Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory.

Non-fibrillar soluble oligomeric forms of amyloid-ß peptide (oAß) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAß initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aß, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAß levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAß to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aß on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aß and tau pathology.

[Polish multicenter study on diabetes type I incidence in he age group 0-14 between 1998 and 1999]. / Wieloosrodkowe badania nad zapadalnoscia na cukrzyce typu 1 w grupie wiekowej 0-14 lat w Polsce w latach 1998-1999.

The increase in diabetes type 1 incidence observed in various centers in Poland and the need for a centralized study covering large population have resulted in the construction of a standardized registry of type 1 diabetes in 1998 within the Polish Multicenter Study in Diabetes Epidemiology. The aim of the study was to present the incidence rates of type 1 diabetes in the age group 0-14 in 7 distinct regions of Poland (Krakow, Wroclaw, Warsaw, Bialystok, Poznan, Rzeszow and Olsztyn centers) with over 30% of the Polish population at risk in 1998 and 1999. The data for the standardized registry were obtained prospectively from paediatric hospital wards and diabetes outpatient units. The incidence rates calculated in 1998 showed the highest value of 14.6 and 14.5/100,000 for Olsztyn and Warsaw, and the lowest (8.4/100,000) for Poznan center. In 1999 the highest value of 14.7/100,000 was noted in Krakow and the lowest (9.3/100,000) in Poznan center. The differences in diabetes type 1 incidence rates between age groups 0-4, 5-9 and 10-14 were found to be significant (p < 0.0005) and were also significant when incidence rates were compared between males and females in these age groups in the whole study area in 1998-1999 (p = 0.002 and p = 0.015 respectively).

[Polish multicenter study on type I diabetes incidence in the age group 15-29 between 1998 and 1999]. / Wieloosrodkowe badania nad zapadalnoscia na cukrzyce typu 1 w grupie wiekowej 15-29 lat w Polsce w latach 1998-1999.

The increase in diabetes type 1 incidence observed in various centers in Poland and the need for a centralized study covering a large population have resulted in the construction of a standardized registry of type 1 diabetes in 1998 within the Polish Multicenter Study in Diabetes Epidemiology. The aim of the study was to evaluate the incidence of type 1 diabetes in the age group 15-29 in 5 distinct regions of Poland (Krakow, Warsaw, Bialystok, Rzeszow and Olsztyn centers) with over 15% of the Polish population at risk in 1998 and 1999. The data for the standardized registry were obtained prospectively from hospital departments and diabetes outpatient units. The incidence rates calculated in 1998 showed the highest value of 11.2/100,000 for Krakow and its region, and the lowest (4.4/100,000) for Bialystok and its region. In 1999 the highest value of 12.3/100,000 was noted in Olsztyn and its region and the lowest (3.4/100,000) in Warsaw. There were significant differences in the incidence rates between the study centers were found. Incidence rates in the whole study area were significantly higher among males as compared with females in 1998 and 1999 (8.9/100,000 vs. 4.9/100,000; p = 0.0001), marked in the age groups 15-19 and 20-24 (p = 0.001 and p = 0.002 respectively). A significant increase in diabetes type 1 incidence (from 4.6/100,000 to 6.9/100,000) was found as compared with results of the "Three Cities Study" (1986-1988).

System of telemedicine services designed for family doctors' practices.

The main goal of the most European telemedicine programs is to increase access to emergency and primary care; however, telemedicine presents both profound opportunities and challenges to general practice/family medicine. The aim of this project is to develop and demonstrate a regional primary care teleconsulting system in Poland linking an academic family medicine center and 10 family doctors' practices (both urban and rural) within a range of 100-200 km, serving a local population of 25,000 individuals. It is designed to support real-time consultations among health care providers via a computer network, provide secure access to multimedia patient records, and facilitate an innovative home monitoring and remote care from doctors to their patients. The entire process (planned for 3 years) includes: selecting the best technology (i.e., teletransmission system, communication protocols, etc.) and equipment; preparing the assumptions and conditions for formats and transmission rates; analysis of the existing techniques of compression and preparing own specific solution; finding an optimal infrastructure (i.e., equipment and communication configuration); implementing the system; evaluation of the medical, economic, organizational, and sociological aspects of the system (i.e., accessibility to primary health care, cost feasibility and cost-effectiveness of telemedicine services, quality of care assessment, etc.). The project offers the potential to improve: access to high-quality primary health care; the patient-physician bond and the attending physician's level of confidence; education of family doctors; use of expensive resources; and a convenient mode of delivering medical services to the patient.

Lymphocyte subsets in patients with lung cancer treated with thiophosphoric acid alkaloid derivatives from Chelidonium majus L. (Ukrain).

Lymphocyte subsets were evaluated in nine men (aged 42-68 years, mean 57 years) with histologically proven lung cancer, previously untreated. Lymphocyte subpopulations were quantified by immunofluorescence using monoclonal antibodies against total T-cells, T-helper and T-suppressor cells. In addition, the percentage of NK cells and the helper/suppressor (H/S) ratio were evaluated. The number of B-cells was determined by surface immunoglobulin immunofluorescence. Chelidonium majus L. (preparation Ukrain) was applied as an intravenous injection every three days. One course consisted of 10 applications of 10 mg each. All immunological tests were performed before and after drug administration. The treatment was generally well tolerated. The results showed an increase in the proportion of total T-cells, and a significant decrease in the percentage of T-suppressor cells. The normalization of the H/S ratio was also noted. However, there were no signs of activation of NK, T-helper and B-cells. The restoration of cellular immunity was accompanied by an improvement in the clinical course of the disease. This effect was particularly pronounced in patients who responded to further chemotherapy. Objective tumour regression (CR+PR) was seen in 44.4% of treated patients. Four out of nine patients (44.4%) died of progressive disease during the course of this study. It is concluded that Ukrain can be immunologically effective in lung cancer patients and can improve human cellular response.

Evaluation of thiophosphoric acid alkaloid derivatives from Chelidonium majus L. ("Ukrain") as an immunostimulant in patients with various carcinomas.

This paper summarizes the preliminary results of two independent clinical trials conducted with the preparation "Ukrain", containing thiophosphoric acid alkaloid derivatives from the plant Chelidonium majus L. (greater celandine), in order to investigate whether it has immunopotentiating properties in cancer patients. A total of twenty-seven patients with various malignancies were treated with "Ukrain" given intravenously in a dose of 10 mg every three days. In all patients the cellular and humoral immune response was studied. There was an increase in both total T-cells and T-helper lymphocytes, a decrease in T-suppressor cells, and normalization of the helper/suppressor (HIS) ratio. A significant increase in erythrocyte-rosette-forming T-cells and NK cells was also demonstrated. Serum immunoglobulin levels, complement components (C3 and C4), and acute phase proteins were not significantly enhanced. Restoration of cellular immunity was accompanied by an improvement in the patients' performance status and in the clinical course of the disease. The treatment was generally well tolerated. The present study shows that some therapeutic benefit from the use of Chelidonium majus ("Ukrain") as an immunostimulant in cancer patients can be achieved.