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1.
Rev. esp. patol ; 56(2): 119-123, Abr-Jun 2023. ilus
Article in Spanish | IBECS | ID: ibc-219166

ABSTRACT

El tumor de células gigantes óseo (TCGO) representa el 4-5% de los tumores óseos primarios, se localiza en la epífisis de huesos largos, cuerpos vertebrales y huesos planos, y es más frecuente en el sexo femenino entre los 20 y 45 años. Presentamos el caso de una mujer de 31 años con dolor torácico de un mes de evolución. En la exploración física se palpó un nódulo en mama derecha y semiología de derrame pleural ipsilateral. El estudio mediante TAC torácica evidenció una masa infiltrante. La lesión fue biopsiada, permitiendo el diagnóstico de TCGO. Debido a la localización y a la morfología, se planteó un amplio diagnóstico diferencial. Adicionalmente, se detectó la mutación del gen de la histona H3F3A, reforzando el diagnóstico. Recibió tratamiento neoadyuvante con denosumab, haciendo posible la posterior resección quirúrgica de la lesión. En la pieza quirúrgica se observaron cambios histológicos, fuente de pitfalls diagnósticos.(AU)


Giant cell tumour of bone (GCTOB) accounts for 4-5% of all primary bone tumours and occurs most frequently in females between 20 and 45 years old. It is found in the epiphyses of the long bones, vertebral bodies and flat bones.We report the case of a 31-year-old woman who presented with a one month history of thoracic pain. On examination, a mass was found in the right breast with signs of an ipsilateral pleural effusion. A thoracic CAT scan revealed an infiltrating mass which was subsequently biopsied and a GCTOB was diagnosed. Due to the localization and the morphology, a wide range of differential diagnoses were considered. Genetic studies detected a mutation of the gene H3F3A, supporting the original diagnosis. The patient underwent treatment with denosumab followed by surgical resection of the mass. The histopathology of the tumour revealed various histological changes which were a source of diagnostic pitfalls.(AU)


Subject(s)
Humans , Female , Adult , Inpatients , Physical Examination , Giant Cell Tumor of Bone , Rib Cage , Denosumab , Tomography, X-Ray Computed , Chest Pain
2.
Rev Esp Patol ; 56(2): 119-123, 2023.
Article in Spanish | MEDLINE | ID: mdl-37061238

ABSTRACT

Giant cell tumour of bone (GCTOB) accounts for 4-5% of all primary bone tumours and occurs most frequently in females between 20 and 45 years old. It is found in the epiphyses of the long bones, vertebral bodies and flat bones. We report the case of a 31-year-old woman who presented with a one month history of thoracic pain. On examination, a mass was found in the right breast with signs of an ipsilateral pleural effusion. A thoracic CAT scan revealed an infiltrating mass which was subsequently biopsied and a GCTOB was diagnosed. Due to the localization and the morphology, a wide range of differential diagnoses were considered. Genetic studies detected a mutation of the gene H3F3A, supporting the original diagnosis. The patient underwent treatment with denosumab followed by surgical resection of the mass. The histopathology of the tumour revealed various histological changes which were a source of diagnostic pitfalls.


Subject(s)
Bone Density Conservation Agents , Bone Neoplasms , Chest Pain , Denosumab , Giant Cell Tumor of Bone , Humans , Female , Adult , Giant Cell Tumor of Bone/drug therapy , Giant Cell Tumor of Bone/pathology , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Chest Pain/diagnostic imaging , Chest Pain/etiology , Biopsy , Tomography, X-Ray Computed , Denosumab/therapeutic use , Bone Density Conservation Agents/therapeutic use , Treatment Outcome
4.
Breast ; 66: 77-84, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36206609

ABSTRACT

BACKGROUND: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone. METHODS: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1. RESULTS: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study. CONCLUSIONS: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2- ABC, including populations of interest (NCT02941926). TRIAL REGISTRATION: ClinicalTrials.gov NCT02941926.


Subject(s)
Breast Neoplasms , Neutropenia , Humans , Female , Middle Aged , Breast Neoplasms/pathology , Letrozole , Receptor, ErbB-2/metabolism , Aminopyridines/adverse effects , Aromatase Inhibitors/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Neutropenia/etiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects
5.
Oncogene ; 41(38): 4349-4360, 2022 09.
Article in English | MEDLINE | ID: mdl-35948648

ABSTRACT

Response to cancer immunotherapy in primary versus metastatic disease has not been well-studied. We found primary pancreatic ductal adenocarcinoma (PDA) is responsive to diverse immunotherapies whereas liver metastases are resistant. We discovered divergent immune landscapes in each compartment. Compared to primary tumor, liver metastases in both mice and humans are infiltrated by highly anergic T cells and MHCIIloIL10+ macrophages that are unable to present tumor-antigen. Moreover, a distinctive population of CD24+CD44-CD40- B cells dominate liver metastases. These B cells are recruited to the metastatic milieu by Muc1hiIL18hi tumor cells, which are enriched >10-fold in liver metastases. Recruited B cells drive macrophage-mediated adaptive immune-tolerance via CD200 and BTLA. Depleting B cells or targeting CD200/BTLA enhanced macrophage and T-cell immunogenicity and enabled immunotherapeutic efficacy of liver metastases. Our data detail the mechanistic underpinnings for compartment-specific immunotherapy-responsiveness and suggest that primary PDA models are poor surrogates for evaluating immunity in advanced disease.


Subject(s)
Carcinoma, Pancreatic Ductal , Liver Neoplasms , Pancreatic Neoplasms , Animals , Carcinoma, Pancreatic Ductal/drug therapy , Humans , Immunotherapy , Interleukin-10 , Interleukin-18/therapeutic use , Liver Neoplasms/therapy , Mice , Pancreatic Neoplasms/drug therapy , Receptors, Immunologic , Pancreatic Neoplasms
6.
Cancers (Basel) ; 13(21)2021 Oct 31.
Article in English | MEDLINE | ID: mdl-34771649

ABSTRACT

BACKGROUND: Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. METHODS: PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000-2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. RESULTS: Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. DISCUSSION: ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. CONCLUSIONS: ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies.

7.
Rev Esp Patol ; 54(3): 182-187, 2021.
Article in Spanish | MEDLINE | ID: mdl-34175030

ABSTRACT

Inflammatory myofibroblastic tumour (IMT) is a rare entity that can occur in practically any location. Although it has an increased incidence in infancy and adolescence, cases of IMT in the head and neck are more frequent in adults. We report the case of a 74-year-old male who presented with a two month history of dysphonia. Laryngoscopy and cervical TAC revealed a nodular lesion affecting the anterior half of the left vocal cord. He underwent endoscopic laser cordectomy. Histopathology concluded that the lesion was an IMT. Cases of IMT in the head and neck are infrequent and in the vocal cord extremely rare, with only a few previously reported cases.


Subject(s)
Granuloma, Plasma Cell/pathology , Laryngeal Neoplasms/pathology , Vocal Cords/pathology , Aged , Dysphonia/etiology , Granuloma, Plasma Cell/diagnostic imaging , Humans , Laryngeal Neoplasms/chemistry , Laryngeal Neoplasms/diagnostic imaging , Male , Tomography, X-Ray Computed , Vocal Cords/chemistry , Vocal Cords/diagnostic imaging
8.
Hip Int ; 31(2): 186-190, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32126845

ABSTRACT

INTRODUCTION: Lower limb-length discrepancy is highly prevalent in the general population. Numerous methods and measurement instruments for its diagnosis appear in the literature, but there has not been an agreement about their validity. The aim of this work is to determine the validity of the Weber-Barstow manoeuvre (WB) of the pelvic measuring device (PMD) and the block method (BM), in comparison with standing anteroposterior telemetry of the lower limbs in subjects with leg-length discrepancy (LLD). METHODS: 71 subjects took part in the study. First, the WB was carried out in the supine position. the LLD was then quantified standing with the PMD and with the BM. Lastly, standing anteroposterior telemetry of the lower limbs was obtained. This was measured with Autocad 2013, using the highest part of the head of the femur and the most distal edge of the bisection of the femur as points of reference. RESULTS: The Kappa index was calculated to check the agreement between the WB manoeuvre and the telemetry. This was 0.52. The relation of the PMD, BM and telemetry difference variables was calculated. A direct relation between the BM and telemetry was shown, with p > 0.05 (0.48 cm and 0.51 cm, respectively). CONCLUSIONS: The WB manoeuvre got acceptable validity results. The PMD was not valid according to the results obtained in this work. The BM achieved a good validity result for the diagnosis of LLD.


Subject(s)
Leg Length Inequality , Leg , Femur , Humans , Leg Length Inequality/diagnostic imaging , Lower Extremity , Radiography
9.
Nat Immunol ; 21(4): 442-454, 2020 04.
Article in English | MEDLINE | ID: mdl-32152508

ABSTRACT

Programmed cell death protein 1 (PD-1) ligation delimits immunogenic responses in T cells. However, the consequences of programmed cell death 1 ligand 1 (PD-L1) ligation in T cells are uncertain. We found that T cell expression of PD-L1 in cancer was regulated by tumor antigen and sterile inflammatory cues. PD-L1+ T cells exerted tumor-promoting tolerance via three distinct mechanisms: (1) binding of PD-L1 induced STAT3-dependent 'back-signaling' in CD4+ T cells, which prevented activation, reduced TH1-polarization and directed TH17-differentiation. PD-L1 signaling also induced an anergic T-bet-IFN-γ- phenotype in CD8+ T cells and was equally suppressive compared to PD-1 signaling; (2) PD-L1+ T cells restrained effector T cells via the canonical PD-L1-PD-1 axis and were sufficient to accelerate tumorigenesis, even in the absence of endogenous PD-L1; (3) PD-L1+ T cells engaged PD-1+ macrophages, inducing an alternative M2-like program, which had crippling effects on adaptive antitumor immunity. Collectively, we demonstrate that PD-L1+ T cells have diverse tolerogenic effects on tumor immunity.


Subject(s)
B7-H1 Antigen/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Immune Tolerance/immunology , Macrophages/immunology , Self Tolerance/immunology , Animals , Cell Differentiation/immunology , Cell Line, Tumor , Female , Humans , Interferon-gamma/immunology , Male , Mice , Mice, Inbred C57BL , Programmed Cell Death 1 Receptor/immunology , Signal Transduction/immunology , Tumor Microenvironment/immunology
10.
Surg Obes Relat Dis ; 15(11): 1923-1932, 2019 11.
Article in English | MEDLINE | ID: mdl-31611184

ABSTRACT

BACKGROUND: Bariatric surgery offers patients with morbid obesity and related diseases short- and long-term benefits to their health and quality of life. Evidence-based medicine is integral in the evaluation of risk versus benefit; however, data are lacking for several high-risk patient populations, including the elderly. OBJECTIVES: This study assessed morbidity and mortality data for patients age ≥70 undergoing laparoscopic sleeve gastrectomy (SG) or laparoscopic Roux-en-Y gastric bypass (RYGB). SETTING: University Hospital, Bronx, New York, United States using national database. METHODS: We used the American College of Surgeons-National Surgical Quality Improvement Project database for years 2005-2016 and identified patients who underwent primary SG or RYGB. Patients age ≥70 were assigned to the over age 70 (AGE70+) cohort and younger patients were assigned to the under age 70 (U70) cohort. Postoperative length of stay and 30-day morbidity and mortality were assessed. RESULTS: A total of 1498 patients age ≥70 underwent nonrevisional bariatric surgery, including 751 (50.1%) SG and 747 (49.9%) RYGB. AGE70+ was associated with increased mortality and increased rates of cardiac, pulmonary, renal, and cerebrovascular morbidity. AGE70+ patients had longer mean length of stay, and were more likely to require transfusion and return to operative room. When stratified by procedure, rates of organ-space surgical site infection, acute renal failure, urinary tract infection, myocardial infarction, deep vein thrombosis/thrombophlebitis, and septic shock were significantly increased in AGE70+ patients undergoing RYGB but not SG. Impaired functional status was associated with increased rates of morbidity and mortality for AGE70+ patients and for U70 patients, although the small number of patients within each category limited statistical analysis. CONCLUSIONS: Evaluation of risk versus benefit is performed on a case-by-case basis, but evidence-based medicine is critical in empowering surgeons and patients to make informed decisions. The overall rate of morbidity and mortality for AGE70+ patients undergoing bariatric surgery was increased relative to U70 patients. Rates of several adverse events, including acute renal failure and myocardial infarction, were increased in AGE70+ patients undergoing RYGB but not SG, suggesting that SG may be the preferred procedure for elderly patients with organ-specific risk factors. The increased rates of morbidity and mortality observed for patients with impaired functional status supports consideration of functional status when evaluating preoperative risk.


Subject(s)
Gastrectomy/methods , Gastric Bypass/methods , Obesity, Morbid/mortality , Obesity, Morbid/surgery , Quality Improvement , Aged , Aged, 80 and over , Bariatric Surgery/methods , Bariatric Surgery/mortality , Body Mass Index , Cohort Studies , Databases, Factual , Female , Follow-Up Studies , Gastrectomy/mortality , Gastric Bypass/mortality , Geriatric Assessment , Hospitals, University , Humans , Incidence , Laparoscopy/methods , Laparoscopy/mortality , Male , Morbidity , New York City , Obesity, Morbid/diagnosis , Patient Safety , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment Outcome
11.
Nat Commun ; 10(1): 1424, 2019 03 29.
Article in English | MEDLINE | ID: mdl-30926808

ABSTRACT

The drivers and the specification of CD4+ T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique TH-program. Specifically, CD11b+CD103- DC predominate in PDA, express high IL-23 and TGF-ß, and induce FoxP3neg tumor-promoting IL-10+IL-17+IFNγ+ regulatory CD4+ T cells. The balance between this distinctive TH program and canonical FoxP3+ TREGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This TH-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b+CD103- DC promote CD4+ T cell tolerance in PDA which may underscore its resistance to immunotherapy.


Subject(s)
Dendritic Cells/immunology , Interleukin-10/metabolism , Interleukin-17/metabolism , Pancreatic Neoplasms/immunology , T-Lymphocytes, Regulatory/immunology , Adenocarcinoma/genetics , Adenocarcinoma/immunology , Adenocarcinoma/pathology , Animals , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/immunology , Carcinoma, Pancreatic Ductal/pathology , Cell Differentiation , Disease Progression , Forkhead Transcription Factors , Gene Expression Regulation, Neoplastic , Humans , Lectins, C-Type/metabolism , Mice, Inbred C57BL , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Phenotype , Signal Transduction , Th17 Cells/immunology , Toll-Like Receptor 2/metabolism , Tretinoin/metabolism , Pancreatic Neoplasms
12.
J Sex Med ; 15(12): 1678-1697, 2018 12.
Article in English | MEDLINE | ID: mdl-30527052

ABSTRACT

BACKGROUND: Previous work showed that muscle-derived stem cells (MDSCs) exposed long-term to the milieu of uncontrolled type 2 diabetes (UC-T2D) in male obese Zucker (OZ) rats, were unable to correct the associated erectile dysfunction and the underlying histopathology when implanted into the corpora cavernosa, and were also imprinted with a noxious gene global transcriptional signature (gene-GTS), suggesting that this may interfere with their use as autografts in stem cell therapy. AIM: To ascertain the respective contributions of dyslipidemia and hyperglycemia to this MDSC damage, clarify its mechanism, and design a bioassay to identify the damaged stem cells. METHODS: Early diabetes MDSCs and late diabetes MDSCs were respectively isolated from nearly normal young OZ rats and moderately hyperglycemic and severely dyslipidemic/obese aged rats with erectile dysfunction. Monolayer cultures of early diabetic MDSCs were incubated 4 days in DMEM/10% fetal calf serum + or - aged OZ or lean Zucker serum from non-diabetic lean Zucker rats (0.5-5%) or with soluble palmitic acid (PA) (0.5-2 mM), cholesterol (CHOL) (50-400 mg/dL), or glucose (10-25 mM). MAIN OUTCOME MEASURE: Fat infiltration was estimated by Oil red O, apoptosis by TUNEL, protein expression by Western blots, and gene-GTS and microRNA (miR)-GTS were determined in these stem cells' RNA. RESULTS: Aged OZ serum caused fat infiltration, apoptosis, myostatin overexpression, and impaired differentiation. Some of these changes, and also a proliferation decrease occurred with PA and CHOL. The gene-GTS changes by OZ serum did not resemble the in vivo changes, but some occurred with PA and CHOL. The miR-GTS changes by OZ serum, PA, and CHOL resembled most of the in vivo changes. Hyperglycemia did not replicate most alterations. CLINICAL IMPLICATIONS: MDSCs may be damaged in long-term UC-T2D/obese patients and be ineffective in autologous human stem cell therapy, which may be prevented by excluding the damaged MDSCs. STRENGTH & LIMITATIONS: The in vitro test of MDSCs is innovative and fast to define dyslipidemic factors inducing stem cell damage, its mechanism, prevention, and counteraction. Confirmation is required in other T2D/obesity rat models and stem cells (including human), as well as miR-GTS biomarker validation as a stem cell damage biomarker. CONCLUSION: Serum from long-term UC-T2D/obese rats or dyslipidemic factors induces a noxious phenotype and miR-GTS on normal MDSCs, which may lead in vivo to the repair inefficacy of late diabetic MDSCs. This suggests that autograft therapy with MDSCs in long-term UT-T2D obese patients may be ineffective, albeit this may be predictable by prior stem cell miR-GTS tests. Masouminia M, Gelfand R, Kovanecz I, et al. Dyslipidemia Is a Major Factor in Stem Cell Damage Induced by Uncontrolled Long-Term Type 2 Diabetes and Obesity in the Rat, as Suggested by the Effects on Stem Cell Culture. J Sex Med 2018;15:1678-1697.


Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Dyslipidemias/complications , Erectile Dysfunction/etiology , Stem Cell Transplantation , Animals , Cell Differentiation , Diabetes Mellitus, Experimental/therapy , Dyslipidemias/physiopathology , Erectile Dysfunction/physiopathology , Humans , Male , Obesity/complications , Penis/physiopathology , Rats , Rats, Zucker
13.
Article in English | MEDLINE | ID: mdl-30158996

ABSTRACT

Anxiety disorders are highly prevalent, chronic, and disabling conditions that impose enormous health and economic costs both on individuals and on society. Medicinal plants are an invaluable source of bioactive metabolites that can be useful as new pharmacological treatment. Teas from Mentha spicata and Plantago major are employed by Colombian populations to treat stress and insomnia. This work was conducted to evaluate their anxiolytic and hypnotic properties. For this, we employed the Elevated Plus-Maze test and the sodium pentobarbital-induced hypnosis method using Wistar rats. Oral administration of M. spicata extract (1000 mg/Kg) significantly increased the exploration and time spent in the open arms, which indicates its anxiolytic activity. On the other hand, both M. spicata and P. major extracts (1000 mg/Kg) remarkably augmented the sleeping time induced by pentobarbital, suggesting a sedative and hypnotic effect of the plants extracts. In addition, the acute toxicological study demonstrated that the doses used did not induce mortality or toxicity effects at hepatic or renal level. The bioactivity seems to be related to several kinds of constituents, mainly phenolic compounds such as flavonoids and tannins. In conclusion, these results reinforce the potential use of these species in the therapy of anxiety.

14.
J Gastrointest Oncol ; 8(5): E73-E79, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29184699

ABSTRACT

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and sebomatricoma. With the exception of one P-NET, all these conditions were associated with LS, as confirmed by immunohistochemistry (IHC) and polymerase chain reaction (PCR). LS is caused by a mutation of a mismatch repair (MMR) gene which leads to a loss of expression of its protein. CRC is the most common tumor, followed by EC. Pancreatic tumors have also been associated with LS. Diagnosis of LS is based on clinical criteria (Amsterdam II and Bethesda) and genetic study (MMR gene mutation). The association between LS and our patient's tumors was confirmed by IHC (loss of expression of proteins MLH1 and its dimer PMS2) and the detection of microsatellite instability (MSI) using PCR.

15.
Biomed Pharmacother ; 89: 1105-1114, 2017 May.
Article in English | MEDLINE | ID: mdl-28298071

ABSTRACT

In Colombia, Bothrops asper is responsible for 70-90% of ophidians accidents reported annually. Envenoming occurs mainly in rural areas where both antivenom and health centers are scarce. Thus, patients are frequently treated by local healers that employ medicinal herbs; including several species belonging to Dracontium genus. In this work, we evaluated the neutralizing activity of Dracontium dubium Kunth against the lethal, inflammatory, coagulant and hemolytic effects produced by B. asper venom. Mice treated with D. dubium extract (500 and 1000µg/g, ip), survived to the administration of lethal doses of venom, with remarkable recovery of macroscopic and histology damage. Furthermore, D. dubium exerted a significant inhibition of inflammatory damage promoted by paw injection of B. asper venom. Such activity might be related to the inhibition of macrophage activation and NO production, as demonstrated using LPS-stimulated RAW 264.7 cells. Moreover, the extract of D. dubium remarkably diminished the indirect hemolytic effect of snake venom. On the other hand, no substantial differences were observed in clotting time of plasma incubated with venom when compared to extract treated plasma. Noteworthy, D. dubium extract did not alter the electrophoretic pattern of venom before the assays. Phytochemistry screening revealed the presence of phenolic compounds, flavonoids, tannins and steroids/triterpenoids, which might explain the bioactivity of the extract. Our results, provides strong evidence that support the employment of D. dubium in folk medicine. Further studies are needed to isolate and identify the metabolites responsible for the activity, in order to provide a useful and accessible treatment for snakebite envenoming in low-income rural areas.


Subject(s)
Antivenins/pharmacology , Araceae/chemistry , Bothrops/metabolism , Plants, Medicinal/chemistry , Protective Agents/pharmacology , Venoms/poisoning , Animals , Blood Coagulation/drug effects , Cell Line , Female , Inflammation/drug therapy , Mice , Mice, Inbred ICR , Plant Extracts/pharmacology , RAW 264.7 Cells , Rats, Wistar
16.
Biomedica ; 33(1): 115-21, 2013.
Article in Spanish | MEDLINE | ID: mdl-23715314

ABSTRACT

INTRODUCTION: Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. OBJECTIVE: To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. MATERIALS AND METHODS: The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. RESULTS: In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. CONCLUSION: The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.


Subject(s)
Diuresis/drug effects , Diuretics/pharmacology , Plant Extracts/pharmacology , Pteridaceae/chemistry , Animals , Chlorides/urine , Colombia , Diuretics/administration & dosage , Diuretics/isolation & purification , Diuretics/toxicity , Drug Evaluation, Preclinical , Ethanol , Female , Furosemide/pharmacology , Kidney/drug effects , Kidney/ultrastructure , Liver/drug effects , Liver/ultrastructure , Medicine, Traditional , Natriuresis/drug effects , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Potassium/urine , Rats , Rats, Wistar , Solvents , Water
17.
Biomédica (Bogotá) ; 33(1): 115-121, ene.-mar. 2013. ilus, graf
Article in Spanish | LILACS | ID: lil-675139

ABSTRACT

Introducción. Ceratopteris pteridoides es un helecho semiacuático de la familia Parkeriacea, ampliamente utilizado en la medicina popular colombiana como diurético y colelitiásico, sobre el cual no existen reportes científicos que avalen su uso popular como diurético. Objetivo. Evaluar el efecto diurético agudo en dosis única y dosis repetidas a corto plazo, de los extractos etanólico y acuoso de C. pteridoides en un modelo in vivo . Materiales y métodos. El extracto etanólico total fue obtenido por maceración de la planta entera de C. pteridoides con etanol y el extracto acuoso fue obtenido por decocción a 60 °C por 15 minutos. Ambos extractos se sometieron a análisis fitoquímico preliminar y estudio histológico posterior a la administración de los extractos durante ocho días consecutivos (1.000 mg/kg). El efecto diurético se evaluó en ratas Wistar, tratadas con los extractos (500 mg/kg), en forma aguda y en dosis repetidas a corto plazo, cuantificando la eliminación de agua y la excreción renal de sodio y potasio por espectrofotometría de absorción atómica y, de cloruros, por titulación mercurimétrica. Resultados. En el modelo agudo, ambos extractos mostraron un significativo efecto diurético y de excreción renal de sodio y potasio en comparación con el control, mientras que con la administración en dosis repetidas a corto plazo mostraron efecto diurético sin eliminación de electrolitos. El estudio histopatológico no sugirió efectos tóxicos hepáticos o renales. Conclusión. Los resultados demuestran la actividad diurética de C. pteridoides y sustentan el uso popular dado a esta planta como diurético en la costa norte colombiana. Se requieren estudios posteriores que permitan aislar e identificar los compuestos responsables de la actividad y los mecanismos de acción involucrados.


Introduction. Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. Objective. To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. Materials and methods. The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. Results. In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. Conclusion. The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.


Subject(s)
Animals , Female , Rats , Diuresis/drug effects , Diuretics/pharmacology , Plant Extracts/pharmacology , Pteridaceae/chemistry , Colombia , Chlorides/urine , Drug Evaluation, Preclinical , Diuretics/administration & dosage , Diuretics/isolation & purification , Diuretics/toxicity , Ethanol , Furosemide/pharmacology , Kidney/drug effects , Kidney/ultrastructure , Liver/drug effects , Liver/ultrastructure , Medicine, Traditional , Natriuresis/drug effects , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Potassium/urine , Rats, Wistar , Solvents , Water
18.
ACS Nano ; 5(8): 6272-8, 2011 Aug 23.
Article in English | MEDLINE | ID: mdl-21790155

ABSTRACT

The packing of spheres is a subject that has drawn the attention of mathematicians and philosophers for centuries and that currently attracts the interest of the scientific community in several fields. At the nanoscale, the packing of atoms affects the chemical and structural properties of the material and, hence, its potential applications. This report describes the experimental formation of 5-fold nanostructures by the packing of interpenetrated icosahedral and decahedral units. These nanowires, formed by the reaction of a mixture of metal salts (Au and Ag) in the presence of oleylamine, are obtained when the chemical composition is specifically Ag/Au = 3:1. The experimental images of the icosahedral nanowires have a high likelihood with simulated electron micrographs of structures formed by two or three Boerdijk-Coxeter-Bernal helices roped on a single structure, whereas for the decahedral wires, simulations using a model of adjacent decahedra match the experimental structures. To our knowledge, this is the first report of the synthesis of nanowires formed by the packing of structures with 5-fold symmetry. These icosahedral nanowire structures are similar to those of quasicrystals, which can only be formed if at least two atomic species are present and in which icosahedral and decahedral packing has been found for bulk crystals.

19.
Nanoscale ; 2(3): 335-42, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20644815

ABSTRACT

Nanoparticles are the cornerstone of nanotechnology. Their crystal structure and relation to shape are still open problems despite a lot of advances in the field. The classical theory of nanoparticle stability predicts that for sizes <1.5-2 nm the icosahedral structure should be the most stable, then between around 2-5 nm, the decahedral shape should be the most stable. Beyond that, face-centered-cubic (FCC) structures will be the predominant phase. However, in the experimental side, icosahedral (I(h)) and decahedral (D(h)) particles can be observed much beyond the 5 nm limit. In fact, it is possible to find I(h) and D(h) particles even in the mesoscopic range. Conversely, it is possible to find FCC particles with a size <1.5 nm. In this paper we review a number of the mechanisms proposed in the literature that allow the stabilization of nanoparticles. Some of the mechanisms are very interrelated and it becomes difficult to distinguish between them.


Subject(s)
Nanoparticles/chemistry , Nanotechnology , Particle Size
20.
J Phys Chem A ; 113(38): 10299-305, 2009 Sep 24.
Article in English | MEDLINE | ID: mdl-19708678

ABSTRACT

Changes in the preferential sites of electrophilic, nucleophilic, and radical attacks on the pristine C60 surface with endohedral doping using 3d transition metal atoms were studied via two useful reactivity indices, namely the Fukui functions and the molecular electrostatic potential. Both of these were calculated at the density functional BPW91 level of theory with the DNP basis set. Our results clearly show changes in the preferential reactivity sites on the fullerene surface when it is doped with Mn, Fe, Co, or Ni atoms, whereas there are no significant changes in the preferential reactivity sites on the C60 surface upon endohedral doping with Cu and Zn atoms. Electron affinities (EA), ionization potentials (IP), and HOMO-LUMO gaps (Eg) were also calculated to complete the study of the endofullerene's surface reactivity. These findings provide insight into endofullerene functionalization, an important issue in their application.

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