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1.
Biol Res ; 47: 56, 2014 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-25418600

RESUMEN

BACKGROUND: The study was conducted to evaluate the in vitro thrombolytic activity, and in vivo analgesic, anti-inflammatory and antipyretic potentials of different hydrocarbon soluble extracts of Litsea glutinosa leaves for the first time widely used in the folkloric treatments in Bangladesh. This work aimed to create new insights on the fundamental mechanisms of the plant extracts involved in these activities. RESULTS: In thrombolytic activity assay, a significant clot disruption was observed at dose of 1 mg/mL for each of the extracts (volume 100 µL) when compared to the standard drug streptokinase. The n-hexane, ethyl acetate, chloroform, and crude methanolic extracts showed 32.23 ± 0.26, 37.67 ± 1.31, 43.13 ± 0.85, and 46.78 ± 0.9% clot lysis, respectively, whereas the positive control streptokinase showed 93.35 ± 0.35% disruption at the dose of 30,000 I.U. In hot plate method, the highest pain inhibitory activity was found at a dose of 500 mg/kg of crude extract (15.54 ± 0.37 sec) which differed significantly (P <0.01 and P <0.001) with that of the standard drug ketorolac (16.38 ± 0.27 sec). In acetic acid induced writhing test, the crude methanolic extract showed significant (P <0.01 and P <0.001) analgesic potential at doses 250 and 500 mg/kg body weight (45.98 and 56.32% inhibition, respectively), where ketorolac showed 64.36% inhibition. In anti-inflammatory activity test, the crude methanolic extract showed significant (P <0.001) potential at doses 250 and 500 mg/kg body weight (1.51 ± 0.04 and 1.47 ± 0.03 mm paw edema, respectively), where ketorolac showed 1.64 ± 0.05 mm edema after 3 h of carrageenan injection. In antipyretic activity assay, the crude extract showed notable reduction in body temperature (32.78 ± 0.46°C) at dose of 500 mg/kg-body weight, when the standard (at dose 150 mg/kg-body weight) exerted 33.32 ± 0.67°C temperature after 3 h of administration. CONCLUSIONS: Our results yield that the crude hydroalcoholic extract has better effects than the other in all trials. In the context, it can be said that the leaves of L. glutinosa possess remarkable pharmacological effects, and justify its traditional use as analgesic, antipyretic, anti-inflammatory, and thrombolytic agent.


Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Antipiréticos/uso terapéutico , Fibrinolíticos/uso terapéutico , Litsea/química , Fitoterapia , Ácido Acético , Animales , Edema/inducido químicamente , Edema/tratamiento farmacológico , Femenino , Fibrinólisis/efectos de los fármacos , Humanos , Masculino , Medicina Tradicional , Metanol , Ratones , Extractos Vegetales/farmacología , Hojas de la Planta/química
2.
Biol Res ; 47: 45, 2014 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-25299748

RESUMEN

BACKGROUND: The study was conducted to evaluate the in vitro antimicrobial activity, cytotoxic, and membrane stabilization activities, and in vivo antiemetic and antipyretic potentials of ethanolic extract, n-hexane and ethyl acetate soluble fractions of Spilanthes paniculata leaves for the first time widely used in the traditional treatments in Bangladesh. RESULTS: In antipyretic activity assay, a significant reduction (P < 0.05) was observed in the temperature in the mice tested. At dose 400 mg/kg-body weight, the n-hexane soluble fraction showed the effect (36.7 ± 0.63°C ) as like as the standard (dose 150 mg/kg-body weight) after 5 h of administration. Extracts showed significant (P < 0.001) potential when tested for the antiemetic activity compared to the standard, metoclopramide. At dose 50 mg/kg-body weight, the standard showed 67.23% inhibition, whereas n-hexane and ethyl acetate soluble fractions showed 37.53% and 24.93% inhibition of emesis respectively at dose 400 mg/kg-body weight. In antimicrobial activity assay, the n-hexane soluble fraction (400 µg/disc) showed salient activity against the tested organisms. It exerts highest activity against Salmonella typhi (16.9 mm zone of inhibition); besides, crude, and ethyl acetate extracts showed resistance to Bacillus cereus and Bacillus subtilis, and Vibrio cholera respectively. All the extracts were tested for lysis of the erythrocytes. At the concentration of 1mg/ml, ethanol extract, and n-hexane and ethyl acetate soluble fractions significantly inhibited hypotonic solution induced lysis of the human red blood cell (HRBC) (27.406 ± 3.57, 46.034 ± 3.251, and 30.72 ± 5.679% respectively); where standard drug acetylsalicylic acid (concentration 0.1 mg/ml) showed 77.276 ± 0.321% inhibition. In case of heat induced HRBC hemolysis, the plant extracts also showed significant activity (34.21 ± 4.72, 21.81 ± 3.08, and 27.62 ± 8.79% inhibition respectively). In the brine shrimp lethality bioassay, the n-hexane fraction showed potent (LC50 value 48.978 µg/ml) activity, whereas ethyl acetate fraction showed mild (LC50 value 216.77 µg/ml) cytotoxic activity. CONCLUSIONS: Our results showed that the n-hexane extract has better effects than the other in all trials. In the context, it can be said that the leaves of S. paniculata possess remarkable pharmacological effects, and justify its folkloric use as antimicrobial, antipyretic, anti-inflammatory, and antiemetic agent. Therefore, further research may be suggested to find possible mode of action of the plant part.


Asunto(s)
Antibacterianos/farmacología , Antieméticos/farmacología , Antipiréticos/farmacología , Asteraceae/química , Citotoxinas/farmacología , Membrana Eritrocítica/efectos de los fármacos , Acetatos , Animales , Artemia/efectos de los fármacos , Asteraceae/clasificación , Bacillus cereus/efectos de los fármacos , Bacillus subtilis/efectos de los fármacos , Bioensayo/mortalidad , Pollos , Pruebas Antimicrobianas de Difusión por Disco , Membrana Eritrocítica/fisiología , Escherichia coli/efectos de los fármacos , Etanol , Hexanos , Calor , Humanos , Medicina Tradicional , Ratones , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/farmacología , Hojas de la Planta/química , Salmonella typhi/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Vibrio cholerae/efectos de los fármacos
3.
Clin Pathol ; 17: 2632010X241228039, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38313416

RESUMEN

Salt enhances the taste as well as the nutritional value of food. Besides, several reports are available on the incidence and epidemiology of various illnesses in relation to salt intake. Excessive salt consumption has been found to be linked with high blood pressure, renal disease, and other cardiovascular disorders due to the result of vascular inflammation. Nevertheless, studies aimed at elucidating the molecular processes that produce vascular inflammation have yet to reach their conclusions. This article emphasizes the significance of investigating the mechanisms underlying both acute and chronic vascular inflammation induced by salt. It also explores the logical inferences behind cellular oxidative stress and the role of endothelial dysfunction as the potential initiator of the inflammatory segments that remain poorly understood. It is therefore hypothesized that salt is one of the causes of chronic vascular inflammation such as atherosclerosis. The hypothesis's secrets, when revealed, can help assure cardiovascular health by proactive efforts and the development of appropriate preventative measures, in combination with medication, dietary and lifestyle adjustments.

4.
Health Sci Rep ; 7(6): e2178, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38915360

RESUMEN

Background: Despite being preventable, cervical cancer remains a leading cause of mortality among Bangladeshi women. This article addresses the trends in Bangladesh's response to the World Health Organization's (WHO) request for the eradication of cervical cancer within the nation. Discussion: When it comes to cervical cancer, healthcare institutions need to be concerned in terms of protocols for diagnosis and treatment, staff education, and available resources. More than a quarter of all female cancers in Bangladesh are caused by cervical cancer, which can be prevented through better healthcare infrastructure, earlier diagnosis, more qualified healthcare professionals, improved urban and rural hospital infrastructure, community-based clinics, expanded affordable vaccinations, school-based delivery systems, adoption of single-dose vaccine schedules, raising awareness, and compiling a registry of previously affected results. WHO applauds Bangladesh's Ministry of Health and Family Welfare for its efforts to develop the National Strategy for cervical cancer prevention and control, which will guide and strengthen the country's activities to prevent and treat cervical cancer. Conclusion: The endeavor to eradicate this global disease burden should not be limited to Bangladesh; all nations should participate collectively to prevent the malignancy from returning and threatening human civilization.

5.
SAGE Open Med ; 12: 20503121241239538, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38533198

RESUMEN

Guillain-Barré syndrome is a rare condition that can be potentially life-threatening. Guillain-Barré syndrome does not have a definitive etiological agent. It is a syndrome that can arise from multiple factors, including various infectious diseases and immunizations. The severity of Guillain-Barré syndrome is exacerbated by these variables, especially in low-income and middle-income countries where healthcare systems are already constrained and struggle to meet the demands of other diseases. The primary aim of our article is to comprehensively examine the life-threatening nature and intensity of Guillain-Barré syndrome by assessing its etiology, progression, and prevalence in low- and middle-income nations while also considering global trends. Furthermore, we proposed the implementation of standard and efficacious treatment and diagnostic resources that are readily accessible and successful in affluent nations and should also be readily accessible in impoverished nations without any unnecessary delay. Our study also emphasized the epidemiological data with molecular epidemiological analysis and the utilization of artificial technology in low- and middle-income nations. The goal was to decrease the incidence of Guillain-Barré syndrome cases and facilitate early detection.

6.
Environ Health Insights ; 18: 11786302241246453, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38585332

RESUMEN

Asia has been alarmed by the resurgence of avian influenza A (H5N1) in Cambodia in 2024. H5N1 could be swiftly transmitted by wild birds to poultry populations along their migration route via infection. Circulation of endemic H5N1 in Asian poultry facilitates recurrent human transmission. Cambodia's role as a reservoir heightens the potential dangers of uncoordinated containment and surveillance across Southeast Asia. This correspondence addresses the risk factors, seasonal patterns, transmission dynamics, and potential pathways for the global dissemination of H5N1. This underscores the criticality of supervising regional initiatives aimed at eliminating the virus from poultry and humans, before its potential escalation into a deadly influenza pandemic across Asia.

7.
Health Sci Rep ; 7(7): e2223, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38946778

RESUMEN

Background: This article explored the possibility that the Mpox virus (MPXV) may initiate or stimulate the consequences of vascular inflammation. In 1970, it was discovered that Macaca cynomolgus primates infected with MPXV also infected humans in the Democratic Republic of the Congo. Discussion: The study demonstrates that MPXV invades host cells via viral proteins and surface receptors, initiating the release of diverse inflammatory mediators such as IL-1, IL-6, TNF-α, CCL2, CXCL2, CXCL8, CXCL10, and so forth probably through endothelial dysfunction by reactive oxygen species production. In general, these mediators have been found to contribute to vascular inflammation and the formation of atherosclerotic plaque at a later stage, which may contribute to the onset of vascular inflammation. Conclusion: The discussed association between vascular inflammation and Mpox has the potential to be an important finding in the field of vascular biology research.

8.
Health Sci Rep ; 7(2): e1912, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38361805

RESUMEN

Background: ChatGPT is an artificial intelligence (AI) language model that has gained popularity as a virtual assistant because of its exceptional capacity to solve problems and make decisions. However, there are some ways in which technological misuse and incorrect interpretations can have potentially hazardous consequences for a user's mental health. Discussion: Because it lacks real-time fact-checking capabilities, ChatGPT may create misleading or erroneous information. Considering AI technology has the potential to influence a person's thinking, we anticipate ChatGPT's future repercussions on mental health by considering instances in which inappropriate usage may lead to mental disorders. While several studies have demonstrated how the AI model may transform mental health care and therapy, certain drawbacks, including bias and privacy violations, have also been identified. Conclusion: Educating people and organizing workshops on AI technology usage, strengthening privacy measures, and updating ethical standards are crucial initiatives to prevent misuse and resultant dire impacts on mental health. Longitudinal research on the potential of these platforms to impact a variety of mental health problems is recommended in the future.

9.
Health Sci Rep ; 7(5): e2077, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38725559

RESUMEN

Background and Aims: Bangladesh has been going through outbreaks of dengue fever cases every year since 2000. Yet this year's (2023) episode of dengue fever has crossed every line concerning fatality. Symptoms of the fever range from high fever, headaches, and muscle aches to deadly dengue hemorrhagic fever (DHF). The present review aims to assess the current pathogenicity and associated risk factors of recent dengue outbreaks in Bangladesh. Methods: To perform this review work, we extracted relevant information from published articles available in PubMed, Scopus, and Google Scholar. We used dengue virus, dengue fever, and dengue outbreaks as keywords while searching for information. Results: This Aedes mosquito-transmitted viral fever is more common in Bangladesh because of the tropical nature and immense burden of populations, resulting in convenient conditions for the reproduction of the vector. The rapid genetic transformation of this RNA virus and the resistance of its vector against insecticides have intensified the situation. The number of hospitalized patients has increased, and the case fatality rate has risen to 0.47%. Inadequate mosquito control measures, plenty of vector breeding sites, and a lack of public awareness have worsened the situation. Routine spraying of effective insecticides in high-risk zones, regular inspection of potential mosquito breeding sites, and public awareness campaigns are the keys to limiting the spread of this virus. Also, the availability of detection kits, improved hospital settings, and trained health professionals are mandatory to keep disease fatalities under control. Conclusion: Dengue fever is a preventable disease. The successful development of a competent vaccine is now a prime need for preventing any future upsurge of the disease. Also, we recommend public awareness, vector control activities, and global collaboration to prevent spread.

10.
Health Sci Rep ; 6(9): e1567, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37711675

RESUMEN

Background: One of the most pressing issues in healthcare today is the prevention of Adenovirus (AdV) infections. Children and the elderly, both of whom have weaker immune systems than healthy adults, are more vulnerable to infection. Discussion: India has been the epicenter of a recent AdV epidemic in the South Asian area. Most of the nations, bordering India are still developing and have very low per capita incomes, yet their citizens often cross into India for trade, medical care, and vacation. Conclusion: We are concerned that an epidemic of the AdV might occur in the Indian subcontinent, spread to other nations, and eventually affect the whole world if effective preventative and diagnostic measures are not taken.

11.
Environ Health Insights ; 17: 11786302231206126, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37822683

RESUMEN

Dhaka, which is the capital and largest metropolis of Bangladesh, has seen an increase in the number of documented cases of respiratory disorders. Every day in Dhaka city, a remarkable number of patients are being diagnosed with poor respiratory conditions. The majority of these patients have no other severe disease history and mostly need to be exposed to outdoor air to meet their occupational requirements, indicating that the ailment may be associated with polluted air. As this is the most pressing issue that must be addressed in order to safeguard public health, we have made an effort to focus on the current situation surrounding the sources of air pollution in the city. Since this is a viewpoint article, we gathered data from various published articles, national dailies, and international reports generated by WHO, CDC, BBC, or other environmental news/report portals to highlight the public health issue related to respiratory health. Poor respiratory health is one of the main consequences of Dhaka's contaminated air, as determined by our analysis.

12.
Health Sci Rep ; 6(7): e1410, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37425230

RESUMEN

Background: Disease prevention and healthcare policy choices cannot be made without epidemiology data. Since it is a growing country with rapidly increasing illness rates, this information is in great demand in Bangladesh. This is because there is a shortage of reliable and sufficient data, leading to inadequate preventive and treatment methods. Discussion: Poor health concerns and economic conditions mean that not all families can afford to provide the nutrition their members need, leading to an increase in the prevalence of many diseases. The outcome is an ever-increasing threat of cardiovascular disease (CVD) issues, the leading cause of death in Bangladesh, even though the underlying causes remain unknown. There is a strong demand for accurate information on CVD patients in Bangladesh, however, there is no effective framework for managing epidemiological data. This prevents an in-depth analysis of the nation's socioeconomic status, dietary practices, and way of life, as well as the implementation of sound healthcare policy. Conclusion: In this article, we present arguments on this important issue using the healthcare systems of the developed world and Bangladesh as examples.

13.
Environ Health Insights ; 17: 11786302231212774, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38035255

RESUMEN

Bangladesh is widely recognized as one of the dengue prone nations, and empirical evidence has consistently demonstrated an upward trend in the severity of the disease over time. With the persistent occurrence of dengue in Bangladesh and the ongoing presence of COVID-19, which has not been fully eradicated and may persist for an uncertain period of time, there is a high probability of co-infection between these 2 illnesses. Given the circumstances, the concurrent occurrence of the COVID-19 and dengue epidemics, along with the potential co-infection, may pose an overwhelming burden on healthcare systems that are already grappling with challenges in meeting the existing demand. Due to a lack of awareness, an inadequate health infrastructure, and ineffective disease prevention initiatives, the country is now more susceptible to the threat posed by a co-infection that has been found to be associated with more severe outcomes, marked by significant morbidity and mortality. The objective of this opinion piece is to explore the gravity of co-infection in Bangladesh, as well as the potential challenges to overcome and the preventative measures that need to be implemented to address the severity. This opinion piece proposes a set of modern preventative strategies that, when integrated with conventional methods, have the potential to mitigate disease severity, avert the occurrence of co-infection between COVID-19 and dengue, and halt the co-epidemics of COVID-19 and dengue.

14.
Clin Pathol ; 16: 2632010X231183314, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37360520

RESUMEN

Viral epidemics of variable frequency and severity have wreaked havoc and panic across the world. The Nipah virus (NiV), which has been linked to multiple outbreaks, mostly in South and Southeast Asia, is regarded as one of the deadliest in the world. In Bangladesh, seasonal outbreaks of encephalitis caused by the NiV have occurred annually since 2003. In particular, NiV has numerous characteristics that highlight its potential as a pandemic danger, such as its human-to-human transmission capability and its propensity to infect humans directly from natural reservoirs and/or from other animals. Numerous types of research investigate the pathophysiology and viral mechanisms of disease progression. The NiV and its disease have been studied thoroughly but attempts to implement preventive techniques have met cultural and social obstacles. This review highlights the NiV outbreaks, and its present status, the preventative and control measures implemented, the potential causes of the outbreaks in Bangladesh, and the precautions that must be taken by both government and nongovernment entities to contain the outbreaks and assure a future with fewer or no occurrences.

15.
Int Immunopharmacol ; 99: 108049, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34426104

RESUMEN

Setting up treatment strategies is the highest concern today to reduce the fatality of COVID-19. Due to a very new kind of virus attack, no specific treatment has been discovered to date. The most crucial way to dominate the disease severity is now the repurposing of drugs. In this review, we focused on the current treatment approaches targeting the crucial causative factors for the disease burden through cytokine storm or cytokine release syndrome. Several vaccines have been developed and have been applied already for prevention purposes, and several are on the way to be developed, although the effects and side effects are under observation. Presently, regulation of the immune response through intervention treatment methods has been adjusted on the basis of the COVID-19 severity stage and generally includes vaccines, immunotherapies including convalescent plasma and immunoglobulin treatment, monoclonal antibodies, cytokine therapy, complement inhibition, regenerative medicine, and repurposed anti-inflammatory and immune-regulatory drugs. Combination therapy is not acceptable in all respects because there is no concrete evidence in clinical trials or in vivo data. Target-specific drug therapies, such as inhibition of cytokine-producing signaling pathways, could be an excellent solution and thus reduce the severity of inflammation and disease severity. Therefore, gathering information about the mechanism of disease progression, possible goals, and drug efficacy of immune-based approaches to combat COVID-19 in the context of orderly review analysis is consequential.


Asunto(s)
Antiinflamatorios/uso terapéutico , Tratamiento Farmacológico de COVID-19 , COVID-19/inmunología , Síndrome de Liberación de Citoquinas/metabolismo , Citocinas/metabolismo , Progresión de la Enfermedad , Reposicionamiento de Medicamentos , Humanos , SARS-CoV-2 , Índice de Severidad de la Enfermedad
16.
FEBS Open Bio ; 11(5): 1374-1381, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33715310

RESUMEN

Leukocytes play an important role in vascular inflammation prior to atherosclerosis. In particular, monocyte adhesion and migration to the endothelium contribute to the development of vascular inflammation. Previously, we showed the importance of neutrophils and complement C5a in the early phase of vascular inflammation in mice fed a high-fat diet. However, the relationship between monocytes and neutrophils is not well understood. In this study, we elucidated the involvement of neutrophils in the migration of monocytes. We observed that C5a induces CCL2 expression in neutrophil-like dHL-60 cells. To investigate the physiological significance of CCL2 secretion, we performed a chemotaxis assay. Interestingly, dHL-60 culture supernatant in the presence of C5a enhanced the migration of THP-1 in comparison with the absence of C5a. Furthermore, CCL2 expression and secretion significantly increased in C5a-stimulated dHL-60 through the phosphorylation of NF-κB p65. Actin polymerization on THP-1 was enhanced by the presence of C5a compared with the absence of C5a when stimulated by a dHL-60-cultured medium. These results suggest that crosstalk between neutrophils and monocytes via CCL2 may play an important role in vascular inflammation.


Asunto(s)
Quimiocina CCL2/metabolismo , Complemento C5a/farmacología , Leucocitos Mononucleares/metabolismo , Diferenciación Celular/fisiología , Línea Celular , Movimiento Celular/fisiología , Células Cultivadas , Quimiocina CCL2/fisiología , Complemento C5a/metabolismo , Complemento C5a/fisiología , Células HL-60 , Humanos , Interleucina-8/metabolismo , Leucocitos/metabolismo , Leucocitos Mononucleares/fisiología , Monocitos/citología , Monocitos/inmunología , Monocitos/metabolismo , Neutrófilos/metabolismo , Células THP-1/metabolismo
17.
Health Sci Rep ; 4(2): e291, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34013069

RESUMEN

BACKGROUND: Schizophrenia (SCZ) is an incurable neuropsychiatric disorder generally described by impaired social behavior and altered recognition of reality. For the first time, this study explored serum levels of antioxidants (vitamin A, E, and C), malondialdehyde (MDA), macro-minerals (calcium, potassium, and sodium), and trace elements (zinc, iron, and selenium) in Bangladeshi patients with SCZ and thereby, discovering any pathophysiological correlation. METHODS: This case-controlled study evaluated 63 patients with SCZ as cases and 63 healthy individuals as controls. Vitamin A and E levels were defined by RP-HPLC. MDA and vitamin C levels were measured by using UV spectrophotometry, and macro and trace elements by atomic absorption spectroscopy. RESULTS: This study found significantly (P ≤ 0.05) elevated MDA levels and decreased levels of antioxidants-vitamin A, C, and E and significantly (P ≤ 0.05) diminished levels of macro and trace elements in cases in contrast to the controls. Serum levels of zinc (Zn), selenium (Se), iron (Fe), potassium (K), calcium (Ca), and sodium (Na) were determined to be 0.33 ± 0.008, 0.0252 ± 0.00060, 0.24 ± 0.01, 64.18 ± 2.72, 36.88 ± 2.56, and 2657.5 ± 53.32 mg/L, respectively, in cases, whereas 0.79 ± 0.03, 0.0650 ± 0.00355,0.78 ± 0.03, 168.01 ± 2.85, 86.43 ± 2.55, and 3200.8 ± 29.96 mg/L, respectively, were determined in controls. Pearson's correlation analysis revealed a negative correlation between Zn and Na, Zn and K, Zn and Ca, Zn and Fe, Zn and Se, Fe and Na, and Fe and Se in patients. CONCLUSIONS: The findings connect that the pathogenesis of SCZ may have a correlation with altered levels of antioxidants, MDA, macro-minerals, and trace elements.

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