RESUMEN
Schistosomiasis represents a public health problem and praziquantel is the only drug used for treatment of all forms of the disease. Thus, the development of new anti-schistosomal agents is of utmost importance to increase the effectiveness, reduce side effects and delay the emergence of resistance. The present study was conducted to report the therapeutic efficacy of PPQ-8, a new synthetic quinoline-based compound against Schistosoma mansoni. Mice were treated with PPQ-8 at day 49 post infection using two treatment regimens (20 and 40 mg/kg). Significant reductions were recorded in hepatic (62.9% and 83.6%) and intestinal tissue egg load (57.4% and 73.5%), granuloma count (75.4% and 89.1%) and diameter (26.2% and 47.3%), in response to the drug regimens, respectively. In addition, both treatment regimens induced significant decrease in liver (23.3% and 32.8%) and spleen (37.5% and 45.3%) indices. Also, there were significant reductions in mature ova, total worm and female count, which were more prominent with the higher dose. The reduction in the level of nitric oxide in the liver by both therapeutic regimens to 22.5% and 47.2% indicates the anti-oxidant activity of PPQ-8. Bright field microscopic examination of worms recovered from infected and PPQ-8-treated mice showed nearly empty intestinal caeca with no observable changes in the tegument. Our findings hold promise for the development of a novel anti-schistosomal drug using PPQ-8, but further in vitro and in vivo studies are needed to elucidate the possible mechanism/s of action and to study the effect of PPQ-8 on other human schistosomes.
Asunto(s)
Antihelmínticos/uso terapéutico , Descubrimiento de Drogas , Quinolinas/uso terapéutico , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Animales , Antihelmínticos/síntesis química , Antioxidantes/síntesis química , Antioxidantes/uso terapéutico , Femenino , Intestinos/parasitología , Hígado/parasitología , Ratones , Ratones Endogámicos BALB C , Recuento de Huevos de Parásitos , Quinolinas/síntesis química , Bazo/parasitologíaRESUMEN
Schistosoma haematobium and Schistosoma mansoni infections have broadly overlapping geographical distributions. Praziquantel is the only treatment for human schistosomiasis, so drug tolerance and/or resistance are major concerns. Artemisinin-naphthoquine phosphate (CO-ArNp), an artemisinin-based combination therapy endorsed by the World Health Organization as a gold standard therapy for malaria, has also been identified as a promising treatment for S. mansoni. In this in vitro study, we tested the effect of 1-40 µg/ml CO-ArNp on S. haematobium worms, and inspected tegumental changes by using scanning electron microscopy (SEM), aiming to determine if this combination therapy has a broad-spectrum antischistosomal activity. Incubation of S. haematobium adults with 20 or 30 µg/ml CO-ArNp caused 100% mortality of worms within 72 or 48 h, respectively. SEM examination showed extensive tegumental alterations such as oedema, constriction, shortening and loss of spines, fissuring, sloughing and perforation, resulting in exposure of the underlying basal lamina, mainly in treated male schistosomes. Besides the well-established potent efficacy, bioavailability, tolerability and safety of the antimalarial artemisinin-naphthoquine phosphate combined therapy, these results may also suggest its possible utilization as a new broad-spectrum antischistosomal agent.
Asunto(s)
1-Naftilamina/análogos & derivados , Aminoquinolinas/farmacología , Antihelmínticos/farmacología , Artemisininas/farmacología , Schistosoma haematobium/efectos de los fármacos , 1-Naftilamina/farmacología , Animales , Reposicionamiento de Medicamentos , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Schistosoma haematobium/ultraestructuraRESUMEN
Fasciola infection (fascioliasis) appeared to be endemic in Egypt. Stool samples of fourty eight patients were coprologically diagnosed. According to Fasciola egg counting per gram stool, the severity of infection was divided into light infection in 60.5%, moderate in 27.1% and severe infection in 12.5%. No significant correlation was detected between severity of infection and patients' sex. Complete blood picture, reticylocytic count, serum iron, immunological assays as anti-nuclear, anti-smooth muscle antibody, anti-mitochondrial anti-body, anti-DNA tests and rheumatoid factor and occult blood in stool were investigated. Normocytic normochromic anaemia was detected in 62.5% of the fascioliasis patients, microcytic hypochromic anaemia in 31.3% and macrocytic one in 6.3%. Highly significant negative correlation (R = -0.68) was detected between haemoglobin concentration and egg count per gram faeces. Human fascioliasis was associated with normocytic normochromic anaemia and to a lesser extent microcytic hypochromic anemia.