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1.
Int J Biol Macromol ; 197: 77-87, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34920072

RESUMO

Self assembling peptidebased hydrogel has been explored for delivering growth factors, anticancer drugs, antibiotics etc. Here, RADA 16-I (RADARADARADARADA), an ionic self complementary peptide that forms a well defined nanohydrogel has been studied for its ability to deliver PDGF-BB in a sustained manner and to destruct biofilm formed by wound specific pathogens. Results of the structural analysis of the nanohydrogel studied through AFM, FeSEM, CD, FT-IR and Rheometry, revealed the hydrogel forming ability of RADA 16-I with stable ß-sheet structure at room temperature. The nanohydrogel was also found to destruct the biofilm formed under in vitro condition using S. aureus, E. coli and P. aeruginosa. The growth factor incorporated in the nanohydrogel followed first order release kinetics and showed sustained release up to 48 h. Angiogenic potential and wound healing ability of PDGF-BB incorporated nanohydrogel was confirmed in both in vitro and in vivo conditions. The animals treated with PDGF-BB incorporated nanohydrogel exhibited 99.5% wound closure at day 21. The content of hydroxyproline and ascorbic acid was significantly high in the treated animals when compared to control and untreated animals. Overall, the study provides the essential information and data for using RADA 16-I for treating chronic wounds.


Assuntos
Hidrogéis
2.
Clin Epidemiol Glob Health ; 12: 100864, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34541381

RESUMO

BACKGROUND: COVID-19 is a new pandemic disease. This disease course and its effect on pregnancy is little known due to limited available data. The objective of this study was to describe the demographic profile of COVID-19 positive mothers admitted in Government Rajaji hospital, Madurai in terms of time, place and person and to assess the general and pregnancy outcome of study population. METHODS: This cross-sectional study was done among 381 COVID-19 positive mothers* admitted during March 22 - August 31, 2020 in dedicated COVID-19 hospital, Madurai. Data was collected using Case Investigation Form (CIF) as a part of Rapid Response Team*(RRT) by Community Medicine* Department and analysed using SPSS version 21. Descriptive statistics done; Chi-square test & Fischer exact test was done to find out association between patient profile and outcomes. RESULTS: Out of 381, 154 (40.4%) belonged to 21-25 years, 192 (50.4%) to rural area, 318 (83.5%) to 3rd trimester,189 (49.6%) Primi gravida. 125 (32.8%) were symptomatic and 153 (80.8%) had at least one comorbidity. Death as general outcome was 3 (0.8%), all of them were referred cases and had comorbidity like GDM/PIH. 10 (2.62%) had abortion or perinatal death, 14 (3.77%) had preterm delivery, 99 (25.98%) babies were born small for gestational age. Increased maternal age had more death but was not statistically significant; All symptomatic mothers (p = 0.000),1st & 2nd trimester (p = 0.000) mothers had statistically significant poor pregnancy outcome*. CONCLUSION: COVID positive mothers with increased age, symptomatic, 1st & 2nd trimester were significantly associated with poor outcome, requires special attention. Early referral must be emphasized to mitigate maternal death.

3.
Hypertension ; 78(5): 1296-1309, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34488433

RESUMO

IL-18 (interleukin-18) is elevated in hypertensive patients, but its contribution to high blood pressure and end-organ damage is unknown. We examined the role of IL-18 in the development of renal inflammation and injury in a mouse model of low-renin hypertension. Hypertension was induced in male C57BL6/J (WT) and IL-18−/− mice by uninephrectomy, deoxycorticosterone acetate (2.4 mg/d, s.c.) and 0.9% drinking saline (1K/DOCA/salt). Normotensive controls received uninephrectomy and placebo (1K/placebo). Blood pressure was measured via tail cuff or radiotelemetry. After 21 days, kidneys were harvested for (immuno)histochemical, quantitative-PCR and flow cytometric analyses of fibrosis, inflammation, and immune cell infiltration. 1K/DOCA/salt-treated WT mice developed hypertension, renal fibrosis, upregulation of proinflammatory genes, and accumulation of CD3+ T cells in the kidneys. They also displayed increased expression of IL-18 on tubular epithelial cells. IL-18−/− mice were profoundly protected from hypertension, renal fibrosis, and inflammation. Bone marrow transplantation between WT and IL-18−/− mice revealed that IL-18-deficiency in non-bone marrow-derived cells alone afforded equivalent protection against hypertension and renal injury as global IL-18 deficiency. IL-18 receptor subunits­interleukin-18 receptor 1 and IL-18R accessory protein­were upregulated in kidneys of 1K/DOCA/salt-treated WT mice and localized to T cells and tubular epithelial cells. T cells from kidneys of 1K/DOCA/salt-treated mice produced interferon-γ upon ex vivo stimulation with IL-18, whereas those from 1K/placebo mice did not. In conclusion, IL-18 production by tubular epithelial cells contributes to elevated blood pressure, renal inflammation, and fibrosis in 1K/DOCA/salt-treated mice, highlighting it as a promising therapeutic target for hypertension and kidney disease.


Assuntos
Células Epiteliais/metabolismo , Hipertensão/fisiopatologia , Inflamação/metabolismo , Interleucina-18/metabolismo , Nefropatias/metabolismo , Albuminúria/induzido quimicamente , Albuminúria/genética , Albuminúria/metabolismo , Animais , Pressão Sanguínea/genética , Pressão Sanguínea/fisiologia , Acetato de Desoxicorticosterona , Hipertensão/induzido quimicamente , Hipertensão/genética , Inflamação/genética , Interleucina-18/genética , Rim/metabolismo , Rim/patologia , Nefropatias/genética , Túbulos Renais/citologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Linfócitos T/imunologia , Linfócitos T/metabolismo
4.
Indian J Radiol Imaging ; 31(4): 1023-1026, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35136521

RESUMO

Piriformis syndrome is a rare cause of sciatica, which results in low backache due to sciatic nerve compression. This syndrome is associated with abnormalities in the piriformis muscle, which cause sciatic nerve entrapment, like anatomical variations, muscle hypertrophy, and inflammation. It can also result from the abnormal course of sciatic nerve itself through normal piriformis muscle. Piriformis syndrome due to pyomyositis of the piriformis muscle is extremely rare and only 23 cases are reported in literature. Herein, we report one such rare case of a patient, with pyomyositis of piriformis muscle, who presented with piriformis syndrome.

5.
J Anaesthesiol Clin Pharmacol ; 37(4): 569-573, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35340959

RESUMO

Background and Aims: To compare the performance characteristics of C-MAC video, McCoy, and Macintosh laryngoscopes in elective cervical spine surgery. The primary objective was to assess the ease of intubation with the three study devices. The secondary objectives were the time to intubation and hemodynamic responses during intubation. Material and Methods: The prospective observational comparative study was conducted in a tertiary care hospital. Adult ASA 1 and 11 patients who underwent elective cervical spine surgery were included in the study. Patients with unstable spine and trauma were excluded. The analysis of variance, Bonferroni test, Chi square test and multiple comparison tests were used to compare the performance characteristics of laryngoscopes. Results: The C-MAC video laryngoscope improved glottis view by improving the modified Cormack-Lehane (CL) score and the percentage of glottis opening (POGO) score compared to McCoy and Macintosh laryngoscopes. The ease of intubation was better with the C-MAC video laryngoscope compared to the McCoy and Macintosh laryngoscopes. The time to intubation was comparable between the three laryngoscopes. The C-MAC video and McCoy laryngoscopes had 100% successful first attempt intubations while it was 90% for the Macintosh laryngoscope. Hemodynamic variables observed during intubation were comparable between the three groups. Conclusion: The use of C-MAC video laryngoscope resulted in better visualization of the glottis and easier tracheal intubation as compared to the Macintosh and McCoy laryngoscopes in cervical spine surgery. Both C-MAC video and McCoy laryngoscopes had 100% successful first attempt intubation.

6.
Clin Proteomics ; 16: 23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31160890

RESUMO

BACKGROUND: Inflammatory arthritis (IA) is an immunological disorder in which loss of immune tolerance to endogenous self-antigens perpetuates synovitis and eventual destruction of the underlying cartilage and bone. Pathological changes in the joint are expected to be represented by synovial fluid (SF) proteins and peptides. In the present study, a mass spectrometry-based approach was utilized for the identification of key protein and peptide mediators of IA. METHODS: Age-matched SF samples from 10 rheumatoid arthritis patients, 10 psoriatic arthritis patients and 10 cadaveric controls were subjected to an integrated proteomic and peptidomic protocol using liquid chromatography tandem mass spectrometry. Significant differentially abundant proteins and peptides were identified between cohorts according to the results of a Mann-Whitney U test coupled to the Benjamini-Hochberg correction for multiple hypothesis testing. Fold change ratios were computed for each protein and peptide according to their log-transformed extracted ion current. Pathway analysis and antimicrobial peptide (AMP) prediction were conducted to clarify the pathophysiological relevance of identified proteins and peptides to IA. RESULTS: We determined that 144 proteins showed significant differential abundance between the IA and control SF proteomes, of which 11 protein candidates were selected for future follow-up studies. Similar analyses applied to our peptidomic data identified 15 peptide sequences, originating from 4 protein precursors, to have significant differential abundance in IA compared to the control SF peptidome. Pathway enrichment analysis of the IA SF peptidome along with AMP prediction suggests a possible mechanistic role of microbes in eliciting an immune response which drives the development of IA. CONCLUSIONS: The discovery-phase data generated herein has provided a basis for the identification of candidates with the greatest potential to serve as novel serum biomarkers specific to inflammatory arthritides. Moreover, these findings facilitate the understanding of possible disease mechanisms specific to each subtype.

7.
Cardiovasc Res ; 115(4): 776-787, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30357309

RESUMO

AIMS: Renal inflammation, leading to fibrosis and impaired function is a major contributor to the development of hypertension. The NLRP3 inflammasome mediates inflammation in several chronic diseases by processing the cytokines pro-interleukin (IL)-1ß and pro-IL-18. In this study, we investigated whether MCC950, a recently-identified inhibitor of NLRP3 activity, reduces blood pressure (BP), renal inflammation, fibrosis and dysfunction in mice with established hypertension. METHODS AND RESULTS: C57BL6/J mice were made hypertensive by uninephrectomy and treatment with deoxycorticosterone acetate (2.4 mg/day, s.c.) and 0.9% NaCl in the drinking water (1K/DOCA/salt). Normotensive controls were uninephrectomized and received normal drinking water. Ten days later, mice were treated with MCC950 (10 mg/kg/day, s.c.) or vehicle (saline, s.c.) for up to 25 days. BP was monitored by tail-cuff or radiotelemetry; renal function by biochemical analysis of 24-h urine collections; and kidney inflammation/pathology was assessed by real-time PCR for inflammatory gene expression, flow cytometry for leucocyte influx, and Picrosirius red histology for collagen. Over the 10 days post-surgery, 1K/DOCA/salt-treated mice became hypertensive, developed impaired renal function, and displayed elevated renal levels of inflammatory markers, collagen and immune cells. MCC950 treatment from day 10 attenuated 1K/DOCA/salt-induced increases in renal expression of inflammasome subunits (NLRP3, ASC, pro-caspase-1) and inflammatory/injury markers (pro-IL-18, pro-IL-1ß, IL-17A, TNF-α, osteopontin, ICAM-1, VCAM-1, CCL2, vimentin), each by 25-40%. MCC950 reduced interstitial collagen and accumulation of certain leucocyte subsets in kidneys of 1K/DOCA/salt-treated mice, including CD206+ (M2-like) macrophages and interferon-gamma-producing T cells. Finally, MCC950 partially reversed 1K/DOCA/salt-induced elevations in BP, urine output, osmolality, [Na+], and albuminuria (each by 20-25%). None of the above parameters were altered by MCC950 in normotensive mice. CONCLUSION: MCC950 was effective at reducing BP and limiting renal inflammation, fibrosis and dysfunction in mice with established hypertension. This study provides proof-of-concept that pharmacological inhibition of the NLRP3 inflammasome is a viable anti-hypertensive strategy.


Assuntos
Anti-Inflamatórios/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Furanos/farmacologia , Hipertensão/prevenção & controle , Rim/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Cloreto de Sódio na Dieta , Sulfonamidas/farmacologia , Albuminúria/etiologia , Albuminúria/metabolismo , Albuminúria/fisiopatologia , Albuminúria/prevenção & controle , Animais , Quimiotaxia de Leucócito/efeitos dos fármacos , Colágeno/metabolismo , Acetato de Desoxicorticosterona , Modelos Animais de Doenças , Fibrose , Compostos Heterocíclicos de 4 ou mais Anéis , Hipertensão/etiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Indenos , Mediadores da Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nefrectomia , Transdução de Sinais , Sulfonas , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismo
8.
Int J Mol Sci ; 19(6)2018 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-29890734

RESUMO

Chronic Kidney Disease (CKD) is a highly prevalent disease with a substantial medical need for new and more efficacious treatments. The Nitric Oxide (NO), soluble guanylyl cyclase (sGC), cyclic guanosine monophosphate (cGMP) signaling cascade regulates various kidney functions. cGMP directly influences renal blood flow, renin secretion, glomerular function, and tubular exchange processes. Downregulation of NO/sGC/cGMP signaling results in severe kidney pathologies such as CKD. Therefore, treatment strategies aiming to maintain or increase cGMP might have beneficial effects for the treatment of progressive kidney diseases. Within this article, we review the NO/sGC/cGMP signaling cascade and its major pharmacological intervention sites. We specifically focus on the currently known effects of cGMP on kidney function parameters. Finally, we summarize the preclinical evidence for kidney protective effects of NO-donors, PDE inhibitors, sGC stimulators, and sGC activators.


Assuntos
Nefropatias/patologia , Rim/patologia , Óxido Nítrico/metabolismo , Transdução de Sinais , Guanilil Ciclase Solúvel/metabolismo , Animais , GMP Cíclico/metabolismo , Humanos , Nefropatias/terapia
9.
Proteomes ; 6(1)2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-29364831

RESUMO

Psoriatic arthritis (PsA) is an inflammatory arthritis which develops in up to one-third of patients suffering from the cutaneous disorder, psoriasis. The complex and heterogeneous nature of PsA renders it difficult to diagnose, leading to poor outcomes and, therefore, warrants an examination into soluble biomarkers, which may facilitate early detection of the disease. Protein biomarkers are a dynamic resource of pathophysiological information able to provide an immediate reflection of pathological changes caused by disease. Investigations of the serum and synovial fluid of PsA patients has provided new insights into the molecular basis of this disease and led to the identification of sensitive diagnostic and prognostic biomarkers. The collection of novel PsA biomarkers identified through proteomic studies has been reviewed below.

10.
Crit Rev Clin Lab Sci ; 54(7-8): 495-505, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29202618

RESUMO

Synovial fluid (SF) is a protein-rich fluid produced into the joint cavity by cells of the synovial membrane. Due to its direct contact with articular cartilage, surfaces of the bone, and the synoviocytes of the inner membrane, it provides a promising reflection of the biochemical state of the joint under varying physiological and pathophysiological conditions. This property of SF has been exploited within numerous studies in search of unique biomarkers of joint pathologies with the ultimate goal of developing minimally invasive clinical assays to detect and/or monitor disease states. Several proteomic methodologies have been employed to mine the SF proteome. From elementary immunoassays to high-throughput analyses using mass spectrometry-based techniques, each has demonstrated distinct advantages and disadvantages in the identification and quantification of SF proteins. This review will explore the role of SF in the elucidation of the arthritis proteome and the extent to which high-throughput techniques have facilitated the discovery and validation of protein biomarkers from osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients.


Assuntos
Artrite , Biomarcadores , Proteômica , Líquido Sinovial , Artrite/diagnóstico , Artrite/metabolismo , Biomarcadores/análise , Biomarcadores/química , Humanos , Líquido Sinovial/química , Líquido Sinovial/metabolismo
11.
J Assoc Physicians India ; 65(3): 92-94, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28462554

RESUMO

Neuroacanthocytosis is a genetic neurodegenerative disorder with syndromes of variable inheritance. These hyperkinetic movement disorders are reported to be very rare. It is associated with choreiform movements, orofacial and lingual dyskinesias and acanthocytes on peripheral smear and normolipoproteinemia. Here we present a similar case.


Assuntos
Acantócitos/patologia , Neuroacantocitose/diagnóstico , Neuroacantocitose/patologia , Adulto , Humanos , Masculino , Neuroacantocitose/tratamento farmacológico , Neuroacantocitose/genética
12.
Pharmacol Res ; 116: 77-86, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27986554

RESUMO

OBJECTIVE: To determine whether a clinically-utilised IL-1 receptor antagonist, anakinra, reduces renal inflammation, structural damage and blood pressure (BP) in mice with established hypertension. METHODS: Hypertension was induced in male mice by uninephrectomy, deoxycorticosterone acetate (2.4mg/d,s.c.) and replacement of drinking water with saline (1K/DOCA/salt). Control mice received uninephrectomy, a placebo pellet and normal drinking water. 10days post-surgery, mice commenced treatment with anakinra (75mg/kg/d, i.p.) or vehicle (0.9% saline, i.p.) for 11days. Systolic BP was measured by tail cuff while qPCR, immunohistochemistry and flow cytometry were used to measure inflammatory markers, collagen and immune cell infiltration in the kidneys. RESULTS: By 10days post-surgery, 1K/DOCA/salt-treated mice displayed elevated systolic BP (148.3±2.4mmHg) compared to control mice (121.7±2.7mmHg; n=18, P<0.0001). The intervention with anakinra reduced BP in 1K/DOCA/salt-treated mice by ∼20mmHg (n=16, P<0.05), but had no effect in controls. In 1K/DOCA/salt-treated mice, anakinra modestly reduced (∼30%) renal expression of some (CCL5, CCL2; n=7-8; P<0.05) but not all (ICAM-1, IL-6) inflammatory markers, and had no effect on immune cell infiltration (n=7-8, P>0.05). Anakinra reduced renal collagen content (n=6, P<0.01) but paradoxically appeared to exacerbate the renal and glomerular hypertrophy (n=8-9, P<0.001) that accompanied 1K/DOCA/salt-induced hypertension. CONCLUSION: Despite its anti-hypertensive and renal anti-fibrotic actions, anakinra had minimal effects on inflammation and leukocyte infiltration in mice with 1K/DOCA/salt-induced hypertension. Future studies will assess whether the anti-hypertensive actions of anakinra are mediated by protective actions in other BP-regulating or salt-handling organs such as the arteries, skin and brain.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Fibrose/tratamento farmacológico , Hipertensão Renal/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Animais , Anti-Hipertensivos/farmacologia , Biomarcadores/metabolismo , Acetato de Desoxicorticosterona/farmacologia , Fibrose/metabolismo , Hipertensão Renal/induzido quimicamente , Hipertensão Renal/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Rim/metabolismo , Nefropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cloreto de Sódio na Dieta/farmacologia
13.
Sultan Qaboos Univ Med J ; 16(2): e175-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27226908

RESUMO

OBJECTIVES: Healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen worldwide and its multidrug resistance is a major concern. This study aimed to determine the clinical characteristics and antibiotic susceptibility profile of healthcare-associated MRSA with emphasis on resistance to macrolide-lincosamide-streptogramin B (MLSB) phenotypes and vancomycin. METHODS: This cross-sectional study was carried out between February 2014 and February 2015 across four tertiary care hospitals in Mangalore, South India. Healthcare-associated infections among 291 inpatients at these hospitals were identified according to the Centers for Disease Control and Prevention guidelines. Clinical specimens were collected based on infection type. S. aureus and MRSA isolates were identified and antibiotic susceptibility tests performed using the Kirby-Bauer disk diffusion method. The minimum inhibitory concentration of vancomycin was determined using the Agar dilution method and inducible clindamycin resistance was detected with a double-disk diffusion test (D-test). RESULTS: Out of 291 healthcare-associated S. aureus cases, 88 were MRSA (30.2%). Of these, 54.6% were skin and soft tissue infections. All of the isolates were susceptible to teicoplanin and linezolid. Four MRSA isolates exhibited intermediate resistance to vancomycin (4.6%). Of the MRSA strains, 10 (11.4%) were constitutive MLSB phenotypes, 31 (35.2%) were inducible MLSB phenotypes and 14 (15.9%) were macrolide-streptogramin B phenotypes. CONCLUSION: Healthcare-associated MRSA multidrug resistance was alarmingly high. In routine antibiotic susceptibility testing, a D-test should always be performed if an isolate is resistant to erythromycin but susceptible to clindamycin. Determination of the minimum inhibitory concentration of vancomycin is necessary when treating patients with MRSA infections.

14.
Int J Phytoremediation ; 18(8): 747-53, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-26587690

RESUMO

Phycoremediation ability of microalgae namely Oscillatoria acuminate and Phormidium irrigum were validated against the heavy metals from tannery effluent of Ranipet industrial area. The microalgae species were cultured in media containing tannery effluent in two different volumes and the parameters like specific growth rate, protein content and antioxidant enzyme activities were estimated. FTIR spectroscopy was carried out to know the sorption sites interaction. The antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) contents were increased in microalgae species indicating the free radical scavenging mechanism under heavy metal stress. SOD activity was 0.502 and 0.378 units/gram fresh weight, CAT activity was 1.36 and 0.256 units/gram fresh weight, GSH activity was 1.286 and 1.232 units/gram fresh weight respectively in the effluent treated microalgae species. Bio sorption efficiency for Oscillatoria acuminate and Phormidium irrigum was 90% and 80% respectively. FTIR analysis revealed the interaction of microalgae species with chemical groups present in the tannery effluent. From the results, the microalgae Oscillatoria acuminate possess high antioxidant activity and bio sorption efficiency when compared to Phormidium irrigum and hence considered useful in treating heavy metals contaminated effluents.


Assuntos
Biodegradação Ambiental , Cianobactérias/metabolismo , Resíduos Industriais , Microalgas/metabolismo , Oscillatoria/metabolismo , Curtume , Poluentes Químicos da Água/metabolismo , Antioxidantes/metabolismo , Catalase/metabolismo , Metais Pesados/metabolismo , Superóxido Dismutase/metabolismo
15.
Hypertension ; 66(5): 1023-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26351030

RESUMO

Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25% increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80% increase in splenic plasma cell numbers, (3) a 500% increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R(-/-)) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R(-/-) (Δ30±4 mm Hg) relative to wild-type (Δ41±5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R(-/-) mice displayed reduced IgG accumulation in the aorta, which was associated with 80% fewer aortic macrophages and a 70% reduction in transforming growth factor-ß expression. BAFF-R(-/-) mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II-induced hypertension by ≈35%. Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension.


Assuntos
Angiotensina II/efeitos adversos , Linfócitos B/patologia , Linfócitos B/fisiologia , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Rigidez Vascular/fisiologia , Transferência Adotiva , Animais , Anticorpos Anti-Idiotípicos/farmacologia , Antígenos CD20/imunologia , Receptor do Fator Ativador de Células B/deficiência , Receptor do Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/metabolismo , Linfócitos B/efeitos dos fármacos , Proliferação de Células , Modelos Animais de Doenças , Hipertensão/metabolismo , Imunoglobulina G/metabolismo , Camundongos , Camundongos Knockout , Baço/patologia , Fator de Crescimento Transformador beta/metabolismo
16.
Am J Physiol Heart Circ Physiol ; 309(5): H906-17, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26071547

RESUMO

Macrophages accumulate in blood vessels during hypertension. However, their contribution to vessel remodeling is unknown. In the present study, we examined the polarization state of macrophages (M1/M2) in aortas of mice during hypertension and investigated whether antagonism of chemokine receptors involved in macrophage accumulation reduces vessel remodeling and blood pressure (BP). Mice treated with ANG II (0.7 mg·kg(-1)·day(-1), 14 days) had elevated systolic BP (158 ± 3 mmHg) compared with saline-treated animals (122 ± 3 mmHg). Flow cytometry revealed that ANG II infusion increased numbers of CD45(+)CD11b(+)Ly6C(hi) monocytes and CD45(+)CD11b(+)F4/80(+) macrophages by 10- and 2-fold, respectively. The majority of macrophages were positive for the M2 marker CD206 but negative for the M1 marker inducible nitric oxide synthase. Expression of other M2 genes (arginase-1, Fc receptor-like S scavenger receptor, and receptor-1) was elevated in aortas from ANG II-treated mice, whereas M1 genes [TNF and chemokine (C-X-C motif) ligand 2] were unaltered. A PCR array to identify chemokine receptor targets for intervention revealed chemokine (C-C motif) receptor 2 (CCR2) to be upregulated in aortas from ANG II-treated mice, while flow cytometry identified Ly6C(hi) monocytes as the main CCR2-expressing cell type. Intervention with a CCR2 antagonist (INCB3344; 30 mg·kg(-1)·day(-1)), 7 days after the commencement of ANG II infusion, reduced aortic macrophage numbers. INCB334 also reduced aortic collagen deposition, elastin loss, and BP in ANG II-treated mice. Thus, ANG II-dependent hypertension in mice is associated with Ly6C(hi) monocyte and M2 macrophage accumulation in the aorta. Inhibition of macrophage accumulation with a CCR2 antagonist prevents ANG II-induced vessel fibrosis and elevated BP, highlighting this as a promising approach for the future treatment of vessel remodeling/stiffening in hypertension.


Assuntos
Aorta/patologia , Pressão Sanguínea , Elastina/metabolismo , Hipertensão/patologia , Macrófagos/metabolismo , Angiotensina II/toxicidade , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos Ly/genética , Antígenos Ly/metabolismo , Aorta/efeitos dos fármacos , Aorta/metabolismo , Arginase/genética , Arginase/metabolismo , Colágeno/genética , Colágeno/metabolismo , Elastina/genética , Fibrose/metabolismo , Fibrose/patologia , Hipertensão/etiologia , Hipertensão/metabolismo , Macrófagos/classificação , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Receptores CCR2/genética , Receptores CCR2/metabolismo
17.
Environ Monit Assess ; 187(6): 325, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25944749

RESUMO

The present study was carried out with the tannery effluent contaminated with heavy metals collected from Ambur industrial area to determine the phycoremediation potential of Arthrospira (Spirulina) platensis. Two different concentrations (50 and 100 %) of heavy metals containing tannery effluent treated with A. platensis were analysed for growth, absorption spectra, biochemical properties and antioxidant enzyme activity levels. The effluent treatments revealed dose-dependent decrease in the levels of A. platensis growth (65.37 % for 50 % effluent and 49.32 % for 100 % effluent), chlorophyll content (97.43 % for 50 % effluent and 71.05 % for 100 % effluent) and total protein content (82.63 % for 50 % effluent and 62.10 % for 100 % effluent) that leads to the reduction of total solids, total dissolved solids and total suspended solids. A. platensis with lower effluent concentration was effective than at higher concentration. Treatment with the effluent also resulted in increased activity levels of antioxidant enzymes, such as superoxide dismutase (14.58 units/g fresh weight for 50 % and 24.57 units/g fresh weight for 100 %) and catalase (0.963 units/g fresh weight for 50 % and 1.263 units/g fresh weight for 100 %). Furthermore, heavy metal content was determined using atomic absorption spectrometry. These results indicated that A. platensis has the ability to combat heavy metal stress by the induction of antioxidant enzymes demonstrating its potential usefulness in phycoremediation of tannery effluent.


Assuntos
Metais Pesados/metabolismo , Spirulina/fisiologia , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Catalase/metabolismo , Monitoramento Ambiental , Indústrias , Metais Pesados/análise , Espectrofotometria Atômica , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/análise
18.
Am J Public Health ; 105(1): 91-95, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25393186

RESUMO

Objectives. We assessed routine HIV testing in Indiana community health centers (CHCs). Methods. CHC medical directors reported HIV services, testing behaviors, barriers, and health center characteristics via survey from April to May 2013. Standard of care testing was measured by the extent to which CHCs complied with national guidelines for routine HIV testing in clinical settings. Results. Most (85.7%) CHCs reported HIV testing, primarily at patient request or if the patient was symptomatic. Routine HIV testing was provided for pregnant women by 60.7% of CHCs. Only 10.7% provided routine testing for adolescents to adults up to age 65 years. Routine testing was reported by 14.3% for gay and bisexual men, although 46.4% of CHCs reported asking patients about sexual orientation. Linkage to care services for HIV-positive patients, counseling for HIV treatment adherence, and partner testing generally was not provided. Conclusions. Most CHCs reported HIV testing, but such testing did not reflect the standard of care, because it depended on patient request or symptoms. One approach in future studies may be to allow respondents to compare current testing with standard of care and then reflect on barriers to and facilitators of adoption and implementation of routine HIV testing.

20.
Sex Transm Dis ; 41(11): 684-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25299417

RESUMO

BACKGROUND: The role of community health centers (CHCs) in preventive health care is central to health reform, yet little is known about how CHCs identify and manage sexually transmitted infections (STIs). METHODS: A survey of Indiana CHCs from April to May 2013 measured reported STI services, clinic expectations for STI testing and management, barriers to screening and management, and partner services. Reported practices were compared with current Centers for Disease Control and Prevention (CDC) guidelines for STI testing in clinical settings. RESULTS: Although most CHCs reported screening for syphilis (75.0%), chlamydia, and gonorrhea (85.7%), screening generally did not reflect CDC guidelines. Chlamydia and gonorrhea testing was provided primarily at patient request or when symptomatic by 67.9% of CHCs. Syphilis testing at 67.9% of CHCs reflected CDC guidelines for adults 65 years or younger and at 53.6% for first-trimester pregnant women. Chlamydia and gonorrhea screening reflected CDC guidelines for 17.9% of CHCs for gay/bisexual men and 60.9% for first-trimester pregnant women. One-third (35%) of CHCs reported not knowing the expectation for screening pregnant women and gay/bisexual men. CONCLUSIONS: It is likely that CHCs are not aware of patient sexual health risks because standard of care screening was observed only for gonorrhea and chlamydia during the first trimester and for syphilis testing when symptoms were present. As CHCs increase their role in preventive care with the implementation of the Affordable Care Act, focus must be upon clinician awareness of patient sexual health and training to identify and manage STIs in their patient populations.


Assuntos
Infecções por Chlamydia/epidemiologia , Serviços de Saúde Comunitária , Gonorreia/epidemiologia , Programas de Rastreamento , Sífilis/epidemiologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/psicologia , Feminino , Gonorreia/diagnóstico , Gonorreia/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Indiana/epidemiologia , Masculino , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Patient Protection and Affordable Care Act , Comportamento Sexual , Parceiros Sexuais , Inquéritos e Questionários , Sífilis/diagnóstico , Sífilis/psicologia , Estados Unidos/epidemiologia
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