scholarly journals Role of Antifungal Combinations in Difficult to Treat Candida Infections

2021 ◽  
Vol 7 (9) ◽  
pp. 731
Author(s):  
Roxana G. Vitale

Candida infections are varied and, depending on the immune status of the patient, a life-threatening form may develop. C. albicans is the most prevalent species isolated, however, a significant shift towards other Candida species has been noted. Monotherapy is frequently indicated, but the patient’s evolution is not always favorable. Drug combinations are a suitable option in specific situations. The aim of this review is to address this problem and to discuss the role of drug combinations in difficult to treat Candida infections. A search for eligible studies in PubMed and Google Scholar databases was performed. An analysis of the data was carried out to define in which cases a combination therapy is the most appropriate. Combination therapy may be used for refractory candidiasis, endocarditis, meningitis, eye infections and osteomyelitis, among others. The role of the drug combination would be to increase efficacy, reduce toxicity and improve the prognosis of the patient in infections that are difficult to treat. More clinical studies and reporting of cases in which drug combinations are used are needed in order to have more data that support the use of this therapeutic strategy.

2020 ◽  
Vol 6 (4) ◽  
pp. 189
Author(s):  
Lohith Kunyeit ◽  
Anu-Appaiah K A ◽  
Reeta P. Rao

Superficial and life-threatening invasive Candida infections are a major clinical challenge in hospitalized and immuno-compromised patients. Emerging drug-resistance among Candida species is exacerbated by the limited availability of antifungals and their associated side-effects. In the current review, we discuss the application of probiotic yeasts as a potential alternative/ combination therapy against Candida infections. Preclinical studies have identified several probiotic yeasts that effectively inhibit virulence of Candida species, including Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, Candida krusei and Candida auris. However, Saccharomyces cerevisiae var. boulardii is the only probiotic yeast commercially available. In addition, clinical studies have further confirmed the in vitro and in vivo activity of the probiotic yeasts against Candida species. Probiotics use a variety of protective mechanisms, including posing a physical barrier, the ability to aggregate pathogens and render them avirulent. Secreted metabolites such as short-chain fatty acids effectively inhibit the adhesion and morphological transition of Candida species. Overall, the probiotic yeasts could be a promising effective alternative or combination therapy for Candida infections. Additional studies would bolster the application of probiotic yeasts.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaofei Shen ◽  
Ke Cao ◽  
Yang Zhao ◽  
Junfeng Du

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Although our understanding in the pathophysiological features of sepsis has increased significantly during the past decades, there is still lack of specific treatment for sepsis. Neutrophils are important regulators against invading pathogens, and their role during sepsis has been studied extensively. It has been suggested that the migration, the antimicrobial activity, and the function of neutrophil extracellular traps (NETs) have all been impaired during sepsis, which results in an inappropriate response to primary infection and potentially increase the susceptibility to secondary infection. On the other hand, accumulating evidence has shown that the reversal or restoration of neutrophil function can promote bacterial clearance and improve sepsis outcome, supporting the idea that targeting neutrophils may be a promising strategy for sepsis treatment. In this review, we will give an overview of the role of neutrophils during sepsis and discuss the potential therapeutic strategy targeting neutrophils.


2021 ◽  
Vol 22 (6) ◽  
pp. 1055-1064
Author(s):  
S. V. Popov ◽  
I. Yu. Shmelkov ◽  
S. V. Khaidukov

Morbidity and mortality rates in invasive mycoses determine the need to improve methods for their timely diagnosis by assessment the patients’ immune status. Evaluation of individual immune status allows the clinician to predict the development and course of fungal infections. At the same time, identification of opportunistic mycosis in immunocompetent patients should require a search for some hidden immune deficiency. Determining the cause of such immune defects can help develop an effective strategy for both etiotropic and immune therapy of patients with invasive mycoses. Currently, the functions of regulatory T lymphocytes that support immunological tolerance in fungal infections remain to be incompletely studied. In this review, we present experimental works which suggest that the regulatory T lymphocytes are able to suppress immune responses to fungi by stimulating the immunosuppressive environment. It was shown that regulatory T lymphocytes use Toll-like receptor 2 to achieve immunosuppression in Candida infections. The balance between the number and function of regulatory T lymphocytes is essential for elimination of fungal pathogens and protection against post-infectious immunopathological conditions. It was found that the regulatory T lymphocytes provide protection at an early stage of Candida infection, since, due to IL-2 suppression, they enhance Th17 differentiation and clearance of fungi. Moreover, at the later stages of infection, the regulatory T lymphocytes have an inhibitory effect. The balance between Th17 and regulatory T lymphocytes in mucosal lining is considered the main factor for distinguishing between commensal carriage and Candida albicans infection. The study is presented which indicate that disseminated candidiasis associated with expansion of regulatory T lymphocytes stimulates a Th17-cell response that controls the course of the disease. The mechanisms that control regulatory T lymphocytes homeostasis are essential for providing effective protection against pathogens, as well as for controlling the immunopathological conditions associated with Candida infection. The review presents data that have established the role of TGF-β1 in increasing the viability of regulatory T lymphocytes, which is correlated with the pronounced immunomodulating role of these cells at the later phase of Candida infections of the mucous membrane. It has been also demonstrated that the pulmonary regulatory Tlymphocytes are induced during cryptococcal infection, which predominantly suppresses Th2 cells, thereby supporting its course. Expansion of the regulatory T lymphocytes upon administration of IL-2/antiIL-2 complex during cryptococcal infection led to a decrease in IgE production and a decrease in allergic airway inflammation. It should be noted that refinement of prognostic value of the regulatory T lymphocytes in human fungal infections may substantiate the basic principles of targeted immunotherapy.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.


Author(s):  
Mohamad Hossein Pourhanifeh ◽  
Kazem Abbaszadeh-Goudarzi ◽  
Mohammad Goodarzi ◽  
Sara G.M. Piccirillo ◽  
Alimohammad Shafiee ◽  
...  

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.


2018 ◽  
Vol 24 (26) ◽  
pp. 3072-3083 ◽  
Author(s):  
Sowndramalingam Sankaralingam ◽  
Angham Ibrahim ◽  
MD Mizanur Rahman ◽  
Ali H. Eid ◽  
Shankar Munusamy

Background: The incidence and prevalence of diabetes mellitus are increasing globally at alarming rates. Cardiovascular and renal complications are the major cause of morbidity and mortality in patients with diabetes. Methylglyoxal (MG) - a highly reactive dicarbonyl compound – is increased in patients with diabetes and has been implicated to play a detrimental role in the etiology of cardiovascular and renal complications. Derived from glucose, MG binds to arginine and lysine residues in proteins, and the resultant end products serve as surrogate markers of MG generation in vivo. Under normal conditions, MG is detoxified by the enzyme glyoxalase 1 (Glo1), using reduced glutathione as a co-factor. Elevated levels of MG is known to cause endothelial and vascular dysfunction, oxidative stress and atherosclerosis; all of which are risk factors for cardiovascular diseases. Moreover, MG has also been shown to cause pathologic structural alterations and impair kidney function. Conversely, MG scavengers (such as N-acetylcysteine, aminoguanidine or metformin) or Nrf2/Glo1 activators (such as trans-resveratrol / hesperetin) are shown to be useful in preventing MG-induced cardiovascular and renal complications in diabetes. However, clinical evidence supporting the MG lowering properties of these agents are limited and hence, need further investigation. Conclusion: Reducing MG levels directly using scavengers or indirectly via activation of Nrf2/Glo1 may serve as a novel and potent therapeutic strategy to counter the deleterious effects of MG in diabetic complications.


2020 ◽  
Vol 21 (2) ◽  
pp. 237-245 ◽  
Author(s):  
Mohamed A. Ragheb ◽  
Marwa H. Soliman ◽  
Emad M. Elzayat ◽  
Mervat S. Mohamed ◽  
Nada El-Ekiaby ◽  
...  

Background: Doxorubicin (DOX) is the most common drugs used in cancer therapy, including Hepatocellular Carcinoma (HCC). Drug resistance, is one of chemotherapy’s significant problems. Emerging studies have shown that microRNAs (miRNAs) could participate in regulating this mechanism. Nevertheless, the impact of miRNAs on HCC chemoresistance is still enigmatic. Objective: Investigating the role of miR-520c-3p in enhancement of anti-tumor effect of DOX against HepG2 cells. Methods: Expression profile for liver related miRNAs (384 miRNAs) has been analyzed on HepG2 cells treated with DOX using qRT-PCR. miR-520c-3p, the most deregulated miRNA, was selected for combination treatment with DOX. Expression level for LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53 was evaluated in miR-520c-3p transfected cells. Cell viability, colony formation, wound healing as well as apoptosis assays have been demonstrated. Furthermore, Mcl-1 protein level was measured using western blot technique. Results: The present data indicated that miR-520c-3p overexpression could render HepG2 cells chemo-sensitive to DOX through enhancing its suppressive effects on proliferation, migration, and induction of apoptosis. The suppressive effect of miR-520c-3p involved altering the expression levels of some key regulators of cell cycle, proliferation, migration and apoptosis including LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53. Interestingly, Mcl-1 was found to be one of the potential targets of miR-520c-3p, and its protein expression level was down-regulated upon miR-520c-3p overexpression. Conclusion: Our data referred to the tumor suppressor function of miR-520c-3p that could modulate chemosensitivity of HepG2 cells toward DOX treatment, providing a promising therapeutic strategy in HCC.


Author(s):  
Enrico Bentivegna ◽  
Michelangelo Luciani ◽  
Valerio Spuntarelli ◽  
Giorgio Sesti ◽  
Flavia Del Porto ◽  
...  

AbstractRight heart thrombus (RHT) in transit is an uncommon condition associated with high mortality. Increased use of echocardiography has allowed an easier detection of RHT; however, there is no consensus about the most appropriate management of this critical situation. Therapeutic strategy should be decided according to patient’s haemodynamic parameters, clinical data, and bleeding risk. This paper, referring to the most current evidences, underlines the difficulty to establish the best therapeutic strategies in RHT among complex patients as there are no relevant guidelines. In some conditions, multidisciplinary management is the best way to find the most correct therapy despite the bad prognosis.


2021 ◽  
Vol 11 (4) ◽  
pp. 1696
Author(s):  
Mario Giosuè Balzanelli ◽  
Pietro Distratis ◽  
Orazio Catucci ◽  
Angelo Cefalo ◽  
Rita Lazzaro ◽  
...  

Due to the promising effects of mesenchymal stem cells (MSCs) in the treatment of various diseases, this commentary aimed to focus on the auxiliary role of MSCs to reduce inflammatory processes of acute respiratory infections caused by the 2019 novel coronavirus (COVID-19). Since early in 2020, COVID-19, a consequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly affected millions of people world-wide. The SARS-CoV-2 infection in children appears to be an unusual event. Despite the high number of affected adult and elderly, children and adolescents remained low in amounts, and marginally touched. Based on the promising role of cell therapy and regenerative medicine approaches in the treatment of several life-threatening diseases, it seems that applying MSCs cell-based approaches can also be a hopeful strategy for improving subjects with severe acute respiratory infections caused by COVID-19.


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