Adipocytokine imbalance and breast cancer in obese women.

CONTEXT: Breast cancer is the most common diagnosis established in women with malignant tumors. AIMS: The purpose is to investigate the blood contents of adiponectin and leptin in women with breast cancer and obesity. SETTINGS AND DESIGN: A total of 140 women aged 40-50 were examined. MATERIALS AND METHODS: Group 1 included 70 women from classes 1 or 2 obesity. Group 2 included 70 women with stage 1 or 2 breast cancer and classes 1 or 2 obesity. The control group included 30 apparently healthy women, with mean age of 42.5 ± 2.5 years. STATISTICAL ANALYSIS USED: Statistical processing of the results obtained was performed using Statistica. RESULTS: Groups 1 and 2 were statistically significantly different from each other across all parameters, except for leptin resistance. In group 2, the course of breast cancer with concomitant obesity is characterized by disrupted adipocytokine homeostasis, which manifests as a 1.94-fold decrease in the blood content of adiponectin (P < 0.05), a 4.14-fold increase in the blood content of leptin (P < 0.05), and an 8.00-fold increase in the leptin/adiponectin ratio (P < 0.05). Poorly differentiated breast tumors exhibit a more pronounced imbalance in the blood levels of adipocytokines. Thus, the serum content of leptin in women with poorly differentiated tumors (G3) was 1.79 times (P < 0.05) higher than in women with moderately differentiated tumors (G2). CONCLUSIONS: The course of breast cancer with concomitant obesity is characterized by disrupted adipocytokine homeostasis and decreased adiponectin concentration in the blood.

The profile of the key pro-inflammatory cytokines in the serum of patients with CD and their association with the disease severity and activity.

BACKGROUND: The epidemiology of Crohn's disease (CD) has changed over the past decades, demonstrating a trend toward increased prevalence in developing countries, while in developed countries, its incidence has stabilized. The study aimed to examine the profile of the key pro-inflammatory cytokines in the serum of patients with CD and establish their association with the severity and activity of the disease. METHODS: A total of 61 patients (29 women (47.5%), 32 men (52.5%) aged from 18 to 40 years (mean age (30.42 ± 2.51) years) with the verified diagnosis of CD in the active phase were examined. The control group consisted of 30 healthy people of corresponding age. RESULTS: CD is characterized by a reliable increase of pro-inflammatory cytokines in blood compared to healthy people: tumor necrosis factor-α (TNF-α) - by 4.45 times (137.46 ± 9.72 vs. 30.88 ± 2.08 pg/ml in healthy people, p < 0,001), interleukin-1α (IL-1α) - by 5.08 times (51.55 ± 4.36 vs. 10.14 ± 0.93 pg/ml, p < 0.001), interleukin-6 (IL-6) - by 2.16 times (20.03 ± 1.81 vs. 9.27 ± 0.52 pg/ml, p < 0.001), interleukin-8 (IL-8) - by 2.04 times (25.74 ± 2.05 vs. 12.62 ± 1.16 pg/ml, p < 0.001), and interferon-γ (IFN-γ) - by 5.30 times (208.63 ± 14.29 vs. 39.35 ± 2.40 pg/ml, p < 0.001). The authors have established direct correlations between the Crohn's disease activity index and blood content of TNF-α (r = 0.84, p < 0.013), INF-γ (r = 0.61, p < 0.028); between TNF-α and INF-γ content (r = 0.67, p < 0.023), IL-1α (r = 0.49, p < 0.042), IL-6 (r = 0.40, p < 0.045), and IL-8 (r = 0.51, p < 0.033); INF-γ and IL-1α (r = 0.53, p < 0.040), IL-6 (r = 0.37, p < 0.039), IL-8 (r = 0.44, p < 0.040). CONCLUSIONS: Patients with CD were found to have multiple cytokines (TNF-α, IL-1α, IL-6, IL-8, and IFN-γ,). The content of cytokines correlated positively with the CD activity index.

Changes in parameters of biochemical and oxidative stress in university students during and after examinations.

The study aimed to evaluate the parameters of lipid peroxidation and antioxidant protection, biochemical parameters, and cortisol and adrenaline content in the blood of students depending on the effect of exam stress. A total of 135 healthy students (72 female (53.3%) and 63 male (46.7%)) aged from 19 to 21 years (mean age 20.16 ± 0.42 years) of the experimental group underwent detailed medical screening and examination before the inclusion in the study. The control group consisted of 30 healthy students (17 female (56.7%) and 13 male (43.3%)) of corresponding age (mean age 20.23 ± 0.54 years), whose medical examination was performed during breaks in the absence of any stress factors. The blood parameters of the experimental group were investigated 1 h before, 1 h after, and 24 h after the exam. The cortisol content in the blood of experimental group students significantly increased 1.37 times (p < 0.05) an hour before the exam and 1.32 times (p < 0.05) an hour after; adrenalin content in blood increased 1.76 times (p < 0.05) and 1.49 times (p < 0.05), respectively. Compared to the control group, intensification of lipid peroxidation processes with a 1.51-fold (p < 0.05) increase in erythrocyte malonic aldehyde content in blood 1 h before and 1.42-fold (p < 0.05) increase an hour after the exam was observed in students due to the effect of exam stress.. Changes in hormonal homeostasis, activation of lipoperoxidation processes with the development of oxidative stress, and the disintegration of antioxidant protection factors are typical for academic stress in students.

Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2.

Olfactory sensory neurons use a chloride-based signal amplification mechanism to detect odorants. The binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide-gated channels and the entry of Ca(2+) into the cilia. Ca(2+) activates a Cl(-) current that produces an efflux of Cl(-) ions and amplifies the depolarization. The molecular identity of Ca(2+)-activated Cl(-) channels is still elusive, although some bestrophins have been shown to function as Ca(2+)-activated Cl(-) channels when expressed in heterologous systems. In the olfactory epithelium, bestrophin-2 (Best2) has been indicated as a candidate for being a molecular component of the olfactory Ca(2+)-activated Cl(-) channel. In this study, we have analysed mice lacking Best2. We compared the electrophysiological responses of the olfactory epithelium to odorant stimulation, as well as the properties of Ca(2+)-activated Cl(-) currents in wild-type (WT) and knockout (KO) mice for Best2. Our results confirm that Best2 is expressed in the cilia of olfactory sensory neurons, while odorant responses and Ca(2+)-activated Cl(-) currents were not significantly different between WT and KO mice. Thus, Best2 does not appear to be the main molecular component of the olfactory channel. Further studies are required to determine the function of Best2 in the cilia of olfactory sensory neurons.

Hyaluronan expression following middle cerebral artery occlusion in the rat.

Hyaluronic acid, a major component of the brain extracellular matrix, is a regulator of angiogenesis, cell differentiation and migration. We used the rat middle cerebral artery occlusion model to show hyaluronan accumulation in stroke-affected areas. Using reverse transcription-polymerase chain reaction and Western blotting we showed up-regulation of hyaluronidase-1 and 2 between 1 h and 21 days after stroke. Hyaluronidase-1 was up-regulated earlier than hyaluronidase-2. The hyaladherins, receptor for hyaluronan-mediated motility and CD44 were also increased after stroke. Using immunohistochemistry, we showed association of hyaluronidases 1/2 and hyaladherins with neurons in the infarcted and peri-infarcted regions and hyaluronidase-1 with microvessels. Hyaluronan synthesis and degradation in the stroke hemisphere might have an impact on neuronal survival, angiogenesis and general tissue remodelling after stroke.

Changes in hyaluronan production and metabolism following ischaemic stroke in man.

The extent of recovery from stroke is dependent on the survival of neurons, particularly in peri-infarcted regions. Angiogenesis is critical for the development of new microvessels and leads to re-formation of collateral circulation, reperfusion and better recovery. Hyaluronan (HA) is an important component of the brain extracellular matrix and a regulator of cellular differentiation, migration, proliferation and angiogenesis. We have found that the production of total HA and low molecular mass 3-10 disaccharides of HA (o-HA) was increased in post-mortem tissue and in the serum of patients 1, 3, 7 and 14 days (peaking at 7 days) after ischaemic stroke. Hyaluronidase activity was also increased in serum samples (peaking after 3 days), which might explain the subsequent increase in o-HA. Affinity-histochemical staining was performed using a HA-specific biotinylated binding protein, and it showed enhanced deposition of HA in blood vessels and intracellularly as well as in the nuclei of peri-infarcted neurons. Western blotting and immunohistochemistry demonstrated upregulation of HA synthases (HAS1 and 2) and hyaluronidases (HYAL1 and 2) in inflammatory cells from both stroke and peri-infarcted regions of the brain. HYAL1 was upregulated in microvesssels and intracellularly in neurons, whilst HAS2 became translocated into the nuclei of neurons in peri-infarcted areas. Receptor for HA-mediated motility was observed intracellularly and in the nuclei of neurons, in the tunica media of larger blood vessels and in the endothelial cells of microvessels in stroke-affected tissue, whilst expression of other receptors for HA, CD44 and tumour necrosis factor-stimulated gene 6 (TSG-6) were mainly increased in infiltrating mononuclear cells from inflammatory regions. The data presented here demonstrate that HA breakdown is a feature of the acute stage of stroke injury. Increased o-HA production soon after stroke may be detrimental through enhancement of the inflammatory response, whilst activation of HA and/or o-HA-induced cellular signalling pathways in neurons and microvessels may impact on the remodelling process by stimulating angiogenesis and revascularization, as well as the survival of susceptible neurons.