Medicines, Volume 5, Issue 2 (June 2018) – 34 articles

Background: Cancer patients often take over-the-counter anti-oxidants as primary treatment or in combination with chemotherapy. Data about such use in glioblastoma is limited. Methods: Cultured U87-MG cells, a primary glioblastoma cell line (MU1454), U87-MG derived stem-like cells (scU87), and MU1454 derived stem-like cell lines (scMU1454) were pre-treated with one of three anti-oxidants—Vitamin D₃, Melatonin, and alpha-lipoic acid (LA)—for 72 h, followed by a 72 h treatment with temozolomide (TMZ). MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assessed cell proliferation. DCFDA Cellular ROS Detection Assay and Glutathione peroxidase (GP×1) activity assessed the anti-oxidant effect of TMZ +/− an anti-oxidant drug. Results: Vitamin D₃ did not affect MU1454, but had slight TMZ synergism for U87-MG. Melatonin 1 mM decreased U87-MG and MU1454 cell proliferation. As pretreatment to TMZ, melatonin 1 mM and 50 nM significantly reduced proliferation. LA 1 mM had a significant effect alone or with TMZ on U87-MG and MU1454. LA 250 uM also reduced proliferation by almost 50%. Melatonin and LA significantly enhanced the responsiveness of scMU1454 to TMZ, while Melatonin 50 nM exerted similar effects on scU87. The anti-oxidants were associated with generally decreased reactive oxygen species and limited GP×1 effects. Conclusions: Anti-oxidants may have synergistic effects with TMZ. LA offers the most promise, followed by melatonin. Full article

Background: Indirect moxibustion (IM) has been previously performed between the spinous process while recording skin temperature of the trunk. However, moxibustion is often applied not only to acupuncture points on the back, but also to points located on the limbs. Thus, there is a need to investigate skin temperature (ST) responses following IM applied to the limbs. Methods: In Experiment 1 (Exp 1), subjects were randomly assigned to three groups: the left IM stimulation, right IM stimulation and control groups. In Experiment 2 (Exp 2), the subjects underwent two experimental sessions consisting of a single stimulation of IM or triple stimulations of IM. The IM stimulation was administered to the ST36 acupuncture point. A thermograph was used to obtain the ST on the lower limbs. Results: In Exp 1, the ST of the lower limbs increased in the stimulation groups whereas there was no increase in the non-stimulation group. In Exp 2, no significant response occurred between the single and triple stimulation of IM groups for all observed sites except for the left ankle ST. Conclusions: Lower limb ST increased following IM application to the ST36 point. No difference was observed between the dosage of the stimulation and ST responses. Full article

Background: Anxiety and depression are conferring an increasing burden on society. Although treatments exist for both conditions, side effects, and difficulties accessing treatment prevent many people from receiving adequate assistance. Nutritional approaches have demonstrated some success in treating anxiety and depression. We plan to investigate whether a micronutrient formula, Daily Essential Nutrients, improves symptoms of anxiety and depression compared to a placebo in a community recruited sample. Methods: This will be a randomized, double blind placebo controlled study (RCT). Two hundred adults will be assigned to either a placebo or micronutrient group (placebo or Daily Essential Nutrients (DEN)) in a 1:1 ratio. Baseline data will be collected for 2 weeks, followed by 10 weeks of placebo or micronutrient intervention. Psychometrics will be used to measure progress and participant safety will be monitored weekly. Results: The primary outcome measures will be total scores on three measures of symptom severity at 10 weeks. Linear mixed modelling will be used to measure between group differences and effect sizes will be calculated using pooled mean scores and standard deviations over the course of the trial. Conclusions: If effective, micronutrients could provide an alternative treatment, with fewer barriers and adverse events than currently available treatments. Full article

Abstract: Background: We are reporting here about a 3-month-old boy with a history of failure to thrive, hypertrophic obstructive cardiomyopathy and neurological misbehaviour including hypotension in body muscles, who was found to have screaming attacks, agitation and restlessness. Methods/Results: Body and ear acupuncture was used both as supporting and integrative therapy to reduce the phases of restlessness and screaming and, simultaneously, the use of hypnotic drugs, as well as to improve the baby’s thriving. Conclusions: Our case has proved that standardised ear and body acupuncture applied by trained acupuncturist paediatricians is a helpful non-pharmacological treatment tool. While acupuncture is typically used in the outpatient setting, it can equally be used in the inpatient setting, as exemplified by the positive outcome of the presented case. Full article

Background: The effect of synchronous chemotherapy in squamous cell carcinoma of the head and neck (SCCHN) has been modelled as additional Biologically Effective Dose (BED) or as a prolonged tumour cell turnover time during accelerated repopulation. Such models may not accurately predict the local control seen when hypofractionated accelerated radiotherapy is used with synchronous chemotherapy. Methods: For the purposes of this study three isoeffect relationships were assumed: Firstly, from the RTOG 0129 trial, synchronous cisplatin chemotherapy with 70 Gy in 35 fractions over 46 days results in equivalent local control to synchronous cisplatin chemotherapy with 36 Gy in 18# followed by 36 Gy in 24# (2# per day) over a total of 39 days. Secondly, in line with primary local control outcomes from the PET-Neck study, synchronous cisplatin chemotherapy with 70 Gy in 35# over 46 days results in equivalent local control to synchronous cisplatin chemotherapy delivered with 65 Gy in 30# over 39 days. Thirdly, from meta-analysis data, 70 Gy in 35# over 46 days with synchronous cisplatin results in equivalent local control to 84 Gy in 70# over 46 days delivered without synchronous chemotherapy. Using the linear quadratic equation the above isoeffect relationships were expressed algebraically to determine values of α, α/β, and k for SCCHN when treated with synchronous cisplatin using standard parameters for the radiotherapy alone schedule (α = 0.3 Gy⁻¹, α/β = 10 Gy, and k = 0.42 Gy₁₀day⁻¹). Results: The values derived for α/β, α and k were 2 Gy, 0.20 and 0.21 Gy⁻¹, and 0.65 and 0.71 Gy₂day⁻¹. Conclusions: Within the limitations of the assumptions made, this model suggests that accelerated repopulation may remain a significant factor when synchronous chemotherapy is delivered with radiotherapy in SCCHN. The finding of a low α/β for SCCHN treated with cisplatin suggests a greater tumour susceptibility to increasing dose per fraction and underlines the importance of the completion of randomized trials examining the role of hypofractionated acceleration in SCCHN. Full article

Background: According to recent studies, reactive oxygen is the leader of human metabolic disease development. The use of natural antioxidants is the best way to stop or prevent this problem. Therefore, the aim of this study was to evaluate the antioxidant and anti-inflammatory activities and to determine the polyphenolic contents of the Bidens engleri and Boerhavia erecta fractions. Methods: Plant fractions were obtained using Soxhlet procedures with hexane, dichloromethane, acetonitrile, ethyl acetate, methanol, and butanol solvent, successively. The different fractions were compared according to their antioxidant, anti-inflammatory activities, total phenolic, and total flavonoid contents. The phenolic contribution to the biological activity was evaluated. Result: The Bidens engleri and Boerhavia erecta fractions showed the highest antioxidant abilities, notably the polar fractions, which inhibited significantly the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-O-azinobis(3-ethylbenzoline-6-sulphonate) (ABTS). The butanol fraction from Bidens engleri and methanol fraction from Boerhavia erecta have presented the best iron (III) reduction power with 211.68 and 198.55 mgAAE/g, respectively. Butanol and acetonitrile were the best solvents for extracting phenolic compounds from Bidens engleri and Boerhavia erecta, respectively. In contrast, dichloromethane was the best solvent for extracting a flavonoid from two plants with anti-COX-2 and anti-LOX-15 active compounds. The phenolic compound contributed significantly to antioxidant activity (r > 0.80). Conclusion: The Bidens engleri and Boerhavia erecta fractions possessed a potential antioxidant for fighting oxidative stress and helping to prevent diabetes, hypertension, and cardiovascular diseases. The uses of this plant could be promoted in Burkina Faso. Full article

Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis. Full article

Evidence of the health and wellbeing benefits of Tai Chi and Qigong (TQ) have emerged in the past two decades, but TQ is underutilized in modern health care in Western countries due to lack of promotion and the availability of professionally qualified TQ instructors. To date, there are no government regulations for TQ instructors or for training institutions in China and Western countries, even though TQ is considered to be a part of Traditional Chinese medicine that has the potential to manage many chronic diseases. Based on an integrative health care approach, the accreditation standard guideline initiative for TQ instructors and training institutions was developed in collaboration with health professionals, integrative medicine academics, Tai Chi and Qigong master instructors and consumers including public safety officers from several countries, such as Australia, Canada, China, Germany, Italy, Korea, Sweden and USA. In this paper, the rationale for organizing the Medical Tai Chi and Qigong Association (MTQA) is discussed and the accreditation standard guideline for TQ instructors and training institutions developed by the committee members of MTQA is presented. The MTQA acknowledges that the proposed guidelines are broad, so that the diversity of TQ instructors and training institutions can be integrated with recognition that these guidelines can be developed with further refinement. Additionally, these guidelines face challenges in understanding the complexity of TQ associated with different principles, philosophies and schools of thought. Nonetheless, these guidelines represent a necessary first step as primary resource to serve and guide health care professionals and consumers, as well as the TQ community. Full article

The increasing devolution of healthcare towards community care has meant that the management of many conditions is conducted within the home either by community nurses or by the patients themselves. The administration of medicines within home healthcare scenarios can however be problematic—especially when considering the delivery of medicines through injection. The possibility of needlestick injury (NSI) has become an ever-present hazard within healthcare settings, with a significant proportion of percutaneous injuries occurring during the handling and disposal of the needle. The emergence of transdermal microneedle systems, however, offers a potentially revolutionary advance and could dramatically improve safety—particularly within home healthcare where there are mounting concerns over the use and disposal of sharps. A mini-review of the advantages proffered by microneedle drug delivery technologies is presented and the potential impact on delivery of medicines within the home is critically appraised. Full article

Background: Leishmaniasis is a complex protozoa disease caused by Leishmania genus (Trypanosomatidae family). Currently, there have been renewed interests worldwide in plants as pharmaceutical agents. In this study, the in vivo efficacy of Solanum spp. is assessed in an L. amazonensis BALB/c mice model for experimental cutaneous leishmaniasis. Methods: Animals were infected with 5 × 10⁶ metacyclic promastigotes and 30-day post-infection, a treatment with 30 mg/kg of Solanum extracts or Glucantime^® (GTM) was applied intralesionally every four days to complete 5 doses. Results: Neither death nor loss of weight higher than 10% was observed. All the tested extracts were able to control the infection, compared with the infected and untreated group. Solanum havanense Jacq. extract showed the highest efficacy and was superior (p < 0.05) to GTM. Solanum myriacanthum Dunal., S. nudum Dunal. and S. seaforthianum Andr. extracts demonstrated a similar effect (p > 0.05) to GTM. An increase of IFN-γ (p < 0.05) was displayed only by animals treated with S. nudum compared to the group treated with a vehicle, while no differences (p > 0.05) were observed for IL-12. Conclusions: In vivo effects of Solanum extracts were demonstrated, suggesting that this genus could be further explored as a new antileishmanial alternative. Full article

The regenerative medicine field has been revolutionized by the direct conversion of one cell type to another by ectopic expression of lineage-specific transcription factors. The direct reprogramming of fibroblasts to induced cardiac myocytes (iCMs) by core cardiac transcription factors (Gata4, Mef2c, Tbx5) both in vitro and in vivo has paved the way in cardiac regeneration and repair. Several independent research groups have successfully reported the direct reprogramming of fibroblasts in injured myocardium to cardiac myocytes employing a variety of approaches that rely on transcription factors, small molecules, and micro RNAs (miRNAs). Recently, this technology has been considered for local repair of the pacemaker and the cardiac conduction system. To address this, we will first discuss the direct reprograming advancements in the setting of working myocardium regeneration, and then elaborate on how this technology can be applied to repair the cardiac pacemaker and the conduction system. Full article

Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD. The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD. Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial. Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden. Full article

Astragali Radix (AR), a Chinese materia medica (CMM) known as Huangqi, is an important medicine prescribed in herbal composite formulae (Fufang) by Traditional Chinese medicine (TCM) practitioners for thousands of years. According to the literature, AR is suggested for patients suffering from “Qi”- and “Blood”-deficiencies, and its clinical effects are reported to be related to anti-cancer cell proliferation, anti-oxidation, relief of complications in cardiovascular diseases, etc. The underlying cell signaling pathways involved in the regulation of these various diseases are presented here to support the mechanisms of action of AR. There are two botanical sources recorded in China Pharmacopoeia (CP, 2015): Astragalus membranaceus (Fisch.) Bge. Var. mongohlicus, (Bge.) Hsiao, and Astragalus membranaceus (Fisch.) Bge. (Fam. Leguminosae), whose extracts of dried roots are processed via homogenization-assisted negative pressure cavitation extraction. Geographic factors and extraction methods have impacts on the pharmaceutical and chemical profiles of AR. Therefore, the levels of the major bioactive constituents of AR, including polysaccharides, saponins, and flavonoids, may not be consistent in different batches of extract, and the pharmaceutical efficacy of these bioactive ingredients may vary depending on the source. Therefore, the present review mainly focuses on the consistency of the available sources of AR and extracts and on the investigation of the biological functions and mechanisms of action of AR and of its major bioactive constituents. Furthermore, it will also include a discussion of the most popular AR composite formulae to further elucidate their chemical and biological profiles and understand the pharmaceutical value of AR. Full article

Background: Iron deficiency is a public health problem in many low- and middle-income countries. Introduction of agro-industrial food by-products, as additional source of nutrients, could help alleviate this micronutrient deficiency, provide alternative sources of nutrients and calories in developed countries, and be a partial solution for disposal of agro-industry by-products. Methods: The aim of this study was to determine iron bioavailability of 5 by-products from Brazilian agro-industry (peels from cucumber, pumpkin, and jackfruit, cupuaçu seed peel, and rice bran), using the in vitro digestion/ Caco-2 cell model; with Caco-2 cell ferritin formation as a surrogate marker of iron bioavailability. Total and dialyzable Fe, macronutrients, the concentrations of iron-uptake inhibitors (phytic acid, tannins, fiber) and their correlation with iron bioavailability were also evaluated. Results: The iron content of all by-products was high, but the concentration of iron and predicted bioavailability were not related. Rice bran and cupuaçu seed peel had the highest amount of phytic acid and tannins, and lowest iron bioavailability. Cucumber peels alone, and with added extrinsic Fe, and pumpkin peels with extrinsic added iron, had the highest iron bioavailability. Conclusion: The results suggest that cucumber and pumpkin peel could be valuable alternative sources of bioavailable Fe to reduce iron deficiency in at-risk populations. Full article

Background: Pharmacological treatment is still the key intervention in the disease management of long-term patients with schizophrenia; however, how it affects sleep and whether gender differences exist remains unclear. Methods: Forty-six long-term outpatients with schizophrenia entered the study. The numbers of antipsychotics, sleep medications, antidepressants, and anxiolytics were analyzed. Moreover, all patients were tested using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Correlation analyses were conducted between the medication used and the scores on the two subjective sleep inventories. Results: A large variability, ranging from 0 to 8, in the total number of psychiatric drugs per person was found between the patients. Despite ongoing pharmacological treatment, the patients scored high on the PSQI, but not on the ESS; this indicates that they report problems with sleep, but not with daytime sleepiness. A significant positive correlation between the use of antipsychotics and the ESS score, but not the PSQI score, was found; moreover, no gender differences were found. Conclusions: A large variability exists in the pharmacological treatment of long-term patients with schizophrenia. To date, patients’ sleep problems have been insufficiently treated, and gender differences have not been adequately accounted for in the pharmacological treatment of schizophrenia. More and larger international clinical studies are warranted to verify the findings of the present preliminary pilot study before any firm conclusions can be drawn and before any changes to the drug treatment of male and female patients with schizophrenia can be recommended. Full article

Background: Burkina Faso is classified among the countries with a high prevalence (˃12%) of hepatitis. Hepatic diseases, such as cirrhosis—related to alcoholism—and hepatitis B and C, are the cause of the increase in cases of liver cancer. They promote the development of cancer by decreasing the natural cell death, causing problems with DNA repair, or by increasing the production of free radical toxins to the cell. According to the World Health Organization (WHO), there were nearly 639,000 deaths from liver cancer worldwide in 2014, hence the need to search for natural hepatoprotective molecules. Objective: To evaluate the hepatoprotective potential of Acanthospermum hispidum extracts on rats and the antioxidant capacity of extracts in vitro and in vivo, and to perform phytochemistry. Methods: The ethanolic and aqueous extracts of the whole Acanthospermum hispidum plant were used to evaluate hepatoprotection. The hepatotoxin used in our case was diethylenitrosamine. The animals were divided into groups of six. The sera of the treated animals were used for the determination of transaminases, and the liver homogenates were used for the determination of antioxidant. The total phenol and flavonoid contents, and the antioxidant properties of the extracts, were evaluated in vitro. Results: The results of the in vitro antioxidant tests showed good antioxidant activity of the ethanolic extract, using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test (0.08 ± 0.0018 μg/mL) and 2,2′-azinobis (3-ethylbenzolin-6-sulphonate) (ABTS) (246.05 ± 1.55 mmol TE/g). The in vivo tests showed, through the evaluation of the antioxidant in vivo and the biochemical parameters, that the ethanolic extract with the highest phenolic content had a good hepatoprotective capacity. Conclusions: The antioxidant activity of Acanthopermum hispidum extracts would justify the observed hepatoprotective activity. These results confirmed that the plant is used in the treatment of liver diseases in traditional medicine in Burkina Faso. Full article

Background: Traditional Chinese medicine (TCM) may be understood as a system of sensations and findings designed to establish the functional vegetative state of the body. This state may be treated by several therapeutic methods such as acupuncture, Chinese pharmacotherapy, dietetics, Tuina, and Qigong. Nowadays, as a result of several evidence-based reported beneficial effects over specific pathological conditions, there is an increasing tendency to integrate some of these practices in Western medicine. The main goal of this study was to perform a bibliometric analysis of TCM scientific production between 1982 and 2016 indexed in PubMed, by analyzing several parameters including time and location distribution, publication quality, experimental design, and treatment methods. Methods: The methodology was based on the quantitative inventory of published scientific research indexed in PubMed medical subject headings (MeSH), sorted within the broad term “Traditional Chinese Medicine” and integrating the following criteria as limit filters: “Species: Humans”, “Article Type: Clinical Trial”. In addition, the articles’ triage was ruled by temporal limitations set between 1945 and 2016. Results: The overall analysis of data allowed observation of an average annual growth of approximately 33%, with a productive peak of 122 articles in 2007. The scientific production was distributed in 27 countries, led by China (76.1%), followed by the United States of America (3.0%) and South Korea (2.1%). A significant amount of references were published in Chinese journals: more than 50%; however, these journals had a low impact factor. The most cited treatments in the keywords section of the articles were phytotherapy (55%) and acupuncture (40%). Conclusion: The increasing demand for TCM seems to be due to factors such as lower side effects and greater efficacy in some patients not responding well to conventional therapy. As a result, a considerable amount of TCM science-based literature has been produced, supporting the rational integration of these practices in Western healthcare systems and research. Our results show that the quality of TCM research and inherent publications have been increasing over the last decades, with a higher incidence of studies published in well-ranked journals. Full article

Thirty years after the rise of the evidence-based medicine (EBM) movement, formal training in philosophy remains poorly represented among medical students and their educators. In this paper, I argue that EBM’s reception in this context has resulted in a privileging of empiricism over rationalism in clinical reasoning with unintended consequences for medical practice. After a limited review of the history of medical epistemology, I argue that a solution to this problem can be found in the method of the 2nd-century Roman physician Galen, who brought empiricism and rationalism together in a synthesis anticipating the scientific method. Next, I review several of the problems that have been identified as resulting from a staunch commitment to empiricism in medical practice. Finally, I conclude that greater epistemological awareness in the medical community would precipitate a Galenic shift toward a more epistemically balanced, scientific approach to clinical research. Full article

Cardiovascular diseases (CVDs) have become prominent in mortality and morbidity rates. Prevalent cardiovascular conditions, such as hypertension, atherosclerosis and oxidative stress, are increasing at an alarming rate. Conventional drugs have been associated with adverse effects, suggesting a need for an alternative measure to ameliorate CVD. A number of plant- and herb-derived preventative food and therapeutic drugs for cardiovascular conditions are progressively used for their various benefits. Naturally derived food and drugs have fewer side effects because they come from natural elements; preventative food, such as grape seed, inhibits changes of histopathology and biomarkers in vital organs whereas therapeutic drugs, for instance Xanthone, improve heart functions by suppressing oxidative stress of myocyte. This review closely examines the various plant- and herb-derived drugs that have assumed an essential role in treating inflammation and oxidative stress for prevalent cardiovascular conditions. Furthermore, the use of plant-derived medicine with other synthetic particles, such as nanoparticles, for targeted therapy is investigated for its effective clinical use in the future. Full article

Background: Garlics and onions have been used for the treatment of diseases caused by parasites and microbes since ancient times. Trypanosomiasis and leishmaniasis are a concern in many areas of the world, especially in poor countries. Methods: Trypanosoma brucei brucei and Leishmania tarentolae were used to investigate the anti-parasitic effects of dichloromethane extracts of Allium sativum (garlic) and Allium cepa (onion) bulbs. As a confirmation of known antimicrobial activities, they were studied against a selection of G-negative, G-positive bacteria and two fungi. Chemical analyses were performed using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (LC-ESI-MS/MS). Results: Chemical analyses confirmed the abundance of several sulfur secondary metabolites in garlic and one (zwiebelane) in the onion extract. Both extracts killed both types of parasites efficiently and inhibited the Trypanosoma brucei trypanothione reductase irreversibly. In addition, garlic extract decreased the mitochondrial membrane potential in trypanosomes. Garlic killed the fungi C. albicans and C. parapsilosis more effectively than the positive control. The combinations of garlic and onion with common trypanocidal and leishmanicidal drugs resulted in a synergistic or additive effect in 50% of cases. Conclusion: The mechanism for biological activity of garlic and onion appears to be related to the amount and the profile of sulfur-containing compounds. It is most likely that vital substances inside the parasitic cell, like trypanothione reductase, are inhibited through disulfide bond formation between SH groups of vital redox compounds and sulfur-containing secondary metabolites. Full article

Background: These days, the desire for naturally occurring antioxidants has significantly increased, especially for use in foodstuffs, cosmetics, and pharmaceutical products, to replace synthetic antioxidants that are regularly constrained due to their carcinogenicity. Methods: The study in hand aimed to appraise the antioxidant effect of two Euphorbia dendroides extracts using reducing power, anti-peroxidation, and DPPH (1,1 Diphenyl 2 Pycril Hydrazil) scavenging essays, in addition to the anticancer activity against two tumor cell lines, namely C6 (rat brain tumor)cells, and Hela (human uterus carcinoma)cell lines. Results: The results indicated that the ethyl acetate extract exhibited antiradical activity of 29.49%, higher than that of n-butanol extract (18.06%) at 100 µg/mL but much lower than that of gallic acid (78.21%).The ethyl acetate extract exhibits better reducing capacity and lipid peroxidation inhibitory activity compared to n-butanol extract but less than all tested standards. Moreover, the ethyl acetate extract was found to have an antiproliferative activity of more than 5-FU (5-fluoro-Uracil) against C6 cells at 250 µg/mL with IC₅₀ and IC₇₅ of 113.97, 119.49 µg/mL, respectively, and good cytotoxic activity against the Hela cell lines at the same concentration. The HPLC-TOF-MS (high performance liquid chromatography-Time-of-flight-Mass Spectrometry) analyses exposed the presence of various compounds, among which Gallic and Chlorogenic acids functioned as major compounds. Conclusions: The two extracts exhibited moderate anticancer abilities and behaved somewhat as average antioxidant agents. Based on the total phenolics and flavonoids contents, as well as HPLC results, it could be concluded that antiproliferative and antioxidant activities depend upon the content of different phenolics and flavonoids. Full article

Kampo medicines prescribed by specialized medical practitioners and Japanese physicians have gradually reemerged in Japan as alternatives to Western medications. Kampo formulations are composed of several plant extracts and, as such, the broad variety of phytochemicals they contain likely act synergistically to provide their beneficial effects. Kampo medicines have traditionally been prescribed for a number of health conditions, including chronic hepatitis, bronchial asthma, anemia, etc. The aim of this article is to review the beneficial effects of Kampos with respect to oral health. Pertinent papers published between 1970 and 2017 were retrieved by searching in PubMed, ScienceDirect, Web of Science, and Scopus using key words followed by evaluation of the relevant articles. In vitro studies have identified a number of properties that give credence to the potential of Kampos for treating or preventing oral diseases/disorders. Given their anti-microbial and anti-inflammatory properties, they may be promising agents for controlling periodontal diseases, oral mucositis, xerostomia, and drug-induced gingival overgrowth. Since some oral diseases have a complex etiology that involves microbial pathogens and the host immune response, agents with dual functionality such as Kampo phytochemicals may offer a therapeutic advantage. Full article

Background: The study was designed to explore any beneficial effect of Ocimum sanctum (Linn) (OS) in experimental pulmonary hypertension (PH) in rats. OS is commonly known as “holy basil” and “Tulsi” and is used in the Indian System of Medicine as antidiabetic, antioxidant, hepatoprotective, adaptogenic, and cardioprotective. Methods: Monocrotaline (MCT) administration caused development of PH in rats after 28 days and rats were observed for 42 days. Treatments (sildenafil; 175 µg/kg, OS; 200 mg/kg) were started from day 29 after the development of PH and continued for 14 days. Parameters to assess the disease development and effectiveness of interventions were echocardiography, right and left ventricular systolic pressures, and right ventricular end diastolic pressure, percentage medial wall thickness (%MWT) of pulmonary artery, oxidative stress markers in lung tissue, NADPH oxidase (Nox-1) protein expression in lung, and mRNA expression of Bcl2 and Bax in right ventricular tissue. Results: OS (200 mg/kg) treatment ameliorated increased lung weight to body weight ratio, right ventricular hypertrophy, increased RVSP, and RVoTD/AoD ratio. Moreover, OS treatment decreases Nox-1 expression and increases expression of Bcl2/Bax ratio caused by MCT. Conclusion: The present study demonstrates that OS has therapeutic ability against MCT-induced PH in rat which are attributed to its antioxidant effect. The effect of OS was comparable with sildenafil. Full article

Background: Natural antioxidants, which can replace synthetic ones due to their potential implications for health problems in children, have gained significant popularity. Therefore, the antioxidant potential of extracts obtained from three brown macroalgae (Ascophyllum nodosum, Fucus vesiculosus and Bifurcaria bifurcata) and two microalgae (Chlorella vulgaris and Spirulina platensis) using ultrasound-extraction as an innovative and green approach was evaluated. Methods: Algal extracts were obtained by ultrasound-assisted extraction using water/ethanol (50:50, v:v) as the extraction solvent. The different extracts were compared based on their antioxidant potential, measuring the extraction yield, the total phenolic content (TPC) and the antioxidant activity. Results: Extracts from Ascophyllum nodosum (AN) and Bifurcaria bifurcata (BB) showed the highest antioxidant potential compared to the rest of the samples. In particular, BB extract presented the highest extraction (35.85 g extract/100 g dry weight (DW)) and total phenolic compounds (TPC) (5.74 g phloroglucinol equivalents (PGE)/100 g DW) yields. Regarding the antioxidant activity, macroalgae showed again higher values than microalgae. BB extract had the highest antioxidant activity in the ORAC, DPPH and FRAP assays, with 556.20, 144.65 and 66.50 µmol Trolox equivalents (TE)/g DW, respectively. In addition, a correlation among the antioxidant activity and the TPC was noted. Conclusions: Within the obtained extracts, macroalgae, and in particular BB, are more suitable to be used as sources of phenolic antioxidants to be included in products for human consumption. The relatively low antioxidant potential, in terms of polyphenols, of the microalgae extracts studied in the present work makes them useless for possible industrial applications compared to macroalgae, although further in vivo studies evaluating the real impact of antioxidants from both macro- and micro-algae at the cellular level should be conducted. Full article

Background: Magnetic resonance (MR)-fusion contouring is the standard of care in prostate stereotactic body radiotherapy (SBRT) for target volume localisation. However, the planning computerised tomography (CT) scan continues to be used for dose calculation and treatment planning and verification. Discrepancies between the planning MR and CT scans may negate the benefits of MR-fusion contouring and it adds a significant resource burden. We aimed to determine whether CT-only contouring resulted in a dosimetric detriment compared with MR-fusion contouring in prostate SBRT planning. Methods: We retrospectively compared target volumes and SBRT plans for 20 patients treated clinically with MR-fusion contouring (standard of care) with those produced by re-contouring using CT data only. Dose was 36.25 Gy in 5 fractions. CT-only contouring was done on two occasions blind to MR data and reviewed by a separate observer. Primary outcome was the difference in rectal volume receiving 36 Gy or above. Results: Absolute target volumes were similar: 63.5 cc (SD ± 27.9) versus 63.2 (SD ± 26.5), Dice coefficient 0.86 (SD ± 0.04). Mean difference in apex superior-inferior position was 1.1 (SD ± 3.5; CI: −0.4–2.6). Small dosimetric differences in favour of CT-only contours were seen, with the mean rectal V36 Gy 0.3 cc (95% CI: 0.1–0.5) lower for CT-only contouring. Conclusions: Prostate SBRT can be successfully planned without MR-fusion contouring. Consideration can be given to omitting MR-fusion from the prostate SBRT workflow, provided reference to diagnostic MR imaging is available. Development of MR-only work flow is a key research priority to gain access to the anatomical fidelity of MR imaging. Full article

The World Health Organization announced that cardiovascular disease is the number one cause of death globally, representing 31% of all global deaths. Coronary artery disease (CAD) affects approximately 5% of the US population aged 40 years and older. With an age-adjusted prevalence of approximately 12%, peripheral artery disease (PAD) affects at least 8 to 12 million Americans. Both CAD and PAD are caused by mainly atherosclerosis, the hardening and narrowing of arteries over the years by lipid deposition in the vascular bed. Despite the significant advances in interventions for revascularization and intensive medical care, patients with CAD or PAD who undergo percutaneous transluminal angioplasty have a persistent high rate of myocardial infarction, amputation, and death. Therefore, new therapeutic strategies are urgently needed for these patients. To overcome this unmet need, therapeutic angiogenesis using angiogenic growth factors has evolved in an attempt to stimulate the growth of new vasculature to compensate for tissue ischemia. After nearly 20 years of investigation, there is growing evidence of successful or unsuccessful gene therapy for ischemic heart and limb disease. This review will discuss basic and clinical data of therapeutic angiogenesis studies employing angiogenic growth factors for PAD patients and will draw conclusions on the basis of our current understanding of the biological processes of new vascularization. Full article

Background: Recent research has evaluated psychological and biological characteristics associated with pain in survivors of breast cancer (BC). Few studies consider their relationship with inflammatory activity. Voluntary facial expressions modify the autonomic activity and this may be useful in the hospital environment for clinical biopsychosocial assessment of pain. Methods: This research compared a BC survivors group under integral treatment (Oncology, Psychology, Nutrition) with a control group to assess the intensity of pain, behavioral interference, anxiety, depression, temperament-expression, anger control, social isolation, emotional regulation, and alexithymia and inflammatory activity, with salivary interleukin 6 (IL-6). Then, a psychophysiological evaluation through repeated measures of facial infrared thermal imaging (IRT) and hands in baseline—positive facial expression (joy)—negative facial expression (pain)—relaxation (diaphragmatic breathing). Results: The results showed changes in the IRT (p < 0.05) during the execution of facial expressions in the chin, perinasal, periorbital, frontal, nose, and fingers areas in both groups. No differences were found in the IL-6 level among the aforementioned groups, but an association with baseline nasal temperature (p < 0.001) was observable. The BC group had higher alexithymia score (p < 0.01) but lower social isolation (p < 0.05), in comparison to the control group. Conclusions: In the low- and medium-concentration groups of IL-6, the psychophysiological intervention proposed in this study has a greater effect than on the high concentration group of IL-6. This will be considered in the design of psychological and psychosocial interventions for the treatment of pain. Full article

Background: Schizophrenia is a severe psychiatric disorder that has a large impact on patients’ lives. In addition to Western medicine, the use of additional treatments, such as acupuncture, in treating the positive, negative, and cognitive symptoms is increasing. Methods: We conducted a systematic review on the use of acupuncture as an add-on treatment for patients with schizophrenia that are in regular care, with a special focus on the treatment of the often accompanying sleep disorders. In this study, we searched the Medline, ScienceDirect, Cochrane Library, Scopus, and ERIC databases with a cut-off date of 31 December 2017, thereby following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results: Our search resulted in 26 eligible studies with 1181 patients with schizophrenia who received acupuncture treatment. Most studies showed limited evidence for the use of acupuncture as add-on therapy in the treatment of the positive, negative, and cognitive symptoms, but beneficial effects have been reported in the treatment of the accompanying sleep disorders. Conclusions: Limited evidence was found for the use of acupuncture as add-on therapy in the treatment of patients with schizophrenia; however, positive results were found in the treatment of sleep disorders, but this result needs to be confirmed in large, randomized, controlled trials. Full article