Schistosomiasis is a major endemic disease that affects hundreds of millions worldwide. Since the treatment and control of this parasitic disease rely on a single drug, praziquantel, it is imperative ...that new effective drugs are developed. Here, we report that phytol, a diterpene alcohol from chlorophyll widely used as a food additive and in medicinal fields, possesses promising antischistosomal properties in vitro and in a mouse model of schistosomiasis mansoni.
In vitro, phytol reduced the motor activity of worms, caused their death and confocal laser scanning microscopy analysis showed extensive tegumental alterations in a concentration-dependent manner (50 to 100 µg/mL). Additionally, phytol at sublethal doses (25 µg/mL) reduced the number of Schistosoma mansoni eggs. In vivo, a single dose of phytol (40 mg/kg) administered orally to mice infected with adult S. mansoni resulted in total and female worm burden reductions of 51.2% and 70.3%, respectively. Moreover, phytol reduced the number of eggs in faeces (76.6%) and the frequency of immature eggs (oogram pattern) was significantly reduced. The oogram also showed increases in the proportion of dead eggs. Confocal microcopy studies revealed tegumental damage in adult S. mansoni recovered from mice, especially in female worms.
The significant reduction in parasite burden by this chlorophyll molecule validates phytol as a promising drug and offers the potential of a new direction for chemotherapy of human schistosomiasis. Phytol is a common food additive and nonmutagenic, with satisfactory safety. Thus, phytol has potential as a safe and cost-effective addition to antischistosomal therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Considering the current state of the worldwide pandemic, it is still common to encounter people wearing face protection masks. Although a safety measure against COVID-19, face masks might be ...compromising our capacity for face recognition. We conducted an online study where 140 participants observed masked and unmasked faces in a within-subjects design and then performed a recognition memory task. The best performance was found when there were no masks either at study and test phase, i.e., at the congruent unmasked condition. The worst performance was found for faces encoded with a mask but tested without it (i.e., masked-unmasked incongruent condition), which can be explained by the disruption in holistic face processing and the violation of the encoding specificity principle. Interestingly, considering the unmasked-masked incongruent condition, performance was probably affected by the violation of the encoding specificity principle but protected by holistic processing that occurred during encoding.
•Scaling-up restoration implies increasing the number and average size of projects.•Restoration demands: technology, training, clear laws and economic instruments.•Restoration needs a broad network ...of stakeholders in both public and private forums.•Restoration involves both economic and social investments over a long period.
Ongoing conversion of tropical forests makes it urgent to invest in ecological restoration on grand scales in order to promote biodiversity conservation and ecosystem services. The 4-year old Atlantic Forest Restoration Pact (AFRP) aims to restore 15,000,000ha of tropical forest in 40 years. The approaches and lessons learned appear transferable, and could help achieve the global restoration targets. Fundamental prerequisites for success include: effective technology undergoing continuous improvement, ongoing teaching, outreach and capacity-building efforts, presence of local intelligentsia, maintaining a clear and transparent legal environment, and presence of effective economic instruments and incentives for landowners. These prerequisites can be achieved by expanding and strengthening the network of stakeholders both in public and private forums that must be aware of macro-economic and social/cultural shifts and trends which may provide opportunities and impose constraints to further restoration activities. Finally, environmental regulations imposing habitat protection and restoration are usually beyond individual land-owners’ possibilities and level of interest. Therefore, forest restoration, even in a biodiversity hotspot, must be approached as a potentially sustainable economic activity. Otherwise, private landowners, and most other stakeholders, will not persevere.
Cumulative data suggest that neuroinflammation plays a prominent role in Alzheimer's disease (AD) pathogenesis. The purpose of this work was to assess if patients with AD present a specific ...cerebrospinal fluid (CSF) cytokine profile and if it correlates to disease progression. We determined the levels of 27 cytokines in CSF of patients with AD and compared them with patients with frontotemporal dementia and nondemented controls. In addition, we correlated the cytokine levels with cognitive status and disease progression after 12 months. Patients with AD had higher levels of proinflammatory and anti-inflammatory cytokines (eotaxin, interleukin IL-1ra, IL-4, IL-7, IL-8, IL-9, IL-10, IL-15, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, platelet-derived growth factor, tumor necrosis factor alfa) compared to nondemented controls. There was a negative correlation between the disease progression and the levels of several cytokines (IL-1β, IL-4, IL-6, IL-9, IL-17A, basic fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma, macrophage inflammatory proteins-1β). To the best of our knowledge, this is the first study reporting a “protective” role of the upregulation of specific intrathecal cytokine levels in AD. This finding supports that a fine “rebalancing” of the immune system represents a new target in AD therapeutic approach.
•AD patients have high levels of pro- and anti-inflammatory cytokines in the CSF.•CSF inflammatory changes are less prominent in patients with frontotemporal dementia.•Pro- and anti-inflammatory cytokines correlated positively with cognition in AD patients.•Cytokine levels correlated negatively with disease progression in AD patients.
Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, ...praziquantel. Since funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, from a screening of 13 marketed diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects on
and
in a murine model of schistosomiasis.
, spironolactone at low concentrations (<10 µM) is able to alter worm motor activity and the morphology of adult schistosomes, leading to parasitic death.
, oral treatment with spironolactone at a single dose (400 mg/kg) or daily for five consecutive days (100 mg/kg/day) in mice harboring either patent or prepatent infections significantly reduced worm burden, egg production, and hepato- and splenomegaly (
0.05 to
0.001). Taken together, with the safety profile of spironolactone, supported by its potential to affect schistosomes, these results indicate that spironolactone could be a potential treatment for schistosomiasis and make it promising for repurposing.
Lissencephaly with cerebellar hypoplasia (LCH) is a rare variant form of lissencephaly, its distinctive neuroradiological phenotype being an important investigation clue regarding the potential ...involved genes, including variants in RELN gene. We report on a case of LCH whose clinical and neuroradiological features led to the identification of a homozygous pathogenic variant in RELN gene that has not been previously reported in the scientific literature.
Background
Left ventricular (LV) lead placement is the most challenging aspect of cardiac resynchronization therapy (CRT) device implantation, with a failure rate of up to 10% due to complex coronary ...anatomies. We describe a modified snare technique for LV lead placement and evaluate its safety and efficacy in cases when standard methods fail.
Methods and Results
A prospective study was conducted of patients indicated for a CRT implant. When LV lead delivery to the target vessel failed using standard techniques, a modified snare technique was employed. Patients were evaluated every 6 months. From 2015 to 2019, 566 CRTs were implanted (26.1% female, 72 ± 10.2 years old, follow‐up duration 18.9 ± 15.8 months). The standard LV implant technique failed in 94 cases (16.6%), of which the modified snare technique was successful in 92 (97.9%). There were no differences between the modified snare and standard techniques in the rates of 30‐day postimplant CRT all‐cause mortality (3.2% vs. 1.7%, p = .33), 4‐year all‐cause mortality (15.9% vs. 15.5%, p = .49), or major acute complications (7.4% vs. 3.8%, p = .12). However, the 4‐year procedural reintervention rate was lower with the modified snare technique (3.2% vs. 10.2%, p < .05), specifically LV implant failure or dislodgement rates (0% vs. 5.3%, p < .05), improving the response rate (71.8% vs. 55.1%, p < .05).
Conclusions
For challenging coronary sinus anatomies that preclude LV lead placement by standard methods, this modified snare alternative was safe and effective, with comparable mortality and complications, but significantly lower procedural reintervention and higher response rates.
In recent years, a class of oxindole-copper and -zinc complex derivatives have been reported as compounds with efficient proapoptotic activity toward different tumor cells (e.g., neuroblastomas, ...melanomas, monocytes). Here we assessed the efficacy of synthesized oxindole-copper(II), -zinc(II), and -vanadyl (VO(2+)) complexes against adult Schistosoma mansoni worms. The copper(II) complexes (50% inhibitory concentrations of 30 to 45 μM) demonstrated greater antischistosomal properties than the analogous zinc and vanadyl complexes regarding lethality, reduction of motor activity, and oviposition.
In many human-modified tropical landscapes, biodiversity conservation and the provision of ecosystem services require large-scale restoration initiatives. Such initiatives must be able to augment the ...amount and the quality of remaining natural habitats. There is thus a growing need for long-term, multi-stakeholder and multi-purpose initiatives that result in multiple ecological and socioeconomic benefits at the biome scale. The Atlantic Forest Restoration Pact (AFRP) is a coalition of 260+ stakeholders, including governmental agencies, private sector, NGOs and research institutions, aimed at restoring 15 million ha of degraded and deforested lands by 2050. By articulating, and then integrating common interests, this initiative has allowed different sectors of society to implement an ambitious vision and create a forum for public and private concerns regarding forest restoration. The AFRP adopts a set of governance tools so multiple actors can implement key processes to achieve long-term and visionary restoration goals. Having overcome some initial challenges, AFRP now has to incorporate underrepresented stakeholders and enhance its efforts to make forest restoration more economically viable, including cases where restoration could be less expensive and profitable. The AFRP experience has resulted in many lessons learned, which can be shared to foster similar initiatives across tropical regions.
Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development ...of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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