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1.
Langenbecks Arch Surg ; 406(1): 197-208, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32997233

RESUMO

PURPOSE: Onflex™ mesh has replaced Polysoft™ patch on the market, without being clinically evaluated thus far in the transinguinal preperitoneal (TIPP) technique. METHODS: All consecutive TIPP registered in our registry during the overlap period of availability of both meshes were included and studied with the chronic postoperative inguinal pain (CPIP) as primary endpoint, assessed with a verbal rating scale (VRS), and included in a patient-related outcome measurement (PROM) phone questionnaire. RESULTS: A total of 181 Onflex cases vs 182 Polysoft cases were studied with a 2-year follow-up rate of 92% vs 88%. The overall rate of pain or discomfort was not statistically different in the 2 studied subgroups (16.5% vs 17.6%; p = 0.71), while moderate or severe pain were significantly more frequent in the Polysoft subgroup (5.5% vs 11.6%; p = 0.01). These symptoms did not interfere with the patient daily life in 16% vs 16.5% of cases, and they were self-assessed as more bothersome than the hernia in only 0.5% vs 0.5% of cases, suggesting an overestimation of the pain by the VRS. Patients assessed the result of their hernia repair as excellent or good in 97.8% vs 96.7% and medium or bad in 2.2% vs 3.3% (p = 0.53). The cumulative recurrence rate was 0% vs 2.2%. Two reoperations (one for early and one for late recurrence) were reported in the Polysoft subgroup (1%), none related to the non-absorbable memory ring. CONCLUSIONS: These results suggest that TIPP with Onflex provides results at least similar than those with Polysoft.


Assuntos
Dor Crônica , Hérnia Inguinal , Dor Crônica/epidemiologia , Dor Crônica/etiologia , Seguimentos , Virilha/cirurgia , Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Humanos , Dor Pós-Operatória/epidemiologia , Recidiva , Sistema de Registros , Telas Cirúrgicas/efeitos adversos
2.
Curr Med Res Opin ; 31(4): 795-807, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25690488

RESUMO

OBJECTIVE: To investigate long-term patterns of antidepressant treatment in patients in primary care in the UK, and to assess their healthcare resource use and disease outcomes. RESEARCH DESIGN AND METHODS: A retrospective longitudinal cohort study was conducted using the Clinical Practice Research Datalink. The study population comprised patients aged ≥18 years with depression receiving a prescription for antidepressant monotherapy between 1 January 2006 and 31 December 2011 with no antidepressants within the preceding 6 months. Recovery was defined by timing of antidepressant prescriptions (≥6 months without treatment). Treatment lines and strategies (switching, combining, augmenting and resuming medication) were analyzed. Healthcare resource use for the different treatment strategies and periods of no therapy was assessed. RESULTS: Data from 123,662 patients (287,564 treatment lines) were analyzed. Switching and resumption of treatment were more frequent than other strategies. Recovery was highest with first-line monotherapy (45% of patients), while as a second-line strategy switching was more successful (43%) than combination or augmentation. In subsequent lines of treatment, switching was associated with successively lower rates of recovery (31% in the third line and 24% from the fourth line onwards). Similar rates were observed for resumption. Healthcare resource use was greater during antidepressant use than treatment-free periods. Augmentation was associated with the highest proportions of patients with a psychiatrist referral, psychologist referral and psychiatric hospitalization. CONCLUSIONS: This study provides extensive real-world information on the prescribing patterns and treatment outcomes for a large cohort of patients treated for depression with antidepressants in primary care. Switching is more frequently used than augmentation or combination treatment, with decreasing effectiveness across successive lines. Key limitations of the study were: (i) risk of selection bias due to the use of inclusion criteria based on depression diagnoses recorded by the practitioner; and (ii) reliance on prescribing patterns as proxies for clinical outcomes, such as recovery.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Atenção Primária à Saúde , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
3.
Hernia ; 17(6): 683-92, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23793928

RESUMO

INTRODUCTION: Little is known about both incidence of chronic pain and quality of life (QoL) after the transinguinal preperitoneal (TIPP) technique using a totally extraperitoneal, parietalized, memory ring patch. MATERIALS AND METHODS: Among 622 (428 unilateral and 194 bilateral) hernia repairs (HR) in 525 patients, 92 % had a postoperative clinical control. Thereafter, two sets of postal self-assessed questionnaires were sent. RESULTS: A total of 531 HR were studied with a mean follow-up of 17 ± 8 months. Only one recurrence was detected. In 151 (28.4 %) HR the patients alleged various symptoms, but in only 10 (1.9 %) HR they considered their discomfort more bothersome than the hernia they had before, and in just 2 (0.4 %) HR they judged their result as bad (one patch removal for sepsis and one for hematoma). Only mild pain (including no painful discomfort such as a foreign body sensation) or moderate pain was frequent. Pain was self-graded as severe in four cases. None of them reported any regular consumption of antalgics. None of them judged their result as bad. Dysesthesia (numbness 19, paresthesia 20) mentioned in 39 HR (7 %), associated with pain in 16 HR, was said to be more bothersome than the hernia treated in just 3 HR (0.6 %). The results of the entire series were self-assessed as good or excellent in 97 % of the HR. CONCLUSION: In our TIPP series, both the incidence of recurrences (0.2 %) and that of severe chronic pain (≤0.7 %) were very low, as well as patients' QoL was excellent. In our experience, the postoperative course was as painless as that of laparoscopic TEP we had been performing previously, but TIPP appeared more suited to day-case surgery.


Assuntos
Dor Crônica/prevenção & controle , Hérnia Inguinal/cirurgia , Herniorrafia/instrumentação , Dor Pós-Operatória/prevenção & controle , Peritônio/cirurgia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor Crônica/diagnóstico , Dor Crônica/epidemiologia , Dor Crônica/etiologia , Feminino , Seguimentos , Herniorrafia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Telas Cirúrgicas , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
4.
Int J Clin Pract ; 66(11): 1079-87, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23067031

RESUMO

AIMS: To investigate switching patterns of major antidepressant treatments and associated factors in a primary care adult population with major depressive disorder (MDD) using data from the General Practitioner Research Database (GPRD). METHODS: A retrospective cohort study was conducted using the GPRD. The study included patients with MDD, aged [18-70], with a new prescription for amitriptyline, citalopram, escitalopram, fluoxetine, paroxetine, sertraline or venlafaxine between January 1, 2001 and September 30, 2003 and having no antidepressant prescription in the 6 months preceding index date. Switching of antidepressant treatment was defined as a prescription of a different antidepressant among all available marketed antidepressant treatment at this time (no restriction of compound) from 1 month before up to 2 months after the calculated end of the previous antidepressant treatment. Survival analysis techniques were used to describe switching of antidepressant and time to switch. Profiles of switchers were described and by-treatment analyses performed. RESULTS: Data from over 59,000 patients showed that 16% switched antidepressants. Seventy-two per cent of switches appeared within 3 months after treatment initiation. Within switchers, median time to switch was 53 days. Switching patients had generally a more severe psychiatric profile, including more previous episodes of depression or other psychiatric disorders. They also had a higher proportion of concurrent psychiatric disorders (especially anxiety) and concomitant prescription of anxiolytics or hypnotics. Patients initially prescribed amitriptyline were almost twice as likely to switch (27%) as patients prescribed venlafaxine (17%) or an SSRI (15%). CONCLUSIONS: This population-based study confirmed that antidepressant switch is more likely to occur within the first 3 months of treatment and in patients with a more severe psychiatric profile. A particular attention paid to these patients within the early phase of treatment may therefore help to improve their management.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Substituição de Medicamentos , Adolescente , Adulto , Distribuição por Idade , Idoso , Transtorno Depressivo Maior/complicações , Feminino , Medicina Geral , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
5.
Bull Soc Pathol Exot ; 104(1): 1-5, 2011 Feb.
Artigo em Francês | MEDLINE | ID: mdl-21188568

RESUMO

A lesional study on human hydatidosis (localization, fertility of cysts, protoscolex viability, and histological structure) focused on 63 human hydatid cysts from patients operated at CHN of Nouakchott was conducted during the period 1997-2007. The authors report the following results: the annual surgical incidence rate was in the order of 1.2% per 100,000 inhabitants. The lung was the primary localization of cyst (52%) followed by the liver (33%), spleen (4%), brain (3%), heart (2%), breasts (2%), kidney (2%), diaphragm (1%), and peritoneum (1%). The pulmonary cysts were larger and more fertile (76%) with protoscoleces also more viable (70%) compared with liver cysts (67-62%). The histology of hydatid cysts revealed in most cases a histological structure consistent with that described in the literature: thick cuticle, membrane proligeous, and capsules visible.


Assuntos
Equinococose/patologia , Doenças dos Animais/parasitologia , Animais , Calcinose/patologia , Camelus/parasitologia , Equinococose/epidemiologia , Equinococose/parasitologia , Equinococose/cirurgia , Equinococose/veterinária , Equinococose Hepática/epidemiologia , Equinococose Hepática/parasitologia , Equinococose Hepática/patologia , Equinococose Hepática/cirurgia , Equinococose Pulmonar/epidemiologia , Equinococose Pulmonar/parasitologia , Equinococose Pulmonar/patologia , Equinococose Pulmonar/cirurgia , Echinococcus granulosus/fisiologia , Fertilidade , Humanos , Incidência , Mauritânia/epidemiologia , Especificidade da Espécie
6.
Environ Microbiol Rep ; 2(1): 185-91, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23766015

RESUMO

The present study focused on the isolation of culturable bacteria from mussels and sea water to identify Vibrionaceae potentially pathogenic for humans. Three sites located on the French Atlantic coast were monitored monthly (twice each month during summer) for 1 year. Environmental parameters were surveyed (water temperature, salinity, turbidity, chlorophyll a) and bacteria were detected by culture and identified by API 20E(®) systems (BioMérieux) and PCR. A total of seven species were detected (Grimontia hollisae, Photobacterium damselae, Vibrio alginolyticus, V. cholerae, V. fluvialis, V. vulnificus and V. parahaemolyticus) and species diversity was higher at the end of summer. Surprisingly, V. cholerae non-O1/non-O139 was detected in spring. No site effect was detected. Using Sørensen similarity indices and statistical analyses, we showed that chlorophyll a had a significant influence on the bacterial community detected in mussels and assemblages were more similar to one another when chlorophyll a values were above 20 µg l(-1) . No significant effect of any parameter was found on the community detected in water samples. Such surveys are essential for the understanding of sanitary crises and detection of emerging pathogens.

7.
J Chir (Paris) ; 146(2): 150-66, 2009 Apr.
Artigo em Francês | MEDLINE | ID: mdl-19552906

RESUMO

INTRODUCTION: The treatment of pseudomyxoma peritonei (PMPs) and appendiceal mucocele (AM) has changed radically. To assess the contribution of preoperative imaging to the treatment strategy and choice of approach, a surgeon and a radiologist different from the initial radiologist examined the files of all patients treated for PMP or AM in four facilities in one district from January 1, 1996, through December 31, 2008. PATIENTS AND METHODS: The study included 27 patients (20 men and seven women, mean age: 63+/-13 years). Eleven patients had an intact AM, seven synchronous PMP (malignant appendiceal lesion in two of seven), six metachronous PMP (five with peritoneal mucinous carcinomatosis and one with diffuse peritoneal adenomucinosis) and three a ruptured AM but not PMP. The incidence of mucin-secreting tumors observed (27 cases in 12 years in a region of 500 000 inhabitants) corresponds to a prevalence of approximately five cases per year per million inhabitants. Acute clinical pictures (7/27) were significantly more frequent for the malignant forms (5/7) (p<0,02). RESULTS AND DISCUSSION: The overall sensitivity of computed tomography (CT) for all the criteria studied was 93%. The predictive value for AM rupture of visualization of thick calcifications was 100%. On the other hand, rupture never occurred when the CT showed an AM under pressure, with thin walls and septa. The predictive value for PMP of "scalloping" was 100%. The diagnostic accuracy of the initial reading was 25/27 for the imaging overall and 25/25 for the CT. Preoperative visualization of the exact size of the intact AM or of diagnostic information about ruptured AM and PMP helped to select an appropriate approach in 25 of 27 cases.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Neoplasias do Apêndice/diagnóstico por imagem , Apêndice/diagnóstico por imagem , Mucocele/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Pseudomixoma Peritoneal/diagnóstico por imagem , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/cirurgia , Apêndice/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucocele/cirurgia , Neoplasias Peritoneais/cirurgia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Pseudomixoma Peritoneal/cirurgia , Ruptura , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
8.
Exp Parasitol ; 122(3): 196-202, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19318094

RESUMO

We have selected piperaquine (PQ) and lumefantrine (LM) resistant Plasmodium berghei ANKA parasite lines in mice by drug pressure. Effective doses that reduce parasitaemia by 90% (ED(90)) of PQ and LM against the parent line were 3.52 and 3.93 mg/kg, respectively. After drug pressure (more than 27 passages), the selected parasite lines had PQ and LM resistance indexes (I(90)) [ED(90) of resistant line/ED(90) of parent line] of 68.86 and 63.55, respectively. After growing them in the absence of drug for 10 passages and cryo-preserving them at -80 degrees C for at least 2 months, the resistance phenotypes remained stable. Cross-resistance studies showed that the PQ-resistant line was highly resistant to LM, while the LM-resistant line remained sensitive to PQ. Thus, if the mechanism of resistance is similar in P. berghei and Plasmodium falciparum, the use of LM (as part of Coartem) should not select for PQ resistance.


Assuntos
Antimaláricos/farmacologia , Resistência a Medicamentos/fisiologia , Etanolaminas/farmacologia , Fluorenos/farmacologia , Plasmodium berghei/efeitos dos fármacos , Quinolinas/farmacologia , Amodiaquina/farmacologia , Amodiaquina/uso terapêutico , Animais , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Modelos Animais de Doenças , Etanolaminas/uso terapêutico , Feminino , Fluorenos/uso terapêutico , Lumefantrina , Malária/tratamento farmacológico , Malária/parasitologia , Masculino , Camundongos , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Quinolinas/uso terapêutico , Inoculações Seriadas/métodos
9.
J Chir (Paris) ; 145(1): 64-6, 2008.
Artigo em Francês | MEDLINE | ID: mdl-18438287
10.
J Chir (Paris) ; 142(4): 248-56, 2005.
Artigo em Francês | MEDLINE | ID: mdl-16335900

RESUMO

Giant diverticula of the small intestine and colon are rare. Four cases treated at our institution in the last year are reported and compared to published cases; specific features and those which differentiate them from abdominal pseudocysts are described. They most commonly present a clinical tableau similar to commonplace diverticular disease. Awareness of this unusual condition and a good CT study are the keys to diagnosis. Giant diverticula may be acquired or congenital. The acquired type is simply a more spectacular version of commonplace diverticulosis while the congenital type, having a muscular wall and myenteric plexus, is more akin to intestinal duplications. Treatment is surgical and, in the case of sigmoid giant diverticula, usually requires a colon resection similar to that required for sigmoid diverticulitis.


Assuntos
Cistos/patologia , Divertículo do Colo/patologia , Doenças do Íleo/patologia , Doenças do Jejuno/patologia , Idoso , Cistos/diagnóstico , Cistos/cirurgia , Diagnóstico Diferencial , Divertículo do Colo/diagnóstico , Divertículo do Colo/cirurgia , Feminino , Humanos , Doenças do Íleo/diagnóstico , Doenças do Íleo/cirurgia , Doenças do Jejuno/diagnóstico , Doenças do Jejuno/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
11.
Endoscopy ; 35(8): 698-700, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12929069

RESUMO

An exceptional cause of obstructive jaundice is reported in the present case. A 51-year-old woman progressively developed jaundice with pruritus, and abdominal ultrasonography revealed dilated intra- and extrahepatic bile ducts. Endoscopic retrograde cholangiography and endoscopic ultrasonography showed a tumor in the distal common bile duct, but failed to determine the nature of the lesion, and the patient underwent a pancreaticoduodenectomy. The final diagnosis was an inflammatory pseudotumor of the common bile duct. Inflammatory pseudotumors are uncommon, without evident pathogenesis, and are described in many organs. The localization in the common bile duct is exceptional. The prognosis is good, and a more conservative approach is possible if the diagnosis is certain before surgery.


Assuntos
Doenças do Ducto Colédoco/complicações , Doenças do Ducto Colédoco/diagnóstico , Granuloma de Células Plasmáticas/complicações , Granuloma de Células Plasmáticas/diagnóstico , Icterícia Obstrutiva/diagnóstico , Icterícia Obstrutiva/etiologia , Doenças do Ducto Colédoco/terapia , Feminino , Granuloma de Células Plasmáticas/terapia , Humanos , Icterícia Obstrutiva/terapia , Pessoa de Meia-Idade
12.
Parasitol Int ; 50(3): 175-83, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11595574

RESUMO

We report the findings of a detailed temporal study on tegumental alterations in juvenile Schistosoma haematobium, induced by artemether, using scanning electron microscopy. Hamsters infected with S. haematobium cercariae for 28 days were treated intragastrically with a single dose of 300 mg/kg artemether. Groups of two hamsters were killed 24 h, 72 h and 7 days after treatment, and schistosomula were recovered from livers by perfusion and subsequent systematic examination of the tissue, before routinely processing for scanning electron microscopic examination. Most schistosomula collected 24 h after artemether administration showed severe tegumental damage, usually including swelling, fusion, vesiculation, peeling and collapse of enlarged sensory structures. After 72 h, tegumental damage had increased and schistosomula generally showed contraction with extensive swelling, erosion and peeling of the tegument. Seven days post-treatment, severe tegumental damage was only seen in a single male specimen with swelling of the worm body and destruction of the oral sucker. The other schistosomula showed only light to moderate damage, suggesting that schistosomula surviving the treatment began to recover. Our findings of tegumental damage following artemether treatment correlate with the efficacy of this novel antischistosomal drug in killing the juvenile stages of S. haematobium and complement recent findings with S. japonicum and S. mansoni.


Assuntos
Artemisininas , Schistosoma haematobium/efeitos dos fármacos , Schistosoma haematobium/ultraestrutura , Esquistossomose Urinária/tratamento farmacológico , Esquistossomicidas/farmacologia , Sesquiterpenos/farmacologia , Animais , Artemeter , Cricetinae , Feminino , Masculino , Microscopia Eletrônica de Varredura , Esquistossomose Urinária/parasitologia , Sesquiterpenos/uso terapêutico
13.
Acta Trop ; 80(1): 9-18, 2001 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11495639

RESUMO

Praziquantel and artemether are safe and efficacious antischistosomal drugs that act against different developmental stages of the parasite: praziquantel against adult worms and artemether against schistosomula. A combined treatment has been suggested as a strategy for transmission control. Recent laboratory experiments with rabbits with a mixed infection of Schistosoma japonicum parasites of different ages confirmed the effectiveness of a combination therapy. In the present work, we assessed the effect of a combined treatment on adult worms of S. japonicum and found significantly higher worm reduction rates than with a single dose of praziquantel. In a next step, we extended the study of the combined treatment to Schistosoma mansoni. A combined treatment with 75 mg/kg praziquantel and 150 mg/kg artemether was administered to hamsters infected with juvenile and adult S. mansoni. The two drugs, administered simultaneously or spaced by 6 h, 1, 3 or 7 days, resulted in significantly higher worm reduction rates than a single treatment with praziquantel. A combination therapy with increased doses of 100 mg/kg praziquantel and 300 mg/kg artemether showed very high worm reduction rates of 90% and above, however, some hamsters died in five different combined treatment experiments, suggesting that these drug concentrations were too high. We conclude that a combined treatment with praziquantel and artemether at the lower doses is safe and more effective than praziquantel alone, which forms a foundation for designing respective clinical trials in humans.


Assuntos
Anti-Helmínticos/uso terapêutico , Artemisininas , Praziquantel/uso terapêutico , Schistosoma japonicum/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/uso terapêutico , Sesquiterpenos/uso terapêutico , Administração Oral , Animais , Anti-Helmínticos/administração & dosagem , Artemeter , Cricetinae , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Masculino , Praziquantel/administração & dosagem , Coelhos , Esquistossomose Japônica/parasitologia , Esquistossomose mansoni/parasitologia , Esquistossomicidas/administração & dosagem , Sesquiterpenos/administração & dosagem , Fatores de Tempo
14.
Acta Trop ; 79(2): 135-41, 2001 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-11369306

RESUMO

Histopathological changes in juvenile Schistosoma haematobium, caused by artemether administered to the infected hamsters, were studied. Hamsters were infected with S. haematobium cercariae, and after 28 days, a single dose of artemether (300 mg/kg) was administered intragastrically. After 24 h, 72 h and 7 days, groups of two hamsters were sacrificed, and livers were removed, fixed and processed routinely, and examined by light microscopy. After 24 h, 93% of the schistosomulae examined showed degeneration, which included swelling of the tegument, adherence of inflammatory cells to the damaged tegument, collapsed and damaged intestine, and infiltration of inflammatory cells, predominantly lymphocytes. After 72 h, the intensity of damage increased, including severe swelling of the tegument, loss of definition in the internal structures, collapse of intestine accompanied by release of pigment particles to the parenchymal tissues, and emergence of dead schistosomulae. Seven days after treatment, the number of dead schistosomulae increased, and most of them developed to an early- or late stage of dead worm granuloma. Meanwhile, 12% of the schistosomulae showed a normal appearance, which suggested that those schistosomulae that had survived the treatment were recovered to normal. The results demonstrated that artemether effectively acts against the juvenile stages of S. haematobium and confirms earlier results with S. japonicum and S. mansoni.


Assuntos
Artemisininas , Fígado/efeitos dos fármacos , Schistosoma haematobium/efeitos dos fármacos , Esquistossomose Urinária/tratamento farmacológico , Esquistossomicidas/uso terapêutico , Sesquiterpenos/uso terapêutico , Animais , Artemeter , Cricetinae , Fígado/patologia , Masculino
15.
Plant Physiol ; 125(4): 1620-32, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11299344

RESUMO

In a previous paper we have shown that epsilon-(phenoxyalkanecarboxylyl)-L-Lys conjugates are potent inhibitors of amino acid transport systems and that it is possible to modulate the uptake inhibition by hydrophobic or hydrophilic additions in the 4-position of the aromatic ring (J.F. Chollet, C. Delétage, M. Faucher, L. Miginiac, J.L. Bonnemain [1997] Biochem Biophys Acta 1336: 331-341). In this report we demonstrate that epsilon-(2,4-dichlorophenoxyacetyl)-L-Lys (2,4D-Lys), one of the largest molecules of the series and one of the most potent inhibitors, is a highly permeant conjugate. Uptake of 2,4D-Lys by broad bean (Vicia faba) leaf discs is mediated by an active carrier system (Km1 = 0.2 mM; Vmax1 = 2.4 nmol x cm(-2) x h(-1) at pH 5.0) complemented by an important diffusive component. Among the compounds tested (neutral, basic, and acidic amino acids, auxin, glutathione, and sugars), only the aromatic amino acids clearly compete with 2,4D-Lys. The conjugate accumulates in the vein network, is exported toward the growing organs, and exhibits a distribution pattern different from that of the herbicide moiety. However, over time 2,4D-Lys progressively splits into 2,4D and lysine. Analyses by high-performance liquid chromatography and liquid scintillation spectrometry of the phloem sap collected from the castor bean system, used as a systemy test, indicate decreasing capacities of 2,4D, 2,4D-Lys, and glyphosate, respectively, to move from the epidermis cell wall to the sieve element. Our results show that it is possible to design synthesis of large-size xenobiotics (approximately 350 D) with a lipophilic pole, exhibiting high mobility within the vascular system.


Assuntos
Fabaceae/fisiologia , Lisina/farmacocinética , Plantas Medicinais , Xenobióticos/farmacocinética , 4-Cloromercuriobenzenossulfonato/farmacologia , Autorradiografia , Transporte Biológico/efeitos dos fármacos , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Cinética , Lisina/análogos & derivados , Lisina/síntese química , Lisina/química , Modelos Moleculares , Conformação Molecular , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/fisiologia , Cloreto de Potássio/farmacologia , Trítio , Xenobióticos/síntese química , Xenobióticos/química
16.
Trans R Soc Trop Med Hyg ; 95(1): 67-71, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11280070

RESUMO

We conducted experiments in vitro to assess the effect of artemether in combination with haemin on adult Schistosoma japonicum, S. mansoni and S. haematobium. When schistosomes were maintained in a medium containing artemether at concentrations of 20 micrograms/mL or less for 72 h, no apparent effect on the schistosomes was seen. When the medium contained 50 or 100 micrograms/mL haemin as well as artemether, the schistosomes showed decreased motor activity 2-24 h after exposure, which was followed by the staining of the whole worm body a reddish-yellow colour, dilatation of the intestine, and extensive vesiculation of the tegument. Some of the schistosomes died 24 h after exposure, and almost all died within 48-72 h. When schistosomes were exposed to the same concentrations of haemin alone, they were stained a light yellow colour but there was no apparent effect on their survival. Our findings suggest that artemether interacts with haemin to exert a toxic effect on the worms, which might be of importance in the further elucidation of the mechanism of action of artemether on schistosomes.


Assuntos
Antiprotozoários/uso terapêutico , Artemisininas , Hemina/uso terapêutico , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose mansoni/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Animais , Artemeter , Combinação de Medicamentos , Feminino , Masculino , Camundongos , Testes de Sensibilidade Parasitária , Polietilenoglicóis/uso terapêutico , Schistosoma haematobium/efeitos dos fármacos , Schistosoma japonicum/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos
17.
J Parasitol ; 86(5): 1125-32, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11128492

RESUMO

A detailed temporal examination was made of alterations induced by artemether in the tegument of adult Schistosoma mansoni worms using scanning electron microscopy (SEM). Mice infected with S. mansoni cercariae 42 days previously were treated intragastrically with artemether at a single dose of 400 mg/kg. Groups of 3 mice were killed at 24 hr, 72 hr, and 7 days after treatment; the worms were collected by perfusion and examined by SEM. Twenty-four hours after artemether treatment, focal damage to the tubercles on the tegumental surface of male worms was seen. In both male and female worms, there was focal swelling and fusion of tegumental ridges, and sometimes peeling. After 72 hr, the damage to the tegument had increased, especially in female worms, with extensive swelling, fusion, and peeling of the tegumental ridges. In the most severely damaged worms, host leukocytes were seen to be adhered to the damaged tegument. Damage to the oral sucker was also occasionally seen in both male and female worms. Seven days after treatment, the appearance of the tegument had returned to normal in some male and female worms, whereas others still showed apparent damage. The results demonstrate that artemether damages the tegument of adult S. mansoni, and the intensity of damage is more severe in female worms than in males.


Assuntos
Artemisininas , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/farmacologia , Sesquiterpenos/farmacologia , Animais , Artemeter , Feminino , Camundongos , Microscopia Eletrônica de Varredura , Schistosoma mansoni/isolamento & purificação , Schistosoma mansoni/ultraestrutura , Esquistossomose mansoni/parasitologia , Esquistossomicidas/uso terapêutico , Sesquiterpenos/uso terapêutico
18.
Int J Parasitol ; 30(9): 1001-6, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10980290

RESUMO

The drug, artemether, has been shown to be active against the juvenile stages of Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals, while it is less effective on adult worms. These findings have been confirmed in randomised controlled trials in humans. Consequently, it could be expected that artemether is also active against Schistosoma haematobium. We present here the first results from experiments assessing the effect of artemether on S. haematobium. Hamsters with a single infection received intra-gastrically an initial dose of 300 mg/kg artemether on day 14, 21 or 28, followed by further doses at varying treatment regimens. In all the treatment groups, the total and female worm reduction rates were highly significant, and ranged from 78 to 100% in hamsters harbouring juvenile schistosomes. Hamsters infected three times with S. haematobium, on days 0, 4 and 9, and repeatedly treated with artemether at the same dose as above, showed highly significant total and female worm reduction rates of between 94 and 99%. Artemether was also active against 77-day-old adult S. haematobium, since its administration on two consecutive days resulted in highly significant total and female worm reduction rates of 76-89%. Our findings confirm that artemether is also active against S. haematobium, especially the schistosomules. These results provide a basis for clinical trials in humans, for further assessment of the potential of artemether for schistosomiasis control.


Assuntos
Artemisininas , Schistosoma haematobium/efeitos dos fármacos , Esquistossomose Urinária/tratamento farmacológico , Esquistossomicidas/farmacologia , Sesquiterpenos/farmacologia , Animais , Artemeter , Côte d'Ivoire , Cricetinae , Feminino , Intestino Grosso/parasitologia , Intestino Delgado/parasitologia , Fígado/parasitologia , Masculino , Esquistossomose Urinária/parasitologia , Esquistossomicidas/uso terapêutico , Sesquiterpenos/uso terapêutico , Caramujos/parasitologia
19.
Acta Trop ; 76(2): 107-17, 2000 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-10936569

RESUMO

Praziquantel administered to the host causes damage to the tegument of Schistosoma mansoni. In this study, the effects of racemic praziquantel (Pra) and its enantiomers, levo-praziquantel (L-Pra) and dextro-praziquantel (D-Pra) were compared using scanning electron microscopy (SEM). Mice infected with S. mansoni for 49 days were treated with a single dose of Pra (300 mg/kg), L-Pra (150 mg/kg) or D-Pra (150 or 600 mg/kg). Groups of three mice were killed after 4 and 24 h, and schistosomes collected by perfusion and examined by SEM. Treatment with Pra or L-Pra, for 4 or 24 h, caused tegumental damage to S. mansoni including severe swelling, vacuolization, fusion of the tegumental ridges and loss or shortening of the spines on the tubercles, collapse and peeling. After treatment with D-Pra at 150 mg/kg, no apparent damage was observed. When the dosage was increased to 600 mg/kg, after 4 h lesions on the tegument similar to those induced by Pra or L-Pra were seen, but less severe. After 24 h, there was evidence of recovery. The study thus clearly showed that L-Pra was more active than D-Pra in causing tegumental damage. D-Pra showed a qualitatively similar activity at a higher concentration. It is possible that this effect was due at least to some extent to the small amount of L-Pra (<2%) which was present in the preparation of D-Pra used.


Assuntos
Anti-Helmínticos/farmacologia , Praziquantel/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Animais , Feminino , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Rotação Ocular , Schistosoma mansoni/ultraestrutura , Esquistossomose mansoni/sangue , Estereoisomerismo
20.
Acta Trop ; 75(3): 341-8, 2000 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-10838218

RESUMO

Alterations in the tegument of 21-day-old Schistosoma mansoni, caused by artemether administered to the infected mice, were studied using scanning electron microscopy (SEM). Mice were infected with S. mansoni cercariae, and after 21 days a single dose of artemether (400 mg/kg) was administered intragastrically. After 24, 72 h and 7 days groups of three mice were killed and the schistosomules collected by perfusion, fixed and processed routinely, and examined by SEM. After 24 h, all male and female worms examined showed alterations in the tegument, characterised by swelling, vesiculation and fusion of tegumental ridges; peeling, erosion and collapse of damaged tegumental surface, and also destruction of the oral sucker and acetabulum. After 72 h, severe damage to the tegument was seen, usually including extensive peeling, swelling and vesiculation, and host leukocytes were adhered to the damaged surface. Some worms were surrounded by clusters of host leukocytes or had even disintegrated. Seven days after treatment, some schistosomules still showed severe tegumental damage, but in some cases the damage was less than at earlier times, which suggested that those schistosomules that had survived were beginning to recover. The ability of artemether to cause severe damage to the tegument correlates with its high efficacy in killing 21-day-old schistosomules.


Assuntos
Artemisininas , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose/tratamento farmacológico , Esquistossomicidas/uso terapêutico , Sesquiterpenos/uso terapêutico , Administração Oral , Fatores Etários , Animais , Artemeter , Feminino , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Schistosoma mansoni/ultraestrutura , Esquistossomose/parasitologia , Fatores de Tempo
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