Mass spectrometry analyses carried out on mass spectrometers equipped with soft ionization sources demonstrated their utility in the assessment of the formation of noncovalent complexes and the ...localization of the binding sites. Direct analyses by mass spectrometry of the noncovalent complex formed in acidic and mildly acidic environments by amyloid beta (1–40) peptide and oleuropein have been previously described, and, in several studies, the absorption, metabolism, excretion, and the implications in the prevention and therapy of Alzheimer’s disease of oleuropein have been investigated. Our paper presents modifications of the method previously employed for noncovalent complex observation, namely, the amyloid beta (1–40) pretreatment, followed by an increase in the pH and replacement of the chemical environment from ammonium acetate to ammonium bicarbonate. The formation of noncovalent complexes with one or two molecules of oleuropein was detected in all chemical solutions used, and the amyloid beta (17–28) binding site was identified via proteolytic experiments using trypsin prior to and after noncovalent complex formation. Our results highlight the importance of further studies on the effect of oleuropein against amyloid beta aggregation.
The conundrum of
's applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization ...of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified,
L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified
L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified
L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain.
Alzheimer's Disease affects approximately 33 million people worldwide and is characterized by progressive loss of memory at the cognitive level. The formation of toxic amyloid oligomers, ...extracellular amyloid plaques and amyloid angiopathy in brain by amyloid beta peptides are considered a part of the identified mechanism involved in disease pathogenesis. The optimal treatment approach leads toward finding a chemical compound able to form a noncovalent complex with the amyloid peptide thus blocking the process of amyloid aggregation. This direction gained an increasing interest lately, many studies demonstrating that mass spectrometry is a valuable method useful for the identification and characterization of such molecules able to interact with amyloid peptides. In the present review we aim to identify in the scientific literature low molecular weight chemical compounds for which there is mass spectrometric evidence of noncovalent complex formation with amyloid peptides and also there are toxicity reduction results which verify the effects of these compounds on amyloid beta toxicity towards cell cultures and transgenic mouse models developing Alzheimer's Disease.
Abstract Chemotherapy-induced neuropathic pain (CINP), a condition with unmet treatment needs, affects over half of cancer patients treated with chemotherapeutics. Researchers have recently focused ...on the endocannabinoid system because of its critical role in regulating our bodies' most important functions, including pain. We used in vitro and in vivo methods to determine the toxicity profile of a synthetic cannabinoid, JWH-182, and whether it could be potentially effective for CINP alleviation. In vitro, we evaluated JWH-182 general toxicity, measuring fibroblast viability treated with various concentrations of compound, and its neuroprotection on dorsal root ganglion neurons treated with paclitaxel. In vivo, we performed an evaluation of acute and 28-day repeated dose toxicity in mice, with monitoring of health status and a complete histopathological examination. Finally, we evaluated the efficacy of JWH-182 on a CINP model in mice using specific pain assessment tests. JWH-182 has an acceptable toxicity profile, in both, in vitro and in vivo studies and it was able to significantly reduce pain perception in a CINP model in mice. However, the translation of these results to the clinic needs further investigation.
Recently, numerous side effects of synthetic drugs have lead to using medicinal plants as a reliable source of new therapy. Pain is a global public health problem with a high impact on life quality ...and a huge economic implication, becoming one of the most important enemies in modern medicine. The medicinal use of plants as analgesic or antinociceptive drugs in traditional therapy is estimated to be about 80% of the world population. The Lamiaceae family, one of the most important herbal families, incorporates a wide variety of plants with biological and medical applications. In this study, the analgesic activity, possible active compounds of Lamiaceae genus, and also the possible mechanism of actions of these plants are presented. The data highlighted in this review paper provide valuable scientific information for the specific implications of Lamiaceae plants in pain modulation that might be used for isolation of potentially active compounds from some of these medicinal plants in future and formulation of commercial therapeutic agents.
This study describes granulocytic anaplasmosis in two dogs naturally infected with
. The 3-year-old dogs (male and female) came from the same household and were referred to the Faculty of Veterinary ...Medicine in Iasi for blood donation. They were subject to standard routine tests: haematology blood test, blood smear, and serological tests (VETSCAN
FLEX4 and IDEXX SNAP 4Dx Plus). The female dog had no medical problems, while the male dog experienced joint pain. The blood smear was negative for tick-borne pathogens, and the haematology findings indicated thrombocytopenia in both dogs, with the male dog also displaying eosinophilia. The two dogs were mildly positive in the ELISA tests for the detection of
spp. antibodies; therefore, the blood samples were tested using the qRT-PCR method for
and
. The qRT-PCR result was negative for
, but it was positive for
. The treatment consisted of the administration of doxycycline for 28 days. In conclusion, the high number of cases with non-specific clinical signs, the different sensitivity and specificity of the immunochromatographic serological tests, as well as the possibility of confusing the morula during the cytological examination, make the molecular test mandatory for precise diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Electroencephalography (EEG) is an objective diagnostic tool in the evaluation of cerebral functionality, both in human and veterinary medicine. For EEG acquisition, different types of electrodes are ...used, as long as they have no impact on the recorded background activity. However, to date, the influence of electrode type on quantitative EEG and cerebral coherence has not been investigated. Twenty EEG traces (ten with needle electrodes and ten with disk electrodes) were recorded from ten mesocephalic vigil dogs in a monopolar montage. Values for interhemispheric coherence for each frequency band were compared between stainless needle and silver disk electrodes traces. Our results show that the values of interhemispheric coherence in vigil dogs are depending of the type of electrodes used in EEG recordings. In the frontal (FP) channel, for delta and theta frequency bands, the registered coherence is significantly higher when stainless needle electrodes are used. Our results might have important consequences in the field of canine neurology and applied neuroscience, as the frontal channel analysis is preferred in aging and behavior studies.
Canine idiopathic head tremor syndrome (CIHTS) represents a benign condition characterized by episodic, uncontrolled movement of the head. Even though the condition might be an expression of a ...partial motor epilepsy, to date, there is a limited number of studies describing the electroencephalographic features. In this report, we describe the case of a dog diagnosed with partial motor epilepsy resembling CIHTS symptomatology, a new slow spike-wave complex pattern similar to that of Lennox-Gastaut syndrome in humans identified on electroencephalographic examination. We also studied the efficacy of phenobarbitone therapy over a period of two years.
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