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1.
J Dent Res ; 103(4): 398-408, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38410924

RESUMO

The quest for finding a suitable scaffold system that supports cell survival and function and, ultimately, the regeneration of the pulp-dentin complex remains challenging. Herein, we hypothesized that dental pulp stem cells (DPSCs) encapsulated in a collagen-based hydrogel with varying stiffness would regenerate functional dental pulp and dentin when concentrically injected into the tooth slices. Collagen hydrogels with concentrations of 3 mg/mL (Col3) and 10 mg/mL (Col10) were prepared, and their stiffness and microstructure were assessed using a rheometer and scanning electron microscopy, respectively. DPSCs were then encapsulated in the hydrogels, and their viability and differentiation capacity toward endothelial and odontogenic lineages were evaluated using live/dead assay and quantitative real-time polymerase chain reaction. For in vivo experiments, DPSC-encapsulated collagen hydrogels with different stiffness, with or without growth factors, were injected into pulp chambers of dentin tooth slices and implanted subcutaneously in severe combined immunodeficient (SCID) mice. Specifically, vascular endothelial growth factor (VEGF [50 ng/mL]) was loaded into Col3 and bone morphogenetic protein (BMP2 [50 ng/mL]) into Col10. Pulp-dentin regeneration was evaluated by histological and immunofluorescence staining. Data were analyzed using 1-way or 2-way analysis of variance accordingly (α = 0.05). Rheology and microscopy data revealed that Col10 had a stiffness of 8,142 Pa with a more condensed and less porous structure, whereas Col3 had a stiffness of 735 Pa with a loose microstructure. Furthermore, both Col3 and Col10 supported DPSCs' survival. Quantitative polymerase chain reaction showed Col3 promoted significantly higher von Willebrand factor (VWF) and CD31 expression after 7 and 14 d under endothelial differentiation conditions (P < 0.05), whereas Col10 enhanced the expression of dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and collagen 1 (Col1) after 7, 14, and 21 d of odontogenic differentiation (P < 0.05). Hematoxylin and eosin and immunofluorescence (CD31 and vWF) staining revealed Col10+Col3+DPSCs+GFs enhanced pulp-dentin tissue regeneration. In conclusion, the collagen-based concentric construct modified by growth factors guided the specific lineage differentiation of DPSCs and promoted pulp-dentin tissue regeneration in vivo.


Assuntos
Fator A de Crescimento do Endotélio Vascular , Fator de von Willebrand , Camundongos , Animais , Células Cultivadas , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismo , Hidrogéis/metabolismo , Camundongos SCID , Colágeno/metabolismo , Diferenciação Celular , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Dentina , Polpa Dentária , Proliferação de Células
2.
Tech Coloproctol ; 27(10): 827-845, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37460830

RESUMO

PURPOSE: Currently, the anal fistula treatment which optimises healing and preserves bowel continence remains unclear. The aim of our study was to compare the relative efficacy of different surgical treatments for AF through a network meta-analysis. METHODS: Systematic searches of MEDLINE, EMBASE and CENTRAL databases up to October 2022 identified randomised controlled trials (RCTs) comparing surgical treatments for anal fistulae. Fistulae were classified as simple (inter-sphincteric or low trans-sphincteric fistulae crossing less than 30% of the external anal sphincter (EAS)) and complex (high trans-sphincteric fistulae involving more than 30% of the EAS). Treatments evaluated in only one trial were excluded from the primary analyses to minimise bias. The primary outcomes were rates of success in achieving AF healing and bowel incontinence. RESULTS: Fifty-two RCTs were included. Of the 14 treatments considered, there were no significant differences regarding short-term (6 months or less postoperatively) and long-term (more than 6 months postoperatively) success rates between any of the treatments in patients with both simple and complex anal fistula. Ligation of the inter-sphincteric fistula tract (LIFT) ranked best for minimising bowel incontinence in simple (99.1% of comparisons; 3 trials, n = 70 patients) and complex anal fistula (86.2% of comparisons; 3 trials, n = 102 patients). CONCLUSIONS: There is insufficient evidence in existing RCTs to recommend one treatment over another regarding their short and long-term efficacy in successfully facilitating healing of both simple and complex anal fistulae. However, LIFT appears to be associated with the least impairment of bowel continence, irrespective of AF classification.


Assuntos
Incontinência Fecal , Fístula Retal , Humanos , Incontinência Fecal/etiologia , Incontinência Fecal/cirurgia , Metanálise em Rede , Cicatrização , Canal Anal/cirurgia , Ligadura/efeitos adversos , Fístula Retal/cirurgia , Fístula Retal/etiologia , Resultado do Tratamento
3.
Mymensingh Med J ; 32(2): 550-555, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37002770

RESUMO

The present invitro type of study has done to check the effect of blood contamination & chlorhexidine combination on the bond strength of brackets bonded with self-etch primer technique. The study consisted of ninety sound human upper premolars (extracted for orthodontic purpose) fixed in a self-cure acrylic block and segregated into three groups of 30 samples each. 0.022 slot metal MBT brackets (Gemini series-3M unitek) were bonded with self-etch primer using Transbond XT composite, CA, USA and light cure for 40 seconds) on clean buccal surface. Teeth were divided into 3 groups-Group A/Control group, Group B, Group C. A computer was used to record the force applied to debond the bonded bracket in the unit of Newton. The analysis of variance indicated that there were significant differences (F value = 6.891, p value=0.002) in bond strengths between the various groups tested. The highest value of shear bond strength occurred when chlorhexidine (Group C) was used to remove the blood contamination (mean=15.874 MPa). When bonding was done in ideal condition (Group A), shear bond strength obtained was slightly lower (mean=14.497 MPa) as compared to Group C. On the other hand, lowest shear bond strength among all three groups occurred when blood contamination (Group B) was removed with water (mean=11.059 MPa). Analysis of the study showed that shear bond strength of orthodontic brackets to enamel significantly decreased during bonding with self-etch primer in blood contamination condition. Self-etch primer displayed considerably superior performance with the use of chlorhexidine instead of water to wash the blood contamination.


Assuntos
Clorexidina , Braquetes Ortodônticos , Humanos , Clorexidina/farmacologia , Condicionamento Ácido do Dente/métodos , Teste de Materiais , Resistência ao Cisalhamento
4.
Epidemiol Infect ; 147: e294, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31637988

RESUMO

Mycetoma is a chronic granulomatous, suppurative and progressive inflammatory disease that usually involves the subcutaneous tissue and bones after traumatic inoculation of the causative organism. In India, actinomycotic mycetoma is prevalent in south India, south-east Rajasthan and Chandigarh, while eumycetoma, which constitutes one third of the total cases, is mainly reported from north India and central Rajasthan. The objective was to determine the epidemiological profile and spectrum of eumycetoma from a tertiary care hospital in Delhi, North India. Thirty cases of eumycetoma were diagnosed by conventional methods of direct microscopy, culture and species-specific sequencing as per standard protocol. The spectrum of fungal pathogens included Exophiala jeanselmei, Madurella mycetomatis, Fusarium solani, Sarocladium kiliense, Acremonium blochii, Aspergillus nidulans, Fusarium incarnatum, Scedosporium apiospermum complex, Curvularia lunata and Medicopsis romeroi. Eumycetoma can be treated with antifungal therapy and needs to be combined with surgery. It has good prognosis if it is timely diagnosed and the correct species identified by culture for targeted therapy of these patients. Black moulds required prolonged therapy. Its low reporting and lack of familiarity may predispose patients to misdiagnosis and consequently delayed treatment. Hence health education and awareness campaign on the national and international level in the mycetoma belt is crucial.


Assuntos
Micetoma/epidemiologia , Doenças Negligenciadas/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Micetoma/diagnóstico , Micetoma/terapia , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/terapia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
5.
J Dent Res ; 97(1): 77-83, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28898112

RESUMO

The induced pluripotent stem cells (iPSCs) have an intrinsic capability for indefinite self-renewal and large-scale expansion and can differentiate into all types of cells. Here, we tested the potential of iPSCs from dental pulp stem cells (DPSCs) to differentiate into functional odontoblasts. DPSCs were reprogrammed into iPSCs via electroporation of reprogramming factors OCT-4, SOX2, KLF4, LIN28, and L-MYC. The iPSCs presented overexpression of the reprogramming genes and high protein expressions of alkaline phosphatase, OCT4, and TRA-1-60 in vitro and generated tissues from 3 germ layers in vivo. Dentin discs with poly-L-lactic acid scaffolds containing iPSCs were implanted subcutaneously into immunodeficient mice. After 28 d from implantation, the iPSCs generated a pulp-like tissue with the presence of tubular dentin in vivo. The differentiation potential after long-term expansion was assessed in vitro. iPSCs and DPSCs of passages 4 and 14 were treated with either odontogenic medium or extract of bioactive cement for 28 d. Regardless of the passage tested, iPSCs expressed putative markers of odontoblastic differentiation and kept the same mineralization potential, while DPSC P14 failed to do the same. Analysis of these data collectively demonstrates that human iPSCs can be a source to derive human odontoblasts for dental pulp research and test bioactivity of materials.


Assuntos
Células-Tronco Pluripotentes Induzidas/fisiologia , Odontoblastos/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/fisiologia , Eletroporação , Feminino , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/farmacologia , Camundongos , Camundongos SCID , Fator 3 de Transcrição de Octâmero/farmacologia , Odontoblastos/metabolismo , Proteínas Proto-Oncogênicas c-myc/farmacologia , Proteínas de Ligação a RNA/farmacologia , Fatores de Transcrição SOXB1/farmacologia , Alicerces Teciduais
6.
Fish Shellfish Immunol ; 70: 252-259, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28882801

RESUMO

White spot syndrome virus, continues to cause huge economic loss to aquaculture industry. In the absence of effective therapeutics to control WSSV, it is important to understand the host pathogen interaction at the molecular level. Suppression subtractive hybridization (SSH) cDNA library was constructed which led to identification of several differentially expressed genes in response to WSSV infection in Penaeus monodon. The genes expressed in SSH cDNA library of shrimp gill and gut tissues belonged to a wide range of biological functions. The three differentially expressed genes, Single von Willebrand factor type C domain protein (pmSVC), P53 protein gene (pmP53) and ADP ribosylation factor (pmArf) were up-regulated against WSSV infection and were further characterized by gene silencing to study the role of these shrimp immune genes on WSSV multiplication. The sequence-specific knock down of pmSVC, pmP53 and pmArf using the dsRNA revealed that in pmSVC-dsRNA inoculated shrimps WSSV replication was more with increased viral copy numbers when compared with pmP53-dsRNA and pmArf -dsRNA inoculated shrimps. The varied response of immune genes to WSSV infection, indicated that host genes may either inhibit virus replication to some extent or might act as a target to facilitate viral pathogenesis.


Assuntos
Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Inativação Gênica , Imunidade Inata , Penaeidae/genética , Penaeidae/imunologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Biblioteca Gênica , Interações Hospedeiro-Patógeno , Interferência de RNA , Replicação Viral
7.
Mol Psychiatry ; 22(8): 1172-1184, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28044059

RESUMO

Clinical evidence suggests that mood and behavioral symptoms in premenstrual dysphoric disorder (PMDD), a common, recently recognized, psychiatric condition among women, reflect abnormal responsivity to ovarian steroids. This differential sensitivity could be due to an unrecognized aspect of hormonal signaling or a difference in cellular response. In this study, lymphoblastoid cell line cultures (LCLs) from women with PMDD and asymptomatic controls were compared via whole-transcriptome sequencing (RNA-seq) during untreated (ovarian steroid-free) conditions and following hormone treatment. The women with PMDD manifested ovarian steroid-triggered behavioral sensitivity during a hormone suppression and addback clinical trial, and controls did not, leading us to hypothesize that women with PMDD might differ in their cellular response to ovarian steroids. In untreated LCLs, our results overall suggest a divergence between mRNA (for example, gene transcription) and protein (for example, RNA translation in proteins) for the same genes. Pathway analysis of the LCL transcriptome revealed, among others, over-expression of ESC/E(Z) complex genes (an ovarian steroid-regulated gene silencing complex) in untreated LCLs from women with PMDD, with more than half of these genes over-expressed as compared with the controls, and with significant effects for MTF2, PHF19 and SIRT1 (P<0.05). RNA and protein expression of the 13 ESC/E(Z) complex genes were individually quantitated. This pattern of increased ESC/E(Z) mRNA expression was confirmed in a larger cohort by qRT-PCR. In contrast, protein expression of ESC/E(Z) genes was decreased in untreated PMDD LCLs with MTF2, PHF19 and SIRT1 all significantly decreased (P<0.05). Finally, mRNA expression of several ESC/E(Z) complex genes were increased by progesterone in controls only, and decreased by estradiol in PMDD LCLs. These findings demonstrate that LCLs from women with PMDD manifest a cellular difference in ESC/E(Z) complex function both in the untreated condition and in response to ovarian hormones. Dysregulation of ESC/E(Z) complex function could contribute to PMDD.


Assuntos
Transtorno Disfórico Pré-Menstrual/genética , Transtorno Disfórico Pré-Menstrual/metabolismo , Proteínas Repressoras/metabolismo , Adulto , Afeto/fisiologia , Linhagem Celular , Estradiol , Feminino , Regulação da Expressão Gênica/genética , Inativação Gênica/fisiologia , Humanos , Ovário/metabolismo , Progesterona , Proteínas Repressoras/genética , Esteroides/metabolismo , Transcriptoma/genética , Regulação para Cima
8.
Clin Exp Nephrol ; 20(2): 273-83, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26351173

RESUMO

BACKGROUND: We performed a discovery phase of urinary proteomic profile in children with idiopathic nephrotic syndrome and validated selected biomarkers. METHODS: Urinary proteomic profile was performed using isobaric tags for relative and absolute quantitation labeling, coupled with liquid chromatography-matrix assisted laser desorption and ionization analysis. Validation of biomarkers apolipoprotein A1, alpha 2 macroglobulin, orosomucoid 2, retinol binding protein 4 and leucine-rich alpha 2-glycoprotein 1 was done by enzyme-linked immunosorbent assay. RESULTS: Apolipoprotein A1 levels of <0.48 µg/mg of creatinine-differentiated steroid-resistant nephrotic syndrome (SRNS) from first episode nephrotic syndrome, area under curve (AUC) [0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity] and a value of <0.24 µg/mg of creatinine could differentiate SRNS from frequently relapsing nephrotic syndrome/steroid dependent nephrotic syndrome [AUC 0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity]. Alpha 2 macroglobulin could differentiate children with SRNS-focal segmental glomerulosclerosis (FSGS) from SRNS-minimal change disease (MCD) at values >3.3 µg/mg of creatinine [AUC 0.84 (CI 0.62-1.0), 90 % sensitivity and 85 % specificity]. Orosomucoid 2 >1.81 µg/mg of creatinine could distinguish SRNS-FSGS from SRNS-MCD [AUC 0.84 (CI 0.62-1.0), sensitivity 90 % and specificity 85.5 %]. RBP 4 value of >1.54 µg/mg of creatinine differentiated SRNS-FSGS from SRNS-MCD [AUC 0.87 (CI 0.68-1.0), sensitivity 90 % and specificity 85.7 %]. CONCLUSIONS: Lower level of apolipoprotein A1 in urine is suggestive of SRNS. Alpha 2 macroglobulin, retinol binding protein 4 and orosomucoid 2 are markers associated with FSGS, with alpha 2 macroglobulin being most predictive.


Assuntos
Biomarcadores/urina , Síndrome Nefrótica/congênito , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Síndrome Nefrótica/urina
9.
Int J STD AIDS ; 27(13): 1145-1152, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-24516076

RESUMO

Long-term use of stavudine is associated with a high incidence of lipodystrophy, warranting its substitution with zidovudine in first-line antiretroviral therapy (ART) regimens. In a prospective observational study, we determined the spectrum and severity of haematological changes after switching from stavudine- to zidovudine-based ART in Indian children aged 2-18 years who had received a stavudine-based ART regimen for at least 48 weeks. They were followed for 48 weeks for changes in haematological parameters and CD4 cell counts after switching to zidovudine. Of the 60 children analysed, 45 (75%) showed a significant fall in Hb (>1 g/dl). A majority developed grade 1 anaemia (14 [31%]) while only three (6%) developed grade 4 anaemia. The lowest Hb was recorded between 12 and 16 weeks with spontaneous improvement noticed after 28 weeks. A significant drop in absolute neutrophil count (5067 cells/mm3 to 3625 cells/mm3; p = 0.004) was also observed but none developed severe neutropenia. No significant changes were observed in platelet and CD4 cell counts. Since the incidence of severe drug toxicity was low with zidovudine and the majority of children recovered without intervention, drug toxicity should not preclude its routine use in poor countries.


Assuntos
Anemia/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Estavudina/administração & dosagem , Zidovudina/administração & dosagem , Anemia/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Criança , Feminino , Testes Hematológicos , Hemoglobinas/análise , Humanos , Incidência , Lipodistrofia/complicações , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Estavudina/efeitos adversos , Resultado do Tratamento , Carga Viral , Zidovudina/efeitos adversos
10.
Saudi J Kidney Dis Transpl ; 26(6): 1270-3, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26586071

RESUMO

Meningitis and associated intracranial bleeding have been rarely reported in patients with steroid-resistant nephrotic syndrome. We present such a case with raised intracranial tension in a 13-year-old child and discuss the management issues. Prompt recognition and appropriate treatment of these complications can be life saving in a child with nephrotic syndrome.


Assuntos
Hemorragias Intracranianas/etiologia , Meningites Bacterianas/etiologia , Síndrome Nefrótica/congênito , Adolescente , Humanos , Hemorragias Intracranianas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Síndrome Nefrótica/complicações
12.
J Appl Microbiol ; 119(4): 991-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26218659

RESUMO

AIMS: To report fungal and aflatoxin contamination in stored tobacco leaves and the potential of Foeniculum vulgare (fennel) seed essential oil (EO) as a plant-based preservative in protection of tobacco during storage. METHODS AND RESULTS: Mycological analysis of tobacco samples was done by surface sterilization and serial dilution tests. The Aspergillus flavus isolates were screened for their toxigenicity. Both in vivo and in vitro tests were done to evaluate antifungal and antiaflatoxigenic efficacy of chemically characterized EO. The mycoflora analysis revealed 108 fungal colonies belonging to five genera and nine species. All A. flavus isolates were found aflatoxigenic during screening. Gas chromatography and mass spectrometry analysis of EO identified 19 components (99·66%); estragole being the major component (47·49%). The EO showed broad fungitoxicity at 1·25 µl ml(-1) and 100% inhibition to AFB1 production as well as ergosterol synthesis at 1·0 µl ml(-1) concentration. EO showed 100% protection of stored tobacco samples from aflatoxin B1 contamination. CONCLUSIONS: The fennel EO can thus be formulated as a plant-based preservative for food items. SIGNIFICANCE AND IMPACT OF THE STUDY: The present investigation comprises the first report on antiaflatoxin efficacy of fennel oil and its potency in the protection of tobacco leaves from fungal and aflatoxin contamination during storage.


Assuntos
Aflatoxina B1/biossíntese , Antifúngicos/farmacologia , Aspergillus flavus/efeitos dos fármacos , Foeniculum/química , Nicotiana/microbiologia , Óleos Voláteis/farmacologia , Doenças das Plantas/prevenção & controle , Extratos Vegetais/farmacologia , Aflatoxina B1/análise , Aspergillus flavus/genética , Aspergillus flavus/metabolismo , Óleos Voláteis/química , Doenças das Plantas/microbiologia , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/microbiologia , Sementes/química , Nicotiana/química
13.
J Food Sci Technol ; 52(4): 2220-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25829603

RESUMO

Mold association, aflatoxin B1 contamination as well as oxidative deterioration of agri-food items during storage and processing are some global task for food industries. In view of the adverse effects of some synthetic preservatives on treated food items and subsequently on consumers health, recently plant based chemicals are encouraged by food industries as better alternatives of synthetics. The present study recommends the combination (1:1:1) of Angelica archangelica essential oil: Phenyl ethyl alcohol (PEA): α- terpineol as botanical preservative against molds, aflatoxin contamination and oxidative deterioration of walnut samples. Eight mold species were procured from stored walnut samples, including some aflatoxigenic Aspergillus flavus strains. The combination inhibited growth of aflatoxigenic strain Aspergillus flavus NKDW-7 and aflatoxin B1 production at 2.25 and 2.0 µL mL(-1) respectively. The IC50 value of the combination was recorded as 3.89 µL mL(-1), showing strong antioxidant potential. The antifungal action of the combination showed > 90 % decrease in ergosterol content in plasma membrane of A. flavus at 2.0 µL mL(-1). The LD50 of the combination, through oral administration on mice, was 9562.9 µL kg(-1) body weight, indication favourable safety profile as a plant based preservative. The combination may be recommended as safe preservative against molds, aflatoxin contamination and oxidative deterioration of walnut samples.

14.
J Food Sci Technol ; 51(9): 2210-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25190885

RESUMO

Essential oils (EOs) from Ageratum conyzoides L., Coleus aromaticus Benth. and Hyptis suaveolens (L.) Poit were extracted and tested against Tribolium castaneum Herbst, the storage grain insect. The EOs were found effective against Tribolium castaneum during in vitro as well as in vivo fumigant testing. The EOs of H. suaveolens and A. conyzoides showed 100 % mortality of test insect at 250 ppm while C. aromaticus at 350 ppm. During in vivo fumigant testing of wheat samples against Tribolium castaneum, the essential oils of A. conyzoides and C. aromaticus completely checked the damage of wheat grains by the insect at 1000 ppm while essential oil of H. suaveolens checked the grain damage completely even at 500 ppm concentration. There was no adverse effect on seed germination as well as on seedling growth of EOs treated seeds showing non-phytotoxic nature of the oils. Hence, these EOs may be recommended as botanical insecticide against insect invasion of stored food commodities, thereby enhancing their shelf life.

15.
Placenta ; 35(7): 461-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24816515

RESUMO

INTRODUCTION: Maternal nutrient restriction and decreased scotophase concentrations of melatonin have been associated with severely compromised pregnancies. We hypothesized that melatonin supplementation in a compromised pregnancy enhances the bradykinin (BK)-induced relaxations of placental arteries thereby ensuring sufficient umbilical blood flow to the developing fetus. METHODS: Pregnant ewes (n = 31) were fed an adequate (ADQ) or nutrient restricted (RES) diet supplemented with 5 mg of melatonin (MEL) or without melatonin (CON) from day 50 to 130 of gestation. On day 130 of gestation, the maternal (caruncular; CAR) and fetal (cotyledonary; COT) placental arteries were suspended in organ chambers for isometric tension recording. RESULTS: There were no treatment or dietary effects on CAR arteries for any vasoactive agent. However, in COT arteries, MEL ewes were more sensitive (P < 0.01) to bradykinin-induced relaxation than CON ewes. There was a melatonin by nutritional level interaction (P < 0.01) with sodium nitroprusside-induced relaxation of COT arteries where CON-RES were more sensitive to sodium nitroprusside compared to CON-ADQ, which was in contrast to when ewes were fed MEL. There was a significant melatonin by nutritional interaction (P = 0.04) for responsiveness to norepinephrine. The sensitivity of the COT arteries to norepinephrine in CON-RES ewes was decreased compared to CON-ADQ. Melatonin supplementation, regardless of maternal dietary intake, resulted in COT arteries having similar responsiveness to CON-RES ewes. CONCLUSION: An increase in placental vessel sensitivity to bradykinin-induced relaxation may contribute to melatonin-induced increases in umbilical artery blood flow.


Assuntos
Fenômenos Fisiológicos da Nutrição Materna , Melatonina/administração & dosagem , Circulação Placentária/efeitos dos fármacos , Angiotensina II/farmacologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bradicinina/farmacologia , Dieta , Feminino , Melatonina/fisiologia , Norepinefrina/farmacologia , Placenta/irrigação sanguínea , Placenta/efeitos dos fármacos , Gravidez , Carneiro Doméstico , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
17.
Atherosclerosis ; 233(2): 704-706, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24583419

RESUMO

BACKGROUND: Impaired endothelial function is the initial step in atherogenesis, which is largely responsible for ischaemic heart disease and thrombotic strokes decades later. METHODS: Fourty two children with first episode nephrotic syndrome (FENS) aged 1-16 years and 40 controls were enrolled. Soluble thrombomodulin (sTM), tissue plasminogen activator (t-PA), plasminogen activator inhibitor -1 (PAI-1) and von-willebrand factor (vWF) levels were measured in plasma in FENS, at 12 weeks of drug induced remission and in steroid resistant nephrotic syndrome (SRNS) patients at diagnosis. RESULTS: PAI-1, sTM, vWF and t-PA were significantly raised at the onset of nephrotic syndrome (p<0.0001). All the markers had a fall after 12 weeks of steroid treatment, but were still raised. Children with SRNS had higher levels of sTM, tPA, vWF as compared to infrequent relapsers, at onset and at 4 weeks of steroid treatment. CONCLUSION: Children with idiopathic nephrotic syndrome have endothelial dysfunction which is largely dependent upon disease activity.


Assuntos
Endotélio Vascular/fisiopatologia , Síndrome Nefrótica/fisiopatologia , Adolescente , Corticosteroides/uso terapêutico , Biomarcadores , Criança , Pré-Escolar , Resistência a Medicamentos , Feminino , Seguimentos , Humanos , Lactente , Lipídeos/sangue , Masculino , Síndrome Nefrótica/sangue , Síndrome Nefrótica/tratamento farmacológico , Inibidor 1 de Ativador de Plasminogênio/sangue , Recidiva , Trombomodulina/sangue , Ativador de Plasminogênio Tecidual/sangue , Fator de von Willebrand/análise
18.
Clin Transl Sci ; 7(2): 132-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24456587

RESUMO

BACKGROUND: Homocysteine metabolism is altered in children with idiopathic nephrotic syndrome. Hyperhomocysteinemia is a risk factor of early atherosclerosis and glomerulosclerosis and may occur at time of first occurrence of idiopathic nephrotic syndrome. METHODS: Thirty children with first episode of idiopathic nephrotic syndrome (FENS) aged 1-16 years along with 30 age- and sex-matched healthy controls were enrolled in this study. Homocysteine and cysteine were measured with HPLC; vitamin B12 and folic acid were measured with electro-chemilumiscence immunoassay. Primary outcome measure was plasma homocysteine level in children with FENS and in controls. Secondary outcome measures were (1) plasma and urine homocysteine and cysteine levels in children with FENS at 12 weeks and 1 year (remission) and (2) plasma and urine levels of vitamin B12 and folic acid in children with FENS, at 12 weeks and 1 year (remission). RESULTS: Plasma homocysteine and cysteine levels were comparable to controls in children with FENS, at 12 weeks and 1-year remission. Plasma levels of vitamin B12 and folic acid were significantly decreased compared to controls in FENS due to increased urinary excretion, which normalize during remission at 12 weeks and 1 year. Urinary homocysteine and cysteine levels were significantly raised in FENS compared to controls and continued to be raised even at 12-week and 1-year remission. CONCLUSION: Homocysteine metabolism is deranged in children with FENS. Renal effects of long-term raised urinary homocysteine levels need to be studied.


Assuntos
Homocisteína/metabolismo , Síndrome Nefrótica/metabolismo , Estudos de Casos e Controles , Criança , Colesterol/sangue , Cisteína/sangue , Cisteína/urina , Demografia , Feminino , Ácido Fólico/sangue , Homocisteína/sangue , Humanos , Masculino , Síndrome Nefrótica/sangue , Síndrome Nefrótica/urina , Proteinúria/sangue , Indução de Remissão , Albumina Sérica/metabolismo , Vitamina B 12/sangue
19.
Pediatr Cardiol ; 35(5): 824-30, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24435507

RESUMO

Oral ibuprofen is being used as an alternative to indomethacin in medical management of patent ductus arteriosus (PDA), but limited data exist on oral efficacy of these drugs for PDA closure in India. To assess and compare the efficacy of oral ibuprofen and oral indomethacin for PDA closure in preterm Indian neonates, we designed a randomized controlled study on clinically diagnosed and echocardiographically confirmed hemodynamically significant PDA in preterm neonates. Patients were assigned to receive either oral ibuprofen at a dosage of 10, 5, 5 mg/kg every 24 h or three doses of oral indomethacin (0.20-0.25 mg/kg every 24 h) starting on the third day of life or when diagnosed. A second course of ibuprofen/indomethacin was given, if PDA failed to close within 48 h after the first course. Patients were monitored for complications like oliguria, bleeding, necrotizing enterocolitis, intraventricular hemorrhage, oxygen dependency, and gastrointestinal side effects. The baseline characteristics were comparable in both groups. Of the 83 children enrolled, 57.8 % received oral ibuprofen and 42.1 % received oral indomethacin. The overall closure rate of PDA was 60 and 65.7 % in the ibuprofen and indomethacin groups, respectively. Closure rate was significantly higher when the drugs were administered at an early postnatal age (<8 days) (83.3 % [p = 0.02] in the indomethacin group and 75 % [p = 0.03] in the ibuprofen group) in neonates >28 weeks (ibuprofen group 66.7 % [p = 0.02]; indomethacin group 65.5 % [p = 0.04]) and in babies with birth weight >1,000 g (ibuprofen group 62.2 %; indomethacin group 70 % [p = 0.04 in both groups]). Complications were similar in both groups. The efficacy of both drugs was similar. Poor closure in our study could be because of genetic differences in pharmacokinetics of drug metabolism in the Indian population. Regimens with higher doses or increased duration of treatment may increase the frequency of closure. Studies with larger numbers of subjects with evaluation of pharmacokinetic parameters are therefore required.


Assuntos
Inibidores de Ciclo-Oxigenase/administração & dosagem , Permeabilidade do Canal Arterial/tratamento farmacológico , Ibuprofeno/administração & dosagem , Indometacina/administração & dosagem , Administração Oral , Inibidores de Ciclo-Oxigenase/efeitos adversos , Inibidores de Ciclo-Oxigenase/uso terapêutico , Feminino , Humanos , Ibuprofeno/efeitos adversos , Ibuprofeno/uso terapêutico , Índia , Indometacina/efeitos adversos , Indometacina/uso terapêutico , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Resultado do Tratamento
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