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1.
Trauma Case Rep ; 47: 100881, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37587922

RESUMO

A 42-year-old hunter with no previous medical history suffered an accidental gunshot injury while hunting. Upon arrival at our Hospital, the following musculosceletal laesions were diagnosed during the primary survey: comminuted right trochanteric and femur neck fracture, femoral and sciatic nerve palsy. The immediate damage control surgery consisted of debridement, jet-lavage, PMMA-chain insertion and extrafocal fixation. Structural neural damage was disclosed. Primarily the skin wound was treated by delayed closure and later the healing was supported by Negative Pressure Wound Therapy. Six weeks after, the extrafocal fixation was removed and antibiotic spacer was inserted. Primary wound healing occurred without any sign of infection. Neurological recovery of the extremity took almost a year. Low grade infection were excluded by serial labs and culture samples. Finally the patient underwent total hip arthroplasty with excellent result.

2.
J Cardiovasc Dev Dis ; 9(9)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36135442

RESUMO

Due to its heterogeneous clinical picture and lengthy evolution, the management of type B aortic dissection represents a clinical challenge, often calling for complex strategies combining medical, endovascular, and open surgical strategies. We present the case of a 45-year-old female who had previously suffered a complicated type B aortic dissection requiring a femoro-femoral crossover bypass and further conservative treatment. Seven years later, due to an aneurysmal development, a staged descending aortic management was strategized, beginning with the implantation of a frozen elephant trunk device due to an insufficient proximal landing zone for endovascular repair. However, the development of a distal stent graft-induced new entry complicated the dissection and led to the formation of a second false lumen, thus prompting an expedited hybrid reconstruction. We describe a hybrid repair strategy tailored to the patient's particular aortic anatomic conformation, combining ilio-visceral debranching and thoracic endovascular aortic repair. Due to a lack of consensus on the ideal management strategy for type B aortic dissection, an individualized approach conducted by an experienced aortic team may generate the best outcome. The appropriate timing and planning of the intervention are the keys to successful results in complex type B aortic dissection cases with an elaborate anatomic conformation.

3.
Sci Rep ; 11(1): 21790, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750427

RESUMO

Our aim was to investigate whether the previously observed higher contrast-to-noise ratio (CNR) and better image quality of Digital Variance Angiography (DVA) - compared to Digital Subtraction Angiography (DSA) - can be used to reduce radiation exposure in lower limb X-ray angiography. This prospective study enrolled 30 peripheral artery disease patients (mean ± SD age 70 ± 8 years) undergoing diagnostic angiography. In all patients, both normal (1.2 µGy/frame; 100%) and low-dose (0.36 µGy/frame; 30%) protocols were used for the acquisition of images in three anatomical regions (abdominal, femoral, crural). The CNR of DSA and DVA images were calculated, and the visual quality was evaluated by seven specialists using a 5-grade Likert scale. For investigating non-inferiority, the difference of low-dose DVA and normal dose DSA scores (DVA30-DSA100) was analyzed. DVA produced two- to three-fold CNR and significantly higher visual score than DSA. DVA30 proved to be superior to DSA100 in the crural region (difference 0.25 ± 0.07, p < 0.001), and there was no significant difference in the femoral (- 0.08 ± 0.06, p = 0.435) and abdominal (- 0.10 ± 0.09, p = 0.350) regions. Our data show that DVA allows about 70% reduction of DSA-related radiation exposure in lower limb X-ray angiography, providing a potential new radiation protection tool for the patients and the medical staff.


Assuntos
Angiografia Digital/métodos , Perna (Membro)/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/diagnóstico por imagem , Estudos Prospectivos , Doses de Radiação , Radiografia Abdominal/métodos , Razão Sinal-Ruído
4.
Ann Vasc Surg ; 73: 509.e11-509.e14, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33333190

RESUMO

Aortic aneurysm rupture into the retroaortic left renal vein (RALRV) is an uncommon phenomenon. We herein present the case of a 66-year-old man with left flank pain, hematuria, fever, and symptoms of acute right-sided heart failure. Computed tomography angiography (CTA) demonstrated an 83-mm infrarenal aortic aneurysm with a fistula in between the aorta and the RALRV. The patient underwent an urgent endovascular aneurysm repair and a proximal cuff extension due to type Ia endoleak. In the early postoperative period, transcaval coil embolization was performed, 3 months later repeated CTA revealed recanalized fistula, after fluid embolization and vascular plug implantation control CTA showed no sign of endoleak. The patient recovered uneventfully, 1-year follow-up CTA demonstrated aneurysm shrinkage and no sign of endoleak.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Embolização Terapêutica , Endoleak/terapia , Procedimentos Endovasculares , Veias Renais , Fístula Vascular/terapia , Idoso , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/etiologia , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Procedimentos Endovasculares/instrumentação , Humanos , Masculino , Veias Renais/diagnóstico por imagem , Stents , Fatores de Tempo , Resultado do Tratamento , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/etiologia
5.
Orv Hetil ; 161(46): 1966-1971, 2020 11 15.
Artigo em Húngaro | MEDLINE | ID: mdl-33190128

RESUMO

Összefoglaló. A patkóvese a vese leggyakrabban eloforduló fejlodési rendellenességeinek egyike. Hasi aortaaneurysmával való együttes elofordulása kifejezetten ritka (a hasi aortaaneurysmás esetek 0,12%-a). Az elso esetben egy 64 éves férfi akut alsó végtagi panaszokkal került felvételre. A CT-angiográfia patkóvesét és thrombotizált infrarenalis aortaaneurysmát igazolt. Az akut mutét során a hasi aortaaneurysma resectióját és aortobifemoralis bypassmutétet végeztünk a patkóvese ishmusának megtartásával. A második esetben hasi panaszokat okozó, mindkét arteria iliaca communisra ráterjedo infrarenalis aortaaneurysma esetén végeztünk aortobiiliacalis rekonstrukciót. Az aneurysma elott elhelyezkedo isthmus tervezetten szétválasztásra került, a poláris veseartériát visszaültettük. A tünetes hasi aortaaneurysma abszolút mutéti indikációt képez. A preoperatív CT- vagy MR-angiográfia kulcsfontosságú mind a mutéti indikáció felállítása, mind pedig a mutét megtervezése szempontjából. A beavatkozás elott pontos képet kell kapnia az érsebésznek az aorta anatómiája mellett a patkóvese vérellátásáról és a húgyúti rendszerrol. Az érsebészeti rekonstrukció esetén a transperitonealis feltárás - foleg akut mutét esetén - több elonnyel rendelkezik, mint a retroperitonealis feltárás. Orv Hetil. 2020; 161(46): 1966-1971. Summary. Horseshoe kidney is one of the most common congenital disorders of the kidney. The simultaneous incidence of horseshoe kidney and abdominal aneurysm is very low (0.12% of all cases of abdominal aortic aneurysm). In the first case, a 64-year-old male patient was admitted with acute lower limb ischaemia. CT-angiography revealed an occluded aortic aneurysm. During the emergency operation, the abdominal aneurysm was resected and an aortobifemoral bypass procedure was performed sparing the kidney's isthmus. In the second case, the abdominal complaints were caused by an infrarenal abdominal aneurysm that involved both common iliac arteries. Aortobiiliac reconstruction was performed with planned separation of the kidney isthmus and reimplantation of the accessory renal artery. Symptomatic abdominal aortic aneurysm is an urgent indication for reconstruction. The preoperative CT- or MR-angiography play a key role in the indication and planning of the reconstruction. It is highly important for the vascular surgeon to have a clear picture of the blood supply of the horseshoe kidney and the urinary tract along with the anatomy of the aorta before the operation. The transperitoneal approach has several advantages over the retroperitoneal approach during vascular reconstruction surgery. Orv Hetil. 2020; 161(46): 1966-1971.


Assuntos
Aneurisma da Aorta Abdominal , Aneurisma Aórtico , Rim Fundido , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Vasculares
6.
Pathol Oncol Res ; 26(4): 2391-2399, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32548697

RESUMO

Acute aortic catastrophes (AAC), mainly ruptured aneurysms and dissections, lead all other vascular conditions in morbidity and mortality, even if intervention occurs. The aim of our study was to give a descriptive overview of the demographic and pathological characteristics of AAC. Between 1994 and 2013, 80,469 autopsies were performed at Semmelweis University hospitals in Budapest. After collecting the autopsy reports we were able to create the AAC database upon which we conducted our analysis. We found 567 cases of AAC. The cause of death in 120 of them was classified as a non-ruptured aorta with malperfusion or distal embolization. Of the remaining 447 cases, in 305 the cause of death was a ruptured aortic aneurysm (rAA), and in 142 it was a ruptured aortic dissection (rAD). The distribution of rAA cases was 34.4% thoracal, 4.3% thoracoabdominal, and 61.3% abdominal. We found female dominance where the rAA was thoracal. In rAD cases, 84% were Stanford A and 16% Stanford B type. In both groups we found different pathological distributions. In the prehospital group, the number of thoracal ruptures was considerable. 88% of the patients with Stanford A dissection died in the prehospital or perioperative period. The most progressive AACs were ruptures of intrapericardial aneurysms and Stanford A dissections., however survival rate can be elevated by using rapid imaging examination and immediate surgical intervention. We want to highlight that our study contains such gender differences, which are worth to be taken into consideration.


Assuntos
Dissecção Aórtica/mortalidade , Dissecção Aórtica/patologia , Ruptura Aórtica/mortalidade , Ruptura Aórtica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Bases de Dados Factuais , Feminino , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
BMC Cardiovasc Disord ; 20(1): 291, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534566

RESUMO

BACKGROUND: Over the span of the last decade, medical research has been increasingly putting greater emphasis on the study of meteorological parameters due to their connection to cardiovascular diseases. The main goal of this study was to explore the relationship between fatal aortic catastrophes and changes in atmospheric pressure and temperature. METHODS: We used a Cox process model to quantify the effects of environmental factors on sudden deaths resulting from aortic catastrophes. We used transfer entropy to draw conclusion about the causal connection between mortality and meteorological parameters. Our main tool was a computer program which we developed earlier in order to evaluate the relationship between pulmonary embolism mortality and weather on data sets comprised of aortic aneurysm (AA) and acute aortic dissection (AAD) cases, where one of these two medical conditions had led to fatal rupture of the aorta. Our source for these cases were the autopsy databases of Semmelweis University, from the time period of 1994 to 2014. We have examined 160 aneurysm and 130 dissection cases in relation to changes in meteorological parameters. The algorythm implemented in our program is based on a non-parametric a Cox process model. It is capable of splitting slowly varying unknown global trends from fluctuations potentially caused by weather. Furthermore, it allows us to explore complex non-linear interactions between meteorological parameters and mortality. RESULTS: Model measures the relative growth of the expected number of events on the nth day caused by the deviation of environmental parameters from its mean value. The connection between ruptured aortic aneurysms (rAA) and changes in atmospheric pressure is more significant than their connection with mean daily temperatures. With an increase in atmospheric pressure, the rate of rAA mortality also increased. The effects of meteorological parameters were weaker for deaths resulting from acute aortic dissections (AAD), although low mean daily temperatures increased the intensity of occurrence for AAD-related deaths. CONCLUSION: The occurrence rate of fatal aortic catastrophes showed a slight dependence on the two examined parameters within our groups.


Assuntos
Aneurisma Aórtico/mortalidade , Dissecção Aórtica/mortalidade , Ruptura Aórtica/mortalidade , Pressão Atmosférica , Estações do Ano , Temperatura , Idoso , Algoritmos , Dissecção Aórtica/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Ruptura Aórtica/diagnóstico por imagem , Feminino , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
8.
Orv Hetil ; 161(7): 269-274, 2020 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-32037870

RESUMO

Treatment of thoracoabdominal aortic aneurysms is one of the most difficult challenges of vascular surgery. Endovascular options for complex aneurysms in urgent situation are limited. Thoracoabdominal giant aortic aneurysms are especially rare phenomena, each of them requires patient-specific treatment. Staged-fashion reconstructions may offer lower rate, especially for spinal cord injury. In our case report, we present a male patient, who had a 19.2 cm maximum diameter modified Crawford type V thoracoabdominal aortic aneurysm with contained rupture. The patient underwent an acute open repair and later a staged endovascular repair successfully. A 64-year-old male patient was admitted to our institution with complaints of chest and lower back pain in stable hemodynamic state. After evaluation, computer tomography angiography revealed a 19.2 cm maximum diameter thoracoabdominal aortic aneurysm, compression signs and hemothorax. Based on the anatomy, the serious compression symptoms and hemothorax associated with the gigantic aneurysm, we decided to perform open aortic repair. To reduce risk of spinal cord ischemia, intraoperatively we chose finishing the full reconstruction in a staged fashion. First, we performed an open repair with a Dacron interpositum distally using an oblique patch involving the visceral orifices. Later we implanted a thoracic endograft. At one-year follow-up, the patient was symptom-free, with no sign of endoleak. Giant aortic aneurysms are rare conditions, especially in the thoracoabdominal region. In the presence of compression symptoms, hemothorax and unsuitable aneurysm anatomy, open repair should be done. Staged repair offers a less invasive approach decreasing the risk of spinal cord ischemia. Orv Hetil. 2020; 161(7): 269-274.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Ruptura Aórtica/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Orv Hetil ; 160(11): 435-437, 2019 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-30852908

RESUMO

The number of patients with end-stage kidney disease requiring hemodialysis has been growing. The use of permanent central venous dialysis catheters has been increasing. Catheters in the central veins may adhere strongly to the vessel wall, so their removal may lead to difficulties. A recently published endovascular method (so-called Hong technique) turns the catheter removal to an easy and fast outpatient method and avoids sternotomy. We successfully removed a catheter inserted into the left subclavian vein 6 years ago which was impossible to extract by the usual techniques. Based on our experience, we recommend the routine use of the Hong technique. Orv Hetil. 2019, 160(11): 435-437.


Assuntos
Cateterismo Venoso Central/instrumentação , Cateteres Venosos Centrais , Remoção de Dispositivo/métodos , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Humanos , Diálise Renal , Veia Cava Superior
10.
Radiology ; 290(1): 246-253, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30325284

RESUMO

Purpose To compare the image quality produced by kinetic imaging in x-ray angiography and the current reference standard digital subtraction angiography (DSA). Materials and Methods This prospective observational crossover study enrolled 42 patients undergoing lower limb x-ray angiography between February and June 2017 (mean age, 68.7 years; age range, 49-89 years; 32 men [mean age, 67.1 years; age range, 49-89 years] and 10 women [mean age, 75 years; age range, 57-85 years]). Signal-to-noise ratios (SNRs) of DSA and kinetic image pairs were compared. Visual quality comparisons were also performed by specialists who used an online questionnaire. Interrater agreement was characterized by percent agreement and Fleiss k. Results A total of 1902 regions of interest were carefully selected in 110 image pairs to calculate and compare the SNRs. Median SNR in raw kinetic images was 3.3-fold and 2.3-fold higher than raw and postprocessed DSA images, respectively. A total of 232 pairs of raw and postprocessed kinetic images were compared. It was indicated that postprocessing improved the quality of kinetic images in 63.9% (2668 of 4176) of the comparisons. Interrater agreement was 75% and Fleiss k was 0.12 (P < .001). Also, 238 pairs of kinetic and DSA images were compared. Kinetic imaging was judged to have provided higher quality images than DSA in 69.0% (2462 of 3570) of the comparisons. The interrater agreement was 81% and Fleiss k was 0.17 (P < .001). Conclusion Kinetic imaging helps to view the same structures as digital subtraction angiography but offers better image quality. The improved signal-to-noise ratio suggests that this approach could reduce radiation exposure and improve the ability to view smaller vessels. © RSNA, 2018 Online supplemental material is available for this article.


Assuntos
Angiografia/métodos , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Cinética , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Estudos Prospectivos , Razão Sinal-Ruído
11.
Orv Hetil ; 159(37): 1501-1505, 2018 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-30196717

RESUMO

INTRODUCTION: There are several statements about the connection between cardiovascular diseases and climate change. On behalf of our observation-based knowledge we hypothesized a relationship between the occurence of aortic aneurysm (AA) rupture and weather changes. AIM: The purpose of our study was to explore the relationship between fatal aortic catastrophe and changes in atmospheric pressure and temperature. By using a new method we could even measure the intensity of the connection. METHOD: We have developed a software earlier to examine the link between pulmonary embolism mortality and the weather on data sets comprised of aortic aneurysm cases, where the medical condition had led to the fatal rupture of the aorta. For the events mentioned earlier we used the autopsy database of Semmelweis University between January 1, 2005 and January 1, 2014. Altogether we examined 152 aneurysm-related aortic catastrophes. We reported the exact day of the incident and the weather conditions on that day and the day before. RESULTS AND CONCLUSION: We have defined that the occurrence rate of fatal aortic catastrophe showed a slight dependence on the two examined parameters within our groups. We have found the connection related to ruptured aortic aneurysm and changes in atmospheric pressure more significant than their connection with mean daily temperatures. With the increase in atmospheric pressure, the rate of AA mortality also increased. In the knowledge of our results we believe that the mathematical model we used can be an effective starting point for population-based and prospective studies. Orv Hetil. 2018; 159(37): 1501-1505.


Assuntos
Aneurisma Aórtico/epidemiologia , Ruptura Aórtica/epidemiologia , Pressão Atmosférica , Tempo (Meteorologia) , Autopsia , Bases de Dados Factuais , Humanos , Fatores de Risco , Estações do Ano
12.
Redox Biol ; 14: 439-449, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29078169

RESUMO

Menthol is a naturally occurring monoterpene alcohol possessing remarkable biological properties including antipruritic, analgesic, antiseptic, anti-inflammatory and cooling effects. Here, we examined the menthol-evoked Ca2+ signals in breast and prostate cancer cell lines. The effect of menthol (50-500µM) was predicted to be mediated by the transient receptor potential ion channel melastatin subtype 8 (TRPM8). However, the intensity of menthol-evoked Ca2+ signals did not correlate with the expression levels of TRPM8 in breast and prostate cancer cells indicating a TRPM8-independent signaling pathway. Menthol-evoked Ca2+ signals were analyzed in detail in Du 145 prostate cancer cells, as well as in CRISPR/Cas9 TRPM8-knockout Du 145 cells. Menthol (500µM) induced Ca2+ oscillations in both cell lines, thus independent of TRPM8, which were however dependent on the production of inositol trisphosphate. Results based on pharmacological tools point to an involvement of the purinergic pathway in menthol-evoked Ca2+ responses. Finally, menthol (50-500µM) decreased cell viability and induced oxidative stress independently of the presence of TRPM8 channels, despite that temperature-evoked TRPM8-mediated inward currents were significantly decreased in TRPM8-knockout Du 145 cells compared to wild type Du 145 cells.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Mentol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Canais de Cátion TRPM/agonistas , Canais de Cátion TRPM/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Cálcio/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo
13.
Phytomedicine ; 34: 44-49, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28899508

RESUMO

BACKGROUND: Transient Receptor Potential Vanilloid 1 (TRPV1) confers noxious heat and inflammatory pain signals in the peripheral nervous system. Clinical trial of resiniferatoxin from Euphorbia species is successfully aimed at TRPV1 in cancer pain management and heading toward new selective painkiller status that further validates this target for drug discovery efforts. Evodia species, used in traditional medicine for hundreds of years, are a recognised source of different TRPV1 agonists, but no antagonist has yet been reported. HYPOTHESIS/PURPOSE: In a search for painkiller leads, we noted for the first time a TRPV1 antagonist activity in the fresh fruits of Tetradium daniellii (Benn.) T.G. Hartley (syn. Evodia hupehensis Dode). METHODS: Through a combination of extraction and purification methods with functional TRPV1-specific Ca2+ uptake assays (bioactivity-guided fractionation/isolation/purification); we isolated a new painkiller candidate that is a distant structural homologue of capsiate exovanilloids and endovanilloids such as anandamide, but a putative competitive inhibitor of the TRPV1. Four additional inactive compounds (N-isobutyl-4,5-epoxy-2E-decadienamide, geranylpsoralen, 8-(7',8'-epoxygeranyloxy)psoralen, and xanthotoxol) were also co-purified with pellitorine. Their structures were established by extensive 1D- and 2D-NMR spectroscopic analysis. RESULTS: 1H- and 13C NMR determination of the chemical structure revealed it to be pellitorine, (2E,4E)-N-(2-methylpropyl)deca-2,4-dienamide, which can compete structurally with algesics released in inflammation. In contrast to previous isolates from Evodia species, pellitorine blocked capsaicin-evoked Ca2+ uptake with an IC50 of 154 µg/ml (0.69 mM/l). N-Isobutyl-4,5-epoxy-2E-decadienamide and geranylpsoralen, 8-(7',8'-epoxygeranyloxy)psoralen, and xanthotoxol did not affect the TRPV1. CONCLUSION: This is the first evidence that pellitorine, an aliphatic alkylamide analogue of capsaicin, can serve as an antagonist of the TRPV1 and may inhibit exovanilloid-induced pain.


Assuntos
Analgésicos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Extratos Vegetais/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Rutaceae/química , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Linhagem Celular , Evodia/química , Ácidos Graxos Insaturados/química , Frutas/química , Humanos , Camundongos Endogâmicos BALB C , Alcamidas Poli-Insaturadas/química
14.
PLoS One ; 12(6): e0179950, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28640864

RESUMO

There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells. This indicates that MCF7 cells not only express functional TRPV1 channels, but also produce endogenous TRPV1 agonists. We investigated the effects of MRS1477 and capsaicin on cell viability, caspase-3 and -9 activities and reactive oxygen species production in MCF7 cells. The fraction of apoptotic cells was increased after 3 days incubation with capsaicin (10 µM) paralleled by increased reactive oxygen species production and caspase activity. These effects were even more pronounced, when cells were incubated with MRS1477 (2 µM) either alone or together with CAPS (10 µM). Capsazepine, a TRPV1 blocker, inhibited both the effect of capsaicin and MRS1477. Whole-cell patch clamp recordings revealed that capsaicin-evoked TRPV1-mediated current density levels were increased after 3 days incubation with MRS1477 (2 µM). However, the tumor growth in MCF7 tumor-bearing immunodeficient mice was not significantly decreased after treatment with MRS1477 (10 mg/ kg body weight, i.p., injection twice a week). In conclusion, in view of a putative in vivo treatment with MRS1477 or similar compounds further optimization is required.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Di-Hidropiridinas/farmacologia , Terapia de Alvo Molecular , Canais de Cátion TRPV/metabolismo , Regulação Alostérica/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Capsaicina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Células MCF-7 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Front Physiol ; 8: 378, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28626428

RESUMO

"Molecular neurosurgery" is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1-expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell.

16.
Magy Seb ; 70(1): 18-23, 2017 03.
Artigo em Húngaro | MEDLINE | ID: mdl-28294661

RESUMO

INTRODUCTION: The Endologix developed an aortoiliac stent graft system that is different than the conventional implantation technique (Nellix, EVAS-endovascular aneurysm sealing system). The first implantation in Hungary has been performed in the beginning of 2016 at Heart and Vascular Center. METHODS: Nellix: two endobags surrounding ballon-expandable covered stent (10 mm) with optional length, biocompatible polymer which is able to be injected into the endobags and a procedure-coordinating console. The instructions for use: aortic neck length: ≥10 mm, neck diameter: 18-32 mm, angulation: ≤60°, blood lumen diameter: ≤60 mm, aneurysm maximal diameter: >50 mm, common iliac artery (CIA) minimal and maximal diameter: ≥9 mm, ≤35 mm. RESULTS: Six elective implantations were performed at our clinic. The average age of the patients were: 68.33 ± 12.44 year, the rate of male was 100%. The reason of implantations was isolated infrarenal aortic aneurysm, CIA aneurysm or both. The average postoperative in-hospital stay were 5.17 ± 1.47 days. In the perioperative period fever and femoral wound healing problem developed in one patient respectively. The average follow-up period were 177.17 ± 96.91 days. There was no endoleak, graft-migration, aneurysm growth, reoperation or death. A stroke with left hemiparesis without residual symptoms developed in one case in the third week after the operation. CONCLUSIONS: Due to the new EVAS technology, according to 30-day and midterm results the system is able to be used in complicated anatomical situations with low perioperative mortality and morbidity, and it can decrease the incidence of endoleaks, graftmigration and aneurysm growth.


Assuntos
Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Aneurisma Ilíaco/cirurgia , Artéria Ilíaca/cirurgia , Stents , Idoso , Idoso de 80 Anos ou mais , Endoleak/etiologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Magy Seb ; 70(1): 5-12, 2017 03.
Artigo em Húngaro | MEDLINE | ID: mdl-28294663

RESUMO

INTRODUCTION: Vascular homografts are used for limb salvage in cases of graft infection after previous reconstructive vascular surgery or inadequate autologous veins. During multi-organ donation the thoracic aorta segment, aortic bifurcation, iliac arteries, femoral arteries, popliteal arteries, femoral veins and greater saphenous veins can be harvested. Our aim was to optimize the use of homografts by analyzing the results of previous procedures. METHODS: The patient information was processed retrospectively, using the clinical computer system. 162 procedures were performed on 144 patients between 2007 and 2014. The short- and long-term patency, hemorrhagic complication rate, amputation rate and mortality was examined in our study. The location, graft type and length of cryopreservation were taken into consideration. Aortoiliac and femoropopliteal reconstructions with arterial and venous homografts were examined. RESULTS: The mean age of the patients was 63.6 ± 10.7 years, the mean follow-up period was 36 ± 28 months. The primary patency rates at the postoperative 1, 3 and 6 months were 83.7%, 75.0% and 63.4%. In this study the arterial and deep venous homografts had better primary patency rates compared to the superficial venous homografts: at the postoperative 1, 3, 6 months the arterial homograft results were 85.6%, 78.6% and 74.3%, the greater saphenous vein homograft results were 81.4%, 70.4% and 47.7% in the same intervals. CONCLUSION: The reconstructive surgical procedures in septic area mean serious challenge for the vascular surgeons. The AB0 compatibility of the graft and the recipient did not result better long-term outcomes compared to the non-compatible grafts. According to our data the ideal choice of homogenous graft is an arterial homograft which was not cryopreserved longer than 6 months.


Assuntos
Artérias/cirurgia , Artérias/transplante , Prótese Vascular/efeitos adversos , Perna (Membro)/irrigação sanguínea , Transplante Homólogo , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Criopreservação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Reoperação , Resultado do Tratamento , Grau de Desobstrução Vascular
18.
Magy Seb ; 70(1): 24-31, 2017 03.
Artigo em Húngaro | MEDLINE | ID: mdl-28294670

RESUMO

INTRODUCTION: Most of the patients with iliofemoral thrombosis treated with anticoagulants only are affected with postthrombotic syndrome (PTS) that worsens the patients' quality of life. In the acute phase of proximal deep venous thrombosis (DVT) catheter-directed (CDT) and pharmacomechanical thrombolysis may be a reasonable alternative therapeutic method. Our aim was to summarize our results using these methods. METHODS: Since 2009 twenty-four patients with iliofemoral DVT were treated with these endovascular procedures and with stenting at our Institution. RESULTS: The median age of the patients was 35.83 ± 15.9 years, the female: male ratio was approximately 2:1. The mean time between the onset of the symptoms and the procedures was eleven days. CDT alone was performed in 8 patients, thrombus aspiration in addition to CDT using AngioJet device in 16 patients; in 19 cases the procedure was completed with venous stenting. During the follow-up we performed US examinations and estimated the severity of PTS by Villalta-scale. The total recanalization-rate was more than 50%, which even improved during the follow-up. The total lysis time and the amount of used recombinant tissue plasminogen activator decreased significantly by applying the AngioJet. We did not find any severe PTS among our patients during the follow-up visits. CONCLUSION: Our data suggests that these methods can be used efficiently and safely in the treatment of acute iliofemoral DVT.


Assuntos
Cateterismo Periférico , Procedimentos Endovasculares/métodos , Veia Femoral/cirurgia , Fibrinolíticos/administração & dosagem , Veia Ilíaca/cirurgia , Stents , Terapia Trombolítica/efeitos adversos , Ultrassonografia de Intervenção/métodos , Trombose Venosa/terapia , Feminino , Veia Femoral/diagnóstico por imagem , Veia Femoral/fisiopatologia , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Humanos , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/fisiopatologia , Masculino , Síndrome Pós-Trombótica/prevenção & controle , Qualidade de Vida , Trombectomia , Terapia Trombolítica/métodos , Resultado do Tratamento , Grau de Desobstrução Vascular/efeitos dos fármacos , Trombose Venosa/diagnóstico , Trombose Venosa/fisiopatologia
19.
FEBS Lett ; 590(16): 2768-75, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27339229

RESUMO

There is enormous interest toward vanilloid agonists of the pain receptor TRPV1 in analgesic therapy, but the mechanisms of their sensory neuron-blocking effects at high or repeated doses are still a matter of debate. Our results have demonstrated that capsaicin and resiniferatoxin form nanomolar complexes with calmodulin, and competitively inhibit TRPV1-calmodulin interaction. These interactions involve the protein recognition interface of calmodulin, which is responsible for all of the cell-regulatory calmodulin-protein interactions. These results draw attention to a previously unknown vanilloid target, which may contribute to the explanation of the paradoxical pain-modulating behavior of these important pharmacons.


Assuntos
Calmodulina/metabolismo , Dor/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Sítios de Ligação , Calmodulina/química , Calmodulina/genética , Capsaicina/metabolismo , Capsaicina/farmacologia , Diterpenos/metabolismo , Diterpenos/farmacologia , Humanos , Dor/tratamento farmacológico , Ligação Proteica , Conformação Proteica , Mapas de Interação de Proteínas/genética , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/química , Canais de Cátion TRPV/genética
20.
Biochim Biophys Acta ; 1863(8): 2054-64, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27180305

RESUMO

Vanilloids including capsaicin and resiniferatoxin are potent transient receptor potential vanilloid type 1 (TRPV1) agonists. TRPV1 overstimulation selectively ablates capsaicin-sensitive sensory neurons in animal models in vivo. The cytotoxic mechanisms are based on strong Na(+) and Ca(2+) influx via TRPV1 channels, which leads to mitochondrial Ca(2+) accumulation and necrotic cell swelling. Increased TRPV1 expression levels are also observed in breast and prostate cancer and derived cell lines. Here, we examined whether potent agonist-induced overstimulation mediated by TRPV1 might represent a means for the eradication of prostate carcinoma (PC-3, Du 145, LNCaP) and breast cancer (MCF7, MDA-MB-231, BT-474) cells in vitro. While rat sensory neurons were highly vanilloid-sensitive, normal rat prostate epithelial cells were resistant in vivo. We found TRPV1 to be expressed in all cancer cell lines at mRNA and protein levels, yet protein expression levels were significantly lower compared to sensory neurons. Treatment of all human carcinoma cell lines with capsaicin didn't lead to overstimulation cytotoxicity in vitro. We assume that the low vanilloid-sensitivity of prostate and breast cancer cells is associated with low expression levels of TRPV1, since ectopic TRPV1 expression rendered them susceptible to the cytotoxic effect of vanilloids evidenced by plateau-type Ca(2+) signals, mitochondrial Ca(2+) accumulation and Na(+)- and Ca(2+)-dependent membrane disorganization. Moreover, long-term monitoring revealed that merely the ectopic expression of TRPV1 stopped cell proliferation and often induced apoptotic processes via strong activation of caspase-3 activity. Our results indicate that specific targeting of TRPV1 function remains a putative strategy for cancer treatment.


Assuntos
Neoplasias da Mama/patologia , Capsaicina/farmacologia , Diterpenos/farmacologia , Células Epiteliais/efeitos dos fármacos , Proteínas de Neoplasias/fisiologia , Neoplasias da Próstata/patologia , Células Receptoras Sensoriais/efeitos dos fármacos , Canais de Cátion TRPV/agonistas , Animais , Apoptose/fisiologia , Mama/metabolismo , Neoplasias da Mama/metabolismo , Células Cultivadas , Células Epiteliais/metabolismo , Feminino , Humanos , Masculino , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Ratos , Ratos Wistar , Proteínas Recombinantes/metabolismo , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPV/biossíntese , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/fisiologia , Gânglio Trigeminal/metabolismo
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