RESUMO
PURPOSE OF THE STUDY: Surgical options for paediatric femoral fractures include fl exible intramedullary nailing (FIN), plating, and external fi xators. Length unstable fractures are usually spiral, long oblique, or comminuted and are often associated with > 2 cm of shortening. The purpose of this study was to see whether FIN is effective for managing unstable femur fractures in children. MATERIAL AND METHODS: An electronic literature search was performed up to 25 February 2022 in Cochrane Library, PubMed, and Embase databases using a combination of MeSH search terms and keywords related to the population (e.g., "child" AND "diaphyses" AND "femur"), and intervention (e.g., "nail" OR "ESIN"). The data extracted included the study details, Demographic data, surgical details, postoperative immobilization, complications, and outcome. RESULTS: Eight studies with a total sample size of 369 patients were reviewed. The mean operative time, blood loss, and length of stay in the hospital were 67.62±12.32 minutes, 33.82±16.82 ml, and 4.9±1.27 days, respectively. The results were excellent in 61.92% of the patients, satisfactory in 32.61%, and poor in 5.43%. 4.54% of patients had major complications requiring reoperation and 32.46% of patients had minor complications. the most common complication was nail prominence seen in 26.30% of patients. Locked Ender's nail was associated with the least reoperation, malunion, and LLD rate compared to other types of FIN. CONCLUSIONS: FIN along with a single walking spica cast is a good choice in all forms of paediatric femoral fracture patterns allowing proper alignment and rotation. Locked Ender's nail is safe and effective for managing unstable paediatric femur fracture. KEY WORDS: pediatric femur fracture, length unstable, fl exible intramedullary nailing, submuscular plating, Flynn criterion.
Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Humanos , Criança , Fêmur , Extremidade Inferior , Fixadores Internos , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/efeitos adversosRESUMO
Cyclic AMP (cAMP) receptor protein (CRP), encoded by crp, is a global regulator that is activated by cAMP, a second messenger synthesized by a class I adenylate cyclase (AC-I) encoded by cyaA in Escherichia coli. cAMP-CRP is required for growth on nonpreferred carbon sources and is a global regulator. We constructed in-frame nonpolar deletions of the crp and cyaA homologs in Vibrio parahaemolyticus and found that the Δcrp mutant did not grow in minimal media supplemented with nonpreferred carbon sources, but the ΔcyaA mutant grew similarly to the wild type. Bioinformatics analysis of the V. parahaemolyticus genome identified a 181-amino-acid protein annotated as a class IV adenylate cyclase (AC-IV) named CyaB, a member of the CYTH protein superfamily. AC-IV phylogeny showed that CyaB was present in Gammaproteobacteria and Alphaproteobacteria as well as Planctomycetes and Archaea. Only the bacterial CyaB proteins contained an N-terminal motif, HFxxxxExExK, indicative of adenylyl cyclase activity. Both V. parahaemolyticus cyaA and cyaB genes functionally complemented an E. coli ΔcyaA mutant. The Δcrp and ΔcyaB ΔcyaA mutants showed defects in growth on nonpreferred carbon sources and in swimming and swarming motility, indicating that cAMP-CRP is an activator. The ΔcyaA and ΔcyaB single mutants had no defects in these phenotypes, indicating that AC-IV complements AC-I. Capsule polysaccharide and biofilm production assays showed significant defects in the Δcrp, ΔcyaBΔcyaA, and ΔcyaB mutants, whereas the ΔcyaA strain behaved similarly to the wild type. This is consistent with a role of cAMP-CRP as an activator of these phenotypes and establishes a cellular role for AC-IV in capsule and biofilm formation, which to date has been unestablished. IMPORTANCE Here, we characterized the roles of CRP and CyaA in V. parahaemolyticus, showing that cAMP-CRP is an activator of metabolism, motility, capsule production, and biofilm formation. These results are in contrast to cAMP-CRP in V. cholerae, which represses capsule and biofilm formation. Previously, only an AC-I CyaA had been identified in Vibrio species. Our data showed that an AC-IV CyaB homolog is present in V. parahaemolyticus and is required for optimal growth. The data demonstrated that CyaB is essential for capsule production and biofilm formation, uncovering a physiological role of AC-IV in bacteria. The data showed that the cyaB gene was widespread among Vibrionaceae species and several other Gammaproteobacteria, but in general, its phylogenetic distribution was limited. Our phylogenetic analysis also demonstrated that in some species the cyaB gene was acquired by horizontal gene transfer.
Assuntos
Adenilil Ciclases , Vibrio parahaemolyticus , Adenilil Ciclases/genética , Adenilil Ciclases/metabolismo , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Filogenia , AMP Cíclico/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteína Receptora de AMP Cíclico/genética , Proteína Receptora de AMP Cíclico/metabolismo , Biofilmes , PolissacarídeosRESUMO
There is no literature on the use of belatacept for sensitized patients or regrafts in kidney transplantation. We present our initial experience in high immunologic risk kidney transplant recipients who were converted from tacrolimus to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were switched from tacrolimus to belatacept at a median of 4 months posttransplant. Renal function improved significantly from a peak mean estimated glomerular filtration rate (eGFR) of 23.8 ± 12.9 mL/min/1.73 m(2) prior to the switch to an eGFR of 42 ± 12.5 mL/min/1.73 m(2) (p = 0.03) at a mean follow-up of 16.5 months postconversion. No new rejection episodes were diagnosed despite a prior history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in 5/6 patients did not show subclinical rejection. No development of donor-specific antibodies (DSA) was noted. In this preliminary investigation, we report improved kidney function without a concurrent increase in risk of rejection and DSA in six sensitized patients converted from tacrolimus to belatacept. Improvement in renal function was noted even in patients with chronic allograft fibrosis without evidence of acute CNI toxicity. Further studies with protocol biopsies are needed to ensure safety and wider applicability of this approach.
Assuntos
Abatacepte/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Complicações Pós-Operatórias/induzido quimicamente , Insuficiência Renal/induzido quimicamente , Tacrolimo/efeitos adversos , Adulto , Idoso , Aloenxertos/efeitos dos fármacos , Aloenxertos/fisiopatologia , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Transplante Homólogo , Resultado do TratamentoRESUMO
Myeloperoxidase (MPO) is an important component of the oxidative antibacterial defense system of granulocytes. Mammalian MPO gene expression has been most extensively studied in human and murine cells. Transcription of the human MPO gene appears to begin at a single initiation site and we have recently described the isolation and characterization of the corresponding human MPO promoter. On the other hand, MPO transcripts in murine myeloid cells show several distinct 5'-termini, suggesting the existence of multiple murine MPO promoters. However, significant levels of endogenous murine MPO promoter activity have not been demonstrated heretofore, although several murine MPO enhancers have been described. We now report the identification and preliminary functional characterization of four distinct murine MPO promoters. Sequence comparison of the human and murine MPO promoter regions reveals homologues of three out of four of these murine promoters within the human MPO gene. However, only one of these sites appears to be functionally active in human myeloid cells, possibly because of the interposition of Alu sequences between the putative promoter sites in the human gene.
Assuntos
Peroxidase/genética , Regiões Promotoras Genéticas/genética , Animais , Sequência de Bases , Linhagem Celular , DNA Complementar/genética , Vetores Genéticos/genética , Células HL-60 , Células HeLa , Humanos , Camundongos , Dados de Sequência Molecular , Análise de Sequência de DNA , Homologia de Sequência , TransfecçãoRESUMO
We recently reported the identification and initial characterization of the human myeloperoxidase (MPO) promoter. The minimal or basic MPO promoter lies within the proximal 128 bp of the 5'-flanking region of the MPO gene. Plasmids containing progressively larger segments of the 5'-flanking region show correspondingly greater MPO promoter activity and increased tissue specificity compared with smaller promoter fragments. These findings suggested the presence of a multiple important regulatory cis-elements in the 5'-flanking region of the MPO gene. We now report results of studies which reveal the presence of seven discrete nuclear protein binding sites (DP1-DP7) within the proximal 600 bp of 5'-flanking MPO DNA. DNase I footprinting and gel shift analyses indicate tissue-specific and/or maturation-specific differences in nuclear protein binding to most of these sites, suggesting that they play a role in transcriptional regulation. Mutation of site DP7 stimulates the activity of a 594-bp MPO promoter construct in transfection studies, whereas mutation of any of the six other sites (DP1-DP6) reduces promoter activity. These results indicate that oligonucleotides DP1-DP7 constitute cis-elements which contribute to the activity of the human MPO promoter.
Assuntos
Peroxidase/genética , Regiões Promotoras Genéticas/genética , Sequência de Bases , Sítios de Ligação , Pegada de DNA , Regulação Enzimológica da Expressão Gênica , Humanos , Dados de Sequência Molecular , Mutação , Proteínas Nucleares/metabolismo , Oligonucleotídeos/genética , Peroxidase/metabolismo , Plasmídeos , TransfecçãoRESUMO
Amygdalar CRF has been implicated in the mediation of stress behaviors. The signal transduction pathways that regulate amygdalar CRF are not well understood. In this report, we have examined the effect of protein kinase A and C activators, dexamethasone, and interleukin 6 on CRF messenger RNA (mRNA) and CRF peptide expression in dissociated amygdalar cultures. The amygdala from E19 rat pups was dissected out bilaterally and dissociated in 0.25% trypsin for 10-15 min and plated. On day 17 in culture, CRF mRNA and peptide were measured following treatment with the following agents: forskolin, the phorbol ester-phorbol 12 myristate 13-acetate (TPA), dexamethasone, and interleukin-6 (IL6). Both forskolin and IL6, but not TPA, increased CRF mRNA in a time- and dose-dependent manner. Secretion and intracellular content of the CRF peptide also increased with both forskolin and IL6 treatment but not with TPA. Dexamethasone treatment did not alter the expression of CRF message or peptide. Transfection of the primary cultures with a rat CRF promoter-luciferase reporter construct followed by treatment with all four agents produced alterations in luciferase expression that were consistent with changes observed at the level of CRF mRNA and peptide. The results suggest that CRF regulation in the amygdala differs from that known to occur in the hypothalamus, and that elevation of IL6 levels within the central nervous system may directly act to stimulate CRF production and secretion from limbic structures such as the amygdala, to promote subsequent behavioral changes.
Assuntos
Tonsila do Cerebelo/metabolismo , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , RNA Mensageiro/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/embriologia , Animais , Colforsina/farmacologia , Técnicas de Cultura , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Interleucina-6/farmacologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Ratos/embriologia , Ratos Sprague-DawleyRESUMO
CRF is a 41-amino acid neuropeptide best known for its hypophysiotropic actions. CRF is widely distributed in the central nervous system in areas beyond the hypothalamus. CRF-binding protein (CRF-BP) regulates the bioavailability of CRF, and knowledge of the regulation of CRF-BP synthesis is an integral component of understanding the actions of CRF. To better study the regulation of CRF and CRF-BP, primary amygdalar cultures were immortalized by transfection with the SV 40 large T antigen. A clonal line that expresses CRF immunoreactivity and messenger RNA was selected. The production of CRF peptide and message by this line is regulated in a manner indistinguishable from primary cultures. We also observed that the immortalized cells express CRF-BP immunoreactivity and messenger RNA. The expression of both CRF and CRF-BP is positively regulated by forskolin and interleukin-6. Unlike CRF, the expression of CRF-BP message and peptide was increased by phorbol 12-myristate 13-acetate or dexamethasone. These results demonstrate that the synthesis of CRF and CRF-BP in this clonal cell line may be regulated in parallel by some agents but not by others. These data also suggest that dexamethasone may decrease the biological availability of CRF in the amygdala by increasing the expression of CRF-BP, rather than by decreasing CRF expression.
Assuntos
Tonsila do Cerebelo/metabolismo , Proteínas de Transporte/biossíntese , Hormônio Liberador da Corticotropina/biossíntese , Regulação da Expressão Gênica , Neurônios/metabolismo , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/embriologia , Animais , Proteínas de Transporte/genética , Linhagem Celular Transformada , Colforsina/farmacologia , Hormônio Liberador da Corticotropina/genética , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Interleucina-6/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Acetato de Tetradecanoilforbol/farmacologia , Transcrição Gênica/efeitos dos fármacosRESUMO
The NPLC-KC human hepatoma cell line expresses corticotropin-releasing factor (CRF) and it has been demonstrated that CRF secretion and synthesis in this cell line increases in response to activators of the protein kinase A (PKA) and C (PKC) pathways as well as interleukin-1 (IL1). CRF expression with all three agents can be inhibited with the synthetic steroid-dexamethasone (DEX). In this report, we have examined the effect of IL1 (beta form) in the presence and absence of DEX on CRF mRNA (mRNA) expression as well as the expression of human glucocorticoid receptor (GR) mRNA and the mRNA of the proto-oncogenes (c-jun and c-fos) that have been implicated in CRF regulation. NPLC-KC cells were incubated with picomolar concentrations of IL1. Following this total RNA was extracted from the cells and Northern Blots were probed with 32P-labelled human DNA probes for the CRF, GR, c-jun and c-fos genes. Levels of mRNA expression were measured using a PhosphoImager and were normalized to mRNA levels of control probe glyceraldehyde-3-phosphate dehydrogenase (GAPD). CRF mRNA was significantly increased with IL1 treatment in a time and concentration dependent manner. CRF mRNA expression increased with increasing concentrations of IL1 over the range of 1-100 pM; expression of CRF mRNA also peaked after 24 h of 100 pM IL1 treatment and reached a level of expression approximately seven times higher than control. This pattern of expression was significantly inhibited in the presence of 100 nM DEX. Levels of the GR, c-fos and c-jun mRNAs were also significantly increased in the presence of IL1 and inhibited when DEX was co-incubated with IL1. The results reveal that IL1 stimulation of CRF mRNA expression by IL1 in the NPLC-KC cell line is accompanied by activation of GR mRNA as well as the mRNA of the immediate early genes--c-fos and c-jun. The results also demonstrate that this cell line may serve as a model system for the molecular mechanisms by which IL1 regulates CRF in central nervous system (CNS) neurons.
Assuntos
Carcinoma Hepatocelular/metabolismo , Hormônio Liberador da Corticotropina/genética , Interleucina-1/farmacologia , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-jun/genética , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/genética , Dexametasona/farmacologia , Humanos , RNA Mensageiro/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
Myeloperoxidase (MPO) is an important antibacterial enzyme found only in granulocytes and monocytes. The human MPO gene is transcribed early during myelogenesis but MPO RNA synthesis ceases at the end of the promyelocyte stage of myeloid maturation. We recently identified a basal MPO promoter and several adjacent cis-elements in the proximal 5'-flanking region of this gene. Transfection studies using constructs containing several kb of 5'-flanking MPO DNA revealed the presence of a DNA segment located between bp (base pair) -4200 and bp -3800 with enhancer activity for the endogenous basal MPO promoter. Deletion studies revealed the core enhancer activity to lie between bp -4100 and bp -3844. The percentage enhancement of promoter activity is greater in MPO-expressing myeloid cells than in MPO-non-expressing myeloid cells or non-myeloid cells. Furthermore. the enhancer confers TPA- or DMSO-responsiveness upon either endogenous or exogenous promoters. DNase I footprinting and transfection experiments identified an AML1 site as a functionally important element within the enhancer. Gelshift competition and supershift experiments demonstrated the binding of the alpha subunit of the transcription factor AML1 to this site in HL-60 cells. This distal enhancer appears likely to play an important role in the control of MPO transcription during myeloid differentiation.
Assuntos
Elementos Facilitadores Genéticos , Regulação Enzimológica da Expressão Gênica , Peroxidase/genética , Sequência de Bases , Diferenciação Celular , Pegada de DNA , Proteínas de Ligação a DNA , Granulócitos/enzimologia , Células HL-60 , Células HeLa , Humanos , Células K562 , Monócitos/enzimologia , Especificidade de Órgãos , Regiões Promotoras Genéticas , Transfecção , Células Tumorais CultivadasRESUMO
Corticotropin-releasing factor-binding protein (CRF-BP) is known to regulate the bioavailability of CRF and may also play a role in stress behaviours. CRF-BP has been localized in the pituitary as well as central nervous system (CNS) limbic and cortical areas, including the amygdala. The signal transduction pathways which regulate amygdalar CRF-BP are not well understood. In this report, we have examined the effect of protein kinase A and C activators, CRF, dexamethasone and interleukin-6 (IL6) on CRF-BP mRNA and protein expression in dissociated fetal amygdalar cultures. CRF-BP mRNA levels were determined by Northern analysis following 12 h treatment with the following agents: forskolin (1-30 microM), CRF (1-1000 nM), phorbol-12-myristate-13-acetate (TPA; 1-50 nM), dexamethasone (1-100 nM) and IL6 (10-500 pM). Significant increases in CRF-BP mRNA were observed in response to forskolin (30 mM), CRF (100, 1000 nM), IL6 (100, 500 pM), TPA (50 nM) and dexamethasone (100 nM; P<0.05 for all; n=3-6 for all). We extended our observations of CRF-BP expression to the protein level by performing semiquantitative Western analysis of total cellular protein after treatment with the same agents. Twenty-four hour treatment with 30 microM forskolin, 1000 nM CRF, 50 nM TPA, 100 pM IL6 or 100 nM dexamethasone significantly increased CRF-BP expression (P<0.05, n=3 for each treatment). The primary cultures were then transfected with a rat CRF-BP-reporter construct containing 3500 base pairs of CRF-BP 5' flanking DNA. Treatment with all five agents produced statistically significant increases above control (P<0.05; n=3 for each). The results suggest that CRF-BP in the amygdala is stimulated by numerous pathways which may play a significant role in promoting behavioural changes.
Assuntos
Tonsila do Cerebelo/citologia , Proteínas de Transporte/genética , Neurônios/fisiologia , Regiões 5' não Traduzidas/genética , Animais , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dexametasona/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Glucocorticoides/farmacologia , Interleucina-6/fisiologia , Neurônios/química , Neurônios/citologia , Gravidez , Proteína Quinase C/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Estresse Fisiológico/fisiopatologiaRESUMO
Four NPY receptor subtypes have been cloned, and shown to be coupled to both Ca2+ and cAMP. However, very little is known about the downstream elements mediating NPY actions. It has recently been demonstrated in our laboratory that intrahypothalamic (i.h.t.) administration of NPY induces hypothalamic CaM kinase activity, cyclic AMP response element binding protein (CREB) phosphorylation and cyclic AMP response element (CRE) binding activity in rat hypothalamic nuclear proteins. In the present study, we have investigated whether these changes in CRE binding transcriptional factors activated by NPY results in gene regulation using a human neuroblastoma cell line (SK-N-BE2). This cell line which expresses the Y2 subtype of NPY receptors was transfected with a fusion gene containing 1.305 kb of human CRF 5' flanking region with a perfect palindromic CRE site linked to firefly luciferase gene. NPY treatment increased CaM kinase II activity, CREB phosphorylation and CRE binding in these cells. In transfected cells, luciferase activity was also increased by NPY (1.8-4-fold) within 4 h of treatment. Moreover, forskolin (7-30-fold), which stimulates cAMP production, and thapsigargin (6-8-fold), which mobilizes intracellular calcium, also increased luciferase activity within 4 h of treatment. PMA (phorbol-12-myristate-13-acetate), an activator of protein kinase-C, induced luciferase activity by 1.8-fold. NPY augmented forskolin-stimulated luciferase activity from 11- to 15-fold, but had no significant effect on thapsigargin-induced luciferase activity. These findings suggest that activation of protein kinase A (PKA) or CaM kinase leads to the induction of fusion gene. NPY treatment upregulated fusion gene expression through Ca2+ pathway in SK-N-BE2 cell line. Pretreatment with CREB antisense, but not the sense oligodeoxynucleotides, inhibited forskolin-, thapsigargin- and NPY-stimulated luciferase activity. However, CREB sense or antisense oligodeoxynucleotide treatment had no effect on PMA-stimulated luciferase activity. Furthermore, NPY induced CRE binding activity and the expression of CRE containing Y1 receptor gene in SK-N-MC cell line. These findings suggest that NPY can upregulate CRE containing reporter gene including Y1 receptor gene and NPY-induced reporter gene regulation in SK-N-BE2 cells is mediated by intracellular Ca2+ and CREB protein.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , AMP Cíclico/genética , Neuropeptídeo Y/farmacologia , Receptores de Neuropeptídeo Y/genética , Animais , Fusão Gênica Artificial , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Colforsina/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Humanos , Neuroblastoma/genética , Neuroblastoma/metabolismo , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Tapsigargina/farmacologia , Transfecção , Células Tumorais Cultivadas , Regulação para Cima/efeitos dos fármacosRESUMO
Previous investigations suggest that neuropeptide Y (NPY) feeding mechanisms and corticotropin releasing factor (CRF) are altered in anorectic tumor-bearing (TB) rats. To better determine the relationship of NPY and CRF synthesis to cancer anorexia we measured mRNA for these peptides in medial and lateral hypothalamus of TB and control rats. NPY and CRF mRNA were reliably detected by Northern blot analysis only in medial hypothalamus, where NPY message was elevated significantly in TB rats. CRF mRNA tended to be reduced in both pair-fed (PF) and TB rats, but did not reach statistical significance. Concentrations of NPY or CRF were not altered significantly in either the lateral or medial hypothalamus of TB or PF rats. These results suggest that the transcription of NPY is elevated in PF rats and is increased further in anorectic TB rats. The lack of significant increases in levels of peptides may be related to dilution, due to measuring a relatively large block of hypothalamic tissue. Alternatively, translation of the signal for NPY production may be inhibited, or degradation of peptide levels may be increased.
Assuntos
Anorexia/complicações , Anorexia/genética , Hipotálamo Médio/metabolismo , Neuropeptídeo Y/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sarcoma Experimental/complicações , Sarcoma Experimental/genética , Animais , Anorexia/metabolismo , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Masculino , Neuropeptídeo Y/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Ratos , Sarcoma Experimental/metabolismo , Fatores de TempoRESUMO
Adaptation in aging may become impaired from abnormal expression of corticotropin-releasing factor (CRF) and altered CRF receptor function. In this study, we measured CRF mRNA levels in Fischer 344 rats at various ages. The brains of these rats were processed for in situ hybridization. Relative to 3-month-old rats, levels of CRF mRNA were significantly decreased in the following brain areas at the following ages: at 24 months in the paraventricular hypothalamus, at 11, 17, and 24 months in the amygdala and at 17 and 24 months in the bed nucleus of the stria terminalis. These changes may contribute to impaired adaptations to stress, cognitive decline and other pathophysiological processes during aging.
Assuntos
Envelhecimento/fisiologia , Química Encefálica/fisiologia , Hormônio Liberador da Corticotropina/genética , Tonsila do Cerebelo/química , Tonsila do Cerebelo/fisiologia , Animais , Expressão Gênica/fisiologia , Masculino , Núcleo Hipotalâmico Paraventricular/química , Núcleo Hipotalâmico Paraventricular/fisiologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Estresse Fisiológico/fisiopatologiaRESUMO
Preliminary data suggest that amygdalar corticotropin-releasing factor (CRF) is regulated by nicotinic agonists. We sought to confirm and extend these observations by determining the effects of various concentrations of nicotine on CRF messenger RNA expression in the AR-5 immortalized amygdalar cell line. Nicotine produced concentration- and time-dependent increases in CRF mRNA. This cell line thus confirms that nicotinic agonists stimulate amygdalar CRF and appears to be a useful model for studying molecular factors important in this interaction.
Assuntos
Tonsila do Cerebelo/metabolismo , Hormônio Liberador da Corticotropina/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Nicotina/farmacologia , RNA Mensageiro/metabolismo , Animais , Northern Blotting , Linhagem Celular Transformada , Cinética , RatosRESUMO
Technology, like society, is heterogeneous. It mirrors the context in which it operates. Micro hydro development in Nepal is a rural energy strategy, which relies on technology and innovation and takes place in a specific social context. In designing this energy strategy, both technology and its social context, therefore, need to be considered seriously. In technical design processes, the interplay between the content (technology) and the context (society) needs to be considered, as the outcome will affect the people. For example, the content--micro hydro system--in the domain of the context--agriculture--provides an arena for an integrated water control system. Thus, it is possible to control water for two purposes: to produce power and to provide irrigation. The end product will be "energy" as a "consumptive" output and improved food security as a "productive" output of water. Therefore, within a sociotechnical framework, energy and irrigation become constitutive outputs of the sacrosanct "water". Thus, the metaphor of power--the "sociotechnical code" of "content" and "context"--can be used with the term "agro-anergy" in the design process of micro hydro systems. Evidence suggests that this interaction can lead to a transformed water use system for both productive and consumptive output for the benefit of rural communities.
Assuntos
Agricultura , Conservação dos Recursos Naturais , Fontes Geradoras de Energia , Abastecimento de Água , Meio Ambiente , Humanos , Nepal , Condições Sociais , Transferência de TecnologiaRESUMO
Tuberculosis (TB) is a common opportunistic infection after renal transplantation. The risk of TB in renal transplant recipients is reported to be 20 to 74 times higher than in the general population. Although extrapulmonary TB occurs frequently, isolated ankle joint TB is a rare form of extrapulmonary TB infection. It is often difficult to diagnose because of its atypical presentation; management is complex, especially with multidrug-resistant TB, the need for a prolonged course of therapy, and the risks of drug interactions and drug toxicity. We report herein a case of a 60-year-old female renal allograft recipient who developed multidrug-resistant ankle joint TB 11 months after her deceased donor renal transplantation. She presented to the emergency department with escalating pain and swelling of the left ankle, difficulty in ambulation, and a low-grade fever. An x-ray of the ankle revealed an effusion and soft tissue swelling. A synovial fluid culture was performed which tested positive for acid fast bacilli which grew a multidrug-resistant form of Mycobacterium tuberculosis. She was initially treated with isoniazid, rifampin, ethambutol, and pyrazinamide; then therapy was tailored secondary to the resistant nature of the organism. She received a combination of extensive debridement of the joint and institution of second-line anti-TB therapy with pyrazinamide, ethambutol, moxifloxacin, and ethionamide. To our knowledge, no other cases of multidrug-resistant TB have been reported in the literature after renal transplantation. This case shows both an atypical presentation of TB and the difficulties in managing a transplant patient with this disease.
Assuntos
Transplante de Rim/efeitos adversos , Insuficiência Renal/cirurgia , Tuberculose Resistente a Múltiplos Medicamentos/terapia , Tuberculose Osteoarticular/terapia , Antituberculosos/administração & dosagem , Creatinina/sangue , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Terapia de Imunossupressão , Imunossupressores/efeitos adversos , Inflamação , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Infecções Oportunistas/tratamento farmacológico , Insuficiência Renal/complicações , Tuberculose Resistente a Múltiplos Medicamentos/complicações , Tuberculose Osteoarticular/complicaçõesRESUMO
Kidney stone analysis is the test done on the stone which cause problems when they block the flow of urine through or out of the kidneys. The stones cause severe pain and are also associated with morbidity and renal damage. There is also no clear understanding on the relative metabolic composition of renal calculi. Hence, the study is aimed to find out the chemical composition of it which can guide treatment and give information that may prevent more stones from forming. The study was carried out on the stones that had been sent to the department of Biochemistry (n = 99; M = 61; F = 38; Mean age: 33.6 +/- 14.4 years) Approximately 98.9% of stones were composed of oxalate, 95.9% of Calcium, 85.8% of phosphate, 62.6% of Urate, 46.4% of Ammonium and very few percentages of Carbonate.
Assuntos
Cálculos Renais/química , Adolescente , Adulto , Idoso , Cálcio/análise , Carbonatos/análise , Criança , Pré-Escolar , Feminino , Humanos , Cálculos Renais/epidemiologia , Masculino , Pessoa de Meia-Idade , Oxalatos/análise , Fosfatos/análise , Compostos de Amônio Quaternário/análise , Ácido Úrico/análise , Adulto JovemRESUMO
Thyroid dysfunction is a major public health problem among Nepalese population. Hence the study is aimed to find out the prevalence of thyroid dysfunction and to investigate the effect of it in serum lipids. Serum fT3, fT4, TSH, total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides (TG) were measured using standardized assays. Overall thyroid dysfunction was detected in 25.7% of the study population with the higher prevalence among females. The distribution of overt hypothyroidism, subclinical hypothyroidism, overt hyperthyroidism and subclinical hyperthyroidism were 3.7%, 14.1%, 3.3% and 4.6% respectively. There was a positive association between hypothyroidism and TC>200, LDL>130 and TG>200mg/dl; 48.4% of hypothyroid patient had hypercholesterolemia and 32.3% had hypertriglyceridemia. The mean TC, LDL and TG levels were increased progressively with the increase in the serum TSH. It was noteworthy in this study that even a slight increase in serum TSH (between 6.2-10 mIU/L) showed significant increase in serum lipid level. However there was no association among patients with hyperthyroidism and control group.
Assuntos
Doenças da Glândula Tireoide/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertrigliceridemia/epidemiologia , Hipotireoidismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Prevalência , Doenças da Glândula Tireoide/epidemiologia , Adulto JovemRESUMO
PIP: A summary of internal migration in Nepal is provided, with attention given to its history since the sixteenth century as well as its volume and patterns as recorded in census data for 1952-1954, 1961, 1971, and 1981. Economic and employment conditions as motivations for migration are considered.^ieng