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1.
J Med Genet ; 60(4): 406-415, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36243518

RESUMEN

BACKGROUND: Schaaf-Yang syndrome (SYS) is caused by truncating mutations in MAGEL2, mapping to the Prader-Willi region (15q11-q13), with an observed phenotype partially overlapping that of Prader-Willi syndrome. MAGEL2 plays a role in retrograde transport and protein recycling regulation. Our aim is to contribute to the characterisation of SYS pathophysiology at clinical, genetic and molecular levels. METHODS: We performed an extensive phenotypic and mutational revision of previously reported patients with SYS. We analysed the secretion levels of amyloid-ß 1-40 peptide (Aß1-40) and performed targeted metabolomic and transcriptomic profiles in fibroblasts of patients with SYS (n=7) compared with controls (n=11). We also transfected cell lines with vectors encoding wild-type (WT) or mutated MAGEL2 to assess stability and subcellular localisation of the truncated protein. RESULTS: Functional studies show significantly decreased levels of secreted Aß1-40 and intracellular glutamine in SYS fibroblasts compared with WT. We also identified 132 differentially expressed genes, including non-coding RNAs (ncRNAs) such as HOTAIR, and many of them related to developmental processes and mitotic mechanisms. The truncated form of MAGEL2 displayed a stability similar to the WT but it was significantly switched to the nucleus, compared with a mainly cytoplasmic distribution of the WT MAGEL2. Based on the updated knowledge, we offer guidelines for the clinical management of patients with SYS. CONCLUSION: A truncated MAGEL2 protein is stable and localises mainly in the nucleus, where it might exert a pathogenic neomorphic effect. Aß1-40 secretion levels and HOTAIR mRNA levels might be promising biomarkers for SYS. Our findings may improve SYS understanding and clinical management.


Asunto(s)
Síndrome de Prader-Willi , Humanos , Síndrome de Prader-Willi/genética , Fenotipo , Mutación , Proteínas/genética , Biomarcadores
2.
Philos Trans A Math Phys Eng Sci ; 381(2259): 20220340, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37691469

RESUMEN

Amyloid fibrils have been associated with human disease for many decades, but it has also become apparent that they play a functional, non-disease-related role in e.g. bacteria and mammals. Moreover, they have been shown to possess interesting mechanical properties that can be harnessed for future man-made applications. Here, the mechanical behaviour of SSTSAA microcrystals has been investigated. The SSTSAA peptide organization in these microcrystals has been related to that in the corresponding amyloid fibrils. Using high-pressure X-ray diffraction experiments, the bulk modulus K, which is the reciprocal of the compressibility ß, has been calculated to be 2.48 GPa. This indicates that the fibrils are tightly packed, although the packing of most native globular proteins is even better. It is shown that the value of the bulk modulus is mainly determined by the compression along the c-axis, that relates to the inter-sheet distance in the fibrils. These findings corroborate earlier data obtained by AFM and molecular dynamics simulations that showed that mechanical resistance varies according to the direction of the applied strain, which can be related to packing and hydrogen bond contributions. Pressure experiments provide complementary information to these techniques and help to acquire a full mechanical characterization of biomolecular assemblies. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 2)'.


Asunto(s)
Amiloide , Compresión de Datos , Animales , Humanos , Difracción de Rayos X , Mamíferos
3.
Philos Trans A Math Phys Eng Sci ; 381(2259): 20220343, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37691466

RESUMEN

Photo-induced enhanced Raman spectroscopy (PIERS) has emerged as a highly sensitive surface-enhanced Raman spectroscopy (SERS) technique for the detection of ultra-low concentrations of organic molecules. The PIERS mechanism has been largely attributed to UV-induced formation of surface oxygen vacancies (Vo) in semiconductor materials, although alternative interpretations have been suggested. Very recently, PIERS has been proposed as a surface probe for photocatalytic materials, following Vo formation and healing kinetics. This work establishes comparison between PIERS and Vo-induced SERS approaches in defected noble-metal-free titanium dioxide (TiO2-x) films to further confirm the role of Vo in PIERS. Upon application of three post-treatment methods (namely UV-induction, vacuum annealing and argon etching), correlation of Vo kinetics and distribution could be established. A proposed mechanism and further discussion on PIERS as a probe to explore photocatalytic materials are also presented. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 2)'.

4.
Australas J Dermatol ; 63(1): 98-101, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34928506

RESUMEN

Collision tumours are a random association of two or more neoplasms arising in the same anatomical site. Dilated pore of Winer (DPW) - an adnexal tumour of pilar origin - has been described in collisions with basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and trichoblastoma. We present a literature review of melanoma-associated skin lesions and describe the first collision of a DPW with a melanoma in situ (MIS) and the sequential dermoscopic examination for diagnosis.


Asunto(s)
Enfermedades del Cabello/patología , Folículo Piloso/patología , Melanoma/patología , Neoplasias Cutáneas/patología , Anciano de 80 o más Años , Femenino , Humanos
5.
Plant Dis ; 2022 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-35130039

RESUMEN

In December 2019, New Jersey became one of the first states to have its industrial hemp (Cannabis sativa L.) plan approved by the U.S. Department of Agriculture (USDA) following enactment of the 2018 Farm Bill that authorized the production of hemp. Following this approval, hemp was legally grown for the first time in 2020. During the growing seasons of 2020 and 2021, powdery mildew-like symptoms were observed during the summer months (Jun to Aug) in greenhouse hemp research and fall months (Aug to Oct) in field production plots on Rutgers Agricultural Experiment Station farms in southern and northern New Jersey. Symptoms were observed on leaves and stems of hemp cultivars 'CB Genius', 'Cherry Wine' and 'Bay Mist'. Symptoms initially appeared as small white patches of mycelia and conidia on the adaxial surface of leaves that gradually spread to entire leaves and stems. Leaf discoloration (e.g., chlorosis) and premature leaf drop were observed. More severe symptoms and damage were observed in the greenhouse than outdoor cultivation. A voucher specimen was deposited in the U.S National Fungus Collections, USDA-ARS, Beltsville, MD (accession number 929187). Morphological examination of the white colonies from the cultivar 'Baymist' was carried out using light microscopy and further characterized by sequencing. This isolate was labelled PMH2. Hyphae were septate, conidiophores were hyaline, unbranched, measuring 130 to 240 µm in length and produced 1 to 4 conidia in chains. Conidia were hyaline, ellipsoid to ovoid in shape and measured 20 to 36 ×10 to 18 µm (n=30). Oil-like drops were present within conidia, although no distinct fibrosin bodies were observed. Chasmothecia were not observed. Morphological observations were consistent with those of Golovinomyces spp. as described by Braun and Cook (2012). Morphological observations (conidiophore and conidial measurements) were also similar to the description of G. ambrosiae on Hemp, as described in Wiseman et al, 2021. Sequencing of internal transcribed spacer (ITS), large ribosomal subunit (28S), intergenic spacer (IGS), beta- tubulin (TUB2) and chitin synthase 1(CHS1) region, were carried out with the primer sets ITS5/ITS4, LSU1/LSU2, IGS-12a/NS1R, TubF1/TubR1 and gCS1a1/gCS1b respectively, as shown by Qiu et al. (2020). Maximum-likelihood phylogenetic analysis confirmed the grouping of the PMH2 isolate within the G. ambrosiae accessions. Each individual gene alignment was treated as a separate partition. Sequences were not concatenated for maximum -likelihood phylogenetic analysis. Sequence data were deposited in GenBank under the accessions OK626453 (ITS), OK626454 (28S), OL456201 (IGS), OL415512 (TUB2) and OL415513(CHS1). To fulfill Koch's postulates, two mature, potted plants of C. sativa cv. 'Alpha Explorer' were inoculated by gently pressing symptomatic hemp leaves onto their leaf surface. They were incubated in an indoor grow room at 23°C and relative humidity of 50%. Non-inoculated healthy plants of C. sativa cv. 'Alpha Explorer' served as control. Inoculated plants developed powdery mildew symptoms within 10 to 12 days, while all control plants were asymptomatic. The powdery mildew on inoculated plants was found to be morphologically similar to the original. G. ambrosiae has been reported on C.sativa in Oregon (Wiseman et al. 2021) and G. ambrosiae (as G. spadiceus) has been reported on Cannabis in Kentucky (Szarka et al. 2019), Ohio (Farinas and Hand 2020) and New York (Weldon et al. 2020). This is the first known report of Golovinomyces ambrosiae causing powdery mildew on hemp in New Jersey. With the recent opening ( Dec15, 2021) of cultivation licensing and retailing of recreational marijuana, the acreage of Hemp production in New Jersey is expected to significantly increase, particularly for greenhouse production. It is important to document the species to develop management strategies to control this disease.

6.
Nano Lett ; 21(19): 8348-8354, 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34582208

RESUMEN

Metal-oxide semiconductors (MOS) are widely utilized for catalytic and photocatalytic applications in which the dynamics of charged carriers (e.g., electrons, holes) play important roles. Under operation conditions, photoinduced surface oxygen vacancies (PI-SOV) can greatly impact the dynamics of charge carriers. However, current knowledge regarding the effect of PI-SOV on the dynamics of hole migration in MOS films, such as titanium dioxide, is solely based upon volume-averaged measurements and/or vacuum conditions. This limits the basic understanding of hole-vacancy interactions, as they are not capable of revealing time-resolved variations during operation. Here, we measured the effect of PI-SOV on the dynamics of hole migration using time-resolved atomic force microscopy. Our findings demonstrate that the time constant associated with hole migration is strongly affected by PI-SOV, in a reversible manner. These results will nucleate an insightful understanding of the physics of hole dynamics and thus enable emerging technologies, facilitated by engineering hole-vacancy interactions.

7.
J Cardiovasc Pharmacol ; 71(1): 19-25, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29040151

RESUMEN

The influence of sex on the vascular response during the progression of myocardial infarction (MI) has not been extensively studied. In this work, we analyzed the differences of the vasoconstriction induced by angiotensin II (Ang II) in the absence and presence of valsartan (200 nM) on the aortic rings of male and female Wistar rats at 2, 4, 24, and 48 hours and 1, 2, 3, and 4 weeks after induction of MI. In the aortic rings of males, an increase was observed in the contractile response that lasts up to 4 weeks; on females, this effect is diminished since 48 hours until reaching sham group values at 2 weeks of coronary occlusion. The incubation of valsartan generated greater reduction on vasoconstriction in males than females. In relation to the determination of infarct areas, we found them between 30% and 40% in all experimental groups. In addition, the index of hypertrophy was determined and no significant changes were observed in female rats, while in males we reported an increase at 2, 3, and 4 weeks. In conclusion, we found differences in vascular reactivity due to sex, as well as on the response of Ang II via AT1 during the evolution of MI.


Asunto(s)
Angiotensina II/farmacología , Aorta/efectos de los fármacos , Infarto del Miocardio/fisiopatología , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Aorta/fisiopatología , Modelos Animales de Enfermedad , Femenino , Masculino , Infarto del Miocardio/patología , Ratas Wistar , Receptor de Angiotensina Tipo 1/agonistas , Receptor de Angiotensina Tipo 1/metabolismo , Factores Sexuales , Factores de Tiempo
8.
Acta Derm Venereol ; 98(4): 416-420, 2018 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-29362810

RESUMEN

Vitiligo is an acquired depigmenting disorder. To date, there is no predictive model for its response rate to narrowband ultraviolet B (NBUVB) phototherapy. The aim of this study was to investigate the different types of response of patients with non-segmental vitiligo undergoing NBUVB 3 times a week. Many patients who were previously considered non-responders were given the opportunity to continue the treatment. Long-term maintenance of treatment and follow-up of a cohort of 579 patients enabled different subtypes of response (very rapid, rapid, average, slow and "non-responders") to be described for the first time, and a predictive model of response to be constructed based on repigmentation rate in the first 48 sessions of NBUVB. Among those patients who did not respond during the first 48 sessions, a new subgroup of patients was found, termed "very-slow" responders, who achieved a low, but significant, level of repigmentation after 96 sessions of NBUVB.


Asunto(s)
Pigmentación de la Piel/efectos de la radiación , Piel/efectos de la radiación , Terapia Ultravioleta , Vitíligo/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Fotograbar , Valor Predictivo de las Pruebas , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Piel/fisiopatología , Terminología como Asunto , Factores de Tiempo , Resultado del Tratamiento , Terapia Ultravioleta/efectos adversos , Vitíligo/clasificación , Vitíligo/diagnóstico , Vitíligo/fisiopatología , Adulto Joven
9.
J Am Acad Dermatol ; 76(5): 879-888, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28216034

RESUMEN

BACKGROUND: Treatment of vitiligo with narrowband ultraviolet B light (NBUVB) is an important component of the current standard of care. However, there are no consistent guidelines regarding the dosing and administration of NBUVB in vitiligo, reflected by varied treatment practices around the world. OBJECTIVE: To create phototherapy recommendations to facilitate clinical management and identify areas requiring future research. METHODS: The Vitiligo Working Group (VWG) Phototherapy Committee addressed 19 questions regarding the administration of phototherapy over 3 conference calls. Members of the Photomedicine Society and a group of phototherapy experts were surveyed regarding their phototherapy practices. RESULTS: Based on comparison and analysis of survey results, expert opinion, and discussion held during conference calls, expert recommendations for the administration of NBUVB phototherapy in vitiligo were created. LIMITATIONS: There were several areas that required further research before final recommendations could be made. In addition, no standardized methodology was used during literature review and to assess the strength of evidence during the development of these recommendations. CONCLUSION: This set of expert recommendations by the VWG is based on the prescribing practices of phototherapy experts from around the world to create a unified, broadly applicable set of recommendations on the use of NBUVB in vitiligo.


Asunto(s)
Terapia Ultravioleta/métodos , Terapia Ultravioleta/normas , Vitíligo/radioterapia , Quimioterapia Adyuvante , Consenso , Humanos , Guías de Práctica Clínica como Asunto , Dosificación Radioterapéutica/normas , Terapia Ultravioleta/efectos adversos
11.
J Phys Chem A ; 120(5): 715-23, 2016 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-26777898

RESUMEN

Anatase:rutile TiO2 junctions are often shown to be more photocatalytically active than anatase or rutile alone, but the underlying cause of this improvement is not fully understood. Herein, we employ transient absorption spectroscopy to study hole transfer across the anatase:rutile heterojunction in films as a function of phase composition. By exploiting the different signatures in the photoinduced absorption of trapped charges in anatase and rutile, we were able to separately track the yield and lifetime of holes in anatase and rutile sites within phase composites. Photogenerated holes transfer from rutile to anatase on submicrosecond time scales. This hole transfer can significantly increase the anatase hole yield, with a 20:80 anatase:rutile composite showing a 5-fold increase in anatase holes observed from the microsecond. Hole transfer does not result in an increase in charge-carrier lifetime, where an intermediate recombination dynamic between that of pure anatase (t1/2 ≈ 0.5 ms) and rutile (t1/2 ≈ 20 ms) is found in the anatase:rutile junction (t1/2 ≈ 4 ms). Irrespective of what the formal band energy alignment may be, we demonstrate the importance of trap-state energetics for determining the direction of photogenerated charge separation across heterojunctions and how transient absorption spectroscopy, a method that can specifically track the migration of trapped charges, is a useful tool for understanding this behavior.

12.
Am J Dermatopathol ; 38(11): 813-819, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27362605

RESUMEN

The face has not been considered a common site of fixed drug eruption, and the authors lack dermatoscopic studies of this condition on the subject. The authors sought to characterize clinical and dermatoscopic features of 8 cases of an eruptive facial postinflammatory lentigo. The authors conducted a retrospective review of 8 cases with similar clinical and dermatoscopic findings seen from 2 medical centers in 2 countries during 2010-2014. A total of 8 patients (2 males and 6 females) with ages that ranged from 34 to 62 years (mean: 48) presented an abrupt onset of a single facial brown-pink macule, generally asymmetrical, with an average size of 1.9 cm. after ingestion of a nonsteroidal antiinflammatory drugs that lasted for several months. Dermatoscopy mainly showed a pseudonetwork or uniform areas of brown pigmentation, brown or blue-gray dots, red dots and/or telangiectatic vessels. In the epidermis, histopathology showed a mild hydropic degeneration and focal melanin hyperpigmentation. Melanin can be found freely in the dermis or laden in macrophages along with a mild perivascular mononuclear infiltrate. The authors describe eruptive facial postinflammatory lentigo as a new variant of a fixed drug eruption on the face.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Dermoscopía , Erupciones por Medicamentos/patología , Dermatosis Facial/patología , Lentigo/patología , Piel/patología , Adulto , Biomarcadores/análisis , Biopsia , Chile , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/metabolismo , Dermatosis Facial/inducido químicamente , Dermatosis Facial/metabolismo , Femenino , Humanos , Hiperpigmentación/inducido químicamente , Hiperpigmentación/patología , Lentigo/inducido químicamente , Lentigo/metabolismo , Masculino , Melaninas/análisis , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Piel/química , Piel/efectos de los fármacos , España
13.
Rev Med Chil ; 143(6): 751-8, 2015 Jun.
Artículo en Español | MEDLINE | ID: mdl-26230558

RESUMEN

BACKGROUND: Allergic Contact Dermatitis is a classic delayed hypersensitivity reaction. AIM: To study the reactivity and evolution in Chilean patients by gender, using the standard European patch test. MATERIALS AND METHODS: The results of the European standard patch test applied to 4,022 patients aged 1 to 93 years (64% female) with Allergic Contact Dermatitis, diagnosed between January 1995 and August 2011, were retrospectively analyzed. RESULTS: From a total of 4,022 patients, 2,439 (60.6%) had a positive reaction. Among reactive patients, 1,854 (76.04%) were female and 584 (23.96%) male. The most common positive allergens were nickel (35.3%), cobalt (15.1%), fragrance mix (14%), chromium (8.7%) and balsam of Peru (8.5%). In females, nickel was the most common reactive antigen (34.28%), and in males, fragrance mix (15.7%). During the period 2003-2011, an increased reactivity to nickel (26.6%) and a decreased reactivity to p-phenylenediamine (29.6%) and fragrance (42.8%), was observed. CONCLUSIONS: Fragrance mix is the most common reactive allergen in males and the third for females. Nickel is the leading allergen in the female group and the second of importance for males, making it the most significant allergen for the Chilean population. We also observed that the reactivity of some allergens evolves and varies over time.


Asunto(s)
Dermatitis Alérgica por Contacto/diagnóstico , Pruebas del Parche , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Chile , Dermatitis Alérgica por Contacto/clasificación , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Adulto Joven
14.
An Bras Dermatol ; 99(4): 546-567, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38521706

RESUMEN

BACKGROUND: Molecularly targeted therapies, such as monoclonal antibodies (mAbs) and Janus Kinase inhibitors (JAKis), have emerged as essential tools in the treatment of dermatological diseases. These therapies modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. This review aims to provide an updated summary of targeted immune therapies for inflammatory skin diseases, considering their pathophysiology, efficacy, dosage, and safety profiles. METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted on PubMed over the past 10 years, focusing on randomized clinical trials, case reports, and case series related to targeted immune therapies in dermatology. Eligibility criteria were applied, and data were extracted from each study, including citation data, study design, and results. RESULTS: We identified 1360 non-duplicate articles with the initial search strategy. Title and abstract review excluded 1150, while a full-text review excluded an additional 50 articles. The review included 143 studies published between 2012 and 2022, highlighting 39 drugs currently under investigation or in use for managing inflammatory skin diseases. STUDY LIMITATIONS: The heterogeneity of summarized information limits this review. Some recommendations originated from data from clinical trials, while others relied on retrospective analyses and small case series. Recommendations will likely be updated as new results emerge. CONCLUSION: Targeted therapies have revolutionized the treatment of chronic skin diseases, offering new options for patients unresponsive to standard treatments. Paradoxical reactions are rarely observed. Further studies are needed to fully understand the mechanisms and nature of these therapies. Overall, targeted immune therapies in dermatology represent a promising development, significantly improving the quality of life for patients with chronic inflammatory skin diseases.


Asunto(s)
Terapia Molecular Dirigida , Enfermedades de la Piel , Humanos , Anticuerpos Monoclonales/uso terapéutico , Dermatólogos , Inhibidores de las Cinasas Janus/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico
15.
Cureus ; 16(5): e59612, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38832162

RESUMEN

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that induces action potentials in the stimulated cortical area and has been approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). The prevalence of MDD in Mexico almost tripled after the COVID-19 pandemic. In this study, we evaluated the safety and therapeutic effects of low-intensity TMS (Li-TMS) - characterized by inducing electric currents below the action potential threshold on the cerebral cortex - in 41 subjects diagnosed with treatment-resistant depression (TRD). A Li-TMS device dispensed repetitive magnetic pulses at 30 mT for 60 minutes during 20 sessions (once daily from Monday to Saturday) with the theta burst pattern. Our results suggest that Li-TMS is a safe therapy with antidepressant effects, demonstrated by the decrease in Beck Depression Inventory (BDI) scores and lessening of depressive symptoms.

16.
Arch Med Res ; 55(1): 102916, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38039802

RESUMEN

Clavulanic acid (CLAV) is a non-antibiotic ß-lactam that has been used since the late 1970s as a ß-lactamase inhibitor in combination with amoxicillin, another ß-lactam with antibiotic activity. Its long-observed adverse reaction profile allows it to say that CLAV is a well-tolerated drug with mainly mild adverse reactions. Interestingly, in 2005, it was discovered that ß-lactams enhance the astrocytic expression of GLT-1, a glutamate transporter essential for maintaining synaptic glutamate homeostasis involved in several pathologies of the central nervous system (CNS). This finding, along with a favorable pharmacokinetic profile, prompted the appearance of several studies that intended to evaluate the effect of CLAV in preclinical disease models. Studies have revealed that CLAV can increase GLT-1 expression in the nucleus accumbens (NAcc), medial prefrontal cortex (PFC), and spinal cord of rodents, to affect glutamate and dopaminergic neurotransmission, and exert an anti-inflammatory effect by modulating the levels of the cytokines TNF-α and interleukin 10 (IL-10). CLAV has been tested with positive results in preclinical models of epilepsy, addiction, stroke, neuropathic and inflammatory pain, dementia, Parkinson's disease, and sexual and anxiety behavior. These properties make CLAV a potential therapeutic drug if repurposed. Therefore, this review aims to gather information on CLAV's effect on preclinical neurological disease models and to give some perspectives on its potential therapeutic use in some diseases of the CNS.


Asunto(s)
Antibacterianos , beta-Lactamas , Ácido Clavulánico/uso terapéutico , Ácido Clavulánico/metabolismo , Ácido Clavulánico/farmacología , Antibacterianos/uso terapéutico , beta-Lactamas/metabolismo , beta-Lactamas/farmacología , Núcleo Accumbens/metabolismo , Glutamatos/metabolismo , Glutamatos/farmacología , Transportador 2 de Aminoácidos Excitadores/metabolismo
17.
RSC Adv ; 14(13): 8615-8640, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38495977

RESUMEN

M1 muscarinic acetylcholine receptor (M1-AChR), a member of the G protein-coupled receptors (GPCR) family, plays a crucial role in learning and memory, making it an important drug target for Alzheimer's disease (AD) and schizophrenia. M1-AChR activation and deactivation have shown modifying effects in AD and PD preclinical models, respectively. However, understanding the pharmacology associated with M1-AChR activation or deactivation is complex, because of the low selectivity among muscarinic subtypes, hampering their therapeutic applications. In this regard, we constructed two quantitative structure-activity relationship (QSAR) models, one for M1-AChR agonists (total and partial), and the other for the antagonists. The binding mode of 59 structurally different compounds, including agonists and antagonists with experimental binding affinity values (pKi), were analyzed employing computational molecular docking over different structures of M1-AChR. Furthermore, we considered the interaction energy (Einter), the number of rotatable bonds (NRB), and lipophilicity (ilogP) for the construction of the QSAR model for agonists (R2 = 89.64, QLMO2 = 78, and Qext2 = 79.1). For the QSAR model of antagonists (R2 = 88.44, QLMO2 = 82, and Qext2 = 78.1) we considered the Einter, the fraction of sp3 carbons fCsp3, and lipophilicity (MlogP). Our results suggest that the ligand volume is a determinant to establish its biological activity (agonist or antagonist), causing changes in binding energy, and determining the affinity for M1-AChR.

18.
Rev Chilena Infectol ; 30(1): 90-3, 2013 Feb.
Artículo en Español | MEDLINE | ID: mdl-23450418

RESUMEN

Tinea nigra is a superficial mycosis caused by Hortaea werneckii. It is an infrequent asymptomatic infection that affects mainly human palms and soles, and it is mostly seen in tropical countries. It has not been reported in Chile yet. The clinical presentation is generally a single macule, not symptomatic, of brown color in palms and soles. We report a case of a Chilean woman that developed brown macules on both soles after travel to the United States and Central America. The diagnosis of Tinea nigra was confirmed by direct microscopic examination and mycological culture. She had a good response to treatment with oral itraconazol.


Asunto(s)
Tiña del Pie/diagnóstico , Adulto , Antifúngicos/uso terapéutico , Femenino , Humanos , Itraconazol/uso terapéutico , Tiña del Pie/tratamiento farmacológico , Tiña del Pie/microbiología
19.
Biomedicines ; 11(2)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36831113

RESUMEN

The leading cause of death in psoriasis is cardiovascular disease. The determinants that induce the increase in this risk are not known. The systemic inflammatory process is dependent on lymphocytes and monocytes, as has been proposed. However, adaptation modules such as mTOR have recently been mentioned as having a role. Other factors, such as WNT and its non-canonical WNT5a-inducing pathway, are relevant in inflammation, cell migration, and neoangiogenesis. Thus, we studied circulating monocytes from untreated severe psoriatic patients and characterized inflammatory cytokines, chemokines, mTOR activity, and the cardiovascular risk marker ADAMTS7. Peripheral blood from ten severely psoriatic patients (Psoriasis severity index greater than 10) was extracted and age- and sex-matched with healthy subjects. Surface and intracellular flow cytometry were performed for cytokine, chemokine receptors, and mTOR activity. ADAMTS7 was measured using ELISA. Psoriatic patients had a higher frequency of WNT5a+ cells in monocytes, which also had higher levels of IL-1ß, IL-6, CXCR3, CCR2, and phosphorylated S6R protein. We found that M1 monocytes are dominant in the WNT5a+ cell group, and intracellular levels of WNT5a were also augmented. Levels of WNT5a were correlated with ADAMTS7, a blood marker related to the pathogenesis of atheromatosis. WNT5a could be relevant to the cardiovascular risk of psoriatic patients considering its association with higher levels of inflammatory cytokines, chemokine receptors and the pro-atherogenic profile of circulating monocytes.

20.
Metabolites ; 13(1)2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36677041

RESUMEN

Psoriasis is a skin disease with occasional involvement of non-cutaneous territories. Beyond the usual, cardiovascular events are more frequent in these patients and correlate only partially with disease activity, suggesting the presence of other unknown factors. We selected ten psoriatic patients without treatment in the last year and matched them for age and gender with eleven healthy subjects. Ficoll-extracted mononuclear cells were analyzed with flow cytometry for monocyte surface phenotype markers, intracellular NFκB/inflammasome-dependent interleukins, and chemotaxis receptor CXCR3. Using ELISA, patient serum was evaluated for ADAMTS7 and CXCL10. Inflammatory M1 monocytes showed higher levels of IL-1ß and IL-6 in psoriatic patients. M2 monocytes also showed higher levels of intracellular inflammatory cytokines. Nevertheless, IL-6 values were higher compared to other monocytes and IL-1ß. The mTORC activation markers ADAMTS7 and S6Rp were higher in psoriatic patients than in healthy controls. In psoriatic patients, serum levels of ADAMTS7 were elevated, and M2 monocytes showed a distinct inflammatory response with higher relative levels of NFκB-dependent IL-6 and less activity of the CXCR3-CXCL10 chemotactic pathway. These data suggest pathways with potential markers for prediction and early detection of cardiovascular risk in psoriatic patients.

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