Purification and characterization of seven bioactive compounds from the newly isolated Streptomyces cavourensis TN638 strain via solid-state fermentation.

The strain TN638 was isolated from Tunisian soil contaminated with industrial wastewater and selected for its potent antimicrobial activity against the tested Gram positive bacteria: Staphylococcus aureus (S. aureus) ATCC 6538 and Listeria monocytogenes (L. monocytogenes) ATCCC 19117, and Gram negative bacteria: Agrobacterium tumefaciens (A. tumefaciens) ATCC 23308 and Salmonella typhimurium (S. typhimurium) ATCC 14028 and fungi: Candida albicans (C. albicans) ATCC 10231, Rhizoctonia solani (R. solani) ATCC 58938 and Fusarium sp. Solide-state fermentation (SSF) dry crude extract of the TN638 strain presents a strong inhibitory activity notably against the phytopathogenic microorganism A. tumefaciens ATCC 23308 and the two pathogenic bacteria S. aureus ATCC 6538 and L. monocytogenes ATCCC 19117 with a zone of inhibition of 48, 34 and 34 mm respectively. According to the morphological characteristic, the complete 16S rRNA gene nucleotide sequence determination [1492 bp deposited in National Center of Biotechnology Information (NCBI) database under the accession no. LN854629.1; https://www.ncbi.nlm.nih.gov/nuccore/LN854629.1/], and the phylogenetic analysis, we can deduce that our isolate is an actinomycete bacterium belonging to the genus Streptomyces and the most closely related strain was Streptomyces cavourensis (S. cavourensis) NRRL 2740T (99.9%). We propose the assignment of our strain as Streptomyces cavourensis (S. cavourensis) TN638 strain. Work-up and purification of the strain extract using different chromatographic techniques afforded seven bio-compounds namely: Cyclo-(Leu-Pro) (1), Cyclo-(Val-Pro) (2), Cyclo-(Phe-Pro) (3), nonactin (4), monactin (5), dinactin (6) and trinactin (7). The chemical structures of compounds 1-7 were confirmed by nuclear magnetic resonance (NMR) 1D and 2D spectroscopy, mass spectrometry, and comparison with literature data. The three purified diketopiperazine (DKP) derivatives (1-3), demonstrated significant antibacterial activity against A. tumefaciens ATCC 23308 and S. typhimurium ATCC 14028. The four pure macrotetrolides (4-7), exhibited strong inhibitory effect against all tested Gram positive and Gram negative bacteria notably against A. tumefaciens ATCC 23308 and S. typhimurium ATCC 14028 with a minimum inhibitory concentration (MIC) around 8 µg/mL quite similar to that of ampicillin. Thus, we propose the use of the (SSF) active extract of the S. cavourensis TN638 strain as safe biological product to control disease caused by plant pathogen A. tumefaciens. Also, the purified active molecules produced by this strain could be used in pharmaceutical field.

Amniotic fluid embolism complicating medical termination of pregnancy.

BACKGROUND: Amniotic fluid embolism is always a severe complication and generally occurs during labour or immediately after childbirth. CLINICAL FEATURES: We report the case of a patient falling victim to amniotic fluid embolism after the medical termination of her pregnancy at 24 weeks of amenorrhea following the discovery of a teratoma-carrying foetus. The amniotic fluid embolism diagnosis was strongly suspected in the face of the sudden onset of severe arterial hypotension, hypoxic respiratory distress, a coma state and disseminated intravascular coagulopathy immediately after the delivery. Additional tests were conducted to support the diagnosis: cytological testing of a peripheral venous sample and maternal broncho-alveolar lavage fluid, dosing of tryptase and alpha-fetoprotein levels as well as screening for insulin-like growth factor binding protein 1. CONCLUSION: Amniotic fluid embolism is a rare and difficult diagnosis, especially in unconventional settings, yet it can be facilitated by screening for amniotic markers and tryptase.

Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol.

One of the most important components of sepsis management is hemodynamic restoration. If the target mean arterial pressure (MAP) is not obtained, the first recommendation is for volume expansion, and the second is for norepinephrine (NE). We describe the methodology of a randomized multicenter trial aiming to assess the hypothesis that low-dose NE given early in adult patients with sepsis will provide better control of shock within 6 hours from therapy starting compared to standard care. This trial includes ICU septic patients in whom MAP decrease below 65 mmHg to be randomized into 2 groups: early NE-group versus standard care-group. The patient's attending clinician will determine how much volume expansion is necessary to meet the target of a MAP > 65 mm Hg. If this target not achieved, after at least 30 ml/kg and guided by the available indices of fluid responsiveness, NE will be used in a usual way. The latter must follow a consensual schedule elaborated by the investigating centers. Parameters to be taken at inclusion and at H6 are: lactates, cardiac ultrasound parameters (stroke volume (SV), cardiac output (CO), E/E' ratio), and P/F ratio. MAP and diuresis are recorded hourly. Our primary outcome is the shock control defined as a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours) within 6 hours. Secondary outcomes: Decrease in serum lactate> 10% from baseline within 6 hours, the received fluid volume within 6 hours, variation of CO and E/E', and 28 days-Mortality. The study is ongoing and aims to include at least 100 patients per arm. This study is likely to contribute to support the indication of early initiation of NE with the aim to restrict fluid intake in septic patients. (ClinicalTrials.gov ID: NCT05836272).

Dewerin and gilbertionol two new secondary metabolites from the stem bark of Gilbertiodendron dewevrei (De Wild) J. Leonard.

The phytochemical investigation of the methanol extract of the stem bark of Gilbertiodendron dewevrei led to the isolation of two new secondary metabolites, 5,7-dihydroxy-4'-methoxyisoflavan-2,4-dione (1) and 23-hydroxy-2-tricosanone (2) along with 19 known compounds (3-21). The structure of these compounds were established by interpretation of their spectral data, mainly HR-TOFESIMS, 1 D NMR (1H, 13C and DEPT) and 2 D NMR (1H-1H COSY, HSQC, HMBC, and NOESY), and by comparison with those reported in the literature. The methanol extract and some isolates were screened for their antiradical, antibacterial, and inhibitory properties against acetylcholinesterase.

Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla.

Over the last decades, endophytic fungi represent a new source of pharmacologically active secondary metabolites based on the underlying assumption that they live symbiotically within their plant host. In the present study, a new endophytic fungus was isolated from Rauwolfia macrophylla, a medicinal plant from Cameroon. The fungus showed a highest homology to Curvularia sp. based on complete nucleotide sequence data generated from the internal transcribed spacer (ITS) of ribosomal DNA region. Large scale fermentation, working-up and separation of the strain extract using different chromatographic techniques afforded three bioactive compounds: 2'-deoxyribolactone (1), hexylitaconic acid (2) and ergosterol (3). The chemical structures of compounds 1-3 were confirmed by 1 and 2D NMR spectroscopy and mass spectrometry, and comparison with corresponding literature data. Biologically, the antimicrobial, antioxidant activities and the acetylcholinesterase inhibitory of the isolated compounds were studied.