Schistosomiasis is one of the world's greatly neglected tropical diseases, and its control is largely dependent on a single drug, praziquantel. Here, we report the in vitro effect of piplartine, an amide isolated from Piper tuberculatum (Piperaceae), on Schistosoma mansoni adult worms. A piplartine concentration of 15.8 μM reduced the motor activity of worms and caused their death within 24h in a RPMI 1640 medium. Similarly, the highest sub-lethal concentration of piplartine (6.3 μM) caused a 75% reduction in egg production in spite of coupling. Additionally, piplartine induced morphological changes on the tegument, and a quantitative analysis carried out by confocal microscopy revealed an extensive tegumental destruction and damage in the tubercles. This damage was dose-dependent in the range of 15.8-630.2 μM. At doses higher than 157.6 μM, piplartine induced morphological changes in the oral and ventral sucker regions of the worms. It is the first time that the schistosomicidal activity has been reported for piplartine.
This randomized, multicenter clinical trial evaluated the effectiveness of 2 treatments for deep caries lesions - partial caries removal (PCR) and stepwise excavation (SW) - with respect to the primary outcome of pulp vitality for a 3-year follow-up period. Inclusion criteria were as follows: patients with permanent molars presenting deep caries lesions (lesion affecting ≥ 1/2 of the dentin on radiographic examination), positive response to a cold test, absence of spontaneous pain, negative sensitivity to percussion, and absence of periapical lesions (radiographic examination). Teeth randomly assigned to PCR (test) received incomplete caries removal and filling in a single session. Outcome success was evaluated by assessment of pulp vitality, determined by pulp sensitivity to a cold test and the absence of periapical lesions. Data were analyzed by a Weibull regression model with shared frailty term (survival analysis). At baseline, 299 treatments were executed: PCR, 152 and SW, 147. By the end of the 3-year follow-up period, 213 teeth had been evaluated. Adjusted survival rates were 91% for PCR and 69% for SW (p = 0.004). These results suggest that there is no need to re-open a cavity and perform a second excavation for pulp vitality to be preserved (Clinical trials registration NCT00887952).
1 The coexistence of both inhibitory A 1 and facilitatory A 2 adenosine receptors in the rat myenteric plexus prompted the question of how adenosine activates each receptor subtype to regulate cholinergic neurotransmission. 2 Exogenously applied adenosine (0.3-300 mM) decreased electrically evoked [ 3 Increasing endogenous adenosine levels, by the addition of (1) the adenosine precursor AMP (30-100 mM), (2) the adenosine kinase inhibitor 5 0 -iodotubercidin (10 mM) or (3) inhibitors of adenosine uptake (dipyridamole, 0.5 mM) and of deamination (erythro-9(2-hydroxy-3-nonyl)adenine, 50 mM), enhanced electrically evoked [ ) attenuated endogenous adenosine formation from AMP, analysed by HPLC, the corresponding reduction in [ 3 H]ACh release only became evident when stimulation of the myenteric plexus was prolonged to over 250 s. 5 In summary, we found that endogenously generated adenosine plays a predominantly tonic facilitatory effect mediated by prejunctional A 2A receptors. Extracellular deamination and cellular uptake may restrict endogenous adenosine actions to the neuro-effector region near the release/ production sites.
Schistosomiasis is one of the most important parasitic infections in humans that occur in many tropical and subtropical countries. Currently, the control of schistosomiasis rests with a single drug, praziquantel, which is effective against adult worms but not the larval stages. Recent studies have shown that piplartine, an amide isolated from plants of the genus Piper (Piperaceae), reveals interesting antischistosomal properties against Schistosoma mansoni adult worms. Here, we report the in vitro antischistosomal activity of piplartine on S. mansoni schistosomula of different ages (3 h old and 1, 3, 5, and 7 days old), and examine alterations on the tegumental surface of worms by means of confocal laser scanning microscopy. Piplartine at a concentration of 7.5 μM caused the death of all schistosomula within 120 h. The lethal effect occurred in a dose-dependent manner and was also dependent on the age of the parasite. Microscopy observation revealed extensive tegumental destruction, including blebbing, granularity, and a shorter body length. This report provides the first evidence that piplartine is able to kill schistosomula of different ages and reinforce that piplartine is a promising compound that could be used for the development of new schistosomicidal agent.
Schistosomiasis, caused by blood flukes of the genus Schistosoma, still imposes a considerable public health burden on large parts of the world. The control of this disease depends almost exclusively on the drug praziquantel, and there are no alternative drugs in sight. Natural compounds have recently attracted significant attention due to their relevance to parasitic infection and potential development into new therapeutic agents. Epiisopiloturine is an imidazole alkaloid isolated from the leaves of Pilocarpus microphyllus (Rutaceae), a native plant from Brazil. Here, we report the in vitro effect of this drug on the survival time of Schistosoma mansoni of different ages, such as 3 h old and 1, 3, 5, and 7 days old schistosomula, 49-day-old adults, and on egg output by adult worms. Epiisopiloturine at a concentration of 300 μg/mL caused the death of all schistosomula within 120 h. Extensive tegumental alterations and death were observed when adult schistosomes had been exposed to 150 μg/mL of the epiisopiloturine. At the highest sub-lethal dose of alkaloid (100 μg/mL), a 100% reduction in egg laying of paired adult worms was observed. Additionally, epiisopiloturine showed selective antischistosomal activity and exhibited no cytotoxicity to mammalian cells. This report provides the first evidence that epiisopiloturine is able to kill S. mansoni of different ages and inhibit worm egg laying.
Schistosomiasis is a neglected tropical disease that remains a considerable public health problem worldwide. Since the mainstay of schistosomiasis control is chemotherapy with a single drug, praziquantel, drug resistance is a concern. Here, we examined the in vitro effects of dermaseptin 01 (DS 01), an antimicrobial peptide found in the skin secretion of frogs of the genus Phyllomedusa, on Schistosoma mansoni adult worms. DS 01 at a concentration of 100 μg/ml reduced the worm motor activity and caused the death of all worms within 48 h in RPMI 1640 medium. At the highest sublethal concentration of antimicrobial peptide (75 μg/ml), a 100% reduction in egg output of paired female worms was observed. Additionally, DS 01 induced morphological alterations on the tegument of S. mansoni, and a quantitative analysis carried out by confocal microscopy revealed extensive destruction of the tubercles in a dose-dependent manner over the concentration range of 50-200 μg/ml. It was the first time that an anthelmintic activity towards schistosomes has been reported for a dermaseptin.
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