DEVELOPMENT OF THE POWDER FORMULAS FOR ACNE TREATMENT.

Given the large enough area of the spread of acne disease, research is needed on the development of the new versions of preparations. Cosmetics and cosmeceuticals of daily use are easy to consume as preventive remedies during mild form of the disease at an early stage. These remedies include powders, which women tend to use every day, and men, if necessary, but quite often. Powder should fit the skin, not be crumbled during the air disturbance and be kept on the face for a relatively long time, have hygroscopicity, that is, they should absorb the sweat and fat. When developing formula of similar powder, we used the available literature data on remedies using for the treatment of acne. There have been studied some technological and rheological properties of powders, such the bulk specific gravity, bulk density and natural angle of slope. Given that all parameters depend on the dispersion and a specific surface of powder, the shape of the particles and their size distributions, we used the particles of all ingredients with a size of 3 to 20 µm. The obtained powder samples are easily applied to the skin, keeping on it for at least 4-5 hours. When applied to the oily skin, there are not observed swelling of starch and coating of pores, as well as the formation of a colloidal structure of bentonite clay. For the first time, a new formula is proposed for acne treating powders containing both plant and mineral components, determining both the structural features of powder and those features that are involved in certain processes that help to increase the pharmacological effect.

INCIDENCE OF TEENAGE PREGNANCY IN GEORGIA AND AUSTRALIA. PATTERNS OF SOCIAL ACCEPTANCE AND RELATED HEALTHCARE CONCERNS.

Teenage pregnancy has been a target for prevention in many countries. Teen motherhood may adversely influence social determinants of health, including education attainment, employment and reliance on welfare support. We compared socioeconomic factors and geographical influencers affecting teenage pregnancy and birth outcomes across Georgia and Australia. Georgia has a teenage pregnancy rate three times higher than Australia. However, there are similar proportions of contraceptive use between Georgian and Australian teenagers as well as increasing rates of sexual health literacy in both countries. Both countries, however, show a comparative deficiency in sexual health literacy for rural populations resulting in earlier sexual experiences in Georgia and higher teenage pregnancy rates in Australia with Indigenous teenage mothers over-represented. More age-appropriate sexual health and contraception education is required in both Georgia and Australia, especially for rural areas, Indigenous populations and ethnic minorities. Further research is needed to supply teenage pregnancy and birth data from Georgian population.

A RARE CASE OF OXYTOCIN-INDUCED MATERNAL CARDIAC BRADYARRHYTHMIA DURING LABOUR.

The report a rare case of oxytocin-induced severe maternal bradyarrhythmia of a young healthy term primigravida with a singleton pregnancy in spontaneous labour. Augmentation of labour was initiated immediately following the diagnosis of poor progression of labour at four centimetres dilatation. An oxytocin infusion was administered as per standard hospital titration protocol. The patient developed ongoing, persistent episodes of severe bradycardia within six hours of commencement of the oxytocin infusion, as detected by routine pulse oximeter for maternal heart rate monitoring and confirmed manually. Oxytocin was ceased as soon this was recognised, and delivery was expedited by emergency caesarean section both for inadequate progress in labour and the inability to continue oxytocin infusion. Despite being theoretically known to cause cardiac arrhythmias, as a side effect, to our knowledge this is the first reported case in published literature of oxytocin-induced maternal bradycardia.

CREATION OF OINTMENT COMPOSITIONS CONTAINING PHENOL COMPOUNDS FOR MEDICAL TREATMENT.

The research was aimed at studying the possibility of obtaining drug ointments with a potential anti-mycotic activity by using thick extracts obtained from the leaves of fustic, hazel, nut and bark of the oak. There were prepared the ointment compositions on different bases. As a methodology for studying the properties of the obtained ointments, there have been used the studies of colloidal stability and resorption of tanning substances in agar. The obtained results allow for making conclusion that the selected ointments are colloidally stable, and the values of movement of zones of biologically active substances in the agar body are large enough. These data allow for forecasting both the possibility of creating the similar ointment systems and their rather high properties. Based on the obtained data, there have been selected the ointment composition variants for further studies.

Reproductive health patterns: Georgia versus Australia.

The review compares a few reproductive indicators - fertility, abortion and contraception in both a developing (Georgia) and a developed (Australia) country. Fertility, abortion and contraception figures in both countries tend to reflect the attitude and the degree of development of each countries sexual health education and their use of effective contraception. Further research is required to accurately evaluate the need and access of Georgian women to modern methods of family planning and their knowledge of the benefits of modern contraception that can assist to reduce pregnancy termination rate. In Australia better insight is needed on how to facilitate a shift to more efficacious long-term contraceptives across all age groups.

[The study of properties of textile wipes "LNR"].

The aim of the research was to investigate the toxicity of textile wipes "LNR". The wipes coated with polymer as well as wipes coated with polymer and drug substance were studied on CBA mice. It was found that both types of "LNR " napkins do not cause any toxic effect, mortality or changes of internal organs of mice in acute and in chronic experiments. The study of the cytotoxic effect of "LNR" wipes according to test of cell survival in tissue culture showed that during contact exposure of the samples on cell wipes "LC" significant inhibition of culture growth observed in sample 1. If to accept for pronounced effect on the growth inhibition of 50% or more, such action has the napkin 1. If to accept for pronounced effect on the growth inhibition of 50% or more, such action has the napkin 1. If to accept for pronounced effect on the growth inhibition of 50% or more, such action has the napkin 1.

[Using of chromatographical methods to study stability, pharmacokinetics and metabolism of propofol (review)].

Propofol (somnopol, diprivan) 2,6-diisoprophilphenol is a preparation of short-term, intravenous narcosis used for local and general anaesthesia through single injection or permanent infusion with the speed of 4-12 mg/kg in an hour. In this study we tried to summarize the experience of using of chromatographical methods (gas chromatography-GCH0, high performance liquid chromatography (HPLC), thin layer chromatography (TLCH) and combination of mass-spectrometry with GCH (GCH-MC) and HPLC (HPL-MC) to study stability, pharmacokinetics and metabolism of propofol. A labour-intensive and important work have been carried out to obtain information about propofol.

[Investigation of conjugation and metabolism of propofol with the method of high performance liquid chromatography].

Propophol (somnopol, diprivan) is widely used in medicine for local and general narcosis through single injection or permanent infusion. Study of conjugation and metabolism of medications is considered as question of great importance, especially for substances used at anaesthesia. To study the above-mentioned questions the total complex of methods of chromatographical analysis, especially, high performance liquid chromatolgraphy (HPLC), are widely used. Objects of investigation were: blood plasma and urine of surgical patients. Method of investigation - HPLC with Ultraviolet-Detector. For investigation of structures of propophol conjugates and its metabolites selective enzymatic and non-selective acid hydrolysis were used. Two metabolites: 2,6-diisoprophil-1,4-bensoxinon and 2,6-diisopropilhydroxinon were determined.

Role of NBCe1 and AE2 in secretory ameloblasts.

The H(+)/base transport processes that control the pH of the microenvironment adjacent to ameloblasts are not currently well-understood. Mice null for the AE2 anion exchanger have abnormal enamel. In addition, persons with mutations in the electrogenic sodium bicarbonate co-transporter NBCe1 and mice lacking NBCe1 have enamel abnormalities. These observations suggest that AE2 and NBCe1 play important roles in amelogenesis. In the present study, we aimed to understand the roles of AE2 and NBCe1 in ameloblasts. Analysis of the data showed that NBCe1 is expressed at the basolateral membrane of secretory ameloblasts, whereas AE2 is expressed at the apical membrane. Transcripts for AE2a and NBCe1-B were detected in RNA isolated from cultured ameloblast-like LS8 cells. Our data are the first evidence that AE2 and NBCe1 are expressed in ameloblasts in vivo in a polarized fashion, thereby providing a mechanism for ameloblast transcellular bicarbonate secretion in the process of enamel formation and maturation.

[New methods of chemical and toxicological study of clonidine (Clophelinum)].

Clophelinum (clonidine) has hypotensive and soothing effect. The literature describes cases of a poisoning with clonidine, the majority of which are of the criminal character. Symptoms of clonidine intoxication differ from poisoning with other substances. Clinical picture of poisoning with clonidine is complex enough. Pathological and histological changes in internal organs in case of poisoning with clonidine are non specific. The methods of sampling, isolation, and qualitative determination need improvement. The aim of the research was investigation of chemical and toxicological properties of Clophelinum to develop new techniques of isolation and identification of clonidine. The technique of isolation is characterized by high degree of isolation (96 %), and technique of identification by high sensitivity (0,1 mkg/ml), which proves their efficiecy.

[Survey of consumer demand for non-steroidal anti-inflammatory preparations].

Subject of marketing research may represent medical means as well as consumers which are characterizing the market. The significant and spread out methods of segmentation is group method with one or some signs, also structural and statistical analysis methods. In the grouping process the geographical, demographic, social-economic and sociological principles are frequently used. Segmentation is the method to represent the difference on the basis of defined principles. 107 persons were participated in the interviews, among them 93 women and 14 men. Their age from 20-up to 60, among them 43 participants were with high education, 22 with technical and 20 with secondary education. The majority of population (51,4%) gets the information about new medicines by advertisements. The sources of getting information are equally from doctors (23,37%) and the chemists (23,37%); from other means this index is very low (1,86%). The population gives the priority to import insteroidic antiphlogistic medical means (45, 78%); less to native medicines (24,3%) and 29,9 % of participants can't give the answer on this question. The population mostly use tablets (78,5%), ampoules (11,21%); capsules (5,6%), ointment (3,75%) and candles (9,94%). Our study showed, that population more often use aspirin, diklophenak, indometacin, ibuprophen, ketoprofen. The main factors on the choosing the medicines are quality and price, producing firm's country prestige.

[Prevalence of severe maternal morbidity in Tbilisi].

Cross-sectional study was performed in all maternity units of Tbilisi, Georgia, with delivering 18,554 women between 1 January 2004 and 1 January 2005. There were 267 cases of severe obstetric morbidity giving a prevalence of 14,2 per 1000 deliveries (95% CI 12,6-16,0). During the study there were 3 maternal deaths. Disease specific morbidities per 1000 deliveries were: severe pre - eclampsia - 5,0 (95% CI 4,1-6,2); hysterectomy during 24 hours after delivery - 4,5 (95% CI 3,6-5,6); hemorrhage - 2,3 (95% CI 1,7-3,1), sepsis 1,3 (95% CI 0,9-2,0); eclampsia - 0,74 (95% CI 0,44-1,25); uterine rupture - 0,16 (95% CI 0,05-0,47); HELLP-syndrome - 0,11 (95% CI 0,03-0,39). Severe obstetric morbidity and its relation to mortality may be more sensitive measures of pregnancy outcome than mortality alone and allows for an effective audit system of maternal care.

[Pharmaceutical market research of non-steroidal anti-inflammatory medical cures in the city of Kutaisi].

Insteroidic antiphlogistic medicines occupies significant segment on pharmacy market. They have been in clinical practice since 1980-es, and are still widely used in treatment of systemic collagenous; myalgia; radiculitis, bursitis, arthritis, podagra and etc. To display the tendency of market development - the goal of the research - we studied the demand and supply in insteroidic antiphlogistic medicines in Kutaisi. The assortments in retail chemist's shops was studied. We also studied price lists and questionnaires of wholesale pharmacy institutions and requirements for the following medicines: aspirin, paracetamol, indometacin, diclophenak, ketoprofen, naproxen, meloksikam, nimesulid, piroksikam. The research was conducted by means of pharmaco-geographic and mathematic-statistic methods. The research showed the need in production of insteroidic antiphlogistic medicines matching the CMP European standards in Georgia to reduce the import of drugs.

Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini.

The human NBC1 (SLC4A4) gene encodes the electrogenic sodium bicarbonate cotransporters kNBC1 and pNBC1, which are highly expressed in the kidney and pancreas, respectively. The HCO3-:Na+ stoichiometry of these cotransporters is an important determinant of the direction of ion flux. Recently we showed in a mouse proximal tubule (mPCT) cell line expressing kNBC1, that 8-Br-cAMP shifts the stoichiometry of the cotransporter from 3:1 to 2:1 via protein kinase A (PKA)-dependent phosphorylation of Ser982. pNBC1 has the identical carboxy-terminal consensus phosphorylation PKA site (KKGS1026), and an additional site in its amino-terminus (KRKT49). In this study we determined the potential role of these sites in regulating the function of pNBC1. The results demonstrated that in mPCT cells expressing pNBC1, PKA-dependent phosphorylation of Ser1026 following 8-Br-cAMP treatment shifted the stoichiometry from 3:1 to 2:1. The effect was electrostatic in nature as replacing Ser1026 with Asp resulted in a similar stoichiometry shift. In addition to shifting the stoichiometry, 8-Br-cAMP caused a significant increase in the 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS)-sensitive basolateral membrane conductance (GDS) of cells expressing pNBC1, but not kNBC1. Although, the effect did not involve phosphorylation of Thr49, which was endogenously phosphorylated, replacing this residue with Asp or Ala abolished the 8-Br-cAMP-induced increase in GDS. In the mPEC pancreatic duct cell line, where endogenous pNBC1 functions with a HCO3-:Na+ stoichiometry of 2:1, 8-Br-cAMP increased GDS by ~90 % without altering the stoichiometry or inducing phosphorylation of the cotransporter. The results demonstrate that phosphorylation of Ser1026 mediates the cAMP-dependent shift in the stoichiometry of pNBC1, whereas Thr49 plays an essential role in the cAMP-induced increase in GDS.

Phosphorylation of Ser(982) in the sodium bicarbonate cotransporter kNBC1 shifts the HCO(3)(-) : Na(+) stoichiometry from 3 : 1 to 2 : 1 in murine proximal tubule cells.

1. Adenosine 3',5'-cyclic monophosphate (cAMP) modulates proximal tubule sodium and bicarbonate absorption by decreasing the rate of apical Na(+)-H(+) exchange and basolateral sodium bicarbonate efflux, through activation of protein kinase A (PKA). The electrogenic sodium bicarbonate cotransporter kNBC1 mediates basolateral sodium and bicarbonate efflux in the proximal tubule by coupling the transport of 1 Na(+) cation to that of 3 HCO(3)(-) anions. In this work we studied the effects of cAMP on the function of kNBC1 expressed heterologously in a proximal tubule cell line. 2. A mouse renal proximal tubule cell line, deficient in electrogenic sodium bicarbonate cotransport function, was transfected with kNBC1. Cells were grown on a permeable support to confluence, mounted in an Ussing chamber and permeabilized apically with amphotericin B. Current through the cotransporter was isolated as the difference current due to the reversible inhibitor dinitrostilbene disulfonate. The HCO(3)(-) : Na(+) stoichiometry of kNBC1 was calculated from its reversal potential by measuring the current-voltage relationships of the cotransporter at different Na(+) concentration gradients. 3. Addition of the potent cAMP agonist 8-Br-cAMP caused the stoichiometry of kNBC1 to shift from 3 HCO(3)(-) : 1 Na(+) to 2 HCO(3)(-) : 1 Na(+). Pretreatment of the cells with the PKA inhibitor H-89 abolished the effect of the agonist on the stoichiometry change. Replacing Ser(982) at the C-terminus consensus PKA phosphorylation site with alanine resulted in a failure of PKA to phosphorylate the transporter and induce a stoichiometry shift. 4. Our data indicate that cAMP modulates the stoichiometry of kNBC1 through activation of PKA. The change in stoichiometry from 3 : 1 to 2 : 1 is predicted to cause a shift in the direction of basolateral membrane sodium bicarbonate transport from efflux to influx. Ser(982) in the C-terminus of kNBC1 is a target for PKA phosphorylation. This is the first example of modulation of the stoichiometry of a membrane transporter by phosphorylation.

Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and kNBC1 in the rat eye.

The human NBC1 gene encodes two electrogenic sodium-bicarbonate cotransport proteins, pNBC1 and kNBC1, which are candidate proteins for mediating electrogenic sodium-bicarbonate cotransport in ocular cells. Mutations in the coding region of the human NBC1 gene in exons common to both pNBC1 and kNBC1 result in a syndrome with a severe ocular and renal phenotype (blindness, band keratopathy, glaucoma, cataracts, and proximal renal tubular acidosis). In the present study, we determined the pattern of electrogenic sodium-bicarbonate cotransporter protein expression in rat eye. For this purpose, pNBC1- and kNBC1-specific antibodies were generated and used to detect these NBC1 protein variants by immunoblotting and immunocytochemistry. pNBC1 is expressed in cornea, conjunctiva, lens, ciliary body, and retina, whereas the expression of kNBC1 is restricted to the conjunctiva. These results provide the first evidence for extrarenal kNBC1 protein expression. The data in this study will serve as a basis for understanding the molecular mechanisms responsible for abnormalities in ocular electrogenic sodium-bicarbonate cotransport in patients with mutations in the NBC1 gene.

The stoichiometry of the electrogenic sodium bicarbonate cotransporter NBC1 is cell-type dependent.

1. The pancreatic variant of the sodium bicarbonate cotransporter, pNBC1, mediates basolateral bicarbonate influx in the exocrine pancreas by coupling the transport of bicarbonate to that of sodium, with a 2 HCO3-:1 Na+ stoichiometry. The kidney variant, kNBC1, mediates basolateral bicarbonate efflux in the proximal tubule by coupling the transport of 3 HCO3- to 1 Na+. The molecular basis underlying the different stoichiometries is not known. 2. pNBC1 and kNBC1 are 93 % identical to each other with 41 N-terminal amino acids of kNBC1 replaced by 85 distinct amino acids in pNBC1. In this study we tested the hypothesis that the differences in stoichiometry are related to the difference between the N-termini of the two proteins. 3. Mouse renal proximal tubule and collecting duct cells, deficient in both pNBC1- and kNBC1-mediated electrogenic sodium bicarbonate cotransport function were transfected with either pNBC1 or kNBC1. Cells were grown on a permeable support to confluence, mounted in an Ussing chamber and permeabilized apically with amphotericin B. Current through the cotransporter was isolated as the difference current due to the reversible inhibitor dinitrostilbene disulfonate. The stoichiometry was calculated from the reversal potential by measuring the current-voltage relationships of the cotransporter at different Na+ concentration gradients. 4. Our data indicate that both kNBC1 and pNBC1 can exhibit either a 2:1 or 3:1 stoichiometry depending on the cell type in which each is expressed. In proximal tubule cells, both pNBC1 and kNBC1 exhibit a 3 HCO3-:1 Na+ stoichiometry, whereas in collecting duct cells, they have a 2:1 stoichiometry. These data argue against the hypothesis that the stoichiometric differences are related to the difference between the N-termini of the two proteins. Moreover, the results suggest that as yet unidentified cellular factor(s) may modify the stoichiometry of these cotransporters.

The stoichiometry of the electrogenic sodium bicarbonate cotransporter pNBC1 in mouse pancreatic duct cells is 2 HCO(3)(-):1 Na(+).

The electrogenic sodium bicarbonate cotransporter pNBC1 is believed to play a major role in the secretion of bicarbonate by pancreatic duct cells, by transporting bicarbonate into the cell across the basolateral membrane. Thermodynamics predict that this function can be achieved only if the reversal potential of the cotransporter is negative to the cell's membrane potential, or equivalently that the HCO3-:Na+ stoichiometry is not larger then 2:However, there are no data available on either the reversal potential or the HCO3-:Na+ stoichiometry of pNBC1 in pancreatic cells. We studied pNBC1 function in mouse pancreatic duct cells. RT-PCR analysis of total RNA revealed that these cells contain the message for pNBC1, but not for kNBC1, NBC2 or NBC3. To measure cotransporter activity, mouse pancreatic duct cells were grown to confluence on a porous substrate, mounted in an Ussing chamber, and the apical plasma membrane permeabilized with amphotericin B. Ion flux through pNBC1 was achieved by applying Na+ concentration gradients across the basolateral plasma membrane. The current through the cotransporter was isolated as the difference current due to the reversible inhibitor dinitrostilbene disulfonate (DNDS). Current-voltage relationships for the cotransporter, measured at three different Na+ concentration gradients, were linear over a range of about 100 mV. The reversal potential data, obtained from these current-voltage relationships, all corresponded to a 2 HCO3-:1 Na+ stoichiometry. The data indicate that pNBC1 is functionally expressed in mouse pancreatic duct cells. The cotransporter operates with a 2 HCO3-:1 Na+ stoichiometry in these cells, and mediates the transport of bicarbonate into the cell across the basolateral membrane.

Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued).

In eukaryotes, it is rare for a single gene to encode two functionally unrelated proteins. p150(Glued) is a component of the dynactin heteromultimeric complex of proteins which is required for dynein-mediated vesicle and organelle transport by microtubules. NBC4 is an electrogenic sodium bicarbonate cotransporter, which regulates intracellular pH. Here we report that NBC4 and p150(Glued) are encoded by the same locus, DCTN1-SLC4A5. We have characterized the genomic organization of the human DCTN1-SLC4A5 locus which spans approximately 230 kilobases on chromosome 2p13 and contains 66 exons. This information should allow the study of potential genomic alterations of DCTN1-SLC4A5 in patients with diseases mapping to this genomic region.

Two C-terminal variants of NBC4, a new member of the sodium bicarbonate cotransporter family: cloning, characterization, and localization.

We report the cloning, characterization, and chromosomal assignment of a new member of the sodium bicarbonate cotransporter (NBC) family, NBC4. The NBC4 gene was mapped to chromosome 2p13 and is a new candidate gene for Alstrom syndrome. Two variants of the transporter have been isolated from human testis and heart, which differ in their C termini. NBC4a encodes a 1137-residue polypeptide and is widely expressed in various tissues, including liver, testis, and spleen. NBC4b is identical to NBC4a except that it has a 16-nucleotide insert, creating a C-terminal frame shift. NBC4b encodes a 1074-residue polypeptide and is highly expressed in heart. Amino acids 1-1046 are common to both NBC4 variants. NBC4a has two protein-interacting domains that are lacking in NBC4b: a proline-rich sequence, PPPSVIKIP (amino acids 1102-1110), and a consensus PDZ-interacting domain, SYSL (1134-1137). NBC4b lacks the stretch of charged residues present in the C terminus of NBC4a and other members of the NBC family. Unlike other members of the NBC family, both NBC4a and NBC4b have a unique glycine-rich region (amino acids 440-469). In comparison with other members of the bicarbonate transport superfamily, NBC4a and NBC4b are most similar structurally to the electrogenic sodium bicarbonate cotransporters (NBC1).