Low Carbohydrate Diets in Cancer Therapeutics: Current Evidence

Low carbohydrate diets have a promising mechanistic rationale in the treatment of cancer with favorable preclinical data. The strongest data suggest synergistic effects of dietary interventions with traditional cancer therapies. Recent prospective clinical trials suggest that low carbohydrate diets are safely and feasibly added within a busy oncology clinic, with hopeful additive effects in treatment enhancement.

Preparation of a Nonclinical Overview Based on Scientific Literature

Current requirements for the registration dossier include submission of a preclinical (nonclinical) overview, including scientific literature data on preclinical studies and actual preclinical data on the medicinal product. For some groups of medicines, scientific literature data may be used instead of actual preclinical data, which may be redundant. One of the important functions of the scientific literature review is the analysis of updated preclinical information on the medicinal product, which reflects the product’s characteristics, supports conclusions on its efficacy or safety, and may affect the results of the benefit/risk assessment. The aim of the study was to determine the optimal format for presenting scientific literature data in a nonclinical overview that would reflect the methodological aspects of preclinical pharmacology and toxicology studies of medicines. The authors analysed the regulations of the Russian Federation and the Eurasian Economic Union containing requirements for the scientific literature review submitted instead of actual preclinical data as part of the registration dossier for a medicinal product. The authors also considered potential difficulties in preparing a nonclinical overview based on scientific literature. In order to systematise scientific literature data, it is recommended to provide pharmacodynamic, pharmacokinetic, and toxicological data using a format consistent with the common technical document. The proposed recommendations help to harmonise the process of preparation and design of a nonclinical overview which should contain data and facts enabling a reasoned assessment of the benefit/risk ratio. The standardised format of literature data presentation will help the developer prepare an adequate nonclinical overview and will speed up assessment of clinical trial or marketing authorisation applications.

Efficacy of Resveratrol in Male Urogenital Tract Dysfunctions: An Evaluation of Preclinical Data

Resveratrol is a polyphenol found naturally in fruits and plants. Recently, studies in humans and animal models have suggested beneficial properties of this polyphenol, such as improvements to metabolic and lipid profiles, along with antioxidant, anti-inflammatory and antiproliferative effects. In the urogenital tract (UGT), resveratrol has also been tested clinically and experimentally as a therapeutic drug in several diseases; however, the translational efficacy of resveratrol, especially in UGT, is still a matter of debate. In the present review, we address the preclinical efficacy of resveratrol in UGT-related dysfunctions, focusing on lower urinary tract symptoms, noncancerous prostatic disease (benign prostatic hyperplasia and prostatitis) and erectile dysfunction. In vitro studies indicate that resveratrol reduces inflammatory markers and oxidative stress, and improves endothelial function in UGT organs and cells isolated from humans and animals. Despite displaying low oral bioavailability, in vivo administration of resveratrol largely improves erectile dysfunction, benign prostatic hyperplasia, prostatitis and voiding impairments, as evidenced in different animal models. Resveratrol also acts as a microbiota modulator, which may explain some of its beneficial effects in vivo. In contrast to the large amount of preclinical data, there are insufficient clinical trials to establish resveratrol treatment efficacy in human UGT-related diseases. In summary, we provide an overview of the in vivo and in vitro efficacy of resveratrol in animal and human UGT dysfunctions, which may support future clinical trials.

Synergistic Interaction in the Analgesic-Like Effects of Maqui Berry and Citrus Is Antagonized by Sweeteners

Although physiologically pain has a protective function, in many diseases, it is one of the most prominent symptoms. Today, new trends are focused on finding more natural alternatives to conventional treatments to alleviate it. Thereby, the purpose of this investigation was to obtain preclinical data of the antinociceptive properties of a lyophilized obtained from a newly designed maqui–citrus beverage alone and added with different sweeteners. To achieve this objective, maqui berry and citrus pharmacological activity were studied separately, as well as the interaction of both ingredients. In addition, due to the controversy generated regarding the intake of sugars, related to different metabolic diseases, the influence of different sweeteners (stevia, sucralose, or sucrose) was studied to determine their possible influence on the bioactive compounds of this product. For the attainment of our goals, a pharmacological evaluation, using the 1% formalin test, a nociceptive pain model in mice, was performed by using a sub-efficacious dosage of Maqui (25 mg/kg, i.p.) alone and combined with citrus, and then compared with the effects obtained in the presence of the different sweeteners. As a result, the antinociceptive response of the maqui was synergized in the presence of citrus in the neurogenic and inflammatory phases of the formalin test. However, this response was partially or totally reduced in the presence of the sweeteners. Our study gives preclinical evidence that a combination of maqui and citrus might exert beneficial actions to relieve pain, whereas the presence of sweeteners could reduce or avoid it.

Why Remdesivir Failed: Preclinical Assumptions Overestimate the Clinical Efficacy of Remdesivir for COVID-19 and Ebola

Remdesivir is a nucleoside monophosphoramidate prodrug that has been FDA-approved for COVID-19. However, the clinical efficacy of remdesivir for COVID-19 remains contentious, as several trials have not found statistically significant differences in either time to clinical improvement or mortality between remdesivir-treated and control groups. Similarly, the inability for remdesivir to provide a clinically significant benefit above other investigational agents in patients with Ebola contrasts with strong, curative preclinical data generated in rhesus macaque models. For both COVID-19 and Ebola, significant discordance between the robust preclinical data and remdesivir’s lackluster clinical performance have left many puzzled. Here, we critically evaluate the assumptions of the models underlying remdesivir’s promising preclinical data and show that such assumptions over-predict efficacy and minimize toxicity of remdesivir in humans. Had the limitations of in vitro drug efficacy testing and species differences in drug metabolism been considered, the underwhelming clinical performance of remdesivir for both COVID-19 and Ebola would have been fully anticipated.