scholarly journals Azithromycin reduces systemic inflammation and provides survival benefit in murine model of polymicrobial sepsis

2018 ◽  
Author(s):  
Anasuya Patel ◽  
Jiji Joseph ◽  
Hariharan Periasamy ◽  
Santosh Mokale

ABSTRACTSepsis is a life threatening systemic inflammatory condition triggered as a result of excessive host immune response to infection. In the past, drugs modulating immune reactions have demonstrated protective effect in sepsis. Azithromycin (macrolide antibiotic) with immunomodulatory activity was therefore evaluated in combination with ceftriaxone in a more clinically relevant murine model of sepsis induced by caecal ligation and puncture (CLP). First, mice underwent CLP and 3 h later were administered with vehicle, sub-effective dose of ceftriaxone (100 mg/kg,subcutaneous) alone or in combination with immunomodulatory dose of azithromycin (100 mg/kg,intraperitoneal). Survival was then monitored for 5 days. Parameters like body temperature, blood glucose, total white blood cell count, plasma glutathione (GSH), plasma and lung myeloperoxidase (MPO) as well as cytokine (interleukin IL-6, IL-1β, tumor necrosis factor-α) levels along with bacterial load in blood, peritoneal fluid and lung homogenate were measured 18 h after CLP challenge. Combination group significantly improved the survival of CLP mice. It attenuated the elevated levels of inflammatory cytokines and MPO in plasma and lung tissue and increased the body temperature, blood glucose and GSH which were otherwise markedly decreased in CLP mice. Ceftriaxone exhibited significant reduction of bacterial count in blood, peritoneal fluid and lung homogenate, while co-administration of azithromycin did not further reduce it. This confirms that survival benefit by azithromycin was due to immunomodulation and not by its antibacterial action. Findings of this study indicate that azithromycin in combination with ceftriaxone could exhibit clinical benefit in sepsis.

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Anasuya Patel ◽  
Jiji Joseph ◽  
Hariharan Periasamy ◽  
Santosh Mokale

ABSTRACTSepsis is a life-threatening systemic inflammatory condition triggered as a result of an excessive host immune response to infection. In the past, immunomodulators have demonstrated a protective effect in sepsis. Azithromycin (a macrolide antibiotic) has immunomodulatory activity and was therefore evaluated in combination with ceftriaxone in a clinically relevant murine model of sepsis induced by cecal ligation and puncture (CLP). First, mice underwent CLP and 3 h later were administered the vehicle or a subprotective dose of ceftriaxone (100 mg/kg of body weight subcutaneously) alone or in combination with an immunomodulatory dose of azithromycin (100 mg/kg intraperitoneally). Survival was monitored for 5 days. In order to assess the immunomodulatory activity, parameters such as plasma and lung cytokine (interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha) concentrations, the plasma glutathione (GSH) concentration, plasma and lung myeloperoxidase (MPO) concentrations, body temperature, blood glucose concentration, and total white blood cell count, along with the bacterial load in blood, peritoneal lavage fluid, and lung homogenate, were measured 18 h after CLP challenge. Azithromycin in the presence of ceftriaxone significantly improved the survival of CLP-challenged mice. Further, the combination attenuated the elevated levels of inflammatory cytokines and MPO in plasma and lung tissue and increased the body temperature and blood glucose and GSH concentrations, which were otherwise markedly decreased in CLP-challenged mice. Ceftriaxone produced a significant reduction in the bacterial load, while coadministration of azithromycin did not produce a further reduction. Therefore, the survival benefit offered by azithromycin was due to immunomodulation and not its antibacterial action. The findings of this study indicate that azithromycin, in conjunction with appropriate antibacterial agents, could provide clinical benefits in sepsis.


2007 ◽  
Vol 19 (1) ◽  
pp. 160
Author(s):  
M. Schmidt ◽  
I. B. Bøgh ◽  
Y. Du ◽  
Y. Zhang ◽  
J. Li ◽  
...  

In several species, nuclear transfer causes a high frequency of fetal loss, high birth weight, malformations, and neonatal death. This study investigates the fetal development of porcine embryos produced by handmade cloning (HMC) and compares the piglets with littermates produced by traditional cloning (TC). HMC embryos were produced from one fetal cell line, LYxD (Landrace/Yorkshire x Duroc) and TC from another (LYDxLYD). For transfer, 11 sows were weaned, and at cycle stage Day 4 after heat, they were anesthetized in lateral recumbence. Through an abdominal incision 40–60 Days 5–7 embryos (69% HMC + 31% TC) were transferred to the upper uterine horn. The tip of the uterine horn was punctured with a blunt 18G needle and a temporary catheter introduced to absorb the blood before inserting an insemination catheter (J-IUIC-351341 Insemi-Cath; Cook Ireland Ltd., Limerick, Ireland) 5–6 cm into the horn and releasing the embryos. Pregnancy was examined by ultrasonography every second week to Day 100. Caesarian sections were performed at Day 115, 24 h after injection of PGF2 (175 �g Estrumate�; Pitman-Moore Ltd., Harefield, UK). The piglets were fed with 15 mL kg-1/3 h colostrum through a stomach tube for the first 12–24 h, until they were left with their dam. Body weight, blood values (oxygen tension, and glucose and hemoglobin concentrations), and body temperature were recorded at birth, 24 h, and 3 weeks of age. The data were analyzed by Fisher's Exact test and are given as LS means � SEM values with a significance level of P < 0.05. The pregnancy rate was 6/11 (55%), with 2 pregnancies developing to term, 2 ongoing (Day 100 and Day 60), and 2 lost (about Day 35). So far, the litter sizes were 3 (1 TC, 2 HMC) and 10 (2 TC, 8 HMC) live piglets, respectively. The mean birth weight of the TC offspring (1045 � 135 g) was lower than that of the HMC piglets (1614 � 177 g) and that of normal piglets on the farm (1520 � 240 g; P < 0.05). One of the HMC piglets of the first litter was rather oversized (2690 g) and another showed rigid flexure of a carpal joint. All other piglets appeared normal on gross morphology and behavior. Blood values were similar for HMC and TC piglets, but the body temperature at Day 0 (36.3 � 0.2 vs. 35.1 � 1.1�C; P < 0.05) and the daily weight gain during the first week (129 � 21 vs. 74 � 13 g; P = 0.06) tended to be higher for the HMC piglets. After 24 hrs, the mean blood glucose concentration was higher in the HMC than in the TC piglets (6.09 � 0.74 vs. 3.67 � 0.19 mmol L-1) and similar to farm piglets of the same age (6.93 � 0.44 mmol L-1), but the difference was not significant after 3 weeks. These preliminary results demonstrate for the first time that HMC in pigs can result in an acceptable pregnancy rate, birth rate, and litter size. The minor differences in birth weight, weight gain, and blood glucose observed between HMC and TC offspring may be explained by the different cell lines used for the 2 methods, and are under current investigation.


Author(s):  
Tushar Deshmukh ◽  
H. S. Fadewar

This Diabetes is such a common dieses found all over the globe, in which blood glucose or in normal terminology the sugar level in blood is increased. It is the condition of the body in which the insulin which is required for the metabolism of the food is not created or body cannot use the insulin produced properly. Doctors say that diabetes can be controlled if it is detected in its early stages. Data mining is the process in which the data can be used for the prediction based on historic data. The intention here is to analysis how various researchers have used the data mining for better prediction of diabetes so that it could be controlled and possible even cured.


Author(s):  
Natalia Prodiana Setiawati ◽  
Joko Santoso ◽  
Sri Purwaningsih

The utilization of local food commodities such as corn and cassava with seaweed addition as a dietary fiber source for producing artificial rice through extrusion technology is an  alternative for food diversification. The research was carried out to find out the best composition (rice, corn, cassava, and seaweed) and temperature of extrusion process on making artificial rice and the influence of dietary fibre on sensory properties and physicochemical. The composition of rice, corn, and cassava in proportion  of 1:3:1 with 20% seaweed, Eucheuma cottonii, addition and temperature extruder of 90 °C were selected as the best product for artificial rice. The  sensory evaluation was 8.02±0.21 (people’s preference). In physicochemical properties, dietary fiber significantly affected on low bulk density and starch digestibility. This condition is very good for health especially in maintaining the stability of blood glucose in the body. Keywords: artificial rice, composition, extrusion, seaweed, dietary fibre, temperature


2018 ◽  
Vol 18 (2) ◽  
pp. 171-175
Author(s):  
Ashraf A. ◽  
Hassan F. ◽  
Batool S. ◽  
Nadeem M. ◽  
Irshad M. ◽  
...  

The objective of present study was to analyze and compare the nephroprotective effects of petroleum ether extracts of seeds of Nigella sativa and Silybum marianum in Swiss albino mice. Petroleum ether extracts of seeds of Nigella sativa and Silybum marianum were administered (200 mg kg–1) orally for 14 days following one dose of cisplatin injection (16 mg kg–1 i.p.) on 4th day. Cisplatin toxicity was identified in mice by loss of body weight, reduced triglycerides levels, elevated blood glucose, blood urea nitrogen and creatinine levels (P < 0.05). Silybum marianum and Nigella sativa significantly enhanced the body weight (9%) of diabetic rats. Silybum marianum had significantly reduced the elevated blood glucose (–106%), and BUN levels (–9%) as compared to the Nigella sativa administration. Silybum marianum extract also significantly elevated the levels of triglycerides (257%) which were much reduced after the cisplatin injection. Histological study showed that the cisplatin treated group demonstrated the necrosis signs in the glomerulus of Bowman’s capsule, hyalinization and severe cellular damage. The animals administered with extracts showed nearly normal kidney architecture, however, the kidney tissues of Silybum marianum-treated animals showed some improvement with slight signs of cellular damages.


2018 ◽  
Vol 24 (27) ◽  
pp. 3223-3231 ◽  
Author(s):  
Luyao Li ◽  
Shiyao Xu ◽  
Tingting Guo ◽  
Shouliang Gong ◽  
Chuan Zhang

Objective: To investigate the effect of dapagliflozin on intestinal microflora in MafA-deficient mice using an animal model of diabetes. Methods: Male MafA-deficient mice were administered dapagliflozin (1.0 mg/kg/d) intragastrically for 6 weeks. Mouse body weights and fasting blood glucose levels were measured, and intestinal short-chain fatty acids were measured by gas chromatography. A series of methods was used to analyse the number of primary harmful bacteria in the faeces, and high-throughput sequencing was used to sequence the changes in intestinal flora. Results: The weight of the mice decreased after dapagliflozin gavage, and fasting blood glucose was significantly lower than that in the control group (P < 0.001). Acetic acid and butyric acid contents in the intestinal tracts of the mice increased, and the growth of harmful microorganisms, such as Clostridium perfringens, enterococci, Enterobacteriaceae, and intestinal enterococci, was inhibited. Blautia is a species found in the experimental group and was significantly different from the control and blank groups as determined by the LDA score from highthroughput sequencing. Conclusion: Dapagliflozin can reduce fasting blood glucose, decrease body weight, increase short-chain fatty acid content, regulate the intestinal microecological balance of the body and promote blood glucose and energy homeostasis.


2020 ◽  
Vol 16 (1) ◽  
pp. 4-12
Author(s):  
Vandana Garg ◽  
Rohit Dutt

Background: Fever, is known as pyrexia, may occur due to infection, inflammation, or any tissue damage and disease states. Normally, the infected or damaged tissue initiates the enhanced formation of pro-inflammatory mediators like cytokines which further increases the synthesis of prostaglandin E2 (PgE2) near the hypothalamic area and thereby trigger the hypothalamus to elevate the body temperature. Objective: Antipyretics are the agents which reduce the elevated body temperature. The most commonly used antipyretic agent, paracetamol, may be fatal due to its side effects. Methods: In this review paper, Chemical Abstracts, Google Scholar, PubMed, and Science Direct were the sources for the published article to collect information regarding antipyretic activity. Results: This review compiles the antipyretic plants that may be useful to treat fever due to various diseases. Conclusion: These medicinal plants could be good alternatives for traditional allopathic antipyretics.


2019 ◽  
Vol 19 (8) ◽  
pp. 1148-1156 ◽  
Author(s):  
Ifeanacho Mercy Onuekwuzu ◽  
Ikewuchi Catherine Chidinma ◽  
Ikewuchi Jude Chigozie

Objective:Traditionally prepared infusions and decoctions are commonly used in the management of diabetes mellitus, in southern Nigeria; one of such is the aqueous extract of the sclerotia of Pleurotus tuberregium (“usu” milk). In this study, the effects of the extract on the body weights, tissue/ organ weights, fasting blood glucose, blood/plasma lipid profiles and atherogenic indices were investigated in normal and alloxan-induced diabetic rabbits.Methods:Diabetes mellitus was induced by the injection of alloxan (120 mg/kg body weight) via the marginal ear vein. The extract was administered orally at 100, 200 and 300 mg/kg to normal and diabetic rabbits; while metformin was administered at 50 mg/kg. The crude extract was analyzed by gas chromatography, coupled to flame ionization detector.Results:Thirty-one known flavonoids were detected, consisting mainly of isoquercetin (28.5%), luteolin (24.3%), quercetin (18.8%) and kaempferol (11.3%). Sitosterol (82.0%) and stigmasterol (12.5%) were the most abundant of the seven phytosterols detected. Compared to the diabetic control, the treatment significantly (p<0.05) lowered the weights of the kidney and liver, as well as the levels of blood glucose and triglyceride, plasma VLDL, LDL and non-HDL cholesterol, atherogenic index of plasma, cardiac risk ratio, atherogenic coefficient and Castelli’s risk index II. It, however, significantly (p<0.05) increased plasma HDL cholesterol, without significantly affecting blood total cholesterol levels.Conclusion:This study showed that the extract was hypoglycemic, and improved lipid profile and atherogenic indices, thus highlighting its cardioprotective potential, thereby supporting its use in the management of diabetes mellitus.


2020 ◽  
Vol 20 (3) ◽  
pp. 446-452
Author(s):  
Seyed S. Mortazavi-Jahromi ◽  
Shahab Alizadeh ◽  
Mohammad H. Javanbakht ◽  
Abbas Mirshafiey

Background: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes. Methods: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR. Results: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05). Conclusion: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.


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