Nasopharyngeal carcinoma in Slovenia, 1990–2003 (results of treatment with conventional two-dimensional radiotherapy)

AimTo review the treatment results and identify prognostic factors for disease control and survival in a cohort of nasopharyngeal carcinoma (NPC) patients from a non-endemic population in Slovenia, diagnosed between 1990 and 2003.BackgroundIn Caucasians, nasopharyngeal carcinoma is a rare malignant tumor. Its diagnosis and treatment are complex and have been dramatically impacted by recent technological advances.Materials and methodsIn the Cancer Registry of Slovenia database, a total of 126 patients with NPC were identified, 93 of whom were available for analysis. All patients were treated with conventional two-dimensional radiotherapy (RT) and 29.3% underwent chemotherapy (ChT).ResultsThe median follow-up time for those alive at the last follow-up examination was 74.5 months. Disease recurred locally in 17 patients, regionally in 4 patients and at distant sites in 18 patients, resulting in 5-year locoregional control (LRC), distant failure-free survival (DFFS) and disease-free survival (DFS) of 73.7%, 78.6% and 59.3%, respectively. Disease-specific survival at 5 years was 59% and overall survival (OS) was 49.7%. In a multivariate analysis, LRC was favorably affected (P < 0.05) by an undifferentiated histology (hazard ratio [HR] = 2.86), DFFS through the absence of neck metastases (HR = 0.28), DFS by younger age (HR = 0.46), and more intensive RT (expressed as the isoeffective dose, EQD_2,T; HR = 2.08). The independent prognosticator for OS was age (≤55 years vs. >55 years, HR = 0.39); in the ≤55 years subgroup, an improved OS was connected to a more intensive RT regimen of EQD_2,T ≥ 66 Gy (HR = 4.17).ConclusionsOur results confirm an independent and favorable effect from an undifferentiated histology, the absence of neck metastases, a younger patient age at diagnosis, and more intensive RT regimens for disease control and survival.     

Trifolium procerum Rochel

Ohne Zusammenfassung     

Predatory mites of the Phytoseiidae family in integrated and ecological pest management systems in orchards in Slovakia

During 2005–2007, 1,332 individuals of predatory mites were found in integrated and ecological orchards in Slovakia. Seven predatory mite species of the family Phytoseiidae, namely Phytoseius echinus, Phytoseiulus macropilis, Euseius finlandicus, Typhlodromus pyri, Paraseiulus triporus, Amblyseius andersoni and Neoseiulella tiliarum, were identified. Out of 1,332 individuals, 519 (39.0%) were found in the apple orchards and 813 (61.0%) in the pear orchards. Out of all predatory mite individuals, 460 (34.5%) were found in the integrated pest management system (IPM) and 872 (65.5%) in the ecological pest management system (EPM). In apple orchards, P. echinus was dominant and constituted 49.3% of the detected mites. In pear orchards, E. finlandicus was dominant and constituted 48.7% of the detected mites. Typhlodromus pyri was also abundant, especially in pear orchards. The other species were less abundant.     

Comparing anti-HIV,antibacterial, antifungal,micellar, and cytotoxic properties of tricarboxylato dendritic amphiphiles

Three series of homologous dendritic amphiphiles—RCONHC(CH₂CH₂COOH)₃, 1(n); ROCONHC(CH₂CH₂COOH)₃, 2(n); RNHCONHC(CH₂CH₂COOH)₃, 3(n), where R = n-C_nH_2n+1 and n = 13–22 carbon atoms—were assayed for their potential to serve as antimicrobial components in a topical vaginal formulation. Comparing epithelial cytotoxicities to the ability of these homologues to inhibit HIV, Neisseria gonorrhoeae, and Candida albicans provided a measure of their prophylactic/therapeutic potential. Measurements of the ability to inhibit Lactobacillus plantarum, a beneficial bacterium in the vagina, and critical micelle concentrations (CMCs), an indicator of the potential detergency of these amphiphiles, provided additional assessments of safety. Several amphiphiles from each homologous series had modest anti-HIV activity (EC₅₀ = 110–130 μM). Amphiphile 2(18) had the best anti-Neisseria activity (MIC = 65 μM), while 1(19) and 1(21) had MICs against C. albicans of 16 and 7.7 μM, respectively. Two measures of safety showed promise as all compounds had relatively low cytotoxic activity (EC₅₀ = 210–940 μM) against epithelial cells and low activity against L. plantarum, 1(n), 2(n), and 3(n) had MICs ? 490, 1300, and 940 μM, respectively. CMCs measured in aqueous triethanolamine and in aqueous potassium hydroxide showed linear dependences on chain length. As expected, the longest chain in each series had the lowest CMC—in triethanolamine: 1(21), 1500 μM; 2(22), 320 μM; 3(22), 340 μM, and in potassium hydroxide: 1(21), 130 μM; 3(22), 40 μM. The CMC in triethanolamine adjusted to pH 7.4 was 400 μM for 1(21) and 3900 μM for 3(16). The promising antifungal activity, low activity against L. plantarum, relatively high CMCs, and modest epithelial cytotoxicity in addition to their anti-Neisseria properties warrant further design studies with dendritic amphiphiles to improve their safety indices to produce suitable candidates for antimicrobial vaginal products.     

Developmental rates of the aphid Aphis pomi (Aphidoidea: Aphididae) and its parasitoid Aphidius ervi (Hymenoptera: Aphidiidae)

Developmental rates of the aphid Aphis pomi and its parasitoid Aphidius ervi were compared at four constant temperatures (15, 20, 25, 30°C). Aphis pomi required 159.07 degree-days (DD) above lover developmental threshold (LDT) of 0.3°C. Aphidius ervi required 229.73 DD above LDT of 5.98°C. Developmental rate of A. pomi is higher than the developmental rate of A. ervi at the same conditions     

Effects of Arginine Vasopressin and Atriopeptin on Chloride Uptake in Cultured Astroglia

Ion and water homeostasis in the CNS is subjected to a neuroendocrine control exerted by neuropeptides formed within the brain. In order to gain information on this neuroendocrine control of Cl^– homeostasis, ³⁶Cl^– uptake was measured in cultured Type-I astrocytes exposed to the neuropeptides [Arg8]Vasopressin (AVP), and atriopeptin (AP) and to various Cl^– transport modifiers. AVP increased while AP decreased ³⁶Cl^– uptake of cultured astrocytes in a dose-dependent manner. Both effects became statistically significant at greater than 10^–9 M concentration of the peptides. For the appearance of the effects at least 30-min exposure was necessary. AVP and AP extinguished each other's effect by almost stochiometric manner. When administered together with AVP, the VIA vasopressin receptor antagonist Manning compound inhibited, while V2 vasopressin receptor agonist did not influence the ³⁶Cl^– uptake-increasing effect of AVP. However, bumetanide, a specific inhibitor of Na⁺-K⁺-2Cl^– cotransport, inhibited the effect of vasopressin and also inhibited the ³⁶Cl^– uptake of AVP non-treated, control cells. Our findings suggest that brain Cl^– homeostasis is controlled by neuroendocrine system in the CNS.     

Estimating the impact of vaccination on acute simian-human immunodeficiency virus/simian immunodeficiency virus infections

The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, for the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in SHIV and SIV infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3- and 2-fold, respectively. This method allows the comparison of vaccination efficacies among different viral strains and animal models in vivo.     

CD4+ target cell availability determines the dynamics of immune escape and reversion in vivo

Infections with human immunodeficiency virus (HIV) and the closely related monkey viruses simian-human immunodeficiency virus (SHIV) and simian immunodeficiency virus (SIV) are characterized by progressive waves of immune responses, followed by viral mutation and "immune escape." However, escape mutation usually leads to lower replicative fitness, and in the absence of immune pressure, an escape mutant (EM) virus "reverts" to the wild-type phenotype. Analysis of the dynamics of immune escape and reversion has suggested it is a mechanism for identifying the immunogens best capable of controlling viremia. We have analyzed and modeled data of the dynamics of wild-type (WT) and EM viruses during SHIV infection of macaques. Modeling suggests that the dynamics of reversion and immune escape should be determined by the availability of target cells for infection. Consistent with this suggestion, we find that the rate of reversion of cytotoxic T-lymphocyte (CTL) EM virus strongly correlates with the number of CD4(+) T cells available for infection. This phenomenon also affects the rate of immune escape, since this rate is determined by the balance of CTL killing and the WT fitness advantage. This analysis predicts that the optimal timing for the selection of immune escape variants will be immediately after the peak of viremia and that the development of escape variants at later times will lead to slower selection. This has important implications for comparative studies of immune escape and reversion in different infections and for identifying epitopes with high fitness cost for use as vaccine targets.