Author Correction: Hyaluronic acid accelerates re-epithelialization and healing of acute cutaneous wounds.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27(3 Suppl): 37-45. doi: 10.26355/eurrev_202304_31320-PMID: 37129334-published online on April 27, 2023. After publication, the authors found some transcription mistakes and applied minor corrections to the Abstract and Discussion sections. The sections have been amended as follows: -       Abstract section: "an average 80% decrease" has been corrected in "an average 86% decrease"; "a small amount of exudate was noted in 91% of wounds" has been corrected in "a small amount of exudate was noted in 10% of wounds". -       Discussion section: "by a reduced wound surface area of 80% at six weeks and a reduced surface area of 95% after eight weeks" has been corrected to "by a reduced wound surface area of 80% at four weeks and a reduced surface area of 86% after six weeks". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31320.

Hyaluronic acid accelerates re-epithelialization and healing of acute cutaneous wounds.

OBJECTIVE: Hyaluronic acid has been efficient in ameliorating and supporting recovery in both chronic and acute lesions. The aim of this study was to assess the effectiveness of hyaluronic acid-based cream and gauze pads in cutaneous wounds. PATIENTS AND METHODS: This retrospective and prospective study examines the use of a 0.2% hyaluronic acid cream or gauze-pads application (Connettivina Bio®). 85 patients participated in the study and were affected by wounds of different etiologies, comprising superficial trauma wounds (20), surgical sutures (15), first- and second-degree burns (15), dermabrasions (30) and ulcers of different etiologies (5). We analyzed the healing process in terms of progression and wound quality. Moreover, we performed biopsies (not on all patients) to evaluate the grade of re-epithelialization. RESULTS: We observed a reduction in the mean surface area of the wounds, precisely 456 mm2 at baseline to 147 mm2 after six weeks with an average 86% [corrected] decrease in the wound surface area. No fibrin tissue was observed, and a small amount of exudate was noted in 10% [corrected] of wounds. Hyaluronic acid cream and gauze-pads-based treatments were well tolerated by patients. All groups showed a decrease of inflammation with a progressive increase of collagen fibers and granulation tissue. CONCLUSIONS: The treatment with hyaluronic acid 0.2% yielded remarkable outcomes in the re-epithelialization of superficial wounds and provided favorable recovery and tolerance for patients.

Spatial distribution and controlling factors of surface water stable isotope values (δ18O and δ2H) across Kazakhstan, Central Asia.

Climate change is expected to alter hydrological and biogeochemical processes in Central Asia (CA), and surface water stable isotope values (δ18O and δ2H) can be used to examine these changes. Spatially extensive stable isotope data, however, are sparse, which constrains the understanding of hydrological processes in transboundary rivers across Kazakhstan. Therefore, we conducted a survey of surface water stable isotopes across the region. River and lake water isotope values exhibit spatial variability that was closely associated with isotope values of precipitation, physiographic factors, landscape characteristics, and local hydrological processes, e.g., evaporation and mixing of waters from different sources. River water was characterized by lower δ18O and δ2H values and higher d-excess relative to lake water, suggesting evaporative enrichment of lake water. Analysis of δ18O versus δ2H for rivers and lakes yielded distinct regressions, (river [RWL], δ2H = 6.08δ18O - 16.7, r2 = 0.837, p < 0.001) and (lake [LWL], δ2H = 6.23δ18O - 22.1, r2 = 0.924, p < 0.001). The slope and intercept of the RWL and LWL were slightly lower than the local meteoric water line [LMWL] (δ2H = 6.96 δ18O - 1.0, r2 = 0.942, p < 0.001). River water δ18O showed a significant negative correlation with elevation and longitude, but not with latitude. The spatial distributions of δ18O and d-excess values showed a remarkable gradient from west to east across Kazakhstan that was associated with moisture moving from the Mediterranean region to Kazakhstan. We also found generally higher δ18O values and lower d-excess values in low-elevation areas because of high evaporation rate in Kazakhstan. These baseline data will be useful for documenting the effects of climate change on the hydrological cycle in Central Asia.

[Endovideosurgery (minimally invasive surgery) in treatment for malignant tumors of female genital organs: a 5-year experience of the clinic of the N.N.Petrov Research Institute of Oncology].

During the period of 2010-2015 laparoscopic surgery was performed in 1263 patients: 1113 with endometrial cancer (588 hysterectomies, 509 hysterectomies with pelvic lymphadenectomy, among them 16 with sentinel lymph node (SLN) mapping with Indocyanine green (ICG)); 86 with cervical cancer (80 nerve-sparing radical hysterectomies (NSRH), among them 15 with SLN mapping, 6 radical vaginal trachelectomies with endovideoassisted lymphadenectomy); 64 with ovarian malignancies. The average operating time in the group of hysterectomies was 101 minutes, in the group of hysterectomies with pelvic lymphadenectomy - 184 minutes, in the group of NSRH - 230 minutes. Average blood loss was less than 50 ml. No intraoperative complications were registered. Asymptomatic lymph cysts were observed in 122 cases. Symptomatic lymph cysts requiring surgical treatment were registered in 9 cases. Inconsistencies of vaginal sutures after radical hysterectomy were in two cases, ureterovaginal fistulas - in two cases. During a 3-year follow-up period twelve recurrences were observed in endometrial cancer patients (12/443; 2,7%), four patients (0,9%) died from disease. After NSRH two local recurrences (2,5%) were registered in patients with cervical cancer, after radical trachelectomy -two local recurrences (33%). One patient became pregnant in the group of vaginal trachelectomies. Therefore laparoscopic approach in treatment of female genital malignacies allows performing an adequate volume of surgery with minimal risk of intra- and postoperative complications, favorable course of the rehabilitation period, and oncological safety.

[RESULTS OF LAPAROSCOPIC SURGERY FOR ENDOMETRIAL CANCER: EXPERIENCE OF THE N. N. PETROV RESEARCH INSTITUTE OF ONCOLOGY].

For the period from September 2010 to September 2014 there were operated 513 patients with endometrial cancer using laparoscopic installation the Karl Storz company. 304 patients (59.2%) underwent hysterectomy with appendages, 209 (40.8%)--hysterectomy with appendages and pelvic lymphadenectomy, including 11 patients (2.2%) with the addition of omentectomy in serous and serous-papillary forms of endometrial cancer. The average age of patients was 58.4 years (44-75 years). Body mass index over 25.0 was determined in 456 patients (88.9%), of whom 183 patients (35.6%) had an excess of body weight, in 159 (31.0%)--obesity of I degree, in 79 (15.5%)--obesity of II degree and in 35 patients (6.8%)--obesity of III degree. There were no reported complications during surgery. The postoperative period in the majority of patients was characterized by the minimal complications and absence of contraindications for adjuvant radiotherapy. During follow-up period there were registered 4 relapses: in 1 patient with serous--papillary form of endometrial cancer during the first year after surgery--in the form of dissemination of tumor in the abdomen and pelvis; in 3 patients--in the form of a cytological detection of glandular cancer cells in vaginal stump. As a result, regardless of age and comorbidities, laparoscopy allows performing to endometrial cancer patients the entire volume of planned radical surgery with minimum damage and with minimal risk of intra- and postoperative complications, favorable and accelerated rehabilitation period.

[LAPAROSCOPIC SURGERY FOR ENDOMETRIAL CANCER IN PATIENTS OVER 70 YEARS OF AGE].

Surgery is the main method in treatment for endometrial cancer. The complexity of treatment of endometrial cancer patients in elderly age is a result of a large number of comorbidities and, as a consequence, the potential possibility of a large number of intra--and postoperative complications. The article presents the international data and the analysis of own results of a use of laparoscopy in surgical treatment of these patients. A comparison with a group of operations performed by laparotomy is carried out as well as it is evaluated the main intra--and perioperative parameters and also complications, and immediate outcomes of patients treated at the Oncogynecology Department of the N.N.Petrov Research Institute of Oncology.

[INDOCYANINE GREEN (ICG) IN THE DETECTION OF SENTINEL LYMPH NODES IN ENDOMETRIAL AND CERVIX CANCER].

We analyzed the international and our own experience of using different dyes in the identification of sentinel lymph nodes in oncogynecological practice. We evaluated the possibility of using indocyanine green (ICG) in the detection of sentinel lymph nodes in patients with endometrial and cervical cancer. The first results of the use of ICG at the Oncogynecology Department of the N.N.Petrov Research Institute of Oncology are presented.

[Laparoscopic radical hysterectomy with pelvic lymph node dissection for endometrial cancer in obese patients].

The results of treatment of 61 endometrial cancer patients with various forms of obesity are presented. Two groups of patients were compared: the first group comprised 26 patients who had undergone the laparoscopic surgery; the second group included 35 patients who had open surgery. Te laparoscopic approach improved the results of surgical treatment of endometrial cancer in patients with obesity. This technique allowed to reduce intraoperative blood loss, to diminish the duration of analgesics' administration, to shorten the period of bowel function recovery, 3 times to reduce the incidence of postoperative complications.

Unexpected characteristics of the IFN-gamma reporters in nontransformed T cells.

Analysis of the IFN-gamma promoter has primarily been conducted by transient expression of reporter constructs in transformed cells. However, the activity of cis elements may differ when expressed transiently compared with their activity within native chromatin. Furthermore, the transcription factors and signaling mechanisms in transformed cells may differ from those in normal T cells. To analyze IFN-gamma promoter regulation in normal T cells, we developed a novel retroviral bottom-strand reporter system to allow the chromatin integration of promoter regions in primary developing T cells. As controls, both the IL-2 and IL-4 promoters were inducible in this system, with the IL-4 reporter having Th2-specific activity. Strikingly, the IFN-gamma promoter exhibited constitutive activity in both Th1 and Th2 subsets, in contrast to the behavior of the endogenous IFN-gamma gene, which is inducible only in Th1 cells. In mapping this activity, we found that the AP-1/GM-CSF site in the distal promoter element is the most critical element for the constitutive activity. Transgenic reporter lines for the IFN-gamma promoter confirmed the constitutive behavior of the isolated IFN-gamma promoter. This constitutive activity was resistant to inhibition by cyclosporin A and was independent of Stat4 and p38 mitogen-activated protein kinase. These results suggest that IFN-gamma promoter regulation may require cis elements residing either downstream or >3.4 kb upstream of the transcriptional start site, involving repression of constitutive activity.

Interleukin-2 expression by a subpopulation of primary T cells is linked to enhanced memory/effector function.

Single cell studies have identified intraclonal heterogeneity of cytokine production by activated T cells. To investigate implications of cytokine heterogeneity for cell fate, an interleukin (IL)-2 promoter-green fluorescent protein (GFP) reporter transgenic model was developed to track IL-2+ and IL-2- T cells during differentiation from naive precursors. Antigen-activated IL-2+ and IL-2- cells had comparable proliferative capacities in primary responses. However, T cells that expressed IL-2 in primary responses demonstrated enhanced antigenic sensitivity and increased expression of effector cytokines in secondary responses in vitro and in vivo. Thus, heterogeneity of activation during a primary response translates into heterogeneous secondary responses, in which enhanced memory/effector function is linked to cells that previously exceeded an activation threshold associated with IL-2 gene transcription.

Memory/effector T cells in TCR transgenic mice develop via recognition of enteric antigens by a second, endogenous TCR.

The majority of clonotypic CD4(+) T cells in the intestinal lamina propria of DO11.10 TCR transgenic mice have an activated/memory phenotype and produce effector cytokines despite the absence of prior exposure to ovalbumin (OVA), the transgene-specific antigen. A small number of splenic T cells have a similar phenotype. Clonotypic T cells from Peyer's patch are intermediate in both phenotype and effector cytokine production. Flow cytometric analysis of cells isolated from thymectomized, OVA-naive DO11.10 mice treated with continuous administration of BrdU indicated that a significant fraction of clonotype-positive T cells in the lamina propria and Peyer's patch were in the cell cycle, with significantly fewer cycling cells in the spleen. Most of the cycling cells from each anatomic site expressed low levels of CD45RB. Effector cytokine expression was enriched in the CD45RB(low) populations. These memory/effector cell populations were eliminated in DO11.10/SCID and DO11.10/RAG-2(-/-) mice, suggesting that recognition of non-OVA antigens through a second, non-clonotypic TCR was driving differentiation of memory/effector cells in naive BALB/c DO11.10 mice. Clonotypic CD4(+) T cells isolated from DO11.10, but not from DO11.10/SCID or DO11.10/RAG-2(-/-) mice, were stimulated to enter the cell cycle by antigen-presenting cells pulsed with an intestinal bacterial antigen extract. These data provide direct evidence that enteric bacterial antigens can activate transgenic T cells through a second, non-clonotypic TCR, and support the notion that the development and turnover of memory/effector cells in vivo is driven by the intestinal flora.

Heterogeneity in the clonal T cell response. Implications for models of T cell activation and cytokine phenotype development.

The T cell can be defined in the context of two properties--the recognition specificity of the T cell receptor (TCR) heterodimer and the functional response of the T cell after TCR stimulation. Once a particular TCR heterodimer is expressed and successfully selected during thymic development, the antigen specificity is fixed for all the clonal progeny of that cell. In contrast, the potential functional responses that may be generated in response to specific antigen in the postthymic environment are quite extensive. These range from programmed cell death to initiation of alternate programs of phenotype development that generate effector populations with distinct cytokine expression patterns and regulatory properties. Recent advances in analytical methods that have permitted multiparametric characterizations of the T cell response at the single cell, rather than population level, have necessitated a modified view of T cell activation and the clonal T cell response, and have generated new insights into the regulation of immunity. In this brief review, we highlight studies that have characterized heterogeneity of the CD4+ T cell clonal response based on single-cell analyses, and discuss implications for models of T cell activation and cytokine phenotype development.

Single-cell analyses of CD4+ T cells from alpha beta T cell receptor-transgenic mice: a distinct mucosal cytokine phenotype in the absence of transgene-specific antigen.

Development of distinct CD4+ T cell cytokine phenotypes may be conditioned by the anatomic site in which activation occurs. A double-label in situ hybridization technique was used to characterize co-expression of cytokine mRNA in antigen-specific responses of Peyer's patch (PP), lamina propria (LP), and splenic (SP) CD4+ T cells isolated from alpha beta T cell receptor-transgenic mice. Interleukin (IL)-2 was the dominant cytokine expressed by antigen-stimulated PP and SP populations, though it was expressed by a minority of the activated T cells. Cells that expressed interferon (IFN)-gamma were less frequent, and IL-4, IL-5, and IL-10 were infrequent. In contrast, cells that expressed IFN-gamma or IL-10 were most frequent in the LP population, with lower frequencies of IL-2, and few IL-4- and IL-5-positive cells. Co-expression of two cytokines by the same cell was the exception, regardless of the anatomic site from which the T cells were isolated. The surface phenotype of transgene-positive T cells isolated from each anatomic site was distinct, despite the absence of in vivo exposure to antigen for which the transgenic T cell receptor is specific. These data suggest that the cytokine responses of CD4+ T cells may be conditioned by the microenvironment, independently of specific antigen, and that the LP CD4+ T population has a distinct cytokine expression pattern with counter-regulatory properties that may be important for homeostasis in mucosal immune tissues.

[An increase in activity of natural killer cells in rats with vitamin A deficiency]. / Povyshenie aktivnosti estestvennykh killerov u krys s nedostatochnost'yu vitamina A.

A study was made of the effect of different supply of rats with vitamin A on the membranotoxic activity of natural killers, which was assessed with the use of target cells K-562 labeled with 3H-uridine incubated jointly with splenocytes. The animals were kept on a semi-synthetic diet deprived of vitamin A. This led to a reduction of the body weight and retinol content in the liver. At the same time the membranotoxic activity of splenocytes rose 1.5-fold as compared with controls kept on a balanced diet. Administration of retinol palmitate to the animals with vitamin A deficiency suppressed the activity of natural killers, raising the retinol content in the liver. The intensity of the effects in question depended on the ratio of the effector cells and targets. The possible mechanisms of the potentiation of natural antitumor resistance in animals with vitamin A deficiency are under discussion.