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1.
Braz. j. biol ; 84: e251197, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1350305

RESUMO

Abstract Birds are among the best bio-indicators, which can guide us to recognize some of the main conservation concerns in ecosystems. Anthropogenic impacts such as deforestation, habitat degradation, modification of landscapes, and decreased quality of habitats are major threats to bird diversity. The present study was designed to detect anthropogenic causative agents that act on waterbird diversity in Tarbella Dam, Indus River, Pakistan. Waterbird censuses were carried out from March 2019 to February 2020 in multiple areas around the dam. A total of 2990 waterbirds representing 63 species were recorded. We detected the highest waterbird richness and diversity at Pehure whereas the highest density was recorded at Kabbal. Human activity impacts seemed to be the main factor determining the waterbird communities as waterbirds were negatively correlated with the greatest anthropogenic impacts. Waterbirds seem to respond rapidly to human disturbance.


Resumo As aves estão entre os melhores bioindicadores, o que pode nos orientar a reconhecer algumas das principais preocupações de conservação dos ecossistemas. Impactos antrópicos como desmatamento, degradação de habitat, modificação de paisagens e diminuição da qualidade dos habitats são as principais ameaças à diversidade de aves. O presente estudo foi desenhado para detectar agentes causadores antropogênicos que atuam na diversidade de aves aquáticas na Represa de Tarbella, rio Indus, Paquistão. Censos de aves aquáticas foram realizados de março de 2019 a fevereiro de 2020 em várias áreas ao redor da barragem. Um total de 2.990 aves aquáticas representando 63 espécies foi registrado. Detectamos a maior riqueza e diversidade de aves aquáticas em Pehure, enquanto a maior densidade foi registrada em Kabbal. Os impactos da atividade humana parecem ser o principal fator determinante das comunidades de aves aquáticas, uma vez que as aves aquáticas foram negativamente correlacionadas com os maiores impactos antrópicos. As aves aquáticas parecem responder rapidamente às perturbações humanas.


Assuntos
Humanos , Ecossistema , Rios , Paquistão , Conservação dos Recursos Naturais
2.
Braz. j. biol ; 83: e249229, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1339374

RESUMO

Abstract Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.


Resumo Os pássaros são indicadores muito valiosos da riqueza de espécies e padrões endêmicos em um determinado ecossistema, o que acaba ajudando o cientista a medir a degradação ambiental. O objetivo do presente estudo foi conhecer o conhecimento humano e a atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão. O estudo foi conduzido em quatro meses consecutivos: novembro de 2019 a fevereiro de 2020. A população de pássaros foi observada em oito cidades residenciais da cidade de Faisalabad, os dados foram coletados por meio de questionário. Faisalabad tem uma população razoavelmente grande de pássaros, e os dados atuais mostram que há uma diferença significativa entre as aves favoritas de áreas residenciais e instituições. O pombo recebeu mais semelhanças na população de pássaros entre os residentes de áreas residenciais, enquanto o myna recebeu menos. A ave mais popular nas instituições de Faisalabad era o pardal, enquanto a ave menos popular era o myna comum. A porcentagem de adaptação de pássaros em áreas residenciais e institucionais de Faisalabad foi a mais alta para papagaios e pardais, respectivamente. As pessoas em áreas residenciais e instituições, por outro lado, se adaptaram menos ao myna comum. Conclui-se que pessoas da área de estudo como pássaros e alimentos oferecidos e alta população de pássaros estão presentes na área de estudo.


Assuntos
Humanos , Animais , Aves , Ecossistema , Paquistão , Cidades , Biodiversidade
3.
Braz. j. biol ; 82: e238096, 2022. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278519

RESUMO

Abstract Pakistan is the country with mega freshwater fish diversity of native and alien species. In the presence of enormous native fishes varies species of exotic fishes have been introduced into the freshwater bodies of Pakistan which are competing with native freshwater fish fauna and making them deprive of food and habitat as well. Intentional or accidental introductions of animals, plants and pathogens away from their native niche is considered as major leading problem for biodiversity of invaded habitat. Three years study (from January 2017 to December 2019) was conducted in freshwater bodies of Province Punjab, Pakistan. Study was designed to know exotic species impacts on the distribution of native species of fishes. During current survey a total of 68 (indigenous and exotic) fish species belonging to 14 families were recorded from head Qadirabad, head Baloki, Islam headworks and Rasul barrage. Statistical analysis showed that Shannon-Wiener diversity index was the highest (1.41) at both Rasul barrage and Islam headworks but, invasive species were present in very less number in these study sites i.e. Oreochromis mozambicus, O. niloticus, Hypophthalmichthys nobilis, Carassius auratus, Ctenophryngdon idella, Cyprinus carpio and H. molitrix. The diversity index showed that comparatively low diversity was present in both area head Qadirabad (1.30) and head Baloki (1.4) due to high pressure of invasive species. Direct observation of species and statistical analysis showed that aliens' species produced negative impact on the local fish fauna diversity, evenness, and numbers. It is concluded that many factors are impacts on the diversity of native fishes, but alien (invasive) species also play a major role to reduction of native species, because aliens' species produce competition for native species. So it is urgent need to analysis the aliens and native food web and roosting sites in Pakistan, in future.


Resumo O Paquistão é um país com ampla diversidade de espécies nativas e exóticas de peixes de água doce. Contudo, diversas espécies de peixes exóticos estão sendo introduzidas nos corpos de água doce paquistanês, as quais estão competindo com a fauna nativa de peixes, tornando-os privados de alimento e habitat. A introdução intencional ou acidental de animais, plantas e patógenos fora de seu nicho nativo é considerada o principal problema da biodiversidade do habitat recém-invadido. Assim, foi realizado um estudo de três anos, de janeiro de 2017 a dezembro de 2019, em corpos de água doce na província de Punjab, Paquistão. A pesquisa foi desenvolvida para conhecer os impactos de espécies exóticas na distribuição de espécies nativas de peixes. Durante a pesquisa, foi registrado um total de 68 espécies de peixes (nativas e exóticas), pertencentes a 14 famílias, nas nascentes dos rios Qadirabad, Baloki e Islam e na barragem de Rasul. A análise estatística mostrou que o índice de diversidade de Shannon-Wiener foi mais alto (1,41) na barragem Rasul (RB) e na nascente do rio Islam (IH); e que a maioria das espécies introduzidas estava presente em um número muito menor, isto é, Oreochromis mossambicus, Oreochromis niloticus, Hypophthalmichthys nobilis, Carassius auratus, Ctenopharyngodon idella, Cyprinus carpio e Hypophthalmichthy smolitrix nessa área de estudo. Por outro lado, o índice Shannon-Wiener mostrou que a diversidade estava baixa nas nascentes dos rios Qadirabad (1,30) e Baloki (1,4) em razão da alta pressão de espécies invasoras. A observação direta das espécies e a análise estatística indicaram que as espécies invasoras produziram impacto negativo na diversidade, uniformidade e números de peixes da fauna local. Conclui-se que muitos fatores impactam na diversidade de peixes nativos, mas as espécies exóticas (invasoras) também desempenham um papel importante na redução das espécies nativas, em razão da competição existente entre elas. Portanto, é urgente uma análise futura das espécies invasoras e da teia alimentar nativa no Paquistão..


Assuntos
Animais , Carpas , Espécies Introduzidas , Paquistão , Ecossistema , Biodiversidade , Peixes , Água Doce
4.
Braz J Biol ; 84: e251197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34852136

RESUMO

Birds are among the best bio-indicators, which can guide us to recognize some of the main conservation concerns in ecosystems. Anthropogenic impacts such as deforestation, habitat degradation, modification of landscapes, and decreased quality of habitats are major threats to bird diversity. The present study was designed to detect anthropogenic causative agents that act on waterbird diversity in Tarbella Dam, Indus River, Pakistan. Waterbird censuses were carried out from March 2019 to February 2020 in multiple areas around the dam. A total of 2990 waterbirds representing 63 species were recorded. We detected the highest waterbird richness and diversity at Pehure whereas the highest density was recorded at Kabbal. Human activity impacts seemed to be the main factor determining the waterbird communities as waterbirds were negatively correlated with the greatest anthropogenic impacts. Waterbirds seem to respond rapidly to human disturbance.


Assuntos
Ecossistema , Rios , Conservação dos Recursos Naturais , Humanos , Paquistão
5.
Braz J Biol ; 83: e249229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34669801

RESUMO

Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.


Assuntos
Aves , Ecossistema , Animais , Biodiversidade , Cidades , Humanos , Paquistão
6.
Braz J Biol ; 82: e238096, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34133555

RESUMO

Pakistan is the country with mega freshwater fish diversity of native and alien species. In the presence of enormous native fishes varies species of exotic fishes have been introduced into the freshwater bodies of Pakistan which are competing with native freshwater fish fauna and making them deprive of food and habitat as well. Intentional or accidental introductions of animals, plants and pathogens away from their native niche is considered as major leading problem for biodiversity of invaded habitat. Three years study (from January 2017 to December 2019) was conducted in freshwater bodies of Province Punjab, Pakistan. Study was designed to know exotic species impacts on the distribution of native species of fishes. During current survey a total of 68 (indigenous and exotic) fish species belonging to 14 families were recorded from head Qadirabad, head Baloki, Islam headworks and Rasul barrage. Statistical analysis showed that Shannon-Wiener diversity index was the highest (1.41) at both Rasul barrage and Islam headworks but, invasive species were present in very less number in these study sites i.e. Oreochromis mozambicus, O. niloticus, Hypophthalmichthys nobilis, Carassius auratus, Ctenophryngdon idella, Cyprinus carpio and H. molitrix. The diversity index showed that comparatively low diversity was present in both area head Qadirabad (1.30) and head Baloki (1.4) due to high pressure of invasive species. Direct observation of species and statistical analysis showed that aliens' species produced negative impact on the local fish fauna diversity, evenness, and numbers. It is concluded that many factors are impacts on the diversity of native fishes, but alien (invasive) species also play a major role to reduction of native species, because aliens' species produce competition for native species. So it is urgent need to analysis the aliens and native food web and roosting sites in Pakistan, in future.


Assuntos
Carpas , Espécies Introduzidas , Animais , Biodiversidade , Ecossistema , Peixes , Água Doce , Paquistão
7.
J Family Med Prim Care ; 9(4): 2071-2078, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32670968

RESUMO

BACKGROUND: The economic transition in Saudi Arabia imposed negative consequences leading to an increase in the prevalence of obesity and its sequelae. Despite the commitment of high authorities in KSA to combat obesity, so far 25% of Saudis are still obese. The association between obesity, disordered eating attitude, and body image needs to be addressed. AIM: To explore the relationship between obesity, eating attitude, and body image satisfaction among students and employees at Princess Nourah University (PNU) and to compare the different modalities of assessing body weight. METHODS: A cross-sectional study using a convenient sampling technique comprised of 550 participants. Obesity was assessed by anthropometric measurements and body composition monitor (BF511). Eating attitude test (EAT26) was used to determine eating attitude while body image satisfaction score was determined using body shape questionnaire (BSQ). RESULTS: Around 382 (69.5%) students and 168 employees participated in the study. Obesity was significantly higher among employees (48.2%) vs students (27.7%) (P < 0.001). Body fat composition showed significant positive correlations ranging from weak-to-moderate (0.13 to 0.44) with other body measurements for students and employees. The disordered eating attitude was maximized among obese compared to other BMI groups (P < 0.05). Percentage of disordered eating attitude score correlated positively with BMI: 35.2% vs 52.3% among underweight and obese, respectively (P = 0.001). There was no statistical difference in eating attitudes between students and employees. BSQ score correlates positively with BMI (P < 0.001), it was 36.73 ± 18.68 vs 57.92 ± 18.50 for underweight and obese, respectively. The effect of BMI on body image score was 19.1%. DISCUSSION AND CONCLUSION: Obesity remains a significant health problem among Saudi females. Increased BMI is associated with increased disordered food attitude and the effect of BMI on body image score was minimal.

8.
Saudi J Biol Sci ; 24(1): 80-89, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28053575

RESUMO

This study was carried out to identify drought-responsive genes in a drought tolerant faba bean variety (Hassawi 2) using a suppressive subtraction hybridization approach (SSH). A total of 913 differentially expressed clones were sequenced from a differential cDNA library that resulted in a total of 225 differentially expressed ESTs. The genes of mitochondrial and chloroplast origin were removed, and the remaining 137 EST sequences were submitted to the gene bank EST database (LIBEST_028448). A sequence analysis identified 35 potentially drought stress-related ESTs that regulate ion channels, kinases, and energy production and utilization and transcription factors. Quantitative PCR on Hassawi 2 genotype confirmed that more than 65% of selected drought-responsive genes were drought-related. Among these induced genes, the expression levels of eight highly up-regulated unigenes were further analyzed across 38 selected faba bean genotypes that differ in their drought tolerance levels. These unigenes included ribulose 1,5-bisphosphate carboxylase (rbcL) gene, non-LTR retroelement reverse related, probable cyclic nucleotide-gated ion channel, polyubiquitin, potassium channel, calcium-dependent protein kinase and putative respiratory burst oxidase-like protein C and a novel unigene. The expression patterns of these unigenes were variable across 38 genotypes however, it was found to be very high in tolerant genotype. The up-regulation of these unigenes in majority of tolerant genotypes suggests their possible role in drought tolerance. The identification of possible drought responsive candidate genes in Vicia faba reported here is an important step toward the development of drought-tolerant genotypes that can cope with arid environments.

9.
IEEE Trans Biomed Eng ; 62(8): 2001-11, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25769144

RESUMO

We describe the acoustic gaits-the natural human gait quantitative characteristics derived from the sound of footsteps as the person walks normally. We introduce the acoustic gait profile, which is obtained from temporal signal analysis of sound of footsteps collected by microphones and illustrate some of the spatio-temporal gait parameters that can be extracted from the acoustic gait profile by using three temporal signal analysis methods-the squared energy estimate, Hilbert transform and Teager-Kaiser energy operator. Based on the statistical analysis of the parameter estimates, we show that the spatio-temporal parameters and gait characteristics obtained using the acoustic gait profile can consistently and reliably estimate a subset of clinical and biometric gait parameters currently in use for standardized gait assessments. We conclude that the Teager-Kaiser energy operator provides the most consistent gait parameter estimates showing the least variation across different sessions and zones. Acoustic gaits use an inexpensive set of microphones with a computing device as an accurate and unintrusive gait analysis system. This is in contrast to the expensive and intrusive systems currently used in laboratory gait analysis such as the force plates, pressure mats and wearable sensors, some of which may change the gait parameters that are being measured.


Assuntos
Acústica , Pé/fisiologia , Marcha/fisiologia , Processamento de Sinais Assistido por Computador , Caminhada/fisiologia , Humanos
10.
PLoS One ; 8(7): e70276, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23894629

RESUMO

BACKGROUND: Free light chains (LCs) are among the many ligands that bind to cubilin/megalin for endocytosis via the clathrin-dependent endosomal/lysosomal pathway. Receptor associated protein (RAP), is a 39 kDA high-affinity, chaperone-like ligand for megalin that assists in the proper folding and functioning of megalin/cubilin. Although RAP is known to inhibit ligand binding to megalin/cubilin, its effect on LC endocytosis has not been shown directly. METHODS AND PRINCIPAL FINDINGS: We investigated whether RAP can block the endocytosis of LC in cultured human proximal tubule cells and whether this can prevent LC cytotoxicity. Immunofluorescence microscopy and flow cytometry showed that fluorescently labeled LC endocytosis was markedly inhibited in HK-2 cells pretreated with human RAP. The effect of RAP was dose-dependent, and was predominantly on endocytosis as it had no effect on the small acid-washable fraction of LC bound to cell membrane. RAP significantly inhibited LC induced cytokine production and phosphorylation of ERK1/2 and p38 MAPK. Prolonged exposure to LC for 48 h resulted in epithelial-to-mesenchymal transformation in HK-2 cells as evidenced by marked reduction in the expression of the epithelial cell marker E-cadherin, and increased the expression of the mesenchymal marker α-SMA, which was also prevented by RAP in the endocytosis medium. CONCLUSIONS: RAP inhibited LC endocytosis by ∼88% and ameliorated LC-induced cytokine responses and EMT in human PTCs. The results not only provide additional evidence that LCs endocytosis occurs via the megalin/cubilin endocytic receptor system, but also show that blocking LC endocytosis by RAP can protect proximal tubule cells from LC cytotoxicity.


Assuntos
Cadeias Leves de Imunoglobulina/metabolismo , Túbulos Renais Proximais/metabolismo , Proteína Associada a Proteínas Relacionadas a Receptor de LDL/metabolismo , Insuficiência Renal/metabolismo , Linhagem Celular , Endocitose , Transição Epitelial-Mesenquimal , Humanos , Interleucina-6/análise , Interleucina-8/análise , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Mieloma Múltiplo/metabolismo
11.
Physiol Rep ; 1(6): e00163, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24400164

RESUMO

We determined whether pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) prevents contrast-induced nephropathy using human renal proximal tubule epithelial (HK-2) cells and homozygous endothelial nitric oxide synthase-deficient (eNOS(-/-)) mice as a novel in vivo model. Cultured HK-2 cells were pretreated with 10(-9)-10(-6) mol/L PACAP or vasoactive intestinal peptide (VIP) for 1 h, and then exposed to ionic (Urografin) or nonionic (iohexol) contrast media at 50 mg iodine/mL for 24 h. Male eNOS(-/-) mice received Urografin (1.85 g iodine/kg) intravenously after water deprivation for 24 h, and PACAP38 (10 µg) intraperitoneally 1 h before and 12 h after Urografin injection. Urografin and iohexol increased lactate dehydrogenase and kidney injury molecule 1 in the culture medium, induced apoptosis, and inhibited cell proliferation in HK-2 cell cultures. PACAP38 and VIP reduced these changes in a dose-dependent manner. PACAP38 was more potent than VIP. In eNOS(-/-) mice, Urografin raised serum creatinine and cystatin C levels, caused renal tubule damage, induced apoptosis, and promoted neutrophil influx. Urografin also increased kidney protein levels of proinflammatory cytokines, and kidney mRNA levels of proinflammatory cytokines, kidney injury biomarkers, and enzymes responsible for reactive oxygen and nitrogen species. PACAP38 significantly reduced these Urografin-induced changes in eNOS(-/-) mice. This study shows that both Urografin and iohexol are toxic to HK-2 cells, but Urografin is more toxic than iohexol. Urografin causes acute kidney injury in eNOS(-/-) mice. PACAP38 protects HK-2 cells and mouse kidneys from contrast media and is a potential therapeutic agent for contrast-induced nephropathy.

12.
Int J Mol Sci ; 15(1): 277-95, 2013 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-24378852

RESUMO

Morphological, nutritional and molecular analyses were carried out to assess genetic diversity among 35 introduced lentil genotypes (Lens culinaris Medik.). The genotypes exhibited significant differences for their field parameters and some of them showed noticeable superiority. The nutritional and proximate analysis showed that some genotypes were excellent sources of proteins, essential amino acids, minerals, anti-oxidants, total phenolic contents (TPC) and total flavonoid contents (TFC) and hence, highlights lentil nutritional and medicinal potential. Sequence-related amplified polymorphism (SRAP) and amplified fragments length polymorphism (AFLP) markers were used to estimate the genetic variability at the molecular level. The existence of a considerable amount of genetic diversity among the tested lentil genotypes was also proven at the molecular level. A total of 2894 polymorphic SRAP and 1625 AFLP loci were successfully amplified using six SRAP and four AFLP primer pair combinations. Polymorphism information content (PIC) values for SRAP and AFLP markers were higher than 0.8, indicating the power and higher resolution of those marker systems in detecting molecular diversity. UPGMA (unweighted pair group method with arithmetic average) cluster analysis based on molecular data revealed large number of sub clusters among genotypes, indicating high diversity levels. The data presented here showed that FLIP2009-64L and FLIP2009-69L could be used as a significant source of yield, total protein, essential amino acids, and antioxidant properties. The results suggest potential lentil cultivation in the central region of Saudi Arabia for its nutritional and medicinal properties, as well as sustainable soil fertility crop.


Assuntos
Variação Genética , Lens (Planta)/genética , Antioxidantes/química , Antioxidantes/metabolismo , Análise por Conglomerados , Flavonoides/química , Flavonoides/metabolismo , Loci Gênicos , Genótipo , Lens (Planta)/crescimento & desenvolvimento , Lens (Planta)/metabolismo , Fenóis/química , Fenóis/metabolismo , Arábia Saudita
13.
Peptides ; 38(2): 395-403, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23023072

RESUMO

We investigated whether pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) ameliorates kidney injury after ischemia/reperfusion (IR) by modulating Toll-like receptor (TLR)-associated signaling pathways. Male C57BL/6 mice were subjected to bilateral renal ischemia for 45 min. PACAP38, 20 µg in 100 µl of saline, was administered i.p. at 24 and 48 h after IR, and mice were euthanized at 72h. In IR mice, PACAP38 maintained serum creatinine near control levels (0.81 ± 0.08 vs. 0.69 ± 0.17 mg/dl in controls, p=NS, vs. 1.8 ± 0.03 in saline-treated IR mice, p<0.01) and significantly reduced the expression of kidney injury biomarkers. PACAP38 significantly reduced the levels of apoptosis and neutrophil infiltration, and protected against tubular damage. With PCR arrays, 59 of 83 TLR-related genes significantly changed their expression after IR. TLR2 increased 162 fold, followed by Fas-associated death domain (37 fold) and TLR6 (24 fold), while ubiquitin-conjugating enzyme E2 variant 1 (UBE2V1) decreased 55 fold. PACAP38 given 24 and 48 h after IR injury significantly reversed these changes in 56 genes, including TLR2, TLR3, TLR4, TLR6, and genes in the NF-κB pathways. The alterations in TLR2, TLR3, TLR6, and UBE2V1 were confirmed by RT-PCR. After IR, PACAP38 also suppressed protein levels of TLR-associated cytokines. PACAP38 reversed the changes in IR-activated TLR-associated NF-κB signaling pathways even when treatment was delayed 24h. Therefore, PACAP38 could be an effective therapeutic for unexpected IR-mediated renal injury. The prominently IR-induced TLR-related genes identified in this study could be novel drug targets.


Assuntos
Rim/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Receptores Toll-Like/metabolismo , Animais , Apoptose/efeitos dos fármacos , Creatinina/sangue , Citocinas/análise , Citocinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Rim/irrigação sanguínea , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/administração & dosagem , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/genética
14.
J Investig Med ; 59(5): 793-802, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21383633

RESUMO

BACKGROUND: Acute and long-term nephrotoxicity is the major dose-limiting factor for cyclosporine A (CsA). We evaluated the protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP)38 on CsA-induced nephrotoxicity in human renal proximal tubule epithelial (human kidney-2) cells and in intact mice. METHODS: Confluent (human kidney-2 cells were exposed to CsA (25-50 µmol/L) in the presence or absence of PACAP38 or vasoactive intestinal peptide (10(-10) to 10(-6) M). For studies in vivo, male BALB/c mice (n = 5 in each group) were given a single intraperitoneal injection of CsA (5 mg/kg body weight). Treatment group received 20 µg of PACAP38 2 hours before exposure to CsA and additional doses daily for 10 days. RESULTS: Cyclosporine A caused oxidative injury, marked morphological alterations, apoptosis, and increased expression of transforming growth factor (TGF)-ß1 in cell cultures. Pituitary adenylate cyclase-activating polypeptide 38 at 10(-8) mol/L restored cell confluency, reduced TGF-ß1 secretion, and preserved cell integrity. In mice, CsA caused tubular injury characterized by loss of tubular epithelial cell brush border membranes, tubular collapse, cellular necrosis, interstitial fibrosis, increased production of TGF-ß1, and elevated serum creatinine (3.39 ± 0.21 vs 0.13 ± 0.02 mg/dL in controls, P < 0.01). Treatment with PACAP38 reduced TGF-ß1 and tumor necrosis factor-α production in kidney, prevented epithelial-mesenchymal transition of the renal cells, and reduced serum creatinine levels to 1.01 ± 0.18 mg/dL, P < 0.01 versus CsA group. CONCLUSIONS: Pituitary adenylate cyclase-activating polypeptide 38 ameliorated renal tubular injury, reduced oxidative injury, and inhibited the expression of TGF-ß1 in CsA-exposed murine kidneys. Pituitary adenylate cyclase-activating polypeptide could be a novel renoprotective and antifibrotic agent for CsA nephrotoxicity.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Ciclosporina/farmacologia , Rim/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Animais , Apoptose , Linhagem Celular , Ensaio de Imunoadsorção Enzimática/métodos , Transição Epitelial-Mesenquimal , Humanos , Imuno-Histoquímica/métodos , Imunossupressores/farmacologia , Marcação In Situ das Extremidades Cortadas , Rim/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo
15.
J Mol Neurosci ; 43(1): 58-66, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20514524

RESUMO

Cisplatin is widely used for cancer chemotherapy, but nephrotoxicity is a major dose-limiting side effect. Our recent studies in vitro have shown that pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorated cisplatin nephrotoxicity and that the renoprotection with PACAP38 was mediated by the PAC(1) receptor and through the p53-dependent and -independent suppression of apoptosis of human renal proximal tubular epithelial cells. In the present studies, PACAP38 prevented the rise in blood urea nitrogen and serum creatinine in mice treated with cisplatin. Cisplatin-exposed mice treated with PACAP38 had relatively well-preserved tubular integrity, even when the treatment started 24 h after cisplatin exposure. PACAP38 also reduced plasma and kidney levels of tumor necrosis factor-α and restored collagen IV levels. The damage to mouse kidney tubules caused by cisplatin involved p53 accumulation and was partially reversed by treatment with PACAP38. PACAP38 ameliorates cisplatin-induced acute kidney injury even when treatment started 24 h after the onset of injury and increases tubular regeneration, which further facilitates restoration of kidney function in addition to its anti-apoptotic effects.


Assuntos
Cisplatino/toxicidade , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/uso terapêutico , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/prevenção & controle , Animais , Células Cultivadas , Matriz Extracelular/química , Humanos , Túbulos Renais/citologia , Túbulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteína Supressora de Tumor p53/genética , Vimentina/genética , Vimentina/metabolismo
16.
Am J Nephrol ; 32(6): 522-32, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20980738

RESUMO

BACKGROUND/AIMS: toll-like receptor 4 (TLR4) and its adaptor protein MyD88 play an important role in ischemia/reperfusion (I/R) injury in the kidney, and pituitary adenylate cyclase-activating polypeptide (PACAP) could ameliorate renal I/R injury. METHODS: primary cultures of proximal tubule epithelial cells (PTEC) were prepared from wild-type and MyD88(-/-) mice, and subjected to hypoxia in vitro. Acute kidney injury (AKI) was induced by I/R in vivo in wild-type mice only. RESULTS: hypoxia resulted in significant increases in cytokine production and apoptosis/necrosis in wild-type PTEC, but these responses were markedly blunted in MyD88(-/-) PTEC. Treatment with PACAP38 before or after hypoxia further suppressed the hypoxia-induced cytokine responses and apoptosis in both MyD88(+/+) and MyD88(-/-) PTEC cultures. PACAP38 significantly inhibited TLR4/MyD88/TRAF6 as well as TRIF and IRF3 expression in mouse kidney and PTEC, and inhibited the secretion and mRNA expression of cytokines in kidneys from mice after I/R, paralleling the cytokine responses in vitro. Moreover, treatment with PACAP38 protected mice from renal failure, histological damage, neutrophil influx and tubule cell apoptosis after I/R. CONCLUSION: our data reveal that the TLR4-mediated cytokine responses to hypoxia are primarily dependent on MyD88 signaling and highlight the pivotal role of MyD88-dependent mechanisms in the coordination of the innate immune responses to ischemic/hypoxic acute renal tubular injury. The renoprotective effect of PACAP in AKI involves both MyD88-dependent and -independent pathways.


Assuntos
Injúria Renal Aguda/fisiopatologia , Fator 88 de Diferenciação Mieloide/fisiologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/fisiologia , Injúria Renal Aguda/patologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Apoptose/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Células do Cúmulo , Células Epiteliais/patologia , Hipóxia , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Interleucina-6/metabolismo , Túbulos Renais Proximais/patologia , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/fisiologia , Traumatismo por Reperfusão/patologia , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo
17.
Nephron Exp Nephrol ; 116(2): e32-41, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20588062

RESUMO

We investigated the effects of human light chain (LC) protein-overload in mice kidney to gain further insights into the molecular mechanisms involved in the pathogenesis of myeloma kidney. Intact male C57BL/6, 10- to 12-week-old mice were given daily intraperitoneal (i.p.) injections of 1 ml of human κ-LCs (1.5 mg/ml, low dose), or (100 mg/ml, high dose) to uninephrectomized mice for 2 weeks. Intact, sham-operated or uninephrectomized control animals were given the same volume (1 ml/day) of saline, human serum albumin (10 mg/ml) or bovine serum albumin (100 mg/ml) i.p. for 2 weeks in place of LCs. The low-dose LC-treated mice had human LCs in their urine and a significant increase in monocyte chemoattractant protein-1 (MCP-1) mRNA in the kidneys. Uninephrectomized mice treated with high-dose κ-LCs showed tubule casts, and foci of intracytoplasmic rhomboid crystals within the proximal tubules, along with cytoskeletal disruptions and alterations in the brush-border membrane, and high concentrations of human κ-LC were present in their sera. High-dose LC treatment also led to increases in serum creatinine and tumor necrosis factor-α levels, and marked increases in interleukin-6 and MCP-1 expression as well as cellular apoptosis in the kidneys. These studies demonstrate that myeloma LC overload over a range of LC concentrations in mice causes significant functional and morphological kidney injury. The model should be helpful in investigating pathophysiologic mechanisms and exploring therapeutic interventions for myeloma kidney and other LC-associated renal disorders.


Assuntos
Cadeias kappa de Imunoglobulina/toxicidade , Nefropatias/induzido quimicamente , Idoso , Animais , Apoptose/efeitos dos fármacos , Quimiocina CCL2/biossíntese , Feminino , Humanos , Interleucina-6/biossíntese , Rim/metabolismo , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Proteinúria/etiologia
18.
Peptides ; 31(4): 592-602, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20034524

RESUMO

Cisplatin nephrotoxicity involves DNA damage, proinflammatory responses and apoptosis/necrosis of renal proximal tubular epithelial cells. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to protect kidneys from ischemic injury and light chain-induced damage by modulating inflammation. Confluent monolayer of HK-2 human renal cells were exposed to 50 microM cisplatin in the presence or absence of either PACAP38 or p53 siRNA. Mice injected with cisplatin were also treated with PACAP38 daily for 3 days. The damage to HK-2 cells caused by cisplatin involved the activation of p53, caspase-7, and poly (ADP-ribose) polymerase-1 (PARP-1). PACAP38 prevented the decrease in the apurinic/apyrimidinic endonuclease-1 by suppressing p53 activation and blocked the cleavage of caspase-7 and PARP-1 in cisplatin-exposed cells. PACAP also markedly inhibited cisplatin-induced apoptotic tubule cell death. Exposure to cisplatin significantly suppressed the expression of fibronectin and collagens I and IV, and altered the integrin repertoire of human renal tubule cells, while PACAP partially reversed the reduction of fibronectin, collagen IV, and the integrin subunits in cells exposed to cisplatin. Experiments with PACAP receptor antagonists and siRNA silencing of p53 showed that the renoprotection with PACAP was mediated by the PAC(1) receptor and through both p53-dependent and -independent suppression of apoptosis. PACAP was renoprotective in vivo and prevented the rise in blood urea nitrogen and creatinine in mice treated with cisplatin. These results suggest that p53 plays a pivotal role in decreased integrin-mediated extracellular matrix component expression in cisplatin-induced tubule cell apoptosis, and reveal a novel aspect of PACAP-mediated renoprotection.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Injúria Renal Aguda/patologia , Animais , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Integrinas/metabolismo , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
19.
Can J Microbiol ; 55(4): 405-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19396240

RESUMO

beta-d-Fructofuranosidase (FFase), an important enzyme of the confectionery and fructose syrup industry, is produced by several microorganisms. However, yeasts are the most used source because of their high sucrose fermentation capacity. In this work, production of FFase was carried out in submerged fermentation using a high enzyme-producing yeast strain. Plackett-Burman statistical experimental design was applied to evaluate the fermentation medium components. The effects of 10 nitrogen sources were studied in a 16-run experimental design. Beef extract, yeast extract, N-Z-amine, tryptone, meat extract, and ammonium acetate were found to have significant effects on enzyme production. Among these, yeast extract, N-Z-amine, and ammonium acetate were the most significant. A maximum FFase activity of 299.4 U/mL was obtained after a 24 h fermentation period.


Assuntos
Meios de Cultura/química , Modelos Biológicos , Nitrogênio/metabolismo , Saccharomyces/crescimento & desenvolvimento , beta-Frutofuranosidase/biossíntese , Fermentação , Microbiologia de Alimentos , Microbiologia Industrial , Saccharomyces/classificação , Saccharomyces/metabolismo
20.
Indian J Pharm Sci ; 70(5): 655-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21394268

RESUMO

A new oral drug delivery system was developed utilizing both the concepts of controlled release and mucoadhesiveness, in order to obtain a unique drug delivery system which could remain in stomach and control the drug release for longer period of time. Captopril microcapsules were prepared with a coat consisting of alginate and a mucoadhesive polymer such as hydroxy propyl methyl cellulose, carbopol 934p, chitosan and cellulose acetate phthalate using emulsification ionic gelation process. The resulting microcapsules were discrete, large, spherical and free flowing. Microencapsulation efficiency was 41.7-89.7% and high percentage efficiency was observed with (9:1) alginate-chitosan microcapsules. All alginate-carbopol 934p microcapsules exhibited good mucoadhesive property in the in vitro wash off test. Drug release pattern for all formulation in 0.1 N HCl (pH 1.2) was diffusion controlled, gradually over 8 h and followed zero order kinetics.

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