Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Chemosphere ; 356: 141767, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537715

RESUMO

The current review highlights the complex behavior of thallium (Tl) in soil and plant systems, offering insight into its hazardous characteristics and far-reaching implications. The research investigates the many sources of Tl, from its natural existence in the earth crust to its increased release through anthropogenic activities such as industrial operations and mining. Soil emerges as a significant reservoir of Tl, with diverse physicochemical variables influencing bioavailability and entrance into the food chain, notably in Brassicaceae family members. Additionally, the study highlights a critical knowledge gap concerning Tl influence on legumes (e.g., soybean), underlining the pressing demand for additional studies in this crucial sector. Despite the importance of leguminous crops in the world food supply and soil fertility, the possible impacts of Tl on these crops have received little attention. As we traverse the ecological complexity of Tl, this review advocates the collaborative research efforts to eliminate crucial gaps and provide solutions for reducing Tl detrimental impacts on soil and plant systems. This effort intends to pave the path for sustainable agricultural practices by emphasizing the creation of Tl-tolerant legume varieties and revealing the complicated dynamics of Tl-plant interactions, assuring the long-term durability of our food systems against the danger of Tl toxicity.


Assuntos
Poluentes do Solo , Solo , Tálio , Tálio/análise , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Produtos Agrícolas/metabolismo , Agricultura , Plantas/metabolismo , Monitoramento Ambiental , Fabaceae/metabolismo , Fabaceae/crescimento & desenvolvimento
2.
Mini Rev Med Chem ; 23(10): 1079-1089, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36788701

RESUMO

It is estimated that viral infections contribute 15-20% of all human cancers. Several types of human papillomaviruse (HPV) are related to the development of many cancer types and their treatment. About 200 HPV viruses have been identified, and each type of virus is integrated with a certain type of clinical lesions affecting the areas of skin and mucous membranes. Infections associated with HPV are known to cause multiple cancer types such as uterine cancer, cervical, vaginal carcinoma, and other varieties of carcinomas such as genital and oropharyngeal, penile, and short-lived carcinomas. Most of the HPV types are considered as high-risk mutants that can provoke cervical cancer in females in addition to significant contribution to other cancer types such as anogenital cancer and tumor in head and neck regions. Among them, high risk human papilloma viruses (HR-HPV) subtypes 16 and 18 play a major role in the etiology of cervical cancer worldwide. Although, cervical cancer incidence and fatality rates vary greatly depending on geographical area, it is the leading cause of mortality in women around the world. In addition, it is epidemiologically similar to a sexually transmitted disease of low infectivity. In this review article, the association of HPV with different types of cancers have been explained, but the main focus remains on cervical cancer.


Assuntos
Infecções por Papillomavirus , Infecções Sexualmente Transmissíveis , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Papillomavirus Humano , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Detecção Precoce de Câncer , Papillomaviridae
3.
Environ Sci Pollut Res Int ; 30(13): 35945-35957, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36538227

RESUMO

Semi-volatile organic compounds (SVOCs) are a major global problem that causes the greatest impact on urban settings and have been linked to bronchial asthma in both children and adults in Pakistan. The association between exposure of polycyclic aromatic hydrocarbons (PAHs) and asthma in the adult population is less clear. The current study aimed to assess the clinico-chemical parameters and blood levels of naphthalene phenanthrene, pyrene, and 1,2-benzanthracene and urinary levels of 1-OH pyrene and 1-OH phenanthrene as well as asthma-related biomarkers immunoglobulin E (IgE), resistin, and superoxide dismutase (SOD) of oxidative stress and other hematologic parameters in adults and their relationship with bronchial asthma. The GC/MS analysis showed higher mean concentrations of blood PAHs in asthma respondents (4.48 ± 1.34, 3.46 ± 1.04, 0.10 ± 0.03, and 0.29 ± 0.09) (ng/mL) as compared to controls (3.07 ± 0.92, 1.71 ± 0.51, 0.06 ± 0.02, and 0.11 ± 0.03) (ng/mL), with p = .006, p = .001, p = .050, and p = .001. Similarly, urinary levels of 1-OHpyr and 1-OHphe were significantly increased in adults with bronchial asthma (0.54 ± 0.16; 0.13 ± 0.04) (µmol/mol-Cr) than in controls (0.30 ± 0.09; 0.05 ± 0.02) (µmol/mol-Cr), with p = .002 and p = .0001, respectively, with a significant positive correlation to asthma severity. The asthma-related biomarkers IgE, resistin, and SOD were significantly higher (p 0.0001, 0.0001, and 0.0001) in people with asthma than in control persons. The findings showed that higher blood and urine PAHs levels were linked to higher asthma risk in adults and significant interaction with participants who smoked, had allergies, had a family history of asthma, and were exposed to dust. The current study's findings will be useful to local regulatory agencies in Lahore in terms of managing exposure and advocating efforts to minimize PAH pollution and manage health.


Assuntos
Asma , Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Criança , Humanos , Adulto , Hidrocarbonetos Policíclicos Aromáticos/análise , Resistina , Pirenos , Biomarcadores , Asma/epidemiologia , Superóxido Dismutase
4.
Environ Sci Pollut Res Int ; 30(4): 8682-8697, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35220536

RESUMO

Air pollution levels rise as a result of industrial and vehicular emissions, epidemiological issues such as asthma become more prevalent in Lahore, Punjab, Pakistan and cause adverse public health effects. Many studies explored the association between air pollutants and frequency of asthma hospital visits, although their effects are unclear. This study examined the link between air pollution, asthma, and socioeconomic and demographic factors. A questionnaire survey was administered among four age groups (15-25, 25-45, 45-60, and over 60 years old) in public and private hospitals of Lahore city. Daily average concentrations of five air pollutants including carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter (PM2.5 and PM10) were recorded at ten fixed air monitoring sites in Lahore city. There were favorable connections between outpatient department (OPD) asthma visits (64%) and levels of outdoor air quality during winter season throughout the study period. The correlation between 1, 29, and 370 asthma patients and average daily air pollution levels found that the condition was more prevalent in females (53%) than males (47%). There was a significant correlation between PM10 exposure and asthma OPD visits in the city (p 0.001), as well as the elevated PM10 levels were substantially linked with OPD asthma visits over the winter season in the city. The hazard index (HI) for all adult population was estimated 0.001132. The study's findings indicate that exposure to ambient air pollution is a significant predictor of asthma hospital visits, particularly among the elderly. Strategies can be developed by policymakers in response to the worrying situation of allergic disease asthma in industrial cities due to air pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Ozônio , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Asma/epidemiologia , Asma/induzido quimicamente , Cidades , Dióxido de Nitrogênio/análise , Ozônio/análise , Material Particulado/análise , Grupos Populacionais , Dióxido de Enxofre/análise , Adolescente , Adulto Jovem
5.
Sci Rep ; 12(1): 2459, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165345

RESUMO

During two consecutive summer and winter seasons in Lahore, the health risk of air and dust-borne polycyclic aromatic hydrocarbons (PAHs) was evaluated. Gas chromatography/mass spectrometry (GS/MS) was used to determine air and dust samples from various functional areas across the city. The mean ∑16PAHs were higher in air 1035.8 ± 310.7 (pg m-3) and dust 963.4 ± 289.0 (ng g-1 d.w.) during winter seasons as compared to summer seasons in air 1010.9 ± 303.3 (pg m-3) and dust matrices 945.2 ± 283.6 (ng g-1 d.w.), respectively. PAHs ring profile recognized 3 and 4 rings PAHs as most dominant in air and dust samples. Estimated results of incremental lifetime cancer risk (ILCR) highlighted high carcinogenic risk among the residents of Lahore via ingestion and dermal contact on exposure to atmospheric PAHs. The total ILCR values in air among children (summer: 9.61E - 02, winter: 2.09E - 02) and adults (summer: 1.45E - 01, winter: 3.14E - 02) and in dust, children (summer: 9.16E - 03, winter: 8.80E - 03) and adults (summer: 1.38E - 02, winter: 1.33E - 02) during the study period. The isomeric ratios in the study area revealed mixed PAH sources, including vehicular emission, petroleum, diesel and biomass combustion. As a result, it is advised that atmospheric PAHs should be monitored throughout the year and the ecologically friendly fuels be used to prevent PAHs pollution and health concerns in the city. The findings of this study are beneficial to the local regulating bodies in terms of controlling the exposure and promoting steps to reduce PAHs pollution and manage health in Lahore.

6.
Health Care Women Int ; 43(1-3): 98-113, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34432612

RESUMO

Polycystic Ovary Syndrome is a complicated female disorder worldwide. Researchers conducted a quantitative study to examine multiple environmental determinants contributing to its symptoms severity. Data of 150 PCOS diagnosed women (16 to 45 years) was gathered from private clinics and hospitals of Lahore, Pakistan. Chi-square, spearman's correlation, and linear regression tests were run. Chicken, fast food and spicy food intake were found to be the significant predictors of PCOS severity (F (1, 148) = 6.903, p = 0.01), (F (1, 148) = 11.400, p = 0.001), and (F (1, 148) = 4.525, p = 0.035) respectively. We also found significant relationships of sedentary lifestyle (p = .034) & BMI (p = 0.025) with PCOS symptoms severity. However, relationship of socioeconomic status (SES) was non-significant with the disease severity. These determinants will direct healthcare professionals in proper management and counseling of PCOS women thus improving their life quality.


Assuntos
Síndrome do Ovário Policístico , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Síndrome do Ovário Policístico/psicologia , Qualidade de Vida/psicologia , Comportamento Sedentário , Índice de Gravidade de Doença
7.
Pak J Pharm Sci ; 34(5): 1767-1776, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34803014

RESUMO

This study was aimed at synthesizing liposomes for the topical delivery of chlorpheneramine maleate using three-level factorial design. Each experiment consisted of a varying proportion of cholesterol, lecithin and a permeation enhancer mixture of Tween80 and polyethylene glycol (PEG1000), and resultant liposomes were extensively characterized. The drug release study was conducted at 6.0 pH, 37±1ºC temperature and 100 rpm rotation speed utilizing a cellophane membrane pouch in a USP type II dissolution apparatus. Among formulations, L5 was considered as the optimal formulation because of high drug loading (99.05%), 87.71% drug release within 4 hours, high drug loading and the optimized formulation was found to be stable during stability testing. This high drug loading and release was achieved at low level of cholesterol and lecithin (0.1: 0.3g) and high level of permeation enhancer mixture (0.2g) as revealed by the surface plots. The drug release from the optimized formulation followed Fickian diffusion as revealed by Korsmeyers-Peppas kinetic model. In summary, combination of PEG1000 and Tween80 with lecithin and cholesterol can be successfully used to develop liposomes that efficiently incorporated chlorpheneramine. This formulation therefore has the potential to be used as a topical anti-allergic product.


Assuntos
Clorfeniramina/química , Composição de Medicamentos/métodos , Antagonistas dos Receptores Histamínicos/química , Lipossomos/química , Administração Tópica , Clorfeniramina/administração & dosagem , Liberação Controlada de Fármacos , Antagonistas dos Receptores Histamínicos/administração & dosagem , Estrutura Molecular
8.
Curr Drug Res Rev ; 13(1): 25-35, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32735534

RESUMO

BACKGROUND: Onychomycosis is by far the most common finger or toe nail fungal infectious disease caused by dermatophytes, non-dermatophytic molds or yeast. It accounts for 50% of the total nail disorders, and affects patients physically, socially, and psychologically and can seriously influence their quality of life. OBJECTIVES: Oral antifungals are routinely used to treat the nail fungal disease; however oral therapy is associated with severe side effects and longer treatment times. In recent years, drug delivery directly into the nail or nail bed has gained attention and various topical products have been tested that can cure the disease when applied topically or transungually. Nevertheless, drug penetration into and through the nail is not straightforward and requires chemicals to improve its permeability or by applying physical stress to promote drug penetration into and through the nail. This lucid review presents an overview of various causes of onychomycosis, current therapeutic approaches, and efforts aimed at increasing the permeability of nails through various strategies such as chemical, physical and mechanical methods for permeation enhancement. CONCLUSION: Various strategies have been proposed for the treatment of onychomycosis, however, much research into a more precise and effective therapy is still required.


Assuntos
Antifúngicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Onicomicose/tratamento farmacológico , Administração Tópica , Antifúngicos/farmacocinética , Química Farmacêutica/métodos , Dermatoses do Pé/tratamento farmacológico , Dermatoses do Pé/microbiologia , Dermatoses da Mão/tratamento farmacológico , Dermatoses da Mão/microbiologia , Humanos , Unhas/metabolismo , Unhas/microbiologia , Permeabilidade
9.
Pak J Pharm Sci ; 33(6): 2651-2657, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33867343

RESUMO

Bone marrow suppression is one of the serious consequences of treatment with cytotoxic chemotherapeutic agents such as doxorubicin (DOX). It is very difficult to treat bone marrow suppression caused by anti-cancer drugs. This study was aimed to evaluate hematological effects particularly the antimyelosuppressant effects of ethanolic extract of papaya seeds at 200, 400 and 600 mg/kg daily dose for three weeks in doxorubicin induced hematopoietic suppression in rat model. Hematological parameters were assessed on weekly basis on days 0, 1, 7, 14 and 21. The alcoholic extract was found to cause remission of induced myelosuppression as indicated by a dose dependent increase in WBCs, neutrophils, lymphocytes, platelets, RBCs, Hb, hematocrit & mean corpuscular volume. However, the maximum dose (600mg/kg) of the extract showed maximum activity (p<0.05) in normalizing hematological parameters when compared with group B (induced group) and group A (controlled animals). These effects were compareable with those produced by Filgrastim 5µgm/kg used as standard or reference drug during these experiments. It is concluded from the results that papaya seeds possess myelostimulant activity and can be used to treat myelosuppression caused by chemotherapy. The drug can also be used for curing anemia, thrombocytopenia and immunological disorders characterized by myelosuppression.


Assuntos
Carica/química , Doxorrubicina/efeitos adversos , Hematopoese/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Contagem de Eritrócitos , Índices de Eritrócitos , Etanol/química , Hematopoese/fisiologia , Contagem de Leucócitos , Contagem de Plaquetas , Ratos , Sementes/química
10.
Arch Virol ; 163(4): 997-1008, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29340806

RESUMO

There are over 10 million hepatitis C virus (HCV)-infected patients in Pakistan. For these patients, a combination of interferon with ribavirin is the most economical and easily available treatment. Single-nucleotide polymorphisms in interleukin genes have been reported to be associated with the pathogenesis and clearance of HCV, and sustained virologic response (SVR). An interleukin 28B (IL28B) gene polymorphism has been shown to modify treatment outcomes, but the effects of interleukin 10 (IL10) polymorphisms have not been previously assessed in the Pakistani population. The present study was conducted with 302 subjects categorized into two groups: 100 healthy volunteers (Group I) and 202 patients with chronic HCV (Group II). Patients within Group II were further divided into two subgroups according to therapeutic response: SVR (responders = 132) and NR (non-responders/relapsers = 70). IL28B (rs8099917, rs12979860) and IL10 (rs1800872, rs1800871, rs1800896) gene polymorphisms were studied in all subjects. A significant difference in the distribution of IL28B rs12979860C/T genotypes between the two groups (p<0.05) was observed, while of the three IL10 polymorphisms, a significant difference was only shown for rs1800896 A/G. Haplotype analysis (IL28B and IL10) showed a significant association of TTGTC and TTGTA when comparing the groups. There was a strong association of the favorable alleles rs8099917T and rs12979860C in the SVR group as compared with the NR group (p<0.05), and rs1800896 also showed an association with the SVR group as compared to the NR group (p<0.004). Haplotype analysis showed significant associations when comparing the SVR and NR subgroups, i.e. TCATC (p=0.009), TTGTA (p=0.005), TCATA (p<0.0005), TCACA (p=0.002), GTGCC (p=0.002) and TCGTC (p=0.005). IL28B (rs8099917 and rs12979860) and IL10 (rs1800896) polymorphisms alone, or in combination, are good predictors of therapeutic response in HCV-3a patients.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interleucina-10/genética , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Antivirais/uso terapêutico , Biomarcadores/metabolismo , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Expressão Gênica , Frequência do Gene , Haplótipos , Hepacivirus/classificação , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/imunologia , Humanos , Interferon-alfa/uso terapêutico , Interferons , Interleucina-10/imunologia , Interleucinas/imunologia , Masculino , Pessoa de Meia-Idade , Paquistão , Polietilenoglicóis/uso terapêutico , Prognóstico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico
11.
Iran J Allergy Asthma Immunol ; 16(4): 313-320, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28865411

RESUMO

In Pakistan about 3.7% of the population is suffering from asthma, a chronic inflammatory disorder of airways. Asthma has wide spectrum of predisposing factors including environment and genetics. Many studies have been performed to determine association of asthma with serum IgE and major histocompatibility complex (MHC) alleles but conflicting results were reported. Therefore, present study was designed to determine frequency of HLA-DQß1*0201 and DQß1*0301 alleles in patients with bronchial asthma. This case control study included 85 asthmatic patients and 85 healthy controls. HLA-DQß1*0201 and DQß1*0301 alleles were detected by allele specific PCR and serum IgE was determined by ELISA. Median and inter-quartile range (IQR) of total IgE level were more increased in asthma patients (585.7 IU/mL and 247.2-848.1 IU/mL) compared to healthy controls (65.1 IU/mL and 28.1-181.3 IU/mL) (p<0.001). Frequency of HLA-DQß1*0201 and -DQß1*0301 alleles was more in healthy controls (32% and 38%, p=0.616) as compared to bronchial asthma patients (28% and 26%, p= 0.09). There was a significant association of IgE levels and HLA-DQß1*0201 allele. Patients positive for HLA-DQß1*0201 allele had low level of serum IgE 357.2 IU/mL (153.9-634.3 IU/mL) compared to the patients negative for this HLA allele i.e. 642.9 IU/mL (289.8-1299.5IU/mL) (p=0.005), whereas, HLA-DQß1*0301 allele was not associated with total serum IgE level (p=0.865). Our findings show that HLA-DQß1*0201 and -DQß1*0301 alleles were not associated with asthma; however, HLA-DQß1*0201 allele was associated with low levels of total serum IgE in the study population.


Assuntos
Alelos , Asma/genética , Asma/imunologia , Frequência do Gene , Cadeias beta de HLA-DQ/genética , Imunoglobulina E/imunologia , Adolescente , Adulto , Asma/sangue , Biomarcadores , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Teste de Histocompatibilidade , Humanos , Imunoglobulina E/sangue , Masculino , Razão de Chances , Paquistão/epidemiologia , Projetos Piloto , Adulto Jovem
12.
Springerplus ; 5(1): 1826, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27818864

RESUMO

AIM: Suppressor of Cytokine Signaling 3 (SOCS3) gene belongs to SOCS family as one of the negative regulators of cytokine signaling and IFN response that function via the JAK-STAT pathway in antiviral response. SOCS3 expression and genetic polymorphism influences the pathogenesis and outcome of antiviral treatment in hepatitis C virus (HCV) infected patients. This study was designed for analysis of SOCS3 gene expression and polymorphism in Pakistani HCV patients. METHODS: This descriptive study was conducted on 250 diagnosed HCV genotype 3a infected subjects. The study population was divided into two major groups on the basis of therapeutic response i.e. sustained virological response (SVR) and non-responders/relapsers (NR). SOCS3 gene mRNA expression analysis was done by using Real time PCR technique, whereas ARMS PCR technique was used for analysis of SOCS3 gene polymorphisms i.e. 8464 A/C (rs12952093), -4874 A/G (rs4969170) and -1383 A/G, (rs4969168). RESULTS: Gene expression analysis of SOCS3 showed that there was statistically significant increase of 2.275-fold and 3.72-fold in relative gene expression for SVR and NR as compared to normal healthy samples (p < 0.001). The distribution of rs4969168, rs4969170 and rs12952093 genotype frequencies between SVR versus NR group were not statistically significant, only the allelic frequency of rs4969170 was statistically significant (p ≤ 0.0001) with therapeutic response. CONCLUSION: The gene expression analysis of SOCS3 showed a clear difference in mRNA expression of SOCS3 as a possible indicator of therapeutic response rather than polymorphism of SOCS3 gene in our studied population.

13.
Infect Immun ; 75(4): 1745-50, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17283086

RESUMO

The development of small-animal models is necessary to understand host responses and immunity to emerging infectious diseases and potential bioterrorism agents. In this report we have characterized a murine model of intestinal ricin intoxication. Ricin administered intragastrically (i.g.) to BALB/c mice at doses ranging from 1 to 10 mg/kg of body weight induced dose-dependent morphological changes in the proximal small intestine (i.e., duodenum), including widespread villus atrophy and epithelial damage. Coincident with epithelial damage was a localized increase in monocyte chemotactic protein 1, a chemokine known to be associated with inflammation of the intestinal mucosa. Immunity to intestinal ricin intoxication was achieved by immunizing mice i.g. with ricin toxoid and correlated with elevated levels of antitoxin mucosal immunoglobulin A (IgA) and serum IgG antibodies. We expect that this model will serve as a valuable tool in identifying the inflammatory pathways and protective immune responses that are elicited in the intestinal mucosa following ricin exposure and will prove useful in the evaluation of antitoxin vaccines and therapeutics.


Assuntos
Quimiocina CCL2/biossíntese , Células Epiteliais/efeitos dos fármacos , Mucosa Intestinal/patologia , Intoxicação/patologia , Ricina/intoxicação , Animais , Antitoxinas/análise , Antitoxinas/sangue , Modelos Animais de Doenças , Duodeno/patologia , Feminino , Histocitoquímica , Imunização , Imunoglobulina A/análise , Imunoglobulina G/sangue , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Intoxicação/imunologia , Ricina/imunologia , Toxoides/administração & dosagem , Toxoides/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA