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Cannabigerol (CBG) is a cannabinoid from the plant Cannabis sativa that lacks psychotomimetic effects. Its precursor is the acidic form, cannabigerolic acid (CBGA), which is, in turn, a biosynthetic precursor of the compounds cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBGA decarboxylation leads to the formation of neutral cannabinoid CBG, through a chemical reaction catalyzed by heat. On the basis of the growing interest in CBG and with the aim of highlighting scientific information on this phytocannabinoid, we focused the content of this article on its pharmacokinetic and pharmacodynamic characteristics and on its principal pharmacological effects. CBG is metabolized in the liver by the enzyme CYP2J2 to produce hydroxyl and di-oxygenated products. CBG is considered a partial agonist at the CB1 receptor (R) and CB2R, as well as a regulator of endocannabinoid signaling. Potential pharmacological targets for CBG include transient receptor potential (TRP) channels, cyclooxygenase (COX-1 and COX-2) enzymes, cannabinoid, 5-HT1A, and alpha-2 receptors. Pre-clinical findings show that CBG reduces intraocular pressure, possesses antioxidant, anti-inflammatory, and anti-tumoral activities, and has anti-anxiety, neuroprotective, dermatological, and appetite-stimulating effects. Several findings suggest that research on CBG deserves to be deepened, as it could be used, alone or in association, for novel therapeutic approaches for several disorders.

Chronic urticaria (CU) is a pathologic condition marked by the emergence of wheals, angioedema, or both for more than six weeks. The improper activation and degranulation of mast cells is the triggering event, which results in the production of various mediators such as histamine, leukotrienes, PAF, chemokines, and cytokines. Antihistamines are currently the most common pharmacological treatment for urticaria, but corticosteroids and monoclonal antibodies can also be employed. Patients who have been taking antihistamines for a long time are often looking for alternatives. Whole plants, portions of plants, or single extracted active compounds are all used in phytomedicine. Plant elements are frequently combined to create formulations that can be utilized to treat a variety of pathological disorders. Anti-inflammatory and/or anti-allergic properties are found in several herbs regularly used in herbal formulations. Antioxidant properties are also present in some of the constituents. Exogenous antioxidants have been shown to improve the progression of autoimmune disorders in numerous studies. The aim of this review is to identify the most common herbs used to treat chronic urticaria, and to characterize their efficacy, mechanisms of action, and risk/benefit ratio in comparison to western treatment, and also to find less often used formulations and assess their therapeutic efficacy, safety profile, and potential for wider use.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and it is involved in several fundamental functions in the central and peripheral nervous systems, and in sensory organs. BDNF regulates the chemosensory systems of mammals and is consistently expressed in those organs. In zebrafish, the key role of BDNF in the biology of the hair cells of the inner ear and lateral line system has recently been demonstrated. However, only some information is available about its occurrence in the olfactory epithelium, taste buds, and cutaneous isolated chemosensory cells. Therefore, this study was undertaken to analyze the involvement of BDNF in the chemosensory organs of zebrafish during the larval and adult stages. To identify cells displaying BDNF, we compared the cellular pattern of BDNF-displaying cells with those immunoreactive for calretinin and S100 protein. Our results demonstrate the localization of BDNF in the sensory part of the olfactory epithelium, mainly in the ciliated olfactory sensory neurons in larvae and adult zebrafish. Intense immunoreaction for BDNF was also observed in the chemosensory cells of oral and cutaneous taste buds. Moreover, a subpopulation of olfactory sensory neurons and chemosensory cells of olfactory rosette and taste bud, respectively, showed marked immunopositivity for calcium-binding protein S100 and calretinin. These results demonstrate the possible role of BDNF in the development and maintenance of olfactory sensory neurons and sensory cells in the olfactory epithelium and taste organs of zebrafish during all stages of development.

Aim: Coffee intake is common during pregnancy. However, the influence of coffee and caffeine on pregnancy has not yet been fully determined. Some studies show that high coffee intake could cause mi...

Simple Summary This study aimed at investigating the prognostic significance of the soluble form of CD200 antigen evaluated at diagnosis in patients with chronic lymphocytic leukemia (CLL). In a large cohort of patients, we found that more aggressive features and a worse prognosis are correlated with higher baseline serum levels of CD200. These data support the relevant role of CD200 not only as a diagnostic tool but also as a prognostic indicator and a potential therapeutic target in CLL. Abstract Membrane-bound CD200 is overexpressed in chronic lymphocytic leukemia (CLL), and there is some evidence that its soluble ectodomain (sCD200) could also be involved in the pathophysiology and the disease. However, very little is known about sCD200’s prognostic significance. sCD200 was tested at diagnosis in 272 patients with CLL and in 78 age- and sex-matched healthy subjects using a specific human CD200 (OX-2 membrane glycoprotein) ELISA kit. A significantly higher concentration of sCD200 was found in CLL patients compared to controls. In our cohort, sCD200 was significantly higher in patients who were older than 66 years, with Binet stage C, unmutated IgVH and unfavorable (del11q or del17p) FISH. Time-to-first treatment and overall survival were significantly shorter in patients with higher sCD200 concentration, using as a cut-off 1281 pg/mL, the median value for sCD200 concentration in the whole CLL cohort. However, the prognostic impact of sCD200 was not confirmed in multivariate analysis. Baseline sCD200 values appeared to have an impact on the response to chemotherapy or chemo-immunotherapy, but not to targeted agents. Collectively, our data show that sCD200 serum levels correlate with more aggressive clinical and biological features and are able to predict a worse prognosis. This work supports the relevant role of CD200 not only as a diagnostic tool but also as a prognostic indicator and a potential therapeutic target in CLL.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are chronic diseases associated with increased morbidity and reduced quality of life. Age may represent a risk factor for adverse events, due to the multimorbidity and polypharmacy, common in elderly patients. Elderly are often not included in clinical trials evaluating efficacy and safety of study drugs for the treatment of inflammatory bowel diseases. Several drugs, such as aminosalicylates, systemic corticosteroids, immunosuppressant drugs, biological drugs and Janus Kinase inhibitors, are available for the management of inflammatory bowel diseases. With the increasing spectrum of therapeutic options, it is therefore important to analyze the evidence regarding the safety of the use of these agents in elderly patients. Selection of immunosuppressive therapy is a challenge in the management of elderly patients with inflammatory bowel diseases, for whom biologics with a lower risk of infection or cancer, such as vedolizumab and ustekinumab, may be preferred in elderly patients. Concomitant therapies and comorbidities must be thoroughly investigated before initiating any immunosuppressive or biological therapy in order to minimize the risk of drug-drug interactions. This review aims to provide an overview of the safety of thiopurines, methotrexate and target therapies as well as their drug-drug interactions in patients with inflammatory bowel diseases.

Objective: Multiple Myeloma (MM) is a haematological disease resulting from the neoplastic transformation of plasma cells. The uncontrolled growth of plasma cells in the bone marrow and the delivery of several cytokines causes bone erosion that often does not regress, even in the event of disease remission. MM is characterised by a multi-step evolutionary path, which starts with an early asymptomatic stage defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease. Data Sources and Study Selection: We have selected scientific publications on the specific topics “alarmis, MGUS, and MM”, drawing from PubMed. The keywords we used were alarmines, MGUS, MM, and immune system. Results: The analysis confirms the pivotal role of molecules such as high-mobility group box-1, heat shock proteins, and S100 proteins in the induction of neoangiogenesis, which represents a milestone in the negative evolution of MM as well as other haematological and non-haematological tumours. Conclusions: Modulation of the host immune system and the inhibition of neoangiogenesis may represent the therapeutic target for the treatment of MM that is capable of promoting better survival and reducing the risk of RRMM.

Antioxidant mechanisms are constituted of enzymes, endogenous, and non-enzymatic, exogenous, which have the role of counterbalancing oxidative stress. Intake of these compounds occurs in the diet. Vegetables, plants, and fruits contain a wide range of alkaloids, polyphenols, and terpenoids which are called “phytochemicals”. Most of these substances are responsible for the positive properties of fruits and vegetables, which are an essential part of a healthy life with roles in ameliorating chronic illnesses and favoring longevity. Nutraceuticals are substances contained in a food or fragment of it influencing health with positive effects on health helping in precenting or treating disorders. We conducted a review illustrating the principal applications of nutraceuticals in autoimmune disorders. Literature reported several studies about exogenous dietary antioxidant supplementation in diverse autoimmune diseases such as rheumatoid arthritis, lupus, diabetes, and multiple sclerosis. In these pathologies, promising results were obtained in some cases. Positive outcomes were generally associated with a reduction of oxidative stress parameters and a boost to antioxidant systems, and sometimes with anti-inflammatory effects. The administration of exogenous substances through food derivates or dietary supplements following scientific standardization was demonstrated to be effective. Further bias-free and extended studies should be conducted that include ever-increasing oxidative stress biomarkers.

Cancer is one of the several comorbidities that have been linked with chronic cutaneous inflammatory diseases namely psoriasis/psoriatic arthritis and hidradenitis suppurativa. Although the chronic inflammatory state, typical of the diseases, may induce pro-tumorigenic effects, the debate whether or not the drugs currently used in clinical practice do in facts increase a patient’s risk of malignancy remains largely unsolved. The therapeutic armamentarium has been greatly enhanced at least in the last two decades with the advent of biologics, a heterogeneous group of laboratory-engineered agents with more in the pipeline, and other targeted small molecules. Among the organ systems, skin results as one of the most commonly affected, non-melanoma skin cancers being the main drug-induced manifestations as side effect in course of these treatments. The objective of the study is to systematically review the cutaneous malignancy risk of the newer therapies through an overview of meta-analyses and observational studies on the topic.

The aim of this study was to evaluate the correlation between marginal gingivitis, oral hygiene parameters, and interleukin-6 (IL-6) levels in gingival crevicular fluid of 40 children. The marginal periodontal pathology was evaluated by gingival index (GI). The status of oral hygiene was estimated by using patient hygiene performance (PHP), brushing frequency (BF), and plaque index (PI). IL-6 levels in gingival crevicular fluid were measured to evaluate the inflammation in marginal gingiva. PHP score showed a significant correlation with GI, BF, and PI. The groups based on PHP ranges were significantly related to IL-6 concentration in crevicular fluid.

Background: Pain is a common symptom in oncologic patients and its management is generally guided with reference to pain individually perceived by patients and expressed through self-reported scales. However, the utility of these tools is limited as it strongly depends on patients’ opinions. For this reason, more objective instruments are desirable. Objective: In this overview, scientific articles indicating potential markers to be used for pain management in cancer were collected and discussed. Methods: Research was performed on principal electronic scientific databases by using the words “pain”, “cancer”, “markers” and “biomarkers” as the main keywords, and findings describing potential biomarkers for the management of cancer pain were reported. Results: Studies on pain markers not specific for cancer typology (inflammatory, genetic markers predicting response to analgesic drugs, neuroimaging markers) and pain markers for specific types of cancer (bone cancer, breast cancer, lung cancer, head and neck cancer, prostate cancer, cancer in pediatrics) have been presented and commented on. Conclusion: This overview supports the view of the involvement of inflammatory mediators in the mechanisms underlying cancer pain. Only a small amount of data from research up till today is available on markers that can help in the management of pain, except for pro-inflammatory cytokines and other inflammatory indexes such as C-reactive protein (CRP). However, biomarkers are a promising strategy useful to predict pain intensity and to objectively quantify analgesic response in guiding decisions regarding individual-tailored treatments for cancer patients.

Potential therapeutic actions of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are based on their activity as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds. THC and CBD lipophilicity and their neurological actions makes them candidates as new medicinal approaches to treat central nervous system (CNS) diseases. However, they show differences about penetrability and disposition in the brain. The present article is an overview about THC and CBD crossing the blood–brain barrier (BBB) and their brain disposition. Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia. Thus supporting the therapeutic potential of CBD for the treatment of ischemic and inflammatory diseases of CNS. Cannabinoids positive effects on cognitive function could be also considered through the aspect of protection of BBB cerebrovascular structure and function, indicating that they may purchase substantial benefits through the protection of BBB integrity. Delivery of these cannabinoids in the brain following different routes of administration (subcutaneous, oral, and pulmonary) is illustrated and commented. Finally, the potential role of cannabinoids in drug-resistance in the clinical management of neurological or psychiatric diseases such as epilepsy and schizophrenia is discussed on the light of their crossing the BBB.

BACKGROUND Gamma-hydroxybutyrate (GHB or sodium oxybate) is both an exogenous and endogenous molecule with neuromodulator properties. In the United States, GHB is an approved drug for the treatment of narcolepsy and narcolepsy with cataplexy in adults. In some European Union countries, sodium oxybate is applied for the treatment of opioid and alcohol withdrawal. OBJECTIVE The aim of the present review was to describe the state of art of the pre-clinical research and the clinical evidence related to GHB used alone or in combination with other treatments in alcohol withdrawal syndrome and alcohol abstinence maintenance. METHOD Internationally published pre-clinical findings and clinical studies investigating the effects of GHB on alcohol withdrawal syndrome and alcohol abstinence maintenance were collected and described considering seven clinical studies involving GHB in the treatment of alcohol withdrawal abstinence and five clinical studies involving GHB in the treatment of alcohol abstinence maintenance. Furthermore, GHB pharmacology and characteristics of abuse were briefly detailed. RESULTS Clinical evidence indicates that GHB is effective in reducing symptoms of alcohol withdrawal syndrome and produces beneficial effects comparable to those of benzodiazepines or chlometiazole. GHB proved effective in increasing alcohol abstinence maintenance and in reducing alcohol craving, but it did not show any influence in relapses of heavy drinkers when given alone. Conversely, it seems to be effective in reducing relapses in alcohol dependent patients when given in combination with naltrexone and escitalopram. CONCLUSION Despite this bunch of evidence, studies are still limited and investigations including a larger number of patients are needed. In addition, some safety concerns, such as insufficiency against hallucinations in alcohol withdrawal and potential development of GHB dependence have to be more investigated.

Products derived from the plant Cannabis sativa are widely appreciated for their analgesic properties and are employed for the treatment of chronic neuropathic pain. Only nabiximols, a product composed of two extracts containing similar percentages of the two cannabinoids cannabidiol and delta-9-tetrahydrocannabinol, is approved by regulatory authorities for neuropathic pain and spasticity due to multiple sclerosis in many European countries and Canada. It is also included in pharmacovigilance systems monitoring the occurrence of adverse drug reactions. However, it is not the same for the great variety of other cannabis preparations widely used for medical purposes. This creates a situation characterized by insufficient knowledge of the safety of cannabis preparations and the impossibility of establishing a correct risk–benefit profile for their medical use in the treatment of chronic neuropathic pain. With the aim to explore this issue more deeply, we collected data on adverse reactions from published clinical studies reporting the use of cannabis for neuropathic relief.

Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes. All bacteriuria in pregnancy should be treated with antimicrobial treatments being safe for both the mother and the fetus. Approximately one every four women receives prescription of antibiotic treatment during pregnancy, nearly 80% of all the prescription medications during gestation. The use of fosfomycin to treat cystitis in pregnancy generally considered safe and effective. Even though use on antibiotics for urinary tract infections is considered generally safe for the fetus and mothers, this opinion is not based on specific studies monitoring the relationship of among urinary infections, consumption of antibiotics, and pregnancy outcomes.On this basis we decided to analyze data from the database of our multicenter study PHYTOVIGGEST, reporting data from 5362 pregnancies, focusing on use of fosfomycin. Principal outcomes of pregnancy in women treated with fosfomycin were taken into consideration.Women who have been treated with urinary antibiotics during the pregnancy were 183. With respect to the total number of pregnancies of our sample, these women represented the percentage of 3.49% (187/5362). Analysis of different outcomes of pregnancy such as gestational age, neonatal weight, and neonatal Apgar index did not show any significant difference. At the same time, analysis of data of pregnancy complicancies (such as urgent cesarean delivery, use of general anesthesia, need to induce labor) did not show any difference in women taking fosfomycin during pregnancy and those not taking it.Our data, based on a large number of pregnancies, confirm the safety use of fosfomycin use in pregnancy.

Background. Cannabidiol (CBD) is a major chemical compound present in Cannabis sativa. CBD is a nonpsychotomimetic substance, and it is considered one of the most promising candidates for the treatment of psychiatric disorders. Objective. The aim of this review is to illustrate the state of art about scientific research and the evidence of effectiveness of CBD in psychiatric patients. Methods. This review collects the main scientific findings on the potential role of CBD in the psychiatric field, and results of clinical trials carried out on psychiatric patients are commented. A research was conducted in the PUBMED, SCOPUS, and ScienceDirect databases using combinations of the words cannabidiol, psychiatry, and neuropsychiatric. Results. Preclinical and clinical studies on potential role of CBD in psychiatry were collected and further discussed. We found four clinical studies describing the effects of CBD in psychiatric patients: two studies about schizophrenic patients and the other two studies carried out on CBD effects in patients affected by generalized social anxiety disorder (SAD). Conclusion. Results from these studies are promising and suggest that CBD may have a role in the development of new therapeutic strategies in mental diseases, and they justify an in-depth commitment in this field. However, clinical evidence we show for CBD in psychiatric patients is instead still poor and limited to schizophrenia and anxiety, and it needs to be implemented with further studies carried out on psychiatric patients.

Citrus bergamia Risso et Poiteau (“Bergamot”) originated from the Mediterranean ecoregion (southern Italy, Calabria). Bergamot essential oil (BEO) is used in perfumes, cosmetics, and for stress reduction. Juice from C. bergamia has been used for hyperlipidemia. We evaluated literature published on C. bergamia clinical applications. Clinical trials on C. bergamia not combined with other substances, published in English, were searched. We selected ten articles, six describing BEO effects on stress, three reporting effects of polyphenolic fraction of C. bergamia juice in hyperlipidemia and the last describing BEO effects in chronic psoriasis. Clinical studies were analyzed following Consolidated Standards of Reporting Trials for herbal therapy. Studies were conducted on small sample sizes and not have high quality level. Analysis indicates that BEO aromatherapy could be safe and useful to reduce stress symptoms. One study suggests its potential supportive role in ultraviolet B therapy against psoriasis. Supplementation with polyphenols from bergamot juice reduces plasma lipids and improves lipoprotein profile in moderate hyperlipidemia. Effectiveness and safety of C. bergamia cannot be definitively drawn because of publication bias and low quality level of the majority of studies. Further large-scale trials with rigorous design are required to define the role of C. bergamia in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.

Background Omega-3 fatty acids (FAs) can produce several beneficial effects and are commonly used for the treatment of migraine symptoms. Although current therapeutic measures for migraine included pharmacological therapies, dietary supplements, and herbal ingredients, dietary patterns, acupuncture, relaxation techniques, biofeedback, and psychotherapy, omega-3 FAs therapeutic role seems to be obtained through the inhibition or reduction of the release of inflammatory cytokines. The present review aims to provide updated information about the effects of omega-3 FAs in migraine treatment, investigating their clinical effects alone or in combination with other substances. Methods Bibliographic research was conducted by examining scientific literature from January 2000 until January 31, 2020. Ten clinical studies were included in the review. Quality assessment of randomized controlled trials was performed by using the JADAD scale. Results Clinical studies methodology is not always of good quality and results show moderate evidence concerning the therapeutic role of omega-3 FAs in migraine. Conclusion Further clinical trials are necessary to implement the knowledge concerning the use of omega-3 fatty acids in the treatment of migraine.

Objective The aim of this review is to analyze preclinical and clinical studies investigating the anxiety effects of Citrus aurantium or Citrus sinensis essential 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 of Citrus aurantium or Citrus sinensis EOs on anxiety disorders. Clinical studies reporting the antianxiety effects of products containing Citrus aurantium or Citrus sinensis EOs in combination with other active substances, including medicinal plants, were excluded. Nine clinical studies fulfilled the criteria adopted for analysis. Results Data show that Citrus aurantium or Citrus sinensis EOs produce anxiolytic effects both in preclinical experiments and in different clinical conditions. Citrus aurantium EO 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 to Citrus sinensis EO 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 with Citrus aurantium or Citrus sinensis on people with anxiety showed that inhalation or oral administration of Citrus aurantium and inhalation of Citrus sinensis can exert beneficial effects on anxiety; however, because of incomplete accuracy in the reporting of methodology, further more complete clinical studies are warranted.

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.

Hydrocodone is one of the most prescribed oral analgesic drugs and it is one of the most abused drugs in general population. It is a mu-opioid agonist predominantly metabolized to the O-demethylated product hydromorphone and to the N-demethylated product norhydrocodone. The purpose of the study is to summarize the preclinical and clinical characteristics of hydrocodone. Pharmacokinetic aspect (terminal half-life, maximum serum concentration, and time to maximum serum concentration) of hydrocodone and the influence of metabolic genetic polymorphism in analgesic response to hydrocodone are also illustrated and commented. Literature on experimental preclinical pharmacology investigating analgesic activity in laboratory animals is furtherly discussed. Moreover, the authors discuss and comment on the updated data regarding safety profile and effectiveness of hydrocodone in the treatment of chronic pain. A bibliographic research was carried out (from February 01, 2018 to August 28, 2018) independently by two researchers (blinded to the authors and initially on results) in the major scientific databases and research engines of peer-reviewed literature on life sciences and biomedical topics, starting from January 1990 to August 2018. Analysis of results of clinical studies suggests that abuse-deterrent extended-release (ER) hydrocodone formulations can be effective and they are well tolerated in the treatment of chronic low back pain. Weaker is the evidence of the analgesic effectiveness of ER hydrocodone on other chronic pain syndromes and non-cancer non-neuropathic chronic pain. In these conditions, hydrocodone showed to have positive effects in non-controlled open studies and needs to be further studied to assess the real strength of results.

Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions.

Background: Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory activities and the modulation of a large number of brain biological targets (receptors, channels) involved in the development and maintenance of neurodegenerative diseases. Objective: The aim of the present review was to describe the state of art about the pre-clinical research, the potential use and, when existing, the clinical evidence related to CBD in the neurological field. Method: Collection of all the pre-clinical and clinical findings carried out investigating the effects of CBD alone, not in combination with other substances, in the neurological arena with the exclusion of studies on neuropsychiatric disorders. Results: Laboratory and clinical studies on the potential role of CBD in Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), Huntington’s disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia, were examined. Conclusion: Pre-clinical evidence largely shows that CBD can produce beneficial effects in AD, PD and MS patients, but its employment for these disorders needs further confirmation from well designed clinical studies. CBD pre-clinical demonstration of antiepileptic activity is supported by recent clinical studies in human epileptic subjects resistant to standard antiepileptic drugs showing its potential use in children and young adults affected by refractory epilepsy. Evidence for use of CBD in PD is still not supported by sufficient data whereas only a few studies including a small number of patients are available.

SUMMARY Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer’s disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials.

Background: Montelukast, a leucotriene receptor antagonist, binds the cysteinyl leucotriene type 1 receptor. Montelukast is commonly prescribed to asthma patients as add-on therapy to inhaled corticosteroids. Several clinical trials emphasized that montelukast can be considered a safe drug. However, recent evidence reconsidered the benefit/risk ratio of the use of montelukast for both paediatric and adult patients. Summary: The present review analyzed the previous published case reports regarding montelukast-induced adverse drug reactions (ADRs). They included agitation, anxiety, depression, sleep disturbance, hallucinations, suicidal thinking and suicidality, tremor, dizziness, drowsiness, neuropathies and seizures. The immune system can be involved, in particular, cases of Churg-Strauss syndrome have been published. Furthermore, it can induce hypersensitivity reactions, including anaphylaxis and eosinophilic infiltration. In addition, hepatobiliary, pancreatic and uropoietic disorders have been observed. Some of these cases are characterized by severe prognosis (i.e. neurological deficit and fatal hepatotoxicity). Key Message: The use of montelukast can be burdened by several ADRs, of which physicians should be aware in their clinical practice. A better understanding of the mechanisms causing ADRs after using montelukast could help researchers and clinicians in defining a risk-reduction strategy aimed to lessen montelukast toxicity. More accurate epidemiological studies, in order to discover risk factors favouring montelukast-associated ADRs, are demanded.

Calendula offi cinalis is a plant belonging to the Asteraceae family. Herbal preparations from Calendula have been used topically as a natural anti-infl ammatory medicine and for the healing of wounds and leg ulcers. Although data on dermal irritation and sensitization are available, the risk of subchronic systemic toxicity following dermal application of Calendula offi cinalis preparations has not been evaluated. The threshold of toxicological concern is only based on a pragmatic risk assessment approach that gained regulatory acceptance for food

We performed a review with the purpose to summarise, analyse and discuss the evidence provided by clinical studies evaluating effectiveness of melatonin in the cure of tinnitus. Due to the fact that there is no satisfactory treatment for tinnitus, clinical research has explored new therapeutic approaches. A search of Pubmed, Medline, Embase, Central and Google Scholar was conducted to find trials published prior March 2014 on melatonin in the treatment of tinnitus. Design of the studies, randomization, allocation concealment procedures and diagnostic instruments (scales for tinnitus evaluation) were critical evaluated. Five clinical studies have been included. Three of them tested effectiveness of melatonin alone, the remaining two along with sulpiride and sulodexide respectively. Considered clinical trials adopted various experimental designs: single arm, randomised placebo-controlled and randomised placebo-controlled followed by crossover. These studies were characterised by several methodological weaknesses. Confirmation of melatonin clinical effectiveness in the treatment of tinnitus cannot be given in the light of the biases observed in the considered evidence. Melatonin seems to improve sleep disturbance linked to tinnitus.

Background : Tranexamic acid is a synthetic lysine derivate that exerts its antifibrinolytic effect by reversible blocking lysine binding sites on plasminogen preventing fibrin degradation. It is widely used for haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis. Aim: The aim of our work was to review the literature regarding the best evidence on tranexamic adverse reactions and to describe them according to the apparatus involved. Methods: The literature was searched for publications on tranexamic acid adverse reactions, adverse events, using MEDLINE, Scopus, Embase, Web of Science and Google Scholar. Results: In the light of the results, seems to be clear that tranexamic acid causes several adverse reactions involving different apparatus. Hypersensitivity reactions, cerebrovascular infarction, myocardial infarction and pulmonary embolism seem to be the more common tranexamic acid adverse reactions. Conclusion: Despite the wide use of tranexamic acid the number of cases reported for type of reaction is relatively low, thus causing a not easy understanding of mechanisms underlying the adverse reaction. Therefore, it would be appropriate to conduct epidemiological studies on a large scale in order to better understand risk factors favoring tranexamic acid adverse reactions and encourage pharmacovigilance in medical practice.

Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions.