception and flinches (a characteristic biphasic response) in which kinins and NO are substantially involved. Although celecoxib was effective against the oedema and pain caused by Tsv, COX-2 does not seem to be involved in the inflammatory response caused by Tsv. (C) 2008 Elsevier Ltd. All rights reserved.

Insulin Affects Tissue Organization and the Kinetics of Epithelial Cell Death in the Rat Ventral Prostate After Castration

Prostate growth and physiology are regulated by steroid hormones and modulated by multiple endocrine factors We investigated the action of insulin on the tissue organization and kinetics of epithelial cells in the rat ventral prostate (VP) in response to castration up to 120 hours after surgery by using an acute protocol of alloxan induced diabetes Diabetes caused a reduction in volume density (Vv(o)/) and volume of the epithelium The effects of castration on the epithelium were accelerated in the diabetic animals as determined by changes in V(o)/, and volume The smooth muscle cells became atrophic and apparently relaxed in response to castration in contrast to the spinous aspect observed in nondiabetic castrated rats Counting of apoptotic nuclei in the epithelium showed the classical apoptosis peak at 72 hours in nondiabetic rats and an advance of the apoptosis peak to 48 hours after castration in diabetic rats Insulin restored the time of the peak to 72 hours These results were confirmed after immunostaining for cleaved caspase 3 and suggest a survival and antiapoptotic effect on VP epithelial cells in both the presence and absence of androgen stimulation This idea is supported by the observation that insulin also reduced the overall rate of apoptosis at all experimental points analyzed before and after castration

The essential role of toll like receptor-4 in the control of Aggregatibacter actinomycetemcomitans infection in mice

Objective: Aggregatibacter actinomycetemcomitans is an oral Gram-negative bacterium that contributes to periodontitis progression. Isolated antigens from A. actinomycetemcomitans could be activating innate immune cells through Toll-like receptors (TLRs). In this study, we evaluated the role of TLR4 in the control of A. actinomycetemcomitans infection. Material and Methods: We examined the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR4(-/-) mice. The production of cytokines was evaluated by ELISA. The bacterial load was determined by counting the number of colony-forming units per gram of tissue. Results: The results showed that TLR4-deficient mice developed less severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly lower bone loss and inflammatory cell migration to periodontal tissues. However, the absence of TLR4 facilitated the A. actinomycetemcomitans dissemination. Myeloperoxidase activity was diminished in the periodontal tissue of TLR4(-/-) mice. We observed a significant reduction in the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta in the periodontal tissue of TLR4(-/-) mice. Conclusion: The results of this study highlighted the role of TLR4 in controlling A. actinomycetemcomitans infection.

Clinical, Histological, and Microbiological Findings in Peri-Implant Disease: A Pilot Study

Objectives: This study is intended to verify the correlation among clinical indices of the peri-implant soft tissues, the histological condition and the presence of 3 pathogens commonly associated with peri-implant diseases (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythia). Materials: Four clinical indices, Gingival Index (GI), Sulcus Bleeding Index, GI modified by Mombelli, and Plaque Index modified by Mombelli (mPI) were evaluated around I dental implant of each subject (n = 10). Subgingival plaque was collected for bacterial analysis (polymerase chain reaction) and a biopsy of peri-implant soft tissues for histological analysis was harvested. The clinical indices and detected pathogens correlated with a developed histological index (HI). Results: There was no statistically significant relationship between the clinical indices (GI, Sulcus Bleeding Index, and GI modified by Mombelli) and the HI, except for the mPI on the central area of lingual aspects (r = 0.85, P = 0.0029). There was a tendency for a positive correlation between the mPI on the central area of buccal aspects and the HI (r = 0.63, P = 0.0544). The counting of lymphocytes and plasmocytes correlated positively with 111, thus suggesting the index reliability. The prevalence of A. actinomycetemcomitans, P. gingivalis, and T. forsythia did not present a significant relationship with the HI. Conclusion: Despite the small number of samples and the poor statistical significance, the mPI seems to be useful for evaluation of inflammatory severity on soft tissue around dental implants as demonstrated by its relationship with the HI. Further studies are necessary to elucidate this subject. (Implant Dent 2009;18:334-344)

Cariogenic Microorganisms and Oral Conditions in Asthmatic Children

This study evaluated the caries risk of asthmatic patients on the basis of mutans streptococci (MS) and lactobacilli levels in saliva samples as well as the index of oral hygiene and dental caries (DMFT index). The study population was composed of 80 asthmatic children, aged 3-15 years, who use specific medication, and 80 matched, healthy control children. The parents were interviewed about oral health-related factors. The World Health Organization criteria were used for dental examinations. The Kohler and Bratthal methodology was used to detect salivary MS levels and dilutions of saliva were done for lactobacilli counting. No differences between asthma and control groups were observed for caries prevalence in children aged 3-6 and 7-10 years, except in severe cases in the younger group. However, higher caries prevalence for permanent dentition was observed in 11- to 15-year-old asthmatic children. An increased dental biofilm was observed in the asthma group, as well as salivary levels of MS. No differences were observed in levels of lactobacilli. No statistical correlations were found between medication, frequency of treatment, method of consumption and caries experience, dental biofilm and salivary levels of MS or lactobacilli. However, there was a correlation between MS levels and treatment duration. The logistic regression revealed that MS level is an important risk factor for increased caries experience. Asthma should be evaluated as a risk factor for caries experience because it can increase the levels of MS and the dental biofilm. Copyright (C) 2011 S. Karger AG, Basel

Antimicrobial Effects of Calcium Hydroxide and Chlorhexidine on Enterococcus faecalis

Introduction: Endodontic treatment is commonly based on nonspecific elimination of intraradicular micro-organisms. Although some authors prefer single-visit root canal operations for endodontic treatment, several studies have shown the importance of intracanal medication between sessions to kill microorganisms that biomechanical preparations alone cannot achieve. The purpose of this study was to evaluate the efficacy of calcium hydroxide Ca(OH)2 and chlorhexidine gel on the elimination of intratubular Enterococcus faecalis. Methods: Human uniradicular teeth contaminated with E. faecalis were treated with Ca(OH)(2), 2% chlorhexidine gel, Ca(OH)(2) plus 2% chlorhexidine gel, or saline (0.9% NaCl) as a negative control. Samples obtained at a depth of 0 to 100 mu m and 100 to 200 mu m from these root canal preparations were analyzed for bacterial load by counting the number of colonyforming units (CFUs) and bacterial viability using fluorescence microscopy. Results: A significant decrease in the number of CFUs and the percentage of viable E. faecalis was observed after treatment with either Ca(OH)(2) or chlorhexidine when compared with the control group. Additionally, chlorhexidine gel had a significantly higher antimicrobial efficacy as measured by the number of CFUs and the percentage of viable cells than Ca(OH)(2). No differences were observed between the antimicrobial properties of chlorhexidine gel with and without the addition of Ca(OH)(2). Conclusion: Both Ca(OH)(2) and chlorhexidine have antimicrobial effects on E. faecalis. Chlorhexidine had increased antimicrobial activity when compared with Ca(OH)(2.) Ca(OH)(2) combined with chlorhexidine showed similar antimicrobial activity to chlorhexidine alone. (J Endod 2010;36:1389-1393)

In Vitro Proliferation and Osteoblastic Phenotype Expression of Cells Derived From Human Vertebral Lamina and Iliac Crest

Study Design. Osteoblastic cells derived from vertebral lamina and iliac crest were isolated and cultured under the same conditions (osteogenic medium, pH, temperature, and CO(2) levels). Objective. To compare proliferation and expression of osteoblastic phenotype of cells derived from vertebral lamina and iliac grafting. Summary of Background Data. Many factors play a role in the success of bone graft in spinal fusion including osteoblastic cell population. Two common sources of graft are vertebral lamina and iliac crest, however, differences in proliferation and osteoblastic phenotype expression between cells from these sites have not been investigated. Methods. Cells obtained from cancellous bone of both vertebral lamina and iliac crest were cultured and proliferation was evaluated by direct cell counting and viability detected by Trypan blue. Alkaline phosphatase (ALP) activity was evaluated by thymolphthalein release from thymolphthalein monophosphate and matrix mineralization by staining with alizarin red S. Gene expression of ALP, osteocalcin, runt-related transcription factor 2, Msh homeobox 2, bone morphogenetic protein 7, intercellular adhesion molecule 1 precursor, osteoprotegerin, and receptor activator of NF-kB ligand was analyzed by real-time PCR. All comparisons were donor-matched. Results. Proliferation was greater at days 7 and 10 in cells from vertebral lamina compared with ones from iliac crest without difference in cell viability. ALP activity was higher in cells from vertebral lamina compared with cells from iliac crest at days 7 and 10. At 21 days, mineralized matrix was higher in cells derived from vertebral lamina than from iliac crest. At day 7, gene expression of ALP, osteocalcin, runt-related transcription factor 2, Msh homeobox 2, bone morphogenetic protein 7, intercellular adhesion molecule 1 precursor, receptor activator of NF-kB ligand, and osteoprotegerin was higher in cells derived from vertebral lamina compared with iliac crest. Conclusion. Cell proliferation and osteoblastic phenotype development in cells derived from cancellous bone were more exuberant in cultures of vertebral lamina than of iliac crest.

The relationship between interimplant distances and vascularization of the interimplant bone

Background Long-term success of the implant restorations is based upon the biology and vasculature of the bone surrounding the implants, especially for the bone between two implants. Purpose The aim of this study was to evaluate how loaded implants placed 2 or 3 mm apart influence bone vessel organization. Material and methods Six mongrel dogs were used for the study. The four mandibular premolars were extracted and 3 months later, four 4.5 x 10 mm implants were placed on each side of the mandible. The implants were placed so that two adjacent implants were 2 mm (group 1) or 3 mm (group 2) distant from each other. After 12 weeks, the implants were loaded with provisional prostheses, then metallic crowns were placed 4 weeks later. Both temporary and metallic restorations were made so that the distance between the contact point and the bone crest was 5 mm. The animals were sacrificed after 8 weeks. The hemi-mandibles were removed and prepared for analysis. The interimplant bone vasculature of the two groups was studied using scanning electron microscopic images fractal analysis. The fractal dimension (D(f)) was calculated using the box-counting method. Results The values of the D(f) for the blood vessels were significantly higher (P <.05) in the specimens of the group 2 (1.969 +/- 0.169) than the group 1 (1.556 +/- 0.246). Conclusion The presence of more blood vessels in the group 2 is another indication that 3 mm is a preferable distance for contiguous implants than the 2 mm distance. To cite this article:Traini T, Novaes AB, Piattelli A, Papalexiou V, Muglia VA. The relationship between interimplant distances and vascularization of the interimplant bone.Clin. Oral Impl. Res. 21, 2010; 822-829.doi: 10.1111/j.1600-0501.2010.01926.x.

Effect of recombinant human bone morphogenetic protein-2 on bone formation in the acute distraction osteogenesis of rat mandibles

Background Distraction osteogenesis (DO) is a method of producing new bone directly from the osteotomy site by gradual traction of the divided bone fragments. Aim The purpose of the present study was to evaluate histomorphometrically whether acute DO would constitute a viable alternative to the conventional continuous distraction treatment and also to verify the capacity of a recombinant human BMP (rhBMP-2) associated with monoolein gel to stimulate bone formation in the acute distraction process. Materials and methods Forty-eight Wistar rats were assigned to three groups: Group 1, treated at a conventional continuous distraction rate (0.5 mm/day), Group 2, treated with acute distraction of 2.5 mm at the time of the surgical procedure, and Group 3, subjected to acute distraction associated with rhBMP-2. The animals from each experimental group were killed at the end of the second or fourth post-operative weeks and the volume fraction of newly formed bone trabeculae was estimated in histological images by a differential point-counting method. Results The results showed that after 2 and 4 weeks, bone volumes in the rhBMP-2 group were significantly higher than in the other groups (P < 0.05), but no significant difference was observed in the volume fraction of newly formed bone between the continuous and acute DO groups. Conclusion In conclusion, the study indicates that rhBMP-2 can enhance the bone formation at acute DO, which may potentially reduce the treatment period and complications related to the distraction procedure. To cite this article:Issa JPM, do Nascimento C, Lamano T, Iyomasa MM, Sebald W, de Albuquerque Jr RF. Effect of recombinant human bone morphogenetic protein-2 on bone formation in the acute distraction osteogenesis of rat mandibles.Clin. Oral Impl. Res. 20, 2009; 1286-1292.doi: 10.1111/j.1600-0501.2009.01799.x.