http://hdl.handle.net/10366/3898 2026-04-23T13:58:26Z 2026-04-23T13:58:26Z Velasco Tirado, Virginia Alonso Sardón, Montserrat López Bernús, Amparo Romero-Alegría, Ángela Burguillo Muñoz, Francisco Javier Muro Álvarez, Antonio Carpio Pérez, Adela Muñoz Bellido, Juan Luis Pardo-Lledias, Javier Cordero, Miguel Belhassen García, Moncef http://hdl.handle.net/10366/163276 2025-04-30T19:22:02Z 2018-07-05T00:00:00Z

[EN] Cystic echinococcosis (CE) is a well-known neglected parasitic disease. However, evidence supporting the four current treatment modalities is inadequate, and treatment options remain controversial. The aim of this work is to analyse the available data to answer clinical questions regarding medical treatment of CE. A thorough electronic search of the relevant literature without language restrictions was carried out using PubMed (Medline), Cochrane Central Register of Controlled Trials, BioMed, Database of Abstracts of Reviews of Effects, and Cochrane Plus databases up to February 1, 2017. All descriptive studies reporting an assessment of CE treatment and published in a peer-reviewed journal with available full-text were considered for a qualitative analysis. Randomized controlled trials were included in a quantitative meta-analysis. We used the standard methodological procedures established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We included 33 studies related to the pharmacological treatment of CE in humans. Of these, 22 studies with levels of evidence 2 to 4 were qualitatively analysed, and 11 randomized controlled trials were quantitatively analysed by meta-analysis. Treatment outcomes are better when surgery or PAIR (Puncture, Aspiration, Injection of protoscolicidal agent and Reaspiration) is combined with benzimidazole drugs given pre- and/or post-operation. Albendazole chemotherapy was found to be the primary pharmacological treatment to consider in the medical management of CE. Nevertheless, combined treatment with albendazole plus praziquantel resulted in higher scolicidal and anti-cyst activity and was more likely to result in cure or improvement relative to albendazole alone.

2018-07-05T00:00:00Z Monsalve Arteaga, Lía Carolina Muñoz Bellido, Juan Luis Vieira Lista, María Carmen Vicente Santiago, María Belén Fernández Soto, Pedro Bas, Isabel Leralta, Nuria Ory Manchón, Fernando de Negredo, Ana Isabel Sánchez Seco, María Paz Alonso Sardón, Montserrat Pérez González, Sonia Jiménez Del Bianco, Ana Blanco Peris, Lydia Álamo Sanz, Rufino Hewson, Roger Belhassen García, Moncef Muro Álvarez, Antonio http://hdl.handle.net/10366/163268 2025-04-30T19:22:03Z 2020-03-01T00:00:00Z

[EN] BackgroundCrimean-Congo haemorrhagic fever virus (CCHFV) is considered an emerging or even a probable re-emerging pathogen in southern Europe. Presence of this virus had been reported previously in Spain in 2010.AimWe aimed to evaluate the potential circulation of CCHFV in western Spain with a serosurvey in asymptomatic adults (blood donors).MethodsDuring 2017 and 2018, we conducted a CCHFV serosurvey in randomly selected asymptomatic blood donors from western Spain. Three assays using specific IgG antibodies against CCHFV were performed: the VectoCrimea ELISA test, an in-house ELISA and indirect immunofluorescence (EuroImmun) test with glycoprotein and nucleoprotein.ResultsA total of 516 blood donors participated in this cross-sectional study. The majority of the study participants were male (68.4%), and the mean age was 46.3 years. Most of the participants came from rural areas (86.8%) and 68.6% had contact with animals and 20.9% had animal husbandry practices. One in five participants (109/516, 21.1%) were engaged in at-risk professional activities such as agriculture and shepherding, slaughtering, hunting, veterinary and healthcare work (mainly nursing staff and laboratory technicians). A total of 15.3% of the participants were bitten by ticks in the days or months before the date of sampling. We detected anti-CCHFV IgG antibodies with two diagnostic assays in three of the 516 individuals and with one diagnostic assay in six of the 516 individuals.ConclusionSeroprevalence of CCHFV was between 0.58% and 1.16% in Castile-León, Spain. This is the first study in western Spain that showed circulation of CCHFV in healthy people.

2020-03-01T00:00:00Z Belhassen García, Moncef Pardo Lledías, Javier Pérez Del Villar, Luis Muro Álvarez, Antonio Velasco Tirado, Virginia Blázquez de Castro, Ana María Vicente Santiago, María Belén García García, Inmaculada Muñoz Bellido, Juan Luis Cordero Sánchez, Miguel http://hdl.handle.net/10366/163260 2025-04-30T19:22:04Z 2014-07-01T00:00:00Z

[EN] Immigrants from undeveloped countries are a growing problem in Europe. Spain has become a frequent destination for immigrants (20% of whom are children) because of its geographic location and its historic and cultural links with Africa and Latin America. Eosinophilia is frequent in adult immigrants, travelers and expatriates coming from tropical areas. However, there are few studies that focus on the incidence and causes of tropical eosinophilia and hyper-IgE in immigrant children.We evaluated, prospectively, the prevalence and causes of eosinophilia and hyper-immunoglobulin E (IgE) in 362 immigrant children coming from Sub-Saharan Africa, Northern Africa and Latin America to Salamanca, Spain, between January 2007 and December 2011.Absolute eosinophilia and hyper-IgE were present in 22.9% and 56.8% of the analyzed children, respectively. The most frequent causes of absolute eosinophilia were filariasis (52.6%), strongyloidiasis (46.8%) and schistosomiasis (28.9%). Filariasis (41.9%), strongyloidiasis (29.6%) and schistosomiasis (22.2%) were the most frequent causes of increased levels of IgE. The area under the ROC curve showed similar values between eosinophil count and IgE levels in the diagnosis of helminthiasis (69% [95% confidence interval (CI) 63%-74%] vs 67% [95% CI 60%-72%], P = 0.24). Eosinophilia and hyper-IgE have a high value as biomarkers of helminthiasis in children coming from tropical and subtropical areas.

2014-07-01T00:00:00Z Belhassen-Garcia, Moncef Balboa Arregui, Óscar Calabuig-Muñoz, Eva Carmena, David Esteban Velasco, Maria Del Carmen Fuentes Gago, Marta Gracia Fumado Pérez, Victoria García Alonso, Jesús García López Hortelano, Milagros González Fernández, Luis Miguel Herrero Martínez, Juan María Iglesias Iglesias, Manuel José Jiménez López, Marcelo López-Vélez, Rogelio Muñoz-Bellvis, Luis Muro, Antonio Pardo-Lledías, Javier Peñaranda-Vera, Maria Perteguer-Prieto, Maria Jesús Picado, Albert Quiñones Sampedro, Jose Edecio Rodríguez-Guardado, Azucena Royo Crespo, Íñigo Salvador, Fernando Sánchez-Montalvá, Adrian Torrús Tendero, Diego Velasco Pelayo, Luis http://hdl.handle.net/10366/163254 2025-04-30T19:22:05Z 2020-07-01T00:00:00Z

[EN] The Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Association of Surgeons (AEC), the Spanish Society of Pneumology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Vascular and Interventional Radiology (SERVEI), and the Spanish Society of Paediatric Infectious Diseases (SEIP) considered it pertinent to issue a consensus statement on the management of cystic echinococcosis (CE) to guide healthcare professionals in the care of patients with CE. Specialists from several fields (clinicians, surgeons, radiologists, microbiologists, and parasitologists) identified the most clinically relevant questions and developed this Consensus Statement, evaluating the available evidence-based data to propose a series of recommendations on the management of this disease. This Consensus Statement is accompanied by the corresponding references on which these recommendations are based. Prior to publication, the manuscript was open for comments and suggestions from the members of the SEIMC and the scientific committees and boards of the various societies involved. [ES] La Sociedad Espanola ˜ de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), la Sociedad Espanola ˜ de Medicina Tropical y Salud Internacional (SEMTSI), la Asociación Espanola ˜ de Cirujanos (AEC), la Sociedad Espanola ˜ de Neumología y Cirugía Torácica (SEPAR), la Sociedad Espanola ˜ de Cirugía Torácica (SECT), la Sociedad Espanola ˜ de Radiología Vascular e Intervencionista (SERVEI) y la Sociedad Espanola ˜ de Infectología Pediátrica (SEIP) han considerado pertinente la elaboración de una declaración de consenso sobre el tratamiento de la equinococosis quística (EQ) que sirva de ayuda al personal sanitario en la atención de pacientes con EQ. Varios tipos de profesionales (médicos, cirujanos, radiólogos, microbiólogos y parasitólogos) han seleccionado las preguntas más clínicamente relevantes y han desarrollado esta Declaración de consenso, en la que evalúan los datos basados en la evidencia disponibles para proponer una serie de recomendaciones sobre el tratamiento de esta enfermedad. Esta Declaración de consenso se acompana˜ de la bibliografía correspondiente que fundamenta estas recomendaciones. Antes de su publicación, el manuscrito estuvo abierto a comentarios y sugerencias de los miembros de la SEIMC y de los comités científicos y juntas directivas de las diferentes sociedades implicadas

2020-07-01T00:00:00Z Vicente Santiago, María Belén López Abán, Julio Chaccour, Juliane Hernández-Goenaga, Juan Nicolas, Patricia Fernández Soto, Pedro Muro Álvarez, Antonio Chaccour, Carlos http://hdl.handle.net/10366/163253 2025-04-30T19:22:05Z 2021-02-24T00:00:00Z

Schistosoma mansoni is less susceptible to the antiparasitic drug ivermectin than other helminths. By inhibiting the P-glycoprotein or cytochrome P450 3A in mice host or parasites in a murine model, we aimed at increasing the sensitivity of S. mansoni to the drug and thus preventing infection. We assigned 124 BALB/c mice to no treatment, treatment with ivermectin only or a combination of ivermectin with either cobicistat or elacridar once daily for three days before infecting them with 150 S. mansoni cercariae each. The assignment was done by batches without an explicit randomization code. Toxicity was monitored. At eight weeks post-infection, mice were euthanized. We determined number of eggs in intestine and liver, adult worms in portal and mesenteric veins. Disease was assessed by counting granulomas/cm2 of liver and studying organ weight indices and total weight. IgG levels in serum were also considered. No difference between groups treated with ivermectin only or in combination with cobicistat or elacridar compared with untreated, infected controls. Most mice treated with ivermectin and elacridar suffered severe neurological toxicity. In conclusion, systemic treatment with ivermectin, even in the presence of pharmacological inhibition of P-glycoprotein or cytochrome P450 3A, did not result in effective prophylaxis for S. mansoni infection in an experimental murine model.

2021-02-24T00:00:00Z Lledías, Javier Pardo Galindo Pérez, Inmaculada Velasco Tirado, Virginia Fuentes Pardo, Lucía Muñoz Bellvís, Luis Varela, Gonzalo Cordero Sánchez, Miguel Belhassen García, Moncef http://hdl.handle.net/10366/163245 2025-04-30T19:22:06Z 2010-03-01T00:00:00Z

The clinical and microbiological characteristics of super-infected hydatid cysts are described. In our cohort, 7.3% of 503 patients had a super-infected cyst. Four patients developed severe sepsis, and two of them died. Escherichia coli, viridans group streptococci, and Enterococcus species in liver cysts and Aspergillus fumigatus in lung cysts were the microorganisms most frequent involved.

2010-03-01T00:00:00Z Rodríguez-Garza, Nancy E Gomez-Flores, Ricardo Quintanilla-Licea, Ramiro Elizondo Luévano, Joel Horacio Romo-Sáenz, César I Marín, Miguel Sánchez-Montejo, Javier Muro Álvarez, Antonio Peláez Lamamie de C. Arroyo, Rafael López Abán, Julio http://hdl.handle.net/10366/163244 2025-04-30T19:22:06Z 2024-12-12T00:00:00Z

Parasitic diseases represent a significant global public health concern. Two clinically important parasites of high prevalence rates are Trichinella spiralis and Strongyloides stercoralis. However, the limitations of currently used nematocidal drugs highlight the urgent need for novel treatment approaches. The present study investigated the in vitro nematocidal activity of methanol extracts from Amphipterygium adstringens, Artemisia ludoviciana, Cymbopogon citratus, Heterotheca inuloides, Jatropha dioica, Justicia spicigera, Larrea tridentata, Mimosa tenuiflora, Psacalium decompositum, Ruta chalepensis, Semialarium mexicanum, and Smilax aspera against T. spiralis L1 and S. venezuelensis L3 (model for S. stercoralis). Most of the plants showed antiparasitic activity, but R. chalepensis crude methanol extract showed the most potent nematocidal activity against both parasites, with a mean lethal concentration (LC50) of 28.2 µg/mL and a selectivity index (SI) of 22.4 for T. spiralis and an LC50 of 244.8 µg/mL and SI of 2.58 for S. venezuelensis. This extract was further separated into n-hexane, chloroform, and methanol partitions by continuous Soxhlet extractions. The n-hexane partition demonstrated the strongest activity against both parasites, with an LC50 of 147.6 µg/mL and an SI of 7.77 against T. spiralis and an LC50 of 39.2 µg/mL and an SI of 3.77 against S. venezuelensis. LC-MS/MS analysis identified coumarins as the main chemical class (53%), and chalepin represented this partition's most abundant compound (29.9%). Overall, this study confirmed the antiparasitic potential of medicinal plants commonly used in Mexico. In addition, it highlights the possibility of obtaining bioactive compounds from plants like R. chalepensis, or the other plants evaluated in this study, as novel treatments against parasitic diseases.

2024-12-12T00:00:00Z Belhassen García, Moncef Gomez-Munuera, Mercedes Pardo-Lledías, Javier Velasco Tirado, Virginia Pérez Persona, Ernesto Galindo-Perez, Inmaculada Alvela-Suárez, Lucía Romero Alegría, Ángela Muñoz Bellvís, Luis Cordero Sánchez, Miguel http://hdl.handle.net/10366/163243 2025-04-30T19:22:07Z 2014-05-17T00:00:00Z

Septic thrombophlebitis of the portal vein or its branches, most often secondary to intra-abdominal infection is known as pylephlebitis. The frequency and the prognosis of this complication are unknown. The aim of this study was to determine the global and relative incidence of the most frequent intra-abdominal infections and the real prognosis of this disease. An observational retrospective study was conducted in a tertiary care hospital (University Hospital of Salamanca, Spain) from January 1999 to December 2008. A total of 7796 patients with intra-abdominal infection were evaluated, of whom 13 (0.6%) had been diagnosed with pylephlebitis. Diverticulitis was the most frequent underlying process, followed by biliary infection. Early mortality was 23%. Survivors had no recurrences, but one of them developed portal cavernomatosis. Pylephlebitis is a rare complication of intra-abdominal infection, with a high early mortality, but with a good prognosis for survivors.

2014-05-17T00:00:00Z Belhassen-Garcia, Moncef Velasco-Tirado, Virginia Alvela-Suaréz, Lucía Carpio-Pérez, Adela Lledías, Javier Pardo Novoa, Nuria Iglesias-Gómez, Alicia Cordero-Sánchez, Miguel http://hdl.handle.net/10366/163241 2025-04-30T19:22:07Z 2011-12-01T00:00:00Z

Background: Pulmonary manifestations of Wegener's granulomatosis (WG) are present in 45% of cases at the onset of the disease, and they reach 85% of the patients during its evolution. Pulmonary affection usually starts with unspecific symptoms such as cough, dyspnea, hemoptysis, and pleuritis. Pulmonary nodules are 1 of the most common manifestations. The prevalence of pleural affection is 10 to 20%. However, spontaneous pneumothorax is extremely rare. Although its real incidence is unknown, according to different classic series, it ranges between 3 and 5% of the cases. Objective: To present a new case of spontaneous pneumothorax in a patient suffering WG and a brief review on this subject. Methods: We report our experience in a case of spontaneous pneumothorax due to WG. We also review the literature through a PubMed search between 1960 and 2010, using a broad range of keywords related to WG and spontaneous pneumothorax. Publications were evaluated for the demographic features of patients, manifestations of the disease, and outcome. Results: Despite the large prevalence of the respiratory involvement, spontaneous pneumothorax is extremely rare, with only 21 cases reported in the literature. Conclusion: Pneumothorax is a rare complication in WG cases, without a clear pathogenic mechanism involved.

2011-12-01T00:00:00Z García Bernalt Diego, Juan Fernández Soto, Pedro Crego Vicente, Beatriz Alonso Castrillejo, Sergio Febrer Sendra, Begoña Gómez-Sánchez, A Vicente, B López Abán, Julio Muro Álvarez, Antonio http://hdl.handle.net/10366/163240 2025-04-30T19:22:08Z 2019-10-14T00:00:00Z

Schistosomiasis is one of the most prevalent Neglected Tropical Disease, affecting approximately 250 million people worldwide. Schistosoma mansoni is the most important species causing human intestinal schistosomiasis. Despite significant efforts in recent decades, the global disease burden of schistosomiasis remains extremely high. This could partly be attributed to the absence of accurate diagnostic tools, primarily in endemic areas. Loop-mediated isothermal amplification (LAMP) is increasingly used in molecular diagnostics as a field-friendly alternative to many other complex molecular methods and it has been proposed as an ideal candidate for revolutionizing point-of-care molecular diagnostics. In a previous work, a LAMP-based method to detect S. mansoni DNA (SmMIT-LAMP) was developed by our research group for early diagnosis of active schistosomiasis in an experimental infection murine model. The SmMIT-LAMP has been further successfully evaluated in both human stool and snail samples and, recently, in human urine samples. In this study, we developed an important improvement for SmMIT-LAMP molecular assay, transforming it into a cold maintenance dry format suitable for potentially manufacturing as kit for ready-to-use for schistosomiasis diagnosis. This procedure could be applied to create dry LAMP kits for a laboratory setting and for diagnostic applications for other neglected tropical diseases.

2019-10-14T00:00:00Z Belhassen García, Moncef Romero-Alegria, Angela Velasco Tirado, Virginia Alonso Sardón, Montserrat López Bernús, Amparo Alvela-Suarez, Lucia Pérez del Villar-Moro, Luis Carpio Pérez, Adela Galindo-Perez, Inmaculada Cordero-Sanchez, Miguel Pardo-Lledías, Javier http://hdl.handle.net/10366/163239 2025-04-30T19:22:08Z 2014-03-14T00:00:00Z

[EN] Cystic hydatid disease is still an important health problem in European Mediterranean areas. In spite of being traditionally considered as a "benign" pathology, cystic echinococcosis is an important cause of morbidity in these areas. Nevertheless, there are few analyses of mortality attributed to human hydatidosis. To describe the epidemiology, the mortality rate and the causes of mortality due to E. granulosus infection in an endemic area. A retrospective study followed up over a period of 14 years (1998-2011). Of the 567 patients diagnosed with hydatid disease over the period 1998-2011, eleven deaths directly related to hydatid disease complications were recorded. Ten patients (90.9%) died due to infectious complications and the remaining one (9.1%) died due to mechanical complications after a massive hemoptysis. We registered a case fatality rate of 1.94% and a mortality rate of 3.1 per 100.000 inhabitants. Hydatidosis is still a frequent parasitic disease that causes a considerable mortality. The main causes of mortality in patients with hydatidosis are complications related to the rupture of CE cysts with supurative collangitis. Therefore, an expectant management can be dangerous and it must be only employed in well-selected patients.

2014-03-14T00:00:00Z Hernández Goenaga, Juan López Abán, Julio Blanco‐Gómez, Adrián Vicente Santiago, María Belén Burguillo Muñoz, Francisco Javier Pérez Losada, Jesús Muro Álvarez, Antonio http://hdl.handle.net/10366/163238 2025-04-30T19:22:09Z 2023-09-30T00:00:00Z

[EN] Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal regions involved, a backcross strategy was employed to generate high variation in schistosomiasis susceptibility. This strategy involved crossing the resistant C57BL/6J mouse strain with the susceptible CBA/2J strain. The resulting F1 females (C57BL/6J × CBA/2J) were then backcrossed with CBA/2J males to generate the backcross (BX) cohort. The BX mice exhibited a range of phenotypes, with disease severity varying from mild to severe disease, lacking a fully resistant group. We observed four levels of infection intensity using cluster and principal component analyses and K-means based on parasitological, pathological, and immunological trait measurements. The mice were genotyped with 961 informative SNPs, leading to the identification of 19 new quantitative trait loci (QTL) associated with parasite burden, liver lesions, white blood cell populations, and antibody responses. Two QTLs located on chromosomes 15 and 18 were linked to the number of granulomas, liver lesions, and IgM levels. The corresponding syntenic human regions are located in chromosomes 8 and 18. None of the significant QTLs had been reported previously.

2023-09-30T00:00:00Z Belhassen García, Moncef Pérez del Villar-Moro, Luis Pardo-Lledías, Javier Gutiérrez Zufiaurre, María Nieves Velasco Tirado, Virginia Cordero-Sanchez, Miguel Muñoz Criado, S Muñoz Bellido, Juan Luis Muro Álvarez, Antonio http://hdl.handle.net/10366/163237 2025-04-30T19:22:09Z 2015-04-01T00:00:00Z

We prospectively studied the prevalence of imported transmissible diseases in 373 immigrant children and adolescents coming from Sub-Saharan Africa, North Africa and Latin America to Salamanca, Spain. The most frequent transmissible diseases in this group were latent tuberculosis (12.7%), chronic hepatitis B virus infection (4.2%), hepatitis C virus infection (2.3%), syphilis (1.5%) and human T-lymphotropic virus type 1 or 2 infections (1.4%). A total of 24.2% of patients had serologic profiles suggesting past hepatitis B virus infection. Anti-human immunodeficiency virus antibodies were not detected in any subject. Largely asymptomatic immigrant children show a high prevalence of communicable diseases. Thus, infectious disease screenings are highly advisable in immigrant children coming from low-income countries.

2015-04-01T00:00:00Z Marín, Miguel Sánchez-Montejo, Javier Ramos, Sergio López Abán, Julio Peláez Lamamie de C. Arroyo, Rafael Muro Álvarez, Antonio http://hdl.handle.net/10366/163236 2025-04-30T19:22:10Z 2024-09-19T00:00:00Z

Background: Strongyloidiasis, a parasitic infection, presents a significant public health challenge in tropical regions due to the limited repertoire of effective treatments. The screening of chemical libraries against the therapeutically relevant third-stage larvae (L3) of the model parasite Strongyloides venezuelensis yielded meager success rates. This situation is reminiscent of Gram-negative bacteria, where drug entry is a limiting factor. Methods: Here, we set out to determine whether similar barriers are in place and establish whether structural and property requirements exist for anti-strongyloides drug discovery. We focused on dyes as their uptake and effects on viability can be independently assessed in the multicellular parasite, thus providing a means to study the possibility of similar entry rules. We tested different dyes in in vitro assays on L3s. Results: We found that staining was necessary to reduce parasite viability, with some dyes achieving anti-strongyloides effects at concentrations similar to those of the reference drug, ivermectin (IV). Some dyes also showed activity against female adults at concentrations well below that of ivermectin. Unfortunately, the most potent dye, Methylene Blue, was unable to prevent the infection in a preliminary in vivo mouse model assay, presumably due to fast dye clearance. Structural analysis showed that positive charges facilitated the access of the compounds to the L3 tissue, thus providing a structural tool for the introduction of activity. For female adults, low globularity is additionally required. As a proof of concept, we added a positive charge to an inactive compound of one of our chemical libraries and re-determined the activity. Conclusions: These findings allow us to establish structural rules for parasite entry that could be of interest for future drug screening or drug development campaigns. These rules might also be applicable to other related parasites.

2024-09-19T00:00:00Z Fuentes Martín, Raúl Ayuda Durán, Pilar Hanes, Robert Gallego-Yerga, Laura Wolterinck, Lisanne Enserink, Jorrit M. Álvarez Lozano, Raquel Peláez Lamamie de C. Arroyo, Rafael Fuentes Martín, Raúl Ayuda-Durán, Pilar Álvarez, Raquel Peláez Lamamie de C. Arroyo, Rafael http://hdl.handle.net/10366/160431 2025-04-30T19:22:11Z 2024-01-01T00:00:00Z

[EN]Agents that cause apoptotic cell death by interfering with tubulin dynamics, such as vinblastine and paclitaxel, are an important class of chemotherapeutics. Unfortunately, these compounds are substrates for multidrug resistance (MDR) pumps, allowing cancer cells to gain resistance to these chemotherapeutics. The indolesulfonamide family of tubulin inhibitors are not excluded by MDR pumps and have a promising activity profile, although their high lipophilicity is a pharmacokinetic limitation for their clinical use. Here we present a new family of N-indolyl-3,4,5- trimethoxybenzenesulfonamide derivatives with modifications on the indole system at positions 1 and 3 and on the sulfonamide nitrogen. We synthesized and screened against HeLa cells 34 novel indolic benzenesulfonamides. The most potent derivatives (1.7 – 109 nM) were tested against a broad panel of cancer cell lines, which revealed that substituted benzenesulfonamides analogs had highest potency. Importantly, these compounds were only moderately toxic to nontumorigenic cells, suggesting the presence of a therapeutic index. Consistent with known clinical anti-tubulin agents, these compounds arrested the cell cycle at G2/M phase. Mechanistically, they induced apoptosis via caspase 3/7 activation, which occurred during M arrest. The substituents on the sulfonamide nitrogen appeared to determine different mechanistic results and cell fates. These results suggest that the compounds act differently depending on the bridge substituents, thus making them very interesting as mechanistic probes as well as potential drugs for further development.

2024-01-01T00:00:00Z Niebla-Cárdenas, Alfonssina Bareke, Halin Juanes Velasco, Pablo Landeira-Viñuela, Alicia Hernández García, Ángela Patricia Montalvillo Álvarez, Enrique Góngora Fernández, Rafael Arroyo Anlló, Eva María Puente González, Ana Silvia Méndez Sánchez, Roberto Fuentes García, Manuel http://hdl.handle.net/10366/155017 2025-04-30T19:22:10Z 2023-01-01T00:00:00Z

[EN] Frailty is a complex physiological syndrome associated with adverse ageing and decreased physiological reserves. Frailty leads to cognitive and physical disability and is a significant cause of morbidity, mortality and economic costs. The underlying cause of frailty is multifaceted, including immunosenescence and inflammaging, changes in microbiota and metabolic dysfunction. Currently, salivary biomarkers are used as early predictors for some clinical diseases, contributing to the effective prevention and treatment of diseases, including frailty. Sample collection for salivary analysis is non-invasive and simple, which are paramount factors for testing in the vulnerable frail population. The aim of this review is to describe the current knowledge on the association between frailty and the inflammatory process and discuss methods to identify putative biomarkers in salivary fluids to predict this syndrome. This study describes the relationship between i.-inflammatory process and frailty; ii.-infectious, chronic, skeletal, metabolic and cognitive diseases with inflammation and frailty; iii.-inflammatory biomarkers and salivary fluids. There is a limited number of previous studies focusing on the analysis of inflammatory salivary biomarkers and frailty syndrome; hence, the study of salivary fluids as a source for biomarkers is an open area of research with the potential to address the increasing demands for frailty-associated biomarkers

2023-01-01T00:00:00Z