Long-term acrylamide exposure exacerbates brain and lung pathology in a mouse malaria model

SUMMARYThe primate malariaPlasmodium knowlesihas a long-standing history as an experimental malaria model. Studies using this model parasite in combination with its various natural and experimental non-human primate hosts have led to important advances in vaccine development and in our understanding of malaria invasion, immunology and parasite–host interactions. The adaptation to long-termin vitrocontinuous blood stage culture in rhesus monkey,Macaca fascicularisand human red blood cells, as well as the development of various transfection methodologies has resulted in a highly versatile experimental malaria model, further increasing the potential of what was already a very powerful model. The growing evidence thatP. knowlesiis an important human zoonosis in South-East Asia has added relevance to former and future studies of this parasite species.

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MINIMAL LUNG PATHOLOGY IN LONG-TERM PRIMATE SURVIVORS OF HEART-LUNG TRANSPLANTATIO

Transplantation Journal ◽

10.1097/00007890-198712000-00030 ◽

1987 ◽

Vol 44 (6) ◽

pp. 852-854 ◽

Cited By ~ 3

Author(s):

Ari Harjula ◽

John C. Baldwin ◽

Henry D. Tazelaar ◽

Bruce A. Reitz ◽

Norman E. Shumway

Keyword(s):

Lung Pathology

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THRESHOLD AND STABILITY RESULTS FOR A MALARIA MODEL IN A POPULATION WITH PROTECTIVE INTERVENTION AMONG HIGH‐RISK GROUPS

Mathematical Modelling and Analysis ◽

10.3846/1392-6292.2008.13.443-460 ◽

2008 ◽

Vol 13 (3) ◽

pp. 443-460 ◽

Cited By ~ 5

Author(s):

Julius Tumwiine ◽

Joseph Y.T. Mugisha ◽

Livingstone S. Luboobi

Keyword(s):

Reproduction Number ◽

Control Strategies ◽

Equilibrium Points ◽

Risk Groups ◽

Preventive Therapy ◽

Vulnerable Groups ◽

Malaria Model ◽

Stability Results ◽

Protective Intervention

We develop a mathematical model for the dynamics of malaria with a varying population for which new individuals are recruited through immigration and births. In the model, we assume that non‐immune travellers move to endemic regions with sprays, smear themselves with jelly that is repellent to mosquitoes on arrival in malarious regions, others take long term antimalarials, and pregnant women and infants receive full treatment doses at intervals even when they are not sick from malaria (commonly referred to as intermittent preventive therapy). We introduce more features that describe the dynamics of the disease for the control strategies that protect the above vulnerable groups. The model analysis is done and equilibrium points are analyzed to establish their local and global stability. The threshold of the disease, the control reproduction number, is established for which the disease can be eliminated.

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Might Routine Vitamin A Monitoring in Cystic Fibrosis Patients Reduce Virus-Mediated Lung Pathology?

Frontiers in Immunology ◽

10.3389/fimmu.2021.704391 ◽

2021 ◽

Vol 12 ◽

Author(s):

Robert E. Sealy ◽

Sherri L. Surman ◽

Peter Vogel ◽

Julia L. Hurwitz

Keyword(s):

Cystic Fibrosis ◽

Vitamin A ◽

Bacterial Infections ◽

Viral Infections ◽

Recessive Gene ◽

Lung Pathology ◽

Cell Integrity ◽

Routine Monitoring ◽

Immune Health

Cystic fibrosis (CF) is an autosomal recessive gene disorder that affects tens of thousands of patients worldwide. Individuals with CF often succumb to progressive lung disease and respiratory failure following recurrent infections with bacteria. Viral infections can also damage the lungs and heighten the CF patient’s susceptibility to bacterial infections and long-term sequelae. Vitamin A is a key nutrient important for immune health and epithelial cell integrity, but there is currently no consensus as to whether vitamin A should be monitored in CF patients. Here we evaluate previous literature and present results from a CF mouse model, showing that oral vitamin A supplements significantly reduce lung lesions that would otherwise persist for 5-6 weeks post-virus exposure. Based on these results, we encourage continued research and suggest that programs for the routine monitoring and regulation of vitamin A levels may help reduce virus-induced lung pathology in CF patients.

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Piperaquine Pharmacodynamics and Parasite Viability in a Murine Malaria Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00056-09 ◽

2009 ◽

Vol 53 (7) ◽

pp. 2707-2713 ◽

Cited By ~ 7

Author(s):

Brioni R. Moore ◽

Kenneth F. Ilett ◽

Madhu Page-Sharp ◽

Jeffrey D. Jago ◽

Kevin T. Batty

Keyword(s):

Immunological Response ◽

Drug Efficacy ◽

Parasite Resistance ◽

Term Survival ◽

Combination Treatments ◽

Parasite Viability ◽

Malaria Model ◽

Time Point

ABSTRACT Piperaquine (PQ) is an important partner drug in antimalarial combination treatments, but the long half-life of PQ raises concerns about drug resistance. Our aim was to investigate the extended antimalarial effect of PQ in a study of drug efficacy, reinoculation outcomes, and parasite viability after the administration of a single dose of PQ in the murine malaria model. Initially, male Swiss mice were inoculated with Plasmodium berghei and at 64 h after parasite inoculation were given PQ phosphate at 90 mg/kg of body weight intraperitoneally. Parasite viability, drug efficacy, reinoculation responses, and parasite resistance were determined at 25, 40, 60, 90, and 130 days after drug administration. At each time point, six mice were reinoculated with 107 P. berghei parasites and blood was harvested from another four mice for viability passage into naïve mice (n = 5 for each blood sample) and from another two mice for determination of the plasma PQ concentration. The efficacy study demonstrated that the residual PQ concentrations did not suppress the infection after 25 days. Viable parasites were present up to 90 days after PQ dosing, although only 50% and 25% of the passaged parasites remained viable at 60 and 90 days postdosing, respectively. Viable parasites passaged into the naïve hosts were generally resistant to PQ when they were exposed to the drug for a second time. PQ was found to have a substantial antimalarial effect in this model, and the effect appears to be sufficient for a host immunological response to be established, resulting in the long-term survival of P. berghei-infected mice.

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Inhalation of sulfur mustard causes long-term T cell-dependent inflammation: Possible role of Th17 cells in chronic lung pathology

International Immunopharmacology ◽

10.1016/j.intimp.2012.03.010 ◽

2012 ◽

Vol 13 (1) ◽

pp. 101-108 ◽

Cited By ~ 33

Author(s):

Neerad C. Mishra ◽

Jules Rir-sima-ah ◽

Gary R. Grotendorst ◽

Raymond J. Langley ◽

Shashi P. Singh ◽

...

Keyword(s):

T Cell ◽

Th17 Cells ◽

Sulfur Mustard ◽

Lung Pathology

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386. Long-term Complications Associated with COVID-19 Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.581 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S261-S262

Author(s):

Smitha Gudipati ◽

Judith L Ranger ◽

Amit T Vahia ◽

Tommy J Parraga Acosta ◽

Zachary W Hanna ◽

...

Keyword(s):

Bacterial Infections ◽

Secondary Infection ◽

Final Analysis ◽

Index Admission ◽

Cardiac Complications ◽

Lung Pathology ◽

Blood Clots ◽

Henry Ford ◽

Discharged Patients

Abstract Background In Michigan, 44,964 (68%) of the 66,269 COVID-19 patients have recovered. However, there is concern that COVID-19 infection may lead to long-term sequelae, including pulmonary defects, cardiac complications, blood clots, and neurocognitive impairment. This study describes the 30-day outcomes of patients who had recovered. Methods From 3/16/2020 to 5/19/2020, a follow-up was attempted for patients who were discharged alive from Henry Ford Hospital in Detroit and had recovered. Recovery was defined as being alive 30 days post symptom-onset. A telephone survey was conducted 30 days post-index admission and recorded in electronic medical records. Oxygen (O2) requirements, symptoms, readmissions and the need for antibiotics for secondary bacterial infections were evaluated. Results 585 patients met inclusion criteria and were contacted by phone; 303 answered their phone (Table 1), but only 266 (45%) completed a full telephone encounter and were included in the final analysis (Table 2). The majority were female (53%), black (80%), and discharged to home (84%). The clinical characteristics of those who completed the survey were as follows: 11% presented with O2 saturation < 90%, 16% had underlying lung pathology, and 57% had a BMI above 30. Patients’ average age was 61 ± 14.3 years. At 30 days post-index admission, 49% were still symptomatic. Of the symptomatic patients, 86% had dyspnea on exertion and 15% required O2 supplementation. 18% of patients were readmitted within 30 days, and 9% developed a secondary infection prior to the phone encounter. No statistically significant differences in demographics or comorbidities were found between symptomatic and asymptomatic cohorts (Tables 1, 2). Conclusion In our study, almost half of the discharged patients remained symptomatic after 30 days with a substantial proportion experiencing pulmonary symptoms. A better understanding of the long-term pulmonary sequelae following COVID-19 infection is needed to design interventions to reduce post-infectious morbidity. Disclosures Indira Brar, MD, Gilead (Speaker’s Bureau)janssen (Speaker’s Bureau)ViiV (Speaker’s Bureau)

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Reference: The role of corticosteroids in a preterm infant with lung pathology in the first three months of life.

10.31219/osf.io/6a8tg ◽

2021 ◽

Author(s):

Femi Adeniyi

Keyword(s):

Bronchopulmonary Dysplasia ◽

Scientific Evidence ◽

Extensive Study ◽

Preterm Neonates ◽

Lung Pathology ◽

Selective Treatment ◽

Term Outcome ◽

Long Term Outcome

Corticosteroids are helpful in the treatment of preterm neonates at risk of bronchopulmonary dysplasia (BPD). However, its usefulness depends on patient selection, the timing of intervention with a corticosteroid, and choice of corticosteroid. In making these clinical choices, one must consider both short and long-term outcomes. Although corticosteroid use has been available for decades in preterm neonatal care, many aspects of corticosteroid use are unresolved due to limited research. Corticosteroids cause upregulation of anti-inflammatory, inhibiting pro-inflammatory mediators at the genomic level. Furthermore, the benefits of using corticosteroids should outweigh the known risks. Here we will discuss the current literature to guide clinical practice—a literature search for evidence through the clinical database on EMBASE, Medline, PubMed, and Cochrane. The keywords are bronchopulmonary dysplasia, corticosteroids, and prematurity.Limitations.There is bias due to limited research available to provide a high level of scientific evidence on the use of different modes of administration, other agents compared to the systemic use of dexamethasone. Conclusion.The consensus in the prevention of BPD is selective treatment after one week of life with dexamethasone. There is limited evidence to suggest the role of prophylaxis hydrocortisone in preventing BPD and advise to be considered in centers with a high risk of BPD. An extensive study into prophylaxis hydrocortisone for prevention of BDP and long-term outcome appears to be promising.The role of instilled steroids with surfactants at birth appears promising in the single-center study. A multicentre double-blinded randomized intratracheal budesonide use at delivery will be valuable.

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Persistence of viral RNA, widespread thrombosis and abnormal cellular syncytia are hallmarks of COVID-19 lung pathology

10.1101/2020.06.22.20136358 ◽

2020 ◽

Cited By ~ 7

Author(s):

Rossana Bussani ◽

Edoardo Schneider ◽

Lorena Zentilin ◽

Chiara Collesi ◽

Hashim Ali ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Viral Rna ◽

Lung Pathology ◽

Vascular Endothelial ◽

Post Mortem ◽

Systematic Analysis ◽

Infected Cells

ABSTRACTCOVID-19 is a deadly pulmonary disease with unique clinical features. A thorough understanding of the molecular and histological correlates of the disease is still missing, especially because post-mortem analysis of COVID-19-affected organs has been so far scant and often anecdotical. Here we report the results of the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. We found that the disease is characterized by extensive alveolar damage and thrombosis of the lung micro- and macro-vasculature. Thrombi were in different stages of organization, consistent with an ongoing, endogenous thrombotic process. In all the analyzed samples, in situ RNA hybridization showed that pneumocytes and vascular endothelial cells had massive presence of viral RNA even at the later stages of the disease. An additional feature of the disease was the presence, in the vast majority of patients, of a large number of dysmorphic pneumocytes, often forming large syncytial elements, a consequence of the fusogenic activity of the viral Spike protein, detected with specific antibodies. Despite occasional presence of virus-positive cells in the heart, no overt signs of viral infection were detected in other organs, which showed common alterations compatible with prolonged hypoxia, multifocal organ disease or previous comorbidities. In summary, COVID-19 is a unique interstitial pneumonia with extensive lung thrombosis, long-term persistence of viral replication in pneumocytes and endothelial cells, along with the presence of infected cellular syncytia in the lung. We propose that several of the COVID-19 disease features are due to the persistence of virus-infected cells in the lungs of the infected individuals for the duration of the disease.

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Lung Fibrosis after COVID-19: Treatment Prospects

Pharmaceuticals ◽

10.3390/ph14080807 ◽

2021 ◽

Vol 14 (8) ◽

pp. 807

Author(s):

Evgeny Bazdyrev ◽

Polina Rusina ◽

Maria Panova ◽

Fedor Novikov ◽

Ivan Grishagin ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Incidence Rate ◽

Lung Fibrosis ◽

Stromal Vascular Fraction ◽

Lung Damage ◽

Medical Community ◽

Lung Pathology ◽

Antifibrotic Therapy ◽

Fibrosis Progression

At the end of 2019, a highly contagious infection began its ominous conquest of the world. It was soon discovered that the disease was caused by a novel coronavirus designated as SARS-CoV-2, and the disease was thus abbreviated to COVID-19 (COVID). The global medical community has directed its efforts not only to find effective therapies against the deadly pathogen but also to combat the concomitant complications. Two of the most common respiratory manifestations of COVID are a significant reduction in the diffusing capacity of the lungs (DLCO) and the associated pulmonary interstitial damage. One year after moderate COVID, the incidence rate of impaired DLCO and persistent lung damage still exceeds 30%, and one-third of the patients have severe DLCO impairment and fibrotic lung damage. The persistent respiratory complications may cause substantial population morbidity, long-term disability, and even death due to the lung fibrosis progression. The incidence of COVID-induced pulmonary fibrosis caused by COVID can be estimated based on a 15-year observational study of lung pathology after SARS. Most SARS patients with fibrotic lung damage recovered within the first year and then remained healthy; however, in 20% of the cases, significant fibrosis progression was found in 5–10 years. Based on these data, the incidence rate of post-COVID lung fibrosis can be estimated at 2–6% after moderate illness. What is worse, there are reasons to believe that fibrosis may become one of the major long-term complications of COVID, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. In this review, we analyze the latest data from ongoing clinical trials aimed at treating post-COVID lung fibrosis and analyze the rationale for the current drug candidates. We discuss the use of antifibrotic therapy for idiopathic pulmonary fibrosis, the IN01 vaccine, glucocorticosteroids as well as the stromal vascular fraction for the treatment and rehabilitation of patients with COVID-associated pulmonary damage.

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