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1.
Nanotechnology ; 28(8): 085704, 2017 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-27976629

RESUMO

The nondestructive imaging of subsurface structures on the nanometer scale has been a long-standing desire in both science and industry. A few impressive images were published so far that demonstrate the general feasibility by combining ultrasound with an atomic force microscope. From different excitation schemes, heterodyne force microscopy seems to be the most promising candidate delivering the highest contrast and resolution. However, the physical contrast mechanism is unknown, thereby preventing any quantitative analysis of samples. Here we show that friction at material boundaries within the sample is responsible for the contrast formation. This result is obtained by performing a full quantitative analysis, in which we compare our experimentally observed contrasts with simulations and calculations. Surprisingly, we can rule out all other generally believed responsible mechanisms, like Rayleigh scattering, sample (visco)elasticity, damping of the ultrasonic tip motion, and ultrasound attenuation. Our analytical description paves the way for quantitative subsurface-AFM imaging.

2.
Phys Rev Lett ; 112(24): 242502, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24996085

RESUMO

Information on the size and shape of the neutron skin on (208)Pb is extracted from coherent pion photoproduction cross sections measured using the Crystal Ball detector together with the Glasgow tagger at the MAMI electron beam facility. On exploitation of an interpolated fit of a theoretical model to the measured cross sections, the half-height radius and diffuseness of the neutron distribution are found to be c(n)=6.70±0.03(stat.) fm and a(n)=0.55±0.01(stat.)(-0.03)(+0.02)(sys.) fm, respectively, corresponding to a neutron skin thickness Δr(np)=0.15±0.03(stat.)(-0.03)(+0.01)(sys.) fm. The results give the first successful extraction of a neutron skin thickness with an electromagnetic probe and indicate that the skin of (208)Pb has a halo character. The measurement provides valuable new constraints on both the structure of nuclei and the equation of state for neutron-rich matter.

3.
J Bioeth Inq ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158656

RESUMO

Prenatal ultrasound is a non-invasive diagnostic examination. Despite the recognized diagnostic value, this technology raises complex ethical questions. The aim of this study is to provide a comprehensive analysis that coherently maps the ethical challenges raised by prenatal ultrasound examination, both 2D and 3D. We performed a systematic literature review. Six databases were systematically searched. The results highlight how concerns related to beneficence, informed consent, and autonomy are mainly related to routine use of prenatal ultrasound in the clinical context, while considerations linked to overmedicalization of pregnancy, discrimination, and fetal ontology were often reported in relation to the impact ultrasound is having on medicine and society. Ethical issues in the context of pre-abortion ultrasound, obstetric practices in low-income settings, and keepsake ultrasound imaging were also greatly discussed. Since prenatal ultrasound practices critically impact pregnant people's autonomy and their role within pregnancy, we conclude that information providing strategies should be developed to appropriately inform pregnant people about the nature, purpose, risks, and choices revolving around prenatal ultrasound. In addition, as it is becoming increasingly difficult to separate the social and clinical dimensions of prenatal ultrasound, future research should focus on examining if and how such dimensions should be reconciled.

4.
Nanotechnology ; 24(36): 365701, 2013 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-23942333

RESUMO

Applying heterodyne force microscopy (HFM), it has been impressively demonstrated that it is possible to obtain subsurface information: 20 nm large gold nanoparticles that were buried 500 nm deep have been imaged. It is the heterodyne signal that contains the subsurface information. We elucidate, both theoretically and experimentally, the sensitivity to the heterodyne signal as a function of the tip-sample distance. This is crucial information for experiments as the distance, and therefore the sensitivity, is tunable. We show that the amplitude of the heterodyne signal has a local maximum in the attractive part of the tip-sample interaction, before it surprisingly reaches an even higher plateau, when the tip-sample interaction is repulsive. This can only be explained by a non-decreasing amplitude of the ultrasonic motion of the tip, although it is in full contact with the surface. We confirm this counterintuitive tip behavior experimentally even on a hard surface like silicon.

5.
Anaesthesia ; 68(5): 527-30, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23573846

RESUMO

The use of extracorporeal membrane oxygenation in adults has increased in popularity and importance for the support of patients with cardiac or pulmonary failure. Although it is now quite commonly used in the intensive care unit, its use has rarely been described as a means of support during anaesthesia and surgery. We report the case of a patient who required curative resection of the oesophagus following previous left pneumonectomy where veno-venous extracorporeal membrane oxygenation was required both during surgery and for the first three days postoperatively. We describe the anaesthetic management of this patient who only had a single lung, review other alternatives and discuss why extracorporeal membrane oxygenation was particularly suited to this case. To the best of our knowledge, the anaesthetic literature to date does not contain a case report of this type.


Assuntos
Anestesia Geral , Carcinoma de Células Escamosas/cirurgia , Esofagectomia/métodos , Oxigenação por Membrana Extracorpórea/métodos , Idoso , Dióxido de Carbono/sangue , Neoplasias Esofágicas/cirurgia , Humanos , Masculino , Espirometria
6.
Nanotechnology ; 23(14): 145704, 2012 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-22434065

RESUMO

Recent experiments in the field of subsurface atomic force microscopy have demonstrated that it is possible to nondestructively image micro- and even nanoparticles that are embedded significantly deep within the bulk of a sample. In order to get insights into the contrast formation mechanism, we performed a finite element analysis and an analytical study, in which we calculated the amplitude and phase variation on the surface of an ultrasound wave that has traveled through the sample. Our calculations were performed as closely as possible to the situation in the experiments to enable a (future) comparison based on our predictions. We show that Rayleigh scattering of acoustic waves accounts for the measured contrast and we verify the characteristic Rayleigh dependences. The numerical results show that the contrast is independent of the depth at which a particle is buried, whereas the analytical study reveals a 1/depth dependence. In addition, we find a large deviation in the width of the particle in the contrast at the surface when applying the numerical or the analytical calculation respectively. These results indicate the importance of both the reflections of sound waves at the sample interfaces and bulk damping, as both are treated differently in our two models.


Assuntos
Microscopia de Força Atômica/métodos , Nanopartículas/análise , Algoritmos , Simulação por Computador , Análise de Elementos Finitos , Modelos Teóricos , Som
7.
Acta Chir Orthop Traumatol Cech ; 79(3): 238-42, 2012.
Artigo em Tcheco | MEDLINE | ID: mdl-22840949

RESUMO

PURPOSE OF THE STUDY: To evaluate the effect of acromial morphology, as assessed on radiographs, on rotator cuff tears. MATERIAL: A total of 200 patients surgically treated for shoulder disorders were enrolled. All were older than 40 years and had good quality shoulder radiographs. Two groups were composed: First, a clinical model group of 136 patients to be investigated for three parameters of rotator cuff injury that was divided into two subgroups. One included 68 patients, with an average age of 53.5 years, in whom surgery revealed no injury to the rotator cuff; the other subgroup of 68 patients, with an average age of 58 years, had a ruptured supraspinatus tendon. Subsequently, a control group of 64 patients (32 with rotator cuff injury and 32 without it) was used to verify the results of the model group. METHODS: Three parameters describing the acromion, i.e., acromion index (AI), lateral acromion angle and acromial slope, were measured on standard radiographs. Tangential antero-posterior and scapular "Y" (supraspinatus outlet) views were taken, the images were digitalised and evaluated using a TomoCon 3.0 Viewer programme, and the results of the two groups were statistically analysed and compared. RESULTS: The difference between the patients with rotator cuff injury and those without it was best shown, in both groups, by significant differences in the acromion index. This was true for both the men and women. The AI values for the patients with rotator cuff injury were 0.66 and 0.65 in the model and control groups, respectively. The same AI value of 0.76 was found for uninjured rotator cuffs in both groups. The two other parameters investigated did not appear to be of any significant validity for assessment of rotator cuff tears. DISCUSSION: The aetiology of injury to the rotator cuff has not been fully understood yet but, undoubtedly, the causes will be many. The shape of the acromion is regarded as one of the important factors. We agree with Nyffeler et al. that a lateral extension of the acromion is most often associated with rotator cuff tears and that the acromion index proposed by these authors is a good parameter to assess this morphological change. CONCLUSIONS: A lateral extension of the acromion plays an important role in the aetiology of degenerative tears of the supraspinatus tendon. The acromion index appears to be the best instrument for assessing this morphological change.


Assuntos
Acrômio/diagnóstico por imagem , Lesões do Manguito Rotador , Acrômio/anatomia & histologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Manguito Rotador/diagnóstico por imagem , Articulação do Ombro/diagnóstico por imagem
8.
Proc Inst Mech Eng H ; 236(12): 1777-1782, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36250719

RESUMO

The purpose of the study was to determine the proportion of engagements of individual breathing sectors during 1-min physically active breathing at rest in 163 healthy, physically active participants (students of Physical Education and Sport). The research analyzed breathing movements through the muscle dynamometer MD03 (Hitron, Plzen, Czech Republic). The proportion of engagements of the individual breathing sector in the group analyzed was determined based on measurement results. The lower breathing sector was engaged at 29.2%, the middle breathing sector at 31.0%, and the upper breathing sector at 39.8%. The largest observed difference between the involvement of individual breath sectors was 10.6% between the lower and upper breathing sectors. The muscle dynamometer MD03 may be instrumental for practising both localized breathing and full breath.


Assuntos
Músculos , Respiração , Humanos , Movimento
9.
Parasite Immunol ; 33(4): 210-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21204850

RESUMO

The role of CD4+ and CD8+ T lymphocytes in the development of a protective immune response against Cryptosporidium muris infection was studied by the reconstitution of severe combined immunodeficient (SCID) mice with well-defined populations of either naive or immune CD8+ or CD4+ T lymphocytes. Adoptive transfer of both naive and immune CD4+ T lymphocyte subpopulations protects SCID mice against cryptosporidiosis. Moreover, a significant biological impact of activated CD8+ T cells against gastric cryptosporidiosis was observed. The significant difference in the course and intensity of the infection in reconstituted SCID mice was found to be dependent on the protective function of both the CD4+ and CD8+ T-cell populations transferred. While SCID mice reconstituted with either immune or naive CD4+ or immune CD8+ T-cell subpopulations resolved the infection within 29, 37 and 51 days post-infection, respectively, those reconstituted with naive CD8+ T cells suffered from chronic infection similar to control SCID mice. Reconstitution with CD4+ T cells resulted in suppression of oocyst excretion and shortening of patent period in comparison with SCID mice reconstituted with CD8+ T cells. Thus, although CD4+ T cells are considered important in protective immunity, our results are the first to demonstrate the involvement of activated CD8+ T lymphocytes in the protection of mice against gastric cryptosporidiosis.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Criptosporidiose/imunologia , Cryptosporidium/imunologia , Estômago/parasitologia , Transferência Adotiva , Animais , Linfócitos T CD4-Positivos/imunologia , Camundongos , Camundongos SCID , Estômago/imunologia
10.
Transplant Proc ; 39(4): 1204-6, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17524933

RESUMO

UNLABELLED: Both tacrolimus (TAC) and sirolimus (SRL) bind to the same immunophilin FKBP12; however, their mechanisms of action are distinct. SRL inhibits mammalian target of rapamycin (TOR), which is an enzyme critical to the immune function. TOR inhibition blocks the signal that mediates T-cell proliferation by preventing cell-cycle progression from G1 to S phase. Moreover, TOR inhibition results in a decrease in antibody production by blocking B-cell proliferation and maturation into antibody producing cells. The use of SRL has resulted in a decrease in the number of rejection episodes. As with other immunosuppressive agents, SRL can cause dose-related side effects, the most notable of which are hypercholesterolemia, hyperlipidemia, anemia, and thrombocytopenia. Thus, therapeutic drug monitoring to assess efficacy and toxicity has became a necessity. SRL blood levels do not correlate with its bioactivity and are affected by the concomitant use of other immunosuppressive drugs. To determine the bioactivity of SRL we have developed an assay to determine the level of Sirolimus per lymphocyte of transplant patients. The levels were correlated with lymphocyte count. METHODS: Whole blood samples from patients on SRL were collected in Ethylene Diamine Tetra-acetic acid (EDTA) vacutainer tubes. Immediately the lymphocytes from 2 mL of blood were separated using 1.5 mL of Ficoll gradient, by centrifugation for 30 minutes at 2500 RPM. The lymphocytes were washed three times with phosphate-bufferd saline and the pellet suspended in 150 microL of Middle East research institute (MERI) drug extraction solution (Beirut, Lebanon), which was then added to 300 microL of IMx solublizing reagent. The cytoplasmic SRL concentrations in lymphocytes were measured using kits supplied from Abbott diagnostics or by high-performance liquid tomography. A corresponding whole blood sample from each patient was used to measure blood levels. To determine the level per lymphocyte, the value obtained was divided by the number of lymphocytes and expressed as Pg/cell. A pharmacokinetic profile for both blood and lymphocytes was constructed for each patient using data corresponding to predose C(0), 1 hour (C(1)) and 2 hours (C(2)) after the dose. The lymphocyte enumeration for C(0), C(1), and C(2) was performed using the FACS Calibur Flow Cytometer from Becton Dickinson. The average dose was 2.86 +/- 1.27 mg/d with a C(0) = 8.05 +/- 4.24, C(1) = 21.9 +/- 8.9 ng/mL, and C(2) = 23 +/- 0.03 ng/mL. Although there was a significant correlation (P=.0975) between the dose and C(0), there was no correlation between the dose and C(0) level on the lymphocyte count P=.897. However, there was a strong correlation between SRL lymphocyte levels (pg/cell) and the lymphocyte count (r(2)=.6.06). The higher the concentration of the drug the lower the lymphocyte counts. The assay is sensitive to within 0.45 pg/cell, reproducible with a coefficient of variance (CV) of 6.4% within assay and 7.5% for intraassay.


Assuntos
Transplante de Rim/imunologia , Linfócitos/metabolismo , Sirolimo/sangue , Monitoramento de Medicamentos , Feminino , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Masculino , Sirolimo/farmacocinética
11.
Transplant Proc ; 39(4): 1233-6, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17524942

RESUMO

Several studies have revealed a decreased incidence of early graft rejection with the use of mycophenate mofetil (MMF). The cost of the drug is, however, prohibitive especially in developing countries with limited resources. We compared the pharmacokinetic profile of a new MMF generic formulation (MMF 500 batch number: 06T3001; Medis Tunis) with those of Cellcept, (batch number: M1427; Hoffmann La Roche, Switzerland) in healthy volunteers. The study was double-blinded to investigator and volunteers. It had a balanced randomized, two-treatment, two-period, two-sequence, single-dose, crossover, comparative oral bioavailability design in adult healthy human volunteers. The study was designed, performed, and monitored by CRO Transmedical s.a.l International (Beirut, Lebanon) in accordance with the Basic Principals defined in the US 21 CFR Part 312.20, and the principals enunciated in the World Medical Association Declaration of Helsinki. We included nonsmoking healthy volunteers between the ages of 22 and 45 years. The subjects were admitted to the hospital one night prior to blood sampling. After volunteers received the same dinner, they were fasted overnight and for 2 hours postdosing. At 8 am each person received a single oral dose of 500 mg of either formulation. Blood samples were collected to construct the pharmacokinetic profiles as follows: 0, 0.15, 0.30, 0.45 minutes and 1, 1.15, 1.30, 2, 4, 6, 10, 12, and 24 hours. Water and food intake were the same for all volunteers during the whole study period. Following an 8-day washout period, the subjects were crossed over. Plasma mycophenolic acid concentrations were determined using a high-performance liquid chromatography validated enzyme-linked immunosorbent assay-based method (TransMedical, Beirut Lebanon). Physical examinations, hematology, urinanalysis, serum chemistry tests, and liver enzymes were performed at screening and at the end of each period. Subjects were monitored for safety and adverse events throughout the study by two physicians (one from the hospital and one from TransMedical). The Cmax, Tmax, and AUC for MMF 500 were 10.14 ng/mL, 51.82 minutes, and 18.33 ng/mL/h vs 10.94 ng/mL, 49.09 minutes, and 17.46 ng/mL/h for CellCept, respectively. The 90% confidence intervals (LSM) of Cmax, Tmax, and AUC for MMF 500 were 92.7%, 105.6%, and 105%, respectively, which is within the Food and Drug Administration (FDA)-assigned range for immunosuppressive drugs (90% to 111%). These results indicated that the products are equivalent and switchable according to FDA rulings.


Assuntos
Medicamentos Genéricos/farmacocinética , Ácido Micofenólico/análogos & derivados , Adulto , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Humanos , Masculino , Ácido Micofenólico/farmacocinética , Valores de Referência , Comprimidos
12.
Ultramicroscopy ; 181: 61-69, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28525802

RESUMO

Within the last three decades Scanning Probe Microscopy has been developed to a powerful tool for measuring surfaces and their properties on an atomic scale such that users can be found nowadays not only in academia but also in industry. This development is still pushed further by researchers, who continuously exploit new possibilities of this technique, as well as companies that focus mainly on the usability. However, although imaging has become significantly easier, the time required for a safe approach (without unwanted tip-sample contact) can be very time consuming, especially if the microscope is not equipped or suited for the observation of the tip-sample distance with an additional optical microscope. Here we show that the measurement of the absolute tip-sample capacitance provides an ideal solution for a fast and reliable pre-approach. The absolute tip-sample capacitance shows a generic behavior as a function of the distance, even though we measured it on several completely different setups. Insight into this behavior is gained via an analytical and computational analysis, from which two additional advantages arise: the capacitance measurement can be applied for observing, analyzing, and fine-tuning of the approach motor, as well as for the determination of the (effective) tip radius. The latter provides important information about the sharpness of the measured tip and can be used not only to characterize new (freshly etched) tips but also for the determination of the degradation after a tip-sample contact/crash.

13.
Ultramicroscopy ; 171: 70-76, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27615394

RESUMO

To make the forces in an Atomic Force Microscope that operates in a dynamic mode with one or multiple vibrations applied to the cantilever, quantitative, one needs to relate a change in resonance frequency of the cantilever to a specific tip-sample interaction. Due to the time dependence of the force between the tip and sample caused by the vibrations, this task is not only difficult, but in fact only possible to solve for certain limiting cases, if one follows common theoretical approaches with a Taylor expansion around the deflection point. Here, we present an analytical method for calculating the resonance frequencies of the cantilever that is valid for any tip-sample interaction. Instead of linearizing the tip-sample interaction locally, we calculate an averaged, weighted linearization taking into account all positions of the tip while vibrating. Our method bridges, therefore, the difficult gap between a free oscillating cantilever and a cantilever that is pushed infinitely hard into contact with a surface, which describes a clamped-pinned boundary condition. For a correct description of the cantilever dynamics, we take into account both the tip mass and the tip moment of inertia. Applying our model, we show that it is possible to calculate the modal response of a cantilever as a function of the tip-sample interaction strength. Based on these modal vibration characteristics, we show that the higher resonance frequencies of a cantilever are completely insensitive to the strength of the tip-sample interaction.

14.
Methods Cell Biol ; 134: 377-89, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27312499

RESUMO

Hemostasis is a coordinated system through which blood is prevented from exiting a closed circulatory system. We have taken advantage of the zebrafish, an emerging model for the study of blood coagulation, and describe three techniques for quantitative analysis of primary and secondary hemostasis. Collectively, these three techniques comprise a toolset to aid in our understanding of hemostasis and pathological clotting.


Assuntos
Coagulação Sanguínea/genética , Hemostasia/genética , Trombose/genética , Animais , Humanos , Larva/genética , Larva/fisiologia , Trombose/fisiopatologia , Peixe-Zebra/genética , Peixe-Zebra/fisiologia
15.
Exp Clin Endocrinol Diabetes ; 113(7): 372-5, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16025397

RESUMO

Oestrogens produce cholestasis by inhibition of bile acid (BA) transport as well as by inhibition of BA synthesis in the liver. The present work was done to clarify the relevance of altered serum BA profile in 28 healthy pregnant women from the 15th to the 40th weeks of pregnancy with increasing oestrogen serum concentrations in comparison to 6 to 8 weeks after delivery with normalized oestrogen status. For the first time 6 free and 10 taurine- and glycine-conjugated BAs were analysed during the normal pregnancy by HPLC with postcolumn derivatisation and fluorescence detection. The primary BAs cholic (CA) and chenodeoxycholic acid (CDCA) as well as their glycine (G-) and taurine (T-) conjugates amount to nearly 70 % of total BAs in serum and were not changed from the 15th to the 40th weeks of pregnancy, but free and G-CDCA increased significantly after delivery. Among the secondary BAs, which were produced in the intestine by bacteria due to dehydroxylation of the primary bile acids CA and CDCA, only taurine-conjugated deoxycholic acid (T-DCA) decreased significantly after delivery. The free BAs, produced by bacteria in the intestine due to deconjugation, were not changed during pregnancy but had doubled in childbed. Some BAs occurred seldom and in small amounts in the serum, but during pregnancy not more frequent than after delivery. Contrary to expectation the increasing oestrogen concentrations did neither enhance total serum bile acids nor change bile acid profile during pregnancy.


Assuntos
Ácidos e Sais Biliares/sangue , Período Pós-Parto/sangue , Gravidez/sangue , Adulto , Estradiol/sangue , Feminino , Humanos , Estatísticas não Paramétricas
16.
Tissue Cell ; 37(2): 135-43, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15748740

RESUMO

The origin of midgut epithelium may begin either from yolk cells (energids), tips of stomo- and proctodaeum (ectoderm), inner layer (endoderm) or from both kinds of the above mentioned cells. The origin of the midgut epithelium in wingless insects (Apterygota) has still not been determined. In Thermobia domestica the formation of midgut is much delayed, and it completes in the post-embryonic stage, while the stomo- and the proctodaeum are well-developed in the embryonic period. The energids, which remain inside the yolk, start to migrate to its periphery, where they arrange singly close to cell membrane. The yolk mass with the energids at the 14th day of embryogenesis are referred to as the primary midgut. During the first instar larval stage more and more energids migrate to the yolk periphery and the cell membrane starts to form numerous foldings surrounding the groups of energids, which in turn lead to formation of isolated regenerative cell groups. Eventually the cell membrane invaginations reach the center of the yolk mass. Large cells of the primary epithelium, surrounding the newly formed midgut lumen are formed. The cells of the primary epithelium are filled with yolk and are equipped with microvilli pointing to the midgut lumen. As the yolk is being digested, the process of the primary epithelium cells degeneration begins. The cells are getting shorter and start to degenerate. The definitive midgut epithelium is formed from proliferating regenerative cells. It consists of regularly spaced regenerative cell groups as well as the epithelial cells. The ultrastructure of both these cell groups has been described.


Assuntos
Sistema Digestório/embriologia , Epitélio/embriologia , Insetos/embriologia , Animais , Sistema Digestório/ultraestrutura , Ectoderma/ultraestrutura , Embrião não Mamífero/ultraestrutura , Desenvolvimento Embrionário , Endoderma/ultraestrutura , Epitélio/ultraestrutura , Insetos/ultraestrutura , Larva/citologia , Metamorfose Biológica , Microvilosidades/ultraestrutura , Modelos Biológicos , Saco Vitelino/ultraestrutura
17.
Transplant Proc ; 37(7): 2988-93, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16213282

RESUMO

According to the US Food and Drug Administration (FDA), if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product, then it is equivalent and can be substituted (switchable) for that drug product. Methods used to define bioequivalence as stated by the FDA rules (FDA 21 CFR 320, 24) are (1) pharmacokinetic (PK) studies in healthy volunteers, (2) comparative clinical trials, and (3) pharmacodynamic (PD) studies (bioactivity). We evaluated the switchability of Equoral (IVAX-USA) with Neoral (Novartis Switzerland using all FDA rules. In a single oral dose, we undertook a comparative bioavailability study of Equoral (IVAX, USA) Neoral (Novartis, USA), and Neoral (Novartis UK). The pharmacokinetics of Equoral and Neoral were determined with blood levels at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 42, and 48 hours. The area under curve (AUC), AUC extrapolated to infinity (AUC0-inf), rate of absorption (Tmax), extent of absorption (Cmax), half time (t1/2) of Equoral and Neoral were all within the 90% confidence interval of 80% to 125% boundaries. A comparative multinational multicenter clinical trial in stable renal transplant patients included 70 patients (22 women and 48 men) of mean age of 33 years (range, 26 to 43) was performed in Turkey, Lebanon, and Pakistan. In this study the ratios of LSM and the 90% confidence intervals for the Nontransformed/Parameters (AUC0-t, AUCinf, Tmax, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, which are within the 80% to 125% FDA acceptance range. For immunosuppressive drugs, the site of action is the lymphocyte and the measurable response is the decrease in lymphocyte count caused by the relative concentration of the drug in the lymphocyte. In a controlled switch, fixed-dose study, both Equoral and Neoral achieved the same concentration in the lymphocytes and caused the same degree of lymphocyte count reduction. The results of the testing (bioavailability-bioequivalence, clinical studies, and pharmacodynamic-bioactivity) required by FDA for interchangeability ("switchability") of immunosuppressive agents suggests that Neoral and Equoral are switchable.


Assuntos
Ciclosporina/farmacocinética , Ciclosporina/uso terapêutico , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Transplante de Rim/fisiologia , United States Food and Drug Administration/normas , Adulto , Área Sob a Curva , Disponibilidade Biológica , Intervalos de Confiança , Sistemas de Liberação de Medicamentos , Feminino , Guias como Assunto , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
18.
Artigo em Inglês | MEDLINE | ID: mdl-16601778

RESUMO

Cyclosporine A (CyA) is a standard component of immunosuppressive regimens. It is a critical-dose drug for which a minor change in absorption can have important clinical consequences. The aim of the study was to compare the pharmacokinetics and safety of the new generic CyA formulation, Equoral capsules, after a switch from original formulation, Neoral capsules, in seventy stable adult renal transplant recipients. The extent and rate of pharmacokinetic parameters for bioequivalence were compared in a non-randomized, steady-state clinical study with fixed non-replicate study design. Pharmacokinetic analysis of CyA have shown that both the rate and extent of absorption of Equoral does not differ significantly from that of Neoral. At identical dosing, the new formulation was found to have geometric means of C(max) 717 ng/ml and AUCtau 3108 ng/ml.h, while corresponding results of comparator were 725 ng/ml and AUCtau 3039 ng/ml.h, respectively. The 90 % confidence intervals of C(max) and AUCtau were within 80- 125 % interval of the mean values. The results suggest that Equoral capsules can be used as an alternative treatment to Neoral capsules in CyA regimen.


Assuntos
Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Transplante de Rim , Absorção , Adulto , Cápsulas , Ciclosporina/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino
19.
Nat Commun ; 6: 6444, 2015 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-25753109

RESUMO

Heterodyne detection schemes are widely used to detect and analyse high-frequency signals, which are unmeasurable with conventional techniques. It is the general conception that the heterodyne signal is generated only by mixing and that beating can be fully neglected, as it is a linear effect that, therefore, cannot produce a heterodyne signal. Deriving a general analytical theory, we show, in contrast, that both beating and mixing are crucial to explain the heterodyne signal generation. Beating even dominates the heterodyne signal, if the nonlinearity of the mixing element (mixer) is of higher order than quadratic. The specific characteristic of the mixer determines its sensitivity for beating. We confirm our results with both a full numerical simulation and an experiment using heterodyne force microscopy, which represents a model system with a highly non-quadratic mixer. As quadratic mixers are the exception, many results of previously reported heterodyne measurements may need to be reconsidered.

20.
Rev Sci Instrum ; 86(3): 033704, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25832235

RESUMO

The application of ultrasound in an Atomic Force Microscope (AFM) gives access to subsurface information. However, no commercially AFM exists that is equipped with this technique. The main problems are the electronic crosstalk in the AFM setup and the insufficiently strong excitation of the cantilever at ultrasonic (MHz) frequencies. In this paper, we describe the development of an add-on that provides a solution to these problems by using a special piezo element with a lowest resonance frequency of 2.5 MHz and by separating the electronic connection for this high frequency piezo element from all other connections. In this sense, we support researches with the possibility to perform subsurface measurements with their existing AFMs and hopefully pave also the way for the development of a commercial AFM that is capable of imaging subsurface features with nanometer resolution.

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