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1.
Radiol Oncol ; 58(2): 206-213, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38613840

RESUMO

BACKGROUND: This retrospective study investigated the efficacy of endovascular treatment with multilayer flow modulators (MFMs) for treating aortic aneurysms in high-risk patients unsuitable for conventional treatments. PATIENTS AND METHODS: Conducted from 2011 to 2019 at a single center, this retrospective observational study included 17 patients who underwent endovascular treatment with MFMs. These patients were selected based on their unsuitability for traditional surgical or endovascular procedures. The study involved meticulous pre-procedural planning, precise implantation of MFMs, and follow-up using CT angiography. The primary focus was on volumetric and flow volume changes in aneurysms, along with traditional diameter measurements. Moreover, the technical success and post-procedural complications were also registered. RESULTS: The technical success rate was 100%, and 30-day procedural complication rate was 17.6%. Post-treatment assessments revealed that 11 out of 17 patients showed a decrease in flow volume within the aneurysm sac, indicative of a favorable hemodynamic response. The median decrease in flow volume was 12 ml, with a median relative decrease of 8%. However, there was no consistent reduction in aneurysm size; most aneurysms demonstrated a median increase in volume for 46 ml and median increase in diameter for 18 mm. CONCLUSIONS: While MFMs offer a potential alternative for high-risk aortic aneurysm patients, their effectiveness in preventing aneurysm expansion is limited. The results suggest that MFMs can provide a stable hemodynamic environment but do not reliably reduce aneurysm size. This underscores the need for ongoing vigilance and long-term monitoring in patients treated with this technology.


Assuntos
Procedimentos Endovasculares , Humanos , Estudos Retrospectivos , Masculino , Feminino , Idoso , Procedimentos Endovasculares/métodos , Resultado do Tratamento , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/fisiopatologia , Angiografia por Tomografia Computadorizada , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Stents
2.
PeerJ ; 11: e16559, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38144180

RESUMO

Background: The foramen spinosum (FS) is a pivotal passage for neurovascular structures within the skull base. We performed a detailed morphometric and morphological analysis of the FS to emphasize its clinical relevance. Materials & Methods: The study was performed on dried skull specimens obtained from the anatomical collections of the Institute of Anatomy and Institute of Forensic Medicine of the University of Ljubljana. The morphometric and morphologic features of FS in 126 whole human skulls and 15 skull halves were analyzed, including dimensions, shape, and other anatomical variations, as well as relationships to surrounding structures. Measurements were done with a digital sliding caliper. Results: The mean length and width of the FS were 2.45 ± 0.65 mm and 2.03 ± 0.53 mm on the right side and 2.49 ± 0.61 mm and 2.08 ± 0.48 mm on the left side. The most frequently observed shape was round (56.7%), followed by oval (28.2%), irregular (8.7%) and drop shaped (6.3%). Several anatomical variations were also noted, including FS duplication, confluences with other foramina, and FS obstruction due to marginal bony outgrowths. Conclusion: The FS exhibits notable interindividual differences in anatomical characteristics which should be considered during neurosurgical procedures and radiological interventions in the skull base.


Assuntos
Base do Crânio , Osso Esfenoide , Humanos , Osso Esfenoide/anatomia & histologia , Base do Crânio/diagnóstico por imagem , Procedimentos Neurocirúrgicos
3.
Biomol Biomed ; 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37902457

RESUMO

It is not well-understood how type 1 diabetes (T1DM) affects skeletal muscle histological phenotype, particularly capillarisation. This study aimed to analyze skeletal muscle myosin heavy chain (MyHC) fibre type changes and 3D capillary network characteristics in experimental T1DM mice. Female C57BL/6J-OlaHsd mice were categorized into streptozotocin (STZ)-induced diabetic (n = 12) and age-matched non-diabetic controls (n =12). The muscle fibre phenotype of the soleus, gluteus maximus, and gastrocnemius muscles were characterized based on the expression of MyHC isoforms, while capillaries of the gluteus maximus were assessed with immunofluorescence staining, confocal laser microscopy and 3D image analysis. STZ-induced diabetic mice exhibited elevated glucose levels, reduced body weight, and prolonged thermal latency, verifying the T1DM phenotype. In both T1DM and non-diabetic mice, the gluteus maximus and gastrocnemius muscles predominantly expressed fast-twitch type 2b fibers, with no significant differences noted. However, the soleus muscle in non-diabetic mice had a greater proportion of type 2a fibers and comparable type 1 fiber densities (26.2 ± 14.6% vs 21.9 ± 13.5%) relative to diabetic mice. T1DM mice showed reduced fiber diameters (P = 0.026), and the 3D capillary network analysis indicated a higher capillary length per muscle volume in the gluteus maximus of diabetic mice compared to controls (P < 0.05). Overall, T1DM induced significant changes in the skeletal muscle, including shifts in MyHC fibre types, decreased fibre diameters, and increased relative capillarisation, possibly due to muscle fibre atrophy. Our findings emphasize the superior detail provided by the 3D analytical method for characterizing skeletal muscle capillary architecture, highlighting caution in interpreting 2D data for capillary changes in T1DM.

4.
Comput Biol Med ; 165: 107375, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37611421

RESUMO

BACKGROUND: The aim of the present study was to predict the time to onset and duration of action of two local anesthetics (lidocaine and bupivacaine) based on experimental dimensions of a typical nerve and experimental octanol/water partition coefficients. METHODS: We began our compilation of experimental data with a numerical solution of the Smoluchowski equation for the transfer of lidocaine and bupivacaine across the axon membrane in the region of the node of Ranvier (axolemma) and across the Schwann cell. The difference between the aqueous and lipid environments of the neuron was simulated by including the coordinate-dependent chemical potential. In the second step, the permeation rates calculated using the diffusion equation were used to solve a system of four ordinary differential equations. This approach allowed us to simulate the cellular environment for a longer time and to compare our model with pharmacokinetic properties (time to onset and duration of action) of local anesthetics from the literature. The behavior of local anesthetics under physiological conditions and in case of local acidosis was also simulated. RESULTS: We demonstrated that local anesthetics cross the axolemma in a time span of less than 1 µs. The time to onset of action, controlled by diffusion from the epineurium to an axon with a typical distance of 500 µm, was 167 s and 186 s for lidocaine and bupivacaine, respectively. The calculated half-life, which is a measure of the duration of action, was 41 min and 328 min for lidocaine and bupivacaine, respectively. CONCLUSIONS: Duration of action is controlled by the storage capacity of lipophilic compartments around the axon, which is higher for bupivacaine but lower in local acidosis. For the latter case, the literature, including textbooks, provides a misinterpretation, namely that protonated species cannot penetrate the membrane.


Assuntos
Bupivacaína , Lidocaína , Bupivacaína/farmacocinética , Lidocaína/farmacocinética , Anestésicos Locais/farmacocinética , Fibras Nervosas Mielinizadas
5.
Front Physiol ; 14: 1070227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36909220

RESUMO

Introduction: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that measures the anisotropy of water diffusion. Clinical magnetic resonance imaging scanners enable visualization of the structural integrity of larger axonal bundles in the central nervous system and smaller structures like peripheral nerves; however, their resolution for the depiction of nerve fascicular morphology is limited. Accordingly, high-field strength MRI and strong magnetic field gradients are needed to depict the fascicular pattern. The study aimed to quantify diffusion tensor indices with high-field strength MRI within different anatomical compartments of the median nerve and determine if they correlate with nerve structure at the fascicular level. Methods: Three-dimensional pulsed gradient spin-echo (PGSE) imaging sequence in 19 different gradient directions and b value 1,150 s/mm2 was performed on a 9.4T wide-bore vertical superconducting magnet. Nine-millimeter-long segments of five median nerve samples were obtained from fresh cadavers and acquired in sixteen 0.625 mm thick slices. Each nerve sample had the fascicles, perineurium, and interfascicular epineurium segmented. The diffusion tensor was calculated from the region-average diffusion-weighted signals for all diffusion gradient directions. Subsequently, correlations between diffusion tensor indices of segmentations and nerve structure at the fascicular level (number of fascicles, fascicular ratio, and cross-sectional area of fascicles or nerve) were assessed. The acquired diffusion tensor imaging data was employed for display with trajectories and diffusion ellipsoids. Results: The nerve fascicles proved to be the most anisotropic nerve compartment with fractional anisotropy 0.44 ± 0.05. In the interfascicular epineurium, the diffusion was more prominent in orthogonal directions with fractional anisotropy 0.13 ± 0.02. Diffusion tensor indices within the fascicles and perineurium differed significantly between the subjects (p < 0.0001); however, there were no differences within the interfascicular epineurium (p ≥ 0.37). There were no correlations between diffusion tensor indices and nerve structure at the fascicular level (p ≥ 0.29). Conclusion: High-field strength MRI enabled the depiction of the anisotropic diffusion within the fascicles and perineurium. Diffusion tensor indices of the peripheral nerve did not correlate with nerve structure at the fascicular level. Future studies should investigate the relationship between diffusion tensor indices at the fascicular level and axon- and myelin-related parameters.

7.
Diagnostics (Basel) ; 13(5)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36900106

RESUMO

The foramen ovale (FO) is a crucial feature of the skull base, serving as a passage for clinically important neurovascular structures. The present study aimed to provide a comprehensive morphometric and morphologic analysis of the FO and highlight the clinical significance of the anatomical characterization. A total of 267 FO were analyzed in skulls obtained from deceased inhabitants of the Slovenian territory. The anteroposterior (length) and the transverse (width) diameters were measured using a digital sliding vernier caliper. Dimensions, shape, and anatomical variations of FO were analyzed. The mean length and width of the FO were 7.13 and 3.71 mm on the right side and 7.20 and 3.88 mm on the left side. The most frequently observed shape was oval (37.1%), followed by almond (28.1%), irregular (21.0%), D-shaped (4.5%), round (3.0%), pear-shaped (1.9%), kidney-shaped (1.5%), elongated (1.5%), triangular (0.7%), and slit-like (0.7%). In addition, marginal outgrowths (16.6%) and several anatomical variations were noted, including duplications, confluences, and obstruction due to a complete (5.6%) or incomplete (8.2%) pterygospinous bar. Our observations revealed substantial interindividual variation in the anatomical characteristics of the FO in the studied population, which could potentially impact the feasibility and safety of neurosurgical diagnostic and therapeutic procedures.

8.
Medicina (Kaunas) ; 59(3)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36984563

RESUMO

Background and Objectives: Bone fractures contribute significantly to the global disease and disability burden and are associated with a high and escalating incidence and tremendous economic consequences. The increasingly challenging climate of orthopaedic training and practice re-echoes the established potential of leveraging computer-based reality technologies to support patient-specific simulations for procedural teaching and surgical precision. Unfortunately, despite the recognised potential of virtual reality technologies in orthopaedic surgery, its adoption and integration, particularly in fracture procedures, have lagged behind other surgical specialities. We aimed to review the available virtual reality systems adapted for orthopaedic trauma procedures. Materials and Methods: We performed an extensive literature search in Medline (PubMed), Science Direct, SpringerLink, and Google Scholar and presented a narrative synthesis of the state of the art on virtual reality systems for bone trauma procedures. Results: We categorised existing simulation modalities into those for fracture fixation techniques, drilling procedures, and prosthetic design and implantation and described the important technical features, as well as their clinical validity and applications. Conclusions: Over the past decade, an increasing number of high- and low-fidelity virtual reality systems for bone trauma procedures have been introduced, demonstrating important benefits with regard to improving procedural teaching and learning, preoperative planning and rehearsal, intraoperative precision and efficiency, and postoperative outcomes. However, further technical developments in line with industry benchmarks and metrics are needed in addition to more standardised and rigorous clinical validation.


Assuntos
Ortopedia , Realidade Virtual , Humanos , Simulação por Computador , Ortopedia/educação , Interface Usuário-Computador , Fixação de Fratura
9.
Diagnostics (Basel) ; 13(3)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36766586

RESUMO

The portal venous system is a network of vessels that carry blood from the capillary beds of the major abdominal organs to the liver. During embryology, the portal venous system can develop aberrantly, leading to vascular connections between the portal and systemic venous circulation known as portosystemic shunts. The purpose of this comparative review with a few short representative case reports was to present the similarities and differences in portosystemic shunts in humans and small animals and their radiologic evaluation. Aberrant vascular connections between the portal and systemic venous circulation enable portal blood to bypass metabolism and detoxification in the liver, leading to significant clinical implications. Portosystemic shunts are very rare in humans, but these connections are much more common in small animals, affecting up to 0.6% of small animals. Portosystemic shunts can be congenital or acquired and are divided into intrahepatic and extrahepatic types. Because of its ability to accurately assess abdominal structures, large vessels, and their flow dynamics without anesthesia, ultrasonography has become the first imaging modality employed for the diagnostic evaluation of portosystemic shunts in both humans and small animals. This is usually followed by contrast-enhanced computed tomographic angiography in order to better define the exact shunt anatomy and to plan treatment. It is important to understand the embryology, anatomy, pathology, and pathophysiology of portosystemic shunts in order to understand the findings of radiologic imaging and to initiate appropriate treatment.

10.
Reg Anesth Pain Med ; 48(7): 359-364, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36657956

RESUMO

BACKGROUND: Injections of local anesthetics into pterygopalatine fossa gained popularity for treating acute and chronic facial pain and headaches. Injury of maxillary artery during pterygopalatine fossa injection can result in pseudoaneurysm formation or acute bleeding. We aimed to identify the optimal approach into pterygopalatine fossa by comparing feasibility and safety of suprazygomatic and two infrazygomatic approaches. METHODS: We analyzed 100 diagnostic CT angiographies of cerebral arteries using 3D virtual reality. Each approach was determined as a target point in pterygomaxillary fissure and an array of outermost edges trajectories leading to it. The primary outcomes were feasibility and safety for each approach. The secondary outcome was the determination of maxillary artery position for each approach to identify the safest needle entry point. RESULTS: Suprazygomatic approach was feasible in 96.5% of cases, while both infrazygomatic approaches were feasible in all cases. Suprazygomatic approach proved safe in all cases, posterior infrazygomatic in 73.5%, and anterior infrazygomatic in 38%. The risk of maxillary artery puncture in anterior infrazygomatic approach was 14.7%±26.4% compared to 7.5%±17.2%. in posterior infrazygomatic with the safest needle entry point in the upper-lateral quadrant in both approaches. CONCLUSION: The suprazygomatic approach proved to be the safest, however not always feasible. The posterior infrazygomatic approach was always feasible and predominantly safe if the needle entry point was just anterior to the condylar process. The anterior infrazygomatic approach was always feasible, however least safe even with an optimal needle entry point just anterior to the coronoid process.


Assuntos
Anestésicos Locais , Fossa Pterigopalatina , Humanos , Estudos de Viabilidade , Punções , Nervo Maxilar
11.
Front Endocrinol (Lausanne) ; 14: 1308373, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38189046

RESUMO

Introduction: The global burden of diabetes mellitus is escalating, and more efficient investigative strategies are needed for a deeper understanding of underlying pathophysiological mechanisms. The crucial role of skeletal muscle in carbohydrate and lipid metabolism makes it one of the most susceptible tissues to diabetes-related metabolic disorders. In tissue studies, conventional histochemical methods have several technical limitations and have been shown to inadequately characterise the biomolecular phenotype of skeletal muscle to provide a holistic view of the pathologically altered proportions of macromolecular constituents. Materials and methods: In this pilot study, we examined the composition of five different human skeletal muscles from male donors diagnosed with type 2 diabetes and non-diabetic controls. We analysed the lipid, glycogen, and collagen content in the muscles in a traditional manner with histochemical assays using different staining techniques. This served as a reference for comparison with the unconventional analysis of tissue composition using Fourier-transform infrared spectroscopy as an alternative methodological approach. Results: A thorough chemometric post-processing of the infrared spectra using a multi-stage spectral decomposition allowed the simultaneous identification of various compositional details from a vibrational spectrum measured in a single experiment. We obtained multifaceted information about the proportions of the different macromolecular constituents of skeletal muscle, which even allowed us to distinguish protein constituents with different structural properties. The most important methodological steps for a comprehensive insight into muscle composition have thus been set and parameters identified that can be used for the comparison between healthy and diabetic muscles. Conclusion: We have established a methodological framework based on vibrational spectroscopy for the detailed macromolecular analysis of human skeletal muscle that can effectively complement or may even serve as an alternative to histochemical assays. As this is a pilot study with relatively small sample sets, we remain cautious at this stage in drawing definitive conclusions about diabetes-related changes in skeletal muscle composition. However, the main focus and contribution of our work has been to provide an alternative, simple and efficient approach for this purpose. We are confident that we have achieved this goal and have brought our methodology to a level from which it can be successfully transferred to a large-scale study that allows the effects of diabetes on skeletal muscle composition and the interrelationships between the macromolecular tissue alterations due to diabetes to be investigated.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Masculino , Projetos Piloto , Músculo Esquelético , Bioensaio , Glicogênio
12.
Int J Mol Sci ; 23(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36233143

RESUMO

Myofascial disease is an important complication associated with obesity and one of the leading causes of physical disability globally. In the face of limited treatment options, the burden of myofascial disorders is predicted to increase along with the escalating prevalence of obesity. Several pathological processes in obesity contribute to modifications in fascial extracellular matrix mechanical and biological properties and functions. Changes in adipose tissue metabolism, chronic inflammatory phenotype, oxidative stress, and other mechanisms in obesity may alter the physiochemical and biomechanical properties of fascial hyaluronan. Understanding the pathophysiological importance of hyaluronan and other components of the fascial connective tissue matrix in obesity may shed light on the etiology of associated myofascial disorders and inform treatment strategies. Given its unique and favorable pharmacological properties, hyaluronan has found a broad range of clinical applications, notably in orthopedic conditions such as osteoarthritis and tendinopathies, which share important pathophysiological mechanisms implicated in myofascial diseases. However, while existing clinical studies uniformly affirm the therapeutic value of hyaluronan in myofascial disorders, more extensive studies in broader pharmacological and clinical contexts are needed to firmly validate its therapeutic adaptation.


Assuntos
Fáscia , Ácido Hialurônico , Matriz Extracelular , Fáscia/metabolismo , Humanos , Ácido Hialurônico/metabolismo , Ácido Hialurônico/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo
13.
Int J Mol Sci ; 23(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36293355

RESUMO

Age, obesity, and diabetes mellitus are pathophysiologically interconnected factors that significantly contribute to the global burden of non-communicable diseases. These metabolic conditions are associated with impaired insulin function, which disrupts the metabolism of carbohydrates, lipids, and proteins and can lead to structural and functional changes in skeletal muscle. Therefore, the alterations in the macromolecular composition of skeletal muscle may provide an indication of the underlying mechanisms of insulin-related disorders. The aim of this study was to investigate the potential of Fourier transform infrared (FTIR) spectroscopy to reveal the changes in macromolecular composition in weight-bearing and non-weight-bearing muscles of old, obese, insulin-resistant, and young streptozotocin (STZ)-induced diabetic mice. The efficiency of FTIR spectroscopy was evaluated by comparison with the results of gold-standard histochemical techniques. The differences in biomolecular phenotypes and the alterations in muscle composition in relation to their functional properties observed from FTIR spectra suggest that FTIR spectroscopy can detect most of the changes observed in muscle tissue by histochemical analyses and more. Therefore, it could be used as an effective alternative because it allows for the complete characterization of macromolecular composition in a single, relatively simple experiment, avoiding some obvious drawbacks of histochemical methods.


Assuntos
Diabetes Mellitus Experimental , Resistência à Insulina , Camundongos , Animais , Diabetes Mellitus Experimental/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Estreptozocina , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Insulina/metabolismo , Lipídeos/química
14.
Pharmaceutics ; 14(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36145571

RESUMO

Little is known regarding the pharmacological properties of extended-release local anesthetics in the setting of diabetic peripheral neuropathy. We investigated and compared the duration of sciatic nerve block following administration of clinically relevant concentrations of liposomal bupivacaine (LB) and bupivacaine hydrochloride (BH) in diabetic mice with peripheral neuropathy. In this prospective, randomized, and double-blind study, twenty-four female C57BL/6J-OlaHsd mice were assigned to a streptozotocin-induced type 1 diabetes group and a control group without diabetes. The presence of peripheral neuropathy was established by assessing the duration of thermal latency of the plantar and tail-flick tests, following which both groups were subdivided into two subgroups in which 35 mg/kg of 1.31% LB and 7 mg/kg of 0.25% BH were respectively administered for sciatic nerve block. The average sensory block duration with BH was 106 min and 117.1 min in the control and diabetic groups, respectively. With LB, the average sensory block duration was 118 min in the control mice, while in mice with diabetic peripheral neuropathy, the average block duration was significantly longer and above the 270 min limit set in our study. Accordingly, sensory block duration was longer with LB compared to BH, and diabetic peripheral neuropathy significantly increased sciatic nerve block duration with LB.

15.
Int J Mol Sci ; 23(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35055038

RESUMO

Obesity is a worrisomely escalating public health problem globally and one of the leading causes of morbidity and mortality from noncommunicable disease. The epidemiological link between obesity and a broad spectrum of cardiometabolic disorders has been well documented; however, the underlying pathophysiological mechanisms are only partially understood, and effective treatment options remain scarce. Given its critical role in glucose metabolism, skeletal muscle has increasingly become a focus of attention in understanding the mechanisms of impaired insulin function in obesity and the associated metabolic sequelae. We examined the current evidence on the relationship between microvascular dysfunction and insulin resistance in obesity. A growing body of evidence suggest an intimate and reciprocal relationship between skeletal muscle microvascular and glucometabolic physiology. The obesity phenotype is characterized by structural and functional changes in the skeletal muscle microcirculation which contribute to insulin dysfunction and disturbed glucose homeostasis. Several interconnected etiologic molecular mechanisms have been suggested, including endothelial dysfunction by several factors, extracellular matrix remodelling, and induction of oxidative stress and the immunoinflammatory phenotype. We further correlated currently available pharmacological agents that have deductive therapeutic relevance to the explored pathophysiological mechanisms, highlighting a potential clinical perspective in obesity treatment.


Assuntos
Resistência à Insulina , Microcirculação , Microvasos/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Biomarcadores , Gerenciamento Clínico , Suscetibilidade a Doenças , Endotélio Vascular/metabolismo , Metabolismo Energético , Matriz Extracelular , Regulação da Expressão Gênica , Homeostase , Humanos , Insulina/metabolismo , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Terapia de Alvo Molecular , Obesidade/terapia , Oxirredução , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo
16.
Acta Chim Slov ; 68(2): 426-432, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34738123

RESUMO

Local anesthetics are one of the most widely used drug classes in clinical practice. Like many other biological molecules, their properties are altered depending on their protonation status, which is dependent on the pH of the environment. We studied the transport energetics of seven local anesthetics from the extracellular fluid across the biological membrane to the axoplasm in order to understand the effect of pH value on their efficacy and other pharmaco-dynamic properties. In this we applied three different methods of solvent reaction field in conjunction with quantum chemical calculations to reproduce experimental values of n-octanol/water partition coefficients for both neutral and protonated forms. Only the SMD method of Cramer and Truhlar was able to reproduce experimental partition coefficient values. The results are discussed in terms of the function of local anesthetics under physiological conditions and in the case of local acidosis.

17.
Biomed Chromatogr ; 35(11): e5198, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34121212

RESUMO

In the present study, we developed a simple and rapid analytical method for the quantification of bupivacaine hydrochloride in human biopsy samples of adipose, muscle, neural, connective and cartilage tissue using liquid chromatography-mass spectrometry. Anesthetics were extracted from the tissue samples using 0.1% formic acid in acetonitrile for protein denaturation and hexane for removal of lipophilic impurities. Analytes were separated adequately on Phenomenex Luna Omega polar C18 column using a gradient mobile phase 0.1% formic acid in water and 0.1% formic acid in acetonitrile. The lower limits of quantification were ≤ 97 ng g-1 tissue for all studied tissues. Intra-day recoveries were between 48.2% and 82.1% with relative standard deviations (RSDs) between 1.47% and 14.28%, whereas inter-day recoveries were between 52.2% and 77.6% with RSDs between 2.98% and 14.79%. The calibration curve showed a linear fit with R2 higher than 0.99 in the concentration range from 0.16 to 100 µg g-1 . Lidocaine hydrochloride was tested as internal standard because its recoveries and matrix effects were comparable to bupivacaine hydrochloride. Post-analytical corrections of measured bupivacaine tissue concentrations can accordingly be made based on recovery of lidocaine as internal standard, with recoveries between 51.2% and 86.9% and RSDs between 1.99% and 16.88%. The developed method could be used to study time-dependent spread of bupivacaine locally or to more distant locations across tissue barriers.


Assuntos
Bupivacaína/análise , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Biópsia , Bupivacaína/química , Bupivacaína/isolamento & purificação , Humanos , Modelos Lineares , Músculo Esquelético/patologia , Tecido Nervoso/patologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Bosn J Basic Med Sci ; 21(6): 730-738, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082690

RESUMO

In obesity, accumulation of lipid droplets in skeletal muscle fibers and a shift towards fast muscle fiber types can both contribute to insulin resistance. However, it is not yet clear how intramyocellular lipid accumulation and fiber type changes are associated. Therefore, we investigated to what extent the lipids accumulated in a fiber type-specific manner in the functionally similar fast-, intermediate- and slow-twitch gastrocnemius, plantaris, and soleus muscles, respectively, in high-fat diet-induced obese 54-week-old female C57BL/6JOlaHsd mice (n = 9) compared to control standard-diet-treated lean mice (n = 9). A high-fat diet was administered for 26 weeks. Fiber-type specific intramyocellular lipid content analysis and muscle fiber typing were performed using histochemical analysis of lipids with Sudan Black and immunohistochemical analysis of myosin heavy chains on serial sections of skeletal muscles. Compared to the lean mice, the lipid accumulation was most prominent in types 2a and 2x/d fibers (p < 0.05) of fast-twitch gastrocnemius and intermediate plantaris muscles in the obese mice, while in slow-twitch soleus muscle, there was no significant lipid accumulation in the obese animals. Furthermore, the slow-twitch soleus muscle of the obese mice with no significant change in muscle fiber diameters exhibited the most pronounced shift towards fast-type myosin heavy chain isoform expression (p < 0.05). In contrast, the fast-twitch and intermediate-twitch gastrocnemius and plantaris muscles, respectively, in which the muscle fiber diameters increased (p < 0.05), were more resistant toward myosin heavy chain expression changes. In conclusion, we demonstrated both muscle- and fiber-type specificity in intramyocellular lipid accumulation in obese mice, suggesting that in obesity, similar muscle fiber types in different muscles accumulate lipids differentially.


Assuntos
Metabolismo dos Lipídeos , Músculo Esquelético/metabolismo , Animais , Dieta Hiperlipídica , Feminino , Teste de Tolerância a Glucose , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Cadeias Pesadas de Miosina/metabolismo
19.
Ginekol Pol ; 92(11): 797-803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33914329

RESUMO

OBJECTIVES: To compare the analgesic profile of remifentanil patient-controlled analgesia (RPCA) and combined spinal-epidural analgesia technique (CSEA) in multiparous women during the entire labour. We hypothesized that CSEA would provide a better and more sustained pain reduction than RPCA. MATERIAL AND METHODS: A prospective observational trial under ID NCT02963337 at a university hospital in Slovenia 2017-2018. Analgesic efficacy, satisfaction with pain-relief, adverse effects, labour progress, and outcomes between RPCA (80) and CSEA (81) were compared. RESULTS: CSEA provided significantly lower pain scores during the entire labour. Compared to baseline, significant pain reduction was recorded in both groups after 15 min. No difference was recorded compared to baseline with RPCA and CSEA after 45 and 90 mins, respectively. CSEA provided higher satisfaction than RPCA (5 [5-5] vs 5 [4-5], p < 0.0001). More patients with CSEA opted for the same technique for the next labour [CSEA; 77 (95%) vs RPCA; 65 (81%), p = 0.003]. No crossovers were observed. RPCA was associated with desaturation (34%), bradypnea (21%) and apnoea (25%), which were transitional and easily managed. None had severe sedation. No differences were recorded in labour progress and outcomes. Apgar scores were reassuring in all neonates (> 8). None had umbilical artery pH < 7.0. CONCLUSIONS: In multiparas, CSEA provided superior analgesia and satisfaction than RPCA. Nevertheless, RPCA provided a satisfactory experience, suggesting it could be used when neuraxial analgesia is not available, preferred, or contraindicated. In that case, constant presence of midwife is mandatory for management of clinically significant hypoventilation.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Dor do Parto , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/métodos , Analgesia Controlada pelo Paciente/métodos , Analgésicos , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Recém-Nascido , Dor do Parto/tratamento farmacológico , Medição da Dor , Satisfação do Paciente , Gravidez , Remifentanil
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