Patterns of pharmaceutical supplies and medicines donations received during a natural disaster.

BACKGROUND: In response to emergencies, such as wildfires, donations of pharmaceuticals often occur. These donations can be given directly by governments, to non-governmental organizations as corporate donations, or by private entities that donate to individual health institutions. OBJECTIVE: This paper aimed to collect, review and analyze pharmaceutical product donations received during the natural disaster caused by wildfires in the San Luis province, Argentina, in September and October 2020. METHODS: A descriptive, cross-sectional, and retrospective study was performed. An introductory approach to good donation practices was also carried out. Medicines were classified and in the case of products that were not suitable for administration, these were discarded. RESULTS: A total of 15,593 units were segregated, of which 52.8% were over-the-counter products and 47.2% were prescription drugs. 86.3% (13,467 units) were accepted, while 13.7% (2126 units) had to be destroyed. The value of donations totaled USD 16,544. The analysis of the results showed that an important part of the donations was irrelevant in the emergency context. Donations were also received in incorrect amounts, which generated a large stock of medicines that couldn't be used. In emergencies, inappropriate donations create additional work during sorting, storage, and distribution, increasing the time professionals need to complete tasks. This extra work can easily overwhelm limited human and logistical resources. CONCLUSIONS: It is important to previously evaluate the real need for donations. In addition, the distribution of donations must be done through pre-established systems and policies. Otherwise, unsolicited and unnecessary drug donations become wasteful and should therefore be avoided.

Mathematical and Pharmacokinetic Approaches for the Design of New 3D Printing Inks Using Ricobendazole.

PURPOSE: 3D printing (3DP) makes it possible to obtain systems that are not achievable with current conventional methods, one of them, sustained release floating systems. Floating systems using ricobendazole (RBZ) as a model drug and a combination of polymers were designed and obtained by melt solidification printing technique (MESO-PP). METHODS: Four different MESO-PP inks were formulated based on combinations of the polymers Gelucire 43/01 and Gelucire 50/13 in different ratios. For each of the formulated inks, physicochemical characterization was performed by thermal analysis (thermogravimetric analysis [TGA] and differential scanning calorimetry [DSC]), fourier transform infrared spectrophotometer (FTIR) and X-ray diffraction (XRD). Pharmaceutical characterization was performed by in vitro assays to determine pharmaceutically relevant parameters. These parameters were calculated by applying mathematical models developed to evaluate in vitro drug release profiles. On the other hand, a physiologically based pharmacokinetic (PBPK) model was developed to predict the in vivo performance of RBZ loaded in the different inks by determining the Cmax, and the AUC0-∞. RESULTS: By increasing the proportion of Gelucire 50/13 co-surfactant in the mixtures (the proportion in Ink 1 was 33%, while the proportion in Ink 4 was 80%), the dissolution capacity of RBZ increases substantially, decreasing flotation times. CONCLUSION: MESO-PP produced ink 1 (50% Gelucire 43/01, 25% Gelucire 50/13 and 25% RBZ), which has a zero-order release (RR = 0.180%/min) and the longest flotation time (545 ± 23 min), and in turn would produce a significant increase in oral absorption of the drug, with an AUC0-∞ 2.16-fold higher than that obtained in animals treated with RBZ loaded in conventional tablets.

Full genome sequence of the first SARS-CoV-2 detected in Mexico.

SARS-CoV-2 was first detected in the city of Wuhan, Hubei Province, China. In this report, we describe the complete genome sequence of the first imported SARS-CoV-2, detected in a Mexican patient who had traveled to Bergamo, Italy. Phylogenetic analysis showed that this isolate belongs to subclade A2a (lineage G) and is closely related to isolates from Finland, Germany and Brazil, all of which were from patients with a history of travel to Italy. This is the first report of the complete genome sequence of this virus in Mexico.

Albendazole solid dispersions against alveolar echinococcosis: a pharmacotechnical strategy to improve the efficacy of the drug.

Alveolar echinococcosis is a neglected parasitic zoonosis caused by Echinococcus multilocularis. The pharmacological treatment is based on albendazole (ABZ). However, the low water solubility of the drug produces a limited dissolution rate, with the consequent failure in the treatment of the disease. Solid dispersions are a successful pharmacotechnical strategy to improve the dissolution profile of poorly water-soluble drugs. The aim of this work was to determine the in vivo efficacy of ABZ solid dispersions using poloxamer 407 as a carrier (ABZ:P407 solid dispersions (SDs)) in the murine intraperitoneal infection model for secondary alveolar echinococcosis. In the chemoprophylactic efficacy study, the ABZ suspension, the ABZ:P407 SDs and the physical mixture of ABZ and poloxamer 407 showed a tendency to decrease the development of murine cysts, causing damage to the germinal layer. In the clinical efficacy study, the ABZ:P407 SDs produced a significant decrease in the weight of murine cysts. In addition, the SDs produced extensive damage to the germinal layer. The increase in the efficacy of ABZ could be due to the improvement of water solubility and wettability of the drug due to the surfactant nature of poloxamer 407. In conclusion, this study is the basis for further research. This pharmacotechnical strategy might in the future offer novel treatment alternatives for human alveolar echinococcosis.

Design and in vitro characterization of ivermectin nanocrystals liquid formulation based on a top-down approach.

The aim of this study was to develop ivermectin (IVM) nanosuspensions (NSs) to improve the dissolution rate of this poorly water-soluble drug. Different NSs combining different stabilizers, i.e. poloxamer 188 (P188), polysorbate 80 (T80), polyvinylpyrrolidone (PVP), and sodium lauryl sulfate (SLS), were prepared by high-pressure homogenization. The stabilizers were selected based on the saturation solubility and IVM stability within 72 h. The screening of formulations was performed by considering the drug content within the nanosize range. The best formulation (IVM:T80:PVP 1:0.5:0.5 wt%) was characterized in terms of the particle size distribution, morphology, crystallinity, drug content, and in vitro dissolution profile. This NS was also evaluated from a stability point of view, by conditioning samples at a constant temperature and relative humidity for six months. The fresh and conditioned best NSs Z-sizes were 174.6 and 215.7 nm, respectively; while both NSs showed low polydispersity indexes. The faster dissolution rate for the IVM NS was attributed to the presence of nanoparticles and changes to the crystal structure (i.e. amorphization) that further improved solubility. The best NS had a 4-fold faster initial dissolution rate than raw IVM, and is thus a promising formulation for the treatment of human and animal parasitic diseases.

Self-dispersible nanocrystals of albendazole produced by high pressure homogenization and spray-drying.

Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment.

Virtual screening with AutoDock Vina and the common pharmacophore engine of a low diversity library of fragments and hits against the three allosteric sites of HIV integrase: participation in the SAMPL4 protein-ligand binding challenge.

To rigorously assess the tools and protocols that can be used to understand and predict macromolecular recognition, and to gain more structural insight into three newly discovered allosteric binding sites on a critical drug target involved in the treatment of HIV infections, the Olson and Levy labs collaborated on the SAMPL4 challenge. This computational blind challenge involved predicting protein-ligand binding against the three allosteric sites of HIV integrase (IN), a viral enzyme for which two drugs (that target the active site) have been approved by the FDA. Positive control cross-docking experiments were utilized to select 13 receptor models out of an initial ensemble of 41 different crystal structures of HIV IN. These 13 models of the targets were selected using our new "Rank Difference Ratio" metric. The first stage of SAMPL4 involved using virtual screens to identify 62 active, allosteric IN inhibitors out of a set of 321 compounds. The second stage involved predicting the binding site(s) and crystallographic binding mode(s) for 57 of these inhibitors. Our team submitted four entries for the first stage that utilized: (1) AutoDock Vina (AD Vina) plus visual inspection; (2) a new common pharmacophore engine; (3) BEDAM replica exchange free energy simulations, and a Consensus approach that combined the predictions of all three strategies. Even with the SAMPL4's very challenging compound library that displayed a significantly lower amount of structural diversity than most libraries that are conventionally employed in prospective virtual screens, these approaches produced hit rates of 24, 25, 34, and 27 %, respectively, on a set with 19 % declared binders. Our only entry for the second stage challenge was based on the results of AD Vina plus visual inspection, and it ranked third place overall according to several different metrics provided by the SAMPL4 organizers. The successful results displayed by these approaches highlight the utility of the computational structure-based drug discovery tools and strategies that are being developed to advance the goals of the newly created, multi-institution, NIH-funded center called the "HIV Interaction and Viral Evolution Center".

Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge.

As part of the SAMPL4 blind challenge, filtered AutoDock Vina ligand docking predictions and large scale binding energy distribution analysis method binding free energy calculations have been applied to the virtual screening of a focused library of candidate binders to the LEDGF site of the HIV integrase protein. The computational protocol leveraged docking and high level atomistic models to improve enrichment. The enrichment factor of our blind predictions ranked best among all of the computational submissions, and second best overall. This work represents to our knowledge the first example of the application of an all-atom physics-based binding free energy model to large scale virtual screening. A total of 285 parallel Hamiltonian replica exchange molecular dynamics absolute protein-ligand binding free energy simulations were conducted starting from docked poses. The setup of the simulations was fully automated, calculations were distributed on multiple computing resources and were completed in a 6-weeks period. The accuracy of the docked poses and the inclusion of intramolecular strain and entropic losses in the binding free energy estimates were the major factors behind the success of the method. Lack of sufficient time and computing resources to investigate additional protonation states of the ligands was a major cause of mispredictions. The experiment demonstrated the applicability of binding free energy modeling to improve hit rates in challenging virtual screening of focused ligand libraries during lead optimization.

Design and development of aqueous nanoformulations for mosquito control.

Microemulsions (ME) are thermodynamically stable isotropic mixtures of oil, water, and surfactant; they would also be attractive as potential insecticidal products due to the high bioviability of the active ingredient, attributable to the small sizes of the oil drops. A laboratory study was conducted in order to compare the biological effect of oil in water (o/w) geranium essential oil (EO) and geraniol MEs and emulsions, against Culex pipiens pipiens mosquito larvae. The systems were based on three nonionic surfactants (Cremophor EL, Brij 35, Tween 80). The MEs showed dispersed phase diameters in the range of 8 to 14 nm and had low PDI values (<0.2). The MEs were analyzed by TEM, indicating that they had nearly spherical morphology. The microemulsified systems based on geranium EO and those of geraniol produced a notable increase of the larvicidal activity when compared with the respectably emulsions, concluding that the biological effect is related with the diameter of the dispersed phase. The smallest drops achieved the highest larvicidal activity, being the aqueous nanoformulations based on geraniol most effective than those of geranium EO. However, geranium microemulsions are preferred due to their residual toxicological profiles. The results indicate that these novel systems could be used in integrated pest management program for the C. pipiens pipiens.

Formulation and optimization of pH-sensitive nanocrystals for improved oral delivery.

The challenge of low water solubility in pharmaceutical science profoundly impacts drug absorption and therapeutic effectiveness. Nanocrystals (NC), consisting of drug molecules and stabilizing agents, offer a promising solution to enhance solubility and control release rates. In the pharmaceutical industry, top-down techniques are favored for their flexibility and cost-effectiveness. However, increased solubility can lead to premature drug dissolution in the stomach, which is problematic due to the acidic pH or enzymes. Researchers are exploring encapsulating agents that facilitate drug release at customized pH levels as a valuable strategy to address this. This study employed wet milling and spray drying techniques to create encapsulated NC for delivering the drug to the intestinal tract using the model drug ivermectin (IVM). Nanosuspensions (NS) were efficiently produced within 2 h using NanoDisp®, with a particle size of 198.4 ± 0.6 nm and a low polydispersity index (PDI) of 0.184, ensuring uniformity. Stability tests over 100 days at 4 °C and 25 °C demonstrated practical viability, with no precipitation or significant changes observed. Cytotoxicity evaluations indicated less harm to Caco-2 cells compared to the pure drug. Furthermore, the solubility of the NC increased by 47-fold in water and 4.8-fold in simulated intestinal fluid compared to the pure active compound. Finally, dissolution tests showed less than 10% release in acidic conditions and significant improvement in simulated intestinal conditions, promising enhanced drug solubility and bioavailability. This addresses a long-standing pharmaceutical challenge in a cost-effective and scalable manner.

Significant progress in improving Atorvastatin dissolution rate: Physicochemical characterization and stability assessment of self-dispersible Atorvastatin/Tween 80® nanocrystals formulated through wet milling and freeze-drying.

Atorvastatin (ATV) is a first-line drug for the treatment of hyperlipidemia. This drug presents biopharmaceutical problems, partly due to its low solubility and dissolution rate. In this work, nanocrystals of ATV stabilized with Tween 80® were designed by wet milling. A full factorial design was applied to optimize the process. Additionally, a cryoprotectant agent (maltodextrin, MTX) was identified, which allowed maintaining the properties of the nanocrystals after lyophilization. The storage stability of the nanocrystals was demonstrated for six months in different conditions. The obtained nanocrystal powder was characterized using SEM, EDXS, TEM, DSC, TGA, FT-IR, and XRD, showing the presence of irregular crystals with semi-amorphous characteristics, likely due to the particle collision process. Based on the reduction in particle size and the decrease in drug crystallinity, a significant increase in water and phosphate buffer (pH 6.8) solubility by 4 and 6 times, respectively, was observed. On the other hand, a noticeable increase in the dissolution rate was observed, with 90 % of the drug dissolved within 60 min of study, compared to 30 % of the drug dissolved within 12 h in the case of the untreated drug or the physical mixture of components. Based on these results, it can be concluded that the nano-milling of Atorvastatin stabilized with Tween 80® is a promising strategy for developing new formulations with improved biopharmaceutical properties of this widely used drug.

3D printed scaffolds as delivery devices for nanocrystals: A proof of concept loading Atorvastatin with enhanced properties for sublingual route of administration.

Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.

Hemoadsorption and continuous venovenous hemodiafiltration in the management of paraquat poisoning during pregnancy: A case report.

We describe the case of a mother in the second trimester of pregnancy with severe paraquat poisoning who ended her pregnancy at term and a healthy newborn. Management was initiated after 34 h of paraquat administration with the HA-230 hemoadsorption cartridge, followed by continuous venovenous hemodiafiltration for 120 h, in addition to cyclophosphamide and methylprednisolone. There was no evidence of adverse effects associated with treatment or extracorporeal therapy, and maternal and fetal well-being was maintained during the 26 days of hospitalization and at the end of pregnancy. This case treated with hemoadsorption and hemodiafiltration for paraquat poisoning during pregnancy is one of the few procedures reported in the literature and can be used as a guide for the management of subsequent cases.

Design and Development of Sublingual Printlets Containing Domperidone Nanocrystals Using 3D Melting Solidification Printing Process (MESO-PP).

Domperidone (DOM) is a drug commonly used to treat nausea and vomiting, as well as gastrointestinal disorders. However, its low solubility and extensive metabolism pose significant administration challenges. In this study, we aimed to improve DOM solubility and avoid its metabolism by developing nanocrystals (NC) of DOM through a 3D printing technology-melting solidification printing process (MESO-PP)-to be delivered via a solid dosage form (SDF) that can be administered sublingually. We obtained DOM-NCs using the wet milling process and designed an ultra-rapid release ink (composed of PEG 1500, propylene glycol, sodium starch glycolate, croscarmellose sodium, and sodium citrate) for the 3D printing process. The results demonstrated an increase in the saturation solubility of DOM in both water and simulated saliva without any physicochemical changes in the ink as observed by DSC, TGA, DRX, and FT-IR. The combination of nanotechnology and 3D printing technology enabled us to produce a rapidly disintegrating SDF with an improved drug-release profile. This study demonstrates the potential of developing sublingual dosage forms for drugs with low aqueous solubility using nanotechnology and 3D printing technology, providing a feasible solution to the challenges associated with the administration of drugs with low solubility and extensive metabolism in pharmacology.

Development of Triamcinolone Acetonide Nanocrystals for Ocular Administration.

Triamcinolone acetonide (TA) is a powerful anti-inflammatory drug used in the treatment of inflammatory ocular disorders; however, its poor aqueous solubility and ocular anatomical barriers hinder optimal treatment. The aim of this work was to obtain triamcinolone acetonide nanocrystals (TA-NC) to improve ocular corticosteroid therapy. Self-dispersible TA-NC were prepared by the bead milling technique followed by spray-drying, exhaustively characterized and then evaluated in vivo in an ocular model of endotoxin-induced uveitis (EIU). Self-dispersible TA-NC presented an average particle size of 257 ± 30 nm, a narrow size distribution and a zeta potential of -25 ± 3 mV, which remained unchanged for 120 days under storage conditions at 25 °C. In addition, SEM studies of the TA-NC showed uniform and spherical morphology, and FTIR and XRDP analyses indicated no apparent chemical and crystallinity changes. The subconjunctival administration of TA-NC in albino male white rabbits showed no clinical signs of ocular damage. In vivo studies proved that treatment with self-dispersible TA-NC alleviated the inflammatory response in the anterior chamber and iris in EUI rabbit eyes. Dispersible TA-NC are a promising approach to obtaining a novel nanometric TA formulation for ocular disorders.

Application of 20% silver nanoclusters in polymethacrylic acid on simulated dentin caries; its penetration depth and effect on surface hardness.

The aims of this study were: To evaluate the surface hardness of simulated dentin caries lesions treated with either silver nanoclusters (AgNCls) synthesized in polymethacrylic acid (PMAA) or 38% silver diammine fluoride (SDF), as well as observe the penetration of the treatment solutions into the simulated caries lesions. Dentin blocks 4 mm thick obtained from caries-free third molars were sectioned and then simulated caries lesions on the occlusal dentin surfaces were created. Each specimen (n = 8) was divided into four sections: (A) treated with 20% AgNCls/PMAA; (B) treated with SDF 38% (FAgamin, Tedequim, Cordoba, Argentina); (C) sound tooth protected by nail-varnish during artificial caries generation (positive control); and (D) artificial caries lesion without surface treatment (negative control). AgNCls/PMAA or SDF were applied on the simulated lesions with a microbrush for 10 s, then excess removed. The surface hardness was measured by means of Vickers indentation test. To trace the depth of penetration, up to 400 µm, of silver ions, elemental composition of the samples was observed using EDX, coupled with SEM, and measured every 50 µm from the surface towards the pulp chamber. Laser Induced Breakdown Spectroscopy (LIBS) was also employed to trace silver ion penetration; the atomic silver line 328.06 nm was used with a 60 µm laser spot size to a depth of 240 µm. Student's-t test identified significant differences between treatment groups for each depth and the Bonferroni test was used for statistical analysis of all groups (p < 0.05). Mean surface hardness values obtained were 111.2 MPa, 72.3 MPa, 103.3 MPa and 50.5 MPa for groups A, B, C and D respectively. There was a significant difference between groups A and C compared with groups B and D, the group treated with AgNCls/PMAA achieved the highest surface hardness, similar or higher than the sound dentin control. A constant presence of silver was observed throughout the depth of the sample for group A, while group B showed a peak concentration of silver at the surface with a significant drop beyond 50 µm. The 20% AgNCls/PMAA solution applied to simulated dentin caries lesions achieved the recovery of surface hardness equivalent to sound dentin with the penetration of silver ions throughout the depth of the lesion.

Enhancing the Functional Properties of Tea Tree Oil: In Vitro Antimicrobial Activity and Microencapsulation Strategy.

In the context of addressing antimicrobial drug resistance in periocular infections, Tea Tree Oil (TTO) has emerged as a promising therapeutic option. This study aimed to assess the efficacy of TTO against bacterial strains isolated from ocular infections, with a particular focus on its ability to inhibit biofilm formation. Additionally, we designed and analyzed microcapsules containing TTO to overcome certain unfavorable physicochemical properties and enhance its inherent biological attributes. The quality of TTO was confirmed through rigorous analysis using GC-MS and UV-Vis techniques. Our agar diffusion assay demonstrated the effectiveness of Tea Tree Oil (TTO) against ocular bacterial strains, including Corynebacterium spp., coagulase-negative Staphylococcus spp., and Staphylococcus aureus, as well as a reference strain of Staphylococcus aureus (ATCC 25923). Notably, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for all tested microorganisms were found to be 0.2% and 0.4%, respectively, with the exception of Corynebacterium spp., which exhibited resistance to TTO. Furthermore, TTO exhibited a substantial reduction in biofilm biomass, ranging from 30% to 70%, as determined by the MTT method. Through the spray-drying technique, we successfully prepared two TTO-containing formulations with high encapsulation yields (80-85%), microencapsulation efficiency (90-95%), and embedding rates (approximately 40%). These formulations yielded microcapsules with diameters of 6-12 µm, as determined by laser scattering particle size distribution analysis, and exhibited regular, spherical morphologies under scanning electron microscopy. Importantly, UV-Vis analysis post-encapsulation confirmed the presence of TTO within the capsules, with preserved antioxidant and antimicrobial activities. In summary, our findings underscore the substantial therapeutic potential of TTO and its microcapsules for treating ocular infections.

3D-Printed Gastroretentive Tablets Loaded with Niclosamide Nanocrystals by the Melting Solidification Printing Process (MESO-PP).

Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology. The results obtained in TGA, DSC, XRD and FT-IR analysis showed no physicochemical interactions or modifications in the crystallinity of NICLO-NCR after inclusion in Gelucire 50/13 ink. This method allowed the incorporation of NICLO-NCRs in a concentration of up to 25% w/w. It achieved a controlled release of NCRs in a simulated gastric medium. Moreover, the presence of NICLO-NCRs after redispersion of the printlets was observed by STEM. Additionally, no effects on the cell viability of the NCRs were demonstrated in the GES-1 cell line. Finally, gastroretention was demonstrated for 180 min in dogs. These findings show the potential of the MESO-PP technique in obtaining slow-release gastro-retentive oral solid dosage forms loaded with nanocrystals of a poorly soluble drug, an ideal system for treating gastric pathologies such as H. pylori.

Virtual target screening: validation using kinase inhibitors.

Computational methods involving virtual screening could potentially be employed to discover new biomolecular targets for an individual molecule of interest (MOI). However, existing scoring functions may not accurately differentiate proteins to which the MOI binds from a larger set of macromolecules in a protein structural database. An MOI will most likely have varying degrees of predicted binding affinities to many protein targets. However, correctly interpreting a docking score as a hit for the MOI docked to any individual protein can be problematic. In our method, which we term "Virtual Target Screening (VTS)", a set of small drug-like molecules are docked against each structure in the protein library to produce benchmark statistics. This calibration provides a reference for each protein so that hits can be identified for an MOI. VTS can then be used as tool for: drug repositioning (repurposing), specificity and toxicity testing, identifying potential metabolites, probing protein structures for allosteric sites, and testing focused libraries (collection of MOIs with similar chemotypes) for selectivity. To validate our VTS method, twenty kinase inhibitors were docked to a collection of calibrated protein structures. Here, we report our results where VTS predicted protein kinases as hits in preference to other proteins in our database. Concurrently, a graphical interface for VTS was developed.

Minimally invasive retrieval of a retained Jackson--Pratt drainage tube using the Sachse urethrotome.

OBJECTIVE: A retained postoperative drain tube, trapped by one or more of the sutures of the abdominal wall closure, is a rare complication of frustrating consequences and potential legal repercussions. There are few reports of techniques for minimally invasive removal of an anchored postoperative drain tube, which not infrequently has been treated by reopening the wound. METHOD/RESULT: A 75 years-old man with a left T2-T3N0M0 renal carcinoma was treated with transperitoneal laparoscopic nephrectomy and a Jackson-Pratt drain was left in place. Drain removal the day after revealed impossible, as if being caught with fascial suture. With the patient under sedation, we introduced a Sachse urethrotome parallel to the drain, and the abdominal fascia was identified, then the polyglycolic stitch anchoring it to the wall could be severed, freeing the drain. CONCLUSIONS: Percutaneous extraction with the Sachse urethrotome of an anchored postoperative drain, should be the first option, before trying a forced traction or using more complex options. This technique is for the first time published in the Spanish bibliography, and we think this possibility should be disclosed to abdominal surgeons.