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.     

Evidence of Hantavirus Infection among Bats in Brazil

Hantaviruses are zoonotic viruses harbored by rodents, bats, and shrews. At present, only rodent-borne hantaviruses are associated with severe illness in humans. New species of hantaviruses have been recently identified in bats and shrews greatly expanding the potential reservoirs and ranges of these viruses. Brazil has one of the highest incidences of hantavirus cardiopulmonary syndrome in South America, hence it is critical to know what is the prevalence of hantaviruses in Brazil. Although much is known about rodent reservoirs, little is known regarding bats. We captured 270 bats from February 2012 to April 2014. Serum was screened for the presence of antibodies against a recombinant nucleoprotein (rN) of Araraquara virus (ARAQV). The prevalence of antibody to hantavirus was 9/53 with an overall seroprevalence of 17%. Previous studies have shown only insectivorous bats to harbor hantavirus; however, in our study, of the nine seropositive bats, five were frugivorous, one was carnivorous, and three were sanguivorous phyllostomid bats.Hantaviruses (family Bunyaviridae) are present throughout the globe in rodents, bats, and shrews.¹ Humans exposed to rodent excreta from hantaviral reservoirs may develop life-threatening diseases. However, none of the other reservoirs are associated with human illness presently.^1,2 Bats (order Chiroptera) are known to harbor a broad diversity of emerging zoonotic pathogens.² Their ability to fly and social behavior favors maintenance, evolution, and spread of pathogens.^1,2 The prevailing hypothesis has been that hantaviruses have coevolved with their rodent reservoirs over millions of years.^1,3 With the recognition of new species of hantavirus in bats in Africa and Asia,⁴ Guo and others⁵ hypothesized that hantaviruses originated primarily in bats and then spilled over into rodents and shrews, but it seems that shrews are the original hosts from which the viruses jumped into both rodents and bats.³ To determine if New World bats in Brazil may harbor hantaviruses, we screened bat sera for antibodies that react against the recombinant nucleoprotein (rN) of Araraquara hantavirus (ARAQV).Bats were collected at five ecologically distinct sites in the northeast region of São Paulo state (sites 1–3) and north region of Minas Gerais state (sites 4 and 5), southeastern Brazil (Figure 1 and 9 and one specimen per species by trap-night was anesthetized to collect blood by cardiac puncture; blood samples were stored in cryovials and flash-frozen in liquid nitrogen. At sites 4 and 5, five specimens per trap-night were randomly selected for blood collection. All bats were handled and sampled according to Sikes and others¹⁰ guidelines. This research project, along with its procedures and protocols, is in accordance with Brazilian environment and wildlife protection laws and regulations, and have been approved by the Chico Mendes Institute of Biodiversity Conservation (Ministry of Environment, Brasília, Distrito Federal, Brazil.), protocols nos. 19838-1 and 41709-3. It has also been approved by the Ethics Committee for Animal Research of University of São Paulo and Federal University of Minas Gerais (nos. 020/2011 and 333/2013, respectively). From 270 captured bats, 53 were bled for detection of immunoglobulin G (IgG) antibodies to rN-ARAQV by indirect enzyme-linked immunosorbent assay (ELISA) using anti-bat (Bethyl Laboratories, Inc., Montgomery, TX) secondary antibody. This ELISA, as previously described, showed 97.2% sensitivity, 100% specificity, 100% positive predictive value, and 98.1% negative predictive value when compared with an IgG-ELISA using rN antigen of Andes virus, which is the serological test for hantavirus most used in South America.^11,12Open in a separate windowFigure 1.Study areas, highlighting the states of São Paulo and Minas Gerais in southeastern Brazil. The map shows cities where bats have been captured.

Table 1

Trap sites general features⁶

Immunophenotypic Profile and Increased Risk of Hospital Admission for Infection in Infants Born to Female Kidney Transplant Recipients

Children born to female kidney recipients are exposed to immunosuppressive drugs during gestation. Little is known about their immune system at birth or in the long term. Twenty‐eight children born to female kidney recipients and 40 full‐term children born to healthy mothers were evaluated. T, B, NK, NKT, γδT cells were assessed by flow cytometry and functional evaluation of T and dendritic cells after in vitro activation was performed at birth and at 8 months of age. At birth, infants born to female kidney recipients showed lower numbers of CD4+ T, NKT and intense reduction of B cells (median cells/mm³, transplant: 153.7 X control: 512.4; p < 0.001). There was also a reduced percentage of activated CD8+ T and of CD4+ regulatory T cells. Activated memory and exhausted memory B cells showed higher percentages among children exposed to immunosuppressors when compared to control group. At 8 months, most immune alterations were no longer observed, but four children still had low numbers of some lymphocyte subsets at this age. Children born to female kidney recipients had 4.351 (95% CI: 1.026–15.225; p = 0.046) higher risk of hospital admission in the first months of life—some, with severe clinical manifestations—than those born to healthy women.