We investigated the potential role of different proteases in the death of cultured rat hippocampa... more We investigated the potential role of different proteases in the death of cultured rat hippocampal pyra-midal neurons induced by /3-amyloid(A~3)(25—35). Both A/1(25—35)- and staurosporine-induced death of these neurons appeared to involve apoptosis, as indicated us-ing Hoechst 33342 and terminal dUDP nick end labeling staining, whereas NMDA-induced death appeared more complex. Two irreversible inhibitors of the interleukin-1~ converting enzyme (ICE) and related proteases, Z-VaI-AIa-Asp-CH2F and acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone, blocked neuronal death produced by A/9(25—35), staurosporine, and NMDA to differing extents. Further-more, MDL 28,170, a selective inhibitor of the calcium-regulated protease calpain, also inhibited death induced by all agents. A~3(25—35)and staurosporine stimulated
BACKGROUND Our work describes the concept of Breast Aesthetic Scale (BAS) as a score for quick an... more BACKGROUND Our work describes the concept of Breast Aesthetic Scale (BAS) as a score for quick and simple objective assessment of results in cosmetic breast surgery. It is obtained by running a software program that we created, based on the previous concept of Objective Breast Cosmesis Scale (OBCS). This was previously described to be used in the context of conservative breast cancer treatment to objectively assess the degree of asymmetry. We describe the implementation of BAS algorithm and study its reproducibility in a set of images. METHODS A new multiplatform software was developed by us and named Breast Aesthetic Scale Calculator (BAS-Calc), which can be executed on Windows Mac, and Linux. A set of 25 photographs were studied with this software twice by 2 different surgeons. Intrarater and interrater variability were studied, as well as concordance with categorization by another symmetry assessment software available called Breast Analyzing Tool®. RESULTS Concordance among rate...
Pharmacovigilance compiles and analyzes spontaneous adverse drug reactions (ADRs) notifications r... more Pharmacovigilance compiles and analyzes spontaneous adverse drug reactions (ADRs) notifications reports on pharmacovigilance databases. Benzodiazepines have been related to skin and subcutaneous tissue disorders ADRs (SSTD-ADRs); tetrazepam was withdrawn in 2013 because of these ADRs. We intended to locate possible associations between cutaneous ADRs and benzodiazepines marketed in USA; for that, we calculated Data mining algorithms (PRR, ROR, IC and EBGM) on benzodiazepines spontaneous notifications reported to the American pharmacovigilance database. ROR yielded signals for eight drugs; PRR and IC for four, and EBGM only one. Clobazam originated a signal for “Stevens-Johnson syndrome” and “Blister”; midazolam for “Toxic epidermal necrolysis”, “DRESS syndrome” and “Erythema”; quazepam for “Erythema multiform” and “Drug eruption”; and tetrazepam “Dermatitis bullous”, “Toxic skin eruption”, “Rash maculopapular” and “Rash erythematous”. Tetrazepam exhibited signals by all Data mining ...
During the last decade, the neuroprotective effects of minocycline have been a matter of an inten... more During the last decade, the neuroprotective effects of minocycline have been a matter of an intense debate. A broad amount of contradictory studies can be found in the scientific literature, going from neuroprotection to the exacerbation of toxicity in diverse experimental models. Such differences could be the result of minocycline acting on multiple pharmacological targets. In the present review we will go over these pharmacological targets and the effects derived from their modulation by minocycline. Among others, its antioxidant activity derived from its chemical structure or its modulator effect on several enzymes such as nitric oxide synthase will be reviewed. Furthermore, the effects of minocycline on the intracellular pathways implicated in neurodegenerative processes including apoptosis stages, activation decision and execution will be addressed. All the mechanisms described herein have not escaped to a scientific community needed of new therapeutic drugs for the treatment o...
Multiple sclerosis is the most frequent chronic inflammatory, demyelinating and neurodegenerative... more Multiple sclerosis is the most frequent chronic inflammatory, demyelinating and neurodegenerative disease in young adults, but has no definitive pharmacological treatment. It is a heterogeneous disease from the immunological, neuropathological and clinical point of view, as well as in terms of its response to different therapies. Over the last two decades, pharmacology has focused on developing drugs that are capable of modifying the course of this disease, with the aim of reducing the frequency of the outbreaks and the speed at which the disability produced by the disease progresses. Nevertheless, today, there are no drugs that are capable of offering a curative effect that can fully stabilise the disease, and neuroprotective and neuroreparative strategies are still in their early stages. In this work we carry out a critical review of the different pathogenic paths involved in multiple sclerosis and we discuss the different pharmacological approaches that have been followed, based ...
Expert Review of Anti-Infective Therapy, Sep 26, 2020
To know the efficacy of different doses of dalbavancin in acute bacterial skin and skin structure... more To know the efficacy of different doses of dalbavancin in acute bacterial skin and skin structure infections (ABSSSIs) and versus other antibiotics. We performed a systematic review of dalbavancin efficacy for ABSSSIs. We selected 10 clinicals trials from MEDLINE and Cochrane databases for qualitative review. Of these, 5 trials compared one or two doses of dalbavancin versus other antibiotics such as vancomycin or linezolid. Treatment outcomes with other antibiotics were not significantly different versus two doses of dalbavancin (OR 1.13; 95% CI 0.75-1.71; p = 0.55) or single dose dalbavancin (OR 0.98; 95% CI 0.19- 5.17; p = 0.98). One dose versus two doses of dalbavancin did not show significant differences in any of the treatment groups. In contrast, the global microbiological assessment results indicated a favorable outcome for two doses of dalbavancin compared to the single dose of dalbavancin (OR 2.96; 95% CI 1.19-7.39; p= 0.02) in both methicillin-resistant and methicillin-su...
Since patients have easier access to information, thanks to the growing development of technology... more Since patients have easier access to information, thanks to the growing development of technology, their concern about everything related to drugs, especially adverse drug reactions, has increased. Resulting of this, authorities and health agencies are increasingly interested in drug safety and early detection of signals. Quantitative signals detection methods are useful for detecting pharmacovigilance signals, which can be analyzed to establish causality between an adverse event and a drug. Goal of this study was to deepen in signal detection of adverse drug reactions potentially associated to benzodiazepines, through the analysis of spontaneous notifications reported to the United States pharmacovigilance database (FAERS); after a previous work of signals detection of only cutaneous adverse reactions associated to this family of drugs, by applying data mining technique and different algorithms. All this, initially motivated by the market withdrawal of medicines containing tetrazep...
La calidad de vida y la adherencia al tratamiento poseen una gran relevancia en aquellos paciente... more La calidad de vida y la adherencia al tratamiento poseen una gran relevancia en aquellos pacientes que presentan enfermedades crónicas. El objetivo de este trabajo es conocer y evaluar ambos parámetros, en una población de pacientes de enfermedad de Parkinson. Para ello, se ha realizado un estudio transversal, a través de los cuestionarios de PDQ-39 y de Morisky-Green, en 95 pacientes de la citada enfermedad pertenecientes a alguna de las asociaciones de pacientes y familias de la provincia de Albacete. Los datos muestran una puntuación media de 33,47% en el PDQ-39, siendo los dominios de peor puntuación los referidos a movilidad y malestar físico. Por otro lado, un 31,6% de los pacientes se clasificaron como adherentes al tratamiento. Respecto a este parámetro, constatamos que, el factor principal relacionado con una adecuada adherencia, fue la importancia dada a su medicación por el propio paciente. No se ha encontrado ninguna asociación entre adherencia y calidad de vida.
After cerebral ischemia, necrotic cell death occurs specially for neurons, mainly due to the depr... more After cerebral ischemia, necrotic cell death occurs specially for neurons, mainly due to the deprivation of oxygen and glucose. Cell necrosis triggers the activation of the immune system followed by an inflammatory response. This reaction is characterized by the activation of astrocytes and microglia together with the infiltration of peripheral immune cells. Both, microglia and inflammatory cells, including circulating peripheral inflammatory cells, get activated and release a plethora of inflammatory mediators, cytokines, chemokines, etc. Such released factors induce the overexpression of adhesion molecules, increasing the blood brain barrier permeability, thus favoring even more inflammatory cell infiltration. In the end, this contributes to increase brain damage. Inflammatory response is nevertheless necessary in order to eliminate cellular debris from both apoptotic and necrotic cells. It seems to be also implicated in the initiation of certain mechanisms responsible for brain r...
We studied potential changes in the subventricular zone (SVZ) stem cell niche of the senescence-a... more We studied potential changes in the subventricular zone (SVZ) stem cell niche of the senescence-accelerated mouse prone-8 (SAM-P8) aging model. Bromodeoxyuridine (BrdU) assays with longtime survival revealed a lower number of label-retaining stem cells in the SAM-P8 SVZ compared with the SAM-Resistant 1 (SAM-R1) control strain. We also found that in SAM-P8 niche signaling is attenuated and the stem cell pool is less responsive to the self-renewal niche factor pigmented epithelium-derived factor (PEDF). Protein analysis demonstrated stable amounts of the PEDF ligand in the SAM-P8 SVZ niche; however, SAM-P8 stem cells present a significant expression decrease of patatin-like phospholipase domain containing 2, a receptor for PEDF (PNPLA2-PEDF) receptor, but not of laminin receptor (LR), a receptor for PEDF (LR-PEDF) receptor. We observed changes in self-renewal related genes (hairy and enhancer of split 1 (Hes1), hairy and enhancer of split 1 (Hes5), Sox2] and report that although these genes are down-regulated in SAM-P8, differentiation genes (Pax6) are up-regulated and neurogenesis is increased. Finally, sheltering mammalian telomere complexes might be also involved given a down-regulation of telomeric repeat binding factor 1 (Terf1) expression was observed in SAM-P8 at young age periods. Differences between these 2 models, SAM-P8 and SAM-R1 controls, have been previously detected at more advanced ages. We now describe alterations in the PEDF signaling pathway and stem cell self-renewal at a very young age, which could be involved in the premature senescence observed in the SAM-P8 model.-Castro-Garcia, P., Díaz-Moreno, M., Gil-Gas, C., Fernández-Gómez, F. J., Honrubia-Gómez, P., Álvarez-Simón, C. B., Sánchez-Sánchez, F., Cano. J. C. C., Rodríguez, F. A., Blanco. V., Jordán, J. Mira, H., Ramírez-Castillejo, C. Defects in subventricular zone pigmented epithelium-derived factor niche signaling in the senescence-accelerated mouse prone-8.
Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple... more Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. We performed a bibliometric study examining the characteristics and trends of the top 100 cited articles that include dimethyl fumarate in the title. On 21 September 2020 we carried out an electronic search in the Web of Science (WOS), seeking articles that include the following terms within the title: dimethyl fumarate, BG-12, or Tecfidera. To focus our investigation on original research, we refined the search to include only articles, early access, others, case report, and clinical trials. We obtained a total of 1115 items, which were cited 7169 times, had a citation density of 6.43 citations/item, and an h-index of 40. Around 2010, there was a jump in the number of published articles per year, rising from 5 articles/year up to 12 articles/year. We sorted all the items by the number of citations and selected the top 100 most cited (T100). The T100 had 4164 citations, with a...
Background: Citicoline is considered an ingredient in particular foods in the USA and is availabl... more Background: Citicoline is considered an ingredient in particular foods in the USA and is available in pharmaceutical form in Europe and Japan. It has been postulated to render positive effects on the nervous system, either by increasing levels of neurotransmitters, or by affording neuroprotection. Methods: Several clinical trials have shown the efficacy and safety of this biomolecule in several neurodegenerative diseases and in acute ischemic stroke. Here, we have performed a systematic review to validate the effect of citicoline on MMSE, memory, attention, and basic activity of daily living. In electronic database searches, we found 14 randomized clinical trials reporting citicoline effects on cognitive function. Findings: A positive effect of citicoline on MMSE in acute ischemic stroke was found, which was not evidenced for Alzheimer disease or vascular dementia. On activities of daily living, citicoline failed to exert beneficial effects in patients with acute ischemic stroke or ...
We investigated the potential role of different proteases in the death of cultured rat hippocampa... more We investigated the potential role of different proteases in the death of cultured rat hippocampal pyra-midal neurons induced by /3-amyloid(A~3)(25—35). Both A/1(25—35)- and staurosporine-induced death of these neurons appeared to involve apoptosis, as indicated us-ing Hoechst 33342 and terminal dUDP nick end labeling staining, whereas NMDA-induced death appeared more complex. Two irreversible inhibitors of the interleukin-1~ converting enzyme (ICE) and related proteases, Z-VaI-AIa-Asp-CH2F and acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone, blocked neuronal death produced by A/9(25—35), staurosporine, and NMDA to differing extents. Further-more, MDL 28,170, a selective inhibitor of the calcium-regulated protease calpain, also inhibited death induced by all agents. A~3(25—35)and staurosporine stimulated
BACKGROUND Our work describes the concept of Breast Aesthetic Scale (BAS) as a score for quick an... more BACKGROUND Our work describes the concept of Breast Aesthetic Scale (BAS) as a score for quick and simple objective assessment of results in cosmetic breast surgery. It is obtained by running a software program that we created, based on the previous concept of Objective Breast Cosmesis Scale (OBCS). This was previously described to be used in the context of conservative breast cancer treatment to objectively assess the degree of asymmetry. We describe the implementation of BAS algorithm and study its reproducibility in a set of images. METHODS A new multiplatform software was developed by us and named Breast Aesthetic Scale Calculator (BAS-Calc), which can be executed on Windows Mac, and Linux. A set of 25 photographs were studied with this software twice by 2 different surgeons. Intrarater and interrater variability were studied, as well as concordance with categorization by another symmetry assessment software available called Breast Analyzing Tool®. RESULTS Concordance among rate...
Pharmacovigilance compiles and analyzes spontaneous adverse drug reactions (ADRs) notifications r... more Pharmacovigilance compiles and analyzes spontaneous adverse drug reactions (ADRs) notifications reports on pharmacovigilance databases. Benzodiazepines have been related to skin and subcutaneous tissue disorders ADRs (SSTD-ADRs); tetrazepam was withdrawn in 2013 because of these ADRs. We intended to locate possible associations between cutaneous ADRs and benzodiazepines marketed in USA; for that, we calculated Data mining algorithms (PRR, ROR, IC and EBGM) on benzodiazepines spontaneous notifications reported to the American pharmacovigilance database. ROR yielded signals for eight drugs; PRR and IC for four, and EBGM only one. Clobazam originated a signal for “Stevens-Johnson syndrome” and “Blister”; midazolam for “Toxic epidermal necrolysis”, “DRESS syndrome” and “Erythema”; quazepam for “Erythema multiform” and “Drug eruption”; and tetrazepam “Dermatitis bullous”, “Toxic skin eruption”, “Rash maculopapular” and “Rash erythematous”. Tetrazepam exhibited signals by all Data mining ...
During the last decade, the neuroprotective effects of minocycline have been a matter of an inten... more During the last decade, the neuroprotective effects of minocycline have been a matter of an intense debate. A broad amount of contradictory studies can be found in the scientific literature, going from neuroprotection to the exacerbation of toxicity in diverse experimental models. Such differences could be the result of minocycline acting on multiple pharmacological targets. In the present review we will go over these pharmacological targets and the effects derived from their modulation by minocycline. Among others, its antioxidant activity derived from its chemical structure or its modulator effect on several enzymes such as nitric oxide synthase will be reviewed. Furthermore, the effects of minocycline on the intracellular pathways implicated in neurodegenerative processes including apoptosis stages, activation decision and execution will be addressed. All the mechanisms described herein have not escaped to a scientific community needed of new therapeutic drugs for the treatment o...
Multiple sclerosis is the most frequent chronic inflammatory, demyelinating and neurodegenerative... more Multiple sclerosis is the most frequent chronic inflammatory, demyelinating and neurodegenerative disease in young adults, but has no definitive pharmacological treatment. It is a heterogeneous disease from the immunological, neuropathological and clinical point of view, as well as in terms of its response to different therapies. Over the last two decades, pharmacology has focused on developing drugs that are capable of modifying the course of this disease, with the aim of reducing the frequency of the outbreaks and the speed at which the disability produced by the disease progresses. Nevertheless, today, there are no drugs that are capable of offering a curative effect that can fully stabilise the disease, and neuroprotective and neuroreparative strategies are still in their early stages. In this work we carry out a critical review of the different pathogenic paths involved in multiple sclerosis and we discuss the different pharmacological approaches that have been followed, based ...
Expert Review of Anti-Infective Therapy, Sep 26, 2020
To know the efficacy of different doses of dalbavancin in acute bacterial skin and skin structure... more To know the efficacy of different doses of dalbavancin in acute bacterial skin and skin structure infections (ABSSSIs) and versus other antibiotics. We performed a systematic review of dalbavancin efficacy for ABSSSIs. We selected 10 clinicals trials from MEDLINE and Cochrane databases for qualitative review. Of these, 5 trials compared one or two doses of dalbavancin versus other antibiotics such as vancomycin or linezolid. Treatment outcomes with other antibiotics were not significantly different versus two doses of dalbavancin (OR 1.13; 95% CI 0.75-1.71; p = 0.55) or single dose dalbavancin (OR 0.98; 95% CI 0.19- 5.17; p = 0.98). One dose versus two doses of dalbavancin did not show significant differences in any of the treatment groups. In contrast, the global microbiological assessment results indicated a favorable outcome for two doses of dalbavancin compared to the single dose of dalbavancin (OR 2.96; 95% CI 1.19-7.39; p= 0.02) in both methicillin-resistant and methicillin-su...
Since patients have easier access to information, thanks to the growing development of technology... more Since patients have easier access to information, thanks to the growing development of technology, their concern about everything related to drugs, especially adverse drug reactions, has increased. Resulting of this, authorities and health agencies are increasingly interested in drug safety and early detection of signals. Quantitative signals detection methods are useful for detecting pharmacovigilance signals, which can be analyzed to establish causality between an adverse event and a drug. Goal of this study was to deepen in signal detection of adverse drug reactions potentially associated to benzodiazepines, through the analysis of spontaneous notifications reported to the United States pharmacovigilance database (FAERS); after a previous work of signals detection of only cutaneous adverse reactions associated to this family of drugs, by applying data mining technique and different algorithms. All this, initially motivated by the market withdrawal of medicines containing tetrazep...
La calidad de vida y la adherencia al tratamiento poseen una gran relevancia en aquellos paciente... more La calidad de vida y la adherencia al tratamiento poseen una gran relevancia en aquellos pacientes que presentan enfermedades crónicas. El objetivo de este trabajo es conocer y evaluar ambos parámetros, en una población de pacientes de enfermedad de Parkinson. Para ello, se ha realizado un estudio transversal, a través de los cuestionarios de PDQ-39 y de Morisky-Green, en 95 pacientes de la citada enfermedad pertenecientes a alguna de las asociaciones de pacientes y familias de la provincia de Albacete. Los datos muestran una puntuación media de 33,47% en el PDQ-39, siendo los dominios de peor puntuación los referidos a movilidad y malestar físico. Por otro lado, un 31,6% de los pacientes se clasificaron como adherentes al tratamiento. Respecto a este parámetro, constatamos que, el factor principal relacionado con una adecuada adherencia, fue la importancia dada a su medicación por el propio paciente. No se ha encontrado ninguna asociación entre adherencia y calidad de vida.
After cerebral ischemia, necrotic cell death occurs specially for neurons, mainly due to the depr... more After cerebral ischemia, necrotic cell death occurs specially for neurons, mainly due to the deprivation of oxygen and glucose. Cell necrosis triggers the activation of the immune system followed by an inflammatory response. This reaction is characterized by the activation of astrocytes and microglia together with the infiltration of peripheral immune cells. Both, microglia and inflammatory cells, including circulating peripheral inflammatory cells, get activated and release a plethora of inflammatory mediators, cytokines, chemokines, etc. Such released factors induce the overexpression of adhesion molecules, increasing the blood brain barrier permeability, thus favoring even more inflammatory cell infiltration. In the end, this contributes to increase brain damage. Inflammatory response is nevertheless necessary in order to eliminate cellular debris from both apoptotic and necrotic cells. It seems to be also implicated in the initiation of certain mechanisms responsible for brain r...
We studied potential changes in the subventricular zone (SVZ) stem cell niche of the senescence-a... more We studied potential changes in the subventricular zone (SVZ) stem cell niche of the senescence-accelerated mouse prone-8 (SAM-P8) aging model. Bromodeoxyuridine (BrdU) assays with longtime survival revealed a lower number of label-retaining stem cells in the SAM-P8 SVZ compared with the SAM-Resistant 1 (SAM-R1) control strain. We also found that in SAM-P8 niche signaling is attenuated and the stem cell pool is less responsive to the self-renewal niche factor pigmented epithelium-derived factor (PEDF). Protein analysis demonstrated stable amounts of the PEDF ligand in the SAM-P8 SVZ niche; however, SAM-P8 stem cells present a significant expression decrease of patatin-like phospholipase domain containing 2, a receptor for PEDF (PNPLA2-PEDF) receptor, but not of laminin receptor (LR), a receptor for PEDF (LR-PEDF) receptor. We observed changes in self-renewal related genes (hairy and enhancer of split 1 (Hes1), hairy and enhancer of split 1 (Hes5), Sox2] and report that although these genes are down-regulated in SAM-P8, differentiation genes (Pax6) are up-regulated and neurogenesis is increased. Finally, sheltering mammalian telomere complexes might be also involved given a down-regulation of telomeric repeat binding factor 1 (Terf1) expression was observed in SAM-P8 at young age periods. Differences between these 2 models, SAM-P8 and SAM-R1 controls, have been previously detected at more advanced ages. We now describe alterations in the PEDF signaling pathway and stem cell self-renewal at a very young age, which could be involved in the premature senescence observed in the SAM-P8 model.-Castro-Garcia, P., Díaz-Moreno, M., Gil-Gas, C., Fernández-Gómez, F. J., Honrubia-Gómez, P., Álvarez-Simón, C. B., Sánchez-Sánchez, F., Cano. J. C. C., Rodríguez, F. A., Blanco. V., Jordán, J. Mira, H., Ramírez-Castillejo, C. Defects in subventricular zone pigmented epithelium-derived factor niche signaling in the senescence-accelerated mouse prone-8.
Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple... more Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. We performed a bibliometric study examining the characteristics and trends of the top 100 cited articles that include dimethyl fumarate in the title. On 21 September 2020 we carried out an electronic search in the Web of Science (WOS), seeking articles that include the following terms within the title: dimethyl fumarate, BG-12, or Tecfidera. To focus our investigation on original research, we refined the search to include only articles, early access, others, case report, and clinical trials. We obtained a total of 1115 items, which were cited 7169 times, had a citation density of 6.43 citations/item, and an h-index of 40. Around 2010, there was a jump in the number of published articles per year, rising from 5 articles/year up to 12 articles/year. We sorted all the items by the number of citations and selected the top 100 most cited (T100). The T100 had 4164 citations, with a...
Background: Citicoline is considered an ingredient in particular foods in the USA and is availabl... more Background: Citicoline is considered an ingredient in particular foods in the USA and is available in pharmaceutical form in Europe and Japan. It has been postulated to render positive effects on the nervous system, either by increasing levels of neurotransmitters, or by affording neuroprotection. Methods: Several clinical trials have shown the efficacy and safety of this biomolecule in several neurodegenerative diseases and in acute ischemic stroke. Here, we have performed a systematic review to validate the effect of citicoline on MMSE, memory, attention, and basic activity of daily living. In electronic database searches, we found 14 randomized clinical trials reporting citicoline effects on cognitive function. Findings: A positive effect of citicoline on MMSE in acute ischemic stroke was found, which was not evidenced for Alzheimer disease or vascular dementia. On activities of daily living, citicoline failed to exert beneficial effects in patients with acute ischemic stroke or ...
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Papers by joaquin Jordan