Hemorrhagic shock secondary to ruptured hypogastric artery pseudoaneurysm. A rare complication of colorectal anastomotic leakage.

Massive bleeding due to rupture of hypogastric artery pseudoaneurysm is an exceptional complication of colorectal anastomotic leakage. A 41-year-old woman with history of rectal cancer surgery, who debuted with massive rectorrhagia and hypovolemic shock due to rupture of a hypogastric artery pseudoaneurysm as a late complication of a colorectal anastomosis leak. The ruptured hypogastric artery pseudoaneurysm should be taken into account in the differential diagnosis of patients with massive rectorrhagia and history of colorectal anastomosis leak. Endovascular embolization is considered the first-line treatment.

La hemorragia masiva por rotura de un pseudoaneurisma de la arteria hipogástrica es una complicación muy rara de la fuga anastomótica colorrectal. Mujer de 41 años con antecedentes de cirugía por cáncer de recto, que debutó con un cuadro de rectorragias masivo y shock hipovolémico secundario a la rotura de un pseudoaneurisma de la arteria hipogástrica como complicación tardía de una fuga de la anastomosis colorrectal. La rotura de un pseudoaneurisma de la arteria hipogástrica se debe tener presente en el diagnostico diferencial de pacientes con rectorragia masiva y antecedentes de dehiscencia de anastomosis colorrectal. La embolización endovascular es actualmente el tratamiento de elección.

Induction of New Aromatic Polyketides from the Marine Actinobacterium Streptomyces griseorubiginosus through an OSMAC Approach.

Using the OSMAC (One Strain Many Compounds) approach, the actinobacterium Streptomyces griseorubiginosus, derived from an unidentified cnidarian collected from a reef near Pointe de Bellevue in Réunion Island (France), was subjected to cultivation under diverse conditions. This endeavour yielded the isolation of a repertoire of 23 secondary metabolites (1-23), wherein five compounds were unprecedented as natural products (19-23). Specifically, compounds 19 and 20 showcased novel anthrone backbones, while compound 23 displayed a distinctive tetralone structure. Additionally, compounds 21 and 22 presented an unusual naphtho [2,3-c]furan-4(9H)-one chromophore. Interestingly, the detection of all these novel compounds (19-23) was exclusively achieved when the bacterium was cultured in FA-1 liquid medium supplemented with the epigenetic modifier γ-butyrolactone. The elucidation of the structural features of the newfound compounds was accomplished through a combination of HRESIMS, 1D and 2D NMR spectroscopy, as well as QM-NMR (Quantum Mechanical-Nuclear Magnetic Resonance) methods and by comparison with existing literature. Moreover, the determination of the relative configuration of compound 23 was facilitated by employing the mix-J-DP4 computational approach.

OSMAC Approach and Cocultivation for the Induction of Secondary Metabolism of the Fungus Pleotrichocladium opacum.

The application of an OSMAC (One Strain-Many Compounds) approach on the fungus Pleotrichocladium opacum, isolated from a soil sample collected on the coast of Asturias (Spain), using different culture media, chemical elicitors, and cocultivation techniques resulted in the isolation and identification of nine new compounds (8, 9, 12, 15-18, 20, 21), along with 15 known ones (1-7, 10, 11, 14, 19, 22-25). Compounds 1-9 were detected in fungal extracts from JSA liquid fermentation, compounds 10-12 were isolated from a solid rice medium, whereas compounds 14 and 15 were isolated from a solid wheat medium. Addition of 5-azacytidine to the solid rice medium caused the accumulation of compounds 16-18, whereas adding N-acetyl-d-glucosamine triggered the production of two additional metabolites, 19 and 20. Finally, cocultivation of the fungus Pleotrichocladium opacum with Echinocatena sp. in a solid PDA medium led to the production of five additional natural products, 21-25. The structures of the new compounds were elucidated by HRESIMS and 1D and 2D NMR as well as by comparison with literature data. DP4+ and mix-J-DP4 computational methods were applied to determine the relative configurations of the novel compounds, and in some cases, the absolute configurations were assigned by a comparison of the optical rotations with those of related natural products.

Gongolarones as antiamoeboid chemical scaffold.

Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1'-methoxyamentadione (5) and 6Z-1'-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC50 values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ2 t to Δ3 t of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba.

May the Force (Field) Be with You: On the Importance of Conformational Searches in the Prediction of NMR Chemical Shifts.

NMR data prediction is increasingly important in structure elucidation. The impact of force field selection was assessed, along with geometry and energy cutoffs. Based on the conclusions, we propose a new approach named mix-J-DP4, which provides a remarkable increase in the confidence level of complex stereochemical assignments-100% in our molecular test set-with a very modest increment in computational cost.

Lactate dehydrogenase A inhibitors with a 2,8-dioxabicyclo[3.3.1]nonane scaffold: A contribution to molecular therapies for primary hyperoxalurias.

Human lactate dehydrogenase A (hLDHA) is one of the main enzymes involved in the pathway of oxalate synthesis in human liver and seems to contribute to the pathogenesis of disorders with endogenous oxalate overproduction, such as primary hyperoxaluria (PH), a rare life-threatening genetic disease. Recent published results on the knockdown of LDHA gene expression as a safe strategy to ameliorate oxalate build-up in PH patients are encouraging for an approach of hLDHA inhibition by small molecules as a potential pharmacological treatment. Thus, we now report on the synthesis and hLDHA inhibitory activity of a new family of compounds with 2,8-dioxabicyclo[3.3.1]nonane core (23-42), a series of twenty analogues to A-type proanthocyanidin natural products. Nine of them (25-27, 29-34) have shown IC50 values in the range of 8.7-26.7 µM, based on a UV spectrophotometric assay, where the hLDHA inhibition is measured according to the decrease in absorbance of the cofactor ß-NADH (340 nm). Compounds 25, 29, and 31 were the most active hLDHA inhibitors. In addition, the inhibitory activities of those nine compounds against the hLDHB isoform were also evaluated, finding that all of them were more selective inhibitors of hLDHA versus hLDHB. Among them, compounds 32 and 34 showed the highest selectivity. Moreover, the most active hLDHA inhibitors (25, 29, 31) were evaluated for their ability to decrease the oxalate production by hyperoxaluric mouse hepatocytes (PH1, PH2 and PH3) in vitro, and the relative oxalate output at 24 h was 16% and 19 % for compounds 25 and 31, respectively, in Hoga1-/- mouse primary hepatocyte cells (a model for PH3). These values improve those of the reference compound used (stiripentol). Compounds 25 and 31 have in common the presence of two hydroxyl groups at rings B and D and an electron-withdrawing group (NO2 or Br) at ring A, pointing to the structural features to be taken into account in future structural optimization.

Squamins C-F, four cyclopeptides from the seeds of Annona globiflora.

Four cyclic octapeptides, squamins C-F, were isolated from the seeds of Annona globiflora Schltdl. These compounds share part of their amino acid sequence, -Pro-Met(O)-Tyr-Gly-Thr-, with previously reported squamins A and B. Their structures were determined using NMR spectroscopic techniques together with quantum mechanical calculations (QM-NMR), ESI-HRMS data and a modified version of Marfey's chromatographic method. All compounds showed cytotoxic activity against DU-145 (human prostate cancer) and HeLa (human cervical carcinoma) cell lines. Clearly, A. globiflora is an important source of bioactive molecules, which could promote the sustainable exploitation of this undervalued specie.

Litosetoenins A-E, Diterpenoids from the Soft Coral Litophyton setoensis, Backbone-Rearranged through Divergent Cyclization Achieved by Epoxide Reactivity Inversion.

Litosetoenins A-E (1-5), five new ring-rearranged serrulatane-type diterpenoids with a common tricyclo[3.0.4]decane core, along with a known diterpenoid glycoside (6), a related known diterpenoid (7), and four known sesquiterpenoids (8-11), were isolated from a Balinese soft coral Litophyton setoensis. Spirolitosetoenin A (5a) and isospirolitosetoenin A (5b), featuring an unprecedented spiro[4,5]decane core, were obtained after treatment of compound 5 with HCl in methanol. The structures of new compounds were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance approach, and chemical methods. A plausible biosynthetic pathway involving an unusual divergent biogenesis was proposed.

Adenocarcinoma of the small intestine in Crohn's disease.

The first case of small-bowel carcinoma (SBC) associated with Crohn's disease (CD) was described by Ginzburg in 1956. Since then, only 220 cases have been published in the literature.

Assessment of risk scores in Covid-19.

OBJECTIVE: To analyse the accuracy of commonly used risk scores (PSI and CURB-65) in predicting mortality and need for ICU admission in Covid-19. MATERIAL AND METHODS: Prospective study of patients diagnosed with Covid-19 pneumonia. Patients were followed until home discharge or death. PSI, CURB-65, SMART-COP and MuLBSTA severity scores were assessed on admission. Risk scores were related to mortality and ICU admission. RESULTS: About 249 patients, 143 males (57.4%) were included. The mean age was 65.6 + 16.1 years. Factors associates with mortality in the multivariate analysis were age > 80 years (OR: 13.9; 95% CI 3.8-51.1) (P = .000), lymphocytes < 800 (OR: 2.9; CI 95% 1.1-7-9) (P = .040), confusion (OR: 6.3; 95% CI 1.6-24.7) (P = .008) and NT-proBNP > 500 pg/mL (OR: 10.1; 95% CI 1.1-63.1) (P = .039). In predicting mortality, the PSI score: AUC 0.874 (95% CI 0.808-0.939) and the CURB-65 score: AUC 0.852 (95% CI 0.794-0.909) were the ones that obtained the best results. In the need for ICU admission, the SMART-COP score: AUC 0.749 (95% CI 0.695-0.820) and the MuLBSTA score: AUC 0.777 (95% CI 0.713-0.840) were the ones that obtained better results, with significant differences with PSI and CURB-65. The scores with the lowest value for ICU admission prediction were PSI with AUC of 0.620 (95% CI 0.549-0.690) and CURB-65 with AUC of 0.604 (95% CI 0.528-0.680). CONCLUSIONS: Prognosis scores routinely used for CAP (PSI and CURB-65) were good predictors for mortality in patients with Covid-19 CAP but not for need of hospitalisation or ICU admission. In the evaluation of Covid-19 pneumonia, we need scores that allow to decide the appropriate level of care.

Prorocentroic Acid, a Neuroactive Super-Carbon-Chain Compound from the Dinoflagellate Prorocentrum hoffmannianum.

Prorocentroic acid (PA) was isolated from the dinoflagellate Prorocentrum hoffmannianum. Relative configurations for its 35 asymmetric centers were determined by analysis of NMR data including heteronuclear couplings and quantum mechanical calculations. PA was tested by using murine cortical neurons grown on microelectrode arrays. Long-term exposure to subtoxic concentrations induced a significant reorganization of neuronal signaling, mainly by changes in the bursting activity. The observed effects could be due to the activation of a plasticity process.

Rare new bicyclic cembranoid ethers and a novel trihydroxy prenylated guaiane from the Xisha soft coral Lobophytum sp.

Seven new cembrane-type diterpenes, lobophytolins C-I (3-9), and one new prenylated-guiane-type diterpene, lobophytolin J (10), along with six known related ones (1, 2, 11-14), have been isolated from the soft coral Lobophytum sp. collected off the Xisha Island in the South China Sea. Their structures were elucidated by extensive spectroscopic analysis and quantum mechanical (QM)-NMR methods. The absolute configuration of lobophytolin H (8) was determined by the application of the modified Mosher's method and chemical transformation. Lobophytolin D (4) exhibited promising cytotoxicities in in vitro bioassays against HT-29, Capan-1, A549, and SNU-398 human cancer cell lines with IC50 values of 4.52, 6.62, 5.17, and 6.15 µM, respectively.

Quantum Mechanical-NMR-Aided Configuration and Conformation of Two Unreported Macrocycles Isolated from the Soft Coral Lobophytum sp.: Energy Calculations versus Coupling Constants.

Two new macrocyclic cembranoids were isolated from the South China Sea soft coral Lobophytum sp. Quantum mechanical-nuclear magnetic resonance (QM-NMR) methods were decisive in their structural elucidation. Better performance in arriving at definitive structures was obtained by QM-NMR methods upon incorporation of 3JHH values. The validity of this approach also supported an alternative conformational proposal versus that obtained by X-ray crystallography.