Possible proteomic biomarkers for the detection of pancreatic cancer in oral fluids.

The 80% mortality rate of pancreatic-cancer (PC) makes early diagnosis a challenge. Oral fluids (OF) may be considered the ultimate body fluid for non-invasive examinations. We have developed techniques to improve visualization of minor OF proteins thereby overcoming major barriers to using OF as a diagnostic fluid. The aim of this study was to establish a short discriminative panel of OF biomarkers for the detection of PC. Unstimulated OF were collected from PC patients and controls (n = 30). High-abundance-proteins were depleted and the remaining proteins were analyzed by two-dimensional-gel-electrophoresis and quantitative dimethylation-liquid-chromatography-tandem mass-spectrometry. Label-free quantitative-mass-spectrometry analysis (qMS) was performed on 20 individual samples (n = 20). More than 100 biomarker candidates were identified in OF samples, and 21 had a highly differential expression profile. qMS analysis yielded a ROC-plot AUC value of 0.91 with 90.0% sensitivity and specificity for a combination of five biomarker candidates. We found a combination of five biomarkers for PC. Most of these proteins are known to be related to PC or other gastric cancers, but have never been detected in OF. This study demonstrates the importance of novel OF depletion methodologies for increased protein visibility and highlights the clinical applicability of OF as a diagnostic fluid.

[SEASONAL DIFFERENCES IN THE EFFECT OF MELATONIN ON THE MORPHO-FUNCTIONAL STATE OF THE THYROID GLAND SPONTANEOUSLY HYPERTENSIVE RATS].

We studied the effect of exogenous melatonin on the indicators of thyroid gland condition of the young spontaneously hypertensive rats in spring and autumn. These data suggested that after 28-day of melatonin administration (5 mg/kg) in different seasons of the year there were divergent effects on the state of the thyroid gland. So, melatonin increased synthetic activity of the gland in the spring. It was indicated by a reduction in the area of the follicular colloid, the inner diameter of the follicles, the number of connective tissue elements, increasing the height of thyrocytes, follicular colloidal index and reduced index accumulation colloid. Spontaneously hypertensive rats were less sensitive to the effects of melatonin in autumn. A significant increase in the number of the connective tissue elements, reduction of the follicular epithelium area and follicular colloidal index showed a decline in the functional activity of the thyroid gland after of melatonin administration in the autumn.

MORPHOLOGICAL CHANGES PANCREAS AFTER OF MELATONIN'S EFFECT IN DIFFERENT SEASONS.

Morphological changes of the pancreas of young rats after exposure of exogenous melatonin in the spring and autumn periods was investigated. Exogenous melatonin (Unipharm Inc., USA) was administered to experimental group of animals daily'at a dose 5 mg/kg. The duration of the experiment was 28 days. It was revealed that the exocrine part of the.pancreas responds differently to the effects of melatonin at different times of the year. Thus, after administration of melatonin in the spring increase of the size of acinus, the height of the epithelium (by 7 %), area exocrinocytes (by 58 %), of their nucleus (by 20 %) and cytoplasm (69 %), the amount of nucleoli in cells (18 %), reduction the amount of connective tissue elements. Melatonin introduction in the autumn decrease in the size of acinus, height and area of exocrinocytes, growth the number of exocrinocytes in the acinus, nucleoli and width layers interlobular connective tissue in the gland. This may indicate that melatonin increases in the spring of the synthetic activity of the exocrine pancreas, whereas in the autumn (for the majority of the morphometric parameters) - somewhat reduces its functional state. The administration of melatonin in the spring (mostly) and in the autumn periods increased the functional activity of the endocrine pancreas. This is indicated by growth in the size of Langerhans islets, increasing the number and density of the (autumn) endocrinocytes.

[EFFECT OF MELATONIN ON AGE-RELATED DYNAMICS OF THE REACTIVE PROPERTIES OF BONE TISSUE].

The effect of melatonin (MT) on the bone tissue (BT) reactive properties was investigated among 80 male Wistar rats at the age of 3, 9, 12 and 16 months. The reactive properties of BT were judged by its ability to polarization under the influence of the alternating electric current. The value of reactance at the frequency of maximum polarization was used as the indicator of BT reactivity. Experimental animals received daily melatonin (Unipharm Inc., USA) at the rate of 1 mg/kg of body mass for 28 days. Freshly isolated femurs of rats served as a material for investigation. Introduction of MT to rats resulted in a significant increase in bone mass and polarization properties of BT. However, the clear tendency to increase the reactance not more than 2.2 % (p < 0.1) compared with the control group among the 3-month old rats were observed, and the increasing the reactance among 9 and 12-month old rats were 6.3% and 12.1% (p < 0.1), respectively. Most significantly, the reactance increased by 21.8% (p < 0.05) among 15-month old animals. Thus the introduction of MT increased the reactivity of BT. This effect had a clear dependence on the age and appeared more among older animals.

[MORPHOFUNCTIONAL STATE OF THE THYROID GLAND AFTER EXPOSURE TO MELATONIN].

Morphofunctional state of the thyroid gland (TG) of young rats after exposure of exogenous melatonin in the spring and autumn periods was investigated. Exogenous melatonin (Unipharm Inc., USA) was administered to experimental group of animals daily at a dose 5 mg/kg. The duration of the experiment was 28 days. It was shown an increase of the cross-section area of follicles by 31% and colloid by 30% (in spring), reduction of the area of follicle epithelium by 12% (in autumn), an increase in the follicle internal diameter and a decline in the thyroid epithelium height by 12% (in autumn) in TG of experimental groups rats. Also it was shown a decline of follicle-colloid index and growth of colloid accumulation index, reduction amount of interfollicular islets. The introduction of melatonin in the spring period brought down the amount of connecting tissue elements. Melatonin introduction in the autumn period reduced the thickness of connective tissue trabecules in TG. The introduction of melatonin in the spring period resulted in more substantial changes in the structure of TG, as compared to an autumn experiment. Thus, melatonin administered both in the spring and in the autumn periods reduces the functional activity and physiological regeneration of TG.

Octreotide, a somatostatin analogue, fails to inhibit hypoxia-induced retinal neovascularization in the neonatal rat.

OBJECTIVE: Octreotide, a somatostatin analogue, has been shown to prevent angiogenesis in diverse in vitro models. We evaluated its effect on retinal neovascularization in vivo, using a neonatal rat retinopathy model. METHODS: We used, on alternating days, hypoxia (10% O2) and hyperoxia (50% O2) during the first 14 days of neonatal rats, to induce retinal neovascularization. Half of the rats were injected subcutaneously with octreotide 0.7 microg/g BW twice daily. At day 18 the eyes were evaluated for the presence of epiretinal and vitreal hemorrhage, neovascularization and epiretinal proliferation. Octreotide pharmacokinetics and its effect on serum growth hormone (GH) and insulin-like growth factor I (IGF-I) were examined in 28 rats. RESULTS: Serum octreotide levels were 667 microg/l two hours after injection, 26.4 microg/l after nine hours and 3.2 microg/l after 14 hours. GH levels were decreased by 40% (p = 0.002) two hours after injection but thereafter returned to baseline. IGF-I levels were unchanged two hours after injection and were elevated by 26% 14 hours after injection (p = 0.02). Epiretinal membranes were highly associated with epiretinal hemorrhages (p < 0.001), while retinal neovascularization was notably associated with vitreal hemorrhages (p < 0.001). CONCLUSIONS: Twice-daily injections of octreotide failed to produce sustained decrease in serum GH, but produced rebound elevation of serum IGF-I. Accordingly, no statistically significant effect of injections on retinal pathology was noted. This finding, however, does not contradict our assumption that GH suppression may decrease the severity of retinopathy.

Gene expression of insulin-like growth factor-I, its receptor and binding proteins in retina under hypoxic conditions.

Hypoxia is the main stimulus for neovascularization in the retina. Insulin-like growth factor-I (IGF-I) is thought to be one of the mediators of this process. Severe persistent hypoxia, as occurs in central retinal artery occlusion, is associated with less retinal neovascularization than relative hypoxia. To study the influence of different types of hypoxia on the IGF system, we used a model of neonatal rat retina that responds with neovascularization to a relative hypoxic stimulus produced by alternating oxygen concentrations in the respired air. We studied the influence of 24-hour hypoxia (10% oxygen), 48-hour hyperoxia (75% oxygen), and relative hypoxia (shifting from 48 hours in 75% oxygen to 24 hours in room air) on the gene expression of IGF-I, IGF-I receptor (IGF-IR), and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in retina using a solution hybridization RNase protection assay. Hypoxia induced a significant increase in retinal IGF-IR (178%), IGFBP-2 (227%), and IGFBP-3 (317%) mRNA; however, retinal IGF-I mRNA was reduced, as well as serum growth hormone (GH). Relative hypoxia caused a similar but less pronounced trend in the gene expression of IGF-IR and the binding proteins, whereas retinal IGF-I mRNA was unchanged and serum GH was elevated. Both hypoxia and relative hypoxia may cause IGF system stimulation in the retina through upregulation of IGF-IR and IGFBPs. This stimulation may result in neovascularization. However, during hypoxia, low levels of tissue oxygenation and reduced local production of IGF-I may impede the neovascularization process.

Pulmonary edema: a complication following dental treatment under general anesthesia.

This article describes pulmonary edema in two young, physically healthy individuals following routine intensive dental treatment under general anesthesia. The etiology, diagnosis, prognosis, and treatment are discussed. This paper demonstrates that young, healthy patients may develop pulmonary edema in the perianesthesia period or even during anesthesia itself. Obstructive events, which occur especially in the post extubation period, may trigger this condition, as may other well-known phenomena. Early diagnosis and intensive treatment are mandatory in order to effectively resolve the situation.