Changes in PGE2 signaling after submandibulectomy alter post–tooth extraction socket healing

Saliva is very important to oral health, and a salivary deficit has been shown to bring serious problems to oral health. There is scant information about the mechanisms through which salivary glands participate in post–tooth extraction socket healing. Therefore, the aim of the present study was to investigate the effect of submandibulectomy (SMx), consisting of the ablation of submandibular and sublingual glands (SMG and SLG, respectively), on PGE2 signaling and other bone regulatory molecules, such as OPG and RANKL, involved in tooth extraction socket healing. Male Wistar rats, 70 g body weight, were assigned to an experimental (subjected to SMx) or a control group (sham operated). One week later, the animals in both groups underwent bilateral extraction of the first mandibular molars. The effect of SMx on different stages of socket healing after tooth extraction (7, 14, and 30 days) was studied by evaluating some parameters of inflammation, including PGE2 and its receptors, and of bone metabolism, as well as by performing bone biomechanical studies. SMx increased TNFα and PGE2 content as well as cyclooxygenase-II (COX-II) expression in tooth socket tissue at almost all the studied time points. SMx also had an effect on mRNA expression of PGE2 receptors at the different time points, but did not significantly alter osteoprotegerin (OPG) and RANKL mRNA expression at any of the studied time points. In addition, an increase in bone mass density was observed in SMx rats compared with matched controls, and the structural and mechanical bone properties of the mandibular socket bone were also affected by SMx. Our results suggest that the SMG/SLG complex regulates cellular activation and differentiation by modulating the production of molecules intervening in tooth extraction socket repair, including the PGE2 signaling system, which would therefore account for the higher density and resistance of the newly formed bone in SMx rat.Fil: Mohn, Claudia Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Troncoso, Gastón Rodolfo. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Bozzini, Clarisa. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Conti, María Inés. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Fernández Solari, José Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Elverdín, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Anemia in patients receiving anticancer treatments: focus on novel therapeutic approaches

Anemia is common in cancer patients and impacts on quality of life and prognosis. It is typically multifactorial, often involving different pathophysiological mechanisms, making treatment a difficult task. In patients undergoing active anticancer treatments like chemotherapy, decreased red blood cell (RBC) production due to myelosuppression generally predominates, but absolute or functional iron deficiency frequently coexists. Current treatments for chemotherapy-related anemia include blood transfusions, erythropoiesis-stimulating agents, and iron supplementation. Each option has limitations, and there is an urgent need for novel approaches. After decades of relative immobilism, several promising anti-anemic drugs are now entering the clinical scenario. Emerging novel classes of anti-anemic drugs recently introduced or in development for other types of anemia include activin receptor ligand traps, hypoxia-inducible factor-prolyl hydroxylase inhibitors, and hepcidin antagonists. Here, we discuss their possible role in the treatment of anemia observed in patients receiving anticancer therapies

Anti-Ro52 antibodies positivity in antisynthetase syndrome: a single centre cohort study

Objectives: Although antisynthetase antibodies (ARS) are the established markers of the so-called antisynthetase syndrome (ASSD), in these patients the concomitant positivity of anti-Ro52 antibodies, reported in up to the 50% of cases, is not rare. Several studies focused on the effect of different ARS specificities on the evolution of ASSD, the most recent showing no effects. On the contrary, the role of co-occurring anti-Ro52 antibodies in ASSD is still debated. We investigated the potential of anti-Ro52 antibodies in identifying a clinical phenotype of ASSD or influencing prognosis, irrespectively to the underlying ARS specificity. Methods: Retrospective analysis of clinical, imaging and laboratory characteristics, therapeutic approaches and outcome at baseline and at last follow-up, of 60 ASSD patients progressively enrolled at our Hospital. Results: We identified 34 anti-Ro+ and 26 anti-Ro- ASSD patients. Classic triad prevalence at baseline was similar between the two groups, whereas interstitial lung disease (ILD) (p value=0.01) and myositis (p value=0.03) were significantly more prevalent in anti-Ro52+ and in anti-Ro52- patients at last follow up, respectively. No differences in therapeutic approaches, oxygen need and ILD patterns were observed. Overall mortality was 25% (15 subjects). No differences in mortality, overall and disease related, between anti-Ro52+ and anti-Ro52- patients were observed (p value=0.764), despite the more frequent ILD occurrence in anti-Ro52+ patients. Survival curves were not different at any time point (Log-rank test, p value 0.98). Conclusions: Anti-Ro52 antibodies affect time course and clinical characteristics of ASSD. Although ILD is significantly more associated to anti-Ro52 antibodies, no difference in mortality was observed compared to anti-Ro52 negative patients

Red Blood Cell Morphologic Abnormalities in Patients Hospitalized for COVID-19

Peripheral blood smear is a simple laboratory tool, which remains of invaluable help for diagnosing primary and secondary abnormalities of blood cells despite advances in automated and molecular techniques. Red blood cells (RBCs) abnormalities are known to occur in many viral infections, typically in the form of mild normo-microcytic anemia. While several hematological alterations at automated complete blood count (including neutrophilia, lymphopenia, and increased red cell distribution width—RDW) have been consistently associated with severity of COVID-19, there is scarce information on RBCs morphological abnormalities, mainly as case-reports or small series of patients, which are hardly comparable due to heterogeneity in sampling times and definition of illness severity. We report here a systematic evaluation of RBCs morphology at peripheral blood smear in COVID-19 patients within the first 72 h from hospital admission. One hundred and fifteen patients were included, with detailed collection of other clinical variables and follow-up. A certain degree of abnormalities in RBCs morphology was observed in 75 (65%) patients. Heterogenous alterations were noted, with spiculated cells being the more frequent morphology. The group with >10% RBCs abnormalities had more consistent lymphopenia and thrombocytopenia compared to those without abnormalities or <10% RBCs abnormalities (p < 0.018, and p < 0.021, respectively), thus underpinning a possible association with an overall more sustained immune-inflammatory “stress” hematopoiesis. Follow-up analysis showed a different mortality rate across groups, with the highest rate in those with more frequent RBCs morphological alterations compared to those with <10% or no abnormalities (41.9%, vs. 20.5%, vs. 12.5%, respectively, p = 0.012). Despite the inherent limitations of such simple association, our results point out towards further studies on erythropoiesis alterations in the pathophysiology of COVID-19

Calcium absorption and bone retention in a model of growing rats: Effect of feeding an experimental yogurt-reduced in lactose-containing galactooligosaccharides (GOS)

GOS are natural prebiotic of maternal milk. They can be enzymatically synthetized in yogurt manufacture from milk lactose obtaining a dairy product reduced in lactose containing prebiotics and potentially probiotics. It was evaluated if this yogurt containing GOS and reduced in lactose (EY) offered some extra advantages as compared to a regular yogurt (RY) in calcium (Ca) and phosphate (Pi) absorption (Abs) and bone retention during normal growth. Male weaning rats received control diet (C), EY or regular yogurt (RY) during 28 days. Results showed no differences in food consumption and body weight between C and yogurts groups. EY showed the highest increase in fecal lactobacillus colonies, in short chain fatty acids production especially propionate and butyrate, in large intestinal crypt deep, and the lowest caecum pH, CaAbs% increased significantly as follows: EY>RY>C (p<0.05); PiAbs% was higher in EY vs. RY. Femur Ca and Pi content, bone mineral content, density and biomechanical parameters were similar in EY and C but lower in RY (p<0.05). The epiphyseal and hypertrophic cartilage widths were lower in EY and RY than in C (p<0.05) while total cartilage width was similar in EY and C. Conclusion: EY reduced in lactose increased mineral Abs attaining C group bone retention and quality while RY diet consumption did not achieve bone growth and quality of C group. Then EY would be a good strategy to attain an adequate peak bone mass during growth, especially in lactose intolerant subjects. Grant of UBACyT and CONICET.Fil: Seijo, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Bonanno, Marina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Vénica, Claudia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Pita Martín de Portela, María Luz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Sanidad Nutricion Bromatologia y Toxicologia. Catedra de Nutricion.; ArgentinaFil: Bozzini, Carlos Eduardo Jose. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Bergamini, Carina Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Wolf, Irma Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Perotti, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Zeni, Susana Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina4º Congreso Argentino de Osteologia; XXXVIII Reunión Anual de la Asociación Argentina de Osteología y XV Congreso Argentino de OsteoporosisCiudad de Buenos AiresArgentinaAsociación Argentina de Osteología y Metabolismo MineralSociedad Argentina de Osteoporosi

Hyperhomocysteinemia and Mortality after Coronary Artery Bypass Grafting

BACKGROUND: The independent prognostic impact, as well as the possible causal role, of hyperhomocysteinemia (HHcy) in coronary artery disease (CAD) is controversial. No previous study specifically has addressed the relationship between HHcy and mortality after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the prognostic impact of HHcy after CABG surgery. METHODOLOGY AND PRINCIPAL FINDINGS: We prospectively followed 350 patients who underwent elective CABG between May 1996 and May 1999. At baseline, fasting total homocysteine (tHcy) levels were measured in all participants, and a post-methionine loading (PML) test was performed in 77.7% of them (n = 272). After a median follow-up of 58 months, 33 patients (9.4%) had died, 25 because of cardiovascular events. HHcy, defined by levels higher than the 90(th) percentile (25.2 µmol/L) of the population's distribution, was significantly associated to total and cardiovascular mortality (P = 0.018 [log-rank test 5.57]; P = 0.002 [log-rank test 9.76], respectively). The PML test had no prognostic value. After multiple adjustment for other univariate predictors by Cox regression, including statin therapy (the most powerful predictor in uni-/multivariate analyses), high-sensitivity C Reactive Protein (hs-CRP) levels, and all known major genetic (MTHFR 677C→T polymorphism) and non-genetic (B-group vitamin status and renal function) tHcy determinants, HHcy remained an independent prognostic factor for mortality (HRs: 5.02, 95% CIs 1.88 to 13.42, P = 0.001). CONCLUSIONS: HHcy is an important prognostic marker after CABG, independent of modern drug therapy and biomarkers

Hyaluronic acid-decorated liposomes as innovative targeted delivery system for lung fibrotic cells

Collagen Tissue Disease-associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS) represent severe lung fibrogenic disorders, characterized by fibro-proliferation with uncontrolled extracellular matrix deposition. Hyaluronic acid (HA) plays a key role in fibrosis with its specific receptor, CD44, overexpressed by CTD-ILD and BOS cells. The aim is to use HA-liposomes to develop an inhalatory treatment for these diseases. Liposomes with HA of two molecular weights were prepared and characterized. Targeting efficiency was assessed toward CTD-ILD and BOS cells by flow cytometry and confocal microscopy and immune modulation by RT-PCR and ELISA techniques. HA-liposomes were internalized by CTD-ILD and BOS cells expressing CD44, and this effect increased with higher HA MW. In THP-1 cells, HA-liposomes decreased pro-inflammatory cytokines IL-1\u3b2, IL-12, and anti-fibrotic VEGF transcripts but increased TGF-\u3b2 mRNA. However, upon analyzing TGF-\u3b2 release from healthy donors-derived monocytes, we found liposomes did not alter the release of active pro-fibrotic cytokine. All liposomes induced mild activation of neutrophils regardless of the presence of HA. HA liposomes could be also applied for lung fibrotic diseases, being endowed with low pro-inflammatory activity, and results confirmed that higher MW HA are associated to an increased targeting efficiency for CD44 expressing LFs-derived from BOS and CTD-ILD patients

Absorción mineral y retención ósea en un modelo de crecimiento normal: efecto del consumo de una dieta a base de yogur experimental reducido en lactosa que contiene galactooligosacáridos (GOS)

Los GOS son prebióticos naturales de la leche materna que aumentan la absorción de Ca.Pueden generarse in situ por acción enzimática sobre la lactosa durante la manufactura de alimentos lácteos fermentados (yogures), generando un alimento reducido en lactosa. Objetivo: comparar las ventajas de consumir durante el crecimiento normal? yogur que contiene GOS y reducido en lactosa (YE), respecto de un yogur regular sin GOS (YC), ambos desarrollados por el Instituto de Lactología Industrial (UNL/CONICET, Santa Fe). Ratas recién destetadas (n=10/grupo) recibieron durante 30 días una dieta control preparada según AIN?93-G (C), una dieta a base de yogur regular sin GOS (YC) o una dieta a base del yogur reducido en lactosa que contenía GOS (YE). Se determinó: consumo de alimentos, peso corporal (PC), desarrollo de lactobacilos (LB), absorción de Ca y Pi (%AbsCa por el método de balance); pH, nivel de ácidos grasos cadena corta (AGCC) (por HPLC-IR) en el contenido cecal y profundidad de criptas intestinales (CI) (µm); DMO y CMO del esqueleto total (Et), columna lumbar (Cl) y tibia proximal (Tp) (por densitometría); porcentaje de volumen óseo por histología (VO) (%) y cartílagos epi!sario (GPC.Th) e hipertró!co (HpZ.Th) (µm); longitud del fémur (LF) (cm); parámetros de biomecánica como fuerza máxima de fractura (N), módulo de elasticidad (Mpa) y rigidez ósea (N/mm). Se aplicó test de normalidad Shapiro-Wilk y de Levene, y se realizó ANOVA para determinar diferencias entre grupos mediante programa SPSS 19.0® para Windows, considerando signi!cativo un p<0,05. Resultados (media ± DE): el consumo de alimentos y los PCs inicial y !nal no fueron signi!cativamente diferentes entre los grupos. YE mostró mayores valores en el peso del ciego, en el número de colonias de LB (p<0,05); en la concentración de AGCC fundamentalmente butirato y propionato (p<0,001) y en la profundidad de las CI (p<0,0001) y menor pH cecal (p<0,01) tanto de YC como del grupo C. La AbsCa en mg/d como porcentual también fue mayor vs. YC y C (p<0,05), lo cual se acompañó por mayor Abs%Pi. La AbsMg fue mayor que YC sin diferencias respecto de C. El YE mostró niveles de CTX similares a C y menores que YC (p<0,05). YE mayor DMO que YC en Et, Cl y Tp (p<0,05) sin diferencias respecto de dichos valores en el grupo C. El CMO Et fue similar en los 3 grupos. El grupo YE mostró mayor VO que los grupos C y YC (p<0,05) mientras que la LF y contenido de Ca y Pi en fémur fue mayor respecto de YC y sin diferencias respecto de C. YE presentó valores signi!cativamente menores en GPC.Th y HpZ.Th vs. C (p<0,05), pero signi!cativamente mayor que YC (p<0,05). YE mostró mayores valores de todos los parámetros de biomecánica respecto de YC (p<0,01) sin diferencias respecto de C. Conclusión: los datos obtenidos con!rman que esta matriz alimentaria simbiótica sería de utilidad en una etapa de la vida crítica para la adquisición de masa ósea como el crecimiento, fundamentalmente en individuos con intolerancia a la lactosa.Fil: Seijo, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Bonanno, Marina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Vénica, Claudia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Pita Martín de Portela, María Luz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Bozzini, Clarisa. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Bergamini, Carina Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Wolf, Irma Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Perotti, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Zeni, Susana Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina4to Congreso Argentino de OsteologíaCiudad de Buenos AiresArgentinaAsociación Argentina de Osteología y Metabolismo Minera

Combined Effect of Hemostatic Gene Polymorphisms and the Risk of Myocardial Infarction in Patients with Advanced Coronary Atherosclerosis

BACKGROUND: Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI. METHODOLOGY/PRINCIPAL FINDINGS: We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen beta -455G>A, FV Leiden and "R2", FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (chi(2) for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential. CONCLUSIONS: The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD