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1.
Artigo em Inglês | MEDLINE | ID: mdl-37974030

RESUMO

BACKGROUND AND HYPOTHESIS: Dysregulated energy metabolism is a recently discovered key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Cystic cells depend on glucose and are poorly able to use other energy sources such as ketone bodies. Raising ketone body concentration reduced disease progression in animal models of polycystic kidney diseases. Therefore, we hypothesized that higher endogenous plasma beta-hydroxybutyrate concentrations are associated with reduced disease progression in patients with ADPKD. METHODS: We analyzed data from 670 patients with ADPKD participating in the DIPAK cohort, a multi-center prospective observational cohort study. Beta-hydroxybutyrate was measured at baseline using nuclear magnetic resonance spectroscopy. Participants were excluded if they had type 2 diabetes, were using disease-modifying drugs (e.g. tolvaptan, somatostatin analogs), were not fasting, or had missing beta-hydroxybutyrate levels, leaving 521 participants for the analyses. Linear regression analyses were used to study cross-sectional associations and linear mixed-effect modeling for longitudinal associations. RESULTS: Of the participants, 61% were female, with an age of 47.3 ± 11.8 years, a height-adjusted total kidney volume (htTKV) of 834 (IQR 495-1327) ml/m, and an estimated glomerular filtration rate (eGFR) of 63.3 ± 28.9 mL/min/1.73m2. The median concentration of beta-hydroxybutyrate was 94 (IQR 68-147) µmol/L. Cross-sectionally, beta-hydroxybutyrate was neither associated with eGFR nor with htTKV. Longitudinally, beta-hydroxybutyrate was positively associated with eGFR slope (B = 0.35 ml/min/1.73m2 (95% CI 0.09 to 0.61), p = 0.007), but not with kidney growth. After adjustment for potential confounders, every doubling in beta-hydroxybutyrate concentration was associated with an improvement in the annual rate of eGFR by 0.33 ml/min/1.73m2 (95% CI 0.09 to 0.57, p = 0.008). CONCLUSION: These observational analyses support the hypothesis that interventions that raise beta-hydroxybutyrate concentration could reduce the rate of kidney function decline in patients with ADPKD.

2.
Immunooncol Technol ; 20: 100397, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37876518

RESUMO

The Association for Cancer Immunotherapy (CIMT) celebrated the 20th anniversary of the CIMT Annual Meeting. CIMT2023 was held 3-5 May 2023 in Mainz, Germany. 1051 academic and clinical professionals from over 30 countries attended the meeting and discussed the latest advances in cancer immunology and immunotherapy research. This report summarizes the highlights of CIMT2023.

3.
Neurosurg Rev ; 46(1): 172, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37439884

RESUMO

Transpetrosal approaches are known to be associated with a significant risk of complications, including CSF leak, facial palsy, hearing impairment, venous injury, and/or temporal lobe injury. We aimed to evaluate the morbidity of the standard combined petrosal approach (CPA), defined as a combination of the posterior (retrolabyrinthine) and the anterior petrosal approach. We performed a systematic review and meta-analysis of articles reporting on clinical series of patients operated on for petroclival meningiomas through CPA. Studies that used the terminology "combined petrosal approach" without matching the aforementioned definition were excluded as well as clinical series that included less than 5 patients. A total of 8 studies were included involving 160 patients. The pooled complication rates were 3% (95% CI, 0.5-5.6) for CSF leak, 8.6% (95% CI, 4.1-13.2%) for facial palsy, 8.2% (95% CI, 3.9-12.6%) for hearing impairment, 2.8% (95% CI, 0.9-6.5%) for venous complications, and finally 4.8% (95%, 1.2-8.4%) for temporal lobe injury. Contrary to the general belief, CPA is associated with an acceptable rate of complications, especially when compared to alternative approaches to the petroclival area. In view of the major advantages like shorter trajectory, multiple angles of surgical attack, and early tumor devascularization, CPA remains an important tool in the armamentarium of the skull base surgeon.


Assuntos
Paralisia Facial , Perda Auditiva , Neoplasias Meníngeas , Meningioma , Humanos , Paralisia Facial/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Meningioma/cirurgia , Meningioma/patologia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Perda Auditiva/cirurgia , Perda Auditiva/etiologia , Osso Petroso/cirurgia
4.
J Transl Med ; 18(1): 271, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620126

RESUMO

BACKGROUND: The tumor immune microenvironment is a heterogeneous entity. Gene expression analysis allows us to perform comprehensive immunoprofiling and may assist in dissecting the different components of the immune infiltrate. As gene expression analysis also provides information regarding tumor cells, differences in interactions between the immune system and specific tumor characteristics can also be explored. This study aims to gain further insights in the composition of the tumor immune infiltrate and to correlate these components to histology and overall survival in non-small cell lung cancer (NSCLC). METHODS: Archival tissues from 530 early stage, resected NSCLC patients with annotated tumor and patient characteristics were analyzed using the NanoString nCounter Analysis system. RESULTS: Unsupervised clustering of the samples was mainly driven by the overall level of inflammation, which was not correlated with survival in this patient set. Adenocarcinoma (AD) showed a significantly higher degree of immune infiltration compared to squamous cell carcinoma (SCC). A 34-gene signature, which did not correlate with the overall level of immune infiltration, was identified and showed an OS benefit in SCC. Strikingly, this benefit was not observed in AD. This difference in OS in SCC specifically was confirmed in two independent NSCLC cohorts. The highest correlation between expression of the 34-gene signature and specific immune cell populations was observed for NK cells, but although a plausible mechanism for NK cell intervention in tumor growth could be established in SCC over AD, this could not be translated back to immunohistochemistry, which showed that NK cell infiltration is scarce irrespective of histology. CONCLUSIONS: These findings suggest that the ability of immune cell infiltration and the interaction between tumor and immune cells may be different between AD and SCC histology and that a subgroup of SCC tumors seems more susceptible to Natural Killer cell recognition and killing, whereas this may not occur in AD tumors. A highly sensitive technique like NanoString was able to detect this subgroup based on a 34-gene signature, but further research will be needed to assist in explaining the biological rationale of such low-level expression signatures.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Humanos , Neoplasias Pulmonares/genética , Prognóstico , Microambiente Tumoral
5.
Arch Virol ; 164(1): 117-126, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30288607

RESUMO

An orthotospovirus distinct from all other orthotospoviruses was isolated from naturally infected alstroemeria plants. Disease symptoms caused by this virus mainly consisted of yellow spots on the leaves based on which the name alstroemeria yellow spot virus (AYSV) was coined. A host range analysis was performed and a polyclonal antiserum was produced against purified AYSV ribonucleoproteins which only reacted with the homologous antigen and not with any other (established or tentative) orthotospovirus from a selection of American and Asian species. Upon thrips transmission assays the virus was successfully transmitted by a population of Thrips tabaci. The entire nucleotide sequence of the M and S RNA segments was elucidated by a conventional cloning and sequencing strategy, and contained 4797 respectively 2734 nucleotides (nt). Simultaneously, a next generation sequencing (NGS) approach (RNAseq) was employed and generated contigs covering the entire viral tripartite RNA genome. In addition to the M and S RNA nucleotide sequences, the L RNA (8865 nt) was obtained. The nucleocapsid (N) gene encoded by the S RNA of this virus consisted of 819 nucleotides with a deduced N protein of 272 amino acids and by comparative sequence alignments to other established orthotospovirus species showed highest homology (69.5% identity) to the N protein of polygonum ringspot virus. The data altogether support the proposal of AYSV as a new orthotospovirus species within a growing clade of orthotospoviruses that seem to share the Middle East basin as a region of origin.


Assuntos
Alstroemeria/virologia , Doenças das Plantas/virologia , Vírus de Plantas/genética , Vírus de Plantas/isolamento & purificação , Animais , Insetos Vetores/virologia , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Tisanópteros/virologia , Nicotiana/virologia
6.
Soc Sci Med ; 195: 34-41, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29125942

RESUMO

Improving health requires changes in the social, physical, economic and political determinants of health behavior. For the realization of policies that address these environmental determinants, intersectoral policy networks are considered necessary for the pooling of resources to implement different policy instruments. However, such network diversity may increase network complexity and therefore hamper network performance. Network complexity may be reduced by network management and the provision of financial resources. This study examined whether network diversity - amidst the other conditions - is indeed needed to address environmental determinants of health behavior. We included 25 intersectoral policy networks in Dutch municipalities aimed at reducing overweight, smoking, and alcohol/drugs abuse. For our fuzzy set Qualitative Comparative Analysis we used data from three web-based surveys among (a) project leaders regarding network diversity and size (n = 38); (b) project leaders and project partners regarding management (n = 278); and (c) implementation professionals regarding types of environmental determinants addressed (n = 137). Data on budgets were retrieved from project application forms. Contrary to their intentions, most policy networks typically addressed personal determinants. If the environment was addressed too, it was mostly the social environment. To address environmental determinants of health behavior, network diversity (>50% of the actors are non-public health) was necessary in networks that were either small (<16 actors) or had small budgets (<€183,172), when both were intensively managed. Irrespective of network diversity, environmental determinants also were addressed by small networks with large budgets, and by large networks with small budgets, when both provided network management. We conclude that network diversity is important - although not necessary - for resource pooling to address environmental determinants of health behavior, but only effective in the presence of network management. Our findings may support intersectoral policy networks in improving health behaviors by addressing a variety of environmental determinants.


Assuntos
Redes Comunitárias/organização & administração , Meio Ambiente , Comportamentos Relacionados com a Saúde , Política de Saúde , Determinantes Sociais da Saúde , Orçamentos/estatística & dados numéricos , Cidades , Redes Comunitárias/economia , Humanos , Países Baixos , Pesquisa Qualitativa
8.
Ann Oncol ; 27(7): 1311-6, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27091807

RESUMO

BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. PATIENTS AND METHODS: We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201). RESULTS: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type. CONCLUSIONS: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.


Assuntos
Biomarcadores Tumorais/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Tomada de Decisão Clínica , Cistectomia , Feminino , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Período Perioperatório , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
9.
Artigo em Inglês | MEDLINE | ID: mdl-26681536

RESUMO

BACKGROUND: According to current understanding the drug-coated balloon carries a sufficient dose of an effective antineoplastic agent, i.e. paclitaxel, to the target lesion. METHODS: Literature review and report on experimental studies simulating the access of coated balloons to the treatment site and studies in pigs. RESULTS: The drug adheres to the balloon membrane and is partially hidden below the folds which are wrapped around the shaft. Upon inflation solid paclitaxel particles are pushed into the vessel wall. Premature loss of paclitaxel and transfer to the vessel wall is controlled by the formulation including an inactive additive. Particles in the tissue dissolve slowly resulting in a terminal half-life of almost 2 months. Premature loss of the drug, dissolution, elimination, efficacy and tolerance are limited by the very low solubility of paclitaxel. From exemplary DCB approximately 10% of drug is lost before the target lesion is reached, 5-20% is transferred into the vessel wall and 10% remain on the balloon after withdrawal. The difference is distributed in the general circulation. Inhibition of neointimal proliferation in animal models is reliable and as persistent as with drug-eluting stents. Histology reveals slight to moderate dose-dependent downstream effects without functional or clinical symptoms. CONCLUSION: For the time being paclitaxel remains the drug of choice, the dose varies between 2 and 3.5 µg/mm² balloon surface. Neither in animal experiments nor in clinical trials problems have been detected in vessel segments treated with overlapping balloons. Future developments are expected improving efficacy in additional disease conditions (e.g., calcified vessels) and vessel territories.

10.
Eur J Pain ; 19(3): 322-33, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25045036

RESUMO

BACKGROUND: Chronic neuropathic pain can lead to anxiety and depression. Drugs that block reuptake of serotonin, norepinephrine and/or dopamine are widely used to treat depression, and have emerged as useful drugs in the treatment of neuropathic pain. This study compared the acute antinociceptive effects of NS18283, a novel triple monoamine reuptake inhibitor (MRI) with indatraline, venlafaxine and escitalopram in a mouse model of neuropathic pain. METHOD: Neuropathic pain-like behaviours were induced in mice by repeated injections of oxaliplatin (OXA), and assessed using the von Frey hair test, the cold plate test and the thermal preference plate test. Anxio/depressive phenotype and antidepressant-like properties of compounds were assessed by the novelty suppressed feeding test and the tail suspension test, respectively. RESULTS: In vivo microdialysis experiments showed that each MRI increased extracellular serotonin, norepinephrine and/or dopamine levels in the cingulate cortex, in agreement with their in vitro reuptake inhibitory properties. Indatraline (3 mg/kg) reversed the full repertoire of OXA-induced neuropathic hypersensitivity. NS18283 (10 mg/kg) reversed OXA-induced mechano-hypersensitivity and cold allodynia. Venlafaxine (16 mg/kg) and escitalopram (4 mg/kg) only reversed cold allodynia and mechano-hypersensitivity, respectively. All MRIs produced antidepressant-like activity in anxio/depressive phenotype of OXA mice. CONCLUSIONS: Acute administration of drugs that enhance the activity of serotonin, norepinephrine and dopamine neurotransmission within nociceptive pathways may provide a broader spectrum of antinociception than dual or selective reuptake inhibitors in animal models of neuropathic pain. Whether similar observations would occur after repeated administration of such compounds in an attempt to simulate dosing in humans, or be compromised by dopaminergic-mediated adverse effects warrants further investigation.


Assuntos
Analgésicos/farmacologia , Citalopram/farmacologia , Hiperalgesia/tratamento farmacológico , Indanos/farmacologia , Metilaminas/farmacologia , Neuralgia/tratamento farmacológico , Inibidores da Captação de Neurotransmissores/farmacologia , Cloridrato de Venlafaxina/farmacologia , Analgésicos/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Citalopram/administração & dosagem , Modelos Animais de Doenças , Indanos/administração & dosagem , Masculino , Metilaminas/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Inibidores da Captação de Neurotransmissores/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Cloridrato de Venlafaxina/administração & dosagem
12.
Kidney Int ; 84(6): 1079-89, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24172683

RESUMO

C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group.


Assuntos
Complemento C3/análise , Glomerulonefrite/imunologia , Glomérulos Renais/imunologia , Pesquisa Biomédica , Biópsia , Comportamento Cooperativo , Glomerulonefrite/diagnóstico , Glomerulonefrite/terapia , Humanos , Cooperação Internacional , Glomérulos Renais/patologia , Valor Preditivo dos Testes , Prognóstico
13.
Br J Pharmacol ; 167(1): 164-82, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22506660

RESUMO

BACKGROUND AND PURPOSE: Positive allosteric modulation of α4ß2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively. EXPERIMENTAL APPROACH: Effects of NS9283 were evaluated in vitro using fluorescence-based Ca(2+) imaging and electrophysiological voltage clamp experiments in Xenopus oocytes, mammalian cells and thalamocortical neurons. In vivo the compound was tested in models covering a range of cognitive domains in mice and rats. KEY RESULTS: NS9283 was shown to increase agonist-evoked response amplitude of (α4)(3) (ß2)(2) nACh receptors in electrophysiology paradigms. (α2)(3) (ß2)(2) , (α2)(3) (ß4)(2) and (α4)(3) (ß4)(2) were modulated to comparable extents, but no effects were detected at α3-containing or any 2α : 3ß stoichiometry nACh receptors. Native nACh receptors in thalamocortical neurons similarly displayed DHßE-sensitive currents that were receptive to modulation. NS9283 had favourable effects on sensory information processing, as shown by reversal of PCP-disrupted pre-pulse inhibition. NS9283 further improved performance in a rat model of episodic memory (social recognition), a rat model of sustained attention (five-choice serial reaction time task) and a rat model of reference memory (Morris water maze). Importantly, the effects in the Morris water maze could be fully reversed with mecamylamine, a blocker of nACh receptors. CONCLUSIONS AND IMPLICATIONS: These results provide compelling evidence that positive allosteric modulators acting at the (α4)(3) (ß2)(2) nACh receptors can augment activity across a broad range of cognitive domains, and that α4ß2 nACh receptor allosteric modulation therefore constitutes a promising therapeutic approach to symptomatic treatment of cognitive impairment.


Assuntos
Agonistas Nicotínicos/farmacologia , Oxidiazóis/farmacologia , Subunidades Proteicas/fisiologia , Piridinas/farmacologia , Receptores Nicotínicos/fisiologia , Regulação Alostérica/efeitos dos fármacos , Animais , Linhagem Celular , Linhagem Celular Tumoral , Cognição/efeitos dos fármacos , Feminino , Células HEK293 , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacocinética , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Oxidiazóis/farmacocinética , Piridinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos , Xenopus laevis
14.
J Med Genet ; 49(1): 37-40, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22114106

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD), due to a heterozygous mutation in PKD1 or PKD2, is usually an adult onset disease. Renal cystic disease is generally milder in PKD2 patients than in PKD1 patients. Recently, several PKD1 patients with a severe renal cystic phenotype due to a second modifying PKD1 allele, or carrying two incomplete penetrant PKD1 alleles, have been described. This study reports for the first time a patient with neonatal onset of PKD homozygous for an incomplete penetrant PKD2 missense variant due to uniparental disomy.


Assuntos
Homozigoto , Mutação de Sentido Incorreto , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Dissomia Uniparental , Sequência de Aminoácidos , Sequência de Bases , Análise Mutacional de DNA , Humanos , Recém-Nascido , Rim/patologia , Masculino , Dados de Sequência Molecular , Linhagem , Receptores de Superfície Celular/genética , Ultrassonografia
15.
Br J Anaesth ; 108(1): 80-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22139005

RESUMO

BACKGROUND: Previously, we showed a significant difference in the measurements of hypnotic depth by the bispectral index (BIS) and auditory-evoked potentials (AEPs) using the A-line autoregressive index during xenon anaesthesia. In the present study, we evaluate the alternative AEP-based auditory-evoked potential index (aepEX) for the measurement of hypnotic depth in patients undergoing general anaesthesia with xenon. METHODS: Forty-two patients undergoing elective abdominal surgery were enrolled in this controlled, double-blinded, randomized, clinical study. Patients were randomized to receive either xenon (n=21) or sevoflurane anaesthesia (n=21). During anaesthesia, BIS values were recorded simultaneously with the aepEX monitoring. The anaesthetist performing the anaesthesia was blinded to the hypnotic depth monitors. After surgery, the incidence of recalls and awareness was evaluated. RESULTS: Patients' characteristics such as gender, age, and weight did not differ between the groups. The aepEX and BIS values behaved similarly during anaesthesia. The comparison of aepEX values during xenon and sevoflurane anaesthesia revealed significantly lower aepEX values in the xenon group after 25 min [xenon: 32.9 (4.8) vs sevoflurane: 39.3 (9.0); P=0.008] and after 35 min [xenon: 31.4 (6.6) vs sevoflurane: 37.0 (6.8); P=0.012]. During anaesthesia, aepEX values correlated with the clinical evaluation of depth of anaesthesia (e.g. >20% changes of the baseline arterial pressure or heart rate, spontaneous breathing and/or intolerance of mechanical ventilation, coughing, abdominal pressing, sweating, eye tearing). CONCLUSIONS: We found the aepEX monitor to provide index in the range of adequate depth of xenon anaesthesia, when combined with remifentanil infusion in intubated patients undergoing elective abdominal surgery.


Assuntos
Anestesia por Inalação , Anestésicos Inalatórios , Monitores de Consciência , Estado de Consciência/efeitos dos fármacos , Xenônio , Adulto , Idoso , Idoso de 80 Anos ou mais , Período de Recuperação da Anestesia , Anestesia Geral , Método Duplo-Cego , Eletroencefalografia/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Consciência no Peroperatório , Masculino , Éteres Metílicos , Pessoa de Meia-Idade , Medição da Dor , Período Pós-Operatório , Sevoflurano , Procedimentos Cirúrgicos Urológicos , Adulto Jovem
16.
Nephrol Dial Transplant ; 26(8): 2445-53, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21393612

RESUMO

BACKGROUND: The renoprotective effect of vasopressin V2 receptor antagonist (V2RA) is currently being tested in a clinical trial in early autosomal dominant polycystic kidney disease (ADPKD). If efficacious, this warrants life-long treatment with V2RA, however, with associated side effects as polydipsia and polyuria. We questioned whether we could reduce the side effects without influencing the renoprotective effect by starting the treatment later in the disease or by lowering drug dosage. METHODS: To investigate this, we administered V2RA OPC-31260 at a high (0.1%) and low (0.05%) dose to a tamoxifen-inducible kidney epithelium-specific Pkd1-deletion mouse model starting treatment at Day 21 (early) or 42 (advanced). After 3 and 6 weeks of treatment, we monitored physiologic and potential renoprotective effects. RESULTS: Initiation of V2RA treatment at advanced stage of the disease lacked renoprotective effects and had less pronounced physiologic effects than early initiation. After 3 weeks on a high dose, cyst ratio and kidney weight were reduced versus untreated controls (18 versus 25%, P = 0.05, and 0.33 versus 0.45 g, P = 0.03, respectively). After 6 weeks of treatment, however, this did not reach significance anymore, even at a high dose (cyst ratio 24 versus 27%, P = 0.12, and kidney weight 0.55 versus 0.66 g, P = 0.38). CONCLUSIONS: Our results suggest that intervention with V2RA should be instituted early in ADPKD and that it might be necessary to further increase the dosage of this drug later in the disease to decrease cyst growth.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos , Benzazepinas/uso terapêutico , Modelos Animais de Doenças , Rim Policístico Autossômico Dominante/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Feminino , Rim/citologia , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Camundongos , Camundongos Knockout , Rim Policístico Autossômico Dominante/terapia , Proteína Quinase C
17.
Plant Dis ; 95(11): 1485, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30731755

RESUMO

During the last decade, lisianthus (Eustoma grandiflorum) has been introduced in Iran in the horticultural cut-flower industry. This crop is currently produced in more than 800 small greenhouses on a surface of an estimated 0.8 km2 in the Pakdasht region (southeast of Teheran Province). Plants exhibiting virus-like symptoms were observed in several greenhouses in 2010. The infected plants produced yellow and necrotic spots on the leaves and became severely deformed because of a strong leaf curling and the production of shorter internodes. Flower breaking has not been observed in the blue flowering plants. Approximately 85% of the plants were apparently infected in the inspected greenhouses. Extracts of infected material inoculated onto some indicator plant species induced mosaic and leaf malformation on Nicotiana benthamiana, mottling on Capsicum annuum, necrotic lesions on Datura stramonium, chlorotic local spots on Vigna unguiculata, systemic necrotic spots on Emilia sonchifolia, chlorotic local spots on Cucumis sativus, and necrotic local lesions on Petunia hybrida. Back-inoculation of infected material on lisianthus seedlings resulted in several chlorotic spots on the inoculated leaves and a severe downward curling of the systemic infected leaves. No symptoms were observed after inoculation of Pisum sativum, Phaseolus vulgaris, Vicia faba, and Chrysanthemum spp. The virus could also be transferred from infected to healthy N. benthamiana plants by pricking leaves with a Pasteur pipette. Spherical tombusvirus-like particles of approximately 29 nm were found by transmission electron microscopy in leaf-dip and partially-purified preparations of infected N. benthamiana. Since Tomato bushy stunt virus (TBSV; genus Tombusvirus, family Tombusviridae) and Moroccan pepper virus (MPV) have been found in Iran, we studied by using ELISA whether our samples matched with TBSV. Since a negative response was obtained, two primers were designed on the basis of the available sequences of the coat protein in the GenBank (Accession No. EU27780) of an MPV isolate from soil in Fars Province, Iran. A reverse transcription (RT)-PCR of total RNA extract from infected lisianthus and N. benthamiana with the primers MPV-R (5'-TTACAACAATGTGGCATCATTG-3') and MPV-F (5'-ATGGCAATGGTAGTAAG AAAC-3') resulted in a DNA fragment of 1,176 bp. This fragment from N. benthamiana was cloned, sequenced (Accession No. HQ663881), and showed a 96% nucleotide and 99% amino acid identity with the coat protein of the soil isolate. MPV was originally found in pepper (1), tomato and pelargonium (4), pear tree (3), and surface water (2). To our knowledge, this is the first report of MPV on lisianthus in Iran and worldwide. This virus, which persists in soil, water, and plant debris, can be considered as a substantial threat for the lisianthus industry in Iran because farmers do not apply strict crop rotation or other sanitation measures. References: (1) H. U. Fischer and B. E. L. Lockhart. Phytopathology 67:1352, 1977. (2) R. Koenig and D.-E. Lesemann. Phytopathol. Z. 112:105, 1985. (3) M. Russo et al. J. Plant Pathol. 84:161, 2002. (4) H. J. Vetten and R. Koenig. 108:215, 1983.

18.
Br J Anaesth ; 105(3): 334-41, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20630890

RESUMO

BACKGROUND: None of the currently available hypnosis monitoring systems have evaluated balanced xenon anaesthesia. We investigated the performance of the bispectral index (BIS) and the composite A-line autoregressive index (cAAI) while comparing balanced xenon with sevoflurane anaesthesia. METHODS: Sixty patients undergoing elective abdominal surgery participated in this registered double-blinded, controlled trial and-after written informed consent-were randomly assigned to one of the study groups (xenon, n=30; sevoflurane, n=30). After induction, general anaesthesia was maintained with xenon 60% or sevoflurane 2.0% in 30% O2. Remifentanil was titrated to clinical needs. BIS and cAAI values were recorded electronically and blinded to the performing physician. Emergence from anaesthesia was evaluated and during 12 h follow-up, patients were questioned twice for signs of recalls. RESULTS: During induction and maintenance of anaesthesia, BIS values in the xenon group were comparable with sevoflurane anaesthesia and within the recommended range. Although the cAAI remained stable in the sevoflurane group, values increased during balanced xenon anaesthesia and exceeded the recommended upper limit after 65 min. Emergence from xenon anaesthesia was significantly faster than from sevoflurane (eye opening at 3.8 vs 10.3 min, P<0.001), and BIS values were concordant with the washout of both anaesthetics. No incident of recall was reported. CONCLUSIONS: During surgery, xenon/remifentanil anaesthesia can be monitored using BIS and cAAI. However, cAAI values changed after about 1 h of anaesthesia. Further studies will be needed to address the question whether auditory signal processing is altered during extended xenon exposure.


Assuntos
Anestésicos Inalatórios/farmacologia , Éteres Metílicos/farmacologia , Monitorização Intraoperatória/métodos , Xenônio/farmacologia , Adolescente , Adulto , Idoso , Período de Recuperação da Anestesia , Método Duplo-Cego , Eletroencefalografia/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Feminino , Humanos , Masculino , Rememoração Mental/efeitos dos fármacos , Pessoa de Meia-Idade , Sevoflurano , Adulto Jovem
20.
Rev. cient. (Maracaibo) ; 19(3): 303-310, mayo-jun. 2009. graf, tab
Artigo em Espanhol | LILACS | ID: lil-548486

RESUMO

El presente trabajo se realizó con la finalidad de evaluar la calidad nutricional de la harina de lenteja de agua (Lemna obscura) como ingrediente en la elaboración de alimento para tilapia roja (Oreochromis spp.). Se prepararon 3 dietas con niveles de inclusión de 15 por ciento (dieta A), 25 por ciento (dieta B) y 35 por ciento (dieta C) y una dieta control exenta de harina de Lemna. Estas fueron isocalóricas e isoproteicas con un nivel de 30 por ciento de proteína. Además se utilizó una dieta comercial (dieta D), con 40 por ciento de proteína, para compararla con las dietas experimentales. Los alevines se alimentaron durante 10 semanas consecutivas y cada catorce días, se evaluaron los parámetros más importantes como ganancia de peso, alimento consumido, factor de conversión alimentaria (FCA) y la relación eficiencia-proteica (REP). La comparación estadística reveló que no hubo diferencias significativas (P>0,05) en los valores de los resultados finales de la conversión entre las dietas Control A, B, C y D. En relación al peso promedio final, hubo diferencias significativas (P<0,05) entre los peces alimentados con la dieta B, con respecto a la dieta control y dieta comercial. No hubo diferencias significativas entre las dietas experimentales (P>0,05). Se demuestra en este estudio que la dieta con un 25 por ciento de inclusión resultó ser más eficiente en cuánto a los parámetros evaluados que la dieta control. Los excedentes de Lemna crecidos en el lago de Maracaibo o cultivados pueden ser utilizados como harina en las dietas para tilapia roja y representa una alternativa para reducir los costos de alimentación, siempre y cuando se utilice en combinación con otros ingredientes de alto contenido proteico.


The present work was carried out with the purpose to evaluate the nutritional quality of duckweed (Lemna obscura) meal as ingredient in the food elaboration for red tilapia (Oreochromis spp.). Three diets were prepared with inclusion levels of 15 percent (diet A), 25 percent (diet B) and 35 percent (diet C) and a control diet free of Lemna meal. The diets were isocaloric and isonitrogenous with 30 percent of protein. Furthermore, commercial diet (diet D) with 40 percent protein was used to compare with experimental diets. The fingerlings were fed during 10 weeks consecutive and fourteen days, were evaluated the most important parameters as weight gain, consumed food, feed convertion ratio (FCR) and the protein efficiency ratio (PER). The statistical comparison revealed that there were no significant differences (P>0.05) in the values of final results of convertion among diets control, A, B, C and D. In relation to weight average final there were significant differences (P<0.05) among the fish fed with the diet B with respect to the control diet and commercial diet. There were no significant differences among experimental diets (P>0.05). This study showed that diet with inclusion level 25 percent resulted to be more efficient in how much to the evaluated parameters that the diet control. The excesses of Lemna grown in the Maracaibo lake or cultivated can be used as meal in the diets for red tilapia and represents one alternative to reduce the feeding costs, as long as it used in combination with other ingredients of high protein content.


Assuntos
Animais , Ração Animal/efeitos adversos , Farinha , Valor Nutritivo , Tilápia , Ciências da Nutrição Animal
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