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1.
Med Care ; 62(6): 404-415, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38728679

RESUMEN

RESEARCH DESIGN: Community-engaged qualitative study using inductive thematic analysis of semistructured interviews. OBJECTIVE: To understand Latine immigrants' recent prenatal care experiences and develop community-informed strategies to mitigate policy-related chilling effects on prenatal care utilization. BACKGROUND: Decreased health care utilization among immigrants due to punitive immigration policies (ie, the "chilling effect") has been well-documented among Latine birthing people both pre and postnatally. PATIENTS AND METHODS: Currently or recently pregnant immigrant Latine people in greater Philadelphia were recruited from an obstetric clinic, 2 pediatric primary care clinics, and 2 community-based organization client pools. Thematic saturation was achieved with 24 people. Participants' pregnancy narratives and their perspectives on how health care providers and systems could make prenatal care feel safer and more comfortable for immigrants. RESULTS: Participants' recommendations for mitigating the chilling effect during the prenatal period included training prenatal health care providers to sensitively initiate discussions about immigrants' rights and reaffirm confidentiality around immigration status. Participants suggested that health care systems should expand sources of information for pregnant immigrants, either by partnering with community organizations to disseminate information or by increasing access to trusted individuals knowledgeable about immigrants' rights to health care. Participants also suggested training non-medical office staff in the use of interpreters. CONCLUSION: Immigrant Latine pregnant and birthing people in greater Philadelphia described ongoing fear and confusion regarding the utilization of prenatal care, as well as experiences of discrimination. Participants' suggestions for mitigating immigration-related chilling effects can be translated into potential policy and programmatic interventions which could be implemented locally and evaluated for broader applicability.


Asunto(s)
Emigrantes e Inmigrantes , Equidad en Salud , Política de Salud , Hispánicos o Latinos , Atención Prenatal , Philadelphia , Humanos , Investigación Cualitativa , Femenino , Embarazo
2.
J Antimicrob Chemother ; 78(7): 1658-1666, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37260299

RESUMEN

BACKGROUND: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). METHODS: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. RESULTS: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen. CONCLUSIONS: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.


Asunto(s)
Infecciones por Escherichia coli , Fosfomicina , Infecciones Urinarias , Humanos , Fosfomicina/efectos adversos , Trometamina/uso terapéutico , Antibacterianos/efectos adversos , Escherichia coli , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Recurrencia
3.
Neuroendocrinology ; 113(7): 705-718, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36716712

RESUMEN

INTRODUCTION: Macroautophagy is a lysosome-mediated degradation process that controls the quality of cytoplasmic components and organelles, with its regulation depending on autophagy-related proteins (Atg) and with Beclin1/Atg6 and microtubule-associated protein light chain 3 (LC3/Atg8) being key players in the mammalian autophagy. As reports on this mechanism in the field of pituitary neuropathology and neuroendocrinology are scarce, our study analyzed the ultrastructural signs of macroautophagy and the expression of Beclin1 and LC3 proteins in human functioning PitNETs and in experimental pituitary tumors. METHODS: A group of humans functioning PitNETs and an experimental lactotroph model in rats of the F344 strain stimulated with estradiol benzoate (BE) were used. Ultrastructural and molecular evidence of the macroautophagic process was evaluated using different techniques. RESULTS: In functioning PitNETs cohort, 60% exhibited evidence of macroautophagy, with a significant difference found for Beclin1 and LC3 between macro- and micro-PitNETs (p < 0.05). In the experimental model, the expression of both Beclin1 and LC3 proteins was immunopositive in normal and tumoral glands when analyzed by immunofluorescence, Western blot, and immunohistochemistry. In the experimental model, protein expression was associated with increased glandular size and weight. CONCLUSIONS: Our study revealed evidence of macroautophagy at the pituitary level and the important role of Beclin1 and LC3 in the progression of functioning PitNETs, implying that this mechanism participate in regulating pituitary cell growth.


Asunto(s)
Macroautofagia , Neoplasias Hipofisarias , Humanos , Ratas , Animales , Beclina-1 , Ratas Endogámicas F344 , Autofagia , Proteínas Asociadas a Microtúbulos/metabolismo , Mamíferos/metabolismo
4.
Int Wound J ; 20(4): 917-924, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36168924

RESUMEN

Sternal surgical wound infection (SSWI) in cardiac surgery is associated with increased morbidity. We investigated the incidence of SSWI, the main germs implicated and predictors of SSWI. Prospective study including patients undergoing full median sternotomy between January 2017 and December 2019. Patients were followed-up for 3 months after hospital discharge. All sternal wound infections up to 90 days after discharge were considered SSWI. 1004 patients were included. During follow-up, 68 (6.8%) patients presented SSWI. Patients with SSWI had a higher incidence of postoperative renal failure (29.4% vs 17.1%, P = .007), a higher incidence of early postoperative reoperation for non-infectious causes (42.6% vs 9.1%, P < .001), longer ICU stay (3 [2-9] days vs 2 [2-4] days, P = .006), and longer hospital stay (24.5 [14.8-38.3] days vs 10 [7-18] days, P < .001). Gram-positive germs were presented in 49% of the cultures, and gram-negative bacteria in 35%. Early reoperation for non-infectious causes (OR 4.90, 95% CI 1.03-23.7), and a longer ICU stay (OR 1.37 95% CI 1.10-1.72) were independent predictors of SSWI. SSWI is rare but leads to more postoperative complications. The need for early reoperation because of non-infectious cause and a longer ICU stay were independently associated with SSWI.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/microbiología , Estudios Prospectivos , Incidencia , Factores de Riesgo , Estudios Retrospectivos , Procedimientos Quirúrgicos Cardíacos/efectos adversos
5.
J Trauma Dissociation ; : 1-13, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36050931

RESUMEN

Schizotypal personality pathology (SZP) is a persistent and debilitating problem for a substantial number of people. Research on SZP has typically emphasized its biological and more specifically genetic origins. However, recent research has highlighted the potential influence of trauma on SZP. This research is promising, although it has thus far focused primarily on type of trauma (e.g., different types of abuse vs. neglect in childhood) rather than who perpetrated the trauma. Previous studies on both personality pathology in general and psychotic-spectrum experiences characteristic of SZP in particular have highlighted the influence of trauma perpetrated by someone with whom the trauma survivor was close (i.e., betrayal trauma), although this has not yet been examined with respect to SZP specifically. In this study we examined this, evaluating the influence of trauma with varying degrees of betrayal on SZP in a sample of adults (N = 364) using structural equation modeling. Results suggest that interpersonal trauma in general was associated with higher levels of SZP. Findings further indicate that for women but not men, trauma with a high degree of betrayal was uniquely associated with SZP. These results underscore the potential role of trauma in SZP and have implications for future research on and intervention with people with high levels of SZP.

6.
J Cell Physiol ; 236(10): 6974-6987, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33682941

RESUMEN

Octreotide (OCT) is used to inhibit hormone secretion and growth in somatotroph tumors, although a significant percentage of patients are resistant. It has also been tested in nonfunctioning (NF) tumors but with poor results, with these outcomes having been associated with SSTR2 levels and impaired signaling. We investigated whether OCT inhibitory effects can be improved by TGF-ß1 in functioning and nonfunctioning somatotroph tumor cells. OCT effects on hormone secretion and proliferation were analyzed in the presence of TGF-ß1 in WT and SSTR2-overexpressing secreting GH3 and silent somatotroph tumor cells. The mechanism underlying these effects was assessed by studying SSTR and TGFßR signaling pathways mediators. In addition, we analyzed the effects of OCT/TGF-ß1 treatment on tumor growth and cell proliferation in vivo. The inhibitory effects of OCT on GH- and PRL-secretion and proliferation were improved in the presence of TGF-ß1, as well as by SSTR2 overexpression. The OCT/TGF-ß1 treatment induced downregulation of pERK1/2 and pAkt, upregulation of pSmad3, and inhibition of cyclin D1. In vivo experiments showed that OCT in the presence of TGF-ß1 blocked tumor volume growth, decreased cell proliferation, and increased tumor necrosis. These results indicate that SSTR2 levels and the stimulation of TGF-ß1/TGFßR/Smad2/3 pathway are important for strengthening the antiproliferative and antisecretory effects of OCT.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Proliferación Celular/efectos de los fármacos , Octreótido/farmacología , Neoplasias Hipofisarias/tratamiento farmacológico , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Somatotrofos/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacología , Animales , Línea Celular , Femenino , Humanos , Ratones Desnudos , Fosforilación , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Ratas , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Transducción de Señal , Somatotrofos/metabolismo , Somatotrofos/patología , Carga Tumoral/efectos de los fármacos
7.
Eur J Orthop Surg Traumatol ; 31(7): 1375-1386, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33555442

RESUMEN

INTRODUCTION: Although bone transport is generally accepted as the gold standard for the treatment of segmental septic bone defects, some aspects of its practical application are still open to debate. We present our results in this field and compare them with the series published so far. MATERIAL AND METHODS: We reviewed all our patients (2010-2018) that underwent a bone transport procedure in the lower limb due to a septic bone defect. We calculated the bone healing index (BHI), the external fixation index (EFI), the rate of complications and the clinical results. We statistically compared our results with 63 publications with a similar scope. RESULTS: Thirty-five patients (30 M/5F) with a mean age of 40 years and a mean follow-up of 45 months were included. Bone segment was 24 T/11F and mean defect was 8.4 cm (7.34 T/ 10.73F). Mean global BHI was 45.62 days/cm (48.16 T/40.09F). Mean EFI was 2.37 months/cm. Results were excellent in 9 patients, good in 23 and bad in 3. Bone graft was used in 60% of the cases. DISCUSSION: The size of our series is similar to previously published ones, although the mean age of our patients is higher and they present a larger bone defect. BHI of our series is similar to that of other series, although EFI is significantly higher. The number of complications is also in line with the existing literature. CONCLUSION: The use of a two-stage technique for managing segmental bone defects of septic origin in the lower extremity is a valid alternative. Our series shows results comparable to the current literature.


Asunto(s)
Osteogénesis por Distracción , Fracturas de la Tibia , Adulto , Trasplante Óseo , Fijadores Externos , Fijación de Fractura , Humanos , Extremidad Inferior , Estudios Retrospectivos , Resultado del Tratamiento
8.
J Cell Physiol ; 233(2): 1402-1413, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28542730

RESUMEN

In this study, we focused on ERß regulation in the adenohypophysis under different estrogenic milieu, by analyzing whether ER modulates the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression and its subcellular localization on anterior pituitary glands from Wistar rats and GH3 lactosomatotroph cells that over-expressed ERß. ERß was regulated in a cyclic manner, and underwent dynamic changes throughout the estrous cycle, with decreased ERß+ cells in estrus and under E2 treatment, but increased in ovariectomized rats. In addition, the ERα/ß ratio increased in estrus and under E2 stimulation, but decreased in ovariectomized rats. Double immunofluorescence revealed that lactotroph and somatotroph ERß+ were significantly decreased in estrus. Also, variations in the PTEN expression was observed, which was diminished with high E2 conditions but augmented with low E2 milieu. The subcellular localization of this phosphatase was cell cycle-dependent, with remarkable changes in the immunostaining pattern: nuclear in arrested pituitary cells but cytoplasmic in stimulated cells, and responding differently to ER agonists, with only DPN being able to increase PTEN expression and retaining it in the nucleus. Finally, ERß over-expression increased PTEN with a noticeable subcellular redistribution, and with a significant nuclear signal increase in correlation with an increase of cells in G0/G1 phase. These results showed that E2 is able to inhibit ERß expression and suggests that the tumoral suppressor PTEN might be one of the signaling proteins by which E2, through ERß, acts to modulate pituitary cell proliferation, thereby adapting endocrine populations in relation with hormonal necessities.


Asunto(s)
Proliferación Celular , Receptor beta de Estrógeno/metabolismo , Ciclo Estral/metabolismo , Lactotrofos/enzimología , Fosfohidrolasa PTEN/metabolismo , Somatotrofos/enzimología , Animales , Células Cultivadas , Estradiol/metabolismo , Estradiol/farmacología , Receptor beta de Estrógeno/agonistas , Receptor beta de Estrógeno/genética , Terapia de Reemplazo de Estrógeno , Femenino , Fase G1 , Lactotrofos/efectos de los fármacos , Masculino , Nitrilos/farmacología , Ovariectomía , Ratas Wistar , Transducción de Señal , Somatotrofos/efectos de los fármacos , Transfección
9.
J Antimicrob Chemother ; 72(3): 906-913, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28062685

RESUMEN

Background: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. Methods: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC. Results: The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC. Conclusions: We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality.


Asunto(s)
Bacteriemia/mortalidad , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/mortalidad , Enterobacteriaceae/enzimología , beta-Lactamasas/biosíntesis , Anciano , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Femenino , Humanos , Klebsiella/enzimología , Klebsiella/aislamiento & purificación , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Sepsis/tratamiento farmacológico
10.
Planta Med ; 83(10): 877-883, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28264204

RESUMEN

The medicinal applications of curcumin, the major component of Curcuma longa, are limited by its poor solubility and low oral bioavailability. In order to overcome this limitation, a method to produce nanocapsules of chitosan loaded with curcumin was developed. Three different molecular weight and deacetylation degree chitosan polymers were used in the formulation in order to prepare curcumin-loaded nanocapsules (mass ratio 1 : 1.4). The best results were achieved using chitosan-Bi with a molecular weight of 710 000 Da. A bimodal distribution was observed in samples; moreover, chitosan-Bi produced the lowest particle size (197 nm). The entrapment efficacy of all chitosan nanocapsules produced reached values between 75 and 92 %. Their rate of drug release at different pH levels (2.0 and 7.4) showed a fast onset of curcumin release. Swiss mice were used to determine oral and total bioavailability of the new curcumin-loaded nanocapsules. Remarkably, the bioavailability of curcumin nanoformulated increased 9-fold compared with no formulated curcumin. These nanocapsules have the ability to cross the blood-brain barrier, and its production is an easy to scale-up procedure using nontoxic materials.


Asunto(s)
Quitosano , Curcumina/administración & dosificación , Nanocápsulas , Animales , Curcumina/química , Liberación de Fármacos , Masculino , Ratones , Nanocápsulas/química
11.
Am J Physiol Endocrinol Metab ; 311(2): E367-79, 2016 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-27302752

RESUMEN

Extensive evidence has revealed variations in the number of hormone-producing cells in the pituitary gland, which occur under physiological conditions such as gestation and lactancy. It has been proposed that new hormone-producing cells differentiate from stem cells. However, exactly how and when this takes place is not clear. In this work, we used immunoelectron microscopy to identify adult pituitary stem/progenitor cells (SC/P) localized in the marginal zone (MZ), and additionally, we detected GFRa2-, Sox2-, and Sox9-positive cells in the adenoparenchyma (AP) by fluorescence microscopy. Then, we evaluated fluctuations of SC/P mRNA and protein level markers in MZ and AP during gestation and lactancy. An upregulation in stemness markers was shown at term of gestation (AT) in MZ, whereas there were more progenitor cell markers in the middle of gestation and active lactancy. Concerning committed cell markers, we detected a rise in AP at beginning of lactancy (d1L). We performed a BrdU uptake analysis in MZ and AP cells. The highest level of BrdU uptake was observed in MZ AT cells, whereas in AP this was detected in d1L, followed by a decrease in both the MZ and AP. Finally, we detected double immunostaining for BrdU-GFRa2 in MZ AT cells and BrdU-Sox9 in the AP d1L cells. Taken together, we hypothesize that the expansion of the SC/P niche took place mainly in MZ from pituitary rats in AT and d1L. These results suggest that the SC niche actively participates in pituitary plasticity during these reproductive states, contributing to the origin of hormone cell populations.


Asunto(s)
Células Madre Adultas/citología , Lactancia/metabolismo , Hipófisis/citología , Preñez/metabolismo , ARN Mensajero/metabolismo , Células Madre Adultas/metabolismo , Células Madre Adultas/ultraestructura , Animales , Plasticidad de la Célula , Femenino , Perfilación de la Expresión Génica , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Proteínas de Homeodominio/genética , Inmunohistoquímica , Captura por Microdisección con Láser , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Hipófisis/metabolismo , Hipófisis/ultraestructura , Embarazo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factor de Transcripción Pit-1/genética
12.
Mol Cell Biochem ; 390(1-2): 1-8, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24623265

RESUMEN

Interest in biochemistry of organoselenium compound has increased in the last decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of diphenyl diselenide (PhSe)2 (5 µmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)2 (5 µmol/kg, subcutaneous administration), MeHg (40 mg/L, in tap water), and MeHg + (PhSe)2. After the treatment (21 days), the animals were killed and the cerebral cortex was analyzed. Electron microscopy indicated an enlarged and fused mitochondria leading to a reduced number of organelles, in the MeHg-exposed mice. Furthermore, cortical creatine kinase activity, a sensitive mitochondrial oxidative stress sensor, was almost abolished by MeHg. Subcutaneous (PhSe)2 co-treatment rescued from MeHg-induced mitochondrial alterations. (PhSe)2 also behaved as an enhancer of mitochondrial biogenesis, by increasing cortical mitochondria content in mouse-receiving (PhSe)2 alone. Mechanistically, (PhSe)2 (1 µM; 24 h) would trigger the cytoprotective Nrf-2 pathway for activating target genes, since astroglial cells exposed to the chalcogen showed increased content of hemeoxygenase type 1, a sensitive marker of the activation of this via. Thus, it is proposed that the (PhSe)2-neuroprotective effect might be linked to its mitoprotective activity.


Asunto(s)
Derivados del Benceno/administración & dosificación , Encéfalo/metabolismo , Hemo-Oxigenasa 1/biosíntesis , Mitocondrias/metabolismo , Compuestos de Organoselenio/administración & dosificación , Animales , Encéfalo/patología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Modelos Animales de Enfermedad , Masculino , Intoxicación del Sistema Nervioso por Mercurio/metabolismo , Intoxicación del Sistema Nervioso por Mercurio/patología , Compuestos de Metilmercurio/toxicidad , Ratones , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos
13.
Exp Cell Res ; 319(19): 3020-34, 2013 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23973924

RESUMEN

Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17ß-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17ß-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K-Akt and NF-κB signaling pathways.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Lipopolisacáridos/farmacología , Hipófisis/metabolismo , Neoplasias Hipofisarias/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Células Cultivadas , Hiperplasia/metabolismo , Interleucina-6/metabolismo , Masculino , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Hipófisis/ultraestructura , Neoplasias Hipofisarias/inmunología , Neoplasias Hipofisarias/ultraestructura , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/fisiología
14.
JPRAS Open ; 41: 98-103, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38984325

RESUMEN

One of the risks of distraction osteogenesis-based techniques is the development of vascular complications, such as pseudoaneurysms associated with the osteotomies performed or the fixation elements of the external fixator used in the procedure. Pseudoaneurysm are formed when the tunica adventitia of the artery is injured, resulting in a gradual and persistent blood extravasation into the surrounding tissues that is encapsulated and connected to the arterial lumen. This report describes a rare case of a late-presentation pseudoaneurysm in the anterior tibial artery resulting from a tibial lengthening procedure aimed at addressing a leg length discrepancy in a 57-year-old female with severe peripheral neuropathy resulting from long-standing poorly controlled diabetes mellitus. We describe the diagnostic process, the treatment options and confirm how the shape of the bony callus can be a reliable indicator of this pathology, as has already been described in the literature.

15.
Am J Physiol Endocrinol Metab ; 305(1): E41-9, 2013 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-23651845

RESUMEN

In the present work, we investigated the effect of 17ß-estradiol (E2) and basic fibroblast growth factor 2 (FGF2) on the lactotroph cell-proliferative response and the related membrane-initiated signaling pathway. Anterior pituitary mixed-cell cultures of random, cycling 3-mo-old female rats were treated with 10 nM E2, E2 membrane-impermeable conjugated BSA (E2-BSA), PPT (ERα agonist), and DPN (ERß agonist) alone or combined with FGF2 (10 ng/ml) for 30 min or 4 h. Although our results showed that the uptake of BrdU into the nucleus of lactotrophs was not modified by E2 or FGF2 alone, a significant increase in the lactotroph uptake of BrdU was observed after E2/FGF2 coincubation, with this effect being mimicked by PPT/FGF2. These proliferative effects were blocked by ICI 182,780 or PD-98059. The involvement of membrane ER in the proliferative response of prolactin cells induced by the steroid and FGF2 coincubation was confirmed using E2-BSA, and the association between ERα and FGF receptor was observed after E2/FGF2 treatment by immunoprecipitation. A significant increase in the ERK1/2 expression was noted after E2, E2-BSA, PPT, and FGF2 alone, which was more noticeable after E2-BSA/FGF2, E2/FGF2, or PPT/FGF2 treatments. This study provides evidence that E2 and FGF2 exert a cooperative effect on the lactotroph proliferation principally by signaling initiated at the plasma membrane triggering a genomic effect mediated by MEK/ERK1/2, a common signaling pathway, that finally regulates the lactotroph population, thus contributing to pituitary plasticity.


Asunto(s)
Membrana Celular/metabolismo , Estradiol/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Lactotrofos/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Adenohipófisis/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Estradiol/farmacología , Receptor alfa de Estrógeno/metabolismo , Femenino , Factor 2 de Crecimiento de Fibroblastos/farmacología , Lactotrofos/citología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Adenohipófisis/citología , Cultivo Primario de Células , Ratas , Ratas Wistar
16.
Int J Exp Pathol ; 94(6): 399-411, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23998365

RESUMEN

Bronchiolar Clara cells play a critical role in lung homoeostasis. The main goal of this study was to evaluate the effects of chronic allergy on these cells and the efficacy of budesonide (BUD) and montelukast (MK) in restoring their typical phenotypes after ovalbumin-induced chronic allergy in mice. Chronic allergy induced extensive bronchiolar Alcian blue-periodic acid-Schiff (AB/PAS)-positive metaplasia. In addition, cells accumulated numerous big electron-lucent granules negative for Clara cell main secretory protein (CC16), and consequently, CC16 was significantly reduced in bronchoalveolar lavage. A concomitant reduction in SP-D and CYP2E1 content was observed. The phenotypic changes induced by allergy were pharmacologically reversed by both treatments; MK was more efficient than BUD in doing so. MK decreased AB/PAS reactivity to control levels whereas they remained persistently elevated after BUD. Moreover, most non-ciliated cells recovered their normal morphology after MK, whereas for BUD normal cells coexisted with 'transitional' cells that contained remnant mucous granules and stained strongly for CC16 and SP-D. Glucocorticoids were also less able to reduce inflammatory infiltration and maintained higher percentage of neutrophils, which may have contributed to prolonged mucin expression. These results show that chronic allergy-induced mucous metaplasia of Clara cells affects their defensive mechanisms. However, anti-inflammatory treatments were able to re-establish the normal phenotype of Clara cell, with MK being more efficient at restoring a normal profile than BUD. This study highlights the role of epithelial cells in lung injuries and their contribution to anti-inflammatory therapies.


Asunto(s)
Acetatos/uso terapéutico , Asma/tratamiento farmacológico , Asma/patología , Bronquios/patología , Budesonida/uso terapéutico , Fenotipo , Quinolinas/uso terapéutico , Acetatos/farmacología , Animales , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Asma/inducido químicamente , Bronquios/efectos de los fármacos , Bronquios/metabolismo , Budesonida/farmacología , Enfermedad Crónica , Ciclopropanos , Citocromo P-450 CYP2E1/metabolismo , Modelos Animales de Enfermedad , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Epitelio/patología , Femenino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/efectos adversos , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Quinolinas/farmacología , Sulfuros , Uteroglobina/metabolismo
17.
Scand J Infect Dis ; 45(7): 567-9, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23270475

RESUMEN

Leishmaniasis is endemic in the Mediterranean region, and the prevalence of latent infection in this area is high. Treatment with tumour necrosis factor (TNF) antagonists represents a major breakthrough in the treatment of several inflammatory diseases, including psoriasis. Reports describing opportunistic leishmaniasis in European patients treated with TNF-α antagonist drugs are rapidly accumulating. We describe a case of cutaneous leishmaniasis in a patient treated with infliximab and corticosteroids.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inmunosupresores/uso terapéutico , Leishmaniasis Cutánea/diagnóstico , Anticuerpos Monoclonales/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Infliximab , Leishmaniasis Cutánea/patología , Masculino , Región Mediterránea , Persona de Mediana Edad , Esteroides/efectos adversos , Esteroides/uso terapéutico
18.
Scand J Infect Dis ; 45(9): 664-71, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23808723

RESUMEN

BACKGROUND: Coagulase-negative staphylococci (CoNS) are common contaminants in blood cultures (BC). A prospective study of patients with ≥ 2 blood culture sets and at least 1 positive CoNS BC was performed to develop an algorithm to assist in determining the clinical significance of CoNS bacteraemia. METHODS: A single reviewer examined the medical records of patients with CoNS bacteraemia (January-June 2010). The determination of clinical significance was made according to CDC/NHSN (US Centers for Disease Control and Prevention/National Healthcare Safety Network) criteria. To explore risk factors associated with clinical significance, a multivariate analysis was performed. The performances of various algorithms were then compared. An algorithm to assist in determining clinical significance was developed. RESULTS: Two hundred and sixty-nine cases were included; 97 (36%) were considered clinically significant bacteraemia (CSB). Predictors of CSB in the multivariate analysis were: time to positivity < 16 h (odds ratio (OR) 4.540, 95% confidence interval (CI) 1.734-11.884), identification of Staphylococcus epidermidis (OR 4.273, 95% CI 2.124-5.593), central venous catheter (OR 4.932, 95% CI 2.467-9.858), > 2 CoNS-positive bottles from different BC sets (OR 1.957, 95% CI 1.401-2.733), and Charlson score ≥ 3 (OR 2.102, 95% CI 1.078-4.099). The algorithm with best sensitivity (62%) and specificity (93%) for determining clinical significance of CoNS included Charlson score ≥ 3, Pitt score ≥ 1, neutropenic patients, presence of central venous catheter, identification of S. epidermidis, and time to positivity < 16 h. The positive predictive value was 83% and the negative predictive value was 81% (likelihood ratio 8.87). CONCLUSION: The use of this algorithm could potentially reduce the misclassification of nosocomial bloodstream infections and inappropriate antibiotic treatment in patients for whom a positive CoNS does not represent a CSB.


Asunto(s)
Bacteriemia/microbiología , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/aislamiento & purificación , Algoritmos , Análisis de Varianza , Bacteriemia/sangre , Bacteriemia/epidemiología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , España/epidemiología , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/epidemiología , Staphylococcus epidermidis/enzimología
19.
Scand J Infect Dis ; 45(8): 623-8, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23596976

RESUMEN

OBJECTIVE: To evaluate the influence of a rapid diagnostic test (RDT) in antibiotic therapeutic decisions in non-paediatric patients with Gram-negative bacteraemia (GNB). PATIENTS AND METHODS: A RDT consisting of a direct antibiogram was used on blood isolates of GNB. GNB were also identified and sensitivity tests were performed according to standard criteria. Information on empirical treatment was registered (T1), as well as the antibiotic administered once the results of the RDT were available (T2). Finally, we noted the ideal antibiotic that the infectious diseases specialist (IDS) would have prescribed (T3). The decision regarding T2 was always taken by the patient's physician or the physician on duty. RESULTS: A RDT was performed for 248 patients. The most frequently isolated bacterium was Escherichia coli (13% producing extended-spectrum beta-lactamase). T1 was considered appropriate in 74% and appropriate but optimizable in 43%. T2 was considered appropriate in 95%, appropriate but optimizable in 36%, and inappropriate in 5%. The cost of the optimizable treatment (T2) was € 2210, while the cost of the ideal treatment would have been € 416; the saving in antibiotic cost of 1 day of treatment would have been € 1694. CONCLUSIONS: Treatment prescribed by a non-IDS after a RDT was inappropriate in 5% and optimizable in 36%. It is our recommendation that information provided by a RDT should be interpreted by an IDS to make the information more beneficial both economically and 'ecologically'.


Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Sangre/microbiología , Niño , Femenino , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Adulto Joven
20.
Int J Pharm ; 636: 122790, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-36863542

RESUMEN

This paper describes the development of a coating for cotton and polypropylene (PP) fabrics based on a polymeric matrix embedded with cuprous oxide nanoparticles (Cu2O@SDS NPs) in order to inactivate SARS-CoV-2 and manufactured by a simple process using a dip-assisted layer-by-layer technology, at low curing temperature and without the need for expensive equipment, capable of achieving disinfection rates of up to 99%. The polymeric bilayer coating makes the surface of the fabrics hydrophilic, enabling the transportation of the virus-infected droplets to achieve the rapid inactivation of SARS-CoV-2 by contact with the Cu2O@SDS NPs incorporated in the coated fabrics.


Asunto(s)
COVID-19 , Nanopartículas , Humanos , SARS-CoV-2 , COVID-19/prevención & control , Textiles , Polímeros
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