Potential use of serum insulin-like growth factor 1 and E-cadherin as biomarkers of colorectal cancer.

AIM: Despite many efforts, reliable biomarkers for the prediction and diagnosis of colorectal cancer (CRC) are still missing. Insulin-like growth factor 1 (IGF-1) and E-cadherin are recognized as potential biomarkers, but their diagnostic capacity is largely unexplored in CRC. The aim of this work is to investigate IGF-1 and E-cadherin levels with respect to various characteristics of CRC and to estimate their diagnostic potential. METHOD: Seventy CRC patients and 75 healthy individuals were enrolled. IGF-1 and E-cadherin were determined using enzyme-linked immunosorbent assay. The predictive and diagnostic capacities of IGF-1 and E-cadherin were estimated by logistic regression analysis and by determination of the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Concentrations of IGF-1 were lower (P = 0.019) while levels of E-cadherin were higher (P < 0.001) in CRC patients than in controls. IGF-1 concentration decreased in parallel with age and progression of CRC (P = 0.023). Also, IGF-1 was higher in men with CRC than in women (P = 0.003). E-cadherin levels were unaffected by variations in either anthropometric characteristics of CRC patients, or localization, grade and stage of the tumour. Both IGF-1 and E-cadherin were independently associated with CRC (P = 0.040; P < 0.001, respectively). The diagnostic accuracy of IGF-1 was estimated as acceptable (AUC = 0.757; P < 0.001), while the diagnostic accuracy of E-cadherin was outstanding (AUC = 0.954; P < 0.001). CONCLUSIONS: Decreased IGF-1 and increased E-cadherin levels were found in CRC patients. IGF-1, but not E-cadherin, concentrations differed according to age, gender and stage of CRC. Both markers were independently associated with the presence of the disease, while E-cadherin demonstrated high diagnostic accuracy.

Inverse association between serum endocan levels and small LDL and HDL particles in patients with type 2 diabetes mellitus.

OBJECTIVE: Determination of lipoprotein size and subclasses distribution can provide more significant information on cardiovascular disease risk than measurement of traditional lipid parameters alone. Accordingly, we aimed to examine their potential relationship with the novel biomarker of endothelial dysfunction, such as endocan in patients with type 2 diabetes mellitus (T2D), since there are no studies concerning this issue. PATIENTS AND METHODS: This case-control study included a total of 42 individuals with T2D and 64 diabetes-free participants. Serum endocan, lipid parameters, and lipoprotein subclasses were measured. RESULTS: Patients with T2D exhibited higher proportion of the smallest high-density lipoprotein (HDL) particles HDL 3c, as compared with diabetes-free participants (p=0.047). Higher serum endocan levels in T2D patients with low small dense low-density lipoprotein (LDL) particles (sdLDL) %, as compared with corresponding group of diabetes-free subjects was shown (p<0.01). Univariate binary logistic analysis revealed significant positive association of endocan and LDL diameter (OR=1.686, p=0.004), and negative associations of endocan with proportions of sdLDL (OR=0.928, p=0.007) and HDL3b (OR=0.789, p=0.009) particles. In a multivariate analysis, LDL diameter and proportions of sdLDL and HDL3b subclasses remained independent predictors of endocan levels in tested population. CONCLUSIONS: The results of our study showed that larger LDL diameters, but lower sdLDL and HDL3b proportions were associated with higher endocan levels in population with T2D. More studies in the future are needed to confirm the observed relationship and to examine its causal nature.

A bioartificial kidney device with polarized secretion of immune modulators.

The accumulation of protein-bound toxins in dialyzed patients is strongly associated with their high morbidity and mortality. The bioartificial kidney device (BAK), containing proximal tubule epithelial cells (PTECs) seeded on functionalized synthetic hollow fibre membranes, may be a powerful solution for the active removal of those metabolites. In an earlier study, we developed an upscaled BAK containing conditionally immortalized human PTEC with functional organic cationic transporter 2. Here, we first extended this development to a BAK device having cells with the organic anionic transporter 1, capable of removing anionic uraemic wastes. We confirmed the quality of the conditionally immortalized human PTEC monolayer by confocal microscopy and paracellular inulin-fluorescein isothiocyanate leakage, as well as by the active transport of anionic toxin, indoxyl sulphate. Furthermore, we assessed the immune safety of our system by measuring the production of relevant cytokines by the cells after lipopolysaccharide stimulation. Upon lipopolysaccharide treatment, we observed a polarized secretion of proinflammatory cytokines by the cells: 10-fold higher in the extraluminal space, corresponding to the urine compartment, as compared with the intraluminal space, corresponding to the blood compartment. To the best of our knowledge, our work is the first to show this favourable cell polarization in a BAK upscaled device.

Mild intracellular acidification by dexamethasone attenuates mitochondrial dysfunction in a human inflammatory proximal tubule epithelial cell model.

Septic acute kidney injury (AKI) associates with poor survival rates and often requires renal replacement therapy. Glucocorticoids may pose renal protective effects in sepsis via stimulation of mitochondrial function. Therefore, we studied the mitochondrial effects of dexamethasone in an experimental inflammatory proximal tubule epithelial cell model. Treatment of human proximal tubule epithelial cells with lipopolysaccharide (LPS) closely resembles pathophysiological processes during endotoxaemia, and led to increased cytokine excretion rates and cellular reactive oxygen species levels, combined with a reduced mitochondrial membrane potential and respiratory capacity. These effects were attenuated by dexamethasone. Dexamethasone specifically increased the expression and activity of mitochondrial complex V (CV), which could not be explained by an increase in mitochondrial mass. Finally, we demonstrated that dexamethasone acidified the intracellular milieu and consequently reversed LPS-induced alkalisation, leading to restoration of the mitochondrial function. This acidification also provides an explanation for the increase in CV expression, which is expected to compensate for the inhibitory effect of the acidified environment on this complex. Besides the mechanistic insights into the beneficial effects of dexamethasone during renal cellular inflammation, our work also supports a key role for mitochondria in this process and, hence, provides novel therapeutic avenues for the treatment of AKI.

First Report of Brown Rot Caused by Monilinia fructicola on Nectarine in Serbia.

In August 2011, nectarine (Prunus persica (L.) Batsch var. nucipersica (Suckow) C. K. Schneid) fruit originated from Oplenac region with symptoms of fruit rot was collected at a green market in Belgrade. Fruit had large, brown, sunken lesions covered with grayish brown tufts. Symptoms resembled those caused by species of Monilinia including M. laxa, M. fructigena, or M. fructicola (2). In order to isolate the causal organism, small superficial fragments of pericarp were superficially disinfected with commercial bleach and placed on potato dextrose agar (PDA). The majority (32 out of 33) isolates formed rosetted non-sporulating colonies with lobed margins resembling those of M. laxa. However, one isolate (Npgm) produced an abundant, grayish-white colony with even margins and concentric rings of sporogenous mycelium, resembling those described for M. fructicola (2). Conidia were one-celled, hyaline, ellipsoid to lemon shaped, 7.38 to 14.76 × 4.92 to 9.84 µm, and borne in branched monilioid chains. The average daily growth on PDA at 24°C was 10.9 mm. A single-spore isolate of Npgm was identified as M. fructicola based on the morphology of colony and conidia, temperature requirements, and growth rate (2). Morphological identification was confirmed by an amplified product of 535 bp using genomic DNA extracted from the mycelium of pure culture and species-specific PCR for the detection of M. fructicola (2). The ribosomal internal transcribed spacer (ITS) region of rDNA of Npgm was amplified and sequenced using primers ITS1/ITS4. Sequence analysis of ITS region revealed 100% nucleotide identity between the isolate Npgm (GenBank Accession No. JX127303) and 17 isolates of M. fructicola from different parts of the world, including four from Europe (FJ411109, FJ411110, GU967379, JN176564). Pathogenicity of the isolate Npgm was confirmed by inoculating five surface-disinfected mature nectarine and five apple fruits by placing a mycelial plug under the wounded skin of the fruit. Nectarine and apple fruits inoculated with sterile PDA plugs served as a negative controls. After a 3-day incubation at 22°C, inoculated sites developed brown lesions and the pathogen was succesfully reisolated. There were no symptoms on the control nectarine or apple fruits. M. fructicola is commonly present in Asia, North and South America, New Zealand, and Australia, while in the EPPO Region the pathogen is listed as an A2 quarantine organism (3). In Europe, the first discovery of M. fructicola was reported in France and since then, it has been found in Hungary, Switzerland, the Czech Republic, Spain, Slovenia, Italy, Austria, Poland, Romania, Germany, and Slovakia (1). Most recently, M. fructicola was found on stored apple fruits in Serbia (4). To our knowledge, this is the first report of M. fructicola decaying peach fruit in Serbia. These findings suggest that the pathogen is spreading on its principal host plants and causing substantial economic losses in the Serbian fruit production. References: (1) R. Baker et al. European Food Safety Authority. Online publication. www.efsa.europa.eu/efsajournal . EFSA J. 9:2119, 2011. (2) M. J. Côté. Plant Dis. 88:1219, 2004. (3) OEPP/EPPO. EPPO A2 list of pests recommended for regulation as quarantine pests. Version 2009-09. http://www.eppo.org/QUARANTINE/listA2.htm . (4). M. Vasic et al. Plant Dis. 96:456, 2012.

[Gabapentin as adjuvant therapy in the treatment of refractory partial epilepsy]. / Gabapentin kao dodatna terapija u lecenju rezistentne parcijalne epilepcije.

With the aim to evaluate the clinical efficacy and tolerability of gabapentin as an adjuvant therapy in patients with refractory partial epilepsy we conducted an open-randomized study, with 12-weeks follow-up period. The study included 18 epilepsy patients with unsatisfactorily controlled seizures, in spite of the treatment with 1 or 2 first line antiepileptic drug. Gabapentin was administered in a total daily dose between 900-1200 mg. Our results showed seizure frequency reduction by more than 50% in 72.2% patients, while the most frequent adverse effects were vertigo (16.67%) and ataxia (11.11%).

[Alpha coma--a prognostic sign?]. / Alfa-koma--prognosticki snacaj?

We present a patient who has developed cardiac arrest after penetrating cardiac wound and consequent coma, with EEG characteristics of alpha coma. At the same time, auditory evoked potentials-brainstem (AEPB), subcortical and cortical were not within physiological range. During the sixth day of coma, alfa rhythm was substituted with theta and delta frequency, followed by the decreased amplitude and prolonged latency of AEPB and complete absence of cortical and subcortical responses. Lethal outcome occurred in the fifth week of coma with neurophysiological characteristics of complete brain dysfunction. Alpha coma, with EEG presentation that only resemble the normal neurophysiological cortical activity, is rather rare neurophysiological finding present mostly in cardiac arrest, metabolic disturbances and intoxication. It is probably caused by pathological pacers of alfa rhythm, so clinical presentation of alfa coma, specially in a case of cardiac arrest, does not predict a favourable outcome.

The influence of prostacyclin (PGI2) on contractile properties of isolated right ventricle of rat heart.

The mechanism of the positive inotropic effect of prostacyclin (PGI2) (2.6 x 10(-6) mol/l) on the isolated right ventricle of rat heart was studied. Our results show that the positive inotropic effect of prostacyclin is produced indirectly through beta adrenoceptors and slow Ca2+ channels, because blockade of slow Ca2+ channels with verapamil (10(-6) mol/l) and beta adrenoceptors with propranolol (10(-6) mol/l) abolishes this effect. Alpha adrenoceptors do not mediate the action of PGI2.

[Prognosis in patients with myelodysplastic syndromes based on cytomorphologic and clinico-biologic parameters]. / Prognoza obolelih od mijelodisplasticnih sindroma na osnovu citomorfoloskih i klinicko-bioloskih parametara.

Under myelodysplastic syndromes we presume a heterogeneous group of malignant hemopathies with clearly described characteristics of the disease given by a cooperative group of French, American and British authors. Myelodysplastic syndromes most frequently occur at older age. Survival of these patients, after the diagnosis is made, is mostly short because the disease evolves into acute leukemia. Myelodysplastic syndrome is characterized by appearance of refractive anemia, leukemia, thrombocytopenia with signs of expressed dishematopoiesis of the bone marrow. Clear criteria which could define forms with fast or slow course leading to acute leukemia don't exist, so there is a need to group patients into those with good or with bad outcome. The investigation included following parameters important for the outlook of the disease: 1. enlargement of lymph nodes, liver and spleen, 2. biochemical examination of peripheral blood, 3. cytomorphologic changes in the peripheral blood cells and bone marrow. By a follow-up of described parameters a statistically significant influence on survival of the sick concerning the degree of present anemia, absolute number of granulocytes, number of thrombocytes, dishematopoiesis of the peripheral blood and bone marrow, lymphadenomegaly, hepatomegaly and splenomegaly was not found. The percentage of blast in the peripheral blood and bone marrow has a statistically significant influence on patients' short survival.

[Cytokines in bronchial asthma]. / Citokini u bronhijalnoj astmi.

Integracions among T cells, B cells and macrophages is central to the immune response. These cells produce a number of biologically active proteins, which form complex network of cell-to-cell interaction, and regulate proliferation and function of the immune systems. Cytokines act on variety of cells type in a non-antigen specific manner. Only helper cells receive antigen specific signal and convert them via lymphokines secretion into antigen-nonspecific mediators of immune response. The followings cytokines have been found in asthamic airways: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alfa, GM-CSH. CD+4 cells are major source of cytokines in astmatic airway. It has been identified that two subsets of helper cells (TH-1 and TH-2) exist, which secret different cytokines profils. Both produce IL-1, IL-3, GM-CSF and TNF-alfa. TH-1 produce IL-2, IFN-gamma and TNF-beta (LT). TH-2 cells produce IL-4, IL-5 and IL-10. IL-4 produced by activited TH-2 subset, mast cells, and basophils is enhanced in asthma and responsible for IgE synthesis and expresion of IgE Fc-R-II. TH-1 specific IFN-gamma inhibits IL-4 induced IgE synthesis whereas TH-2 specific IL-10 supresses IFN-gamma secretion. IL-3, IL-4 and IL-5 stimulate the growth of mucosal mast cells and eosinophils. The presence of activated T cells and eosinophils in BAL-fluid as well as increased amount of IFN-gamma and slL-2R in circulation correlate with severity of disease. Interplay between T cells and inflammatory cells through the cytokines is crucial in regulating of inflammatory processes in allergic asthma.

[The neurohumoral status in depression]. / Neurohumoralni status depresija.

In 66 patients with endogenous depression (34 males and 32 females) the concentrations of biogene amine metabolites (vanilmandelic acid (VMA), 5-hydroxyindole acetic acid (5-HIIA), adrenaline and noradrenaline) were examined in 24-hrs urine and hormone in the serum: iodothyronine (T-3), thyroxine (T-4), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), cortisol, prolactin and growth hormones. The examination was performed prior to the initiation of antidepressant therapy and 30 days after its application. The biogene amine metabolites were in reference values before initiation of the therapy, although values of 5-HIIA in women and were closer to the lower limit. Thirty days after the initiation of the antidepressant therapy the statistically significant difference was found at the level of p < 0.05 for adrenalin in men and for VMA and 5-HIIA in women. The hormone values before initiation of the therapy showed increased values of growth hormone, cortisol in men and of thyroglobulin, growth hormone and cortisol in women. At the end of the antidepressant therapy the statistically significant difference was found at the level of p < 0.05 for thyroglobulin and TSH in men and for thyroglobulin, growth hormone and cortisol in women. By comparing the results obtained before and after the antidepressant therapy, the statistically significant difference was found at the level of p < 0.05 for Tg in men and for Tg, T-3, prolactin and growth hormone compared to the women. It has been concluded that in patients with endogenous depression the important role in pathogenesis of the disease have some neurobiogenic disorders.

The effect of physostigmine on the haemorrhagic hypovolemia in anaesthetized rabbits.

1. The effects of physostigmine (70 micrograms kg-1, intravenously) on mean arterial blood pressure, blood volume and survival were studied in anaesthetized rabbits subjected to haemorrhagic hypovolemia. 2. It was found that physostigmine increased the mean arterial blood pressure, increased the residual blood volume, decreased the haematocrit values and increased the survival of the animals. 3. The increase of blood pressure might be due to a general adrenergic activation produced by physostigmine, whereas the increase in plasma volume might be due to changes in pre- to postcapillary resistance ratio. 4. The beneficial effect of physostigmine might also be due to antagonism of humoral factors known to aggravate the hypovolemia (e.g. endogenous opioids).

[Selenium toxicity in domestic animals]. / Toksicnost selena kod domacih zivotinja.

The earliest written report of selenium poisoning is thought to be the description by Marco Polo of a necrotic hoof disease of horses that occurred in China in 13. century. However recognition of Se as toxic principle come in the early 1930s. Severity of Se poisoning depends on chemical forms of the element, species of animals and routes of administration. The soluble Se salts (Na2SeO3 and Na2SeO4) appear to be among the more toxic compounds; the Se inherent in grains and selenoamino acids (selenomethionine and selenocystine) appear to have relative moderate toxicity; the poorly soluble forms (e.g., elemental Se, Na2Se, SeS2 and diphenyl selenide) are among the least toxic of the Se compounds. In general, toxicity of Se compounds are substantially less when they are administered orally than when they are given parenterally. Rosenfeld and Beath described three clinical types of Se intoxication: acute selenosis, subacute selenosis (i.e., blind staggers type), and chronic selenosis (i.e., alkali disease type). Acute poisoning occurs when high Se content plants are consumed in large quantities within short period. Accidental acute poisoning occurs as consequence of errors in formulation of a Se supplemented diet. The most characteristic sign of acute selenosis is garlic breath due to the pulmonary excretion of volatile Se metabolites. Other signs include lethargy, excessive salivation, vomiting, dyspnea, muscle tremors and respiratory distress. Pathological findings are: congestion of the liver and kidney, fatty degeneration and focal necrosis of the liver, endocarditis and myocarditis. Subacute selenosis ("blind staggers") occurs as a consequence of exposure to large doses of Se over a longer period of time and manifests with neurological signs (e.g., blindness, ataxia, disorientation) and respiratory distress. This form of selenosis is most frequently observed in grazing animals that have consumed Se-accumulated plants. Chronic selenosis ("alkali disease") comes about when animals consume moderate levels of Se (more than 5 mg/kg and less than 40 mg/kg) for period of weeks or months. The usual clinical signs of chronic selenosis in horses, cattle and swine are: loss of hair (horses and cattle lose long hair from the mane and tails), emaciation, hoof lesions and lameness. In advanced cases liver cirrhosis, atrophy of the heart and anemia occur. In swine symmetrical poliomyclomalacia of cervical and lumbal/sacral spinal cord segment has been seen. Sheep seen to be more tolerant and get milder form of the disease. They lose appetite and have reduced gain. In growing chicks reduced gain and feed intake, rough feathers, and characteristics of nervousness has been observed. Reduced egg production, embryonic deformations and reduced hatchability has been observed in hens.(ABSTRACT TRUNCATED AT 400 WORDS)

[Relation between body mass, body height and the blood picture to vital capacity in students exposed to air pollution]. / Odnos telesne mase, telesne visine i krvne slike prema vitalnom kapacitetu kod ucenika izlosenih aerozagadjenju.

The authors examined the relationship between body mass, body height, haemogram and vital capacity in two groups of pupils exposed to long aeropollution. The first group consisted of children with low vital capacity. In the second group the spirometric test was normal. The authors found differences between these two groups in relation to body mass and hemoglobin concentration.

[Evaluation of drug therapy in epilepsy]. / Evaluacija medikamentozne terapije epilepsije.

Supposing that in evaluation of therapeutical efficacy of the definite antiepileptics the most important is its clinical effect, the aim the study was to analyse retrospectively correlation of clinical effects, EEG characteristics and serum carbamazepine concentration in a group of patients with subtherapeutical and in a group with therapeutical antiepileptic concentrations. The results of the study have shown no positive direct correlation among clinical effects, EEG characteristics and serum drug concentrations. It has been concluded that in evaluation of therapeutical carbamazepine efficacy of the essential importance is its clinical effects.

[The status of the respiratory organs in students in Sabac exposed to increased air pollution]. / Stanje kisajnih organa kod ucenika iz Sapca izlozenih povecanjom aerozagadjenju.

The authors followed up the health of 322 elementary-school pupils at Sabac who were exposed to increased air pollution with chemical agents (ammonia, fluor hydrogen, chloracetic acid, sulfur dioxide, soot). The mean annual concentration of these gases were above or insignificantly under maximally permitted values. The results of the examination were as follows: recurrent cough in 12.4 per cent of cases and clinical signs of chronic or obstructive bronchitis in 8.4 per cent of children. Values of vital capacity were under normal in 27.6 per cent of cases and almost in the half of children vital capacity was at the lower normal limit. FEV1/FVC was under normal in 15 per cent of cases and at the lower normal limit in about 18.6 per cent of children. In spite of a great number of children with positive cutaneous tests to inhalation allergens with Prick's method IgE was within normal limits in these children. Thus, a significant noxious effect of allergic components on respiratory organs should be excluded. This was also confirmed by spirometric measurements of the two subsequent maximal expiriums when differences of +/- 3% were registered. However, in children with allergic bronchitis the value dispersion was by 2-3 times greater. Consequently, the authors concluded that damaged respiratory organs in children at Sabac appeared in a greater number of cases than in other places and that these damages were due to increased concentrations of different chemical air pollution agents.

[Use of low dose lasers in physiatry]. / Primena lasera niske snage u fizijatriji.

The prospective study comprised 105 patients treated for six months in the out-patient and in-patient institutions suffering from the syndrome manifested in pain and disturbed functions due to the diseases of the nerve-muscle and bone-connective tissue systems. The group of patients with the vertebro-basilar syndrome was selected by a single-blind controlled trial while the rest constituted the group whose results were preliminary presented. Two modes of laser photobiostimulation were applied: local stimulation and stimulation of acupuncture points. Evaluation of effects were performed by following up subjective troubles, clinical examinations, laboratory analyses and in patients with the vertebro-basilar syndrome by rheoencephalography in addition. The application of the mentioned methods in different pathological states have shown positive results in 78% of patients with analgesic, spasmolytic and antiadematous effects. In patients with the vertebro-basilar syndrome disappearance of subjective troubles was followed by the improved perfusion in the vertebro-basilar system with the mean increase of the amplitude of the rheoencephalographic curve of 0.063 +/- 0.018 oms and the mean shortening of the anacrotic phase of 0.048 +/- 0.019 seconds.