NK cell function is controlled by the cell expression of killer immunoglobulin-like receptors (KIRs) and their ligation with the corresponding HLA ligands. Various malignancies have been associated with certain KIRs surface cell expression and various KIR/HLA ligand combinations. Prior research using case/control study design demonstrates the role of KIR and KIR HLA ligands as genetic factor involved in tumor susceptibility. The objective of this study was to investigate the family-based association of KIRs, HLA class I ligands and KIR/ligand combinations with leukemia diagnosis in families having a leukemia diagnosed child. Sixty-seven families that met the index leukemia case criteria (acute lymphoblastic leukemia, ALL, n = 45; acute myeloid leukemia, AML, n = 13; chronic myeloid leukemia, CML, n = 9; first degree healthy relatives n = 159) were examined. Our study consisted of two phases. In Phase1 case-control study, we primarily compared patients to their healthy siblings to asses if a marker or genotype may be associated with leukemia, excluding the impact of the environment. Phase 2 consisted of a secondary family-based association study. KIR genotyping was performed by PCR-SSP method. KIR HLA ligands were defined by direct method using PCR-SSP method and/or indirect base on high resolution typing of HLA-A, -B, -C alleles. Results of phase 1 showed an increase in the frequency of KIR genotype (with a ratio = 0.57; higher frequency for inhibitory KIRs vs. activating KIRs) among leukemia patients compared to healthy siblings. Results of the phase 2 familial study observed an association between HLA-C1+/BBw4+/ABw4+ haplotype (a mediator of inhibitory signals) and leukemia. Also, we concluded that the absence of HLA-ABw4 alleles was related to leukemia development.
The paper analyzes the distributional effects of social transfers in Bulgaria in the period 2000-2014, using income inequality decomposition by factor components. The results suggest that social transfers mitigate income inequality, but this effect varies depending on the type of transfer. Pensions exert the strongest influence due to their significant share in total income, which also rises over time. Family allowances are pro-poor in nature, but because of their small share in beneficiaries’ total income, their impact on overall inequality is much weaker. “Other social benefits” have the weakest inequality-reducing effect, which is due to their higher concentration towards the richest decile and increasing share in total income. Despite the inequality-decreasing impact of social transfers, we argue that they should not be regarded as the sole remedy for the sharp income disparities in the country, but need to be accompanied by relevant active labor market policies.
The AIM was to study the effects of lamotrigine on bicuculline and pentylenetetrazol models of epilepsy.
Material and methods: Mice divided in 8 groups (n = 6) were pretreated intraperitoneally 30 min before pentylenetetrazol (50 mg/kg) or bicuculline (1 mg/kg) with saline 0.1ml/10 g body weight or lamotrigine 10 mg/kg, 15 mg/kg or 20 mg/kg, respectively. The seizure intensity and latency to the seizures 60 min after bicuculline or pentylenetetrazol injection were observed. The following scale for seizure intensity was used: 1 - excitation; 2 - body tremor; 3 - clonic seizures of forelimbs; 4 - heavy clonic seizures with rotations; 5 - tonic seizures of forelimbs; 6 - tonic seizures of limbs.
Results: The controls showed bicuculline-induced seizure intensity up to 5. Lamotrigine in the higher doses used decreased the seizure intensity (p < 0.05). Lamotrigine in all doses studied did not change the latency period of the first bicuculline seizure compared with the control. Controls treated with pentylenetetrazol showed seizure intensity up to 4. Lamotrigine in the highest dose decreased the pentylenetetrazol-induced seizure intensity (p < 0.05). Lamotrigine in all studied doses increased the latency to the first pentylenetetrazol- induced seizure compared with the controls (p < 0.05). Both convulsing drugs influence the brain GABA-ergic transmitter system by competitively blocking GABAA receptors. Lamotrigine inhibits glutamate transmission and sodium channels. Both neurotransmissions - glutamate and GABA are closely related in seizure control.
The conclusion is that lamotrigine has an anticonvulsive effect on both bicuculline and pentylenetetrazol seizure models, suppressing seizure intensity and influencing the latency to the first seizure.
The high frequency (3.0-5.0%) of congenital anomalies (CA) and intellectual disabilities (IDs), make them a serious problem, responsible for a high percentage (33.0%) of neonatal mortality. The genetic cause remains unclear in 40.0% of cases. Recently, molecular karyotyping has become the most powerful method for detection of pathogenic imbalances in patients with multiple CAs and IDs. This method is with high resolution and gives us the opportunity to investigate and identify candidate genes that could explain the genotype-phenotype correlations. This article describes the results from analysis of 81 patients with congenital malformations (CMs), developmental delay (DD) and ID, in which we utilized the CytoChip ISCA oligo microarray, 4 × 44 k, covering the whole genome with a resolution of 70 kb. In the selected group of patients with CAs, 280 copy number variations (CNVs) have been proven, 41 were pathogenic, 118 benign and 121 of unknown clinical significance (average number of variations 3.5). In six patients with established pathogenic variations, our data revealed eight pathogenic aberrations associated with the corresponding phenotype. The interpretation of the other CNVs was made on the basis of their frequency in the investigated group, the size of the variation, content of genes in the region and the type of the CNVs (deletion or duplication).
Background: Parkinson’s disease (PD) is the second most common neurode-generative disease, usually detected by its motor symptoms. The non-motor symptoms, including cognitive deficits, have been of great interest to researchers in the last few decades.
Aim: To assess the effect of pramipexole on learning and memory in naïve and haloperidol-challenged rats.
Materials and methods: Male Wistar rats divided into 9 groups (n=8): naïve - saline, pramipexole 0.5; 1 and 3 mg/kg bw; Haloperidol groups - saline, haloperidol, haloperidol + pramipexole 0.5; 1 and 3 mg/kg bw. Two-way active avoidance test (TWAA) and activity cage were performed. The studied parameters were: number of conditioned and unconditioned responses, vertical and horizontal movements. Statistical analysis was done using SPSS 19.
Results: The naïve experimental groups significantly increased the number of conditioned responses during the tests for short- and long-term memory, compared with the saline groups (p<0.05). During the short-memory test only the animals with the lowest dose of PMX significantly increased the number of unconditioned responses whereas during the long-term memory test all experimental groups increased the number of escapes in comparison with the saline groups (p<0.05). Challenge dose of haloperidol attenuates learning and memory in pramipexol treated rats. Only the highest dose of pramipexol showed significant increase in conditioned and unconditioned responses compared with the haloperidol group (p<0.05).
Conclusion: Pramipexole improves learning and memory in naïve rats by enhancing dopaminergic neurotransmission. This is probably not the only mechanism involved. This is confirmed by the decrease in learning and memory ability in rats with haloperidol-challenge.
Data provided by the European Commission show that public expenditures for food supplements have been constantly increasing over the last decade.
The aim of the present study was to analyze the major food supplements regulations in the European Union and in Bulgaria. Relevant publications were searched and found in MEDLINE/PubMed, Scopus Database, Web of Knowledge, and in Internet-based search with predefined keywords. Numerous authors support the opinion that there is a real risk that low quality products may be distributed in countries with poor production control. Bulgarian national legislation have 6 regulations with different legal force for provision of healthy and safe food supplements on the market. Currently, the European Community is concerned about food products, including FS, launched on the market because the citizens require reliable protection of their health. This concern provoked the European Parliament and the Council to undertake a number of legislative initiatives in the field of production and control of food products. It is necessary to set more precise quality and safety criteria in future strategies associated with those products.