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1.
Nat Commun ; 11(1): 4907, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999289

RESUMO

Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.


Assuntos
Materiais Biomiméticos/administração & dosagem , Matriz Extracelular/química , Neoplasias/terapia , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/efeitos da radiação , Materiais Biomiméticos/química , Materiais Biomiméticos/efeitos da radiação , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Quimiorradioterapia/métodos , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos da radiação , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/química , Fibrinogênio/efeitos da radiação , Géis , Humanos , Injeções Intravenosas , Metabolômica , Camundongos , Neoplasias/metabolismo , Trombina/administração & dosagem , Trombina/química , Trombina/efeitos da radiação , Terapia por Ultrassom/métodos , Ondas Ultrassônicas
2.
PLoS One ; 15(9): e0239456, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976517

RESUMO

The use of ultrasound-stimulated microbubble therapy has successfully been used to target tumor vasculature and enhance the effects of radiation therapy in tumor xenografts in mice. Here, we further investigate this treatment using larger, more clinically relevant tumor models. New Zealand white rabbits bearing prostate tumor (PC3) xenografts received a single treatment of either ultrasound-stimulated microbubbles (USMB), ionizing radiation (XRT; 8Gy), or a combination of both treatments (USMB+XRT). Treatment outcome was evaluated 24 hours after treatment using histopathology, immunolabeling, 3D Doppler ultrasound and photoacoustic imaging. A second cohort of rabbits received multiple treatments over a period of three weeks, where USMB treatments were delivered twice weekly with daily XRT treatments to deliver a fractionated 2Gy dose five days per week. A significant decrease in vascular function, observed through immunolabeling of vascular endothelial cells, was observed in tumors receiving the combined treatment (USMB+XRT) compared to control and single treatment groups. This was associated with an increase in cell death as observed through in situ end labeling (ISEL), a decrease in vascular index measured by Power Doppler imaging, and a decrease in oxygen saturation. In rabbits undergoing the long-term fractionated combined treatment, a significant growth delay was observed after 1 week and a significant reduction in tumor size was observed after 3 weeks with combined therapy. Results demonstrated an enhancement of radiation effect and superior anti-tumor effect of the combination of USMB+XRT compared to the single treatments alone. Tumor growth was maximally inhibited with fractionated radiotherapy combined with the ultrasound-stimulated microbubble-based therapy.


Assuntos
Microbolhas/uso terapêutico , Neoplasias da Próstata/radioterapia , Terapia por Ultrassom/métodos , Animais , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Terapia Combinada/métodos , Células Endoteliais/efeitos da radiação , Humanos , Masculino , Camundongos , Células PC-3 , Coelhos , Ondas Ultrassônicas
3.
Niger J Clin Pract ; 23(9): 1237-1242, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32913162

RESUMO

Aims: We evaluated and compared EndoActivator, CanalBrush, and passive ultrasonic irrigation (PUI) in the removal of calcium hydroxide and calcium hydroxide with iodoform and p-chlorophenol paste (Calcipast Forte) from artificial standardized grooves in the apical third of root canals. Materials and Methods: A total of 34 mandibular premolars were prepared and then split longitudinally. A standardized groove was prepared in the apical part of both segments. The grooves were filled with either calcium hydroxide or Calcipast Forte, and the segments were reassembled. CanalBrush, EndoActivator, or PUI were used. The amount of remaining medicament was evaluated using a four-grade scoring system. Results: None of the irrigation methods could completely remove the pastes from the grooves. More Calcipast Forte paste was detected compared with calcium hydroxide (P < 0.01). PUI was the least effective method in removing Calcipast Forte. Conclusions: It was more difficult to remove Calcipast Forte than a water-based calcium hydroxide paste.


Assuntos
Hidróxido de Cálcio/química , Clorofenóis , Cavidade Pulpar/patologia , Hidrocarbonetos Iodados , Materiais Restauradores do Canal Radicular/química , Irrigantes do Canal Radicular/administração & dosagem , Terapia por Ultrassom/métodos , Humanos , Irrigantes do Canal Radicular/química , Preparo de Canal Radicular/instrumentação , Preparo de Canal Radicular/métodos , Irrigação Terapêutica/métodos , Terapia por Ultrassom/instrumentação , Ultrassom , Água
4.
Cochrane Database Syst Rev ; 9: CD006946, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32944940

RESUMO

BACKGROUND: Engorgement is the overfilling of breasts with milk, often occurring in the early days postpartum. It results in swollen, hard, painful breasts and may lead to premature cessation of breastfeeding, decreased milk production, cracked nipples and mastitis. Various treatments have been studied but little consistent evidence has been found on effective interventions. OBJECTIVES: To determine the effectiveness and safety of different treatments for engorgement in breastfeeding women. SEARCH METHODS: On 2 October 2019, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. SELECTION CRITERIA: All types of randomised controlled trials and all forms of treatment for breast engorgement were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility, extracted data, conducted 'Risk of bias' assessment and assessed the certainty of evidence using GRADE. MAIN RESULTS: For this udpate, we included 21 studies (2170 women randomised) conducted in a variety of settings. Six studies used individual breasts as the unit of analysis. Trials examined a range of interventions: cabbage leaves, various herbal compresses (ginger, cactus and aloe, hollyhock), massage (manual, electromechanical, Oketani), acupuncture, ultrasound, acupressure, scraping therapy, cold packs, and medical treatments (serrapeptase, protease, oxytocin). Due to heterogeneity, meta-analysis was not possible and data were reported from single trials. Certainty of evidence was downgraded for limitations in study design, imprecision and for inconsistency of effects. We report here findings from key comparisons. Cabbage leaf treatments compared to control For breast pain, cold cabbage leaves may be more effective than routine care (mean difference (MD) -1.03 points on 0-10 visual analogue scale (VAS), 95% confidence intervals (CI) -1.53 to -0.53; 152 women; very low-certainty evidence) or cold gel packs (-0.63 VAS points, 95% CI -1.09 to -0.17; 152 women; very low-certainty evidence), although the evidence is very uncertain. We are uncertain about cold cabbage leaves compared to room temperature cabbage leaves, room temperature cabbage leaves compared to hot water bag, and cabbage leaf extract cream compared to placebo cream because the CIs were wide and included no effect. For breast hardness, cold cabbage leaves may be more effective than routine care (MD -0.58 VAS points, 95% CI -0.82 to -0.34; 152 women; low-certainty evidence). We are uncertain about cold cabbage leaves compared to cold gel packs because the CIs were wide and included no effect. For breast engorgement, room temperature cabbage leaves may be more effective than a hot water bag (MD -1.16 points on 1-6 scale, 95% CI -1.36 to -0.96; 63 women; very low-certainty evidence). We are uncertain about cabbage leaf extract cream compared to placebo cream because the CIs were wide and included no effect. More women were satisfied with cold cabbage leaves than with routine care (risk ratio (RR) 1.42, 95% CI 1.22 to 1.64; 152 women; low certainty), or with cold gel packs (RR 1.23, 95% CI 1.10 to 1.38; 152 women; low-certainty evidence). We are uncertain if women breastfeed longer following treatment with cold cabbage leaves than routine care because CIs were wide and included no effect. Breast swelling and adverse events were not reported. Compress treatments compared to control For breast pain, herbal compress may be more effective than hot compress (MD -1.80 VAS points, 95% CI -2.07 to -1.53; 500 women; low-certainty evidence). Massage therapy plus cactus and aloe compress may be more effective than massage therapy alone (MD -1.27 VAS points, 95% CI -1.75 to -0.79; 100 women; low-certainty evidence). In a comparison of cactus and aloe compress to massage therapy, the CIs were wide and included no effect. For breast hardness, cactus and aloe cold compress may be more effective than massage (RR 0.66, 95% CI 0.51 to 0.87; 102 women; low-certainty evidence). Massage plus cactus and aloe cold compress may reduce the risk of breast hardness compared to massage alone (RR 0.38, 95% CI 0.25 to 0.58; 100 women; low-certainty evidence). We are uncertain about the effects of compress treatments on breast engorgement and cessation of breastfeeding because the certainty of evidence was very low. Among women receiving herbal compress treatment, 2/250 experienced skin irritation compared to 0/250 in the hot compress group (moderate-certainty evidence). Breast swelling and women's opinion of treatment were not reported. Medical treatments compared to placebo Protease may reduce breast pain (RR 0.17, 95% CI 0.04, 0.74; low-certainty evidence; 59 women) and breast swelling (RR 0.34, 95% CI 0.15 to 0.79; 59 women; low-certainty evidence), whereas serrapeptase may reduce the risk of engorgement compared to placebo (RR 0.36, 95% CI 0.14 to 0.88; 59 women; low-certainty evidence). We are uncertain if serrapeptase reduces breast pain or swelling, or if oxytocin reduces breast engorgement compared to placebo, because the CIs were wide and included no effect. No women experienced adverse events in any of the groups receiving serrapeptase, protease or placebo (low-certainty evidence). Breast induration/hardness, women's opinion of treatment and breastfeeding cessation were not reported. Cold gel packs compared to control For breast pain, we are uncertain about the effectiveness of cold gel packs compared to control treatments because the certainty of evidence was very low. For breast hardness, cold gel packs may be more effective than routine care (MD -0.34 points on 1-6 scale, 95% CI -0.60 to -0.08; 151 women; low-certainty evidence). It is uncertain if women breastfeed longer following cold gel pack treatment compared to routine care because the CIs were wide and included no effect. There may be little difference in women's satisfaction with cold gel packs compared to routine care (RR 1.17, 95% CI 0.97 to 1.40; 151 women; low-certainty evidence). Breast swelling, engorgement and adverse events were not reported. AUTHORS' CONCLUSIONS: Although some interventions may be promising for the treatment of breast engorgement, such as cabbage leaves, cold gel packs, herbal compresses, and massage, the certainty of evidence is low and we cannot draw robust conclusions about their true effects. Future trials should aim to include larger sample sizes, using women - not individual breasts - as units of analysis.


Assuntos
Doenças Mamárias/terapia , Transtornos da Lactação/terapia , Terapia por Acupuntura , Brassica , Doenças Mamárias/etiologia , Crioterapia/métodos , Feminino , Humanos , Massagem , Mastodinia/terapia , Ocitocina/uso terapêutico , Peptídeo Hidrolases/uso terapêutico , Fitoterapia/métodos , Folhas de Planta , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Ultrassom/métodos
5.
Cochrane Database Syst Rev ; 7: CD009169, 2020 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-32623724

RESUMO

BACKGROUND: This is an update of a Cochrane Review published in 2014. Chronic non-specific low back pain (LBP) has become one of the main causes of disability in the adult population around the world. Although therapeutic ultrasound is not recommended in recent clinical guidelines, it is frequently used by physiotherapists in the treatment of chronic LBP. OBJECTIVES: The objective of this review was to determine the effectiveness of therapeutic ultrasound in the management of chronic non-specific LBP. A secondary objective was to determine the most effective dosage and intensity of therapeutic ultrasound for chronic LBP. SEARCH METHODS: We performed electronic searches in CENTRAL, MEDLINE, Embase, CINAHL, PEDro, Index to Chiropractic Literature, and two trials registers to 7 January 2020. We checked the reference lists of eligible studies and relevant systematic reviews and performed forward citation searching. SELECTION CRITERIA: We included randomised controlled trials (RCTs) on therapeutic ultrasound for chronic non-specific LBP. We compared ultrasound (either alone or in combination with another treatment) with placebo or other interventions for chronic LBP. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias of each trial and extracted the data. We performed a meta-analysis when sufficient clinical and statistical homogeneity existed. We determined the certainty of the evidence for each comparison using the GRADE approach. MAIN RESULTS: We included 10 RCTs involving a total of 1025 participants with chronic LBP. The included studies were carried out in secondary care settings in Turkey, Iran, Saudi Arabia, Croatia, the UK, and the USA, and most applied therapeutic ultrasound in addition to another treatment, for six to 18 treatment sessions. The risk of bias was unclear in most studies. Eight studies (80%) had unclear or high risk of selection bias; no studies blinded care providers to the intervention; and only five studies (50%) blinded participants. There was a risk of selective reporting in eight studies (80%), and no studies adequately assessed compliance with the intervention. There was very low-certainty evidence (downgraded for imprecision, inconsistency, and limitations in design) of little to no difference between therapeutic ultrasound and placebo for short-term pain improvement (mean difference (MD) -7.12, 95% confidence interval (CI) -17.99 to 3.75; n = 121, 3 RCTs; 0-to-100-point visual analogue scale (VAS)). There was also moderate-certainty evidence (downgraded for imprecision) of little to no difference in the number of participants achieving a 30% reduction in pain in the short term (risk ratio 1.08, 95% CI 0.81 to 1.44; n = 225, 1 RCT). There was low-certainty evidence (downgraded for imprecision and limitations in design) that therapeutic ultrasound has a small effect on back-specific function compared with placebo in the short term (standardised mean difference -0.29, 95% CI -0.51 to -0.07 (MD -1.07, 95% CI -1.89 to -0.26; Roland Morris Disability Questionnaire); n = 325; 4 RCTs), but this effect does not appear to be clinically important. There was moderate-certainty evidence (downgraded for imprecision) of little to no difference between therapeutic ultrasound and placebo on well-being (MD -2.71, 95% CI -9.85 to 4.44; n = 267, 2 RCTs; general health subscale of the 36-item Short Form Health Survey (SF-36)). Two studies (n = 486) reported on overall improvement and satisfaction between groups, and both reported little to no difference between groups (low-certainty evidence, downgraded for serious imprecision). One study (n = 225) reported on adverse events and did not identify any adverse events related to the intervention (low-certainty evidence, downgraded for serious imprecision). No study reported on disability for this comparison. We do not know whether therapeutic ultrasound in addition to exercise results in better outcomes than exercise alone because the certainty of the evidence for all outcomes was very low (downgraded for imprecision and serious limitations in design). The estimate effect for pain was in favour of the ultrasound plus exercise group (MD -21.1, 95% CI -27.6 to -14.5; n = 70, 2 RCTs; 0-to-100-point VAS) at short term. Regarding back-specific function (MD - 0.41, 95% CI -3.14 to 2.32; n = 79, 2 RCTs; Oswestry Disability Questionnaire) and well-being (MD -2.50, 95% CI -9.53 to 4.53; n = 79, 2 RCTs; general health subscale of the SF-36), there was little to no difference between groups at short term. No studies reported on the number of participants achieving a 30% reduction in pain, patient satisfaction, disability, or adverse events for this comparison. AUTHORS' CONCLUSIONS: The evidence from this systematic review is uncertain regarding the effect of therapeutic ultrasound on pain in individuals with chronic non-specific LBP. Whilst there is some evidence that therapeutic ultrasound may have a small effect on improving low back function in the short term compared to placebo, the certainty of evidence is very low. The true effect is likely to be substantially different. There are few high-quality randomised trials, and the available trials were very small. The current evidence does not support the use of therapeutic ultrasound in the management of chronic LBP.


Assuntos
Dor Crônica/terapia , Dor Lombar/terapia , Terapia por Ultrassom/métodos , Adulto , Viés , Terapia por Estimulação Elétrica , Terapia por Exercício , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Ultrassom/efeitos adversos
6.
Proc Natl Acad Sci U S A ; 117(29): 16848-16855, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32631991

RESUMO

In certain medical applications, transmitting an ultrasound beam through the skin to manipulate a solid object within the human body would be beneficial. Such applications include, for example, controlling an ingestible camera or expelling a kidney stone. In this paper, ultrasound beams of specific shapes were designed by numerical modeling and produced using a phased array. These beams were shown to levitate and electronically steer solid objects (3-mm-diameter glass spheres), along preprogrammed paths, in a water bath, and in the urinary bladders of live pigs. Deviation from the intended path was on average <10%. No injury was found on the bladder wall or intervening tissue.


Assuntos
Cálculos Renais/terapia , Terapia por Ultrassom/métodos , Ondas Ultrassônicas , Animais , Suínos , Transdutores , Terapia por Ultrassom/instrumentação
7.
Prostate ; 80(12): 986-992, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32557725

RESUMO

BACKGROUND: Focal therapies for prostate cancer (PC) can reduce adverse events and do not lead to androgen-independent progression. Ultrasound could be used for cancer treatments if the repetition frequency is fitted to the purpose. We investigated the possible therapeutic effect of ultrasound irradiation on PC cells. MATERIALS AND METHODS: We irradiated two PC cell lines, androgen-dependent LNCaP and -independent PC-3 with ultrasound (3.0 W/cm2 , 3 MHz, irradiation time rate: 20%) for 2 minutes for 1 day or 3 consecutive days at a repetition frequency of 1, 10, or 100 Hz in vitro. Cell proliferation and apoptosis were determined after irradiation. RESULTS: Cell proliferation of PC-3 was significantly inhibited after 1 day (P < .0001) and 3 days (P < .0001) of 10 Hz ultrasound irradiation, and that of LNCaP after 1 day (P < .0001) and 3 days (P < .0001) of irradiation. LNCaP was more sensitive to ultrasound at both lower and higher cell density but PC-3 was only sensitive at a lower cell density (P < .01). Irradiation with 10 Hz ultrasound-induced significantly more PC-3 apoptotic cells than control (1 day, P = .0137; 3 days, P = .0386) rather than irradiation with 1 Hz. Apoptosis via caspase-3 was induced at 10 Hz in 1-day (P < .05) irradiation in both cell lines. CONCLUSIONS: Ultrasound irradiation with even 1 day of 10 Hz significantly inhibited cell proliferation in both LNCaP and PC-3, especially by the remarkable induction of apoptosis in vitro. Our study indicated that ultrasound irradiation can be a therapeutic option for PC and further studies in vivo will be undertaken.


Assuntos
Neoplasias da Próstata/radioterapia , Terapia por Ultrassom/métodos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Humanos , Masculino , Células PC-3 , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/radioterapia
8.
Anticancer Res ; 40(6): 3163-3167, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487611

RESUMO

BACKGROUND/AIM: Ultrasonically activated surgical devices (USADs) have become indispensable instruments for gastrointestinal surgery. In this study, we investigated the oncological safety of the use of USADs. MATERIALS AND METHODS: We harvested and cultivated the splashes and mist scattered from an USAD when cutting MKN45-derived cancer nodules. Seven days later, we observed viable cancer cells and the total number of cells was counted. The histopathology of the nodules cut by the USAD was also examined. RESULTS: The existence of viable cancer cells was confirmed by ex vivo cell culture. The number of viable cancer cells was reduced by slow grasping of the USAD. The surface of cancerous tissue cut by the USAD was partially heat-denatured, however, there were some parts in which cancerous tissue was exposed on the surface. CONCLUSION: Surgeons should recognize the possibility that cancer cells may be scattered by USAD use.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Terapia por Ultrassom/métodos , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Gástricas/patologia
10.
Ultrasonics ; 107: 106167, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32402858

RESUMO

Current in vitro sonication experiments show immense variability in experimental set-ups and methods used. As a result, there is uncertainty in the ultrasound field parameters experienced by sonicated samples, poor reproducibility of these experiments and thus reduced scientific value of the results obtained. The scope of this narrative review is to briefly describe mechanisms of action of ultrasound, list the most frequently used experimental set-ups and focus on a description of factors influencing the outcomes and reproducibility of these experiments. The factors assessed include: proper reporting of ultrasound exposure parameters, experimental geometry, coupling medium quality, influence of culture vessels, formation of standing waves, motion/rotation of the sonicated sample and the characteristics of the sample itself. In the discussion we describe pros and cons of particular exposure geometries and factors, and make a few recommendations as to how to increase the reproducibility and validity of the experiments performed.


Assuntos
Terapia por Ultrassom/métodos , Técnicas de Cultura de Células , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Técnicas In Vitro , Modelos Biológicos , Reprodutibilidade dos Testes , Sonicação
11.
Psychopharmacology (Berl) ; 237(7): 2043-2053, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32419116

RESUMO

RATIONALE: In rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism. OBJECTIVES: We investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen. METHODS: In phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm. RESULTS: Sub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback. CONCLUSIONS: This study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.


Assuntos
Estimulação Acústica/métodos , Haloperidol/toxicidade , Transtornos Psicomotores/induzido quimicamente , Transtornos Psicomotores/terapia , Terapia por Ultrassom/métodos , Vocalização Animal/fisiologia , Animais , Modelos Animais de Doenças , Antagonistas de Dopamina/toxicidade , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Masculino , Transtornos Psicomotores/psicologia , Ratos , Ratos Wistar
12.
Proc Natl Acad Sci U S A ; 117(17): 9180-9182, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32284421

RESUMO

The blood-brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer's disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions.


Assuntos
Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Terapia por Ultrassom/métodos , Idoso , Doença de Alzheimer/metabolismo , Transporte Biológico , Barreira Hematoencefálica/fisiologia , Encéfalo/fisiologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Hipocampo/metabolismo , Humanos , Masculino , Microbolhas , Pessoa de Meia-Idade , Ondas Ultrassônicas , Ultrassonografia
13.
Complement Ther Med ; 49: 102295, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32147037

RESUMO

The aim of the study was to compare the effect of high-intensity laser therapy (HILT) and a combination of transcutaneous nerve stimulation (TENS) and ultrasound (US) treatment on pain, range of motion (ROM) and functional activity on cervical pain associated with cervical disc herniation (CDH). A total of 40 patients (22 women and 18 men) affected by CDH were enrolled in this study. Patients were randomly divided into two groups. In group 1 (20 subjects), patients received 20 sessions of HILT plus exercise, while in group 2 (20 subjects), a combination of US, TENS and exercise were applied. The outcomes were cervical segment ROM, pain level measured by visual analogue scale (VAS), and functional activity measured by neck pain and disability scale (NPADS) before and after the therapy. The level of statistical significance was set as p < 0.05. There was no difference for cervical ROM, VAS and NPADS values between the groups at the baseline (p> 0.05). After the treatment, cervical ROM, VAS and NPADS values were significantly improved in both groups (p < 0.05). When the groups were compared in terms of post treatment VAS, NPADS and ROM values, no statistical significance was found between the two groups (p> 0.05). Both of therapeutic modalities demonstrated analgesic efficacy and improved the function in patients affected by CDH after 4 weeks of therapy (total 20 treatment sessions in 5 days a week). Both the HILT plus exercise program and the TENS / US plus exercise program were found to be effective in improving cervical range of motion and quality of life by reducing pain. These two treatment programs have similar effects in the treatment of cervical pain associated with CDH and can be used as an alternative to each other in clinical applications. However; It is clear that futher studies are needed to investigate the principles of application of HILT to painful areas or tissues (amount of area applied, dose applied, energy delivered, number of pulses, duration of session, frequency of sessions) and to exclude the effects of exercise treatment on the results of both treatment groups.


Assuntos
Deslocamento do Disco Intervertebral/terapia , Terapia a Laser/métodos , Cervicalgia/terapia , Manejo da Dor/métodos , Estimulação Elétrica Nervosa Transcutânea/métodos , Terapia por Ultrassom/métodos , Adolescente , Adulto , Terapia Combinada , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular , Método Simples-Cego , Adulto Jovem
14.
Int J Nanomedicine ; 15: 419-432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021188

RESUMO

Background: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments. Purpose: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer. Methods: The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity® microbubbles and polyethylene glycol (PEG)-coated iron oxide nanoparticles were used to induce cell sonoporation and MFH, respectively. Assessment of cell membrane permeabilization was evaluated via fluorescence microscopy, iron uptake by cells was quantified by UV-Vis spectroscopy, and cell viability was determined using automatic cell counting. Results: Notable reductions in cancer cell viability were observed when ultrasound was incorporated. For example, the treatment US+PES reduced cell viability by 37% compared to the non-toxic effect of the drug. Similarly, the treatment US+MFH using mild hyperthermia (41°C), reduced cell viability by an additional 18% when compared to the effect of MH alone. Significant improvements were observed for the combination of US+PES+MFH with cell viability reduced by an additional 26% compared to the PES+MFH group. The improved cytotoxicity was attributed to enhanced drug/nanoparticle intracellular delivery, with iron uptake values nearly twice those achieved without ultrasound. Various treatment schedules were examined, and all of them showed substantial cell death, indicating that the time elapsed between sonoporation and magnetic field exposure was not significant. Conclusion: Superior cancer cell-killing patterns took place when ultrasound was incorporated thus demonstrating the in vitro ultrasonic potentiation of PES and mild MFH. This work demonstrated that ultrasound is a promising non-invasive enhancer of PES/MFH combination treatments, aiming to establish a sono-thermo-chemotherapy in the treatment of ovarian cancer.


Assuntos
Antineoplásicos/farmacologia , Hipertermia Induzida/métodos , Neoplasias Ovarianas/terapia , Sulfonamidas/farmacologia , Terapia por Ultrassom/métodos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Feminino , Humanos , Magnetismo , Microbolhas/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico
15.
J Med Ultrason (2001) ; 47(2): 319-325, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31912320

RESUMO

PURPOSE: Patients suffering from lateral epicondylitis exhibit diminished mobility due to pain. The aim of the study was to compare the efficacy of both shockwave and ultrasound therapies in patients with lateral epicondylitis. METHODS: The shockwave group consisted of 117 patients, 63 patients constituted the ultrasound group, and 18 patients made up the control group. The "University of Peloponnese Pain, Functionality and Quality of Life Questionnaire" was used for the evaluation of pain, functionality, and quality of life on a five-point Likert scale, pre-treatment, post-treatment, and at 4-week follow-up. RESULTS: The pain was reduced and the functionality and quality of life were improved in both the shockwave and ultrasound groups post-treatment (p < 0.001) and at 4-week follow-up (p < 0.001), but the results in the ultrasound group were not as pronounced as in the shockwave group (p < 0.001). CONCLUSION: Both radial shockwave and ultrasound therapies were significantly effective in patients with lateral epicondylitis. However, ultrasound therapy was less effective than shockwave therapy.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas/métodos , Cotovelo de Tenista/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Manejo da Dor/métodos , Medição da Dor , Qualidade de Vida , Cotovelo de Tenista/complicações , Resultado do Tratamento , Terapia por Ultrassom/métodos , Adulto Jovem
16.
Curr Opin Urol ; 30(2): 149-156, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31905177

RESUMO

PURPOSE OF REVIEW: Burst wave lithotripsy and ultrasonic propulsion of kidney stones are novel, noninvasive emerging technologies to separately or synergistically fragment and reposition stones in an office setting. The purpose of this review is to discuss the latest refinements in technology, to update on testing of safety and efficacy, and to review future applications. RECENT FINDINGS: Burst wave lithotripsy produced consistent, small passable fragments through transcutaneous applications in a porcine model, while producing minimal injury and clinical trials are now underway. A more efficient ultrasonic propulsion design that can also deliver burst wave lithotripsy effectively repositioned 95% of stones in 18 human participants (18 of 19 kidneys) and clinical trials continue. Acoustic tractor beam technology is an emerging technology with promising clinical applications through the manipulation of macroscopic objects. SUMMARY: The goal of the reviewed work is an office-based system to image, fragment, and reposition urinary stones to facilitate their natural passage. The review highlights progress in establishing safety, effectiveness, and clinical benefit of these new technologies. The work is also anticipating challenges in clinical trials and developing the next generation of technology to improve on the technology as it is being commercialized today.


Assuntos
Litotripsia/métodos , Terapia por Ultrassom/métodos , Cálculos Urinários/cirurgia , Acústica , Animais , Modelos Animais de Doenças , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Litotripsia/instrumentação , Litotripsia/tendências , Litotripsia a Laser , Suínos , Terapia por Ultrassom/instrumentação , Ultrassonografia , Ureteroscopia , Cálculos Urinários/diagnóstico por imagem
17.
Trials ; 21(1): 113, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992331

RESUMO

BACKGROUND: Periodontal diseases are regarded as the most common diseases of mankind. The prevalence rate of periodontal disease assumes a clear growth tendency, increasing by 57.3% from 1990 to 2010. Thereby, effective periodontal therapy is still a long-term task and a difficult problem. The goals of periodontal therapy are to eliminate the infectious and inflammatory processes of periodontal diseases. Root planing, in order to eliminate the "infected cementum," has been an important step in the treatment of periodontitis since the 1970s. However, along with the understanding of the effects of endotoxin on the root surface, the necessity of manual root planing has been gradually queried. Ultrasonic instruments, which are more recent innovations, would not remove the cementum excessively, and are also more time-saving and labor-saving compared to using hand instruments. Hence, an increasing number of dentists prefer to do scaling with ultrasonic instruments only. However, the necessity of root planing remains emphasized in the international mainstream views of periodontal mechanical treatment. Therefore, this study is devoted to compare the clinical effect of ultrasonic subgingival debridement and ultrasonic subgingival scaling combined with manual root planing, which takes the implementation of root planing as the only variable and is more in line with the current clinical situation, thus hoping to provide some valuable reference to dentists. METHODS/DESIGN: Forty adult patients who fit the inclusion criteria are being recruited from the Peking University Hospital of Stomatology (Beijing, China). By means of randomization tables, one quadrant of the upper and lower teeth is the test group and the other is the control group. Test group: ultrasonic subgingival scaling combined with manual root planing. CONTROL GROUP: ultrasonic subgingival debridement. In a 24-week follow-up period, plaque index, probing depth, clinical attachment loss, bleeding index, furcation involvement, mobility, and patient-reported outcome (Visual Analog Scale for pain and sensitivity) will be observed and documented. DISCUSSION: This study evaluates the effectiveness of ultrasonic subgingival scaling combined with manual root planing and ultrasonic subgingival debridement alone in the nonsurgical treatment of periodontitis with a split-mouth design after 1, 3 and 6 months. The result of the trial should potentially contribute to an advanced treatment strategy for periodontitis with an ideal clinical outcome. TRIAL REGISTRATION: International Clinical Trials Registry Platform (ICTRP), ID: ChiCTR1800017122. Registered on 12 July 2018.


Assuntos
Raspagem Dentária/métodos , Desbridamento Periodontal/métodos , Periodontite/terapia , Aplainamento Radicular/métodos , Terapia por Ultrassom/métodos , Terapia Combinada , Humanos
18.
ACS Appl Mater Interfaces ; 12(5): 5642-5657, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31940169

RESUMO

Retinoblastoma (RB) is prone to delayed diagnosis or treatment and has an increased likelihood of metastasizing. Thus, it is crucial to perform an effective imaging examination and provide optimal treatment of RB to prevent metastasis. Nanoparticles that support diagnostic imaging and targeted therapy are expected to noninvasively integrate tumor diagnosis and treatment. Herein, we report a multifunctional nanoparticle for multimodal imaging-guided low-intensity focused ultrasound (LIFU)/immunosynergistic RB therapy. Magnetic hollow mesoporous gold nanocages (AuNCs) conjugated with Fe3O4 nanoparticles (AuNCs-Fe3O4) were prepared to encapsulate muramyl dipeptide (MDP) and perfluoropentane (PFP). The multimodal imaging capabilities, antitumor effects, and dendritic cell (DC) activation capacity of these nanoparticles combined with LIFU were explored in vitro and in vivo. The biosafety of AuNCs-Fe3O4/MDP/PFP was also evaluated systematically. The multifunctional magnetic nanoparticles enhanced photoacoustic (PA), ultrasound (US), and magnetic resonance (MR) imaging in vivo and in vitro, which was helpful for diagnosis and efficacy evaluation. Upon accumulation in tumors via a magnetic field, the nanoparticles underwent phase transition under LIFU irradiation and MDP was released. A combined effect of AuNCs-Fe3O4/MDP/PFP and LIFU was recorded and verified. AuNCs-Fe3O4/MDP/PFP enhanced the therapeutic effect of LIFU and led to direct apoptosis/necrosis of tumors, while MDP promoted DC maturation and activation and activated the ability of DCs to recognize and clear tumor cells. By enhancing PA/US/MR imaging and inhibiting tumor growth, the multifunctional AuNC-Fe3O4/MDP/PFP nanoparticles show great potential for multimodal imaging-guided LIFU/immunosynergistic therapy of RB. The proposed nanoplatform facilitates cancer theranostics with high biosafety.


Assuntos
Nanopartículas Multifuncionais , Imagem Multimodal/métodos , Retinoblastoma , Terapia por Ultrassom/métodos , Acetilmuramil-Alanil-Isoglutamina/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fluorcarbonetos/química , Humanos , Nanopartículas de Magnetita/química , Camundongos , Camundongos Nus , Nanopartículas Multifuncionais/química , Nanopartículas Multifuncionais/metabolismo , Nanopartículas Multifuncionais/toxicidade , Retinoblastoma/diagnóstico por imagem , Retinoblastoma/metabolismo , Nanomedicina Teranóstica/métodos
19.
PLoS One ; 15(1): e0227315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940386

RESUMO

PURPOSE: Preoperative neck ultrasound (US) for lateral cervical lymph nodes is recommended for all patients undergoing thyroidectomy for thyroid malignancy, but it is operator dependent. We aimed to develop a radiomics signature using US images of the primary tumor to preoperatively predict lateral lymph node metastasis (LNM) in patients with conventional papillary thyroid carcinoma (cPTC). METHODS: Four hundred consecutive cPTC patients from January 2004 to February 2006 were enrolled as the training cohort, and 368 consecutive cPTC patients from March 2006 to February 2007 served as the validation cohort. A radiomics signature, which consisted of 14 selected features, was generated by the least absolute shrinkage and selection operator (LASSO) regression model in the training cohort. The discriminating performance of the radiomics signature was assessed in the validation cohort with the area under the receiver operating characteristic curve (AUC). RESULTS: The radiomics signature was significantly associated with lateral cervical lymph node status (p < 0.001). The AUC of its performance in discriminating metastatic and non-metastatic lateral cervical lymph nodes was 0.710 (95% CI: 0.649-0.770) in the training cohort and was 0.621 (95% CI: 0.560-0.682) in the validation cohort. CONCLUSIONS: The present study showed that US radiomic features of the primary tumor were associated with lateral cervical lymph node status. Although their discriminatory performance was slightly lower in the validation cohort, our study shows that US radiomic features of the primary tumor alone have the potential to predict lateral LNM.


Assuntos
Linfonodos/efeitos da radiação , Câncer Papilífero da Tireoide/radioterapia , Terapia por Ultrassom/métodos , Ondas Ultrassônicas , Adulto , Feminino , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Pescoço/efeitos da radiação , Pescoço/cirurgia , Nomogramas , Curva ROC , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Tireoidectomia
20.
Plast Reconstr Surg ; 145(2): 348e-359e, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31985636

RESUMO

BACKGROUND: The authors developed a noncontact low-frequency ultrasound device that delivers high-intensity mechanical force based on phased-array technology. It may aid wound healing because it is likely to be associated with lower risks of infection and heat-induced pain compared with conventional ultrasound methods. The authors hypothesized that the microdeformation it induces accelerates wound epithelialization. Its effects on key wound-healing processes (angiogenesis, collagen accumulation, and angiogenesis-related gene transcription) were also examined. METHODS: Immediately after wounding, bilateral acute wounds in C57BL/6J mice were noncontact low-frequency ultrasound- and sham-stimulated for 1 hour/day for 3 consecutive days (10 Hz/90.6 Pa). Wound closure (epithelialization) was recorded every 2 days as the percentage change in wound area relative to baseline. Wound tissue was procured on days 2, 5, 7, and 14 (five to six per time point) and subjected to histopathology with hematoxylin and eosin and Masson trichrome staining, CD31 immunohistochemistry, and quantitative polymerase-chain reaction analysis. RESULTS: Compared to sham-treated wounds, ultrasound/phased-array-treated wounds exhibited significantly accelerated epithelialization (65 ± 27 percent versus 30 ± 33 percent closure), angiogenesis (4.6 ± 1.7 percent versus 2.2 ± 1.0 percent CD31 area), and collagen deposition (44 ± 14 percent versus 28 ± 13 percent collagen density) on days 5, 2, and 5, respectively (all p < 0.05). The expression of Notch ligand delta-like 1 protein (Dll1) and Notch1, which participate in angiogenesis, was transiently enhanced by treatment on days 2 and 5, respectively. CONCLUSIONS: The authors' noncontact low-frequency ultrasound phased-array device improved the wound-healing rate. It was associated with increased early neovascularization that was followed by high levels of collagen-matrix production and epithelialization. The device may expand the mechanotherapeutic proangiogenesis field, thereby helping stimulate a revolution in infected wound care.


Assuntos
Pele/lesões , Terapia por Ultrassom/métodos , Cicatrização/fisiologia , Ferimentos e Lesões/terapia , Animais , Colágeno/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/fisiologia , Pele/metabolismo , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia
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