Immunosuppressive effect of polycyclic aromatic hydrocarbons by induction of apoptosis of pre-B lymphocytes of bone marrow

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants, distinguished by genotoxic, hepatotoxic, nephrotoxic and immunotoxic effects. Especially secondary toxicity after bioactivation by microsomal monooxygenases (dependent on cytochromes P450) is characteristic of them. The immunotoxic effect is the result of very global impact on immunological reactivity of an organism and immunosuppression by induction of apoptosis of pre-B lymphocytes represents one of its particular forms. It has been proved that the effect of PAH is caused mostly by the following mechanisms: enzymatic induction by the way of activation of AhR (Aromatic hydrocarbon Receptor); alteration of cellular DNA; development of oxidative stress; increase in the concentration of intercellular calcium and decline of activity of NF-kappaB (Nuclear Factor-kappa B). Most sensitive to these changes are particularly B-lymphocytic precursors and pre-B lymphocytes. Intensity of entire manifestations is also considerably dependent on the presence and intensity of mechanisms of active or passive resistance of cells.     

Effects of melanotan II,a melanocortin agonist,on grooming and exploration in rats after repeated restraint/immobilization

2 mg/kg melanotan II (MTII, administered i.p.), a cyclic peptide analog of α-melanocyte stimulating hormone, at a single dose increased grooming in naive rats placed in an unfamiliar open-field device without changing locomotion or rearing. Male rats exposed to restraint/immobilization stress (IS) for 1 h on three consecutive days displayed increased grooming after the second stressor exposure, compared to pre-stress levels. MTII, administered to the rats after IS, enhanced the grooming response compared both to the pre- and post-stress values. The increase was greatest after the first dose and declined over the following two applications. As to the locomotion of rats in the entire experimental space, IS reduced the distance moved only after the first two stressor exposures; MTII did not influence these alterations. Locomotion in the central part of arena was not reduced by the stressor or by MTII, on the contrary, there was an increase in both groups after the third intervention. The only observed change in rearing was an increase in the MTII group after the third restraint exposure. Thus, MTII selectively increased grooming without markedly affecting the spatio-temporal structure of locomotor behavior in the open-field. The decline of MTII enhanced grooming over the three test days may be interpreted in terms of adaptation to the stressor and of the developing tolerance to the peptide.     

Hereditary pancreatitis: Report of a family from Turkey

Chronic pancreatitis is a rare disease in children and is usually secondary to underlying diseases such as hereditary pancreatitis, cystic fibrosis, hyperlipidemia, prolonged malnutrition, gallstones or anomalies of the biliary-pancreatic duct system. Hereditary pancreatitis is a common cause of chronic pancreatitis in children but is often unrecognized until months or years later. We report here a family with hereditary pancreatitis in which four members are affected.     

Protracted neurocardiogenic reaction

Vasovagal reactions following catheterization procedures are relatively common complications, mostly in their milder forms. We present a case report of a young male undergoing selective coronarography with a dramatic postprocedural course including haemodynamic instability, and especially very late normalization of the neurological status.     

Zoonotic Dirofilaria repens (Nematoda: Filarioidea) in Aedes vexans mosquitoes,Czech Republic

The surveillance of vectors for arthropod-borne pathogens is nowadays an important tool in surveillance programmes throughout Europe. Whereas many studies have been performed to screen arthropods for viruses or bacterial pathogens, only limited information is available concerning the geographical distribution and vector range of pathogenic filariae in Central Europe. To consider the prevalence of filarial parasites in mosquito vectors, we performed a molecular survey of mosquitoes for filarial DNA. Mosquito collection was conducted at six study sites in the South Moravian region (Czech Republic) close to the borders with Slovakia and Austria from 2009 to 2011. Molecular screening of mosquitoes was conducted using conventional PCR with primers designed to amplify the mitochondrial cytochromoxidase subunit I gene as well as the partial 5.8S ribosomal RNA gene. A total of 13,222 mosquitoes belonging to six species were captured and distributed into 237 pools with different numbers of individuals. Overall, four pools were positive for Dirofilaria repens (a minimum infection rate 0.03 %) at two study sites (both natural and urban). Another filarial parasite detected during a study into Aedes vexans mosquitoes revealed the closest homology to Setaria spp. We detected specific D. repens DNA in Ae. vexans mosquitoes for the first time in the Czech Republic and confirmed the circulation of Dirofilaria spp. in a natural focus of infection providing an epidemiological link between autochthonous canine cases and mosquito vectors in the area studied.     

NT-proBNP levels on admission predicts pulmonary hypertension persistence in patients with acute pulmonary embolism

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a rare, but due to its unfavorable prognosis, feared complication of thromboembolic disease. We assessed the incidence and risk factors for pulmonary hypertension (PH) in a cohort of consecutive patients admitted with pulmonary embolism to the tertiary University Hospital.MethodsIn our cohort of 120 consecutive patients with proved pulmonary embolism (PE) we studied the course of biochemical and echocardiographic parameters with regard to risk factors predicting pulmonary hypertension at the end of hospitalization.ResultsEchocardiographic signs of pulmonary hypertension were present at the time of discharge in more than one half (50.8%) of patients admitted with pulmonary embolism. Predictors of persisting pulmonary hypertension were initial pulmonary hypertension, high initial NT-proBNP levels and age.ConclusionResidual pulmonary hypertension at discharge was present in 50.8% cases, at this time there was a strong relationship between PH and elevated NT-proBNP on admission. The patients will be followed-up and possible development of CTPEH will be evaluated at 6, 12 and 24-month period.     

The metabolism of flubendazole in human liver and cancer cell lines

Flubendazole (FLU), a benzimidazole anthelmintic drug widely used in veterinary medicine, has been approved for the treatment of gut‐residing nematodes in humans. In addition, FLU is now considered a promising anti‐cancer agent. Despite this, information about biotransformation of this compound in human is lacking. Moreover, there is no information regarding whether cancer cells are able to metabolize FLU in order to deactivate it. For these reasons, the present study was designed to identify all metabolites of Phase I and Phase II of FLU in human liver and in various cancer cells using ultra high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) analysis. Precision‐cut human liver slices and 9 cell lines of different origin (breast, colon, oral cavity) were used as in vitro model systems. Our study showed that FLU with a reduced carbonyl group (FLUR) is the only FLU metabolite formed in the human liver. All human cancer cell lines were able to form FLUR. In addition, methylated FLUR was detected in breast cells MCF7 and intestinal SW480 cells. The accumulation of FLU and its reduction to FLUR markedly differed among cells. The extent of FLU reduction was in a good correlation with the detected expression level of carbonyl reductase 1. In most cases, FLU entered in a higher amount and was reduced to a lesser extent in proliferating (metastatic) cells than in differentiated (non‐cancerous, non‐metastatic) ones. These results support the promising potential of FLU in anti‐cancer therapy.     

Long-term seizure outcome after stereotactic amygdalohippocampectomy

Background

The aim of the study was to evaluate the long-term seizure outcome and complications after stereotactic radiofrequency amygdalohippocampectomy (SAHE) performed for mesial temporal lobe epilepsy (MTLE).

Methods

The article describes the cases of 61 patients who were treated at our institution during the period 2004–2010. Mean post-operative follow-up was 5.3 years.

Results

At the last postsurgical visit, 43 (70.5 %) patients were Engel Class I, six (9.8 %) Class II, nine (14.8 %) Class III and three (4.9 %) Class IV. The surgery was complicated by four intracranial haematomas. One of them caused acute hydrocephalus and was treated by shunting and resolved without sequelae. After SAHE, we performed open epilepsy surgery and re-thermo lesions in three and two patients, respectively (8.2 %). There were two cases of meningitis which required antibiotic treatment. In six patients psychiatric disorders developed and one of these committed suicide due to postoperative depression.

Conclusions

Our results provide preliminary evidence for good long-term seizure outcomes after SAHE. SAHE could be an alternative therapy for MTLE.     

Influence of physiological and supraphysiological hyperinsulinemia on skin microcirculation in healthy volunteers

AIM: To examine skin perfusion in dependency on insulinemia in healthy subjects.METHODS: All volunteers were informed in detail about the procedures and signed informed consent. The protocol of this study was approved by the ethical committee. In our study, a two stage hyperinsulinemic euglycemic clamp was performed, with insulinemia 100 and 250 mIU/mL and glycemia 5.0 mmol/L (3% standard deviation). Before the clamp and in steady states, microcirculation was measured by laser Doppler flowmetry and transcutaneous oximetry and energy expenditure was measured by indirect calorimetry. Results (average and standard deviation) were evaluated with paired t-test.RESULTS: Physiological (50 mIU/L) insulinemia led to higher perfusion in both tests; hyperemia after heating to 44%-1848% (984-2046) vs 1599% (801-1836), P < 0.05, half time of reaching peak perfusion after occlusion release 1.2 s (0.9-2.6) vs 4.9 s (1.8-11.4), P < 0.05. Supraphysiological (150 mIU/L) insulinemia led to even higher perfusion in both tests; hyperemia after heating to 44%-1937% (1177-2488) vs 1599% (801-1836), P < 0.005, half time to reach peak perfusion after occlusion release 1.0 s (0.7-1.1) vs 4.9 s (1.8-11.4), P < 0.005. A statistically significant increase occurred in tissue oxygenation in both insulinemia. The difference in perfusion and oxygenation between physiological and supraphysiological hyperinsulinemia was not statistically significant.CONCLUSION: The post occlusive hyperemia test in accordance with heating test showed significantly increasing skin perfusion in the course of artificial hyperinsulinemia. This effect rises non-linearly with increasing insulinemia. Dependency on the dose was not statistically significant.