МОДЕЛИРОВАНИЕ КОЖНЫХ РАН В ЭКСПЕРИМЕНТЕ

Stem Cells in Tissue Repair and Regeneration

Translation from animal studies of novel pharmacological therapies to clinical trials in cardiac arrest: A systematic review

Several large-scale, double-blind, placebo-controlled trials have shown convincingly that neither β-carotene1–3⇓⇓ nor vitamin E, alone3–5⇓⇓ or in combination with other antioxidant vitamins,6 reduces the risk of fatal or nonfatal infarction (or other hard clinical end points) in an unselected population of people with established coronary heart disease (CHD) or at high risk of CHD. Two end point trials, much smaller trials that used vitamin E, have reported positive results,7,8⇓ and one trial, which used ultrasound, showed that a combination of vitamins E and C slowed the progression of carotid artery lesions.9However, these are far outweighed by the negative results in the other, much larger trials. Certainly there is no basis for recommending vitamin E supplementation to patients with CHD, especially because it may blunt the effectiveness of hypolipidemic therapy with statins and niacin.6 A surprisingly large fraction of cardiologists (≈40%) have been recommending such regimens10 despite warnings that this use was premature.11 At first glance, it might seem that these negative results close the book and that additional clinical trials of any antioxidants would be pointless. Closer examination, we believe, will show that such a conclusion would be premature and inappropriate.12 The hypothesis that oxidative modification of LDL plays a significant role in atherogenesis in humans is not necessarily disproved by the failure of these particular clinical trials any more than a negative trial of an ineffectual antibiotic in Pneumococcal pneumonia would prove that pneumonia is not a bacterial disease. The oxidative modification hypothesis is not that vitamin E will ameliorate the human disease but that oxidative modification of LDL and/or other oxidative events play a significant role in human atherogenesis as it does in animal models of atherogenesis. A corollary of the hypothesis is …

Background: Various physical phenomena come into use in medicine; however, to date, universal physical methods have not been developed to optimize the course of the wound healing at all treatment stages. In combustiology, the first stage of burn treatment is debridement; then it is important to create an optimal biological environment, normalize blood circulation, suppress pathogenic flora, and stimulate proliferative processes in the wound.Objective: To determine the effectiveness of low-temperature argon plasma (LTAP) and ultrasonic cavitation in deep burn wound treatment based on clinical observations and cytological findings.Materials and methods: We studied impression smears from burn wounds of 36 patients with deep burns of various etiologies who were treated using LTAP and ultrasonic cavitation in the Thermal Injuries Unit at the Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine (Saint Petersburg, Russian Federation) between 2022 and 2023.Results: We found that cytogram findings in the study area changed from the inflammatory type to the regenerative-inflammatory one on day 3-7 when LTAP and ultrasonic cavitation were used, while such change in the control area was observed only after 10 days of treatment. Thanks to the use of LTAP and ultrasound after necrosectomy for deep dermal burns, the wound preparation for autologous skin grafting takes less time than it does with standard methods of local burn wound care. Ultrasonic cavitation should be used in cases of severe exudation and slough, whereas LTAP should be used when reparative processes in a burn wound slow down.Conclusions: Burn wound treatment using ultrasonic cavitation and LTAP enables to prepare the wound surface for autologous skin grafting with a high engraftment rate. The procedure allows to effectively and atraumatically debride the wound and suppress pathogenic microflora. Further research is planned in patients with large deep burn wounds.

The Development and Impact of Tuberculosis Vaccines

The article describes the advantages and features of experimental models of thermal burns using in vitro, ex vivo and in vivo test systems. An objective assessment of the application of each approach depending on the type of study is given. For example, cell culture models are simple but do not fully reflect the structure of human skin, which limits their translational value. Ex vivo models, such as skin explants, provide the necessary architectonics to study intercellular interactions, but they also have drawbacks, primarily related to short viability. In general, in vitro and ex vivo models have limitations in reproducing all aspects of burn wound pathogenesis and healing. In this regard, laboratory animals, primarily mice, rats, and pigs, are widely used to study burn wound pathology, its effects on the body, and the efficacy of therapy. The decision to use experimental animal models is made taking into account their translational relevance to humans. In rodents, wound healing occurs mainly by contraction, in contrast to the re-epithelialisation and granulation seen in humans, which contributes to faster wound healing in rodents. The significant similarities between certain properties of pig and human skin make the latter a relevant test system in pharmacodynamic studies of thermal burn wounds.

Introduction. Posttraumatic epilepsy: treatable epileptogenesis.

N-docosanol (Abreva) for herpes labialis: Problems and questions

Cancer immunologists have made enormous efforts to prove that innate and adaptive immune cells recognize tumor cells and induce tumor rejection in experimental animal models. These observations provided the rationale to study the role of the immune system in the control of tumor growth in cancer patients and to develop immunotherapeutic strategies to treat patients with cancers. Several lines of evidence suggest that anti-tumor immune responses may correlate with better clinical outcome in patients with cancers. Among them is the correlation between the presence of tumor-infiltrating T cells and the improved clinical outcome for patients with solid tumors [1–3]. In addition, a number of immunotherapies, such as high-dose IL-2 [4] and TA-specific monoclonal antibodies (mAb) [5], have provided long-term clinical benefits to a minority of cancer patients. Most importantly, the recent approval by the US FDA of the mAb ipilimumab directed against the co-inhibitory molecule CTLA-4 for patients with unresectable or metastatic melanoma represents a major breakthrough for mAb-based therapies in oncology practice [6]. The successful outcome of the randomized phase III clinical trial with ipilumumab has provided the much-needed incontrovertible clinical evidence that in humans, as in experimental animal models, the host’s immune system can control tumor growth. Furthermore, it has infused a considerable amount of optimism among tumor immunologists and clinical oncologists about the clinical potential of immunotherapy for the treatment of advanced cancers. However, there are also many examples of spontaneous or vaccine-induced TA-specific T- and B-cell immune responses that do not correlate with improved clinical status [7–9]. This discrepancy between immune and clinical responses underlines the need to better dissect the molecular and cellular events leading to tumor rejection in humans. Such an endeavor has greatly benefited from the molecular identification of TA expressed by human tumor cells, which are recognized by T cells and antibodies [5, 10, 11]. As a result, TA-specific immunotherapies have been implemented in clinical trials with molecularly defined cancer vaccines, TA-specific mAb and adoptive transfer of TA-specific T cells. Novel generations of cancer vaccines with molecularly defined TAs and potent adjuvants like toll-like receptor ligands appear to stimulate strong TA-specific T-cell responses but have shown evidence of clinical benefits in only a minority of patients with advanced cancer [7, 8, 12]. The adoptive transfer of TA-specific T cells remains technically challenging and the promising data obtained in terms of objective clinical responses and durability of responses from small monocentric clinical trials will need to be further confirmed in large multicenter clinical trials [13]. TA-specific mAb are clinically effective in a number of hematological malignancies and solid tumors and are routinely used in the clinic [5]. We now have a better understanding of the multiple mechanisms of tumor-induced immune escape, which are likely to cause the failure of the spontaneous or vaccine-induced immune responses to promote tumor regression in humans. In the tumor microenvironment, a number of negative regulators dampens anti-tumor immune responses and/or their therapeutic efficacy, including the production of cytokines (like TGF-β or IL-10), suppressive cells (regulatory T cells, myelosuppressive dendritic cells), defective antigen presentation by tumor cells (HLA or tumor antigen loss, antigen processing machinery defects), amino-acid catabolizing enzymes (indoleamine-2-3dioxygenase, arginase) and co-inhibitory pathways (like CTLA-4/CD28, PD-1/PD-L1) [14–17]. As a consequence, a number of therapies to specifically target these pathways are being developed to enhance TA-specific immune responses and to increase the likelihood of clinical benefits. In this article, commissioned to recognize National Cancer Survivors Day (the first Sunday in June each year, 5 June in 2011, see www.ncsdf.org), we will comment on the successes of immunotherapy of cancer in the clinical setting. In addition, we will discuss the challenges to optimize the use of cancer immunotherapies in the clinic.

A Historical Perspective on Sepsis

Non-healing wounds are associated with high morbidity and might greatly impact a patient’s well-being and economic status. For many years, scientific research has focused on developing and testing several natural and synthetic materials that enhance the rate of wound healing or eliminate healing complications. Honey has been used for thousands of years as a traditional remedy for many ailments. Recently, honey has reemerged as a promising wound care product especially for infected wounds and for wounds in diabetic patients. In addition to its proposed potent broad-spectrum antibacterial properties, honey has been claimed to promote wound healing by reducing wound hyperaemia, oedema, and exudate, and by stimulating angiogenesis, granulation tissue formation and epithelialisation. Several animal models, including large animals, dogs and cats, and different species of laboratory animals have been used to investigate the efficacy and safety of various natural and synthetic agents for wound healing enhancement. Interpreting the results obtained by these studies is, however, rather difficult and usually hampered by many limiting factors including great variation in types and origins of honey, the type of animal species used as models, the type of wounds, the number of animals, the number and type of controls, and variation in treatment protocols. In this article, we provide a comprehensive review of the most recent findings and applications of published experimental and clinical trials using honey as an agent for wound healing enhancement in different animal models.

This study aims to investigate the types of wounds and wound care in earthquake victims rescued from collapsed buildings after the 2023 Kahramanmaras earthquake. Between February 8th, 2023 and March 1st, 2023, a total of 94 patients (46 males, 48 females; mean age: 40.2±15.5 years; range, 16 to 77 years) with earthquake-related wounds who were trapped under rubble were retrospectively analyzed. Data including age, sex, duration of being trapped under rubble, type and location of the wound, bacterial cultures from deep tissue, and wound care methods used were recorded. The mean duration of being trapped under rubble was 58±38.1 h. Wounds were most commonly located on the lower extremities, followed by the upper extremities. The most common type of wounds were abrasions, followed by necrotic wounds due to crushing. Wound and skin antiseptics, debridement and negative pressure wound therapy (NPWT) were the most common wound care methods used. Various types of injuries and wounds may occur after natural disasters. Chronic wound care is as important as the management of life-threatening acute pathologies. Preparations should be made properly for the long-term treatment of patients after disasters. Methods such as NPWT, debridement creams containing collagenase, wound and skin antiseptics, and hyperbaric oxygen therapy can provide satisfactory short-term results. A broader and more intense application of these treatments is thought to be beneficial, particularly in crush injuries.

Recognizing trigeminal trophic syndrome

A delayed wound healing process can lead to detrimental complications in chronic wound patients such as tissue necrosis and systemic infections. Application of immunonutrition (IN) in experimental animal models and chronic wound patients has shown promising and improved wound healing processes. IN restores the supply of essential nutrients that are critical for cell growth and tissue repair in the wounded subjects. Several commonly found nutrients in IN formulations include polyunsaturated fatty acids (PUFAs), essential amino acids, trace elements such as zinc and vitamins. Recently, some studies suggested the use of traditionally used herbs like curcumin in IN recipes due to its efficient wound healing properties. The roles and functions of IN in wound healing encompass recruitment of white blood cells, platelets and fibroblasts into the wounded area during the coagulation and inflammation phases, enhancement of fibroblast proliferation, collagen synthesis and neovascularization in the proliferation phase; and lastly, regulation of tissue re-epithelization for wound closure and recovery. In this review, the roles and functions of individual nutrients were deliberately discussed alongside their mechanisms of action in wound healing. This aims to provide a more holistic insight into the potentials of those nutrients when used as part of IN for major wound patients. Despite its remarkable effects in wound healing, several criteria should be considered in an IN formulation: the type and severity of wounds, administration timing and mode of administration, and concoction of immune-boosting nutrients in order to ensure the optimal wound healing effects. Keywords: Wound healing; immunonutrition; PUFAs; amino acids; vitamins

The experimental study of cerebral ischemia plays an important role for understanding the pathogenesis of ischemic brain injury, but its correlation with the clinical therapeutic strategies has certain limitations. One of its main reasons is that the experimental models and methods can not or only partially repeat the pathophysiological processes of natural cerebral ischemia. In order to promote the understanding and interpretation of the experimental data, we review the commonly used experimental animal models and modeling methods and mainly elaborate the methods of current different in vivo and in vitro clinical evaluation. Based on these studies, we believe that the standardized clinical evaluations are hugely important for assessing the experimental results and clinical transformation. Key words: Brain ischemia; Brain injury; Disease models, animal