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1.
Shock ; 61(6): 885-893, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38662580

RESUMEN

ABSTRACT: Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) sham, 2) sepsis (cecal ligation and puncture) without subsequent resuscitation, and 3) sepsis with lactated Ringer plus norepinephrine resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output and glomerular filtration rate were measured noninvasively. Mean arterial pressure, total renal blood flow, cortical perfusion, medullary perfusion, and medullary tissue oxygen tension (mtPO 2 ) were determined for 12 h. Cecal ligation and puncture decreased mean arterial pressure and cardiac output by more than 50%, with a proportional increase in renal vascular resistance and a 60-80% reduction in renal blood flow, cortical perfusion, medullary perfusion, and mtPO 2 compared to sham. Cecal ligation and puncture also decreased glomerular filtration rate by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO 2 , changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to cecal ligation and puncture develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.


Asunto(s)
Lesión Renal Aguda , Animales Recién Nacidos , Fluidoterapia , Norepinefrina , Resucitación , Sepsis , Animales , Porcinos , Sepsis/terapia , Sepsis/fisiopatología , Resucitación/métodos , Fluidoterapia/métodos , Lesión Renal Aguda/terapia , Lesión Renal Aguda/metabolismo , Inflamación , Riñón/metabolismo , Circulación Renal , Tasa de Filtración Glomerular
3.
Eur J Intern Med ; 120: 99-106, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37872034

RESUMEN

BACKGROUND AND AIMS: Controversial data have been reported regarding the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Inflammatory Bowel Disease (IBD) population and IBD-related risk factors. The aim of the study was to assess the prevalence and risk factors associated with NAFLD and liver fibrosis in IBD participants compared with non-IBD controls. METHODS: Cross-sectional, case-control study including 741 IBD cases and 170 non-IBD controls, matched by sex and age. All participants underwent liver ultrasound, transient elastography and laboratory tests. A logistic regression multivariable analysis was performed adjusting for classic metabolic risk factors and history of systemic steroid use. RESULTS: The prevalence of NAFLD and significant liver fibrosis was 45 % and 10 % in IBD group, and 40 % and 2.9 % in non-IBD group (p = 0.255 and 0.062, respectively). Longer IBD duration (aOR 1.02 95% CI (1.001-1.04)) and older age at IBD diagnosis (aOR 1.02 95 % CI (1.001-1.04)) were independent risk factors for NAFLD in IBD group. Crohn´s Disease was an independent risk factor for significant liver fibrosis in participants with IBD and NAFLD (aOR 3.97 95 % CI (1.78-8.96)). NAFLD occurred at lower BMI levels in IBD group with NAFLD compared to non-IBD group with NAFLD (aOR 0.92 95 % CI (0.87-0.98)). CONCLUSIONS: Although we found no differences in the prevalence of NAFLD and liver fibrosis between IBD group and non-IBD group, our findings suggest that liver fibrosis progression should be closely monitored in patients with concomitant CD and NAFLD, more in particular in those with long standing active disease.


Asunto(s)
Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Estudios de Casos y Controles , Estudios Transversales , Factores de Riesgo , Enfermedades Inflamatorias del Intestino/complicaciones , Cirrosis Hepática/complicaciones , Prevalencia
4.
Iran J Parasitol ; 18(2): 211-216, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37583630

RESUMEN

Background: Human cysticercosis (CC) is a global public health problem, especially in Latin America, including Brazil. We aimed to analyze the seroprevalence of CC among school-age children and adolescents. Methods: We analyzed the presence of specific IgG antibodies against Taenia solium metacestodes in 500 serum samples from elementary school children and adolescents in Jataí City, state of Goiás, Brazil. IgG antibodies against the antigenic extract of the parasite were detected and analyzed by ELISA, and specific peptides were identified by confirmatory Western Blotting test. Results: Of the 500 study participants, 205 (41%) were male, and 295 (59%) were female. Participants aged between 4 and 18 years (mean age 8.4 years). The percentage of serum samples reactive by ELISA was 37.2%. These samples were analyzed by Western Blotting, which confirmed that the seropositivity rate was 6.2% (95% CI 2.4-14.7) in 31 samples reactive for CC-specific bands, determined in serum samples from 18 male (5-11 years old) and 13 female (4-12 years old) students. Conclusion: The CC seroprevalence demonstrated in schoolchildren suggests that this parasitosis is endemic in the study area. Further investigations are necessary to clarify the local epidemiology of this parasitosis.

5.
Acta Parasitol ; 68(3): 718-722, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37531007

RESUMEN

PURPOSE: Chronic alcoholism is a well-known risk factor for strongyloidiasis, in these patients the disease is potentially more severe, probably due to the breakdown of local protective barriers and immunosuppression caused by alcohol, which can lead to autoinfection and dissemination. The aim of this study was to evaluate multiple stool sampling and a specific parasitological assay agar plate culture (APC) for the diagnosis of Strongyloides stercoralis in alcoholics. METHODS: APC was compared to sedimentation technique (HPJ; Hoffman, Pons and Janer), as parasitological methods to detect S. stercoralis infection in alcoholic individuals. Three stool samples from 60 alcoholic and 60 non-alcoholic individuals were analyzed. RESULTS: S. stercoralis larvae were observed in 11 (18.3%) alcoholic individuals and 1 (1.7%) nonalcoholic individual (P = 0.0042). In view of the combined results, sensitivity for the APC method was 63.6% (CI 31.6-87.6%) with the first sample reaching 100% (CI 67.8-100%) after analyzing three fecal samples. The HPJ sensitivity was 36.4% (CI 12.4-68.4) in the first sample, reaching 72.7% (CI 39.3-92.7) after three samples analyzed. CONCLUSION: The present results suggest that in alcoholic patients, it is important to repeat stool sampling with specific techniques, especially using the APC method, to avoid misdiagnosis in cases that could evolve to disseminated strongyloidiasis.


Asunto(s)
Alcohólicos , Alcoholismo , Strongyloides stercoralis , Estrongiloidiasis , Animales , Humanos , Estrongiloidiasis/diagnóstico , Alcoholismo/diagnóstico , Factores de Riesgo , Heces
6.
Mol Cancer ; 22(1): 127, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37559050

RESUMEN

BACKGROUND: Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. METHODS: Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. RESULTS: From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. CONCLUSIONS: Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02638766.


Asunto(s)
Antineoplásicos , Tumores del Estroma Gastrointestinal , Sarcoma , Adulto , Humanos , Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/genética , Sarcoma/tratamiento farmacológico
7.
J Parasit Dis ; 47(3): 520-526, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37520210

RESUMEN

Rodents infected with Strongyloides venezuelensis are experimental models applied to strongyloidiasis research. This study evaluated oral and subcutaneous dexamethasone (DEX) treatments to establish immunosuppression in an experimental model of Strongyloides hyperinfection. Rattus norvegicus Wistar were divided: G I (-): untreated and uninfected animals, G II (+): untreated and infected, G III (o -) orally treated and uninfected, G IV (o +) orally treated and infected, G V (sc -) subcutaneously treated and uninfected, G VI (sc +) subcutaneously treated and infected. For oral administration, DEX was diluted in sterile water (5 µg/ml) and made available to the animals on intervals in experimental days - 5-0, 8-13 and 21-26. For subcutaneous administration, animals received daily injections of DEX disodium phosphate (2 mg/kg). Infection was established by the subcutaneous inoculation of 3000 S. venezuelensis filarioid larvae. Groups were evaluated by egg per gram of feces and parasite females counts and IgG, IgG1 and IgG2a detection. GIV (o +) had egg peaks count on days 13 and 26 and maintained egg elimination until the last experimental day. Parasitic females recovery at day 30 was significantly higher in G IV (o +) when compared to G VI (sc +). Levels of IgG, IgG1 and IgG2a of all groups, except the positive control GII (+), were below the detection threshold. Pharmacological immunosuppression induced by oral administration of DEX produced high parasitic burden, and is a noninvasive method, useful to establish immunosuppression in strongyloidiasis hyperinfection model in rats.

8.
Cancers (Basel) ; 15(13)2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37444477

RESUMEN

The aim of the systematic review is to assess the prevalence and risk factors of liver fibrosis in patients with Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD) and to discuss the role of liver fibrosis in the progression to hepatocellular carcinoma (HCC). We performed a structured search in PubMed, Web of Science, Embase, and Scopus up to 3 March 2023 to identify observational studies reporting liver fibrosis in patients with NAFLD and IBD. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) score. A total of 23 studies met our inclusion criteria, including 629,781 patients. A total of 10 cross-sectional, 3 case-control, and 10 cohort studies were included. Fourteen studies had a NOS score ≥ 7 points. NAFLD was diagnosed in 2162/6332 (34.1%) IBD participants. However, NAFLD diagnosis was established in 924/2962 (31.2%) healthy individuals without IBD. Advanced liver fibrosis was found in 116 (11.6%) of 992 IBD patients with NAFLD. Most studies found an association between NAFLD and classic cardiovascular risk factors such as older age, male sex, higher BMI, diabetes, hypertension and dyslipidemia. In addition, metabolic syndrome features were also associated with an increased risk of significant and advanced liver fibrosis. Although no strong association between NAFLD and IBD therapy was reported, some studies associated NAFLD with IBD diagnosis, Crohn's Disease, a complicated course of IBD, disease activity, and IBD duration. Advanced liver fibrosis was also associated with Crohn's disease in several studies. In conclusion, NAFLD and advanced liver fibrosis are prevalent and clinically relevant extraintestinal manifestations, so its diagnosis and potential progression to HCC should be carefully considered in daily clinical practice.

9.
Foods ; 12(6)2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36981159

RESUMEN

Phenolic compounds have a positive effect on obesity, diabetes, and cardiovascular diseases because of their antioxidant and anti-inflammatory capacity. The prevalence of these diseases has increased in the last years in the Mexican population. Therefore, the Mexican diet must be assessed as provider of phenolic compounds. To assess this, a survey of phenolic compound intake was validated and applicated to 973 adults (798 females) between 18 and 79 years old. We compared the phenolic compound intake of 324 participants with more diseases (239 females) and 649 participants with healthier condition (559 females). The groups differed in sex, age, and scholarship. Males, older participants, and those with lower schooling reported suffering from more diseases. Regarding phenolic compound intake analyses, the participants with healthier conditions displayed a higher phenolic compound intake than the other group in all foods assessed. In addition, the regression model showed that the phenolic compounds intake of Mexican dishes, such as arroz con frijol or enchiladas, positively affected health status, suggesting that this traditional food is beneficial for the participant's health condition. However, the weight effect of PCI was different for each disease. We conclude that, although PCI of Mexican food positively affects health conditions, this effect depends on sex, age, and participants' diseases.

10.
Histol Histopathol ; 38(10): 1079-1097, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36975173

RESUMEN

Solitary fibrous tumor (SFT) is a rare type of mesenchymal lesion with variable clinical presentation in which specific clinicopathologic factors have been related to patient outcome. SFT shares an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging. Although molecular studies provide significant clues, especially in the differential diagnosis with other neoplasms, a thorough hematoxylin and eosin analysis and the integration of phenotypical, clinical, and radiological features remain an essential tool in SFT diagnosis. In this review, we discuss some emerging issues still under debate in SFT.


Asunto(s)
Hemangiopericitoma , Lagartos , Neoplasias Meníngeas , Neoplasias de los Tejidos Blandos , Tumores Fibrosos Solitarios , Humanos , Animales , Tumores Fibrosos Solitarios/diagnóstico , Tumores Fibrosos Solitarios/genética , Tumores Fibrosos Solitarios/patología , Hemangiopericitoma/diagnóstico , Hemangiopericitoma/patología , Medición de Riesgo , Neoplasias de los Tejidos Blandos/diagnóstico , Diagnóstico Diferencial
11.
Diagn Microbiol Infect Dis ; 106(1): 115927, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36966628

RESUMEN

We report the detection of IgG, IgG1, IgG4 and IgE anti-Strongyloides stercoralis as complementary tool for screening in patients with diabetes in hyperendemic areas for strongyloidiasis. A panel of 119 serum samples were analyzed: 76 from patients with DM2 and 43 patients with other endocrine diseases and a positive correlation for total IgG levels with IgG4 (rs = 0.559; P = 0.024; n = 16) and IgG and IgE (rs = 0.585; P < 0.0001; n = 76) was found in the diabetes group.


Asunto(s)
Diabetes Mellitus , Strongyloides stercoralis , Estrongiloidiasis , Animales , Humanos , Inmunoglobulina G , Anticuerpos Antihelmínticos , Ensayo de Inmunoadsorción Enzimática , Estrongiloidiasis/diagnóstico , Estrongiloidiasis/epidemiología , Inmunoglobulina E
12.
Am J Clin Pathol ; 160(1): 18-34, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-36893014

RESUMEN

OBJECTIVES: We explored features of the angiosarcoma (AS) tumor microenvironment to discover subtypes that may respond to immunotherapy. METHODS: Thirty-two ASs were included. Tumors were studied by histology, immunohistochemistry (IHC), and gene expression profile using the HTG EdgeSeq Precision Immuno-Oncology Assay. RESULTS: Comparing cutaneous and noncutaneous ASs, the second group showed 155 deregulated genes, and unsupervised hierarchical clustering (UHC) delineated two groups: the first mostly cutaneous AS and the second mainly noncutaneous AS. Cutaneous ASs showed a significantly higher proportion of T cells, natural killer cells, and naive B cells. ASs without MYC amplification revealed a higher immunoscore in comparison with ASs with MYC amplification. PD-L1 was significantly overexpressed in ASs without MYC amplification. UHC showed 135 deregulated genes differentially expressed when comparing ASs from the non-head and neck area with patients who had AS in the head and neck area. ASs from the head and neck area showed high immunoscore. PD1/PD-L1 content was significantly more highly expressed in ASs from the head and neck area. IHC and HTG gene expression profiling revealed a significant correlation between PD1, CD8, and CD20 protein expression but not PD-L1. CONCLUSIONS: Our HTG analyses confirmed a high degree of tumor and microenvironment heterogeneity. Cutaneous ASs, ASs without MYC amplification, and ASs located in the head and neck area seem to be the most immunogenic subtypes in our series.


Asunto(s)
Hemangiosarcoma , Neoplasias Cutáneas , Humanos , Antígeno B7-H1 , Hemangiosarcoma/genética , Pronóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Microambiente Tumoral
13.
Cancers (Basel) ; 15(3)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36765829

RESUMEN

Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.

14.
J Cutan Pathol ; 50(3): 230-237, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36377830

RESUMEN

Merkel cell carcinoma (MCC) is an infrequent, aggressive cutaneous neoplasm, that typically affects the photodamaged skin of elderly individuals, and immunosuppressed patients. Because a subset of MCC is closely related to UV radiation, MCC can develop concurrently with other tumors, most commonly, as a combined tumor with squamous cell carcinoma (SCC). These combined tumors appear to represent a distinct disease process from pure MCC, as they are mostly Merkel cell polyomavirus (MCPyV) negative, and show a more aggressive behavior. We present two additional cases of combined MCC and SCC with nodal metastases, one of which was MCPyV positive. Two different subtypes of MCC have been proposed based on their origin: a true neuroendocrine carcinoma, that is MCPyV positive and has a dermal origin, and a UV-related SCC with neuroendocrine differentiation. This theory could explain why MCC can develop concurrently with SCC, and why these combined cases are generally MCPyV negative. However, it fails to explain the minority of combined MCC and SCC tumors that are MCPyV positive. Because both our patients had a history of chronic UV exposure, we hypothesize that UV radiation probably played a major role in the pathogenesis of these tumors, while MCPyV integration probably acted as an additional trigger.


Asunto(s)
Carcinoma de Células de Merkel , Carcinoma de Células Escamosas , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Neoplasias Cutáneas , Infecciones Tumorales por Virus , Humanos , Anciano , Carcinoma de Células de Merkel/patología , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/patología , Metástasis Linfática , Piel/patología
16.
Polymers (Basel) ; 14(19)2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36236029

RESUMEN

Urothelial tumour of the upper urinary tract is a rare neoplasm, but unfortunately, it has a high recurrence rate. The reduction of these tumour recurrences could be achieved by the intracavitary instillation of adjuvant chemotherapy after nephron-sparing treatment in selected patients, but current instillation methods are ineffective. Therefore, the aim of this in vitro study is to evaluate the cytotoxic capacity of a new instillation technology through a biodegradable ureteral stent/scaffold coated with a silk fibroin matrix for the controlled release of mitomycin C as an anti-cancer drug. Through a comparative study, we assessed, in urothelial carcinoma cells in a human cancer T24 cell culture for 3 and 6 h, the cytotoxic capacity of mitomycin C by viability assay using the CCK-8 test (Cell counting Kit-8). Cell viability studies in the urothelial carcinoma cell line confirm that mitomycin C embedded in the polymeric matrix does not alter its cytotoxic properties and causes a significant decrease in cell viability at 6 h versus in the control groups. These findings have a clear biomedical application and could be of great use to decrease the recurrence rate in patients with upper tract urothelial carcinomas by increasing the dwell time of anti-cancer drugs.

17.
Rev. gastroenterol. Peru ; 42(4)oct. 2022.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1423952

RESUMEN

Presentamos el caso de un varón de 64 años quien, tras un primer episodio de pancreatitis aguda necrotizante, reingresa a los 20 días por cuadro de dolor epigástrico intenso y posteriormente episodio de hemorragia digestiva alta en forma de hematemesis y melenas con inestabilización hemodinámica. Se realiza en ese momento gastroscopia urgente objetivándose probable fistula gastrointestinal en bulbo duodenal con coágulo adherido sin sangrado activo en ese momento por lo que se realiza angio-TC urgente que revela colección peripancreática necrótica con presencia de sangrado activo en su interior, procedente de la arteria pancreatoduodenal. La arteriografía urgente identificó imagen compatible con pseudoaneurisma arterial dependiente de la rama de arteria pancreatoduodenal, que fue embolizada con éxito. Desgraciadamente el paciente falleció en las horas posteriores, como consecuencia de un shock séptico secundario a colección pancreática infectada.


We present the case of a 64-year-old man who, after a first episode of acute pancreatitis, was readmitted 20 days later due to severe epigastric pain and later an episode of upper gastrointestinal bleeding in the form of hematemesis and melena with hemodynamic instability. An urgent gastroscopy was performed at that time, revealing a probable gastrointestinal fistula in the duodenal bulb with an adherent clot without active bleeding at that time, so an urgent CT angiography was performed that revealed a necrotic peripancreatic collection with the presence of active bleeding inside from the pancreatoduodenal artery. Urgent arteriography identified an image compatible with arterial pseudoaneurysm dependent on the pancreaticoduodenal artery branch, which was successfully embolized. Unfortunately, the patient died a few hours later as a result of septic shock secondary to an infected pancreatic collection.

18.
Polymers (Basel) ; 14(15)2022 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-35956574

RESUMEN

A major limitation of the treatment of low-grade upper tract urothelial carcinoma is the difficulty of intracavitary instillation of adjuvant therapy. Therefore, the aim of this in vitro study was to develop and to assess a new design of biodegradable ureteral stent coated with a silk fibroin matrix for the controlled release of mitomycin C as a chemotherapeutic drug. For this purpose, we assessed the coating of a biodegradable ureteral stent, BraidStent®, with silk fibroin and subsequently loaded the polymeric matrix with two formulations of mitomycin to evaluate its degradation rate, the concentration of mitomycin released, and changes in the pH and the weight of the stent. Our results confirm that the silk fibroin matrix is able to coat the biodegradable stent and release mitomycin for between 6 and 12 h in the urinary environment. There was a significant delay in the degradation rate of silk fibroin and mitomycin-coated stents compared to bare biodegradable stents, from 6-7 weeks to 13-14 weeks. The present study has shown the feasibility of using mitomycin C-loaded silk fibroin for the coating of biodegradable urinary stents. The addition of mitomycin C to the coating of silk fibroin biodegradable stents could be an attractive approach for intracavitary instillation in the upper urinary tract.

19.
Polymers (Basel) ; 14(16)2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-36015581

RESUMEN

The insertion of a ureteral stent provides acute care by restoring urine flow and alleviating urinary retention or dysfunction. The problems of encrustation, bacterial colonization and biofilm formation become increasingly important when ureteral stents are left in place for a longer period of time. One way to reduce encrustation and bacterial adherence is to modify the stent surface with a diamond-like carbon coating, in combination with copper doping. The biocompatibilities of the Elastollan® base material and the a-C:H/Cu-mulitilayer coating were tested in synthetic urine. The copper content in bladder tissue was determined by atomic absorption spectroscopy and in blood and in urine by inductively coupled plasma mass spectrometry. Encrustations on the materials were analyzed by scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. A therapeutic window for copper ions of 0.5-1.0 mM was determined to kill bacteria without affecting human urothelial cells. In the rat animal model, it was found that copper release did not reach toxic concentrations in the affecting tissue of the urinary tract or in the blood. The encrustation behavior of the surfaces showed that the roughness of the amorphous carbon layer with the copper doping is probably the causal factor for the higher encrustation.

20.
Polymers (Basel) ; 14(9)2022 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-35566810

RESUMEN

Background: When trying to modify urinary stents, certain pre-clinical steps have to be followed before clinical evaluation in humans. Usually, the process starts as an in silico assessment. The urinary tract is a highly complex, dynamic and variable environment, which makes a computer simulation closely reflecting physiological conditions extremely challenging. Therefore, the pre-clinical evaluation needs to go through further steps of in vitro, ex vivo and in vivo assessments. Methods and materials: Within the European Network of Multidisciplinary Research to Improve Urinary Stents (ENIUS), the authors summarized and evaluated stent assessment models in silico, in vitro, ex vivo and in vivo. The topic and relevant sub-topics were researched in a systematic literature search in Embase, Scope, Web of Science and PubMed. Clinicaltrials.gov was consulted for ongoing trials. Articles were selected systematically according to guidelines with non-relevant, non-complete, and non-English or Spanish language articles excluded. Results: In the first part of this paper, we critically evaluate in vitro stent assessment models used over the last five decades, outlining briefly their strengths and weaknesses. In the second part, we provide a step-by-step guide on what to consider when setting up an ex vivo model for stent evaluation on the example of a biodegradable stent. Lastly, the third part lists and discusses the pros and cons of available animal models for urinary stent evaluation, this being the final step before human trials. Conclusions: We hope that this overview can provide a practical guide and a critical discussion of the experimental pre-clinical evaluation steps needed, which will help interested readers in choosing the right methodology from the start of a stent evaluation process once an in silico assessment has been completed. Only a transparent multidisciplinary approach using the correct methodology will lead to a successful clinical implementation of any new or modified stent.

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