Combination therapy with relaxin and methylprednisolone augments the effects of either treatment alone in inhibiting subepithelial fibrosis in an experimental model of allergic airways disease

2012 ◽  
Vol 124 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Simon G. Royce ◽  
Amelia Sedjahtera ◽  
Chrishan S. Samuel ◽  
Mimi L. K. Tang
Keyword(s):  
Combination Therapy ◽  
Experimental Model ◽  
Murine Model ◽  
Symptom Control ◽  
Airway Remodelling ◽  
Novel Therapies ◽  
Collagen Deposition ◽  
Airway Reactivity ◽  
Improve Symptom ◽  
Subepithelial Fibrosis

Although CSs (corticosteroids) demonstrate potent effects in the control of airway inflammation in asthma, many patients continue to experience symptoms and AHR (airway hyper-responsiveness) despite optimal treatment with these agents, probably due to progressive airway remodelling. Identifying novel therapies that can target airway remodelling and/or airway reactivity may improve symptom control in these patients. We have demonstrated previously that the anti-fibrotic hormone RLN (relaxin) can reverse airway remodelling (epithelial thickening and subepithelial fibrosis) and AHR in a murine model of AAD (allergic airways disease). In the present study, we compared the effects of RLN with a CS (methylprednisolone) on airway remodelling and AHR when administered independently or in combination in the mouse AAD model. Female mice at 6–8 weeks of age were sensitized and challenged to OVA (ovalbumin) over a 9-week period and treated with methylprednisolone, RLN, a combination of both treatments or vehicle controls. Methylprednisolone was administered intraperitoneally on the same day as nebulization for 6 weeks, whereas recombinant human RLN-2 was administered via subcutaneously implanted osmotic mini-pumps from weeks 9–11. RLN or methylprednisolone alone were both able to significantly decrease subepithelial thickness and total lung collagen deposition; whereas RLN but not methylprednisolone significantly decreased epithelial thickness and AHR. Additionally, combination therapy with CS and RLN more effectively reduced subepithelial collagen thickness than either therapy alone. These findings demonstrate that RLN can modulate a broader range of airway remodelling changes and AHR than methylprednisolone and the combination of both treatments offers enhanced control of subepithelial fibrosis.

581 Effects of acoustic immune priming with low-intensity focused ultrasound (LOFU) and trabectedin on a murine model of osteosarcoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A616-A616
Author(s):  
Shannon Keisling
Keyword(s):  
Radiation Therapy ◽  
Heat Shock ◽  
Combination Therapy ◽  
Murine Model ◽  
Heat Shock Response ◽  
Cell Activation ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Therapy Group ◽  
Shock Response

BackgroundOsteosarcoma is the most common primary bone tumor and has a peak incidence in adolescence. The prognosis for recurrent and metastatic disease is poor and over one-third of patients with localized disease at presentation will recur after treatment with metastases. LOFU produces non-lethal, transient mechanical and thermal stress to cause protein misfolding, endoplasmic reticulum stress, and induction of the heat shock response (refs). Trabectedin is directly tumoricidal through inhibiting transcription and DNA repair, modulates the tumor microenvironment by selectively depleting M2 macrophages, and inhibits the transcription factor heat shock factor 1 (HSF1) (refs). We hypothesized that combination therapy would synergistically intensify the unfolded protein response and heat shock response to facilitate antigen presenting cell activation and efficient presentation to cytotoxic T cells. To examine this, experiments are being conducted to investigate the effect of LOFU in combination with trabectedin and/or radiation therapy (RT) in a murine model of osteosarcoma.MethodsPalpable (<5 mm) subcutaneous K7M2 murine osteosarcoma tumors in BALB/c mice were treated with a) LOFU, b) trabectedin (intravenous (IV) or intratumoral (IT)), c) LOFU + trabectedin, and d) radiation. Tumor growth (ANOVA (Kruskal-Wallis) with Dunn’s test for multiple comparisons), pulmonary metastases (Fisher’s exact test) and survival (Kaplan-Meier) were measured and analyzed in GraphPad Prism.ResultsMean tumor volume in the combination therapy group (428 mm3) was less than nontreated controls (887 mm3), LOFU alone (670 mm3), trabectedin alone (1218 mm3, p=0.0386). Radiation therapy resulted in complete ablation of the tumors. None of the combination therapy mice had grossly detectable lung metastases at time of death but metastases were present in the trabectedin only (20%), LOFU only (50%), and control (50%) groups (not statistically significant).ConclusionsCombination therapy with trabectedin and LOFU yielded smaller tumor size and fewer pulmonary metastases compared to individual therapies alone.

Advance care planning for patients with COVID-19: a communication guide

2021 ◽  
pp. 1-6
Author(s):  
Natasha Palipane ◽  
Abi Ponnampalampillai ◽  
Srirupa Gupta
Keyword(s):  
Advance Care Planning ◽  
Symptom Control ◽  
Patient Choice ◽  
High Morbidity ◽  
Care Planning ◽  
Goals Of Care ◽  
Disease Trajectory ◽  
Improve Symptom ◽  
Inappropriate Admissions ◽  
Advance Care

In view of the high morbidity and mortality associated with COVID-19, early and honest conversations with patients about goals of care are vital. Advance care planning in its traditional manner may be difficult to achieve given the unpredictability of the disease trajectory. Despite this, it is crucial that patients' care wishes are explored as this will help prevent inappropriate admissions to hospital and to critical care, improve symptom control and advocate for patient choice. This article provides practical tips on how to translate decisions around treatment escalation plans into conversations, both face-to-face and over the phone, in a sensitive and compassionate manner. Care planning conversations for patients with COVID-19 should be individualised and actively involve the patient. Focusing on goals of care rather than ceilings of treatment can help to alleviate anxiety around these conversations and will remind patients that their care will never cease. Using a framework such as the ‘SPIKES’ mnemonic can help to structure this conversation. Verbally conveying empathy will be key, particularly when wearing personal protective equipment or speaking to relatives over the phone. It is also important to make time to recognise your own emotions during and/or after these conversations.

scholarly journals A contribution to the study of acute schistosomiasis (an experimental trial)

1987 ◽  
Vol 82 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Zilton A. Andrade ◽  
Theomira Mauadie de Azevedo
Keyword(s):  
Schistosoma Mansoni ◽  
Experimental Model ◽  
Murine Model ◽  
Single Infection ◽  
Coagulative Necrosis ◽  
Histological Changes ◽  
Experimental Trial ◽  
Repeated Infections ◽  
Major Factors ◽  
Inflammatory Changes

In an attempt to establish an experimental model of acute schistosomiasis, sequential histological changes were investigated in the skin, lung, liver and spleen of mice infected with 30 or 100 cercariae of Schistosoma mansoni according to four sets of experiments: single infection, repeated infections, unisexual infection and infection in mice born from infected mothers. Animals were killed every other day from exposure up to 50 days after infection. Only mild, isolated, focal inflammatory changes were found before the appearance of mature eggs in the liver, even when repeated infections were made. Severe changes of reactive hepatitis and splenitis appeared suddenly when the first mature eggs were deposited, around the 37th to 42nd day after infection. The mature eggs induced lytic and coagulative necrosis of hepatocytes around them which was soon followed by dense infiltration of eosinophils. So, mature egg-induced lesions appeared as the major factors in the pathogenesis of acute schistosomiasis in mice. Mice born from infected mothers were apparently able to rapidly modulate the egg-lesions, forming early fibrotic granulomas. The murine model of acute schistosomiasis appeared adequate for the study of pathology and pathogenesis of acute schistosomiasis.

scholarly journals Visual Design and Anthropomorphism in a Mobile Pulmonary Rehabilitation Support Intervention

2021 ◽  
Author(s):  
Cindy Chong ◽  
Danielle Lottridge ◽  
Jim Warren ◽  
Rosie Dobson
Keyword(s):  
Pilot Study ◽  
Pulmonary Rehabilitation ◽  
Symptom Control ◽  
Exercise Program ◽  
Smartphone Application ◽  
Study Data ◽  
Text Messages ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Improve Symptom

Pulmonary rehabilitation is a behavioral intervention that can improve symptom control and quality of life for patients with chronic obstructive pulmonary disease (COPD), but access, uptake and adherence are problematic. Our team has pursued the development of a mobile phone-based intervention (mobile pulmonary rehabilitation, mPR) with iterative design and a pilot study. The mPR intervention is delivered through two technologies: text messages (SMS) and a smartphone application. Our user-centered design analysis of pilot study data led to several insights. First, patients’ replies to the SMS suggested that messages were anthropomorphised and provided social support. Second, the smartphone application could help patients by clearly visualizing the exercise program, alternative exercises, and progress to date. We demonstrate the design iterations made to meet these requirements and we present feedback obtained from experts and from four COPD patients. We discuss implications for the design of mobile pulmonary rehabilitation interventions.

scholarly journals Clinical difference between single subtype and mixed subtype chronic urticaria: A retrospective study

2021 ◽  
Vol 0 ◽  
pp. 1-6
Author(s):  
Manyun Mao ◽  
Yan Yuan ◽  
Yangjian Xiao ◽  
Cong Peng ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Chronic Urticaria ◽  
Symptom Control ◽  
Life Quality ◽  
Clinical Difference ◽  
Improve Symptom ◽  
Comprehensive Knowledge ◽  
Positive Rate ◽  
Common Group ◽  
Urticaria Activity Score

Background: The subtypes of chronic urticaria share a common clinical expression, but may show differences phenotypically. Meanwhile, two or more different subtypes of chronic urticaria can coexist in any given patient which may involve different phenotypes. Aims: The study aims to compare the two phenotypes in terms of demographics, clinical profile and treatment response. Methods: In this retrospective study, 2678 chronic urticaria patients were divided into the single subtype chronic urticaria group and mixed subtype chronic urticaria group as was appropriate.The differences in the clinical features, possible causes, urticaria activity score of seven days, dermatology life quality index score, laboratory investigations and response to treatments were evaluated among the two groups. Results: An obvious female predominance was detected in chronic urticaria, especially in mixed subtype chronic urticaria patients. Of the 2678 chronic urticaria patients, there were 837(31.25%) mixed subtype chronic urticaria. Chronic spontaneous urticaria combined with symptomatic dermographism was the most common group in the mixed subtype chronic urticaria. Patients with mixed subtype chronic urticaria were more likely to have associated chest tightness/shortness of breath and showed greater urticaria activity. In patients with single subtype chronic urticaria, the positive rate of family history with allergic rhinitis, asthma or urticaria was lower. Based on evaluation of the treatment, control with second-generation antihistamines at licensed doses was achieved in only 38.83% of mixed subtype chronic urticaria patients, compared with 56.32% of patients with single subtype. Limitations: First, this study was a single-center design retrospective study. Second, omalizumab treatment was not included. Third, the differences between different subtypes of mixed subtype chronic urticaria were not discussed in detail. Conclusion: This study showed that mixed subtype chronic urticaria had some distinct features. Comprehensive knowledge about it may help us define effective therapeutic strategies and improve symptom control and the quality of life for chronic urticaria patients.

scholarly journals Metformin Enhances Antidepressant/Antipsychotic Combination Therapy of Schizophrenia With Comorbid Depression in a Murine Model

2020 ◽  
Vol 14 ◽  
Author(s):  
Chunhua Zhou ◽  
Dezhi Kong ◽  
Rong Xue ◽  
Min Chen ◽  
Gongying Li ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Murine Model ◽  
Comorbid Depression

scholarly journals Integration of palliative care into the neuro-oncology practice: patterns in the United States

2014 ◽  
Vol 1 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Tobias Walbert
Keyword(s):  
Quality Of Life ◽  
Palliative Care ◽  
Brain Tumor ◽  
End Of Life ◽  
Symptom Control ◽  
Tumor Patients ◽  
Life Phase ◽  
Improve Symptom ◽  
Oncology Practice

Abstract Background Between 80%–85 percent of all adult brain tumors are high-grade gliomas (HGGs). Despite aggressive treatment with surgical resection, radiotherapy and chemotherapy, the survival of patients with HGG is limited. Brain tumor patients develop unique symptoms and needs throughout their disease trajectory, and the majority lose the ability to communicate during the end-of-life phase. Palliative care (PC) is a proactive and systematic approach to manage issues that are important to patients and families affected by serious illness. The goal is to improve quality of life and symptom control and thereby reduce suffering. Most PC interventions take place during the end-of-life phase; however, newer data suggest that early PC interventions might improve symptom control and quality of life. Methods A literature review focusing on PC, hospice care, and end-of-life care was performed with the aim to describe the integration of PC into neuro-oncology practice. Results Recently there has been increased interest in the effects of PC and brain tumor patients. The origins, methodology, and conceptual models of delivering PC and how it might be applied to the field of neuro-oncology were reviewed. Patterns of referral and utilization in neuro-oncology are described based on the findings of a recent survey. Conclusions Despite a very high symptom burden, many HGG patients do not receive the same level of PC and have fewer interactions with PC services than other cancer populations. Early PC interventions and structured advance-care planning might improve symptom control and quality of life for brain tumor patients.

Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 639-647 ◽  
Author(s):  
Simon C. Pitchford ◽  
Yanira Riffo-Vasquez ◽  
Ana Sousa ◽  
Stefania Momi ◽  
Paolo Gresele ◽  
...  
Keyword(s):  
Murine Model ◽  
Airway Remodeling ◽  
Allergic Inflammation ◽  
Leukocyte Recruitment ◽  
Corticosteroid Administration ◽  
Reticular Fiber ◽  
Allergic Lung Inflammation ◽  
Fiber Deposition ◽  
Subepithelial Fibrosis ◽  
Platelet Depletion

Abstract Asthma is associated with airway remodeling. Evidence of platelet recruitment to the lungs of asthmatics after allergen exposure suggests platelets participate in various aspects of asthma; although their importance is unknown in the context of airway remodeling, their involvement in atherosclerosis is established. Studies from our laboratory have shown a requirement for platelets in pulmonary leukocyte recruitment in a murine model of allergic lung inflammation. Presently, the effects of platelet depletion and corticosteroid administration on airway remodeling and lung function were examined. Ovalbumin (OVA)–sensitized mice, exposed to aerosolized OVA for 8 weeks, demonstrated epithelial and smooth muscle thickening, and subepithelial reticular fiber deposition in the distal airways. The depletion of platelets via an immunologic (antiplatelet antisera) or nonimmunologic (busulfan) method, markedly reduced airway remodeling. In contrast, dexamethasone administration did not affect epithelial thickening or subepithelial fibrosis, despite significantly inhibiting leukocyte recruitment. Thus, pathways leading to certain aspects of airway remodeling may not depend on leukocyte recruitment, whereas platelet activation is obligatory. OVA-sensitized mice exhibited airway hyperresponsiveness (AHR) compared with shamsensitized mice following chronic OVA exposure. Neither platelet depletion nor dexamethasone administration inhibited chronic AHR; thus, mechanisms other than inflammation and airway remodeling may be involved in the pathogenesis of chronic AHR.

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