scholarly journals Chronic Sulfasalazine Treatment in Mice Induces System xc− - Independent Adverse Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Lise Verbruggen ◽  
Lindsay Sprimont ◽  
Eduard Bentea ◽  
Pauline Janssen ◽  
Azzedine Gharib ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Therapeutic Potential ◽  
Negative Impact ◽  
Chronic Administration ◽  
Systemic Circulation ◽  
The Body ◽  
Ample Evidence ◽  
Anti Inflammatory ◽  
First Time

Despite ample evidence for the therapeutic potential of inhibition of the cystine/glutamate antiporter system xc− in neurological disorders and in cancer, none of the proposed inhibitors is selective. In this context, a lot of research has been performed using the EMA- and FDA-approved drug sulfasalazine (SAS). Even though this molecule is already on the market for decades as an anti-inflammatory drug, serious side effects due to its use have been reported. Whereas for the treatment of the main indications, SAS needs to be cleaved in the intestine into the anti-inflammatory compound mesalazine, it needs to reach the systemic circulation in its intact form to allow inhibition of system xc−. The higher plasma levels of intact SAS (or its metabolites) might induce adverse effects, independent of its action on system xc−. Some of these effects have however been attributed to system xc− inhibition, calling into question the safety of targeting system xc−. In this study we chronically treated system xc− - deficient mice and their wildtype littermates with two different doses of SAS (160 mg/kg twice daily or 320 mg/kg once daily, i.p.) and studied some of the adverse effects that were previously reported. SAS had a negative impact on the survival rate, the body weight, the thermoregulation and/or stress reaction of mice of both genotypes, and thus independent of its inhibitory action on system xc−. While SAS decreased the total distance travelled in the open-field test the first time the mice encountered the test, it did not influence this parameter on the long-term and it did not induce other behavioral changes such as anxiety- or depressive-like behavior. Finally, no major histological abnormalities were observed in the spinal cord. To conclude, we were unable to identify any undesirable system xc−-dependent effect of chronic administration of SAS.

Integrating Focusing and Differentiation: A Therapeutic Path for Couples in Intimate Relationships

2018 ◽  
Vol 3 ◽  
Author(s):  
Evi Zohar
Keyword(s):  
Couples Therapy ◽  
Therapeutic Potential ◽  
Well Being ◽  
Point Of View ◽  
The Body ◽  
Self Awareness ◽  
Emotional Healing ◽  
Felt Sense ◽  
Inner World

Continuing the workshop I've given in the WPC Paris (2017), this article elaborates my discussion of the way I interlace Focusing with Differentiation Based Couples Therapy (Megged, 2017) under the systemic view, in order to facilitate processes of change and healing in working with intimate couples. This article presents the theory and rationale of integrating Differentiation (Bowen, 1978; Schnarch, 2009; Megged, 2017) and Focusing (Gendlin, 1981) approaches, and its therapeutic potential in couple's therapy. It is written from the point of view of a practicing professional in order to illustrate the experiential nature and dynamics of the suggested therapeutic path. Differentiation is a key to mutuality. It offers a solution to the central struggle of any long term intimate relationship: balancing two basic life forces - the drive for individuality and the drive for togetherness (Schnarch, 2009). Focusing is a body-oriented process of self-awareness and emotional healing, in which one learns to pay attention to the body and the ‘Felt Sense’, in order to unfold the implicit, keep it in motion at the precise pace it needs for carrying the next step forward (Gendlin, 1996). Combining Focusing and Differentiation perspectives can cultivate the kind of relationship where a conflict can be constructively and successfully held in the inner world of each partner, while taking into consideration the others' well-being. This creates the possibility for two people to build a mutual emotional field, open to changes, permeable and resilient.

scholarly journals Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats

2021 ◽  
Vol 22 (16) ◽  
pp. 8899
Author(s):  
Marina Gabaglio ◽  
Erica Zamberletti ◽  
Cristina Manenti ◽  
Daniela Parolaro ◽  
Tiziana Rubino
Keyword(s):  
Adverse Effects ◽  
Chronic Administration ◽  
Female Rats ◽  
Acid Decarboxylase ◽  
Long Term Effects ◽  
Gabaergic Neurotransmission ◽  
Long Term Consequences ◽  
Adolescent Exposure ◽  
Long Term Adverse Effects

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.

scholarly journals The Immune System Can Hear Noise

2021 ◽  
Vol 11 ◽  
Author(s):  
Andi Zhang ◽  
Tianyuan Zou ◽  
Dongye Guo ◽  
Quan Wang ◽  
Yilin Shen ◽  
...  
Keyword(s):  
Immune System ◽  
Adverse Effects ◽  
Immune Function ◽  
Noise Exposure ◽  
The Body ◽  
Intensity Noise ◽  
Short Term ◽  
Non Hodgkin Lymphoma ◽  
Exposure During Pregnancy

As a stressor widely existing in daily life, noise can cause great alterations to the immune system and result in many physical and mental disorders, including noise-induced deafness, sleep disorders, cardiovascular diseases, endocrine diseases and other problems. The immune system plays a major role in maintaining homeostasis by recognizing and removing harmful substances in the body. Many studies have shown that noise may play vital roles in the occurrence and development of some immune diseases. In humans, both innate immunity and specific immunity can be influenced by noise, and different exposure durations and intensities of noise may exert various effects on the immune system. Short-term or low-intensity noise can enhance immune function, while long-term or high-intensity noise suppresses it. Noise can lead to the occurrence of noise-induced hearing loss (NIHL) through the production of autoantibodies such as anti-Hsp70 and anti-Hsp60 and exert adverse effects related to other immune-related diseases such as some autoimmune diseases and non-Hodgkin lymphoma. The neuroendocrine system, mainly including the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary (SAM) system, is involved in the mechanisms of immune-related diseases induced by noise and gut microbiota dysfunction. In addition, noise exposure during pregnancy may be harmful to the immune system of the fetus. On the other hand, some studies have shown that music can improve immune function and alleviate the adverse effects caused by noise.

scholarly journals Zanjabeel (Zingiber officinale Roscoe.): An Evidence-Based Review of Anti-nociceptive, Anti-inflammatory, Antioxidant, and Antimicrobial Properties

2021 ◽  
pp. 26-35
Author(s):  
Fatima Khan ◽  
Mohd Nayab ◽  
Abdul Nasir Ansari
Keyword(s):  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Plant Secondary Metabolites ◽  
Zingiber Officinale ◽  
Extensive Study ◽  
The Body ◽  
Wide Range ◽  
Zingiber Officinale Roscoe ◽  
Medicinal Properties ◽  
Anti Inflammatory

Ginger has been appreciated for over 2500-3000 years in many parts of the world due to its numerous scientific properties. The ginger plant (Zingiber officinale Roscoe) belongs to the Zingiberaceae family. It is a known food and flavoring ingredient reputed for its wide range of medicinal properties that have been widely used in Chinese, Ayurvedic, and Unāni Tibb worldwide, since antiquity. Ginger has long been used to cure a variety of ailments, including diarrhea, stomach discomfort, indigestion, and nausea. It is a versatile herb with phenomenal phytotherapeutic and medicinal properties. Active ingredients available in ginger such as 6-gingerol, 6-shogaol, 6-paradol, and zingerone are responsible for upgrading enzyme actions and balancing circulation through rejuvenating the body with physical re-strengthening. Gingerols, the key phenolic plant secondary metabolites responsible for its distinct flavor and health benefits, are found in the rhizome of ginger Extensive study has been undertaken over the last two decades to uncover bioactive ingredients and the therapeutic potential of ginger. This review considers ginger's chemical composition and the most recent study findings on its possible health advantages, such as analgesic, anti-inflammatory, antibacterial, and antioxidant properties due to its phytochemistry. Overall, clinical trials are needed to confirm these prospective various health advantages of ginger in human subjects and the most efficacious dosage, based on the current body of scientific literature.

A dynamic simulation of bisphenol A dosimetry in neuroendocrine organs

2004 ◽  
Vol 20 (1-5) ◽  
pp. 29-40 ◽  
Author(s):  
Joseph C Hutter ◽  
Hoan My Luu ◽  
Chung S Kim
Keyword(s):  
Bisphenol A ◽  
Time Course ◽  
Systemic Circulation ◽  
The Body ◽  
Rapid Decline ◽  
Tissue Uptake ◽  
Hydrophobic Compounds ◽  
Neuroendocrine Organs ◽  
Oral Doses

Bisphenol A (BPA) is a known xenoestrogen with similar properties to 17b-estradiol. BPA and estrogen are hydrophobic compounds, and this affects the pharmacokinetics of both compounds in mammals. In a previous study we measured the distribution of BPA in female F344 rats exposed to oral doses of 0.1, 10 and 100 mg/kg. The results showed distribution to target neuroendocrine organs at all doses tested. Using these results, we developed a pharmacokinetic model to predict the dynamic uptake and excretion of BPA by various routes of exposure (po, iv, sc, ip). The model was able to simulate the entire time course (48 h) following various routes of exposure in rats over the dose ranges tested. The model indicated that the ultimate tissue uptake of BPA was established by the rapid initial transfer of free BPA into tissues. After free BPA enters the systemic circulation, metabolism and excretion reactions cause a relatively short duration and rapid decline. This period is followed by a slower long-term decline characteristic of BPA’s biphasic pharmacokinetics. Plasma protein and tissue binding reactions established the long-term half-life of BPA in the body. Route differences in tissue uptake were directly related to the competition between transfer and binding reactions during the absorption phase.

scholarly journals A Novel Korean Red Ginseng Compound Gintonin Inhibited Inflammation by MAPK and NF-κB Pathways and Recovered the Levels of mir-34a and mir-93 in RAW 264.7 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Evelyn Saba ◽  
Bo Ra Jeon ◽  
Da-Hye Jeong ◽  
Kija Lee ◽  
Youn-Kyoung Goo ◽  
...  
Keyword(s):  
Signal Transduction ◽  
The Body ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
Therapeutic Effects ◽  
Raw 264.7 ◽  
Korean Red Ginseng ◽  
Health Promoting ◽  
Anti Inflammatory ◽  
First Time

The beneficial health promoting effects of ginseng from vitalizing the body to enhancing long life have been well explored very rapidly in the past few years. Up till now many ginsenosides have been discovered for their marvelous therapeutic effects. However during past three years, a novel ginseng compound has been discovered, called gintonin, that differs from other ginsenosides on the basis of its signal transduction and chemical nature. Gintonin has been widely studied for its anti-Alzheimer’s disease activities and other neuropathies. However, its anti-inflammatory activity remained unexplored. In our study we have reported for the first time the anti-inflammatory activity of gintonin on RAW 264.7 cells. We found that gintonin potently suppresses the nitric oxide production without any cytotoxicity at given doses and also efficiently suppressed the levels of proinflammatory cytokines. Moreover, it mediaes its signal transduction via MAPK and NF-κB pathways and revives the levels of mir-34a and mir-93. These findings are valuable for the anti-inflammatory effects of this new compound with particular reference to microRNA involvement in the ginseng family.

scholarly journals Indicators of humoral immunity of patients with neonatal sepsis under different conditions of environmental pollution of parents' places of residence

2020 ◽  
pp. 66-69
Author(s):  
O.V. Vlasova ◽  
Keyword(s):  
Adverse Effects ◽  
Environmental Pollution ◽  
Humoral Immunity ◽  
Neonatal Sepsis ◽  
The Body ◽  
Group I ◽  
Regional Centers ◽  
Group Ii ◽  
Water And Soil Pollution

The aim is to determine the indicators of humoral immunity of patients with neonatal sepsis under different conditions of environmental pollution of their parents' places of residence. Materials and methods. 260 patients with neonatal sepsis born to parents who lived in different environmental conditions were examined. An environmental risk factor (CER) was proposed as a group-forming feature of a comprehensive assessment of the long+term load of anthropogenic air, water and soil pollution in the regions of the region on the body of parents of newborns, taking into account the environmental situation in regional centers. Results. The level of IgA in the serum of patients with neonatal sepsis in group I was 0.82±0.11 g/l against 1.54±0.23 g/l (p<0.05) in group II, the level of IgG in children I groups — 4.27±0.45 g/l against 6.67±0.77 g/l (p<0.05) of group II. The decrease in IgM content had no significant differences, but there was a tendency to reduce its level in children of group I. Conclusions. The constant residence of parents in areas with a high risk of adverse effects of these environmental factors on their body (ERF<2.0) contributed to a decrease in the level of immunoglobulins A, M, G in the serum of patients with neonatal sepsis, compared with newborns whose parents lived in areas with a low risk of adverse effects (ERF<2.0), and were more likely to have severe neonatal sepsis. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the author. Key words: neonatal sepsis, pollution, immunoglobulins.

scholarly journals Sub-acute and long-term effects of ayahuasca on mental health and well-being in healthy ceremony attendants: A replication study

2021 ◽  
Author(s):  
Kim I. van Oorsouw ◽  
Malin V. Uthaug ◽  
Natasha L. Mason ◽  
Nick J. Broers ◽  
Johannes G. Ramaekers
Keyword(s):  
Mental Health ◽  
Therapeutic Potential ◽  
Well Being ◽  
Altered States Of Consciousness ◽  
Altered States ◽  
Long Term Effects ◽  
States Of Consciousness ◽  
First Time ◽  
Health And Well Being

Abstract Background and aims There is a growing body of evidence suggesting that the psychedelic plant tea, ayahuasca, holds therapeutic potential. Uthaug et al. (2018) demonstrated that a single dose of ayahuasca improved mental health sub-acutely and 4-weeks post-ceremony in healthy participants. The present study aimed to replicate and extend these findings. A first objective was to assess the sub-acute and long-term effects of ayahuasca on mental health and well-being in first-time and experienced users. A second aim was to extend the assessment of altered states of consciousness and how they relate to changes in mental health. Method Ayahuasca ceremony attendants (N = 73) were assessed before, the day after, and four weeks following the ceremony. Results We replicated the reduction in self-reported stress 4-weeks post ceremony, but, in contrast, found no reduction in depression. Also, increased satisfaction with life and awareness the day after the ceremony, and its return to baseline 4 weeks later, were replicated. New findings were: reduced ratings of anxiety and somatization, and increased levels of non-judging 4-weeks post-ceremony. We replicated the relation between altered states of consciousness (e.g., experienced ego dissolution during the ceremony) and mental health outcomes sub-acutely. The effects of ayahuasca did not differ between experienced and first-time users. Conclusion Partly in line with previous findings, ayahuasca produces long-term improvements in affect in non-clinical users. Furthermore, sub-acute mental health ratings are related to the intensity of the psychedelic experience. Although findings replicate and highlight the therapeutic potential of ayahuasca, this needs to be confirmed in placebo-controlled studies.

scholarly journals Biochemical parameters of blood plasma of the male population living on the territory of the Aral Sea

2020 ◽  
Vol 100 (4) ◽  
pp. 100-105
Author(s):  
Zhanbol Sabirov ◽  
◽  
Aliya Eshmagambetova ◽  
Gul'zhazira Turlybekova ◽  
Nazira Duzbayeva ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Biochemical Parameters ◽  
Negative Impact ◽  
Metabolic Stress ◽  
The Body ◽  
Ecological Crisis ◽  
Aral Sea ◽  
Male Population ◽  
Significant Percentage

The Aral Sea ecological disaster zone affects the health status of the population living in this zone. Biochemical parameters are indicators of the metabolic functionality of the body. The article presents data about the biochemical parameters of blood plasma in the male population living in the ecological crisis zone of the Aral Sea region. It is shown that when determining the majority of indicators of biochemical analysis within the physiological norm, there is a significant percentage of people with deviations in these indicators. Such data make it possible to assume about the factors that can affect the entire population and have massive manifestations. Certainly, these factors, include the negative impact of the environment on public health. An increase in gamma — glutamyltransferase was found in 41 % of the subjects, an increase in cholesterol in 38 % and an increase in triglycerides in 34 %. In the inhabitants of the Aral Sea, a correlation was found between the biochemical parameters of blood serum from the dose of chemicals. It was shown that long-term chemical load in the crisis zone of the Aral Sea region causes a deviation of protein metabolism. The results obtained indicate a significant percentage of people with metabolic stress in the process of adaptation to high chemical load.

Terpenoids from Dicliptera chinensis (L.) Nees Grown in Vietnam and their Anti-inflammatory Activities

2018 ◽  
Vol 11 (2) ◽  
pp. 4052-4062
Author(s):  
Loi Vu Duc ◽  
Tung Bui Thanh ◽  
Tung Nguyen Huu
Keyword(s):  
Therapeutic Potential ◽  
Inhibitory Effects ◽  
Chromatographic Methods ◽  
Ic50 Values ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
First Time

The main goal of this study was to isolate and screen the therapeutic potential of some terpenoids from Dicliptera chinensis (L.) Nees grown in Vietnam. From the leaves of Dicliptera chinensis (L.) Nees (Acanthaceae) collected in Nam Dinh province, one new terpenoid (1) together with five known (2-6) were isolated by chromatographic methods. These compounds were identified as 6-hydroxy-1,12-oleanadien-3-on (1), 1β,4β-dihydroxyeudesm-11-ene (2), 3β-hydroxylup-20(29)-en (3), stigmast-5,22-dien-3-β-ol (4), rutaevine (5), mangiferin (6). All of them were isolated from this plant for the first time. Compound 4 showed signficant potential for COX-2 inhibitory effects with IC50 values of 7.32± 1.82 µg/mL. These pilot results suggest the potential of Dicliptera terpenoids for treating inflamatory conditions. 

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