Antiangiogenic, Anti-Inflammatory and Antioxidant Properties of Bidens tripartite Herb, Galium verum Herb and Rumex hydrolapathum Root.

Plants are commonly used in folk medicine. Research indicates that the mechanisms of biological activity of plant extracts may be essential in the treatment of various diseases. In this respect, we decided to test the ethanolic extracts of Bidens tripartita herb (BTH), Galium verum herb (GVH), and Rumicis hydrolapathum root (RHR) on angiogenic, anti-inflammatory, and antioxidant properties and their total polyphenols content. In vitro studies using endothelial cells were used to see tested extracts' angiogenic/angiostatic and anti-inflammatory properties. The DPPH assay and FRAP analysis were used to detect antioxidant properties of extracts. The Folin-Ciocalteu analysis was used to determine the content of total polyphenols. The results of gas chromatography-mass spectrometry analysis was also presented. In vitro study demonstrated that BTH, GVH, and RHR ethanolic extracts significantly increased cell invasiveness, compared with the control group. Increased endothelial proangiogenic invasiveness was accompanied by reduced metalloproteinase inhibitor 1 (TIMP-1) and raised in metalloproteinase 9 (MMP-9). Only BTH and GVH significantly reduced cell proliferation, while BTH and RHR facilitated migration. Additionally, tested extracts reduced the production of proangiogenic platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF). The most potent anti-inflammatory capacity showed BTH and GVH, reducing proinflammatory interleukin 8 (CXCL8) and interleukin 6 (Il-6), compared to RHR extract that has slightly less inhibited CXCL8 production without affecting IL-6 production. Moreover, we confirmed the antioxidant properties of all examined extracts. The highest activity was characterized by RHR, which has been correlated with the high content of polyphenols. In conclusion, the modifying influence of examined extracts can be promising in disorders with pathogenesis related to angiogenesis, inflammation and free radicals formation. BTH is the best choice among the three tested extracts with its antiangiogenic and anti-inflammatory properties.

[Age-related macular degeneration--a complex genetic disease]. / Zwyrodnienie plamki zwiazane z wiekiem (AMD)--choroba o wieloczynnikowym podlozu genetycznym.

Age-related macular degeneration (AMD,) is the most common cause of severe visual loss and blindness in the population over 60 years old, especially in the developed world. Two types of AMD are distinguished: the dry (non-exudative or atrophic) and the wet (exudative or neovascular) form. Family and twins studies have shown that the susceptibility for this disease is genetically influenced and the heritability has been estimated to be up to 75%. Until now, many of the candidate-genes associated with AMD have been discovered using studies on genetically engineered and naturally mutated animals, linkage studies, studies of monogenic degenerative retinal diseases and association studies. Recently genes have been described that significantly contribute to the etiopathogenesis of AMD: CFH, PLEKHA1/LOC387715/HTRA1 and C2/BF genes. AMD is considered to be a genetic complex disease in which multiple genes and environmental factors play a role in pathogenesis. Identification of other genes involved in development of AMD will improve our knowledge about new pathways and pathological mechanisms of the disease, as well as avenues for novel more effective treatments. The aim of this article is to survey published data on genetic aspect of AMD, with emphasis of several recently discovered genes described to be particularly important in the pathogenesis of AMD, and /or somehow associated with the occurrence of the disease.

[Bevacizumab: progress in the treatment of metastatic cancer and hope for patients with proliferative retinopathy]. / Bewacizumab--postep w leczeniu nowotworówz przerzutami i nadzieja pacjentów z retinopatiaproliferacyjna.

The formation of new blood vessels from pre-existing vasculature (neoangiogenesis) accompanies many diseases, including cancer and proliferative retinopathy. Knowledge of the molecular mechanisms of angiogenesis and angiogeneic factors, especially vascular endothelial growth factor (VEGF), enables the design of drugs more potent and specific in their action and less cytotoxic. Among angiogenesis inhibitors are drugs made by means of genetic engineering, i.e. monoclonal antibodies, devoid of unwanted actions that occur during chemotherapy. One of monoclonal antibodies successfully used in clinical trials in patients with metastatic colorectal cancer is bevacizumab. Because of its inhibitory potential regarding angiogenesis it may be useful in the treatment of age-related macular degeneration (AMD). Although anti-VEGF agents have already been used in AMD therapy, there are several arguments, primarily financial, favoring bevacizumab's applicability in ophthalmology.

Influence of parathyroidectomy on blood pressure and function of the transplanted kidney in patients with tertiary hyperparathyroidism.

BACKGROUND: Tertiary hyperparathyroidism is one of the causes of bone demineralisation, nephrolithiasis and a potential risk factor influencing blood pressure and excretory graft function in patients after kidney transplantation (Tx). The aim of the study is to analyse the influence of parathyroidectomy (PTx) on graft function and blood pressure control in these patients. METHODS: 392 subsequent patients after kidney Tx were included into this analysis. Records of 84 patients (21.4%) with elevated plasma calcium concentration (> 2.6 mmol/l) during observation were reviewed. In 39 patients (9.9%) calcaemia remained elevated for over 1 year after kidney Tx. Eleven patients (2.81%) were referred for PTx. In 2 cases PTx were performed within the first 6 months, while the 9 others undergone surgery between 16 and 36 months after Tx. We have evaluated the influence of PTx on renal allograft excretory function, blood pressure and the number of antihypertensive drugs in kidney transplant patients. RESULTS: In 7 out of 11 patients the indication for PTx was renal osteodystrophy, while in other cases the indication was the asymptomatic hypercalcaemia. Shortly after surgery normalisation of calcaemia was observed in all cases. However the creatinine clearance did not changed shortly after PTx (64 +/- 12 vs. 63 +/- 16 ml/min), and a slight deterioration of transplanted kidney excretory function was observed in 2 patients. 12 months after PTx deterioration of GFR (5320 ml/min) of borderline significance was found. All patients before PTx suffered from arterial hypertension, ten of them were receiving antihypertensive drugs (average 1.6 medicine per patient). Two weeks after PTx a transient decline of both systolic and diastolic blood pressures (-13 +/- 14 mmHg; p = 0.02 and -46 mmHg; p = 0.06, respectively) was observed. However there was a negative correlation between initial plasma calcium concentration and decline of diastolic blood pressure (R = -0.884; p = 0.0003). Six and twelve months after PTx blood pressure values were at the same magnitude as before PTx. CONCLUSIONS: (1) Parathyroidectomy and normalisation of calcaemia did not influence significantly the excretory allograft kidney function. (2) Patients benefit from PTx only with the transient improvement of their blood pressure control.

Assessment of subclinical acute kidney injury after abdominal aortic aneurysm surgery using novel markers: L-FABP and H-FABP.

BACKGROUND: One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Even small rises in serum creatinine are associated with increased mortality. The aim of this study was to assess the dynamics of AKI after elective AAA surgery using novel markers. METHODS: The study group consisted of 22 patients with AAA. We measured urinary liver- (u-L-FABP) and heart-type fatty acid-binding proteins (u-H-FABP) before, during and within 3 days after surgery. RESULTS: We found an abrupt and significant elevation of both urine FABPs normalized to urinary creatinine; u-L-FABP reached its peak value 2 hours after aortic clamp release {137.79 (38.57-451.79) vs. 9.94 (6.82-12.42) ng/mg baseline value, p<0.05; values are medians (lower-upper quartile)}. The peak value of u-H-FABP was reported 72 hours after aortic clamp release {16.462 (4.182-37.595) vs. 0.141 (0.014-0.927) ng/mg baseline value, p<0.05}. The serum creatinine level did not changed significantly during the investigation period. CONCLUSIONS: The significant rise of both u-L-FABP and u-H-FABP after AAA surgery indicates renal proximal and distal tubule injury in this population. Our results suggest that, after AAA surgery, the distal tubules could be more affected than the proximal ones. u-FABPs could serve as sensitive biomarkers of kidney tubular injury and may allow to detect the very early phases of AKI.

Endothelium injury and inflammatory state during abdominal aortic aneurysm surgery: scrutinizing the very early and minute injurious effects using endothelial markers - a pilot study.

INTRODUCTION: One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Acute kidney injury is an inflammatory process whose pathogenesis involves endothelial cells (EC). The aim of this study was to assess the dynamics of endothelium injury markers measured during elective AAA surgery which might confirm the inflammatory character of AKI. MATERIAL AND METHODS: The study group consisted of 14 patients with AAA. We measured plasma soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin as well as the levels of von Willebrand factor (vWF) before, during (including intra-abdominal vein levels before and after aortic clamp removal) and within 2 days after surgery. RESULTS: We have found a biphasic response of ICAM-1, VCAM-1 and P-selectin with an initial fall and subsequent rise. However, only VCAM-1 changes were significant compared to its baseline value. The maximum decrease of VCAM-1 was observed in the renal vein 5 min after aortic clamp removal (335.42 ±129.63 ng/ml vs. 488.90 ±169.80 ng/ml baseline value, p < 0.05), and the highest rise 48 h after aortic clamp removal (721.46 ±333.99 vs. baseline, p < 0.05). CONCLUSIONS: Vascular cell adhesion molecule-1 turned out to be the most sensitive indicator of EC injury and inflammatory status after AAA surgery. During AAA surgery, soluble forms of P-selectin, ICAM-1 and VCAM-1 demonstrate a biphasic response with an initial fall and subsequent rise. These soluble forms could have a modulatory effect on the development of inflammation.

Acute kidney injury after abdominal aortic aneurysm surgery: detailed assessment of early effects using novel markers.

INTRODUCTION:  One of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Even small rises in serum creatinine after surgery are associated with increased mortality. OBJECTIVES:  The aim of the study was to assess the dynamics of AKI after elective AAA surgery using novel markers. PATIENTS AND METHODS:  The study group consisted of 14 patients with AAA. We measured serum neutrophil gelatinase­associated lipocalin (NGAL) before, during (including intra­abdominal vein levels before and after removal of aortic clamp), and within 2 days after surgery.  Moreover, we assessed urinary NGAL, interleukin 18 (IL­18), and liver­type fatty acid­binding protein (L­FABP) before, during, and within 3 days after surgery. RESULTS:  We observed a marked but nonsignificant increase in serum NGAL directly after clamp removal (75.21 ±55.83 vs. 46.37 ±21.60 ng/ml baseline value, P >0.05) and significantly elevated plasma NGAL at 2 hours (91.54 ±76.54 vs. baseline, P <0.05), 12 hours (100.78 ±44.92 vs. baseline, P <0.05) and 24 hours (89.46 ±94.18 vs. baseline, P <0.05) after clamp release. There was also significant elevation of urinary IL­18 at 2 hours (51.60 [12.12-527.16] vs. 25.99 [9.34-187.80] pg/ml at baseline, P <0.05); L­FABP at 2 hours (47.10 [5.40-500.00] vs. 5.50 (2.20-27.20) ng/ml at baseline, P <0.05) and 12 hours (39.00 [5.20-500.00] vs. baseline, P <0.05); NGAL at 12 hours (20.75 [5.00-176.10] vs. 5.85 [1.40-16.00] ng/ml at baseline, P <0.05) and 24 hours (13.95 [3.90-163.30] vs. baseline, P <0.05) after clamp release. CONCLUSIONS:  Elective AAA surgery may induce AKI. Novel markers can facilitate early detection of AKI, thus allowing to start therapy at an appropriate time point.