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1.
Ethn Health ; 24(4): 405-414, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-28669237

RESUMEN

OBJECTIVE: Anaemia is one of the most common health problems worldwide, with a high prevalence in Africa and South East Asia, including Thailand. Thai women of childbearing age have an increased risk of anaemia due to several factors including underlying health problems, lifestyles and poor diet. Therefore, we investigated the prevalence of anaemia among female students of Chulalongkorn University (aged 18-22) and categorized causes of the anaemia. DESIGN: 400 Thai female student-volunteers, without known underlying diseases were subjected to blood tests; complete blood count, Haemoglobin typing and serum ferritin level. Bloods, having haemoglobin under 12 g/dl and hematocrit under 36%, were designated as anaemia. Then causes of anaemia are categorized into 3 groups; Iron deficiency, Thalassemia and Others. RESULTS: We found that 21% of the volunteers were anaemic. In 85 anaemic volunteers, they were classified as Iron deficiency anaemia (IDA); with low serum ferritin levels 42.4%, Thalassemia; total of 6 types 25.9%, IDA and Thalassemia 2.3% and Others 29.4% in which haemoglobin typing and serum ferritin level were normal. CONCLUSION: Iron deficiency anaemia (IDA) is the major cause of anaemia in Thai female students in our study. Several students were gradually developing anaemia where their haematocrit (Hct) and haemaglobin (Hb) were within reference range but mean corpuscular volume (MCV), mean corpuscular haemaglobin (MCH) and serum ferritin fell below reference range, indicating latent iron deficiency. A few volunteers had both IDA and Thalassemia and also Thalassemia with iron overloaded where health can be deteriorated without knowledge of having these conditions or proper health care. To improve their health, universities or public organizations should provide education and/or screen for anaemia. With the knowledge and understanding of their health issues or underling diseases, students themselves can prevent serious health conditions, improve university performances, and improve their quality of life.


Asunto(s)
Anemia Ferropénica/epidemiología , Hemoglobinas/análisis , Adulto , Anemia Ferropénica/sangre , Índices de Eritrocitos , Femenino , Humanos , Prevalencia , Tailandia/epidemiología , Talasemia/sangre , Universidades , Adulto Joven
2.
Biomed Pharmacother ; 173: 116455, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38503234

RESUMEN

The sigma-1 receptor (σ-1R), a chaperone protein located at the mitochondria-associated membrane (MAM) of the endoplasmic reticulum, can interact with and modify the signaling pathways of various proteins, thereby modulating many disease pathologies, including Alzheimer's disease (AD). The σ-1R ligand dipentylammonium (DPA) was analyzed for its anti-AD properties using PC12 cells (in vitro) and Caenorhabditis elegans (in vivo) models along with molecular docking (in silico) analysis. DPA at 1 and 10 µM concentrations was able to significantly potentiate NGF-induced neurite growth length by 137.7 ± 12.0 and 187.8 ± 16.4, respectively, when compared to the control 76.9 ± 7.4. DPA also regulated neurite damage caused by Aß(25-35) treatment in differentiated PC12 cells by improving cell viability and neurite length. In C. elegans, DPA could significantly extend the median and maximum lifespan of Aß transgenic strain CL2006 without impacting wild-type nematodes. Additionally, it could significantly reduce the paralysis phenotype of another Aß transgenic strain, CL4176, thereby improving the overall health in AD pathogenesis. This effect depended on σ-1R, as DPA could not modulate the lifespan of σ-1R mutant TM3443. This was further confirmed using agonist PRE084 and antagonist BD1047, wherein the agonist alone could extend the lifespan of CL2006, while the antagonist suppressed the effect of DPA in CL2006. Interestingly, neither had an TM3443. Further, molecular docking analysis showed that DPA had a similar binding affinity as that of PRE084, BD1047 and pentazocine against the σ-1R receptor in humans and C. elegans, which collectively suggests the anti-AD properties of DPA.


Asunto(s)
Enfermedad de Alzheimer , Compuestos de Amonio , Etilenodiaminas , Fármacos Neuroprotectores , Receptores sigma , Animales , Ratas , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Receptor Sigma-1 , Caenorhabditis elegans , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ligandos , Simulación del Acoplamiento Molecular , Animales Modificados Genéticamente/metabolismo , Técnicas de Cultivo de Célula , Péptidos beta-Amiloides/metabolismo , Receptores sigma/metabolismo
3.
Sci Rep ; 14(1): 13462, 2024 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-38862591

RESUMEN

There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out to date, with seven of those being randomized placebo-controlled studies. This systematic review and meta-analysis covers the literature from the outbreak of SARS-CoV-2 in late 2019 until January 2024. Search terms related to fluvoxamine, such as its trade names and chemical names, along with words related to COVID-19, such as SARS-CoV-2 and coronavirus, were used in literature databases including PubMed, Google Scholar, Scopus, and the ClinicalTrials.gov database from NIH, to identify the trials used in the subsequent analysis. Clinical deterioration and death data were extracted from these studies where available and used in the meta-analysis. A total of 7153 patients were studied across 14 studies (both open-label and double-blind placebo-controlled). 681 out of 3553 (19.17%) in the standard care group and 255 out of 3600 (7.08%) in the fluvoxamine-treated group experienced clinical deterioration. The estimated average log odds ratio was 1.087 (95% CI 0.200 to 1.973), which differed significantly from zero (z = 2.402, p = 0.016). The seven placebo-controlled studies resulted in a log odds ratio of 0.359 (95% CI 0.1111 to 0.5294), which differed significantly from zero (z = 3.103, p = 0.002). The results of this study identified fluvoxamine as effective in preventing clinical deterioration, and subgrouping analysis suggests that earlier treatment with a dose of 200 mg or above provides the best outcomes. We hope the outcomes of this study can help design future studies into respiratory viral infections and potentially improve clinical outcomes.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Fluvoxamina , SARS-CoV-2 , Fluvoxamina/uso terapéutico , Humanos , COVID-19/mortalidad , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/efectos de los fármacos , Resultado del Tratamiento , Deterioro Clínico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación
4.
Heliyon ; 9(4): e15233, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37035364

RESUMEN

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has been affecting people globally, and the Philippines is one of the countries greatly struck by the virus. The continued rise of new positive cases has drawn attention to the urgent need for healthcare management to cope with this challenge. Severity prediction could help improve medical decision-making and optimise the patient's treatment plan with a good clinical outcome. This study aimed to identify the determinants of COVID-19 disease severity. Methods: Demographic characteristics and laboratory findings were collected from electronic medical records and paper forms of all confirmed COVID-19 cases reported by the University of Perpetual Help DALTA Medical Center between the September 1, 2020 and the October 31, 2021. We performed statistical analyses and interpretation of data to compare severe and non-severe groups. Results: 5,396 confirmed cases were examined. Most of the severe cases were elderly, male, had blood type A, and with comorbidities. Cycle threshold (Ct) values were lower in the severe group. Most patients had higher-than-normal levels of all blood parameters except platelet, white blood cell (WBC), neutrophil, and lymphocyte counts. Age, sex, ABO blood groups, comorbidities, open reading frame 1 ab (ORF1ab) and nucleocapsid (N) gene Ct values, ferritin, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, white blood cell (WBC) count, neutrophil count, and lymphocyte count were significantly associated with disease severity. In multivariate analysis, age groups >60 and 30-59 years, presence of comorbidities, CRP level >5 ng/mL, and PCT >0.05 ng/mL were identified as disease severity predictors. Conclusions: Based on our results, age, comorbidities, CRP, and PCT level may be utilised as primary assessment factors for possible hospital admission and close monitoring upon testing. Early detection of these risk factors may provide strategic interventions that help reduce mortality, hospital admissions, and more expensive and extensive treatments.

5.
CNS Drugs ; 37(5): 399-440, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37166702

RESUMEN

The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure. The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor. Both proteins are highly expressed in neuronal tissues. As such, they have become targets for treating neurological diseases, including Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), multiple sclerosis (MS), Rett syndrome (RS), developmental and epileptic encephalopathies (DEE), and motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). In recent years, there have been many pre-clinical and clinical studies of sigma receptor (1 and 2) ligands for treating neurological disease. Drugs such as blarcamesine, dextromethorphan and pridopidine, which have sigma-1 receptor activity as part of their pharmacological profile, are effective in treating multiple aspects of several neurological diseases. Furthermore, several sigma-2 receptor ligands are under investigation, including CT1812, rivastigmine and SAS0132. This review aims to provide a current and up-to-date analysis of the current clinical and pre-clinical data of drugs with sigma receptor activities for treating neurological disease.


Asunto(s)
Esclerosis Amiotrófica Lateral , Enfermedad de Huntington , Trastornos del Neurodesarrollo , Receptores sigma , Humanos , Receptores sigma/metabolismo , Receptores sigma/uso terapéutico , Neuronas/metabolismo , Trastornos del Neurodesarrollo/tratamiento farmacológico , Trastornos del Neurodesarrollo/metabolismo
6.
Int J Mol Sci ; 13(4): 5074-5097, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22606031

RESUMEN

The Herb Rhinacanthus nasutus (L.) Kurz, which is native to Thailand and Southeast Asia, has become known for its antioxidant properties. Neuronal loss in a number of diseases including Alzheimer's disease is thought to result, in part, from oxidative stress. Glutamate causes cell death in the mouse hippocampal cell line, HT-22, by unbalancing redox homeostasis, brought about by a reduction in glutathione levels, and amyloid-ß has been shown to induce reactive oxygen species (ROS) production. Here in, we show that ethanol extracts of R. nasutus leaf and root are capable of dose dependently attenuating the neuron cell death caused by both glutamate and amyloid-ß treatment. We used free radical scavenging assays to measure the extracts antioxidant activities and as well as quantifying phenolic, flavonoid and sterol content. Molecules found in R. nasutus, lupeol, stigmasterol and ß-sitosterol are protective against glutamate toxicity.


Asunto(s)
Acanthaceae/metabolismo , Síndromes de Neurotoxicidad/tratamiento farmacológico , Triterpenos Pentacíclicos/farmacología , Sitoesteroles/farmacología , Estigmasterol/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides , Animales , Antioxidantes/farmacología , Línea Celular , Ácido Glutámico/toxicidad , Glutatión/metabolismo , Hipocampo/citología , Ratones , Fármacos Neuroprotectores/farmacología , Síndromes de Neurotoxicidad/prevención & control , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
7.
Expert Opin Ther Targets ; 26(12): 1087-1097, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36620917

RESUMEN

BACKGROUND: Childhood cancer has a cure rate of as low as 15% in low-income countries, suggesting a need for cheaper treatment options. Fluoxetine is a thoroughly safety-tested drug that may target the sigma-1 receptor (σ1-R). RESEARCH DESIGN AND METHODS: Using the human leukemic cell line, Jurkat, we investigated the effects of fluoxetine on cell survival using XTT and trypan blue staining. Apoptosis was measured using AnnexinV/PI staining and western blot analysis of caspase cleavage. IL-2 secretion of Jurkat cells in response to PHA/PMA was measured using ELISA, and the expression of AKT/pAKT and the σ1-R were measured using western blotting. RESULTS: Fluoxetine-induced apoptosis and G-2 cell cycle arrest. Fluoxetine reduced IL-2 secretion dose-dependently and could be further potentiated by σ1-R antagonist BD1047 (P < 0.05). Fluoxetine inhibited pAKT six hours post-treatment (P < 0.05). The expression of the σ1-R showed a significant increase between 12 to 48 hours in Jurkat cells (P < 0.05). At the same time, there was a substantial increase in autophagy. CONCLUSIONS: Fluoxetine may have the potential for acute leukemia treatment. Co-treatment with a σ1-R antagonist increases fluoxetine-induced apoptosis, possibly targeting AKT phosphorylation and autophagy activation.


Asunto(s)
Fluoxetina , Leucemia Linfoide , Humanos , Niño , Fluoxetina/farmacología , Interleucina-2/farmacología , Citocinas , Proteínas Proto-Oncogénicas c-akt , Regulación hacia Arriba , Reposicionamiento de Medicamentos , Autofagia , Apoptosis , Receptor Sigma-1
8.
Sci Rep ; 11(1): 596, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33436817

RESUMEN

Bacopa monnieri (Linn.) Wettst. has been used in traditional medicine as a drug to enhance and improve memory. In this regard, this study aims to provide B. monnieri's efficacy as a neuroprotective drug and as a nootropic against various neurological diseases. Literatures were collected, following Prisma guidelines, from databases, including Scopus, PubMed, Google Scholar, and Science Direct and were scrutinized using a quality scoring system. Means, standard deviations and 'n' numbers were extracted from the metrics and analyzed. Jamovi computer software for Mac was used to carry out the meta-analysis. The selected studies suggested that the plant extracts were able to show some improvements in healthy subjects which were determined in Auditory Verbal Learning Task, digit span-reverse test, inspection time task and working memory, even though it was not significant, as no two studies found statistically significant changes in the same two tests. B. monnieri was able to express modest improvements in subjects with memory loss, wherein only a few of the neuropsychological tests showed statistical significance. B. monnieri in a cocktail with other plant extracts were able to significantly reduce the effects of Alzheimer's disease, and depression which cannot be solely credited as the effect of B. monnieri. Although in one study B. monnieri was able to potentiate the beneficial effects of citalopram; on the whole, currently, there are only limited studies to establish the memory-enhancing and neuroprotective effects of B. monnieri. More studies have to be done in the future by comparing the effect with standard drugs, in order to establish these effects clinically in the plant and corroborate the preclinical data.


Asunto(s)
Antidepresivos/farmacología , Bacopa/química , Disfunción Cognitiva/prevención & control , Depresión/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Nootrópicos/farmacología , Extractos Vegetales/farmacología , Humanos , Metaanálisis como Asunto
9.
Expert Opin Ther Targets ; 25(6): 435-449, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34236922

RESUMEN

Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor.Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs.Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.


Asunto(s)
Antivirales/uso terapéutico , Autofagia , Tratamiento Farmacológico de COVID-19 , Hospitalización/estadística & datos numéricos , Receptores sigma/fisiología , COVID-19/mortalidad , COVID-19/virología , Humanos , SARS-CoV-2/aislamiento & purificación , Receptor Sigma-1
10.
Expert Opin Ther Targets ; 24(10): 1009-1028, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32746649

RESUMEN

INTRODUCTION: The sigma receptors are found abundantly in the central nervous system and are targets for the treatment of various diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), depression, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). However, for many of these diseases, other receptors and targets have been the focus of the most, such as acetylcholine esterase inhibitors in Alzheimer's and dopamine replacement in Parkinson's. The currently available drugs for these diseases have limited success resulting in the requirement of an alternative approach to their treatment. AREAS COVERED: In this review, we discuss the potential role of the sigma receptors and their ligands as part of a multi receptor approach in the treatment of the diseases mentioned above. The literature reviewed was obtained through searches in databases, including PubMed, Web of Science, Google Scholar, and Scopus. EXPERT OPINION: Given sigma receptor agonists provide neuroprotection along with other benefits such as potentiating the effects of other receptors, further development of multi-receptor targeting ligands, and or the development of multi-drug combinations to target multiple receptors may prove beneficial in the future treatment of degenerative diseases of the CNS, especially when coupled with better diagnostic techniques.


Asunto(s)
Encefalopatías/tratamiento farmacológico , Terapia Molecular Dirigida , Receptores sigma/agonistas , Animales , Encefalopatías/fisiopatología , Humanos , Ligandos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacología , Receptores sigma/metabolismo
11.
Nutrients ; 12(12)2020 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-33317106

RESUMEN

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) (Rn) is an herbaceous shrub native to Thailand and much of South and Southeast Asia. It has several synonyms and local or common names. The root of Rn is used in Thai traditional medicine to treat snake bites, and the roots and/or leaves can be made into a balm and applied to the skin for the treatment of skin infections such as ringworm, or they may be brewed to form an infusion for the treatment of inflammatory disorders. Rn leaves are available to the public for purchase in the form of "tea bags" as a natural herbal remedy for a long list of disorders, including diabetes, skin diseases (antifungal, ringworm, eczema, scurf, herpes), gastritis, raised blood pressure, improved blood circulation, early-stage tuberculosis antitumor activity, and as an antipyretic. There have been many studies investigating the roles of Rn or compounds isolated from the herb regarding diseases such as Alzheimer's and other neurodegenerative diseases, cancer, diabetes and infection with bacteria, fungi or viruses. There have, however, been no clinical trials to confirm the efficacy of Rn in the treatment of any of these disorders, and the safety of these teas over long periods of consumption has never been tested. This review assesses the recent research into the role of Rn and its constituent compounds in a range of diseases.


Asunto(s)
Acanthaceae , Diabetes Mellitus/tratamiento farmacológico , Infecciones/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Humanos , Hojas de la Planta , Raíces de Plantas
13.
EXCLI J ; 12: 102-14, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-26417220

RESUMEN

Ursolic acid (UA) is a pentacyclic triterpenoid carboxylic acid that is found in plants and herbal products. It is one of the chemopreventive agents, which can suppress cancer cell proliferation and induce apoptosis. UA possesses various biological activities including anticancer, anti-inflammatory, anti-oxidative and hepatoprotective activity. We investigated the effect of UA on cytokine production via the MAPK pathways in Jurkat leukemic T-cells, showing that UA inhibited cell growth and proliferation of Jurkat cells, as well as suppressing PMA/PHA induced IL-2 and TNF-α production in a concentration and time dependent manner. The inhibition of IL-2 and TNF-α production by UA involved the c-Jun N-terminal kinase (JNK) pathway, but not the extracellular-signal regulated protein kinase (ERK) pathway. Future utilization of UA as a chemopreventive or therapeutic agent may provide an alternative option for leukemia treatments.

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