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1.
Braz. j. biol ; 82: e235612, 2022. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1153466

RESUMO

Abstract The experiment was carried out on mango cv. Dusehri to investigate the effect of N, P and K fertilizers on vegetative, reproductive growth, yield and fruit quality. Eight different fertilizer combinations such as T1 (control), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) and T8 (NPK) were used. Individual or combine fertilizer application of N (1000 g), P (750 g) and K (750 g) were applied during growing season in February and August. All the treatments significantly influenced on vegetative growth, flowering, fruiting, yield and other physiochemical attributes of mango as compared to control. Least effect was observed with individual fertilizer application while combine fertilizer treatments enhanced most of the investigated parameters. Especially, qualitative traits showed non-significant differences between treated and untreated mango trees. However, among the different treatments T8 (NPK) showed significance for fruiting aspects such as maximum size of growth flushes (177.51 mm), total number of panicles/tree (845), total number of flowers/panicle (974), sex ratio (69.18%), fruit retention (13.85%), total number of fruits/tree (379), yield (82 kg/tree), fruit weight (197.5 g), pulp weight (135.5 g) and physiochemical parameters namely TSS (24.53), Vit. C (57.63 mg/100 mL) and total sugar (20.84%). In general, combine application of NPK (T8) were the most effective in enhancing fruiting aspects, yield, physiochemical characteristics as well as improved fruit quality of mango trees.


Resumo O experimento foi realizado em manga cv. Dusehri para investigar o efeito dos fertilizantes N, P e K no crescimento vegetativo, reprodutivo, produtividade e de qualidade do fruto. Foram utilizadas oito combinações diferentes de fertilizantes: T1 (controle), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) e T8 (NPK). Cada tratamento de N (1.000 g), P (750 g) e K (750 g) foi aplicado duas vezes durante a estação de crescimento em fevereiro e agosto. Todos os tratamentos influenciaram significativamente o crescimento vegetativo, floração, frutificação, produtividade e outros atributos físico-químicos da manga em relação ao controle. Menos efeito foi observado com a aplicação individual de fertilizante, enquanto os tratamentos combinados aumentaram a maioria dos parâmetros investigados. Especialmente as características qualitativas mostraram diferenças não significativas entre mangueiras tratadas e não tratadas. No entanto, entre os diferentes tratamentos, T8 (NPK) apresentou significância para aspectos de frutificação, como tamanho máximo de folgas de crescimento (177,51 mm), número total de panículas/árvore (845), número total de flores/panícula (974), razão sexual (69,18%), retenção de frutos (13,85%), número total de frutos/árvore (379), produção (82 kg/árvore), peso do fruto (197,5 g) e peso da polpa (135,5 g), além de parâmetros físico-químicos, como TSS (24,53), vitamina C (57,63 mg/100 mL) e açúcar total (20,84%). Em geral, a aplicação combinada de NPK (T8) foi a mais eficaz no aprimoramento dos aspectos de frutificação, produtividade, características físico-químicas, além da melhoria da qualidade dos frutos das mangueiras.

2.
Ann R Coll Surg Engl ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955242

RESUMO

INTRODUCTION: We aim to identify any changes in outcome for patients undergoing nonelective surgery at the start of the UK pandemic in our district general hospital. This was a single-centre retrospective cohort review of a UK district general hospital serving a population of over 250,000 people. METHODS: Participants were all patients undergoing a surgical procedure in the acute theatre list between 23 March to 11 May in both 2019 and 2020. Primary outcome was 90-day postoperative mortality. Secondary outcomes include time to surgical intervention and length of inpatient stay. RESULTS: A total of 132 patients (2020) versus 141 (2019) patients were included. Although overall 90-day postoperative mortality was higher in 2020 (9.8%) compared with 2019 (5.7%), this difference was not statistically significant (p=0.196). In 2020, eight patients tested positive for COVID-19 either as an inpatient or within 2 weeks of discharge, of whom five patients died. Time to surgical intervention was significantly faster for NCEPOD (National Confidential Enquiry into Patient Outcome and Death) code 3 patients in 2020 than in 2019 (p=0.027). There were no significant differences in mean length of inpatient stay. CONCLUSIONS: We found that patients were appropriately prioritised using NCEPOD classification, with no statistically significant differences in 90-day postoperative mortality and length of inpatient stay compared with the 2019 period. A study on a larger scale would further elucidate the profile and outcomes of patients requiring acute surgery to generate statistical significance.

3.
Braz J Biol ; 82: e235612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681899

RESUMO

The experiment was carried out on mango cv. Dusehri to investigate the effect of N, P and K fertilizers on vegetative, reproductive growth, yield and fruit quality. Eight different fertilizer combinations such as T1 (control), T2 (N), T3 (P), T4 (K), T5 (NP), T6 (NK), T7 (PK) and T8 (NPK) were used. Individual or combine fertilizer application of N (1000 g), P (750 g) and K (750 g) were applied during growing season in February and August. All the treatments significantly influenced on vegetative growth, flowering, fruiting, yield and other physiochemical attributes of mango as compared to control. Least effect was observed with individual fertilizer application while combine fertilizer treatments enhanced most of the investigated parameters. Especially, qualitative traits showed non-significant differences between treated and untreated mango trees. However, among the different treatments T8 (NPK) showed significance for fruiting aspects such as maximum size of growth flushes (177.51 mm), total number of panicles/tree (845), total number of flowers/panicle (974), sex ratio (69.18%), fruit retention (13.85%), total number of fruits/tree (379), yield (82 kg/tree), fruit weight (197.5 g), pulp weight (135.5 g) and physiochemical parameters namely TSS (24.53), Vit. C (57.63 mg/100 mL) and total sugar (20.84%). In general, combine application of NPK (T8) were the most effective in enhancing fruiting aspects, yield, physiochemical characteristics as well as improved fruit quality of mango trees.


Assuntos
Mangifera , Animais , Aves , Fertilizantes , Frutas , Árvores
4.
Braz. j. biol ; 81(1): 125-136, Feb. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1153313

RESUMO

Abstract Citrulline is a non-essential amino acid, involved in key biological functions in plants and humans. Rootstocks have a major impact on citrulline accumulation in grafted watermelon. Information regarding rootstock induced changes in citrulline metabolism is elusive. To understand the regulatory mechanism, parallel changes in the expression profiles of citrulline metabolic genes and citrulline content of watermelon were monitored during the development of self-rooted watermelon and watermelon grafted onto pumpkin, wild and bottle gourd rootstocks. Results demonstrated that rootstocks regulated the expression profiles in different ways to influence the citrulline content. GAT, NAGPR, ASS3 ASS2 and Asl2 showed the negative correlation with citrulline content in pumpkin grafted watermelon. Pumpkin rootstock promoted the citrulline content by high down-regulation and synergistic effect of ASS2, ASS3, ASL1 and ASl2 genes. In wild grafted watermelon, citrulline was accumulated as a result of down regulation of GAT, NAGS and ASL2 genes, which showed an inverse correlation with citrulline. In gourd grafted watermelon, changes in citrulline content were observed to be linked with lower expressions of GAT, NAGK, ASS2, ASS3, ASL1 and ARG which were negatively correlated with citrulline content. Our study will provide the basis to understand the molecular mechanism of citrulline accumulation in various rootstocks.


Resumo A citrulina é um aminoácido não essencial, envolvida em importantes funções biológicas de plantas e seres humanos. Os porta-enxertos têm um grande impacto no acúmulo de citrulina na melancia enxertada. Informações sobre alterações induzidas por porta-enxertos no metabolismo da citrulina ainda não foram descritas. Para entender o mecanismo regulatório, foram monitoradas mudanças paralelas nos perfis de expressão dos genes metabólicos de citrulina e no teor de citrulina da melancia durante o desenvolvimento da melancia e da melancia enxertada em porta-enxertos de abóbora, silvestre e cabaça. Os resultados demonstraram que o porta-enxerto regulou os perfis de expressão de diferentes maneiras para influenciar no conteúdo de citrulina. GAT, NAGPR, ASS3, ASS2 e ASL2 apresentaram correlação negativa com o teor de citrulina em melancia enxertada de abóbora. O porta-enxerto de abóbora promoveu o conteúdo de citrulina por meio de baixa regulação e efeito sinérgico de duas famílias de genes ASS e ASL. Na melancia enxertada, a acumulação de citrulina resultou na regulação negativa de GAT, NAGS e ASL2, que mostraram uma correlação inversa com a citrulina. Na melancia enxertada, observou-se que as alterações no conteúdo de citrulina foram associadas a menores expressões de GAT, NAGK, ASS2, ASS3, ASL1 e ARG, que foram negativamente correlacionadas com o conteúdo de citrulina. Esses resultados fornecem a base para identificar o mecanismo molecular do acúmulo de citrulina em vários porta-enxertos.

6.
Eur Rev Med Pharmacol Sci ; 24(24): 13098-13100, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33378063

RESUMO

COVID-19 is rapidly spreading throughout the world since December 2019. It has hit South Asian countries with faded impact, which can be attributed to (a) availability of kits, (b) number of people tested for COVID-19, (c) immunity, (d) environmental conditions and (e) vaccination.


Assuntos
/estatística & dados numéricos , Umidade , Malária/imunologia , Temperatura , Vacinas contra a Tuberculose/uso terapêutico , Tuberculose/prevenção & controle , Ásia Ocidental/epidemiologia , /imunologia , Meio Ambiente , Humanos , Malária/epidemiologia , Prevalência , Kit de Reagentes para Diagnóstico/provisão & distribução , Tuberculose/epidemiologia
9.
QJM ; 113(8): 546-550, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32569363

RESUMO

BACKGROUND: COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. AIMS: To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. METHODS: We conducted a retrospective, case-control, single-center study in patients with severe to critical COVID-19 disease treated with tocilizumab. Disease severity was defined based on the amount of oxygen supplementation required. The primary endpoint was the overall mortality. Secondary endpoints were mortality in non-intubated patients and mortality in intubated patients. RESULTS: A total of 193 patients were included in the study. Ninety-six patients received tocilizumab, while 97 served as the control group. The mean age was 60 years. Patients over 65 years represented 43% of the population. More patients in the tocilizumab group reported fever, cough and shortness of breath (83%, 80% and 96% vs. 73%, 69% and 71%, respectively). There was a non-statistically significant lower mortality in the treatment group (52% vs. 62.1%, P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, P = 0.024). Bacteremia was more common in the control group (24% vs. 13%, P = 0.43), while fungemia was similar for both (3% vs. 4%, P = 0.72). CONCLUSION: Our study showed a non-statistically significant lower mortality in patients with severe to critical COVID-19 disease who received tocilizumab. When intubated patients were excluded, the use of tocilizumab was associated with lower mortality.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Imunossupressores/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Estudos de Casos e Controles , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Oxigenoterapia , Pandemias , Pneumonia Viral/mortalidade , Receptores de Interleucina-6/antagonistas & inibidores , Índice de Gravidade de Doença , Resultado do Tratamento
11.
Braz J Biol ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321067

RESUMO

Citrulline is a non-essential amino acid, involved in key biological functions in plants and humans. Rootstocks have a major impact on citrulline accumulation in grafted watermelon. Information regarding rootstock induced changes in citrulline metabolism is elusive. To understand the regulatory mechanism, parallel changes in the expression profiles of citrulline metabolic genes and citrulline content of watermelon were monitored during the development of self-rooted watermelon and watermelon grafted onto pumpkin, wild and bottle gourd rootstocks. Results demonstrated that rootstocks regulated the expression profiles in different ways to influence the citrulline content. GAT, NAGPR, ASS3 ASS2 and Asl2 showed the negative correlation with citrulline content in pumpkin grafted watermelon. Pumpkin rootstock promoted the citrulline content by high down-regulation and synergistic effect of ASS2, ASS3, ASL1 and ASl2 genes. In wild grafted watermelon, citrulline was accumulated as a result of down regulation of GAT, NAGS and ASL2 genes, which showed an inverse correlation with citrulline. In gourd grafted watermelon, changes in citrulline content were observed to be linked with lower expressions of GAT, NAGK, ASS2, ASS3, ASL1 and ARG which were negatively correlated with citrulline content. Our study will provide the basis to understand the molecular mechanism of citrulline accumulation in various rootstocks.

12.
Metallomics ; 12(3): 416-426, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-31976503

RESUMO

Animals carefully control homeostasis of Cu, a metal that is both potentially toxic and an essential nutrient. During infection, various shifts in Cu homeostasis can ensue. In mice infected with Candida albicans, serum Cu progressively rises and at late stages of infection, liver Cu rises, while kidney Cu declines. The basis for these changes in Cu homeostasis was poorly understood. We report here that the progressive rise in serum Cu is attributable to liver production of the multicopper oxidase ceruloplasmin (Cp). Through studies using Cp-/- mice, we find this elevated Cp helps recover serum Fe levels at late stages of infection, consistent with a role for Cp in loading transferrin with Fe. Cp also accounts for the elevation in liver Cu seen during infection, but not for the fluctuations in kidney Cu. The Cu exporting ATPase ATP7B is one candidate for kidney Cu control, but we find no change in the pattern of kidney Cu loss during infection of Atp7b-/- mice, implying alternative mechanisms. To test whether fungal infiltration of kidney tissue was required for kidney Cu loss, we explored other paradigms of infection. Infection with the intravascular malaria parasite Plasmodium berghei caused a rise in serum Cu and decrease in kidney Cu similar to that seen with C. albicans. Thus, dynamics in kidney Cu homeostasis appear to be a common feature among vastly different infection paradigms. The implications for such Cu homeostasis control in immunity are discussed.

13.
Trop Biomed ; 37(2): 273-281, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33612797

RESUMO

Contagious bovine pleuropneumonia (CBPP) is a highly contagious disease of cattle caused by Mycoplasma mycoides subsp. mycoides. It is characterized by anorexia, fever, dyspnea, polypnea, cough, and nasal discharges. Gross lesions in the lung such as marbling, sequestra, thickening of interlobular septa, and consolidation are evident. Serological tests including complement fixation test and competitive enzyme-linked immunosorbent assay and molecular tests such as polymerase chain reactions are used for diagnostic purposes. In this study, lung samples of suspected large ruminants (cattle n=560, buffalo n=293) were collected from abattoirs of three districts of Punjab namely Lahore, Kasur and Jhang. PCR was performed with specific primers, targeting the 16S ribosomal RNA gene to detect the positive cases. The results indicated that 49 samples (8.75%) of cattle were positive, with maximum prevalence was observed in Jhang with 16 positive samples (10.06%), but CBPP was not detected in any buffalo sample. High prevalence of disease was seen in cattle of more than seven years of age, in female cattle, and in cross-bred cattle. Age and gender were found significantly associated (P<0.05) with the prevalence of the disease. Gene sequencing of identified 5 isolates of Mycoplasma mycoides subsp. mycoides had more than 99% similarities with the strains isolated from China, Italy, Australia and Tanzania and were categorized into a monophyletic group but strain isolated from Portugal had more than 55% variable regions, hence clustered separately. This study confirms the presence of contagious bovine pleuropneumonia in the country which can be a threat to the livestock export market and warrants the implementation of control measures to mitigate the economic losses associated with the disease.

14.
J Biol Regul Homeost Agents ; 33(3): 929-933, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184098

RESUMO

Newcastle disease (ND) and avian influenza (AI) are globally considered as a serious threat to the chicken and other avian species. The paramyxovirus type 1 and orthomyxovirus type A are RNA viruses, which cause ND and AI infection, respectively.


Assuntos
Coinfecção/veterinária , Influenza Aviária/patologia , Doença de Newcastle/patologia , Tropismo Viral , Animais , Galinhas , Coinfecção/virologia , Vírus da Influenza A Subtipo H9N2 , Vírus da Doença de Newcastle
15.
Trop Biomed ; 36(4): 1081-1086, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33597477

RESUMO

Ticks are important ectoparasites which transmit many disease pathogen to animals; these are labelled tick borne diseases (TBD). Tick induced damage to skin and hides has not received attention. Skin and hides are important for the leather product industry, particularly in Pakistan. Due to economic importance and financial loss by ticks in leather industry, the present study was designed to investigate skin and hides damage due to ticks at microscopic level. Naturally tick infested tissue samples of hides and skin were collected from slaughter houses. Primary lesions at tick feeding sites showed epidermal edema with adjacent dermal edema. Histopathological examination revealed degeneration of epidermal layer down to the basal layer. Epidermal and sub dermal layers often displayed focal necrosis infiltrated with neutrophils and mononuclear cells at tick bite sites. Hyperplasia of keratinocytes was also seen at sites of ruptured epidermis. Quality of leather depends upon the grain (Outer) surface skin/hides. Ticks infestation damages the outer surface, due to bites, inflammatory responses, and secondary bacterial infections that often become established at feeding sites. Control of ticks should be given consideration to reduce infestation induced losses in the leather industry in Pakistan.

16.
J Contemp Dent Pract ; 19(10): 1174-1180, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30498171

RESUMO

INTRODUCTION: The closed reduction of a displaced nasal fracture is a preferred method in oral and maxillofacial surgery. This prospective study was conducted to evaluate the treatment outcome following closed reduction of nasal bone fractures. MATERIALS AND METHODS: A total of 20 patients with nasal bone fracture who underwent closed reduction were included in the study. The cases were operated under local or general anesthesia. The outcome of treatment was evaluated pre- and postoperatively through systematic follow-ups. Clinical assessment was done to evaluate functional (airway patency, nasal obstruction, crepitus) as well as esthetic parameters (facial symmetry, swelling, and nasal deviation). Functional and esthetic satisfaction of patients was assessed using visual analog scale (VAS) pre- and post-operatively. RESULTS: It was observed that there was significant improvement in both functional and esthetic parameters following closed reduction of nasal fractures. CONCLUSION: The present study suggested that closed reduction of nasal bone fracture is very effective in the management of nasal bone fractures. However, further studies with larger sample size in different clinical situations should be considered to confirm the efficacy of the same. CLINICAL SIGNIFICANCE: Closed reduction can be a viable and more conservative alternative in management of nasal fractures.


Assuntos
Redução Fechada/métodos , Fraturas Ósseas/cirurgia , Osso Nasal/lesões , Procedimentos Cirúrgicos Ortognáticos/métodos , Adulto , Estética/psicologia , Feminino , Fraturas Ósseas/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
17.
J Biol Regul Homeost Agents ; 32(6): 1545-1549, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30574763

RESUMO

TThe efficacy of the two commonly used commercial vaccines for Newcastle disease (ND) and low path avian influenza (LPAI) H9N2 were evaluated against field virus in broiler chicks. One hundred one-dayold commercial broiler chicks were divided into four groups (A to D) with an equal number of birds per group. Group A and B were vaccinated against H9N2 and NDV, respectively, at day 7 of age while group C served as positive infected control for H9N2 and group D for NDV. Serum samples from birds in all groups were tested for presence of antibodies against H9N2 and NDV at day 21 of age. Subsequently, on day 28 of age, groups A and C were challenged with the field strain of H9N2 virus, and Group B and D with NDV. Birds were monitored for a period of 2 weeks for development of any clinical signs and mortality. The geometric mean titer were high in groups A (4.90) and B (7.3), and low in the unvaccinated groups C (0.7) and D (1.1). The highest and lowest value of H9N2 antibody titer detected through ELISA were 1.498 and 0.502, respectively. The S/P ratios greater than 0.5 were considered positive. The highest and lowest value for NDV antibody titer detected through ELISA were 783 and 882, respectively. Serum samples with titer greater than 396 were considered positive and indicated vaccination or other exposure to NDV. On histological examination severe congestion, necrosis, degeneration, hemorrhages and leukocyte infiltration were observed in intestine, lungs, trachea and bursa of Fabricius of the non-vaccinated group post-infection. Mild tissues changes were observed in the vaccinated group. It can be concluded from the findings that the commonly used commercial vaccines may provide effective protection against the circulating H9N2 and ND virus in broiler birds by producing protective antibody titer.


Assuntos
Vírus da Influenza A Subtipo H9N2 , Vacinas contra Influenza/uso terapêutico , Influenza Aviária/prevenção & controle , Doença de Newcastle/prevenção & controle , Vacinas Virais/uso terapêutico , Animais , Anticorpos Antivirais/sangue , Galinhas/virologia , Paquistão
18.
J Neonatal Perinatal Med ; 11(3): 317-321, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30040744

RESUMO

BACKGROUND: Normal saline bolus is commonly used in clinical practice for treating hypotension in very preterm infants during resuscitation at an early age despite the paucity of high quality evidence supporting this practice. OBJECTIVES: To determine the effects of early (<7 days after birth) saline boluses given to very preterm infant (VPI) from 23 to 31 weeks GA. METHOD: This is a population-based cohort analysis of the use of normal saline boluses given to VPI. The outcomes were extracted from the Perinatal Follow-Up Program Database which included all VPI from Halifax County admitted to the NICU at the IWK Health Centre, Halifax, Nova Scotia, Canada between January 2006 to December 2010. We excluded infants with major congenital anomalies and those not offered resuscitation in the delivery room. Our primary outcome was the composite of death or disability by 18-36 months while secondary outcomes were neonatal death, BPD, CP, IVH, PVL, ROP, BSITD III (Bayley Scales of Infant and Toddler Development®, Third Edition) Cognitive, Motor and Language score. RESULTS: Death or disability in those who received saline bolus occurred in 15 (53.6%) compared with 9 (32.1%) in non saline group. Significantly higher rates of CP (p = 0.04), lower scores on the BSITDIII for motor (p = 0.04) and language scales (p = 0.03) were noted for infants who received saline boluses. Cognitive scores approached significance (p = 0.05) with lower scores in the saline bolus group. CONCLUSION: Significant differences were found between the two groups in terms of long term neurodevelopmental outcome and one of the short-term outcome (i.e. BPD). Given the limitations of this retrospective study and the small sample size, a larger cohort from Canadian Neonatal Network database is warranted to evaluate the effects of using normal saline boluses during early life on neurodevelopmental.


Assuntos
Paralisia Cerebral/fisiopatologia , Desenvolvimento Infantil/fisiologia , Deficiências do Desenvolvimento/fisiopatologia , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Doenças do Prematuro/fisiopatologia , Solução Salina Hipertônica/uso terapêutico , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/prevenção & controle , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/prevenção & controle , Crianças com Deficiência/estatística & dados numéricos , Medicina Baseada em Evidências , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/prevenção & controle , Masculino , Análise por Pareamento , Nova Escócia/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
19.
J Biol Chem ; 292(40): 16626-16637, 2017 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-28798231

RESUMO

Salivary gland inflammation is a hallmark of Sjögren's syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated nonselective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1ß and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome. Here, our results show that in primary mouse submandibular gland (SMG) epithelial cells, P2X7R activation also induces the assembly of the NLRP3 inflammasome and the maturation and release of IL-1ß, a response that is absent in SMG cells isolated from mice deficient in P2X7Rs (P2X7R-/-). P2X7R-mediated IL-1ß release in SMG epithelial cells is dependent on transmembrane Na+ and/or K+ flux and the activation of heat shock protein 90 (HSP90), a protein required for the activation and stabilization of the NLRP3 inflammasome. Also, using the reactive oxygen species (ROS) scavengers N-acetyl cysteine and Mito-TEMPO, we determined that mitochondrial reactive oxygen species are required for P2X7R-mediated IL-1ß release. Lastly, in vivo administration of the P2X7R antagonist A438079 in the CD28-/-, IFNγ-/-, NOD.H-2h4 mouse model of salivary gland exocrinopathy ameliorated salivary gland inflammation and enhanced carbachol-induced saliva secretion. These findings demonstrate that P2X7R antagonism in vivo represents a promising therapeutic strategy to limit salivary gland inflammation and improve secretory function.


Assuntos
Células Epiteliais/metabolismo , Interleucina-1beta/metabolismo , Antagonistas do Receptor Purinérgico P2X/farmacologia , Piridinas/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Síndrome de Sjogren/metabolismo , Glândula Submandibular/metabolismo , Tetrazóis/farmacologia , Animais , Antígenos CD28/genética , Antígenos CD28/metabolismo , Modelos Animais de Doenças , Células Epiteliais/patologia , Inflamassomos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Transporte de Íons/efeitos dos fármacos , Transporte de Íons/genética , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Potássio/metabolismo , Receptores Purinérgicos P2X7/genética , Síndrome de Sjogren/genética , Síndrome de Sjogren/patologia , Sódio/metabolismo , Glândula Submandibular/patologia
20.
Transl Oncol ; 10(4): 686-692, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28683435

RESUMO

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer and encapsulated Na3[1-(2`-B10H9)-2-NH3B10H8] within the liposomal core. Mice were irradiated 30 hours after the second injection in a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. Despite relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.

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