Aging voice and the laryngeal muscle atrophy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Periapical lesions decrease insulin signaling in rat skeletal muscle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cimetidine-induced Leydig cell apoptosis and reduced EG-VEGF (PK-1) immunoexpression in rats: evidence for the testicular vasculature atrophy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genome-wide scan for visceral leishmaniasis in mixed-breed dogs identifies candidate genes involved in T helper cells and macrophage signaling

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

High-intensity resistance training attenuates dexamethasone-induced muscle atrophy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Downhill running excessive training inhibits hypertrophy in mice skeletal muscles with different fiber type composition

The aim of this study was to verify the effects of running overtraining protocols performed in downhill, uphill, and without inclination on the proteins related to hypertrophy signaling pathway in extensor digitorum longus (EDL) and soleus of C57BL/6 mice. We also performed histological and stereological analyses. Rodents were divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR). The incremental load, exhaustive, and grip force tests were used as performance evaluation parameters. 36 h after the grip force test, EDL and soleus were removed and immediately used for immunoblotting analysis or stored at -80°C for histological and stereological analyses. For EDL, OTR/down decreased the protein kinase B (Akt) and tuberous sclerosis protein 2 (TSC2) phosphorylation (p), and increased myostatin, receptor-activated Smads (pSMAD2-3), and insulin receptor substrate-1 (pIRS-1; Ser307/636). OTR/down also presented low and high relative proportions of cytoplasm and connective tissue, respectively. OTR/up increased the mammalian target of rapamycin (pmTOR), 70-kDa ribosomal protein S6 kinase 1 (pS6K1) and pSMAD2-3, and decreased pTSC2. OTR decreased pTSC2 and increased pIRS-1 (Ser636). For soleus, OTR/down increased S6 ribosomal protein (pS6RP) and pSMAD2-3, and decreased pIRS-1 (Ser639). OTR/up decreased pS6K1, pS6RP and pIRS-1 (Ser639), and increased pTSC2 (Ser939), and pSMAD2-3. OTR increased pS6RP, 4E-binding protein-1 (p4E-BP1), pTSC2 (Ser939), and pSMAD2-3, and decreased pIRS-1 (Ser639). In summary, OTR/down inhibited the skeletal muscle hypertrophy with concomitant signs of atrophy in EDL. The effects of OTR/up and OTR depended on the analyzed skeletal muscle type. J. Cell. Physiol. 9999: 1-12, 2015. © 2015 Wiley Periodicals, Inc.

Histomorphometric study of role of lactoferrin in atrophy of the intestinal mucosa of rats

The purpose of this work was to study the effects of oral administration of lactoferrin (Lf) in rats subjected to atrophy of the small intestine induced by a diet based on soy protein concentrate as the main protein source. We used 24 male Wistar rats aged 40 days, kept in individual cages under appropriate conditions of temperature, light and humidity. The animals were divided into four groups (n = 6); 1) group SL received soy-based food and, once a day, a supplement of 200mg/kg of Lf administered by gavage; 2) group Si received the soy feed without supplement of Lf; 3) group CL received a diet based on casein plus Lf; 4) group Ci received the casein diet without supplement of Lf. At the end of fifteen days, a 10 mm segment of the initial portion of the small intestine was sectioned and subjected to morphometry of the intestinal crypts and villi and assessment of the number and size of myofibroblasts. Comparison between groups showed that the length of the villi was similar in groups Ci and CL and higher in CL than in SL; SL than in Si, in Ci than in SL, and in Ci than in Si to Ci. The crypt depth was similar in SL and CL, SL and Ci and Ci and CL and was higher in Si than in Ci and in Si than in SL. The number of myofibroblasts was higher in SL than in CL, in SL than in Si, in CL than in Ci, and in SL than in and Ci; between Ci and Si there was no difference. The area of myofibroblasts was similar between the groups SL and CL and Si and Ci and higher in SL than in Si, and in Cl than in and Ci, and in SL than in Ci. All statistical analysis assumed significance when p < 0.05. From these results, we conclude that lactoferrin increases the number and size of the pericrypt myofibroblasts and stimulates rapidly the regeneration of atrophied villi.

Reconstruction of maxillary ridge atrophy caused by dentoalveolar trauma, using autogenous block bone graft harvested from chin: a case report

Background Dentoalveolar trauma, especially when involving front teeth, negatively affect the patient’s life; in particular, tooth avulsion is a complex injury that affects multiple tissues, and no treatment option offers stable long-term outcomes. The aim of this study was to report a case of reconstruction of atrophic anterior alveolar ridge after tooth loss, performed with autograft harvested from the chin, and subsequent prosthetic rehabilitation with the use of an osseointegrated implant. Case report A 23-years-old Caucasian girl, presented an atrophic alveolar bone in the area of tooth 11, as a result of tooth resorption 10 years after a tooth reimplantation procedure. Reconstruction was performed with autogenous bone harvested from the chin. After 6-months healing period to allow autograft incorporation, a dental implant was inserted. After further 6- months, a screw-retained implant supported metal-ceramic prosthesis was fabricated. Results The prosthetic rehabilitation was successful, and after a follow-up period of 5 years, the achieved result was stable.Conclusion It can be concluded that the autogenous bone graft harvested from the chin, is a safe and effective option for alveolar ridge defects reconstruction, allowing a subsequent placement of a dental implant supporting a prosthetic restoration.

Reconstruction of maxillary ridge atrophy caused by sequela of dentoalveolar trauma with autogenous bone graft harvested from mentum

Dentoalveolar traumatisms, particularly those that affect the anterior teeth, interfere adversely in the patient s life.Among them, tooth avulsion is pointed out because it is characterized as a complex injury that affects multiple tissues, andbecause there is no effective treatment available for its resolution with a stable long-term outcome.Aim/Hypothesis: The aim of the present study was to relate a clinical case of complete reconstruction of atrophy of the alveolarbone corresponding to tooth 11, lost by tooth resorption 10 years after the tooth reimplantation procedure.Material and methods: Reconstruction was performed with autogenous bone harvested from the mentum donor site. Surgicalaccess began in the receptor area with a Newman mucoperiosteal incision using a scalpel blade 15 mounted in a scalpel handlefor detachment and exposure of the receptor site. Extensive bone resorption was observed in the vestibular-palatine direction,proved by the thinness of the receptor bed. Decorticalization of the vestibular bone plate was performed. After preparing thereceptor bed, and incision was made in the mucosa in the depth of the anterior vestibular fornix, then a perpendicular muscleperiostealincision to detach and exposure the donor area. The bone graft necessary for reconstruction of the donor area wasdelimited, followed by monocortical osteotomy and the monocortical graft was removed. The next stage was to perform shapingfor passive graft accommodation and fixation by means of two bicortical screws. After fixation of the graft the sharp angles wererounded off in order to avoid possible exposure and/or fenestrations of the reconstructed area, then the receptor and donor areawere sutured. After the 6-month period to allow incorporation of the autogenous graft, an osseointegrated dental implant wasinserted. At the end of the 6-month period of waiting for osseointegration to occur, the process of fabricating the screw-retainedmetal ceramic

Genomic gains in prostatic carcinoma and proliferative inflammatory atrophy in dogs

The dog can spontaneously develop prostate cancer and consequently can be used as an experimental model for prostatic diseases associated with aging, including benign prostate hyperplasia (BPH) and prostate carcinoma (PCa). DNA copy number variations (CNVs) have been used to identify genes associated with cancer development and progression. DNA microarray based comparative genomic hybridization (aCGH) is a technique that allows to identify copy number of thousands of genes throughout the genome. aCGH was used to identify genomic regions with significantly different DNA copy number in three benign prostatic hyperplasia (BPH), four proliferative inflammatory atrophy (PIA), and 14 canine prostate carcinoma (PCa). Five histologically normal prostate tissue were used as reference. Genomic DNA was extracted from formalin fixed and paraffin embedded samples and CNVs data was evaluated in Canine Genome CGH Microarray 4x44K (G2519F, Design ID021193, Agilent). Data analysis was performed using Genomic Workbench Standard Edition 5.0.14 (Agilent). PCa showed higher number of altered genes related to canonical diseases process, cellular functions and molecular pathways as well as greater inter-relationship between genes, compared with PIA and BPH. In conclusion, PCa showed a more complex genotype, being losses the most frequent genomic changes. Some discrepancies between genomic alterations in human and canine carcinomas may indicate the different clinical behavior of these tumors in these two species. In addition, it was observed was an ascending pattern of genomic complexity in BPH, PIA and CA consistent with a model of multistep tumor progression.

Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Signaling via cAMP in Fungi: Interconnections with Mitogen-Activated Protein Kinase Pathways

The cAMP signal transduction pathway controls a wide variety of processes in fungi. For example, considerable progress has been made in describing the involvement of cAMP pathway components in the control of morphogenesis in Saccharomyces cerevisiae, Ustilago maydis, and Magnaporthe grisea. These morphological processes include the establishment of filamentous growth in S. cerevisiae and U. maydis, and the differentiation of an appressorial infection structure in M. grisea. The discovery that appressorium formation requires cAMP signaling provides an immediate connection to fungal virulence. This connection may have broader implications among fungal pathogens because recent work indicates that cAMP signaling controls the expression of virulence traits in the human pathogen Cryptococcus neoformans. In this fungus, cAMP also influences mating, as has been found for Schizosaccharomyces pombe and as may occur in U. maydis. Finally, cAMP and mitogen- activated protein kinase pathways appear to function coordinately to control the response of certain fungi, e.g., Saccharomyces cerevisiae and Schizosaccharomyces pombe, to environmental stress. There are clues that interconnections between these pathways may be common in the control of many fungal processes.

Linker for Activation of T-cell Family Member2 (LAT2) a Lipid Raft Adaptor Protein for AKT Signaling, Is an Early Mediator of Alkylphospholipid Anti-leukemic Activity

Lipid rafts are highly ordered membrane domains rich in cholesterol and sphingolipids that provide a scaffold for signal transduction proteins; altered raft structure has also been implicated in cancer progression. We have shown that 25 mu M 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate (ODPC), an alkylphospholipid, targets high cholesterol domains in model membranes and induces apoptosis in leukemia cells but spares normal hematopoietic and epithelial cells under the same conditions. We performed a quantitative (SILAC) proteomic screening of ODPC targets in a lipid-raft-enriched fraction of leukemic cells to identify early events prior to the initiation of apoptosis. Six proteins, three with demonstrated palmitoylation sites, were reduced in abundance. One, the linker for activation of T-cell family member 2 (LAT2), is an adaptor protein associated with lipid rafts in its palmitoylated form and is specifically expressed in B lymphocytes and myeloid cells. Interestingly, LAT2 is not expressed in K562, a cell line more resistant to ODPC-induced apoptosis. There was an early loss of LAT2 in the lipid-raft-enriched fraction of NB4 cells within 3 h following treatment with 25 mu M ODPC. Subsequent degradation of LAT2 by proteasomes was observed. Twenty-five mu M ODPC inhibited AKT activation via myeloid growth factors, and LAT2 knockdown in NB4 cells by shRNA reproduced this effect. LAT2 knockdown in NB4 cells also decreased cell proliferation and increased cell sensitivity to ODPC (7.5X), perifosine (3X), and arsenic trioxide (8.5X). Taken together, these data indicate that LAT2 is an early mediator of the anti-leukemic activity of alkylphospholipids and arsenic trioxide. Thus, LAT2 may be used as a target for the design of drugs for cancer therapy. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.019661, 1898-1912, 2012.

Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss

Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1a), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3 beta) in the liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. Conversely, training reduced both TRB3 expression and TRB3 and Akt association. The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1a association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). Finally, exercised animals demonstrated increased at basal and insulin-induced GSK3 beta phosphorylation levels and glycogen content at 24?h after the last session of exercise. Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss. J. Cell. Physiol. 227: 29172926, 2012. (C) 2011 Wiley Periodicals, Inc.