As estatinas são os agentes mais eficazes para a redução de colesterol no tratamento de doenças cardiovasculares, e algumas destas moléculas podem ser produzidas através de processos biológicos como o cultivo semi-sólido de fungos filamentosos. O objetivo deste estudo foi determinar a capacidade de produção de estatinas e compostos antimicrobianos por cinco cepas de fungos isolados de Cana de Açúcar. Para isso, extratos obtidos a partir dos cultivos foram analisados por métodos analíticos como CLAE e RMN para determinar a presença de estatinas; adicionalmente, os extratos foram testados contra diferentes modelos biológicos incluindo bactérias, leveduras, fungos filamentosos, células de ovário de hamster chinês, e parasitas. De acordo com os resultados obtidos, os cinco fungos avaliados não produzem estatinas, e em relação ao biomonitoramento dos extratos foi observado um efeito biológico sobre os parasitas e as células de mamífero, no entanto, é possível que o efeito obtido seja uma resposta dos compostos do substrato dos cultivos (Farelo de trigo). / Statins are the most effective cholesterol lowering agents for the treatment of cardiovascular disease, and some of these molecules can be produced through biological process such as the solid state fermentation. The aim of this study was determinate the capability of production of statins and antimicrobials compounds by five strains of fungi isolated from Brazilian sugar cane. For this purpose, extracts were obtained from the cultures and analyzed through analytical methods as HPLC and NMR in order to determinate the presence of statins; in addition, the extracts were tested against different biological models including bacteria, yeast, filamentous fungi, chinese hamster ovary cells, and parasites. According to the results obtained, the five fungal strains tested did not produce statins, and the extracts produced a biological effect against the parasites and mammalian cells, nevertheless it is possible that this effect observed was a response of the compounds from the culture substrate (wheat bran).

O objetivo do trabalho foi avaliar a ocorrência de resíduos de antimicrobianos (RA) no leite no pós-parto (PP) de vacas leiteiras tratadas no período seco (PS). Utilizou-se 74 animais distribuídos em 3 grupos: (1) 0,25 g de cefalônio anidro, (2) 100 mg de hidroiodeto de penetamato + 280 mg de penicilina benetamina + 100 mg de sulfato de framicetina, (3) 297,92 mg de benzilpenicilina procaína + 121,95 mg de monoidrato sódico de nafcilina + 34,23 mg de sulfato de diidroestreptomicina. Na secagem realizaram-se os testes de CMT e Tamis e foram colhidas amostras para exame microbiológico. No PP realizou-se o mesmo procedimento além da colheita das amostras para RA. Para análise dos RA utilizou-se o Delvotest®SP. A ocorrência de RA no leite dos quartos mamários (QM) de animais tratados na secagem nas propriedades A, B e C foi: 18%, 22,2% e 26,5%, com média de 19,4%. A ocorrência de RA foi maior, quando o PS foi menor que 60 dias (P< 0,0015) e quando o intervalo tratamento colheita (ITC) foi menor que 70 dias (P< 0,0189). Os resultados evidenciaram que a presença de RA no leite ocorreu predominantemente em todos os QM e em pelo menos três deles, aumentando a possibilidade de contaminação dos tanques de pequena mistura. Não foi detectada diferença estatística quanto aos medicamentos utilizados, produção na secagem, produção na lactação, presença de processo inflamatório e infecção intramamária. O PS preconizado como ideal por proporcionar à glândula mamária tempo necessário para involução, colostrogênese e nova lactação (60 dias), não constitui garantia de isenção de RA no leite no PP, uma vez que, 19,4% dos QM tratados na secagem, com PS entre 60 a 70 dias, apresentaram RA no leite. E ao ser realizada a análise custo: benefício verificou-se que a utilização do teste de triagem antes da liberação do leite para consumo, comparado ao descarte de leite, mostrou-se economicamente mais interessante. / The aim of this study was to evaluate the occurrence of antimicrobials residues (AR) used in dry cow therapy, in the postpartum (PP) milk of dairy cows. Seventy-four animals were assigned in 3 groups: (1) 0,25 g de cefalônio anidro, (2) 100 mg de hidroiodeto de penetamato + 280 mg de penicilina benetamina + 100 mg de sulfato de framicetina, (3) 297,92 mg de benzilpenicilina procaína + 121,95 mg de monoidrato sódico de nafcilina + 34,23 mg de sulfato de diidroestreptomicina). Stripcup and CMT exams were carried out, either at the drying off and PP. Milk samples for microbiological examination were collected in both periods. In the PP, milk samples were collected to evaluated the occurrence of AR. Samples were screened for AR using Delvotest®SP. The occurrence of AR in milk of mammary quarters (MQ) treated at drying off in farms A, B and C were 18%, 22.2% and 26.5% respectively, with 19,4% average. The AR occurrence was higher when the dry period (DP) was less than 60 days (P< 0,0015) and when postpartum sampling Interval (PSI) was less than 70 days (P< 0,0189). The results showed that AR in milk, due to drying therapy, predominantly occurred in all MQ and in at least three of them, increasing the possibility of contamination of bulk tanks. It was not detected any statistical difference in relation to: the antibiotics used, production at drying off, milk production during lactation, and presence of inflammatory process and intramammary infection. The DP praised as ideal for providing the mammary gland time to involution, colostrogenesis and new lactation (60 days), does not constitute guarantee for AR absence in milk in PP, when 19,4% of the MQ with DP between 60 to 70 days, had presented AR in milk. A cost: benefit analysis verified that the use of the test was useful and was economically more interesting compared with a longer period of milk discarding.

As estatinas são os agentes mais eficazes para a redução de colesterol no tratamento de doenças cardiovasculares, e algumas destas moléculas podem ser produzidas através de processos biológicos como o cultivo semi-sólido de fungos filamentosos. O objetivo deste estudo foi determinar a capacidade de produção de estatinas e compostos antimicrobianos por cinco cepas de fungos isolados de Cana de Açúcar. Para isso, extratos obtidos a partir dos cultivos foram analisados por métodos analíticos como CLAE e RMN para determinar a presença de estatinas; adicionalmente, os extratos foram testados contra diferentes modelos biológicos incluindo bactérias, leveduras, fungos filamentosos, células de ovário de hamster chinês, e parasitas. De acordo com os resultados obtidos, os cinco fungos avaliados não produzem estatinas, e em relação ao biomonitoramento dos extratos foi observado um efeito biológico sobre os parasitas e as células de mamífero, no entanto, é possível que o efeito obtido seja uma resposta dos compostos do substrato dos cultivos (Farelo de trigo). / Statins are the most effective cholesterol lowering agents for the treatment of cardiovascular disease, and some of these molecules can be produced through biological process such as the solid state fermentation. The aim of this study was determinate the capability of production of statins and antimicrobials compounds by five strains of fungi isolated from Brazilian sugar cane. For this purpose, extracts were obtained from the cultures and analyzed through analytical methods as HPLC and NMR in order to determinate the presence of statins; in addition, the extracts were tested against different biological models including bacteria, yeast, filamentous fungi, chinese hamster ovary cells, and parasites. According to the results obtained, the five fungal strains tested did not produce statins, and the extracts produced a biological effect against the parasites and mammalian cells, nevertheless it is possible that this effect observed was a response of the compounds from the culture substrate (wheat bran).

O objetivo do trabalho foi avaliar a ocorrência de resíduos de antimicrobianos (RA) no leite no pós-parto (PP) de vacas leiteiras tratadas no período seco (PS). Utilizou-se 74 animais distribuídos em 3 grupos: (1) 0,25 g de cefalônio anidro, (2) 100 mg de hidroiodeto de penetamato + 280 mg de penicilina benetamina + 100 mg de sulfato de framicetina, (3) 297,92 mg de benzilpenicilina procaína + 121,95 mg de monoidrato sódico de nafcilina + 34,23 mg de sulfato de diidroestreptomicina. Na secagem realizaram-se os testes de CMT e Tamis e foram colhidas amostras para exame microbiológico. No PP realizou-se o mesmo procedimento além da colheita das amostras para RA. Para análise dos RA utilizou-se o Delvotest®SP. A ocorrência de RA no leite dos quartos mamários (QM) de animais tratados na secagem nas propriedades A, B e C foi: 18%, 22,2% e 26,5%, com média de 19,4%. A ocorrência de RA foi maior, quando o PS foi menor que 60 dias (P< 0,0015) e quando o intervalo tratamento colheita (ITC) foi menor que 70 dias (P< 0,0189). Os resultados evidenciaram que a presença de RA no leite ocorreu predominantemente em todos os QM e em pelo menos três deles, aumentando a possibilidade de contaminação dos tanques de pequena mistura. Não foi detectada diferença estatística quanto aos medicamentos utilizados, produção na secagem, produção na lactação, presença de processo inflamatório e infecção intramamária. O PS preconizado como ideal por proporcionar à glândula mamária tempo necessário para involução, colostrogênese e nova lactação (60 dias), não constitui garantia de isenção de RA no leite no PP, uma vez que, 19,4% dos QM tratados na secagem, com PS entre 60 a 70 dias, apresentaram RA no leite. E ao ser realizada a análise custo: benefício verificou-se que a utilização do teste de triagem antes da liberação do leite para consumo, comparado ao descarte de leite, mostrou-se economicamente mais interessante. / The aim of this study was to evaluate the occurrence of antimicrobials residues (AR) used in dry cow therapy, in the postpartum (PP) milk of dairy cows. Seventy-four animals were assigned in 3 groups: (1) 0,25 g de cefalônio anidro, (2) 100 mg de hidroiodeto de penetamato + 280 mg de penicilina benetamina + 100 mg de sulfato de framicetina, (3) 297,92 mg de benzilpenicilina procaína + 121,95 mg de monoidrato sódico de nafcilina + 34,23 mg de sulfato de diidroestreptomicina). Stripcup and CMT exams were carried out, either at the drying off and PP. Milk samples for microbiological examination were collected in both periods. In the PP, milk samples were collected to evaluated the occurrence of AR. Samples were screened for AR using Delvotest®SP. The occurrence of AR in milk of mammary quarters (MQ) treated at drying off in farms A, B and C were 18%, 22.2% and 26.5% respectively, with 19,4% average. The AR occurrence was higher when the dry period (DP) was less than 60 days (P< 0,0015) and when postpartum sampling Interval (PSI) was less than 70 days (P< 0,0189). The results showed that AR in milk, due to drying therapy, predominantly occurred in all MQ and in at least three of them, increasing the possibility of contamination of bulk tanks. It was not detected any statistical difference in relation to: the antibiotics used, production at drying off, milk production during lactation, and presence of inflammatory process and intramammary infection. The DP praised as ideal for providing the mammary gland time to involution, colostrogenesis and new lactation (60 days), does not constitute guarantee for AR absence in milk in PP, when 19,4% of the MQ with DP between 60 to 70 days, had presented AR in milk. A cost: benefit analysis verified that the use of the test was useful and was economically more interesting compared with a longer period of milk discarding.

La nanotechnologie possède la potentialité d’améliorer la sécurité, les procédés, l’emballage alimentaire et le concept d’ingrédient fonctionnel. La nano-encapsulation d’agents actifs, est un concept innovant permettant de protéger les agents actifs d’une dégradation éventuelle pendant le procédé de fabrication de l’aliment et son stockage. Le principal objectif de ce travail est de développer et d’optimiser une méthode de marquage fluorescent afin d’effectuer des études de transfert dans différents films de bio-polymères et dans l’aliment et de nano-encapsuler la nisine. La nano-encapsulation de la nisine dans différents nano-liposomes par micro-fluidisation (CCDS) est une technique innovante pour la fabrication de nano-systèmes de re-largage. L’incorporation de nisine sous forme de nano-émulsion est une méthode efficace de contrôle des flores pathogènes sans altérer les caractéristiques des films d’HPMC. La nisine Z a été marquée par un composé fluorescent, et a une masse moléculaire de 3713,3. Des études en microscopie confocale ont permis de démontrer que l’interaction de la nisine avec les membranes bactériennes se situait au niveau de site de division de la cellule. L’HPMC, le chitosane, le caséinate et l’acide poly-lactique agissent comme des réservoirs et libèrent progressivement la nisine afin d’obtenir un effet inhibiteur durable. Le choix du biopolymère affecte la biodispinibilité du composé à la surface et à l’intérieur de l’aliment. La prochaine révolution concernant la sécurité alimentaire par l’emballage mettra en avant le dernier concept technologique « 3-BIOs » qui se réfère aux notions Bioactif - Biodégradable - Bionanocomposite / Food nanotechnology has the potential to improve food safety and bio-security, food processing, food packaging and functional ingredients. Nano-encapsulation of active agents is an innovative concept to protect them against possible denaturation during processing and storage. The overall objective of the present work was to optimize and develop fluorescent labeling and encapsulation of nisin for molecular transfer study in different packaging based on biopolymers and in the food. Nanoencapsulation of nisin in different nanoliposomes by using continuous cell disruption system (CCDS) has provided an innovative method for nano-delivery systems fabrication. Incorporation of nisin in nano-emulsion form (encapsulated and free) can possibly be an effective approach to control pathogen without compromising the basic physico-chemical attributes of composite HPMC coatings. The fluorescently labeled nisin Z prepared had a molecular weight of 3717.3 Da. Confocal microscopic studies demonstrated the interaction of nisin with the bacterial membranes at the cell-division sites as possible mechanism of action against food borne pathogen. HPMC, CTS, SC and PLA packaging bio-membranes act as a reservoir and progressively release nisin to sustain a constant inhibitory effect. Choice of biopolymer is significant in providing requisite bioavailability of antimicrobial compounds at exterior surface and inside the food system. Based on the present study results, the emerging revolution concerning food safety through packaging possibly will rely on « 3-BIOs » blend with nanotechnology, which refers to Bioactive, Biodegradable and Bio-nanocomposite

SecA ATPase is a critical member of the Sec system, which is important in the translocation of membrane and secreted polypeptides/proteins in bacteria. Small molecule inhibitors can be very useful research tools as well as leads for future antimicrobial agent development. Based on previous virtual screening work, we optimized the structures of two hit compounds and obtained SecA ATPase inhibitors with IC50 in the single digit micromolar range. These represent the first low micromolar inhibitors of bacterial SecA and will be very useful for mechanistic studies. Post synthetic modification is an important and efficient way of DNA functionalization especially in DNA aptamer selection. In this research, the feasibility of norbornene (Neo) modified thymidine triphosphate incorporation was described. Besides, substituted tetrazines have been found to undergo facile inversed electron demand Diels-Alder reactions with "tunable" reaction rates. This finding paves the way to utilize tetrazine conjugation reactions for not only DNA but also other labeling work.

No description available.

The commonest prescribed group of drugs is antimicrobials. Various studies have shown that they are overused globally. Since Primary health care represents the first tier of the health care system, evaluation of antimicrobial use in primary health w e settings is a necessity to ensure rational and cost-effective use of these agents in the treatment of infectious diseases. It has been reported by Hooton and Levy (2001 : 1088) that 20% to 50% of antimicrobials are inappropriately used in developing countries. According to Rebana et al. (1998: 175) the increasing overuse of antimicrobials has resulted in an enormous escalation in the total costs of drugs contributing to 15% to 30 % of the total health budget. Hooton and Levy (2001: 1087) reported in a study that inappropriate use and overuse of antimicrobials are risk factors for the emergence of antibiotic resistant bacteria. There is a high incidence of infectious diseases in developing countries that are due to the rapid spread of resistant strains through over-crowding, poor sanitation and unsafe sexual practices (Liu et al., 1999: 540). The general objective of the study was the analysis and interpretation of the usage and related costs of antimicrobial prescriptions in a private primary health w e setting in South Africa. The study is a non-experimental, quantitative, retrospective drug utilisation review of antimicrobial usage in a private primary health care setting. Data were obtained from the central database of a private primary health care service provider. Data of nine randomly selected clinics, situated in different geographical areas of South Africa, were extracted for the period 1st January to 31st December 2001. The study population was made of the total patient population of patients using antimicrobials during this one year period. Antimicrobial usage was analysed according to: number of patients, age and gender distribution, diagnosis, pharmacological groups. The total number of patients who visited the nine clinics during the year was 83 655 of which 59.50% were females and 40.22% males. In 0.28% of the cases gender was not indicated. Patients in age groups 6 (20-40 years) and 7 (40-60 years) accounted for the highest number of patients (66.31%, n = 54 964). A total of 515 976 medicine items costing R1 716 318.90 were prescribed, of these, 18.69%, (N=96 423) were antimicrobials costing 60.89%, (R1 045 108.00). Of the total number of patients that visited the nine clinics, 65.34% (N=54 663) were prescribed antimicrobials. The total number of diagnoses (140 723) where antimicrobials were prescribed accounted for 68.52% (N46 42 1). The highest number of antimicrobial prescriptions according to pharmacological and age groups were: penicillins followed by sulphonamides and tetracyclines. The diagnoses with the highest number of antimicrobial prescriptions were the respiratory tract infections (viral influenza, acute bronchitis and upper respiratory tract infection) and pelvic inflammatory disease The prescribing of antimicrobials in respiratory tract infections could indicate overuse and inappropriate use of these drugs. Because most of these infections are caused by viruses or other non-bacterial agents, are self limiting. Therefore, the use of antibiotics courses is neither necessary nor appropriate in these conditions. The overuse and inappropriate use of such drugs have an effect on the health of the patients needing cure, and the general budget on health care service. It is recommended that further studies are conducted on antimicrobial prescribing and use. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.

In this project the factors influencing the stability and antimicrobial activity of allyl isothiocyanate (AITC) against Campylobacter jejuni, Salmonella or Listeria monocytogenes as well as factors that enhance sinigrin (glucosinolate in Oriental mustard) hydrolysis by these pathogens were investigated. The minimum inhibitory concentration (MIC) of AITC against 5 strains of each of Salmonella or L. monocytogenes, ranged from 60-100 ppm at 37 ºC. This was reduced to 10-40 ppm at 21 ºC and a further reduction to 5-10 ppm against strains of L. monocytogenes was observed at 4 ºC. This was attributed to greater stability of AITC as temperature was decreased. C. jejuni strains were more susceptible to AITC with MICs of 0.63-1.25 ppm and 2.5-5 ppm at 37 and 42 ºC, respectively. AITC was more inhibitory at ≤ 21 ºC against Salmonella with acidic pH or against L. monocytogenes with neutral pH. C. jejuni, Salmonella and L. monocytogenes strains and mixtures had the ability to degrade sinigrin to form inhibitory concentrations of AITC, and sinigrin hydrolysis was significantly enhanced by higher incubation temperature (21 ºC > 10 ºC > 4 ºC), the presence of 10 mM ferric or ferrous irons, and the presence of < 0.25% glucose. This project also investigated the antimicrobial activity of AITC or Oriental mustard extract alone or combined with ethylenediamine tetraacetic acid (EDTA), malic acid and acetic acid in edible antimicrobial coatings against C. jejuni and Salmonella on fresh, refrigerated, vacuum-packed chicken breasts or L. monocytogenes on refrigerated, cured roast chicken. Malic acid improved the antimicrobial activity of Oriental mustard extract against L. monocytogenes, while EDTA improved its activity against Salmonella. Incorporation of 25 to 50 µl/g AITC or 100 to 250 mg/g Oriental mustard extract in 0.5%κ-carrageenan/2%chitosan coatings, prepared using 1.5% malic or acetic acid, reduced L. monocytogenes on cooked, cured, vacuum-packed chicken slices 4.2 to > 7.0 log10 CFU/g, compared to uncoated chicken by 70 d at 4 ºC. In addition, 0.2%κ-carrageenan/2%chitosan coatings (prepared using a 1% acetic acid solution) containing 250 mg/g mustard extract or 50 µl/g AITC reduced Salmonella numbers on vacuum-packed chicken breasts 3.0 log10 CFU/g by 21 d at 4 ºC. Further, 0.2%κ-carrageenan/2%chitosan coatings containing 50 or 100 µl/g AITC reduced numbers of C. jejuni on fresh, vacuum-packed chicken breasts > 5.0 log10 CFU/g (C. jejuni cells were not detected) after 5 d storage at 4 ºC, while coatings containing 200 to 300 mg/g Oriental mustard extract or 25 µl/g AITC reduced C. jejuni numbers by 3.6 to 4.6 log10 CFU/g. Numbers of lactic acid and aerobic bacteria on poultry meat products were significantly reduced by the coatings. It is clear that κ-carrageenan/chitosan coatings containing either AITC, mustard extract alone or combined with EDTA, malic or acetic acid significantly reduced C. jejuni and Salmonella on fresh, refrigerated, vacuum-packed chicken breasts and L. monocytogenes on refrigerated, cured roast chicken, and consequently enhanced their safety.

The commonest prescribed group of drugs is antimicrobials. Various studies have shown that they are overused globally. Since Primary health care represents the first tier of the health care system, evaluation of antimicrobial use in primary health w e settings is a necessity to ensure rational and cost-effective use of these agents in the treatment of infectious diseases. It has been reported by Hooton and Levy (2001 : 1088) that 20% to 50% of antimicrobials are inappropriately used in developing countries. According to Rebana et al. (1998: 175) the increasing overuse of antimicrobials has resulted in an enormous escalation in the total costs of drugs contributing to 15% to 30 % of the total health budget. Hooton and Levy (2001: 1087) reported in a study that inappropriate use and overuse of antimicrobials are risk factors for the emergence of antibiotic resistant bacteria. There is a high incidence of infectious diseases in developing countries that are due to the rapid spread of resistant strains through over-crowding, poor sanitation and unsafe sexual practices (Liu et al., 1999: 540). The general objective of the study was the analysis and interpretation of the usage and related costs of antimicrobial prescriptions in a private primary health w e setting in South Africa. The study is a non-experimental, quantitative, retrospective drug utilisation review of antimicrobial usage in a private primary health care setting. Data were obtained from the central database of a private primary health care service provider. Data of nine randomly selected clinics, situated in different geographical areas of South Africa, were extracted for the period 1st January to 31st December 2001. The study population was made of the total patient population of patients using antimicrobials during this one year period. Antimicrobial usage was analysed according to: number of patients, age and gender distribution, diagnosis, pharmacological groups. The total number of patients who visited the nine clinics during the year was 83 655 of which 59.50% were females and 40.22% males. In 0.28% of the cases gender was not indicated. Patients in age groups 6 (20-40 years) and 7 (40-60 years) accounted for the highest number of patients (66.31%, n = 54 964). A total of 515 976 medicine items costing R1 716 318.90 were prescribed, of these, 18.69%, (N=96 423) were antimicrobials costing 60.89%, (R1 045 108.00). Of the total number of patients that visited the nine clinics, 65.34% (N=54 663) were prescribed antimicrobials. The total number of diagnoses (140 723) where antimicrobials were prescribed accounted for 68.52% (N46 42 1). The highest number of antimicrobial prescriptions according to pharmacological and age groups were: penicillins followed by sulphonamides and tetracyclines. The diagnoses with the highest number of antimicrobial prescriptions were the respiratory tract infections (viral influenza, acute bronchitis and upper respiratory tract infection) and pelvic inflammatory disease The prescribing of antimicrobials in respiratory tract infections could indicate overuse and inappropriate use of these drugs. Because most of these infections are caused by viruses or other non-bacterial agents, are self limiting. Therefore, the use of antibiotics courses is neither necessary nor appropriate in these conditions. The overuse and inappropriate use of such drugs have an effect on the health of the patients needing cure, and the general budget on health care service. It is recommended that further studies are conducted on antimicrobial prescribing and use. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.