RESUMEN
Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.
Asunto(s)
Carcinoma de Células Renales , Epigenómica , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Epigenómica/métodos , Metilación de ADN/genética , Diferenciación Celular , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino , Epigénesis Genética , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-fosRESUMEN
Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into emergent aggressive variant prostate cancer (AVPC), which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflect and retain key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. We compared 15 NE versus 33 AdCa samples, which included six different PDX tumors for each group in biological replicates, and identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of concordance from PDX tumor-matched protein and mRNA revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa. IMPLICATIONS: Overall, our study highlights the importance of protein-based identification when compared with RNA and provides a rich resource of new and feasible targets for clinical assay development and in understanding the underlying biology of these tumors.
Asunto(s)
Fosfoproteínas , Proteoma , Humanos , Masculino , Proteoma/metabolismo , Animales , Ratones , Fosfoproteínas/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Xenoinjertos , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteómica/métodosRESUMEN
This study aimed to investigate the impact of ambient lead (Pb) exposure on progesterone (P4) and pregnancy-associated glycoprotein 1 (PAG1) and their relationship with abortion in Egyptian Zaraibi goats (C. hircus). To achieve this, 40 female goats (does) were mated with highly fertile male goats, resulting in a total of 28 pregnant goats. Eight of them aborted, and each of the 12 pregnant goats gave birth to one kid, whereas the remaining eight gave birth to twins. The levels of PAG1, P4, and Pb in serum were estimated by enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and inductively coupled plasma mass spectrometry (ICP-MS) respectively. Statistically, the repeated measure two-way ANOVA, regression analysis, correlation coefficient, and receiver operating characteristic (ROC) curves were applied. The current data demonstrated that the levels of blood Pb in aborted goats were significantly higher than those in non-aborted goats at the early, mid, and late gestations, and this was followed by significant decreases in serum PAG1 and P4. Furthermore, there were substantial inverse associations between blood Pb concentration and levels of PAG1 and P4, with markedly negative correlation coefficients of - 0.88 and - 0.77, respectively, in aborted goats. The threshold level of Pb required to cause abortion was ≥ 32.08 µg/dl, but for PAG1 and P4 were respectively ≤ 0.95 ng/ml and ≤ 0.48 ng/ml. Additionally, threshold levels of ≥ 12.34 ng/ml and ≥ 31.52 ng/ml for P4 and PAG1, respectively, were needed to deliver twins. In conclusion, pollution-induced increases in Pb bioavailability resulted in dramatic decreases in P4 and PAG1 levels, leading to abortions. PAG1 and P4 levels are also key factors in determining whether Zaraibi goats will give birth to twins.
Asunto(s)
Ácido Aspártico Endopeptidasas , Proteínas Gestacionales , Progesterona , Animales , Femenino , Embarazo , Cabras , PlomoRESUMEN
Resistance to androgen deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform to emergent aggressive variant prostate cancer (AVPC) which has neuroendocrine (NE)-like features. To this end, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflects and retains key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. When we compared 15 NE versus 33 AdCa PDX samples, we identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of protein and RNA concordance from these tumors revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa.
RESUMEN
PURPOSE: In patients with metastatic prostate cancer (mPC), ATM and BRCA2 mutations dictate differences in PARPi inhibitor response and other therapies. We interrogated the molecular features of ATM- and BRCA2-mutated mPC to explain the divergent clinical outcomes and inform future treatment decisions. EXPERIMENTAL DESIGN: We examined a novel set of 1,187 mPCs after excluding microsatellite-instable (MSI) tumors. We stratified these based on ATM (n = 88) or BRCA2 (n = 98) mutations. As control groups, mPCs with mutations in 12 other homologous recombination repair (HRR) genes were considered non-BRCA2/ATM HRR-deficient (HRDother, n = 193), whereas lack of any HRR mutations were considered HRR-proficient (HRP; n = 808). Gene expression analyses were performed using Limma. Real-world overall survival was determined from insurance claims data. RESULTS: In noncastrate mPCs, only BRCA2-mutated mPCs exhibited worse clinical outcomes to AR-targeted therapies. In castrate mPCs, both ATM and BRCA2 mutations exhibited worse clinical outcomes to AR-targeted therapies. ATM-mutated mPCs had reduced TP53 mutations and harbored coamplification of 11q13 genes, including CCND1 and genes in the FGF family. BRCA2-mutated tumors showed elevated genomic loss-of-heterozygosity scores and were often tumor mutational burden high. BRCA2-mutated mPCs had upregulation of cell-cycle genes and were enriched in cell-cycle signaling programs. This was distinct from ATM-mutated tumors. CONCLUSIONS: Tumoral ATM and BRCA2 mutations are associated with differential clinical outcomes when patients are stratified by treatments, including hormonal or taxane therapies. ATM- and BRCA2-mutated tumors exhibited differences in co-occurring molecular features. These unique molecular features may inform therapeutic decisions and development of novel therapies.
Asunto(s)
Genes BRCA2 , Neoplasias de la Próstata , Masculino , Humanos , Mutación , Proteína BRCA2/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Biomarcadores de Tumor/genética , Proteínas de la Ataxia Telangiectasia Mutada/genéticaRESUMEN
Gene behavior is governed by activity of other genes in an ecosystem as well as context-specific cues including cell type, microenvironment, and prior exposure to therapy. Here, we developed the Algorithm for Linking Activity Networks (ALAN) to compare gene behavior purely based on patient -omic data. The types of gene behaviors identifiable by ALAN include co-regulators of a signaling pathway, protein-protein interactions, or any set of genes that function similarly. ALAN identified direct protein-protein interactions in prostate cancer (AR, HOXB13, and FOXA1). We found differential and complex ALAN networks associated with the proto-oncogene MYC as prostate tumors develop and become metastatic, between different cancer types, and within cancer subtypes. We discovered that resistant genes in prostate cancer shared an ALAN ecosystem and activated similar oncogenic signaling pathways. Altogether, ALAN represents an informatics approach for developing gene signatures, identifying gene targets, and interpreting mechanisms of progression or therapy resistance.
Asunto(s)
Ecosistema , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Genes myc , Genómica , Transducción de Señal/genética , Microambiente Tumoral/genéticaRESUMEN
This study aimed to assess the predictive factors of successful sperm retrieval in non-obstructive azoospermia with a history of bilateral cryptorchidism. This retrospective study included 103 patients with azoospermia who had micro-dissection testicular sperm extraction between January 2010 and January 2020. The median (range) age of the patients and their wives in the study group was 33 (21-44) and 24 (19-33) years, respectively. The patients with low testosterone level (<3 ng/dl) were prescribed with human chorionic gonadotropin 5,000 IU injection every 3 days for 3 months. Those with persistent low testosterone even after hormonal stimulation were excluded. Sperms were retrieved from 64 (62%) patients, whilst failed in 39 (38%) patients. On univariate analysis, the median testicular volume was significantly larger in the successful group versus the failed group (p < .001), serum FSH and serum LH were significantly lower in the successful group (p = .001), serum testosterone was significantly higher in the successful group compared to the failed group (p < .001) and the age of orchidopexy was lower in the successful group versus the failed group (p = .016). On multivariate analysis, the average testicular volume and the serum testosterone levels were independent factors for successful sperm retrieval.
Asunto(s)
Azoospermia , Criptorquidismo , Criptorquidismo/complicaciones , Criptorquidismo/cirugía , Humanos , Masculino , Estudios Retrospectivos , Recuperación de la Esperma , Espermatozoides , Testículo/cirugía , TestosteronaRESUMEN
Testicular impairment is a serious complication of diabetes that is mediated by oxidative stress and inflammation. Physalis has antioxidative and anti-inflammatory actions. Thus, the present study investigated the ameliorative role of Physalis juice (PJ) prepared from the fruits against testicular damages in streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were divided randomly into five groups (n=6): control, orally administered 5 mL PJ/kg daily (PJ), injected intraperitoneally with a single dose of 55 mg STZ/kg without treatment (STZ), or treated daily with PJ (STZ+PJ) or with 500 mg metformin/kg (STZ+Met), for 28 days. The STZ group showed a marked elevation in the blood glucose level by 230%, whereas remarkable declines in the serum levels of testosterone (44%), follicle-stimulating hormone (FSH) (48%), and luteinizing hormone (LH) (36%), as compared to controls. In comparison to controls, the testis of the STZ group showed remarkable declines in the testis weight (15%), the glutathione (GSH) content (45%), mRNA and protein levels of B-cell lymphoma-2 (Bcl-2) (48 and 35%), mRNA and activities of superoxide dismutase (SOD) (63 and 40%), catalase (CAT) (56 and 31%), glutathione peroxidase (GPx) (51 and 44%), and glutathione reductase (GR) (62 and 43%), whereas marked elevations in the levels of interleukin-1 beta (IL-1ß (169%), tumor necrosis factor-alfa (TNFα) (85%), nitric oxide (NO) (96%), malondialdehyde (MDA) (83%), mRNA and protein levels of Bcl-2-associated X protein (Bax) (400 and 61%), and mRNA level of caspase-3 (Cas-3) (370%). Some histopathological alterations were observed in the testicular tissue of the STZ group. In contrast, PJ markedly alleviated all the abovementioned disturbances. In conclusion, PJ at a dose of 5 mL/kg attenuated the diabetes-associated testicular impairments, which may be due to its antioxidative, anti-inflammatory, and antiapoptotic actions.
Asunto(s)
Diabetes Mellitus Experimental , Physalis , Animales , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Estreptozocina/metabolismo , Testículo/metabolismoRESUMEN
OBJECTIVE: This report presents the results of a randomized prospective study comparing synchronous transurethral cystolitholapaxy and transurethral resection of the prostate (TURP) with transurethral cystolitholapaxy plus medical treatment for benign prostatic hyperplasia (BPH) in patients with concomitant vesical stone(s) and BPH. PATIENTS AND METHODS: The study included 100 patients with bladder stone(s) < 2.5 cm associated with BPH. Eligible patients were divided randomly into two groups: group I (n = 50 patients) underwent simultaneous transurethral cystolitholapaxy and TURP, and group II (n = 50 patients) underwent transurethral cystolitholapaxy and received postoperative tamsulosin plus finasteride. RESULTS: The mean follow-up was 20.1 ± 5.3 months. No statistically significant differences were found between the 2 groups regarding the preoperative parameters (age, prostatic volume, bladder stone characteristics, prostate-specific antigen level, International Prostate Symptom Score, peak urinary flow rate, and post-void residual urine volume). Both groups experienced statistically significant postoperative improvement in IPSS, post-void residual (PVR) urine volume, and peak flow rate compared with the preoperative parameters (P < 0.001 for all parameters). However, patients in group 1 had a more pronounced improvement (P < 0.001 for all parameters). Thus, 15 patients in group 2 underwent TURP during follow-up. PVR urine and prostate volume predicted the failure of medical therapy and the need for TURP. CONCLUSION: Synchronous transurethral cystolitholapaxy and TURP revealed better results than transurethral cytolitholapaxy plus medical therapy. Cystolitholapaxy without TURP should not be indicated especially in patients with significant PVR urine volumes and larger prostates.
Asunto(s)
Hiperplasia Prostática , Resección Transuretral de la Próstata , Cálculos de la Vejiga Urinaria , Humanos , Masculino , Estudios Prospectivos , Próstata/cirugía , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Resultado del Tratamiento , Cálculos de la Vejiga Urinaria/complicaciones , Cálculos de la Vejiga Urinaria/cirugíaRESUMEN
INTRODUCTION: The rapid worldwide spread of COVID-19 motivated medical professionals to pursue and authenticate appropriate remedies and treatment protocols. This article aims to analyze the potential benefits of one treatment protocol developed by a group of care providers caring for severe COVID-19 patients. METHODS: The clinical findings of COVID-19 patients who were transferred to a specialized care hospital after unsuccessful treatment in previous institutions, were analyzed. The specialized care hospital used a treatment protocol including hydroxyurea, a medication commonly used for sickle cell treatment, to improve respiratory distress in the COVID-19 patients. None of the COVID-19 patients included in the analyzed data were diagnosed with sickle cell, and none had previously taken hydroxyurea for any other conditions. RESULTS: In all presented cases, patients reverted to their baseline respiratory health after treatment with the hydroxyurea protocol. There was no significant difference in the correlation between COVID-19 and hydroxyurea. However, deaths were extremely low for those taking hydroxyurea. CONCLUSIONS: Fatality numbers were extremely low for those taking hydroxyurea; death could be attributed to other underlying issues.
RESUMEN
Neuropathy is considered a critical complication of diabetes mellitus (DM). Scientific studies are needed to relieve these painful complications. The current study aims to estimate the ameliorative role of Physalis juice (PJ) against neurological impairment in streptozotocin (STZ)-induced diabetic rats. Type 1 DM was induced after one week of injecting rats with 55 mg STZ/kg body weight. PJ-treated rats were orally administered 5 ml PJ/kg body weight per day for 28 days after induction of diabetes. A small piece of the cerebral cortex of rats was fixed and used for histopathological investigations. The remaining portion of the cerebral cortex was homogenized for biochemical and molecular analyses. As compared to the controls, STZ-injected rats showed significant elevations in the levels of blood glucose, tumor necrosis factor alfa, interleukin-1ß, malondialdehyde, nitric oxide, and expression levels of caspase-3 and B-cell lymphoma-2 associated X-protein. Additionally, remarkable declines in the levels of brain-derived neurotrophic factor, monoamines, B-cell lymphoma-2, glutathione, as well as the activities and gene expression levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in STZ-treated rats were reported. Moreover, some histopathological alterations were observed in the brain cortex of the STZ-treated rats. On the other hand, the administration of PJ substantially reduced the blood glucose and alleviated the above-mentioned alterations in all the studied parameters of the cerebral cortex. In conclusion, an oral administration of 5 ml PJ/kg revealed a neuroprotective action against neurodegenerative diabetes-induced complications in rats, which might be due to the reported antioxidative and anti-inflammatory actions of PJ. Thus, further therapeutic studies are recommended to apply PJ in the treatment regimen of diabetes.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Physalis/efectos de los fármacos , Estreptozocina/farmacología , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Hipoglucemiantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Physalis/metabolismo , Extractos Vegetales/farmacología , RatasRESUMEN
The consumption of inadequately thermally treated fish is a public health risk due to the possible propagation of Anisakis larvae. The present study demonstrated the physiological and histopathological changes that accompanied an oral inoculation of crude extracts from fresh and thermally treated Anisakis Type II (L3) in rats. Worms were isolated from a marine fish and examined and identified using light and scanning electron microscopy. The study was performed in 6 rat groups: control (I), garlic oil (GO) inoculated (II), fresh L3 inoculated (III), thermally treated L3 inoculated (IV), fresh L3 + GO inoculated (V), and a thermally treated L3 + GO inoculated (VI) groups. Rats inoculated with fresh and thermally treated L3 showed abnormal liver and kidney functions associated with the destruction of normal architecture. GO produced a protective effect in rat groups inoculated with L3 extracts + GO via the amelioration of liver and kidney functions, which was confirmed by the marked normal structure on histology. Cooking of L3-infected fish induced severe alterations compared to uncooked fish. The administration of garlic before and after fish eating is recommended to avoid the dangerous effect of anisakids, even if they are cooked.
Asunto(s)
Compuestos Alílicos , Anisakiasis , Anisakis , Sulfuros , Compuestos Alílicos/farmacología , Compuestos Alílicos/uso terapéutico , Animales , Anisakiasis/tratamiento farmacológico , Anisakiasis/prevención & control , Anisakis/efectos de los fármacos , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Culinaria , Peces/parasitología , Parasitología de Alimentos , Larva , Ratas , Ratas Wistar , Sulfuros/farmacología , Sulfuros/uso terapéuticoRESUMEN
This study aimed to assess the effectiveness of low-intensity extracorporeal shockwave therapy (Li-ESWT) in the management of erectile dysfunction in diabetic patients with mixed vasculogenic and neurogenic causes as confirmed by nerve conduction and Doppler studies. This randomised controlled trial included 42 patients 41-55 years of age with a confirmed diagnosis of erectile dysfunction and diabetic polyneuropathy. They were randomly allocated to one of two groups: shock wave group (n = 21) treated with Li-ESWT plus pelvic floor muscle training and control Group (n = 21) treated with pelvic floor muscle exercise and sham therapy by a shock wave. The erectile function was scored according to the five-item version of the International Index of Erectile Function (IIEF-5). Colour-coded duplex sonography was used for the evaluation of penile perfusion of the two cavernous arteries. The assessment was done before and three months after treatment. IIEF-EF increased significantly in the study group (p < .001), but not in the control group (p = .194). Peak systolic velocity increased significantly in the two groups; however, the post-treatment peak systolic velocity was significantly higher in the study group compared to the control group (p < .001, for both arteries).
Asunto(s)
Diabetes Mellitus , Disfunción Eréctil , Tratamiento con Ondas de Choque Extracorpóreas , Disfunción Eréctil/etiología , Disfunción Eréctil/terapia , Humanos , Masculino , Erección Peniana , Pene/diagnóstico por imagenRESUMEN
Nickel oxide nanoparticles (NiONPs) are involved in several applications but still have some adverse effects. Apigenin (APG) is a widespread natural product with antioxidative, anticancer, and anti-inflammatory properties. The present work aimed to study the protective role of APG against the NiONP-induced toxicity in male Wistar rats. Rats were randomly distributed to one control group and three treated groups. The treated groups were orally administered NiONPs (100 mg/kg) alone, APG (25 mg/kg) alone, or APG 1 h before NiONPs, once daily for 28 days. Blood, liver, and kidney were collected after 7, 14, and 28 days of administration for Ni accumulation, hematological, biochemical, histological, and transmission electron microscopy (TEM) investigations. As compared to the controls, the administration of NiONPs alone significantly elevated the levels of Ni, malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, creatinine, urea, blood urea nitrogen, and the activity of alanine and aspartate aminotransferases as well as the count of white blood cells. Besides, marked reductions in the activity of superoxide dismutase, and the levels of glutathione, high-density lipoprotein cholesterol, total proteins, albumin, globulin, hemoglobin, packed cell volume, and red blood cell count were reported. Histologically, the liver and kidney of rats administered NiONPs alone showed remarkable disturbances. According to TEM, subcellular alterations were observed in the liver and kidney of rats administered NiONPs alone. In contrast, APG administering before NiONPs substantially alleviated all the studied parameters. In conclusion, APG can ameliorate the NiONP-induced hepatotoxicity and nephrotoxicity in male Wistar rats.
Asunto(s)
Apigenina , Nanopartículas , Animales , Antioxidantes/metabolismo , Apigenina/metabolismo , Glutatión/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Níquel , Estrés Oxidativo , Ratas , Ratas WistarRESUMEN
Abstract The consumption of inadequately thermally treated fish is a public health risk due to the possible propagation of Anisakis larvae. The present study demonstrated the physiological and histopathological changes that accompanied an oral inoculation of crude extracts from fresh and thermally treated Anisakis Type II (L3) in rats. Worms were isolated from a marine fish and examined and identified using light and scanning electron microscopy. The study was performed in 6 rat groups: control (I), garlic oil (GO) inoculated (II), fresh L3 inoculated (III), thermally treated L3 inoculated (IV), fresh L3 + GO inoculated (V), and a thermally treated L3 + GO inoculated (VI) groups. Rats inoculated with fresh and thermally treated L3 showed abnormal liver and kidney functions associated with the destruction of normal architecture. GO produced a protective effect in rat groups inoculated with L3 extracts + GO via the amelioration of liver and kidney functions, which was confirmed by the marked normal structure on histology. Cooking of L3-infected fish induced severe alterations compared to uncooked fish. The administration of garlic before and after fish eating is recommended to avoid the dangerous effect of anisakids, even if they are cooked.
Resumo O consumo de peixe inadequadamente tratado termicamente representa um risco para a saúde pública, com a possibilidade da propagação de larvas de Anisakis. O presente estudo demonstrou as alterações fisiológicas e histopatológicas acompanhadas de inoculação oral de extractos brutos de Anisakis tipo II (L3) frescos e termicamente tratados em ratos. Os vermes foram isolados de um peixe marinho, examinados e identificados por microscopia de luz e eletrônica de varredura. O estudo foi conduzido em 6 grupos de ratos: controle (I), óleo de alho (GO) inoculado (II), L3 fresco inoculado (III), L3 tratado termicamente inoculado (IV), L3 fresco + GO inoculado (V), e um grupo L3 + GO tratado termicamente inoculado (VI). Observou-se que ratos inoculados com L3 fresco e tratados termicamente mostraram funções hepáticas e renais anormais, associadas à destruição da sua arquitetura normal. GO produziu um efeito protector em grupos de ratos inoculados com extractos L3 + GO através da melhoria das funções do fígado e dos rins, o que foi confirmado pela estrutura normal marcada da sua histologia. A cozedura de peixes infectados com L3 induziu alterações mais graves do que os peixes não cozidos. Recomenda-se a administração de alho antes e depois do consumo de peixe, para evitar o efeito perigoso dos anisakids, mesmo que sejam cozidos.
Asunto(s)
Animales , Ratas , Sulfuros/farmacología , Anisakis/efectos de los fármacos , Anisakiasis/prevención & control , Anisakiasis/tratamiento farmacológico , Compuestos Alílicos/uso terapéutico , Compuestos Alílicos/farmacología , Sulfuros/uso terapéutico , Parasitología de Alimentos , Ratas Wistar , Culinaria , Peces/parasitología , Larva , Antihelmínticos/uso terapéutico , Antihelmínticos/farmacologíaRESUMEN
BACKGROUND: Resin composite preheating is an innovative method that could be clinically beneficial by improving the handling properties, marginal adaptation, and surface properties of uncured nanofilled resin composite materials. There is conflict and unclear information regarding the effect of preheating on the microhardness, fracture toughness and surface roughness of nanofilled resin composites. Thus, it is important to assess whether dental clinicians can adopt preheating procedures without compromising composite mechanical strength. Objective: The purpose of this study was to evaluate the effect of preheating on microhardness, fracture toughness and surface roughness of nanofilled resin composite. MATERIAL AND METHODS: In this study, one commercial nanofilled resin composite Filtek Z350 XT was used. A total of 28 disc-shaped specimens were fabricated in a Teflon mold (10 mm diameter x 2 mm thick) for Vickers microhardness indentation test and surface roughness test. The samples were divided into two groups of 14 samples each, one group of samples was light-cured at room temperature (24ºC) without preheating (non-heated group), and the other group was light-cured after preheating (preheated group). Vickers hardness measurements of 14 specimens (n=7) either preheated or non-heated of the top and bottom surfaces was measured by means of microhardness tester by applying 100 g load for 10 s. Surface Roughness measurements (Ra) were obtained from 14 specimens (n=7) either preheated or non-heated with the atomic force microscope. Fourteen single-edge-notched-beam specimens were prepared for fracture toughness test (n=7) either preheated or non-heated with measurements (2.5 x 5 x 25 mm3) and a crack 2.12 mm in length. The specimens were tested via three-point bending mode, using a universal testing machine at crosshead speed of 1.0 mm/min until failure occurred. RESULTS: Independent sample t- tests revealed no significant difference between non-heated and preheated groups for all tests (p>0.05). However, for Vickers hardness test, there were significant differences between top and bottom surfaces for non-heated and preheated groups (p<0.05). Moreover, surface roughness average Ra (nm) mean values of preheated group was higher than non-heated group but no significant difference between them was found (p>0.05). CONCLUSIONS: Preheating procedure did not negatively affect microhardness, fracture toughness and surface roughness of nanofilled resin composites so preheating is recommended for the other potential clinical advantages. Key words:Preheating, nanofilled composites, microhardness, fracture toughness, surface roughness.
RESUMEN
Red palm weevil (RPW), Rhynchophorus ferrugineus, is one of the most destructive pests of cultivated palm trees. The application of synthetic insecticides is currently a main strategy for RPW control. In this study we estimated the distribution of acetylcholinesterase (AChE), as a detoxifying enzyme and the target site of inhibition by insecticides, using ASChI as substrate in different organs of the pest including whole gut, cuticle, fat body, head and haemolymph. The activity ranged from 314.9 to 3868 U in individual organs while the specific activity ranged from 99 to 340.8 U/mg proteins; the cuticle had the highest enzyme level. During larval development, the 11th instar larvae had the highest enzyme content with 5630 U in the cuticle, with a specific activity of 140 U/mg protein. The two major AChE isoenzymes were purified by chromatography on gel filtration and ion exchange columns. They had specific activities of 3504.3 and 2979 U/mg protein, molecular weights of 33 and 54â¯kDa and activation energies of 8.3 and 4.4â¯kcal/mol, respectively. Both isoenzymes had monomeric forms, optimum activity at pH 8.0 and 40⯰C, were completely inhibited by Hg2+ and Cu2 and showed similar trends towards the inhibitors eserine, BW284C51 and iso-OMPA. The catalytic properties were compared with those previously recorded for different insect species. This work will pave the way for more studies for improving the understanding of insecticide resistance and developing the field application of synthetic insecticides for controlling R. ferrugineus to ensure successful application.
Asunto(s)
Acetilcolinesterasa/química , Acetilcolinesterasa/aislamiento & purificación , Proteínas de Insectos/química , Proteínas de Insectos/aislamiento & purificación , Gorgojos/enzimología , Animales , Catálisis , Cationes , Cobre/química , Hemolinfa , Concentración de Iones de Hidrógeno , Hidrólisis , Insecticidas , Isoenzimas/química , Cinética , Larva , Mercurio/química , Peso Molecular , Especificidad por Sustrato , TemperaturaRESUMEN
Nanomaterial applications are a fast-developing field. In spite of their powerful advantages, many open questions regarding how these small-sized chemicals may influence the environment and human health. However, scarce reports are available on the potential hazards of combined nanoparticles, taken into consideration that nickel oxide (NiO) and cobalt (II, III) oxide (Co3O4) nanoparticles (NPs) are already used together in many applications. Hence, the present work was designed to study the probable changes in some biological, hematological, and serum biochemical variables throughout 2 weeks following an oral administration of 0.5 g and 1.0 g of NiO-NPs or/and Co3O4-NPs per kilogram body weight of rats. As compared with the controls, the exposure to NiO-NPs or Co3O4-NPs solely caused significant elevations in the relative weights of brain (RBW), kidney (RKW) and liver (RLW), water consumption (WC), red blood cells (RBCs) count, hemoglobin (Hb) content, packed cell volume (PCV), and serum levels of low-density lipoprotein cholesterol (LDL-C), glucose, creatinine, urea, and uric acid as well as serum activities of aspartate and alanine aminotransferases (ASAT and ALAT). In addition, remarkable declines in the total body weight (TBW), feed consumption (FC), white blood cells (WBCs) count, serum levels of total protein (TP), albumin, albumin/globulin ratio, total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) were caused by administration of NiO-NPs or Co3O4-NPs, separately. On contrary, the co-administration of NiO-NPs and Co3O4-NPs together caused less noticeable changes in most of studied variables as compared with those administered NiO-NPs or Co3O4-NPs, individually. In conclusion, the exposure to a combination of NiO-NPs and Co3O4-NPs suppressed the adverse effects of the individual NPs on the studied variables.
Asunto(s)
Cobalto/toxicidad , Nanopartículas del Metal/toxicidad , Níquel/toxicidad , Animales , Humanos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Óxidos/metabolismo , Ratas , Pruebas de ToxicidadRESUMEN
The present study was conducted to investigate the effect of incorporating Cicer arietinum in the diet on the testicular functions of the male mice. Seventy-two mice were divided equally into four groups that were daily fed a diet containing 0, 20, 30 and 50% of C. arietinum seeds, respectively. After 7, 14 and 21 days of starting the experiments, the mice were anesthetized and euthanized to collect the blood, testes, epididymis and seminal vesicles. The present results showed that the increased percentage of C. arietinum in the diet caused significant elevations in the serum levels of testosterone and luteinizing hormone (LH), sperm concentration, sperm motility as well as the testicular levels of antioxidants including glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT), in comparison to the controls. On the other hand, marked reductions in the sperm abnormality, testicular levels of malondialdehyde (MDA), the percentage of DNA damage in tail and tail moment (TM) were observed in the mice that received a diet containing C. arietinum as compared to the controls. Both the sperms and testes of the mice fed a diet containing C. arietinum in the diet showed a normal intact appearance of the electrophoresed genomic DNA on agarose, as those of the controls. In conclusion, C. arietinum is not only a safe ingredient in the fast-food but also an enhancer of the testicular functions.
Asunto(s)
Cicer/química , Fármacos para la Fertilidad/farmacología , Fertilidad/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Catalasa/metabolismo , Ensayo Cometa , ADN/química , ADN/metabolismo , Epidídimo/efectos de los fármacos , Epidídimo/metabolismo , Fertilidad/fisiología , Glutatión/agonistas , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Hormona Luteinizante/sangre , Masculino , Malondialdehído/antagonistas & inhibidores , Malondialdehído/metabolismo , Ratones , Semillas/química , Vesículas Seminales/efectos de los fármacos , Vesículas Seminales/metabolismo , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Motilidad Espermática/fisiología , Espermatogénesis/fisiología , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/sangreRESUMEN
BACKGROUND: This study aims to investigate the detailed computed tomography (CT) measurement of the nasopharynx (NP) in normal adult detecting mean of its dimension and relation of that measurement to that of the sphenoid sinus. METHODOLOGY/PRINCIPAL: A normal paranasal CT scan and a straight nasal septum of 128 individuals (256 sphenoid sinuses) were included in the study. Axial images were acquired with multiplanar reformates to obtain delicate details in coronal and sagittal planes for all subjects. Measurement of the width, length, and anteroposterior dimensions of the NP and sphenoid sinuses were taken separately. RESULTS: In 128 studied CT of adult subjects, the mean height of the NP was 19.4619â±â4.52661 and mean depth was 21.80714â±â4.62324 while the mean width was 25.31951â±â3.80521. No significant relations between diameters of NP and sphenoid sinuses were found. CONCLUSION: The detailed CT measurement of the NP in normal adult is an easy and reliable measurement. This study put the base of CT measurement of NP for further work to describe changes in such measures in patients with nasal and paranasal sinus anomalies.