Sulfobetaine polymers for effective permeability into multicellular tumor spheroids (MCTSs)

Multicellular tumor spheroids (MCTSs) are attractive for drug screening before animal tests because they emulate an in vivo microenvironment. The permeability of the MCTSs and tumor tissues by the candidate...

Pharmacological Tuning of Adenosine Signal Nuances Underlying Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) roughly represents half of the cardiac failure events in developed countries. The proposed ‘systemic microvascular paradigm’ has been used to explain HFpHF presentation heterogeneity. The lack of effective treatments with few evidence-based therapeutic recommendations makes HFpEF one of the greatest unmet clinical necessities worldwide. The endogenous levels of the purine nucleoside, adenosine, increase significantly following cardiovascular events. Adenosine exerts cardioprotective, neuromodulatory, and immunosuppressive effects by activating plasma membrane-bound P1 receptors that are widely expressed in the cardiovascular system. Its proven benefits have been demonstrated in preclinical animal tests. Here, we provide a comprehensive and up-to-date critical review about the main therapeutic advantages of tuning adenosine signalling pathways in HFpEF, without discounting their side effects and how these can be seized.

Therapeutic efficacy of CT-P59 against P.1 variant of SARS-CoV-2

P.1. or gamma variant also known as the Brazil variant, is one of the variants of concern (VOC) which appears to have high transmissibility and mortality. To explore the potency of the CT-P59 monoclonal antibody against P.1 variant, we tried to conduct binding affinity, in vitro neutralization, and in vivo animal tests. In in vitro assays revealed that CT-P59 is able to neutralize P.1 variant in spite of reduction in its binding affinity against a RBD (receptor binding domain) mutant protein including K417T/E484K/N501Y and neutralizing activity against P.1 pseudoviruses and live viruses. In contrast, in vivo hACE2 (human angiotensin-converting enzyme 2)-expressing TG (transgenic) mouse challenge experiment demonstrated that a clinically relevant or lower dosages of CT-P59 is capable of lowering viral loads in the respiratory tract and alleviates symptoms such as body weight losses and survival rates. Therefore, a clinical dosage of CT-P59 could compensate for reduced in vitro antiviral activity in P.1-infected mice, implying that CT-P59 has therapeutic potency for COVID-19 patients infected with P.1 variant.

Anti-parasitic activity of nano Citrullus colocynthis and nano Capparis spinose against Trichomonas vaginalis in vitro

The use of plant extracts and the benefit of their unique properties in treating various pathogens is the return to mother nature, and an attempt to overcome the problems of side effects resulting from the use of chemical drugs and the ability of some pathogens to resist these drugs. Nanotechnology has strengthened the ability of drugs to reach the target and reduced the size and amount of dose needed for treatment.Nano-extracts of Citrullus colocynthis and Capparis spinosa at concentrations of (100,250 and 500) ppm prepared to the treatment Trichomonas vaginalis in vitro at the time (12 , 24, 72)h. Results compared with the use of 0.1% of metronidazole (500 mg).The results showed that the concentrations (100,250, 500) ppm of C. colocynthis had an inhibitory activity for the growth rate (43.77, 69.15, 89.89) at the time (12, 24 and 72) hours, respectively. The inhibitory activity of C. spinosa was (43.18, 67.41, 87.04) at the same time and concentration, compared with metronidazole (43.47, 70.40, 87.04) at the same time. Neither plants showed severe effects in hemolysis.From the results, it can be concluded that either plant can be used as an alternative to metronidazole after completing human and animal tests.

Integrative review of the use of NMDA antagonists for TBI treatment

Introduction: The kinetic energy of TBI generates mechanical deformation, which causes release of glutamate, activating ionotropic receptors, principally NMDA receptors, favoring the flow of Ca++ and Na+ into the cell, producing edema. Then, the neurotoxicity generated by glutamate release can be avoided by NMDA antagonists. Objectives: To define if NMDA antagonists are promising for the treatment of TBI by literature analysis and to verify if there are reports of adverse reactions. Methodology: The review utilized the Scielo and Pubmed databases and the keywords used were: NMDA antagonist, Brain edema and Brain injury. The review contains 5 animal tests and 5 clinical studies. Results: Animal tests: CP-98,133 minimized edema, motor damage and is promising in the treatment of memory dysfunction after TBI. The NPS 1506 reduced edema in 24h, without altering the necrosis significantly. Ketamine decreased the volume of necrosis without altering the edema. HU-211 reduced the edema slightly. Clinical studies: NPS 1506 showed a neuroprotective profile and no serius effects. Traxoprodil decreased the mortality rate by 7%. CP-101.606 improved the patient’s condition, without adverse effects. Conclusion: Although NMDA antagonists demonstrate effectiveness in TBI treatment, more studies about adverse effects and efficiency are still needed. Among those analyzed, traxoprodil, NPS-1506 and CP-101.606 still don’t present serious adverse effects and demonstrate effectiveness, proving promising for new studies.