METHODS FOR SIMULATION OF ACUTE BRAIN ISCHEMIA: PATHOPHYSIOLOGICAL SUBSTANTIATION OF SELECTION AND IMPORTANCE FOR CLINICAL PRACTICE

Author(s):  
Б.И. Гельцер ◽  
Э.В. Слабенко ◽  
Ю.В. Заяц ◽  
В.Н. Котельников

Одним из основных требований к разработке экспериментальных моделей цереброваскулярных заболеваний является их максимальная приближенность к реальной клинической практике. В работе систематизированы данные по основным методам моделирования острой ишемии головного мозга (ОИГМ), представлена их классификация, анализируются данные о преимуществах и недостатках той или иной модели. Обсуждаются результаты экспериментальных исследований по изучению патогенеза ОИГМ с использованием различных моделей (полной и неполной глобальной, локальной и мультифокальной ишемии) и способов их реализации (перевязка артерий, клипирование, коагуляция, эмболизация и др.). Особое внимание уделяется «стабильности» последствий острого нарушения мозгового кровообращения: необратимых ишемических повреждений головного мозга или обратимых с реперфузией заданной продолжительности. Отмечается, что важное значение в этих исследованиях должно принадлежать современным методам прижизненной визуализации очагов острого ишемического повреждения, что позволяет оценивать динамику патологического процесса. Предлагаемый метод отвечает требованиям гуманного обращения с животными. Подчеркивается, что выбор релевантной модели ОИГМ определяется задачами предстоящего исследования и технологическими ресурсами научной лаборатории. Development of experimental models for acute forms of cerebrovascular diseases is essential for implementation of methods for their prevention and treatment. One of the principal requirements to such models is their maximum approximation to actual clinical practice. This review systematized major models of acute cerebral ischemia (ACI), their classification, and presented information about their advantages and shortcomings. Also, the review presented results of experimental studies on pathophysiological mechanisms of different types of modeled ACI (complete and incomplete global, local, and multifocal ischemia) and methods for creating these models (arterial ligation, clipping, coagulation, embolization, etc.). Particular attention was paid to “stability” of the consequences of acutely impaired cerebral circulation - an irreversible ischemic brain injury or a reversible injury with reperfusion of a given duration. The authors emphasized that in such studies, a special significance should be given to intravital imaging of acute ischemic damage foci using modern methods, which allow assessing the dynamics of the pathological process and meet the requirements to humane treatment of animals. The choice of a relevant ACI model is determined by objectives of the planned study and the technological resources available at the research laboratory.

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 238
Author(s):  
Dragan Copic ◽  
Maria Laggner ◽  
Polina Kalinina ◽  
Katharina Klas ◽  
Erwin Tschachler ◽  
...  

Ichthyoses comprise a broad spectrum of keratinization disorders due to hereditary defects of cornification. Until now, mutations in more than 50 genes, mostly coding for structural proteins involved in epidermal barrier formation, have been identified as causes for different types of these keratinization disorders. However, due to the high heterogeneity and difficulties in the establishment of valid experimental models, research in this field remains challenging and translation of novel findings to clinical practice is difficult. In this review, we provide an overview of existing models to study hereditary cornification defects with focus on ichthyoses and palmoplantar keratodermas.


Author(s):  
Adrian Alecu ◽  
Romeo Brezeanu

This article discusses the series of tests on animal experimental models carried out by our group to evaluate the effect of homeopathic preparations selected according to traditional criteria of pathogenetic similarity. Our overall experience indicates that it is not difficult to carry out experimental studies assaying homeopathic medicines in randomized placebo-controlled tests returning statistically analyzable results. The basic requirement for this purpose is to select validated experimental models. The simplest and most reliable ones are the ones arising from common daily clinical practice or those taken from classical pharmacological studies modified as to fit the goals of a homeopathic assay. By proceeding in this way it will be possible to build a sound body of evidence for the biological effects of high dilutions.


Author(s):  
Adrian Alecu ◽  
Romeo Brezeanu ◽  
Gabriela Marcus ◽  
Adriana Cojocaru ◽  
Mariana Alecu

This article discusses the series of tests on animal experimental models carried out by our group to evaluate the effect of homeopathic preparations selected according to traditional criteria of pathogenetic similarity. Our overall experience indicates that it is not difficult to carry out experimental studies assaying homeopathic medicines in randomized placebo-controlled tests returning statistically analyzable results. The basic requirement for this purpose is to select validated experimental models. The simplest and most reliable ones are the ones arising from common daily clinical practice or those taken from classical pharmacological studies modified as to fit the goals of a homeopathic assay. By proceeding in this way it will be possible to build a sound body of evidence for the biological effects of high dilutions.


2016 ◽  
Vol 13 (03) ◽  
pp. 118-120
Author(s):  
W. Wölwer ◽  
W. Gaebel ◽  
V. Toeller

Summary Background: The provision of mental healthcare for patients with schizophrenia is still characterized both by knowledge gaps and by treatment gaps in everyday clinical practice. Aim: This article discusses the different types of treatment gaps in schizophrenia and describes actions taken to overcome these gaps especially in Europe.


2019 ◽  
Vol 16 (7) ◽  
pp. 587-595 ◽  
Author(s):  
Roberto Santangelo ◽  
Alessandro Dell'Edera ◽  
Arianna Sala ◽  
Giordano Cecchetti ◽  
Federico Masserini ◽  
...  

Background: The incoming disease-modifying therapies against Alzheimer’s disease (AD) require reliable diagnostic markers to correctly enroll patients all over the world. CSF AD biomarkers, namely amyloid-β 42 (Aβ42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau181), showed good diagnostic accuracy in detecting AD pathology, but their real usefulness in daily clinical practice is still a matter of debate. Therefore, further validation in complex clinical settings, that is patients with different types of dementia, is needed to uphold their future worldwide adoption. Methods: We measured CSF AD biomarkers’ concentrations in a sample of 526 patients with a clinical diagnosis of dementia (277 with AD and 249 with Other Type of Dementia, OTD). Brain FDG-PET was also considered in a subsample of 54 patients with a mismatch between the clinical diagnosis and the CSF findings. Results: A p-tau181/Aβ42 ratio higher than 0.13 showed the best diagnostic performance in differentiating AD from OTD (86% accuracy index, 74% sensitivity, 81% specificity). In cases with a mismatch between clinical diagnosis and CSF findings, brain FDG-PET partially agreed with the p-tau181/Aβ42 ratio, thus determining an increase in CSF accuracy. Conclusions: The p-tau181/Aβ42 ratio alone might reliably detect AD pathology in heterogeneous samples of patients suffering from different types of dementia. It might constitute a simple, cost-effective and reproducible in vivo proxy of AD suitable to be adopted worldwide not only in daily clinical practice but also in future experimental trials, to avoid the enrolment of misdiagnosed AD patients.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hiroko Yuzawa ◽  
Yousuke Hirose ◽  
Tomonori Kimura ◽  
Keisuke Shinozaki ◽  
Moe Oguchi ◽  
...  

Abstract Background In continuous renal replacement therapy (CRRT), administration of anticoagulants is necessary for achieving a certain level of filter lifetime. Generally, anticoagulant doses are controlled to keep activated partial thromboplastin time and other indicators within a certain target range, regardless of the membrane materials used for the filter. However, in actual clinical practice, the filter lifetime varies significantly depending on the membrane material used. The objective of this study was to demonstrate that the minimum anticoagulant dose necessary for prolonging the filter lifetime while reducing the risk of hemorrhagic complications varies depending on the type of membrane. Methods In three beagles, hemodiafiltration was performed with hemofilters using polysulfone (PS), polymethylmethacrylate (PMMA), and AN69ST membranes separately. The minimum dose of nafamostat mesylate (NM) that would allow for 6 h of hemodiafiltration (required dose) was investigated for each membrane material. Results The NM doses required for 6 h of hemodiafiltration were 2 mg/kg/h for the PS membrane, 6 mg/kg/h for the PMMA membrane, and 6 mg/kg/h for the AN69ST membrane. Conclusion For hemodiafiltration performed in beagles, the required NM dose varied for each filter membrane material. Using the optimal anticoagulant dose for each membrane material would allow for safer CRRT performance.


2021 ◽  
Vol 10 (8) ◽  
pp. 1613
Author(s):  
Alessandro Crosio ◽  
Giulia Ronchi ◽  
Benedetta Elena Fornasari ◽  
Simonetta Odella ◽  
Stefania Raimondo ◽  
...  

As a consequence of trauma or surgical interventions on peripheral nerves, scar tissue can form, interfering with the capacity of the nerve to regenerate properly. Scar tissue may also lead to traction neuropathies, with functional dysfunction and pain for the patient. The search for effective antiadhesion products to prevent scar tissue formation has, therefore, become an important clinical challenge. In this review, we perform extensive research on the PubMed database, retrieving experimental papers on the prevention of peripheral nerve scarring. Different parameters have been considered and discussed, including the animal and nerve models used and the experimental methods employed to simulate and evaluate scar formation. An overview of the different types of antiadhesion devices and strategies investigated in experimental models is also provided. To successfully evaluate the efficacy of new antiscarring agents, it is necessary to have reliable animal models mimicking the complications of peripheral nerve scarring and also standard and quantitative parameters to evaluate perineural scars. So far, there are no standardized methods used in experimental research, and it is, therefore, difficult to compare the results of the different antiadhesion devices.


Author(s):  
Natalia Nowak ◽  
Masayuki Yamanouchi ◽  
Eiichiro Satake

AbstractExtracellular vesicle (EV)-based therapy was hypothesized as a promising regenerative approach which has led to intensive research of EVs in various pathologies. In this study, we performed a comprehensive systematic review of the current experimental evidence regarding the protective properties of EVs in chronic kidney disease (CKD). We evaluated the EV-based experiments, EV characteristics, and effector molecules with their involvement in CKD pathways. Including all animal records with available creatinine or urea data, we performed a stratified univariable meta-analysis to assess the determinants of EV-based therapy effectiveness. We identified 35 interventional studies that assessed nephroprotective role of EVs and catalogued them according to their involvement in CKD mechanism. Systematic assessment of these studies suggested that EVs had consistently improved glomerulosclerosis, interstitial fibrosis, and cell damage, among different CKD models. Moreover, EV-based therapy reduced the progression of renal decline in CKD. The stratified analyses showed that the disease model, administered dose, and time of therapeutic intervention were potential predictors of therapeutic efficacy. Together, EV therapy is a promising approach for CKD progression in experimental studies. Further standardisation of EV-methods, continuous improvement of the study quality, and better understanding of the determinants of EV effectiveness will facilitate preclinical research, and may help development of clinical trials in people with CKD. Graphical Abstract


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.


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