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1.
Arch Pharm (Weinheim) ; 357(4): e2300503, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38251950

RESUMO

A series of 1,1'-biphenyl-3-carboxamide and furan-phenyl-carboxamide analogs were synthesized using an optimized scheme and confirmed by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry techniques. The synthesized peptidomimetics analogs were screened in vitro to understand the inhibitory potential of pancreatic lipase (PL). Analogs were assessed for the PL inhibitory activity based on interactions, geometric complementarity, and docking score. Among the synthesized analogs, 9, 29, and 24 were found to have the most potent PL inhibitory activity with IC50 values of 3.87, 4.95, and 5.34 µM, respectively, compared to that of the standard drug, that is, orlistat, which inhibits PL with an IC50 value of 0.99 µM. The most potent analog, 9, exhibited a competitive-type inhibition with an inhibition constant (Ki) of 2.72 µM. In silico molecular docking of analog 9 with the PL (PDB ID:1LPB) showed a docking score of -11.00 kcal/mol. Analog 9 formed crucial hydrogen bond interaction with Ser152, His263, π-cation interaction with Asp79, Arg256, and π-π stacking with Phe77, Tyr114 at the protein's active site. The molecular dynamic simulation confirmed that analog 9 forms stable interactions with PL at the end of 200 ns with root mean square deviation values of 2.5 and 6 Å. No toxicity was observed for analog 9 (concentration range of 1-20 µM) when tested by MTT assay in RAW 264.7 cells.


Assuntos
Peptidomiméticos , Humanos , Relação Estrutura-Atividade , Peptidomiméticos/farmacologia , Simulação de Acoplamento Molecular , Lipase , Obesidade/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química
2.
J Antimicrob Chemother ; 78(6): 1476-1479, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37071590

RESUMO

BACKGROUND: We conducted a nationwide cross-sectional study to estimate pretreatment drug resistance (PDR) prevalence in adults initiating ART in Sri Lanka following the WHO's recommendations. METHODS: HIV drug resistance was determined on dried blood spots (DBSs) using population-based sequencing of the protease and reverse transcriptase genes and interpretation was based on Stanford HIVdb v9.0. Analyses were weighted to adjust for multistage sampling and genotypic failure rate. We used logistic regression to assess differences between groups. RESULTS: Overall, in 10% (15 of 150) of patients initiating ART, HIV drug resistance mutations were detected. The prevalence of resistance to NNRTI drugs efavirenz/nevirapine was 8.4% (95% CI 4.6-15.0) but differed among those reporting having prior antiretroviral (ARV) exposure (24.4%, 95% CI 13.8-39.5) compared with 4.6% (95% CI 1.6-12.8) for those reporting as being ARV naive (OR 4.6, 95% CI 1.3-16.6, P = 0.021). PDR to efavirenz/nevirapine was also nearly twice as high among women (14.1%, 95% CI 6.1-29.4) compared with men (7.0%, 95% CI 3.1-14.7) (P = 0.340) and three times high among heterosexuals (10.4%, 95% CI 2.4-35.4) compared with MSM (3.8%, 95% CI 1.1-12.7) (P = 0.028). NRTI PDR prevalence was 3.8% (95% CI 1.1-12.1) and no PI PDR was observed in the study. CONCLUSIONS: A high prevalence of efavirenz/nevirapine PDR was reported, especially in patients with prior ARV exposure, in women and those reporting being heterosexual. These findings highlight the need to fast-track the transition to the WHO-recommended dolutegravir-based first-line ART.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Minorias Sexuais e de Gênero , Adulto , Masculino , Humanos , Feminino , Nevirapina/uso terapêutico , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Homossexualidade Masculina , Prevalência , Estudos Transversais , Sri Lanka/epidemiologia , HIV-1/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Mutação , Farmacorresistência Viral/genética
3.
J Postgrad Med ; 69(4): 205-214, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37675667

RESUMO

Background: Diarrhea in kidney transplant recipients (KTRs) can be associated with significant morbidity. Material and Methods: We evaluated 198 KTRs for a history of diarrhea post-kidney transplant at a tertiary care center in western India over 1 year. A protocol-based evaluation of diarrhea was done with respect to clinical features, diagnostic evaluation, associated acute allograft dysfunction, and its impact on long-term allograft function. Primary outcomes of interest were: chronic allograft injury (CAI) and the need for mycophenolate mofetil (MMF) withdrawal. We also assessed the effect of MMF withdrawal on the risk of the development of CAI. Results: Eighty-five of 198 (42.5%) recipients experienced diarrhea and a total of 140 diarrheal episodes were evaluated. The mean age of these 85 recipients was 38 ± 12 years and 72 (84.7%) were males. 73 of 85 recipients were on MMF at the time of diarrhea and in 35 (48%) of them MMF withdrawal was needed for chronic and persistent symptoms. Diarrhea was attributed to infective etiologies in 90 of 140 (64.2%) cases. Among the microbiologically confirmed infective diarrheal episodes, giardia and cryptosporidium were the common pathogens in 11/28 (39%) and 6/28 (21.4%) episodes respectively. One hundred and twenty-eight episodes out of 140 (91.4%) episodes were complicated by acute allograft dysfunction. Forty-one of 85 recipients (48.2%) developed chronic allograft injury and 12 (14.1%) developed allograft rejection (acute and/or chronic). Probability of chronic allograft injury was higher in those with MMF withdrawal. Conclusion: Diarrhea post-kidney transplant adversely affects graft function, especially after MMF withdrawal.


Assuntos
Criptosporidiose , Cryptosporidium , Transplante de Rim , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Transplante de Rim/efeitos adversos , Imunossupressores/efeitos adversos , Criptosporidiose/etiologia , Ácido Micofenólico/efeitos adversos , Fatores de Risco , Diarreia/etiologia , Diarreia/induzido quimicamente
4.
Osteoporos Int ; 33(7): 1521-1533, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35249146

RESUMO

Dialysis patients have compromised bone health that increases their fracture risk due to low bone mass and deterioration in bone microarchitecture. Through meta-analyses of published studies, we conclude that dialysis patients suffer from impaired compartmental bone parameters compared with healthy controls. INTRODUCTION: We performed meta-analyses to determine the effect of chronic kidney disease (CKD) patients under dialysis on the trabecular and cortical parameters of radius and tibia. METHODS: This is a meta-analysis of cross-sectional and prospective clinical studies. PubMed, Web of Science, Google Scholar, and Scopus were searched using various permutation combinations. Dialysis patients were compared with non-CKD healthy controls using quantitative computed tomography. High-resolution peripheral quantitative computed tomography (HR-pQCT) and pQCT data of dialysis patients were dissected from eligible studies for pooled analysis of each parameter. RESULTS: Ten studies met the inclusion criteria that included data from 457 dialysis patients and 2134 controls. Pooled analysis showed a significant decrease (a) in total vBMD at distal radius [standard deviation of the mean (SDM) = -0.842, p = 0.000] and tibia (SMD = -0.705, p = 0.000) and (b) in cortical vBMD (SDM = -1.037, p = 0.000) at radius of dialysis patients compared with control. There were strong correlations between total vBMD and microarchitecture parameters at tibia in dialysis patients. CONCLUSIONS: At radius and tibia, bone mass, microarchitecture, and geometry at trabecular and cortical envelopes displayed impairments in dialysis patients compared with control. Tibial vBMD may have diagnostic value in dialysis. HR-pQCT and pQCT may be used to further understand the compartmental bones response to CKD-induced loss at different stages of CKD.


Assuntos
Diálise Renal , Insuficiência Renal Crônica , Absorciometria de Fóton , Densidade Óssea/fisiologia , Estudos Transversais , Humanos , Estudos Prospectivos , Rádio (Anatomia)/diagnóstico por imagem , Diálise Renal/efeitos adversos , Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
5.
Clin Exp Dermatol ; 47(3): 516-521, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34480806

RESUMO

Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.


Assuntos
Leishmaniose/terapia , Antiprotozoários/uso terapêutico , Terapia Combinada , Crioterapia , Quimioterapia Combinada , Temperatura Alta/uso terapêutico , Humanos , Imunoterapia , Leishmaniose/tratamento farmacológico , Fotoquimioterapia
6.
Clin Exp Dermatol ; 47(1): 110-113, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34236726

RESUMO

The management of pemphigus vulgaris (PV) is challenging. This study aimed to evaluate the immunomodulating effects of metformin on PV. The study was conducted in two phases: in the first phase, patients received routine first-line treatment (prednisolone plus azathioprine) for 2 months, then in the second phase, metformin was added to this regimen for another 2 months. After addition of metformin to the first-line medications, significant reductions were seen in serum IgG1 (reduced from 534.92 ± 134.83 mg/dL to 481.58 ± 130.46 mg/dL, P < 0.001), IgG4 (51.83 ± 27.26 mg/dL to 44.50 ± 26.05 mg/dL, P < 0.001) and interferon-γ (277.99 ± 108.71 pg/mL to 45.05 ± 17.080 pg/mL, P = 0.03) concentrations. The suppressant effect of metformin was greatest on IgG4 (coefficient of variation 1.28), the dominant subclass of IgG involved in PV. Metformin could have immunomodulating effects on PV with controlling effects on steroid complications.


Assuntos
Imunoglobulina G/sangue , Interferon gama/sangue , Metformina/uso terapêutico , Pênfigo/sangue , Pênfigo/tratamento farmacológico , Adulto , Feminino , Humanos , Imunoglobulina G/efeitos dos fármacos , Interferon gama/efeitos dos fármacos , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Pênfigo/imunologia , Estudos Prospectivos
7.
BMC Biol ; 19(1): 72, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849538

RESUMO

BACKGROUND: Membrane protrusions that occur on the dorsal surface of a cell are an excellent experimental system to study actin machinery at work in a living cell. Small GTPase Rac1 controls the membrane protrusions that form and encapsulate extracellular volumes to perform pinocytic or phagocytic functions. RESULTS: Here, capitalizing on rapid volumetric imaging capabilities of lattice light-sheet microscopy (LLSM), we describe optogenetic approaches using photoactivable Rac1 (PA-Rac1) for controlled ruffle generation. We demonstrate that PA-Rac1 activation needs to be continuous, suggesting a threshold local concentration for sustained actin polymerization leading to ruffling. We show that Rac1 activation leads to actin assembly at the dorsal surface of the cell membrane that result in sheet-like protrusion formation without any requirement of a template. Further, this approach can be used to study the complex morpho-dynamics of the protrusions or to investigate specific proteins that may be enriched in the ruffles. Deactivating PA-Rac1 leads to complex contractile processes resulting in formation of macropinosomes. Using multicolour imaging in combination with these approaches, we find that Myo1e specifically is enriched in the ruffles. CONCLUSIONS: Combining LLSM and optogenetics enables superior spatial and temporal control for studying such dynamic mechanisms. Demonstrated here, the techniques implemented provide insight into the complex nature of the molecular interplay involved in dynamic actin machinery, revealing that Rac1 activation can generate untemplated, lamellar protrusions.


Assuntos
Membrana Celular , Actinas/metabolismo , Membrana Celular/metabolismo , Proteínas rac1 de Ligação ao GTP/genética
8.
Anaesthesia ; 76(8): 1068-1076, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33891312

RESUMO

Accidental dural puncture following epidural insertion can cause a post-dural headache that is defined by the International Headache Society as self-limiting. We aimed to confirm if accidental dural puncture could be associated with persistent headache and back pain when compared with matched control parturients. We performed a prospective multicentre cohort study evaluating the incidence of persistent headache following accidental dural puncture at nine UK obstetric units. Parturients who sustained an accidental dural puncture were matched with controls who had undergone an uneventful epidural insertion. Participants were followed-up at six-monthly intervals for 18 months. Primary outcome was the incidence of persistent headache at 18 months. Ninety parturients who had an accidental dural puncture were matched with 180 controls. The complete dataset for primary analysis was available for 256 (95%) participants. Incidence of persistent headache at 18 months was 58.4% (52/89) in the accidental puncture group and 17.4% (29/167) in the control group, odds ratio (95%CI) 18.4 (6.0-56.7), p < 0.001, after adjustment for past history of headache, Hospital Anxiety and Depression Scale (depression) and Hospital Anxiety and Depression Scale (anxiety) scores. Incidence of low back pain at 18 months was 48.3% (43/89) in the accidental puncture group and 17.4% (29/167) in the control group, odds ratio (95%CI) 4.14 (2.11-8.13), with adjustment. We have demonstrated that accidental dural puncture is associated with long-term morbidity including persistent headache in parturients. This challenges the current definition of post-dural puncture headache as a self-limiting condition and raises possible clinical, financial and medicolegal consequences.


Assuntos
Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Anestesia Epidural/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Dor Lombar/epidemiologia , Cefaleia Pós-Punção Dural/epidemiologia , Adulto , Causalidade , Estudos de Coortes , Comorbidade , Feminino , Humanos , Incidência , Estudos Prospectivos , Reino Unido/epidemiologia , Adulto Jovem
9.
Hautarzt ; 72(5): 393-402, 2021 May.
Artigo em Alemão | MEDLINE | ID: mdl-33822278

RESUMO

Facial rejuvenation is gaining immense popularity among patients and clinicians. Botulinum toxins derived from bacteria are well-tolerated options as minimally invasive interventions for facial rejuvenation or other aesthetic procedures. These products have revolutionized aesthetic treatments. Several types of botulinum toxins (BoNT) are available. Currently type A and B are clinically used and only BoNT­A products are approved for use for cosmetic indications in the Germany and the United States. Each product is unique in terms of its composition. Understanding the various BoNT­A products is essential in choosing the optimal treatment for our patients. In this article we discuss different BoNT­A products used for aesthetic intervention.


Assuntos
Toxinas Botulínicas Tipo A , Técnicas Cosméticas , Dermatologia , Envelhecimento da Pele , Toxinas Botulínicas Tipo A/uso terapêutico , Estética , Alemanha , Humanos , Rejuvenescimento
10.
J Fluoresc ; 29(4): 837-843, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31309389

RESUMO

A novel Isophthaloyl-based symmetrical (12E,21E)-N1',N3'-bis(2-hydroxybenzylidene) isophthalohydrazide, receptor (1) was synthesized and characterized using various spectroscopic technique. The reorganization ability of receptor (1) was evaluated in semi-aqueous medium and shows significant enhancement in fluorescence intensity for Zn (II) ion over various metal ions in CH3CN:H2O (1:1, v/v). The 1:2 binding stoichiometry between receptor (1) and Zn (II) ion was established using Job's plot and the proposed complex structure was calculated by applying Density Functional Theory (DFT) method. The binding constant (Ka) of receptor (1) with Zn (II) ion was established with the Benesi-Hildebrand plot, Scatchard and Connor's plot and the values are 1.00 × 104 M-1, 1.05× 104 M-1 and 1.05× 104 M-1 respectively. The limit of detection (LOD) and limit of quantification (LOQ) of receptor (1) and Zn (II) ion was 0.292 µM and 0.974 µM respectively. The binding mode was due to photo-induced electron transfer (PET) and the coordination of Zn (II) ion with C = N hydroxyl group of receptor (1). Electrochemical analysis of metal free receptor (1) and with Zn (II) ion also confirmed the formation of complex.

11.
Bratisl Lek Listy ; 120(1): 19-25, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30685988

RESUMO

Historically, it was thought that neurogenesis ceased by the end of development, but it is currently understood that neurogenesis continues throughout the life of an individual. This continued growth arises from neural stem or progenitor cells (NSCs) located in specific regions of the adult brain, including the subventricular zone and the dentate gyrus of the hippocampus. Increased understanding of the nature of these cells and their reaction to environmental stimuli is of paramount importance in the effort to discern their role and potential use in repair following neurological disruption. Neurosphere suspension culture is identified as an effective way of actualizing a self-renewing population of neural stem cells. This study demonstrated that adult rat neural stem cells could be effectively induced to differentiate into cells of astrocytic lineage through exposure to fetal bovine serum (FBS), and that the same population of precursor cells could be induced toward neuronal lineage through exposure to dibutyryl cyclic adenosine monophosphate (dcAMP). There were also observations noted regarding difficulty inducing cell attachment following enzymatic digestion of neurospheres, and potential effects on various types of assays, including migration assays (Fig. 7, Ref. 31). Keywords: neural, stem cell, neurosphere, adult rat, cell culture, cell differentiation.


Assuntos
Diferenciação Celular , Células-Tronco Neurais , Neurogênese , Animais , Encéfalo , Células Cultivadas , Ratos
12.
AAPS PharmSciTech ; 19(7): 3187-3198, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30143947

RESUMO

Celecoxib (CXB), a COX-2 inhibitor, is primarily indicated for long-term treatment of rheumatoid arthritis (RA). The effective therapeutic efficacy of CXB on RA via oral administration shows adverse systemic complications, and therefore, local application of CXB has been recommended. The aim of the present study was to develop and characterize solid lipid nanoparticles (SLNs) with enhanced skin permeation potential of CXB. The particle size, polydispersity index (PDI), and percentage drug entrapment (PDE) of the developed SLNs (CXB-SLNs) were found to be 240 nm, < 0.3, and ~ 86% respectively. The developed SLNs exhibited sustained release up to 70% at the end of 48 h. Drug permeation was found to be 45% for SLN gel and 31% for conventional gel. The dermatokinetic studies also confirmed enhanced permeation of CXB in the epidermis and dermis and revealed superiority of the developed SLN gel vis-à-vis the conventional gel. Further, in the CFA-induced arthritis rat model, % arthritis index (AI) of the CXB-SLN gel formulation was found to be very less (18.54%) as compared to untreated (187.34%) and conventional gel-treated (91.61%) animals. In conclusion, the current study can provide a suitable alternative for the development of an effective topical formulation of CXB in lipid nanocarriers.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Celecoxib/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Celecoxib/química , Celecoxib/farmacocinética , Portadores de Fármacos , Adjuvante de Freund/imunologia , Lipídeos/química , Masculino , Ratos , Ratos Wistar , Pele/metabolismo
13.
Oral Dis ; 23(8): 1087-1098, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28580710

RESUMO

OBJECTIVE: To generate a nomogram for predicting the risk of neck node metastasis in pathologically node-negative patients using a combination of variables comprising of protein expression, ultrastructural alterations and clinicopathological parameters. MATERIALS AND METHODS: Surgically removed oral tumours (n = 103) were analysed for the expression of desmosomal and hemidesmosomal assembly proteins by immunohistochemistry and ultrastructural alterations by transmission electron microscopy (TEM). Protein expression, ultrastructural alterations and clinicopathological variables were used to construct nomogram from the training set in 75 patients. Clinical utility of the nomogram was validated in a discrete set of 28 patients. RESULTS: Univariate and multivariate analyses were performed on the training set, and obtained significant variables comprising of integrin ß4 expression (p = .027), number of hemidesmosomes (p = .027)/desmosomes (p = .046), tumour differentiation grade (p = .033) and tumour thickness (p = .024) were used for construction of the nomogram. The area under the curve was calculated for both training 0.821 (95% CI 0.725-0.918) and validation sets 0.880 (95% CI 0.743-1.000). The nomogram demonstrated a predictive accuracy of 73.3% and 78.6% with the sensitivity of 81.4% and 83.3% in the training and validation sets, respectively. CONCLUSIONS: The nomogram constructed on postsurgical tumour samples will be a value addition to histopathology for the detection of neck node metastasis in pathologically node-negative patients.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Nomogramas , Área Sob a Curva , Carcinoma de Células Escamosas/ultraestrutura , Desmossomos/metabolismo , Desmossomos/ultraestrutura , Feminino , Hemidesmossomos/metabolismo , Hemidesmossomos/ultraestrutura , Humanos , Integrina beta4/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/ultraestrutura , Pescoço , Gradação de Tumores , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco
14.
AAPS PharmSciTech ; 18(6): 2291-2302, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28101725

RESUMO

Hydrogen sulfide (H2S) targets both underlying factors in glaucoma pathogenesis by reducing elevated intraocular pressure (IOP) and providing retinal neuroprotection, whereas the current clinical approaches targets only reducing IOP. Therefore, H2S could be a potential superior candidate for glaucoma pharmacotherapy. However, H2S could be toxic in a concentration greater than 200 µM and its donors are unstable in water. Therefore, this study investigated the preparation and characterization of a non-aqueous in situ gelling sustained-release delivery system for H2S donors. The delivery system was prepared by dissolving GYY 4137, a H2S donor, in poly lactide-co-glycolide polymer (PLGA) (Resomer® RG 502H) solution prepared by dissolving polymer in a mixture of benzyl alcohol and benzyl benzoate in a ratio of 7:3, respectively. The GYY 4137 formulation was characterized for syringeability/injectability, change in pH and tonicity, moisture content, GYY 4137 degradation, and toxicity using rheometer, pH and osmometer, Karl Fisher titrimeter, NMR spectrometer, and Y79 retinoblastoma cells, respectively. The formulation was easily syringeable and injectable as evidenced by rheological data (plastic flow pattern with 43.89 ± 3.21 cP viscosity and 1.12 ± 0.15 Pa yield value). The pH, tonicity, and moisture content values were within acceptable range. NMR spectroscopy indicated presence of 4-methoxyphenylphosphonic acid (GYY 4137 degradation product). The GYY 4137 formulation did not show any significant (p < 0.05) toxicity except the solvent mixture. A sustained release of H2S was observed up to 72 h. The in situ gel forming PLGA-based system can be manipulated to achieve sustained release of H2S from its donor GYY 4137.


Assuntos
Preparações de Ação Retardada , Glaucoma/tratamento farmacológico , Morfolinas/administração & dosagem , Compostos Organotiofosforados/administração & dosagem , Cromatografia Líquida de Alta Pressão , Sulfeto de Hidrogênio/análise , Concentração de Íons de Hidrogênio
15.
Microb Ecol ; 71(3): 700-10, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26467244

RESUMO

The patterns and drivers of bacterial strain dominance remain poorly understood in natural populations. Here, we cultured 1292 Bradyrhizobium isolates from symbiotic root nodules and the soil root interface of the host plant Acmispon strigosus across a >840-km transect in California. To investigate epidemiology and the potential role of accessory loci as epidemic drivers, isolates were genotyped at two chromosomal loci and were assayed for presence or absence of accessory "symbiosis island" loci that encode capacity to form nodules on hosts. We found that Bradyrhizobium populations were very diverse but dominated by few haplotypes-with a single "epidemic" haplotype constituting nearly 30 % of collected isolates and spreading nearly statewide. In many Bradyrhizobium lineages, we inferred presence and absence of the symbiosis island suggesting recurrent evolutionary gain and or loss of symbiotic capacity. We did not find statistical phylogenetic evidence that the symbiosis island acquisition promotes strain dominance and both symbiotic and non-symbiotic strains exhibited population dominance and spatial spread. Our dataset reveals that a strikingly few Bradyrhizobium genotypes can rapidly spread to dominate a landscape and suggests that these epidemics are not driven by the acquisition of accessory loci as occurs in key human pathogens.


Assuntos
Bradyrhizobium/genética , Fabaceae/microbiologia , Simbiose , Bradyrhizobium/classificação , Bradyrhizobium/isolamento & purificação , Bradyrhizobium/fisiologia , California , Ilhas Genômicas , Genótipo , Filogenia , Nódulos Radiculares de Plantas/microbiologia
16.
Clin Radiol ; 71(10): 941-952, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27450410

RESUMO

The lymphatic system of the abdomen comprises of the cisterna chyli, its major and minor lymphatic tributaries, and lymph nodes. Disorders of the lymphatic system of the abdomen are rarely encountered and consist of primary and secondary types. Abdominal lymphangiomas constitute the majority and have characteristic imaging features. Complicated lymphangiomas may pose a diagnostic dilemma. Generalised systemic lymphangiomatosis is a rare condition and affects major organs with a poor prognosis. Retroperitoneal lymphangiectasia in the appropriate setting might predict underlying infection, such as filariasis. Other acquired conditions include iatrogenic or treatment-induced chylocoele. Chylous ascites can be secondary to multiple causes and can be confirmed by biochemical testing and lymphangiogram in appropriate settings.


Assuntos
Cavidade Abdominal/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Sistema Linfático/diagnóstico por imagem , Humanos
17.
Clin Exp Ophthalmol ; 43(9): 820-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26126999

RESUMO

BACKGROUND: The aim of this study is to evaluate the safety profile of Brilliant Blue G (BBG) with and without exposure to light (L) on three different retinal cell lines. METHOD: ARPE-19, R28 and MIO-M1 cells were treated with BBG: 0.125 mg/mL (0.5x clinical concentration), 0.25 mg/mL (1x) or 0.5 mg/mL (2x) with or without surgical illumination of halogen light exposure for 10 min, 15 min or 30 min. Cells were further cultured after 24 h and then analysed for cell viability, late stages of apoptosis and mitochondrial damage associated with early apoptosis using assays that measure trypan blue dye exclusion, increases in caspase-3/7 activity or changes in mitochondrial membrane potential (ΔΨm), respectively. RESULT: All three cell lines that were exposed to BBG in the presence or absence of light exposure for 30 min were found to have cell viability and caspase-3/7 activity levels similar to the untreated cultures. The mitochondrial membrane potential (ΔΨm) was decreased significantly at the 2x + L dose and 2x dose in all three retinal cell lines compared to their respective untreated control cells. At the lower doses of BBG, with or without exposure to light, the ΔΨm values were similar to the untreated control cultures. CONCLUSION: Exposure to BBG dye concentrations that are used clinically (0.125 mg/mL and 0.25 mg/mL) in the presence up to 30 min of surgically equivalent light intensity is safe for retinal cells.


Assuntos
Células Ependimogliais/efeitos da radiação , Indicadores e Reagentes/farmacologia , Luz , Retina/efeitos da radiação , Epitélio Pigmentado da Retina/efeitos da radiação , Corantes de Rosanilina/farmacologia , Animais , Apoptose , Caspase 3/metabolismo , Caspases Iniciadoras/metabolismo , Sobrevivência Celular , Células Cultivadas , Células Ependimogliais/efeitos dos fármacos , Células Ependimogliais/metabolismo , Humanos , Potenciais da Membrana , Mitocôndrias/fisiologia , Ratos , Retina/efeitos dos fármacos , Retina/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo
18.
Int J Dent Hyg ; 13(1): 25-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25046241

RESUMO

OBJECTIVE: To compare the effectiveness of abrasive component (perlite/calcium carbonate) and enzymatic component (papain and bromelain) of whitening toothpaste in removal of extrinsic stains. METHODS: This study is a randomized, triple blind and parallel group study in which 90 subjects aged 18-40 years were included. At baseline, stains scores were assessed by Macpherson's modification of Lobene Stain Index and subjects were randomly assigned to two groups with 45 subjects in each. Group 1 used whitening toothpaste with enzymatic action and group 2 with abrasive action. After 1 month, stain scores were assessed for the effectiveness of the two toothpastes and 2 months later to check the stain prevention efficacy. Wilcoxson's test was used to compare between baseline 1 and 2 months stain scores, and Mann-Witney U-test was applied for intragroup comparison. RESULTS: The mean baseline total stain score for the subjects allocated to the enzymatic toothpaste was 37.24 ± 2.11 which reduced to 30.77 ± 2.48 in 1 month, and for the abrasive paste, total stain reduced from 35.08 ± 2.96 to 32.89 ± 1.95. The reductions in total stain scores with both the pastes were significant compared with baseline stain scores (at 1 month Group 1, P = 0.0233 and Group 2, P = 0.0324; at 2 months, Group 1 P = 0.0356). Both the toothpastes proved to be equally good in removal of extrinsic stains; however, the enzymatic paste showed better results as compared to abrasive toothpaste. CONCLUSION: Whitening toothpaste with abrasive action and enzymatic action are equally effective in removal of extrinsic stains; however, whitening toothpaste with abrasive action needs to be used with caution.


Assuntos
Óxido de Alumínio/uso terapêutico , Bromelaínas/uso terapêutico , Carbonato de Cálcio/uso terapêutico , Papaína/uso terapêutico , Dióxido de Silício/uso terapêutico , Clareadores Dentários/uso terapêutico , Descoloração de Dente/tratamento farmacológico , Cremes Dentais/uso terapêutico , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Ácido Silícico/uso terapêutico , Descoloração de Dente/prevenção & controle , Escovação Dentária/instrumentação , Escovação Dentária/métodos , Resultado do Tratamento , Adulto Jovem
19.
Dis Esophagus ; 27(6): 505-10, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23020509

RESUMO

Current guidelines for endoscopic surveillance of Barrett's esophagus (BE) recommend that patients with newly diagnosed BE undergo confirmatory esophagogastroduodenoscopy (EGD) to exclude the presence of dysplasia. The extent to which confirmatory endoscopy alters management and detects missed dysplasia in newly diagnosed BE has not been reported. The frequency with which confirmatory endoscopy changed surveillance management in patients with newly diagnosed BE was assessed. A two center cohort analysis was conducted on patients newly diagnosed with BE. The rate of dysplasia on confirmatory endoscopy for patients who had nondysplastic BE was obtained. Demographic and endoscopic variables were assessed for association with dysplasia detection using Firth logistic regression model. Out of the 146 patients newly diagnosed with BE and initially determined to be without dysplasia, 12 had dysplasia on the confirmatory second EGD (8.2%). Eleven of 12 cases with dysplasia on confirmatory endoscopy had long-segment BE (LSBE). Among all the LSBE cases in our cohort, 11 had newly diagnosed dysplasia on confirmatory EGD, 29.7% (11/37). The average number of biopsies obtained from the 11 LSBE cases with dysplasia was comparable with the rest of the LSBE cases without dysplasia (6.73 and 5.42, respectively, P-value 0.205). The rate of dysplasia detection in short-segment BE (SSBE) was much lower, 0.95% (1 out of 105). There were no cases of high-grade dysplasia (HGD) or cancer detected in any SSBE case. HGD was detected on confirmatory EGD in two cases, both were LSBE. Segment length was the only statistically significant factor to predict the presence of dysplasia on confirmatory endoscopy (odds ratio 9.158, P. 0.008). Confirmatory EGD in newly diagnosed LSBE had significant rate of dysplasia detection (29.7%) in this cohort. Among patients with SSBE, there was a low rate of dysplasia detection with confirmatory EGD, less than 1% of cases. No additional cases of HGD or esophageal carcinoma in SSBE cases were detected. This suggests that the yield of confirmatory EGD is greater in patients with LSBE.


Assuntos
Esôfago de Barrett/patologia , Esofagoscopia , Esôfago/patologia , Lesões Pré-Cancerosas/patologia , Idoso , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População
20.
J Assoc Physicians India ; 62(4): 347-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25327042

RESUMO

Pulmonary opacities have many causes we are presenting a case of pulmonary opacity in a patient of breathlessness; who was on amiodarone for atrial fibrillation (AF).


Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/terapia
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