scholarly journals Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

2018 ◽  
Vol 2018 ◽  
pp. 1-29 ◽  
Author(s):  
Martina Perše ◽  
Željka Večerić-Haler
Keyword(s):  
Treatment Strategies ◽  
Kidney Injury ◽  
Rodent Model ◽  
The Body ◽  
Future Research ◽  
Cisplatin Nephrotoxicity ◽  
Dosage Regimens ◽  
Chronic Kidney Injury ◽  
Underlying Mechanisms ◽  
Insight Into

Cisplatin is an antitumor drug used in the treatment of a wide variety of malignancies. However, its primary dose-limiting side effect is kidney injury, which is a major clinical concern. To help understand mechanisms involved in the development of kidney injury, cisplatin rodent model has been developed. Given the complex pathogenesis of kidney injury, which involves both local events in the kidney and interconnected and interdependent systemic effects in the body, cisplatin rodent model is indispensable in the investigation of underlying mechanisms and potential treatment strategies of both acute and chronic kidney injury. Cisplatin rodent model is well appreciated and widely used model due to its simplicity. It has many similarities to human cisplatin nephrotoxicity, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using cisplatin model. The present paper is aimed at giving a concise insight into the complex characteristics of cisplatin rodent model and heterogeneity of cisplatin dosage regimens as well as outlining factors that can severely influence the outcome of the model and the study. Challenges for future research are also mentioned.

Biophysical Insight into Protein Folding, Aggregate Formation and its Inhibition Strategies

2021 ◽  
Vol 28 ◽  
Author(s):  
Syed Mohammad Zakariya ◽  
Aiman Zehr ◽  
Rizwan Hasan Khan
Keyword(s):  
Protein Folding ◽  
Amyloid Fibrils ◽  
Three Dimensional ◽  
The Body ◽  
Aggregate Formation ◽  
Structural Characterisation ◽  
Current Scenario ◽  
Underlying Mechanisms ◽  
Quality Control Mechanism ◽  
Insight Into

: The failure of protein to correctly fold into its functional and unique three dimensional form leads to misfolded or partially folded protein. When these rogue proteins and polypeptides escape the quality control mechanism within the body, they result in aberrant aggregation of proteins into characteristic amyloid fibrils. This is the main cause for the number of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s and Huntington’s diseases. This review aims to summarise the underlying mechanisms of protein folding, misfolding and aggregation. It also highlights the recent technologies for the structural characterisation and detection of amyloid fibrils in addition to the various factors responsible for the aggregate formation and the strategies to combat the aggregation process. Besides, the journey from origin to the current scenario of protein aggregation is also concisely discussed.

scholarly journals HIV-related cardiovascular diseases: the search for a unifying hypothesis

2020 ◽  
Vol 318 (4) ◽  
pp. H731-H746 ◽  
Author(s):  
Leanne Dominick ◽  
Natasha Midgley ◽  
Lisa-Mari Swart ◽  
Devon Sprake ◽  
Gaurang Deshpande ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Treatment Strategies ◽  
Well Being ◽  
Cardiovascular Complications ◽  
Future Research ◽  
Cvd Risk ◽  
Significant Research ◽  
Sub Saharan ◽  
Underlying Mechanisms

Although the extensive rollout of antiretroviral (ARV) therapy resulted in a longer life expectancy for people living with human immunodeficiency virus (PLHIV), such individuals display a relatively increased occurrence of cardiovascular diseases (CVD). This health challenge stimulated significant research interests in the field, leading to an improved understanding of both lifestyle-related risk factors and the underlying mechanisms of CVD onset in PLHIV. However, despite such progress, the precise role of various risk factors and mechanisms underlying the development of HIV-mediated CVD still remains relatively poorly understood. Therefore, we review CVD onset in PLHIV and focus on 1) the spectrum of cardiovascular complications that typically manifest in such persons and 2) underlying mechanisms that are implicated in this process. Here, the contributions of such factors and modulators and underlying mechanisms are considered in a holistic and integrative manner to generate a unifying hypothesis that includes identification of the core pathways mediating CVD onset. The review focuses on the sub-Saharan African context, as there are relatively high numbers of PLHIV residing within this region, indicating that the greater CVD risk will increasingly threaten the well-being and health of its citizens. It is our opinion that such an approach helps point the way for future research efforts to improve treatment strategies and/or lifestyle-related modifications for PLHIV.

Belichaamde ervaringen van patiënten met ernstige chronische vermoeidheid na kanker

KWALON ◽  
2020 ◽  
Vol 25 (3) ◽  
Author(s):  
Tom Bootsma ◽  
Melanie Schellekens ◽  
Rosalie van Woezik ◽  
Marije van der Lee ◽  
Jenny Slatman
Keyword(s):  
Interpretative Phenomenological Analysis ◽  
Phenomenological Study ◽  
Chronic Fatigue ◽  
The Body ◽  
Future Research ◽  
Cancer Related Fatigue ◽  
Embodied Experiences ◽  
After Cancer ◽  
Insight Into ◽  
Philosophical Phenomenology

Embodied experiences of patients with severe chronic fatigue after cancer. An interpretive phenomenological study This article presents a phenomenological study on embodied experiences based on interviews with 25 patients with severe chronic cancer-related fatigue (CCRF). Insight into the patient’s perspective can help to facilitate personalized treatment in CCRF. Theoretically resorting to philosophical phenomenology, we explored embodied experiences of living with CCRF. Using interpretative phenomenological analysis, we identified four superordinate themes: (1) Worn out; (2) Diminishment of one’s ‘I can’; (3) Socially invisible objectification of the body; and (4) Restoring one’s ‘I can’. For clinical practice, these results suggest that focusing on the body and restoring one’s ‘I can’ could be helpful during treatment of CCRF. Future research should focus on measuring individual patterns of CCRF symptoms in order to personalize treatment.

Saline alone vs saline plus mannitol hydration for the prevention of acute cisplatin nephrotoxicity: A randomized trial.

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 242-242
Author(s):  
Bradley Beeler ◽  
Wilfred P. Delacruz ◽  
Frederick L. Flynt ◽  
Sandra Terrazzino ◽  
Naomi Hullinger ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Injury ◽  
The Body ◽  
Prospective Data ◽  
Cisplatin Nephrotoxicity ◽  
Discontinuation Of Treatment ◽  
Adequate Hydration ◽  
Before And After ◽  
Group A ◽  
To Receive

242 Background: Cisplatin is a widely used chemotherapeutic in treating malignancies. A common side effects of cisplatin is kidney injury, or nephrotoxicity. This can be a reason for discontinuation of treatment. The majority of the cisplatin is removed from the body by urination. Mannitol is a compound that has been thought to help negate cisplatin-induced nephrotoxicity. Mannitol is a diuretic, causing increased amount of urination, enhancing excretion of cisplatin. Mmultiple studies that indirectly looked into the effect of mannitol in preventing kidney damage in patients receiving cisplatin. However, there are limited prospective data that evaluate the effect of mannitol in preventing cisplatin-induced nephrotoxicity. In this study, we determine the effects of pre-hydration with mannitol on reducing the risk of cisplatin-induced nephrotoxicity, as opposed to normal saline pre-hydration in patients receiving cisplatin. Methods: 50 patients eligible to receive chemotherapy with cisplatin chemotherapy were identified and randomized to receive 1L saline alone (A) or saline plus mannitol (B) before and after chemotherapy. (1) NS 1 Liter pre chemo- > chemo - > NS 1 Liter post chemo; (2) NS + Mannitol pre chemo - > chemo - > NS + Mannitol post chemo. Serum creatinine and BUN were drawn on days 1 (baseline), 5, and 14 Results: Renal function as measured by BUN/Cr ration, GFR, creatinine, and BUN between group (A) and (B) are similar at baseline (BL), day 1, 5, and 14. Cisplatin caused acute decline in renal function as determined by ser Cr, BUN to ser Cr ratio and GFR, however, the addition of mannitol to NS pre-hydration did not change the outcome. The decline in renal function is limited to grade 1 and most patients recover. Conclusions: Mannitol does not prevent acute nephrotoxicity in patients receiving cisplatin. This underscores the importance of adequate hydration in patients treated with cisplatin.[Table: see text]

scholarly journals SARS CoV-2 Organotropism Associated Pathogenic Relationship of Gut-Brain Axis and Illness

2020 ◽  
Vol 7 ◽  
Author(s):  
Pottathil Shinu ◽  
Mohamed A. Morsy ◽  
Pran Kishore Deb ◽  
Anroop B. Nair ◽  
Manoj Goyal ◽  
...  
Keyword(s):  
Cardiac Injury ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Enteric Infection ◽  
Pneumonia Patient ◽  
Loss Of Appetite ◽  
Relationship Of ◽  
Insight Into ◽  
Maculopapular Exanthema

COVID-19 has resulted in a pandemic after its first appearance in a pneumonia patient in China in early December 2019. As per WHO, this global outbreak of novel COVID-19 has resulted in 28,329,790 laboratory-confirmed cases and 911,877 deaths which have been reported from 210 countries as on 12th Sep 2020. The major symptoms at the beginning of COVID-19 are fever (98%), tussis (76%), sore throat (17%), rhinorrhea (2%), chest pain (2%), and myalgia or fatigue (44%). Furthermore, acute respiratory distress syndrome (61.1%), cardiac dysrhythmia (44.4%), shock (30.6%), hemoptysis (5%), stroke (5%), acute cardiac injury (12%), acute kidney injury (36.6%), dermatological symptoms with maculopapular exanthema (36.1%), and death can occur in severe cases. Even though human coronavirus (CoV) is mainly responsible for the infections of the respiratory tract, some studies have shown CoV (in case of Severe Acute Respiratory Syndrome, SARS and Middle East Respiratory Syndrome, MERS) to possess potential to spread to extra-pulmonary organs including the nervous system as well as gastrointestinal tract (GIT). Patients infected with COVID-19 have also shown symptoms associated with neurological and enteric infection like disorders related to smell/taste, loss of appetite, nausea, emesis, diarrhea, and pain in the abdomen. In the present review, we attempt to evaluate the understanding of basic mechanisms involved in clinical manifestations of COVID-19, mainly focusing on interaction of COVID-19 with gut-brain axis. This review combines both biological characteristics of the virus and its clinical manifestations in order to comprehend an insight into the fundamental potential mechanisms of COVID-19 virus infection, and thus endorse in the advancement of prophylactic and treatment strategies.

scholarly journals Energetic dysfunction in sepsis: a narrative review

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sebastien Preau ◽  
Dominique Vodovar ◽  
Boris Jung ◽  
Steve Lancel ◽  
Lara Zafrani ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Organ Dysfunction ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Substrate Utilization ◽  
Future Research ◽  
Targeted Treatments ◽  
Organ Specific ◽  
Future Research Directions ◽  
Poor Outcomes

Abstract Background Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions. Main text Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described. Conclusions Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.

scholarly journals Drug Dosing Rationality Based on Jelliffe Equation in Acute Kidney Injury

2019 ◽  
Vol 8 (4) ◽  
pp. 175
Author(s):  
Dealinda Husnasya ◽  
Mawardi Ihsan
Keyword(s):  
Acute Kidney Injury ◽  
Steady State ◽  
Drug Concentration ◽  
Kidney Injury ◽  
Drug Dosage ◽  
The Body ◽  
Observation Study ◽  
Minimum Effective Concentration ◽  
Dosage Regimens ◽  
Rational Drug

Patients with Acute Kidney Injury (AKI) experience changes in unstable kidney function which is characterized by instability of serum creatinine values that affect the concentration of drugs in the body. Therefore, adjusting the dosage and frequency of the drug is an important concern. This study aimed to determine the proportion of rational drug dosage regimens in hospitalized patients with AKI. This research was a retrospective observation study with cross sectional design. Sample collection was carried out using simple random sampling method for patients who were hospitalized with AKI during January 1st till December 31, 2017. Data analysis was carried out descriptively to see the proportion and description of the rationality of each dosage regimen given to patients. This research was conducted at the dr. Sardjito General Hospital Yogyakarta. The results showed that the proportion of rational drug dosage regimens given to 100 inpatients with AKI was 60.00% based on literature and 94.12% based on predictive steady-state concentration calculation. Irrationality of the dosing regimen because of administration interval was 52.84%; because of dose was 17.05%; and because of both were 30.11%. The irrationality based on predictive steady concentration showed that drug concentration below minimum effective concentration was 33.33% and over minimum toxic concentration was 66.67%. The proportion of rational drug dosage regimens given to 100 inpatients with AKI based on literature and calculation of predictive steady-state concentrations were quite high. However, some dosing regimens were still irrationally prescribed with the irrationality form were generally in the form of irrational delivery interval with excessive drug concentration.

scholarly journals Opioid-Induced Constipation in Oncological Patients: New Strategies of Management

2019 ◽  
Vol 20 (12) ◽  
Author(s):  
Ricard Mesía ◽  
Juan Antonio Virizuela Echaburu ◽  
Jose Gómez ◽  
Tamara Sauri ◽  
Gloria Serrano ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Opioid Analgesics ◽  
Future Research ◽  
Randomized Controlled ◽  
Oncological Patients ◽  
Typical Treatment ◽  
Underlying Mechanisms ◽  
Effective Assessment ◽  
Chronic Use ◽  
New Strategies

Opinion statementCancer-associated pain has traditionally been treated with opioid analgesics, often in escalating doses. Opioid-induced constipation (OIC) is a common problem associated with chronic use of opioid analgesics. Typical treatment strategies to alleviate constipation are based on dietary changes, exercise, and laxatives. However, laxatives have a nonspecific action and do not target underlying mechanisms of OIC. This article will review prevalent, clinical presentation and recommendations for the treatment of OIC. An independent literature search was carried out by the authors. We reviewed the literature for randomized controlled trials that studied the efficacy of laxatives, naloxone, and naloxegol in treating OIC. Newer strategies addressing the causal pathophysiology of OIC are needed for a more effective assessment and management of OIC. Finally, traditional recommended therapies are appraised and compared with the latest pharmacological developments. Future research should address whether naloxegol is more efficacious by its comparison directly with first-line treatments, including laxatives.

scholarly journals (Mesenchymal) Stem Cell-Based Therapy in Cisplatin-Induced Acute Kidney Injury Animal Model: Risk of Immunogenicity and Tumorigenicity

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Ž. Večerić-Haler ◽  
A. Cerar ◽  
M. Perše
Keyword(s):  
Immune Response ◽  
Acute Kidney Injury ◽  
Animal Models ◽  
Animal Studies ◽  
Therapeutic Strategy ◽  
Kidney Injury ◽  
The Body ◽  
Model Risk ◽  
Cisplatin Nephrotoxicity ◽  
Cell Based Therapy

Pathogenesis of AKI is complex and involves both local events in the kidney as well as systemic effects in the body that are interconnected and interdependent. Despite intensive investigations there is still no pharmacological agent that could provide complete protection against cisplatin nephrotoxicity. In the last decade mesenchymal stem cells (MSCs) have been proposed as a potentially useful therapeutic strategy in various diseases, including acute kidney injury. Although MSCs have potent immunosuppressive properties, animal studies also suggest that transplanted MSCs may elicit immune response. Interestingly, tumorigenicity of transplanted MSCs in animal studies has been rarely studied. Since the risk of tumorigenicity of particular therapy as well as the immune response to solid or cell grafts is a major issue in clinical trials, the aim of the present paper is to critically summarize the results of MSC transplantation on animal models of AKI, particularly cisplatin-induced animal models, and to expose results and main concerns about immunogenicity and tumorigenicity of transplanted MSCs, two important issues that need to be addressed in future studies.

scholarly journals MCMs in Cancer: Prognostic Potential and Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Si Yu ◽  
Guanqun Wang ◽  
Yue Shi ◽  
Haifeng Xu ◽  
Yongchang Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Replication Initiation ◽  
Current Evidence ◽  
Future Research ◽  
Hallmarks Of Cancer ◽  
Minichromosome Maintenance ◽  
Proliferation Markers ◽  
A Cell ◽  
Underlying Mechanisms ◽  
Insight Into

Enabling replicative immortality and uncontrolled cell cycle are hallmarks of cancer cells. Minichromosome maintenance proteins (MCMs) exhibit helicase activity in replication initiation and play vital roles in controlling replication times within a cell cycle. Overexpressed MCMs are detected in various cancerous tissues and cancer cell lines. Previous studies have proposed MCMs as promising proliferation markers in cancers, while the prognostic values remain controversial and the underlying mechanisms remain unascertained. This review provides an overview of the significant findings regarding the cellular and tumorigenic functions of the MCM family. Besides, current evidence of the prognostic roles of MCMs is retrospectively reviewed. This work also offers insight into the mechanisms of MCMs prompting carcinogenesis and adverse prognosis, providing information for future research. Finally, MCMs in liver cancer are specifically discussed, and future perspectives are provided.

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