Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 44
Filter
1.
Obes Surg ; 33(11): 3649-3657, 2023 11.
Article in English | MEDLINE | ID: mdl-37798512

ABSTRACT

We aimed to assess the impact of Helicobacter pylori infection on postoperative outcomes following laparoscopic sleeve gastrectomy (LSG). We searched Cochrane, Scopus, and PubMed databases, reviewed 1026 studies, and thoroughly analyzed 42 of them. Our final analysis included 13 studies comprising 6199 patients. We found that H. pylori infection was correlated with higher rates of risk of overall postoperative complications (OR 1.56; 95% CI 1.13, 2.16; P = 0.007) and staple line leak (OR 1.89; 95% CI 1.05, 3.41; P = 0.03). There were no significant differences in hospital length of stay or postoperative bleeding rates. Despite observed correlations between H. pylori positivity in gastric specimen and postoperative complications in LSG, definitive causation remains elusive, emphasizing the need for prospective randomized studies evaluating the effect of preoperative H. pylori screening and eradication.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Laparoscopy , Obesity, Morbid , Humans , Helicobacter Infections/complications , Prospective Studies , Obesity, Morbid/surgery , Gastrectomy/adverse effects , Postoperative Complications/surgery , Retrospective Studies , Treatment Outcome
2.
Plant Physiol Biochem ; 188: 12-20, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-35963050

ABSTRACT

The large economic costs and environmental impacts of iron-chelate treatments has led to the search for alternative methods and compounds to control iron (Fe) deficiency chlorosis. Strawberry plants (Fragaria x ananassa) were grown in Hoagland's nutrient solution in a greenhouse with two levels of Fe: 0 and 10 µM Fe(III)-EDDHA. After 20 days, plants growing without Fe showed typical symptoms of Fe deficiency chlorosis in young leaves. Then, the adaxial and abaxial sides of one mature or one young leaf in each plant were brushed with 10 mM malic (MA), citric (CA) or succinic (SA) acids. Eight applications were done over a two-week period. At the end of the experiment, the newly emerged (therefore untreated), young and mature leaves were sampled for nutritional and metabolomic analysis, to assess the effectiveness of treatments. Leaf regreening was monitored using a SPAD-502 apparatus, and the activity of the ferric chelate-reductase activity (FCR) was measured using root tips. Iron deficiency negatively affected biomass and leaf chlorophyll but did not increase FCR activity. Application of succinic acid alleviated the decrease in chlorophyll observed in other treatments, and the overall nutritional balance in the plant was also changed. The concentrations of two quinic acid derivatives increased under Fe deficiency and decreased in plants treated with succinic acid, and thus they are proposed as Fe stress markers. Data suggest that foliage treatments with carboxylates may be, in some cases, environmentally friendly alternatives to Fe(III)-chelates. The importance of Fe mobilization pathways in the formulation of new fertilizers is also discussed.


Subject(s)
Anemia, Hypochromic , Fragaria , Anemia, Hypochromic/metabolism , Chlorophyll/metabolism , Ferric Compounds/pharmacology , Fragaria/metabolism , Iron/metabolism , Plant Leaves/metabolism , Plant Roots/metabolism , Succinates/metabolism , Succinates/pharmacology
3.
New Phytol ; 225(4): 1699-1714, 2020 02.
Article in English | MEDLINE | ID: mdl-31610019

ABSTRACT

Although biochemically related, C4 and crassulacean acid metabolism (CAM) systems are expected to be incompatible. However, Portulaca species, including P. oleracea, operate C4 and CAM within a single leaf, and the mechanisms behind this unique photosynthetic arrangement remain largely unknown. Here, we employed RNA-seq to identify candidate genes involved exclusively or shared by C4 or CAM, and provided an in-depth characterization of their transcript abundance patterns during the drought-induced photosynthetic transitions in P. oleracea. Data revealed fewer candidate CAM-specific genes than those recruited to function in C4 . The putative CAM-specific genes were predominantly involved in night-time primary carboxylation reactions and malate movement across the tonoplast. Analysis of gene transcript-abundance regulation and photosynthetic physiology indicated that C4 and CAM coexist within a single P. oleracea leaf under mild drought conditions. Developmental and environmental cues were shown to regulate CAM expression in stems, whereas the shift from C4 to C4 -CAM hybrid photosynthesis in leaves was strictly under environmental control. Moreover, efficient starch turnover was identified as part of the metabolic adjustments required for CAM operation in both organs. These findings provide insights into C4 /CAM connectivity and compatibility, contributing to a deeper understanding of alternative ways to engineer CAM into C4 crop species.


Subject(s)
Arabidopsis Proteins/physiology , Crassulacean Acid Metabolism/physiology , Photosystem II Protein Complex/physiology , Plant Leaves/metabolism , Portulaca/physiology , Adaptation, Physiological , Chlorophyll A/genetics , Chlorophyll A/metabolism , Gene Expression Regulation, Plant/physiology , Plant Stems/physiology , Plant Transpiration , RNA, Plant/genetics , RNA, Plant/metabolism
4.
Sci Rep ; 9(1): 17673, 2019 11 27.
Article in English | MEDLINE | ID: mdl-31776429

ABSTRACT

This study proposed to determine global microRNA (miRNA) expression and miRNA-regulated pathways in Intestinal Neuronal Dysplasia type B (IND-B). Fifty patients (0-15 years old) with IND-B were included in the study. Peripheral blood samples were collected from all 50 patients and from 10 healthy asymptomatic children (controls). Rectal biopsies were collected from 29/50 patients; biopsy tissues were needle microdissected to isolate the different intestinal layers, for molecular analysis. Global miRNA expression was determined using TaqMan arrays. Correlation analysis between miRNA expression in plasma and biopsy samples as well as among tissues derived from the distinct intestinal layers was performed. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated genes and enriched pathways biologically relevant to IND-B pathogenesis. miRNAs were statistically significantly deregulated (FC ≥ 2 and p ≤ 0.05) in submucosal and muscular layers: over-expressed (miR-146a and miR-146b) and under-expressed (miR-99a, miR-100, miR-130a, miR-133b, miR-145, miR-365, miR-374-5p, miR-451). Notably, let-7a-5p was highly over-expressed in patient plasma compared to healthy controls (FC = 17.4). In addition, miR-451 was significantly under-expressed in both plasma and all biopsy tissues from the same patients. Enriched pathways (p < 0.01) were axon guidance, nerve growth factor signalling, NCAM signalling for neurite out-growth, neuronal system and apoptosis. miRNA expression is deregulated in the submucosa and muscular layers of the rectum and detected in plasma from patients with IND-B. Biologically enriched pathways regulated by the identified miRNAs may play a role in IND-B disease pathogenesis, due to the activity related to the neurons of the enteric nervous system.


Subject(s)
Computational Biology/methods , Intestinal Diseases/genetics , Intestinal Diseases/pathology , MicroRNAs/genetics , Nervous System Diseases/genetics , Nervous System Diseases/pathology , Transcriptome , Adolescent , Apoptosis , Axon Guidance , Biopsy , Child , Child, Preschool , Female , Gene Expression Profiling , Humans , Infant , Infant, Newborn , Intestinal Diseases/blood , Male , Nerve Growth Factors/metabolism , Nervous System Diseases/blood , Neural Cell Adhesion Molecules/metabolism , Rectum/pathology
5.
Article in English | MEDLINE | ID: mdl-31585636

ABSTRACT

Red and processed meat consumption has been strongly related to increase the risk of colorectal cancer (CRC), although its impact is largely unknown. Hemin, an iron-containing porphyrin, is acknowledged as a putative factor of red and processed meat pro-carcinogenic effects. The aim of this study was to investigate the effects of high dietary hemin on the promotion/progression stages of 1,2-dimethylhydrazine (1,2-DMH)-induced colon carcinogenesis. Twenty-four Wistar male rats were given four subcutaneous 1,2-DMH injections and received either balanced diet or balanced diet supplemented with hemin 0.5 mmol/kg for 23 weeks. Colon specimens were analyzed for aberrant crypt foci (ACF) and tumor development. Dietary hemin significantly increased ACF number and fecal water cytotoxicity/genotoxicity in Caco-2 cells when compared to 1,2-DMH control group. However, tumor incidence, multiplicity and cell proliferation did not differ between 1,2-DMH + hemin and 1,2-DMH control group. Gene expression analysis of 91 target-genes revealed that only three genes (Figf, Pik3r5 and Tgfbr2) were down-regulated in the tumors from hemin-fed rats compared to those from 1,2-DMH control group. Therefore, the findings of this study show that high hemin intake promotes mainly DNA damage and ACF development and but does not change the number nor incidence of colon tumors induced by 1,2-DMH in male rats.


Subject(s)
Aberrant Crypt Foci/chemically induced , Colonic Neoplasms/chemically induced , DNA Damage , Hemin/toxicity , Precancerous Conditions/chemically induced , 1,2-Dimethylhydrazine , Animal Feed , Animals , Caco-2 Cells , Cocarcinogenesis , Comet Assay , Down-Regulation/drug effects , Feces , Humans , Male , Phosphatidylinositol 3-Kinase/genetics , Rats , Rats, Wistar , Receptor, Transforming Growth Factor-beta Type II/biosynthesis , Receptor, Transforming Growth Factor-beta Type II/genetics , Red Meat , Time Factors , Vascular Endothelial Growth Factor D/biosynthesis , Vascular Endothelial Growth Factor D/genetics
6.
G Ital Dermatol Venereol ; 154(6): 696-713, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31210470

ABSTRACT

INTRODUCTION: Atopic dermatitis (AD) is a common chronic, pruritic inflammatory dermatosis. The inflammatory response is characterized by a T helper 2 (Th2) immune response phenotype. EVIDENCE ACQUISITION: To assess current available data on dupilumab, the writers of this article did a comprehensive search in different databases, including Medline, EMBASE, SCOPUS, and clinical trial registries. All relevant articles identified were then manually reviewed. Information regarding dupilumab mechanism of action, pharmacokinetics, clinical efficacy, safety, and future trends was then summarized. EVIDENCE SYNTHESIS: Topical therapy is the main treatment in mild-to-moderate AD, but many cases of moderate-to-severe require systemic treatments. Dupilumab is the first biologic approved for the treatment of adults with moderate-to-severe AD. It inhibits IL-4 and IL-13 signaling pathways and reduces Th2 response. Clinical trials have demonstrated significantly improved clinical and patient-reported outcomes. The addition of application of topical corticosteroids results in a more significant improvement in signs and symptoms of AD than with use of dupilumab in monotherapy. The vast majority of patients improves under dupilumab, and almost 40% of patients achieve clear or nearly clear skin. In addition to its effectiveness, dupilumab also has a favorable safety profile. Frequent adverse events reported in the clinical trials were mostly mild-to-moderate and included nasopharyngitis, upper respiratory tract infection, injection site reactions, and conjunctivitis. CONCLUSIONS: In general, rates of adverse events occurred with similar frequency between the treatment and placebo groups. Conjunctivitis seems to be a dupilumab-specific side effect and so far has only been observed in atopic dermatitis patients (not in asthma or nasal polyposis). There were no major serious safety concerns identified in phase III clinical trials. Trials in the pediatric population are ongoing and are highly awaited.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Dermatitis, Atopic/drug therapy , Dermatologic Agents/administration & dosage , Adult , Animals , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/pharmacology , Dermatitis, Atopic/pathology , Dermatologic Agents/adverse effects , Dermatologic Agents/pharmacology , Humans , Interleukin-13/immunology , Interleukin-4/immunology , Severity of Illness Index
7.
PLoS One ; 14(5): e0217421, 2019.
Article in English | MEDLINE | ID: mdl-31150430

ABSTRACT

Despite progress in treatment strategies, only ~24% of pancreatic ductal adenocarcinoma (PDAC) patients survive >1 year. Our goal was to elucidate deregulated pathways modulated by microRNAs (miRNAs) in PDAC and Vater ampulla (AMP) cancers. Global miRNA expression was identified in 19 PDAC, 6 AMP and 25 paired, histologically normal pancreatic tissues using the GeneChip 4.0 miRNA arrays. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated pathways. Target gene expression was validated in 178 pancreatic cancer and 4 pancreatic normal tissues from The Cancer Genome Atlas (TCGA). 20 miRNAs were significantly deregulated (FC≥2 and p<0.05) (15 down- and 5 up-regulated) in PDAC. miR-216 family (miR-216a-3p, miR-216a-5p, miR-216b-3p and miR-216b-5p) was consistently down-regulated in PDAC. miRNA-modulated pathways are associated with innate and adaptive immune system responses in PDAC. AMP cancers showed 8 down- and 1 up-regulated miRNAs (FDR p<0.05). Most enriched pathways (p<0.01) were RAS and Nerve Growth Factor signaling. PDAC and AMP display different global miRNA expression profiles and miRNA regulated networks/tumorigenesis pathways. The immune response was enriched in PDAC, suggesting the existence of immune checkpoint pathways more relevant to PDAC than AMP.


Subject(s)
Adaptive Immunity/genetics , Carcinoma, Pancreatic Ductal/genetics , Immunity, Innate/genetics , MicroRNAs/metabolism , Pancreatic Neoplasms/genetics , Adult , Aged , Ampulla of Vater/pathology , Carcinoma, Pancreatic Ductal/pathology , Computational Biology , Down-Regulation , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/immunology , Gene Regulatory Networks/immunology , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Pancreatic Neoplasms/pathology , Retrospective Studies , Up-Regulation
8.
Nutr Res ; 61: 41-52, 2019 01.
Article in English | MEDLINE | ID: mdl-30683438

ABSTRACT

Previous studies have shown that early life intake of high-fat diet or western-style diet (WD) enhances the development of mammary tumors in adult female rats. Thus, we hypothesized that maternal WD throughout pregnancy and the lactation period could speed up the development of MNU-induced mammary tumors and alter their gene expression. For this, the present study investigated the gene expression profile of chemically-induced mammary tumors in female rat offspring from dams fed a WD or a control diet. Pregnant female Sprague-Dawley rats received a WD (high-fat, low-fiber and oligoelements) or a control diet from gestational day 12 until post-natal day (PND) 21. At PND 21, female offspring received a single dose of N-Methyl-N-Nitrosourea (MNU, 50 mg/kg body weight) and were fed a control diet for 13 weeks. Tumor incidence, multiplicity, and latency were recorded and mammary gland samples were collected for histopathology and gene expression analysis. Tumor multiplicity and histological grade were significantly higher and tumor latency was lower in WD offspring compared to control offspring. Transcriptome profiling identified 57 differentially expressed genes in tumors from WD offspring as compared to control offspring. There was also an increase in mRNA expression of genes such as Emp3, Ccl7, Ets1, Abcc5, and Cyr61, indicative of more aggressive disease detected in tumors from WD offspring. Thus, maternal WD diet increased MNU-induced mammary carcinogenesis in adult female offspring through transcriptome changes that resulted in a more aggressive disease.


Subject(s)
Diet, High-Fat , Diet, Western , Mammary Neoplasms, Animal/etiology , Maternal Nutritional Physiological Phenomena , Pregnancy Complications , Prenatal Exposure Delayed Effects/genetics , Transcriptome , Animals , Female , Gene Expression Profiling , Genes, Neoplasm , Lactation , Mammary Neoplasms, Animal/chemically induced , Mammary Neoplasms, Animal/pathology , Methylnitrosourea , Mothers , Neoplasm Grading , Pregnancy , RNA, Messenger/metabolism , Rats, Sprague-Dawley
9.
Food Chem Toxicol ; 112: 11-18, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29269057

ABSTRACT

The risk of developing colorectal cancer (CRC) could be associated with red and processed meat intake. Experimental data supports that hemin iron, found abundantly in red meat, promotes CRC in mice and rats, while indole-3 carbinol (I3C) and synbiotics (syn) exert anti-carcinogenic activities in most studies of colon carcinogenesis. This study aimed to investigate the modifying effects of I3C and syn (inulin + Bifidobacterium lactis), given separately or together, on dimethylhidrazine (DMH)-induced colon carcinogenesis in hemin-fed rats. All animals were given four subcutaneous DMH injections and then, two weeks after carcinogen exposure, they began a basal diet containing hemin, hemin + I3C, hemin + syn, or hemin + I3C + syn for 23 weeks. The combination of I3C + syn significantly increased fecal water genotoxicity, tumor volume and invasiveness when compared to the hemin-fed control group. The groups fed I3C or syn alone had a significant reduction in the number of preneoplastic aberrant crypt foci (ACF) lesions compared to the hemin-fed group. Dietary I3C also reduced fecal water genotoxicity. Gene expression analysis of colorectal tumors demonstrated that the combination of dietary I3C + syn increased transcript levels for Raf1 and decreased tumor progression and invasiveness related to the genes Cdh1 and Appl1. This analysis also revealed that the Tnf and Cdh1 genes were significantly up- and down-regulated, respectively, in tumors of rats that received I3C, in comparison with the hemin-fed group. These findings reveal that the joint administration of I3C and syn enhanced the development of colon tumors induced by DMH in hemin-fed rats, while they potentially reduced ACF development when given alone.


Subject(s)
Anticarcinogenic Agents/administration & dosage , Cocarcinogenesis , Colonic Neoplasms/etiology , Hemin/adverse effects , Indoles/administration & dosage , Red Meat/adverse effects , Synbiotics/administration & dosage , Adaptor Proteins, Signal Transducing/genetics , Animals , Caco-2 Cells , Cadherins/genetics , Carcinogens/toxicity , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Comet Assay , Dimethylhydrazines/toxicity , Disease Progression , Gene Expression Profiling , Hemin/administration & dosage , Humans , Lipid Peroxidation , Male , Neoplasm Invasiveness/genetics , Nerve Tissue Proteins/genetics , Proto-Oncogene Proteins c-raf/genetics , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/genetics
10.
J Am Soc Mass Spectrom ; 28(11): 2508-2514, 2017 11.
Article in English | MEDLINE | ID: mdl-28756543

ABSTRACT

Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool to study host-guest supramolecular interactions. ESI-MS can be used for detailed gas-phase reactivity studies, to clarify the structure, or simply to verify the formation of complexes. Depending on the structure of the host and of the guest, negative and/or positive ESI are used. Here we report the unexpected formation of host-guest complexes between cucurbit[n]urils (n = 7, 8, CB[n]) and amine, styryl pyridine, and styryl pyridine dimer cations, under negative ESI. Non-complexed CB[n] form double charged halide (Br-, Cl-, F-) adducts. Under negative ESI, halide ions interact with CB[n] outer surface hydrogen atoms. One to one host-guest complexes (1:1) of CB[n] with positive charged guests were also observed as single and double charged ions under negative ESI. The positive charge of guests is neutralized by ion-pairing with halide anions. Depending on the number of positive charges guests retain in the gas phase, one or two additional halide ions are required for neutralization. Complexes 1:2 of CB[8] with styryl pyridines retain two halide ions in the gas phase, one per guest. Styryl pyridine dimers form 1:1 complexes possessing a single extra halide ion and therefore a single positive charge. Negative ESI is sensitive to small structural differences between complexes, distinguishing between 1:2 complexes of styryl pyridine-CB[8] and corresponding 1:1 complexes with the dimer. Negative ESI gives simpler spectra than positive ESI and allows the determination of guest charge state of CB[n] complexes in the gas phase. Graphical Abstract ᅟ.

11.
Mod Pathol ; 30(7): 978-985, 2017 07.
Article in English | MEDLINE | ID: mdl-28304401

ABSTRACT

Intestinal neuronal dysplasia type B is a controversial entity expressed by complex changes in the enteric nervous system. Diagnosis depends on rectal biopsy histopathology and diagnostic criteria, both qualitative and quantitative, have changed over time, hindering the diagnostic practice. We analyzed the morphological criteria for the histological diagnosis of intestinal neuronal dysplasia type B in a series of patients with intestinal neuronal dysplasia type B according to the 1990 Frankfurt Consensus criteria and verified the applicability of the numerical criteria proposed by Meier-Ruge et al in 2004 and 2006. Qualitative criteria adopted for the histological diagnosis of intestinal neuronal dysplasia type B included hyperplasia of the submucous plexus with hyperganglionosis and hypertrophy of the nerve trunks. Quantitative criteria considered more than 20% giant ganglia in the submucosa, with more than eight neurons each on 25 ganglia, and children aged over 1 year. Distal colon surgical specimens from 29 patients, aged 0-16 years, diagnosed with intestinal neuronal dysplasia type B were retrospectively analyzed using sections processed for conventional histology (H&E) and calretinin immunohistochemistry. Hyperplasia of the submucosal nerve plexi with hyperganglionosis and hypertrophy of the nerve trunks was observed in all cases. Ganglia with small, immature neurons were detected in the majority of cases. Quantitative analysis confirmed hyperganglionosis (mean number=10.7 neurons per ganglion) and hypertrophy of the nerve trunks (median=44.6 µm thickness). Neurons showed immunostaining for calretinin, but neuron counts in calretinin-stained sections were lower compared with H&E (P<0.01). No significant differences were verified between children aged under and over 1 year regarding hyperganglionosis (P=0.79), neuron counts (P=0.36), and immature ganglia (P=0.66). Only one patient met the numerical criteria proposed by Meier-Ruge et al in 2004 and 2006. In conclusion, the numerical criteria showed limited applicability when transposed to conventional histopathology. Children aged over 1 year presented very similar histological features of neuronal immaturity to younger children, questioning the need for an age criterion when diagnosing intestinal neuronal dysplasia type B.


Subject(s)
Colon/pathology , Enteric Nervous System/pathology , Intestinal Diseases/diagnosis , Nervous System Diseases/diagnosis , Neurons/pathology , Adolescent , Child , Child, Preschool , Female , Ganglia/pathology , Humans , Infant , Infant, Newborn , Intestinal Diseases/pathology , Intestinal Mucosa/pathology , Male , Nervous System Diseases/pathology , Retrospective Studies
12.
Rapid Commun Mass Spectrom ; 30(17): 1963-8, 2016 09 15.
Article in English | MEDLINE | ID: mdl-27384507

ABSTRACT

RATIONALE: Biogenic polyamines in drinks have been implicated in undesirable physiological effects. Methods for their detection and quantification usually involve derivatization, pre-concentration and clean-up. To assist the evaluation of the potential risk of distillates, it was important to develop a simple and fast analytical method, which is described in this study. METHODS: Biogenic polyamines were selectively encapsulated after addition of a nanocontainer, cucurbit[7]uril (50 µM), to the distilled drink samples, which were acidified with HCl (pH 3) prior addition of the nanocontainer. The quantification of polyamines was achieved by direct infusion electrospray ionization quadrupole ion trap mass spectrometry in the multiple reaction monitoring mode, using encapsulated amantadine as internal standard, and by monitoring signals originating from their host-guest complexes. RESULTS: Six point calibration curves, ranging from 0.5 µM to 20 µM of polyamines in water and ethanol/water (50:50), were used to establish instrument response. The method was validated by analysis of fortified Arbutus spirits. Samples of Arbutus and grape pomace spirits were also analyzed. Linear responses were observed for all polyamines and were similar in water, hydro-alcoholic solutions and fortified Arbutus spirits. Putrescine the simple polyamine was detected only in grape pomace distillate samples. CONCLUSIONS: A quantitative method was developed for rapid and simple analysis of biogenic polyamines in distilled drinks. The detection limits depend on the ionization properties of the samples. Encapsulated amantadine can be used to probe these properties and method application. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Alcoholic Beverages/analysis , Biogenic Polyamines/analysis , Nanostructures/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Amantadine , Macrocyclic Compounds/chemistry
13.
Chem Biol Interact ; 245: 59-65, 2016 Feb 05.
Article in English | MEDLINE | ID: mdl-26751708

ABSTRACT

Cisplatin (Cisp) is an effective antitumor drug; however, it causes severe nephrotoxicity. Minimization of renal toxicity is essential, but the interference of nephroprotective agents, particularly antioxidants, with the antitumor activity of cisplatin is a general concern. We have recently demonstrated that the anti-hypertensive and antioxidant drug carvedilol (CV) protects against the renal damage and increases the survival of tumor-bearing mice without impairing the tumor reduction by cisplatin. So far, reports on the antioxidant mechanism of CV are controversial and there are no data on the impact of CV on the antitumor mechanisms of cisplatin. Therefore, this study addresses the effect of CV on mechanisms underlying the tumor control by cisplatin. CV did not interfere with the biodistribution or the genotoxicity of cisplatin. We also addressed the antioxidant mechanisms of CV and demonstrated that it does not neutralize free radicals, but is an efficient chelator of ferrous ions that are relevant catalyzers in cisplatin nephrotoxicity. The present data suggest that oxidative damage and genotoxicity play different roles in the toxicity of cisplatin on kidneys and tumors and therefore, some antioxidants might be safe as chemoprotectors. Altogether, our studies provide consistent evidence of the beneficial effect of CV on animals treated with cisplatin and might encourage clinical trials.


Subject(s)
Antineoplastic Agents/toxicity , Antioxidants/therapeutic use , Carbazoles/therapeutic use , Cisplatin/toxicity , Kidney/drug effects , Propanolamines/therapeutic use , Sarcoma 180/drug therapy , Animals , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Carbazoles/pharmacology , Carvedilol , Cisplatin/pharmacokinetics , Cisplatin/pharmacology , Kidney/pathology , Male , Propanolamines/pharmacology , Sarcoma 180/pathology , Tissue Distribution
14.
Chem Biol Interact ; 229: 119-31, 2015 Mar 05.
Article in English | MEDLINE | ID: mdl-25665769

ABSTRACT

Both types of diabetes are associated with higher incidence of some types of cancer. Treating cancer in diabetic patients without aggravating diabetes-related complications is a challenge for clinicians. Additionally, little is known about how diabetes affects the treatment of cancer. One of the most effective chemotherapeutic drugs is cisplatin, which is nephrotoxic. Studies suggest that diabetes acts as a protective factor against the nephrotoxicity of cisplatin, but the mechanisms involved have not been elucidated yet. This renal protection has been attributed to decreased accumulation of cisplatin in the kidneys, which could be associated with deficient active transport of proximal tubular cells or to pharmacokinetic alterations caused by diabetes. However, it is uncertain if diabetes also compromises the antitumor activity of cisplatin. To address this issue, we developed a mouse model bearing cisplatin-induced nephrotoxicity, Sarcoma 180 and streptozotocin-induced diabetes. Four groups of treatment were defined: (i) control, (ii) diabetic, (iii) cisplatin and (iv) diabetic treated with cisplatin. The following parameters were evaluated: renal function, oxidative stress, apoptosis, renal histopathology, tumor remission, survival rate, genotoxicity and platinum concentration in tumor and several organs. Results indicate that diabetes protects against the renal damage induced by cisplatin, while also compromises its antitumor effectiveness. This is the first study to demonstrate this effect.


Subject(s)
Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Cisplatin/pharmacokinetics , Cisplatin/therapeutic use , Diabetes Mellitus, Experimental/complications , Kidney Diseases/chemically induced , Sarcoma 180/complications , Sarcoma 180/drug therapy , Animals , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Cell Line, Tumor , Cisplatin/toxicity , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Kidney Diseases/metabolism , Kidney Diseases/pathology , Male , Mice , Oxidative Stress/drug effects , Sarcoma 180/metabolism , Sarcoma 180/pathology , Tissue Distribution
15.
Front Plant Sci ; 5: 665, 2014.
Article in English | MEDLINE | ID: mdl-25520728

ABSTRACT

Ethylene metabolism in higher plants is regulated by a wide array of endogenous and environmental factors. During most physiological processes, ethylene levels are mainly determined by a strict control of the rate-limiting biosynthetic steps responsible for the production of 1-aminocyclopropane-1-carboxylic acid (ACC) and its subsequent conversion to ethylene. Responsible for these reactions, the key enzymes ACC synthase and ACC oxidase are encoded by multigene families formed by members that can be differentially regulated at the transcription and post-translational levels by specific developmental and environmental signals. Among the wide variety of environmental cues controlling plant ethylene production, light quality, duration, and intensity have consistently been demonstrated to influence the metabolism of this plant hormone in diverse plant tissues, organs, and species. Although still not completely elucidated, the mechanisms underlying the interaction between light signal transduction and ethylene evolution appears to involve a complex network that includes central transcription factors connecting multiple signaling pathways, which can be reciprocally modulated by ethylene itself, other phytohormones, and specific light wavelengths. Accumulating evidence has indicated particular photoreceptors as essential mediators in light-induced signaling cascades affecting ethylene levels. Therefore, this review specifically focuses on discussing the current knowledge of the potential molecular mechanisms implicated in the light-induced responses affecting ethylene metabolism during the regulation of developmental and metabolic plant responses. Besides presenting the state of the art in this research field, some overlooked mechanisms and future directions to elucidate the exact nature of the light-ethylene interplay in higher plants will also be compiled and discussed.

16.
Nutr Cancer ; 66(8): 1293-303, 2014.
Article in English | MEDLINE | ID: mdl-25333700

ABSTRACT

The present study investigated whether maternal exposure to western style diet (WD) increases susceptibility to mammary carcinogenesis induced by N-methyl-N-nitrosourea (MNU) in female offspring. Pregnant female Sprague-Dawley rats received WD diet or control diet from gestational day 12 until postnatal day (PND) 21. At PND 21, female offspring received a single dose of MNU (50 mg/kg body weight) and were fed chow diet until PND 110. Mammary gland structures were assessed on whole-mount preparations in the offspring at PND 21, and tumor morphology was examined at PND 110. Immunohistochemical analysis for cell proliferation (PCNA), apoptosis (cleaved caspase-3) and estrogen receptor alpha (ER-α) was performed in mammary terminal end buds (TEBs) at PND 21, and PCNA, ER-α, and p63 analysis in mammary tumors at PND 110. Maternal WD intake induced a significant increase in the number of TEBs (P = 0.024) and in PCNA labeling index (P < 0.020) in the mammary glands at PND 21. Tumor multiplicity, tumor weight, and PCNA labeling indexes were significantly higher in the WD offspring than that of the control offspring (P < 0.05). These findings indicate that maternal western style diet potentially enhanced the development of mammary tumors induced by MNU in female offspring, possibly by affecting the mammary gland differentiation.


Subject(s)
Diet, Western/adverse effects , Mammary Neoplasms, Experimental/pathology , Maternal Nutritional Physiological Phenomena , Animals , Apoptosis , Carcinogenesis , Caspase 3/genetics , Caspase 3/metabolism , Cell Differentiation , Cell Proliferation , Disease Susceptibility/etiology , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Female , Mammary Neoplasms, Experimental/chemically induced , Methylnitrosourea/toxicity , Pregnancy , Rats , Rats, Sprague-Dawley
17.
Plast Reconstr Surg ; 133(6): 1502-1507, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24867732

ABSTRACT

BACKGROUND: The aim of this study was to assess the correlation between impact factor and the level of evidence of articles in plastic surgery journals. METHODS: The four plastic surgery journals with the top impact factors in 2011 were selected. Articles were selected using the PubMed database between January 1 and December 31, 2011. The journal evidence index was calculated by dividing the number of randomized clinical trials by the total number of articles published in the specific journal, multiplied by 100. This index was correlated to the impact factor of the journal and compared with the average of the other journals. Two investigators independently evaluated each journal, followed by a consensus and assessment of the interexaminer concordance. The kappa test was used to evaluate the concordance between the two investigators and Fisher's exact test was used to evaluate which journal presented the highest number of randomized clinical trials. RESULTS: The journal evidence index values were as follows: Plastic and Reconstructive Surgery, 1.70; Journal of Plastic, Reconstructive and Aesthetic Surgery, 0.40; Aesthetic Plastic Surgery, 0.56; and Annals of Plastic Surgery, 0.35. The impact factors of these journals in 2011 were as follows: Plastic and Reconstructive Surgery, 3.382; Journal of Plastic, Reconstructive and Aesthetic Surgery, 1.494; Aesthetic Plastic Surgery, 1.407; and Annals of Plastic Surgery, 1.318. After consensus, the quantity of adequate studies was low and similar between these journals; only the journal Plastic and Reconstructive Surgery showed a higher journal evidence index. CONCLUSIONS: The journal Plastic and Reconstructive Surgery exhibited the highest journal evidence index and had the highest impact factor. The number of adequate articles was low in all of the assessed journals.


Subject(s)
Evidence-Based Medicine , Journal Impact Factor , Periodicals as Topic/statistics & numerical data , Humans , Periodicals as Topic/standards , Randomized Controlled Trials as Topic , Surgery, Plastic
18.
Food Chem Toxicol ; 64: 20-6, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24275088

ABSTRACT

Coffee has been inversely related to the incidence of human liver disease; however, whether caffeine is the component responsible for the beneficial effects of coffee remains controversial. This study evaluated the beneficial effects of coffee or caffeine in a medium-term bioassay for rat liver fibrosis/carcinogenesis induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4). One week after the DEN injection, the groups started to receive conventional coffee, instant coffee or 0.1% caffeine ad libitum for 24 weeks. The groups receiving conventional coffee or caffeine presented a significant reduction in collagen content and mRNA expression of collagen I. The groups receiving instant coffee or caffeine had a significant reduction in the size and area of pre-neoplastic lesions and in the mean number of neoplastic lesions. A significant increase in liver bax protein levels was observed in the groups receiving instant coffee or caffeine as compared to the control group. These data indicate that the most pronounced hepatoprotective effect against fibrosis was observed in the groups receiving conventional coffee and 0.1% caffeine, and the greatest effects against liver carcinogenesis were detected in the groups receiving instant coffee and 0.1% caffeine.


Subject(s)
Caffeine/pharmacology , Carcinogenesis/drug effects , Coffee , Liver Cirrhosis/prevention & control , Liver Neoplasms, Experimental/prevention & control , Animals , Blotting, Western , Collagen/metabolism , Glutathione Transferase/metabolism , Liver Neoplasms, Experimental/enzymology , Male , Precancerous Conditions/enzymology , Precancerous Conditions/metabolism , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction
19.
J Pediatr Gastroenterol Nutr ; 58(5): 603-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24345837

ABSTRACT

Many difficulties occur during the evaluation of rectal biopsies for the diagnosis of Hirschsprung disease. We investigated whether the introduction of calretinin (CR) immunohistochemistry in a diagnostic panel could decrease the rate of inconclusive results. Data from 82 patients undergoing rectal biopsies before and after CR introduction were analyzed. Inconclusive results were obtained in 17 of 45 rectal biopsies (37.8%) in the series of cases before CR introduction and in 5 of 42 rectal biopsies (11.9%) in the series of cases after CR (P < 0.006). The inclusion of CR in the histopathologic panel may improve the diagnostic accuracy of Hirschsprung disease.


Subject(s)
Calbindin 2/analysis , Hirschsprung Disease/diagnosis , Rectum/pathology , Adolescent , Adult , Biopsy , Child , Child, Preschool , Hirschsprung Disease/metabolism , Hirschsprung Disease/pathology , Humans , Immunohistochemistry , Infant , Young Adult
20.
Chem Biol Interact ; 206(1): 90-9, 2013 Oct 25.
Article in English | MEDLINE | ID: mdl-24012798

ABSTRACT

Cisplatin is an effective anticancer drug which has been used to treat a wide range of tumors for the last 30 years. However, its use is associated with nephrotoxicity. Protective strategies have been reported, but their impact on the antitumor activity of cisplatin has not been clarified. We have previously reported the protective potential of carvedilol against cisplatin nephrotoxicity in tumor-free rats. Therefore, in the present study we used a tumor-bearing model to investigate the impact of carvedilol on the antitumor activity of cisplatin. The renal damage induced by cisplatin and the protective effect of carvedilol were demonstrated by the levels of blood urea nitrogen and plasma creatinine as well as by renal histopathology and immunohistochemistry. The mechanism of protection was associated with significantly decreased (i) oxidative stress markers, (ii) Bax expression, (iii) caspase-3 activity and (iv) TUNEL labeling for apoptosis. More importantly, evaluation of tumor mass, tumor remission rate and the survival curve showed that carvedilol did not impair the antitumor action of cisplatin. These findings suggest that the mechanisms underlying the nephrotoxic and the antitumor activity of cisplatin might be different. This is the first study to report such findings. Compared to other reported potential cytoprotectors against cisplatin-induced nephrotoxicity, carvedilol stands out due to the fact that it is already clinically-employed and well tolerated by the patients. Based on these features and on the present findings, carvedilol is a very promising candidate for future clinical trials as nephroprotector in patients treated with cisplatin.


Subject(s)
Antineoplastic Agents/pharmacology , Carbazoles/pharmacology , Cisplatin/pharmacology , Kidney/drug effects , Neoplasms, Experimental/drug therapy , Propanolamines/pharmacology , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Carbazoles/chemistry , Carvedilol , Cisplatin/administration & dosage , Cisplatin/chemistry , Dose-Response Relationship, Drug , Kidney/metabolism , Male , Mice , Molecular Structure , Neoplasms, Experimental/pathology , Oxidative Stress/drug effects , Propanolamines/chemistry , Structure-Activity Relationship , Xenograft Model Antitumor Assays
SELECTION OF CITATIONS
SEARCH DETAIL
...