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1.
Phys Rev Lett ; 132(15): 155102, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38683000

RESUMEN

We present the first experimental study of plasmoid formation in a magnetic reconnection layer undergoing rapid radiative cooling, a regime relevant to extreme astrophysical plasmas. Two exploding aluminum wire arrays, driven by the Z machine, generate a reconnection layer (S_{L}≈120) in which the cooling rate far exceeds the hydrodynamic transit rate (τ_{hydro}/τ_{cool}>100). The reconnection layer generates a transient burst of >1 keV x-ray emission, consistent with the formation and subsequent rapid cooling of the layer. Time-gated x-ray images show fast-moving (up to 50 km s^{-1}) hotspots in the layer, consistent with the presence of plasmoids in 3D resistive magnetohydrodynamic simulations. X-ray spectroscopy shows that these hotspots generate the majority of Al K-shell emission (around 1.6 keV) prior to the onset of cooling, and exhibit temperatures (170 eV) much greater than that of the plasma inflows and the rest of the reconnection layer, thus providing insight into the generation of high-energy radiation in radiatively cooled reconnection events.

2.
Langenbecks Arch Surg ; 408(1): 8, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36602631

RESUMEN

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder and accounts for 5-10% of all cases of kidney failure. 50% of ADPKD patients reach kidney failure by the age of 58 years requiring dialysis or transplantation. Nephrectomy is performed in up to 20% of patients due to compressive symptoms, renal-related complications or in preparation for kidney transplantation. However, due to the large kidney size in ADPKD, nephrectomy can come with a considerable burden. Here we evaluate our institution's experience of laparoscopic nephrectomy (LN) as an alternative to open nephrectomy (ON) for ADPKD patients. MATERIALS AND METHODS: We report the results of the first 12 consecutive LN for ADPKD from August 2020 to August 2021 in our institution. These results were compared with the 12 most recent performed ON for ADPKD at the same institution (09/2017 to 07/2020). Intra- and postoperative parameters were collected and analyzed. Health related quality of life (HRQoL) was assessed using the SF36 questionnaire. RESULTS: Age, sex, and median preoperative kidney volumes were not significantly different between the two analyzed groups. Intraoperative estimated blood loss was significantly less in the laparoscopic group (33 ml (0-200 ml)) in comparison to the open group (186 ml (0-800 ml)) and postoperative need for blood transfusion was significantly reduced in the laparoscopic group (p = 0.0462). Operative time was significantly longer if LN was performed (158 min (85-227 min)) compared to the open procedure (107 min (56-174 min)) (p = 0.0079). In both groups one postoperative complication Clavien Dindo ≥ 3 occurred with the need of revision surgery. SF36 HRQol questionnaire revealed excellent postoperative quality of life after LN. CONCLUSION: LN in ADPKD patients is a safe and effective operative procedure independent of kidney size with excellent postoperative outcomes and benefits of minimally invasive surgery. Compared with the open procedure patients profit from significantly less need for transfusion with comparable postoperative complication rates. However significant longer operation times need to be taken in account.


Asunto(s)
Laparoscopía , Riñón Poliquístico Autosómico Dominante , Insuficiencia Renal , Humanos , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/cirugía , Calidad de Vida , Estudios Retrospectivos , Nefrectomía/métodos , Laparoscopía/métodos , Complicaciones Posoperatorias/etiología , Insuficiencia Renal/complicaciones , Insuficiencia Renal/cirugía , Pérdida de Sangre Quirúrgica , Riñón
3.
Philos Trans A Math Phys Eng Sci ; 380(2233): 20210307, 2022 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-35965463

RESUMEN

Transmission models for infectious diseases are typically formulated in terms of dynamics between individuals or groups with processes such as disease progression or recovery for each individual captured phenomenologically, without reference to underlying biological processes. Furthermore, the construction of these models is often monolithic: they do not allow one to readily modify the processes involved or include the new ones, or to combine models at different scales. We show how to construct a simple model of immune response to a respiratory virus and a model of transmission using an easily modifiable set of rules allowing further refining and merging the two models together. The immune response model reproduces the expected response curve of PCR testing for COVID-19 and implies a long-tailed distribution of infectiousness reflective of individual heterogeneity. This immune response model, when combined with a transmission model, reproduces the previously reported shift in the population distribution of viral loads along an epidemic trajectory. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.


Asunto(s)
Prueba de COVID-19 , COVID-19 , Humanos , Inmunidad
4.
J Chem Phys ; 156(21): 214505, 2022 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-35676146

RESUMEN

Ionic liquids (ILs) are salts, composed of asymmetric cations and anions, typically existing as liquids at ambient temperatures. They have found widespread applications in energy storage devices, dye-sensitized solar cells, and sensors because of their high ionic conductivity and inherent thermal stability. However, measuring the conductivity of ILs by physical methods is time-consuming and expensive, whereas the use of computational screening and testing methods can be rapid and effective. In this study, we used experimentally measured and published data to construct a deep neural network capable of making rapid and accurate predictions of the conductivity of ILs. The neural network is trained on 406 unique and chemically diverse ILs. This model is one of the most chemically diverse conductivity prediction models to date and improves on previous studies that are constrained by the availability of data, the environmental conditions, or the IL base. Feature engineering techniques were employed to identify key chemo-structural characteristics that correlate positively or negatively with the ionic conductivity. These features are capable of being used as guidelines to design and synthesize new highly conductive ILs. This work shows the potential for machine-learning models to accelerate the rate of identification and testing of tailored, high-conductivity ILs.

5.
Surg Endosc ; 35(12): 6763-6769, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33289054

RESUMEN

BACKGROUND: In order to efficiently perform laparoscopic microwave ablation of liver tumours precise positioning of the ablation probe is mandatory. This study evaluates the precision and ablation accuracy using the innovative laparoscopic stereotactic navigation system CAS-One-SPOT in comparison to 2d ultrasound guided laparoscopic ablation procedures. METHODS: In a pig liver ablation model four surgeons, experienced (n = 2) and inexperienced (n = 2) in laparoscopic ablation procedures, were randomized for 2d ultrasound guided laparoscopic or stereotactic navigated laparoscopic ablation procedures. Each surgeon performed a total of 20 ablations. Total attempts of needle placements, time from tumor localization till beginning of ablation and ablation accuracy were analyzed. RESULTS: The use of the laparoscopic stereotactic navigation system led to a significant reduction in total attempts of needle placement. The experienced group of surgeons reduced the mean number of attempts from 2.75 ± 2.291 in the 2d ultrasound guided ablation group to 1.45 ± 1.191 (p = 0.0302) attempts in the stereotactic navigation group. Comparable results could be observed in the inexperienced group with a reduction of 2.5 ± 1.50 to 1.15 ± 0.489 (p = 0.0005). This was accompanied by a significant time saving from 101.3 ± 112.1 s to 48.75 ± 27.76 s (p = 0.0491) in the experienced and 165.5 ± 98.9 s to 66.75 ± 21.96 s (p < 0.0001) in the inexperienced surgeon group. The accuracy of the ablation process was hereby not impaired as postinterventional sectioning of the ablation zone revealed. CONCLUSION: The use of a stereotactic navigation system for laparoscopic microwave ablation procedures of liver tumors significantly reduces the attempts and time of predicted correct needle placement for novices and experienced surgeons without impairing the accuracy of the ablation procedure.


Asunto(s)
Ablación por Catéter , Laparoscopía , Neoplasias Hepáticas , Cirugía Asistida por Computador , Animales , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Microondas/uso terapéutico , Porcinos
6.
J Appl Microbiol ; 125(5): 1455-1465, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29877011

RESUMEN

AIM: The present study aimed to isolate and screen endophytes from Trachyspermum ammi with the ability to inhibit alpha glucosidase enzyme and evaluate their insecticidal potential. METHODS AND RESULTS: Endophytic fungi isolated from T. ammi were screened for alpha glucosidase inhibitory activity. Maximum inhibition (96%) was observed in an isolate AZ-9, identified to be Exophiala spinifera on morphological and molecular basis. Production of fungal metabolites was carried out in malt extract broth followed by extraction with ethyl acetate. Brown coloured gummy residue obtained after evaporation of ethyl acetate was partially soluble in water yielding white precipitates. The precipitate exhibiting α-glucosidase inhibitory activity was purified by repeated washing and centrifugation. The insecticidal activity of inhibitor was evaluated on Spodoptera litura (Fab.) by feeding this pest on diet amended with inhibitor. It resulted in significant larval mortality as well as deformities in emerging adults. A reduction in vivo digestive enzyme activity was also observed. Nutritional analysis revealed the toxic effect of AZ-9 inhibitor on various food utilization parameters of S. litura. A significant reduction was recorded in relative growth and consumption rate of S. litura. CONCLUSIONS: This is the first report on production of an alpha glucosidase inhibitor from E. spinifera with insecticidal activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The study highlights the importance of endophytes in providing protection against insect pests to the host. It also suggests the insecticidal potential of alpha glucosidase inhibitor from E. spinifera against polyphagous pest S. litura.


Asunto(s)
Exophiala/química , Inhibidores de Glicósido Hidrolasas , Insecticidas , Spodoptera , Animales , Endófitos/química , Exophiala/metabolismo , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Larva , Pruebas de Toxicidad , alfa-Glucosidasas/metabolismo
7.
Int J Phytoremediation ; 20(9): 909-913, 2018 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-29873532

RESUMEN

The aquatic plant Hydrocotyle vulgaris was evaluated for its efficacy in removing prometryn from nutrient solution. Under optimized experimental conditions, up to 94.0% of the initial prometryn was removed from the hydroponic culture medium by H. vulgaris in 30 days. The concentration of prometryn decreased from the initial level of 0.55 ± 0.013 mg/L to 0.036 ± 0.001 mg/L at the end of the experimental period. The removal kinetics followed first-order kinetic equation (Ct = 0.4569e-0.09t). Half-life (t1/2) of prometryn was greatly shortened from 27.16 days (without plant) to 5.58 days (with H. vulgaris). Approximately 22% of the initial prometryn residue was found in H. vulgaris tissue, while 11.7% was degraded by the plant in 30 days. The metabolites of prometryn detected were 2,4-diamino-1,3,5-triazine (in the hydroponic culture medium) and 2,4,6-trihydroxy-1,3,5-triazine (in plant tissue) after 30 days. The results indicate that H. vulgaris can be used for phytoextraction of prometryn and could potentially be effective in removing other s-trazine pesticides from contaminated aquatic ecosystems.


Asunto(s)
Centella , Prometrina , Biodegradación Ambiental , Ecosistema , Hidroponía , Humedales
8.
Bull Environ Contam Toxicol ; 96(4): 550-5, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26810796

RESUMEN

2,4-bis(Isopropylamino)-6-methylthio-s-triazine (prometryn) poses a risk to aquatic environments in several countries, including China, where its use is widespread, particularly due to its chemical stability and biological toxicity. Vetiver grass (Chrysopogon zizanioides L.) was tested for its potential for phytoremediation of prometryn. Vetiver grass was grown in hydroponic media in a greenhouse, in the presence of prometryn, with appropriate controls. Plant uptake and removal of prometryn from the media were monitored for a period of 67 days. The results showed that the removal of the prometryn in the media was expedited by vetiver grass. The removal half-life (t1/2) was shortened by 11.5 days. Prometryn removal followed first-order kinetics (Ct = 1.8070e(-0.0601t)). This study demonstrated the potential of vetiver grass for the phytoremediation for prometryn.


Asunto(s)
Chrysopogon/crecimiento & desarrollo , Hidroponía/métodos , Prometrina/análisis , Contaminantes del Suelo/análisis , Biodegradación Ambiental , China , Chrysopogon/metabolismo
9.
Placenta ; 154: 66-73, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38905849

RESUMEN

INTRODUCTION: Recurrent pregnancy loss (RPL) is defined as the spontaneous loss of two or more consecutive pregnancies before 20 weeks of gestation, and affects 7.46 % of the Indian population. About 40-50 % of RPL cases are idiopathic making it a therapeutic challenge for clinicians. This study focuses on elucidating the role of hypoxia-associated placental angiogenesis in these idiopathic RPL cases. METHODS: Whole blood and product of conception (POCs) were collected from RPL patients (N = 87) and cases of voluntary abortions (medically terminated pregnancy, MTP; n = 110) as controls with informed consent. Serum separated from whole blood was used to study the ROS-antioxidant status in the cases and controls through colorimetric assays and ELISA. The mRNA extracted from placental tissue samples were used to determine the hypoxic and angiogenic status in cases and controls through real time PCR. Statistical analysis was also carried out to correlate the differential hypoxic status between RPL and MTP cohorts with the expression of angiogenic factors (VEGFA, VEGFR1 and VEGFR2). RESULTS: HIF1α mRNA expression was found to be upregulated in the RPL cases. While the serum levels of H2O2 (p = 0.012), guanine oxides and lipid hydroperoxides (LPO) were increased in the RPL cases, reduced glutathione (GSH) was found to be significantly decreased (p = 0.012). Additionally, AUROC analysis also shows an excellent discriminatory ability of 0.850 for serum H2O2 levels. VEGF-A and VEGF-R1 mRNA expression was also found to be downregulated in the RPL cases compared to MTP. DISCUSSION: This study indicates that increased oxidative stress may lead to aberrations in the VEGF pathway resulting in improper placentation in RPL cases, and subsequently, pregnancy loss.

10.
Mymensingh Med J ; 33(1): 133-139, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38163784

RESUMEN

Post-ERCP acute pancreatitis (PEP) is a common and serious complication with high morbidity and mortality rates. There is a paucity of data on the frequency of PEP in a resource constraint setting like Bangladesh. Hence we have conducted a prospective study to determine the frequency of PEP and the factors associated with its occurrence. This prospective, observational study was carried out in Gastroenterology Department of Dhaka Medical College & Hospital, Dhaka, Bangladesh from April 2018 to December 2018 on the consecutive patients who underwent ERCP. PEP and its severity were diagnosed according to consensus definition. Serum lipase was done in all patients before procedure and 24 hours after procedure or if patient develops abdominal pain after the procedure which became earlier. Total 168 patients were included (mean age 46.97±14.35 years; male 72(43.0%). The most common indication of ERCP was choledocholithiasis 97(58.0%) followed by malignant biliary obstruction 45(27.0%), recurrent pyogenic cholangitis 8(5.0%), chronic pancreatitis 4(2.3%), biliary ascariasis 4(2.3%) and others 10(6.0%). Overall post ERCP complication rate was 46(27.3%) including cholangitis 29(17.3%), pancreatitis 16(9.5%), bleeding 12(7.1%), aspiration pneumonia 4(2.4%) and death 3(1.8%). Regarding the severity of PEP, 50.0%, 43.7% and 6.3% patients developed mild, moderate and severe pancreatitis respectively. Number of cannulation attempts >5 times [22(48%) vs. 17(14%); p=0.001], cannulation attempts duration more than 10 minutes [25(55%) vs. 27(22%); p=0.001], unintentional passage of guide wire into the pancreatic duct [8(17%) vs. 18(15%); p=0.001], pancreatic duct contrast injection [12(26%) vs. 2(1.6%); p=0.001] and pre-cut sphincterotomy [16(35%) vs. 6(4.9%); p=0.001] were significantly different between the patients who developed PEP compared to those who did not. In multiple logistic regressions analysis, pancreatic duct contrast injection was significantly associated with PEP [OR 25.523 with 95% CI (4.049- 100.0%)]. Around ten percent patients had developed PEP. Regarding the severity half of them were mild, 44.0% patients had moderate and 6.0% patient had severe type of pancreatitis. Difficult cannulation, unintentional passage of guide wire into the pancreas, pancreatic duct contrast injection and pre-cut sphincterotomy were associated with PEP. Among them pancreatic duct contrast injection had independent significance in the causation of PEP.


Asunto(s)
Colangitis , Pancreatitis , Adulto , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Aguda , Bangladesh/epidemiología , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangitis/complicaciones , Hospitales , Pancreatitis/epidemiología , Pancreatitis/etiología , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Femenino
11.
Appl Radiat Isot ; 204: 111140, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38070360

RESUMEN

Double differential neutron fluence distributions were measured in the 7Li(p,n)7Be reaction for proton beam energies 7, 9 and 12 MeV. Seven liquid scintillator based detectors were employed to measure neutron fluence distributions using the Time of Flight technique. Neutron ambient dose equivalents were determined from the measured fluence distribution using ICRP (International Commission on Radiological Protection) recommended fluence to dose equivalent conversion coefficients. Neutron dose equivalents were also measured using a conventional BF3 detector based REM counter. Ambient dose equivalent measured by the REM counter is found to be in agreement with that determined from the neutron fluence spectra within their uncertainties. Angular distributions of the ambient dose equivalents were also determined from the measured fluence distributions at different angles.

12.
Appl Opt ; 52(36): 8747-58, 2013 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-24513939

RESUMEN

The increasing scale of cryogenic detector arrays for submillimeter and millimeter wavelength astrophysics has led to the need for large aperture, high index of refraction, low loss, cryogenic refracting optics. Silicon with n=3.4, low loss, and high thermal conductivity is a nearly optimal material for these purposes but requires an antireflection (AR) coating with broad bandwidth, low loss, low reflectance, and a matched coefficient of thermal expansion. We present an AR coating for curved silicon optics comprised of subwavelength features cut into the lens surface with a custom three-axis silicon dicing saw. These features constitute a metamaterial that behaves as a simple dielectric coating. We have fabricated silicon lenses as large as 33.4 cm in diameter with micromachined layers optimized for use between 125 and 165 GHz. Our design reduces average reflections to a few tenths of a percent for angles of incidence up to 30° with low cross polarization. We describe the design, tolerance, manufacture, and measurements of these coatings and present measurements of the optical properties of silicon at millimeter wavelengths at cryogenic and room temperatures. This coating and lens fabrication approach is applicable from centimeter to submillimeter wavelengths and can be used to fabricate coatings with greater than octave bandwidth.

13.
Chirurgie (Heidelb) ; 94(8): 669-674, 2023 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-37142798

RESUMEN

The liver is involved in about 20% of cases of blunt abdominal trauma. The management of liver trauma has changed significantly in the past three decades towards conservative treatment. Up to 80% of all liver trauma patients can now be successfully treated by nonoperative management. Decisive for this is the adequate screening and assessment of the patient and the injury pattern as well as the provision of the appropriate infrastructure. Hemodynamically unstable patients require immediate exploratory surgery. In hemodynamically stable patients, a contrast-enhanced computed tomography (CT) should be performed. If active bleeding is detected angiographic imaging and embolization should be performed to stop the bleeding. Even after initially successful conservative management of liver trauma, subsequent complications can occur that make surgical inpatient treatment necessary.


Asunto(s)
Traumatismos Abdominales , Embolización Terapéutica , Heridas no Penetrantes , Humanos , Embolización Terapéutica/métodos , Hígado/diagnóstico por imagen , Hígado/lesiones , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/terapia , Traumatismos Abdominales/diagnóstico por imagen , Traumatismos Abdominales/terapia , Tomografía Computarizada por Rayos X
14.
Int J Surg ; 102: 106643, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35490950

RESUMEN

AIMS: Opportunity cost (OC) analysis is key when evaluating surgical techniques. Operating room (OR) time is one potential source of OC in laparoscopic surgery. This study quantifies differences in OR time between 3D- and 2D-imaging technology in laparoscopic surgery, translates these into OC and models the economic impact in real-world hospitals. METHODS: First a systematically performed literature review and meta-analysis were conducted. Then, methods to translate OR time savings into OC were theorised and a budget impact model was created. After that, the potential time savings of real-world hospital case mixes were extrapolated. Finally, the opportunity costs of not using 3D-imaging in laparoscopic surgery were evaluated. RESULTS: Average OR time saving per laparoscopic procedure was -19.4 min (-24.3; -14.5) (-14%) in favour of 3D. The Budget Impact Model demonstrated an economic impact of using 3D-laparoscopy instead of 2D laparoscopy, ranging from £183,045-£866,316 in the British and 73,049€-437,829€ in German hospitals, modelling a mixture of cost savings and performing additional procedures (earning additional revenue). CONCLUSION: The OC analysis revealed significant economic benefits of introducing 3D-imaging technology in laparoscopic surgery, on the basis that average procedure time is reduced. Utilising the saved OR time to perform additional procedures was the biggest driver of OC. Hospital case mix and procedure volume indicated the magnitude of the OC.


Asunto(s)
Laparoscopía , Quirófanos , Análisis Costo-Beneficio , Alemania , Hospitales , Humanos , Laparoscopía/métodos , Tecnología , Reino Unido
15.
Rev Sci Instrum ; 93(10): 103530, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319372

RESUMEN

We present a technique to measure the time-resolved velocity and ion sound speed in magnetized, supersonic high-energy-density plasmas. We place an inductive ("b-dot") probe in a supersonic pulsed-power-driven plasma flow and measure the magnetic field advected by the plasma. As the magnetic Reynolds number is large (RM > 10), the plasma flow advects a magnetic field proportional to the current at the load. This enables us to estimate the flow velocity as a function of time from the delay between the current at the load and the signal at the probe. The supersonic flow also generates a hydrodynamic bow shock around the probe, the structure of which depends on the upstream sonic Mach number. By imaging the shock around the probe with a Mach-Zehnder interferometer, we determine the upstream Mach number from the shock Mach angle, which we then use to determine the ion sound speed from the known upstream velocity. We use the sound speed to infer the value of Z̄Te, where Z̄ is the average ionization and Te is the electron temperature. We use this diagnostic to measure the time-resolved velocity and sound speed of a supersonic (MS ∼ 8), super-Alfvénic (MA ∼ 2) aluminum plasma generated during the ablation stage of an exploding wire array on the Magpie generator (1.4 MA, 250 ns). The velocity and Z̄Te measurements agree well with the optical Thompson scattering measurements reported in the literature and with 3D resistive magnetohydrodynamic simulations in GORGON.

16.
Front Neuroendocrinol ; 31(1): 44-60, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19896496

RESUMEN

Ghrelin, a peptide hormone predominantly produced by the stomach, was isolated as the endogenous ligand for the growth hormone secretagogue receptor. Ghrelin is a potent stimulator of growth hormone (GH) secretion and is the only circulatory hormone known to potently enhance feeding and weight gain and to regulate energy homeostasis following central and systemic administration. Therapeutic intervention with ghrelin in catabolic situations may induce a combination of enhanced food intake, increased gastric emptying and nutrient storage, coupled with an increase in GH thereby linking nutrient partitioning with growth and repair processes. These qualities have fostered the idea that ghrelin-based compounds may have therapeutic utility in treating malnutrition and wasting induced by various sub-acute and chronic disorders. Conversely, compounds that inhibit ghrelin action may be useful for the prevention or treatment of metabolic syndrome components such as obesity, impaired lipid metabolism or insulin resistance. In recent years, the effects of ghrelin on glucose homeostasis, memory function and gastrointestinal motility have attracted considerable amount of attention and revealed novel therapeutic targets in treating a wide range of pathologic conditions. Furthermore, discovery of ghrelin O-acyltransferase has also opened new research opportunities that could lead to major understanding of ghrelin physiology. This review summarizes the current knowledge on ghrelin synthesis, secretion, mechanism of action and biological functions with an additional focus on potential for ghrelin-based pharmacotherapies.


Asunto(s)
Peso Corporal/fisiología , Metabolismo Energético/fisiología , Ghrelina/fisiología , Homeostasis/fisiología , Proteína Relacionada con Agouti , Secuencia de Aminoácidos , Animales , Glucemia/metabolismo , Barrera Hematoencefálica , Caquexia , Ingestión de Alimentos/fisiología , Motilidad Gastrointestinal , Ghrelina/química , Hormona de Crecimiento Humana/metabolismo , Humanos , Resistencia a la Insulina , Datos de Secuencia Molecular , Neuropéptido Y , Obesidad , Receptores de Ghrelina , Aumento de Peso
17.
Allergy ; 66(7): 853-61, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21276008

RESUMEN

BACKGROUND: We recently showed that poly(ADP-ribose)polymerase-1 (PARP-1) may play a role in allergen (ovalbumin)-induced airway eosinophilia, potentially through a specific effect on IL-5 production. We also reported that while IL-5 replenishment promotes reversal of eosinophilia in lungs of PARP-1(-/-) mice, IL-4 or Immunoglobulin E replenishment do not, suggesting a potentially significant regulatory relationship between PARP-1 and IL-5. OBJECTIVE: To explore the mechanism by which PARP-1 regulates IL-5 production and to determine how PARP-1 inhibition blocks allergen-induced eosinophilia. METHODS: This study was conducted using a murine model of allergic airway inflammation and primary splenocytes. RESULTS: PARP-1 knockout-associated reduction in IL-5 upon allergen exposure occurs at the mRNA level. Such an effect appears to take place after IL-4 receptor activation as PARP-1 inhibition exerted no effect on JAK1/JAK3 activation. Signal transducer and activator of transcription-6 (STAT-6) protein was severely downregulated in spleens of PARP-1(-/-) mice without any effect on mRNA levels, suggesting an effect on protein integrity rather than gene transcription. Interestingly, the degradation of STAT-6 in PARP-1(-/-) mice required allergen stimulation. Additionally, PARP-1 enzymatic activity appears to be required for STAT-6 integrity. The downregulation of STAT-6 coincided with mRNA and protein reduction of GATA-binding protein-3 and occupancy of its binding site on the IL-5 gene promoter. IL-4 was sufficient to induce STAT-6 downregulation in both PARP-1(-/-) mice and isolated splenocytes. Such degradation may be mediated by calpain, but not by proteasomes. CONCLUSION: These results demonstrate a novel function of PARP-1 in regulating IL-5 expression during allergen-induced inflammation and explain the underlying mechanism by which PARP-1 inhibition results in IL-5 reduction.


Asunto(s)
Asma/inmunología , Asma/fisiopatología , Calpaína/metabolismo , Interleucina-5/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Factor de Transcripción STAT6/metabolismo , Alérgenos/inmunología , Animales , Asma/metabolismo , Modelos Animales de Enfermedad , Eosinofilia/inmunología , Femenino , Humanos , Inflamación/inmunología , Interleucina-5/antagonistas & inhibidores , Interleucina-5/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/genética , Sistema Respiratorio/inmunología , Sistema Respiratorio/fisiopatología
19.
J Exp Med ; 184(6): 2399-404, 1996 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-8976194

RESUMEN

Recent studies have shown that protein kinase C (PKC) delta is proteolytically activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. However, the relationship of PKC delta cleavage to induction of apoptosis is unknown. The present studies demonstrate that full-length PKC delta is cleaved at DMQD330N to a catalytically active fragment by the cysteine protease CPP32. The results also demonstrate that overexpression of the catalytic kinase fragment in cells is associated with chromatin condensation, nuclear fragmentation, induction of sub-G1 phase DNA and lethality. By contrast, overexpression of full-length PKC delta or a kinase inactive PKC delta fragment had no detectable effect. The findings suggest that proteolytic activation of PKC delta by a CPP32-like protease contributes to phenotypic changes associated with apoptosis.


Asunto(s)
Apoptosis , Caspasas , Cisteína Endopeptidasas/metabolismo , Proteínas del Helminto/metabolismo , Isoenzimas/metabolismo , Proteína Quinasa C/metabolismo , Secuencia de Aminoácidos , Proteínas de Caenorhabditis elegans , Caspasa 1 , Caspasa 3 , Activación Enzimática , Células HeLa , Humanos , Isoenzimas/química , Cinética , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Reacción en Cadena de la Polimerasa , Proteína Quinasa C/química , Proteína Quinasa C-delta , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , Transfección
20.
Nature ; 430(6996): 1 p following 165; discussion 2 p following 165, 2004 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-15243972

RESUMEN

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.


Asunto(s)
Depresores del Apetito/farmacología , Regulación del Apetito/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Péptido YY/farmacología , Animales , Animales Endogámicos , Apetito/efectos de los fármacos , Apetito/fisiología , Depresores del Apetito/uso terapéutico , Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ambiente , Humanos , Metaanálisis como Asunto , Ratones , Obesidad/tratamiento farmacológico , Fragmentos de Péptidos , Péptido YY/administración & dosificación , Péptido YY/sangre , Péptido YY/uso terapéutico , Ratas , Reproducibilidad de los Resultados , Estrés Fisiológico/complicaciones , Estrés Fisiológico/fisiopatología
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