Features of therapeutic correction of GERD: focus on cytoprotection (with a clinical case)

Тo date, the possible links of the pathogenesis of this disease have been well studied and described, which predetermine certain approaches to the treatment of various variants of gastroesophageal reflux disease (GERD). Effective drug therapy for GERD includes proton pump inhibitors (PPI). However, PPI monotherapy is not always effective. One approach is to increase the PPI dose. At the same time, combination therapy with the addition of drugs that affect the protective properties of the esophageal mucosa seems to be more rational. It is known that in the development of GERD, the violation of cytoprotection of the esophageal mucosa is one of the key links in pathogenesis. Consequently, the issue of combination therapy of PPIs with drugs that increase the protective properties of the mucous barrier along with acid suppression becomes relevant. An example of such an approach is the appointment of rebamipide, the action of which is to regulate the synthesis of prostaglandins through COX-2 mediated mechanisms, influence on endothelial growth factor, increase the expression of tight intercellular contact proteins in epithelial cells of the mucous membrane, reduce the level of interleukin-8 and free oxygen radicals, directed to protect the mucous membrane of the gastrointestinal tract and restore its natural barrier properties. The effectiveness of the combination of PPI and rebamipide contributes to a greater regression of complaints in patients with GERD and a lower frequency of disease relapses than with PPI monotherapy. This article provides a review of the literature on the features of GERD therapy, primarily with an emphasis on the correction of the cytoprotective properties of the esophageal mucosa, including against the background of the use of nonsteroidal anti-inflammatory drugs (NSAID), and a clinical case analysis with a discussion of rational pharmacological correction.

Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders

Background: Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking induces also oxidative stress. Hypothesis/Objective : The present study aims at investigating the potential association between neurotrophins, neuroinflammation and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Methods: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as free oxygen radicals test (FORT) and free oxygen radicals defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β and TNF-α) involved in neuroinflammatory and oxidative processes have been investigated. Results: We demonstrated in pre-pubertal FASD children low serum levels of NGF and BDNF, respect to healthy controls. These changes were associated with higher serum presence of TNF-α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10 and IL-1α1 in the analyzed female compared to male children. Conclusion: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

Controlled spermatozoa–oocyte interaction improves embryo quality in sheep

The current protocols of in vitro fertilization and culture in sheep rely on paradigms established more than 25 years ago, where Metaphase II oocytes are co-incubated with capacitated spermatozoa overnight. While this approach maximizes the number of fertilized oocytes, on the other side it exposes them to high concentration of reactive oxygen species (ROS) generated by active and degenerating spermatozoa, and positively correlates with polyspermy. Here we set up to precisely define the time frame during which spermatozoa effectively penetrates and fertilizes the oocyte, in order to drastically reduce spermatozoa-oocyte interaction. To do that, in vitro matured sheep oocytes co-incubated with spermatozoa in IVF medium were sampled every 30 min (start of incubation time 0) to verify the presence of a fertilizing spermatozoon. Having defined the fertilization time frame (4 h, data from 105 oocytes), we next compared the standard IVF procedures overnight (about 16 h spermatozoa/oocyte exposure, group o/nIVF) with a short one (4 h, group shIVF). A lower polyspermic fertilization (> 2PN) was detected in shIVF (6.5%) compared to o/nIVF (17.8%), P < 0.05. The o/nIVF group resulted in a significantly lower 2-cell stage embryos, than shIVF [34.6% (81/234) vs 50.6% (122/241) respectively, P < 0.001]. Likewise, the development to blastocyst stage confirmed a better quality [29% (70/241) vs 23.5% (55/234), shIVF vs o/nIVF respectively] and an increased Total Cell Number (TCN) in shIVF embryos, compared with o/n ones. The data on ROS have confirmed that its generation is IVF time-dependent, with high levels in the o/nIVF group. Overall, the data suggest that a shorter oocyte-spermatozoa incubation results in an improved embryo production and a better embryo quality, very likely as a consequence of a shorter exposure to the free oxygen radicals and the ensuing oxidative stress imposed by overnight culture.

Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study

Environmental stimuli, including sex hormones and oxidative stress (OS), affect bone balance, modifying the epigenetic profiles of key osteogenic genes. Nonetheless, the interplay between sex steroids, epigenome and OS has yet be fully elucidated. This paper aims to study in vitro the role of sex steroids in OS-induced alteration in bone cells’ homeostasis, and to assess the possible contribution of epigenetic modifications. Toward this purpose, osteoblast (MC3T3-E1) and osteocyte (MLOY-4) cell lines were exposed to two different sources of free oxygen radicals, i.e., tert-butyl hydroperoxide and dexamethasone, and the protective effect of pre-treatment with androgens and estrogens was evaluated. In particular, we analyzed parameters that reflect bone cell homeostasis such as cell viability, cell migration, transcriptomic profile, transcriptional activity, and epigenetic signature. Our findings indicate that estrogens and androgens counteract OS effects. Using partially overlapping strategies, they reduce OS outcomes regarding cell viability, cell migration, the transcriptomic profile of gene families involved in bone remodeling, and epigenetic profile, i.e., H3K4me3 level. Additionally, we demonstrated that the protective effect of steroids against OS on bone homeostasis is partially mediated by the Akt pathway. Overall, these results suggest that the hormonal milieu may influence the mechanisms of age-related bone disease.

Oleuropein multicompartment nanovesicles enriched with collagen as a natural strategy for the treatment of skin wounds connected with oxidative stress

Aim: Collagen-enriched transfersomes, glycerosomes and glytransfersomes were specifically tailored for skin delivery of oleuropein. Methods: Vesicles were prepared by direct sonication and their main physicochemical and technological properties were measured. Biocompatibility, protective effect and promotion of the healing of a wounded cell monolayer were tested in vitro using fibroblasts. Results: Vesicles were mainly multicompartment, small (∼108 nm), slightly polydispersed (approximately 0.27) and negatively charged (~-49 mV). Oleuropein was incorporated in high amounts (approximately 87%) and vesicles were stable during four months of storage. In vitro studies confirmed the low toxicity of formulations (viability ≥95%), their effectiveness in counteracting nitric oxide generation and damages caused by free oxygen radicals, especially when collagen glytransfersomes were used (viability ~100%). These vesicles also promoted the regeneration of a wounded area by promoting the proliferation and migration of fibroblasts. Conclusion: Collagen-enriched vesicles are promising formulations capable of speeding up the healing of the wounded skin.

Evaluation of Antioxidant Prophylactic Effects of Parsley (Petroselinum Crispum) on Sepsis Following Cecal Ligation and Puncture

Background and Aims. Sepsis causes release of free oxygen radicals that destroy membrane integrity.We evaluated the antioxidant effects of parsley, Petroselinum crispum(Pc), which has been used therapeutically for centuries in Anatolia, using a rat model of sepsis caused by cecal ligation and puncture (CLP).Methods.Wistar albino rats were separated into four groups of eight: a sham group with incised and sutured abdomen, a Pc extract(PcE) group was given 2 g/kg parsley extract for 14 days by gastric gavage, a CLP group with sepsis caused by CLP and a PcE + CLP group given parsley extract for 14 days, then made septic by CLP. PcE is given for 14 days and then sepsis is performed by the CLP procedure. Results. The groups were compared in terms of hemogram, biochemical and histological characteristics. It has been proven that the administration of PcE before CLP-induced sepsis increases neutrophil, PLT counts and TAS levels which decrease with sepsis and decreases biochemical changes (BUN, AST, ALT, LDH, TOS, OSI) which increase with sepsis, to have a protective effect on sepsis . In the PcE + CLP group, the severity of intestinal infiltration was decreased significantly compared to the CLP group; epithelial damage was similar to the CLP group. In the PcE + CLP group, the crypt and villus length was greater and the decrease in Paneth cell degranulation intensity was found to be more than for the CLP group ; also, the morphology of the cells was similar to the Sham group. Discussion. PcE exhibit potential for prophylaxis for sepsis.

Hydrogen Peroxide: Its Use in an Extensive Acute Wound to Promote Wound Granulation and Infection Control – Is it Better Than Normal Saline?

Background: Hydrogen peroxide (H2O2) is used as a topical antiseptic in contaminated wounds caused by road traffic accidents. It kills bacteria by producing oxidation through local, nascent, free oxygen radicals. It also removes dirt from the wound due to its frothing action. H2O2 is synthesized by various cells as an active biochemical agent that affects cell biological behavior through complex chemical reactions. H2O2 has also been used as a wound cleaning agent, removing debris, preventing infection, and causing hemostasis due to its exothermic reaction with blood. Despite its widespread use, there is scanty literature on its use to promote granulation tissue formation. Objective: In the orthopaedics literature, studies on H2O2 use are very limited and its potential is underestimated. In the present study, we would like to report our protocol of use of H2O2 for its tremendous potential for stimulating granulation and early wound healing. Material and Methods: A total of 53 patients with large acute extensive lower limb contaminated wounds reported to the emergency department have been included with and without lower limb fracture. In group A (43 patients) wound management was done using 7% H2O2 and group B (10 patients) was treated by only saline dressing as a control group. Results: In the present study, daily dressing by 7% H2O2 solution and provide solution gives excellent results compared to the Saline group. Granulation tissue appeared much earlier with a mean SD 6.3 ± 6.8 days in the hydrogen peroxide group as compared to the Saline group where granulation tissue appeared in 9.3 ± 8.4 days. Conclusion: Spontaneous wound healing is a controlled balance between destructive and healing processes. It is mandatory to remove damaged tissue to promote healing by secondary intention and minimize infection. The dynamic effect of H2O2 promotes faster healing, stimulates granulation, and minimizes infection by oxidative stress.

Oxidative Stress as a Common Key Event in Developmental Neurotoxicity

The developing brain is extremely sensitive to many chemicals. Perinatal exposure to neurotoxicants has been implicated in several neurodevelopmental disorders, including autism spectrum disorder, attention-deficit hyperactive disorder, and schizophrenia. Studies of the molecular and cellular events related to developmental neurotoxicity have identified a number of “adverse outcome pathways,” many of which share oxidative stress as a key event. Oxidative stress occurs when the balance between the production of free oxygen radicals and the activity of the cellular antioxidant system is dysregulated. In this review, we describe some of the developmental neurotoxins that target the antioxidant system and the mechanisms by which they elicit stress, including oxidative phosphorylation in mitochondria and plasma membrane redox system in rodent models. We also discuss future directions for identifying adverse outcome pathways related to oxidative stress and developmental neurotoxicity, with the goal of improving our ability to quickly and accurately screen chemicals for their potential developmental neurotoxicity.

Study of Highly Sensitive Formaldehyde Sensors Based on ZnO/CuO Heterostructure via the Sol-Gel Method

Formaldehyde (HCHO) gas sensors with high performance based on the ZnO/CuO heterostructure (ZC) were designed, and the sensing mechanism was explored. FTIR results show that more OH− and N–H groups appeared on the surface of ZC with an increase in Cu content. XPS results show that ZC has more free oxygen radicals (O*) on its surface compared with ZnO, which will react with more absorbed HCHO molecules to form CO2, H2O and, electrons, accelerating the oxidation-reduction reaction to enhance the sensitivity of the ZC sensor. Furthermore, electrons move from ZnO to CuO in the ZC heterostructure due to the higher Fermi level of ZnO, and holes move from CuO to ZnO until the Fermi level reaches an equilibrium, which means the ZC heterostructure facilitates more free electrons existing on the surface of ZC. Sensing tests show that ZC has a low detection limit (0.079 ppm), a fast response/recovery time (1.78/2.90 s), and excellent selectivity and sensitivity for HCHO detection at room temperature. In addition, ambient humidity has little effect on the ZC gas sensor. All results indicate that the performance of the ZnO sensor for HCHO detection can be improved effectively by ZC heterojunction.

Protective Effects of Nanosof® Suspension on Cultured Cells Exposed to H2O2

Nanoparticle and nanomaterial-based treatments have improved a lot recently in terms of bioavailability, effectiveness, and reduced toxic and side effects. Many studies found a protective effect of fullerene C60 derivatives as potent free radical scavengers in biological systems and also showed neuroprotective properties when tested on in vivo models of ischemic stroke. This study assessed the antioxidant effects of Nanosof® powder suspension, an oxygenated fullerene compound, on various cell types exposed to exogenous free oxygen radicals. Cor.4U® cardiomyocytes and bEnd.3, BV-2, HEK293/hERG1 cell lines were treated with Nanosof® powder suspension alone or during exposure to 100 µM H2O2 for 24 h, in order to check the nanoparticle capacity to neutralize reactive oxygen species, using MTS or MTT to assess viability. We found no significant change in the viability of cells treated with Nanosof® compared to control. In the presence of H2O2, Nanosof® increased cell viability compared to H2O2 exposure alone. Nanosof® treatment showed no side effect; moreover, it exerted a protective effect on all three tested cell lines and Cor.4U® cardiomyocytes, indicating that treatment with this oxygenated fullerene may benefit various conditions.