Characterization and Antibacterial Activity of a Glycoside Antibiotic from Streptomyces variabilis PO-178

In the present study, characterization and antibacterial activity of a glycoside antibiotic from fermentation broth of bioactive Streptomyces variabilis PO-178 recovered previously from Western Ghat soil of Agumbe, Karnataka, India was investigated. Mass cultivation of the strain PO-178 was carried out in Starch casein nitrate broth. The fermentation broth was extracted using butanol solvent in a separation funnel. The concentrated butanol extract was subjected to chromatographic techniques viz., thin layer and silica gel column chromatography for purification of bioactive components. Out of 3 fractions (A, B and C) obtained, only one fraction (C) displayed inhibitory activity against Staphylococcus aureus and Pseudomonas aeruginosa. The bioactive fraction C was subjected to spectral analysis (LC-MS, IR, 1H-NMR and 13C-NMR) in order to determine the structure. On the basis result of spectral analysis, the purified fraction was predicted as a glycoside antibiotic with molecular weight 514 and molecular formula C24H34O12. The antibiotic displayed marked inhibitory activity against S. aureus as revealed by wider zones of inhibition and low minimum inhibitory concentration value

Pre-operative Radiotherapy And Deep Inferior Epigastric Artery Perforator (DIEP) flAp study (PRADA): Aesthetic outcome and patient satisfaction at one year.

INTRODUCTION: The optimal combination of radiotherapy and breast reconstruction has not yet been defined. Post-mastectomy radiotherapy (PMRT) has deleterious effects on breast reconstruction, leading to caution amongst surgeons. Pre-operative radiotherapy (PRT) is a growing area of interest, is demonstrated to be safe, and spares autologous flaps from radiotherapy. This study evaluates the aesthetic outcome of PRT and deep inferior epigastric artery perforator (DIEP) flap reconstruction within the Pre-operative Radiotherapy And Deep Inferior Epigastric artery Perforator (DIEP) flAp (PRADA) cohort. METHODS: PRADA was an observational cohort study designed to evaluate the feasibility and safety of PRT for women undergoing neoadjuvant chemotherapy and DIEP reconstruction. Panel evaluation of 3D surface images (3D-SIs) and patient-reported outcome measures (BREAST-Q) for a subset of women in the study were compared with those of a DIEP-PMRT cohort who had undergone DIEP reconstruction and PMRT. RESULTS: Seventeen out of 33 women from the PRADA study participated in this planned substudy. Twenty-eight women formed the DIEP-PMRT cohort (median follow-up 23 months). The median (inter-quartile range [IQR]) 'satisfaction with breasts' score at 12 months for the PRADA cohort was significantly better than the DIEP-PMRT cohort (77 [72-87] versus 64 [54-71], respectively), p=0.01). Median [IQR] panel evaluation (5-point scale) was also significantly better for the PRADA cohort than for the DIEP-PMRT cohort (4.3 [3.9-4.6] versus 3.6 [2.8-4] p=0.003). CONCLUSIONS: Aesthetic outcome for the PRADA cohort was reported to be 'good' or 'excellent' in 93% of cases using a bespoke panel assessment with robust methodology. Patient satisfaction at one year is encouraging and superior to DIEP-PMRT at 23 months. Switching surgery-radiotherapy sequencing leads to similar breast aesthetic outcomes and warrants further large-scale, multi-centre evaluation in a randomised trial

Glucoregulation after canine islet transplantation:Contribution of insulin secretory capacity, insulin action, and the entero-insular axis

The physiological glucoregulatory mechanisms after islet transplantation have been incompletely investigated, We studied the insulin secretory capacity (ISC) by intravenous arginine stimulation during 35-mM glucose clamps, insulin action during hyperinsulinemic euglycemic clamps, and mixed-meal stimulation at 6-9 mo after intrasplenic islet autotransplantation in 8 dogs, as compared with 30 controls, The enteroinsular axis in the recipients was examined by infusion of porcine glucose-dependent insulinotropic polypeptide (GIP) and human glucagon-like peptide-1 (GLP-1) (7-36 amide) under 8.5-mM glycemic clamp conditions in order to mimic the postprandial glycemia after transplantation. The grafts comprised 25% of the native islet mass, and the ISC likewise averaged 25% of the control value, The postprandial insulin response, in contrast, had increased to 140% after transplantation-albeit with a concomitant glucose excursion to approximately 8.5 mM, Insulin action declined on average by 45% posttransplant. The ISC correlated both with the postprandial glucose excursion and insulin action in the grafted dogs, Insulin action did not correlate with the postprandial glucose excursion, Infusion of GIP had no effect, but GLP-1 nearly doubled glucose-stimulated insulin, Thus, a hyperglycemia-enhanced insulinotropic effect of GLP-1, and perhaps other gut hormones, may account for the difference in the insulin response to the intravenous and oral challenges, Because the ISC reflects the engrafted islet mass and appears to be the primary determinant of glucose tolerance, transplantation of higher islet doses should allow prolonged near-normal glucoregulation-at least, in the autotransplant setting. (C) 1997 Elsevier Science Inc

Noradrenergic and cholinergic reinnervation of islet grafts in diabetic rats

Grafted islets become denervated due to the islet transplantation procedure. The aim of the present study was 1) to examine whether islet grafts in the liver, the spleen, and under the kidney capsule in rats become reinnervated following the transplantation and experimental procedures used in our laboratory, 2) whether there is any difference in reinnervation at these different sites, and 3) how these results relate to previous physiological experiments. Isogeneic isolated islets were transplanted into diabetic Albino Oxford rats, resulting in normoglycaemia. After at least 5 wk, graft-receiving organs were removed and several antibodies were employed to detect insulin, neuron-specific proteins, and cholinergic and noradrenergic nerve fibers. Islets in all three receiving organs contained viable insulin-positive B-cells. Neuron-specific enolase (NSE) as well as the growth-associated protein B-50 was observed at all sites. The cholinergic marker choline acetyltransferase (ChAT) was localized in islets grafts at all sites, but with the lowest density in the spleen. Staining for the noradrenergic markers tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) was observed in islet grafts at all sites with the lowest density in grafts under the kidney capsule. All these neurochemical substances were most frequently observed in fibers associated with blood vessels, which may be the route along which nerves grow into the graft. It can be concluded that 1) islet grafts in the liver, in the spleen and under the kidney capsule become reinnervated; 2) the innervation pattern of the islet grafts differs only slightly from that in the control pancreatic islets; and 3) in combination with our previously physiological data, we can conclude that these nerve fibers are, at least partly, functionally active

Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study

BACKGROUND: Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. METHODS: We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. FINDINGS: Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. FUNDING: Cancer Research UK, National Institute for Health Research

Antioxidant, antimicrobial and anticancer activity of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to investigate in vitro antioxidant, antimicrobial and anticancer activity of the acetone extracts of the lichens <it>Cladonia furcata, Lecanora atra </it>and <it>Lecanora muralis</it>.</p> <p>Methods</p> <p>Antioxidant activity was evaluated by five separate methods: free radical scavenging, superoxide anion radical scavenging, reducing power, determination of total phenolic compounds and determination of total flavonoid content. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method against six species of bacteria and ten species of fungi. Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using MTT method.</p> <p>Results</p> <p>Of the lichens tested, <it>Lecanora atra </it>had largest free radical scavenging activity (94.7% inhibition), which was greater than the standard antioxidants. Moreover, the tested extracts had effective reducing power and superoxide anion radical scavenging. The strong relationships between total phenolic and flavonoid contents and the antioxidant effect of tested extracts were observed. Extract of <it>Cladonia furcata </it>was the most active antimicrobial agent with minimum inhibitory concentration values ranging from 0.78 to 25 mg/mL. All extracts were found to be strong anticancer activity toward both cell lines with IC₅₀values ranging from 8.51 to 40.22 μg/mL.</p> <p>Conclusions</p> <p>The present study shows that tested lichen extracts demonstrated a strong antioxidant, antimicrobial and anticancer effects. That suggest that lichens may be used as as possible natural antioxidant, antimicrobial and anticancer agents to control various human, animal and plant diseases.</p