scholarly journals Re-investigating the coughing rat model of pertussis to understand Bordetella pertussis pathogenesis

2021 ◽  
Author(s):  
Jesse M. Hall ◽  
Jason Kang ◽  
Sophia M. Kenney ◽  
Ting Y. Wong ◽  
Graham J. Bitzer ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Rat Model ◽  
Vaccine Efficacy ◽  
Whooping Cough ◽  
Pulmonary Inflammation ◽  
Whole Body ◽  
Sprague Dawley ◽  
Disease Manifestation ◽  
Sprague Dawley Rats ◽  
Whole Body Plethysmography

Bordetella pertussis ( Bp ) is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP; DTaP; Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the re-emergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. Emergence of genetically diverging strains combined with waning aP vaccine efficacy call for re-evaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged seven-week-old Sprague-Dawley rats with 10 8 viable Tohama 1 and D420 and measured the hallmark signs/symptoms of Bp infection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole body plethysmography. Onset of cough occurred between 2-4 days after Bp challenge averaging five coughs per fifteen minutes, with peak coughing occurring at day eight post infection averaging upward of thirteen coughs per fifteen minutes. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days post challenge. The rats exhibited increased bronchial restriction following Bp infection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti- Bp IgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences between Bp strains.

scholarly journals Re-investigating the coughing rat model of pertussis to understand Bordetella pertussis pathogenesis

2021 ◽  
Author(s):  
Jesse Hall ◽  
Jason Kang ◽  
Sophia M Kenney ◽  
Ting Y. Wong ◽  
Graham J Bitzer ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Rat Model ◽  
Vaccine Efficacy ◽  
Whooping Cough ◽  
Pulmonary Inflammation ◽  
Whole Body ◽  
Sprague Dawley ◽  
Disease Manifestation ◽  
Sprague Dawley Rats ◽  
Whole Body Plethysmography

Bordetella pertussis (Bp) is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP; DTaP; Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the re-emergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. Emergence of genetically diverging strains combined with waning aP vaccine efficacy call for re-evaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged seven-week-old Sprague-Dawley rats with 108 viable Tohama 1 and D420 and measured the hallmark signs/symptoms of Bp infection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole body plethysmography. Onset of cough occurred between 2-4 days after Bp challenge averaging five coughs per fifteen minutes, with peak coughing occurring at day eight post infection averaging upward of thirteen coughs per fifteen minutes. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days post challenge. The rats exhibited increased bronchial restriction following Bp infection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti-Bp IgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences between Bp strains.

scholarly journals The Customizable E-cigarette Resistance Influences Toxicological Outcomes: Lung Degeneration, Inflammation, and Oxidative Stress-Induced in a Rat Model

2019 ◽  
Vol 172 (1) ◽  
pp. 132-145 ◽  
Author(s):  
Silvia Cirillo ◽  
Fabio Vivarelli ◽  
Eleonora Turrini ◽  
Carmela Fimognari ◽  
Sabrina Burattini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Low Voltage ◽  
Pulmonary Inflammation ◽  
Bronchial Epithelium ◽  
Sprague Dawley ◽  
Public Health Agencies ◽  
Toxicological Effects ◽  
Inflammatory Status ◽  
Sprague Dawley Rats

Abstract Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain “tips for vaping safety” cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.

scholarly journals Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink
Keyword(s):  
Control Period ◽  
Whole Body ◽  
Renal Nerves ◽  
Experimental Hypertension ◽  
Sympathetic Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Hypertension Development

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

Triggering receptor expressed on myeloid cells-1 (TREM-1) contributes to Bordetella pertussis inflammatory pathology

2021 ◽  
Author(s):  
Danisha Gallop ◽  
Karen Scanlon ◽  
Jeremy Ardanuy ◽  
Alexander B. Sigalov ◽  
Nicholas H. Carbonetti ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Inflammatory Responses ◽  
Whooping Cough ◽  
Pulmonary Inflammation ◽  
Myeloid Cells ◽  
Cell Surface Receptor ◽  
Bacterial Burden ◽  
Emerging Pathogens ◽  
Pertussis Infection ◽  
Bacterial Control

Whooping cough (pertussis) is a severe pulmonary infectious disease caused by the bacteria Bordetella pertussis . Pertussis infects an estimated 24 million people annually, resulting in >150,000 deaths. The NIH placed pertussis on the list of emerging pathogens in 2015. Antibiotics are ineffective unless administered before the onset of the disease characteristic cough. Therefore, there is an urgent need for novel pertussis therapeutics. We have shown that sphingosine-1-phosphate receptor (S1PR) agonists reduce pertussis inflammation, without increasing bacterial burden. Transcriptomic studies were performed to identify this mechanism and allow for the development of pertussis therapeutics which specifically target problematic inflammation without sacrificing bacterial control. These data suggested a role for triggering receptor expressed on myeloid cells-1 (TREM-1). TREM-1 cell surface receptor functions as an amplifier of inflammatory responses. Expression of TREM-1 is increased in response to bacterial infection of mucosal surfaces. In mice, B. pertussis infection results in TLR9-dependent increased expression of TREM-1 and its associated cytokines. Interestingly, S1PR agonists dampen pulmonary inflammation and TREM-1 expression. Mice challenged intranasally with B. pertussis and treated with ligand-dependent (LP17) and ligand-independent (GF9) TREM-1 inhibitors showed no differences in bacterial burden and significantly reduced TNF-α and CCL-2 expression compared to controls. Mice receiving TREM-1 inhibitors showed reduced pulmonary inflammation compared to controls indicating that TREM-1 promotes inflammatory pathology, but not bacterial control, during pertussis infection. This implicates TREM-1 as a potential therapeutic target for the treatment of pertussis.

Exercise training attenuates diet-induced reduction in metabolic rate

1990 ◽  
Vol 68 (6) ◽  
pp. 2612-2617 ◽  
Author(s):  
D. L. Ballor ◽  
L. J. Tommerup ◽  
D. P. Thomas ◽  
D. B. Smith ◽  
R. E. Keesey
Keyword(s):  
Energy Expenditure ◽  
Exercise Training ◽  
Dietary Restriction ◽  
Food Restriction ◽  
Whole Body ◽  
Daily Energy Expenditure ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Daily Energy ◽  
Whole Body Metabolism

The combined influence of exercise training and dietary restriction on daily energy expenditure was evaluated by exposing 48 male Sprague-Dawley rats to one of three food intake conditions [ad libitum (AL), moderately restricted (MR), or severely restricted (SR)] and to one of two exercise conditions [treadmill exercised (E) or cage confined (CC)]. After 10 wk of exercise and dietary restriction, the MR-CC and MR-E rats weighed 84 and 86%, respectively, of AL-CC, whereas the SR-CC and SR-E rats weighed 66 and 68% of AL-CC. Dietary restriction and subsequent weight loss produced significant reductions in both total and resting daily energy expenditure. Exercise partially reversed this effect, but the extent of this reversal diminished as the severity of dietary restriction was increased. These results raise the distinct possibility that inconsistencies in the current literature concerning the effects of exercise on whole body metabolism during periods of dietary restriction might be reconciled by an appreciation and an understanding of the influence that duration of exercise training and severity of food restriction have on this measure.

Buprenorphine alleviation of pain does not compromise the rat monoarthritic pain model

2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
M.S. Berke ◽  
Klas S.P. Abelson
Keyword(s):  
Rat Model ◽  
Joint Stiffness ◽  
Positive Control ◽  
Negative Control ◽  
Pain Tolerance ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
A Minor

Abstract Aims This study investigated the effects of buprenorphine treatment on pain and welfare parameters and model specific parameters in a rat model of monoarthritis to eliminate unnecessary pain from this model. Methods 32 male Sprague Dawley rats were divided into four groups: (1) A negative control without arthritis receiving no analgesia. (2) A positive monoarthritic control group receiving no analgesia, but subcutaneous saline injections twice a day. (3) A positive control with monoarthritis receiving subcutaneous carprofen once a day and saline once a day. (4) A group with monoarthritis receiving subcutaneous buprenorphine twice a day. Monoarthritis was induced with an injection of 0.02 ml Complete Freund’s Adjuvant intra-articularly in the left tibiotarsal joint. Treatment with analgesia was initiated at day 15 and the rats were euthanized at day 23. Results The induced monoarthritis elicited a pronounced acute inflammation. Several parameters such as bodyweight, mobility, stance, joint-stiffness and lameness scores were affected. A marked mechanical hyperalgesia in the tarsal area was observed by Electronic Von Frey testing, but no severe compromise of the animal welfare was seen at any time. Signs of chronic development began to appear from day 10 after the monoarthritic induction. No significant change in serum cytokines and faecal corticosterone measurements was found after administration of buprenorphine. A minor decrease in body weight was seen, and a higher pain tolerance to mechanical stimuli was observed, indicating pain alleviation. The histological examination confirmed monoarthritic development in all monoarthritic rats and revealed periarticular lesions suggesting diffusion of adjuvant from intra-articular injection site to the periphery. Conclusions The study demonstrated that buprenorphine has an analgesic effect in the adjuvant induced monoarthritic rat model, without obvious interference with the development of arthritis.

scholarly journals Mumefural Improves Blood Flow in a Rat Model of FeCl3-Induced Arterial Thrombosis

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3795
Author(s):  
Jihye Bang ◽  
Won Kyung Jeon
Keyword(s):  
Blood Flow ◽  
Blood Vessels ◽  
Rat Model ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Sprague Dawley ◽  
Fiber Damage ◽  
Sprague Dawley Rats ◽  
Related Proteins

Mumefural (MF), a bioactive component of the processed fruit of Prunus mume Sieb. et Zucc, is known to inhibit platelet aggregation induced by agonists in vitro. In this study, we investigated the anti-thrombotic effects of MF using a rat model of FeCl3-induced arterial thrombosis. Sprague–Dawley rats were intraperitoneally injected with MF (0.1, 1, or 10 mg/kg) 30 min before 35% FeCl3 treatment to measure the time to occlusion using a laser Doppler flowmeter and to assess the weight of the blood vessels containing thrombus. MF treatment significantly improved blood flow by inhibiting occlusion and thrombus formation. MF also prevented collagen fiber damage in injured vessels and inhibited the expression of the platelet activation-related proteins P-selectin and E-selectin. Moreover, MF significantly reduced the increased inflammatory signal of nuclear factor (NF)-κB, toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in blood vessels. After administration, MF was detected in the plasma samples of rats with a bioavailability of 36.95%. Therefore, we suggest that MF may improve blood flow as a candidate component in dietary supplements for improving blood flow and preventing blood circulation disorders.

scholarly journals Seoritae Extract Reduces Prostate Weight and Suppresses Prostate Cell Proliferation in a Rat Model of Benign Prostate Hyperplasia

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hoon Jang ◽  
Woong-Jin Bae ◽  
Seung-Mo Yuk ◽  
Dong-Seok Han ◽  
U-Syn Ha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Reductase Activity ◽  
Sprague Dawley ◽  
Prostate Hyperplasia ◽  
Prostate Cell ◽  
Beneficial Effects ◽  
Prostate Weight ◽  
Sprague Dawley Rats ◽  
Health Promoting

Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.

scholarly journals Association between Chronic Acetaminophen Exposure and Allergic Rhinitis in a Rat Model

2015 ◽  
Vol 6 (3) ◽  
pp. ar.2015.6.0131 ◽  
Author(s):  
Nadieska Caballero ◽  
Kevin C. Welch ◽  
Patrick S. Carpenter ◽  
Swati Mehrotra ◽  
Tom F. O'Connell ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Mast Cells ◽  
Rat Model ◽  
Group Versus ◽  
Inferior Turbinate ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Increased Risk ◽  
Hematoxylin And Eosin

Background Several population studies demonstrated an increased risk of allergic rhinitis in patients exposed to acetaminophen. However, no histologic studies have been conducted to assess the relationship between acetaminophen exposure and allergic rhinitis. Objective In this study, we investigated the association between chronic acetaminophen exposure and the development of allergic rhinitis in a rat model. Methods Ten female Sprague-Dawley rats were randomly assigned to either a control (n = 5) or an acetaminophen group (n = 5). The acetaminophen group received 200 mg/kg/day of acetaminophen suspended in yogurt via oral gavage for 120 days. The control group received only the yogurt vehicle. Allergic behavioral responses, including nose rub, eye rub, ear scratching, and neck and/or face scratching, were quantified. The rats were killed, and the noses were harvested. The portion of the nose, including the nasal septum and the inferior turbinates, was embedded in paraffin, sectioned, and stained with hematoxylin and eosin to quantify the inflammatory infiltrate. Results The average number of allergic responses per animal was 13.2 in the acetaminophen group versus 6.2 in the control group (p = 0.032). All the rats in the acetaminophen group (100%) had mast cells infiltrating the lamina propria of the inferior turbinate, whereas mast cells were detected in only 40% of the animals in the control group. The average number of mast cells per animal in the acetaminophen group was 134 versus 21 in the control group (p = 0.048). Conclusions Our study was the first to demonstrate a histologic association between chronic exposure to acetaminophen and rhinitis. Further research to elucidate the mechanism that underlies these findings is necessary.

Sign in / Sign up

Export Citation Format

Share Document