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1.
J Chem Inf Model ; 60(1): 421-433, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31873008

RESUMO

Acute encephalitis syndrome outbreak has emerged as a major health concern on both national and international scales. Brain inflammation/infections caused by Japanese encephalitis virus (JEV) can lead to death. The cases are growing in numbers globally, and this emergent health concern requires an effective and viable vaccine to strengthen the body's immune system against this deadly virus. Proteomic analyses of JEV revealed the envelope protein as a potential target for vaccine development by patient samples analysis. Hence, in this study, we aimed to design a multiepitope subunit vaccine for acute encephalitis using the advanced structural biology and immunoinformatics approaches. We report the multiepitope subunit vaccine consisted of the putative T-cell epitope (MHC-1 and MHC-2 restricted) and B-cell epitope and with high antigenicity and immunogenicity. The TAP affinity epitopes along with adjuvants were engineered to the vaccine, to ensure the ease transportation inside the host and elicitation of a strong immune response. The specificity of vaccine construct was evaluated by molecular docking with major histocompatibility complex (MHC) receptors and host membrane receptor TLR2. High docking scores and a close interaction to the binding groove of receptors confirmed the potency and specificity of the vaccine. Also, molecular dynamics simulation studies confirmed the stable interaction of vaccine with TLR2 for a long run (100 ns), which showed the prolonged elicitation of the strong immune response. Peptide dynamics studies showed the flexible, strong, and stable binding of vaccine with minimal deviation in root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and secondary structure estimation (SSE) plots till 100 ns simulation run. The in silico immune simulation approach based on the position-specific scoring matrix and machine learning methods resulted in the strong immune response reinforcement statistics of immune cells (T-cells, B-cells population, and memory cells) in response to vaccine candidate. The favorable results and well-correlated data of varied in silico techniques paved for a potent multiepitope vaccine and helped us to propose the mechanism of action of designed vaccine and generation of the immune response against acute encephalitis syndrome.

2.
Mol Ther Nucleic Acids ; 18: 661-672, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31704587

RESUMO

The successful management of tuberculosis (TB) requires efficient diagnosis and treatment. Further, the increasing prevalence of drug-resistant TB highlights the urgent need to develop novel inhibitors against both drug-susceptible and drug-resistant forms of disease. Malate synthase (MS), an enzyme of the glyoxylate pathway, plays a vital role in mycobacterial persistence, and therefore it is considered as an attractive target for novel anti-TB drug development. Recent studies have also ascribed an adhesin function to MS and established it as a potent diagnostic biomarker. In this study, a panel of Mycobacterium tuberculosis (Mtb) MS-specific single-stranded DNA aptamers was identified by Systematic Evolution of Ligands by EXponential enrichment (SELEX). The best-performing G-quadruplex-forming 44-mer aptamer, MS10, was optimized post-SELEX to generate an 11-mer aptamer, MS10-Trunc. This aptamer was characterized by various biochemical, biophysical, and in silico techniques. Its theranostic activity toward Mtb was established using enzyme inhibition, host cell binding, and invasion assays. MS10-Trunc aptamer exhibited high affinity for MS (equilibrium dissociation constant [KD] ∼19 pM) and displayed robust inhibition of MS enzyme activity with IC50 of 251.1 nM and inhibitor constant (Ki) of 230 nM. This aptamer blocked mycobacterial entry into host cells by binding to surface-associated MS. In addition, we have also demonstrated its application in the detection of tuberculous meningitis (TBM) in patients with sensitivity and specificity each of >97%.

3.
J Cutan Aesthet Surg ; 12(1): 42-48, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057268

RESUMO

Background: Androgenetic alopecia (AGA) is a non-scarring alopecia with a characteristic pattern in genetically predisposed men and women. Hormonal abnormalities namely hyperandrogenism, hair cycle defects, genetic predisposition, and follicular miniaturization have been implicated as the causative factors for AGA. Aim: To analyze women with patterned hair loss and correlate their clinical findings with the histopathology and biochemical parameters. Materials and Methods: Female patients between 18 and 45 years of age with a history of hair loss on the crown, temporal area, and recession of hairline were clinically examined. These patients were then subjected to histopathological examination, and on confirmation of diagnosis of female pattern hair loss (FPHL), they were included in the study. Their morning blood sample was taken on 3rd-5th day of the menstrual cycle for hormonal analysis. The study was carried out on 30 patients and 30 age- and sex-matched controls. Results: A statistically significant difference was observed between the mean values of dehydroepiandrosterone sulfate, prolactin, androstenedione, and free triiodothyronine of cases and controls. The most common histopathological finding in our study was an increase in the percentage of telogen hair. Conclusion: The biochemical findings in our study corroborate the role of hyperandrogenism as one of the major etiological factors in FPHL with the role of adrenal androgens being central, and therefore all female patients with FPHL should be evaluated for underlying hormonal imbalances. The role of histopathology in FPHL can be used as a prognostic marker.

4.
Int J Nanomedicine ; 14: 2103-2113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988611

RESUMO

Background: Tuberculous meningitis (TBM) is the most devastating manifestation of extra-pulmonary tuberculosis. About 33% of TBM patients die due to very late diagnosis of the disease. Conventional diagnostic methods based on signs and symptoms, cerebrospinal fluid (CSF) smear microscopy or liquid culture suffer from either poor sensitivity or long turnaround time (up to 8 weeks). Therefore, in order to manage the disease efficiently, there is an urgent and unmet need for a rapid and reliable diagnostic test. Methods: In the current study, to address the diagnostic challenge of TBM, a highly rapid and sensitive structural switching electrochemical aptasensor was developed by combining the electrochemical property of methylene blue (MB) with the molecular recognition ability of a ssDNA aptamer. To demonstrate the clinical diagnostic utility of the developed aptasensor, a blinded study was performed on 81 archived CSF specimens using differential pulse voltammetry. Results: The electrochemical aptasensor developed in the current study can detect as low as 10 pg HspX in CSF background and yields a highly discriminatory response (P<0.0001) for TBM and not-TBM categories with ~95% sensitivity and ~97.5% specificity and has the ability to deliver sample-to-answer in ≤30 minutes. Conclusion: In summary, we demonstrate a new aptamer-based electrochemical biosensing strategy by exploiting the target-induced structural switching of H63 SL-2 M6 aptamer and electroactivity of aptamer-tagged MB for the detection of HspX in CSF samples for the diagnosis of TBM. Further, the clinical utility of this sensor could be extended for the diagnosis of other forms of tuberculosis in the near future.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Testes Diagnósticos de Rotina/métodos , Técnicas Eletroquímicas/métodos , Mycobacterium tuberculosis/genética , Tuberculose Meníngea/diagnóstico , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , DNA Bacteriano/genética , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/microbiologia
5.
Anal Biochem ; 564-565: 80-87, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30352198

RESUMO

Pleural tuberculosis (pTB) is diagnosed by using a composite reference standard (CRS) since microbiological methods are grossly inadequate and an accurate diagnostic test remains an unmet need. The present study aimed to evaluate the utility of Mycobacterium tuberculosis (Mtb) antigen and DNA-based tests for pTB diagnosis. Patients were classified as 'Definite TB', 'Probable TB' and 'Non-TB' disease according to the CRS. We assessed the performance of in-house antigen detection assays, namely antibody-based Enzyme-Linked ImmunoSorbent Assay (ELISA) and aptamer-based Aptamer-Linked Immobilized Sorbent Assay (ALISA), targeting Mtb HspX protein and DNA-based tests namely, Xpert MTB/RIF and in-house devR-qPCR. ROC curves were generated for the combined group of 'Definite TB' and 'Probable TB' vs. 'Non-TB' disease group and cut-off values were derived to provide specificity of ≥98%. The sensitivity of ALISA was ∼93% vs. ∼24% of ELISA (p-value ≤0.0001). devR-qPCR exhibited a sensitivity of 50% vs. ∼22% of Xpert (p-value ≤0.01). This novel aptamer-based ALISA test surpasses the sensitivity criterion and matches the specificity requirement spelt out in the 'Target product profile' for extrapulmonary tuberculosis samples by Unitaid (Sensitivity ≥80%, Specificity 98%). The superior performance of the aptamer-based ALISA test indicates its translational potential to bridge the existing gap in pTB diagnosis.


Assuntos
Aptâmeros de Nucleotídeos/genética , Tuberculose Pleural/diagnóstico , Adulto , Proteínas de Bactérias/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Tuberculose Pleural/microbiologia
6.
Tuberculosis (Edinb) ; 112: 27-36, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30205966

RESUMO

Tuberculous meningitis (TBM) is the most severe manifestation of tuberculosis and its diagnosis remains a challenge even today due to the lack of an adequate test. HspX antigen of Mycobacterium tuberculosis was previously established as a reliable diagnostic biomarker for TBM in an ELISA test format using anti-HspX polyclonal antibodies. Towards overcoming the limitations of batch-to-batch variation and challenges of scalability in antibody generation, we utilized Systematic Evolution of Ligands by EXponential enrichment (SELEX) to develop high affinity DNA aptamers against HspX as an alternative diagnostic reagent. Post-SELEX optimization of the best-performing aptamer candidate, H63, established its derivative H63 SL-2 M6 to be superior to its parent. Aptamer H63 SL-2 M6 displayed a specific and high affinity interaction with HspX (Kd ∼9.0 × 10-8 M). In an Aptamer Linked Immobilized Sorbent Assay (ALISA), H63 SL-2 M6 significantly differentiated between cerebrospinal fluid specimens from TBM and non-TBM subjects (n = 87, ***p < 0.0001) with ∼100% sensitivity and ∼91% specificity. Notably, ALISA exhibited comparable performance with previously reported antibody-based ELISA and qPCR. Altogether, our findings establish the utility of HspX aptamer for the reliable diagnosis of TBM and pave the way for developing an aptamer-based point-of-care test for TBM.


Assuntos
Antígenos de Bactérias/líquido cefalorraquidiano , Aptâmeros de Nucleotídeos/síntese química , Proteínas de Bactérias/líquido cefalorraquidiano , Mycobacterium tuberculosis/metabolismo , Técnica de Seleção de Aptâmeros , Tuberculose Meníngea/diagnóstico , Antígenos de Bactérias/genética , Aptâmeros de Nucleotídeos/genética , Aptâmeros de Nucleotídeos/metabolismo , Proteínas de Bactérias/genética , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/microbiologia
7.
Indian J Med Res ; 147(5): 484-495, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-30082573

RESUMO

Background & objectives: Data on bone mineral density (BMD) and sarcopenia are scant from young females with HIV. This study was conducted to determine occurrence, predictors and impact of body composition alterations on osteoporosis in pre-menopausal women with HIV. Methods: A total of 214 females with serologically documented HIV infection were screened, of whom 103 pre-menopausal women, 25-45 yr age, clinically stable, having at least one year follow up data, underwent hormonal and dual-energy X-ray absorptiometry analysis for BMD and body composition. Seventy five matched controls were also evaluated. Results: Females with HIV had significantly lower BMD and. Z: -score at lumbar spine (LS), total femur, neck of femur (NOF), and radius ultra-distal (UD) compared to controls. Osteoporosis at least at one site was observed in 34.95 per cent patients, compared to eight per cent in controls (P<0.001). Most common site of osteoporosis in females with HIV was radius UD (24.27%), followed by radius 33 per cent (17.48%), radius total (15.53%) and greater trochanter, NOF and LS (6.80% each). HIV patients had significantly lower bone mineral content, lean mass (LM), fat per cent, android (A) fat, gynoid (G) fat, and A/G ratio. LM and fat mass (FM) were -15.65 and -11.54 per cent lower in HIV patients, respectively. Osteoporosis patients had significantly higher use of antiretroviral therapy and lower LM, FM and fat per cent. On logistic regression, LM followed by A/G ratio and BMI were the best predictors of osteoporosis. Sarcopenia was observed in 17.5 per cent patients. Interpretation & conclusions: Our results showed that osteoporosis and sarcopenia were significant problems in young women with HIV. HIV was associated with greater LM loss, which was critical for bone health. Sarcopenia may predict low BMD in HIV.


Assuntos
Infecções por HIV/complicações , Osteoporose/complicações , Absorciometria de Fóton , Adulto , Composição Corporal , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Índia , Pessoa de Meia-Idade , Minerais , Pré-Menopausa , Reprodutibilidade dos Testes
8.
J Lab Physicians ; 10(3): 346-350, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30078974

RESUMO

BACKGROUND: No data is available evaluating the difference in serum versus plasma sample assay of commonly tested parameters in the emergency department, where the sample processing time can be significantly reduced if plasma is used for analysis instead of conventionally used serum. Hence, this study aimed to evaluate the differences in serum versus plasma sample estimation of commonly evaluated biochemical parameters using dry chemistry technology. MATERIALS AND METHODS: Paired blood samples were collected from a single venipuncture of 405 patients admitted to the emergency department. Dry chemistry autoanalyzer (Vitros-350, Ortho Clinical Diagnostics) was used to process all the samples. RESULTS: Data from 401 patients were analyzed. Percentage differences between serum versus plasma samples for all analytes ranged from 0.0% to 57.44% and were <±4% for a majority of parameters, except uric acid (-6.25%), albumin (+11.90%), chloride (-5.05%), phosphorus (-6.06%), creatine phosphokinase (CPK) total (-57.44%), amylase (-37.53%), lipase (-42.74%), lactate dehydrogenase (LDH) (-8.53%), and C-reactive protein (-7.44%). For albumin, CPK total, amylase, and lipase, the difference between serum and plasma samples was more than the accepted upper range recommended by College of American Pathologists. CONCLUSION: Glucose, urea, creatinine, bilirubin, total protein, serum glutamate-pyruvate transaminase, total cholesterol, high-density lipoprotein cholesterol, triglycerides, sodium, and CPK-mb can be reliably assayed from either serum or plasma samples in emergency/routine practice. CPK total, amylase, and lipase should always be assayed from serum and not plasma due to significant variations. Uric acid, chloride, phosphorous, and LDH only in emergency situations should be assayed from plasma. For routine assays, serum should be preferred.

9.
Indian J Med Res ; 147(2): 142-150, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29806602

RESUMO

Background & objectives: : Adrenal insufficiency (AI) is rarely diagnosed in patients with HIV infection, in spite of autopsy studies showing very high rates of adrenal involvement. This study was aimed to determine the presence, patterns and predictors of AI in patients with HIV infection. Methods: : Consecutive HIV patients, 18-70 yr age, without any severe co-morbid state, having at least one-year follow up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. Results: : From initially screened 527 patients, 359 patients having good immune function were analyzed. Basal morning cortisol <6 µg/dl (<165 nmol/l; Group 1), 6-11 µg/dl (165-300 nmol/l; Group 2), 11-18 µg/dl (300-500 nmol/l; Group 3) and ≥18 µg/dl (500 nmol/l; Group 4) were observed in 13, 71, 199 and 76 patients, respectively. Adrenocorticotropic hormone (ACTH) stimulation test revealed 87 patients (24.23%) to have AI. AI in groups 1-4 was 100, 56.34, 17.09 and 0 per cent, respectively. AI patients were more likely to be females (P< 0.05), having longer disease duration (P< 0.05), immune reconstitution inflammatory syndrome, hyperkalaemia (P< 0.01), lower fasting glucose (P< 0.01), dehydroepiandrosterone sulphate (DHEAS) and vitamin D. Regression analysis revealed morning cortisol and DHEAS to be best predictors of AI (P=0.004 and 0.028, respectively). Interpretation & conclusions: : AI is a significant problem in HIV-infected individuals, observed in nearly a quarter of patients. Diagnosis warrants high index of suspicion and low threshold for screening, especially in those having low DHEAS and hyperkalaemia. Morning cortisol is a reasonable screening test, with ACTH stimulation warranted to confirm diagnosis, especially in patients with morning cortisol <11 µg/dl (300 nmol/l).


Assuntos
Insuficiência Adrenal/epidemiologia , Infecções por HIV/epidemiologia , Adolescente , Insuficiência Adrenal/complicações , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/virologia , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Sulfato de Desidroepiandrosterona/metabolismo , Feminino , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Hidrocortisona/administração & dosagem , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Indian J Med Res ; 148(4): 411-421, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30666003

RESUMO

Background & objectives: Dyslipidaemia is a major contributor to cardiovascular morbidity, which is increased in HIV. Data on dyslipidaemia in Indians with HIV are scant. This study was undertaken to determine the predictors of dyslipidaemia and lipoatrophy in Indians with HIV infection and their relation with body composition parameters. Methods: A total of 382 consecutive patients with HIV infection were screened, of whom 257 clinically stable patients, without any acute comorbidity, having at least one year follow up underwent biochemical and DEXA analysis. Results: The most common dyslipidaemia was hypertriglyceridaemia (47.08%), followed by hypercholesterolaemia [total cholesterol (TC)] (38.91%) and low high-density lipoprotein (HDL) cholesterol (38.52%), in patients having median age 37 (32-42) yr and HIV duration 57 (33-101) months. Patients with at least one dyslipidaemia (78.99%) had significantly higher insulin resistance (IR), per cent body fat, per cent trunk fat (PTF) and trunk limb fat ratio (TLFR). Baseline CD4 count and delta CD4 count (change in CD4 count 6-12 months following ART) had significant inverse correlation with triglycerides and TC. Patients with highest triglycerides and cholesterol quartiles had significantly higher immune reconstitution, metabolic syndrome, IR, trunk fat mass (FM), PTF and TLFR, with comparable total FM. Logistic regression revealed that body mass index, HIV duration and PTF were independent predictors of hypertriglyceridaemia, with only PTF being significant predictor of hypercholesterolaemia. Every unit increase in PTF was associated with 13 and 4.1 per cent increased hypertriglyceridaemia and hypercholesterolaemia. Lipoatrophy was present in 8.57 per cent patients and was a poor predictor of dyslipidaemia. Interpretation & conclusions: : High occurrence of dyslipidaemia was observed in patients with HIV on anti retroviral therapy. Central adiposity (TFM) was the most important predictor of dyslipidaemia in these patients.


Assuntos
Tecido Adiposo/patologia , Distribuição da Gordura Corporal , Extremidades/fisiopatologia , Infecções por HIV/epidemiologia , Hipercolesterolemia/epidemiologia , Hipertrigliceridemia/epidemiologia , Tronco/fisiopatologia , Adulto , Atrofia , Índice de Massa Corporal , Contagem de Linfócito CD4 , LDL-Colesterol/sangue , Comorbidade , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Índia , Resistência à Insulina , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Triglicerídeos/sangue
11.
Endokrynol Pol ; 68(6): 642-651, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29022646

RESUMO

INTRODUCTION: This study evaluated prevalence and predictors of osteoporosis and sarcopenia in men with HIV. MATERIAL AND METHODS: 220 men with HIV were screened, of which 115 men, 30-50 years-age, having at least 1-year follow-up, underwent hormonal and DEXA analysis. 40 controls were also evaluated. RESULTS: Males with HIV had significantly lower BMD and Z-scores at all sites. Osteoporosis was diagnosed in 64.35%; commonest site being radius total (49.56%), followed by radius 33% (45.21%), radius ultra distal (36.52%), lumbar spine (19.13%), neck of femur (17.39%), total femur and greater trochanter (7.82% each). HIV patients had significantly lower fat mass (FM), lean mass (LM), total fat percent, bone mineral content, gynoid fat, percent skeletal muscle mass (PSMM). Men with osteoporosis had higher use of anti retroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS), tuberculosis, lower FM, LM and PSMM. Logistic regression revealed PSMM, age and delta (Δ) CD4 count (change in CD4 count after 6-12 months of ART, compared to pre-ART) were best predictors of osteoporosis. Greater PSMM was associated with decreased osteoporosis, without adjusting for any variable (Model-1), adjusting for disease duration, tuberculosis and IRIS (Model-2), and model-2 plus gonadotropins and sex steroids (Model-3). Greater ΔCD4 count and age were associated with increased osteoporosis after adjusting for different models. Sarcopenia was observed in 40% men and none in controls. CONCLUSIONS: Men with decreased skeletal mass, age, severe immune dysfunction at diagnosis, having rapid increase in CD4 count following ART and IRIS have higher risk of osteoporosis in the long run.


Assuntos
Infecções por HIV/complicações , Osteoporose/epidemiologia , Sarcopenia/etiologia , Adulto , Fatores Etários , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Prevalência , Fatores de Risco
12.
Indian J Med Res ; 145(6): 804-814, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29067983

RESUMO

BACKGROUND & OBJECTIVES: Data on hypogonadism among human immunodeficiency virus (HIV)-infected Indians are not available. This study was aimed to evaluate the occurrence, pattern and predictors of hypogonadism in HIV-infected Indians. METHODS: Consecutive stable HIV-infected patients, 18-70 yr age, without any severe comorbid state, having at least one year follow up data at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. RESULTS: From initially screened 527 patients, 359 patients (225 males; 134 females), having disease duration of 61.44±39.42 months, 88.58 per cent on highly active antiretroviral therapy (HAART), 40.67 per cent having tuberculosis history and 89.69 per cent with vitamin D insufficiency were analyzed. Testosterone <300 ng/dl was documented in 39.11 per cent males. Primary, hypogonadotropic hypogonadism (HypoH) and compensated hypogonadism were observed in 7.56, 31.56 and 12.44 per cent males, respectively. Males with hypogonadism were significantly older (P=0.009), and had higher opportunistic infections (P<0.001) with longer disease duration (P=0.05). Menstrual abnormalities were observed in 40.3 per cent females, who were significantly older (P<0.001), had lower CD4 count (P=0.038) and higher tuberculosis history (P=0.005). Nearly 46.3, 16.2 and 13 per cent women with menstrual abnormalities were in peri-/post-menopausal state, premature ovarian insufficiency (POI) and HypoH, respectively. Age, CD4 count at diagnosis and 25(OH)D were best predictors of male hypogonadism. Age and CD4 count increment in first 6-12 months following HAART were the best predictors of POI. INTERPRETATION & CONCLUSIONS: Hypogonadism was observed to be a significant problem in HIV-infected men and women in India, affecting 39 and 29 per cent patients, respectively. HypoH was the most common form in males whereas ovarian failure being the most common cause in females.


Assuntos
Infecções por HIV/sangue , Infecções por HIV/fisiopatologia , Hipogonadismo/sangue , Hipogonadismo/fisiopatologia , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Hipogonadismo/complicações , Hipogonadismo/virologia , Índia/epidemiologia , Masculino , Ciclo Menstrual/fisiologia , Pessoa de Meia-Idade , Testosterona/sangue , Vitamina D/sangue , Adulto Jovem
13.
Future Microbiol ; 12: 1201-1218, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28972418

RESUMO

Pleural tuberculosis (pTB) is a grave form of extrapulmonary tuberculosis. Microbiological tests are usually found to be inadequate for pTB diagnosis. The absence of a uniform 'composite reference standard' is challenging; therefore, diagnosis is usually performed using a combination of diversified criteria. Nucleic acid tests vary in diagnostic accuracy and have not yet been integrated into clinical decision making. This review assesses the varied criteria used for pTB classification and the challenges afflicting pleural fluid-based DNA diagnostic tests, namely, PCR and Xpert® MTB/RIF. In the 58 studies (PCR: n = 33; Xpert: n = 25) analyzed, reference standards were heterogeneous and PCR/Xpert pooled sensitivity values (range: 0-100%) were inadequate. However, the consistent high specificity of Xpert (range: 90-100%) indicated its utility as a 'rule-in' test. There is an urgent need to evaluate existing and new molecular tests in well-designed studies  to accurately assess their utility for pTB diagnosis. To conclude, rapid and accurate tests are warranted for pTB diagnosis.


Assuntos
Técnicas de Diagnóstico Molecular/normas , Mycobacterium tuberculosis/genética , Ácidos Nucleicos/análise , Tuberculose Pleural/diagnóstico , DNA Bacteriano/análise , DNA Bacteriano/isolamento & purificação , Humanos , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/patogenicidade , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Tuberculose Pleural/classificação , Tuberculose Pleural/microbiologia
14.
Indian J Endocrinol Metab ; 21(4): 545-550, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28670538

RESUMO

BACKGROUND AND OBJECTIVE: Hyperprolactinemia affects the reproductive endocrine axis; however, the degree of dysfunction may vary depending on etiology. The aim of the present study was to analyze menstrual cyclicity in patients with prolactinoma and drug-induced hyperprolactinemia (DIH). METHODOLOGY: Patients with prolactinoma and DIH were retrospectively analyzed for menstrual cyclicity at presentation and response to therapy. RESULTS: Of 128 females with hyperprolactinemia, 58 had prolactinoma (41 microadenoma and 17 macroadenoma) and 39 had DIH. Patients with prolactinoma had higher prolactin levels and increased frequency of oligomenorrhea (77.5% vs. 46%) as compared to DIH. Patients with macroprolactinoma had more severe menstrual disturbances compared to microprolactinoma. A higher percentage of patients with microprolactinoma and DIH achieved regular menstrual cycles compared to macroprolactinoma postcabergoline treatment (85% and 90% vs. 65%). There was no correlation between time to regularization of menstrual cycles with age, menstrual cycle length, duration of menstrual irregularity, or initial prolactin level in patients with prolactinoma. Linear regression analysis showed a significant association between time to regularization of menstrual cycles with time to normalization of prolactin levels (P = 0.001). CONCLUSION: There is a prompt restoration of menstrual cycles in patients with microprolactinoma and DIH. Patients with macroprolactinoma have more severe menstrual disturbances and lesser frequency of cycle restoration postcabergoline treatment compared to microprolactinoma and DIH.

15.
J Clin Res Pediatr Endocrinol ; 9(4): 350-354, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28529200

RESUMO

Prevalence of hyperprolactinemia in children with subclinical hypothyroidism (ScH) is not known. This study aimed to determine the occurrence and predictors of hyperprolactinemia in euthyroid children and in children with ScH and overt primary hypothyroidism (OPH). Serum prolactin levels were estimated in consecutive children <18 years of age undergoing thyroid function evaluation and diagnosed to have normal thyroid function, ScH, or OPH. Children with pituitary adenomas, secondary hypothyroidism, multiple pituitary hormone deficiency, comorbid states, and drug-induced hyperprolactinemia were excluded. From the initially screened 791 children, hormonal data from 602 children who fulfilled all criteria were analyzed. Seventy-one (11.79%) of these had ScH, and 33 (5.48%) had OPH. Occurrence of hyperprolactinemia was highest in the OPH group (51.51%), followed by ScH (30.98%) and euthyroid children (4.41%) (p<0.001). Median (25th-75th percentiles) levels for prolactin in euthyroid, ScH, and OPH children were 13.3 (9.4-17.95), 19.15 (15.97-30.12), and 28.86 (17.05-51.9) ng/mL, respectively (p<0.001). In children, prolactin levels were comparable in males and females. An age-related increase in serum prolactin was noted in euthyroid children, which was statistically significant in post-pubertal (16-18 years) children. Area under the curve for thyroid stimulating hormone (TSH) in predicting hyperprolactinemia in children was 0.758 (95% confidence interval: 0.673-0.829; p<0.001). TSH ≥4.00 mIU/L had a sensitivity of 69.4% and specificity of 77.6% in detecting hyperprolactinemia. Hyperprolactinemia is common in children with ScH and OPH. TSH ≥4.00 mIU/L has a good sensitivity and specificity in predicting hyperprolactinemia in children. More studies are needed to establish if hyperprolactinemia should be an indication for treating ScH in children.


Assuntos
Hiperprolactinemia/epidemiologia , Hipotireoidismo/epidemiologia , Adolescente , Doenças Assintomáticas , Criança , Pré-Escolar , Feminino , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/complicações , Hipotireoidismo/sangue , Hipotireoidismo/complicações , Incidência , Lactente , Masculino , Prolactina/sangue , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue
16.
Paediatr Int Child Health ; 37(3): 193-198, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28145154

RESUMO

BACKGROUND: Children with cerebral palsy (CP) are vulnerable to developing vitamin D deficiency. There is little information on the prevalence and severity of vitamin D deficiency in these patients. OBJECTIVE: To study vitamin D status in children with CP with special reference to their intake of anti-epileptic drugs (AED) and ambulatory status. METHODS: The relative effects of AED use and ambulatory status on the vitamin D status of 120 children with CP aged 2-10 years were examined in this observational study. The patients were classified into four groups (30 in each) on the basis of AED use and ambulatory status: ambulatory (CPA), ambulatory receiving AED (CPAD), non-ambulatory (CPNA) and non-ambulatory receiving AED (CPNAD). A control group of 30 age-matched healthy children was also included. Parameters assessed included dietary calcium intake, sun exposure, serum total and ionised calcium (tCa, iCa), inorganic phosphate (iP), alkaline phosphatase (ALP), parathormone (PTH), 25 hydroxy vitamin D [25(OH)D] levels and a wrist radiograph to detect rickets. Vitamin D status was defined on the basis of serum 25(OH)D levels as normal (>50 nmol/L), mild deficiency (25-50 nmol/L), moderate deficiency (12.5-25 nmol/L), severe deficiency (<12.5 nmol/L). RESULTS: Median (IQR) serum 25 (OH)D levels in patients with CP were 35.6 (26.75-64) nmol/L compared with 60 (37-69.25) nmol/L in controls (p = 0.04). Sixty per cent of children with CP and 36.7% of controls were vitamin D-deficient [25(OH)D < 50 nmol/L]. Children with CP had a significantly lower dietary calcium intake and sun exposure than controls (p < 0.0001 each). Serum tCa and iCa levels were significantly lower (p = 0.01 and p < 0.001, respectively) and PTH and ALP levels significantly higher (p = 0.04 and p = 0.001, respectively) in children with CP than in controls. Patients in the CPNAD group were the worst affected, 83.3% of them being vitamin D-deficient with median (IQR) 25(OH)D levels of 33.5 (12.5-45.25) nmol/L. Also, 53.3% of them had raised ALP and 17.2% raised PTH levels. CONCLUSION: Children with CP are highly vulnerable to vitamin D deficiency. In these patients, AED use and lack of sun exposure contribute towards poor vitamin D status, the effect being more pronounced when they co-exist.


Assuntos
Anticonvulsivantes/administração & dosagem , Paralisia Cerebral/complicações , Paralisia Cerebral/terapia , Deficiência de Vitamina D/induzido quimicamente , Deficiência de Vitamina D/epidemiologia , Caminhada , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos
17.
Nutrition ; 34: 76-81, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28063517

RESUMO

OBJECTIVE: The aim of this study was to determine the changes in serum vitamin D distribution at an institute in India over the past 6 y and compare it with global trends. METHODS: We conducted an audit of 25-hydroxyvitamin D (25-OHD), calcium, and plasma intact parathyroid hormone (iPTH) reporting from January 2011 to February 2016. References for review were identified through searches of PubMed, Medline, and Embase for articles published until February 2016 using keywords "hypervitaminosis D" (MeSH Terms) OR "vitamin D toxicity" (All Fields) OR "vitamin-D intoxication" (All Fields). RESULTS: Reports of 25-OHD from 5527 patients were analyzed. Calcium and iPTH were available for 5501 (99.5%) and 1787 (32.3%) patients, respectively. Vitamin D deficiency and insufficiency were observed in 59.4 and 77.3%. Hypervitaminosis D (25-OHD >250 nmol/L) was noted in 225 (4.1%) patients, of whom 151 (2.7%) had vitamin D intoxication (25-OHD >375 nmol/L). We found that 46.22% (104 of 225) patients with hypervitaminosis D and 62.25% (94 of 151) with vitamin D intoxication had elevated calcium or suppressed iPTH. Orthopedic, pediatric, and surgery patients had the highest rates of hypervitaminosis D (7.9, 7.2, and 7% respectively; P < 0.001). An increasing trend for hypervitaminosis D was observed (1.48, 3.62, 3.90, 4.78, 6.21, and 7.82% in 2011, 2012, 2013, 2014, 2015, and 2016, respectively). A similar steady upward trend in 25-OHD has been reported in Ireland, England, Canada, and Australia. However, hypervitaminosis D reports are scant and have not increased over the years in the developed world. CONCLUSION: There is a global secular trend of increases in 25-OHD over years. There is a disturbing trend of increased hypervitaminosis D at an Indian institute. Empiric, unmonitored, prolonged vitamin D supplementation, using non-recommended supraphysiological doses, especially when administered intramuscularly, should be discouraged.


Assuntos
Transtornos Nutricionais/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Cálcio/sangue , Bases de Dados Factuais , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Humanos , Índia/epidemiologia , Transtornos Nutricionais/diagnóstico , Hormônio Paratireóideo/sangue , Prevalência , Estações do Ano , Vitamina D/administração & dosagem , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico
18.
Eur J Intern Med ; 35: 106-110, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27473607

RESUMO

BACKGROUND AND AIMS: Hyperprolactinemia has been reported in 0-57% of primary hypothyroidism. Data on hyperprolactinemia in subclinical hypothyroidism (ScH) is scant and inconsistent. This study aimed to determine the prevalence and predictors of hyperprolactinemia in ScH. METHODS: Consecutive patients diagnosed to have normal thyroid function, ScH or overt primary hypothyroidism underwent serum prolactin, gonadotropins, testosterone and estradiol estimation. Patients with pregnancy, pituitary adenomas, secondary hypothyroidism, hyperthyroidism, comorbid states and drug-induced hyperprolactinemia were excluded. RESULTS: From initially screened 4950 patients, hormonal data from 2848 individuals who fulfilled all criteria were analyzed. The occurrence of hyperprolactinemia (females:males) was highest in primary hypothyroidism (42.95%:39.53%) (n=192), followed by ScH (35.65%:31.61%) (n=770) and euthyroid individuals (2.32%:2.02%) (n=1886) (P<0.001). Hyperprolactinemia in ScH with TSH 5-7.5, 7.5-10 and >10mIU/L (females: males) was 25.56%:20.73%, 49.07%:50% and 61.43%:35.71% respectively (P<0.001). Significant positive correlation between TSH and prolactin was noted in ScH and primary hypothyroidism. In females, testosterone was lowest in patients with primary hypothyroidism. In males, serum estradiol was significantly higher, and testosterone significantly lower in men with ScH and primary hypothyroidism. Regression analysis revealed serum TSH followed by free T4, to be best predictors of serum prolactin in both sexes. CONCLUSION: Hyperprolactinemia is common in ScH, especially in those with TSH>7.5mIU/L. ROC analysis confirmed that TSH≥7.51mIU/L in females and ≥8.33mIU/L in males had a sensitivity of ≈50% with a very high specificity of >90% in detecting hyperprolactinemia. Prolactin screening may be warranted in ScH with TSH>7.5mIU/L, and may form an indication for treating ScH.


Assuntos
Hiperprolactinemia/sangue , Hiperprolactinemia/epidemiologia , Hipotireoidismo/complicações , Prolactina/sangue , Tireotropina/sangue , Adulto , Estradiol/sangue , Feminino , Humanos , Índia/epidemiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores Sexuais , Testosterona/sangue , Testes de Função Tireóidea , Adulto Jovem
19.
Saudi J Kidney Dis Transpl ; 27(2): 362-70, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26997392

RESUMO

Chronic kidney disease (CKD) has attained epidemic proportions in India due to increased incidence of diabetes and hypertension (HTN). It was surmised that identification of only high-risk groups (HRGs) through a questionnaire would be sufficient to identify cases of kidney damage (KD). The study attempted to device a questionnaire to classify the subjects in to HRG and low-risk group (LRG) and assess the extent of early KD. The central government employees were classified into HRG and LRG based on "SCreening for Occult REnal Disease (SCORED)" and "EXTENDED" questionnaire formulated after addition of 10 more parameters apart from diabetes and HTN. Urine examination by dipstick, quantitative microalbumin, serum creatinine, and estimated glomerular filtration rate were assessed to determine KD. The data were analyzed for risk-group classification. Sensitivity was calculated based on the number of KD cases in the HRG. Of the 1104 employees screened, 58% and 42% were classified in HRG and LRG, respectively. There were 306 KD cases of whom, 65% were in the HRG. The sensitivity of the EXTENDED questionnaire to detect CKD was much higher (60%) compared to the SCORED questionnaire (25%). The prevalence of KD according to stage was: stage-1, 13.4%; stage-2, 9.9%; and late stages (3, 4, and 5), 4.5%. Microalbuminuria and dipstick-positive proteinuria showed statistically higher proportion in the HRG (25% and 4.1%) than in the LRG (19% and 1%, respectively) (P <0.05). Although the EXTENDED questionnaire was more sensitive in detecting KD, only screening the high-risk population will leave behind 35% of KD cases. There is, therefore, a need for mass screening at regular intervals.


Assuntos
Emprego , Governo , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Programas de Rastreamento/métodos , Saúde do Trabalhador , Inquéritos e Questionários , Adulto , Doenças Assintomáticas , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
20.
J Obstet Gynaecol ; 36(6): 833-838, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26982394

RESUMO

There is no data on menstrual cyclicity post oral contraceptive (OC) withdrawal with nonhormonal options in PCOS patients. OC could affect obesity, insulin and gonadotropins factors integral to pathogenesis of PCOS, thereby adversely affecting the HPG axis. Menstrual cycles of PCOS patients were retrospectively studied post OCP. Patients developing regular versus irregular cycles post OC were compared. Forty-eight PCOS patients were followed for an average of 1.9 years post OC. Thirty-six (75%) achieved regular cycles over a period of one year with other nonhormonal options like spironolactone and metformin. Seven patients required no treatment. Patients who continued to have irregular cycles had a longer pre OC cycle length (p < 0.01) and a greater duration of menstrual irregularity (p < 0.02), though age, BMI and hormones were similar in the two groups. In conclusion, spironolactone and metformin are effective nonhormonal options for regular periods post OC. Around 15% PCOS may not require any treatment post OC.


Assuntos
Ciclo Menstrual/efeitos dos fármacos , Distúrbios Menstruais/tratamento farmacológico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/complicações , Espironolactona/uso terapêutico , Adolescente , Adulto , Anticoncepcionais Orais Hormonais/administração & dosagem , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Distúrbios Menstruais/etiologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/fisiopatologia , Estudos Retrospectivos , Suspensão de Tratamento , Adulto Jovem
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