Immunomodulatory and endocrine effects of deep brain stimulation and spinal cord stimulation - A systematic review.

INTRODUCTION: Deep Brain Stimulation (DBS) and Spinal Cord Stimulation (SCS) represent burgeoning treatments for diverse neurological disorders. This systematic review aims to consolidate findings on the immunological and endocrine effects of DBS and SCS, shedding light on the intricate mechanisms of neuromodulation. MATERIALS AND METHODS: This systematic review, aligned with PRISMA protocols, synthesizes findings from 33 references-20 on DBS and 13 on SCS-to unravel the immunological and endocrine impacts of neuromodulation. RESULTS: DBS interventions exhibited divergent effects on cytokines, with an increase in hepcidin levels and a variable impact on the IL-6/IL-10 ratio. While some studies reported elevated IL-6, animal studies consistently demonstrated a reduction in IL-1ß and IL-6, with no significant changes in TNF-α and an increase in IL-10. Noteworthy hormonal changes included decreased corticosterone and ACTH concentrations and increased oxytocin levels following DBS of the hypothalamus. SCS mirrored similar effects on interleukins, indicating a reduction in IL-6 and IL-1ß and an increase in IL-10 levels. Additionally, SCS led to reduced VEGF levels and elevated expression of neurotrophic factors such as BDNF and GDNF, particularly under burst stimulation. CONCLUSIONS: Both DBS and SCS exert anti-inflammatory effects, manifesting as a decrease in pro-inflammatory cytokines alongside the stimulation of anti-inflammatory cytokine synthesis. These findings, observed in both animal and human models, imply that neurostimulation may modify the trajectory of neurological diseases by modulating local immune responses in an immunomodulatory and endocrine manner. This comprehensive exploration sets the stage for future research endeavors in this evolving domain.

Decrease in Nitric Oxide Production as a Key Mediator in the Pathogenesis of Preeclampsia and a Potential Therapeutic Target: A Case-Control Study.

Pregnancy-induced hypertension (GH) complicates 6−10% of all pregnancies and, in 2019, was responsible for approximately 28,000 deaths. The most common cause of gestational hypertension is pre-eclampsia (PE), which afflicts 2−8% of all pregnancies and is one of the three leading causes of maternal morbidity and mortality worldwide. The aim of this study was to clarify how NO metabolism changes during the course of PE. Due to the short half-life of NO, we measured the concentrations of its stable metabolites, nitrite and nitrate (NOx). Out of 100 enrolled patients: 58 pregnant women with a diagnosed early form of PE formed a study group, and 42 healthy pregnant women formed a control group. NOx concentrations were significantly lower in the PE group than in the control group, with mean values of 5.33 and 27.64 µmol/L, respectively (p < 0.0001). The decrease in NO is most likely the result and mediator of systemic endothelial dysfunction. The impairment of NO metabolism in PE appears to play an important role in its pathogenesis. Therefore, it is a potential therapeutic target.

Pulmonary artery targeted therapy in treatment of COVID-19 related ARDS. Literature review.

INTRODUCTION: The most grievous complication of the COVID-19 is the acute respiratory distress syndrome. A specific, rescue treatment for rapidly deteriorating patients should emerge to improve respiratory function and help patients to survive the most challenging period. Drugs used in targeted therapy of pulmonary arterial hypertension (PAH) appears to be suitable for this task and this article describes their potential for treatment of severe cases of COVID-19. METHODS: The authors reviewed the following databases for randomized controlled trials, reviews and meta-analyses published up to July 2020: Pubmed, Scopus, Google Scholar, Cochrane Database and ClinicalKey. The authors included every study contributory to the assessment of the potential of drugs used in targeted PAH therapy in treatment of COVID-19. RESULTS: Endothelin receptor antagonists, phosphodiesterase 5 inhibitors, riociguat and prostacyclin have proven ani-inflammatory effect and reduce pulmonary artery blood pressure, lung oedema and remodelling. Bosentan shows antiviral properties and sildenafil, as well as epoprostenol, inhibits apoptosis of lung epithelial cells. Among patients with lung lesions the decrease of pulmonary blood pressure can lead to increase of ventilation/perfusion mismatch and decrease of blood oxygenation. CONCLUSIONS: Among all assessed drugs bosentan, sildenafil and epoprostenol appear to be most promising and a combination of these drugs should be considered due to synergism. The targeted PAH therapy in treatment of COVID-19 associated ARDS could be a useful tool saving lives of patients with severe SARS-CoV-2 infection, however, its introduction should be investigated and monitored very carefully as it can lead to transient deterioration of patient condition.

Potential of herbal products in prevention and treatment of COVID-19. Literature review.

The COVID-19 epidemic is the greatest pandemic that human kind experienced for decades, with high morbidity and mortality. Despite recent development of vaccines there is still many severe cases of COVID-19. Unfortunately there is still no standardized therapies and treatment of severe cases is very challenging. The aim of this study is to indicate if herbs administered alone or as a complementary therapy could be used as prophylaxis or treatment of SARS-CoV-2 infection. Over 85% of patients with COVID-19 in China used Traditional Chinese Medicine (TCM), and a most common herb is Glycyrrhiza glabra, which in vitro inhibits replication of different enveloped viruses, including coronaviruses. Glycyrrhizin in vitro connects and changes conformation of ACE2 receptors, which are vital for SARS-CoV-2 penetration into host cells. Pelargonium sidoides show immunomodulatory and antiviral properties in clinical and in vitro studies, and it inhibits replication of HCo-229E coronavirus. Glycyrrhiza glabra in combination with standard therapies significantly reduces the hospitalization rate and occurrence of COVID-19 symptoms. As complementary therapies lianhuaqingwen capsules and jinhua qinggan granules reduces hospitalization rates, time to symptoms recovery and improve patient psychological comfort. In view of SARS-CoV-2 other herbs are not effective, e.g. maxingshigan-yinqiaosan, or therapeutic concentration would be impossible to achieve, e.g. ephedra herb, or there is simply no proper data. Therefore, Liquorice and Pelargonium sidoides are effective against coronaviruses and could be possibly used as prophylaxis and treatment of COVID-19, while lianhuaqingwen capsules and jinhua qinggan granules can be useful as a complementary therapy to conventional treatment.

C-reactive protein as a diagnostic and prognostic factor of endometrial cancer.

Endometrial cancer (EC) is the sixth most commonly occurring cancer in women and its morbidity and mortality are continuously increasing. Considering experience with different types of cancers, C-reactive protein (CRP) appears to be a promising diagnostic and prognostic factor. Aiming to investigate its potential in view of EC authors of this paper reviewed databases for metanalysis, randomized controlled trials and review articles. Studies indicate CRP > 3.33 mg/l correlates with the EC incidence with HR = 2.29 (p < 0.05). Moreover, High-sensitivity CRP assay allows to detect CRP in very low concentrations and distinguish patients with endometriosis, soft tissue sarcomas and possibly EC. Perioperational CRP, as well as its changes are independent prognostic factors for EC. However, CRP-to-albumin ratio as well as Glasgow Prognostic Score (GPS) have greater prognostic value that CRP alone. Additionally, CRP is possibly a mediator of carcinogenesis and cancer progression through activation of inter alia FcgRs/MAPK/ERK, FcgRs/IL-6/AKT/STAT3 and FcgRs/NF-κB/NLRP3 pathways.

The Role of NF-κB in Uterine Spiral Arteries Remodeling, Insight into the Cornerstone of Preeclampsia.

Preeclampsia is one of the three leading causes of maternal morbidity and mortality worldwide. It afflicts 2-8% of pregnancies and is the most common cause of gestational hypertension. This article is focused on nuclear factor kappa B (NF-κB), its role in normal and pathological spiral arteries remodelling and development of preeclampsia, with evaluation if it is a promising therapeutic target. NF-κB is a key mediator of placentation. Since insemination, it stimulates production of proinflammatory cytokines by the uterine epithelium, which leads to activation of macrophages, uterine natural killer cells (uNKs), and other leukocytes. The trophoblast/uNK/macrophage crosstalk is crucial for implantation and spiral arteries remodeling, and NF-κB regulates that process through modification of cytokine expression, as well as cell phenotype and function. In the course of preeclampsia, the remodeling processes is disturbed by excessive inflammation and increased NF-κB activation. The pathological remodeling leads to uteroplacental dysfunction, release of proinflammatory cytokines into the maternal circulation, endothelial stress, and development of preeclampsia. The analysis of genetic and environmental inductors of NF-κB helps to distinguish preeclampsia risk groups. Furthermore, a selective inhibition of NF-κB or NF-κB activating pathways alleviates symptoms of preeclampsia in rat models; therefore, this could be an efficient therapeutic option.

Cenobamate: Neuroprotective Potential of a New Antiepileptic Drug.

Central nervous system (CNS) injuries annually afflict approximately 2.7 million people in United States only, inflicting costs of nearly 100 billion US dollars. The gravity of this problem is a consequence of severe and prolonged disability of patients due to a scarce regeneration of CNS, along with the lack of efficient neuroprotective and neuroregenrative therapies. Therefore, the first and most important task in managing the CNS injury is reduction of the damaged area, and apoptosis of neurons occurs not only during the trauma, but in great extent within the following minutes and hours. This process, called secondary injury phase, is a result of trauma-induced metabolic changes in nervous tissue and neuron apoptosis. Cenobamate is a new antiepileptic drug approved by FDA on November 21, 2019. Regardless of its primary purpose, cenobamate, as a blocker of voltage-gated sodium channels and positive modulator of GABAa receptors, it appears to be a promising neuroprotective agent. Moreover, through activation of PI3K/Akt-CREB-BDNF pathway, it leads to the increase of anti-apoptotic factor levels and the decrease of pro-apoptotic factor levels, which induce inhibition of apoptosis and increase neuron survival. Similarly to riluzole, cenobamate could be an important part of a perioperative procedure in neurosurgery, decreasing the occurrence of neurological deficits. Provided that cenobamate will be effective in aforementioned conditions, it could improve treatment outcomes of millions of patients every year, thereby an extensive investigation of its efficacy as a neuroprotective treatment after central nervous system trauma should follow.

The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia.

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of these diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate the crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1ß, IL-18, and gasdermin D. Production of these proinflammatory chemokines is the beginning of a local and general inflammation, which results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. The NLRP3 inflammasome is a critical complex in the mediation of the inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Herein, the presented article delineates molecular mechanisms of these processes, indicating directions of future advance.

Methyldopa as an inductor of postpartum depression and maternal blues: A review.

PURPOSE: Pregnancy and time period right after labour are connected with some dangerous states, such as: pregnancy-induced hypertension (PIH), which afflict 6-10 % of pregnant women and mood disorders where postpartum depression occurs among 10-15 % of women after labour and so-called baby blues afflicts around 43 % of them. Scientists tried to link those diseases which afflicts thousands of women per year, and the linking factor appears to be methyldopa which is the first choice treatment of PIH. Recent study showed that 778 % of pregnant women treated with methyldopa suffered to postpartum depression. Aim of this article is to delineate mechanisms through which methyldopa induce mood disorders. METHODS: Authors reviewed following databases for randomized controlled trials and review articles published up to February 2019: Pubmed, Scopus, Google Scholar, Cochrane Database and ClinicalKey. Keywords used to research were: postpartum depression, methyldopa, depression, baby blues, pregnancy-induced hypertension, gestational hypertension, VEGF, nitric oxide, prolactin, hyperprolactinaemia. Selection of studies was based on relevance, year of publication, and reliability of methodology. Authors included every study contributory to assessment of scale of the problem of postpartum depression and baby blues, along with connection of those diseases with usage of methyldopa. RESULTS: Methyldopa alterate neurotrophic factors levels, impairs cerebral blood flow, and through dopamine level reduction it impairs reward system and increase prolactin release. Moreover, methyldopa leads to catecholamines depletion which impairs neurons function and increase concentration of nitric oxide (NO) which have neurotoxic properties. CONCLUSIONS: Epidemiological, as well as pharmacological studies confirmed important role of methyldopa in induction of postpartum depression and baby blues through hormone alteration, reduced cerebral blood flow and neurons function impairment. This study proves how important for women's health is this problem and how complex is its mechanism.

Possible Effects of Proton Pump Inhibitors on Hearing Loss Development.

Considered safe and often available as over-the-counter (OTC) drugs, proton pump inhibitors (PPI) are one of the most frequently used medicines. Over recent years much research analyzing PPI has been conducted and these studies shed light on PPI side effects and the mechanisms of these processes. In this study we summarize the findings of these studies and through deduction present some hypotheses on the impact of PPI on health. Of particular interest is the impact of PPI on hearing loss development. However, despite this side effect being localized, its mechanisms are complex, systemic and involve changes in whole body. This paper summarizes how through, inter alia, alterations in the circulatory system, respiratory system, central nervous system and metabolism PPI can cause hearing impairment, which can occur in every age group and is connected with long-term use of this group of drugs. This article also discusses the role PPI plays in the acceleration of presbycusis development, in relation to the fact that older people are the group who most frequently use PPI in long term. Hearing loss negatively impacts affects quality of life, especially among older patients who are also the most afflicted group; administration of PPI should therefore be considered carefully, taking into consideration all potential benefits and side effects.