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Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between urate-lowering therapy and all-cause mortality in different chronic diseases to match its users and non-users in a real-world setting. Overall, 11 studies were included, which reported adjusted hazard ratios for all-cause mortality over at least 12 months. Meta-analysis of all included studies showed no effect of the therapy on all-cause mortality. However, subgroup analyses showed its beneficial effect in patients with chronic kidney disease (14% risk reduction) and hyperuricemia (14% risk reduction), but not in patients with heart failure (28% risk increase). Urate-lowering therapy reduces all-cause mortality among patients with hyperuricemia and chronic kidney disease, but it seems to increase mortality in patients with heart failure and should be avoided in this subgroup.
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Causas de Morte , Hiperuricemia , Xantina Oxidase , Humanos , Xantina Oxidase/antagonistas & inibidores , Hiperuricemia/tratamento farmacológico , Hiperuricemia/mortalidade , Hiperuricemia/sangue , Causas de Morte/tendências , Inibidores Enzimáticos/uso terapêutico , Fatores de Risco , Alopurinol/uso terapêutico , Supressores da Gota/uso terapêutico , Febuxostat/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Ácido Úrico/sangue , Insuficiência Renal Crônica/mortalidade , AdultoRESUMO
Background: Obesity is a risk factor for many diseases, diagnosed by calculating body mass index (BMI). Methods: To find an association between BMI and mortality in adults, we searched PubMed for articles published in the 21st century. Our review included 82 original studies, comprising 2.7 million patients and 23.4 million patient years. Results: The meta-analysis showed a U-shaped relationship between BMI and all-cause mortality risk, with the lowest mortality in the BMI range of 25-30 kg/m2. Subgroup analysis showed a J-shaped relationship, with greater risk in the highest BMI range (>35 kg/m2). Among the elderly, BMI values <20 kg/m2 were associated with the highest risk. Among diabetic patients, a U-shaped relationship was noticed, again with the highest risk in the lowest (<20 kg/m2) and highest BMI range (>35 kg/m2). Among patients with cardiovascular disease, the risk increased with BMI values <25 kg/m2 but did not noticeably change for BMI exceeding that value. Among cancer patients, the relationship was less pronounced than in other subgroups, with a slightly higher risk (>35 kg/m2). Conclusions: Our results show that the lowest mortality is observed among patients with BMI 25-30 kg/m2. Reduction of body mass should not be a universal recommendation in clinical practice, but it should be individualized.
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Due to the difficulties in retrieving both the time-dependent shapes of the vessels and the generation of numerical meshes for such cases, most of the simulations of blood flow in the cardiac arteries use static geometry. The article describes a methodology for generating a sequence of time-dependent 3D shapes based on images of different resolutions and qualities acquired from ECG-gated coronary artery CT angiography. The precision of the shape restoration method has been validated using an independent technique. The original proposed approach also generates for each of the retrieved vessel shapes a numerical mesh of the same topology (connectivity matrix), greatly simplifying the CFD blood flow simulations. This feature is of significant importance in practical CFD simulations, as it gives the possibility of using the mesh-morphing utility, minimizing the computation time and the need of interpolation between boundary meshes at subsequent time instants. The developed technique can be applied to generate numerical meshes in arteries and other organs whose shapes change over time. It is applicable to medical images produced by other than angio-CT modalities.
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Vasos Coronários , Hemodinâmica , Humanos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Angiografia Coronária/métodos , Próteses e Implantes , Tomografia Computadorizada por Raios XRESUMO
The tumor microenvironment is considered one of the main players in cancer development and progression and may influence the behavior of cancer cells. Periostin (POSTN) is an extracellular matrix protein, and its main functions are induction of fibrillogenesis, fibroblastic cell proliferation and migration, enhancing regeneration in normal tissue, and promoting metastasis in case of neoplasia. POSTN has already been studied in humans in several normal tissues, inflammatory processes, and neoplasms, revealing an important role in tumor progression in various types of cancer, such as colon, lung, head and neck, breast, ovarian, and prostate. In these latter, high levels of POSTN are usually associated with a more aggressive tumor behavior, tumor advanced stages, and poor prognosis, while in human bladder urothelial carcinoma (BUC), unlike in most tumors, POSTN expression seems to be downregulated. The expression of this marker has been poorly investigated in veterinary medicine; thus, this study aimed to immunohistochemically investigate the presence and the intensity of POSTN expression in canine BUCs and to determine a possible relationship between POSTN expression and histopathological features such as mitotic count and muscular and vascular invasions. For the present retrospective study, archived samples from 45 canine BUCs and 6 non-neoplastic canine bladders were considered for histological evaluation and immunohistochemical examination for the expression of POSTN. POSTN expression was semi-quantitatively assessed considering both the percentage of the neoplastic stroma positive for POSTN and the intensity of the immunohistochemical labeling. Histologically, 38 out of 45 tumors were papillary and 7 out of 45 were non-papillary. All tumors were infiltrating, being that 21 were muscle-invasive, and a significant correlation between this feature and vascular invasion emerged (P = 0.0001). In normal bladder tissue, as reported in humans, a thick and strongly positive belt of POSTN was visible, and in canine BUCs, stating that the expression is comparable with human benign as well as malignant bladder tissue, a general decrease in POSTN expression was observed except for a strongly labeled ring of POSTN observed around some neoplastic nodules infiltrating the muscle layer. Moreover, POSTN expression and mitotic count were significatively inversely correlated (P = 0.0015). The fact that POSTN protein is less expressed in urothelial carcinomas than in the normal bladder supports what was reported in human BUCs and, together with the negative correlation between mitotic count and protein expression that emerged in the present retrospective study, encourages further prospective follow-up studies to verify the possible role of POSTN in canine BUCs as a prognostic marker, and also as a possible target for the development of future anticancer therapies.
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Introduction: Testin is a protein involved in cell mobility, adhesion and colony formation. In rats, testin presence has been reported in the testes, and its possible role in spermatogenesis has been suggested. Studies in humans also suggest a possible role of testin as a cancer suppressor protein. In the dog, which represents both an important pet species and a good animal model for studying biological and pathological testicular processes, the presence of testin has never been reported. Material and Methods: In the present study, the expression of testin in foetal, prepubertal, adult and aged canine testes was investigated. Testes from 5 adult and 3 aged dogs, from 2 one-month-old puppies and from 2 foetuses miscarried at the end of pregnancy were immunohistochemically examined with a commercial antibody against testin. Results: Testin was intensely expressed in Sertoli cells in every testis examined. Spermatids were also positive for testin in mature dogs and in the testicular areas of the aged ones which were not atrophic. Weak expression of testin was also detected in all testes examined. Conclusion: The present study, the first demonstrating the presence of testin in canine testes, provides the basis for further dog-human comparative research and for studies on the role of this protein in canine physiology, reproduction and testicular pathologies.
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Hospital mortality in sepsis varies between 30-45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment strategy (iNO + low-dose steroid) on the lungs in a long-term porcine endotoxic shock model. As metalloproteinases (MMPs) are involved in the initiation of multiple organ dysfunction in septic shock, we evaluated the influence of this combination therapy on MMP2 and MMP9 activity and proIL-1ß maturation. A shock-like condition was established in 23 animals by continuous infusion of E. coli lipopolysaccharide (LPS) for 10 h. Then the animals were observed for 10 h. Twelve pigs received iNO and hydrocortisone (iNO treatment started 3 h after the initial LPS infusion and continued until the end of the experiment). Eleven pigs were controls. Pigs treated with iNO and hydrocortisone displayed less inflammatory infiltrates in the lungs than the controls and a lower level of IL-1ß. The proMMP2 was significantly decreased in the iNO and hydrocortisone group. The amount of an active MMP9 (~ 60 kDa) was decreased in the iNO and hydrocortisone group. Total gelatinolytic activity was lower in the iNO and hydrocortisone group. Reduced MMP activity was accompanied by a 2.5-fold decrease of the active IL-1ß form (17 kDa) in the pulmonary tissue of iNO combined with hydrocortisone exposed pigs. We demonstrated that in a porcine endotoxemia model the NO inhalation combined with intravenous hydrocortisone led to the attenuation of the inflammatory cascade induced by bacterial LPS. The decrease in pulmonary MMPs activities was accompanied by reduced proIL-1ß processing.
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Endotoxemia , Sepse , Choque Séptico , Animais , Suínos , Hidrocortisona , Óxido Nítrico/farmacologia , Lipopolissacarídeos/farmacologia , Metaloproteinase 9 da Matriz/uso terapêutico , Endotoxemia/tratamento farmacológico , Endotoxemia/induzido quimicamente , Escherichia coli , Pulmão , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Administração por InalaçãoRESUMO
BACKGROUND: Testicular tumours are common in dogs and, among them, interstitial cell tumours, seminomas and sustentacular cell tumours are the most reported. Mesenchymal testicular tumours are rarely reported in humans as in veterinary medicine where only three cases of sarcomas (leiomyomas and leomyosarcomas) have been described in two stallions and in a ram. CASE PRESENTATION: The present cases regarded a 12-year-old mixed-breed dog and a 10-year-old American Staffordshire Terrier that underwent bilateral orchiectomy. Formalin fixed testes were referred for histopathological diagnosis. At gross examination, in one of the testes of both dogs, a white, firm and variably cystic testicular mass, effacing and replacing the testicular parenchyma was detected. Samples were collected from both neoplastic and contralateral testes, routinely processed for histology and serial sections were also examined immunohistochemically with primary antibodies against cytokeratins, vimentin, Von Willebrand factor, inhibin-α, α-smooth muscle actin, smooth muscle myosin and desmin. Histopathological features as well as the immunohistochemical results, positive for vimentin, actin, myosin and desmin, confirmed the mesenchymal origin and the myoid phenotype of both testicular tumours supporting the diagnoses of leiomyosarcoma. CONCLUSIONS: To the authors knowledge these are the first cases of primary testicular sarcoma reported in the canine species. However, even rare, these tumours deserve to be considered in routine diagnosis when a testicular spindle cell tumour is observed. The immunohistochemical panel applied was useful to distinguish the present tumours from undifferentiated Sertoli cell tumours confirming the diagnosis of leiomyosarcoma.
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Doenças do Cão , Leiomiossarcoma , Sarcoma , Tumor de Células de Sertoli , Neoplasias Testiculares , Animais , Cães , Masculino , Actinas , Desmina , Doenças do Cão/diagnóstico , Doenças do Cão/cirurgia , Doenças do Cão/patologia , Imuno-Histoquímica , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/veterinária , Sarcoma/veterinária , Tumor de Células de Sertoli/patologia , Tumor de Células de Sertoli/veterinária , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/veterinária , VimentinaRESUMO
Hyperthyroidism is considered the most common endocrinopathy in middle-aged and old cats. The increased level of thyroid hormones influences many organs, including the heart. Cardiac functional and structural abnormalities in cats with hyperthyroidism have indeed been previously described. Nonetheless, myocardial vasculature has not been subjected to analysis. Also, no comparison with hypertrophic cardiomyopathy has been previously described. Although it has been shown that clinical alterations resolve after the treatment of hyperthyroidism, no detailed data have been published on the cardiac pathological or histopathological image of field cases of hyperthyroid cats that received pharmacological treatment. The aim of this study was to evaluate the cardiac pathological changes in feline hyperthyroidism and to compare them to alterations present in cardiac hypertrophy due to hypertrophic cardiomyopathy in cats. The study was conducted on 40 feline hearts divided into three groups: 17 hearts from cats suffering from hyperthyroidism, 13 hearts from cats suffering from idiopathic hypertrophic cardiomyopathy and 10 hearts from cats without cardiac or thyroid disease. A detailed pathological and histopathological examination was performed. Cats with hyperthyroidism showed no ventricular wall hypertrophy in contrast to cats with hypertrophic cardiomyopathy. Nonetheless, histological alterations were similarly advanced in both diseases. Moreover, in hyperthyroid cats more prominent vascular alterations were noted. In contrast to hypertrophic cardiomyopathy, the histological changes in hyperthyroid cats involved all ventricular walls and not mainly the left ventricle. Our study showed that despite normal cardiac wall thickness, cats with hyperthyroidism show severe structural changes in the myocardium.
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Cardiomiopatia Hipertrófica , Doenças do Gato , Hipertireoidismo , Gatos , Animais , Cardiomiopatia Hipertrófica/veterinária , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/patologia , Miocárdio/patologia , Hipertireoidismo/veterinária , Hipertireoidismo/patologia , Doenças do Gato/patologiaRESUMO
Breast cancer is one of the major causes of cancerrelated mortality among women worldwide. It metastasizes to distant organs, particularly to bone tissue. Nitrogencontaining bisphosphonates are mainly used as an adjuvant therapy to inhibit skeletalrelated events; however, there is increasing evidence to suggest that these compounds also exert antitumor effects. In previous studies, the authors synthesized two novel aminomethylidenebisphosphonates (BPs), namely benzene1,4bis[aminomethylidene(bisphosphonic)] acid (WG12399C) and naphthalene1,5bis[aminomethylidene(bisphosphonic)] acid (WG12592A). Both BPs exhibited notable antiresorptive activity in a mouse model of osteoporosis. The present study aimed to assess the in vivo anticancer activity of WG12399C and WG12592A in 4T1 breast adenocarcinoma model. WG12399C exerted an antimetastatic effect by reducing the number of spontaneous lung metastases by ~66% in comparison to the control. In the experimental metastasis model of 4T1luc2tdTomato cells, this compound reduced the incidence of tumor metastases in the lungs by approximately half in comparison to the control. Both WG12399C and WG12595A also significantly reduced the size and/or number of bone metastatic foci. Their proapoptotic and antiproliferative activity may, at least in part, explain the observed effects. Incubation with WG12399C induced an almost 6fold increase in caspase3 activity in 4T1 cells. Moreover, cells treated with WG12399C or WG12595A exhibited a 2fold reduction in invasiveness through Matrigel. Furthermore, both the BPs were able to sensitize the 4T1 cells to cytostatics. In summary, the results of the present study indicate that the examined aminomethylideneBPs may be of particular interest in the context of combined treatment in breast cancer therapy.
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Neoplasias Ósseas , Neoplasias Pulmonares , Animais , Camundongos , Feminino , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos/farmacologia , Neoplasias Pulmonares/secundário , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB CRESUMO
Cardiovascular diseases are the leading cause of mortality in the world, mainly due to atherosclerosis and its consequences. The article presents the numerical model of the blood flow through artificial aortic valve. The overset mesh approach was applied to simulate the valve leaflets motion and to realize the moving mesh, in the aortic arch and the main branches of cardiovascular system. To capture the cardiac system's response and the effect of vessel compliance on the outlet pressure, the lumped parameter model has been also included within the solution procedure. Three different turbulence modeling approaches were used and compared - the laminar, k-ϵ and k-ω model. The simulation results were also compared with the model excluding the moving valve geometry and the importance of the lumped parameter model for the outlet boundary condition was analyzed. Proposed numerical model and protocol was found as suitable for performing the virtual operations on the real patient vasculature geometry. The time-efficient turbulence model and overall solving procedure allows to support the clinicians in making decisions about the patient treatment and to predict the results of the future surgery.
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Valva Aórtica , Próteses Valvulares Cardíacas , Humanos , Valva Aórtica/cirurgia , Hemodinâmica , Resistência Vascular , Modelos Cardiovasculares , Velocidade do Fluxo Sanguíneo/fisiologia , Simulação por ComputadorRESUMO
BACKGROUND/AIM: Foxp3 is a transcription factor responsible for the formation of T regulatory lymphocytes. Foxp3 expression can be associated with either neoplastic progression or regression. The aim of the study was to evaluate Foxp3 expression in soft tissue tumours (fibromas and fibrosarcomas) of skin and subcutaneous tissue in dogs and to describe its relationship with tumour malignancy grade. MATERIALS AND METHODS: The study was conducted on 71 skin and subcutaneous tumours including 31 fibromas and 40 fibrosarcomas. The samples underwent histological and immunohistochemical evaluation using anti-Foxp3, anti-Ki, and vimentin antibodies. RESULTS: Cytoplasmic expression of Foxp3 protein in the cutaneous and subcutaneous fibrosarcomas in dogs was confirmed. Moreover, a positive relationship between the expression of Foxp3 and tumour malignancy grade and between Foxp3 and Ki-67 expression was noted. CONCLUSION: A positive correlation between the Foxp3 expression intensity and malignancy grade suggests a significant role of Foxp3 in the carcinogenesis of skin and subcutaneous fibrosarcomas in dogs. Increased expression of Foxp3 may have a positive effect on the progression of cancer.
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Fibroma , Fibrossarcoma , Fatores de Transcrição Forkhead , Animais , Cães , Pele , Tela Subcutânea , Fatores de Transcrição Forkhead/genéticaRESUMO
Introduction: An analysis of samples originating from domestic and exotic animals from Lower Silesia but also from other parts of Poland was carried out based on research conducted in 2014-2017. Material and Methods: The materials used for the study were 11,338 tumour samples taken in vivo during surgery and as biopsies and posthumously during necropsies. They were sent to the Department of Pathology at Wroclaw University of Environmental and Life Sciences for histopathological diagnosis. Results: The largest group were canine tumours, of which there were 9,745 (85.95%), followed by feline tumours, totalling 1,397 (12.32%), tumours from exotic animals (186; 1.64%), from horses (7; 0.06%), and from cows (2; 0.02%). A significant number of cases of animals suffering from more than one tumour were also found, which had not been frequently diagnosed previously. Conclusion: The number of neoplasms diagnosed in pets and exotic animals is increasing every year. The average animal age at diagnosis continues to fall. The greatest number of neoplasms were diagnosed in mixed-breed dogs and cats, and the number of tumours in a pure breed strictly correlated with breed's popularity in the research period. Mesenchymal tumours are still the most prevalent type of tumours in dogs, while in cats epithelial tumours predominate. The neoplasm case pattern in animals conforms to that in humans in the same area.
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Statins are lipid-lowering medications used for the prevention of cardiovascular disease (CVD), but the pleiotropic effects of statins might be beneficial in other chronic diseases. This meta-analysis investigated the association between statin use and mortality in different chronic conditions. Eligible studies were real-world studies that compared all-cause mortality over at least 12 months between propensity score-matched statin users and non-users. Overall, 54 studies were included: 21 in CVD, 6 in chronic kidney disease, 6 in chronic inflammatory diseases, 3 in cancer, and 18 in other diseases. The risk of all-cause mortality was significantly reduced in statin users (hazard ratio: 0.72, 95% confidence interval: 0.66−0.76). The reduction in mortality risk was similar in CVD studies (0.73, 0.66−0.76) and non-CVD studies (0.70, 0.67−0.79). There were no significant differences in the risk reduction between cohorts with different diseases (p = 0.179). The greatest mortality reduction was seen in studies from Asia (0.61, 0.61−0.73) and the lowest in studies from North America (0.78, 0.73−0.83) and Australia (0.78, 0.62−0.97). There was a significant heterogeneity (I2 = 95%, tau2 = 0.029, p < 0.01). In conclusion, statin use was associated with a significantly reduced risk of all-cause mortality in real-world cohorts with CVD and non-CVD.
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Pathogenic properties of orthologues to S. aureus staphylococcal enterotoxin C (SEC) and staphylococcal enterotoxin L (SEL) produced by S. epidermidis are largely unexplored. We assessed the enteropathogenic effects of S. epidermidis SECepi and SELepi and S. aureus SEC3 and SEL after oral administration to Balb/c mice. Intestinal sections from SE-treated mice were analyzed histopathologically. The T cell lineage markers (αß and γδ TCR CD3, CD4, CD8), T-cell activation marker CD69 and proliferation-related marker CD71 were assessed in intraepithelial lymphocytes (IEL), mesenteric lymph nodes (MLN) and spleens (SPL). Serum concentrations of SEC and SEL were determined. Ortologous S. epidermidis and S. aureus SEs exerted a number of common histopathological changes in the mouse gut. Atrophy, generation of villi gap and edema of the villi were the most prominent effects of SE treatment observed in mouse gut sections. The most marked effect of ortologous S. epidermidis and S. aureus SEs on the number of goblet cells, crypt depth and villi height was noted in the mice duodenum and jejunum. We indicate early changes of TCRαß CD4-CD8a+ T and TCRαß CD4+CD8a+ T cells in response to both S. aureus and S. epidermidis SEs. Upon the treatment with SEs, markers of T cell activation and proliferation were upregulated in both αß and γδ T cell populations derived from IEL and MLN. We demonstrated that S. epidermidis-encoded SEs applied via oral route exert pathological changes in mice gut similarly to S. aureus-encoded SEs. For the first time we indicated that SEL co-produced together with SEC by both S. aureus and S. epidermidis induces some elements of mice gut immune response and contributes to gastrointestinal tract damage. Our results indicate the potential involvement of CoNS-encoded enterotoxins in the pathogenesis of SFP.
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Infecções Estafilocócicas , Staphylococcus aureus , Animais , Enterotoxinas , Camundongos , Staphylococcus epidermidisAssuntos
Desfibriladores Implantáveis , Marca-Passo Artificial , Eletrônica , Coração , Humanos , PolôniaRESUMO
ABSTRACT: The inhibitor of apoptosis family proteins (IAPs) plays a crucial role in the process of carcinogenesis by regulating apoptosis and maintaining the tissue balance.In this study, a transcriptomic analysis of IAP-encoding genes in colon cancer was performed using oligonucleotide microarrays.Adenocarcinoma and healthy colon tissue samples were collected from 32 patients (16 females and 16 males) who underwent surgery due to colon cancer. The mRNA was extracted from tissue samples and tested using oligonucleotide microarrays (Affymetrix). The results were validated using the qRT-PCR technique. Hierarchical grouping was used to allocate 37 samples of normalized mRNA concentrations into 4 groups, with statistically significant differences in gene expression between these groups. The group of genes associated with colon cancer, including IAP-encoding gene - BIRC5 (Survivin), was selected for further testing.Our study confirmed an increased expression of BIRC5 in colon cancer tissue when compared to the control group. Increased levels of Neuronal Apoptosis Inhibitory Proteins were detected only in low-stage colon cancer, while the expression of Human X Chromosome-Encoded inhibitor of apoptosis family proteins decreased in colon cancer.The transcriptional activity of IAP-encoding genes varied, depending on the severity of colon cancer. The concentration of mRNA, encoding BIRC5 was elevated in samples obtained from more advanced colon cancer. Hence BIRC5 could be used as a complementary parameter for the diagnosis and prognosis of colon cancer.
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Apoptose/genética , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Proteínas Inibidoras de Apoptose/genética , Survivina/genética , Biomarcadores Tumorais , Neoplasias do Colo/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Proteína Inibidora de Apoptose Neuronal , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Osteoporosis is a skeletal disease associated with excessive bone turnover. Among the compounds with antiresorptive activity, nitrogen-containing bisphosphonates play the most important role in antiosteoporotic treatment. In previous studies, we obtained two aminomethylidenebisphosphonates-benzene-1,4-bis[aminomethylidene(bisphosphonic)] (WG12399C) acid and naphthalene-1,5-bis[aminomethylidene(bisphosphonic)] (WG12592A) acid-which showed a significant antiproliferative activity toward J774E macrophages, a model of osteoclast precursors. The aim of these studies was to evaluate the antiresorptive activity of these aminobisphosphonates in ovariectomized (OVX) Balb/c mice. The influence of WG12399C and WG12592A administration on bone microstructure and bone strength was studied. Intravenous injections of WG12399C and WG12592A bisphosphonates remarkably prevented OVX-induced bone loss; for example, they sustained bone mineral density at control levels and restored other bone parameters such as trabecular separation. This was accompanied by a remarkable reduction in the number of TRAP-positive cells in bone tissue. However, a significant improvement in the quality of bone structure did not correlate with a parallel increase in bone strength. In ex vivo studies, WG12399C and WG12592A remarkably bisphosphonates reduced osteoclastogenesis and partially inhibited the resorptive activity of mature osteoclasts. Our results show interesting biological activity of two aminobisphosphonates, which may be of interest in the context of antiresorptive therapy.
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Osso Esponjoso , Diferenciação Celular/efeitos dos fármacos , Difosfonatos/farmacologia , Osteoclastos/metabolismo , Osteoporose Pós-Menopausa , Animais , Osso Esponjoso/metabolismo , Osso Esponjoso/patologia , Linhagem Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , OvariectomiaRESUMO
Negotiation scoring systems are fundamental tools used in negotiation support to facilitate parties searching for negotiation agreement and analyzing its efficiency and fairness. Such a scoring system is obtained in prenegotiation by implementing selected multiple criteria decision-aiding methods to elicit the negotiator's preferences precisely and ensure that the support is reliable. However, the methods classically used in the preference elicitation require much cognitive effort from the negotiators, and hence, do not prevent them from using heuristics and making simple errors that result in inaccurate scoring systems. This paper aims to develop an alternative tool that allows scoring the negotiation offers by implementing a sorting approach and the reference set of limiting profiles defined individually by the negotiators in the form of complete packages. These limiting profiles are evaluated holistically and verbally by the negotiator. Then the fuzzy decision model is built that uses the notion of increasing the preference granularity by introducing a series of limiting sub-profiles for corresponding sub-categories of offers. This process is performed automatically by the support algorithm and does not require any additional preferential information from the negotiator. A new method of generating reference fuzzy scores to allow a detailed assignment of any negotiation offer from feasible negotiation space to clusters and sub-clusters is proposed. Finally, the efficient frontier and Nash's fair division are used to identify the recommended packages for negotiation in the bargaining phase. This new approach allows negotiators to obtain economically efficient, fair, balanced, and reciprocated agreements while minimizing information needs and effort.
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BACKGROUND/AIM: Endosialin is present in human fibrosarcoma neoplastic cells. This study aimed to analyse the expression of selected cellular proteins found in fibrosarcomas and soft-tissue fibroids in dogs. MATERIALS AND METHODS: A total of 71 skin tumours obtained from dogs were used. The samples included 31 fibromas and 40 fibrosarcomas. Histopathological evaluation was performed according to World Health Organization guidelines. Immunohistochemistry was performed with anti-endosialin, Ki-67, cyclo-oxygenase 2 and vimentin antibodies and assessed using the semi-quantitative scale. RESULTS: Endosialin expression was observed in 82.5% of fibrosarcomas and in 35% of fibromas. A significant positive correlation was found between the expression of endosialin in fibrosarcoma neoplastic cells and the degree of histological malignancy and the expression of the Ki-67 and cyclo-oxygenase 2 antigen. Expression of vimentin confirmed mesenchymal origin of this tumours. CONCLUSION: The results of our research suggest that endosialin is involved in the carcinogenesis of fibrosarcoma in dogs.
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Fibroma , Fibrossarcoma , Neoplasias Cutâneas , Animais , Cães , Fibroma/genética , Fibroma/veterinária , Fibrossarcoma/genética , Fibrossarcoma/veterinária , Imuno-HistoquímicaRESUMO
BACKGROUND: Partial resection of the ovary carries a possible risk of fertility reduction. We studied the influence of open ovarian biopsy on ovarian reserve, including anti-Müllerian hormone and follicle-stimulating hormone serum level evaluation, in a prepubertal rat model. METHODS: Interventions - the initial surgery was unilateral ovarian biopsy (38 rats, group B1, B2) or unilateral ovarian biopsy and ovarian resection of the contralateral gonad (38 rats, group BR1, BR2). The second operation was bilateral ovarian resection and total resection of the remaining ovary. All rats had hormone serum levels evaluated. The control group had only a blood test taken and bilateral ovarian resection done at the second intervention (30 rats, group C1, C2). The collected tissue was examined estimating follicle count and anti-Müllerian hormone immunoexpression. RESULTS: Anti-Müllerian hormone levels were significantly lower at the second intervention in the group BR2 but significantly higher in the group C2. Follicle-stimulating hormone levels were significantly higher in all but one group (BR2). CONCLUSIONS: Biopsy itself might not reduce ovarian reserve if done properly but we should know its possible negative effects in the case of a single remaining ovary.