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The transition period is a critical metabolic phase for dairy ruminants, especially those with high production levels. In spite of this, little is still known about dairy water buffalo. The aim of this study was to evaluate the effect of a commercial feed additive based on diatomaceous earth and hydrolyzed yeasts on health status, milk quality and immune response of buffalo cows during the transition period. Eighty healthy Water buffaloes (Bubalus bubalis) of Italian Mediterranean breed were included in the trial. They were subdivided in two groups: one group received the additive (n = 40) while the control group (n=40) received a placebo. The trial lasted 120 days, from 60 days before calving to 60 days in milk. Blood samples were collected from each buffalo at -60d (60 days from the expected calving), -30 d, 0 d (calving), +15 d, +30 d, and +60 d (respectively, i.e., 15, 30 and 60 days in milking). The biochemical as well as the oxidative profile, and the antioxidant power and enzymatic activity were evaluated in the samples obtained. Moreover, acute phase proteins, reactive proteins and Interleukine plasma levels were determined. Peripheral blood mononuclear cells (PBMC) and monocytes were isolated and viability, reactive oxygen species (ROS) and reactive nitrogen species (RNS) were measured on PMBC and monocytes. The introduction of additives enhanced the total antioxidant capacity and enzyme activity, while no differences were observed in oxidation products throughout the trial. Additionally, it significantly reduced the synthesis of ROS in polymorphonuclear cells, supporting a potential positive response in animals experiencing inflammation. The impact of oxidation on the products was not evident. Despite higher enzyme levels in plasma, this did not necessarily correspond to significantly increased enzymatic activity, but rather indicated a higher potential. From these results, it was evident that the transition period in buffaloes differs notably from what reported in literature for cows, probably due to the absence of common postpartum production diseases in dairy cows and lower metabolic challenges linked to lower milk production in buffaloes. Few parameters exhibited notable changes during the transition period in buffaloes, notably certain antioxidant enzymes, PBMC viability, PBMC ROS production, and Hp levels.
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Background: The necessity of using central venous catheters (CVCs) in hemodialysis, coupled with their associated complications, remains a critical concern in nephrology. This study aims to compare the short-term prognosis of tunneled (T-CVC) and non-tunneled (NT-CVC) CVCs in acute hemodialysis patients, specifically focusing on infection rates, malpositioning, and lumen thrombosis within the first three weeks post-insertion. Methods: A retrospective analysis was conducted on 176 CVCs placed between January and December 2023 at the Policlinico di Modena and the Ospedale Civile di Baggiovara. Patient demographics, CHA2DS2-VASc scores, and comorbid conditions were recorded at the time of catheter placement. Outcomes assessed included catheter-related infections, malpositioning, and lumen thrombosis. Statistical analyses, including Chi-square tests, Fisher's exact tests, and Kaplan-Meier survival analysis, were performed to evaluate differences between T-CVCs and NT-CVCs. Results: The sample comprised 43% females with a mean age of 69.3 years (SD 13.9) and a mean CHADS-VASC score of 3.72 (SD 1.4). Hypertension (90%) was the most prevalent comorbidity. Of the 176 CVCs, 127 were T-CVCs and 49 were NT-CVCs. Infection rates were 3.15% for T-CVCs and 8.16% for NT-CVCs (p = 0.07). Malpositioning occurred in 0.79% of T-CVCs and 4.08% of NT-CVCs (p = 0.47). There was one case of lumen thrombosis in the NT-CVC group. Kaplan-Meier analysis indicated a significant divergence in infection-related catheter survival favoring T-CVCs after ten days (p = 0.034). Conclusions: While non-tunneled CVCs do not significantly alter short-term prognosis compared to tunneled CVCs, the latter show a better infection-related survival rate beyond ten days. Therefore, primary insertion of T-CVCs may be preferable when resources and clinical conditions permit, although NT-CVCs remain a viable option when immediate T-CVC insertion is challenging.
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Chronic kidney disease (CKD) is a significant challenge for pediatric endocrinologists, as children with CKD may present a variety of endocrine complications. Growth failure is common in CKD, and its severity is correlated with the degree of renal insufficiency. Management strategies include addressing reversible comorbidities, optimizing nutrition, and ensuring metabolic control. Kidney replacement therapy, including transplantation, determines a significant improvement in growth. According to a recent Consensus Statement, children with CKD stage 3-or on dialysis older >6 months-are eligible for treatment with recombinant growth hormone (rGH) in the case of persistent growth failure. Treatment with rGH may be considered for those with height between the 3rd and 10th percentile and persistent growth deceleration. In children who received kidney transplantation but continue to experience growth failure, initiation of GH therapy is recommended one year post-transplantation if spontaneous catch-up growth does not occur and steroid-free immunosuppression is not an option. In children with CKD, due to nephropathic cystinosis and persistent growth failure, GH therapy should be considered at all stages of CKD. Potential adverse effects and benefits must be regularly assessed during therapy. Treatment with GH is safe in children with CKD. However, its general efficacy is still controversial. All possible problems with a negative impact on growth should be timely addressed and resolved, whenever possible with a personalized approach to the patient. GH therapy may be useful in promoting catch-up growth in children with residual growth potential. Future research should focus on refining effective therapeutic strategies and establishing consensus guidelines to optimize growth outcomes in this population.
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Background: The primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels. Methods: 68 pediatric patients aged 6-18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited. Depressive profile and parental stress were assessed using Children's Depression Inventory, Second Edition (CDI-2) and Parenting Stress Index-Short Form (PSI-SF). Results: The group with epilepsy showed significantly high depressive symptoms and parental stress compared to controls. The patients with headache in comorbidity experienced more depressive symptoms than those with epilepsy only. Conclusion: Depressive symptoms are more prevalent in patients who have comorbid epilepsy and primary headache; therefore, the neurological/psychological mechanisms underlying this condition should be further investigated. The simultaneous presence of epilepsy, headache and depressive symptoms impacts the quality of life of patients and their parents, increasing parental stress and family management.
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We investigate the therapeutic potential of Aloin A and Aloin B, two natural compounds derived from Aloe vera leaves, focusing on their neuroprotective and anticancer properties. The structural differences between these two epimers suggest that they may exhibit distinct pharmacological properties. Our investigations revealed that both epimers are not stable in aqueous solution and tend to degrade rapidly, with their concentration decreasing by over 50% within approximately 12 h. These results underscore the importance of addressing issues such as the need for encapsulation into effective drug delivery systems to enhance stability. ThT fluorescence experiments showed that neither compound was able to inhibit Aß amyloid aggregation, indicating that other mechanisms may be responsible for their neuroprotective effects. Next, an equimolar mixture of Aloin A and Aloin B demonstrated an ability to inhibit proteasome in tube tests, which is suggestive of potential anticancer properties, in accordance with antiproliferative effects observed in neuroblastoma SH-SY5Y and HeLa cell lines. Higher water stability and increased antiproliferative activity were observed by encapsulation in carbon dot nanoparticles, suggesting a promising potential for further in vivo studies.
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Emodina , Fármacos Neuroprotectores , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Emodina/farmacología , Emodina/análogos & derivados , Emodina/química , Células HeLa , Línea Celular Tumoral , Estabilidad de Medicamentos , Antineoplásicos/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Péptidos beta-Amiloides/metabolismo , Nanopartículas/química , Aloe/química , Complejo de la Endopetidasa Proteasomal/metabolismoRESUMEN
The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.
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Envejecimiento , Mitocondrias Musculares , Músculo Esquelético , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Ratas Wistar , Resveratrol , Sirtuina 1 , Animales , Resveratrol/farmacología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Masculino , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Sirtuina 1/metabolismo , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Ratas , Estilbenos/farmacología , Antioxidantes/farmacología , Peroxirredoxinas/metabolismo , ADN Mitocondrial/metabolismo , Estrés Oxidativo/efectos de los fármacos , Dinaminas/metabolismo , Dinámicas Mitocondriales/efectos de los fármacosRESUMEN
BACKGROUND: Autosomal-dominant spinocerebellar ataxia (ADCA) due to intronic GAA repeat expansion in FGF14 (SCA27B) is a recent, relatively common form of late-onset ataxia. OBJECTIVE: Here, we aimed to: (1) investigate the relative frequency of SCA27B in different clinically defined disease subgroups with late-onset ataxia collected among 16 tertiary Italian centers; (2) characterize phenotype and diagnostic findings of patients with SCA27B; (3) compare the Italian cohort with other cohorts reported in recent studies. METHODS: We screened 396 clinically diagnosed late-onset cerebellar ataxias of unknown cause, subdivided in sporadic cerebellar ataxia, ADCA, and multisystem atrophy cerebellar type. We identified 72 new genetically defined subjects with SCA27B. Then, we analyzed the clinical, neurophysiological, and imaging features of 64 symptomatic cases. RESULTS: In our cohort, the prevalence of SCA27B was 13.4% (53/396) with as high as 38.5% (22/57) in ADCA. The median age of onset of SCA27B patients was 62 years. All symptomatic individuals showed evidence of impaired balance and gait; cerebellar ocular motor signs were also frequent. Episodic manifestations at onset occurred in 31% of patients. Extrapyramidal features (17%) and cognitive impairment (25%) were also reported. Brain magnetic resonance imaging showed cerebellar atrophy in most cases (78%). Pseudo-longitudinal assessments indicated slow progression of ataxia and minimal functional impairment. CONCLUSION: Patients with SCA27B in Italy present as an adult-onset, slowly progressive cerebellar ataxia with predominant axial involvement and frequent cerebellar ocular motor signs. The high consistency of clinical features in SCA27B cohorts in multiple populations paves the way toward large-scale, multicenter studies.
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Progresión de la Enfermedad , Humanos , Persona de Mediana Edad , Italia/epidemiología , Masculino , Femenino , Anciano , Estudios de Cohortes , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/epidemiología , Adulto , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/epidemiología , Ataxia Cerebelosa/diagnóstico por imagen , Ataxia Cerebelosa/fisiopatología , Edad de Inicio , Factores de Crecimiento de Fibroblastos , Degeneraciones EspinocerebelosasRESUMEN
A structure-based drug design approach was focused on incorporating phenyl ring heterocyclic bioisosteres into coumarin derivative 1, previously reported as potent dual AChE-MAO B inhibitor, with the aim of improving drug-like features. Structure-activity relationships highlighted that bioisosteric rings were tolerated by hMAO B enzymatic cleft more than hAChE. Interestingly, linker homologation at the basic nitrogen enabled selectivity to switch from hAChE to hBChE. In the present work, we identified thiophene-based isosteres 7 and 15 as dual AChE-MAO B (IC50 = 261 and 15 nM, respectively) and BChE-MAO B (IC50 = 375 and 20 nM, respectively) inhibitors, respectively. Both 7 and 15 were moderately water-soluble and membrane-permeant agents by passive diffusion (PAMPA-HDM). Moreover, they were able to counteract oxidative damage induced by both H2O2 and 6-OHDA in SH-SY5Y cells and predicted to penetrate into CNS in a cell-based model mimicking blood-brain barrier. Molecular dynamics (MD) simulations shed light on key differences in AChE and BChE recognition processes promoted by the basic chain homologation from 7 to 15.
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Acetilcolinesterasa , Butirilcolinesterasa , Inhibidores de la Colinesterasa , Diseño de Fármacos , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/síntesis química , Humanos , Acetilcolinesterasa/metabolismo , Relación Estructura-Actividad , Butirilcolinesterasa/metabolismo , Estructura Molecular , Relación Dosis-Respuesta a Droga , Simulación de Dinámica Molecular , Cumarinas/química , Cumarinas/farmacología , Cumarinas/síntesis química , Línea Celular TumoralRESUMEN
INTRODUCTION: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation. CONCLUSIONS: This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.
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Ácidos Nucleicos Libres de Células , ADN Mitocondrial , Diálisis Peritoneal , Humanos , Diálisis Peritoneal/efectos adversos , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/sangre , ADN Mitocondrial/genética , Biomarcadores , MicroARNs/genética , ADN Bacteriano/genética , Peritonitis/genética , Peritoneo/metabolismo , Peritoneo/patologíaRESUMEN
Polyphenols, the main antioxidants of diet, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of four polyphenolic compounds on ROS production and on the levels of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of breast cancer. THP-1 differentiated macrophages were activated by LPS and simultaneously treated with different doses of a green tea extract (GTE), resveratrol (RSV), curcumin (CRC) and an olive fruit extract (oliplus). By using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, we found that all of the tested compounds showed antioxidant activity in vitro. In addition, GTE, RSV and CRC were able to counteract ROS production induced by H2O2 in THP-1 cells. As assessed by a zymographic analysis of THP-1 supernatants and by an "in-gel zymography" of a pool of sera from patients with breast cancer, the antioxidant compounds used in this study inhibited both the activity and expression of MMP-2 and MMP-9 through different mechanisms related to their structures and to their ability to scavenge ROS. The results of this study suggest that the used antioxidants could be promising agents for the prevention and complementary treatment of breast cancer and other diseases in which MMPs play a pivotal role.
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Antioxidantes , Neoplasias de la Mama , Macrófagos , Femenino , Humanos , Antioxidantes/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Curcumina/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Resveratrol/farmacología , Células THP-1RESUMEN
Erythrocytes (RBCs) have a highly specialized and organized membrane structure and undergo programmed cell death, known as eryptosis. Our preliminary data show a significant increase in the eryptosis during peritoneal dialysis (PD)-associated peritonitis. The objectives of the present study were assessment of the incrementation of eryptosis in PD patients with peritonitis, evaluation of the relationship between systemic eryptosis in peritonitis and specific peritonitis biomarkers in PD effluent (PDE), and confirmation of the induction of eryptosis by peritonitis in a vitro setting. We enrolled 22 PD patients with peritonitis and 17 healthy subjects (control group, CTR). For the in vivo study, eryptosis was measured in freshly isolated RBCs. For the in vitro study, healthy RBCs were exposed to the plasma of 22 PD patients with peritonitis and the plasma of the CTR group for 2, 4, and 24 h. Eryptosis was evaluated by flow cytometric analyses in vivo and in vitro. PDE samples were collected for biomarkers analysis.The percentage of eryptotic RBCs was significantly higher in PD patients with peritonitis than in CTR (PD patients with peritonitis: 7.7; IQR 4.3-14.2, versus CTR: 0.8; IQR 0.7-1.3; p < 0.001). We confirmed these in vivo results by in vitro experiments: healthy RBCs incubated with plasma from PD patients with peritonitis demonstrated a significant increase in eryptosis compared to healthy RBCs exposed to plasma from the control group at all times. Furthermore, significant positive correlations were observed between eryptosis level and all analyzed peritoneal biomarkers of peritonitis. We investigated a potential connection between systemic eryptosis and peritoneal biomarkers of peritonitis. Up-regulation of inflammatory markers could explain the increased rate of systemic eryptosis during PD-related peritonitis.
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Biomarcadores , Eriptosis , Eritrocitos , Diálisis Peritoneal , Peritonitis , Humanos , Peritonitis/metabolismo , Peritonitis/etiología , Peritonitis/patología , Masculino , Femenino , Diálisis Peritoneal/efectos adversos , Persona de Mediana Edad , Eritrocitos/metabolismo , Biomarcadores/sangre , Anciano , Adulto , Inflamación/metabolismo , Inflamación/patología , Inflamación/etiología , Estudios de Casos y ControlesRESUMEN
Background: Patients with end-stage kidney disease (ESKD) have altered immunity. Patients on hemodialysis (HD) present a coexistence of immunodeficiency and activation of the immune system. We evaluated the immunophenotypic profile induced by the medium cut-off of Theranova filter during a single HD session in the same individual. Methods: This pilot observational study explored 11 patients (75 ± 8 years and 73% male). Blood samples were collected prior to (predialytic, PRE) and after 4 h (postdialytic, POST) standard HD session with a medium cut-off, polyarylethersulfone and polyvinylpyrrolidone blend, BPA-free membrane. We performed an immunophenotyping characterization by using flow cytometry. We evaluated eryptosis RBCs and HLA-DR expression on monocytes and Treg cells. Results: The percentages of eryptosis in lymphocytes (CD3+), lymphocyte T helper (CD3+ and CD4+) cells, and monocytes (CD45+ and CD14+) were similar pre- and post-HD. On the contrary, HLA-DR expression and Treg cell numbers significantly decreased after HD. Conclusions: Many studies have focused on the comparison between healthy volunteers and HD patients, but very few have focused on the changes that occur after an HD session in the same individual. With this pilot observational study, we have revealed an immunomodulation driven by HD treatment with Theranova filter. Our preliminary results can be considered to be a hypothesis, generating and stimulating further studies with better designs and larger populations.
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Adjuvant endocrine therapy (ET) represents the standard of care for almost all hormone receptor (HR)+/HER2- breast cancers, and different agents and durations are currently available. In this context, the tailoring and optimization of adjuvant endocrine treatment by reducing unnecessary toxic treatment while taking into account the biological heterogeneity of HR+/HER2- breast cancer represents a clinical priority. There is therefore a significant need for the integration of biological biomarkers in the choice of adjuvant ET beyond currently used clinicopathological characteristics. Several gene expression assays have been developed to identify patients with HR+/HER2- breast cancer who will not derive benefit from the addition of adjuvant chemotherapy. By enhancing risk stratification and predicting therapeutic response, genomic assays have also shown to be a promising tool for optimizing endocrine treatment decisions. In this study, we review evidence supporting the use of most common commercially available gene expression assays [Oncotype DX, MammaPrint, Breast Cancer Index (BCI), Prosigna, and EndoPredict] in tailoring adjuvant ET. Available data on the use of genomic tests to inform extended adjuvant treatment choice based on the risk of late relapse and on the estimated benefit of a prolonged ET are discussed. Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low-risk patients is reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.
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Antineoplásicos Hormonales , Biomarcadores de Tumor , Neoplasias de la Mama , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Quimioterapia Adyuvante/métodos , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/farmacología , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Medicina de Precisión/métodosRESUMEN
BACKGROUND: Environmental exposures to non-biodegradable and biodegradable plastics are unavoidable. Microplastics (MPs) and nanoplastics (NPs) from the manufacturing of plastics (primary sources) and the degradation of plastic waste (secondary sources) can enter the food chain directly or indirectly and, passing biological barriers, could target both the brain and the gonads. Hence, the worldwide diffusion of environmental plastic contamination (PLASTAMINATION) in daily life may represent a possible and potentially serious risk to human health. OBJECTIVE: This review provides an overview of the effects of non-biodegradable and the more recently introduced biodegradable MPs and NPs on the brain and brain-dependent reproductive functions, summarizing the molecular mechanisms and outcomes on nervous and reproductive organs. Data from in vitro, ex vivo, non-mammalian and mammalian animal models and epidemiological studies have been reviewed and discussed. RESULTS: MPs and NPs from non-biodegradable plastics affect organs, tissues and cells from sensitive systems such as the brain and reproductive organs. Both MPs and NPs induce oxidative stress, chronic inflammation, energy metabolism disorders, mitochondrial dysfunction and cytotoxicity, which in turn are responsible for neuroinflammation, dysregulation of synaptic functions, metabolic dysbiosis, poor gamete quality, and neuronal and reproductive toxicity. In spite of this mechanistic knowledge gained from studies of non-biodegradable plastics, relatively little is known about the adverse effects or molecular mechanisms of MPs and NPs from biodegradable plastics. CONCLUSION: The neurological and reproductive health risks of MPs/NPs exposure warrant serious consideration, and further studies on biodegradable plastics are recommended.
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Reproducción , Humanos , Animales , Reproducción/efectos de los fármacos , Reproducción/fisiología , Sistema Nervioso Central/efectos de los fármacos , Microplásticos/toxicidad , Plásticos/toxicidad , Contaminantes Ambientales/toxicidad , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
In neurodegenerative diseases, using a single molecule that can exert multiple effects to modify the disease may have superior activity over the classical "one molecule-one target" approach. Herein, we describe the discovery of 6-hydroxybenzothiazol-2-carboxamides as highly potent and selective MAO-B inhibitors. Variation of the amide substituent led to several potent compounds having diverse side chains with cyclohexylamide 40 displaying the highest potency towards MAO-B (IC50 = 11 nM). To discover new compounds with extended efficacy against neurotoxic mechanisms in neurodegenerative diseases, MAO-B inhibitors were screened against PHF6, R3 tau, cellular tau and α-synuclein (α-syn) aggregation. We identified the phenethylamide 30 as a multipotent inhibitor of MAO-B (IC50 = 41 nM) and α-syn and tau aggregation. It showed no cytotoxic effects on SH-SY5Y neuroblastoma cells, while also providing neuroprotection against toxicities induced by α-syn and tau. The evaluation of key physicochemical and in vitro-ADME properties revealed a great potential as drug-like small molecules with multitarget neuroprotective activity.
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Neuroblastoma , Enfermedades Neurodegenerativas , Humanos , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/química , Neuroprotección , Monoaminooxidasa/metabolismo , Relación Estructura-ActividadRESUMEN
Polyimides are a polymer class that has been extensively investigated as a membrane material for gas separation owing to its interesting permselective properties in a wide range of operation temperatures and pressures. In order to improve their properties, the addition of different filler types is currently studied. p-tert-Butylcalix[n]arene macrocycles (PTBCs) with different cavity sizes (PTBC4, PTBC6, PTBC8) were used as fillers in a commercial thermoplastic polyimide, with a concentration in the range 1-9 wt%, to develop nanocomposite membranes for gas separation. The selected macrocycles are attractive organic compounds owing to their porous structure and affinity with organic polymers. The nanocomposite membranes were prepared in the form of films in which the polymeric matrix is a continuous phase incorporating the dispersed additives. The preparation was carried out according to a pre-mixing approach in a mutual solvent, and the solution casting was followed by a controlled solvent evaporation. The films were characterized by investigating their miscibility, morphology, thermal and spectral properties. The gas transport through these films was examined as a function of the temperature and also time. The results evidenced that the incorporation of the chosen nanoporous fillers can be exploited to enhance molecular transport, offering additional pathways and promoting rearrangements of the polymeric chains.
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Chronic exposure to manganese (Mn) leads to its accumulation in the central nervous system (CNS) and neurotoxicity with not well-known mechanisms. We investigated the involvement of matrix metalloproteinase (MMP)-2 and -9 in Mn neurotoxicity in an in vivo model of rats treated through an intraperitoneal injection, for 4 weeks, with 50 mg/kg of MnCl2 in the presence or in the absence of 30 mg/kg of resveratrol (RSV). A loss of weight was observed in Mn-treated rats compared with untreated and RSV-treated rats. A progressive recovery of body weight was detected in rats co-treated with Mn and RSV. The analysis of brain homogenates indicated that RSV counteracted the Mn-induced increase in MMP-9 levels and reactive oxygen species production as well as the Mn-induced decrease in superoxide dismutase activity and glutathione content. In conclusion, Mn exposure, resulting in MMP-9 induction with mechanisms related to oxidative stress, represents a risk factor for the development of CNS diseases.
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Fármacos Neuroprotectores , Síndromes de Neurotoxicidad , Resveratrol , Animales , Ratas , Manganeso/toxicidad , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/prevención & control , Estrés Oxidativo , Resveratrol/farmacologíaRESUMEN
AIM: The current study aims to investigate the effect of Executive Functions (EFs) on Health Related Quality of Life (HRQoL) in a cohort of children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to identify possible factors that impact HRQoL specifically related to epilepsy-related variables and EFs skills. MATERIAL AND METHOD: The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) and The Behavior Rating Inventory of Executive Function (BRIEF-2 and BRIEF-P) were completed by the parents of 129 patients with SeLECTS. Demographic variables and epilepsy-related variables were collected. RESULTS: Our sample performed in the average range across all the subscales and summary scores of the PedsQL and performed in the normal range of the BRIEF questionnaire. We observed that a lower functioning in EFs was associated with lower overall HRQoL scores. We explored the relationship between epilepsy characteristics and scores on the PedsQL. We found that the use of antiseizure medications (ASMs), longer duration of the treatment, and a higher seizure frequency were associated with a lower HRQoL. Moreover, we observed that executive dysfunction was a significant predictor of reduced HRQoL. CONCLUSION: Our results suggest the importance of the identification of patients with SeLECTS with a high level of risk for a poor HRQoL. We may now add executive dysfunction to the list of known risk factors for poor HRQoL in children with SeLECTS, along with such factors as seizure frequency, recent seizures, use of ASMs and longer duration of therapy. The early identification of children with SeLECTS at risk of a poor HRQoL could allow the activation of adequate interventions.
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Disfunción Cognitiva , Epilepsia , Niño , Humanos , Función Ejecutiva/fisiología , Calidad de Vida , Epilepsia/tratamiento farmacológico , Convulsiones , Encuestas y CuestionariosRESUMEN
Iodine is a vital microelement and a powerful antiseptic with a rapid and broad spectrum of action. The development of iodophor compounds to improve the solubility and stability of iodine is still challenging. Here, we report the synthesis of a novel cationic ß-cyclodextrin bearing a choline-like pendant (ß-CD-Chol) designed to complex and deliver iodine to bacterial cells. The characterization of ß-CD-Chol and the investigation of the inclusion complex with iodine were performed by NMR spectroscopy, mass spectrometry, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. The functionalization with the positively charged unit conferred improved water-solubility, mucoadhesivity, and iodine complexation efficiency to the ß-CD scaffold. The water-soluble ß-CD-Chol/iodine complex efficiently formed both in solution and by solid-vapor reaction. The solid complex exhibited a significant stability for months. Iodine release from the inclusion complex was satisfactory and the bactericidal activity was proved against a Staphylococcus epidermidis strain. The absence of cytotoxicity tested on human keratinocytes and the improved mucoadhesivity make ß-CD-Chol a promising drug delivery system and an appealing iodophor candidate for iodine-based antisepsis including mucosa disinfection.
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Yodo , beta-Ciclodextrinas , Humanos , Colina , beta-Ciclodextrinas/química , Yodo/farmacología , Yodo/química , Solubilidad , Antibacterianos/farmacología , Yodóforos , Agua/química , Rastreo Diferencial de Calorimetría , 2-Hidroxipropil-beta-Ciclodextrina/químicaRESUMEN
Peritoneal dialysis (PD) is performed as a home-based treatment and in this context, telemedicine has been proven helpful for improving clinicians' surveillance and maintaining PD patients in their home setting. The new e-health devices make remote patient monitoring (RPM) for automated peritoneal dialysis (APD) treatment possible, evaluating the data at the end of every treatment and adapting the prescription at distance if necessary. This paper aims to share a method for improving clinical surveillance and enabling PD patients to receive their treatment at home. In the present case series, we delineate the clinical protocol of the Vicenza PD Center regarding patient characteristics, timing, and the purpose of the APD-RPM. We present the Vicenza PD Center's experience, illustrating its application through three case reports as exemplars. Telemedicine helps to carefully allocate healthcare resources while removing the barriers to accessing care. However, there is a risk of data overload, as some data might not be analyzed because of an increased workload for healthcare professionals. A proactive physician's attitude towards the e-health system has to be supported by clinical instructions and legislative rules. International and national guidelines may suggest which patients should be candidates for RPM, which parameters should be monitored, and with what timing. According to our experience, we suggest that the care team should define a workflow that helps in formulating a correct approach to RPM, adequately utilizing resources. The workflow has to consider the different needs of patients, in order to assure frequent remote control for incident or unstable patients, while prevalent and stable patients can perform their home treatment more independently, helped by periodic and deferred clinical supervision.