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1.
Rev Sci Instrum ; 94(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38065162

RESUMO

A diagnostic for extreme ultraviolet spectroscopy was fielded on the sheared-flow-stabilized (SFS) fusion Z-pinch experiment (FuZE-Q) for the first time. The spectrometer collected time-gated plasma emission spectra in the 5-40 nm wavelength (30-250 eV) range for impurity identification, radiative power studies, and for plasma temperature and density measurements. The unique implementation of the diagnostic included fast (10 ns risetime) pulsed high voltage electronics and a multi-stage differential pumping system that allowed the vacuum-coupled spectrometer to collect three independently timed spectra per FuZE-Q shot while also protecting sensitive internal components. Analysis of line emission identifies oxygen (N-, C-, B-, Be-, Li-, and He-like O), peaking in intensity shortly after maximum current (>500 kA). This work provides a foundation for future high energy spectroscopy experiments on SFS Z-pinch devices.

2.
Rev Sci Instrum ; 94(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37972020

RESUMO

Currently, the world's only source of low-energy antiprotons is the AD/ELENA facility located at CERN. To date, all precision measurements on single antiprotons have been conducted at this facility and provide stringent tests of fundamental interactions and their symmetries. However, magnetic field fluctuations from the facility operation limit the precision of upcoming measurements. To overcome this limitation, we have designed the transportable antiproton trap system BASE-STEP to relocate antiprotons to laboratories with a calm magnetic environment. We anticipate that the transportable antiproton trap will facilitate enhanced tests of charge, parity, and time-reversal invariance with antiprotons and provide new experimental possibilities of using transported antiprotons and other accelerator-produced exotic ions. We present here the technical design of the transportable trap system. This includes the transportable superconducting magnet, the cryogenic inlay consisting of the trap stack and detection systems, and the differential pumping section to suppress the residual gas flow into the cryogenic trap chamber.

3.
Phys Rev E ; 107(6-2): 065209, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37464717

RESUMO

Using three-dimensional (3D) magnetohydrodynamic simulations, we study how a pit on a metal surface evolves when driven by intense electrical current density j. Redistribution of j around the pit initiates a feedback loop: j both reacts to and alters the electrical conductivity σ, through Joule heating and hydrodynamic expansion, so that j and σ are constantly in flux. Thus, the pit transforms into larger striation and filament structures predicted by the electrothermal instability theory. Both structures are important in applications of current-driven metal: The striation constitutes a density perturbation that can seed the magneto-Rayleigh-Taylor instability, while the filament provides a more rapid path to plasma formation, through 3D j redistribution. Simulations predict distinctive self-emission patterns, thus allowing for experimental observation and comparison.

4.
Phys Rev Lett ; 130(25): 255101, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37418744

RESUMO

Electrothermal instability plays an important role in applications of current-driven metal, creating striations (which seed the magneto-Rayleigh-Taylor instability) and filaments (which provide a more rapid path to plasma formation). However, the initial formation of both structures is not well understood. Simulations show for the first time how a commonly occurring isolated defect transforms into the larger striation and filament, through a feedback loop connecting current and electrical conductivity. Simulations have been experimentally validated using defect-driven self-emission patterns.


Assuntos
Citoesqueleto , Plasma
5.
Artigo em Inglês | MEDLINE | ID: mdl-37288385

RESUMO

Abstract: The BASE collaboration at the antiproton decelerator/ELENA facility of CERN compares the fundamental properties of protons and antiprotons with ultra-high precision. Using advanced Penning trap systems, we have measured the proton and antiproton magnetic moments with fractional uncertainties of 300 parts in a trillion (p.p.t.) and 1.5 parts in a billion (p.p.b.), respectively. The combined measurements improve the resolution of the previous best test in that sector by more than a factor of 3000. Very recently, we have compared the antiproton/proton charge-to-mass ratios with a fractional precision of 16 p.p.t., which improved the previous best measurement by a factor of 4.3. These results allowed us also to perform a differential matter/antimatter clock comparison test to limits better than 3%. Our measurements enable us to set limits on 22 coefficients of CPT- and Lorentz-violating standard model extensions (SME) and to search for potentially asymmetric interactions between antimatter and dark matter. In this article, we review some of the recent achievements and outline recent progress towards a planned improved measurement of the antiproton magnetic moment with an at least tenfold improved fractional accuracy.

6.
Hand Surg Rehabil ; 41S: S90-S97, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34343724

RESUMO

Palliative tendon transfer is an integral part of radial nerve palsy treatment. It can be considered in the first weeks when the possibility of nerve repair by direct suture or nerve grafting is not feasible or reasonable. Mostly, it is discussed secondarily when it is too late for nerve surgery and motor recovery cannot be expected, or after failure or incomplete recovery after nerve repair. The goal of tendon transfers is to restore wrist, finger and thumb extension. For wrist extension, the use of pronator teres is well accepted. The best tendon transfer for finger extension is debated. This can be restored doing a flexor carpi ulnaris (FCU), flexor carpi radialis or flexor digitorum superficialis (FDS) to extensor digitorum communis transfer. Regarding thumb extension and abduction, a palmaris longus (PL) or one FDS tendon to the rerouted extensor pollicis longus (EPL) transfer can be performed. If a transfer is done on the EPL without rerouting it, abduction can be restored by doing a tendon transfer to the abductor pollicis longus (APL) or an APL tenodesis. The different tendon transfer options are selected based on the surgeon's preference, and most importantly, discussed with the patients to define the objectives together. The transfer is chosen based on the clinical examination (high or low radial nerve palsy, tendon available for transfer like PL, wrist mobility) and based on the patient's needs and expectations (activities requiring the FCU, finger independence, independence of thumb extension or abduction). If the surgical rules and the postoperative instructions for rehabilitation are followed, tendon transfers for radial nerve palsy regularly produce very satisfactory results.


Assuntos
Neuropatia Radial , Transferência Tendinosa , Mãos , Humanos , Neuropatia Radial/cirurgia , Transferência Tendinosa/métodos , Tendões , Articulação do Punho/cirurgia
7.
Hand Surg Rehabil ; 41S: S118-S127, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34311132

RESUMO

Ulnar claw hand usually occurs when the ulnar nerve is damaged distally. Claw hand deformity is characterized by metacarpophalangeal hyperextension and interphalangeal flexion, making it impossible to oppose the fingers and thumb. Bouvier's test is used to guide the procedure. Palliative surgery requires prior preparation of paralytic hands. In case of a positive Bouvier's test, Zancolli's lasso technique is preferred because of its effectiveness. Capsuloplasty with anteroposterior transosseous fixation is used if the bone is strong enough and when flexor digitorum profondus muscle is inactive and does not allow flexor digitorum superficialis tendon transfer. In case of a negative Bouvier's test with interphalangeal extension deficit of 45° of less, direct interossei muscle restoration techniques by active transfers are performed. If the interphalangeal extension deficit is more than 45°, proximal interphalangeal arthrodesis is indicated. Wartenberg first described actively irreducible abduction of the little finger. Wartenberg's sign is seen when ulnar paralysis occurs, and during ulnar nerve regeneration. Treatment of isolated Wartenberg's sign consists of re-routing the extensor digiti minimi. Among the other techniques, Belmahi's "tie lasso" is preferred when flexible claw hand is associated with Wartenberg's sign.


Assuntos
Deformidades Adquiridas da Mão , Mãos , Dedos/inervação , Mãos/cirurgia , Deformidades Adquiridas da Mão/etiologia , Deformidades Adquiridas da Mão/cirurgia , Humanos , Tendões/cirurgia , Nervo Ulnar/cirurgia
8.
BMJ Mil Health ; 167(6): 393-397, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32086267

RESUMO

INTRODUCTION: The objective was to report on the experience of the French Army Health Service in the management of blast injury of the hands related to warfare explosive devices. METHODS: A retrospective study was conducted in the Percy Military Hospital (role 4 medical treatment facility) among French soldiers who presented with a combat-related blast injury of the hand between 2002 and 2018. The functional result was assessed by the disabilities of the arm, shoulder and hand (DASH) and the Orthotics and Prosthetics User Survey (OPUS, upper extremity functional status) scores. Proximal amputations (PAs) and distal amputations (DAs) were distinguished for the analysis. RESULTS: Fifteen patients with a mean age of 31±8 years were included. They totalised 20 blasted hands. There were 16 traumatic amputations: 8 in each of the PA and DA groups. Twelve patients had additional injuries, four of which were polytraumatic. Skin closure time and flap use were higher in the DA group. Only one thumb reconstruction was performed. At a mean follow-up of 6.5±4 years, the number of amputees wearing a prosthesis was higher in the PA group. The mean DASH and OPUS scores were 35.5%±24.0% and 64.0%±19.0%, respectively, with no difference between the two groups. CONCLUSION: The severity of hand blasts related to warfare explosive devices requires the systematic application of damage control surgery. PAs are frequent and secondary reconstruction options are limited. The functional result is poor and similar between proximal and distal amputees.


Assuntos
Traumatismos por Explosões , Substâncias Explosivas , Serviços de Saúde Militar , Adulto , Traumatismos por Explosões/epidemiologia , Humanos , Estudos Retrospectivos , Guerra , Adulto Jovem
9.
Epidemiol Infect ; 148: e260, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33050975

RESUMO

In Germany, sheep are the main source of human Q fever epidemics, but data on Coxiella burnetii (C. burnetii) infections and related risk factors in the German sheep population remain scarce. In this cross-sectional study, a standardised interview was conducted across 71 exclusively sheep as well as mixed (sheep and goat) farms to identify animal and herd level risk factors associated with the detection of C. burnetii antibodies or pathogen-specific gene fragments via univariable and multivariable logistic regression analysis. Serum samples and genital swabs from adult males and females of 3367 small ruminants from 71 farms were collected and analysed using ELISA and qPCR, respectively. On animal level, univariable analysis identified young animals (<2 years of age; odds ratio (OR) 0.33; 95% confidence interval (CI) 0.13-0.83) to reduce the risk for seropositivity significantly (p < 0.05). The final multivariable logistic models identified lambing all year-round (OR 3.46/3.65; 95% CI 0.80-15.06/0.41-32.06) and purchases of sheep and goats (OR 13.61/22.99; 95% CI 2.86-64.64/2.21-239.42) as risk factors on herd level for C. burnetii infection detected via ELISA and qPCR, respectively.


Assuntos
Coxiella burnetii/isolamento & purificação , Febre Q/veterinária , Doenças dos Ovinos/microbiologia , Animais , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Alemanha/epidemiologia , Masculino , Razão de Chances , Reação em Cadeia da Polimerase/veterinária , Febre Q/epidemiologia , Fatores de Risco , Ovinos , Doenças dos Ovinos/epidemiologia
11.
Epidemiol Infect ; 148: e75, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32172709

RESUMO

A prevalence study was conducted on German sheep flocks including goats if they cohabitated with sheep. In addition, a novel approach was applied to identify an infection at the herd-level before lambing season with preputial swabs, suspecting venereal transmission and ensuing colonisation of preputial mucosa with Coxiella (C.) burnetii. Blood samples and genital swabs were collected from breeding males and females after the mating season and were analysed by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR) respectively. In total, 3367 animals were sampled across 71 flocks. The true herd-level prevalence adjusted for misclassification probabilities of the applied diagnostic tests using the Rogan-Gladen estimator for the prevalence estimate and a formula by Lang and Reiczigel (2014) for the confidence limits, ranged between 31.3% and 33% (95% confidence interval [95% CI] 17.3-45.5) detected by the ELISA and/or qPCR. Overall 26-36.6% (95% CI 13-56.8) were detected by ELISA, 13.9% (95% CI 4.5-23.2) by the qPCR and 7.9-11.2% (95% CI 0.08-22.3) by both tests simultaneously. The range of results is due to data obtained from literature with different specifications for test quality for ELISA. Among eight farms with females shedding C. burnetii, three farms (37.5%) could also be identified by preputial swabs from breeding sires. This indicates less reliability of preputial swabs if used as a single diagnostic tool to detect C. burnetii infection at the herd-level.


Assuntos
Coxiella burnetii/isolamento & purificação , Febre Q/veterinária , Doenças dos Ovinos/microbiologia , Animais , Feminino , Genitália Feminina/microbiologia , Genitália Masculina/microbiologia , Alemanha/epidemiologia , Doenças das Cabras/diagnóstico , Doenças das Cabras/epidemiologia , Doenças das Cabras/microbiologia , Cabras , Masculino , Prevalência , Febre Q/diagnóstico , Febre Q/epidemiologia , Febre Q/microbiologia , Ovinos , Doenças dos Ovinos/diagnóstico , Doenças dos Ovinos/epidemiologia
12.
Anim Genet ; 51(1): 111-116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31793009

RESUMO

Equine recurrent uveitis (ERU) is characterized by intraocular inflammation that often leads to blindness in horses. Appaloosas are more likely than any other breed to develop insidious ERU, distinguished by low-grade chronic intraocular inflammation, suggesting a genetic predisposition. Appaloosas are known for their white coat spotting patterns caused by the leopard complex spotting allele (LP) and the modifier PATN1. A marker linked to LP on ECA1 and markers near MHC on ECA20 were previously associated with increased ERU risk. This study aims to further investigate these loci and identify additional genetic risk factors. A GWAS was performed using the Illumina Equine SNP70 BeadChip in 91 horses. Additive mixed model approaches were used to correct for relatedness. Although they do not reach a strict Bonferroni genome-wide significance threshold, two SNPs on ECA1 and one SNP each on ECA12 and ECA29 were among the highest ranking SNPs and thus warranted further analysis (P = 1.20 × 10-5 , P = 5.91 × 10-6 , P = 4.91 × 10-5 , P = 6.46 × 10-5 ). In a second cohort (n = 98), only an association with the LP allele on ECA1 was replicated (P = 5.33 × 10-5 ). Modeling disease risk with LP, age and additional depigmentation factors (PATN1 genotype and extent of roaning) supports an additive role for LP and suggests an additive role for PATN1. Genotyping for LP and PATN1 may help predict ERU risk (AUC = 0.83). The functional role of LP and PATN1 in ERU development requires further investigation. Testing samples across breeds with leopard complex spotting patterns and a denser set of markers is warranted to further refine the genetic components of ERU.


Assuntos
Doenças dos Cavalos/genética , Cavalos/genética , Canais de Cátion TRPM/genética , Uveíte/veterinária , Alelos , Animais , Cruzamento , Estudos de Casos e Controles , Estudos de Associação Genética/veterinária , Predisposição Genética para Doença , Genótipo , Cor de Cabelo , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Uveíte/genética
13.
Struct Dyn ; 6(6): 064303, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31832487

RESUMO

Most chemical and biochemical reactions in nature and in industrial processes are driven by thermal effects that bring the reactants above the energy barrier for reaction. In aqueous solutions, this process can also be triggered by the laser driven temperature jump (T-jump) method, in which the water vibrational (stretch, bend, or combination) modes are excited by a short laser pulse, leading to a temperature increase in the irradiated volume within a few picoseconds. The combination of the laser T-jump with X-ray spectroscopic probes would add element-specificity as well as sensitivity to the structure, the oxidation state, and the spin state of the intermediates of reactions. Here, we present preliminary results of a near infrared pump/X-ray absorption spectroscopy probe to study the ligand exchange of an octahedral aqueous Cobalt complex, which is known to pass through intermediate steps yielding tetrahedral chlorinated as final species. The structural changes of the chemical reaction are monitored with great sensitivity, even in the presence of a mild local increase in temperature. This work opens perspectives for the study of non-light-driven reactions using time-resolved X-ray spectroscopic methods.

14.
Science ; 364(6441)2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31097641

RESUMO

The Kuiper Belt is a distant region of the outer Solar System. On 1 January 2019, the New Horizons spacecraft flew close to (486958) 2014 MU69, a cold classical Kuiper Belt object approximately 30 kilometers in diameter. Such objects have never been substantially heated by the Sun and are therefore well preserved since their formation. We describe initial results from these encounter observations. MU69 is a bilobed contact binary with a flattened shape, discrete geological units, and noticeable albedo heterogeneity. However, there is little surface color or compositional heterogeneity. No evidence for satellites, rings or other dust structures, a gas coma, or solar wind interactions was detected. MU69's origin appears consistent with pebble cloud collapse followed by a low-velocity merger of its two lobes.

15.
Phys Rev E ; 97(5-1): 053208, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29906862

RESUMO

A direct observation of the stratified electrothermal instability on the surface of thick metal is reported. Aluminum rods coated with 70µm Parylene-N were driven to 1 MA in 100ns, with the metal thicker than the skin depth. The dielectric coating suppressed plasma formation, enabling persistent observation of discrete azimuthally correlated stratified thermal perturbations perpendicular to the current whose wave numbers, k, grew exponentially with rate γ(k)=0.06ns^{-1}-(0.4ns^{-1}µm^{2}rad^{-2})k^{2} in ∼1g/cm^{3}, ∼7000K aluminum.

16.
Eur J Cancer Care (Engl) ; 27(4): e12852, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29667288

RESUMO

Treatment of cancer-related symptoms represents a major challenge for physicians. The purpose of this pilot study was to determine whether a brief bedside visual art intervention (BVAI) facilitated by art educators improves mood, reduces pain and anxiety in patients with haematological malignancies. Thirty-one patients (21 women and 10 men) were invited to participate in a BVAI where the goal of the session was to teach art technique for ~30 min. Primary outcome measures included the change in visual analog scale, the State-Trait Anxiety Inventory and the Positive and Negative Affect Schedule scale, from baseline prior to and immediately post-BVAI. Total of 21 patients (19 women and two men) participated. A significant improvement in positive mood and pain scores (p = .003 and p = .017 respectively) as well as a decrease in negative mood and anxiety (p = .016 and p = .001 respectively) was observed. Patients perceived BVAI as overall positive (95%) and wished to participate in future art-based interventions (85%). This accessible experience, provided by artists within the community, may be considered as an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain, and future studies with balanced gender participation may support the generalisability of these findings.


Assuntos
Afeto , Ansiedade/terapia , Arteterapia/métodos , Dor do Câncer/terapia , Neoplasias Hematológicas/terapia , Adulto , Idoso , Ansiedade/psicologia , Dor do Câncer/psicologia , Feminino , Neoplasias Hematológicas/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Adulto Jovem
17.
Front Pharmacol ; 8: 649, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28983248

RESUMO

Background/Objective: The cardiac Na+/Ca2+ exchanger (NCX) has been identified as a promising target to counter arrhythmia in previous studies investigating the benefit of NCX inhibition. However, the consequences of NCX inhibition have not been investigated in the setting of altered NCX expression and function, which is essential, since major cardiac diseases (heart failure/atrial fibrillation) exhibit NCX upregulation. Thus, we here investigated the effects of the NCX inhibitor SEA0400 on the Ca2+ transient amplitude and on proarrhythmia in homozygous NCX overexpressor (OE) and heterozygous NCX knockout (hetKO) mice compared to corresponding wild-types (WTOE/WThetKO). Methods/Results: Ca2+ transients of field-stimulated isolated ventricular cardiomyocytes were recorded with fluo-4-AM or indo-1-AM. SEA0400 (1 µM) significantly reduced NCX forward mode function in all mouse lines. SEA0400 (1 µM) significantly increased the amplitude of field-stimulated Ca2+ transients in WTOE, WThetKO, and hetKO, but not in OE (% of basal; OE = 98.7 ± 5.0; WTOE = 137.8 ± 5.2*; WThetKO = 126.3 ± 6.0*; hetKO = 140.6 ± 12.8*; *p < 0.05 vs. basal). SEA0400 (1 µM) significantly reduced the number of proarrhythmic spontaneous Ca2+ transients (sCR) in OE, but increased it in WTOE, WThetKO and hetKO (sCR per cell; basal/+SEA0400; OE = 12.5/3.7; WTOE = 0.2/2.4; WThetKO = 1.3/8.8; hetKO = 0.2/5.5) and induced Ca2+ overload with subsequent cell death in hetKO. Conclusion: The effects of SEA0400 on Ca2+ transient amplitude and the occurrence of spontaneous Ca2+ transients as a proxy measure for inotropy and cellular proarrhythmia depend on the NCX expression level. The antiarrhythmic effect of SEA0400 in conditions of increased NCX expression promotes the therapeutic concept of NCX inhibition in heart failure/atrial fibrillation. Conversely, in conditions of reduced NCX expression, SEA0400 suppressed the NCX function below a critical level leading to adverse Ca2+ accumulation as reflected by an increase in Ca2+ transient amplitude, proarrhythmia and cell death. Thus, the remaining NCX function under inhibition may be a critical factor determining the inotropic and antiarrhythmic efficacy of SEA0400.

18.
Parasitol Res ; 116(11): 2927-2932, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28932909

RESUMO

In order to assess the residual effects of fipronil 1% on tsetse fly survival, male Glossina palpalis gambiensis were released on non-treated and treated cattle, with 0.1 ml of fipronil/kg b.w. as a pour-on formulation. In a second trial, the female fecundity performances were evaluated by feeding teneral females on the same cattle. These females were then mated and their production parameters monitored, as well as the survival of freshly emerged flies. Fipronil had a significant effect on tsetse fly survival (p < 0.001). Over a period of 30 days, up to 40% of tsetse fly mortality was observed within 72 h after tsetse were released. The residual effects ranged between 51 and 74 days when tsetse flies were released twice within a 15-day interval in the presence of a treated animal. When tsetse flies were fed on treated cattle through a parafilm membrane, 92 days after the treatment, no significant effect of fipronil was observed on the reproductive performance of females, i.e., as well as on fecundity (p = 0.948) and emergence rates (p = 0.743), or puparial weight (p = 0.422). This was also the case for the survival of young flies, with no difference observed between the two groups. After this study, it is confirmed that fipronil is highly effective against tsetse flies. Its efficacy in controlling ticks is already known but other externalities such as the control of biting insects add value to its use.


Assuntos
Inseticidas , Pirazóis , Moscas Tsé-Tsé/efeitos dos fármacos , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Doenças dos Bovinos/prevenção & controle , Feminino , Fertilidade/efeitos dos fármacos , Masculino
19.
J Periodontal Res ; 52(6): 1032-1041, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28643938

RESUMO

BACKGROUND AND OBJECTIVES: Epidemiological studies suggest a close association between periodontitis and prediabetes/insulin resistance (IR) but whether periodontitis causes prediabetes in humans is not known. Using various animal models, we have recently established that periodontitis can be an initiator of prediabetes, which is characterized by glucose intolerance, hyperinsulinemia and IR. In addition, our in vitro studies indicated that Porphyromonas gingivalis (Pg) induced insulin secretion in MIN6 ß cells and this induction was in part SerpinE1 (plasminogen activator inhibitor 1, PAI1) dependent. However, the mechanism(s) by which periodontitis induces prediabetes is not known. As α and ß cells in pancreatic islets are the major modulators of glucose levels, we investigated whether experimental periodontitis by oral application of a periodontal pathogen caused molecular and/or cellular alterations in pancreatic islets and whether SerpinE1 was involved in this process. MATERIAL AND METHODS: We induced periodontitis in C57BL/6 mice by oral application of a periodontal pathogen, Pg, and determined changes that occurred in islets following 22 weeks of Pg application. Pancreatic islet architecture was determined by 2-D and 3-D immunofluorescence microscopy and SerpinE1 and its target, urokinase plasminogen activator (uPA), as well as insulin, glucagon and Pg/gingipain in islets were detected by immunofluorescence. The presence of apoptotic islet cells was determined by both histochemical and immunofluorescence TUNEL assays. To investigate further the direct effect of Pg on apoptosis and the involvement of SerpinE1 in this process, we used SerpinE1 knockdown and scrambled control clones of the MIN6 pancreatic ß-cell line. RESULTS: Pg/gingipain was detected in both the periodontium and pancreas in the experimental group. Islets from animals that were administered Pg orally (experimental group) developed significant changes in islet architecture, upregulation of SerpinE1, and increased ß-cell apoptosis compared with the control group. We also observed that exposure of MIN6 cells to Pg in vitro resulted in apoptosis. However, apoptosis was significantly reduced when SerpinE1 expression by MIN6 cells was knocked down. CONCLUSION: Oral application of the periodontal pathogen Pg to C57BL/6 mice induces periodontitis, translocation of Pg/gingipain to the pancreas and results in complex alterations in pancreatic islet morphology. SerpinE1 appears to be involved in this process.


Assuntos
Ilhotas Pancreáticas/patologia , Periodontite/complicações , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Porphyromonas gingivalis/metabolismo , Estado Pré-Diabético/etiologia , Animais , Apoptose , Infecções por Bacteroidaceae/complicações , Western Blotting , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência
20.
Clin Pharmacol Ther ; 100(5): 419-422, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27500791

RESUMO

The American Association of Pharmaceutical Scientists/International Transporter Consortium Joint Workshop on Drug Transporters in absorption, distribution, metabolism, and excretion was held with the objective of discussing innovative advances in transporter pharmacology. Specific topics included (i) transporters at the blood-brain barrier (BBB); (ii) emerging transport proteins; (iii) recent advances in achieving hepatoselectivity and optimizing clearance for organic anion-transporting polypeptide (OATP) substrates; (iv) utility of animal models for transporter studies; and (v) clinical correlation of transporter polymorphisms. Here, we present state-of-the-art highlights from this workshop in these key areas of focus.


Assuntos
Barreira Hematoencefálica/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Modelos Animais , Transportadores de Ânions Orgânicos/metabolismo , Animais , Humanos , Proteínas de Membrana Transportadoras/genética , Estados Unidos
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