Suresh L. Mehta, Anil K. Chokkalla, Saivenkateshkomal Bathula
et al.
Transient focal ischemia decreased microRNA-7 (miR-7) levels, leading to derepression of its major target α-synuclein (α-Syn) that promotes secondary brain damage. Circular RNA CDR1as is known to regulate miR-7 abundance and function. Hence, we currently evaluated its functional significance after focal ischemia. Transient middle cerebral artery occlusion (MCAO) in adult mice significantly downregulated both CDR1as and miR-7 levels in the peri-infarct cortex between 3 and 72 h of reperfusion. Interestingly, neither pri-miR-7a nor 7b was altered in the ischemic brain. Intracerebral injection of an AAV9 vector containing a CDR1as gene significantly increased CDR1as levels by 21 days that persisted up to 4 months without inducing any observable toxicity in both sham and MCAO groups. Following transient MCAO, there was a significant increase in miR-7 levels and CDR1as binding to Ago2/miR-7 in the peri-infarct cortex of AAV9-CDR1as cohort compared with AAV9-Control cohort at 1 day of reperfusion. CDR1as overexpression significantly suppressed post-stroke α-Syn protein induction, promoted motor function recovery, decreased infarct size, and curtailed the markers of apoptosis, autophagy mitochondrial fragmentation, and inflammation in the post-stroke brain compared with AAV9-Control-treated cohort. Overall, our findings imply that CDR1as reconstitution is neuroprotective after stroke, probably by protecting miR-7 and preventing α-Syn-mediated neuronal death.
Tesfay Mehari Atey, Gregory M. Peterson, Mohammed S. Salahudeen
et al.
Introduction: Partnered pharmacist medication charting (PPMC), a process redesign hypothesised to improve medication safety and interdisciplinary collaboration, was trialed in a tertiary hospital’s emergency department (ED).Objective: To evaluate the health-related impact and economic benefit of PPMC.Methods: A pragmatic, controlled study compared PPMC to usual care in the ED. PPMC included a pharmacist-documented best-possible medication history (BPMH), followed by a clinical conversation between a pharmacist and a medical officer to jointly develop a treatment plan and chart medications. Usual care included medical officer-led traditional medication charting in the ED, without a pharmacist-obtained BPMH or clinical conversation. Outcome measures, assessed after propensity score matching, were length of hospital or ED stay, relative stay index (RSI), in-hospital mortality, 30-day hospital readmissions or ED revisits, and cost.Results: A total of 309 matched pairs were analysed. The median RSI was reduced by 15.4% with PPMC (p = 0.029). There were no significant differences between the groups in the median length of ED stay (8 vs. 10 h, p = 0.52), in-hospital mortality (1.3% vs. 1.3%, p > 0.99), 30-day readmission rates (21% vs. 17%; p = 0.35) and 30-day ED revisit rates (21% vs. 19%; p = 0.68). The hospital spent approximately $138.4 for the cost of PPMC care per patient to avert at least one medication error bearing high/extreme risk. PPMC saved approximately $1269 on the average cost of each admission.Conclusion: Implementing the ED-based PPMC model was associated with a significantly reduced RSI and admission costs, but did not affect clinical outcomes, noting that there was an additional focus on medication reconciliation in the usual care group relative to current practice at our study site.
Duncan C. Humphries, Duncan C. Humphries, Ross Mills
et al.
Rationale: Galectin-3 (Gal-3) drives fibrosis during chronic lung injury, however, its role in acute lung injury (ALI) remains unknown. Effective pharmacological therapies available for ALI are limited; identifying novel concepts in treatment is essential. GB0139 is a Gal-3 inhibitor currently under clinical investigation for the treatment of idiopathic pulmonary fibrosis. We investigate the role of Gal-3 in ALI and evaluate whether its inhibition with GB0139 offers a protective role. The effect of GB0139 on ALI was explored in vivo and in vitro.Methods: The pharmacokinetic profile of intra-tracheal (i.t.) GB0139 was investigated in C57BL/6 mice to support the daily dosing regimen. GB0139 (1–30 µg) was then assessed following acute i.t. lipopolysaccharide (LPS) and bleomycin administration. Histology, broncho-alveolar lavage fluid (BALf) analysis, and flow cytometric analysis of lung digests and BALf were performed. The impact of GB0139 on cell activation and apoptosis was determined in vitro using neutrophils and THP-1, A549 and Jurkat E6 cell lines.Results: GB0139 decreased inflammation severity via a reduction in neutrophil and macrophage recruitment and neutrophil activation. GB0139 reduced LPS-mediated increases in interleukin (IL)-6, tumor necrosis factor alpha (TNFα) and macrophage inflammatory protein-1-alpha. In vitro, GB0139 inhibited Gal-3-induced neutrophil activation, monocyte IL-8 secretion, T cell apoptosis and the upregulation of pro-inflammatory genes encoding for IL-8, TNFα, IL-6 in alveolar epithelial cells in response to mechanical stretch.Conclusion: These data indicate that Gal-3 adopts a pro-inflammatory role following the early stages of lung injury and supports the development of GB0139, as a potential treatment approach in ALI.
Kyoung Mi Moon, Ju-Hye Yang, Min-Kyeong Lee
et al.
Maclurin is rich in some edible fruits such as <i>Morus alba</i> (white mulberry) and <i>Garcinia mangostana</i>. Although maclurin showed anti-cancer and antioxidant effects, its roles in ultraviolet (UV)-induced melanogenesis have not been studied. Here, we investigated the effects of maclurin in melanogenesis using skin cells and a three-dimensional human skin model. When the cytotoxicity of maclurin was examined in B16F10 cells, no cytotoxicity was found up to 20 μM. Maclurin suppressed UVB-mediated tyrosinase activation and melanin accumulation in B16F10 cells without changes in mRNA levels of melanogenesis-related genes including tyrosinase, TRP1, TRP2, CREB, and MITF. Moreover, maclurin reduced melanin contents in melan-a cells, a cell line for normal melanocytes. When applied to a human skin model consisting of the epidermis and melanocytes, maclurin significantly reduced UVB-induced melanin accumulation (~47%) in a concentration-dependent manner based on microscopic observation and Fontana-Masson staining. Protein–ligand docking simulation followed by binding residue analysis showed that maclurin may bind to inactivate tyrosinase by forming multiple hydrogen bonds and hydrophobic and aromatic interactions with the residues of tyrosinase. Together, our study suggests that maclurin may be applied as an anti-melanogenic agent.
D. I. Medina-Ibarra, I. Chouvarda, J. S. Murguia
et al.
Electroencephalography (EEG) signals convey information related to different processes that take place in the brain. From the EEG fluctuations during sleep, it is possible to establish the sleep stages and identify short events, commonly related to a specific physiological process or pathology. Some of these short events (called A-phases) present an organization and build up the concept of the Cyclic Alternating Pattern (CAP) phenomenon. In general, the A-phases abruptly modify the EEG fluctuations, and a singular behavior could occur. With the aim to quantify the abrupt changes during A-phases, in this work the wavelet analysis is considered to compute Hölder exponents, which measure the singularity strength. We considered time windows of 2s outside and 5s inside A-phases onset (or offset). A total number of 5121 A-phases from 9 healthy participants and 10 patients with periodic leg movements were analyzed. Within an A-phase the Hölder numerical value tends to be 0.6, which implies a less abrupt singularity. Whereas outside of A-phases, it is observed that the Hölder value is approximately equal to 0.3, which implies stronger singularities, i.e., a more evident discontinuity in the signal behavior. In addition, it seems that the number of singularities increases inside of A-phases. The numerical results suggest that the EEG naturally conveys singularities modified by the A-phase occurrence, and this information could help to conceptualize the CAP phenomenon from a new perspective based on the sharpness of the EEG instead of the oscillatory way.
Farid Dabaghian, Amir Azadi, Mohammad Mehdi Zarshenas
Background: Alzheimer’s disease (AD) is the most common type of dementia that has been cited in traditional Persian medicine (TPM) manuscripts under the heading "Farāmūshkārī", "Fesād-e-Zekr" and "Nesiān". Since AD is a significant challenge for health professionals, searching for natural and effective compounds is crucial. Objective: Given the importance of AD, this study has provided a standardized plant-based tablet based on TPM. Methods: Related preparations were extracted from leading pharmaceutical manuscripts of TPM. Out of 127 gathered compound formulations, a preparation containing Bunium persicum (Boiss.) B.Fedtsch. (Persian cumin) and Piper nigrum L. (black pepper) was selected from the Canon of Medicine of Avicenna. After evaluating various excipients for tablet preparation, the proportions of Persian cumin (40 %), black pepper (40 %), hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone (PVP) as solution binder (20 %) were chosen. The final formulation was undergone through ethanol and dichloromethane and essential oil extractions to prepare for HPTLC fingerprints and GC assessments, respectively. The total alkaloid in the tablet's ethanol extract was also determined via spectrophotometry. Results: The final tablet was standardized via GC based on trans-caryophyllene (29.22 %) and g-terpinene (17.72 %). Each tablet contains an average of 0.041 mg of trans-caryophyllene and 0.018 mg of g-terpinene. The amount of the total alkaloid in each tablet was determined 0.06 mg, equivalent to atropine. Conclusion: This prepared simple natural formulation can be considered a traditional-based product to be evaluated clinically and presented as a memory enhancer supplement.
Reduced myocardial miR-221 expression is associated with severe cardiac fibrosis in heart failure patients. We aimed to demonstrate its mechanisms in cardioprotection and remodeling following myocardial infarction (MI). Using in vitro hypoxia and reoxygenation (H/R) of H9c2 and rat cardiac fibroblast (cFB) models, we found that miR-221 protects H9c2 through combined anti-apoptotic and anti-autophagic effects and cFB via anti-autophagic effects alone in H/R. It inhibits myofibroblast (myoFB) activation as indicated by lowering α-smooth muscle actin (α-SMA) expression, gel contraction, and collagen synthesis (Sircol assay). In vivo, following left coronary artery ligation (MI), rats were treated with miR-221 mimics (intravenous [i.v.], 1 mg/kg). With treatment, miR-221 increased by ∼15-fold in infarct and peri-infarct zones at day 2 post-MI. At days 7 and 30 post-MI, miR-221 reduced infarct size, fibrosis, and α-SMA+ cells in both infarct and remote myocardium. Left ventricle (LV) function was preserved as indicated by ejection fraction, infarct thickness, LV developed pressure, ±dP/dt, and end diastolic pressure. We demonstrated the anti-apoptotic and anti-autophagic effects were due to combined mechanisms of direct targeting on Bak1 and P53 and inhibition of phosphorylation at Ser46 and direct targeting on Ddit4, respectively. miR-221 enhances cardiomyocyte survival and protects cardiac function post-MI. It enhances cFB survival yet inhibits their activation, thus reducing adverse cardiac fibrosis. Keywords: myocardial infarction, microRNA, apoptosis, autophagy, cardioprotection, cardiac remodeling, p-53, Ddit4, microRNA-221
Arianna Mencattini, Fabrizio Mattei, Giovanna Schiavoni
et al.
The increasing interest for microfluidic devices in medicine and biology has opened the way to new time-lapse microscopy era where the amount of images and their acquisition time will become crucial. In this optic, new data analysis algorithms have to be developed in order to extract novel features of cell behavior and cell–cell interactions. In this brief article, we emphasize the potential strength of a new paradigm arising in the integration of microfluidic devices (i.e., organ on chip), time-lapse microscopy analysis, and machine learning approaches. Some snapshots of previous case studies in the context of immunotherapy are included as proof of concepts of the proposed strategies while a visionary description concludes the work foreseeing future research and applicative scenarios.
J Matthijs Biesbroek, Dirk R Rutgers, Sander van Gulik
et al.
Short-lasting unilateral neuralgiform headache with autonomic symptoms (SUNA) is a rare form of trigeminal autonomic cephalalgia. SUNA is frequently associated with a trigeminal neurovascular conflict and rarely occurs secondary to other intracranial pathology. We report a patient with SUNA that was associated with ipsilateral meningeal inflammation caused by idiopathic hypertrophic pachymeningitis (HP). During the 9-year follow-up, she experienced multiple episodes of SUNA, most of which occurred during exacerbations of the pachymeningitis. This is the third case of SUNA associated with HP reported in the literature. Based on this observation, we suggest that in patients presenting with SUNA, besides dedicated magnetic resonance imaging (MRI) of the trigeminal nerve, gadolinium-enhanced brain MRI should be performed to rule out HP.
Seyede Somayeh Jalil-Abkenar, Mohammad Ashori, Saeed Hasanzadeh
Objective The purpose of the present research was to investigate the relationship of the resources management strategies and achievement goals orientation in predicting academic achievement in students with hearing impairment.
Materials & Methods The present research is a descriptive-analytical correlation study. The study population included students with hearing impairment who were aged 15-18 years. Eighty students (46 boys and 34 girls) were selected by convenient sampling method from Tehran province. The instruments of present research were resources management strategies questionnaire and achievement goals orientation questionnaire-revised. Data were analyzed by using mean, standard deviation, correlation coefficient, and stepwise regression along with SPSS (version 19).
Results The normality of variables was tested. The Kolmogorov-Smirnov test showed that all variables were normal. The findings showed that resource management strategies (effort regulation and help-seeking) and achievement goals orientation (mastery approach goal and performance avoidance) have a positive and significant relationship with academic achievement (p<0.05). Mastery approach, effort regulation, help seeking and performance avoidance goal predicted 0.53 percent of the variance in academic achievement (p<0.05), and mastery approach goal had the most contribution to the prediction of academic achievement (p<0.001).
Conclusion Variables such as resource management strategies and achievement goals orientation have a crucial role in predicting academic achievement in students with hearing impairment.
Christian Galasso, Cinzia Corinaldesi, Clementina Sansone
As is the case for terrestrial organisms, carotenoids represent the most common group of pigments in marine environments. They are generally biosynthesized by all autotrophic marine organisms, such as bacteria and archaea, algae and fungi. Some heterotrophic organisms also contain carotenoids probably accumulated from food or partly modified through metabolic reactions. These natural pigments are divided into two chemical classes: carotenes (such as lycopene and α- and β-carotene) that are composed of hydrogen and carbon; xanthophylls (such as astaxanthin, fucoxanthin and lutein), which are constituted by hydrogen, carbon and oxygen. Carotenoids, as antioxidant compounds, assume a key role in the protection of cells. In fact, quenching of singlet oxygen, light capture and photosynthesis protection are the most relevant biological functions of carotenoids. The present review aims at describing (i) the biological functions of carotenoids and their benefits for human health, (ii) the most common carotenoids from marine organisms and (iii) carotenoids having large success in pharmaceutical, nutraceutical and cosmeceutical industries, highlighting the scientific progress in marine species cultivation for natural pigments production.
Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. In the present study, we report that pekinenin E (PE), a casbane diterpenoid derived from the roots of Euphorbia pekinensis, has a strong antitumor activity against human HCC cells both in vitro and in vivo. PE suppressed the growth of human HCC cells Hep G2 and SMMC-7721. In addition, PE-mediated endoplasmic reticulum (ER) stress caused increasing expressions of C/EBP homologous protein (CHOP), leading to apoptosis in HCC cells both in vitro and in vivo. Inhibition of ER stress with CHOP small interfering RNA or 4-phenyl-butyric acid partially reversed PE-induced cell death. Furthermore, PE induced S cell cycle arrest, which could also be partially reversed by CHOP knockdown. In all, these findings suggest that PE causes ER stress-associated cell death and cell cycle arrest, and it may serve as a potent agent for curing human HCC.
Matthias Helmschrott,1 Rasmus Rivinius,1 Thomas Bruckner,2 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology, Pneumology, 2Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: A calcineurin inhibitor (CNI)-based immunosuppression combined with mammalian target of rapamycin inhibitors (mTORs) seems to be attractive in patients after heart transplantation (HTX) in special clinical situations, for example, in patients with adverse drug effects of prior immunosuppression. Previous studies in patients after HTX detected advantageous effects regarding renal function of a tacrolimus (TAC)-based vs cyclosporine-A (CSA)-based immunosuppression (in combination with mycophenolate mofetil). However, data regarding renal function after HTX in mTOR/CNI patients remain limited. Aim: Primary end point of the present study was to analyze renal function in HTX patients 1 year after switch to an mTOR/CNI-based immunosuppression. Methods: Data of 80 HTX patients after change to mTOR/CNI-based immunosuppression were retrospectively analyzed. Renal function was assessed by measured serum creatinine and by estimated glomerular filtration rate (eGFR) calculated from Modification of Diet in Renal Disease equation. Results: Twenty-nine patients received mTOR/CSA-based treatment and 51 patients received mTOR/TAC-based therapy. At time of switch and at 1-year follow-up, serum creatinine and eGFR did not differ significantly between both study groups (all P=not statistically significant). Analysis of variances with repeated measurements detected a similar change of renal function in both study groups. Conclusion: The present study detected no significant differences between both mTOR/CNI study groups, indicating a steady state of renal function in HTX patients after switch of immunosuppressive regimen. Keywords: heart transplantation, cyclosporine A, tacrolimus, risk factors
Sung Rae Kim,1 Myoung Jin Ho,2 Sang Hyun Kim,1 Ha Ra Cho,2 Han Sol Kim,2 Yong Seok Choi,2 Young Wook Choi,1 Myung Joo Kang2 1Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, 2College of Pharmacy, Dankook University, Cheonan, Chungnam, South Korea Abstract: Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA) injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA) in the synovial cavity. PRX-loaded NPs consisting of poly(lactic-co-glycolic acid), Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w) of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 µm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration–time curve (AUC0–24 h) and maximum plasma concentration (Cmax) of PRX after IA injection of the cationic NPs were <70% (P<0.05) and 60% (P<0.05), respectively, compared to those obtained from drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing with the cationic NPs was 3.2-fold (P<0.05) and 1.8-fold (P<0.05) higher than that from drug solution and neutrally charged NPs, respectively. Therefore, we recommend the IA cationic NP therapy as an effective alternative to traditional oral therapy with PRX, as it increases drug retention selectively in the joint. Keywords: piroxicam, polymeric nanoparticles, electrostatic interaction, intra-articular injection, local delivery, hyaluronic acid
Jozić Tanja L., Terzić Branka M., Mitrović Predrag M.
et al.
Introduction Rhabdomyolysis is a rare, but serious and potentially fatal adverse reaction of the statin application that may be developed in any time of therapy. It is characterized by massive destruction of muscles associated with the large increase of creatine kinase (CK) leading to myoglobinuria and potential acute renal failure. Combined statin-fibrate therapy increases the risk of rhabdomyolysis, especially in elderly and diabetic patients. Case report An 81-year-old male was admitted to Coronary Care Unit of the Emergency Center, Clinical Center of Serbia (CCS) with the clinical picture and electrocardiogram of the acute anterior wall myocardial infarction complicated with pulmonary edema. Laboratory tests on admission showed higher elevated values of serum creatinine 179 μmol/L and BUN 9.2 mmol/L (eGFR 32 mL/min/1.73m2), CK 309 U/L (on day 2: 3476 U/L) and mixed hyperlipidemia (total cholesterol 10.3 mmol/L, HDL 2.26 mmol/L, TG 4.85 mmol/L). The patient was treated with thrombolysis medication therapy (Alteplase), anticoagulant and dual antiplatelet therapy, diuretics, organic nitrates, angiotensin-converting enzyme (ACE) inhibitors, antibiotics, and proton pump inhibitors. During seven days, his therapy included combined pravastatin 20 mg and fenofibrate (160 mg), which was discontinued due to pains and weakness of muscles and significantly elevated CC to 7080 U/L (upper limit 200 U/L), but no significant deterioration of renal function was observed. Discontinuation of therapy resulted in CC level normalization and improvement of clinical condition. Conclusion Combined statin and fibrate therapy requires strict clinical control and monitoring of CK i transaminases. Four-time or higher increase of CK requires discontinuation of therapy. In addition, patients are advised to report immediately any pains in muscles, sensibility, weakness or cramps.
Mohammad Reza khodaei-Ardakani, Mohammad Kamran-Derakhshan, Omid Rezaei
et al.
Objective: There is evidence for differential executive function in Bipolar I Disorder (BID) and schizophrenia that may tend different cognitive deficits and abnormalities. The objective of this sudsy was to compare the executive function of BID and schizophrenic patients.
Materials & Methods: We studied 50 patients with BID, and 50 with schizophrenia participants in outpatients' clinic of Rouzbeh hospital. All participants completed the Wisconsin Card Sorting Test (WCST) the Persian version. The participants were mach in three basic variables which had most contributions in cognitive conditions in patients. They were Age, educational status and period of illness.
Results: The two patient groups had compared performance on the WCST in compared with general population (P<0/05). In the WCST, schizophrenic patients showed impairment executive function than BID patients (P<0/05).
Conclusion: findings indicated that schizophrenic patients had more dysfunctions executive function than the Bipolar disorder I patients. Although, both disorders may show impairment in executive function, but the dysfunction in schizophrenia greater than Bipolar I Disorder patients.
Connor M. Callaghan, Robert E. Leggett, Robert M. Levin
Considering how popular grapes are in terms of their antioxidant benefits, we compared concord, purple, red, and green grapes for total antioxidant capacity (TAC) and carbohydrate concentration. All grapes were acquired from commercial sources and samples of each were separated into skinned and not skinned groups. Each whole grape and the skins were individually homogenized and then separated into pulp and supernatant fractions. Each fraction was analyzed for total TAC and carbohydrates. The concord grapes and purple grapes had significantly higher TAC in the homogenates than did the red or green grapes. The concord grapes and green grapes had significantly higher TAC in the pulp than in the cytosol whereas the red and purple grapes had approximately the same amount. The majority of the TAC of the purple and red grapes was in the skin whereas the concord and green grapes had approximately the same TAC in the skin and pulp. The concord and purple grapes had the highest TAC when compared to the red and green grapes, whereas the red and green grapes had approximately the same total TAC.
Reading the patient package inserts (PPIs) is a key source of information about medications for patients. They should be clear and understandable to the general population. Objectives: The aims of this study were to obtain base-line data on the extent of reading PPIs by consumers and possible factors that might affect this; to explore the attitude of the Palestinian public and healthcare professionals towards the patient package inserts (PPIs); and to review a random sample of PPIs for the availability of different information.Methods: The first part of the study was a cross-sectional self-administered questionnaire. The questionnaire for consumers included 15 items. The questionnaire for healthcare professionals included 10 items and it was very similar to that of consumers with some modifications. In the second part, a random sample of PPIs was reviewed. In our community pharmacies, where medications are arranged according to their producing company, a researcher was asked to choose randomly 10-15 medications for every company to check for the availability of pharmacological, pharmaceutical and clinical information. Results: A total of 304 healthcare professionals out of 320 (95.0%) and 223 consumers out of 240 (92.9%) accepted to answer the survey. Forty five percent consumers reported that they always read the PPIs, and 29.3% said that they read the PPIs most of the times. Increased rate of reading the leaflet was found among females (P = 0.047). The preferred language for the PPIs was Arabic for most of the consumers (89.6%) while it was English for most of the healthcare professionals (80.8%). 35.9% of the consumers and 43.6% of the healthcare professionals found the font size suitable. 42.3% of the consumers and 25.5% of the healthcare professionals said that they found the information in the PPIs useful and enough. The PPIs of 135 randomly sampled medications were reviewed. Many important sections were not found in the PPIs' sample. Conclusion: A high percentage of consumers read the PPIs, but still this needs to be improved. People would appreciate a more detailed and clear PPI. Pharmacists should advocate reading the PPIs but they need to provide consumers with detailed counseling to compensate for the missing information in some of the PPIs. Authorities and manufacturers should implement appropriate measures to regulate the quality and quantity of information in the PPIs.
Therapeutics. Pharmacology, Pharmacy and materia medica