A comparison of the levels of hepatocyte growth factor in serum in patients with type 1 diabetes mellitus with different stages of diabetic retinopathy

INTRODUCTION: The aim of this study was to evaluate the blood concentration of hepatocyte growth factor (HGF) in patients at various stages of retinopathy. We hypothesised that the high level of HGF found in diabetic patients may be an important marker of retinopathy progression and that HGF level may be an index of the risk of proliferative retinopathy. MATERIAL AND METHODS: The participants in the study were 76 patients with type 1 diabetes mellitus. Of these, 35 patients were without retinopathy and formed Group 1. Of the remaining 41 patients with retinopathy, 20 patients had non-proliferative diabetic retinopathy (NPDR) and formed Group 2, while 21 patients had proliferative diabetic retinopathy (PDR) and formed Group 3. We evaluated the concentration of HGF In the peripheral blood by an enzyme-linked immunosorbent assay. RESULTS: Mean serum concentrations of HGF in the control group were significantly lower than in the type 1 diabetic patients. We found a significant increase in HGF serum concentrations in diabetic patients with PDR compared with the control group. Mean serum HGF concentrations were significantly higher in diabetic subjects with PDR than in diabetic patients without retinopathy. CONCLUSION: HGF concentration is increased in patients with type 1 diabetes mellitus with proliferative retinopathy, and concentrations increase with the progression of retinopathy, suggesting that HGF plays a role in the pathogenesis of proliferative diabetic retinopathy.     

Pancreatic endocrine tumors - management guidelines (recommended by the Polish Network of Neuroendocrine Tumors)

Pancreatic endocrine tumors (PETs) are rare neoplasms of this organ. The majority of PETs are tumors without hormonal activity. In this publication, we present the diagnostic and therapeutic guidelines for the management of these tumors proposed by the Polish Network of Neuroendocrine Tumors. These guidelines refer to biochemical and location diagnostics, including scintygraphy of somatostatin receptors, endoscopic ultrasonography and other anatomical and functional imaging methods. High importance is attached to correct histopathological diagnosis which determines further management of patients with PETs. Antitumor therapy requires multidirectional procedure, and therefore the rules of surgical treatment, biotherapy, chemotherapy and peptide receptor radionuclide therapy are discussed.     

Incretin hormones in the treatment of type 2 diabetes. Part II. Incretins - new possibilities for pharmacotherapy of type 2 diabetes

In the pathogenesis of diabetes type 2, increasing insulin resistance is accompanied by dysfunction of pancreatic islet b cells. It is hypothesized that at the basis of this pathology lies an incretin defect of insulinotropic gut-derived hormones, relying on decreased secretion of GLP-1 (glucagon-like peptide 1), with preserved insulinotropic effect, whereas GIP (glucose-dependent insulinotropic polypeptide) secretion remains within physiological limits, but its action is mostly impaired due to total loss of possibility for stimulation of the second phase insulin secretion. Possibilities for pharmacological correction of incretin defect create an opportunity of causative treatment of diabetes and provide basis for development of research on a new group of drugs which promote hypoglycemia. In the presence of these findings there are many ongoing clinical studies with the use of GLP-1 analogues or GLP-1 receptors activators (GLP-1 agonists), as well as the inhibitors of dipeptidyl peptidase IV (DPP-IV), the enzyme responsible for incretin proteolysis, in the treatment of type 2 diabetes. Multidirectional, glucoregulative mechanism of action of these drugs, aiming at the pathogenesis of the disease, restores the proper function of the intestinal-pancreatic axis in subjects with type 2 diabetes and ensures good metabolic control and improvement in quality of life in this group of patients.     

Type II secretory pathway for surface secretion of DraD invasin from the uropathogenic Escherichia coli Dr+ strain

The virulence of the uropathogenic Escherichia coli Dr(+) IH11128 strain is associated with the presence of Dr fimbrial structures and a DraD invasin which can act as a fimbrial capping domain at the bacterial cell surface. However, a recent study suggests that the DraD protein is surface exposed in two forms: fimbria associated and fimbria nonassociated (prone to interaction with the N-terminal extension of the DraE protein located on the fimbrial tip). The actual mechanism of DraD surface secretion is presently unknown. We identified a previously unrecognized type II secretory pathway (secreton) in the uropathogenic E. coli Dr(+) strain which is well conserved among gram-negative bacteria and used mainly for secretion of virulence determinants. An active secreton is composed of 12 to 15 different proteins, among which GspD functions as an outer-membrane channel to permit extrusion of proteins in a folded state. Therefore, we inactivated the pathway by inserting the group II intron into a gspD gene of the type II secretion machinery by site-specific recombination. DraD secretion by the E. coli Dr(+) and gspD mutant strains was determined by immunofluorescence microscopy (with antibodies raised against DraD) and an assay of cell binding between bacteria and HeLa cells. The specificity of DraD-mediated bacterial binding for the integrin receptor was confirmed by examination of the adhesion of DraD-coated beads to HeLa cells in the presence and absence of alpha(5)beta(1) monoclonal antibodies. The investigations that we performed showed that type II secretion in E. coli Dr(+) strains leads to DraD translocation at the bacterial cell surfaces.     

Sulfonamides with the N-alkyl-N′-dialkylguanidine moiety as 5-HT7 receptor ligands

A series of arylsulfonamides containing guanidine incorporated in the structure of secondary amines (piperidine, piperazine) was synthesized on SynPhase Lanterns and evaluated for 5-HT_1A, 5-HT_2A, and 5-HT₇ receptors. The results demonstrated that N-alkyl-N′-dialkylguanidines displayed good 5-HT₇/5-HT_1A selectivity and may be regarded as promising structural core for development of 5-HT₇ ligands.     

Organic cation/carnitine transporter OCTN3 is present in astrocytes and is up-regulated by peroxisome proliferators-activator receptor agonist

In the brain β-oxidation, which takes place in astrocytes, is not a major process of energy supply. Astrocytes synthesize important lipid metabolites, mainly due to the processes taking place in peroxisomes. One of the compounds necessary in the process of mitochondrial β-oxidation and export of acyl moieties from peroxisomes is l-carnitine. Two Na-dependent plasma membrane carnitine transporters were shown previously to be present in astrocytes: a low affinity amino acid transporter B^0,+ and a high affinity cation/carnitine transporter OCTN2. The expression of OCTN2 is known to increase in peripheral tissues upon the stimulation of peroxisome proliferators-activator receptor α (PPARα), a nuclear receptor known to up-regulate several enzymes involved in fatty acid metabolism. The present study was focused on another high affinity carnitine transporter—OCTN3, its presence, regulation and activity in astrocytes. Experiments using the techniques of real-time PCR, Western blot and immunocytochemistry analysis demonstrated the expression of octn3 in rat astrocytes and, out of two rat sequences ascribed as similar to mouse OCTN3, XM_001073573 was found in these cells. PPARα activator–2-[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]acetic acid (WY-14,643) stimulated by 50% expression of octn3, while, on the contrary to peripheral tissues, it did not change the expression of octn2. This observation was correlated with an increased Na-independent activity of carnitine transport. Analysis by transmission electron microscopy showed an augmented intracellular localization of OCTN3 upon PPARα stimulation, mainly in peroxisomes, indicating a physiological role of OCTN3 as peroxisomal membrane transporter. These observations point to an important role of OCTN3 in peroxisomal fatty acid metabolism in astrocytes.     

A consensus map of chromosome 6R in rye (Secale cereale L.)

Four F₂ mapping populations derived from crosses between rye inbred lines DS2×RXL10, 541×Ot1-3, S120×S76 and 544×Ot0-20 were used to develop a consensus map of chromosome 6R. Thirteen marker loci that were polymorphic in more than one mapping population constituted the basis for the alignment of the four maps using the JoinMap v. 3.0 software package. The consensus map consists of 104 molecular marker loci including RFLPs, RAPDs, AFLPs, SSRs, ISSRs, SCARs, STSs and isozymes. The average distance between the marker loci is 1.3 cM, and the total map length is 135.5 cM. This consensus map may be used as a source of molecular markers for the rapid development of new maps of chromosome 6R in any mapping population.     

Improved pre-concentration and detection methods for volatile sulphur breath constituents

Suitability of different types of pre-concentration (solid phase microextraction and sorbent trapping) and detection (flame photometric detector (FPD) and mass selective detector (MSD)) for gas chromatographic determination of sulphur-containing compounds (H₂S, MeSH, EtSH, DMS, COS and CS₂) in breath-gas was assessed in this study. Several factors like influence of humidity, influence of oxygen, or stability of target compounds in extraction vessels (SPME vials and sorbent tubes) were investigated. Despite poor stability of VSCs in SPME vials and matrix effects (unfavorable influence of humidity), SPME was found to be a fast and reliable enrichment method, which coupled with mass selective detector provided satisfactory LODs of target compounds at the ppt level (from 0.15 ppb for CS₂ to 2.3 ppb for H₂S). Application of sorbent trapping with two-bed sorbent tubes containing Tenax TA and Carboxen 1000 gave excellent LODs (0.03–0.3 ppb for 200 ml sample and MSD). Stability of investigated VSCs in sorbents was found to be very poor (30–40% losses after 2 h). FPD showed satisfactory sensitivity only when it was coupled with sorbent trapping. Breath samples were collected into Tedlar bags in a CO₂-controlled manner. Humidity was removed during sampling (permeation dryer – Nafion) to avoid unfavorable water dependent effects during analysis.