scholarly journals Evaluation of an in vivo model for ventricular shunt infection: a pilot study using a novel antimicrobial-loaded polymer

2019 ◽  
Vol 131 (2) ◽  
pp. 587-595 ◽  
Author(s):  
Rajiv R. Iyer ◽  
Noah Gorelick ◽  
Karen Carroll ◽  
Ari M. Blitz ◽  
Sarah Beck ◽  
...  
Keyword(s):  
Animal Model ◽  
Experimental Animal ◽  
Control Animal ◽  
Shunt Infection ◽  
The Other ◽  
Neurological Deficits ◽  
In Vivo Model ◽  
Ventricular Catheter ◽  
Catheter Implantation

OBJECTIVEVentricular shunt infection remains an issue leading to high patient morbidity and cost, warranting further investigation. The authors sought to create an animal model of shunt infection that could be used to evaluate possible catheter modifications and innovations.METHODSThree dogs underwent bilateral ventricular catheter implantation and inoculation with methicillin-sensitive Staphylococcus aureus (S. aureus). In 2 experimental animals, the catheters were modified with a polymer containing chemical “pockets” loaded with vancomycin. In 1 control animal, the catheters were polymer coated but without antibiotics. Animals were monitored for 9 to 11 days, after which the shunts were explanted. MRI was performed after shunt implantation and prior to catheter harvest. The catheters were sonicated prior to microbiological culture and also evaluated by electron microscopy. The animals’ brains were evaluated for histopathology.RESULTSAll animals underwent successful catheter implantation. The animals developed superficial wound infections, but no neurological deficits. Imaging demonstrated ventriculitis and cerebral edema. Harvested catheters from the control animal demonstrated > 104 colony-forming units (CFUs) of S. aureus. In the first experimental animal, one shunt demonstrated > 104 CFUs of S. aureus, but the other demonstrated no growth. In the second experimental animal, one catheter demonstrated no growth, and the other grew trace S. aureus. Brain histopathology revealed acute inflammation and ventriculitis in all animals, which was more severe in the control.CONCLUSIONSThe authors evaluated an animal model of ventricular shunting and reliably induced features of shunt infection that could be microbiologically quantified. With this model, investigation of pathophysiological and imaging correlates of infection and potentially beneficial shunt catheter modifications is possible.

scholarly journals Development of a Novel Human CD147 Transgenic NSG Mouse Model to test SARS-CoV-2 Infection and Immune Responses

2021 ◽  
Author(s):  
Saiaditya Badeti ◽  
Hsiang-chi Tseng ◽  
Peter Romanienko ◽  
Ghassan Yehia ◽  
Dongfang Liu
Keyword(s):  
Animal Model ◽  
Mouse Model ◽  
Immune Responses ◽  
Viral Entry ◽  
In Vivo Model ◽  
High Risk Populations ◽  
Functional Receptor ◽  
Nsg Mouse ◽  
Low Expression

Abstract An animal model that can mimic the SARS-CoV-2 infection in humans is critical to understanding the newly emerged, rapidly spreading SARS-CoV-2 and development of therapeutic strategies. Studies show that the spike (S) proteins of SARS-CoV (SARS-CoV-S-1-S) and SARS-CoV-2 (SARS-CoV-2-S) bind to human angiotensin-converting enzyme 2 (hACE2, a well-recognized, functional receptor for SARS-CoV and SARS-CoV-2) to mediate viral entry. Several hACE2 transgenic (hACE2Tg) mouse models are being widely used, which is clearly invaluable. However, the hACE2Tg mouse model cannot fully explain: 1) low expression of ACE2 observed in human lung and heart, but lung or heart failure occurs frequently in severe COVID-19 patients); 2) low expression of ACE2 on immune cells, but lymphocytopenia occurs frequently in COVID-19 patients; and 3) hACE2Tg mice do not develop strong clinical disease following SARS-CoV-2 infection in contrast to SARS-CoV-1. Moreover, one of most outstanding features of coronaviruses is the diversity of receptor usage, which includes the newly proposed human CD147 (hCD147) as a receptor for SARS-CoV-2-S. It is still debatable whether CD147 can serve as a functional receptor for SARS-CoV-2 infection or entry. Here we successfully generated a hCD147Tg mouse model in the NOD-scid IL2Rgammanull (NSG) background. In this hCD147Tg-NSG mouse model, the hCD147 genetic sequence was placed following the endogenous mouse promoter for mouse CD147 (mCD147), which creates an in vivo model that may better recapitulate physiological expression of CD147 proteins at the molecular level compared to the existing and well-studied K18-hACE2-B6 model. In addition, the hCD147Tg-NSG mouse model allows further study of SARS-CoV-2 in the immunodeficiency condition which may assist our understanding of this virus in the context of high-risk populations with immunosuppressed conditions. The hCD147Tg-NSG mouse mode can serve as an additional animal model for interrogate whether CD147 serve as an independent functional receptor or accessory receptor for SARS-CoV-2 entry and immune responses.

scholarly journals Lemon Balm Extract and Its Major Chemical Compound, Rosmarinic Acid, Alleviate Damages of Liver in an Animal Model of Nonalcoholic Steatohepatitis (NASH) (P06-093-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gyhye Yoo ◽  
Myungsuk Kim ◽  
Ahmad Randy ◽  
Yang-Ju Son ◽  
Chi Rak Hong ◽  
...  
Keyword(s):  
Animal Model ◽  
Chemical Compound ◽  
Rosmarinic Acid ◽  
Hepg2 Cells ◽  
In Vivo Model ◽  
World Population ◽  
Lemon Balm ◽  
Major Chemical

Abstract Objectives The non-alcoholic fatty liver disease (NAFLD) comprises the broad histopathological states of liver, that ranging from asymptomatic hepatic steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. In some studies, they suppose that almost 25–30% of world population is underlying NAFLD. Lemon balm (Melissa officinalis) is the herb that has some traditional medicinal usages. Also rosmarinic acid (RA; O-caffeoyl-3,4-dihydroxyphenyl lactic acid), the major chemical compound of lemon balm, already reported that it has the potency on anti-obesity and -inflammatory. Hence, we evaluate the whether lemon balm extract (LBE) and RA could suppress the pathogenesis of NASH using an in vitro and in vivo model. Methods In vitro model: The palmitic acid (PA) exposed HepG2 hepatocellular carcinoma cells can imitate the lipid accumulation in hepatocytes. PA exposed HepG2 cells were exposed with or without LBE or RA. In vivo model: The methionine- and choline-deficient (MCD) diet fed db/db C57BL/6 J mice model was used. This model is known as it can mimic well symptoms of human NAFLD. The LBE or RA were treated by oral gavage. Results With the MCD diet only, the severe liver damage was caused by progression of NASH in animal model. LBE and RA treatments alleviated the oxidative stress in the MCD diet-fed db/db mice and PA-exposed HepG2 cells by increasing the expression of antioxidant enzymes (NRF2, SOD) and augmented lipolysis-related gene (PPARα, PGC-1α, CPT-1 L) expression. In addition, LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis (α-SMA, COL1A1) and fatty acid synthesis (SREBP-1c, CPT-1 L) and activated AMP-activated protein kinase in vitro and in vivo. Also, the histopathological results were ameliorated by treatment of LBE or RA. Conclusions LBE and RA modulate lipid metabolism via AMPK activation and suppress inflammation via changes in NRF2 and NF-κB signalling. Importantly, the extract of lemon balm obtained with 20% EtOH showed effectiveness similar to that of RA at high concentrations. Therefore, LBE may be a good candidate for the treatment and prevention of NASH. Funding Sources This work was supported by the National Research Council of Science & Technology (NST) funded by the Korea Government (MSIP) (grant No. CRC-15-01-KIST). Supporting Tables, Images and/or Graphs

scholarly journals In Vitro and In Vivo Activity of Single and Dual Antimicrobial Agents Against KPC-producing Klebsiella pneumoniae

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S379-S379
Author(s):  
Farzad Moussavi ◽  
Sarath Nath ◽  
Daniel Abraham ◽  
David Landman ◽  
John Quale
Keyword(s):  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Survival Rates ◽  
Polymyxin B ◽  
The Other ◽  
In Vivo Model ◽  
Serious Infections ◽  
Time Kill

Abstract Background Options for treatment of infections due to KPC-producing K. pneumoniae are limited, and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods Using clinically-relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime-avibactam, meropenem, rifampin, and amikacin alone and in combination. Four isolates of KPC-producing K. pneumoniae were studied, including two isolates that were resistant to polymyxin B and had ceftazidime-avibactam MICs of 8 µg/mL. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower MICs of ceftazidime-avibactam. Results Two isolates that were resistant to polymyxin B and with ceftazidime-avibactam MICs of 8 µg/mL were also resistant to amikacin and meropenem. When ceftazidime-avibactam was combined with either amikacin or meropenem, synergy was observed in vitro, and these combinations were associated with improved survival with the in vivo model. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower MICs of ceftazidime-avibactam. At concentrations four times the MIC, ceftazidime-avibactam had bactericidal activity in vitro; at one fourth the MIC, synergy was observed when combined with meropenem. Improved survival rates were observed with therapy with ceftazidime-avibactam, particularly when combined with a second agent for one isolate. In the in vivo model, polymyxin B with or without rifampin or meropenem, was ineffective against polymyxin B resistant strains. Conclusion Pending clinical studies, combining ceftazidime-avibactam with another agent (e.g., a carbapenem) should be encouraged when treating serious infections due to these pathogens, especially for isolates with ceftazidime-avibactam MICs near the susceptibility breakpoint. Disclosures All authors: No reported disclosures.

scholarly journals Potential neuroprotective effect of Anakinra in spinal cord injury in an in vivo experimental animal model

Neurosciences ◽  
2015 ◽  
Vol 20 (2) ◽  
pp. 124-130 ◽  
Author(s):  
Askin Hasturk ◽  
Erdal Yilmaz ◽  
Erhan Turkoglu ◽  
Murat Arikan ◽  
Guray Togral ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Animal Model ◽  
Experimental Animal ◽  
Neuroprotective Effect ◽  
Experimental Animal Model ◽  
Cord Injury

scholarly journals Leptin Inhibit the Effect of Pioglitazone in Reducing MMP-9 and MMP-13 of IL-1β-Induced Chondrocytes

1970 ◽  
pp. 12
Author(s):  
Rena Normasari ◽  
Anis Murniati
Keyword(s):  
Animal Model ◽  
Risk Factor ◽  
Joint Pain ◽  
The Other ◽  
Leptin Resistance ◽  
Main Risk Factor ◽  
Common Cause ◽  
Ppar Γ

Osteoarthritis (OA) is the most common cause of joint pain, but there’s still no satisfying treatment that can inhibit degradation of articular cartilage in OA. One approach that is being widely studied is through activation of PPAR-γ. Many studies have shown effect of PPAR-γ on OA either in vitro or in vivo in animal model. On the other hand, the main risk factor of OA is obesity. Obesity generally followed by increased of leptin level due to leptin resistance. The aim of this study is to examine the effect of pioglitazone as PPAR-γ agonist in reducing the level of MMP-9 and MMP-13 in OA chondrocyte with hyperleptinemia. MMP-9 and MMP-13 are key role enzymes that degrades cartilage in OA. This study use IL-1β-induced chondrocyte exposed to pioglitazone. Pioglitazone 0,1μM, 1μM, and 10μM reduce MMP-9 and MMP-13 level. Whereas pioglitazone together with leptin 10μg/ml reduce the decrease level of MMPs compared to the group without leptin. Leptin inhibit the effect of pioglitazone in reducing the level of MMPs.Keywords: OA, leptin, pioglitazone, MMP-9, MMP-13

scholarly journals Biochemical and histopathological evaluation of an in vivo model of breast cancer

2021 ◽  
Vol 16 (1) ◽  
pp. 202-210
Author(s):  
Neha Sharma ◽  
Anila Negi ◽  
Dharambir Kashyap ◽  
Amanjit Bal ◽  
Shalmoli Bhattacharyya
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Animal Model ◽  
Triple Negative ◽  
Mammary Tissue ◽  
In Vivo Model ◽  
Mammary Tumours ◽  
Significant Difference ◽  
In Vivo Animal Model

Though, the clinical management of breast cancer has improved significantly over the past 30 years, it still remains the leading cause of cancer-related female death worldwide. Prevention is the fundamental issue in breast cancer control, for which identification markers in terms of initiation and promotion are necessary. To understand this, an animal model which can recapitulate the early symptoms of breast cancer development and progression is required. Present study is an attempt to develop a convenient and economical in-vivo animal model of breast cancer suitable to conduct such study. Female Wistar and SD rats were injected with different doses and routes of administration of 7, 12-Dihydroxymethylbenz (a) anthracene (DMBA). Animals were observed for the presence of visible/palpable tumours in mammary glands. Various parameters (Tumor morphology, oxidative stress and histopathological studies were studied in different tissues (mammary, lungs, kidney, liver) after the appearance of mammary tumours in rats. After 14 weeks all the animals developed breast carcinomas. The results of this study revealed a significant difference in oxidative stress parameters between DMBA treated and control groups and these alterations were strain dependent. The H&E staining of mice mammary tissue showed development of metaplastic triple negative breast cancer. Immunohistochemistry observation confirmed the triple negative nature of mammary tumours developed in the mice. Data confirmed that DMBA can be used as breast cancer initiator and present model can be further exploited to screen potential anti-breast cancer compounds in vivo.

In Vitro Platelet Binding Compared with In Vivo Thrombus Imaging Using αIIbβ3-Targeted Radioligands

1998 ◽  
Vol 80 (11) ◽  
pp. 845-851 ◽  
Author(s):  
Jan Romano ◽  
Alan Maurer ◽  
Linda Knight
Keyword(s):  
Animal Model ◽  
The Other ◽  
Organ Distribution ◽  
Pulmonary Emboli ◽  
Binding Studies ◽  
Platelet Binding ◽  
Αiibβ3 Integrin ◽  
Surprising Finding

SummaryRadioligands for the αIIbβ3 integrin on platelets are being studied for their ability to image venous thrombi and pulmonary emboli. One such radioligand, 123I-bitistatin, was previously shown to have higher thrombotic uptake in an animal model than other disintegrins, but the reason for this difference was not clear. The purpose of this study was to evaluate three labeled disintegrins, bitistatin, kistrin and barbourin, to look for in vitro differences in platelet binding which could explain the in vivo behavior.Disintegrins labeled with 125I were compared in vitro for extent of binding to platelets and rates of binding and dissociation. These findings were related to organ distribution and image quality for imaging thrombotic lesions, following administration of 123I-disintegrins in an animal model. Fibrinogen at 8.8 μmol/l was able to displace 125Ibarbourin and 125I-kistrin more rapidly from ADP-stimulated platelets, with half-times of 3.5 and 10.7 min, compared with 125I-bitistatin (31.6 min). At equivalent concentrations in whole blood, a higher percentage of bitistatin bound to platelets compared with the other two. In vivo, kistrin and barbourin had significantly lower thrombus:muscle and pulmonary embolus:lung ratios in images compared with bitistatin. There was evidence of more metabolic deiodination of labeled kistrin and barbourin in vivo compared with bitistatin. A surprising finding was that conventional in vitro platelet binding studies did not predict the relative in vivo behavior of labeled disintegrins.The results suggest that labeled bitistatin has improved targeting of thrombi because it is less easily displaced from stimulated platelets, permitting longer lesion retention. It also appears to have a greater association with resting platelets in the blood, which may increase bioavailability and delay metabolic breakdown.

An Animal Model That Predicts Unit Engraftment in Double Unit Cord Blood Transplant Recipients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 176-176
Author(s):  
S. Chaudhury ◽  
J.N. Barker ◽  
A. de Baisre ◽  
R.J. O’Reilly ◽  
Malcolm A.S. Moore
Keyword(s):  
Animal Model ◽  
Cord Blood ◽  
Single Unit ◽  
Mononuclear Cells ◽  
Cell Number ◽  
In Vivo Model ◽  
Clinical Unit ◽  
Cord Blood Transplant ◽  
Nog Mice

Abstract Patients receiving double unit cord blood transplant (DCBT) have demonstrated improved engraftment and survival compared to single unit historical controls despite the fact that only one unit is responsible for sustained donor engraftment. However, the mechanism of this advantage and unit predominance is not understood. Therefore, we investigated DCBT in NOD/SCID/IL2Rγc−/− (NOG) mice using mononuclear cells (MNC) from each unit of clinical double unit allografts with correlation of the murine engraftment with which unit engrafted in the patients. Our hypothesis was that the animal model would correlate with clinical unit engraftment. Nine patients with high-risk hematologic malignancies received myeloablative (n=5) or non-myeloablative (n=4) conditioning according to age and diagnosis, and 4–6/6 HLA-matched double unit allografts. Patients consented to ≤ 5% of each unit being used for research purposes. A minimum of 1 million MNC per mouse were transplanted by tail vein injection into sublethally irradiated NOG mice: each unit alone and then in combination in the same proportion as transplanted into the patients according to the relative TNC/kg of each unit. Experiments were established in duplicate or triplicate according to cell number available. Mice were sacrificed at 4–6 weeks and engraftment was determined by FACS analysis for human CD45+. In both human and murine DCBT recipients the contribution of each unit to engraftment was measured by quantitative PCR for informative short tandem repeat (qSTR) regions that distinguished each donor. Consistent with prior clinical studies all patients demonstrated donor engraftment by STR evaluation of day +21 bone marrow (BM) with one unit predominating (designated the “winner”). The average percent human engraftment in the murine experiments is shown in the Table (W = winning and L = losing unit as seen in the patients, DCBT is W+L). Notably, in 9/9 (100%) experiments, while each unit engrafted when transplanted alone, a single unit predominated when given as a double unit transplant which correlated with clinical unit predominance. Interestingly, there was no improvement in engraftment of the winner with the double unit co-transplant as compared to the winner transplanted alone. No. BM: (W) Spleen: (W) BM: (L) Spleen: (L) BM: DCBT (W+L) Spleen: DCBT (W+L) BM & Spleen: DCBT (W+L) Winner % 1 31% 34% 27% 33% 24% 30% 100% & 100% 2 12% 12% 10% 2% 2% 16% 100% & 100% 3 5% 6% 1% 12% 15% 2% 100% & 100% 4 21% 29% 17% 24% 20% 26% 100% & 100% 5 33% 52% 20% 32% 31% 45% 100% & 100% 6 7% 11% 7% 14% 15% 25% 100% & 100% 7 25% 44% 46% 57% 45% 72% 100% & 100% 8 22% 53% 48% 78% 27% 22% 83% & 91% 9 88% 74% 68% 70% 38% 82% 100% & 100% Therefore, for the first time we have established a reliable in vivo model of DCBT using clinical specimens that predicts clinical engraftment. To date, the data suggests that unit predominance is due to an inherent advantage of the winning unit (exact mechanism to be determined) and that the presence of the losing unit does not augment the engraftment of the winner. This experimental model should permit further investigation of double unit biology.

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