115 research outputs found
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats.
"Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant
reduction of SARS-CoV-2 replication in vitro by ivermectin
concentrations not achievable with safe doses orally. Inhaled
therapy has been used with success for other antiparasitics. An
ethanol-based ivermectin formulation was administered once to 14
rats using a nebulizer capable of delivering particles with
alveolar deposition. Rats were randomly assigned into three
target dosing groups, lower dose (80-90\xC2\xA0mg/kg), higher
dose (110-140\xC2\xA0mg/kg) or ethanol vehicle only. A
toxicology profile including behavioral and weight monitoring,
full blood count, biochemistry, necropsy and histological
examination of the lungs was conducted. The pharmacokinetic
profile of ivermectin in plasma and lungs was determined in all
animals. There were no relevant changes in behavior or body
weight. There was a delayed elevation in muscle enzymes
compatible with rhabdomyolysis, that was also seen in the
control group and has been attributed to the ethanol dose which
was up to 11\xC2\xA0g/kg in some animals. There were no
histological anomalies in the lungs of any rat. Male animals
received a higher ivermectin dose adjusted by adipose weight and
reached higher plasma concentrations than females in the same
dosing group (mean C" - " 86.2\xC2\xA0ng/ml vs.
26.2\xC2\xA0ng/ml in the lower dose group and 152\xC2\xA0ng/ml
vs. 51.8\xC2\xA0ng/ml in the higher dose group). All subjects
had detectable ivermectin concentrations in the lungs at seven
days post intervention, up to 524.3\xC2\xA0ng/g for high-dose
male and 27.3\xC2\xA0ng/g for low-dose females. nebulized
ivermectin can reach pharmacodynamic concentrations in the lung
tissue of rats, additional experiments are required to assess
the safety of this formulation in larger animals.
Diseño de una metodología basada en imagen para el análisis de la arquitectura muscular
La simulación computacional de la respuesta activa y pasiva del músculo esquelético, mediante elementos finitos, requiere definir con exactitud la orientación de las fibras musculares, pues se relaciona directamente con la fuerza desarrollada por el tejido (Kumagai 2000). En este trabajo se presenta una metodología para determinar la orientación de las fibras musculares de los músculos del manguito rotador de ratón
Generation of a Sprague-Dawley-GFP rat iPS cell line
We generated a rat iPSC line called ATCi-rSD95 from transgenic Sprague-Dawley GFP fetal fibroblasts. Established ATCi-rSD95 cells present a normal karyotype, silencing of the transgenes and express pluripotency-associated markers. Additionally, ATCi-rSD95 cells are able to form teratoma with differentiated cells derived from the three germ-layers that maintain the GFP expression
Slow Release Ivermectin Formulation for Malaria Control: a Pilot Study in 80-kg Pigs
Vector control with long-lasting insecticidal nets (LLINs) and
indoor residual spraying are responsible for more than two
thirds of the reduction seen in malaria prevalence in Africa
over the last 15 years (1)....
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats
Ivermectin is a widely used antiparasitic drug with known efcacy against several single-strain RNA
viruses. Recent data shows signifcant reduction of SARS-CoV-2 replication in vitro by ivermectin
concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for
other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using
a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into
three target dosing groups, lower dose (80–90 mg/kg), higher dose (110–140 mg/kg) or ethanol vehicle
only. A toxicology profle including behavioral and weight monitoring, full blood count, biochemistry,
necropsy and histological examination of the lungs was conducted. The pharmacokinetic profle
of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes
in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with
rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose
which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any
rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher
plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/
ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had
detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for
high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic
concentrations in the lung tissue of rats, additional experiments are required to assess the safety of
this formulation in larger animals
Isolation and characterization of Sprague-Dawley and Wistar Kyoto GFP rat embryonic stem cells
We generated two rat embryonic stem cell (ESC) lines: ATCe-SD7.8 from Sprague-Dawley strain and ATCe-WK1 from Wistar Kyoto strain. Cells were marked with enhanced green fluorescent protein (eGFP) by transduction with a lentiviral vector. Cells present a normal karyotype and express pluripotency-associated markers. Pluripotency was tested in vivo with the teratoma formation assay. Cells maintain eGFP expression upon differentiation to the three-germ layers. These cells can be a useful tool for cell therapy studies and chimera generation as they can be easily tracked by eGFP expression
Nebulized ivermectin for COVID‑19 and other respiratory diseases, a proof of concept, dose‑ranging study in rats
Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals
Targeting cattle for malaria elimination: marked reduction of Anopheles arabiensis survival for over six months using a slow-release ivermectin implant formulation
BACKGROUND: Mosquitoes that feed on animals can survive and
mediate residual transmission of malaria even after most humans
have been protected with insecticidal bednets or indoor residual
sprays. Ivermectin is a widely-used drug for treating parasites
of humans and animals that is also insecticidal, killing
mosquitoes that feed on treated subjects. Mass administration of
ivermectin to livestock could be particularly useful for
tackling residual malaria transmission by zoophagic vectors that
evade human-centred approaches. Ivermectin comes from a
different chemical class to active ingredients currently used to
treat bednets or spray houses, so it also has potential for
mitigating against emergence of insecticide resistance. However,
the duration of insecticidal activity obtained with ivermectin
is critical to its effectiveness and affordability. RESULTS: A
slow-release formulation for ivermectin was implanted into
cattle, causing 40 weeks of increased mortality among Anopheles
arabiensis that fed on them. For this zoophagic vector of
residual malaria transmission across much of Africa, the
proportion surviving three days after feeding (typical mean
duration of a gonotrophic cycle in field populations) was
approximately halved for 25 weeks. CONCLUSIONS: This implantable
ivermectin formulation delivers stable and sustained
insecticidal activity for approximately 6 months. Residual
malaria transmission by zoophagic vectors could be suppressed by
targeting livestock with this long-lasting formulation, which
would be impractical or unacceptable for mass treatment of human
populations
Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae
Mass administration of endectocides, drugs that kill
blood-feeding arthropods, has been proposed as a complementary
strategy to reduce malaria transmission. Ivermectin is one of
the leading candidates given its excellent safety profile. Here
we provide proof that the effect of ivermectin can be boosted at
two different levels by drugs inhibiting the cytochrome or ABC
transporter in the mammal host and the target mosquitoes. Using
a mini-pig model, we show that drug-mediated cytochrome P450/ABC
transporter inhibition results in a 3-fold increase in the time
ivermectin remains above mosquito-killing concentrations. In
contrast, P450/ABC transporter induction with rifampicin
markedly impaired ivermectin absorption. The same
ketoconazole-mediated cytochrome/ABC transporter inhibition also
occurs outside the mammal host and enhances the mortality of
Anopheles gambiae. This was proven by using the samples from the
mini-pig experiments to conduct an ex-vivo synergistic bioassay
by membrane-feeding Anopheles mosquitoes. Inhibiting the same
cytochrome/xenobiotic pump complex in two different organisms to
simultaneously boost the pharmacokinetic and pharmacodynamic
activity of a drug is a novel concept that could be applied to
other systems. Although the lack of a dose-response effect in
the synergistic bioassay warrants further exploration, our study
may have broad implications for the control of parasitic and
vector-borne diseases
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