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1.
Hum Mol Genet ; 32(15): 2473-2484, 2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37162340

RESUMEN

Growth hormone (GH) binding to GH receptor activates janus kinase 2 (JAK2)-signal transducer and activator of transcription 5b (STAT5b) pathway, which stimulates transcription of insulin-like growth factor-1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3) and insulin-like growth factor acid-labile subunit (IGFALS). Although STAT5B deficiency was established as an autosomal recessive disorder, heterozygous dominant-negative STAT5B variants have been reported in patients with less severe growth deficit and milder immune dysfunction. We developed an in vivo functional assay in zebrafish to characterize the pathogenicity of three human STAT5B variants (p.Ala630Pro, p.Gln474Arg and p.Lys632Asn). Overexpression of human wild-type (WT) STAT5B mRNA and its variants led to a significant reduction of body length together with developmental malformations in zebrafish embryos. Overexpression of p.Ala630Pro, p.Gln474Arg or p.Lys632Asn led to an increased number of embryos with pericardial edema, cyclopia and bent spine compared with WT STAT5B. Although co-injection of WT and p.Gln474Arg and WT and p.Lys632Asn STAT5B mRNA in zebrafish embryos partially or fully rescues the length and the developmental malformations in zebrafish embryos, co-injection of WT and p.Ala630Pro STAT5B mRNA leads to a greater number of embryos with developmental malformations and a reduction in body length of these embryos. These results suggest that these variants could interfere with endogenous stat5.1 signaling through different mechanisms. In situ hybridization of zebrafish embryos overexpressing p.Gln474Arg and p.Lys632Asn STAT5B mRNA shows a reduction in igf1 expression. In conclusion, our study reveals the pathogenicity of the STAT5B variants studied.


Asunto(s)
Factor de Transcripción STAT5 , Pez Cebra , Animales , Humanos , Pez Cebra/genética , Pez Cebra/metabolismo , Factor de Transcripción STAT5/genética , Factor de Transcripción STAT5/metabolismo , Hormona del Crecimiento , Transducción de Señal/genética , ARN Mensajero , Factor I del Crecimiento Similar a la Insulina/genética
2.
Cancer Metastasis Rev ; 42(1): 49-85, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36701089

RESUMEN

Decades of research on oncogene-driven carcinogenesis and gene-expression regulatory networks only started to unveil the complexity of tumour cellular and molecular biology. This knowledge has been successfully implemented in the clinical practice to treat primary tumours. In contrast, much less progress has been made in the development of new therapies against metastasis, which are the main cause of cancer-related deaths. More recently, the role of epigenetic and microenviromental factors has been shown to play a key role in tumour progression. Free radicals are known to communicate the intracellular and extracellular compartments, acting as second messengers and exerting a decisive modulatory effect on tumour cell signalling. Depending on the cellular and molecular context, as well as the intracellular concentration of free radicals and the activation status of the antioxidant system of the cell, the signalling equilibrium can be tilted either towards tumour cell survival and progression or cell death. In this regard, recent advances in tumour cell biology and metastasis indicate that redox signalling is at the base of many cell-intrinsic and microenvironmental mechanisms that control disseminated tumour cell fate and metastasis. In this manuscript, we will review the current knowledge about redox signalling along the different phases of the metastatic cascade, including tumour cell dormancy, making emphasis on metabolism and the establishment of supportive microenvironmental connections, from a redox perspective.


Asunto(s)
Neoplasias , Humanos , Neoplasias/patología , Oxidación-Reducción , Antioxidantes/metabolismo , Oncogenes , Radicales Libres , Metástasis de la Neoplasia
3.
Helicobacter ; 29(2): e13060, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38581134

RESUMEN

BACKGROUND: Treatment of Helicobacter pylori gastric infection is complex and associated with increased rates of therapeutic failure. This research aimed to characterize the H. pylori infection status, strain resistance to antimicrobial agents, and the predominant lesion pattern in the gastroduodenal mucosa of patients with clinical suspicion of refractoriness to first- and second-line treatment who were diagnosed and treated in a health center in Guayaquil, Ecuador. METHODS: A total of 374 patients with upper gastrointestinal symptoms and H. pylori infection were preselected and prescribed one of three triple therapy regimens for primary infection, as judged by the treating physician. Subsequently, 121 patients who returned to the follow-up visit with persistent symptoms after treatment were studied. RESULTS: All patients had H. pylori infection. Histopathological examination diagnosed chronic active gastritis in 91.7% of cases; premalignant lesions were observed in 15.8%. The three triple therapy schemes applied showed suboptimal efficacy (between 47.6% and 77.2%), with the best performance corresponding to the scheme consisting of a proton pump inhibitor + amoxicillin + levofloxacin. Bacterial strains showed very high phenotypic resistance to all five antimicrobials tested: clarithromycin, 82.9%; metronidazole, 69.7%; amoxicillin and levofloxacin, almost 50%; tetracycline, 38.2%. Concurrent resistance to clarithromycin-amoxicillin was 43.4%, to tetracycline-metronidazole 30.3%, to amoxicillin-levofloxacin 27.6%, and to clarithromycin-metronidazole 59.2%. CONCLUSIONS: In vitro testing revealed resistance to all five antibiotics, indicating that H. pylori exhibited resistance phenotypes to these antibiotics. Consequently, the effectiveness of triple treatments may be compromised, and further studies are needed to assess refractoriness in quadruple and concomitant therapies.


Asunto(s)
Antiinfecciosos , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Claritromicina/farmacología , Claritromicina/uso terapéutico , Metronidazol/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Levofloxacino/farmacología , Ecuador , Antibacterianos/farmacología , Amoxicilina/farmacología , Tetraciclina/uso terapéutico , Tetraciclina/farmacología , Quimioterapia Combinada
4.
Scand J Gastroenterol ; 59(3): 260-268, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37933161

RESUMEN

OBJECTIVE: Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. METHODS: Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. RESULTS: A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. CONCLUSIONS: Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.


Asunto(s)
Colitis Ulcerosa , Ustekinumab , Humanos , Ustekinumab/uso terapéutico , Colitis Ulcerosa/cirugía , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Resultado del Tratamiento , Inducción de Remisión , Proteína C-Reactiva
5.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38723766

RESUMEN

AIMS: The aim of the study is to evaluate the clinical and biochemical response of inflammatory bowel disease patients treated with vedolizumab, 16 weeks after transitioning from intravenous (iv) to subcutaneous (sc). METHODS: An observational, prospective, single-center cohort study was performed. Patients with inflammatory bowel disease and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. RESULTS: Forty-three patients were included, 12 of them (27.9%) chose to transition to sc formulation. All included patients remained in remission during follow-up. At week 16 no significant differences were found in terms of calprotectin levels in patients on iv treatment (mean 146.6±SD 45.9) vs. sc (159.26±53.9) (p=0.9). Vedolizumab serum levels at week 16 were higher in the sc group (22,364.3±5141.6) vs. iv (11,425.9±1514.2) (p=0.009). At week 16, 9 (75%) of the patients in the sc group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. Four patients (12.9%) in the iv group and 2 (16.6%) in the sc group presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site. CONCLUSION: In our experience, vedolizumab sc is a convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation.

6.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38710465

RESUMEN

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

7.
Scand J Gastroenterol ; 58(6): 656-663, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36519504

RESUMEN

BACKGROUND: Data regarding bowel preparation in patients with Inflammatory Bowel Disease (IBD) are scarce. AIM: To compare efficacy, safety, and tolerability of low-volume preparations in patients with IBD. METHODS: Single-center, randomized, prescriber, and colonoscopist-blinded clinical trial. IBD outpatients undergoing colonoscopy were randomized 1:1:1 to receive 1 Liter-polyethylene glycol-ascorbate (1L-PEG), 2 Liters-PEG, or sodium picosulfate (SP). The primary endpoint was percentage of quality cleansing assessed via the Boston Bowel Preparation Scale (BBPS ≥6, segments ≥2). Secondary endpoints were total high quality cleansing (BBPS 8 or 9), high-quality segmental BBPS (≥2), and patients' tolerability, symptoms, and satisfaction, assessed by questionnaires. Safety was monitored by adverse event reporting, laboratory evaluation at colonoscopy, and telephonic follow-up. RESULTS: Ninety-two patients were included (33 1L-PEG, 28 2L-PEG, and 31 SP). No significant differences between preparations were observed in quality or high-quality total BBPS or high-quality segmental BBPS. Complete intake of the solution was higher for SP (p = 0.006) and lower for 1L-PEG (p = 0.02) compared to 2L-PEG intake (p = 0.55). Clinically irrelevant hyponatremia was higher in the SP group (p < 0.0001). SP instructions were easier to understand from patient's point of view (p = 0.01). Willingness to retake was higher with SP (p < 0.0001) and less for 1L-PEG (p < 0.0001). No serious adverse events were reported. CONCLUSIONS: We observed no differences in efficacy between low-volume preparations in patients with IBD. Complete intake was higher for SP and lower for 1L-PEG. SP and 2L-PEG instructions were better understood and graded, and SP was more likely to be retaken. Willingness to retake was lower for 1L-PEG. No serious adverse events were reported. SUMMARY: No differences in terms of efficacy were regarded in this clinical trial comparing low-volume preparations for colonoscopy in patients with IBD: however, Sodium Pisoculfate is better tolerated and accepted from patient's point of view. No serious adverse events were reported.


Asunto(s)
Catárticos , Enfermedades Inflamatorias del Intestino , Humanos , Catárticos/efectos adversos , Pacientes Ambulatorios , Polietilenglicoles/efectos adversos , Colonoscopía , Enfermedades Inflamatorias del Intestino/inducido químicamente
8.
J Am Pharm Assoc (2003) ; 63(6): 1706-1714.e3, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37499978

RESUMEN

BACKGROUND: Care access remains a major social determinant of health. Safety net clinics may not be numerically sufficient to meet the health care demand for vulnerable populations. Community pharmacists remain a trusted health care provider and serve as first-line care access points. To date, Georgia care access points by safety net clinics and community pharmacies have not been compared. OBJECTIVES: This study sought to evaluate care access across Georgia. County health outcomes and health factor rankings were compared with mortality prevalence of respiratory disease, diabetes mellitus, kidney disease, and a composite of ambulatory care sensitive conditions emergency department (ER) utilization and hospital discharge. In addition, this study sought to determine whether care access points improve if community pharmacies were to provide primary care services. DESIGN AND OUTCOME MEASURES: Geographic information systems mapping was used to locate safety net clinics and community pharmacies. Care access difference was analyzed using a 2-sample t test and health outcomes and rankings were evaluated using ordinary least square regression analysis. RESULTS: A significant difference in care access points was found between safety net clinics and community pharmacies across the state of Georgia (P < 0.05). Mortality prevalence for respiratory disease (P < 0.01), diabetes mellitus (P < 0.1), kidney disease (P < 0.05), ER utilization (P < 0.01), and hospital discharge (P < 0.01) was lower in counties in the top 50% than the bottom 50% health outcome ranking and health factor ranking. Approximately 95% of counties (n = 151) would experience more than a 50% increase in primary care access points by way of community pharmacies. CONCLUSION: Community pharmacies are well positioned to address primary care disease states, reduce health care resource strain, and decrease preventable health care resource utilization. Leveraging pharmacists to provide primary care services can address care access issues and may improve care quality and reduce preventable hospitalizations and ER utilization in Georgia.


Asunto(s)
Servicios Comunitarios de Farmacia , Diabetes Mellitus , Enfermedades Renales , Farmacias , Humanos , Georgia , Farmacéuticos , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Evaluación de Resultado en la Atención de Salud
9.
Br J Neurosurg ; : 1-5, 2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-38140886

RESUMEN

BACKGROUND: CNS ganglioneuroblastoma in an extremely rare embryonal tumour, specifically in the pediatric population. Bad prognosis is documented due to aggressiveness and absence of protocolized treatment at the moment. CLINICAL DESCRIPTION: We present the case of a 5-year-old boy who presented with sudden loss of consciousness. CT scan was performed showing a large posterior fossa lesion with several intraventricular focal lesions, suggesting metastases, the largest one located inside the III ventricle. The patient underwent a posterior fossa resection of the lesion and a subtotal resection of the III ventricle lesion, with adjuvant chemotherapy. The evolution was poor and the patient finally died 3 months after diagnosis. CONCLUSION: Ganglioneuroblastoma is extremely likely to recur quickly and extensively. There is little knowledge about treatment options but is documented that gross total resection followed by adjuvant radiotherapy and chemotherapy is the best management in these patients.

10.
Rev Esp Enferm Dig ; 115(8): 444-449, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36645081

RESUMEN

BACKGROUND AND AIMS: response to the SARS-CoV-2 vaccine can be altered in patients with immune-mediated diseases, such as inflammatory bowel disease, and in patients under immunosuppressive treatment. The aims of this study were to evaluate the serologic response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease, to analyze the influence of immunosuppressive drugs on response, and to describe any adverse events in this population. METHODS: this was a prospective study that included adult patients with inflammatory bowel disease. Baseline characteristics, concomitant treatments and previous COVID-19 symptoms were collected. Patients underwent serological testing before the first and after the second vaccine dose. RESULTS: a total of 265 patients were consecutively included. Patients received one of the following vaccines: messenger RNA vaccines from Pfizer/BioNTech and Moderna; and adenovirus vaccines from AstraZeneca and Janssen. All adverse events were mild, and the most frequent was injection site pain in 141 (86 %) patients. The seroconversion rate according to the treatment that patients were receiving was: 100 % for those without treatment, 92.5 % for patients treated with mesalazine, 90.3 % for those receiving immunomodulators, 88.9 % for patients with biological monotherapy and 92.5 % for patients on combined treatment. The generation of antibodies according to the vaccine administered was: Pfizer 92.9 %, Moderna 93.3 %, AstraZeneca 98.4 %, and Janssen 12.5 %. CONCLUSION: the antibody response after vaccination against SARS-CoV-2 is high in patients with inflammatory bowel disease. However, patients treated with immunosuppressive or biologic drugs had a lower response. Adverse events were frequent, but not serious.


Asunto(s)
COVID-19 , Enfermedades Inflamatorias del Intestino , Adulto , Humanos , Vacunas contra la COVID-19/efectos adversos , Estudios Prospectivos , COVID-19/prevención & control , SARS-CoV-2 , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inmunosupresores/efectos adversos , Vacunación , Prueba de COVID-19
11.
Environ Monit Assess ; 195(10): 1209, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37707612

RESUMEN

The current cadmium (Cd) regulations in chocolate threaten the cacao supply chain in several Latin American countries. The factors contributing to Cd accumulation in cacao beans have been poorly studied in Central America. The objective of this research was to identify the location of Cd hotspots as well as soil properties and management practices influencing the Cd concentration in cacao beans. A survey was carried out and soil, leaf, and beans were sampled from 150 farms in the three principal cacao-producing regions in Costa Rica. Total soil Cd concentration ranged from <0.1 to 1.05 (average 0.22 mg kg-1) which is typical of uncontaminated soils. Bean Cd concentration ranged from 0.12 to 3.23 (average 0.56 mg kg-1) and 22% of the samples exceeded the selected threshold of 0.80 mg kg-1, located mostly in the Huetar Caribe and Huetar Norte regions. Variability in bean Cd concentration was better explained by total soil Cd and soil organic carbon (SOC) (R2 = 0.62, p < 0.05). In addition, bean Cd concentration was affected by leaf nutrient content and management practices. Leaf Zn and P were positively correlated with bean Cd while K and Mn were negatively correlated (p < 0.05). Farm altitude and orchard age were also negatively correlated with bean Cd. Overall, this study shows that bean Cd contamination does not reach the extent observed in other Latin American countries such as Ecuador, Colombia, or Honduras. Nevertheless, research is needed in hotspot areas to assess the feasibility of potential mitigation strategies, particularly the use of mineral or organic soil amendments, which may allow better for planning in existing plantations or the expansion into new cacao-growing areas in the country.


Asunto(s)
Cacao , Costa Rica , Cadmio , Granjas , Carbono , Suelo , Monitoreo del Ambiente
12.
Semin Cancer Biol ; 73: 86-100, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33434641

RESUMEN

Evidence demonstrates the importance of lipid metabolism and signaling in cancer cell biology. De novo lipogenesis is an important source of lipids for cancer cells, but exogenous lipid uptake remains essential for many cancer cells. Dietary lipids can modify lipids present in tumor microenvironment affecting cancer cell metabolism. Clinical trials have shown that diets rich in polyunsaturated fatty acids (PUFA) can negatively affect tumor growth. However, certain n-6 PUFAs can also contribute to cancer progression. Identifying the molecular mechanisms through which lipids affect cancer progression will provide an opportunity for focused dietary interventions that could translate into the development of personalized diets for cancer control. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. Mitochondria controls ATP generation, redox homeostasis, metabolic signaling, apoptotic pathways and many aspects of autophagy, and it has been recognized to play a key role in cancer. The purpose of this review is to summarize the current evidence linking dietary lipids effects on mitochondrial aspects with consequences for cancer progression and the molecular mechanisms that underlie this association.


Asunto(s)
Grasas de la Dieta , Metabolismo de los Lípidos/fisiología , Mitocondrias/metabolismo , Neoplasias , Animales , Grasas de la Dieta/efectos adversos , Grasas de la Dieta/metabolismo , Progresión de la Enfermedad , Humanos , Neoplasias/metabolismo , Neoplasias/patología
13.
Genet Med ; 24(12): 2516-2525, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36149413

RESUMEN

PURPOSE: Cushing's disease (CD) is often explained by a single somatic sequence change. Germline defects, however, often go unrecognized. We aimed to determine the frequency and associated phenotypes of genetic drivers of CD in a large cohort. METHODS: We studied 245 unrelated patients with CD (139 female, 56.7%), including 230 (93.9%) pediatric and 15 (6.1%) adult patients. Germline exome sequencing was performed in 184 patients; tumor exome sequencing was also done in 27 of them. A total of 43 germline samples and 92 tumor samples underwent Sanger sequencing of specific genes. Rare variants of uncertain significance, likely pathogenic (LP), or pathogenic variants in CD-associated genes, were identified. RESULTS: Germline variants (13 variants of uncertain significance, 8 LP, and 11 pathogenic) were found in 8 of 19 patients (42.1%) with positive family history and in 23 of 226 sporadic patients (10.2%). Somatic variants (1 LP and 7 pathogenic) were found in 20 of 119 tested individuals (16.8%); one of them had a coexistent germline defect. Altogether, variants of interest were identified at the germline level in 12.2% of patients, at the somatic level in 7.8%, and coexisting germline and somatic variants in 0.4%, accounting for one-fifth of the cohort. CONCLUSION: We report an estimate of the contribution of multiple germline and somatic genetic defects underlying CD in a single cohort.


Asunto(s)
Neoplasias , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Femenino , Humanos , Secuenciación del Exoma , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Neoplasias/genética , Fenotipo , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/epidemiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/genética
14.
Bull Math Biol ; 84(9): 100, 2022 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-35951127

RESUMEN

We study single-frequency oscillations and pattern formation in the glycolytic process modeled by a reduction in the well-known Sel'kov's equations (Sel'kov in Eur J Biochem 4:79, 1968), which describe, in the whole cell, the phosphofructokinase enzyme reaction. By using averaging theory, we establish the existence conditions for limit cycles and their limiting average radius in the kinetic reaction equations. We analytically establish conditions on the model parameters for the appearance of unstable nonlinear modes seeding the formation of two-dimensional patterns in the form of classical spots and stripes. We also establish the existence of a Hopf bifurcation, which characterizes the reaction dynamics, producing glycolytic rotating spiral waves. We numerically establish parameter regions for the existence of these spiral waves and address their linear stability. We show that as the model tends toward a suppression of the relative source rate, the spiral wave solution loses stability. All our findings are validated by full numerical simulations of the model equations. Finally, we discuss in vitro evidence of spatiotemporal activity patterns found in glycolytic experiments, and propose plausible biological implications of our model results.


Asunto(s)
Conceptos Matemáticos , Modelos Biológicos , Glucólisis , Cinética
15.
Rev Invest Clin ; 74(5): 244-257, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36328029

RESUMEN

Abstract: Cushing's disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. For this purpose, multiple clinical, biochemical, imaging, histopathological, molecular, and genetic features have been evaluated over the years. Only a handful of them, however, have been sufficiently validated for their application in the routine care of patients with CD. This review summarizes the current status of the established and potential biomarkers of CD, bases for their use, proposed and/or established utility, as well as advantages and barriers for their implementation in the clinic. (Rev Invest Clin. 2022;74(5):244-57).


Asunto(s)
Adenoma , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Humanos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/terapia , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/etiología , Adenoma/patología , Pronóstico , Biomarcadores
16.
Actas Esp Psiquiatr ; 50(2): 68-91, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35312994

RESUMEN

Armed conflicts (AC) in the world are still active and lead to the growth of violence, with a possible impact on mental health (MH).


Asunto(s)
Conflictos Armados , Salud Mental , Adulto , Conflictos Armados/psicología , Humanos , Violencia/psicología
17.
Semin Cancer Biol ; 60: 28-40, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31400500

RESUMEN

Metastasis is the main cause of cancer-related deaths. Disseminated tumor cells (DTCs), which seed metastasis, can remain undetected in a dormant state for decades after treatment of the primary tumor and their persistence is the main cause of late relapse and death in a substantial proportion of cancer patients. Understanding the mechanisms underlying the survival of dormant DTCs is of utmost importance to develop new therapies that effectively kill DTCs while in a quiescent state, therefore preventing metastatic disease and minimizing the chance of future relapses. Besides key interactions with the local microenvironment, dormant DTCs must integrate survival mechanisms to remain viable for long periods of time. Here, the pro-survival role of autophagy in tumor cell dissemination and dormant DTC maintenance are discussed, as well as the implications of the current knowledge for future research efforts.


Asunto(s)
Autofagia , Susceptibilidad a Enfermedades , Neoplasias/etiología , Neoplasias/metabolismo , Transducción de Señal , Animales , Supervivencia Celular , Progresión de la Enfermedad , Epigénesis Genética , Humanos , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias/patología , Microambiente Tumoral
18.
Dig Dis ; 39(3): 204-210, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32836225

RESUMEN

Bakground and Aim: Predictors of the need for surgery in sticturing Crohn's disease (SCD) are lacking. Bowel ultrasound (US) is a harmless, noninvasive, and inexpensive diagnostic procedure that has proven to be a valuable tool in the management of Crohn's disease (CD). Our aim was to identify ultrasonographic findings in SCD that may associate with a higher risk of surgery, allowing us to make early choices regarding treatment election in this specific group of patients. MATERIALS AND METHODS: This was a retrospective, case-control study. Twenty-four patients diagnosed with SCD between 2013 and 2017 with a past history of stricture-related surgery were included and then matched with 46 non-operated controls. Prior US from patients in both groups were analyzed. US features considered for analysis were as follows: bowel wall thickness, degree of parietal vascularization (measured by Doppler activity), prestenotic dilation, involvement of mesenteric fat, and newly detected concomitant fistulas or abscess. RESULTS: Doppler activity (p < 0.001), enteroenteric fistulas (p = 0.04), enteromesenteric fistulas (p = 0.003), and associated abscess (p = 0.004) were significantly associated with the need for surgery in the short-term period. Multivariate analysis showed strong association of these features with the risk of surgery but failed to reach statistical significance. CONCLUSION: US features may potentially be used as point-of-care tools to aid clinicians in the assessment of the surgical risk in patients with SCD.


Asunto(s)
Abdomen/cirugía , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/cirugía , Fístula/diagnóstico por imagen , Fístula/cirugía , Ultrasonografía Doppler , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo
19.
Alzheimers Dement ; 17(4): 653-664, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33226734

RESUMEN

INTRODUCTION: A growing number of dominantly inherited Alzheimer's disease (DIAD) cases have become known in Latin American (LatAm) in recent years. However, questions regarding mutation distribution and frequency by country remain open. METHODS: A literature review was completed aimed to provide estimates for DIAD pathogenic variants in the LatAm population. The search strategies were established using a combination of standardized terms for DIAD and LatAm. RESULTS: Twenty-four DIAD pathogenic variants have been reported in LatAm countries. Our combined dataset included 3583 individuals at risk; countries with highest DIAD frequencies were Colombia (n = 1905), Puerto Rico (n = 672), and Mexico (n = 463), usually attributable to founder effects. We found relatively few reports with extensive documentation on biomarker profiles and disease progression. DISCUSSION: Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America.


Asunto(s)
Enfermedad de Alzheimer , Genes Dominantes/genética , Heterogeneidad Genética , Predisposición Genética a la Enfermedad , Fenotipo , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Humanos , América Latina/epidemiología , Mutación/genética
20.
Rev Esp Enferm Dig ; 113(4): 246-250, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33207884

RESUMEN

INTRODUCTION: the Rutgeerts score is used to assess post-surgical recurrence of Crohn's disease (CD). The score initially consisted of four grades, with a subsequent sub-classification of grade 2, under which ulcers confined to the anastomosis (i2a) are considered to be of a probable ischemic origin. The aim of this study was to assess whether ulcers confined to the anastomosis appear at the same frequency in patients undergoing surgery for other causes and can therefore be attributed to post-surgical changes. MATERIAL AND METHODS: this was a retrospective cohort study with patients who had undergone colonoscopy as per clinical practice between 2017 and 2018. There were two cohorts, one cohort of patients to assess the post-surgical recurrence of CD and another cohort for follow-up after colorectal cancer (CRC) treated with ileocolonic anastomosis. RESULTS: a total of 185 patients were included; 33 % had undergone surgery for CD and 67 % had undergone surgery for CRC. Fifty-six percent of patients were male. Of the patients in the group with ulcers confined to the anastomosis, 75 % had CD and 25 % had been operated on for CRC; the difference was statistically significant (p < 0.0001). In turn, of the patients operated on for CRC, 95 % had no anastomotic lesions compared to 18 % of patients with CD. These differences reached statistical significance (p < 0.0001). CONCLUSIONS: In our experience, the occurrence of ulcers on the ileocolonic anastomosis is uncommon in patients that have undergone surgery for CRC, in comparison to patients operated on due to CD. It is possible that these alterations in CD cannot therefore be attributed to solely ischemic or post-surgical phenomena.


Asunto(s)
Enfermedad de Crohn , Anastomosis Quirúrgica , Colon/cirugía , Colonoscopía , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/cirugía , Humanos , Íleon/cirugía , Masculino , Recurrencia , Estudios Retrospectivos
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