scholarly journals The Contribution of Host Cells to Pneumocystis Immunity: An Update

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 52 ◽  
Author(s):  
Patricia Otieno-Odhiambo ◽  
Sean Wasserman ◽  
J. Claire Hoving
Keyword(s):  
Treatment Strategies ◽  
Pneumocystis Pneumonia ◽  
Host Cells ◽  
Causative Organism ◽  
Aids Patients ◽  
Host Immune Responses ◽  
Life Threatening ◽  
New Treatment ◽  
Poor Outcomes ◽  
Immunodeficiency Syndrome

Pneumocystis is a ubiquitous atypical fungus that is distributed globally. The genus comprises morphologically similar but genetically heterogeneous species that have co-evolved with specific mammalian hosts as obligate intra-pulmonary pathogens. In humans, Pneumocystis jirovecii is the causative organism of Pneumocystis pneumonia (PCP) in immunocompromised individuals, a serious illness frequently leading to life-threatening respiratory failure. Initially observed in acquired immunodeficiency syndrome (AIDS) patients, PCP is increasingly observed in immunocompromised non-AIDS patients. The evolving epidemiology and persistently poor outcomes of this common infection will require new strategies for diagnosis and treatment. A deeper understanding of host immune responses and of the cells that mediate them will improve the chance of developing new treatment strategies. This brief review provides an update on recent studies on the role of host immunity against Pneumocystis.

scholarly journals COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks

2020 ◽  
Vol 21 (14) ◽  
pp. 4953 ◽  
Author(s):  
Markus Blaess ◽  
Lars Kaiser ◽  
Martin Sauer ◽  
René Csuk ◽  
Hans-Peter Deigner
Keyword(s):  
Viral Entry ◽  
Cathepsin L ◽  
Treatment Strategies ◽  
Disease Process ◽  
Host Cells ◽  
Cytokine Release ◽  
Early Administration ◽  
Lysosomal Ph ◽  
New Treatment ◽  
Exposure Prophylaxis

In line with SARS and MERS, the SARS-CoV-2/COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide. SARS-CoV-2 infection/COVID-19 provides numerous therapeutic targets, each of them promising, but not leading to the success of therapy to date. Neither an antiviral nor an immunomodulatory therapy in patients with SARS-CoV-2 infection/COVID-19 or pre-exposure prophylaxis against SARS-CoV-2 has proved to be effective. In this review, we try to close the gap and point out the likely relationships among lysosomotropism, increasing lysosomal pH, SARS-CoV-2 infection, and disease process, and we deduce an approach for the treatment and prophylaxis of COVID-19, and cytokine release syndrome (CRS)/cytokine storm triggered by bacteria or viruses. Lysosomotropic compounds affect prominent inflammatory messengers (e.g., IL-1B, CCL4, CCL20, and IL-6), cathepsin-L-dependent viral entry of host cells, and products of lysosomal enzymes that promote endothelial stress response in systemic inflammation. As supported by recent clinical data, patients who have already taken lysosomotropic drugs for other pre-existing conditions likely benefit from this treatment in the COVID-19 pandemic. The early administration of a combination of antivirals such as remdesivir and lysosomotropic drugs, such as the antibiotics teicoplanin or dalbavancin, seems to be able to prevent SARS-CoV-2 infection and transition to COVID-19.

Laryngeal cancer in acquired immunodeficiency syndrome

2009 ◽  
Vol 20 (8) ◽  
pp. 582-584 ◽  
Author(s):  
S Shushan ◽  
U Cinamon ◽  
D Levy ◽  
M Sokolov ◽  
Y Roth
Keyword(s):  
Combined Therapy ◽  
Head And Neck Carcinoma ◽  
Curative Treatment ◽  
Aids Patients ◽  
Alcohol Abusers ◽  
Neck Carcinoma ◽  
Life Threatening ◽  
History Of ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

With improved survival, more AIDS patients, especially heavy smokers and alcohol abusers, may be confronted with laryngeal squamous cell carcinoma. Since curative treatment may require aggressive combined therapy, these patients, often suffering from immunosupression and poor general condition, present unique therapeutic challenges. The objective of the study was to describe treatment dilemmas. This case report presents a detailed description of an AIDS patient with carcinoma of the larynx. A patient with T3N0M0 laryngeal carcinoma and AIDS underwent tracheotomy and biopsy, followed by severe neck and pulmonary infection. After convalescence, radiotherapy was administered, with no evidence of a disease during a 3.5-year follow-up. During his remaining life, the patient developed severe psychoaffective disorder, his immune state deteriorated until he demised from sepsis. In conclusion, patients with HIV infection, especially having a history of tobacco or alcohol abuse, should be carefully examined for head and neck carcinoma that is likely to be more aggressive. Following surgery, AIDS patients may have worse wound healing and a greater tendency to contract infections. Radiotherapy and especially chemotherapy may cause life-threatening complications. Although early detection may increase survival, curative treatment should involve many disciplines and extra caution.

scholarly journals An Overview of Peptide-Based Molecules as Potential Drug Candidates for Multiple Sclerosis

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5227
Author(s):  
Annarita Del Gatto ◽  
Michele Saviano ◽  
Laura Zaccaro
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Treatment Strategies ◽  
Autoimmune Encephalitis ◽  
Demyelinating Diseases ◽  
Experimental Autoimmune Encephalitis ◽  
Drug Candidates ◽  
Life Threatening ◽  
New Treatment ◽  
Experimental Autoimmune

Multiple sclerosis (MS) belongs to demyelinating diseases, which are progressive and highly debilitating pathologies that imply a high burden both on individual patients and on society. Currently, several treatment strategies differ in the route of administration, adverse events, and possible risks. Side effects associated with multiple sclerosis medications range from mild symptoms, such as flu-like or irritation at the injection site, to serious ones, such as progressive multifocal leukoencephalopathy and other life-threatening events. Moreover, the agents so far available have proved incapable of fully preventing disease progression, mostly during the phases that consist of continuous, accumulating disability. Thus, new treatment strategies, able to halt or even reverse disease progression and specific for targeting solely the pathways that contribute to the disease pathogenesis, are highly desirable. Here, we provide an overview of the recent literature about peptide-based systems tested on experimental autoimmune encephalitis (EAE) models. Since peptides are considered a unique therapeutic niche and important elements in the pharmaceutical landscape, they could open up new therapeutic opportunities for the treatment of MS.

scholarly journals Modern Myoma Treatment in the Last 20 Years: A Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmed El-Balat ◽  
Rudy Leon DeWilde ◽  
Iryna Schmeil ◽  
Morva Tahmasbi-Rad ◽  
Sandra Bogdanyova ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Cellular Level ◽  
Review Of The Literature ◽  
Human Species ◽  
Theoretical Concepts ◽  
Uterine Smooth Muscle ◽  
Healthcare Burden ◽  
The Past ◽  
Life Threatening ◽  
New Treatment

Myomas, also known as fibroids, are a specific characteristic of the human species. No other primates develop fibroids. At a cellular level, myomas are benign hyperplastic lesions of uterine smooth muscle cells. There are interesting theoretical concepts that link the development of myomas in humans with the highly specific process of childbirth from an upright position and the resulting need for greatly increased “expulsive” forces during labor. Myomas might be the price our species pays for our bipedal and highly intelligent existence. Myomas affect, with some variability, all ethnic groups and approximately 50% of all women during their lifetime. While some remain asymptomatic, myomas can cause significant and sometimes life-threatening uterine bleeding, pain, infertility, and, in extreme cases, ureteral obstruction and death. Traditionally, over 50% of all hysterectomies were performed for fibroids, leading to a significant healthcare burden. In this article, we review the developments of the past 20 years with regard to multiple new treatment strategies that have evolved during this time.

RAISING AWARENESS ON THE URGENT NEED TO IMPLEMENT FRAILTY INTO CLINICAL PRACTICE

2013 ◽  
pp. 1-4
Author(s):  
THE ORLANDO FRAILTY CONFERENCE GROUP
Keyword(s):  
Clinical Practice ◽  
Treatment Strategies ◽  
Frail Elders ◽  
Raising Awareness ◽  
Frail Older Persons ◽  
Cognitive Exercise ◽  
Underlying Causes ◽  
Hospital Stays ◽  
New Treatment ◽  
Poor Outcomes

Frailty has been linked to longer hospital stays and increased mortality in hospitalized patients. Frailtywas found at the most common condition leading to death, followed by organ failure, cancer, other causes,advanced dementia, and sudden death. Yet despite evidence linking frailty to poor outcomes, frailty is notimplemented clinically in most countries. Since many people are not identified as frail, they frequently are treatedinappropriately in health care settings. Participants in the international conference on frailty emphasized theimportance of raising awareness about frailty among geriatricians, general practitioners, and other primary careproviders in order to implement frailty in clinical practice. The following recommendations were agreed upon: 1.Prioritize the identification of frail older persons in community settings, hospitals, and specialty clinics in orderto ensure that people with frailty are treated appropriately and have access to interventional studies; 2. Buildfrailty clinics as a means of providing optimal management of frail elders; 3. Develop intervention programsincorporating physical and cognitive exercise, social support, and nutrition for people in the earliest stages offrailty in order to slow or reverse frailty; 4. Build stronger basic and clinical research programs in order to betterunderstand the underlying causes of frailty, identify therapeutic targets, and develop new treatment strategies

scholarly journals Potential Impact of Human Cytomegalovirus Infection on Immunity to Ovarian Tumours and Cancer Progression

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 351
Author(s):  
Momodou Cox ◽  
Apriliana E. R. Kartikasari ◽  
Paul R. Gorry ◽  
Katie L. Flanagan ◽  
Magdalena Plebanski
Keyword(s):  
Cancer Progression ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Screening Method ◽  
Treatment Strategies ◽  
Tumour Microenvironment ◽  
World Population ◽  
Host Immune Responses ◽  
Life Threatening ◽  
Potential Impact

Ovarian cancer (OC) is one of the most common, and life-threatening gynaecological cancer affecting females. Almost 75% of all OC cases are diagnosed at late stages, where the 5-year survival rate is less than 30%. The aetiology of the disease is still unclear, and there are currently no screening method nor effective treatment strategies for the advanced disease. A growing body of evidence shows that human cytomegalovirus (HCMV) infecting more than 50% of the world population, may play a role in inducing carcinogenesis through its immunomodulatory activities. In healthy subjects, the primary HCMV infection is essentially asymptomatic. The virus then establishes a life-long chronic latency primarily in the hematopoietic progenitor cells in the bone marrow, with periodic reactivation from latency that is often characterized by high levels of circulating pro-inflammatory cytokines. Currently, infection-induced chronic inflammation is considered as an essential process for OC progression and metastasis. In line with this observation, few recent studies have identified high expressions of HCMV proteins on OC tissue biopsies that were associated with poor survival outcomes. Active HCMV infection in the OC tumour microenvironment may thus directly contribute to OC progression. In this review, we highlight the potential impact of HCMV infection-induced immunomodulatory effects on host immune responses to OC that may promote OC progression.

Is there a Role for Epigenetic Enhancement of Immunomodulatory Approaches to Cancer Treatment?

2017 ◽  
Vol 18 (1) ◽  
pp. 5-15 ◽  
Author(s):  
Kirsty J. Flower ◽  
Sadaf Ghaem-Maghami ◽  
Robert Brown
Keyword(s):  
Expression Patterns ◽  
Immune Surveillance ◽  
Treatment Strategies ◽  
Tumour Microenvironment ◽  
The Body ◽  
Host Cells ◽  
Specific Gene ◽  
Host Immune System ◽  
A Cell ◽  
New Treatment

The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance. One such mechanism of non-efficacy or resistance is the epigenetic silencing of a specific gene required in the immunotherapy response pathway. Epigenetics is the study of the control of expression patterns in a cell via mechanisms not involving a change in DNA sequence. All tumour types show aberrant epigenetic regulation of genes involved in all the hallmarks of cancer, including immunomodulation. Inhibition of key enzymes involved in maintenance of epigenetic states is another important area of research for new treatment strategies for cancer. Could epigenetic therapies be used to successfully enhance the action of immunomodulatory agents in cancer, and are they acting in the way we imagine? An understanding of the effects of epigenetic therapies on immunological pathways in both the tumour and host cells, especially the tumour microenvironment, will be essential to further develop such combination approaches.

scholarly journals Blocking HMGB1/RAGE Signaling by Berberine Alleviates A1 Astrocyte and Attenuates Sepsis-Associated Encephalopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Shi ◽  
Huan Xu ◽  
María José Cavagnaro ◽  
Xingmei Li ◽  
Jia Fang
Keyword(s):  
Cognitive Impairment ◽  
Clinical Problem ◽  
Multiple Organ ◽  
Therapeutic Drug ◽  
Host Immune Responses ◽  
Neuron Activation ◽  
Tnf Α ◽  
Life Threatening ◽  
Novel Target ◽  
Poor Outcomes

As a life-threatening multiple organ dysfunction attributable to maladjusted host immune responses to infection, sepsis is usually the common pathway to serious prognosis and death for numerous infectious diseases all over the world. Sepsis-associated encephalopathy (SAE) is frequently complicated by septic conditions, and is one of the most important reasons for increased mortality and poor outcomes in septic patients which is still an urgent clinical problem need to be solved. In this research, a conspicuously discovery of treatment-related translational use for berberine was elaborated. The results revealed that berberine treatment significantly restored cognitive impairment in sepsis mice. Reduced expression levels of TNF-α, IL-1α, and C1qA were exhibited in the hippocampus of the berberine treatment group, and attenuated effect of declining neo-neuron, activation of microglia and astrocytes in the hippocampus of mice with sepsis were also found. Moreover, berberine inhibits microglia-stressed A1 astrocytes by inhibiting HMGB1 signaling was revealed, then the molecular mechanism of HMGB1/RAGE signaling inhibition leads to the better outcome of SAE was elucidated. To summarize, this research indicated that berberine targets HMGB1/RAGE signaling to inhibit microglia-stressed A1 astrocyte and neo-neuron decline, which consequently alleviates sepsis-induced cognitive impairment. Collectively, berberine may serve as potential therapeutic drug and HMGB1/RAGE signaling would be a novel target for medicine development for treating SAE.

scholarly journals P104 A review of patients referred to Rheumatology with haemophagocytic lymphohistiocytosis who were treated with anakinra successfully

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Dominik Kurzeja ◽  
James Perera ◽  
Kavya Pillai ◽  
Sanaah Amin ◽  
Richard Stratton ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Primary Diagnosis ◽  
Royal Free Hospital ◽  
Female Ratio ◽  
Hospital Patients ◽  
Threatening Condition ◽  
Life Threatening ◽  
Poor Outcomes

Abstract Background/Aims  Haemophagocytic lymphohistiocytos (HLH) is a potentially life-threatening condition characterised by over-activation of the innate immune system. It can be classified into primary HLH, often inherited, or secondary which is triggered by non-genetic causes, such as chronic immunosuppression, malignancy or infection.Primary HLH is more frequently observed in infants, however, secondary HLH is more commonly observed in adults. Diagnosis is often delayed, most likely due to the rarity of the condition and is usually prompted by serological abnormalities, including hyperferritinaemia, organ and bone marrow dysfunction.Treatment options are limited; however, the Royal Free Hospital has observed a number of secondary HLH cases who were successfully treated with steroids and anakinra. Methods  A retrospective search of clinic letters and patient records was undertaken using electronic care records. We also searched through pharmacy records of patients treated with anakinra at the Royal Free Hospital. Patients with a documented diagnosis of HLH prior to March 2020 who had been referred to Rheumatology were included. We excluded patients after March 2020 due to patients with COVID-19 having similar overlap of symptoms and biomarkers as those with HLH. We identified key demographic details, laboratory, pathology investigations,the course of hospital admission, primary diagnosis and follow-up data. The diagnosis was confirmed withan H-score and bone marrow biopsy where possible. Results  We identified nine adult cases with adocumented diagnosis of HLH whohad been admitted to the Royal Free Hospitaland referred to Rheumatology. They had allbeen subsequently followed up in outpatientclinic.Ages of patients ranged from 19 to 58 with a male to female ratio of 2:1. The predominant underlying pathology was adultonsetStill’s disease(78%), with the remaining cases being secondary to HIV (22%). Bone marrow aspirate was performed in all patients and 78% of patients aspirated had bone marrowappearances in keeping with HLH.Ferritin levels varied from 532 micrograms/Lto 93309 micrograms/L with a median ferritin of 5045.5 micrograms/L.H-Scores were variable witha median score of 171.5 (96-238).All patients received steroids as part of their treatment. Anakinra (interleukin-1 receptor antagonist) was delivered intravenously(6/9) or subcutaneously (3/9). Conclusion  We present data from nine cases of HLH treated with anakinra who survived their admission and have been subsequently followed up in clinic. We found that the majority of these patients had an underlying diagnosis of adult onset Still’s disease. Anakinra was used successfully as part of their treatment both intravenously as well as subcutaneously. Further work is needed comparing patients with good and poor outcomes to establish identifiable prognostic markers as well as effective treatment strategies. Disclosure  D. Kurzeja: None. J. Perera: None. K. Pillai: None. S. Amin: None. R. Stratton: None. A. Singh: None.

scholarly journals A preliminary study on the characteristics of Th1/Th2 immune response in cerebrospinal fluid of AIDS patients with cryptococcal meningitis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aixin Li ◽  
Wenjiao Zhu ◽  
Jiming Yin ◽  
Xiaojie Huang ◽  
Lijun Sun ◽  
...  
Keyword(s):  
Immune Response ◽  
Cerebrospinal Fluid ◽  
Antifungal Therapy ◽  
Cryptococcal Meningitis ◽  
Treatment Strategies ◽  
Cytokine Network ◽  
Aids Patients ◽  
Th2 Immune Response ◽  
Common Opportunistic Infection ◽  
Immunodeficiency Syndrome

Abstract Background Cryptococcal Meningitis (CM) is a common opportunistic infection in the late stage of acquired immunodeficiency syndrome (AIDS). Despite the wide use of effective antiretroviral and antifungal therapy in AIDS patients, CM is still a major morbidity and mortality cause. Understanding the immune response in cryptococcal infection may help to improve the treatment strategies. Methods We established a prospective cohort of twelve AIDS patients with CM (HIV + CM+) admitted to the hospital from 2019 to 2020. All patients were examined at the baseline, 2 weeks, and 4 weeks thereafter. The level of 19 cytokines in cerebrospinal fluid (CSF) were recorded to analyze the characteristics and dynamic changes of Th1/Th2 immune response. Meanwhile, six AIDS patients without CM (HIV + CM-) and seventeen healthy subjects (HIV-CM-) were included as control groups for CSF assessment. Results The HIV+ CM+ group had higher CSF IFN-γ, TNF-α, IL-6, IL-7, IL-8, IL-10, IL-12 (P40), IL-15, IL-18, CCL2 levels but lower IL-4 when compared with the HIV-CM- group at baseline. And they also had a higher level of IL-12 (P40) and IL-17A compared with HIV + CM- patients. Except one patient dropped out of the study, eleven HIV + CM+ patients received induction antifungal therapy and regular CSF testing, and the mortality rate was 9.1% (1/11) and 18.2% (2/11) respectively at week 2 and week 4. Compared with baseline CSF cytokines, IL-2, IL-13, IL-17A, and VEGF-A decreased in week 2, and the VEGF-A levels further decreased in week 4. But there was no difference in the levels of all cytokines between survivors and the dead. Conclusion No evidence of Th1/Th2 imbalance was found in AIDS patients with CM. However, the CSF cytokine network may provide new clues for the treatment of AIDS patients with CM. Trial registration This trial was prospectively registered in 2019.7.16. The registered number is ChiCTR1900024565.

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