• Title/Summary/Keyword: Escherichia coli-induced sepsis

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IM-133N - A Useful Herbal Combination for Eradicating Disease-triggering Pathogens in Mice via Immunotherapeutic Mechanisms

  • Firashathulla, Syed;Inamdar, Mohammed Naseeruddin;Rafiq, Mohamed;Viswanatha, Gollapalle Lakshminarayanashastry;Kumar, Lakkavalli Mohan Sharath;Babu, Uddagiri Venkanna;Ramakrishnan, Shyam;Paramesh, Rangesh
    • Journal of Pharmacopuncture
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    • v.19 no.1
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    • pp.21-27
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    • 2016
  • Objectives: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. Methods: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM-133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. Results: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM-133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, ${\beta}$-sitosterol, nonaeicosanol, ${\beta}$-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. Conclusion: These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders.

Effect of Inhaled Nitric Oxide on Hemodynamics, Gas Exchange and Pulmonary Inflammation in Newborn Piglets with Escherichia coli Induced Septic Lungs (패혈성 폐가 유도된 신생자돈에서 외인성 Nitric Oxide 흡입의 혈역학, 가스교환 및 폐 염증에 대한 효과)

  • Chang, Yun Sil;Ko, Sun Young;Park, Won Soon
    • Clinical and Experimental Pediatrics
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    • v.46 no.8
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    • pp.777-783
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    • 2003
  • Purpose : The aim of this study was to evaluate the effect of inhaled nitric oxide(iNO) on gas exchange, hemodynamics and pulmonary inflammation in newborn piglets with E. coli induced septic lung. Methods : Twenty three instrumented and ventilated piglets were randomized into three groups : CON(n=6), PCON(n=9), and PNO(n=8). In the piglets of the PCON and PNO groups, E. coli septic lung was induced by endotracheal instillation of E. coli. Ten ppm iNO was given continuously in the PNO group after endotracheal instillation of E. coli. All animals were mechanically ventilated for six hour with a peak inspiratory pressure of 30 $cmH_2O$, frequency of 25 breaths/min, $FiO_2$ 1.0 and a positive end-expiratory pressure of 4 $cmH_2O$. All measurements were made at one hour intervals during the experiment. At the end of the experiment, lung tissue was harvested for the analysis of myeloperoxidase activity, indicative of lung inflammation. Results : All piglets with pulmonary instillation of E. coli developed E. coli sepsis. Piglets in the PCON group developed progresseve pulmonry hypertension, hypoxemia and hypercarbia compared to the CON group due to increased pulmonary vascular resistance, intrapulmonary shunt fraction and physiologic dead space fraction. iNO did not reverse pulmonary hypertension in the PNO group. However iNO significantly improved oxygenation, which was attributed to marked improvement of venous admixture and partial attenuation of increase in dead space fraction. Increased myeloperoxidase activity in PCON compared to CON was significantly attenuated in PNO. Conclusion : iNO improves oxygenation and lung inflammation in newborn piglets with E. coli induced septic lung.