Alcohol Consumption and Periodontitis: Quantification of Periodontal Pathogens and Cytokines

Background: There are few studies on periodontal status related to microbiologic and immunologic profiles among individuals not or occasionally using alcohol and those with alcohol dependence. The aim of this study is to determine the effect of alcohol consumption on the levels of subgingival periodontal pathogens and proinflammatory cytokines (interleukin [IL]‐1β and tumor necrosis factor [TNF]‐α) in the gingival fluid among individuals with and without periodontitis. Methods: This observational analytic study includes 88 volunteers allocated in four groups (n = 22): individuals with alcohol dependence and periodontitis (ADP), individuals with alcohol dependence and without periodontitis (ADNP), individuals not or occasionally using alcohol with periodontitis (NAP), and individuals not or occasionally using alcohol without periodontitis (NANP). Levels of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Eikenella corrodens, and Fusobacterium nucleatum were determined by real‐time polymerase chain reaction on the basis of the subgingival biofilm, and IL‐1β and TNF‐α were quantified by enzyme‐linked immunosorbent assay in gingival fluid samples. Results: Individuals with alcohol dependence showed worse periodontal status and higher levels of P. intermedia, E. corrodens, F. nucleatum, and IL‐1β than non‐users. No significant correlations between TNF‐α and bacterial levels were observed. However, in the ADP group, higher levels of E. corrodens were correlated with higher levels of IL‐1β. Conclusion: A negative influence of alcohol consumption was observed on clinical and microbiologic periodontal parameters, as well as a slight influence on immunologic parameters, signaling the need for additional studies.     

Exenatide and Sitagliptin Decrease Interleukin 1β, Matrix Metalloproteinase 9, and Nitric Oxide Synthase 2 Gene Expression But Does Not Reduce Alveolar Bone Loss in Rats With Periodontitis

Background: New drugs for the treatment of diabetes, glucagon‐like peptide‐1 (GLP‐1) receptor agonists and inhibitors of dipeptidyl peptidase‐4 (DPP‐4) have shown pleiotropic effects on bone metabolism and anti‐inflammatory properties. The aim of this study is to evaluate the effects of exenatide (GLP‐1 agonist) and sitagliptin (DPP‐4 inhibitor) during periodontitis induction by ligature insertion in rats. Methods: Forty rats were divided into four groups: 1) animals with induced periodontitis that received exenatide (EG); 2) animals with induced periodontitis that received sitagliptin (SG); 3) animals with induced periodontitis and without drug treatment (LG); and 4) animals without induced periodontitis and without drug treatment (controls). The drugs were administered for 28 days. On the day the animals were sacrificed, blood was collected for analysis of glucose and DPP‐4 levels. The gene expressions of prostaglandin‐endoperoxide synthase 2, tissue inhibitor of metalloproteinase 1, Dpp4, nitric oxide synthase 2 (Nos2), interleukin 1β (Il1b), and matrix metalloproteinase 9 (Mmp9) in the gingiva; support and alveolar bone loss; connective tissue attachment; and the quantity of gingival collagen were evaluated. Results: Exenatide and sitagliptin treatments have led to a lower percentage of weight gain but did not influence glycemia. Sitagliptin reduced the serum concentration of DPP‐4. Interestingly, although the gene expression profile has revealed a downregulation of Mmp9, Nos2, and Il1b in both EG and SG compared to LG, a significant protective effect was not observed on alveolar bone and collagen tissue in this model. Conclusion: Regardless of the reduction of the expression of Il1b, Nos2, and Mmp9, the drugs were not effective in the stabilization or reduction of alveolar bone loss and collagen degradation in rats.     

Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro.

We made a retrospective longitudinal study from January 2000 to January 2003 to examine cases of immune reconstitution syndrome (IRS) and its incidence rate in tuberculosis (TB)-human immunodeficiency virus (HIV) co-infected patients. The incidence rate (IR) was calculated using a Poisson regression. The confidence interval (CI) that was stipulated was 95%. IRS occurred in 10/84 HIV and TB-positive patients; nine of them were on highly active anti-retroviral therapy (HAART) during a mean of 61.7 (+/- 59) days following the introduction of antiretrovirals. Lymph-node enlargement was the sole clinical manifestation. CD4 counts were <100 cells/mm(3)in 50% of the patients, at the time of TB diagnosis. All but two patients were treated with prednisone, and recovered from TB within a mean of 91 days (+/- 30 days). One relapse of TB was observed, but there were no IRS-related deaths. The incidence rate was higher (IR=11.18; CI, 1.41-88.76) in patients that had superficial lymph node enlargement at the moment of TB diagnosis (not associated with TB), extrapulmonary TB (IR=1.97; CI, 0.44-8.79), were antiretroviral naive (IR=1.85; CI, 0.48-7.16), and CD4 counts <100 cells/mm(3) (IR=1.50; CI, 0.40-5.59), although with a wide CI. IRS was frequent in our sample, occurred more frequently in HIV-naive patients with lymph-node enlargement and extrapulmonary TB. No cases of new pulmonary lesions or worsening of pulmonary infiltrates were observed.     

Gonadotropins and Growth Hormone Family Characterization in an Endangered Siluriform Species,Steindachneridion parahybae (Pimelodidae): Relationship With Annual Reproductive Cycle and Induced Spawning in Captivity

The aim of this study was to identify and characterize pituitary cells of Steindachneridion parahybae females in captivity, highlighting the possible relationship with reproductive disorders at this level, since this species shows oocyte final maturation, ovulation and spawning dysfunction in captivity. The localization and distribution of growth hormone (GH), prolactin (PRL), somatolactin (SL), β‐luteinizing hormone (β‐LH), and β‐follicle stimulating hormone (β‐FSH) immunoreactive (‐ir) cells in the adenohypophysis was studied by immunohistochemical and Western blot methods. In addition, cellular morphometric analyses and semi‐quantification of ir‐cells optical density (OD) during the annual reproductive cycle and after artificial induced spawning (AIS) were performed. Results showed that the distribution and general localization of pituitary cell types were similar to that of other teleost species. However, the morphometrical study of adenohypophysial cells showed differences along the reproductive cycle and following AIS. In general, females at the vitellogenic stage presented greater OD values for GH, PRL and SL than at other maturation stages (previtellogenic and regression stages), probably indicating an increased cellular activity during this stage. Conversely, β‐LH OD did not vary during the annual reproductive cycle. After AIS, β‐LH, SL and GH ir‐cells showed an increase in OD values suggesting a possible involvement on oocyte final maturation, ovulation and spawning or a feedback control on the brain‐pituitary‐gonads axis. Reproductive dysfunction in S. parahybae females in captivity may be due to alteration of the synthesis pathways of β‐LH. In addition, GH family of hormones could modulate associated mechanisms that influence the reproductive status in this species. Anat Rec, 298:1644–1658, 2015. © 2015 Wiley Periodicals, Inc.     

Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients

AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IBD)patients from southeastern Brazil.METHODS:A total of 219 consecutive patients with IBD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IBD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among Brazilian patients.Variants genes*2and*3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population.     

Novel Treatments with Small Molecules in Psoriatic Arthritis

Current treatment options for patients with active psoriatic arthritis (PsA) include synthetic disease-modifying antirheumatic drugs and biologic agents. Propelled by increased understanding of immunopathogenesis of PsA, new therapeutic agents targeting different biologic pathways have been evaluated. This article discusses novel small-molecule, orally available treatments that are currently in clinical development for the treatment of psoriasis and PsA. This includes the phosphodiesterase 4 inhibitor apremilast and Janus kinase (JAK) inhibitors. Apremilast has demonstrated significant improvements in patients with moderate to severe psoriasis and PsA in phase II and III clinical trials and has recently been approved for the treatment of PsA. Tofacitinib, an oral inhibitor of JAK3, JAK1, and, to a lesser degree, JAK2, approved for the treatment of rheumatoid arthritis in several countries, has demonstrated positive results in psoriasis in phase II studies. Studies in PsA are ongoing. With these new developments, treatment options will continue to improve in the future.     

IsdC from Staphylococcus lugdunensis Induces Biofilm Formation under Low-Iron Growth Conditions

Staphylococcus lugdunensis is a coagulase-negative staphylococcus that is a commensal of humans and an opportunistic pathogen. It can cause a spectrum of infections, including those that are associated with the ability to form biofilm, such as occurs with endocarditis or indwelling medical devices. The genome sequences of two strains revealed the presence of orthologues of the ica genes that are responsible for synthesis of poly-N-acetylglucosamine (PNAG) that is commonly associated with biofilm in other staphylococci. However, we discovered that biofilm formed by a panel of S. lugdunensis isolates growing in iron-restricted medium was susceptible to degradation by proteases and not by metaperiodate, suggesting that the biofilm matrix comprised proteins and not PNAG. When the iron concentration was raised to 1 mM biofilm formation by all strains tested was greatly reduced. A mutant of strain N920143 lacking the entire locus that encodes iron-regulated surface determinant (Isd) proteins was defective in biofilm formation under iron-limited conditions. An IsdC-null mutant was defective, whereas IsdK, IsdJ, and IsdB mutants formed biofilm to the same level as the parental strain. Expression of IsdC was required both for the primary attachment to unconditioned polystyrene and for the accumulation phase of biofilm involving cell-cell interactions. Purified recombinant IsdC protein formed dimers in solution and Lactococcus lactis cells expressing only IsdC adhered to immobilized recombinant IsdC but not to IsdJ, IsdK, or IsdB. This is consistent with a specific homophilic interaction between IsdC molecules on neighboring cells contributing to accumulation of S. lugdunensis biofilm in vivo.