Les Chondrichtyens sont des espèces d’intérêt de par leur position phylogénétique à la base des Vertébrés. Au cours de cette thèse réalisée sur un petit requin, la petite roussette, l’étude des protéines Nanos, essentielles pour le maintien de la lignée germinale chez les Ostéichtyens, a mis en évidence la présence de deux protéines Nanos1 (1A et 1B) chez les Chondrichtyens, résultant d’une duplication du gène en amont des Gnathostomes. Chaque paralogue a révélé des profils d’expression spécifiques suggérant une spécification génique. De plus, la niche des spermatogonies souches (SSCs) a été mieux caractérisée et de nouveaux marqueurs de pluripotence tels que SSEA4 et Sox2 ont été détectés dans les SSCs potentielles chez cette espèce. Une culture primaire enrichie en spermatogonies de la zone germinative a montré une hétérogénéité d’expression des facteurs de SSC analysés (GFRα1, SSEA4, POU2, Nanos1A, Nanos1B, c-Kit), suggérant une hétérogénéité des cellules souches et/ou des progéniteurs. Afin de valider le caractère souche de ces cellules en culture, un test fonctionnel de transplantation a été initié. Le développement de cette technologie, pour la première fois chez un Chondrichtyen, ouvre de nouvelles perspectives en termes de préservation de ces espèces. Enfin, la recherche de facteurs à potentiel thérapeutique au niveau testiculaire chez la petite roussette a permis l’identification d’un peptide capable de réguler la glycémie et l’insulinémie de souris présentant un diabète de type 2, mais son mode d’action reste à explorer. L’ensemble des résultats confirme l’intérêt de la petite roussette pour l’étude évolutive de la niche germinale, essentielle au maintien de la gamétogenèse, et la recherche de molécules à potentiel thérapeutique. / Chondrichthyes are species of interest because of their phylogenetic position at the base of the Vertebrates. In this thesis, based on a small shark, the small spotted dogfish, the study of Nanos proteins, essential for the maintenance of the germ line in Osteichthyes, showed the presence of two Nanos1 proteins (1A and 1B) in Chondrichthyes, resulting from a gene duplication upstream of the Gnathostomata. Each paralog revealed specific expression profiles suggesting a gene specification. In addition, the spermatogonial stem cells (SSCs) niche was better characterized and new pluripotency markers such as SSEA4 and Sox2 were detected in potential SSCs in this species. A primary culture of the germinative zone enriched in spermatogonia showed a heterogeneity of expression of the analysed SSC factors (GFRα1, SSEA4, POU2, Nanos1A, Nanos1B, c-Kit), suggesting heterogeneity of stem cells and / or progenitors. In order to validate the stemness potential of these cells in culture, a functional transplantation test was initiated. The development of this technology, for the first time in a Chondrichthyes, opens new perspectives in terms of preservation of these species. Finally, the search of potential therapeutic factors in the dogfish testis led to the identification of a peptide able to regulate blood glucose and insulin levels in mice presenting type 2 diabetes, but its mode of action remains to be explored. All the results confirm the interest of the small spotted dogfish for the evolutionary study of the germinal niche, essential to the maintenance of gametogenesis, and the search for molecules with therapeutic potential.

Aloe vera is found in the Northern Africa and the Mediterranean areas while Aloe ferox is found in Southern Africa. Aloe ferox and Aloe vera prepared by different methods have been shown to possess the following properties: Stimulatory effects on different cell types (e.g human fibroblasts, rat adrenal cells, calf pulmonary artery endothelial cells etc.), wound healing, antimicrobial, antioxidant, antidiabetics etc. In this study solvent extracted gel powders and whole leaf juice of Aloe ferox and Aloe vera prepared specifically without bitter components were tested. The aim was to assess if the samples could be used orally for therapeutic purposes with regards to wound healing, antimicrobial and antioxidant properties avoiding the laxative effects of the bitter components. The following were used: Human lymphocytes cells to determine cytotoxicity effects, chicken fibroblasts cells for potential wound healing properties, Candida albicans, Staphylococcus aureus and Pseudomona aeruginosa microorganisms for antimicrobial properties and ORAC, DPPH, TEAC and chemiluminescence assays for antioxidant properties. Most of the results obtained were contrary to the bulk of the literature available about these beneficial plants’ extract. Bitter components have been reported to stimulate different cell types and to have antimicrobial and antioxidant properties. Thus the removal has been suggested as the main reason why the effects of the tested extracts did not correspond to much of the reported literature. From the results obtained from various aspects of this study it could be concluded that the removal of bitter components contributed to the apparently contradictory results. From this study it might be concluded that the four Aloe extract samples tested could not be used therapeutically for wound healing, antimicrobial or antioxidant properties. However they could still be effective for cosmetics purposes as obtained from the literature. / Dissertation (MSc)--University of Pretoria, 2014. / gm2014 / Pharmacology / unrestricted

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In Brazil, the percentage of elderly people is increasing considerably over the years. As a consequence, it is observes the increasing of chronical diseases such as diabetes mellitus. It is a disease that requires special attention, because it exposes elderly people to a long care period and to the continued use of medicines, sometimes using multidrugs. Moreover, elderly people are often affected by other comorbidities, by complications of the disease and its treatment. Objective. Analyze the use of medicines by the elderly people with diabetes mellitus in the city of Goiania, Goias, Brazil. Methodology. It is a population-based cross-sectional study carried out with a sample of 173 elderly individuals with diabetes mellitus and medications referred, selected by cluster. Data were collected by household interviews from December 2009 to April 2010 and they were analyzed by the Software Stata 12.0. The identified medicines were classified according to the Anatomical Therapeutic Chemical classification of the World Health Organization. The study was approved by Ethics Committee of the Federal University of Goias . Results. The mean age of old people with diabetes mellitus was 72.5 years and 61.8% were female. The most used medicines were acetylsalicylic acid (20.2%), enalapril (19.1%), dipyrone (13.3%), simvastatin (13.3%), levothyroxine sodium (12.7%), captopril (11.0%), atenolol (11.0%), hydrochlorothiazide (10.4%), losartan (9.8%) and paracetamol (9.8%). Approximately two thirds of the subjects used drugs for treatment of diabetes mellitus, and biguanides, sulfonylureas and insulins that have been most frequently used, showing respective values of 37.0%, 34.7% e 15.0%. Insulin alone was used in 7.5% of the elderly. It was found that 20.2% of the subjects used glibenclamide, an inappropriate medicine for old people. Exclusively oral antidiabetic therapy was observed in 51.5% of the individuals: 68.5% oral monotherapy and 31.5% combined oral therapy. The exclusive use of oral antidiabetic occurred with the utilization of metformin in monotherapy (15.6%), glibenclamide in monotherapy (11.0%) and combined therapy using metformin and glibenclamide (8.1%). The polypharmacy frequency was 38.7%. It was observed that women, unmarried, aged over 75 years and those who were not engaged in physical activity, hypertensive individuals, dyslipidaemic and those who had any hospitalization in the last 12 months had a higher median number of drugs used (p <0.05). However, after multivariate analysis hypertension was he only variable with statistical significance. Older people with diabetes mellitus and hypertension had 3.28 times more likely to use five or more medications than those without hypertension. Conclusion. This study allowed us to identify the profile of utilization of medicines by elderly people with diabetes mellitus as well to verify that metformin, alone or in combination, was the drug most often used for diabetes mellitus and indicated factors that may compromise the safety of antidiabetic pharmacotherapy in this population. Thus, health actions need to be developed, it is essential the work of the pharmacist in the multidisciplinary team to promotion of rational use of medicines and ensuring the safety of the elderly with diabetes mellitus. / Introdução. No Brasil, o percentual de idosos vem aumentando consideravelmente com o passar dos anos. Como consequência, observa-se o aumento de casos de doenças crônicas não transmissíveis, como o diabetes mellitus. Trata-se de uma doença que requer atenção especial, visto que expõe os idosos a um longo período de cuidados e ao uso continuado de medicamentos, muitas vezes com uso de múltiplos fármacos. Soma-se a isso o fato de idosos serem, frequentemente, acometidos por outras comorbidades, complicações da doença e de seu tratamento. Objetivo. Analisar o uso de medicamentos por idosos com diabetes mellitus do município de Goiânia, Goiás. Metodologia. Estudo transversal de base populacional realizado com amostra de 173 idosos com diabetes mellitus e uso de medicamentos referidos, selecionados por conglomerado. Os dados foram coletados por meio de entrevistas domiciliares, no período de dezembro de 2009 a abril de 2010 e analisados pelo Software Stata 12.0. Os medicamentos identificados foram classificados segundo Classificação Anatômica Terapêutica Química da Organização Mundial da Saúde. A pesquisa foi aprovada pelo Comitê de Ética em Pesquisa da Universidade Federal de Goiás. Resultados. A média de idade dos idosos com diabetes mellitus foi de 72,5 anos e 61,8% eram mulheres. Os fármacos mais utilizados foram o ácido acetilsalicílico (20,2%), enalapril (19,1%), dipirona (13,3%), sinvastatina (13,3%), levotiroxina sódica (12,7%), captopril (11,0%), atenolol (11,0%), hidroclorotiazida (10,4%), losartana (9,8%) e paracetamol (9,8%). Aproximadamente dois terços dos idosos usavam medicamentos para tratamento do diabetes mellitus, sendo as biguanidas, as sulfonilureias e as insulinas os fármacos que foram mais frequentemente utilizados, apresentando respectivamente, valores de 37,0%, 34,7% e 15,0%. A insulina isoladamente foi utilizada por 7,5% dos idosos. Verificou-se que 20,2% dos idosos faziam uso de glibenclamida, medicamento inapropriado para uso em idosos. A terapia antidiabética exclusivamente oral foi observada em 51,5% dos idosos, sendo 68,5% em monoterapia oral e 31,5% de terapia combinada oral. O uso exclusivo de antidiabéticos orais deu-se com a utilização da metformina em monoterapia (15,6%), glibenclamida em monoterapia (11,0%) e terapia combinada entre metformina e glibenclamida (8,1%). A frequência de polifarmácia foi de 38.7%. Observou-se que mulheres, não casados, idosos com mais de 75 anos, não praticantes de atividade física, hipertensos, dislipidêmicos e aqueles que tiveram alguma internação nos últimos doze meses apresentaram maior mediana de número de medicamentos utilizados (p< 0,05). Entretanto, após análise multivariada somente a variável hipertensão apresentou significância estatística. Os idosos com diabetes mellitus e hipertensão tiveram 3,28 vezes mais chance de usarem cinco ou mais medicamentos do que aqueles sem hipertensão. Conclusão. O estudo possibilitou identificar o perfil de utilização de medicamentos por idosos com diabetes mellitus, identificar que a metformina, isolada ou em combinação, foi o medicamento para diabetes mellitus mais frequentemente usado e indicou fatores que podem comprometer a segurança da farmacoterapia antidiabética nesta população. Dessa forma, ações de saúde precisam ser desenvolvidas, sendo essencial o trabalho do farmacêutico na equipe multiprofissional para promoção do uso racional de medicamentos e a garantia da segurança do idoso com diabetes mellitus.

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The aim of the study was to evaluate type 2 diabetes mellitus (DM) medicine management in Government Clinics in Maseru, Lesotho. A two-dimensional research method was employed, consisting of a literature review and an empirical investigation. The objective of the literature review was to provide information on the pathophysiology, signs and symptoms, diagnosis, treatment and clinical management of DM. The empirical investigation consisted of a descriptive pharmacoepidemiological study, in which data for analysis was collected retrospectively from patients‘ medical records (―bukanas‖) at dispensing points, a using data collection tool. The selected study sites were Domiciliary Health Center, Mabote, Likotsi, and Qoaling filter clinics in Maseru district of Lesotho. Data on costs of antidiabetic agents was collected from purchase invoices provided by the pharmacy department of Domiciliary Health Center. Results showed that the overall ratio of males to females was 1.3. There were no statistical difference in DM prevalence between males and females in the different clinics (p = 0.48). The mean age of males and females was 57.5 ± 14.2 years and 58.6 ± 11.3 years, respectively (Cohen‘s d = 0.07). DM was more prevalent in patients 59 to 69 years for both males and females, with the exception of Mabote and Qoaling filter clinics, where DM was more prevalent in patients 49 to 59 years. These differences in prevalence were not statically significant. Overall, 20% (n = 69) of the study sample had DM alone, while 80.0% of patients had DM concurrently with hypertension. The odds ratio implicated that women were 1.7 times more likely to have hypertension concurrently with Type 2 Diabetes Mellitus. The mean blood glucose level at 95% confidence interval for females and males were 10.1 ± 5.9 mmol/L (95% CI: 10.1–11.7) and 10.9 ± 6.2 mmol/L (95% CI: 11.0–14.0) respectively. The difference in the mean blood glucose levels of males vs. females was not statistically significant (p = 0.07). In both males and females there were outliers as high as 33.3 mmol/L. Metformin 850 mg given three times, metformin 500 mg three times a day, glibenclamide 10 mg daily and glibenclamide 5 mg twice daily are oral hypoglycaemic agents that were first, second, third and fourth choice treatment of DM at all four study sites at a frequency of 54.2% (n = 160), 27.7% (n = 82), 4% (n = 12) and 2.7% (n = 27), respectively. Actraphane® 20 units in the morning and 10 units in the evening was prescribed at a frequency of 11.6% (n = 432) in comparison to other Actraphane®-containing regimens. The frequencies of prescribing metformin and Actraphane® as combination therapies represented 10.6% (n = 40), 7.1% (n = 27), and 6.6% (n = 25), respectively, for Actraphane® 20 units in the morning and 10 units in the evening, plus metformin 500 mg three times per day; Actraphane® 20 units in the morning and 10 units in the evening plus metformin 850 mg three times per day; and Actraphane® 30 units in the morning and 15 units in the evening plus metformin 850 mg three times per day. The combination therapy of metformin and glibenclamide were prescribed at frequencies of 24.6% (n = 172), 22.9% (n = 160), and 13.4% (n = 94) respectively for glibenclamide 10 mg daily plus metformin 850 mg three times per day, glibenclamide 5 mg daily plus metformin 850 mg three times per day, and glibenclamide 5 mg once a day plus metformin 500 mg three times per day as first, second and third choice treatments at all study sites. The total cost incurred for all the oral drugs prescribed alone within different regimens was M75.6 with the weighted average cost per patient of M0.81 ± 2.06 per day compared to the cost of Actraphane® which was M40 660.52 per month at a weighted average daily cost of M21.43 ± 6.23 per patient. The overall cost of Actraphane® and metformin combination therapy amounted to M50 676.50, at an average cost per patient of M21.77 ± 6.80 per day. The cost of combination therapy consisting of metformin and glibenclamide amounted to M377.10, at a weighted average cost amounting to M0.49 ± 0.16 per patient, per day. Based on the results of this study some conclusions were reached on the prevalence of DM, prescribing patterns and the cost of antidiabetic agents. Recommendations pertaining to the clinics and further research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

The aim of the study was to evaluate type 2 diabetes mellitus (DM) medicine management in Government Clinics in Maseru, Lesotho. A two-dimensional research method was employed, consisting of a literature review and an empirical investigation. The objective of the literature review was to provide information on the pathophysiology, signs and symptoms, diagnosis, treatment and clinical management of DM. The empirical investigation consisted of a descriptive pharmacoepidemiological study, in which data for analysis was collected retrospectively from patients‘ medical records (―bukanas‖) at dispensing points, a using data collection tool. The selected study sites were Domiciliary Health Center, Mabote, Likotsi, and Qoaling filter clinics in Maseru district of Lesotho. Data on costs of antidiabetic agents was collected from purchase invoices provided by the pharmacy department of Domiciliary Health Center. Results showed that the overall ratio of males to females was 1.3. There were no statistical difference in DM prevalence between males and females in the different clinics (p = 0.48). The mean age of males and females was 57.5 ± 14.2 years and 58.6 ± 11.3 years, respectively (Cohen‘s d = 0.07). DM was more prevalent in patients 59 to 69 years for both males and females, with the exception of Mabote and Qoaling filter clinics, where DM was more prevalent in patients 49 to 59 years. These differences in prevalence were not statically significant. Overall, 20% (n = 69) of the study sample had DM alone, while 80.0% of patients had DM concurrently with hypertension. The odds ratio implicated that women were 1.7 times more likely to have hypertension concurrently with Type 2 Diabetes Mellitus. The mean blood glucose level at 95% confidence interval for females and males were 10.1 ± 5.9 mmol/L (95% CI: 10.1–11.7) and 10.9 ± 6.2 mmol/L (95% CI: 11.0–14.0) respectively. The difference in the mean blood glucose levels of males vs. females was not statistically significant (p = 0.07). In both males and females there were outliers as high as 33.3 mmol/L. Metformin 850 mg given three times, metformin 500 mg three times a day, glibenclamide 10 mg daily and glibenclamide 5 mg twice daily are oral hypoglycaemic agents that were first, second, third and fourth choice treatment of DM at all four study sites at a frequency of 54.2% (n = 160), 27.7% (n = 82), 4% (n = 12) and 2.7% (n = 27), respectively. Actraphane® 20 units in the morning and 10 units in the evening was prescribed at a frequency of 11.6% (n = 432) in comparison to other Actraphane®-containing regimens. The frequencies of prescribing metformin and Actraphane® as combination therapies represented 10.6% (n = 40), 7.1% (n = 27), and 6.6% (n = 25), respectively, for Actraphane® 20 units in the morning and 10 units in the evening, plus metformin 500 mg three times per day; Actraphane® 20 units in the morning and 10 units in the evening plus metformin 850 mg three times per day; and Actraphane® 30 units in the morning and 15 units in the evening plus metformin 850 mg three times per day. The combination therapy of metformin and glibenclamide were prescribed at frequencies of 24.6% (n = 172), 22.9% (n = 160), and 13.4% (n = 94) respectively for glibenclamide 10 mg daily plus metformin 850 mg three times per day, glibenclamide 5 mg daily plus metformin 850 mg three times per day, and glibenclamide 5 mg once a day plus metformin 500 mg three times per day as first, second and third choice treatments at all study sites. The total cost incurred for all the oral drugs prescribed alone within different regimens was M75.6 with the weighted average cost per patient of M0.81 ± 2.06 per day compared to the cost of Actraphane® which was M40 660.52 per month at a weighted average daily cost of M21.43 ± 6.23 per patient. The overall cost of Actraphane® and metformin combination therapy amounted to M50 676.50, at an average cost per patient of M21.77 ± 6.80 per day. The cost of combination therapy consisting of metformin and glibenclamide amounted to M377.10, at a weighted average cost amounting to M0.49 ± 0.16 per patient, per day. Based on the results of this study some conclusions were reached on the prevalence of DM, prescribing patterns and the cost of antidiabetic agents. Recommendations pertaining to the clinics and further research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

Diabetes mellitus belongs to diseases frequently occurring in childhood and adulthood. Insufficient knowledge of this disease and an unsatisfactory compensation for diabetes leads to development of late complications that have a negative impact on one's, as well as the family's, life and create an economic problem for society as a whole. The thesis focuses on the main characteristics of the disease, symptoms, diagnosis and treatment. Complications of the disease, including advice for patients themselves and their prevention are described in more detail. Social aspects (work inclusion of a diabetic, invalidity and reduced work capacity, driving of motor vehicles) are also emphasised. The research part containing 18 questions aims to find out to what extent the Czech public is informed about the problematic areas of this disease. It also assesses the feasibility of obtaining information from individuals of different ages and places of residence (city vs. village) regarding diabetes. These hypotheses were stated within the scope of the research: 1. Individuals older than 50 years of age are better informed about diabetes than individuals of a younger age. 1. Individuals living in a city have a better access to information concerning diabetes than individuals living in a village. The data was obtained from questionnaire research, in which respondents older than 18 years of age participated. The data collection took place in Bechyně Spa Ltd. 58 % of the resultant questionnaires were completed by women and 42 % by men.