Cutting edge: the ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by protein kinase C theta and NF-kappa B

The rapid and robust immunoregulatory cytokine response of Va14Ja18 natural T (iNKT) cells to glycolipid Ags determines their diverse functions. Unlike conventional T cells, iNKT lymphocyte ontogeny absolutely requires NF-kappa B signaling. However, the precise role of NF-kappa B in iNKT cell function and the identity of upstream signals that activate NF-kappa B in this T cell subset remain unknown. Using mice in which iNKT cell ontogeny has been rescued despite inhibition of NF-kappa B signaling, we demonstrate that iNKT cell function requires NF-kappa B in a lymphocyte-intrinsic manner. Furthermore, the ontogeny of functional iNKT cells requires signaling through protein kinase C theta, which is dispensable for conventional T lymphocyte development. The unique requirement of protein kinase C theta implies that signals emanating from the TCR activate NF-kappa B during iNKT cell development and function. Thus, we conclude that NF-kappa B signaling plays a crucial role at distinct levels of iNKT cell biology.     

Fulminant meningococcal sepsis in a young child--a case report

We are presenting a case of isolated fulminant meningococcal sepsis with two and a half year old child. Initial symptoms were obscure and common to many medical conditions, but also previously described as symptoms of meningococcal sepsis. Unrecognizing the seriousness of the condition child died at home, within few hours after examination and discharge from the hospital. Autopsy and microbiological findings unquestionably proved that the child died from septic shock caused by fulminant meningococcal sepsis.     

Insulin administration in the mild hyperglycaemia changes expression of proinflammatory adhesion molecules on human aortic endothelial cells

An overexpression of cell adhesion molecules (CAMs) on the surface of endothelial cells is one of the first steps in a high glucose-mediated endothelial dysfunction in diabetic patients. The effect of insulin administration in the condition of elevated glucose concentration on the E-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) expression on human aortic endothelial cells (HAEC) was investigated. Cells were cultured for 4 h in a medium supplemented with homocysteine (7 pM) and different concentration of glucose (5.5, 8.0, 12.0 and 16.5 mM respectively) with or without insulin (1 mlU/mL) addition. Expression of CAMs was analysed by flow-cytometry using monoclonal antibodies. Controls were CAMs expression in the medium with a corresponding glucose concentration. Obtained results show that short-term exposure of HAECs to moderate high glucose concentrations results in increased expression of E-selectin (2-fold), VCAM-1 (3-fold) and ICAM-1 (47%). At the same time, HAEC grown with 12 mM glucose expressed lesser E-selectin and, more ICAM-1 (for 64%) and VCAM-1 (41%) molecules. 16.5 mM glucose decreased expression of all investigated adhesion molecules. Addition of insulin was not changed expression of CAMs in a medium with 5.5 mM glucose. In conditions of elevated glucose concentration (12 mM), addition of insulin significantly dropped E-selectin (27%) and increased VCAM-1 (23%) expression. In conclusion, moderate elevated glucose concentration increased expression of cell adhesion molecules on HAEC. Insulin administration in the mild hyperglycaemia reduces an expression of the proinflammatory adhesion molecule E-selectin which could contribute in deceleration of macrovascular complications development in diabetic patients.     

Modeling EEG fractal dimension changes in wake and drowsy states in humans—a preliminary study

Aim of this preliminary study was to examine and compare topographic distribution of Higuchi's fractal dimension (FD, measure of signal complexity) of EEG signals between states of relaxed wakefulness and drowsiness, as well as their FD differences. The experiments were performed on 10 healthy individuals using a fourteen-channel montage. An explanation is offered on the causes of the detected FD changes. FD values of 60 s records belonging to wake (Hori's stage 1) and drowsy (Hori's stages 2-4) states were calculated for each channel and each subject. In 136 out of 140 epochs an increase in FD was obtained. Relationship between signal FD and its relative alpha amplitude was mathematically modeled and we quantitatively demonstrated that the increase in FD was predominantly due to a reduction in alpha activity. The model was generalized to include other EEG oscillations. By averaging FD values for each channel across 10 subjects, four clusters (O2O1; T6P4T5P3; C3F3F4C4F8F7; T4T3) for the wake and two clusters (O2O1P3T6P4T5; C3C4F4F3F8T4T3F7) for the drowsy state were statistically verified. Topographic distribution of FD values in wakefulness showed a lateral symmetry and a partial fronto-occipital gradient. In drowsiness, a reduction in the number of clusters was detected, due to regrouping of channels T3, T4, O1 and O2. Topographic distribution of absolute FD differences revealed largest values at F7, O1 and F3. Reorganization of channel clusters showed that regionalized brain activity, specific for wakefulness, became more global by entering into drowsiness. Since the global increase in FD during wake-to-drowsy transition correlated with the decrease of alpha power, we inferred that increase of EEG complexity may not necessarily be an index of brain activation.     

Condom use and its consistency among metropolitan high school students in Croatia, 1997-2001: has anything changed?

Sexually active adolescents face serious health risks associated with unprotected sexual intercourse, such as HIV infection and other sexually transmitted diseases (STDs), as well as unwanted pregnancy. To assess protective behavior among urban adolescents in Croatia we surveyed over 4000 high-school students, 15-19 years of age, in two waves: 2070 in 1997 and 1972 in 2001. The survey was carried out in various types of secondary schools in the capital city. The analyses suggest statistically significant increase in HIVIAIDS related knowledge in the observed period. A slight but significant increase was also observed in the acceptance of condom use. Both changes were more substantial among female students. In regards to protective behavior, we found significant increase in condom use, as well as in its consistency. Still, a large proportion of students did not use condom at last sexual intercourse (40% in 2001). In addition to generational effect, number of sexual partners, sexual victimization and mother's education (only in the case of young women) were identified as correlates of condom use consistency. While mother's education had positive effect, having 4 or more partners and having survived sexual violence decreased the likelihood of consistent condom use. In conclusion, the authors discuss the relevance of systematic school-based prevention of sexual risk taking among Croatian adolescents.     

High glucose protects single beating adult cardiomyocytes against hypoxia

In the heart, the opening of sarcolemmal ATP-sensitive K(+) (K(ATP)) channels seems to be crucial for the cardiac protection against hypoxia/ischaemia. In the present study, we have exposed cardiomyocytes under hypoxia to high extracellular glucose (30 mM). Under these conditions, intracellular concentration of 1,3-bisphosphoglycerate has increased confirming stimulation of glycolysis. Perforated patch-clamp electrophysiology revealed that hypoxia induces whole-cell K(+) current in cardiomyocytes more efficiently in the presence than in the absence of high glucose. Glucose significantly promoted survival of cardiomyocytes exposed to hypoxia. HMR 1098, an antagonist of sarcolemmal K(ATP) channels, inhibited glucose-induced activation of whole-cell K(+) current during hypoxia as well as glucose-mediated cytoprotection. An inhibitor of glyceraldehyde 3-phosphate dehydrogenase, iodoacetate, inhibited glycolysis in hypoxia and blocked the activation of sarcolemmal K(ATP) channels. Based on the obtained results, we conclude that the activation of sarcolemmal K(ATP) channels is involved in glucose-mediated cardioprotection.     

Fractures in late medieval skeletal populations from Serbia

Bone fractures were analyzed from skeletal remains of 861 adult individuals from six cemeteries dating to the Late Medieval period in Serbia. Results of the study were compared to other cemetery populations (635 individual skeletons) of the same date and region in an attempt to understand fracture patterns. The association of types of fractures and their prevalence with sex, age at death, cemetery site, and information deriving from historical sources are discussed. Results showed that the long bone fracture frequency was 0.7%, and the majority of the fractures were the result of direct force. This rate is similar to some studies of contemporary British skeletal samples. However, it is much lower than for some other Old World sites. Cranial vault fractures had a rate of 6.7%, and of the facial skeleton, 1.3%; the frontal bone was the most affected of bones of the cranial vault. Injuries were more common on the upper extremities (0.8%) compared to the lower (0.6%). However, the fibula was the most fractured bone (2.8%), followed by the ulna (2.4%). This pattern is similar to three of six Late Medieval urban sites in Britain. These findings suggest that this rural community was exposed to a low risk of trauma, probably related mostly to accidents sustained during farming, and rarely to interpersonal violence.     

Could determinants of PCS and MCS serve for public health intervention regarding chronic diseases in Croatia?

The aim of this article was to identify parameters that determinate PCS and MCS values, and analyze 5-year changes in those values according to the age, sex and geographic region. Cohort of 3229 participants was obtained from the CAHS 2003-2008. Results revealed no statistically significant differences between same age group, sex, and different region regarding PCS and MCS. When chronic conditions were in the model difference was present, PCS being more influenced by all conditions but bronchial asthma. The strongest influence comes from musculoskeletal conditions; followed by weak heart. Values for PSC and MSC decreased in 2008 compared with 2003, but only in few cases decrease was statistically significant. Values of PCS and MCS are higher in men in all regions, but they show higher variability than woman. Our results support the findings that data obtained through SF-36 could be the useful for public health interventions regarding chronic diseases.