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1.
Curr Ther Res Clin Exp ; 88: 18-25, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29632620

RESUMEN

BACKGROUND: The protective potential of lazaroids has been reported in previous studies on ischemia/reperfusion and induced hemorrhagic shock protocols. OBJECTIVES: The present study is the first experimental protocol on the effects of the antioxidant factor U-74389G on the small intestine of swine models in a hemorrhagic shock protocol and resuscitation with 3 different types of fluids. METHODS: The study included 49 Landrace breed swine that were divided into groups of 7 each. Hemorrhage was provoked 45 minutes after starting the surgical protocol (0 minutes), followed by resuscitation starting 30 minutes after haemorrhage ceased by using 3 different fluids. Three groups (Group A, resuscitation using blood; Group B, resuscitation with Ringer's lactate solution; and Group C, resuscitation with hypertonic saline solution) underwent resuscitation with fluid alone, and another 3 groups (named A', B,' and C') were administered lazaroid U-74389G in addition to fluid. Control Group S underwent all the surgical procedures without hemorrhagic shock. Vital signs, complete blood count, and biochemical markers were analyzed, and tissue samples of the small intestine were collected from all animals. Further, malondialdehyde, tumor necrosis factor-α, and levels of inflammation in the tissue sample were measured. RESULTS: In Group S-A-A' and Group S-C-C', the analysis did not show statistically significant differences in the percentage changes of histopathology, malondialdehyde, and tumor necrosis factor-α through time. In Group S-B-B', the malondialdehyde levels in the small intestine were reduced in both the B and B' groups, without lazaroid (Group B) (P = 0.038) and lazaroid (Group B') (P = 0.011), compared with Group S (control), but the group without lazaroid (Group B) had greater reduction in malondialdehyde levels than the group treated with lazaroid (Group B'). With regard to the biochemistry results, 24% reduction was observed for alkaline phosphatase (P = 0.022) in Group A' treated with lazaroid compared with that in the untreated group. Lastly, for the complete blood count parameters, a 14% reduction in white blood cells was observed in Group B', which was treated with lazaroid in all phases (P = 0.015) (absolute value = 6.23) compared with Group B (absolute value = 13.74). CONCLUSIONS: Despite few initial findings of this study suggesting that administration of lazaroid U-74389G may have some potential in attenuation of the effects of hemorrhagic shock in the small intestine of swine models, no differences remained after correction for multiple comparisons was made. Therefore, further research is required to investigate this result thoroughly.

2.
J Surg Res ; 193(2): 667-74, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25277360

RESUMEN

BACKGROUND: Crohn disease is still incurable. Compounds with anti-inflammatory and/or antioxidative effects are tested in various preclinical models of the disease. Our aim was to investigate the effects of sildenafil and lazaroid U-74389G in an experimental rat model of trinitrobenzenesulfonic acid-induced colitis. MATERIALS AND METHODS: Trinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for the rats belonging to the first group. For 6 days, the animals in group 3 were administered daily sildenafil orally, the rats in group 4 were administered daily U-74389G intravenously, and the rats in group 5 were coadministered daily sildenafil orally and intravenous U-74389G. The rats in groups 1 and 2 were not administered any treatment. During the study, the weights were recorded as a marker of clinical condition. The colon damage was evaluated using macroscopic colon mucosal damage index (CMDI), microscopic (Geboes score), and biochemical methods (tissue tumor necrosis factor [TNF]-α and malondialdehyde [MDA]). RESULTS: Sildenafil reduced TNF-α tissue levels and increased body weight. U-74389G reduced TNF-α, the macroscopic index of mucosal damage score (CMDI) and increased body weight. The combined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-α and MDA, lowered CMDI and microscopic Geboes score, and increased body weight. CONCLUSIONS: U-74389G demonstrated a significant anti-inflammatory activity related to its ability to reduce colonic TNF-α, CMDI score, and improve weight change. We confirmed that sildenafil has anti-inflammatory capacity by reducing colonic TNF-α and by improving body weight. Finally, the combined treatment showed superior effects by reducing colonic TNF-α, colonic MDA, CMDI score, Geboes score, and by improving weight.


Asunto(s)
Antioxidantes/uso terapéutico , Colitis/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Piperazinas/uso terapéutico , Pregnatrienos/uso terapéutico , Sulfonas/uso terapéutico , Animales , Colitis/inducido químicamente , Colitis/patología , Colon/metabolismo , Colon/patología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Masculino , Malondialdehído/metabolismo , Purinas/uso terapéutico , Distribución Aleatoria , Ratas Wistar , Citrato de Sildenafil , Ácido Trinitrobencenosulfónico , Factor de Necrosis Tumoral alfa/metabolismo
3.
J Surg Res ; 195(1): 228-34, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25659614

RESUMEN

BACKGROUND: Ischemia-reperfusion injury caused by severe hemorrhagic shock and subsequent resuscitation leads to deterioration of hepatic homeostasis and possibly to liver failure. The present study focuses on determining whether there is a different biological response to hemorrhagic shock by different sources of hemorrhage, hepatic hemorrhage (HH) versus peripheral hemorrhage. METHODS: Twenty-one male swine (Sus scrofa domesticus) were randomly allocated in three groups as follows: sham group (S, n = 5), central venous hemorrhage group, (CVH) (n = 8), and HH group (n = 8). Hepatectomy of the left liver lobe was carried out in groups CVH and HH, and the animals were subjected to controlled bleeding from the internal jugular vein and the traumatic liver surface, respectively. After 10 min of hemorrhage, shock was maintained for 30 min at mean arterial pressure levels of 30 mm Hg-40 mm Hg and resuscitation was initiated with crystalloids and colloids. Hemodynamic parameters and fluid balance were monitored throughout the 6 h of total duration of the experiment. Blood samples were collected at 0-, 40-, and 360-min time points for transaminases, albumin, and interleukin-6 measurement. Hepatic tissue was harvested at the end of the experiment for oxidative marker and proliferation analysis. RESULTS: Although blood loss was comparable between the two groups, the amount of fluids needed for resuscitation was higher for the HH group. Inflammatory response, measured by interleukin-6, was found higher in HH group. Oxidative stress markers did not reveal statistically significant difference between the two groups. Liver hemorrhage decreased hepatocellular proliferation measured by proliferating cell nuclear antigen. CONCLUSIONS: Our study provides evidence that HH entails worse consequences for the hepatocytes than systemic hemorrhage. Higher needs for resuscitation fluids, decreased proliferation, and augmented inflammatory response when HH takes place are findings with possible clinical importance in liver surgery and trauma.


Asunto(s)
Hepatectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/metabolismo , Choque Hemorrágico/etiología , Choque Hemorrágico/metabolismo , Animales , Pérdida de Sangre Quirúrgica , Modelos Animales de Enfermedad , Hemodinámica , Hígado/metabolismo , Hígado/patología , Masculino , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/terapia , Distribución Aleatoria , Resucitación , Choque Hemorrágico/patología , Choque Hemorrágico/terapia , Porcinos
4.
JOP ; 16(2): 176-84, 2015 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-25791552

RESUMEN

CONTEXT: The potential of lazaroid U-74389G in attenuating injury after ischemia and reperfusion has been reported in various organs. OBJECTIVE: The present study focuses specifically on the pancreas and aims to examine any effects of U-74389G in a swine model of pancreatic ischemia and reperfusion, encompassing ischemic preconditioning. METHODS: Twelve pigs, weighing 28-35 kg, were randomized into two experimental groups. Group A (control group, n=6): Two periods of ischemic preconditioning (5 min each) separated by a 5-min rest interval; then ischemia time 30 min and reperfusion for 120 min. Group B (n=6): the same as above, with U-74389G intravenous injection in the inferior vena cava immediately prior to the initiation of reperfusion. Blood sampling and pancreatic biopsies were conducted at 0, 30, 60, 90 and 120 min after reperfusion. RESULTS: Repeated-measures ANOVA was undertaken to evaluate differences between the two study groups. No statistically significant differences were noted concerning the histopathological parameters in the control and therapy groups (P=0.563 for edema, P=0.241 for hemorrhage, P=0.256 for leukocyte infiltration, P=0.231 for acinar necrosis and P=0.438 for vacuolization). In accordance with the above, serum metabolic data (glucose, creatinine, urea, total and direct bilirubin, total calcium, amylase, lipase, SGOT/AST, SGPT/ALT, ALP, GGT, LDH, CRP, insulin) were not significantly different between the two groups; similarly, tumor necrosis factor-α values (P=0.705) and tissue malondialdehyde levels (P=0.628) did not differ between the two groups. CONCLUSION: This swine model of pancreatic ischemia and reperfusion, encompassing preconditioning, indicates that U-74389G lazaroid does not seem to exert protective effects from pancreatic damage.

5.
J Surg Res ; 187(2): 450-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24332939

RESUMEN

BACKGROUND: Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack. The aim of our study was to evaluate the therapeutic potential of 21-aminosteroid U-74389G in pancreatic injury after ischemia and reperfusion of the organ in a swine model. MATERIALS AND METHODS: Twelve pigs (weighing 28-35 kg) were randomized into the following two experimental groups: group A (control group, n = 6): ischemia of pancreas (30 min) followed by reperfusion for 120 min; and group B (n = 6): ischemia of pancreas (30 min), U-74389G intravenous injection (10 mg/kg) in the inferior vena cava, and reperfusion for 120 min. Tissue and blood sampling was conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated measures analysis of variance was performed for the evaluation of differences between the two groups. RESULTS: Histopathologic evaluation did not reveal a statistically significant difference concerning hemorrhage (P = 0.193), leukocyte infiltration (P = 0.838), acinar necrosis (P = 0.183), and vacuolization (P = 0.185) in the pancreatic tissue between the two groups; nevertheless, edema seemed to be more pronounced in the U-74389G group (P = 0.020). Serum metabolic data in the control and therapy groups were not significantly different; accordingly, tissue malondialdehyde levels (P = 0.705) and tumor necrosis factor α values (P = 0.863) did not differ between the two groups. CONCLUSIONS: On the basis of the histologic data and the absence of reduction in the malondialdehyde and tumor necrosis factor α levels, it is concluded that the administration of U-74389G does not seem to exert a sizable therapeutic effect in attenuating pancreatic damage from ischemia-reperfusion injury.


Asunto(s)
Antioxidantes/farmacología , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Pregnatrienos/farmacología , Daño por Reperfusión/tratamiento farmacológico , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Femenino , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Pancreatitis Aguda Necrotizante/metabolismo , Pancreatitis Aguda Necrotizante/patología , Distribución Aleatoria , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Sus scrofa , Insuficiencia del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismo
6.
Scand J Gastroenterol ; 49(1): 3-14, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24354966

RESUMEN

Total parenteral nutrition (TPN) represents a therapeutic modality that could save the life of a patient with inflammatory bowel disease (IBD) facing severe nutritional problems, by restoring the patient's impaired nutritional status. TPN does not compete with enteral nutrition (EN), the latter being the first choice for all patients having anatomically intact and functionally normal digestive tract. TPN allows bowel rest while supplying adequate calorific intake and essential nutrients, and removes antigenic mucosal stimuli. The value of TPN in malnourished patients with intestinal failure due to CD is beyond doubt. However, it is difficult to suggest TPN as a sole treatment for active CD. An increased rate of remission could not be expected by applying TPN. The utility of TPN is restricted to certain cases involving efforts to close enterocutaneous or other complicated fistulas in patients with fistulizing CD, the treatment of short bowel syndrome following extensive resections for CD, or when EN is impractical for other reasons. There are no advantages of TPN therapy over EN therapy regarding fistula healing. TPN has no influence on the surgical intervention rate and little benefit by bypassing the intestinal passage could be expected. Also TPN shows no advantage if the disease is chronically active. However, an optimal supply of nutrients improves bowel motility, intestinal permeability and nutritional status, and reduces inflammatory reactions. TPN might be associated with an increased risk of adverse events, although TPN undertaken by experienced teams does not cause more complications than does EN.


Asunto(s)
Colitis Ulcerosa/terapia , Enfermedad de Crohn/terapia , Nutrición Parenteral Total , Carbohidratos/administración & dosificación , Cateterismo Venoso Central , Cateterismo Periférico , Grasas/administración & dosificación , Glutamina/administración & dosificación , Humanos , Nutrición Parenteral Total/efectos adversos , Nutrición Parenteral Total/métodos , Proteínas/administración & dosificación , Oligoelementos/administración & dosificación , Vitaminas/administración & dosificación
7.
Am J Emerg Med ; 32(8): 871-7, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24857249

RESUMEN

BACKGROUND: In addition to its role in the endogenous control of erythropoiesis, recombinant human erythropoietin (rh-EPO) has been shown to exert tissue protective properties in various experimental models. However, its role in the cardiac arrest (CA) setting has not yet been adequately investigated. AIM: The aim of this study is to examine the effect of rh-EPO in a pig model of ventricular fibrillation (VF)-induced CA. METHODS: Ventricular fibrillation was electrically induced in 20 piglets and maintained untreated for 8 minutes before attempting resuscitation. Animals were randomized to receive rh-EPO (5000 IU/kg, erythropoietin [EPO] group, n = 10) immediately before the initiation of chest compressions or to receive 0.9% Sodium chloride solution instead (control group, n = 10). RESULTS: Compared with the control, the EPO group had higher rates of return of spontaneous circulation (ROSC) (100% vs 60%, P = .011) and higher 48-hour survival (100% vs 40%, P = .001). Diastolic aortic pressure and coronary perfusion pressure during cardiopulmonary resuscitation were significantly higher in the EPO group compared with the control group. Erythropoietin-treated animals required fewer number of shocks in comparison with animals that received normal saline (P = .04). Furthermore, the neurologic alertness score was higher in the EPO group compared with that of the control group at 24 (P = .004) and 48 hours (P = .021). CONCLUSION: Administration of rh-EPO in a pig model of VF-induced CA just before reperfusion facilitates ROSC and improves survival rates as well as hemodynamic variables.


Asunto(s)
Circulación Sanguínea/efectos de los fármacos , Eritropoyetina/uso terapéutico , Paro Cardíaco/tratamiento farmacológico , Animales , Presión Sanguínea/efectos de los fármacos , Reanimación Cardiopulmonar , Modelos Animales de Enfermedad , Femenino , Paro Cardíaco/etiología , Porcinos , Resultado del Tratamiento , Fibrilación Ventricular/complicaciones
8.
World J Gastroenterol ; 30(8): 779-793, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38516237

RESUMEN

In this editorial, we comment on the article entitled "Advances and key focus areas in gastric cancer immunotherapy: A comprehensive scientometric and clinical trial review (1999-2023)," which was published in the recent issue of the World Journal of Gastroenterology. We focused on the results of the authors' bibliometric analysis concerning gastric cancer immunotherapy, which they analyzed in depth by compiling the relevant publications of the last 20 years. Before that, we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer (GC) in different countries, attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm. We then briefly discuss the conservative treatment (chemotherapy) of the various forms of this malignant neoplasm. We describe the treatment of resectable tumors, locally advanced neoplasms, and unresectable (advanced) cases. Special attention is given to modern therapeutic approaches with emphasis on immunotherapy, which seems to be the future of GC treatment, especially in combination with chemotherapy. There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications, the countries in which the studies were conducted, the authors, and the scientific centers of origin, as well as the clinical studies in progress. Finally, an attempt is made to draw some con-clusions and to point out possible future directions.


Asunto(s)
Neoplasias Gástricas , Humanos , Inmunoterapia/métodos , Neoplasias Gástricas/patología
9.
World J Gastroenterol ; 30(15): 2068-2080, 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38681984

RESUMEN

The treatment of patients with inflammatory bowel disease (IBD), especially those with severe or refractory disease, represents an important challenge for the clinical gastroenterologist. It seems to be no exaggeration to say that in these patients, not only the scientific background of the gastroenterologist is tested, but also the abundance of "gifts" that he should possess (insight, intuition, determination, ability to take initiative, etc.) for the successful outcome of the treatment. In daily clinical practice, depending on the severity of the attack, IBD is treated with one or a combination of two or more pharmaceutical agents. These combinations include not only the first-line drugs (e.g., mesalazine, corticosteroids, antibiotics, etc) but also second- and third-line drugs (immunosuppressants and biologic agents). It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied. Therefore, a part of these patients are going to surgery. In recent years, several small-size clinical studies, reviews, and case reports have been published combining not only biological agents with other drugs (e.g., immunosuppressants or corticosteroids) but also the combination of two biological agents simultaneously, especially in severe cases. In our opinion, it is at least a strange (and largely unexplained) fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few. As mentioned above, there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations. The appropriate dosage, the duration of the administration, the suitable timing for checking the clinical and laboratory outcome, as well as the treatment side-effects, should be the subject of intense clinical research shortly. In this editorial, we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients. We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.


Asunto(s)
Quimioterapia Combinada , Inmunosupresores , Enfermedades Inflamatorias del Intestino , Humanos , Quimioterapia Combinada/métodos , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Resultado del Tratamiento , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/diagnóstico , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/administración & dosificación , Índice de Severidad de la Enfermedad , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Productos Biológicos/uso terapéutico , Productos Biológicos/administración & dosificación
10.
World J Gastrointest Oncol ; 16(3): 583-597, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38577465

RESUMEN

During the last few years, epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages, the so-called "early-onset cancer". This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms, mainly stomach and in a lesser degree pancreas, and biliary tract. It should be emphasized that data concerning digestive neoplasms, except for those referring to the colon and stomach, could be characterized as rather insufficient. The exact magnitude of the shift in younger ages is expected to become clearer shortly, as long as relevant epidemiological data from many parts of the world would be available. The most important question concerns the etiology of this phenomenon, since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many countries. The existing data support the assumption that a number of environmental factors may play a primary role in influencing carcinogenesis, sometimes from childhood. Changes that have appeared in the last decades related mainly to eating habits, consistency of gut microbiome and an increase of obese people interacting with genetic factors, ultimately favor the process of carcinogenesis. Even these factors however, are not entirely sufficient to explain the age-related changes in the frequency of digestive neoplasms. Studies of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are required. In this article, we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible pathogenesis. Finally, we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

11.
Nutrients ; 16(11)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38892572

RESUMEN

It is well established that the preoperative nutritional status of gastric cancer (GC) patients significantly affects the prognosis of the operated patients, their overall survival, as well as the disease-specific survival. Existing data support that preoperative assessment of nutritional status and early correction of nutritional deficiencies exert a favorable effect on early postoperative outcomes. A variety of relevant indices are used to assess the nutritional status of GC patients who are candidates for surgery. The guidelines of almost all international organizations recommend the use of oral enteral nutrition (EN). Oncologically acceptable types of gastrectomy and methods of patient rehabilitation should take into account the expected postoperative nutritional status. The majority of data support that perioperative EN reduces complications and hospital stay, but not mortality. Oral EN in the postoperative period, albeit in small amounts, helps to reduce the weight loss that is a consequence of gastrectomy. Iron deficiency with or without anemia and low serum levels of vitamin B12 are common metabolic sequelae after gastrectomy and should be restored. EN also significantly helps patients undergoing neoadjuvant or adjuvant antineoplastic therapy. The occurrence of the so-called "postgastrectomy syndromes" requires dietary modifications and drug support. This review attempts to highlight the benefits of EN in GC patients undergoing gastrectomy and to emphasize the type of necessary nutritional management, based on current literature data.


Asunto(s)
Nutrición Enteral , Gastrectomía , Estado Nutricional , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Nutrición Enteral/métodos , Gastrectomía/efectos adversos , Desnutrición/etiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Síndromes Posgastrectomía/etiología , Evaluación Nutricional
12.
Diagnostics (Basel) ; 14(4)2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38396441

RESUMEN

Translational perspective: Ischemic heart disease remains a major medical problem with high mortality rates. Beside the great efforts devoted to research worldwide and the use of numerous experimental models, an absolute understanding of myocardial infarction and tissue loss has not yet been achieved. Furthermore, the regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in the medical (and especially cardiovascular) community. In a novel experimental rat model, the beneficial effect of mesenchymal stem cell transplantation (MSCT) in a surgically induced ischemic myocardium was documented. From a clinical perspective, this work supports the surgical administration of MSCT in the infarcted area during coronary artery bypass surgery. AIMS: The regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in cardiovascular research. We developed a novel experimental rat model and used it to examine the effect of mesenchymal stem cell transplantation (MSCT) on myocardial ischemia evaluated by SPECT-CT and immunohistochemistry. METHODS AND RESULTS: An open thoracotomy took place for forty adult female Wistar rats with (n = 30) or without (n = 10) surgical ligation of the left anterior descending coronary artery (LAD) in order to cause myocardial ischemia. Myocardial viability was evaluated via SPECT/CT 7 days before surgery, as well as at 7 and 14 days post-surgery. At day 0, 15 animals received homologous stem cells injected at the ischemic myocardium area. A SPECT/CT evaluation showed decreased activity of the myocardial cells in the left ventricle one week post-infarction. Regeneration of the ischemic myocardium fifteen days post-infarction was recorded only in animals subjected to stem cell transplantation. These findings were also confirmed by histology and immunohistochemical analysis, with the significantly higher expression of GATA4 and Nkx2.5. CONCLUSIONS: The positive effect of mesenchymal stem cell transplantation in the ischemic myocardium was recorded. The application of SPECT-CT allowed a clear evaluation of both the quality and quantity of the living myocardium post-infarction, leading to a new approach in the research of cardiovascular diseases. From a clinical perspective, MSCT may be beneficial when accompanied by myocardial revascularization procedures.

13.
In Vivo ; 37(2): 649-654, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36881049

RESUMEN

BACKGROUND/AIM: Myocardial infarction, an acute medical situation with a high mortality rate worldwide, has been extensively studied in modern cardiovascular research, using different experimental models. However, a deep understanding of myocardial activity loss has not been fully investigated. We have developed a novel experimental rat model for noninvasive assessment of myocardial ischemia based on single photon emission computed tomography (SPECT/CT), in order to further understand and evaluate myocardial activity before and after surgical induction of myocardial ischemia. MATERIALS AND METHODS: Thirty adult female Wistar rats underwent open thoracotomy with (n=20) or without (n=10) surgical ligation of the left anterior descending coronary artery (LAD). The myocardial ischemia was confirmed with ECG and myocardial viability was evaluated via SPECT/CT at 7 days before as well as at 7 and 14 days post-surgery, after which animals were sacrificed and myocardial ischemic injury was further assessed histologically. RESULTS: All animals were evaluated with anatomical and functional criteria based on the SPECT/CT imaging results. A successful surgical technique causing ischemia and loss of myocardial function in all animals undergoing a LAD ligation was established. Furthermore, evaluation of the viable myocardium with SPECT/CT confirmed the reduction of functional myocardial cells of the left ventricle post-infarction, which was also documented histologically. CONCLUSION: Using our technique, the validity of this animal model to induce and evaluate myocardial ischemia was demonstrated. Our choice to apply SPECT-CT qualitative and quantitative evaluation of myocardial function leads to a new approach in experimentation with an anticipated significant impact in the ongoing cardiovascular laboratory research.


Asunto(s)
Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Femenino , Ratas , Animales , Ratas Wistar , Isquemia Miocárdica/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Miocardio
14.
Stud Health Technol Inform ; 302: 576-580, 2023 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-37203751

RESUMEN

The objective of this study was to compare different convolutional neural networks (CNNs), as employed in a Python-produced deep learning process, used on white light images of colorectal polyps acquired during the process of a colonoscopy, in order to estimate the accuracy of the optical recognition of particular histologic types of polyps. The TensorFlow framework was used for Inception V3, ResNet50, DenseNet121, and NasNetLarge, which were trained with 924 images, drawn from 86 patients.


Asunto(s)
Pólipos del Colon , Humanos , Pólipos del Colon/diagnóstico por imagen , Pólipos del Colon/patología , Colonoscopía/métodos , Redes Neurales de la Computación
15.
Nutrients ; 14(3)2022 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-35276978

RESUMEN

BACKGROUND: Pancreatic cancer represents the most lethal malignancy among all digestive cancers. Despite the therapeutic advances achieved during recent years, the prognosis of this neoplasm remains disappointing. An enormous amount of experimental (mainly) and clinical research has recently emerged referring to the effectiveness of various plants administered either alone or in combination with chemotherapeutic agents. Apart from Asian countries, the use of these plants and herbals in the treatment of digestive cancer is also increasing in a number of Western countries as well. The aim of this study is to review the available literature regarding the efficacy of plants and herbals in pancreatic cancer. METHODS: The authors have reviewed all the experimental and clinical studies published in Medline and Embase, up to June 2021. RESULTS: More than 100 plants and herbals were thoroughly investigated. Favorable effects concerning the inhibition of cancer cell lines in the experimental studies and a favorable clinical outcome after combining various plants with established chemotherapeutic agents were observed. These herbals and plants exerted their activity against pancreatic cancer via a number of mechanisms. The number and severity of side-effects are generally of a mild degree. CONCLUSION: A quite high number of clinical and experimental studies confirmed the beneficial effect of many plants and herbals in pancreatic cancer. More large, double-blind clinical studies assessing these natural products, either alone or in combination with chemotherapeutic agents should be conducted.


Asunto(s)
Antineoplásicos , Neoplasias Pancreáticas , Antineoplásicos/uso terapéutico , Asia , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Fitoterapia , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
J Surg Res ; 166(2): 265-74, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21092988

RESUMEN

Mesenteric ischemia occurs in a number of clinically relevant pathophysiologic processes, including sepsis, hemorrhage, intestinal transplantation, severe burns, and mesenteric thrombosis. The readmission of molecular oxygen into an ischemic tissue promotes the oxidation of resuscitated tissue with certain pathophysiologic mechanisms. Depending on the duration and the intensity of ischemia, reoxygenation of the intestine that has been reperfused may further induce tissue injury. Intestinal ischemia and reperfusion injury can accelerate complex processes between the endothelium and different cell types leading to microvascular injury, cellular necrosis, and apoptosis. The injury due to reperfusion is found predominantly in the intestinal mucosa and submucosa, causing endothelial detachment. The 21-aminosteroids (lazaroids) are a family of compounds that inhibit lipid membrane peroxidation. Many of the performed studies show conflicting results, which reflect differences in experimental design, evolving time that (I/R) is induced, total or partial vascular occlusion, dosage of the lazaroid, and the exact period of time that the lazaroid is administered.


Asunto(s)
Antioxidantes/farmacología , Intestinos/efectos de los fármacos , Pregnatrienos/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Antioxidantes/química , Modelos Animales de Enfermedad , Mucosa Intestinal/metabolismo , Pregnatrienos/química , Daño por Reperfusión/metabolismo
17.
Sci Rep ; 11(1): 6210, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33737662

RESUMEN

Our understanding of pilonidal sinus disease (PSD) is based on a paper published 29 years ago by Karydakis. Since then, surgeons have been taught that hair more easily penetrates wet skin, leading to the assumption that sweating promotes PSD. This postulate, however, has never been proven. Thus we used pilocarpine iontophoresis to assess sweating in the glabella sacralis. 100 patients treated for PSD and 100 controls were matched for sex, age and body mass index (BMI). Pilocarpine iontophoresis was performed for 5 min, followed by 15 min of sweat collection. PSD patients sweated less than their matched pairs (18.4 ± 1.6 µl vs. 24.2 ± 2.1 µl, p = 0.03). Men sweated more than women (22.2 ± 1.2 µl vs. 15.0 ± 1.0 µl in non-PSD patients (p < 0.0001) and 20.0 ± 1.9 µl vs. 11.9 ± 2.0 µl in PSD patients (p = 0.051)). And regular exercisers sweated more than non-exercisers (29.1 ± 2.9 µl vs. 18.5 ± 1.6 µl, p = 0.0006 for men and 20.7 ± 2.3 µl vs. 11.4 ± 1.4 µl, p = 0.0005 for women). PSD patients sweat less than matched controls. Thus sweating may have a protective effect in PSD rather than being a risk factor.


Asunto(s)
Cabello/patología , Seno Pilonidal/patología , Región Sacrococcígea/patología , Piel/patología , Adolescente , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Ejercicio Físico/fisiología , Femenino , Cabello/fisiopatología , Humanos , Iontoforesis/métodos , Masculino , Persona de Mediana Edad , Agonistas Muscarínicos/farmacología , Pilocarpina/farmacología , Seno Pilonidal/etiología , Seno Pilonidal/fisiopatología , Región Sacrococcígea/fisiopatología , Factores Sexuales , Piel/fisiopatología , Sudoración/efectos de los fármacos , Sudoración/fisiología
18.
In Vivo ; 34(5): 2423-2429, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32871768

RESUMEN

BACKGROUND: Healing is related to gastrointestinal anastomotic leak, which is a severe and common complication. This study aimed to investigate the feasibility and the impact of deserosalization on healing of jejuno-jejunal anastomoses in an animal model. MATERIALS AND METHODS: Seven swine underwent three types of side-to-side jejuno-jejunal anastomosis twice and survived seven days. Three different types of jejuno-jejunal side-to-side anastomoses were performed twice at 20-cm distance from each other in each animal: no serosa removal, one-sided, and two-sided serosa removal, respectively. Bursting pressure, tissue hydroxyproline concentration, and pathology scores were evaluated. RESULTS: Hydroxyproline tissue concentration was a mean±standard deviation of 0.37±0.09, 0.38±0.08, and 0.30±0.05 nmoI/ml respectively (p<0.05). Bursting pressure was a mean±standard deviation of 59.02±8.60, 73.20±11.09, and 100.01±7.49 mmHg, respectively (p<0.001). The histopathological assessment did not find any statistically significant differences. CONCLUSION: Deserosalization in jejuno-jejunal anastomosis was technically feasible and seemed to improve mechanical strength and collagen deposition in this experimental porcine model. Further investigation is warranted.


Asunto(s)
Intestino Delgado , Cicatrización de Heridas , Anastomosis Quirúrgica , Animales , Colágeno , Colon/cirugía , Proyectos Piloto , Porcinos
19.
In Vivo ; 34(5): 2475-2484, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32871775

RESUMEN

BACKGROUND/AIM: U-74389G and ascorbic acid protect the cells from oxidation. This study aimed to depict their role in ischemia-reperfusion injury in a renal rat model. MATERIALS AND METHODS: Sixty Wistars rats were randomized into six groups of 10 animals each. Group A Ischemia 30 min, reperfusion 60 min; Group B Ischemia 30 min, reperfusion 120 min; Group C Ischemia 30 min, ascorbic acid administration, reperfusion 60 min; Group D Ischemia 30 min, ascorbic acid administration, reperfusion 120 min; Group E Ischemia 30 min, U-74389G administration, reperfusion 60 min; Group F Ischemia 30 min, U-74389G administration, reperfusion 120 min. We then collected tissue and blood samples. RESULTS: Histology and the significantly decreased malondialdehyde and tumor necrosis factor-α levels indicated that ascorbic acid was superior to U-74389G, at pre-defined time intervals. CONCLUSION: Ascorbic acid and U-74389G ameliorated renal damage induced by ischemia-reperfusion injury, suggesting a therapeutic effect.


Asunto(s)
Pregnatrienos , Daño por Reperfusión , Animales , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Modelos Animales de Enfermedad , Pregnatrienos/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico
20.
J Invest Surg ; 33(5): 391-403, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30499737

RESUMEN

Purpose of the study: Tissue reconstruction after burns, tumor excisions, infections or injuries is a frequent surgical challenge to avoid Ischemia-reperfusion injury. Lazaroids and sildenafil, through their mechanisms of action, have been studied for their protective effects on various organs subjected to IRI. In this study, we aimed to evaluate the therapeutic potential of U-74389G and sildenafil in a swine model of ischemia and reperfusion injury of latissimus dorsi flap. Materials and methods: Forty-two Landrace male pigs, weighing 28-35 kg, were equally (n = 6) randomized into the following groups: (a) Group I: control, (b) Group II: administration of U-74389G after ischemia, (c) Group III: administration of sildenafil after ischemia, (d) Group IV: administration of U-74389G and sildenafil after ischemia, (e) Group V: administration of U-74389G prior to ischemia, (f) Group VI: administration of sildenafil prior to ischemia, and (g) Group VII: administration of U-74389G and sildenafil prior to ischemia. Blood and tissue sampling was conducted before ischemia, 15 and 30 min after occlusion, 30, 60, 90, and 120 min after reperfusion. Results: Statistically significant reduction (p < 0.05) was detected in lymphocytes and polymorphonuclear leukocytes concentrations as well as in the appearance of edema after histopathologic evaluation of the ischemic tissue, especially in the groups of combined treatment. Measurements of malondialdeyde and tumour necrosis factor alpha in tissues revealed a significant decrease (p < 0.001) of these markers in the treatment groups when compared to the control, particularly in the latest estimated timepoints. Conclusions: The synergistic action of U-74389G and sildenafil seems protective and promising in cases of flap IRI during tissue reconstruction surgery.


Asunto(s)
Antioxidantes/farmacología , Pregnatrienos/farmacología , Daño por Reperfusión/prevención & control , Citrato de Sildenafil/farmacología , Colgajos Quirúrgicos/irrigación sanguínea , Animales , Antioxidantes/uso terapéutico , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Humanos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Pregnatrienos/uso terapéutico , Daño por Reperfusión/patología , Citrato de Sildenafil/uso terapéutico , Músculos Superficiales de la Espalda/irrigación sanguínea , Músculos Superficiales de la Espalda/patología , Músculos Superficiales de la Espalda/trasplante , Colgajos Quirúrgicos/patología , Colgajos Quirúrgicos/trasplante , Porcinos , Factor de Necrosis Tumoral alfa/metabolismo
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