Monocyte chemotactic protein-1 and soluble adhesion molecules as possible prognostic markers of the efficacy of antiviral treatment in chronic hepatitis C

AIM: To explain the role of Monocyte chemotactic protein-1 (MCP-1) and soluble adhesion molecules in chronic hepatitis C during the treatment of interferon alpha (IFNα) 2 b and ribavirin (RBV).METHODS: Concentrations of MCP-1, soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1), sPselectin, interleukin (IL) 6, and ILl0 in serum were estimated in the group of 40 patients with chronic hepatitis C treated with IFNalpha2 b and RBV in 0, 16, 32, 48 wk of the therapy.RESULTS: In chronic hepatitis C, before and during the treatment, the serum levels of MCP-1 and sP-selectin in responders were similar to those of healthy subjects. In nonresponders (NR), MCP-1 increased in the course of IFN(α+RBV treatment, differences were statistically significant as compared to responders. MCP-1 correlated statistically with the activity of periportal inflammation (r= 0.35, P<0.05) but not with staging of liver fibrosis, sICAM-1 positively correlated with inflammatory activity and fibrosis in NR. sP-selectin did not correlate with histological findings in the liver. The MCP-1 correlated with the soluble form of sP-selectin concentrations (r= 6, P<0.001) and with IL-10 level in NR (r = 0.4, P<0.05). There was no correlation observed between the concentration of MCP-1 and sICAM-1, IL-6 during the treatment.CONCLUSION: MCP-1 concentration may be a prognostic marker of the efficacy of IFN+RBV therapy in patients with chronic hepatitis C.     

The evaluations of concentrations IL-5 and IL-6 in toxoplasmosis

The immune system, its cellular and humoral response, is engaged by the host organism to fight against parasitic invasions. The group examined consisted of 38 women aged 19-39 years infected with Toxoplasma gondii. The diagnosis was established basing on serologic examination. Blood for analysis was collected before antiparasitic treatment. Control group consisted of 40 healthy women aged 18-46 years. The concentrations of IgM, IgG and IgE were assayed using a set of VIDAS (bioMerieux) according to the ELFA method. The concentrations of IL-5, IL-6 were assayed using a set of Quantikine human (R&D Systems) according to the immunoenzymatic methods with labeled antibodies. The present study revealed that in toxoplasmosis the concentration of IgE, IL-5 and IL-6 contents in blood serum was 2-times higher, than in healthy controls.     

Soluble adhesion molecules ICAM-1, VCAM-1, P-selectin in children with Helicobacter pylori infection

AIM: To assess the sICAM-1, sVCAM-1, and sP-selectin levels in children with Helicobacter pylori (H pylori) infection and to evaluate their significance for the morphological changes found in gastric mucosa. METHODS: The study included 106 children: 59 children (55.7%) with chronic gastritis and positive IgG against H pylori, 29 children (27.3%) after previous H pylori infection without the bacterium colonization but with positive IgG against H pylori, and 18 children (17%) with functional disorders of the gastrointestinal system but with normal IgG against H pylori. Endoscopic and histopathological evaluation of gastric mucosa was performed based on the Sydney System classification. The evaluation of sP-selectin, sICAM-1, sVCAM-1 levels in the sera of children was carried out using ELISA test. RESULTS: The assessment of gastritis activity degrees indicated statistically significant values in the antrum and corpus (P＜0.001) of children examined. Serum sVCAM-1 levels were higher in group with gastritis due to H pylori infection than in group without infection and differed statistically (P＜0.05). Serum sVCAM-1 levels proved to be the highest among other adhesive molecules in infected children and decreased after eradication of H pylori. Serum sICAM-1 levels were similar in all examined groups. Serum sP-selectin levels were similar in children with and without H pylori infection. CONCLUSION: Assessment of adhesive molecules (sP-selectin, sICAM-1, sVCAM-1) in the sera of children with active H pylori infection can show the participation of sVCAM-1 in the pathogenesis of gastric mucosal inflammation. sP-selectin and sICAM-1 concentrations in the sera of children with H pylori infection after eradication cannot reveal any significant differences as compared to healthy children.     

Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models

PURPOSE: The purpose of this study was to characterize the activity of the Bcl-2 protein family inhibitor ABT-263 in a panel of small cell lung cancer (SCLC) xenograft models. EXPERIMENTAL DESIGN: A panel of 11 SCLC xenograft models was established to evaluate the efficacy of ABT-263. Single agent activity was examined on a continuous dosing schedule in each of these models. The H146 model was used to further evaluate dose and schedule, comparison to standard cytotoxic agents, and induction of apoptosis. RESULTS: ABT-263 exhibited a range of antitumor activity, leading to complete tumor regression in several models. Significant regressions of tumors as large as 1 cc were also observed. The efficacy of ABT-263 was also quite durable; in several cases, minimal tumor regrowth was noted several weeks after the cessation of treatment. Antitumor effects were equal or superior to that of several clinically approved cytotoxic agents. Regression of large established tumors was observed through several cycles of therapy and efficacy was retained in a Pgp-1 overexpressing line. Significant efficacy was observed on several dose and therapeutic schedules and was associated with significant induction of apoptosis. CONCLUSIONS: ABT-263 is a potent, orally bioavailable inhibitor of Bcl-2 family proteins that has recently entered clinical trials. The efficacy data reported here suggest that SCLC is a promising area of clinical investigation with this agent.     

Optimal classes of chemotherapeutic agents sensitized by specific small-molecule inhibitors of akt in vitro and in vivo

Akt is a serine/threonine kinase that transduces survival signals from survival/growth factors. Deregulation and signal imbalance in cancer cells make them prone to apoptosis. Upregulation or activation of Akt to aid the survival of cancer cells is a common theme in human malignancies. We have developed small-molecule Akt inhibitors that are potent and specific. These Akt inhibitors can inhibit Akt activity and block phosphorylation by Akt on multiple downstream targets in cells. Synergy in apoptosis induction was observed when Akt inhibitors were combined with doxorubicin or camptothecin. Akt inhibitor-induced enhancement of topoisomerase inhibitor cytotoxicity was also evident in long-term cell survival assay. Synergy with paclitaxel in apoptosis induction was evident in cells pretreated with paclitaxel, and enhancement of tumor delay by paclitaxel was demonstrated through cotreatment with Akt inhibitor Compound A (A-443654). Combination with other classes of chemotherapeutic agents did not yield any enhancement of cytotoxicity. These findings provide important guidance in selecting appropriate classes of chemotherapeutic agents for combination with Akt inhibitors in cancer treatment.     

Distant metastases to the parotid gland--review of the literature and report of own two cases

Metastatic tumors to the parotid gland are very uncommon and it accounts for 8% of all cancers of parotid gland. The parotid gland and its lymph nodes are possible sites of metastases from head and neck cancers. However, metastasis from distant primary neoplasm below clavicle is possible, too. The authors presented the two cases of distant metastases to the parotid gland. The women with breast cancer and metastases to the parotid gland 11 years after surgery, radio- and chemotherapy of breast cancer. She died 7 months after parotid surgery of systemically advanced disease. The man with metastasis of malignant melanoma of unknown primary site. He underwent total parotid surgery with the tumor and lymph nodes. He died 7 months after surgery. In spite of intensive exam the primary location of the melanoma was unknown. The authors described pathophysiology of distant metastases to the parotid gland with special attention to possibilities of treatment and survival.     

Optimal parameters for the clinical test of dynamic visual acuity in patients with a unilateral vestibular deficit

OBJECTIVE: To determine the influence of frequency and direction of head movement and type of vision chart on the score of a clinical test of dynamic visual acuity (DVA). METHODS: The subjects were 31 healthy individuals (22 to 79 years old) and 10 patients (19 to 70 years old) with a unilateral vestibular deficit owing to surgical resection of an acoustic neuroma. They read a Snellen or an E-chart while their head was passively moved +/- 20 degrees back and forth in the horizontal or vertical direction at one of four frequencies (0.5, 1.0, 1.5, and 2.0 Hz). The DVA score was the difference in the number of lines on the vision chart that could be read with the head passively moved versus with the head immobile. RESULTS: Four healthy subjects had a low DVA score during horizontal head movements at the fastest frequency (2.0 Hz) with the Snellen chart. In patients, DVA scores significantly decreased as head movement frequency increased from 0.5 to 1.0 Hz and from 1.0 to 1.5 Hz, during horizontal and vertical movements, and with both vision charts (p < .001). The DVA scores of healthy subjects were more consistent across three trials with the E-chart than with the Snellen chart at 1.0 and 0.5 Hz (horizontal movements, p < .01) and at 1.5 and 1.0 Hz (vertical movements, p < .01). CONCLUSIONS: This study provides new indications on the optimal parameters for the clinical test of DVA. From the results, it is recommended that DVA be tested during horizontal and vertical head movements at a frequency of 1.5 Hz with the E-chart.     

Analysis of chronic seizure onsets after intrahippocampal kainic acid injection in freely moving rats

PURPOSE: The goal of this study was to analyze the transition period between interictal and ictal activity in freely moving rats with recurrent spontaneous seizures after unilateral intrahippocampal kainic acid (KA) injection. METHODS: Pairs of tungsten electrodes (50 microm O/D) were implanted bilaterally under anesthesia at symmetrical points in the dentate gyrus (DG) and CA1 regions of anterior and posterior hippocampi and entorhinal cortex of adult Wistar rats. Stimulating electrodes were placed in the right angular bundle and KA was injected into the right posterior CA3 area of hippocampus after 1 week of baseline EEG recording. Beginning 24 h after injection, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for 60 days. RESULTS: Seventy percent of seizures started locally in the DG ipsilateral to injection, with an increase in frequency of interictal EEG spikes (hypersynchronous type, HYP), and 26% of seizures started with a decrease of EEG amplitude with parallel increase in frequency (low-voltage fast type, LVF). During HYP seizures, a significant increase was observed in amplitude of beta-gamma range frequencies, ripple frequency, and fast ripple (FR) frequency, whereas during LVF seizure, an increase was noted only in the beta-gamma range. In all cases but one, an EEG wave preceded ripple and FR oscillations. Before seizure onset, the amplitude of DG-evoked responses to single pulses decreased, whereas the amplitude of the response to the second pulse delivered at 30-ms interval increased. CONCLUSIONS: If ripple and FR oscillations indicate the seizure-generating neuronal substrate, these areas must be small and widespread, so that the probability of recording from them directly is very low. The decreased response to electrical stimulation before seizures could indicate a protective inhibitory mechanism that contains or prevents seizure occurrence. The presence of decreased paired-pulse suppression could indicate a network predisposition to follow an external input with a certain frequency.     

The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease

Depth recordings in patients with Parkinson's disease (PD) have demonstrated prominent oscillatory activity in the beta frequency (13-35 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesized to contribute to bradykinesia, it is unclear to what extent the LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded both LFPs and multi-neuronal activity from microelectrodes inserted into STN in six PD patients (8 sides) during functional neurosurgery. As microelectrodes passed from above STN into STN, there was a pronounced increase in beta frequency band LFP activity. Furthermore, spike-triggered averages of LFP activity suggested that the discharges of neurons in STN were locked to beta oscillations in the LFP. The LFP is therefore likely to represent synchronous activity in populations of neurons in the STN of patients with PD.