Antiviral and antibacterial activity of hand sanitizer and surface disinfectant formulations.

Emergent diseases caused by viral and bacterial infections have proven to be a current and future challenge. The occurrence of these diseases is usually accompanied by the lack of vaccines and dedicated therapies leaving prevention as the best strategy to adopt. In that context, and apart from confinement and physical distancing measures, an increase in hygiene actions, namely hand and surface cleaning and disinfection can reduce the infection spread originated from our day-to-day routines. However, during crisis situations the high disinfectants demand can very likely lead to having them running out of stock. This impels many individuals and companies to produce their own disinfectants. Here, we explore the main components of a disinfection formulation, both for hand-rub and surface cleaning. Alcohol and non-alcohol based formulations are described, including the possibility to fine tune the properties of the final product in order to increase public acceptance while maintaining product efficacy. The action mechanisms of the main active principles are also described conjugating information from experimental and theoretical data. Overall, the main aspects to develop a disinfectant formulation are addressed, as well as their function, helping formulation developers to better understand the impact of their choices.

Acupuncture and electroacupuncture for anxiety disorders: A systematic review of the clinical research.

Anxiety disorders are one of the most common mental health concerns with a major contribution to the global burden of disease. When not treated, anxiety can be aggravated to more serious and complicated health problems. Pharmacology and psychotherapy stand for the conventional treatment for anxiety disorders but these present limited efficacy, especially in the case of chronic anxiety, with high relapse rates and often causing adverse side effects. Clinical research studies render acupuncture as a valid treatment therapy for anxiety disorders without significant adverse effects. The objective of this paper is to review the literature on the effectiveness of acupuncture and electroacupuncture for the treatment of patients with anxiety disorders in order to find strong scientific evidence for its regular practice in Western culture. The systematic review of the clinical research was focused on published clinical trials (controlled, randomized and non-randomized) regarding the treatment of anxiety with acupuncture. Only clinical trials where anxiety was treated as the therapeutic target, and not as a secondary measurement or being associated with other health condition or disease, were considered. Two authors extracted the data independently and exclusion and inclusion criteria were set. The search rendered 1135 papers addressing anxiety as a primary therapeutic target. After review, 13 papers were identified to match exclusion and inclusion criteria and were selected for this analysis. Methodology, design, and quality of the research were highly variable and are discussed and compared. Overall, there is good scientific evidence encouraging acupuncture therapy to treat anxiety disorders as it yields effective outcomes, with fewer side effects than conventional treatment. More research in this area is however needed.

Increased breast cancer cell toxicity by palladination of the polyamine analogue N (1),N (11)-bis(ethyl)norspermine.

Breast cancer is one of the most common malignant tumor forms among women and many women succumb to their disease. Thus, new anticancer agents that can efficiently improve patient survival are of the utmost importance. In this study, the effects of the polyamine analogues N (1),N (11)-bis(ethyl)norspermine (BENSpm) and N (1)-cyclo-propylmethyl-N (11)-ethylnorspermine (CPENSpm) and the synthesized dinuclear complexes Pd2BENSpm (Pd-BENSpm), Pt2CPENSpm (Pt-CPENSpm) and Pd2Spm (Pd-Spm) were investigated in normal-like breast epithelial MCF-10A cells and the breast cancer cell lines JIMT-1 and L56BR-C1. The overall data show that palladination of BENSpm resulted in enhanced cytotoxicity, in contrast to platination of CPENSpm that reduced cytotoxicity, which might be explained by differences in the cellular uptake of Pd-BENSpm and Pt-CPENSpm. BENSpm and Pd-BENSpm treatment reduced the CD44(+)CD24(-) putative cancer stem cell population, evaluated by flow cytometry. Furthermore, Pd-BENSpm was the most efficient compound regarding induction of DNA damage and decrease in colony formation in soft agar. Pt-CPENSpm and Pd-Spm, on the other hand, were shown to be the least toxic compounds of all tested. Pd-Spm efficiently reduced the cellular glutathione levels, which probably was a consequence of its metabolic inactivation by conjugation to this endogenous thiol. The normal-like cells were found to be less sensitive to the agents than the breast cancer cells. Our findings show that Pd-BENSpm exhibits promising anticancer effects which render it suitable for further optimization to develop a new metal-based chemotherapeutic drug for breast cancer treatment.

Biologic activity of a dinuclear Pd(II)-spermine complex toward human breast cancer.

A dinuclear palladium-based complex (Pd(2) -Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF-7 and MDA-MB-231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd(2) -Spm is more effective against the estrogen receptors [ER(-)] cell line MDA-MB-231, while cDDP displayed better results for the ER(+) MCF-7 cell line. It was shown that, like cDDP, Pd(2) -Spm triggers phosphorylation of H2AX, indicating that this compound damages DNA. Apart from DNA, Pd(2) -Spm also targets the cytoskeleton having a greater impact on cell morphology than cDDP. Pd(2) -Spm and cDDP have opposite antiproliferative activities in the presence of the PI3K inhibitor wortmannin. Furthermore, Pd(2) -Spm at an optimized concentration displays a rapid antiproliferative effect as opposed to cDDP, which seems to have a slower kinetics. The results point to a distinct mechanism of action for each of these complexes, which may explain their synergistic action when coadministrated.

Conformational and vibrational study of cis-diamminedichloropalladium(II).

A conformational and vibrational analysis of cis-diamminedichloropalladium(ii) (cDDPd) is reported. Several theoretical methods (from Hartree-Fock to Møller-Plesset and Density Functional Theory) combined with different all-electron basis-sets are evaluated, in view of determining the best suited strategy for accurately representing this molecule. This choice is based on the best compromise between accuracy and computational requirements. Different scaling models were tested for obtaining the best scaling schemes of the vibrational modes to be used in this type of inorganic systems. The structural parameters and vibrational results predicted by the calculations are compared with the corresponding experimental data, namely X-ray structure and vibrational spectra. Finally, a complete assignment of the cDDPd vibrational spectra is presented.

Characterization of Pt-, Pd-spermine complexes for their effect on polyamine pathway and cisplatin resistance in A2780 ovarian carcinoma cells.

We have previously showed that platinum drugs up-regulate SSAT and SMO and down-regulate ODC and SAMDC in the polyamine pathway. Several studies including our own established that platinum drugs combined with polyamine analog DENSPM produces synergistic increase in SSAT activity with polyamine depletion. Since polyamine pathway is an important therapeutic target, we investigated whether agents containing both platinum and polyamines have similar effects on the polyamine pathway. Two complexes i) Pt-spermine with two cisplatin molecules linked to a spermine in the center and ii) Pd-spermine with similar structure i, but Pd (II) substituted for Pt (II) were analyzed with respect to their effect on the expression of genes in polyamine pathway, SSAT and SMO protein expression, SSAT activity and polyamine pools. Pt-, Pd-spermine complexes induced significant down-regulation of SMO, arginase 2 and NRF-2, with no change in SSAT, while cisplatin as a single agent or in combination with DENSPM induced significant up-regulation of SSAT and SMO. The SSAT activity was not induced by either Pt- or Pd-spermine in A2780 cells; SMO protein levels were significantly elevated compared to the no-drug control and to a similar extent as cisplatin/DENSPM. The Pd-spm treatment induced a fall in putrescine levels to 33%, spermidine to 62% and spermine to 72% while Pt-spm did not induce such a decline. Comparative cytotoxicity studies in A2780 cells indicated the potency to be cisplatin> Pd-Spm>Pt-Spm. Although both complexes exhibit a lower potency, the degree of resistance itself is much lower for Pt-spermine and Pd-spermine in that order (2.5 and 7.5, respectively) compared to cisplatin ( approximately 12) as tested in cisplatin resistant A2780/CP cells. These studies suggest that Pd (II)-polyamine complexes may constitute a promising group of inorganic compounds for further studies in the development of novel chemotherapy/adjuvant chemotherapy strategies.

Helianthus tuberosus and polyamine research: past and recent applications of a classical growth model.

The earliest studies concerning polyamines (PAs) in plants were performed by using in vitro cultured explants of Helianthus tuberosus dormant tuber. This parenchyma tissue was particularly useful due to its susceptibility to several growth substances, including PAs. During tuber dormancy, PA levels are too low to sustain cell division; thus Helianthus represents a natural PA-deficient model. When cultivated in vitro in the presence of auxins, Helianthus tuber dormant parenchyma cells at the G(0) stage start to divide synchronously acquiring meristematic characteristics. The requirement for auxins to induce cell division can be substituted by aliphatic PAs such as putrescine, spermidine or spermine. Cylinders or slices of explanted homogeneous tuber parenchyma were cultured in liquid medium for short-term studies on the cell cycle, or on solid agar medium for long-term experiments. Morphological and physiological modifications of synchronously dividing cells were studied during the different phases of the cell cycle in relation to PAs biosynthesis and oxidation. Long-term experiments led to the identification of the PAs as plant growth regulators, as the sole nitrogen source, as tuber storage substances and as essential factors for morphogenetic processes and cell homeostasis. More recently this system was used to study the effects on plant cell proliferation of platinum- or palladium-derived drugs (cisplatin and platinum or palladium bi-substituted spermine) that are used in human cancer cell lines as antiproliferative and cytotoxic agents. Cisplatin was the most active both in cell proliferation inhibition and on PA metabolism. Similar experiments were performed using three agmatine analogous. Different effects of these compounds were observed on cell proliferation, free PA levels and enzyme activities, leading to a hypothesis of a correlation between their chemical structure and the agmatine metabolism in plants.

Use of effective core potential calculations for the conformational and vibrational study of platinum(II) anticancer drugs. cis-Diamminedichloroplatinum(II) as a case study.

In the light of the recognized anticancer properties of cisplatin-type inorganic systems, the exact knowledge of their conformational preferences is of the utmost importance for understanding their biological activity. The present study reports the use of theoretical (quantum mechanical) calculations for achieving this goal. An alternative calculation method to the use of the AE basis sets, both accurate and computationally feasible, was presently tested for the conformational and vibrational study of cis-diamminedichloroplatinum(II). Effective core potentials (ECPs) were used, within the HF methodology and, within the B3LYP and mPW1PW DFT protocols. The DFT methods (particularly mPW1PW) were found to be the best choice for describing cDDP (as compared to the HF methodology).

Conformational and vibrational study of platinum(II) anticancer drugs: cis-diamminedichloro-platinum(II) as a case study.

A conformational and vibrational analysis of cisplatin [cis-diamminedichloro-platinum(II)] (cDDP) is reported. Several theory methods (from Hartree-Fock to Moller-Plesset and density functional theory) combined with different all-electron basis sets are evaluated, in view of determining the best suited strategy for accurately representing this molecule. This choice is based on the best compromise between accuracy and computational requirements. Different scaling models of the cDDP vibrational modes were tested for obtaining the best scaling factors to be used in this type of inorganic systems. The structural parameters and vibrational results predicted by the calculations are compared with the corresponding experimental data, namely, x-ray structure, and Raman and inelastic neutron scattering spectra. Finally, a complete assignment of the cDDP vibrational spectra is presented.

Phenolic esters with potential anticancer activity--the structural variable.

The conformational preferences of several potential anticancer dihydroxycinnamic esters with a variable length alkyl chain were studied by quantum-mechanical (DFT) calculations (both for the isolated molecule and for aqueous solutions). The orientation of the hydroxyl ring substituents and of the alkyl ester moiety relative to the carbonyl group showed these to be the most determinant factors for the overall stability of this type of phenolic systems, strongly dependent on an effective pi-electron delocalization. Compared to the parent caffeic acid (dihydroxycinnamic acid), esterification was found to lead to a higher conformational freedom, and to affect mainly the energy barrier corresponding to the (O=)C-OR internal rotation. No particular differences were verified to occur upon lengthening of the ester alkyl chain, except when this is branched instead of linear. The vibrational spectra of the whole series of compounds were simulated, based on their calculated harmonic vibrational frequencies, and a preliminary assignment was performed.

The MAP kinase Mkc1p is activated under different stress conditions in Candida albicans.

Candida albicans is an opportunistic pathogen that has adapted to live and grow in the human body as its natural environment. Under these conditions, this fungus faces numerous challenges, including oxidative, osmotic and enzymic processes that may damage external and internal structures. In view of the key role of MAP kinase signalling pathways in the physiology of C. albicans, the effect of agents mimicking in vivo environmental conditions on the activation of the p42-44 MAP kinases has been analysed. It has been found that Mkc1p is phosphorylated in the presence of oxidative stress, changes in osmotic pressure, cell wall damage and a decrease in the growth temperature. This phosphorylation is dependent on Pkc1p, indicating that both proteins operate in the same signalling pathway in C. albicans. Under some stimuli, the phosphorylation of Mkc1p required the presence of Hog1p, the MAP kinase of the high osmolarity glycerol (HOG) pathway. This suggests the existence of a new regulatory role, at least under some conditions, for these MAP kinase pathways in yeast.