Mycoplasma hominis peritonitis after oocyte donation.

We report the case of a young, immunocompetent, non-pregnant woman diagnosed with acute abdomen 3 weeks after an ultrasound-guided transvaginal oocyte retrieval (TVOR). Peritoneal fluid, obtained during exploratory laparoscopy, yielded Mycoplasma hominis as the sole pathogen. The patient's symptoms and signs improved after 24-hour treatment with intravenous clindamycin, ampicillin and gentamycin. Complete resolution was achieved with oral doxycycline for 14 days.

S-Dihydrodaidzein and 3-(1,3-benzoxazol-2-yl)-benzamide, Two New Potential ß-estrogen Receptor Ligands with Anti-adipogenic Activity.

BACKGROUND: The elucidation of molecular pathways associated with adipogenesis has evidenced the relevance of estrogen and estrogen receptor beta (ERß). The positive effects of ERß ligands on adipogenesis, energy expenditure, lipolysis, food intake, and weight loss, make ERß an attractive target for obesity control. From ligand-based virtual screening, molecular docking, and molecular dynamic simulations, six new likely ERß ligands (C1 to C6) have been reported with potential for pharmacological obesity treatment. OBJECTIVE: In this study, the effect of molecules C1-C6 on adipogenesis using the murine 3T3-L1 cell line was evaluated. METHODS: Cell viability was assessed by MTT assays. Lipid accumulation and gene expression were investigated by ORO staining and real-time quantitative RT-PCR experiments, respectively. RESULTS: Cell viability was not significantly affected by C1-C6 at concentrations up to 10 µM. Interestingly, treatment with 10 µM of C1 (S-Dihydrodaidzein) and C2 (3-(1,3-benzoxazol-2-yl)- benzamide) for 72 h inhibited adipocyte differentiation; moreover, ORO staining evidenced a reduced intracellular lipid accumulation (40% at day 7). Consistently, mRNA expression of the adipogenic markers, PPARγ and C/EBPα, was reduced by 50% and 82%, respectively, in the case of C1, and by 83% and 59%, in the case of C2. CONCLUSION: Altogether, these results show the two new potential ß-estrogen receptor ligands, C1 and C2, to exhibit anti-adipogenic activity. They could further be used as lead structures for the development of more efficient drugs for obesity control.

Novel Pitolisant-Derived Sulfonyl Compounds for Alzheimer Disease.

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder characterized by cognitive decline, memory loss, behavioral changes, and other neurological symptoms. Considering the urgent need for new AD therapeutics, in the present study we designed, synthesized, and evaluated multitarget compounds structurally inspired by sulfonylureas and pitolisant with the aim of obtaining multitarget ligands for AD treatment. Due to the diversity of chemical scaffolds, a novel strategy has been adopted by merging into one structure moieties displaying H3R antagonism and acetylcholinesterase inhibition. Eight compounds, selected by their binding activity on H3R, showed a moderate ability to inhibit acetylcholinesterase activity in vitro, and two of the compounds (derivatives 2 and 7) were also capable of increasing acetylcholine release in vitro. Among the tested compounds, derivative 2 was identified and selected for further in vivo studies. Compound 2 was able to reverse scopolamine-induced cognitive deficits with results comparable to those of galantamine, a drug used in clinics for treating AD. In addition to its efficacy, this compound showed moderate BBB permeation in vitro. Altogether, these results point out that the fragment-like character of compound 2 leads to an optimal starting point for a plausible medicinal chemistry approach for this novel strategy.

Primary Peritoneal Serous Cancer: A Case Report of a Tumor in the Rectovaginal Septum.

Peritoneal cancer is the invasion by malignant cells of serous membrane that lines the abdominal cavity, the viscera, and the coelom of the amniotes. Histologically, it is indistinguishable from ovarian counterpart, although in the former, it commonly involves the ovary only superficially, or it may totally lack an ovarian component, but with extensive involvement of the peritoneum, calcified perihepatic peritoneal nodules, or involvement of the omentum, in most cases. The current study describes the case of a 54-year-old female patient referring a history of colitis and dairy intolerance. A transvaginal ultrasound and a computed tomography (CT) scan revealed a tumor measuring 70 × 61 × 63 mm. CA-125 serum levels were 880 U/ml. Laparotomy surgery was indicated, and tumor was found at the level of the rectovaginal septum without evidence of metastasis. Tumor dissection and protective colostomy with loop sigmoid colon were performed. A pathological study gave a diagnosis of a high-grade peritoneal serous carcinoma with a micropapillary pattern. The present study describes the case of papillary serous peritoneal cancer presented as a single tumor mass without extensive involvement of the peritoneum. Additionally, the need for routine tests for its diagnosis and documenting hormonal alterations as the cause of its origin are suggested.

Diagnostic Efficacy of High-Resolution Computed Tomography Densitometry for Diagnosing Otosclerosis.

OBJECTIVES: The purpose of this study is to evaluate the reliability of temporal bone density measurements for diagnosing otosclerosis. MATERIALS AND METHODS: A retrospective case-control study is presented. Bone density was measured in Hounsfield units (HUs) by using high-resolution computed tomography in eight regions of interest (ROI) where otosclerotic foci are usually localized. The density of 113 otosclerotic ears was compared with that of 33 nonotosclerotic ears to determine sensitivity and specificity. Furthermore, the binormal receiver operating characteristic curve of each ROI's density was calculated to estimate the diagnostic value for osteosclerosis. In addition, the radiological density of seven cases-where radiological visual examination exhibited no findings but surgery confirmed stapes fixation-was compared with nonotosclerotic controls. RESULTS: ROI densities were significantly lower in otosclerotic patients compared with nonotosclerotic controls. The area under the curve of the fissula ante fenestram (FAF) presented the highest diagnostic performance: 1,871 HU cut-off value (area under the curve = 0.986), 96.64% sensitivity, and 100% specificity. Significantly lower densities in the FAF area were observed in the seven cases with negative radiology but intraoperatively confirmed otosclerosis. CONCLUSION: The high-resolution computed tomography density of the FAF is a reliable measurement for diagnosing otosclerosis. A value less than 1,871 HU exhibited the highest sensitivity and specificity in a European Caucasian population.

Total Antioxidant Capacity in Obese and Non-Obese Subjects and Its Association with Anthropo-Metabolic Markers: Systematic Review and Meta-Analysis.

The total antioxidant capacity (TAC) has been related to the development of and complications associated with chronic diseases, but its importance during obesity is not entirely clear. We conducted a systematic review and meta-analysis to clarify whether there are differences or similarities in the TAC between subjects with obesity (SO) and subjects with normal weight (NW). Following the recommendations of PRISMA and Cochrane, we performed a systematic search in the PubMed, Scopus, Web of Science, Cochrane, and PROSPERO databases, identifying 1607 studies. Among these, 22 studies were included in the final analysis, comprising 3937 subjects (1665 SO and 2272 NW) in whom serum TAC was measured, and from these 19,201 subjects, the correlation of serum TAC with anthropo-metabolic parameters was also estimated. The Newcastle-Ottawa method was used for the evaluation of the risk of bias. Using a random-effect model (REM), TAC was reduced in SO independently of age (SMD, -0.86; 95% CI -1.38 to -0.34; p = 0.0012), whereas malondialdehyde (SMD, 1.50; 95% CI 0.60 to 2.41), oxidative stress index (SMD, 1.0; 95% CI 0.16 to 1.84), and total oxidant status (SMD, 0.80; 0.22 to 1.37) were increased. There were seven significant pooled correlations of TAC with anthropometric and metabolic parameters: weight (r = -0.17), hip circumference (r= -0.11), visceral adipose index (r = 0.29), triglycerides (r = 0.25), aspartate aminotransferase (r = 0.41), alanine aminotransferase (r = 0.38), and uric acid (r = 0.53). Our results confirm a decrease in TAC and an increase in markers of oxidative stress in SO and underpin the importance of these serum biomarkers in obesity.

Exploring Novel Drug Combinations: The Therapeutic Potential of Selanyl Derivatives for Leishmania Treatment.

This work describes the design, synthesis, and biological activities of new selenoester derivatives and its homologs thioesters. Thirty-two compounds were developed following an economical synthetic route, achieving small molecules, with structural characteristics similar to those present in antileishmanial drugs such as miltefosine (MIL) and paromomycin (PMN). These compounds were tested in vitro against strains of Leishmania major (L. major) and Leishmania infantum (L. infantum). The L. infantum strain (causative agent of visceral leishmaniasis) exhibited the highest sensitivity. Thus, four selanylacetic acid derivatives (A4, A5, A6 and A8) presented IC50 values below 40 µM in this strain. These derivatives also demonstrated low toxicity and high selectivity in PMA-differentiated THP-1 macrophages. The A4-A6 and A8 derivatives were evaluated in order to determine their pharmacological behavior, using drug combination studies with the reference drugs amphotericin B (AMB), MIL and PMN. Compounds A6 and A8 presented a potent synergistic interaction with MIL, which is the only oral drug available for the treatment of visceral leishmaniasis. Therefore, compounds A6 and A8 present significant potential as therapeutic candidates for the treatment of leishmaniasis based on their remarkable leishmanicidal characteristics and pharmacological synergism.

Preparation of Selenium-Based Drug-Modified Polymeric Ligand-Functionalised Fe3O4 Nanoparticles as Multimodal Drug Carrier and Magnetic Hyperthermia Inductor.

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents.

Next generation of selenocyanate and diselenides with upgraded leishmanicidal activity.

Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration, high costs and drug resistance. Therefore, there is an urgent demand for safer and more effective novel drugs. Previous studies indicated that selenium compounds are promising derivatives for innovative therapy in leishmaniasis treatment. With this background, a new library of 20 selenocyanate and diselenide derivatives were designed based on structural features present in the leishmanicidal drug miltefosine. Compounds were initially screened against promastigotes of L. major and L. infantum and their cytotoxicity was evaluated in THP-1 cells. Compounds B8 and B9 were the most potent and less cytotoxic and were further screened for the intracellular back transformation assay. The results obtained revealed that B8 and B9 showed EC50 values of 7.7 µM and 5.7 µM, respectively, in L. major amastigotes, while they presented values of 6.0 µM and 7.4 µM, respectively, against L. infantum amastigotes. Furthermore, they exerted high selectivity (60 < SI > 70) towards bone marrow-derived macrophages. Finally, these compounds exhibited higher TryR inhibitory activity than mepacrine (IC50 7.6 and 9.2 µM, respectively), and induced nitric oxide (NO) and reactive oxygen species (ROS) production in macrophages. These results suggest that the compounds B8 and B9 could not only exert a direct leishmanicidal activity against the parasite but also present an indirect action by activating the microbicidal arsenal of the macrophage. Overall, these new generation of diselenides could constitute promising leishmanicidal drug candidates for further studies.

Virtual Screening of Benzimidazole Derivatives as Potential Triose Phosphate Isomerase Inhibitors with Biological Activity against Leishmania mexicana.

Leishmania mexicana (L. mexicana) is a causal agent of cutaneous leishmaniasis (CL), a "Neglected disease", for which the search for new drugs is a priority. Benzimidazole is a scaffold used to develop antiparasitic drugs; therefore, it is interesting molecule against L. mexicana. In this work, a ligand-based virtual screening (LBVS) of the ZINC15 database was performed. Subsequently, molecular docking was used to predict the compounds with potential binding at the dimer interface of triosephosphate isomerase (TIM) of L. mexicana (LmTIM). Compounds were selected on binding patterns, cost, and commercial availability for in vitro assays against L. mexicana blood promastigotes. The compounds were analyzed by molecular dynamics simulation on LmTIM and its homologous human TIM. Finally, the physicochemical and pharmacokinetic properties were determined in silico. A total of 175 molecules with docking scores between -10.8 and -9.0 Kcal/mol were obtained. Compound E2 showed the best leishmanicidal activity (IC50 = 4.04 µM) with a value similar to the reference drug pentamidine (IC50 = 2.23 µM). Molecular dynamics analysis predicted low affinity for human TIM. Furthermore, the pharmacokinetic and toxicological properties of the compounds were suitable for developing new leishmanicidal agents.

Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds.

Nowadays, oxidative cell damage is one of the common features of cancer and Alzheimer's disease (AD), and Se-containing molecules, such as ebselen, which has demonstrated strong antioxidant activity, have demonstrated well-established preventive effects against both diseases. In this study, a total of 39 Se-derivatives were synthesized, purified, and spectroscopically characterized by NMR. Antioxidant ability was tested using the DPPH assay, while antiproliferative activity was screened in breast, lung, prostate, and colorectal cancer cell lines. In addition, as a first approach to evaluate their potential anti-Alzheimer activity, the in vitro acetylcholinesterase inhibition (AChEI) was tested. Regarding antioxidant properties, compound 13a showed concentration- and time-dependent radical scavenging activity. Additionally, compounds 14a and 17a showed high activity in the melanoma and ovarian cancer cell lines, with LD50 values below 9.2 µM. Interestingly, in the AChEI test, compound 14a showed almost identical inhibitory activity to galantamine along with a 3-fold higher in vitro BBB permeation (Pe = 36.92 × 10-6 cm/s). Molecular dynamics simulations of the aspirin derivatives (14a and 14b) confirm the importance of the allylic group instead of the propargyl one. Altogether, it is concluded that some of these newly synthesized Se-derivatives, such as 14a, might become very promising candidates to treat both cancer and AD.

Comparative genomics and interactomics of polyadenylation factors for the prediction of new parasite targets: Entamoeba histolytica as a working model.

Protein-protein interactions (PPI) play a key role in predicting the function of a target protein and drug ability to affect an entire biological system. Prediction of PPI networks greatly contributes to determine a target protein and signal pathways related to its function. Polyadenylation of mRNA 3'-end is essential for gene expression regulation and several polyadenylation factors have been shown as valuable targets for controlling protozoan parasites that affect human health. Here, by using a computational strategy based on sequence-based prediction approaches, phylogenetic analyses, and computational prediction of PPI networks, we compared interactomes of polyadenylation factors in relevant protozoan parasites and the human host, to identify key proteins and define potential targets for pathogen control. Then, we used Entamoeba histolytica as a working model to validate our computational results. RT-qPCR assays confirmed the coordinated modulation of connected proteins in the PPI network and evidenced that silencing of the bottleneck protein EhCFIm25 affects the expression of interacting proteins. In addition, molecular dynamics simulations and docking approaches allowed to characterize the relationships between EhCFIm25 and Ehnopp34, two connected bottleneck proteins. Interestingly, the experimental identification of EhCFIm25 interactome confirmed the close relationships among proteins involved in gene expression regulation and evidenced new links with moonlight proteins in E. histolytica, suggesting a connection between RNA biology and metabolism as described in other organisms. Altogether, our results strengthened the relevance of comparative genomics and interactomics of polyadenylation factors for the prediction of new targets for the control of these human pathogens.

Childhood proliferative fasciitis of the orbit mimicking sarcoma: a case report.

Proliferative fasciitis (PF) is a benign fibroblastic reaction with histological and clinical characteristics that overlap with those of malignant soft tissue tumors; thus, it is referred to as a pseudosarcomatous reaction. It continues to be an important cause of diagnostic error and overtreatment. The childhood PF subtype has some distinct histological and immunohistochemical characteristics that make differential diagnosis with malignant tumors even harder, especially with sarcoma. These proliferations generally occur in the lower limbs, and the periorbital region is a rare location of appearance. Here, we describe a case of childhood subtype PF in a 16-year-old girl located in the periorbital area. To the best of our knowledge, this is the first reported case of childhood subtype PF in the periorbital area, and the third case if PF subtypes are not taken into account.

Optimization of Thermoultrasound Process of Soursop (Annona muricata) Nectar and Comparison of Its Physicochemical Properties and In Vitro Bioaccessibility of Antioxidants with Pasteurized Sample.

Research background: Soursop nectar contains antioxidants and is preserved by pasteurization. However, this technology impairs its physicochemical properties and bioactive compounds. An alternative is therefore thermoultrasound, which could counteract these effects. The thermosonicated nectar was compared with a pasteurized one and the in vitro bioaccessibility of antioxidants was estimated. Experimental approach: The soursop nectar (25 %) was processed and the response surface methodology was used to determine the optimal conditions for thermoultrasound treatment (TUS). The TUS (75-90 % amplitude, 3.15-15 min) was applied, and 2 % stevia and 6 % agave inulin were added as sweeteners. The microbiological, physicochemical, enzymatic and antioxidant properties were analyzed. The properties of thermosonicated nectar obtained under optimal conditions were compared with pasteurized nectar. In addition to the above determinations, microstructure, total dietary fiber (TDF) and in vitro bioaccessibility of antioxidants were determined. Results and conclusions: The response variables that fit the mathematical model were L*, b*, chroma (C*), total phenolic content (TPC) and antioxidant activity determined by ABTS•+, DPPH˙ and Fe(III) reducing antioxidant power (FRAP). The L* and DPPH˙ were affected by quadratic time and TPC by time (p<0.0001). The optimum TUS condition was 82 % amplitude for 9.15 min and the responses variables were L*, b* and C* (45.48, 3.55 and 3.62, respectively), TPC expressed as gallic acid equivalents (38.40 mg/100 mL), ABTS•+ expressed as Trolox equivalents (TE) (31.28 µmol/100 mL), DPPH˙ expressed as TE (124.22 µmol/100 mL) and FRAP expressed as Fe(II) (3.06 µmol/100 mL). Compared to the pasteurized sample, thermosonicated sample had high values of L* (45.56), h° (-56.49), TPC (26.63 mg/100 mL), ABTS•+ and DPPH˙ (22.03 and 129.22 µmol/100 mL, respectively), FRAP (3.10 µmol/100 mL) and low pectin methylesterase (PME) activity (0.28 U/mL). For in vitro bioaccessibility, thermosonicated nectar showed high absorption of TPC (15.26/100 mL) and high antioxidant activity determined by ABTS (34.92 µmol/100 mL) and FRAP (7.88 µmol/100 mL). Novelty and scientific contribution: The thermoultrasound improves the physicochemical properties and in vitro bioaccessibility of antioxidants in soursop nectar. On the other hand, as an alternative, this beverage offers low-calorie alternative with prebiotic properties that benefits consumer health.

Norbornene and Related Structures as Scaffolds in the Search for New Cancer Treatments.

The norbornene scaffold has arisen as a promising structure in medicinal chemistry due to its possible therapeutic application in cancer treatment. The development of norbornene-based derivatives as potential chemotherapeutic agents is attracting significant attention. Here, we report an unprecedented review on the recent advances of investigations into the antitumoral efficacy of different compounds, including the abovementioned bicyclic scaffold in their structure, in combination with chemotherapeutic agents or forming metal complexes. The impact that structural modifications to these bicyclic compounds have on the antitumoral properties and the mechanisms by which these norbornene derivatives act are discussed in this review. In addition, the use of norbornene, and its related compounds, encapsulation in nanosystems for its use in cancer therapies is here detailed.

Unveiling a New Selenocyanate as a Multitarget Candidate with Anticancer, Antileishmanial and Antibacterial Potential.

Currently, cancer, leishmaniasis and bacterial infections represent a serious public health burden worldwide. Six cinnamyl and benzodioxyl derivatives incorporating selenium (Se) as selenocyanate, diselenide, or selenide were designed and synthesized through a nucleophilic substitution and/or a reduction using hydrides. Ferrocene was also incorporated by a Friedel-Crafts acylation. All the compounds were screened in vitro for their antiproliferative, antileishmanial, and antibacterial properties. Their capacity to scavenge free radicals was also assessed as a first approach to test their antioxidant activity. Benzodioxyl derivatives 2a-b showed cytotoxicity against colon (HT-29) and lung (H1299) cancer cell lines, with IC50 values below 12 µM, and were also fairly selective when tested in nonmalignant cells. Selenocyanate compounds 1-2a displayed potent antileishmanial activity in L. major and L. infantum, with IC50 values below 5 µM. They also exhibited antibacterial activity in six bacterial strains, notably in S. epidermidis with MIC and MBC values of 12.5 µg/mL. Ferrocene-containing selenide 2c was also identified as a potent antileishmanial agent with radical scavenging activity. Remarkably, derivative 2a with a selenocyanate moiety was found to act as a multitarget compound with antiproliferative, leishmanicidal, and antibacterial activities. Thus, the current work showed that 2a could be an appealing scaffold to design potential therapeutic drugs for multiple pathologies.