Gold-based therapy: From past to present

Despite an abundant literature on gold nanoparticles use for biomedicine, only a few of the gold-based nanodevices are currently tested in clinical trials, and none of them are approved by health agencies. Conversely, ionic gold has been used for decades to treat human rheumatoid arthritis and benefits from 70-y hindsight on medical use. With a view to open up new perspectives in gold nanoparticles research and medical use, we revisit here the literature on therapeutic gold salts. We first summarize the literature on gold salt pharmacokinetics, therapeutic effects, adverse reactions, and the present repurposing of these ancient drugs. Owing to these readings, we evidence the existence of a common metabolism of gold nanoparticles and gold ions and propose to use gold salts as a “shortcut” to assess the long-term effects of gold nanoparticles, such as their fate and toxicity, which remain challenging questions nowadays. Moreover, one of gold salts side effects (i.e., a blue discoloration of the skin exposed to light) leads us to propose a strategy to biosynthesize large gold nanoparticles from gold salts using light irradiation. These hypotheses, which will be further investigated in the near future, open up new avenues in the field of ionic gold and gold nanoparticles-based therapies.

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Long-Term Effects of Middle Ear Tendon Resection on Middle Ear Myoclonic Tinnitus, Hearing, and Hyperacusis

Audiology and Neurotology ◽

10.1159/000487260 ◽

2017 ◽

Vol 22 (6) ◽

pp. 343-349 ◽

Cited By ~ 2

Author(s):

Dong-Kee Kim ◽

Jung Mee Park ◽

Jung Ju Han ◽

Yun Min Chung ◽

Jung Min Kim ◽

...

Keyword(s):

Middle Ear ◽

Complete Recovery ◽

Stress Index ◽

Therapeutic Effects ◽

Long Term Effects ◽

Vas Scores ◽

The Mean ◽

High Control

Objective: To evaluate the therapeutic effects of middle ear tendon resection (METR) on middle ear myoclonic tinnitus (MEMT) and to investigate its long-term effects on hearing and hyperacusis. Materials and Methods: Thirty-seven patients with MEMT with a mean age of 33.2 ± 11.8 years were included in this study. METR was performed on all 37 MEMT patients (41 ears) between November 2004 and August 2016. The mean follow-up period was 16.1 months. We examined changes in tinnitus and accompanying stress and depression in patients after surgery, and examined the hearing changes and the occurrence of complications including hyperacusis. Results: After surgery, 34 (91.9%) patients exhibited complete resolution of MEMT during their follow-up period, and 3 patients showed a partial response. The mean Visual Analog Scale (VAS) scores for tinnitus severity, the Tinnitus Handicap Inventory (THI), and stress index decreased significantly after surgery (p < 0.05, paired t test). No patient developed hearing loss or hyperacusis following surgery. Preexisting hyperacusis even improved in most of the patients with intractable MEMT after surgery. Recurrence of the symptom occurred in only 1 patient, who underwent revision surgery with improvement. We observed 1 case of postoperative delayed facial palsy with complete recovery in 2 weeks. Conclusions: METR seems to be an effective and safe treatment option for intractable MEMT, considering its high control rate of tinnitus and no long-term harmful effects on hearing and hyperacusis.

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Citicoline in the Treatment of Mild Cognitive Impairment in Blood Relatives of Patients with Alzheimer’s Disease: Immediate and Long-Term Effects of Course Therapy

Psychiatry ◽

10.30629/2618-6667-2021-19-4-42-51 ◽

2021 ◽

Vol 19 (4) ◽

pp. 42-51

Author(s):

N. D. Seleznеva ◽

I. F. Roshchina ◽

E. V. Ponomareva ◽

S. Iv. Gavrilova

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Functioning ◽

Cognitive Dysfunction ◽

Therapeutic Effects ◽

Long Term Effects ◽

Voluntary Attention

The aim was to study immediate and long-term (post-therapeutic) effects of a three-month course of therapy with citicoline in 1st-degree relatives of patients with Alzheimer’s disease (AD). All the included relatives of patients with AD revealed signs of minimal cognitive dysfunction (MCD) and mild cognitive decline syndrome (MCI — Mild Cognitive Impairment, ICD-10 code F06.7). Study participants: the study involved 90 first-degree relatives: 24 with MCI and 66 with MCD. Study design: an open-label comparative multidisciplinary study of the six-month dynamics of cognitive functioning of two groups of relatives who received a three-month course of citicoline therapy. The baseline indicators of the cognitive functioning of relatives with MCI syndrome and MKD were compared with the indicators at the end of the three-month course of therapy with citicoline at a daily dose of 1000 mg as well as 3 months after the end of the course of treatment. Methods: clinical, psychopathological, neuropsychological, psychometric, genetic, statistical ones. Results: а significant positive effect of the course therapy with citicoline on the cognitive impairment of 1st degree AD-patients’ relatives with minimal cognitive dysfunction and more pronounced cognitive impairments met the diagnostic criteria for MCI syndrome has been found. A significantly greater value of both immediate and long-term therapeutic effect of MKD compared with MCI in relatives was established by psychometric and neuropsychological indicators characterizing voluntary memorization of verbal and visual stimuli, optical and spatial activity, voluntary attention, and associative verbal thinking. Conclusion: the results of the study can be used as the basis for a model of prevention of the progression of cognitive deficit and the development of dementia in persons with a high risk of developing AD, i.e. in individuals with both genetic risk and signs of cognitive impairment.

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Sustainable Effects of Human Dental Pulp Stem Cell Transplantation on Diabetic Polyneuropathy in Streptozotocine-Induced Type 1 Diabetes Model Mice

Cells ◽

10.3390/cells10092473 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2473

Author(s):

Masaki Hata ◽

Maiko Omi ◽

Yasuko Kobayashi ◽

Nobuhisa Nakamura ◽

Megumi Miyabe ◽

...

Keyword(s):

Dental Pulp ◽

Diabetic Polyneuropathy ◽

Dorsal Root Ganglion Neurons ◽

Therapeutic Effects ◽

Long Term Effects ◽

Post Transplantation ◽

Diabetes Model ◽

Human Dental Pulp ◽

Ganglion Neurons

Dental pulp stem cells (DPSCs) are suitable for use in regenerative medicine. Cryopreserved human DPSCs (hDPSCs) ameliorate diabetic polyneuropathy, and the effects of hDPSC transplantation are related to VEGF and NGF secretion. This study evaluated the long-term effects of a single transplantation of hDPSCs on diabetic polyneuropathy. hDPSCs were obtained from human third molars extracted for orthodontic treatment, which were then transplanted into the unilateral hindlimb skeletal muscles 8 weeks after streptozotocin injection in nude mice. The effects of hDPSC transplantation were analyzed at 16 weeks post-transplantation. DPSC transplantation significantly improved delayed nerve conduction velocity, decreased blood flow, and increased sensory perception thresholds. Furthermore, the hDPSC-conditioned medium promoted the neurite outgrowth of dorsal root ganglion neurons. In conclusion, the therapeutic effects of hDPSC transplantation with a single injection last for prolonged periods and may be beneficial in treating long-term diabetic polyneuropathy.

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The viability of pronatalism as a response to population growth decline in the Canadian context

10.32920/ryerson.14662695 ◽

2021 ◽

Author(s):

Katharine Emma Blair

Keyword(s):

Population Growth ◽

Labour Force ◽

Population Decline ◽

Labour Force Participation ◽

Long Term Effects ◽

Demographic Trends ◽

Canadian Context ◽

Growth Decline ◽

Near Future

A decrease in fertility over the last thirty years has led to projections for population growth decline and possible population decline in the near future. Although immigration has traditionally been seen as a source of growth for Canada, current demographic trends suggest a more comprehensive approach may be needed. A pronatalist policy may help offset the long term effects of population decline if used in tandem with increased immigration and increased support for arriving immigrants. In order to be successful such a policy would need to address both the direct and indirect barriers to fertility as experienced by women and families while encouraging increased labour force participation by women.

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Preparation and Evaluation of Physicochemical Properties of the Doxepin Mucoadhesive Gel

Jundishapur Journal of Natural Pharmaceutical Products ◽

10.5812/jjnpp.66864 ◽

2020 ◽

Vol 15 (4) ◽

Author(s):

Majid Rajaee ◽

Amir Talachi ◽

Abbas Pardakhty ◽

Ehsan Mohajeri ◽

Negar Dehghannoudeh ◽

...

Keyword(s):

Physicochemical Properties ◽

Oral Mucosa ◽

Slow Release ◽

Hydroxypropyl Methylcellulose ◽

Poloxamer 407 ◽

Therapeutic Effects ◽

Long Term Effects ◽

Preparation And Evaluation

Background: Oral mucositis is a common debilitating complication of cancer chemotherapy and radiotherapy that can reduce the quality of patient’s lives. Hence, treating this condition plays an important role in increasing the patient’s tolerance. Objectives: Doxepin mucoadhesive gel is useful for treating oral mucosa inflammation caused by long-term effects of chemotherapy, which has low adverse effects. Methods: Doxepin gel’s formulation was prepared with various concentrations of poloxamer 407 and hydroxypropyl methylcellulose in deionized water. The prepared gels were evaluated for pH, appearance, viscosity, spreadability, stability, and drug release. Results: After providing gels containing doxepin, formulations 1, 2, 8, and 9 had low quality and, thus, were removed from the study. Based on qualitative evaluations, formulations 3 and 4 did not meet the criteria for mucoadhesive gel and were removed from the study. The best formulation contained 17% w/w poloxamer 407, 10% w/w hydroxypropyl methylcellulose, and 5% w/w doxepin. Conclusions: Suitable physicochemical properties of prepared doxepin mucoadhesive gel enable it to well cover inflamed and damaged oral mucosa. On the other hand, doxepin’s slow release from formulation (8 hours) can increase therapeutic effects and reduce side effects, which can heal and soothe inflammations of the oral mucosa and be useful in cancer patient’s treatment.

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Long-Term Effects of TCM Yangqing Kangxian Formula on Bleomycin-Induced Pulmonary Fibrosis in Rats via Regulating Nuclear Factor-κB Signaling

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/2089027 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 5

Author(s):

Meng Li ◽

Ya Li ◽

JianSheng Li ◽

Peng Zhao ◽

Yunping Bai ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Nuclear Factor Kappa B ◽

Nuclear Factor Κb ◽

Cell Populations ◽

Therapeutic Effects ◽

Nuclear Factor ◽

Long Term Effects ◽

Treatment Groups ◽

Nuclear Factor Kappa

Objective. We aimed to evaluate the therapeutic effects and long-term effects of YKF and dissect the potential mechanisms. Materials and Methods. IPF rats were given YKF, prednisone, or pirfenidone, respectively, from day 1 to day 42, followed by a 28-day nonintervention interval through day 70. Forced vital capacity (FVC), histopathology, hydroxyproline (HYP) contents, lung coefficient, blood inflammatory cell populations, inflammatory cytokine levels of the lung tissues, and the expression of proteins involved in nuclear factor- (NF-) κB signaling pathway were evaluated on days 7, 14, 28, 42, and 70. Results. HYP contents, Ashcroft scores, lung coefficient, and pulmonary fibrosis blood cell populations increased significantly in IPF rats, while FVC declined. All the above-mentioned parameters were improved in treatment groups from day 7 up to day 70, especially in YKF group. The mRNA and protein expressions of tumor necrosis factor- (TNF-) α significantly decreased, while interferon- (IFN-) γ significantly increased, and phosphorylations of cytoplasm inhibitor of nuclear factor kappa-B kinase β (IKKβ), inhibitor of nuclear factor kappa-B α (IκBα), and NF-κB were obviously downregulated in YKF group from day 7 to day 70. Conclusion. YKF has beneficial protective and long-term effects on pulmonary fibrosis by anti-inflammatory response and alleviating fibrosis.

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Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

10.31234/osf.io/aewtm ◽

2021 ◽

Author(s):

Devon Stoliker ◽

Gary F. Egan ◽

Karl Friston ◽

Adeel Razi

Keyword(s):

Neural Plasticity ◽

Message Passing ◽

Functional Neuroimaging ◽

Effective Connectivity ◽

Predictive Coding ◽

Therapeutic Effects ◽

Long Term Effects ◽

Cortical Hierarchy ◽

The Brain

Neuroimaging studies of psychedelics have advanced our understanding of hierarchical brain organisation and the mechanisms underlying their subjective and therapeutic effects. The primary mechanism of action of classic psychedelics is binding to serotonergic 5HT2A receptors. Agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy that can have a profound effect on hierarchical message passing in the brain. Here, we review the cognitive and neuroimaging evidence for the effects of psychedelics; in particular, their influence on selfhood and subject-object boundaries—known as ego dissolution—surmised to underwrite their subjective and therapeutic effects. Agonist of 5HT2A receptors, located at the apex of the cortical hierarchy may have a particularly powerful effect on sentience and consciousness. These effects can endure well after the pharmacological half life, suggesting that psychedelics may have long-term effects on neural plasticity – that may play a role in their therapeutic efficacy. Psychologically, this may be accompanied by a surrender of ego resistance that increases the repertoire of perceptual hypotheses, including those that undergird selfhood. We consider the interaction between serotonergic neuromodulation and sentience through the lens of hierarchical predictive coding, which speaks to the value of psychedelics in understanding how we make sense of the world—and specific predictions about effective connectivity in cortical hierarchies that can be tested using functional neuroimaging.

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Long-Term Effect of a Vaccine Targeting Endothelin-1 Receptor Type A in Pulmonary Arterial Hypertension

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.683436 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yong Dai ◽

Zhihua Qiu ◽

Wenrui Ma ◽

Chang Li ◽

Xiao Chen ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Therapeutic Vaccine ◽

Systolic Pressure ◽

Therapeutic Effects ◽

Long Term Effects ◽

Mice Model ◽

Immune Mediated ◽

Pulmonary Arterial

Background: Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented the remodeling of pulmonary arterioles (PAs) and right ventricle (RV) without significant immune-mediated damage in experimental pulmonary arterial hypertension (PAH) mice models.Objective: Here, we aim to further evaluate the long-term effects of ETRQβ-002.Methods: PAH mice model was induced by a combination of subcutaneous injection with Sugen5416 and chronic hypoxic conditions (10% O2). PAH mice were immunized with ETRQβ-002 at different time points, and the experiment lasted for 21 weeks. Hemodynamic, histological, and biochemical analyses were conducted to evaluate the long-term effects of ETRQβ-002.Results: We demonstrated that the titer of the specific antibody against ETR-002 could be maintained chronically after periodic booster immunization in PAH mice. Long-term reduction of right ventricular systolic pressure and amelioration of PA remodeling by ETRQβ-002 were confirmed. Moreover, we found that ETRQβ-002 also exerted antiproliferation, anti-inflammation, and antifibrosis effects in PA remodeling. Besides, ETRQβ-002 durably limited pathological RV hypertrophy and fibrosis. Finally, no immune-mediated damage was observed in hepatic or renal function or by pathology in liver and kidney during the long-term administration of ETRQβ-002.Conclusion: Our findings indicate that ETRQβ-002 provides long-term therapeutic effects in Sugen/hypoxia-induced PAH animals and offers a promising clinical prospect for PAH treatment.

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The viability of pronatalism as a response to population growth decline in the Canadian context

10.32920/ryerson.14662695.v1 ◽

2021 ◽

Author(s):

Katharine Emma Blair

Keyword(s):

Population Growth ◽

Labour Force ◽

Population Decline ◽

Labour Force Participation ◽

Long Term Effects ◽

Demographic Trends ◽

Canadian Context ◽

Growth Decline ◽

Near Future

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Long-Term Efficacy and Complications of Radiofrequency Thermocoagulation at Different Temperatures for the Treatment of Trigeminal Neuralgia

Biochemistry Research International ◽

10.1155/2020/3854284 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Tao Hong ◽

Yuanyuan Ding ◽

Peng Yao

Keyword(s):

Trigeminal Neuralgia ◽

Large Scale ◽

Masticatory Muscles ◽

Therapeutic Effects ◽

Long Term Effects ◽

Analgesic Effects ◽

Radiofrequency Thermocoagulation ◽

Facial Numbness ◽

Lethal Complications

Trigeminal neuralgia (TN) is a common neuropathic pain that seriously affects the daily life of patients. Many invasive treatments are currently available for patients who respond poorly to oral carbamazepine or oxcarbazepine. Among them, radiofrequency (RF) treatment is a viable option with reliable initial and long-term clinical efficacy. The long-term analgesic effects of radiofrequency thermocoagulation (RFT) at high temperatures (≥80°C) are not superior to those at relatively low temperatures (60–75°C). In contrast, the higher the temperature, the greater the risk of complications, especially facial numbness, masticatory muscles weakness, and corneal hypoesthesia. Some patients even experience irreversible lethal complications. Therefore, we recommend low-temperature RFT (60–75°C) for treatment of TN. The therapeutic effects of pulsed radiofrequency (PRF) are controversial, whereas PRF (≤75°C) combined with RFT can improve long-term effects and decrease the incidence of complications. However, large-scale clinical trials are needed to verify the efficacy of the combination of PRF and RFT.

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