Hypertension is considered a major public health issue due to its high prevalence and subsequent risk of cardiovascular and kidney diseases. Thus, the search for new antihypertensive compounds remains of great interest. Snake venoms provide an abundant source of lead molecules that affect the cardiovascular system, which makes them prominent from a pharmaceutical perspective. Such snake venom components include bradykinin potentiating peptides (proline-rich oligopeptides), natriuretic peptides, phospholipases A₂, serine-proteases and vascular endothelial growth factors. Some heparin binding hypotensive factors, three-finger toxins and 5′ nucleotidases can also exert blood pressure lowering activity. Great advances have been made during the last decade regarding the understanding of the mechanism of action of these hypotensive proteins. Bradykinin potentiating peptides exert their action primarily by inhibiting the angiotensin-converting enzyme and increasing the effect of endogenous bradykinin. Snake venom phospholipases A₂ are capable of reducing blood pressure through the production of arachidonic acid, a precursor of cyclooxygenase metabolites (prostaglandins or prostacyclin). Other snake venom proteins mimic the effects of endogenous kallikrein, natriuretic peptides or vascular endothelial growth factors. The aim of this work was to review the current state of knowledge regarding snake venom components with potential antihypertensive activity and their mechanisms of action.

Background: The development of drug resistance by bacterial strains is a public health issue, being the main cause for the decrease in effectiveness of numerous antibiotics. In this context, it is essential to find new drugs with better antibacterial activity. Objective: The authors proposed to cover relevant literature, published following the review article written by Rani et al., illustrating chemical structures and antibacterial activity of some imidazole derivatives. Method: Approximately 100 scientific articles, presenting more than 150 compounds have been reviewed. The most relevant data have been extracted and systematically arranged in figures and tables. Results: The reviewed studies used a broad number of bacterial strains, however Staphylococcus aureus as Gram-positive, and Escherichia coli as Gram-negative bacterial strains were most frequently used to assess the activity of these compounds. Conclusion: Some of the compounds showed promising results against both Gram-positive and Gram-negative bacterial strains, thus further analysis should be performed in terms of toxicity, pharmacokinetics and pharmacodynamics. Additional screening of these imidazole derivatives could lead to useful compounds with potential broad-spectrum antibacterial activity against resistant pathogens.

The enantioseparation of four phthalimide derivatives (thalidomide, pomalidomide, lenalidomide and apremilast) was investigated on five different polysaccharide-type stationary phases (Chiralpak AD, Chiralpak AS, Lux Amylose-2, Chiralcel OD and Chiralcel OJ-H) using neat methanol (MeOH), ethanol (EtOH), 1-propanol (PROP), 2-propanol (IPA) and acetonitrile (ACN) as polar organic mobile phases and also in combination. Along with the separation capacity of the applied systems, our study also focuses on the elution sequences, the effect of mobile phase mixtures and the hysteresis of retention and selectivity. Although on several cases extremely high resolutions (R_s > 10) were observed for certain compounds, among the tested conditions only Chiralcel OJ-H column with MeOH was successful for baseline-separation of all investigated drugs. Chiral selector- and mobile-phase-dependent reversals of elution order were observed. Reversal of elution order and hysteresis of retention and enantioselectivity were further investigated using different eluent mixtures on Chiralpak AD, Chiralcel OD and Lux Amylose-2 column. In an IPA/MeOH mixture, enantiomer elution-order reversal was observed depending on the eluent composition. Furthermore, in eluent mixtures, enantioselectivity depends on the direction from which the composition of the eluent is approached, regardless of the eluent pair used on amylose-based columns. Using a mixture of polar alcohols not only the selectivities but the enantiomer elution order can also be fine-tuned on Chiralpak AD column, which opens up the possibility of a new type of chiral screening strategy.

Local inflammation is a well-known symptom of envenomation by snakes of the family Viperidae, attributed primarily to the phospholipase A₂s, metalloproteinases and L-amino acid oxidases contained in their venom. The inflammatory effect of snake venoms has been associated with a marked increase of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α. To determine the impact of Vipera ammodytes ammodytes snake venom on the expression of inflammation-related genes, we incubated human U937 monocyte cells with dilutions of snake venom. Gene expression was quantified for 28 different genes using a TaqMan^® Array Human Cytokine Network 96-well Plate in a RT-qPCR system. Our results have demonstrated that 1.0 μg/mL Vipera ammodytes ammodytes venom solution induces a notable change in the expression of several cytokine network genes. Among the upregulated genes, there were several that encode interleukins, interferons, and tumor necrosis factors. We further report the downregulation of three interleukin-related genes. Our findings come as supportive information for the known complex effect of snake venoms on the human cytokine network. It also provides relevant new information regarding the expression of genes that have not been previously associated with the effect of snake venoms.

Polioxometalaţii sunt compuşi anorganici importanţi care prezintă o gamă largă de proprietăţi farmacologice incluzând efecte antivirale, antibacteriene, antiparazitare sau antitumorale, chiar dacă mecanismul molecular de acţiune nu este pe deplin înţeles. Scop: În această lucrare am evaluat acţiunea antibacteriană a unor compuşi polioxowolframici saturaţi (POW), datorită faptului că dezvoltarea rezistenţei bacteriilor faţă de antibiotice reprezintă în prezent o problemă majoră de sănătate. Material şi metodă: Acţiunea antibacteriană a fost studiată prin metoda difuziei în agar ca posibilă metodă de screening şi prin metoda microdiluţiilor. Prin microdiluţii au fost calculate concentrația minimă inhibitorie şi concentrația minimă bactericidă pentru fiecare compus. Totodată am comparat fiabilitatea celor două metode de testare faţă de compuşii POW. Rezultate: Cea mai bună acţiune antibacteriană a prezentat-o H4[SiW12O40]*nH2O, iar cea mai slabă Na3[PW12O40]*nH2O, dar în schimb cu o acţiune foarte bună pe Staphylococcus spp., în special pe MRSA. POW îşi exercită acţiunea antibacteriană la concentraţii relativ mari, iar acţiunea lor este dependentă de specia bacteriană, având activitate foarte bună pe Staphylococcus spp. Cea mai fiabilă metodă pentru evaluarea acţiunii antibacteriene a POW este cea a microdiluţiilor. POW îşi pot găsi aplicaţie practică în decontaminarea spitalelor sau ca agenţi antibacterieni in vivo

Solid pharmaceutical formulations with class II active pharmaceutical ingredients (APIs) face dissolution challenges due to limited solubility, affecting in vivo behavior. Robust computational tools, via data mining, offer valuable insights into product performance, complementing traditional methods and aiding in scale-up decisions. This study utilizes the design of experiments (DoE) to understand fluidized hot-melt granulation manufacturing technology. Exploratory data analysis (MVDA) highlights similarities and differences in tablet manufacturability and dissolution profiles at both the lab and pilot scales. The study sought to gain insights into the application of multivariate data analysis by identifying variations among batches produced at different manufacturing scales for this technology. DoE and MVDA findings show that the granulation temperature, time, and Macrogol type significantly impact product performance. These factors, by influencing particle size distribution, become key predictors of product quality attributes such as resistance to crushing, disintegration time, and early-stage API dissolution in the profile. Software-aided data mining, with its multivariate and versatile nature, complements the empirical approach, which is reliant on trial and error during product scale-up.