A new antiviral hypothesis and radioactive iodine therapy to other cancers, such as breast cancer, lung cancer, and glioblastoma multiforme (GBM)?

Radioactive iodine therapy (RIT) is an effective, safe, and cheap method in benign and malignant thyroid diseases. There is still an unresolved question of whether RIT treatment also plays a role in the treatment of, for example, breast cancer, lung cancer, or glioblastoma multiforme (GBM). These studies are currently being carried out in rats in combination with genes, but it may be an interesting challenge to assess "pure" RIT alone, thanks to the expression of sodium iodide symporter (NIS), is effective in other organ nodules, both benign and malignant. Cloning of the NIS in 1996 provided an opportunity to use NIS as a powerful theranostic transgene. In addition, NIS is a sensitive reporter gene that can be monitored by high-resolution PET imaging using the radiolabels [¹²4I]sodium iodide ([¹²4I]NaI) or [18F] tetrafluoroborate ([¹8F]TFB). Based on published positron emission tomography (PET) results, [¹²4I]sodium iodide and internally synthesized [18F]TFB were compared in an orthotopic animal model of NIS-expressing glioblastoma. The results showed improved image quality using [¹8F]TFB. Based on these results, we will be able to extend the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumour models with low-volume disease such as GBM. Is it possible to treat RIT alone without using the NIS gene in GBM? After all, the NIS symporter was detected not only in the thyroid gland, but also in different tumours. The administration of RIT is completely harmless; the only complication is hypothyroidism. Indeed, recently it has been shown that, for example, in the case of thyroid cancer, the maximum RIT is 37000 MBq (1000 mCi). When beneficial effects of therapy in GBM are not possible (e.g. neurosurgery, modulated electro-hyperthermia, chemotherapy, immunotherapy, cancer vaccines, or oncolytic viruses), could RIT provide a "revolution" using NIS?

Effects of Low-Dose Atorvastatin on the Peripheral Blood Mononuclear Cell Secretion of Angiogenic Factors in Type 2 Diabetes.

The aim of this study was to investigate the influence of statins on the secretion of angiogenesis mediators by the peripheral blood mononuclear cells (PBMCs) derived from patients suffering from type 2 diabetes. The study group comprised 30 participants and included: 10 statin-treated patients with diabetes, 10 statin-free diabetic subjects, and 10 statin-free non-diabetic individuals. PBMCs isolated from the blood were cultured in vitro in standard conditions and in an environment mimicking hyperglycemia. Culture supernatants were evaluated for VEGF, MCP-1, Il-10, and Il-12 by flow cytometry using commercial BDTM. Cytometric Bead Array tests. The secretion of VEGF, MCP-1 and Il-12 by PBMCs, cultured both in standard and hyperglycemic conditions, was significantly lower in the statin-treated patients with type 2 diabetes in comparison with the statin-free diabetic patients. Conversely, the secretion of Il-10 was higher in the statin-treated than in the statin-free diabetic patients. VEGF, MCP-1 and Il-12 levels in PBMCs supernatants from the glucose-containing medium were higher than those from the standard medium in each of the diabetic groups. The results of the study suggest that statins in low doses exhibit an antiangiogenic activity, reducing the secretion of potent proangiogenic factors, such as VEGF and MCP-1, and increasing the secretion of antiangiogenic Il-10 by PBMCs, also under hyperglycemic conditions characteristic for type 2 diabetes.

The Effect of Homocysteine on the Secretion of Il-1ß, Il-6, Il-10, Il-12 and RANTES by Peripheral Blood Mononuclear Cells-An In Vitro Study.

The contemporary theory of the inflammatory-immunological pathomechanism of atherosclerosis includes the participation of interleukin-1ß (Il), Il-6, Il-10, Il-12, RANTES, and homocysteine in this process. The knowledge on the direct effect of hyperhomocysteinemia on inflammatory-state-related atherosclerosis is rather scarce. Our study is the first to account for the effects of homocysteine on the secretion of Il-10 and RANTES in vitro conditions. For this purpose, human mitogen-stimulated peripheral blood mononuclear cells (PBMNCs) were cultured in vitro and exposed to homocysteine at high concentrations. Subsequently, the concentrations of cytokines were assayed in the cell culture supernatant using flow cytofluorimetry. It has been shown that, in the presence of homocysteine, the secretion of IL-1, IL-6 and RANTES by PBMNCs was increased, whereas IL-10 concentration was significantly lower than that of the supernatant derived from a mitogen-stimulated cell culture without homocysteine. The secretion of Il-12 by PBMNCs exposed exclusively to mitogen, did not differ from homologous cells also treated with homocysteine. Therefore, in our opinion, high-concentration homocysteine affects the progression of atherosclerosis by increasing the secretion of proinflammatory cytokines secreted by PBMNCs, such as Il-1ß, Il-6, RANTES, and by attenuating the secretion of Il-10.

Expression profiling of ileal mucosa in asthma reveals upregulation of innate immunity and genes characteristic of Paneth and goblet cells.

BACKGROUND: The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. METHODS: Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). RESULTS: Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn's disease ileum when our results were compared to another dataset (p = 3.66 × 10-7). CONCLUSION: Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn's disease.

Sirtuin 1 as the mechanism of action of agents used in the diabetes mellitus pharmacotherapy.

SIRT1 (sirtuin 1, a member of histone deacetylase III family) is responsible for deacetylation of lysine in histones and the conservation of DNA in the state of transcriptionally inactive heterochromatin. SIRT1 is also capable of deacetylation of transcription factors, as well as other regulatory proteins. The SIRT1 activity plays a unique role in the prevention of metabolic memory, reducing many pathways leading to chronic diabetic complications or diseases concomitant with diabetes. Factors modifying expression and/or activity of SIRT1 may be especially helpful for patients with diabetes. This article attempts to sum up the current state of knowledge about agents commonly used in the treatment of type 2 diabetes which might have an impact on the SIRT1 expression and activity. It is the review of several studies regarding drug-induced pleiotropic activity and the way in which their interference with cellular pathways gives us better understanding of this activity, as well as the influence of therapy on the course of the disease.

Ileal Lactase Expression Associates with Lactase Persistence Genotypes.

(1) Background: Lactose digestion depends on persistence genotypes (including rs4988235), the frequency of which exhibits broad geographical variability. However, little is known about the relationship between lactase (LCT) genotypes and intestinal expression of LCT. We aimed to investigate ileal expression of LCT depending on main genetic polymorphisms (rs4988235, rs3754689, rs3739022), age, sex, smoking status, body mass index (BMI), and the expression of other genes; (2) Methods: phenotype, array-based genotype, and ileal mucosal biopsy expression data were obtained from the CEDAR study; (3) Results: analyses included 196 healthy Europeans (53.6% women) aged 53.0 ± 13.6 years with a mean BMI of 25.6 ± 4.2 kg/m2, of whom 17.4% were smoking. Ileal LCT expression was mostly independent of age, sex, BMI, or smoking. Rs4988235 homozygous minor allele (GG) associated with lower LCT expression (vs. AG p = 2.2 × 10-6, vs. AA p = 1.1 × 10-7). Homozygous major allele of rs3754689 (GG) was related to higher LCT expression (vs. AG p = 1.7 × 10-5, vs. AA p = 0.0074). Rs3754689 genotype did not modify LCT expression (GG vs. AG p = 0.051) in rs4988235-heterozygous subgroup. Interestingly, CD14, which is a marker of monocytes and macrophages, was the strongest negative transcriptomic correlate of LCT expression (r = -0.57, pFDR = 1.1 × 10-14); (4) Conclusions: both rs4988235 and rs3754689 associated with ileal LCT expression, which did not seem related to age, sex, smoking, or BMI. The inverse correlation between LCT and CD14 expression in the ileum is striking and requires further investigation.

Pain in People with Advanced Dementia: The Opinions of Kazakh Medical Students.

PURPOSE: The medical students' attitude toward pain in people with advanced dementia, while constituting an important factor in care, has rarely been assessed to date. The aim of our study was thus to perform such assessment in medical students in Kazakhstan, to enable an improvement of the existing curriculum (like we previously did in Poland). MATERIALS AND METHODS: We analyzed the knowledge about pain using a short anonymous questionnaire, which was completed by 112 students of the Medical University of Aktobe, Kazakhstan. RESULTS: On average, students listed symptoms of 1.4 ± 1.2 (out of 6 analyzed) pain areas (median 2.0). The symptoms related to changes in mental status were suggested the most often (57 students: 50.9%). The students who indicated these symptoms also listed a higher number of symptoms from the remaining domains (1,1 ± 1.0 [median 1.0] vs 0.6 ± 0.8 [median 0.0]; p<0.01). Observational methods in the assessment of the severity of pain in people with dementia were indicated by 44 students (39.3%), but only one participant (0.9%) was able to name an observational scale for pain assessment. Correct answers regarding pain treatment rules were presented by 18 students (16.0%), and the answers of the next 47 participants (42.0%) were very general but suggested the same treatment no matter what the cognitive status. CONCLUSION: The study revealed gaps in the knowledge of Kazakh medical students regarding pain in advanced stages of dementia. Demographic changes, combined with the coexistence of pain with dementia, indicate that medical students worldwide must have sufficient knowledge and skills to adequately care for the continually growing number of people with these conditions. It is imperative in countries like Kazakhstan, where the dementia burden was unrecognized until now, but it will blow up in the near future.

The impact of dapagliflozin on glucose excursions related to early proatherogenic derangement in the aortic wall.

INTRODUCTION: Cardiovascular risk in the course of diabetes depends greatly on glycemic variability which is even more significant than chronic hyperglycemia. Optimal management of diabetes involves a multidisciplinary approach focused in particular on decreasing the risk of atherosclerosis. Therefore, our purpose was to evaluate the impact of dapagliflozin on glucose excursions and related proatherogenic changes in the aortic wall. METHODS AND MATERIALS: Animal model of type 2 diabetes rich-fat/STZ rats was used. Wistar rats were randomized into 3 groups: dapagliflozin-treated with glucose excursions, placebo-treated with glucose excursions and placebo-treated with stable diabetes. Dapagliflozin was administered once a day, 1 mg/kg, for 8 consecutive weeks. Glucose levels were measured twice a week at fasting and postprandially. The samples of aortas were taken for histopathological and immunochemistry examinations at the end of the experiment. The derangement in the aortic wall and the distribution of CD68+ cells in the aorta were considered early signs of atherosclerosis. RESULTS: Dapagliflozin reduced glucose excursion to the level characteristic for stable, well-controlled diabetes. It was related to a significant decrease in histopathological changes which were observed in the placebo-treated rats with glucose variability. Dapagliflozin significantly reduced also the accumulation of CD68+ macrophages in the aortic adventitia. CONCLUSION: Dapagliflozin provides not only mere beneficial regulation of metabolic status with the depletion of glucose variability, but is also helpful in the prevention of early atherosclerosis related to the course of diabetes type 2.

Simvastatin attenuates the aberrant expression of angiogenic factors induced by glucose variability.

AIM: Over the last few years, studies have indicated that fluctuant hyperglycemia is very likely to increase the risk of cardiovascular complications of diabetes. Statins are widely used in diabetes for the prevention of cardiovascular complications, but it is still not clear whether simvastatin could also prevent glycaemic variability - induced aberrant angiogenesis which plays a significant role in the development of atherosclerosis. METHODS: Wistar rats were divided into four groups: (1) simvastatin-treated (20 mg/kg for 8 consecutive weeks) type 2 diabetes rat model with daily glucose excursions, (2) placebo-treated type 2 diabetes rat model with daily glucose excursions, (3) placebo-treated stable well-controlled type 2 diabetes rat model and (4) placebo-treated non-diabetic rats. Daily glucose fluctuations and several angiogenic factors: cVEGF, mRNA VEGF, VEGF-R1, VEGF-R2, TGF-beta expression, circulating endothelial and progenitor endothelial cells were measured in all groups. RESULTS: Simvastatin decreased several factors enhanced by glucose excursions: circulating VEGF, mRNA TGF-beta expression in the myocardium and mRNA VEGFR-2 expression in the aorta. Simvastatin increased some factors attenuated by glucose fluctuations: mRNA VEGF expression and mRNA VEGFR-1 expression in the myocardium and in the aorta. In the simvastatin-treated group with glycaemic variability, the percentage of circulating endothelial cells was lower and the percentage of progenitor endothelial cells in peripheral blood was higher than in the placebo-treated rats with glucose-fluctuations. CONCLUSIONS: Simvastatin used in the rat model of type 2 diabetes with glucose variability reduces glucose variability and limits glucose fluctuations-induced changes in the expression of angiogenic factors in the cardiovascular system.

New arguments for beneficial effects of alpha-lipoic acid on the cardiovascular system in the course of type 2 diabetes.

PURPOSE: Alpha-lipoic acid (ALA), widely known as an antioxidant, modifies also serum levels of angiogenic factors in type 2 diabetic patients. These pharmacological activities may influence the status of the cardiovascular system. Taking into consideration that diabetes is related to the increased cardiovascular risk we investigated several effects of ALA on angiogenic factors in the myocardium and in the aortal wall using a rat model of type 2 diabetes. METHODS: Diabetes was induced in Wistar rats by a fat-rich diet and by intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). Animals were divided into 3 groups: ALA-treated type 2 diabetes rat model, placebo-treated type 2 diabetes rat model and placebo-treated non-diabetic rats. ALA was administered orally once a day, 20 mg/kg, for 8 consecutive weeks. mRNA VEGF, VEGF-R1 and VEGF-R2 expression was measured in the myocardium and the aortal wall, simultaneously with circulating VEGF and circulating endothelial cells (cEC) and endothelial progenitor cells (cEPC). RESULTS: ALA induced pro-angiogenic effect in the myocardium of rats with diabetes increasing mRNA VEGF expression and decreasing mRNA VEGFR-1 expression, while in the aortal wall ALA increased mRNA VEGFR-2 and VEGFR-1 expression. cVEGF in the ALA-treated group was higher comparing to both control groups. It was revealed that cEC percentage in the ALA-treated group was decreased with no effect on the percentage of cEPC. CONCLUSIONS: In summary, the current data provide novel findings about potential beneficial effects of ALA on angiogenic factors in the cardiovascular system, especially on myocardium, in the course of type 2 diabetes.

Homocysteine as a non-classical risk factor for atherosclerosis in relation to pharmacotherapy of type 2 diabetes mellitus.

AIMS: The aim of our study was to evaluate which of the pharmacotherapeutic methods that are frequently used to treat type 2 diabetes is associated with the most beneficial profile in relation to pro-atherogenic homocysteine levels. PATIENTS AND METHODS: We measured the serum homocysteine level in 182 patients with type 2 diabetes treated with metformin (89), treated with insulin in combination with metformin (31), receiving sulfonylureas (31) and treated conventionally with insulin (31). The total homocysteine levels in the serum were assayed. To exclude the influence of selected metabolic and anthropometric factors on the differences between the examined groups, multivariate analysis of covariance was used (ANCOVA). In this analysis, serum homocysteine concentration was the dependent variable, while diabetes duration, waist circumference, HbA1c, 1,5-anhydro-D-glucitol, fasting glycaemia and peptide C were used as covariates. RESULTS: The serum homocysteine levels in patients treated with insulin in monotherapy were significantly higher than what was observed in the metformin treated subjects and in the patients receiving insulin combined with metformin. The analysis of covariance also confirmed that the differences between the therapeutic groups were affected by waist circumference and the C-peptide levels. CONCLUSION: We conclude that conventional insulin therapy may have a negative effect on pro-atherogenic homocysteine levels in patients with type 2 diabetes. This study revealed that pro-atherogenic homocysteine levels may not only be modified by pharmacotherapy of type 2 diabetes, but also by beta cell secretory function and abdominal obesity.

[Undesirable pharmacokinetic drug-to-drug interactions affecting the effectiveness and safety of anti-infectious pharmacotherapy]. / Niepozadane farmakokinetyczne interakcje wplywajace na skutecznosc i bezpieczenstwo leczenia zakazen.

The occurence of pharmacokinetic drug-to-drug interactions is the serious clinical problem in the course of pharmacotherapy of infections. Its essential part is the influence of such interactions on the effectiveness and safety of antimicrobial therapy. The aim of study was to present, the most significant on clinical hand, examples of interactions and their mechanisms between antimicrobial agents and other drugs on stages of absorption, distribution, biotransformation and elimination, leading to the decreased antimicrobial activity and ineffective pharmacotherapy or to the increased antimicrobial activity and to the increased risk of adverse effects due to agents used for anti-infectious pharmacotherapy.

[Ibrutinib - new tool in hematologist hand, new challenges for internist].

Chronic lymphocytic leukemia is the most common cancer of the lymphatic tissue in adults. The peak incidence falls on the 65-70 year old. Therefore, the majority of patients with chronic lymphocytic leukemia (CLL) has at least one coexisting disease. Successful oncological and supportive treatment, that is common in recent years, significantly prolongs the survival. This paper presents ibrutinib - a new drug used to treat CLL. The aim of this paper is, to show an example of this drug, meaning and benefits of modern methods of pharmacotherapy in the treatment of oncology.

Eryngium creticum – ethnopharmacology, phytochemistry and pharmacological activity. A review

Abstract Eryngium creticum Lam. (E. cyaneum Sibth. & Sm., E. syriacum Lam.), Saniculoideae, Apiaceae is of great importance in the traditional Greco – Arab medicine. This study was carried out in order to contribute to the ethnopharmacological knowledge of this medicinal species. This review describes the botanical characterization and distribution, as well as critically assesses the phytochemical properties and biological activities of E. creticum, a species that has been used in traditional medicine for many decades. Possible trends and perspectives for future research of this plant are discussed, as well. E. creticum has been found to contain several chemical constituents, mostly sesquiterpenes, monoterpenes, aldehydes, coumarins, sitosterols and sugars. Eryngo with its bioactive compounds possesses a wild range of biological activities. It was reported that in traditional medicine E. creticum was applied mainly as the remedy for snake and scorpion bites. Some published studies have shown a broad spectrum of biological and pharmacological activities, including anti-snake and anti-scorpion venom, as well as antibacterial, antifungal and antileishmanial effects. Other have indicated antihyperglycemic, hypoglycemic and antioxidant activities of this species. The in vitro studies and in vivo models have provided a simple bioscientific explanation for its various ethnopharmacological uses.

The Impact of Pharmacotherapy of Type 2 Diabetes Mellitus on IL-1ß, IL-6 and IL-10 Secretion.

BACKGROUND: The aim of this study was to assess the impact of pharmacotherapy of diabetes on atherosclerosis, as reflected in interleukin (IL)-1ß, IL-6 and IL-10 serum levels. METHODS: We studied patients with type 2 diabetes, treated with metformin, insulin combined with metformin and conventional insulin. IL-1ß, IL-6 and IL-10 serum levels were assayed using BD™ Cytometric Bead Array. Multivariate analysis of covariance was performed to exclude the impact of some metabolic and anthropometric factors on differences in cytokines concentrations among the participants receiving different pharmacotherapy. RESULTS: The serum concentrations of IL-1ß and IL-6 were significantly higher and IL-10 serum levels were significantly lower in the insulin-treated group than in other therapeutic groups. Covariance analysis confirmed that differences in IL-1ß and IL-6 levels were determined by pharmacotherapy and fasting plasma glucose, whereas in IL-10 levels by the therapy only. Additionally, peptide C modified differences in IL-1ß levels and HbA1c in IL-6 concentrations. CONCLUSION: This study revealed that both pharmacotherapy and glycemic control may modify some pro-atherogenic factors, such as IL-1ß and IL-6. The therapy with metformin and insulin combined with metformin seems to be much more beneficial in terms of their impact on pro-inflammatory cytokines secretion in comparison to conventional insulinotherapy.

Family, anthropometric and biochemical factors affecting birth weight of infants born to GDM women.

OBJECTIVES: Gestational diabetes mellitus (GDM) affects up to 25% of all pregnancies worldwide. If untreated, GDM leads to increased complication rates both, in the mother and the fetus. Early diagnosis and adequate management of GDM are essential to avoid macrosomia. Nonetheless, neonates born to GDM mothers often have high birth weight. The aim of the study was to evaluate selected factors which can affect neonatal birth weight. MATERIAL AND METHODS: The study included 152 women with GDM and 58 healthy pregnant controls. Anthropometric data of both parents, maternal biochemical parameters, and neonatal birth weight were collected. RESULTS: The independent factors influencing neonatal birth weight were pregnancy duration, maternal smoking, as well as birth weight and current weight of the father. The risk of delivering a large for gestational age (LGA) infant increases with the diagnosis of GDM, higher maternal pre-pregnancy weight, and higher fasting glycaemia. No correlation between maternal fasting glycaemia, HbA1c, 1,5-AG, lipids and neonatal birth weight was found. CONCLUSIONS: Risk factors for LGA include gestational diabetes, high maternal pre-pregnancy weight, and current body weight of the father. Neither HbA1c nor 1,5-AG were reliable predictors of neonatal birth weight and occurrence of LGA in the studied population.

Thymic emigration patterns in patients with type 2 diabetes treated with metformin.

Recent data suggest that thymic output, which provides the naive T cells necessary for the normal functioning of T-cell-dependent immunosurveillance cellular immunity including anti-cancer protection, can be disturbed in the course of type 2 diabetes. Metformin, an anti-diabetic drug commonly confirmed as an agent with many potential anti-cancer activities, might be helpful in this immune correction. The profile of thymic output was evaluated in the current study on the basis of the signal-joint T-cell receptor excision circle (sjTREC) concentration in peripheral blood polymorphonuclear cells and thymic emigrant content in peripheral blood evaluated from CD127 and/or CD132 antigen expression. It was revealed that recent thymic emigrants and more differentiated CD127(+) CD132(+) cell populations were decreased among naive T cells and CD8(+) T cells, whereas RTE count was increased in CD4(+) T cells, and the CD127(+) CD132(+) cell population was less numerous than in non-diabetic participants. Terminally differentiated thymic emigrants, i.e. CD127(-) CD132(+) cells, were increased in naive T cells and in CD8(+) T cells. Metformin affects mainly the early phases of thymic export, increasing CD127(+) CD132(-) and CD127(+) CD132(+) cell populations in naive T cells and the CD127(+) CD132(-) population in CD4(+) T lymphocytes. It could be concluded that type 2 diabetes deteriorates thymic immunostasis. The decreased thymic output could be compensated by metformin, especially with regard to CD4(+) naive T cells. It is the first time that therapy with metformin has been documented by us as particularly useful in the control and normalization of thymus function, regarding correction of early populations of thymic emigrants.

Alpha-lipoic acid modifies circulating angiogenic factors in patients with type 2 diabetes mellitus.

AIMS: In recent years interest has been focused on angiogenesis as a process involved in coronary artery disease (CAD) and diabetic distal sensorimotor polyneuropathy (DSPN). Recent studies have demonstrated the possible angiogenesis-modulating potential of alpha-lipoic acid (ALA) for DSPN and CAD. The aim of our study was to investigate the influence of ALA on serum angiogenic factors in patients with DM-2 (type 2 diabetes) with CAD and DSPN. METHODS: Sixty patients with type 2 DM (T2DM) and CAD and 25 non-diabetic subjects were studied. Thirty patients with T2DM, CAD and DSPN were given 600 mg of ALA a day for 90 days. VEGF, bFGF, MCP-1, angiogenin, IL-12 and IL-10 concentrations in the sera were measured by flow cytometry. RESULTS: ALA significantly increased VEGF, bFGF and IL-10 and decreased MCP-1 serum concentrations in patients with T2DM and CAD and DSPN. VEGF and IL-10 serum levels, both before and after ALA-treatment, were higher in this group than in T2DM and CAD patients, while circulating bFGF was higher and MCP-1 serum level lower in patients with T2DM and CAD and DSPN only in the post-ALA-treatment, compared to the T2DM and CAD group. CONCLUSIONS: ALA may influence angiogenesis in type 2 diabetic patients through an effect on some circulating factors including VEGF, bFGF, MCP-1 and IL-10.

Increased circulating RANTES in type 2 diabetes.

AIM: The pro-atherogenic role of RANTES, a chemokine expressing pleiotropic activities, in the course of type 2 diabetes-related atherosclerosis has been well documented. However, it is not known which of the diabetes-related factors primarily influence serum RANTES levels in patients with type 2 diabetes. Our aim was to investigate relationships between several factors known to be related to an increased risk of atherosclerosis and serum RANTES levels in type 2 diabetic patients. METHODS: A total of 168 subjects were examined, which included 138 patients with type 2 diabetes and 30 non-diabetic controls. Measurements of venous, fasting, plasma glucose, HbA1c, lipid profile, 1,5-anhydro-D-glucitol (1,5-AG) plasma levels, homocysteine and the fasting, serum C-peptide levels were performed. Serum concentrations of RANTES were assayed using BD(TM) Cytometric Bead Array tests. Peripheral insulin resistance was expressed according to a new index defined by Ohkura et al. RESULTS: RANTES levels in type 2 diabetic patients correlated with 1,5-AG, fasting glycaemia, HbA1c and the Ohkura index. Multivariate regression analysis was performed taking into consideration several factors related to the inflammatory process and atherosclerosis, namely the patient's age, diabetes duration, waist circumference, 1,5-AG, HbA1c, lipid profile parameters, serum homocysteine levels and Ohkura index, as independent variables potentially influencing serum RANTES levels in type 2 diabetic patients. It is shown that RANTES concentrations in the serum is primarily dependent upon 1,5-AG plasma levels. CONCLUSION: Our results suggest that increased serum levels of RANTES in type 2 diabetic patients are closely related to postprandial (acute) hyperglycaemia.

Circulating monocyte chemotactic protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1) and angiogenin in type 2 diabetic patients treated with statins in low doses.

Statins are known as agents promoting a biphasic dose-dependent effect on angiogenesis under experimental conditions. Dysregulation of angiogenesis plays an important role in the development of atherosclerosis and it may be affected by metabolic factors. The aim of this research was to explain how low doses of statins modify serum concentrations of pro-angiogenic factors MCP-1 and angiogenin in type 2 diabetic patients. Measurements of metabolic control parameters were performed in 30 patients with type 2 diabetes treated with low doses of statin, and in 34 statin-free patients with type 2 diabetes. The serum levels of MCP-1 and VCAM-1 in statin-treated patients were lower than those of the statin-free group. ANCOVA results revealed that these effects were dependent only on the use of statins. In type 2 diabetic subjects, overall positive correlation was found between total cholesterol or LDL serum concentration and MCP-1 serum level. The angiogenin concentration in the serum did not show differences and was comparable in both groups. The angiogenin serum level correlated negatively with HDL, LDL and with HbA1c. Multivariate regression analysis indicated that angiogenin serum levels in type 2 diabetic patients were determined mainly by HbA1c, HDL-cholesterol and diabetes duration. It has been shown that statins used in low doses in type 2 diabetic subjects decrease MCP-1 and VCAM-1serum levels, most likely due to the statins-related effect on the lipid profile, while angiogenin serum levels in this group are determined rather by the current metabolic control.