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1.
Genes (Basel) ; 14(10)2023 10 20.
Article in English | MEDLINE | ID: mdl-37895317

ABSTRACT

Diabetic foot syndrome (DFS) is one of the most serious macroangiopathic complications of diabetes. The primary treatment option is revascularization, but complementary therapies are still being sought. The study group consisted of 18 patients diagnosed with ischemic ulcerative and necrotic lesions in DFS. Patients underwent revascularization procedures and, due to unsatisfactory healing of the lesions, were randomly allocated to two groups: a group in which bicistronic VEGF165/HGF plasmid was administered and a control group in which saline placebo was administered. Before gene therapy administration and after 7, 30, 90, and 180 days, color duplex ultrasonography (CDU) was performed, the ankle-brachial index (ABI) and transcutaneous oxygen pressure (TcPO2) were measured, and DFS changes were described and documented photographically. In the gene therapy group, four out of eight patients (50%) healed their DFS lesions before 12 weeks. During this time, the ABI increased by an average of 0.25 and TcPO2 by 30.4 mmHg. In the control group, healing of the lesions by week 12 occurred in six out of nine patients (66.67%), and the ABI increased by an average of 0.14 and TcPO2 by 27.1 mmHg. One major amputation occurred in each group. Gene therapy may be an attractive option for complementary treatment in DFS.


Subject(s)
Complementary Therapies , Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/genetics , Diabetic Foot/therapy , Diabetic Foot/diagnosis , Saphenous Vein , Wound Healing , Genetic Therapy
2.
Proc (Bayl Univ Med Cent) ; 36(1): 103-105, 2023.
Article in English | MEDLINE | ID: mdl-36578588

ABSTRACT

Endovascular aneurysm repair (EVAR) has become one of the most important treatments for aortic abdominal aneurysm. This method has some possible complications, including a type II endoleak (T2E). When coexisting with arteriovenous fistulas (AVF), T2E can lead to serious hemodynamic consequences and organ failure. This report describes the management of a patient with T2E coexisting with AVF following an EVAR and re-EVAR procedure. Although T2E itself may be treated with a conservative approach in some cases, in the presented patient an operative approach was necessary because of coexisting AVF. In addition, due to unusual hemodynamic conditions created by concomitant ACF and T2E, fistula closure was obtained as a result of transarterial inferior mesenteric artery embolization. Post-EVAR imaging, including ultrasound and computed tomography angiography, has proven to be essential when caring for these patients.

3.
Article in English | MEDLINE | ID: mdl-36232122

ABSTRACT

One of the most serious problems in people with diabetes is diabetic foot syndrome. Due to the peripheral location of atherosclerotic lesions in the arterial system of the lower extremities, endovascular treatment plays a dominant role. However, carrying out these procedures is not always possible and does not always bring the expected results. Gene therapy, which stimulates angiogenesis, improves not only the inflow from the proximal limb but also the blood redistribution in individual angiosomes. Due to the encouraging results of sequential treatment consisting of intramuscular injections of VEGF/HGF bicistronic plasmids followed by a month of ANG1 plasmids, we decided to use the described method for the treatment of critical ischemia of the lower limbs in the course of diabetes and, more specifically, in diabetic foot syndrome. Twenty-four patients meeting the inclusion criteria were enrolled in the study. They were randomly divided into two equal groups. The first group of patients was subjected to gene therapy, where the patients received intramuscular injections of pIRES/VEGF165/HGF plasmids and 1 month of ANG-1 plasmids. The remaining patients constituted the control group. Gene therapy was well tolerated by most patients. The wounds healed significantly better in Group 1. The minimal value of ABI increased significantly in Group 1 from 0.44 ± 0.14 (± standard deviation) to 0.47 ± 0.12 (with p = 0.028) at the end of the study. There were no significant differences in the control group. In the gene treatment group, PtcO2 increased significantly (from 28.71 ± 10.89 mmHg to 33.9 ± 6.33 mmHg with p = 0.001), while in Group 2, no statistically significant changes were found. The observed resting pain decreased significantly in both groups (Group 1 decreased from 6.80 ± 1.48 to 2.10 ± 1.10; p < 0.001; the control group decreased from 7.44 ± 1.42 to 3.78 ± 1.64 with p < 0.001). In our study, we evaluated the effectiveness of gene therapy with the growth factors described above in patients with CLI in the course of complicated DM. The therapy was shown to be effective with minimal side effects. No serious complications were observed.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Diabetes Mellitus/therapy , Diabetic Foot/drug therapy , Genetic Therapy/adverse effects , Genetic Therapy/methods , Hepatocyte Growth Factor/genetics , Hepatocyte Growth Factor/therapeutic use , Humans , Ischemia/therapy , Lower Extremity/blood supply , Plasmids/genetics , Plasmids/therapeutic use , Vascular Endothelial Growth Factor A/genetics
4.
Vasc Endovascular Surg ; 56(2): 220-224, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34779321

ABSTRACT

The development of aneurysms of thoracoabdominal aorta (TAAA) in a post-transplant patient is a rare clinical situation and requires special attention. Endovascular treatment is the most suitable option for these patients due to numerous comorbidities. Particular emphasis should be placed on the ejection fraction as one of the main criteria for qualifying for surgery. The treatment itself remains a major challenge relating to anatomical constrains; however, it is possible in select patients in experienced centers.


Subject(s)
Aortic Aneurysm, Thoracic , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Heart Transplantation , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/etiology , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/adverse effects , Heart Transplantation/adverse effects , Humans , Postoperative Complications , Prosthesis Design , Risk Factors , Treatment Outcome
5.
Biomed Pharmacother ; 143: 112186, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34649339

ABSTRACT

INTRODUCTION: Patients with peripheral artery disease have poor prognosis despite advances in vascular surgery. Therefore, attempts have been made at using gene and cell therapy to stimulate angiogenesis in the lower limbs in patients with critical lower limb ischemia (CLI). METHODS: The study included 30 rats divided into 3 groups. An intramuscular injection of a therapeutic gene or cells in the right hind limb was administered in each group: angiopoietin-1 (ANG1) plasmid in group 1, ANG1/vascular endothelial growth factor (ANG1/VEGF) bicistronic construct in group 2, and naked plasmid in group 3 (control). After 3 months of follow-up, tissue samples were harvested, and vessels that stained positively for CD34 cells were quantified. RESULTS: The highest CD34+ cell count was noted in the ANG1/VEGF group (98.26 cells), followed by the ANG1 group (80.31) and control group (47.93). The CD34+ cell count was significantly higher in the ANG1/VEGF and ANG1 groups than in the control group. There was no significant difference in the CD34+ cell count between the ANG1/VEGF and ANG1 groups. CONCLUSION: Our study confirmed that therapy with ANG1 plasmid alone or ANG1/VEGF bicistronic construct is safe and effective in a rat model. The therapy resulted in the recruitment of more CD34+ vascular endothelial cells than in the control group receiving naked plasmid.


Subject(s)
Angiopoietin-1/biosynthesis , Antigens, CD34/metabolism , Cell Movement , Endothelial Progenitor Cells/metabolism , Genetic Therapy , Ischemia/therapy , Muscle, Skeletal/blood supply , Neovascularization, Physiologic , Vascular Endothelial Growth Factor A/biosynthesis , Angiopoietin-1/genetics , Animals , Disease Models, Animal , Female , Gene Transfer Techniques , Genetic Vectors , Hindlimb , Injections, Intramuscular , Ischemia/genetics , Ischemia/metabolism , Ischemia/physiopathology , Male , Rats, Inbred BUF , Vascular Endothelial Growth Factor A/genetics
6.
Sci Rep ; 11(1): 15519, 2021 07 30.
Article in English | MEDLINE | ID: mdl-34330941

ABSTRACT

There is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). Serum samples were collected from 23 adult individuals with established diagnosis of brain death and 24 patients in coma with Glasgow Coma Scale 3 or 4, with no other clinical symptoms of brain death for at least 7 days after sample collection. Serum metabolomic profiles were investigated using proton nuclear magnetic resonance (NMR) spectroscopy. The results obtained were examined by univariate and multivariate data analysis (PCA, PLS-DA, and OPLS-DA). Metabolic profiling allowed us to quantify 43 resonance signals, of which 34 were identified. Multivariate statistical modeling revealed a highly significant separation between coma patients and brain-dead individuals, as well as strong predictive potential. The findings not only highlight the potential of the metabolomic approach for distinguishing patients in coma from those in the state of brain death but also may provide an understanding of the pathogenic mechanisms underlying these conditions.


Subject(s)
Brain Death/blood , Coma/blood , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Metabolome/physiology , Metabolomics/methods , Middle Aged , Multivariate Analysis , Young Adult
7.
J Cardiovasc Transl Res ; 14(3): 409-415, 2021 06.
Article in English | MEDLINE | ID: mdl-32875492

ABSTRACT

Critical leg ischemia (CLI) complicated by diabetes mellitus (DM), which is a very common and dangerous disease, represents the ultimate stage of peripheral arterial disease. Patients are treated with antiplatelet drugs, statins and limb revascularization, but a significant number of patients are not candidate for revascularization. Literature shows that in such cases, gene therapy could be a perfect therapeutic option. The aim of our study was to evaluate efficacy of double vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) gene therapy in patients with CLI complicated by DM. We observed that 90 days after administration, serum level of VEGF and ankle-brachial index increased significantly (p < 0.001) and rest pain decreased significantly compared with the control group (p < 0.002). Moreover considerable improvement in vascularization was observed in computed tomography angiography (P = 0.04). Based on the results of this study, we suggest that the therapy with pIRES/VEGF165/HGF bicistronic plasmid administration is a safe and effective method of treatment of patients with both CLI and DM. Graphical abstract.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Genetic Therapy , Hepatocyte Growth Factor/genetics , Ischemia/therapy , Neovascularization, Physiologic , Peripheral Arterial Disease/therapy , Vascular Endothelial Growth Factor A/genetics , Aged , Aged, 80 and over , Biomarkers/blood , Blood Glucose/metabolism , Critical Illness , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/physiopathology , Female , Functional Status , Humans , Internal Ribosome Entry Sites/genetics , Ischemia/blood , Ischemia/genetics , Ischemia/physiopathology , Male , Middle Aged , Peripheral Arterial Disease/blood , Peripheral Arterial Disease/genetics , Peripheral Arterial Disease/physiopathology , Plasmids/genetics , Poland , Recovery of Function , Time Factors , Treatment Outcome , Vascular Endothelial Growth Factor A/blood
8.
Ann Vasc Surg ; 60: 346-354, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31200059

ABSTRACT

BACKGROUND: Prognosis of peripheral artery disease (PAD), especially critical limb ischemia (CLI), is very poor despite the development of endovascular therapy and bypass surgery. Many patients result in having leg amputation. We decided to investigate the safety and efficacy of plasmid of internal ribosome entry site/vascular endothelial growth factor (VEGF) 165/hepatocyte growth factor (HGF) gene therapy (GT) in patients suffered from CLI. METHODS: Administration of plasmid of internal ribosome entry site/VEGF165/HGF was performed in 12 limbs of 12 patients with rest pain and ischemic ulcers due to CLI. Plasmid was injected into the muscles of the ischemic limbs. The levels of VEGF in serum and the ankle-brachial index (ABI) were measured before and after treatment. RESULTS: Mean (±SD) plasma levels of VEGF increased nonsignificantly from 258 ± 81 pg/L to 489 ± 96 pg/L (P > 0.05) 2 weeks after therapy, and the ABI improved significantly from 0.27 ± 0.20 to 0.50 ± 0.22 (P < 0.001) 3 months after therapy. Ischemic ulcers healed in 9 limbs. Amputation was performed in 3 patients because of advanced necrosis and wound infection. However, the level of amputations was lowered below knee in these cases. Complications were limited to transient leg edema in 3 patients and fever in 2 patients. CONCLUSIONS: Intramuscular administration of plasmid of internal ribosome entry site/VEGF165/HGF is safe, feasible, and effective for patients with critical leg ischemia.


Subject(s)
Genetic Therapy , Hepatocyte Growth Factor/genetics , Ischemia/therapy , Leg Ulcer/therapy , Lower Extremity/blood supply , Peripheral Arterial Disease/therapy , Vascular Endothelial Growth Factor A/genetics , Adult , Aged , Amputation, Surgical , Ankle Brachial Index , Critical Illness , Female , Genetic Therapy/adverse effects , Hepatocyte Growth Factor/blood , Humans , Internal Ribosome Entry Sites , Ischemia/diagnosis , Ischemia/genetics , Ischemia/physiopathology , Leg Ulcer/diagnosis , Leg Ulcer/genetics , Leg Ulcer/physiopathology , Male , Middle Aged , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/genetics , Peripheral Arterial Disease/physiopathology , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome , Vascular Endothelial Growth Factor A/blood , Wound Healing
9.
Adv Clin Exp Med ; 26(2): 269-276, 2017.
Article in English | MEDLINE | ID: mdl-28791845

ABSTRACT

BACKGROUND: One of the underestimated causes of chronic pelvic pain (CPP) in women may be pelvic congestion syndrome (PCS) that is defined as the presence of varicose of ovarian and pelvic veins associated with chronic pain in the region of the pelvis. This pain is present longer than 6 months and intensifies with prolonged standing, coitus and menstruation. The disease constitutes a diagnostic as well as therapeutic problem, thus posing a challenge for the clinician. Transcatheter ovarian vein embolization might be a safe and effective option for PCS treatment. OBJECTIVES: The objective of this study was to evaluate the efficacy of ovarian vein embolization ovarian as a method of the PCS treatment. MATERIAL AND METHODS: Between 2002-2012, 11 embolization procedures were performed in 10 women (age range: 34-43; median age 39) with the diagnosis of PCS. One patient underwent embolization procedure twice. In 1 case the combined therapy of endovascular embolization and surgical phlebectomy of vulvar varices was performed. RESULTS: There were no major intrainterventional complications. In all the patients (100%) a significant improvement in the clinical status was noted. The procedure improved the quality of life in the patients. Three women (30%) had a mild recurrence of the symptoms at mid-term follow-up. Among 8 women who had complained of dyspareunia prior to embolization 6 patients reported complete pain relief, in other 2 cases the pain subsided partially. There was a significant decrease in the severity of symptoms associated with hemorrhoids. CONCLUSIONS: We consider embolization of insufficient ovarian veins an effective and safe way of treatment in a well-selected group of patients with PCS.


Subject(s)
Embolization, Therapeutic/methods , Ovary/blood supply , Pelvis/blood supply , Varicose Veins/diagnosis , Varicose Veins/therapy , Adult , Chronic Pain/prevention & control , Female , Humans , Pain Measurement , Pelvic Pain/prevention & control , Phlebography , Retrospective Studies , Syndrome , Treatment Outcome , Varicose Veins/diagnostic imaging
10.
Pol J Pathol ; 68(4): 326-329, 2017.
Article in English | MEDLINE | ID: mdl-29517203

ABSTRACT

The aim of the study was to investigate how an intramuscular injection of plasmids with genes coding various pro-angiogenic factors: angiopoetin-1 (ANGPT1), vascular endothelial growth factor (VEGF165) and hepatic growth factor (HGF), influences the production of ANGPT1. 40 Healthy Fisher rats received i.m. injections containing plasmids encoding pro-angiogenic genes in thigh muscles. They were divided into four equal groups. The first group received the plANGPT1 plasmid and the second group- the pIRES/ANGPT1/VEGF165 bicistronic plasmid. The pIRES/VEGF165/HGF bicistronic plasmid was administered to the third group and an empty plasmid (control group) to the fourth group. The animals were euthanized after 12 weeks. In each group, the number of vessels stained with the anti-ANGPT1 antibody was assessed under an optical microscope. The anti-ANGPT1 antibodies stained the vessels in all the groups. There were on average 14.1 ±2.3 vessels in the the plANGPT1 group, 32.5 ±10.5 in the pl/RESANGPT1/VEGF group and 30.8 ±13.3 in the plRES/HGV/VEGF group. There were on average 7.3 ±2.3 stained vessels (p < 0.0001) in the control group . The VEGF plays a role in the induction of the production of ANGPT1. The administration of plasmids only encoding ANGPT1 does not induce its production.


Subject(s)
Angiopoietin-1/biosynthesis , Blood Vessels/metabolism , Muscle, Skeletal/blood supply , Neovascularization, Physiologic , Vascular Endothelial Growth Factor A/biosynthesis , Angiopoietin-1/genetics , Animals , Gene Transfer Techniques , Hepatocyte Growth Factor/biosynthesis , Hepatocyte Growth Factor/genetics , Humans , Injections, Intramuscular , Rats, Inbred F344 , Signal Transduction , Vascular Endothelial Growth Factor A/genetics
11.
Adv Clin Exp Med ; 25(4): 611-5, 2016.
Article in English | MEDLINE | ID: mdl-27629833

ABSTRACT

BACKGROUND: Chronic limb ischemia is a serious clinical problem. Patients who do not qualify for standard treatment may benefit from novel gene therapies. OBJECTIVES: This study evaluated angiogenesis following intramuscular injections of angiogenic plasmid Ang-1 in Fisher rats. MATERIAL AND METHODS: Twenty rats had plasmids injected intramuscularly in their hind limbs. The study group consisted of 10 animals which received the Ang-1 plasmid, while the control group consisted of 10 rats that received an empty plasmid. All the animals were euthanized after 12 weeks and tissue samples from the hind limb thigh muscles and internal organs were harvested for histological and immunohistochemical examinations. To assess the angiogenesis the number of vessels in the hind limb muscles visualized by the SMA and FVIII markers was counted for each animal in five separate microscopic fields. RESULTS: There were no pathological lesions or any signs of neoplastic angiogenesis in any of the 20 rats. The number of vessels visualized by the FVIII marker in the study group was two times higher than in the control group (median: 12, range: 7-25 vs. median: 6, range: 2-15; p < 0.0001). The median estimated that the number of vessels visualized by the SMA marker is 63% higher in the study group compared to the control group (median: 6.5, range: 1-12 vs. median: 4, range: 0-10; p = 0.0008). CONCLUSIONS: Intramuscular injections of Ang-1 plasmids induced angiogenesis in the rat hind limb muscles.


Subject(s)
Angiopoietin-1/metabolism , Neovascularization, Physiologic/physiology , Animals , Hindlimb/blood supply , Plasmids , Rats , Rats, Inbred F344
12.
Vasa ; 45(3): 223-8, 2016.
Article in English | MEDLINE | ID: mdl-27129067

ABSTRACT

BACKGROUND: We present the methods and results of the surgical management of extracranial carotid artery aneurysms (ECCA). Postoperative complications including early and late neurological events were analysed. Correlation between reconstruction techniques and morphology of ECCA was assessed in this retrospective study. PATIENTS AND METHODS: In total, 32 reconstructions of ECCA were performed in 31 symptomatic patients with a mean age of 59.2 (range 33-84) years. The causes of ECCA were divided among atherosclerosis (n = 25; 78.1%), previous carotid endarterectomy with Dacron patch (n = 4; 12.5%), iatrogenic injury (n = 2; 6.3%) and infection (n = 1; 3.1%). In 23 cases, intervention consisted of carotid bypass. Aneurysmectomy with end-to-end suture was performed in 4 cases. Aneurysmal resection with patching was done in 2 cases and aneurysmorrhaphy without patching in another 2 cases. In 1 case, ligature of the internal carotid artery (ICA) was required. RESULTS: Technical success defined as the preservation of ICA patency was achieved in 31 cases (96.9%). There was one perioperative death due to major stroke (3.1%). Two cases of minor stroke occurred in the 30-day observation period (6.3%). Three patients had a transient hypoglossal nerve palsy that subsided spontaneously (9.4%). At a mean long-term follow-up of 68 months, there were no major or minor ipsilateral strokes or surgery-related deaths reported. In all 30 surviving patients (96.9%), long-term clinical outcomes were free from ipsilateral neurological symptoms. CONCLUSIONS: Open surgery is a relatively safe method in the therapy of ECCA. Surgical repair of ECCAs can be associated with an acceptable major stroke rate and moderate minor stroke rate. Complication-free long-term outcomes can be achieved in as many as 96.9 % of patients. Aneurysmectomy with end-to-end anastomosis or bypass surgery can be implemented during open repair of ECCA.


Subject(s)
Aneurysm/surgery , Carotid Artery Diseases/surgery , Vascular Surgical Procedures , Adult , Aged , Aged, 80 and over , Aneurysm/complications , Aneurysm/diagnosis , Aneurysm/mortality , Carotid Artery Diseases/complications , Carotid Artery Diseases/diagnosis , Carotid Artery Diseases/mortality , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Stroke/etiology , Time Factors , Treatment Outcome , Vascular Surgical Procedures/adverse effects , Vascular Surgical Procedures/mortality
13.
Arch Med Sci ; 11(2): 325-31, 2015 Apr 25.
Article in English | MEDLINE | ID: mdl-25995748

ABSTRACT

INTRODUCTION: Our study was designed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell (MNC) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia (CLI). MATERIAL AND METHODS: Thirty-two patients with CLI persisting for 12-48 months (average time 27.5 months) were randomized into 2 groups, each group consisting of 16 patients. In the first group, administration of autologous bone marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed. The patients from the second group were treated pharmacologically with pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was performed before and finally 3 months after treatment. The pain was evaluated using the Visual Analog Scale (VAS) before and after 3 months. RESULTS: Ankle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 (p < 0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1. In this group angiography showed the development of collateral vessels. Ischemic ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not improve in any patient; moreover the complete healing of skin ulcers was not found in any of the patients of this group. Amputation was performed in 4 (25.0%) patients in group 1, and in 8 patients (50%) from group 2. CONCLUSIONS: These data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe, and a more feasible and effective method of treatment than the conventional therapy. However, both therapies are limited by the degree of microcirculation damage.

14.
World J Gastroenterol ; 20(1): 163-74, 2014 Jan 07.
Article in English | MEDLINE | ID: mdl-24415869

ABSTRACT

AIM: To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases (IBD). METHODS: Serum and urine samples were collected from 24 patients with ulcerative colitis (UC), 19 patients with the Crohn's disease (CD) and 17 healthy controls. The activity of UC was assessed with the Simple Clinical Colitis Activity Index, while the activity of CD was determined using the Harvey-Bradshaw Index. The analysis of serum and urine samples was performed using proton nuclear magnetic resonance (NMR) spectroscopy. All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine. Prior to the chemometric analysis, both data sets were unit variance scaled. The differences in metabolite fingerprints were assessed using partial least-squares-discriminant analysis (PLS-DA). Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models. Metabolites responsible for separation in models were tested using STATISTICA 10 with the Mann-Whitney-Wilcoxon test and the Student's t test (α = 0.05). RESULTS: The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models (P value 0.002 for serum and 0.003 for urine). The metabolites that allowed to distinguish these groups were: N-acetylated compounds and phenylalanine (up-regulated in serum), low-density lipoproteins and very low-density lipoproteins (decreased in serum) as well as glycine (increased in urine) and acetoacetate (decreased in urine). The significant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation (P value < 0.001 for serum and 0.003 for urine). The metabolites that were found to be the strongest biomarkers included in this case: leucine, isoleucine, 3-hydroxybutyric acid, N-acetylated compounds, acetoacetate, glycine, phenylalanine and lactate (increased in serum), creatine, dimethyl sulfone, histidine, choline and its derivatives (decreased in serum), as well as citrate, hippurate, trigonelline, taurine, succinate and 2-hydroxyisobutyrate (decreased in urine). No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples, although one metabolite (formate) in univariate statistical analysis was significantly lower in serum of patients with active CD, and two metabolites (alanine and N-acetylated compounds) were significantly higher in serum of patients with CD when comparing jointly patients in the remission and active phase of the diseases. Contrary to the results obtained from the serum samples, the analysis of urine samples allowed to distinguish patients with IBD in remission from healthy control subjects. The metabolites of importance included in this case up-regulated acetoacetate and down-regulated citrate, hippurate, taurine, succinate, glycine, alanine and formate. CONCLUSION: NMR-based metabolomic fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.


Subject(s)
Colitis, Ulcerative/diagnosis , Crohn Disease/diagnosis , Metabolomics , Adolescent , Adult , Aged , Area Under Curve , Biomarkers/blood , Biomarkers/urine , Case-Control Studies , Colitis, Ulcerative/blood , Colitis, Ulcerative/therapy , Colitis, Ulcerative/urine , Crohn Disease/blood , Crohn Disease/therapy , Crohn Disease/urine , Diagnosis, Differential , Discriminant Analysis , Female , Humans , Least-Squares Analysis , Magnetic Resonance Spectroscopy , Male , Metabolomics/methods , Middle Aged , Poland , Predictive Value of Tests , Prognosis , ROC Curve , Remission Induction , Severity of Illness Index , Young Adult
15.
Postepy Hig Med Dosw (Online) ; 67: 982-95, 2013 Sep 18.
Article in Polish | MEDLINE | ID: mdl-24088542

ABSTRACT

Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.


Subject(s)
Endothelium, Vascular/cytology , Stem Cells/cytology , Vascular Diseases/pathology , Arteries/cytology , Arteries/enzymology , Cell Differentiation , Disease Progression , Humans , Neointima/pathology , Organogenesis , Stem Cell Niche , Vascular Diseases/therapy
16.
Adv Clin Exp Med ; 22(2): 203-8, 2013.
Article in English | MEDLINE | ID: mdl-23709376

ABSTRACT

BACKGROUND: There is no data available explaining the correlation between the intensity of exercise training and kidney transplant recipients' health and fitness condition. MATERIAL AND METHODS: A retrospective study was performed using a questionnaire form. The questionnaire was filled out by members of the Polish department of the World Transplant Games Federation and the Polish Association of People on Dialysis and After Kidney Transplantation. 167 patients (Age: 36 ± 11 yrs, Males: 52%) were enrolled in the study. RESULTS: Even two hours of exercise per week after the transplantation statistically significantly ameliorated the recipients' self-reported health (p = 0.007) and fitness condition (p < 0.0001). The amount of time devoted weekly to sports positively correlated with the patient's health and fitness condition (p = 0.00325 and p = 0.00123 respectively). People who did not exercise had higher BMI levels than those who practiced sports (25.8 ± 5.2 and 24 ± 3.99 respectively, p = 0.0003) but the weekly training time did not correlate with the BMI of kidney transplant recipients (r = -0.08, p = 0.275). CONCLUSIONS: Regular physical activity did not deteriorate the graft's function in the examined patients. The results of this study bring us to the conclusion that physical activity can be recommended for all kidney transplant recipients that do not have other serious comorbidities which would restrain them from practicing sports.


Subject(s)
Exercise , Health Status , Kidney Transplantation , Physical Fitness , Sports , Adult , Body Mass Index , Female , Humans , Male , Middle Aged , Retrospective Studies , Surveys and Questionnaires
17.
Endokrynol Pol ; 64(2): 129-38, 2013.
Article in English | MEDLINE | ID: mdl-23653276

ABSTRACT

INTRODUCTION: The aim of this study was to assess the safety and efficacy of combined autologous bone marrow mononuclear cell and VEGF165 gene therapy in patients with diabetes mellitus suffering from critical limb ischaemia (CLI). MATERIAL AND METHODS: The administration of mononuclear cells (MNCs) and naked VEGF165 plasmid was performed in 16 limbs of 16 patients with rest pain and ischaemic ulcers due to diabetes. MNCs and plasmid were injected into the muscles of the ischaemic limbs. The levels of VEGF in serum and the ankle-brachial index (ABI) were measured before and after treatment. The Visual Analogue Scale (VAS) was used to evaluate pain sensation. CT angiography was performed before and after three months of therapy. RESULTS: Mean (± SD) plasma levels of VEGF increased non-significantly from 257 ± 80 pg/L to 391 ± 82 pg/L (p 〉 0.05) two weeks after therapy. The ABI improved significantly from 0.26 ± 0.22 to 0.49 ± 0.30 (p 〈 0.001) three months after therapy. A decrease in rest pain was observed in all patients; mean VAS decreased from 6.3 ± 1.4 to 1.2 ± 1.1 after three months (p 〈 0.002). Angiograms showed the development of collateral vessels in 12 limbs. Ischaemic ulcers healed in 12 limbs. Amputation was performed in four patients only, because of advanced wound infection. However, the level of amputations was lowered below knee level in these cases. Complications were limited to transient leg oedema in two patients and fever in two patients. CONCLUSIONS: Intramuscular bone marrow MNCs autotransplantation combined with the administration of phVEGF165 gene is safe, feasible and effective for patients with diabetes and CLI.


Subject(s)
Bone Marrow Transplantation/methods , Diabetes Mellitus/therapy , Diabetic Foot/therapy , Ischemia/therapy , Vascular Endothelial Growth Factor A/therapeutic use , Aged , Bone Marrow , Female , Genetic Therapy/methods , Humans , Ischemia/etiology , Lower Extremity , Male , Middle Aged , Pain Measurement , Transplantation, Autologous/methods , Treatment Outcome
18.
Arch Med Sci ; 9(6): 1071-7, 2013 Dec 30.
Article in English | MEDLINE | ID: mdl-24482652

ABSTRACT

INTRODUCTION: The decision on the time and choice of strategy of treatment of abdominal aortic aneurysm must be especially carefully balanced. The aim of the study was to evaluate the tissue factor (TF) plasma level as a potential factor useful in anticipation of abdominal aortic aneurysm and/or iliac arterial aneurysm via comparison of plasma TF level in patients with ruptured and non-ruptured aneurysms. MATERIAL AND METHODS: The study included 33 patients with aneurysm (17 operated on electively because of non-ruptured aneurysm and 16 operated on emergently due to ruptured aneurysm), 33 claudicant patients with atherosclerosis of the abdominal aorta and iliac arteries with normal diameter of arteries, and 30 healthy controls. Plasma TF level was assessed by ELISA method using the IMUBIND Tissue Factor ELISA Kit (American Diagnostica Inc.). RESULTS: The study showed an increased TF level in patients with aneurysm (134 ±54 pg/ml) and in patients with atherosclerosis without concomitant aneurysm (91 ±30 pg/ml) in comparison with the control group (62 ±20 pg/ml), respectively p < 0.001 and p = 0.008. A significantly higher TF plasma level was observed in patients with ruptured abdominal aortic aneurysms (160 ±57 pg/ml) as compared to patients with non-ruptured aortic aneurysms (109 ±39 pg/ml) or peripheral arterial occlusive disease (91 ±30 pg/ml), respectively p < 0.001 and p < 0.001. The difference in TF level between the group with non-ruptured aortic aneurysms (109 ±39 pg/ml) and the patients with atherosclerosis without aneurysm (91 ±30 pg/ml) was not statistically significant. CONCLUSIONS: No difference in TF level between patients with non-ruptured AAA/IAA and patients with aortic and iliac atherosclerosis without aneurysm indicates that an increased TF plasma level is not specific for any of the above-mentioned vascular pathologies.

19.
Polim Med ; 42(2): 139-42, 2012.
Article in Polish | MEDLINE | ID: mdl-23016445

ABSTRACT

One of the most common and serious complications after implantation of aortic or aorto-femoral prosthesis are aortoduodenal fistula. Secondary aorto-duodenal fistula is the most commonly observed form of a fistula between the abdominal aorta and gastrointestinal tract. 76 years old male with infected vascular prosthesis was admitted to Clinic with syndroms of active bleeding from aorto-duodenal fistula. Because of general condition, patient was qualified to endovascular procedure, and a new stentgraft was implanted. After the procedure patient was treated with antibiotic compatible with inoculation from blood and he did not gave agreement for further surgical operations. He lived next 28 months and died because of lung cancer.


Subject(s)
Aortic Diseases/therapy , Blood Vessel Prosthesis/adverse effects , Duodenal Diseases/therapy , Intestinal Fistula/therapy , Vascular Fistula/therapy , Aged , Aortic Diseases/etiology , Duodenal Diseases/etiology , Endovascular Procedures , Fatal Outcome , Fistula , Follow-Up Studies , Humans , Intestinal Fistula/etiology , Lung Neoplasms/etiology , Male , Prosthesis-Related Infections/etiology , Reoperation , Vascular Fistula/etiology
20.
Postepy Hig Med Dosw (Online) ; 66: 469-74, 2012 Jul 02.
Article in English | MEDLINE | ID: mdl-22922147

ABSTRACT

INTRODUCTION: The experiment was designed in order to determine the immunological processes that occur during the healing in synthetic vascular grafts, especially to establish the differences in the location of the complement system proteins between the proximal and distal anastomosis and the differences in the arrangement of inflammatory cells in those anastomoses. The understanding of those processes will provide a true basis for determining risk factors for complications after arterial repair procedures. MATERIAL/METHODS: The experiment was carried out on 16 dogs that underwent implantation of unilateral aorto-femoral bypass with expanded polytetrafluoroethylene (ePTFE). After 6 months all animals were euthanized to dissect the vascular grafts. Immunohistochemical assays and electron microscopic examinations were performed. RESULTS: Immunohistochemical findings in the structure of neointima between anastomoses of vascular prostheses demonstrated significant differences between humoral and cellular responses. The area of proximal anastomosis revealed the presence of fibroblasts, but no macrophages were detected. The histological structure of the proximal anastomosis indicates that inflammatory processes were ended during the prosthesis healing. The immunological response obtained in the distal anastomosis corresponded to the chronic inflammatory reaction with the presence of macrophages, myofibroblasts and deposits of complement C3. DISCUSSION: The identification of differences in the presence of macrophages and myofibroblasts and the presence of the C3 component between the anastomoses is the original achievement of the present study. In the available literature, no such significant differences have been shown so far in the humoral and cellular immune response caused by the presence of an artificial vessel in the arterial system.


Subject(s)
Blood Vessel Prosthesis , Complement C3/immunology , Complement System Proteins/immunology , Macrophages/immunology , Neointima/immunology , Neointima/pathology , Wound Healing/immunology , Anastomosis, Surgical , Animals , Aorta, Abdominal/immunology , Aorta, Abdominal/surgery , Aorta, Abdominal/ultrastructure , Biocompatible Materials , Blood Vessel Prosthesis/adverse effects , Collagen/immunology , Complement Activation/immunology , Dogs , Femoral Artery/immunology , Femoral Artery/surgery , Immunity, Cellular , Immunity, Humoral , Inflammation/immunology , Myofibroblasts/immunology , Polytetrafluoroethylene
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