Effectiveness of the ELLA Training for the Promotion of Emotional and Social Competences in Lithuanian Preschool Children.

By developing the emotional and social competences of children of preschool age, one can expect the prevention of emotional and behavioral problems and a better social and academic adaptation. The aim of this study was to evaluate the effectiveness of the ELLA training for the promotion of emotional and social competences in 3-6-year-old children in preschool education institutions in Lithuania. In total, 140 children aged 3-6 years participated in the quasi-experimental study, of which 86 children were assigned to the experimental group and 54 were assigned to the control group.

Inclusion Complexes of Gold(I)-Dithiocarbamates with β-Cyclodextrin: A Journey from Drug Repurposing towards Drug Discovery.

The gold(I)-dithiocarbamate (dtc) complex [Au(N,N-diethyl)dtc] was identified as the active cytotoxic agent in the combination treatment of sodium aurothiomalate and disulfiram on a panel of cancer cell lines. In addition to demonstrating pronounced differential cytotoxicity to these cell lines, the gold complex showed no cross-resistance in therapy-surviving cancer cells. In the course of a medicinal chemistry campaign on this class of poorly soluble gold(I)-dtc complexes, >35 derivatives were synthesized and X-ray crystallography was used to examine structural aspects of the dtc moiety.

Parametric modeling and optimal experimental designs for estimating isobolograms for drug interactions in toxicology.

In toxicology and related areas, interaction effects between two substances are commonly expressed through a combination index [Formula: see text] evaluated separately at different effect levels and mixture ratios. Often, these indices are combined into a graphical representation, the isobologram. Instead of estimating the combination indices at the experimental mixture ratios only, we propose a simple parametric model for estimating the underlying interaction function.

Beta-aminoketones as prodrugs for selective irreversible inhibitors of type-1 methionine aminopeptidases.

We identified and characterized β-aminoketones as prodrugs for irreversible MetAP inhibitors that are selective for the MetAP-1 subtype. β-Aminoketones with certain structural features form α,β-unsaturated ketones under physiological conditions, which bind covalently and selectively to cysteines in the S1 pocket of MetAP-1. The binding mode was confirmed by X-ray crystallography and assays with the MetAPs from Escherichia coli, Staphylococcus aureus and both human isoforms.

Enhanced anti-tumour effects of Vinca alkaloids given separately from cytostatic therapies.

Background And Purpose: In polychemotherapy protocols, that is for treatment of neuroblastoma and Ewing sarcoma, Vinca alkaloids and cell cycle-arresting drugs are usually administered on the same day. Here we studied whether this combination enables the optimal antitumour effects of Vinca alkaloids to be manifested.

Experimental Approach: Vinca alkaloids were tested in a preclinical mouse model in vivo and in vitro in combination with cell cycle-arresting drugs.

Glucocorticoids augment survival and proliferation of tumor cells.

Background: Glucocorticoids are widely used for cancer patients, although they can reduce the efficacy of anticancer treatment.

Materials And Methods: We characterized non-apoptotic actions of glucocorticoids on tumor cell lines, primary tumor cells and an in vivo model, together with molecular signaling studies.

Results: Glucocorticoids enhanced cell proliferation in 9/17 cell lines and significantly promoted tumor cell proliferation in a pre-clinical mouse model of lung carcinoma.

Antibiotic susceptibility testing of Bifidobacterium thermophilum and Bifidobacterium pseudolongum strains: broth microdilution vs. agar disc diffusion assay.

There is urgent need for having available suitable methods and data regarding the susceptibility levels of antibiotic resistant and sensitive strains of bifidobacteria. Based on a defined standard operation procedure, agar disc diffusion and broth microdilution were compared in order to evaluate the antimicrobial susceptibility profiles of 82 B. pseudolongum and 80 B.

Antibiotic susceptibility of Bifidobacterium thermophilum and Bifidobacterium pseudolongum isolates from animal sources.

The widespread use of antimicrobial substances has led to resistant populations of microorganisms in several ecosystems. In animal husbandry, the application of antibiotics has contributed to resistance development in pathogenic and commensal bacteria. These strains or their resistance genes can be spread along several ecological routes, including the food chain.

Antitumoral activity of non-platinum xanthate complexes.

To establish structure-activity relationships, derivatives of bis(O-alkyldithiocarbonato)platinum(II) complexes were analyzed. Eighteen bis(O-alkyldithiocarbonato) metal complexes were synthesized, and their cytotoxic activity on two human cancer cell lines was compared with the corresponding platinum bis(O-alkyldithiocarbonato) complexes and cisplatin. Complexes were synthesized with palladium, gold, nickel, copper, rhodium, and bismuth.

Synthesis of 5-nitro-2-furancarbohydrazides and their cis-diamminedichloroplatinum complexes as bitopic and irreversible human thioredoxin reductase inhibitors.

The human selenoprotein thioredoxin reductase is involved in antioxidant defense and DNA synthesis. As increased thioredoxin reductase levels are associated with drug sensitivity to cisplatin and drug resistance in tumor cells, this enzyme represents a promising target for the development of cytostatic agents. To optimize the potential of the widely used cisplatin to inhibit the human thioredoxin reductase and therefore to overcome cisplatin resistance, we developed and synthesized four cis-diamminedichloroplatinum complexes of the lead 5-nitro-2-furancarbohydrazide 8 selected from high-throughput screening.

Stimulation of CD95-induced apoptosis in T-cells by a subtype specific neutral sphingomyelinase inhibitor.

Neutral sphingomyelinase (nSMase) has been supposed to be involved in the activation of anti-apoptotic genes and, thus, could well sustain autoimmune reactions by preventing activation induced death of autoreactive T-cells. When screening cellular extracts for SMase activity in the range between pH 6.5 and 8.

Synthesis and structure-activity relationship of novel antitumoral platinum xanthate complexes.

To establish structure-activity relationships, derivatives of a recently described sulfur-containing antitumoral platinum complex, bis(O-ethyldithiocarbonato)platinum(II), named thioplatin, were analyzed. Twenty different bis(O-alkyldithiocarbonato)platinum(II) complexes were synthesized and tested for cytotoxic activity in a panel of six human tumor lines. Derivatives with up to 7-fold increased activity compared to thioplatin and up to 25-fold more activity than cisplatin were identified.

Neutral sphingomyelinase inhibitor C11AG prevents lipopolysaccharide-induced macrophage activation.

Stimulation of macrophages by lipopolysaccharide (LPS) leads to the synthesis of proinflammatory cytokines and nitric oxide (NO) and, as a consequence, to endotoxic shock. We provide evidence that LPS stimulates the activity of a membrane-associated neutral sphingomyelinase (nSMase) and that this activity is mandatory for the liberation of nuclear factor-kappa B (NF kappa B) and the induction of inducible NO-synthase (iNOS). With the aid of a newly developed, selective inhibitor of nSMase, C11AG, we could distinguish between nSMase-dependent and -independent LPS-induced signals.

Antitumoral activity of a sulphur-containing platinum complex with an acidic pH optimum.

Unlabelled: Platinum complexes are essential tools for cancer treatment despite their toxic side effects. Here we describe a new platinum complex with sulphurs as complexing atoms (thioplatin).

Purpose: To demonstrate that the antitumoral activity of a new sulphur-containing platinum compound (thioplatin) depends on a slightly acidic pH.

Neutral sphingomyelinase-inhibiting guanidines prevent herpes simplex virus-1 replication.

We synthesized a series of new guanidinium derivatives and studied the inhibitory activity on both neutral sphingomyelinase and herpes simplex virus-1 (HSV-1) replication. The lipophilic quality of the molecules was found to be correlated with the inhibitory potential of the compounds. Undecylidene-aminoguanidine was superior to derivatives with 10, 8 or 6 carbon atoms whereas propylidene-aminoguanidine was completely inactive.

The antiviral, antitumoural xanthate D609 is a competitive inhibitor of phosphatidylcholine-specific phospholipase C.

The effect of the antiviral, antitumoural xanthate D609 on the activity of phospholipase A2, C (PC- and Pi-specific) and D was investigated. D609 is the first model substance of a new concept of antiviral therapy that interferes with cellular regulation mechanisms, rather than with virus coded enzymes. Exclusively phosphatidylcholine (PC) specific phospholipase C (PC-PLC) was found to be inhibited in a dose-dependent manner.

Experimental treatment of equine sarcoid using a xanthate compound and recombinant human tumour necrosis factor alpha.

A xanthate compound with antiviral and antitumoural activities, tricyclodecan-9-yl-xanthogenate (D609) in combination with the potassium salt of the lauric acid (KC12) and, in a further investigation, the above-mentioned substances together with recombinant human TNF alpha (rh-TNF alpha), were tested on equine sarcoid tumours for therapeutic efficacy. A pilot investigation on 5 healthy horses showed that the compounds were well-tolerated; apart from a local, temporary oedema at the injection site, no other clinical symptoms were observed after subcutaneous administration of volumes from 0.1 to 10 ml per injection.

TNF accelerates the S-phase of the cell cycle in tumor cells.

The reduction of glucose supply induced the killing of tumor cells by tumor necrosis factor (TNF) in vivo and in vitro. In contrast, normal cell lines were resistant to TNF regardless of the presence or absence of glucose. Epidermal growth factor (EGF) did not exert a cytotoxic effect on tumor cells in the absence of glucose.

Lauric acid inhibits the maturation of vesicular stomatitis virus.

In the presence of lauric acid (C12), the production of infectious vesicular stomatitis virus (VSV) was inhibited in a dose-dependent manner. The inhibitory effect was reversible; after removal of C12 the antiviral effect disappeared. In addition, the chain length of the monocarboxylic acids proved to be crucial, as those with shorter or longer chains were less effective or had no antiviral activity.

Hexadecylphosphocholine differs from conventional cytostatic agents.

Alkylphosphocholines, and especially their main representative hexadecylphosphocholine (HPC), show high anticancer activity in methylnitrosourea (MNU)-induced autochthonous rat mammary carcinoma. The regression of MNU-induced rat mammary carcinoma during HPC treatment can be evaluated by computed tomography and sonography. This allows a noninvasive monitoring of therapy in vivo (tumor size, morphology, and blood supply).

Glucose depletion enhances the anti-tumor effect of TNF.

Treatment of human carcinoma xenotransplants in athymic mice with recombinant human tumor necrosis factor (rh TNF) causes necrosis mainly in the central parts of the tumors, while peripheral sections remain mitotically active. As tumors are known to be supplied with adequate glucose exclusively in their periphery, the influence of the lack of glucose on the cytotoxic activity of rh TNF was studied. The absence of glucose enhanced the killing of tumor cell lines by rh TNF in tissue culture.

Binding of NF-kB to the HIV-1 LTR is not sufficient to induce HIV-1 LTR activity.

Human immunodeficiency virus type 1 (HIV-1) spends a significant part of its life cycle as latent provirus in nonactivated cells. It induction requires mitogen stimulation. TPA treatment induces HIV-1 transcription by protein kinase C (PKC)-mediated activation of the cellular transcription factor NF-kB.

Medium chain length fatty acids stimulate triacylglycerol synthesis in tissue culture cells.

In the presence of undecanoic acid (C11) or lauric acid (C12) the synthesis of triacylglycerols was stimulated up to 10-fold both in tumor cell lines and in normal cell lines. Monocarboxylic acids of shorter or longer chain length either had no effect at all or were less effective. The increased triacylglycerol production was demonstrated, on the one hand, by the incorporation of radiolabeled glycerol into triacylglycerols and, on the other, by the incorporation of radiolabeled monocarboxylic acids, the incorporation of all (1-14C)-labeled monocarboxylic acids (C6, C12, C16, C18) regardless of their chain length, being preferentially enhanced by C11 and C12.

Activation of latent papillomavirus genomes by chronic mechanical irritation.

The skin of animals of a laboratory strain of Mastomys natalensis carrying endogenous, latent papillomavirus genomes was irritated by scratching with glasspaper. Hyperproliferation of the epidermis and amplification of viral DNA followed this treatment, and in approximately 27% of the animals virus-producing papillomas were induced.

Systemic treatment of a human epidermoid non-small cell lung carcinoma xenograft with a xanthate compound causes extensive intratumoral necrosis.

Therapeutic effects were obtained after systemic treatment of athymic mice bearing an epidermoid non-small cell human lung carcinoma (NSCLC) xenograft with tricyclodecan-9-yl xanthogenate (D609) and the potassium salt of a fatty (dodecanoic) acid. Extensive intratumoral necrosis was observed 3 days after the treatment.