1 |
Hereditary ichthyosis : Causes, Skin Manifestations, Treatments and Quality of LifeGånemo, Agneta January 2002 (has links)
<p>Hereditary ichthyosis is a collective name for many dry and scaly skin disorders ranging in frequency from common to very rare. The main groups are autosomal recessive lamellar ichthyosis, autosomal dominant epidermolytic hyperkeratosis and ichthyosis vulgaris, and x-linked recessive ichthyosis. Anhidrosis, ectropion and keratodermia are common symptoms, especially in lamellar ichthyosis, which is often caused by mutations in the transglutaminase 1 (TGM1) gene. The aim of this work was to study patients with different types of ichthyosis regarding (i) the patho-aetiology (TGM1 and electron microscopy [EM] analysis), (ii) skin signs and symptoms (clinical score and subjective measure of disease activity), (iii) quality of life (questionnaires DLQI, SF-36 and NHP and face-to-face interviews) and (iv) a search for new ways of topical treatment. Patients from Sweden and Estonia with autosomal recessive congenital ichthyosis (n=83) had a broader clinical spectrum than anticipated, but a majority carried TGM1 mutations. Based on DNA analysis and clinical examinations the patients were classified into three groups, which could be further subdivided after EM analysis. Our studies indicate that patients with ichthyosis have reduced quality of life as reflected by DLQI and by some domains of SF-36, by NHP and the interviews. All the interviewees reported that their skin disease had affected them negatively to varying degrees during their entire lives and that the most problematic period was childhood. All patients with ichthyosis use topical therapy. In a double-blind study creams containing either 5% urea or 20% propylene glycol were found inferior to a cream formulation containing lactic acid 5% and propylene glycol 20% both regarding clinical improvement and thinning of the skin barrier. Improved topical therapy may reduce the need of more toxic, oral drugs. Future studies should elucidate whether this increases the quality of life of ichthyosis patients, especially if combined with more detailed information about the aetiology and inheritance of the diseases.</p>
|
2 |
Hereditary ichthyosis : Causes, Skin Manifestations, Treatments and Quality of LifeGånemo, Agneta January 2002 (has links)
Hereditary ichthyosis is a collective name for many dry and scaly skin disorders ranging in frequency from common to very rare. The main groups are autosomal recessive lamellar ichthyosis, autosomal dominant epidermolytic hyperkeratosis and ichthyosis vulgaris, and x-linked recessive ichthyosis. Anhidrosis, ectropion and keratodermia are common symptoms, especially in lamellar ichthyosis, which is often caused by mutations in the transglutaminase 1 (TGM1) gene. The aim of this work was to study patients with different types of ichthyosis regarding (i) the patho-aetiology (TGM1 and electron microscopy [EM] analysis), (ii) skin signs and symptoms (clinical score and subjective measure of disease activity), (iii) quality of life (questionnaires DLQI, SF-36 and NHP and face-to-face interviews) and (iv) a search for new ways of topical treatment. Patients from Sweden and Estonia with autosomal recessive congenital ichthyosis (n=83) had a broader clinical spectrum than anticipated, but a majority carried TGM1 mutations. Based on DNA analysis and clinical examinations the patients were classified into three groups, which could be further subdivided after EM analysis. Our studies indicate that patients with ichthyosis have reduced quality of life as reflected by DLQI and by some domains of SF-36, by NHP and the interviews. All the interviewees reported that their skin disease had affected them negatively to varying degrees during their entire lives and that the most problematic period was childhood. All patients with ichthyosis use topical therapy. In a double-blind study creams containing either 5% urea or 20% propylene glycol were found inferior to a cream formulation containing lactic acid 5% and propylene glycol 20% both regarding clinical improvement and thinning of the skin barrier. Improved topical therapy may reduce the need of more toxic, oral drugs. Future studies should elucidate whether this increases the quality of life of ichthyosis patients, especially if combined with more detailed information about the aetiology and inheritance of the diseases.
|
3 |
Avaliação anti-leishmania in vitro e in vivo de Libidibia ferrea e estudo de formulações tópicas para o tratamento da forma cutânea da Leishmaniose.Wyrepkowski, Claudia Dantas Comandolli 24 September 2016 (has links)
Submitted by Izabel Monteiro (izabel_22@hotmail.com) on 2016-08-03T15:01:33Z
No. of bitstreams: 1
Tese - Claudia Dantas Comandolli Wyrepkowski.pdf: 5493553 bytes, checksum: 2facc8046c9c0fe6bc72cf077d977196 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-08-17T15:41:32Z (GMT) No. of bitstreams: 1
Tese - Claudia Dantas Comandolli Wyrepkowski.pdf: 5493553 bytes, checksum: 2facc8046c9c0fe6bc72cf077d977196 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-08-17T15:48:18Z (GMT) No. of bitstreams: 1
Tese - Claudia Dantas Comandolli Wyrepkowski.pdf: 5493553 bytes, checksum: 2facc8046c9c0fe6bc72cf077d977196 (MD5) / Made available in DSpace on 2016-08-17T15:48:18Z (GMT). No. of bitstreams: 1
Tese - Claudia Dantas Comandolli Wyrepkowski.pdf: 5493553 bytes, checksum: 2facc8046c9c0fe6bc72cf077d977196 (MD5)
Previous issue date: 2016-09-24 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / The American Cutaneous Leishmaniasis (ACL) is a protozoonosis caused by parasites of the
genus Leishmania, which is transmitted by the bite of the sand fly insect. The LTA, patients
can present cutaneous form, with localized skin lesions that may progress to chronic lesions.
The treatment of choice is pentavalent antimony and drugs of second choice are pentamidine
and amphotericin B, but all have side effects and require parenteral administration. Natural
products are presented as an alternative for the treatment of many diseases, and there are
studies that demonstrate potential against Leishmania. In the Amazon region, Libidibia
ferrea (Mart. Ex Tul) LP Queiroz stands out for its economic and pharmacological
importance, due to anti-inflammatory and antimicrobial reported. This study aimed to
evaluate the activity of extracts and fractions of L. ferrea against promastigotes and
amastigotes of L. (L.) amazonensis and L. (V.) guyanensis also conducting its chemical
characterization, and study the effect in topical formulations containing pentamidine,
extracts and most promising fractions. And hexane extracts were prepared methanolic the
epicarp, leaves and branches of L. ferrea, who underwent in vitro bioassays against
promastigotes and amastigotes of L. (L.) amazonensis and L. (V) guyanensis, the counting
method direct. The most active extracts were evaluated in vitro for cytotoxic activity in J774
macrophage lineage. The extracts and active fractions were analyzed by TLC assay, the
quantized flavonoid and phenolic content, and analyzed by NMR and HPLC. The in vivo
assays employed as an animal model hamsters infected with L. (L.) amazonensis. They were
prepared and evaluated by topical application on lesions initially hydrating and anhydrous
emulsions containing pentamidine isethionate (10%). The results of the bioassays showed
that the methanolic extract from epicarp (EpMeOH) showed a higher activity against species
of Leishmania, with EC50 15.01 µg/ml against L (L.) amazonensis. This extract had the
highest concentration of phenolic (5.14%). A 2-DCM fraction also demonstrated activity
with EC50 12.77 µg/mL against L. (L.) amazonensis. No cytotoxic activity was observed in
macrophages for both samples. The moisturizing emulsions containing pentamidine were
most effective, although viable parasites were detected and all groups after eight days of
treatment. These moisturizing emulsions were used as a base for creams with addition of
2.5% of EpMeOH extract and evaluated in two areas with skin lesions - snout and paw. The
groups treated with cream EpMeOH extract (2.5%) and placebo showed differences in
lesion volume compared to the control group after 20 days of treatment, but showed the
presence of parasites, with no statistical difference between the control group. These results
suggest that the treatment time and extract concentration to be increased beyond the
proportion of use of EpMeOH extract in a more hydrophilic formulation. The hydrogel
EpMeOH was then evaluated for lesions on the snout of hamsters as well as cream Fr2.
After 40 days of treatment, the groups treated with these topical formulations showed
significant differences between the control group and between their respective placebos, as
volume, clinical aspect of the lesion, and as the parasitic quantification. Minor inflammatory
infiltrate was observed in the hydrogel EpMeOH. This study identified extracts promising
in the treatment of experimental cutaneous leishmaniasis and supports pointing new
opportunities and innovation serving as a basis for herbal formulations to treat this neglected
disease. / A Leishmaniose Tegumentar Americana (LTA) é uma protozoonose causada por parasitas
do gênero Leishmania, que são transmitidos ao homem pela picada do inseto flebotomíneo.
Na LTA, os pacientes podem apresentar a forma cutânea, com lesões localizadas na pele que
podem evoluir para lesões crônicas. O tratamento de primeira escolha são antimoniais
pentavalentes e os fármacos de segunda escolha são pentamidina e anfotericina B, porém
todos apresentam efeitos colaterais e requerem administração parenteral. Os produtos
naturais apresentam-se como uma alternativa para o tratamento de inúmeras enfermidades, e
há trabalhos que demonstram potencial contra Leishmania. Na região Amazônica, a espécie
Libidibia ferrea (Mart. ex Tul) LP Queiroz destaca-se pela sua importância econômica e
farmacológica, devido à atividade anti-inflamatória e antimicrobiana relatada. O presente
trabalho teve por objetivo avaliar a atividade de extratos e frações de L. ferrea contra
promastigotas e amastigotas de L. (L.) amazonensis e L. (V.) guyanensis, realizando também
a sua caracterização química, e estudar o efeito in vivo de formulações tópicas contendo
pentamidina, os extratos e frações mais promissoras. Foram preparados extratos hexânicos e
metanólicos do epicarpo, folhas e galhos de L. ferrea, os quais foram submetidos a
bioensaios in vitro contra promastigotas e amastigotas de L. (L.) amazonensis e L. (V.)
guyanensis, pelo método da contagem direta. Os extratos mais ativos foram avaliados in
vitro quanto a atividade citotóxica em macrófagos de linhagem J774. Os extratos e frações
ativos foram analisados por CCDC, quantificados o teor de fenólicos e flavonoides, e
analisados por RMN e CLAE. Os ensaios in vivo empregaram hamsters como modelo
animal, infectados com L. (L.) amazonensis. Foram preparadas e avaliadas por aplicação
tópica nas lesões, inicialmente, emulsões hidratantes e anidras contendo isetionato de
pentamidina (10%). Os resultados dos bioensaios demostraram que o extrato metanólico de
epicarpo (EpMeOH) apresentou maior atividade frente as espécies de Leishmania, com EC50
de 15,01 µg/mL contra L (L.) amazonensis. Este extrato apresentou a maior concentração de
fenólicos (5,14%). A fração 2-DCM demonstrou também atividade, com EC50 12,77 µg/mL
contra L. (L.) amazonensis. Não foi observada atividade citotóxica em macrófagos para
ambas as amostras. As emulsões hidratantes contendo pentamidina foram mais eficientes,
embora fossem detectados parasitas viáveis em todos os grupos após oito dias de tratamento.
Estas emulsões hidratantes foram utilizadas como base para cremes com adição de 2,5% do
extrato EpMeOH e avaliados em duas áreas com lesões cutâneas - focinho e pata. Os grupos
tratados com creme com extrato EpMeOH (2,5%) e o placebo mostraram diferenças quanto
ao volume da lesão quando comparados ao grupo controle após 20 dias de tratamento, mas
mostraram a presença de parasitas, sem diferença estatística entre o grupo controle. Estes
resultados sugerem que o tempo de tratamento e a concentração do extrato devem ser
aumentadas, além da proporção do uso do extrato EpMeOH em uma formulação mais
hidrofílica. O hidrogel EpMeOH foi avaliado em lesões no focinho de hamsters, assim como
emulsão Fr2. Após 40 dias de tratamento, os grupos tratados com estas formulações tópicas
mostraram diferenças estatísticas entre o grupo controle e também entre seus respectivos
placebos, quanto ao volume, aspecto clínico da lesão, e quanto à quantificação parasitária.
Menor infiltrado inflamatório foi observado no grupo hidrogel EpMeOH. Este estudo
permitiu identificar o extratos promissores no tratamento da leishmaniose tegumentar
experimental e corrobora apontando novas oportunidades e inovação servindo como base
para formulações de fitoterápicos para o tratamento desta doença negligenciada.
|
Page generated in 0.059 seconds