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OBJECTIVES: This meta-analysis was aimed at investigating the effectiveness and safety of phrenic nerve infiltration (PNI) against ipsilateral shoulder pain (ISP) after thoracic surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Operating room. PARTICIPANTS: Patients undergoing thoracic surgery. INTERVENTIONS: PNI. MEASUREMENTS AND MAIN RESULTS: MEDLINE, Cochrane Library, and EMBASE databases were searched from inception through December 2021. The primary outcome was the overall incidence of ISP, with secondary outcomes including incidence and severity of ISP at postoperative 6, 24, and 48 hours. Six RCTs involving 482 patients undergoing thoracic surgery were included. Pooled results found a significantly lower incidence of overall ISP in patients with PNI (ie, 23.6%) compared to those without (ie, 53.2%; risk ratio: 0.46, 95% confidence interval: 0.34-0.61; I2â¯=â¯19%; 6 RCTs; nâ¯=â¯474; certainty of evidenceâ¯=â¯high). At postoperative 6, 24, and 48 hours, there was also a significantly lower incidence of ISP in the PNI group than in the control group (certainty of evidence for all outcomesâ¯=â¯high). Besides, the severity of ISP was lower in the PNI group at 6 (certainty of evidenceâ¯=â¯moderate) and 24 hours (certainty of evidenceâ¯=â¯high), with insufficient data for analysis at 48 hours because of only 1 trial. CONCLUSION: This meta-analysis showed that PNI not only reduced the incidence but also improved the severity of ipsilateral shoulder pain after thoracic surgery with a prophylactic effect lasting up to 48 hours. The limited number of included studies warrants further research to support these findings.
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Dor de Ombro , Procedimentos Cirúrgicos Torácicos , Humanos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Nervo Frênico , Período Pós-Operatório , Dor de Ombro/diagnóstico , Dor de Ombro/epidemiologia , Dor de Ombro/etiologia , Procedimentos Cirúrgicos Torácicos/efeitos adversosRESUMO
With the rapid development of technology, unmanned aerial vehicles (UAVs) have become more popular and are applied in many areas. However, there are some environments where the Global Positioning System (GPS) is unavailable or has the problem of GPS signal outages, such as indoor and bridge inspections. Visual inertial odometry (VIO) is a popular research solution for non-GPS navigation. However, VIO has problems of scale errors and long-term drift. This study proposes a method to correct the position errors of VIO without the help of GPS information for vertical takeoff and landing (VTOL) UAVs. In the initial process, artificial landmarks are utilized to improve the positioning results of VIO by the known landmark information. The position of the UAV is estimated by VIO. Then, the accurate position is estimated by the extended Kalman filter (EKF) with the known landmark, which is used to obtain the scale correction using the least squares method. The Inertial Measurement Unit (IMU) data are used for integration in the time-update process. The EKF can be updated with two measurements. One is the visual odometry (VO) estimated directly by a landmark. The other is the VIO with scale correction. When the landmark is detected during takeoff phase, or the UAV is returning to the takeoff location during landing phase, the trajectory estimated by the landmark is used to update the scale correction. At the beginning of the experiments, preliminary verification was conducted on the ground. A self-developed UAV equipped with a visual-inertial sensor to collect data and a high-precision real time kinematic (RTK) to verify trajectory are applied to flight tests. The experimental results show that the method proposed in this research effectively solves the problems of scale and the long-term drift of VIO.
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Bile acid metabolism is a key pathway modulated by intestinal microbiota. Peptacetobacter (Clostridium) hiranonis has been described as the main species responsible for the conversion of primary into secondary fecal unconjugated bile acids (fUBA) in dogs. This multi-step biochemical pathway is encoded by the bile acid-inducible (bai) operon. We aimed to assess the correlation between P. hiranonis abundance, the abundance of one specific gene of the bai operon (baiCD), and secondary fUBA concentrations. In this retrospective study, 133 fecal samples were analyzed from 24 dogs. The abundances of P. hiranonis and baiCD were determined using qPCR. The concentration of fUBA was measured by gas chromatography-mass spectrometry. The baiCD abundance exhibited a strong positive correlation with secondary fUBA (ρ = 0.7377, 95% CI (0.6461, 0.8084), p < 0.0001). Similarly, there was a strong correlation between P. hiranonis and secondary fUBA (ρ = 0.6658, 95% CI (0.5555, 0.7532), p < 0.0001). Animals displaying conversion of fUBA and lacking P. hiranonis were not observed. These results suggest P. hiranonis is the main converter of primary to secondary bile acids in dogs.
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Purpose: Ultrasound-guided interscalene nerve block (UISB) is commonly used to alleviate postoperative pain during shoulder arthroscopy. This retrospective observational study aimed to evaluate the intraoperative advantages and analgesic effects of preoperative UISB. Patients and Methods: In this retrospective observational study, a total of 170 patients underwent shoulder arthroscopy at a tertiary medical center in southern Taiwan throughout 2019. After applying the exclusion criteria, 142 of these cases were included, with 74 and 68 in the UISB group and control groups, respectively. The primary outcome was the evaluation of intraoperative morphine milligram equivalent (MME) consumption. Secondary outcomes were sevoflurane consumption, the use of intraoperative antihypertensive drugs, and postoperative visual analog scale (VAS) scores in the post-anesthesia care unit (PACU) and in the ward at 24 h after surgery. Results: Preoperative UISB effectively reduced opioids and volatile gases during surgery, supported by a 48.1% and 14.8% reduction in the median intraoperative MME and sevoflurane concentrations, respectively, and showed less need for antihypertensive drugs. The preoperative UISB group also showed significantly better performance on the VAS in both the PACU and ward. Conclusion: Taken together, the preoperative UISB reduced not only intraoperative MME and sevoflurane consumption but also had satisfactory VAS scores in both the PACU and ward without any symptomatic respiratory complications. In summary, preoperative UISB is a reliable adjuvant analgesic technique and a key factor in achieving opioid-sparing and sevoflurane-sparing anesthesia and multimodal analgesia during shoulder arthroscopy.
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DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs (n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI < 0 with any targeted taxa outside the reference interval, RI), mild-moderate changes (R = 0.24, 0 < DI < 2), and significant dysbiosis (R = 0.54, 0.73, and 0.91 for DI > 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing in dogs.
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PURPOSE: To investigate the efficacy of plasmin and sulfur hexafluoride (SF(6)) on the vitreoretinal junction, as well as the long-term safety in the eye and effect on the recipient's general health after application in the eye. METHODS: The study design included four groups of rabbits with three animals in each group. Group 1 received an intravitreal injection (IVI) of plasmin and SF(6) in the right eye; group 2 received an IVI of plasmin in the right eye; group 3 received an IVI of SF(6) in the right eye; and group 4 received an IVI of balanced salt solution in the right eye, which served as a normal control. Long-term safety (up to approximately three months) after plasmin and/or SF(6) injection was evaluated morphologically by clinical examination, histology, and immunohistochemistry, and functionally by electroretinograms (ERGs). General health evaluations after intravitreal injection included the assessment of weight gain, food intake, body temperature, and complete blood count analysis. RESULTS: Plasmin plus SF(6) injection resulted in complete posterior vitreous detachment (PVD), whereas plasmin or SF(6) injection alone resulted in only partial PVD. Balanced salt solution did not induce PVD. Eighty days after intravitreal injection, there were no major differences among the eyes of the three groups of animals compared with the normal control animals upon clinical evaluation, or regarding retinal morphology and ERGs. The lenses examined remained clear for up to 80 days following the intravitreal injection of plasmin plus SF(6), except one eye in the plasmin-treated group. ERGs decreased transiently one week after intravitreal injection in groups 1 through 3, but animals recovered fully to normal status afterward. General health was not affected after the injection of plasmin plus SF(6). CONCLUSIONS: Efficient vitreoretinal separation could be achieved, and an acceptable long-term safety profile was noted after plasmin plus SF(6) injection in the eye. No major ocular toxicity or systemic toxicity was found after the injection of plasmin plus SF(6). These results provide good support for the future clinical use of plasmin plus SF(6) for treatment of a variety of vitreoretinopathies.
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Fibrinolisina/administração & dosagem , Cristalino/efeitos dos fármacos , Retina/efeitos dos fármacos , Hexafluoreto de Enxofre/administração & dosagem , Corpo Vítreo/efeitos dos fármacos , Descolamento do Vítreo/induzido quimicamente , Animais , Combinação de Medicamentos , Eletrorretinografia , Imuno-Histoquímica , Injeções Intravítreas , Cristalino/citologia , Microscopia Eletrônica de Varredura , Proteólise/efeitos dos fármacos , Coelhos , Retina/citologia , Corpo Vítreo/citologiaRESUMO
BACKGROUND: Topical treatment with vitamin C has been used to treat photoaged skin and as a skin whitener, but no standard procedure exists for percutaneous delivery. OBJECTIVE: To compare skin histology and the permeation of ascorbic acid 2-glucoside (AA2G) after fractional and conventional carbon dioxide (CO(2) ) laser pretreatment. METHODS: The effect on porcine skin of treatment with different strengths of fractional and conventional CO(2) laser treatment was examined using scanning electron microscopy and transmission electron microscopy. Permeation of AA2G through porcine skin was tested in vitro using a Franz diffusion chamber. In vivo changes in fluorescein thiocyanate permeability in nude mice were examined using confocal laser scanning microscopy. RESULTS: Fractional CO(2) laser treatment with four or fewer passes caused less disruption than conventional laser treatment at the same fluence. AA2G permeation using four passes of fractional laser treatment was similar to that seen with conventional CO(2) laser treatment of the same fluence. Changes in permeability and in depth of permeation were higher with conventional than fractional laser treatment. CONCLUSION: Fractional CO(2) laser treatment can cause similar transdermal delivery of AA2G to conventional laser treatment with less skin disruption and a different pattern of histologic change.
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Ácido Ascórbico/análogos & derivados , Lasers de Gás , Absorção Cutânea/efeitos da radiação , Pele/ultraestrutura , Administração Cutânea , Animais , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacocinética , Feminino , Técnicas In Vitro , Camundongos , Camundongos Nus , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Pele/efeitos da radiação , Sus scrofaRESUMO
The rising prevalence of osteoporosis, which can lead to osteoporotic fractures, increases morbidity, mortality, and socioeconomic burden. Multiple factors influencing bone mass have already been identified. The aim of this study was to investigate whether exercise habits and weight-control behaviors can lower the incidence of osteoporosis in the general population. This retrospective study recruited all participants aged 35-70 years who underwent dual-energy X-ray absorptiometry (DXA) from Taiwan Biobank (TWB). The final analysis consisted of 3320 eligible participants divided into two groups; demographic characteristics, prevalence of clinical symptoms, comorbidities, and daily behavior were collected using a self-reported questionnaire. After propensity score matching with a 1:1 ratio, 1107 out of 2214 individuals were classified into the osteoporosis group. Age, body fat rate, body shape, diabetes mellitus, and social status were found to affect the incidence of osteoporosis. Subjects with a habit of regular exercise and weight-control behavior showed decreased odds of osteoporosis. (odds ratio: 0.709 and 0.753, 95% confidence interval: 0.599-0.839 and 0.636-0.890). In the general population, regular exercise or weight-control behavior lowers the incidence of osteoporosis.
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Bancos de Espécimes Biológicos , Osteoporose , Adulto , Idoso , Exercício Físico , Humanos , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/prevenção & controle , Pontuação de Propensão , Fatores de Proteção , Estudos Retrospectivos , Taiwan/epidemiologiaRESUMO
The adductor canal block (ACB) is effective for treating postoperative pain during arthroscopic knee surgery, but its impact on anesthesia course and the optimal administration timing are unknown. This retrospective study addressed these questions. The aim of this study was to compare the effects of preoperative ACB and postoperative ACB on anesthesia course and postoperative recovery. We allocated 215 adult patients who underwent arthroscopic knee surgery under sevoflurane anesthesia between January 2019 and December 2019 to three groups. Group A received general anesthesia without ACB, Group B received ACB before general anesthesia induction, and Group C received ACB in the post-anesthesia recovery unit (PACU). Group B consumed significantly less sevoflurane (0.19 mL/kg/h) and milligram morphine equivalents (0.08 MME) intraoperatively than Groups A (0.22 mL/kg/h; 0.10 MME, respectively) and C (0.22 mL/kg/h; 0.09 MME, respectively). Groups B and C had lower visual analogue scale (VAS) scores upon PACU discharge than Group A. Dynamic, but not at-rest VAS scores, were significantly higher in Group A. Opioid consumption was similar in the ward, but Group A requested more intravenous parecoxib for pain relief. Length of hospital stay was similar. Thus, preoperative ACB reduced the amount of volatile anesthetic required and maintained stable hemodynamics intraoperatively. Preoperative or postoperative ACB improved postoperative pain control. Consequently, preoperative ACB is optimal for intraoperative stress suppression and postoperative pain control.
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Artroplastia do Joelho , Bloqueio Nervoso , Adulto , Anestesia Geral , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Estudos RetrospectivosRESUMO
The internal elastic lamina (IEL) of vein grafts may be modified when exposed to arterialized hemodynamics. We investigated changes of the IEL in the inferior vena cava (IVC) of rats with aortocaval fistulae (ACF). In the IVC of ACF rats, both a markedly increased flow velocity and a mildly increased pressure were demonstrated. In the lower segment where hemodynamic changes were prominent, neointimal hyperplasia was prominently found. The IEL of the IVC in sham-operated rats, observed by confocal microscopy, was composed of parallel elastic fibers. In ACF rats, the IEL degenerated progressively after surgery. The elastic fibers were stretched and gradually became sparse, a change that was more prominent in the lower segment. Eight weeks after surgery, the IEL hardly existed in some areas of the lower segment. Electron microscopy revealed decreased densities and diameters of elastic fibers. Reverse transcriptase-polymerase chain reaction analysis revealed an up-regulation of potent elastases, cathepsins K and S, and matrix metalloproteinase-2 in the IVC of ACF rats. Results of immunohistochemical studies localized cathepsin expression predominantly to the luminal endothelium lining the IEL, suggesting involvement of elastinolysis in the degradation of the IEL. We demonstrated the degradation of the IEL in the vein graft of ACF rats, especially in the segment exposed to prominent hemodynamic changes. IEL degradation may contribute to the development of neointimal hyperplasia in vein grafts.
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Fístula Arteriovenosa/patologia , Tecido Elástico/patologia , Rejeição de Enxerto , Doenças Vasculares/fisiopatologia , Veias/cirurgia , Veia Cava Inferior/patologia , Animais , Catepsinas/metabolismo , Tecido Elástico/ultraestrutura , Hemodinâmica , Técnicas Imunoenzimáticas , Masculino , Metaloproteinase 2 da Matriz/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Veia Cava Inferior/metabolismoRESUMO
This retrospective study aimed at identifying the predictors of oxygen desaturation (OD) (i.e., SpO2â<â95%) in patients with obstructive sleep apnea (OSA) requiring deep sedation and developing an algorithm to predict OD.We studied 66 OSA patients undergoing propofol-induced deep sedation for drug-induced sleep endoscopy (DISE). The patients were divided into prediction (nâ=â35) and validation (nâ=â31) groups. Patient characteristics and polysomnographic parameters were analyzed with receiver operating characteristic curve and Chi-squared test to identify significant predictors of OD for developing an algorithm in the prediction group. The predictive accuracy, sensitivity, positive predictive value, and negative predictive value of the algorithm were determined in the validation group.Six polysomnographic predictors of OD were identified, including Apnea-Hypopnea Index of total sleep time (AHI-TST), AHI at the stage of rapid eye movement (AHI-REM), percentage of time with oxygen saturation <90% (mO2â<â90%), average SpO2, lowest SpO2, and desaturation index. Stepwise multiple logistic regression analysis demonstrated that low average SpO2 (<95.05%) and high AHI-REM (>16.5 events/h) were independent predictors of OD. The algorithm thus developed showed that patients with an average SpO2â<â95.05% and those with an average SpO2â≥â95.05% together with an AHI-REMâ>â16.5 events/h would be at risk of OD under sedation. The predictive accuracy, sensitivity, positive predictive value, and negative predictive value were 84%, 100%, 83%, 100%, respectively.For patients with OSA, average SpO2 and AHI-REM may enable clinicians to predict the occurrence of oxygen desaturation under deep sedation. Future large-scale studies are needed to validate the findings.
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Algoritmos , Sedação Profunda/efeitos adversos , Oxigênio/sangue , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , China/epidemiologia , Sedação Profunda/métodos , Endoscopia/métodos , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Polissonografia/instrumentação , Valor Preditivo dos Testes , Propofol/administração & dosagem , Estudos Retrospectivos , Apneia Obstrutiva do Sono/diagnóstico , Sono REMRESUMO
BACKGROUND AND PURPOSE: The purpose of this study was to identify the quantitative amount of glucose load, which maintained the blood glucose levels between 100 and 180 mg/dL in patients with and without diabetes mellitus (DM) undergoing living donor liver transplantation (LDLT). METHODS AND PATIENTS: The anesthesia records of 477 adult LDLT patients were reviewed retrospectively. The total amount of glucose loads and the changes in blood glucose between groups were compared by using Mann-Whitney U test. One-year patient survival between groups was compared with Pearson's χ2 test. A P value of <.05 was considered statistically significant. RESULTS: Eighty patients diagnosed with DM, who were all type II except one, were placed in group 1 (G1); and 397 patients without DM were placed in group 2 (G2). Table 1 shows that G1 received significantly less glucose loads in comparison to G2, but all the measured blood glucose levels, except in the reperfusion phase, were significantly higher in G1 than in G2. Both groups received glucose loads of 0.342 ± 0.191 and 0.774 ± 0.191 mg/kg/min for G1 and G2, respectively. No difference in 1-year survival between groups was observed. CONCLUSION: Patients with DM required significantly lower glucose loads compared to patients without DM.
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Glicemia/análise , Diabetes Mellitus/cirurgia , Glucose/administração & dosagem , Hepatopatias/cirurgia , Transplante de Fígado/métodos , Adulto , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Hepatopatias/sangue , Hepatopatias/mortalidade , Transplante de Fígado/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto JovemRESUMO
OBJECTIVE: The aim of this retrospective study is to evaluate and compare the incidence of acute kidney injury (AKI), defined as increase serum creatinine (SCr) of 0.3 mg/dl or increase in SCr to ≥1.5 times from baseline within 48 hour, in adult living donor liver transplantation patients performed with total cross clamp vs side clamp of the inferior vena cava (IVC). METHODS AND PATIENTS: Sixty adult living donor liver transplantation (LDLT) patients were divided into 2 groups: 30 patients in total IVC clamping (G1) and 30 in IVC side clamping (G2) during the anhepatic phase. Patients' characteristic, hemodynamic changes in percentage (%) as a result of different methods of IVC clamping, urine output during anhepatic phase were compared by using the Student t test, and the incidence of AKI were compared by using the χ2 test between groups. P value <.05 was regarded as significant. RESULTS: The negative impact of the 2 different ways of IVC clamping was significantly more severe in G1 compared to G2; consequently, the urine output of G1 was significantly less than G2. Although there was significantly more urine output of G2 during the anhepatic phase, the incidence of the postoperative AKI between groups was similar. CONCLUSION: The side clamp of the IVC had a significantly less negative impact on the hemodynamic parameters and provided sufficient urine output during the anhepatic phase (2.24 ± 3.17 vs 0.39 ± 0.33 mL/kg/h) compared to the total clamp of the IVC. But this favorable data did not protect the patient suffering from postoperative AKI in LDLT.
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Injúria Renal Aguda/etiologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Complicações Pós-Operatórias/etiologia , Injúria Renal Aguda/epidemiologia , Adulto , Feminino , Humanos , Incidência , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Veia Cava Inferior/cirurgiaRESUMO
Toluene is a widely used industrial organic solvent and is ubiquitous in our environment. The neurobehavioral and neurotoxic effects of toluene are well recognized; however, its genotoxicity is still under discussion. Toluene biotransformation leads to the generation of reactive oxygen species that cause oxidative stress and DNA damages. Individuals with different immunogenetic backgrounds have different sensitivities to toxic chemical exposure. Previous studies have suggested that allergic stimulation may influence the threshold for toluene sensitivity due to the modulation of neurotrophin-related genes. Therefore, we aimed to investigate toluene-induced genotoxicity in different brain regions following acute and chronic exposure in vivo and to further examine whether allergic stimulation may influence the sensitivity to toluene-induced genotoxicity. In this present study, we found that exposure of toluene induced oxidative DNA damages resulting in genotoxicity in different brain regions including cortex, cerebellum, and hippocampus using comet assay. Higher genotoxicity induced by toluene was observed in the hippocampus of control mice compared to OVA-immunized mice. These results provide evidence that toluene-induced genotoxicity may contribute to its neurotoxicity in different immunogenetic individuals.
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Encéfalo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Hipersensibilidade/genética , Tolueno/toxicidade , Animais , Encéfalo/metabolismo , Ensaio Cometa , Modelos Animais de Doenças , Hipersensibilidade/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacosRESUMO
BACKGROUND: To evaluate the effects of needle electrical intramuscular stimulation (NEIMS) on myofascial trigger points (MTrPs) and their epidermal blood flow. METHODS: Forty adult patients with active MTrPs in the upper trapezius or levator scapulae underwent 4 weekly NEIMS sessions. Visual analog scale (VAS) and pain pressure threshold (PPT), along with cervical and shoulder range of motion (ROM) were used as outcome measures. Microcirculatory changes were also evaluated by laser Doppler flowmetry of the epidermal area above these MTrPs. Data were collected before and after each treatment. Paired t tests were used to compare pre- and post-treatment data. Outcomes were presented as box plots displaying medians and 25th to 75th percentile values. RESULTS: VAS and PPT pain significantly improved immediately after each treatment; effects persisted till the end of the experiment. NEIMS treatment also had immediate and mid-term positive effects on cervical and shoulder ROM. There was an overall negative correlation between epidermal blood flow and VAS score before the first treatment. Regional blood flow significantly increased immediately but temporarily after each treatment. CONCLUSION: NEIMS did have positive effects on myofascial pain syndrome, but the data did not indicate that increased regional microcirculation was the possible therapeutic mechanism.
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Terapia por Estimulação Elétrica , Síndromes da Dor Miofascial/terapia , Cervicalgia/terapia , Dor de Ombro/terapia , Adulto , Humanos , Microcirculação , Pessoa de Meia-Idade , Síndromes da Dor Miofascial/fisiopatologia , Cervicalgia/fisiopatologia , Medição da Dor , Limiar da Dor , Amplitude de Movimento Articular , Dor de Ombro/fisiopatologia , Pele/irrigação sanguíneaRESUMO
In this study, we developed a fully thermoplastic microfiltration chip for the separation of blood plasma from human blood. Spiral microchannels were manufactured on a PMMA substrate using a micromilling machine, and a commercial polycarbonate membrane was bonded between two thermoplastic substrates. To achieve an excellent bonding between the commercial membrane and the thermoplastic substrates, we used a two-step injection and curing procedure of UV adhesive into a ring-shaped structure around the microchannel to efficiently prevent leakage during blood filtration. We performed multiple filtration experiments using human blood to compare the influence of three factors on separation efficiency: hematocrit level (40%, 23.2%, and 10.9%), membrane pore size (5 µm, 2 µm, and 1 µm), and flow rate (0.02 ml/min, 0.06 ml/min, 0.1 ml/min). To prevent hemolysis, the pressure within the microchannel was kept below 0.5 bars throughout all filtration experiments. The experimental results clearly demonstrated the following: (1) The proposed microfiltration chip is able to separate white blood cells and red blood cells from whole human blood with a separation efficiency that exceeds 95%; (2) no leakage occurred during any of the experiments, thereby demonstrating the effectiveness of bonding a commercial membrane with a thermoplastic substrate using UV adhesive in a ring-shaped structure; (3) separation efficiency can be increased by using a membrane with smaller pore size, by using diluted blood with lower hematocrit, or by injecting blood into the microfiltration chip at a lower flow rate.
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OBJECTIVE: We sought to clarify the response of endothelial connexins to hyperlipidemia and lipid-lowering therapy. METHODS AND RESULTS: Aortic endothelial gap junctions were analyzed by en face immunoconfocal microscopy and electron microscopy in C57BL/6 mice subjected to the following regimens: (1) normal chow (NC) for 3 months (3 mo), (2) NC for 9 mo, (3) NC for 3 mo, followed by a cholesterol-enriched diet (CED) for 6 mo, (4) NC for 3 mo and CED for 6 mo, with simvastatin in the final week, and (5) (in apoprotein E [apoE]-deficient mice) NC and examined at 3 mo and 7 to 9 mo. In wild-type mice, connexin37 (Cx37) and Cx40 were markedly downregulated in the CED-fed animals compared with those fed NC (CED vs 9-mo NC, 77% reduction in Cx37 and 65% reduction in Cx40; both P<0.01). After simvastatin treatment, Cx40 remained depressed, but Cx37 recovered to 94% of the level found in non-cholesterol-fed animals (P<0.01). Electron microscopy demonstrated that gap junctions were smaller in animals fed the CED compared with those given simvastatin and with controls fed NC (P<0.01). Endothelial connexins were rare in the atherosclerotic plaques of apoE-deficient mice. CONCLUSIONS: Mouse aortic endothelial gap junctions and connexins are downregulated during long-term hyperlipidemia. Short-term treatment with simvastatin leads to recovery of Cx37 expression but not Cx40 expression.
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Conexinas/metabolismo , Endotélio Vascular/metabolismo , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Sinvastatina/administração & dosagem , Animais , Aorta/patologia , Conexinas/efeitos dos fármacos , Regulação para Baixo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/ultraestrutura , Feminino , Junções Comunicantes/metabolismo , Junções Comunicantes/ultraestrutura , Hiperlipidemias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Imunoeletrônica , Distribuição Tecidual , Proteína alfa-5 de Junções Comunicantes , Proteína alfa-4 de Junções ComunicantesRESUMO
We investigated the phenotypic features of cardiomyocytes, including the gap junctions, in the myocardial sleeve of thoracic veins. Single cardiomyocytes, isolated from the canine pulmonary veins (PV) and superior vena cava (SVC) using digestive enzymes, were examined by immunoconfocal microscopy using antisera against connexin43 (Cx43), Cx40, and other cell markers. The results showed that isolated cardiomyocytes displayed rod shapes of various sizes, ranging from <50 microm to >200 microm in length, and all the cells expressed alpha-actinin and vinculin. Gap junctions made of various amounts of Cx43 and Cx40 were found at the cell borders. These two connexins were extensively co-localized. Comparison between the thoracic veins showed that cells of the SVC contained more Cx43 gap junctions (total Cx43 gap junctions area per cell surface area, 4.0 +/- 0.2% vs 1.5 +/- 0.2%; p<0.01). In addition, for single-nucleus cells, those from the PV were longer (103.7 +/- 3.6 vs 85.0 +/- 3.1 microm; p<0.01) but narrower (14.4 +/- 0.5 vs 16.9 +/- 0.9 microm; p<0.01). In conclusion, canine thoracic veins contain cardiomyocytes with differences in shape and gap junctions, suggesting that the electrical conduction properties may be different between the thoracic veins.
Assuntos
Conexina 43/biossíntese , Vasos Coronários/metabolismo , Junções Comunicantes/metabolismo , Células Musculares/metabolismo , Músculo Liso Vascular/metabolismo , Animais , Conexina 43/imunologia , Vasos Coronários/citologia , Vasos Coronários/ultraestrutura , Cães , Soros Imunes , Imuno-Histoquímica , Microscopia Confocal , Células Musculares/ultraestrutura , Músculo Liso Vascular/citologia , Músculo Liso Vascular/ultraestrutura , Veias Pulmonares/citologia , Veias Pulmonares/metabolismo , Veias Pulmonares/ultraestrutura , Tórax , Veia Cava Superior/citologia , Veia Cava Superior/metabolismo , Veia Cava Superior/ultraestruturaRESUMO
BACKGROUND: Neuronal migration, the process by which neurons migrate from their place of origin to their final position in the brain, is a central process for normal brain development and function. Advances in experimental techniques have revealed much about many of the molecular components involved in this process. Notwithstanding these advances, how the molecular machinery works together to govern the migration process has yet to be fully understood. Here we present a computational model of neuronal migration, in which four key molecular entities, Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration process. RESULTS: The model simulated the dynamic migration process, consistent with in-vivo observations of morphological, cellular and population-level phenomena. Specifically, the model reproduced migration phases, cellular dynamics and population distributions that concur with experimental observations in normal neuronal development. We tested the model under reduced activity of Lis1 and DCX and found an aberrant development similar to observations in Lis1 and DCX silencing expression experiments. Analysis of the model gave rise to unforeseen insights that could guide future experimental study. Specifically: (1) the model revealed the possibility that under conditions of Lis1 reduced expression, neurons experience an oscillatory neuron-glial association prior to the multipolar stage; and (2) we hypothesized that observed morphology variations in rats and mice may be explained by a single difference in the way that Lis1 and DCX stimulate bipolar motility. From this we make the following predictions: (1) under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar migration in rats, and (2) under enhanced DCX expression in mice we predict a normal or a higher bipolar migration. CONCLUSIONS: We present here a system-wide computational model of neuronal migration that integrates theory and data within a precise, testable framework. Our model accounts for a range of observable behaviors and affords a computational framework to study aspects of neuronal migration as a complex process that is driven by a relatively simple molecular program. Analysis of the model generated new hypotheses and yet unobserved phenomena that may guide future experimental studies. This paper thus reports a first step toward a comprehensive in-silico model of neuronal migration.
Assuntos
Encéfalo/citologia , Movimento Celular , Modelos Neurológicos , Neurônios/fisiologia , Animais , Encéfalo/crescimento & desenvolvimento , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/fisiologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Neuropeptídeos/fisiologia , Ratos , Proteína Reelina , Biologia de Sistemas , Ácido gama-Aminobutírico/metabolismoRESUMO
PURPOSE: To investigate the clearance of vascular endothelial growth factor (VEGF) after the induction of posterior vitreous detachment by plasmin and/or SF(6). METHODS: The study design included four groups of rabbits: group 1 received an intravitreal injection of plasmin and SF(6) in the right eye, group 2 received an intravitreal injection of plasmin in the right eye, group 3 received an intravitreal injection of SF(6) in the right eye, and group 4 received an intravitreal injection of balanced salt solution in the right eye. Intravitreal injection of human VEGF (50 µL, 10 ng/µL) was performed in study eyes and control eyes 1 month after plasmin and/or SF(6) injection. Serum and vitreous samples were collected on days 1, 3, and 7 after VEGF injection to determine the serum and vitreous concentrations of VEGF. RESULTS: One day after VEGF injection, residual human VEGF concentration in the vitreous cavity was significantly lower in the plasmin- and SF(6)-treated eyes (group 1) and the plasmin-treated eyes (group 2) when compared with the control eyes (group 4) (P = 0.047 and 0.027, respectively). Three days after VEGF injection, the residual VEGF concentration in the vitreous cavity was still significantly lower in the plasmin- and SF(6)-treated eyes (group 1) when compared with the control eyes (group 4) (P = 0.025). CONCLUSIONS: Eyes treated with plasmin exhibit a more rapid clearance of exogenous VEGF than control eyes. This finding suggests a novel treatment for retinopathies associated with vitreous traction and VEGF elevation.