Clinical Trial of a New Diuretic,Furosemide: Comparison with Hydrochlorothiazide and Mercaptomerin

A clinical trial was carried out with the object of comparing the effects of furosemide, a new oral diuretic agent, with those of mercaptomerin and hydrochlorothiazide. Eleven edematous patients were chosen for the study and the diuretics were rotated, each drug being preceded by a one- to three-day control period. The patients served as their own controls. Urine electrolytes, body weight, and blood chemistry were monitored.Furosemide was shown to be an effective diuretic in this clinical study; under the conditions of the trial a single oral dose of 80 mg. of furosemide produced a natriuretic response in a 24-hour period equivalent to that achieved with a single oral dose of 100 mg. of hydrochlorothiazide or a single dose of 2.0 c.c. (80 mg. of mercury) of mercaptomerin given intramuscularly.     

Receptor-Interacting Protein Kinase 3 Deficiency Delays Cutaneous Wound Healing

Wound healing consists of a complex, dynamic and overlapping process involving inflammation, proliferation and tissue remodeling. A better understanding of wound healing process at the molecular level is needed for the development of novel therapeutic strategies. Receptor-interacting protein kinase 3 (RIPK3) controls programmed necrosis in response to TNF-α during inflammation and has been shown to be highly induced during cutaneous wound repair. However, its role in wound healing remains to be demonstrated. To study this, we created dorsal cutaneous wounds on male wild-type (WT) and RIPK3-deficient (Ripk3 ^-/-) mice. Wound area was measured daily until day 14 post-wound and skin tissues were collected from wound sites at various days for analysis. The wound healing rate in Ripk3 ^-/- mice was slower than the WT mice over the 14-day course; especially, at day 7, the wound size in Ripk3 ^-/- mice was 53% larger than that of WT mice. H&E and Masson-Trichrome staining analysis showed impaired quality of wound closure in Ripk3 ^-/- wounds with delayed re-epithelialization and angiogenesis and defected granulation tissue formation and collagen deposition compared to WT. The neutrophil infiltration pattern was altered in Ripk3 ^-/- wounds with less neutrophils at day 1 and more neutrophils at day 3. This altered pattern was also reflected in the differential expression of IL-6, KC, IL-1β and TNF-α between WT and Ripk3 ^-/- wounds. MMP-9 protein expression was decreased with increased Timp-1 mRNA in the Ripk3 ^-/- wounds compared to WT. The microvascular density along with the intensity and timing of induction of proangiogenic growth factors VEGF and TGF-β1 were also decreased or delayed in the Ripk3 ^-/- wounds. Furthermore, mouse embryonic fibroblasts (MEFs) from Ripk3 ^-/- mice migrated less towards chemoattractants TGF-β1 and PDGF than MEFs from WT mice. These results clearly demonstrate that RIPK3 is an essential molecule to maintain the temporal manner of the normal progression of wound closure.     

Investigation of the microbial metabolism of carbon dioxide and hydrogen in the kangaroo foregut by stable isotope probing

Kangaroos ferment forage material in an enlarged forestomach analogous to the rumen, but in contrast to ruminants, they produce little or no methane. The objective of this study was to identify the dominant organisms and pathways involved in hydrogenotrophy in the kangaroo forestomach, with the broader aim of understanding how these processes are able to predominate over methanogenesis. Stable isotope analysis of fermentation end products and RNA stable isotope probing (RNA-SIP) were used to investigate the organisms and biochemical pathways involved in the metabolism of hydrogen and carbon dioxide in the kangaroo forestomach. Our results clearly demonstrate that the activity of bacterial reductive acetogens is a key factor in the reduced methane output of kangaroos. In in vitro fermentations, the microbial community of the kangaroo foregut produced very little methane, but produced a significantly greater proportion of acetate derived from carbon dioxide than the microbial community of the bovine rumen. A bacterial operational taxonomic unit closely related to the known reductive acetogen Blautia coccoides was found to be associated with carbon dioxide and hydrogen metabolism in the kangaroo foregut. Other bacterial taxa including members of the genera Prevotella, Oscillibacter and Streptococcus that have not previously been reported as containing hydrogenotrophic organisms were also significantly associated with metabolism of hydrogen and carbon dioxide in the kangaroo forestomach.     

Nifedipine loaded chitosan microspheres prepared by emulsification phase-separation

A high yield of nifedipine-chitosan microspheres could be obtained using an emulsification phase-separation method. A high level of entrapment of nifedipine in the microspheres was achieved. The microspheres exhibited excellent swelling properties. Differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy confirmed that at 1.84% loading, nifedipine was dispersed molecularly. The microspheres exhibited faster release at low loadings compared to high loadings. Fitting the data to the coupled Fickian/case II equation, showed that at low loadings polymer relaxation coefficients (k₂) were high. As the polymer content increased in the microspheres, the value of n (diffusional exponent characteristic of the release mechanism) approached one, which is indicative of zero order.     

In silico identification and study of potential anti-mosquito juvenile hormone binding protein (MJHBP) compounds as candidates for dengue virus - Vector insecticides

Dengue has become a huge global health burden. It is currently recognized as the most rapidly spreading mosquito-borne viral disease. Yet, there are currently no licensed vaccines or specific therapeutics to manage the virus, thus, scaling up vector control approaches is important in controlling this viral spread. This study aimed to identify and study in silico, potential anti-mosquito compounds targeting Juvenile hormone (JH) mediated pathways via the Mosquito Juvenile Hormone Binding Protein (MJHBP). The study was implemented using series of computational methods. The query compounds included pyrethroids and those derived from ZINC and ANPDB databases using a simple pharmacophore model in Molecular Operating Environment (MOE). Molecular docking of selected compounds’ library was implemented in MOE. The resultant high-score compounds were further validated by molecular dynamics simulation via Maestro 12.3 module and the respective Prime/Molecular Mechanics Generalized Born Surface Area (Prime/MM-GBSA) binding energies computed. The study identified compounds-pyrethroids, natural and synthetic - with high docking energy scores (ranging from 10.91–12.34 kcal/mol). On further analysis of the high-ranking (in terms of docking scores) compounds using MD simulation, the compounds - Ekeberin D4, Maesanin, Silafluofen and ZINC16919139- revealed very low binding energies (?122.99, ?72.91 -104.50 and,-74.94 kcal/mol respectively), fairly stable complex and interesting interaction with JH-binding site amino acid residues on MJHBP. Further studies can explore these compounds in vitro/in vivo in the search for more efficient mosquito vector control.     

Novel glycan biomarkers for the detection of lung cancer

Lung cancer has a poor prognosis and a 5-year survival rate of 15%. Therefore, early detection is vital. Diagnostic testing of serum for cancer-associated biomarkers is a noninvasive detection method. Glycosylation is the most frequent post-translational modification of proteins and it has been shown to be altered in cancer. In this paper, high-throughput HILIC technology was applied to serum samples from 100 lung cancer patients, alongside 84 age-matched controls and significant alterations in N-linked glycosylation were identified. Increases were detected in glycans containing Sialyl Lewis X, monoantennary glycans, highly sialylated glycans and decreases were observed in core-fucosylated biantennary glycans, with some being detectable as early as in Stage I. The N-linked glycan profile of haptoglobin demonstrated similar alterations to those elucidated in the total serum glycome. The most significantly altered HILIC peak in lung cancer samples includes predominantly disialylated and tri- and tetra-antennary glycans. This potential disease marker is significantly increased across all disease groups compared to controls and a strong disease effect is visible even after the effect of smoking is accounted for. The combination of all glyco-biomarkers had the highest sensitivity and specificity. This study identifies candidates for further study as potential biomarkers for the disease.     

The presence of the past: youth,memory making and the politics of self-determination in southeastern Nigeria

This article focuses on recent reconstructions of Igbo ‘memory’ by the Movement for the Actualization of the Sovereign state of Biafra (MASSOB). MASSOB is a second-generation Igbo separatist movement that draws on a collection of ‘memory repertoires’ to agitate for the self-determination and exit of the Igbo ethnic group from the Nigerian state into an alternative political and administrative arrangement known as the Republic of Biafra. The core issues relate to dual narratives generated by the Nigerian–Biafran War. While the state shapes the official history, memories and narratives of the war to suit its own vision, interests and politics, MASSOB contests these official views as the sole legitimate framework for remembering and interpreting the war, but still connects to the war as a war of Igbo national liberation. These contestations provide the context for the enactment of memory claims and counterclaims, and their association with political violence in contemporary Nigeria.