ASSOCIATION BETWEEN URTICARIA AND INFECTIONS (REVIEW).

Urticaria is a common disease with 20% of prevalence and marked effects on quality of life. The burden of chronic urticaria for patients, their family and friends, the healthcare system and society is substantial. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear. The remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Chronic viral infections including hepatitis B and C have been reported to be associated with CSU. More research is needed to make definitive recommendations regarding the role of infections and their management in case of urticaria and urticarial vasculitis. The routine screening of parasitic, bacterial or viral infections in CU is not recommended, however, testing a patient with urticaria for certain infections is a physician's choice based on the specific characteristics of the patient, such are clinical symptoms and laboratory results, dietary and cultural habits, country of origin and residency, traveling history.

2020 ARIA CARE PATHWAYS FOR ALLERGIC RHINITIS - GEORGIA.

Allergic rhinitis is the most common chronic disease worldwide. Treatment guidelines have improved the knowledge on rhinitis and have had a significant impact on AR management. In 20 years, ARIA has considerably evolved from the first multi-morbidity guideline in respiratory diseases to the digital transformation of health and care. Allergic rhinitis in Georgia, Next-generation ARIA-GRADE guidelines and ARIA, 2020 care pathways for Allergen Immunotherapy have been discussed in this review.

THE STUDY OF THE IMMUNE CORRECTIVE PROPERTIES OF GREEK WALNUT (JUGLANS REGIA L.) SEPTA ON THE EXPERIMENTAL MODEL OF LEUKOPENIA.

From the positive effects of the drugs prepared from various parts of walnut described for a wide variety of diseases, their antitumor effect is remarkable. This feature can be used for treatment of leukopenia caused by radiotherapy and/or chemotherapy. Therefore, to study the immunocorrective properties of Greek walnut, the walnut septa were selected, aqueous extract of which has been studied on experimental model of leukopenia in white mice caused by a single injection of cyclophosphamide. The material of the study were the blood and bone marrow smears from intact and tested adult mice stained by Giemsa's dye. The quantity of leukocytes in peripheral blood were determined by the counting chamber under the light microscope with standard protocol. Cloud-point extraction, HPLC analysis and UV-visible spectrophotometry were used to study the composition of the walnut septa extract. It has been established that the Greek walnut septa extract has the correction ability of suppressed myelopoiesis in white mice caused by injection of cyclophosphamide. The blood formula normalization process by the mentioned extract is provided by the fast increasing in number of immature (band neutrophil) and mature neutrophils in the peripheral blood. It was shown that walnut septa extract stimulates the division, differentiation and maturation of blast forms of myeloid as well as lymphoid line in the bone marrow of mice with leukopenia. Cloud-point extraction and liquid-chromatographic analysis revealed the presence of hydrophilic and hydrophobic components in the walnuts septum extract.

Trends in the prevalence of childhood asthma and allergy in Western part of Georgia.

Internatinal time trend analyses, using the ISAAC (Phase Three) protocol, have yielded variable results and observed a rise in prevalence especially in areas where allergic diseases were previously less common. In 2003 and 2012, we performed cross-sectional studies in Kutaisi (western part of Georgia) schoolchildren aged 6-7 and 13-14 yr., using the validated ISAAC methodology, aiming to provide the prevalence trends of asthma and allergy in this population. Both cross-sectional studies were carried out in the same city, same season and used identical methodologies. In 2003, number of participants in 6-7 and 13-14 yrs old groups was 2666 and 2650 and in 2012 - 3039 and 2339 correspondently. Significant alteration in prevalence of asthma related symptoms was obtained in both age groups. The symptom of severe asthma had increased only in 13-14 year old adolescents and was not change in 6-7 year old group. There were significant increases (all to p < 0.001) in the symptoms of current sneezing (16.4% vs 8.7% and 28.4% vs 15.3% in 6-7 yr group and 13-14 yr group correspondently) and rhinoconjunctivitis (5.2% vs 2.9% and 9.6% vs 4.5% yr group and 13-14 yr group correspondently). Symptoms of current eczema (affecting flexural dermatitis) were increased in both age groups. The prevalence of asthma and allergies markedly increase among both age groups of schoolchildren in the western part of Georgia. The exact reasons for such trends remain to be explored.

Pancreatic cell proteome - qualitative characterization and function.

The macromolecular protein complex form adult white rat pancreas has been obtained and partially characterized. The most important distinguishing characteristics of the complex is the thermostability of its components. Using polyacrylamid gel by electrophoresis and chromatography of hydrophobic interaction has been established, that the components with relatively high (45-60 kD) molecular weight, are hydrophobic, while the low molecular weight components (11-12 kD) corresponds to hydrophilic proteins according to its column retention time. Participation of TPC in the regulation of the homotypic cell growth was determined. It is shown that the pancreatic TPC through inhibition of transcription decreases cell mitotic activity in growing rats. It is also shown that this complex is involved in pancreas regeneration processes. On the basis of the qualitative characteristics and cell growth regulatory function of this macromolecular protein complex described by us, it can be considered as a pancreatic cell proteome.

Risk factors of asthma in Georgian schoolchildren.

All existing contemporary data are indicating a relatively low prevalence of asthma in Georgia. The aim of the study, which was undertaken as part of ISAAC Phase II, was to assess some potential risk factors of asthma among schoolchildren in Georgia. In this study the current wheezing was revealed in 9.2% of 9 to 11-year-old children. The presence of asthma symptoms was strongly associated with presence of symptoms of rhino-conjunctivitis (OR=8.60, 95% CI=4.82-15.33, p=0.000) and eczema (OR=5.30, 95% CI=2.80-10.04, p=0.000). The logistic regression analysis revealed that environmental factor such as dampness/moulds at home, in addition to family history of allergy, was significant risk factor for asthma in Georgia. Future epidemiological study of risk factors for asthma, at both the host and environmental level, is desirable in order to help detect strategies of allergen avoidance.

Viruses and bacteria in acute asthma exacerbations--a GA² LEN-DARE systematic review.

A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

Prevalence of asthma and allergies among adolescents in Georgia: comparison between two surveys.

Since healthcare costs for asthma and allergies are a heavy burden for a society, it is a general interest to know whether this temporal trend is still ongoing or whether a plateau has been reached over the last decade. We therefore aimed to follow the trends in the prevalence of asthma, allergic rhino-conjunctivitis, and atopic eczema in Georgian schoolchildren of 13-14 years of age between 1996 and 2003. Surveys were carried out according to the ISAAC methodology in Tbilisi and Kutaisi centres. The mean prevalence increased steadily for current wheezing from 3.6% to 5.6% (p=0.0001) and current rhino-conjunctivitis from 4.6% to 5.7% (p=0.008), while the prevalence of current atopic eczema has remained actually constant, 4.1% and 4.3%, respectively. The prevalence of allergic diseases showed diverging gender trends. The prevalence of rhino-conjunctivitis and eczema in girls has decreased, while in boys increased. The prevalence changes, particularly the increasing pattern, were more evident in Tbilisi vs. Kutaisi centre. The differences could be associated with so-called westernization processes in the capital of Georgia. The investigation of risk factors at regional level could be important in order to undertake preventive measures.

ISAAC I and III in Georgia: time trends in prevalence of asthma and allergies.

ISAAC I and III surveys were carried out in schoolchildren aged 6-7 years from two centres of Georgia to estimate time trends and geographic variations in the prevalence of asthma, rhino-conjunctivitis and atopic eczema symptoms. A standard core questionnaire was used following the ISAAC methodology and was completed by the schoolchildren's parents. The prevalence of symptoms of allergic diseases in Phase I and Phase III was compared. The average prevalence of "current wheezing" almost not changed over 7 years, however there was some heterogeneity across the centres, particularly in Tbilisi centre the prevalence of current wheezing increased by 2.6% and in Kutaisi (it decreased by 2.4%. The symptoms of current rhino-conjunctivitis slightly decreased, but not statistically significant. More significant reduction was observed for symptoms atopic eczema, which was revealed in both centres. The results indicate that the epidemiological features of asthma and allergies in Georgia are changing, although the causes are still uncertain. Different patterns of time trends between centres suggested that there may be local differences in risk factors.

Possible role of endogenous growth inhibitors in regeneration of organs: searching for new approaches.

A hydrophilic protein component (12-17 kDa) of the thermostable protein complex (TSPC) of different organs (heart, liver, kidney, brain) of adult white rats has been identified using hydrophobic interaction chromatography (HIC). Chromatograms and spectra of the myocardial hydrophilic component of different animals (snail, pigeon, rat, pig) detected within the UV region (190-360 nm) have shown that in different organs of the same animal species as well as in the same organ (e.g. heart) of different species, TSPC contains identical hydrophilic components, i.e. there is clearly a phylogenetically conserved group of thermostable proteins that regulates proliferation processes.

Investigation of binding process of chlorpromazine to bovine serum albumin by means of passive and active experiments.

The association process of chlorpromazine with bovine serum albumin by both onefactoral passive and multifactoral active experiments were investigated in model systems. The dependence of absolute concentration of the free fraction of chlorpromazine on the total concentration of chlorpromazine is described by the increasing function, but the dependence of the relative concentration (free/total) on this factor is influenced by external characteristics. The concentrations of chlorpromazine, bovine serum albumin and Tritons' mixture, as principal factors of a multifactoral experiment, influence the absolute and relative values of the free fraction of chlorpromazine non-additively, ie the interaction of factors is significant.

Cloud-point extraction for the determination of the free fraction of antiepileptic drugs in blood plasma and saliva.

A method for the determination of the free fraction of antiepileptic drugs in plasma and saliva was developed. The separation of free and protein-bound fractions was obtained by cloud-point extraction under optimum conditions of pH, surfactant type, and concentration. It is shown that the free fraction of carbamazepine and of phenobarbital in plasma coincides with the drug concentration in saliva. The dependence of the free fraction in plasma on the administered dose was studied. The influence of the simultaneous administration of the two drugs on their free concentrations was revealed: In the presence of carbamazepine the free fraction of phenobarbital is decreased markedly whereas phenobarbital does not influence the behavior of carbamazepine.

Interaction of carbamazepine and phenobarbital in rabbits.

The interaction of carbamazepine and phenobarbital in rabbits was investigated. The drugs were administered to the rabbit orally as a single dose. By simultaneous administration the sequence of drugs was varied, with an interval between doses of 15 min. The doses of carbamazepine and phenobarbital were 100 and 25 mg, respectively. It was established that phenobarbital appears to be an inductor for carbamazepine independently sequence of administration of the drugs. Carbamazepine reveals inductive properties for phenobarbital in the case where phenobarbital enteres in the organism first. It was ascertained also that, by simultaneous administration, these drugs reduce absorption of each other in plasma.

Interaction of carbamazepine and chlorpromazine in rabbits.

The interaction of carbamazepine and chlorpromazine in rabbits has been studied. The drugs were administrated as single oral doses (200 mg of each drug). The sequence of administration of the drugs was varied. It has been established that by simultaneous administration these drugs decrease absorption of each other in plasma. This may be explained by competition of the drugs to transfer from the gastrointestinal tract into plasma, as well as by the formation of complexes, more or less stable and more or less bound to gastrointestinal tissues. Carbamazepine intensifies the biotransformation of chlorpromazine, which may be caused by the ability of carbamazepine to induce microsomal liver enzymes. Chlorpromazine suppresses the biotransformation of carbamazepine, however. This may be caused by intensive capture of chlorpromazine by liver tissues and by its intensive biotransformation, which in turn is conditioned by its surface-active nature and by the increase of its metabolism with carbamazepine. Therefore the biotransformation of chlorpromazine is increased and metabolism of carbamazepine is reduced. The sequence of administration of the drugs affects their pharmacokinetics significantly.

Determination of ferrocene-A in the blood serum of rabbits using reversed-phase microcolumn HPLC.

Ferrocene-A (ferrocenyl-1-phenyl-1-dioxy-1,4-butin-2) has shown significant antitumour and antibacterial activity. To facilitate studies in this field a simple and rapid liquid chromatographic procedure was developed, allowing the determination of ferrocene-A in the blood serum. The procedure was based on a reversed-phase high-performance liquid chromatography (HPLC) method, with UV detection at 210 nm. The mobile phase ethanol-0.01 M KH2PO4 60:40 (v/v) provides the complete separation of ferrocene-A, internal standard and endogenous compounds of serum. The recovery of ferrocene-A from serum using a hexaneisoamyl alcohol mixture was 90%. The proposed method is convenient for pharmacological and pharmacokinetic applications.

Simultaneous determination of carbamazepine and carbamazepine 10,11-epoxide by using microcolumn HPLC: study of pharmacokinetics of carbamazepine in a volunteer.

A highly-sensitive microcolumn HPLC method for the simultaneous determination of carbamazepine and carbamazepine-10,11-epoxide in human serum and saliva is described. The method was successfully employed for the study of pharmacokinetics of carbamazepine in humans. After oral administration of 100 and 200 mg of carbamazepine to a volunteer, multiple peaks were observed on the kinetic curves. They were symbathic in the serum and saliva. This indicated the presence of multiple peaks which characterize both free and protein-bound fractions of the drug. The existence of multiple peaks on the kinetic curves implies that the kinetic of carbamazepine cannot be described with the one-compartment linear model. Nevertheless, each peak was treated within the range of a one-compartment linear model of absorption and the results obtained were compared with published data. For the elucidation of the nature of multiple peaks the graphical differentiation of ascending and descending branches of all peaks were carried out. On this basis of the dependence of the absorption and elimination rates on time was constrained. The analysis of experimental data resulted in the following conclusions: (a) the presence of multiple peaks on the kinetic curves is induced by the interrupted character of carbamazepine absorption that is caused by the very poor solubility of carbamazepine; (b) the elimination of the drug from blood serum occurs in two phases. Binding of carbamazepine with tissues takes place in the first phase, and biotransformation and excretion occurs in the second phase. It is possible that the presence of multiple peaks on the kinetic curves is partially caused also by redistribution of the drug from the comparatively easily accessible to the less accessible tissues. This requires further investigation.

[The optimization of the treatment of epilepsy with carbamazepine in puberty]. / K optimizatsii lecheniia épilepsii karbamazepinom v pubertatnom periode.

A study was made of the pharmacokinetics of carbamazepine (CBZ) in epileptic patients in the pubertal period. In a group of patients with fully controlled fits, the concentrations of CBZ ranged within the mean values of the therapeutic concentration. Meanwhile in a group with an incomplete therapeutic effect and without any effect, the mean dose of CBZ per kg weight was even higher than that in the group with fully controlled fits. The lack of the clinical effect in part of the patients in the pubertal period on the intake of the seemingly high total doses of CBZ is not to be regarded as a cause of refusing to take it. The dose should be raised under pharmacological control.

Use of normal-phase microcolumn high-performance liquid chromatography for the study of hydrolytic stability, metabolic profiling and pharmacokinetics of an antiepileptic drug, benzonal.

A normal-phase microcolumn HPLC method is proposed for the quantitative determination of the most frequently used antiepileptic drugs and some compounds developed recently. The main advantage of this method, in comparison with other micro-scale HPLC techniques for antiepileptic drugs, is that it is used under isocratic conditions at room temperature (22 degrees C). The hydrolytic stability of benzonal (BZ) has been studied using this method together with mass spectrometry (MS), and IR, UV and NMR spectroscopy. Three pathways of hydrolytic degradation were established in alkaline conditions, whereas in an acid medium only one of these routes was followed. An investigation of the metabolic profiling of BZ in guinea-pigs showed that the drug undergoes fast hydrolysis in the intestinal tract forming phenobarbitone (PB) and benzoic acid (BA). Only PB was detected in brain tissue and it is probably responsible for the whole therapeutic effect. The pharmacokinetic parameters of this metabolite (PB) were determined in guinea-pigs, and their identity with the pharmacokinetic parameters of PB as the parent drug was confirmed.