RESUMO
BACKGROUND: Colorectal cancer stands as one of the most prevalent malignant tumors affecting the digestive tract, posing a significant threat to human health. Its incidence and fatality rates rank third and second, respectively, among malignant tumors. This study seeks to analyze the efficacy of combining fluorouracil intraperitoneal perfusion chemotherapy with intravenous chemotherapy in patients following radical resection of colorectal cancer. METHODS: This retrospective study analyzed the medical records of 65 patients who underwent radical resection of colorectal cancer at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2011 to January 2013. These patients were divided into two groups based on their treatment methods: the control group (CG, n = 31, receiving intravenous chemotherapy) and the observation group (OG, n = 32, receiving fluorouracil intraperitoneal perfusion chemotherapy + intravenous chemotherapy). After 6 cycles of treatment, the study compared clinical symptoms, Karnofsky score, body weight, adverse reactions, local recurrence, and liver metastasis between the two groups. RESULTS: The OG demonstrated superior efficacy in controlling recurrence and metastasis compared to the CG (p < 0.05). However, there were no significant differences observed in clinical symptoms, quality of life, body weight, and drug safety between the two groups (p > 0.05). CONCLUSION: Intraperitoneal infusion chemotherapy with fluorouracil significantly impacts the control of recurrence and metastasis following radical resection of colorectal cancer. It also offers valuable references for developing clinical treatment protocols for these patients.
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Neoplasias Colorretais , Fluoruracila , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Qualidade de Vida , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Perfusão , Peso CorporalRESUMO
The study aimed to evaluate the immediate effects of a dry needling (DN) therapy session on biomechanical properties, muscle power, perfusion, and pressure pain threshold of the gastrocnemius muscle with latent trigger points. Twenty mixed martial arts athletes (MMA) were randomly divided into two groups: experimental (eDN, n = 10) and sham (qDN, n = 10) to undergo one session of DN either with a real or a qazi needle. The measurements were taken at rest, 1-5 minutes after the DN (Post1-5min) and 24h after the DN (Post24h). DN significantly increased the muscle perfusion (Post1-5min and Post24h, p < 0.001), reduced its tone (Post1-5min and Post24h, p < 0.001) and stiffness (Post1-5min, p < 0.05; Post24 h, p < 0.001), and improved its elasticity (Post1-5min and Post24h, p < 0.001). DN also caused a significant increase in pressure pain threshold (Post1-5min, p < 0.001; Post24h, p < 0.05) and in muscle power (Post24h, p < 0.01). The DN session increased the blood perfusion and improved the biomechanical properties of the gastrocnemius muscle, which led to improved muscle power. The DN also had an analgesic effect. These effects were maintained at 24 h, which suggests that DN could facilitate muscle recovery in a post-exercise period of MMA athletes.
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Indução Percutânea de Colágeno , Pontos-Gatilho , Humanos , Método Simples-Cego , Músculo Esquelético , Perfusão , AtletasRESUMO
Orthotopic liver transplantation remains the definitive treatment for patients with end-stage liver disease. Unfortunately, the increasing demand for donor livers and the limited supply of viable organs have both led to a critical need for innovative strategies to expand the pool of transplantable organs. The mitochondrion, central to hepatic cellular function, plays a pivotal role in hepatic ischemic injury, with impaired mitochondrial function and oxidative stress leading to cell death. Mitochondrial protection strategies have shown promise in mitigating IRI and resuscitating marginal organs for transplant. Machine perfusion (MP) has been proven a valuable tool for reviving marginal organs with very promising results. Evaluation of liver viability during perfusion traditionally relies on parameters including lactate clearance, bile production, and transaminase levels. Nevertheless, the quest for more comprehensive and universally applicable viability markers persists. Normothermic regional perfusion has gained robust attention, offering extended recovery time for organs from donation after cardiac death donors. This approach has shown remarkable success in improving organ quality and reducing ischemic injury using the body's physiological conditions. The current challenge lies in the absence of a reliable assessment tool for predicting graft viability and post-transplant outcomes. To address this, exploring insights from mitochondrial function in the context of ischemia-reperfusion injury could offer a promising path toward better patient outcomes and graft longevity. Indeed, hypoxia-induced mitochondrial injury may serve as a surrogate marker of organ viability following oxygenated resuscitation techniques in the future.
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Preservação de Órgãos , Traumatismo por Reperfusão , Humanos , Preservação de Órgãos/métodos , Fígado , Traumatismo por Reperfusão/prevenção & controle , Isquemia , Metabolismo Energético , Mitocôndrias , Perfusão/métodosAssuntos
Carcinoma , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Peritoneais/terapia , Perfusão , Gastrectomia , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Taxa de SobrevidaRESUMO
BACKGROUND: Normothermic machine perfusion (NMP) is a promising pretransplant kidney quality assessment platform, but it remains crucial to increase its diagnostic potential while ensuring minimal additional injury to the already damaged kidney. Interventions that alter tubular transport can influence renal function and injury during perfusion. This study aimed to determine whether furosemide and desmopressin affect renal function and injury during NMP. METHODS: Eighteen porcine kidneys (n = 6 per group) were subjected to 30 min of warm ischemia and 4 h of oxygenated hypothermic perfusion before being subjected to 6 h of NMP. Each organ was randomized to receive no drug, furosemide (750 mg), or desmopressin (16 µg) during NMP. RESULTS: Compared with the other groups, the addition of furosemide resulted in significantly increased urine output, fractional excretion of sodium and potassium, and urea clearance during NMP. Urinary neutrophil gelatinase-associated lipocalin levels decreased significantly with furosemide supplementation compared with the other groups. The addition of desmopressin did not result in any significantly different outcome measurements compared with the control group. CONCLUSIONS: This study showed that the addition of furosemide affected renal function while attenuating tubulointerstitial injury during NMP. Therefore, furosemide supplementation may provide renal protection and serve as a functional test for pretransplant kidney viability assessment during NMP.
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Furosemida , Rim , Preservação de Órgãos , Perfusão , Animais , Furosemida/farmacologia , Suínos , Perfusão/métodos , Rim/efeitos dos fármacos , Rim/patologia , Preservação de Órgãos/métodos , Desamino Arginina Vasopressina/farmacologia , Transplante de Rim , Isquemia Quente/efeitos adversosRESUMO
This work presents the dual-phase lag-based non-Fourier bioheat transfer model of brain tissue subjected to interstitial laser ablation. The finite element method has been utilized to predict the brain tissue's temperature distributions and ablation volumes. A sensitivity analysis has been conducted to quantify the effect of variations in the input laser power, treatment time, laser fiber diameter, laser wavelength, and non-Fourier phase lags. Notably, in this work, the temperature-dependent thermal properties of brain tissue have been considered. The developed model has been validated by comparing the temperature obtained from the numerical and ex vivo brain tissue during interstitial laser ablation. The ex vivo brain model has been further extended to in vivo settings by incorporating the blood perfusion effects. The results of the systematic analysis highlight the importance of considering temperature-dependent thermal properties of the brain tissue, non-Fourier behavior, and microvascular perfusion effects in the computational models for accurate predictions of the treatment outcomes during interstitial laser ablation, thereby minimizing the damage to surrounding healthy tissue. The developed model and parametric analysis reported in this study would assist in a more accurate and precise prediction of the temperature distribution, thus allowing to optimize the thermal dosage during laser therapy in the brain.
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Hipertermia Induzida , Terapia a Laser , Hipertermia Induzida/métodos , Lasers , Temperatura , Perfusão , Modelos Biológicos , Temperatura AltaRESUMO
Several studies reported an increase in skin glow, pore shrinkage, and an improvement in oily skin with its mesobotox-like use. The authors aimed to determine the extent of late changes in skin perfusion in the superficial dermis when Botulinium toxin A (Btx-A) is injected into the skin with mesotherapy, independent of any stimulant and surgery, using a laser Doppler flowmeter for analysis. Btx-A was applied to the right cheek and saline mesotherapy to the left cheeks of a total of 9 subjects. Two weeks later, their contribution to skin circulation was measured by the laser Doppler flowmeter. Although it was more on the side where Btx-A was applied, an increase in vascularity was observed on both sides of the subjects and no statistical difference could be found between the right and left cheeks in the late period.
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Toxinas Botulínicas Tipo A , Pele , Humanos , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/uso terapêutico , Fluxometria por Laser-Doppler , PerfusãoRESUMO
In the current transition to intensified upstream processing, the risks of adopting traditional single-use systems for high-titer, long-duration perfusion cultures, have thus far not been considered. This case study uses the Failure Modes and Effects Analysis (FMEA) method to evaluate the risks associated with implementing upstream single-use technology. The simulated model process was used to compare the risk level of single-use technology for a traditional fed-batch cell culture with that for perfusion culture, under the same annual protein production conditions. To provide a reasonable source of potential risk for FMEA, all single-use upstream operations for both fed-batch and perfusion processes were investigated using an analytical method developed to quantify the impact of process parameters and operating conditions on single-use system specifications and to ensure objectivity. Many of the risks and their levels, were similar in long-duration perfusion cultures and fed-batch cultures. However, differences were observed for high-risk components such as daily sampling and installation. The result of this analysis indicates that the reasons for risk are different for fed-batch cultures and perfusion cultures such as larger bioreactors in fed-batch and longer runs in perfusion, respectively. This risk assessment method could identify additional control measures and be part of a holistic contamination control strategy and help visualize their effectiveness.
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Produtos Biológicos , Animais , Cricetinae , Reatores Biológicos , Técnicas de Cultura Celular por Lotes/métodos , Anticorpos Monoclonais , Perfusão , CricetulusRESUMO
Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5-68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17-92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.
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Hipertermia Induzida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Mitomicina/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Perfusão , Organoides/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos RetrospectivosRESUMO
INTRODUCTION: Hyperthermia treatment planning (HTP) tools can guide treatment delivery, particularly with locoregional radiative phased array systems. Uncertainties in tissue and perfusion property values presently lead to quantitative inaccuracy of HTP, leading to sub-optimal treatment. Assessment of these uncertainties would allow for better judgement of the reliability of treatment plans and improve their value for treatment guidance. However, systematically investigating the impact of all uncertainties on treatment plans is a complex, high-dimensional problem and too computationally expensive for traditional Monte Carlo approaches. This study aims to systematically quantify the treatment-plan impact of tissue property uncertainties by investigating their individual contribution to, and combined impact on predicted temperature distributions. METHODS: A novel Polynomial Chaos Expansion (PCE)-based HTP uncertainty quantification was developed and applied for locoregional hyperthermia of modelled tumours in the pancreatic head, prostate, rectum, and cervix. Patient models were based on the Duke and Ella digital human models. Using Plan2Heat, treatment plans were created to optimise tumour temperature (represented by T90) for treatment using the Alba4D system. For all 25-34 modelled tissues, the impact of tissue property uncertainties was analysed individually i.e., electrical and thermal conductivity, permittivity, density, specific heat capacity and perfusion. Next, combined analyses were performed on the top 30 uncertainties with the largest impact. RESULTS: Uncertainties in thermal conductivity and heat capacity were found to have negligible impact on the predicted temperature ( < 1 × 10-10 °C), density and permittivity uncertainties had a small impact (< 0.3 °C). Uncertainties in electrical conductivity and perfusion can lead to large variations in predicted temperature. However, variations in muscle properties result in the largest impact at locations that could limit treatment quality, with a standard deviation up to almost 6 °C (pancreas) and 3.5 °C (prostate) for perfusion and electrical conductivity, respectively. The combined influence of all significant uncertainties leads to large variations with a standard deviation up to 9.0, 3.6, 3.7 and 4.1 °C for the pancreatic, prostate, rectal and cervical cases, respectively. CONCLUSION: Uncertainties in tissue and perfusion property values can have a large impact on predicted temperatures from hyperthermia treatment planning. PCE-based analysis helps to identify all major uncertainties, their impact and judge the reliability of treatment plans.
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Hipertermia Induzida , Neoplasias , Masculino , Feminino , Humanos , Hipertermia Induzida/métodos , Incerteza , Reprodutibilidade dos Testes , PerfusãoRESUMO
BACKGROUND: No reflow in capillaries (no reflow) is the lack of tissue perfusion that occurs once central hemodynamics are restored. This prevents oxygen transfer and debt repayment to vital tissues after shock resuscitation. Since metabolic swelling of cells and tissues can cause no reflow, it is a target for study in shock. We hypothesize no reflow secondary to metabolic cell swelling causes the problem not addressed by current strategies that increase central hemodynamics alone. METHODS: Anesthetized swine were bled until plasma lactate reached 7.5 mM to 9 mM. Intravenous low volume resuscitation solutions were administered (6.8 mL/kg over 5 minutes) consisting of; (1) lactated Ringer (LR), (2) autologous whole blood, (3) high-dose vitamin C (200 mg/kg), or (4) 10% PEG-20k, a polymer-based cell impermeant that corrects metabolic cell swelling. Outcomes were macrohemodynamics (MAP), plasma lactate, capillary flow in the gut and tongue mucosa using orthogonal polarization spectral imaging (OPSI), and survival to 4 hours. RESULTS: All PEG-20k resuscitated swine survived 240 minutes with MAP above 60 mm Hg compared with 50% and 0% of the whole blood and LR groups, respectively. The vitamin C group died at just over 2 hours with MAPs below 40 and high lactate. The LR swine only survived 30 minutes and died with low MAP and high lactate. Capillary flow positively correlated ( p < 0.05) with survival and MAP. Sublingual OPSI correlated with intestinal OPSI and OPSI was validated with a histological technique. DISCUSSION: Targeting micro-hemodynamics in resuscitation may be more important than macrohemodynamics. Fixing both is optimal. Sublingual OPSI is clinically achievable to assess micro-hemodynamic status. Targeting tissue cell swelling that occurs during ATP depletion in shock using optimized osmotically active cell impermeants in crystalloid low volume resuscitation solutions improves perfusion in shocked tissues, which leverages a primary mechanism of injury.
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Choque Hemorrágico , Animais , Suínos , Choque Hemorrágico/tratamento farmacológico , Microcirculação , Soluções Cristaloides/uso terapêutico , Hemodinâmica , Lactato de Ringer , Edema , Perfusão , Lactatos , Ácido Ascórbico/uso terapêutico , Ressuscitação/métodos , Soluções Isotônicas/farmacologia , Soluções Isotônicas/uso terapêuticoRESUMO
Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.
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Hipertermia Induzida , Laparoscopia , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Neoplasias Gástricas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Adulto , Neoplasias Gástricas/cirurgia , Neoplasias Peritoneais/secundário , Quimioterapia Intraperitoneal Hipertérmica , Hipertermia Induzida/métodos , Terapia Combinada , Laparoscopia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Perfusão , Procedimentos Cirúrgicos de Citorredução , Taxa de SobrevidaRESUMO
BACKGROUND: Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. METHODS: Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689. FINDINGS: Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive). INTERPRETATION: In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy. FUNDING: UK National Institute of Health Research Health Technology Programme.
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Angioplastia Coronária com Balão , Ocimum basilicum , Doença Arterial Periférica , Masculino , Humanos , Feminino , Idoso , Isquemia Crônica Crítica de Membro , Isquemia/cirurgia , Doença Arterial Periférica/complicações , Doença Arterial Periférica/cirurgia , Fatores de Risco , Perfusão , Dor , Resultado do TratamentoRESUMO
A 2-year-old female American white pekin (Anas platyrhynchos domesticus) was assessed for a 2-month history of chronic lameness and swelling involving the left leg. Radiographic images of the left leg showed soft tissue swelling of the digits and tarsometatarsus with osteolysis of the tarsometatarsal-phalangeal joint. A complete blood count revealed marked leukocytosis and hyperproteinemia. A Streptococcus species was isolated from a bacterial culture of fluid obtained from the left tarsometatarsal-phalangeal joint. Biweekly intravenous regional limb perfusions of the left leg with ampicillin-sulbactam and amikacin were performed on the patient. Despite initial improvement in left leg lameness and swelling, follow-up radiographic images showed progressive osteolysis of the tarsometatarsal-phalangeal joint and associated digits. Surgical placement of antibiotic-impregnated calcium sulfate beads into the left tarsometatarsal-phalangeal joint was next performed with concurrent, repeated intravenous regional limb perfusion using the same antibiotic. Following the placement of antibiotic-impregnated beads and continued intravenous regional limb perfusion, the duck had decreased lameness and swelling of the left leg. Repeated antibiotic treatment through intravenous regional limb perfusion and concurrent placement of antibiotic-impregnated calcium sulfate beads is a practical treatment option for complicated distal limb infections in avian species. This therapeutic protocol has great potential in treating aggressive distal leg infections in many avian species because regional limb perfusion alone may not penetrate the joint adequately to achieve complete resolution of infection.
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Osteoartrite , Osteólise , Tenossinovite , Feminino , Animais , Antibacterianos/uso terapêutico , Sulfato de Cálcio , Patos , Tenossinovite/tratamento farmacológico , Tenossinovite/veterinária , Coxeadura Animal , Osteólise/tratamento farmacológico , Osteólise/veterinária , Perfusão/veterinária , Osteoartrite/tratamento farmacológico , Osteoartrite/veterináriaRESUMO
Pancreatic cancer (PC) is the fourth leading cause of cancer death, and the 5 year survival rate is only 4%. Chemotherapy is the treatment option for the majority of PC patients diagnosed at an advanced stage, whereas the desmoplastic stroma of PC could block the perfusion of chemotherapeutic agents to tumor tissues and contribute generally to chemoresistance. Therefore, the clinical status of PC calls for an urgent exploration in the effective treatment strategy. Chemo-phototherapy is an emerging modality against malignant tumors, but owing to the low targeting ability of theranostic agents or unspecific accumulation in the tumor region, majority of chemo-phototherapy techniques have disappointing therapeutic efficiencies. Herein, we have explored CD71-specific targeting aptamers and paclitaxel (PTX)-modified polydopamine (PDA) nanospheres with the conjugation of peptidomimetic AV3 (termed Apt-PDA@PTX/AV3 bioconjugates) to specifically target and combat PC in vivo by synergistic chemo-phototherapy. After the delivery of nanotheranostic agents to the tumor microenvironment (TME) or subsequent endocytic uptake by PC cells, a simultaneous release of AV3 and PTX from Apt-PDA@PTX/AV3 bioconjugates via near-infrared (NIR) irradiation can decrease desmoplastic stroma to enhance tumor perfusion and tumor-killing effects. Meanwhile, PDA cores utilize NIR laser to create unendurable hyperthermia within TME to "cook" tumors. Taken together, the current study finally suggests that our Apt-PDA@PTX/AV3 bioconjugates could act as a novel therapeutic approach by synergistic chemo-phototherapy for the programmable inhibition of PC.
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Hipertermia Induzida , Nanopartículas , Nanosferas , Neoplasias Pancreáticas , Humanos , Hipertermia Induzida/métodos , Fototerapia/métodos , Paclitaxel/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos , Perfusão , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
BACKGROUND: This study aims to compare the effects of medical ozone (MO) therapy and hyperbaric oxygen (HBO) therapy in an experimental testicular torsion model by measuring the oxidant and antioxidant markers and examining the histopathological tissue damage findings. METHODS: Thirty-two Wistar rats are used and are divided into four groups; (1) sham group (SG), (2) only ischemia/reperfusion (I/R) by testicular torsion, (3) HBO administered group, and (4) MO administered group. No torsion was conducted in the SG. In all other groups, rats underwent testicular torsion followed by detorsion to create an I/R model. After I/R, HBO was injected in the HBO group, and in the MO group, intraperitoneal ozone was applied. At the end of 1 week, testicular tissues were obtained for biochemical analyzes and histopathological examinations. Biochemically, malondialdehyde (MDA) levels were measured for oxidant activity, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were measured for antioxidant activity. Furthermore, the testicles were evaluated histopathologically. RESULTS: Both HBO and MO have significantly decreased MDA levels, compared with sham and I/R groups, resulting in decreased oxidation effects. The antioxidant GSH-Px levels in the HBO and MO groups were significantly higher than in the sham and I/R groups. In addition, the antioxidant SOD levels in the HBO group were significantly higher than sham, I/R, and MO groups. Therefore, the antioxidant effect of HBO was observed to be superior to MO, specifically considering SOD levels. Histopathologically, there was no significant difference between the groups (p>0.05). CONCLUSION: The study may extrapolate that both HBO and MO are antioxidant agents that can be used in testicular torsion. HBO treatment might improve the cellular antioxidant capacity due to increased antioxidant marker levels more than MO therapy. However, further studies are needed with a larger sample size.
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Oxigenoterapia Hiperbárica , Ozônio , Torção do Cordão Espermático , Animais , Humanos , Masculino , Ratos , Antioxidantes , Isquemia , Oxidantes , Oxigênio , Ozônio/uso terapêutico , Perfusão , Ratos Wistar , Torção do Cordão Espermático/terapiaRESUMO
BACKGROUND: Although ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation, EVLP itself can lead to inflammation in the lung. Heat shock proteins (HSPs) have anti-inflammatory effects and can reduce ischemic reperfusion injury in the donor's lungs after transplantation. In this study, the effects of transient hyperthermia during EVLP on the expression of HSPs and inflammatory pathways were examined. METHODS: Fifteen male Sprague-Dawley rats were randomly divided into three groups: sham (n = 5), normothermic EVLP (37 °C, n = 5), and transient hyperthermia during EVLP (42 °C, n = 5). Lung function analyses regarding PaO2/FiO2 ratio, compliance, and pulmonary vascular resistance were conducted. The expression levels of HSPs and inflammatory cytokines were also evaluated. The degree of lung injury was histopathologically evaluated. Transcriptome analysis was performed on lung tissues from the sham (n = 2), normothermic EVLP (n = 2), and heat stress-EVLP (n = 2) groups. RESULTS: There were no significant differences in functional or histological parameters between the three groups. The expression of HSPs had significantly increased, especially that of HSPs 40 and 60 in the heat stress EVLP group; this was consistent with the inflammatory response. Inflammatory cytokine levels were significantly higher during EVLP and intensified with transient hyperthermia. CONCLUSION: Transient hyperthermia during EVLP has no protective effect on the donor lung graft or activation of the inflammatory pathway at the gene level.
Assuntos
Hipertermia Induzida , Transplante de Pulmão , Masculino , Ratos , Animais , Perfusão/métodos , Ratos Sprague-Dawley , Pulmão/fisiologia , CitocinasRESUMO
The placental passage of protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. The study compound did not affect placental viability or functionality, as glucose consumption, lactate production, and beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.
Assuntos
Troca Materno-Fetal , Placenta , Gravidez , Humanos , Feminino , Espectrometria de Massas em Tandem , Perfusão/métodosRESUMO
OBJECTIVES: To investigate lung perfusion in systemic sclerosis (SSc). METHODS: The study population included 101 patients who underwent dual-energy CT (DECT) in the follow-up of SSc with pulmonary function tests obtained within 2 months. Fifteen patients had right heart catheterization-proven PH. RESULTS: Thirty-seven patients had no SSc-related lung involvement (Group A), 56 patients had SSc-related interstitial lung disease (Group B) of variable extent (Group B mild: ≤ 10% of lung parenchyma involved: n = 17; Group B moderate: between 11 and 50%: n = 31; Group B severe: > 50%: n = 8), and 8 patients had PVOD/PCH (Group C). Lung perfusion was abnormal in 8 patients in Group A (21.6%), 14 patients in Group B (25%), and 7 patients in Group C (87.5%). In Group A and Group B mild (n = 54), (a) patients with abnormal lung perfusion (n = 14; 26%) had a higher proportion of NYHA III/IV scores of dyspnea (7 [50%] vs 7 [17.5%]; p = 0.031) and a shorter mean walking distance at the 6MWT (397.0 [291.0; 466.0] vs 495.0 [381.0; 549.0]; p = 0.042) but no evidence of difference in the DLCO% predicted (61.0 [53.0; 67.0] vs 68.0 [61.0; 78.0]; p = 0.055) when compared to patients with normal lung perfusion (n = 40; 74%); (b) a negative correlation was found between the iodine concentration in both lungs and the DLCO% predicted but it did not reach statistical significance (r = -0.27; p = 0.059) and no correlation was found with the PAPs (r = 0.16; p = 0.29) and walking distance during the 6MWT (r = -0.029; p = 0.84). CONCLUSIONS: DECT lung perfusion provides complementary information to standard HRCT scans, depicting perfusion changes in SSc patients with normal or minimally infiltrated lung parenchyma. KEY POINTS: ⢠In a retrospective observational study of 101 consecutive patients with SSc, dual-energy CT pulmonary angiography was obtained to evaluate lung perfusion. ⢠Lung perfusion was abnormal in 14 out of 54 patients (26%) with no or mild SSc-related lung infiltration. ⢠Patients with abnormal perfusion and no or mild SSc-related lung infiltration had more severe scores of dyspnea and shorter walking distance than patients with similar lung findings and normal perfusion, suggesting the presence of small vessel vasculopathy.
Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Dispneia , Perfusão , Tomografia Computadorizada por Raios XRESUMO
The aim of the current study was to establish a controlled and reproducible model to study metabolic changes during oxygen-glucose deprivation (OGD) in rat brain using a nuclear magnetic resonance (NMR)-compatible perfusion system. Rat brains were cut into 400-µm thick slices and perfused with artificial cerebrospinal fluid (aCSF) in a 10-mm NMR tube inside a 600-MHz NMR spectrometer. Four experimental conditions were tested: (1) continuous perfusion with aCSF with glucose and normoxia, and (2) 30-, (3) 60-, or (4) 120-min periods of OGD followed by reperfusion of aCSF containing glucose and normoxia. The energetic state of perfused brain slices was measured using phosphorus (31 P) NMR and metabolite changes were measured using proton (1 H) NMR. aCSF samples were collected every 30 min and analyzed using 1 H NMR. The sample temperature was maintained at 36.7 ± 0.1°C and was checked periodically throughout the experiments. Brain slice histology was compared before and after OGD in the perfusion system using hematoxylin-eosin-saffron staining. NMR data clearly distinguished three severity groups (mild, moderate, and severe) after 30, 60, and 120 min of OGD, respectively, compared with the control group. 31 P NMR spectra obtained from controls showed that phosphocreatine levels were stable for 5 h inside the perfusion system. Control 1 H NMR spectra showed that lactate, N-acetylaspartic acid, glutamate, γ-aminobutyric acid, and creatine metabolite levels were stable over time, with lactate levels having a tendency to gradually increase due to the recirculation of the aCSF in the perfusion system. A controlled and reproducible perfusion system was established to study the energetic and metabolic changes in rat brain slices during and after OGD of varying severity.