Facial symmetry evaluation after experimentally displaced condylar process fracture in methotrexate treated rats

PURPOSE: To investigate the facial symmetry of high and low dose methotrexate (MTX) treated rats submitted to experimentally displaced mandibular condyle fracture through the recording of cephalometric measurements. METHODS: One hundred male Wistar rats underwent surgery using an experimental model of right condylar fracture. Animals were divided into four groups: A - saline solution (1mL/week); B - dexamethasone (DEX) (0,15mg/Kg); C - MTX low dose (3 mg/Kg/week); D - MTX high dose (30 mg/Kg). Animals were sacrificed at 1, 7, 15, 30 and 90 days postoperatively (n=5). Body weight was recorded. Specimens were submitted to axial radiographic incidence, and cephalometric mensurations were made using a computer system. Linear measurements of skull and mandible, as well as angular measurements of mandibular deviation were taken. Data were subjected to statistical analyses among the groups, periods of sacrifice and between the sides in each group (alpha=0.05). RESULTS: Animals regained body weight over time, except in group D. There was reduction in the mandibular length and also changes in the maxilla as well as progressive deviation in the mandible in relation to the skull basis in group D. CONCLUSION: Treatment with high dose methotrexate had deleterious effect on facial symmetry of rats submitted to experimentally displaced condylar process fracture.

Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias

FUNDAMENTO: A redução da frequência cardíaca (FC) na angiografia por tomografia das artérias coronarianas (ATCCor) é fundamental para a qualidade de imagem. A eficácia dos bloqueadores de cálcio como alternativas para pacientes com contraindicações aos betabloqueadores não foi definida. OBJETIVOS: Comparar a eficácia na redução da FC e variabilidade RR do metoprolol e diltiazem na ATCCor. MÉTODOS: Estudo prospectivo, randomizado, aberto, incluiu pacientes com indicação clínica de ATCCor, em ritmo sinusal, com FC>70bpm e sem uso de agentes que interferissem com a FC. Cinquenta pacientes foram randomizados para grupos: metoprolol IV 5-15 mg ou até FC≤60 bpm(M), e diltiazem IV 0,25-0,60mg/kg ou até FC≤60 bpm (D). Pressão arterial (PA) e FC foram aferidas na condição basal, 1min, 3min e 5min após agentes, na aquisição e após ATCCor. RESULTADOS: A redução da FC em valores absolutos foi maior no grupo M que no grupo D (1, 3, 5min, aquisição e pós-exame). A redução percentual da FC foi significativamente maior no grupo M apenas no 1 min e 3 min após início dos agentes. Não houve diferença no 5 min, durante a aquisição e após exame. A variabilidade RR percentual do grupo D foi estatisticamente menor do que a do grupo M durante a aquisição (variabilidade RR/ FC média da aquisição). Um único caso de BAV, 2:1 Mobitz I, revertido espontaneamente ocorreu (grupo D). CONCLUSÃO: Concluímos que o diltiazem é uma alternativa eficaz e segura aos betabloqueadores na redução da FC na realização de angiografia por tomografia computadorizada das artérias coronarianas. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)

DNA repair mechanisms protect our genome from carcinogenesis

Human cells are constantly exposed to DNA damage. Without repair, damage can result in genetic instability and eventually cancer. The strong association between the lack of DNA damage repair, mutations and cancer is dramatically demonstrated by a number of cancer-prone human syndromes, such as xeroderma pigmentosum (XP), ataxia-telangiectasia (AT) and Fanconi anemia (FA). This review focuses on the historical discoveries related with these three diseases and describes their impact on the understanding of DNA repair mechanisms and the causes of human cancer. As deficiencies in DNA repair are also often related with progeria symptoms, unrepaired damage and aging are somehow related. Several other pathologies associated with DNA repair defects, genetic instability and increased cancer risk are also discussed. In fact, studies with cells from these many syndromes have helped in understanding important levels of protection against cancer and aging, although little help has actually been conferred to the patients in terms of therapy. Finally, the recent advances in combined basic and translational research on DNA repair and chemotherapy are presented.

Preload Evaluation of Different Screws in External Hexagon Joint

Purpose: This study compared the maintenance of tightening torque in different retention screw types of implant-supported crowns. Materials and Methods: Twelve metallic crowns in UCLA abutments cast with cobalt-chromium alloy were attached to external hexagon osseointegrated implants with different retention screws: group A: titanium alloy retention screw; group B: gold alloy retention screw with gold coating; group C: titanium alloy retention screw with diamond-like carbon film coating; and group D: titanium alloy retention screw with aluminum titanium nitride coating. Three detorque measurements were obtained after torque insertion in each replica. Data were evaluated by analysis of variance (ANOVA), Tukey's test (P < 0.05), and t test (P < 0.05). Results: Detorque value reduced in all groups (P < 0.05). Group A retained the highest percentage of torque in comparison with the other groups (P < 0.05). Groups B and D retained the lowest percentage of torque without statistically significant difference between them (P < 0.05). Conclusions: All screw types exhibited reduction in the detorque value. The titanium screw maintained the highest percentage of torque whereas the gold-coated screw and the titanium screw with aluminum titanium nitride coating retained the lowest percentage. (Implant Dent 2012;21:46-50)

N-Acetylcysteine protects the peritoneum from the injury induced by hypertonic dialysis solution

Background: Oxidative stress has been implicated in the development of peritoneal damage. The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) in a rat peritoneal infusion model. Methods: Eighteen male Wistar rats were divided in 3 groups: (i) control group; (ii) HDS group, receiving peritoneal dialysis solution (PDS); and (iii) HDS+NAC group, receiving PDS and oral NAC. Six weeks later they were evaluated for dialysate to plasma urea ratio (D/P), ratio of glucose concentration in peritoneal fluid (G1/G0), thiobarbituric acid reactive substances in plasma and urine and histology of peritoneal membrane. Results: The HDS+NAC group presented a lower increase in solute transport (D/P 0.51 +/- 0.1, and G1/GO 0.35 +/- 0.06) in comparison with the HDS group (D/P 0.67 +/- 0.1; p=0.03, and G1/G0 0.27 +/- 0.07; p=0.01). The HDS+NAC group showed lower thiobarbituric acid reactive substance concentrations compared with the HDS group. In the treated group, the peritoneal membrane presented lower thickness. Conclusions: Functional and histological peritoneal changes were significantly reduced by the treatment with NAC.

Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions

Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. In fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Is missing maxillary lateral incisor in complete cleft lip and palate a product of genetics or local environment?

Objective: To test the null hypothesis: Subjects with isolated complete unilateral cleft lip and palate (UCLP) show no differences in overall frequency of tooth agenesis (hypodontia), comparing a subsample with cleft-side maxillary lateral incisor (MxI2) agenesis to a subsample without cleftside MxI2 agenesis. Findings could clarify the origins of cleft-side MxI2 agenesis. Materials and Methods: Tooth agenesis was identified from dental radiographs of 141 subjects with UCLP. The UCLP cohort was segregated into four categories according to the status and location of MxI2 in the region of the unilateral cleft: group M: subjects with one tooth, located on the mesial side of the alveolar cleft; group D: subjects with one tooth, located on the distal side of the alveolar cleft; group MD: subjects with two teeth present, one mesial and one distal to the cleft; and group ABS: subjects with lateral incisor absent (agenesis) in the cleft area. Results: The null hypothesis was rejected. Among UCLP subjects, there was a twofold increase (P < .0008) in overall frequency of tooth agenesis outside the cleft region in a subsample with cleftside MxI2 agenesis (ABS), compared to a subsample presenting with no agenesis of the cleft-side MxI2 (M+D+MD). Conclusions: Cleft-side MxI2 agenesis in CLP subjects appears to be largely a genetically controlled anomaly associated with cleft development, rather than a collateral environmental consequence of the adjacent cleft defect, since increased hypodontia involving multiple missing teeth observed remote from a cleft clearly has a significant genetic basis. (Angle Orthod. 2012;82:959-963.)

Constipation Is More Frequent Than Diarrhea in Patients Fed Exclusively by Enteral Nutrition: Results of an Observational Study

Background: Digestive complications in enteral nutrition (EN) can negatively affect the nutrition clinical outcome of hospitalized patients. Diarrhea and constipation are intestinal motility disorders associated with pharmacotherapy, hydration, nutrition status, and age. The aim of this study was to analyze the frequency of these intestinal motility disorders in patients receiving EN and assess risk factors associated with diarrhea and constipation in hospitalized patients receiving exclusive EN therapy in a general hospital. Materials and Methods: The authors performed a sequential and observational study of 110 hospitalized adult patients fed exclusively by EN through a feeding tube. Patients were categorized according to the type of intestinal transit disorder as follows: group D (diarrhea, 3 or more watery evacuations in 24 hours), group C (constipation, less than 1 evacuation during 3 days), and group N (absence of diarrhea or constipation). All prescription drugs were recorded, and patients were analyzed according to the type and amount of medication received. The authors also investigated the presence of fiber in the enteral formula. Results: Patients classified in group C represented 70% of the study population; group D comprised 13%, and group N represented 17%. There was an association between group C and orotracheal intubation as the indication for EN (P<.001). Enteral formula without fiber was associated with constipation (logistic regression analysis: P<.001). Conclusion: Constipation is more frequent than diarrhea in patients fed exclusively by EN. Enteral diet with fiber may protect against medication-associated intestinal motility disorders. The addition of prokinetic drugs seems to be useful in preventing constipation. (Nutr Clin Pract. XXXX;xx:xx-xx)

The presence of genes encoding for different virulence factors in clonally related Escherichia coli that produce CTX-Ms

Successful international clones have recently emerged among Escherichia coli that produce CTX-M beta-lactamases as important causes of community-onset urinary tract and bloodstream infections. One hundred and seven isolates that belong to sequence types (STs) ST38, ST131, ST405, ST648, and 38 nonrelated CTX-M producing E. coli from Canada and the Netherlands were assigned to phylogenetic groups and tested for the presence of genes encoding for virulence factors (VFs) using established multiplex polymerase chain reaction. The STs E. coli were significantly more resistant to antibiotics-ST38, ST405, and ST648 belonged to phylogenetic group D while ST131 belonged to B2. Secreted autotransporter toxin (sat), aerobactin receptor, and pathogenicity island marker were significantly more common among the STs; the heat-resistant agglutinin (hra) was present in ST38, sat, and uropathogenic-specific protein, and putative adhesin-siderophore receptor was more common in ST131, while outer membrane protease T was present in ST648. ST131 had a significantly higher VF score. In conclusion, the precise role of these VFs remains to be elucidated; however, we have identified certain putative VFs that possibly contribute to the fitness and success of certain sequence types. (C) 2012 Elsevier Inc. All rights reserved.

Cessation of physical exercise changes metabolism and modifies the adipocyte cellularity of the periepididymal white adipose tissue in rats

All of the adaptations acquired through physical training are reversible with inactivity. Although significant reductions in maximal oxygen uptake (VO2max) can be observed within 2 to 4 wk of detraining, the consequences of detraining on the physiology of adipose tissue are poorly known. Our aim was therefore to investigate the effects of discontinuing training (physical detraining) on the metabolism and adipocyte cellularity of rat periepididymal (PE) adipose tissue. Male Wistar rats, aged 6 wk, were divided into three groups and studied for 12 wk under the following conditions: 1) trained (T) throughout the period; 2) detrained (D), trained during the first 8 wk and detrained during the remaining 4 wk; and 3) age-matched sedentary (S). Training consisted of treadmill running sessions (1 h/day, 5 days/wk, 50–60%VO2max). The PE adipocyte size analysis revealed significant differences between the groups. The adipocyte cross-sectional area (in µm2) was significantly larger in D than in the T and S groups (3,474 ± 68.8; 1,945.7 ± 45.6; 2,492.4 ± 49.08, respectively, P < 0.05). Compared with T, the isolated adipose cells (of the D rats) showed a 48% increase in the ability to perform lipogenesis (both basal and maximally insulin-stimulated) and isoproterenol-stimulated lipolysis. No changes were observed with respect to unstimulated lipolysis. A 15% reduction in the proportion of apoptotic adipocytes was observed in groups T and D compared with group S. The gene expression levels of adiponectin and PPAR-gamma were upregulated by factors of 3 and 2 in D vs. S, respectively. PREF-1 gene expression was 3-fold higher in T vs. S. From these results, we hypothesize that adipogenesis was stimulated in group D and accompanied by significant adipocyte hypertrophy and an increase in the lipogenic capacity of the adipocytes. The occurrence of apoptotic nuclei in PE fat cells was reduced in the D and T rats; these results raise the possibility that the adipose tissue changes after detraining are obesogenic.

Parenteral administration of vitamins A, D and E on the oxidative metabolism and function of polymorphonuclear leukocytes in swine

The weaning period of piglets is characterized by physiological alterations, such as decreased weight gain, increased reactive oxygen species (ROS) and increased serum cortisol levels with possible effects on the immune response. The effect of parenteral administration of vitamins A, D and E on production performance, oxidative metabolism, and the function of polymorphonuclear leukocytes (PMNLs) was assessed in piglets during the weaning period. The sample was comprised of 20 male piglets that were given an injectable ADE vitamin combination (135,000 IU vitamin A, 40,000 IU vitamin D and 40mg vitamin E/animal) at 20 and 40 days of age. Weight gain, concentration of reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and the microbicidal and phagocytic activity of PMNLs were assessed. No difference was observed in the average piglet weight during the study; however, a greater percentage of weight gain was observed after weaning in the treated group. The concentrations of GSH and SOD did not differ between groups, although lipid peroxidation was greater in the control group at 60 days of age. The investigated variables of oxidative metabolism were correlated as follows: -0.41 for GSH and MDA, -0.54 for GSH and SOD and 0.34 for MDA and SOD. The intensity of intracellular ROS production, the percentage of ROS-producing PMNLs and the intensity of phagocytosis by PMNLs did not differ between treatment groups. Administration of the injectable ADE combination improved the percentage of weight gain between 20 and 40 days of age, decreased oxidative stress at 60 days of age and did not influence the function of PMNLs in piglets.

A Randomized, Naturalistic, Parallel-Group Study for the Long-Term Treatment of Panic Disorder With Clonazepam or Paroxetine

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [ SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

Modulation transfer function and optical quality after bilateral implantation of a+3.00 D versus a+4.00 D multifocal intraocular lens

PURPOSE: To determine whether the improvement in intermediate vision after bilateral implantation of an aspheric multifocal intraocular lens (IOL) with a +3.00 diopter (D) addition (add) occurs at the expense of optical quality compared with the previous model with a +4.00 D add. SETTING: Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil. DESIGN: Prospective randomized double-masked comparative clinical trial. METHODS: One year after bilateral implantation of Acrysof Restor SN6AD1 +3.00 D IOLs or Acrysof Restor SN6AD3 +4.00 D IOLs, optical quality was evaluated by analyzing the in vivo modulation transfer function (MTF) and point-spread function (expressed as Strehl ratio). The Strehl ratio and MTF curve with a 4.0 pupil and a 6.0 mm pupil were measured by dynamic retinoscopy aberrometry. The uncorrected and corrected distance visual acuities at 4 m, uncorrected and distance-corrected near visual acuities at 40 cm, and uncorrected and distance-corrected intermediate visual acuities at 50 cm, 60 cm, and 70 cm were measured. RESULTS: Both IOL groups comprised 40 eyes of 20 patients. One year postoperatively, there were no statistically significant between-group differences in the MTF or Strehl ratio with either pupil size. There were no statistically significant between-group differences in distance or near visual acuity. Intermediate visual acuity was significantly better in the +3.00 D IOL group. CONCLUSION: Results indicate that the improvement in intermediate vision in eyes with the aspheric multifocal +3.00 D add IOL occurred without decreasing optical quality over that with the previous version IOL with a +4.00 D add.

Weedy Hosts and Prevalence of Potential Leafhopper Vectors (Hemiptera: Cicadellidae) of a Phytoplasma (16SrIX group) Associated With Huanglongbing Symptoms in Citrus Groves

Huanglongbing (HLB) is a severe citrus (Citrus spp.) disease associated with the bacteria genus Candidatus Liberibacter, detected in Brazil in 2004. Another bacterium was found in association with HLB symptoms and characterized as a phytoplasma belonging to the 16SrIX group. The objectives of this study were to identify potential leafhopper vectors of the HLB-associated phytoplasma and their host plants. Leafhoppers were sampled every other week for 12 mo with sticky yellow cards placed at two heights (0.3 and 1.5 m) in the citrus tree canopy and by using a sweep net in the ground vegetation of two sweet orange, Citrus sinensis (L.) Osbeck, groves infected by the HLB-phytoplasma in Sao Paulo state. Faunistic analyses indicated one Agalliinae (Agallia albidula Uhler) and three Deltocephalinae [Balclutha hebe (Kirkaldy), Planicephalus flavicosta (Stal), and Scaphytopius (Convelinus) marginelineatus (Stal)] species, as the most abundant and frequent leafhoppers (Hemiptera: Cicadellidae). Visual observations indicated an association of leafhopper species with some weeds and the influence of weed species composition on leafhopper abundance in low-lying vegetation. S. marginelineatus and P. flavicosta were more frequent on Sida rhombifolia L. and Althernantera tenella Colla, respectively, whereas A. albidula was observed more often on Conyza bonariensis (L.) Cronq. and B. hebe only occurred on grasses. DNA samples of field-collected S. marginelineatus were positive by polymerase chain reaction and sequencing tests for the presence of the HLB-phytoplasma group, indicating it as a potential vector. The association of leafhoppers with their hosts may be used in deciding which management strategies to adopt against weeds and diseases in citrus orchards.

Broad and Cross-Clade CD4(+) T-Cell Responses Elicited by a DNA Vaccine Encoding Highly Conserved and Promiscuous HIV-1 M-Group Consensus Peptides

T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4(+) T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4(+) T-cell epitopes in vaccines. A successful HIV-1 vaccine should also be designed to overcome viral genetic diversity and be able to confer immunity in a high proportion of immunized individuals from a diverse HLA-bearing population. In this study, we rationally designed a multiepitopic DNA vaccine in order to elicit broad and cross-clade CD4(+) T-cell responses against highly conserved and promiscuous peptides from the HIV-1 M-group consensus sequence. We identified 27 conserved, multiple HLA-DR-binding peptides in the HIV-1 M-group consensus sequences of Gag, Pol, Nef, Vif, Vpr, Rev and Vpu using the TEPITOPE algorithm. The peptides bound in vitro to an average of 12 out of the 17 tested HLA-DR molecules and also to several molecules such as HLA-DP, -DQ and murine IA(b) and IA(d). Sixteen out of the 27 peptides were recognized by PBMC from patients infected with different HIV-1 variants and 72% of such patients recognized at least 1 peptide. Immunization with a DNA vaccine (HIVBr27) encoding the identified peptides elicited IFN-gamma secretion against 11 out of the 27 peptides in BALB/c mice; CD4(+) and CD8(+) T-cell proliferation was observed against 8 and 6 peptides, respectively. HIVBr27 immunization elicited cross-clade T-cell responses against several HIV-1 peptide variants. Polyfunctional CD4(+) and CD8(+) T cells, able to simultaneously proliferate and produce IFN-gamma and TNF-alpha, were also observed. This vaccine concept may cope with HIV-1 genetic diversity as well as provide increased population coverage, which are desirable features for an efficacious strategy against HIV-1/AIDS.