Clinical Pharmacology ofCitrus aurantiumandCitrus sinensisfor the Treatment of Anxiety

Objective. The aim of this review is to analyze preclinical and clinical studies investigating the anxiety effects ofCitrus aurantiumorCitrus sinensisessential oils (EOs).Design. The bibliographic research was made on the major scientific databases. Analysis included only articles written in English and published on peer-reviewed scientific journals describing preclinical experiments and clinical trials carried out to investigate the antianxiety effects ofCitrus aurantium or Citrus sinensisEOs on anxiety disorders. Clinical studies reporting the antianxiety effects of products containingCitrus aurantiumorCitrus sinensisEOs in combination with other active substances, including medicinal plants, were excluded. Nine clinical studies fulfilled the criteria adopted for analysis.Results. Data show thatCitrus aurantiumorCitrus sinensisEOs produce anxiolytic effects both in preclinical experiments and in different clinical conditions.Citrus aurantiumEO aromatherapy reduced anxiety level in the great part of stress conditions studied (subjects affected by chronic myeloid leukemia and preoperative patients) except for a sample of patients subjected to colonoscopy. Exposition toCitrus sinensisEO in clinical studies shows to be positive in reducing anxiety level in patients waiting for dental treatment as well as in healthy volunteers submitted to an anxiogenic situation.Conclusions. Overview of clinical trials conducted withCitrus aurantiumorCitrus sinensison people with anxiety showed that inhalation or oral administration ofCitrus aurantiumand inhalation ofCitrus sinensiscan exert beneficial effects on anxiety; however, because of incomplete accuracy in the reporting of methodology, further more complete clinical studies are warranted.

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Harnessing Intranasal Delivery Systems of Sumatriptan for the Treatment of Migraine

BioMed Research International ◽

10.1155/2022/3692065 ◽

2022 ◽

Vol 2022 ◽

pp. 1-9

Author(s):

Sara Assadpour ◽

Mohammad Reza Shiran ◽

Peyman Asadi ◽

Javad Akhtari ◽

Amirhossein Sahebkar

Keyword(s):

Clinical Studies ◽

Large Fraction ◽

Hepatic Metabolism ◽

Oral Route ◽

Delivery Systems ◽

Clinical Effects ◽

Beneficial Effects ◽

Wide Range ◽

Preclinical And Clinical Studies ◽

Novel Delivery Systems

Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.

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OZONE THERAPY: GENERAL PROTOCOLS BASED ON EVIDENCES

Journal of Ozone Therapy ◽

10.7203/jo3t.2.2.2018.11125 ◽

2018 ◽

Vol 2 (2) ◽

Author(s):

Silvia Menendez Cepero

Keyword(s):

Nitric Oxide ◽

Clinical Studies ◽

Senile Dementia ◽

Biological Effects ◽

Redox Balance ◽

Regulation Of Transcription ◽

Ozone Therapy ◽

Beneficial Effects ◽

Common Purpose ◽

Preclinical And Clinical Studies

Ozone has been used as a therapeutical agent for the treatment of different diseases and beneficial effects have been observed. However, ozone biological effects remain controversial due to the scarce knowledge of its biochemical and pharmacodynamic mechanisms. Taking into account that ozone therapy is gathering more interest, day by day, and it has been used in apparently nonrelated diseases with beneficial effects, the National Center for Scientific Research (Havana, Cuba) in collaboration with different research centers and health institutions have studied the ozone toxicology and its pharmacological actions as well as its biochemical mechanisms. The most remarkable experiences, in preclinical and clinical studies, developed in Cuba during the last 30 years, in order to prove unequivocally ozone therapy validity, are presented in this lecture. On the basis of the oxidant properties of ozone, we postulate that controlled ozone administration (named as ozone oxidative pre-/postconditioning mechanism) is able to promote a slight and transient oxidative stress which in turn re-establishes the signalling pathways which have been lost in pathological conditions, preserving the cellular redox balance (increasing antioxidant endogenous system), mitochondrial function as well as the regulation of transcription factors and the modulation of the immunological system. It is evident that membrane-associated ozone peroxides, 4-hydroxialkenals, superoxide anion, nitric oxide, among others, are going to play an important role in cellular signals as well as in the pathology of different diseases. Regulation of these biomolecules by ozone preconditioning has been demonstrated in several preclinical and clinical studies as ischaemia-reperfusion phenomenom, parkinson, senile dementia, disk herniation, retinitis pigmentosa, ischemic cardiopathy, arterial insufficiencies, diabetes, osteoarthritis, asthma, vestibulocochlear syndrome, among others. Nitric oxide modulation, as well as the increase in A1 adenosine receptors achieved with this therapy has an important role in brain blood flux, in the formation of memory, in the release of neurotransmitters and in the inflammatory processes. Ozone therapy seems to induce a simultaneous resuscitation of functions that had gone wrong, reactivating and re-equilibrating physiological activities. This lecture contributes to clarify the ozone mechanism of action and its different pharmacology effects. It is concluded that ozone therapy can be useful in the treatment of several diseases, either as adjuvant of ortodox medicine or taking part positively in those where conventional therapy has had no success, all this with a common purpose: to favour the patients and contribute to a better quality of life.

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Clot-Derived Contaminants in Transplanted Bone Marrow Mononuclear Cells Impair the Therapeutic Effect in Stroke

Stroke ◽

10.1161/strokeaha.119.026669 ◽

2019 ◽

Vol 50 (10) ◽

pp. 2883-2891 ◽

Cited By ~ 4

Author(s):

Yuka Okinaka ◽

Akie Kikuchi-Taura ◽

Yukiko Takeuchi ◽

Yuko Ogawa ◽

Johannes Boltze ◽

...

Keyword(s):

Bone Marrow ◽

Clinical Trials ◽

Mononuclear Cells ◽

Blood Clot ◽

Experimental Stroke ◽

Bone Marrow Mononuclear Cell ◽

Therapeutic Effects ◽

Beneficial Effects ◽

Preclinical And Clinical Studies ◽

Possible Cause

Background and Purpose— The beneficial effects of bone marrow mononuclear cell (BM-MNC) transplantation in preclinical experimental stroke have been reliably demonstrated. However, only overall modest effects in clinical trials were observed. We have investigated and reported a cause of the discrepancy between the preclinical and clinical studies. Methods— To investigate the possible cause of low efficacy of BM-MNC transplantation in experimental stroke, we have focused on blood clot formation, which is not uncommon in human bone marrow aspirates. To evaluate the effects of clot-derived contaminants in transplanted BM-MNC on stroke outcome, a murine stroke model was used. Results— We show that BM-MNC separated by an automatic cell isolator (Sepax2), which does not have the ability to remove clots, did not attenuate brain atrophy after stroke. In contrast, manually isolated, clot-free BM-MNC exerted therapeutic effects. Clot-derived contaminants were also transplanted intravenously to poststroke mice. We found that the transplanted contaminants were trapped at the peristroke area, which were associated with microglial/macrophage activation. Conclusions— Clot-derived contaminants in transplanted BM-MNC nullify therapeutic effects in experimental stroke. This may explain neutral results in clinical trials, especially in those using automated stem cell separators that lack the ability to remove clot-derived contaminants. Visual Overview— An online visual overview is available for this article.

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Modulating Metabolism to Improve Cancer-Induced Muscle Wasting

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/7153610 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Fabio Penna ◽

Riccardo Ballarò ◽

Marc Beltrá ◽

Serena De Lucia ◽

Paola Costelli

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Cancer Patients ◽

Clinical Studies ◽

Cancer Cachexia ◽

Muscle Wasting ◽

Muscle Metabolism ◽

Preclinical Models ◽

Oncologic Patients ◽

Clinical Conditions

Muscle wasting is one of the main features of cancer cachexia, a multifactorial syndrome frequently occurring in oncologic patients. The onset of cachexia is associated with reduced tolerance and response to antineoplastic treatments, eventually leading to clinical conditions that are not compatible with survival. Among the mechanisms underlying cachexia, protein and energy dysmetabolism play a major role. In this regard, several potential treatments have been proposed, mainly on the basis of promising results obtained in preclinical models. However, at present, no treatment yet reached validation to be used in the clinical practice, although several drugs are currently tested in clinical trials for their ability to improve muscle metabolism in cancer patients. Along this line, the results obtained in both experimental and clinical studies clearly show that cachexia can be effectively approached by a multidirectional strategy targeting nutrition, inflammation, catabolism, and inactivity at the same time. In the present study, approaches aimed to modulate muscle metabolism in cachexia will be reviewed.

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The Challenges and Effects of Ascorbic Acid Treatment of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Preclinical and Clinical Studies

Frontiers in Nutrition ◽

10.3389/fnut.2021.734558 ◽

2021 ◽

Vol 8 ◽

Author(s):

Lin Gao ◽

Eric Chong ◽

Sayali Pendharkar ◽

Anthony Phillips ◽

Lu Ke ◽

...

Keyword(s):

Clinical Trials ◽

Acute Pancreatitis ◽

Ascorbic Acid ◽

Organ Failure ◽

Clinical Studies ◽

Primary Outcome ◽

Meta Analysis ◽

Length Of Hospital Stay ◽

Preclinical Studies ◽

Preclinical And Clinical Studies

Background: Oxidative stress has been implicated in the pathogenesis of acute pancreatitis (AP), and ascorbic acid (AA), as an important endogenous antioxidant substance, has been shown to reduce AP severity in preclinical studies. However, the effects of AA supplementation in clinical settings remain controversial.Methods: PubMed, EMBASE, MEDLINE, and SCOPUS databases were searched, and both preclinical and clinical studies were included. For clinical trials, the primary outcome was incidence of organ failure, and for preclinical studies, the primary outcome was histopathological scores of pancreatic injuries.Results: Meta-analysis of clinical trials showed that compared with controls, AA administration did not reduce the incidence of organ failure or mortality during hospitalization but was associated with significantly reduced length of hospital stay. Meta-analysis of preclinical studies showed that AA supplementation reduced pancreatic injury, demonstrated as decreased histological scores and serum amylase, lipase levels.Conclusion: AA administration has no effect on survival or organ failure in patients with AP but may reduce the length of hospital stay. However, the evidence to date remains sparse, scattered, and of suboptimal quality, making it difficult to draw any firm conclusion on the clinical benefits of AA in AP.

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Corticostriatal circuitry in regulating diseases characterized by intrusive thinking

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2016.18.1/pkalivas ◽

2016 ◽

Vol 18 (1) ◽

pp. 65-76 ◽

Cited By ~ 12

Keyword(s):

Clinical Trials ◽

Nucleus Accumbens ◽

Drug Addiction ◽

Clinical Studies ◽

Clinical Symptoms ◽

Neuropsychiatric Disorders ◽

Preclinical Models ◽

Drug Seeking ◽

Positive Effects ◽

Preclinical And Clinical Studies

Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.

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Russian and International Regulatory Recommendations for the Development and Marketing Authorisation of COVID-19 Vaccines in the Context of the Pandemic

BIOpreparations Prevention Diagnosis Treatment ◽

10.30895/2221-996x-2020-20-4-228-244 ◽

2020 ◽

Vol 20 (4) ◽

pp. 228-244

Author(s):

A. A. Soldatov ◽

Zh. I. Avdeeva ◽

V. P. Bondarev ◽

V. A. Merkulov ◽

V. D. Mosyagin ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Studies ◽

Marketing Authorisation ◽

Fast Track ◽

Vaccine Development ◽

The United States ◽

The European Union ◽

Regulatory Requirements ◽

Good Tolerability ◽

Preclinical And Clinical Studies

The progress of the COVID-19 pandemic initiated research to develop vaccines against this novel coronavirus infection. The WHO and national regulatory authorities in many countries have elaborated guidelines to speed up the development and authorisation of COVID-19 vaccines.The aim of the study was to analyse international and Russian regulatory recommendations for the development and fast-track approval of COVID-19 vaccines in the context of the pandemic, as well as to summarise the preliminary published results of the first stages of preclinical and clinical studies. The paper analyses approaches to fast-track approval of medicines in the face of the pandemic in Russia, the European Union, and the United States. It summarises regulatory requirements for the quality of COVID-19 vaccines, as well as for preclinical, and clinical studies. It describes the first results of COVID-19 vaccine development. The analysed regulatory documents allow for accelerated authorisation due to reduction of time spent on evaluation of vaccine quality, safety, and efficacy. Another option is the so-called conditional marketing authorisation when a vaccine is registered based on incomplete preclinical and clinical data provided that all the studies will be completed after the vaccine authorisation. The paper summarises the results of clinical trials of COVID-19 vaccines. The few published preliminary results of the first phases of COVID-19 vaccine clinical trials demonstrate the vaccines’ good tolerability, safety, and immunogenicity. Evaluation of adenovirusbased vaccines showed that almost half of the volunteers had had high antibody titers to adenovirus before the study, which resulted in milder adverse reactions and low immunogenicity. In addition, the immune response was weaker in the older group of subjects (45–60 years) as compared to the subjects younger than 45 years. The results of the analysis of regulatory requirements for the development and marketing authorisation of COVID-19 vaccines in the context of the pandemic, as well as of national and international regulatory approaches to vaccine development and authorisation can be used as a basis for the development of Russian requirements for COVID-19 vaccines in the context of the pandemic.

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Buprenorphine: prospective novel therapy for depression and PTSD

Psychological Medicine ◽

10.1017/s0033291720000525 ◽

2020 ◽

Vol 50 (6) ◽

pp. 881-893

Author(s):

Caitlin A. Madison ◽

Shoshana Eitan

Keyword(s):

Clinical Studies ◽

Therapeutic Potential ◽

Kappa Opioid Receptor ◽

Mental Illnesses ◽

Bibliographic Databases ◽

Medical Conditions ◽

Endogenous Opioid ◽

Beneficial Effects ◽

Ability To Act ◽

Preclinical And Clinical Studies

AbstractBackgroundDepression and post-traumatic stress disorder (PTSD) are leading causes of disability and loss of life by suicide. Currently, there are less than satisfactory medical solutions to treat these mental disorders. Here, we explore recent preclinical and clinical studies demonstrating the potential of using buprenorphine to treat major depressive disorder, treatment-resistant depression, and PTSD.MethodBibliographic databases were searched to include preclinical and clinical studies demonstrating the therapeutic potential of buprenorphine and the involvement of the kappa opioid receptor (KOR) in mediating these effects.ResultsOriginal clinical studies examining the effectiveness of buprenorphine to treat depression were mixed. The majority of participants in the PTSD studies were males and suffer from chronic pain and/or substance use disorders. Nonetheless, these recent studies and analyses established proof of concept warranting farther investigations. Additionally, KOR likely mediates the antidepressant and some of the anxiolytic effects of buprenorphine. Still, it appears that the full spectrum of buprenorphine's beneficial effects might be due to activity at other opioid receptors as well.ConclusionsPharmaceuticals' abilities to treat medical conditions directly relates to their ability to act upon the endogenous biological systems related to the conditions. Thus, these recent findings are likely a reflection of the central role that the endogenous opioid system has in these mental illnesses. Further studies are necessary to study the involvement of endogenous opioid systems, and specifically KOR, in mediating buprenorphine's beneficial effects and the ability to treat these medical conditions while minimizing risks for misuse and diversion.

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Natural Compounds for Alzheimer’s Disease Therapy: A Systematic Review of Preclinical and Clinical Studies

International Journal of Molecular Sciences ◽

10.3390/ijms20092313 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2313 ◽

Cited By ~ 37

Author(s):

Stephanie Andrade ◽

Maria João Ramalho ◽

Joana Angélica Loureiro ◽

Maria do Carmo Pereira

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Studies ◽

Neurodegenerative Disorder ◽

Natural Compounds ◽

Continuous Increase ◽

Beneficial Effects ◽

Wide Range ◽

Relevant Role ◽

Preclinical And Clinical Studies

Alzheimer’s Disease (AD) is a neurodegenerative disorder related with the increase of age and it is the main cause of dementia in the world. AD affects cognitive functions, such as memory, with an intensity that leads to several functional losses. The continuous increase of AD incidence demands for an urgent development of effective therapeutic strategies. Despite the extensive research on this disease, only a few drugs able to delay the progression of the disease are currently available. In the last years, several compounds with pharmacological activities isolated from plants, animals and microorganisms, revealed to have beneficial effects for the treatment of AD, targeting different pathological mechanisms. Thus, a wide range of natural compounds may play a relevant role in the prevention of AD and have proven to be efficient in different preclinical and clinical studies. This work aims to review the natural compounds that until this date were described as having significant benefits for this neurological disease, focusing on studies that present clinical trials.

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Antioxidant Food Components for the Prevention and Treatment of Cardiovascular Diseases: Effects, Mechanisms, and Clinical Studies

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6627355 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Dan-Dan Zhou ◽

Min Luo ◽

Ao Shang ◽

Qian-Qian Mao ◽

Bang-Yan Li ◽

...

Keyword(s):

Clinical Trials ◽

Natural Products ◽

Cardiovascular Diseases ◽

Bioactive Compounds ◽

Clinical Studies ◽

Experimental Studies ◽

Epigallocatechin Gallate ◽

Epidemiological Studies ◽

Beneficial Effects ◽

High Prevalence

Cardiovascular diseases (CVDs) have gained increasing attention because of their high prevalence and mortality worldwide. Epidemiological studies revealed that intake of fruits, vegetables, nuts, and cereals could reduce the risk of CVDs, and their antioxidants are considered as the main contributors. Moreover, experimental studies showed that some antioxidant natural products and their bioactive compounds exerted beneficial effects on the cardiovascular system, such as polyphenols, polysaccharides, anthocyanins, epigallocatechin gallate, quercetin, rutin, and puerarin. The mechanisms of action mainly included reducing blood pressure, improving lipid profile, ameliorating oxidative stress, mitigating inflammation, and regulating gut microbiota. Furthermore, clinical trials confirmed the cardiovascular-protective effect of some antioxidant natural products, such as soursop, beetroot, garlic, almond, and green tea. In this review, we summarized the effects of some antioxidant natural products and their bioactive compounds on CVDs based on the epidemiological, experimental, and clinical studies, with special attention paid to the relevant mechanisms and clinical trials.

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