Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Dose Response ; 21(3): 15593258231185457, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37654727

RESUMO

Nanoparticles have shown promising potential for efficient drug delivery, circumventing biological interferences like immunological and renal clearance and mechanical and enzymatic destruction. However, a handful of research papers have questioned the biomedical use of metal-based nanoparticles like cadmium telluride quantum dots (CdTe-QDs) for their cytotoxic, genotoxic, and carcinogenic potential. Herein, we examined the effects of CdTe-QD NPs on gene expression profile of hepatocellular carcinoma (Huh-7) cell line. Huh-7 cells were treated with CdTe-QD NPs (10 µg/ml for 6, 12, and 24 hours, and 25 µg/ml for 6 and 12 hours), and transcriptomic analysis was performed using microarray to evaluate the global gene expression profile. Differential expressed genes (DEGs) were observed for both the doses (10 and 25 µg/ml) of CdTe-QD NPs at different time points. Gene ontology (GO) analysis revealed that genes involved in molecular function of cell cycle, organizational injury and abnormalities, cell death and survival, gene expression, cancer, organismal survival, and cellular development were differentially expressed. Overall, we have demonstrated differential expression of several genes, involved in maintaining cell survival, metabolism, and genome integrity. These findings were confirmed by RT-qPCR study for some canonical pathway genes signifying possible implication in NP toxicity-mediated cell survival and inhibition of cell death.

2.
Saudi Med J ; 44(4): 363-367, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37062555

RESUMO

OBJECTIVES: To investigate the prevalence of rs2015 (T>G) and rs2241703 (G>A) polymorphisms in the miRNA-SIRT2 gene in Saudi Arabia and their possible associations with type 2 diabetes mellitus (T2DM). METHODS: Blood samples were collected from 428 participants from Jazan University Hospital, Jazan, Saudi Arabia between September 2021 and June 2022 and subjected to TaqMan single-nucleotide polymorphisms (SNP) genotyping assay for rs241703 (G>A) and rs2015 (G>T). Genotype frequencies were determined in control (n=217). RESULTS: The A allele of rs2241703 was undetected in our population, and all samples carried the GG genotype. The rs2015 SNP frequency was 29.4% for GG, 45.6% for GT, and 24% for TT. However, logistic regression analysis of the dominant inheritance model showed no association between the T allele and T2DM calculated odds ratio [OR]=0.80, 95% confidence interval=0.53 to 1.20, p=0.301). CONCLUSION: Although rs2241703 SNP of Sirtuins 2 is not present, rs2015 SNP is highly prevalent in Saudi Arabia, but no direct link was identified with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , MicroRNAs , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , MicroRNAs/genética , Predisposição Genética para Doença , Arábia Saudita/epidemiologia , Sirtuína 2/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Frequência do Gene , Estudos de Casos e Controles
3.
J Multidiscip Healthc ; 16: 1075-1084, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37096238

RESUMO

Background: The emergence of COVID-19 posed a threat to millions of lives worldwide. The pandemic impacts extended to affect people's psychological well-being, resulting in significant behavioural change. This study was designed to assess the knowledge regarding COVID-19 precautions among the College of Applied Medical Science students at Jazan University and to evaluate the general, psychosocial, and behavioral changes due to COVID-19. Methods: This is an observational study targeting 630 undergraduate students randomly selected during January 2020, using stratified random sampling. Data were collected using an online questionnaire. Linear regression models were used to evaluate the predictors of three outcome measures: knowledge, attitudes, and practice scores. Results: Knowledge of COVID-19 revealed that the students with correct answers ranged from 48.9 to 95%. Furthermore, significant gender differences are found regarding shortness of breath, fatigue, persistent chest discomfort, headache, and malaise (p < 0.05). Knowledge scores differed significantly across gender and academic level (p < 0.05) and so does attitude scores (p < 0.05). No significant difference was observed between practice scores according to socio-demographic background (p > 0.05). The linear regression model showed that females had significantly higher knowledge, attitudes, and practice scores (p < 0.05) as well as those within the 21-23 age group and above (p < 0.05). Students residing in urban and semi-urban places had significantly higher scores for knowledge, attitudes, and practice (p < 0.05). Conclusion: The results demonstrated moderate knowledge about COVID-19 among study participants, with significant differences between the responses of males and females and among the urban and rural populations. Outcomes suggest the need for interventions to bridge students' knowledge about COVID-19 and practice gaps. Students were concerned about basic life amenities and the inability to provide for their dear ones regarding behavioral changes.

4.
Int J Gen Med ; 16: 875-879, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910568

RESUMO

Introduction: Autoimmune hypothyroidism (AHT) is a widespread disease that disproportionately affects women over men. It is characterized by the presence of autoantibodies that lead to the dysfunction of the thyroid gland. The exact cause of this process is unknown; however, some factors, such as genetic factors, may be to blame. The uncoupling protein 2 (UCP2) gene encodes uncoupling protein 2, which has been linked to several pathogeneses; however, the link between UCP2-866 G/A polymorphism and AHT has yet to be investigated. Thus, we investigate the potential relationship between UCP2-866 G/A polymorphism and AHT. Methods: A total of 158 subjects participated in this study, they were either control or AHT patient, and genotyping was performed using a polymerase chain reaction. Results: The frequencies of UCP2-866 G/G, G/A, and A/A in the control subject were 34%, 51%, and 15%, respectively, whereas these frequencies in the AHT were 43%, 46%, and 10%. Conclusion: The study concludes a significant relationship between UCP2-866 G/A polymorphism and AHT, with a carrier subject of the -866 A allele being 3 times more likely to suffer from AHT than wild-type carriers in the study population.

5.
Hum Fertil (Camb) ; : 1-10, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36576330

RESUMO

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated trans-membrane ATP gated anion channel present in most epithelia, which transports chloride and bicarbonate ions across the apical membrane. Mutations in the CFTR protein are known to result in defective expression or function, notably the inhibition of chloride and bicarbonate transport. This can result in cystic fibrosis (CF), a disorder characterised by thickness of the mucus lining of the epithelial cells of the alimentary and respiratory tracts, sweat ducts and reproductive organs. As a consequence, there is a reduction in fluid transport at the apical surface. While the most devastating effect of CF is mortality, about 98% of men with CF are infertile, consequent of early blockage of or failure to develop the mesonephrotic ducts as well as the vas deferens. The effect of CF of female fertility is less well-understood. This review highlights the genetics and pathophysiology as well as the mechanism of action of CF on female infertility.

6.
Ann Clin Lab Sci ; 52(5): 815-824, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36261180

RESUMO

OBJECTIVE: Vitamin D has a pivotal role in maintaining healthy bones and in the modulation of multiple physiologic processes. Vitamin D deficiency has become a global burden that affects all members of society. This study aimed to investigate the prevalence and correlation of vitamin D deficiency with hematological and biochemical parameters in young adult college students. Hundred and fourteen students (77 men and 37 women) were recruited. MATERIALS AND METHODS: The socio-demographic and clinicopathologic features of the students were evaluated using a pre-tested and validated questionnaire, and samples were collected for complete blood count (CBC), vitamin D, calcium, parathyroid hormone, and phosphorus measurements. RESULTS: Vitamin D deficiency was more prevalent in men (53.2%) than in women (48.7%). Calcium and parathyroid hormone levels were within the normal range, and 26% and 22% of male and female participants, respectively, had low phosphorus levels. Vitamin D showed a positive correlation with calcium in men (r=0.3927; P=0.005) and women (r=0.4122; P=0.0566). Although, vitamin D status had no impact on most of CBC parameters, significant positive correlation was observed with eosinophils in women. CONCLUSIONS: Vitamin D deficiency is very prevalent among college students, therefore health education and public awareness campaigns on the consequences of vitamin D deficiency on health and well-being are required.


Assuntos
Deficiência de Vitamina D , Vitamina D , Feminino , Adulto Jovem , Masculino , Humanos , Cálcio , Prevalência , Deficiência de Vitamina D/epidemiologia , Hormônio Paratireóideo , Vitaminas , Fósforo
7.
Drug Des Devel Ther ; 16: 1963-1974, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783198

RESUMO

Introduction: Numerous drugs with potent toxicity against cancer cells are available for treating malignancies, but therapeutic efficacies are limited due to their inefficient tumor targeting and deleterious effects on non-cancerous tissue. Therefore, two improvements are mandatory for improved chemotherapy 1) novel delivery techniques that can target cancer cells to deliver anticancer drugs and 2) methods to specifically enhance drug efficacy within tumors. The loading of inert drug carriers with anticancer agents and peptides which are able to bind (target) tumor-related proteins to enhance tumor drug accumulation and local cytotoxicity is a most promising approach. Objective: To evaluate the anticancer efficacy of Chitosan nanoparticles loaded with human growth hormone hGH fragment 176-191 peptide plus the clinical chemotherapeutic doxorubicin in comparison with Chitosan loaded with doxorubicin alone. Methods: Two sets of in silico experiments were performed using molecular docking simulations to determine the influence of hGH fragment 176-191 peptide on the anticancer efficacy of doxorubicin 1) the binding affinities of hGH fragment 176-191 peptide to the breast cancer receptors, 2) the effects of hGH fragment 176-191 peptide binding on doxorubicin binding to these same receptors. Further, the influence of hGH fragment 176-191 peptide on the anticancer efficacy of doxorubicin was validated using viability assay in Human MCF-7 breast cancer cells. Results: In silico analysis suggested that addition of the hGH fragment to doxorubicin-loaded Chitosan nanoparticles can enhance doxorubicin binding to multiple breast cancer protein targets, while photon correlation spectroscopy revealed that the synthesized dual-loaded Chitosan nanoparticles possess clinically favorable particle size, polydispersity index, as well as zeta potential. Conclusion: These dual-loaded Chitosan nanoparticles demonstrated greater anti-proliferative activity against a breast cancer cell line (MCF-7) than doxorubicin-loaded Chitosan. This dual-loading strategy may enhance the anticancer potency of doxorubicin and reduce the clinical side effects associated with non-target tissue exposure.


Assuntos
Antineoplásicos , Neoplasias da Mama , Quitosana , Hormônio do Crescimento Humano , Nanopartículas , Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Quitosana/farmacologia , Doxorrubicina , Feminino , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Nanopartículas/química , Peptídeos/uso terapêutico
8.
Genes (Basel) ; 13(6)2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35741842

RESUMO

The Dombrock (DO) blood group system has two primary antigens, Doa and Dob, which can cause delayed hemolytic transfusion reactions. The paucity of specific monospecific antibodies can hamper the typing based on these antigens. Thus, blood group genotyping (BGG) was investigated as a possible solution. Sequence-specific primers were designed to target a single nucleotide polymorphism (rs11276) on the ART4 gene encoding the DO*A and DO*B alleles. Blood samples (n = 150) from randomly selected volunteer donors were used. DNA was extracted and resulting PCR products were purified and sequenced. The allelic frequencies of DO*A and DO*B were (n = 122, 40.67%) and (n = 178, 59.33%), respectively. The distributions of DO genotypes were as follows: DO*A/DO*A (n = 20), 13.33%; DO*B/DO*B (n = 48), 32.00%; and DO*A/DO*B (n = 82), 54.67%. In conclusion, this study reports on the allelic frequencies of DO*A and DO*B of the DO blood group system in Jazan Province, Kingdom of Saudi Arabia. Furthermore, this study reports on the prevalence of each genotype, of which DO*A/DO*B was the most abundant. This study contributes significantly to build the current blood donor database in Southwestern Saudi Arabia. Moreover, it may assist in providing safe blood to polytransfused patients and reduce the risk of the red cell alloimmunization.


Assuntos
Doadores de Sangue , Antígenos de Grupos Sanguíneos , Alelos , Antígenos de Grupos Sanguíneos/genética , Genótipo , Humanos , Arábia Saudita/epidemiologia
9.
Front Nutr ; 9: 863029, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35614977

RESUMO

Background: Breast cancer is one of the leading causes of death worldwide, it affects both men and women. In Saudi Arabia, breast cancer has been the most prevalent type of cancer in women, for the past few years. Dietary habits and cultural beliefs vary according to region, and further studies are required to demonstrate the relationship between these dietary habits and cultural beliefs and the risk of developing breast cancer. This study is aimed to discover the relationship between preventive dietary factors of the Mediterranean diet and rates of breast cancer among postmenopausal women in the Makkah region of Saudi Arabia. Methods: A case-control study was conducted in King Abdulla Medical City Hospital, Makkah, Saudi Arabia and included 432 Saudi female participants: 218 in the control group and 214 breast cancer patients. All participants were postmenopausal, around the same age, and all were ethnically Arab Saudis. Data were obtained using a self-administered validated questionnaire. Results: Study results showed that a diet that includes 1-2 servings of legumes weekly, 1-5 servings of fish weekly, 1-5 servings of dairy products daily, 3-5 servings of fruits and vegetables daily, and more than one cup of black tea and coffee per day significantly (p < 0.05) reduces the risk of breast cancer. Conclusion: This study demonstrates that consuming a Mediterranean diet, which includes legumes, fish, fruits and vegetables, black tea, coffee, and low intake of dairy products, works as a preventive factor against breast cancer in postmenopausal females from the Makkah region.

11.
Healthcare (Basel) ; 11(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36611495

RESUMO

The current study was designed to validate the Arabic version of the Diabetes Self-Management Scale (DSMS) using Rasch and confirmatory factor analyses. This included person and item fit, separation, and reliability; rating scale functionality to evidence substantive validity; unidimensional structure to evidence structural validity; and item technical quality to evidence content validity. The study was conducted between September 2021 and March 2022. Utilizing AMOS-based confirmatory factor analysis (CFA), the study also assured the dimensionality of the DSMS. The participants were 103 diabetic patients in Saudi Arabia with a mean age of 44.72 years (standard deviation = 17.35). The analysis was performed using a trichotomous rating scale, and only one item exhibited a misfit (DSMS14). The item difficulty range was -1.0 to +1.0 logits, while the person's ability range was -3.0 to +3.0 logits. The first construct proved one Rasch dimension, which was explained and further analyzed using AMOS-CFA for the one-factor model. The DSMS was shown to be beneficial as a screening instrument for patient-reported diabetes self-management, despite several flaws that need to be addressed to improve the scale further.

12.
Int J Gen Med ; 14: 9315-9319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887679

RESUMO

PURPOSE: Knowledge of the prevalence of blood group antigens in a given population is important for the prevention of hemolytic reactions. The MNS blood group system (002) has four polymorphic antigens-M, N, S, and s. Anti-S and anti-s antibodies may result in immediate and delayed hemolytic transfusion reactions, and hemolytic disease of the fetus and newborn may occur. The present study investigated the frequencies of the main antigens and phenotypes of the MNS blood group system. SUBJECTS AND METHODS: We randomly obtained 149 samples from anonymous Saudi blood donors living in Jazan Province. Serotyping was conducted using a gel card to investigate (M, N, S, and s) antigens and phenotypes. RESULTS: The frequencies of MNS antigens were as follows: M = 89.26%, N = 51.67%, S = 61.07%, and s = 82.55%. Regarding the MNS phenotypes, nine phenotypes were observed in the study population. The most common phenotype was M+N-S+s+ (n = 36, 24.16%), in contrast to the least common phenotype M+N-S-s- (n = 1, 0.67%). The prevalence of the MNS phenotypes in the current study population was highly and significantly different from that in Europeans (P = 0.044) and African Americans (P = 0.000). CONCLUSION: In summary, this study reports the frequencies of the MNS antigens and phenotypes in Jazan Province, Saudi Arabia. The most common phenotype was M+N-S+s+, whereas the least observed phenotype was M+N-S-s-. The outcomes of this study may assist the blood banks in Jazan Province to establish an extended phenotyping protocol including the MNS antigens, in particular S and s antigens, to preclude any alloimmunization events.

13.
Drug Deliv ; 28(1): 2119-2126, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34612775

RESUMO

Albendazolum (ABZ) is a BCS class II drug. It has challenging biopharmaceutical properties, which include poor solubility and dissolution rate. These properties have laid the ground for developing a supersaturated self-nanoemulsifying drug delivery system (S-SNEDDS) to form oil-in-water nanoemulsion in situ to improve the oral bioavailability of ABZ. Based on the ABZ solubility, emulsifying ability, and stability after dispersion in an aqueous phase, an optimal self-nanoemulsifying drug delivery system (SNEDDS) consisting of oleic acid, Tween® 20, and PEG 600 (X:Y:Z, w/w) was identified, having 10% (w/w) hydroxypropyl methylcellulose (HPMC) E15 lv as its precipitation inhibitor. The optimized system possessed a small mean globule size value (89.2 nm), good dispersion properties (polydispersity index (PDI): 0.278), and preserved the supersaturated state of ABZ. S-SNEDDS was transformed into solid supersaturated self-nanoemulsifying drug delivery systems (SS-SNEDDS) using microcrystalline cellulose as a solid material. The developed S-SNEDDS were characterized for globule size, pH, turbidity, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and flow properties. The data obtained from the results suggest that this S-SNEDDS formulation can enhance the solubility and oral bioavailability of ABZ for appropriate clinical application.


Assuntos
Albendazol/administração & dosagem , Emulsões/química , Nanopartículas/química , Celulose/química , Química Farmacêutica , Portadores de Fármacos/química , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Ácido Oleico/química , Tamanho da Partícula , Polietilenoglicóis/química , Polissorbatos/química
14.
Asian Pac J Cancer Prev ; 22(1): 119-123, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507688

RESUMO

OBJECTIVES: The association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the development of type 2 diabetes mellitus (T2DM) has been debated vigorously but still remains controversial. Therefore, the current study was designed to determine the possible association between ACE I/D polymorphism and T2DM and hypertension (HTN) in a population of Saudi Arabian participants. METHODS: A total of 143 individuals were recruited for the study, consisting of 74 controls and 69 patients with T2DM. Genotyping was performed via polymerase chain reaction. RESULTS: The genotype frequencies for DD, ID and II in controls were 52.7%, 39.2% and 8.1%, whereas in T2D patients it was 52.2%, 40.6% and 7.2% respectively. The DD frequency was highest out of the three genotypes in both the controls and the T2DM patients. CONCLUSION: There was no significant difference found in the genotype and allele frequencies between cases and controls, suggesting that insertion/deletion polymorphism in the ACE gene may not be associated with an increased susceptibility to type 2 diabetes in our study population.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/patologia , Mutação INDEL , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Arábia Saudita
15.
Asian Pac J Cancer Prev ; 21(10): 3099-3108, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33112573

RESUMO

PURPOSE: DNA damage is a continuous process occurring within the cells caused by intrinsic and extrinsic factors, but it gets repaired regularly. If the DNA repair process is faulty, the incidences of damages/mutations can accumulate in cells resulting in cell transformation. It is hypothesized that the negative variations in DNA repair pathways in even at one point viz. genetic, translational or posttranslational stage may fairly be crucial for the beginning and development of carcinogenesis. Therefore, we investigated the potential of tobacco specific nitrosamines (TSNs) related carcinogens to interact with the enzymes involved in DNA repair mechanisms in the current study. METHODS: The derivatives of cigarettes' smoke like NNK and NNAL are very well known and recognized carcinogens. Therefore, almost 120 enzymes playing crucial role in the DNA repair process have been analysed for their reactivity with NNK and NNAL. RESULTS: The molecular docking study helped to screen out,  07 possible DNA repair enzyme targets for NNK, and 12for NNAL. Present study revealed the loss of activity of DNA repair enzymes in the presence of NNK and NNAL, and this accumulation may induce the tendency of DNA damage which can lead the transformation of exposed normal cells in to cancerous cells. This study also demonstrated the protective potential of nanoparticles like SWCNTs/MWCNTs against TSN's induced toxicity; here SWCNT against NNK (-17.16 Kcal/Mol) and MWCNT against NNK -17.01 Kcal/Mol were showing maximum binding affinities than the known biomolecular target of NNK 1UGH (Uracil-DNA glycosylase,-7.82Kcal/Mol). CONCLUSION: CNTs can be applied as chemo-preventive agents against environmental and tobacco induced carcinogens owing to their scavenging potential and warrants for in vivo and in vitro experimental validation of the results obtained from the present study.
.


Assuntos
Carcinógenos/toxicidade , Enzimas Reparadoras do DNA/deficiência , Reparo do DNA , Nanotubos de Carbono/química , Produtos do Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/prevenção & controle , Dano ao DNA , Enzimas Reparadoras do DNA/química , Enzimas Reparadoras do DNA/efeitos dos fármacos , Enzimas Reparadoras do DNA/metabolismo , Humanos , Domínios e Motivos de Interação entre Proteínas , Poluição por Fumaça de Tabaco/análise
16.
Int J Health Sci (Qassim) ; 14(4): 11-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32694967

RESUMO

OBJECTIVES: Autoimmune hypothyroidism (AHT) is a common endocrine disorder. Although the exact cause of AHT is not yet understood, genetic factors may play a major role. Uncoupling protein 2 (UCP2) is a member of mitochondrial protein family involved in the regulation of cellular metabolism. An important functional polymorphism in the UCP2 gene, 45-bp insertion/deletion (ins/del) polymorphism, has been linked to certain clinical conditions. However, an association between the 45-bp ins/del polymorphism and AHT has not yet been established. METHODS: In this study, about 259 blood samples were collected from, patients with AHT and age-matched healthy control subjects. DNA was extracted for UCP2 45-bp ins/del polymorphisms genotyping, using a standard polymerase chain reaction technique. The distribution of different genotypes was determined in both groups and possible association with AHT was also assessed by logistic regression analysis using the Del/Del variant as a reference genotype. RESULTS: The frequency of the UCP2 45-bp ins/del polymorphism in the total study population was 49.04%, 40.15%, and 10.81% for Del/Del, Ins/Del, and Ins/Ins genotypes, respectively. The logistic regression analysis showed crude odds ratios (ORs), respectively, with their 95% confidence intervals (CIs) and P-values in codominant (Del/Ins) (OR = 1.53, CI = 0.89-2.60, P = 0.17), codominant (Ins/Ins) (OR = 0.75, CI = 0.34-1.74, P = 0.53), dominant (OR = 1.30, CI = 0.79-2.16, P = 0.37), and recessive (OR = 0.62, CI = 0.29-1.36, P = 0.30) inheritance models tested, where none of which were statistically significant. CONCLUSION: Our data revealed the distribution of the UCP2 45-bp ins/del polymorphisms in Jazan area and confirmed the lack of association between these genetic variants and the development of AHT.

17.
J Immunol ; 201(11): 3175-3183, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30381479

RESUMO

A major manifestation of autoimmune polyendocrine syndrome type 1 (APS1) is hypoparathyroidism, which is suggested to result from aberrant immune responses against the parathyroid glands. The calcium-sensing receptor (CaSR), which plays a pivotal role in maintaining calcium homeostasis by sensing blood calcium levels and regulating release of parathyroid hormone (PTH), is an autoantibody target in APS1. In this study, the aim was to characterize the binding sites, specificity, functional affinity, IgG subclass, and functional effects of CaSR autoantibodies using phage-display technology, ELISA, and bioassays. The results indicated that CaSR autoantibody binding sites were at aa 41-69, 114-126, 171-195, and 260-340 in the extracellular domain of the receptor. Autoantibodies against CaSR epitopes 41-69, 171-195, and 260-340 were exclusively of the IgG1 subclass. Autoantibody responses against CaSR epitope 114-126 were predominantly of the IgG1 with a minority of the IgG3 subclass. Only autoantibodies recognizing CaSR epitopes 114-126 and 171-195 affected receptor activity; inositol-phosphate accumulation was increased significantly in HEK293-CaSR cells, and PTH secretion from PTH-C1 cells was reduced significantly when either were incubated with purified Ab and Ca2+ compared with Ca2+ alone. In conclusion, although the majority of APS1 patients do not have CaSR-stimulating autoantibodies, the hypoparathyroid state in a small minority of patients is the result of functional suppression of the parathyroid glands.


Assuntos
Epitopos de Linfócito B/metabolismo , Imunoglobulina G/metabolismo , Hormônio Paratireóideo/metabolismo , Poliendocrinopatias Autoimunes/imunologia , Receptores de Detecção de Cálcio/metabolismo , Adolescente , Adulto , Autoanticorpos/metabolismo , Cálcio/metabolismo , Criança , Pré-Escolar , Epitopos de Linfócito B/imunologia , Feminino , Células HEK293 , Humanos , Hipoparatireoidismo , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Poliendocrinopatias Autoimunes/genética , Receptores de Detecção de Cálcio/imunologia , Fatores de Transcrição/genética , Adulto Jovem , Proteína AIRE
18.
J Clin Endocrinol Metab ; 99(3): 1064-71, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24423312

RESUMO

CONTEXT: Previous studies have identified the calcium-sensing receptor (CaSR) and NALP5 as parathyroid autoantibody targets in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). However, although NALP5 antibodies have been associated with the occurrence of hypoparathyroidism (HP) in APECED, it is unclear whether CaSR antibodies are a specific or sensitive marker for APECED-associated HP. OBJECTIVE: The objective of the study was to identify associations between the presence of CaSR and NALP5 antibodies and the disease manifestations and demographic characteristics of Finnish APECED patients. DESIGN, SUBJECTS, AND METHODS: This was a case-control study including 44 APECED patients and 38 age- and sex-matched healthy controls. Antibodies against the CaSR and NALP5 were detected using immunoprecipitation assays and radioligand binding assays, respectively. RESULTS: CaSR and NALP5 antibodies were detected in 16 of 44 (36%) and 13 of 44 (30%) patients, respectively. No statistically significant associations were found between the presence of CaSR or NALP5 antibodies and the disease manifestations of APECED including HP (P > .05). For the diagnosis of HP, CaSR and NALP5 antibodies had specificities of 83% and 50%, respectively, and sensitivities of 39% and 26%, respectively. A significant association between both a shorter APECED and HP duration (<10 y) and positivity for CaSR antibodies was noted (P = .019 and P = .0061, respectively). CONCLUSION: Neither CaSR nor NALP5 antibodies were found to be specific or sensitive markers for HP in APECED. Further investigations are required to determine the exact role of the autoimmune response against the CaSR and NALP5 in the pathogenesis of this autoimmune syndrome.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Poliendocrinopatias Autoimunes/epidemiologia , Receptores de Detecção de Cálcio/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Finlândia/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais , Proteínas Nucleares , Poliendocrinopatias Autoimunes/sangue , Estudos Soroepidemiológicos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...