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Natural herbs have garnered significant research recently as their components target multiple disease signaling pathways, making them highly potential for various disease prevention and treatment. Embelin, a naturally occurring benzoquinone isolated from Embelia ribes, has shown promising biological activities such as antitumor, antidiabetic, anti-oxidant, and antimicrobial. Various mechanisms have been reported, including monitoring genes that synchronize the cell cycle, upregulating multiple anti-oxidant enzymes, suppressing genes that prevent cell death, influencing transcription factors, and preventing inflammatory biomarkers. However, the hydrophobic nature of embelin leads to poor absorption and limits its therapeutic potential. This review highlights a wide range of nanocarriers used as delivery systems for embelin, including polymeric nanoparticles, liposomes, nanostructured lipid carriers, micelles, nanoemulsion, and metallic nanoparticles. These embelin nanomedicine formulations have been developed in preclinical studies as a possible treatment for many disorders and characterized using various in vitro, ex vivo, and in vivo models. [ABSTRACT FROM AUTHOR]

Natural herbs have garnered significant research recently as their components target multiple disease signaling pathways, making them highly potential for various disease prevention and treatment. Embelin, a naturally occurring benzoquinone isolated from Embelia ribes, has shown promising biological activities such as antitumor, antidiabetic, anti-oxidant, and antimicrobial. Various mechanisms have been reported, including monitoring genes that synchronize the cell cycle, up-regulating multiple anti-oxidant enzymes, suppressing genes that prevent cell death, influencing transcription factors, and preventing inflammatory biomarkers. However, the hydrophobic nature of embelin leads to poor absorption and limits its therapeutic potential. This review highlights a wide range of nanocarriers used as delivery systems for embelin, including polymeric nanoparticles, liposomes, nanostructured lipid carriers, micelles, nanoemulsion, and metallic nanoparticles. These embelin nanomedicine formulations have been developed in preclinical studies as a possible treatment for many disorders and characterized using various in vitro, ex vivo, and in vivo models.

Bergaptol (5-hydroxypsoralen or 5-hydroxyfuranocoumarin) is a naturally occurring furanocoumarin widely found in citrus fruits, which has multiple health benefits. Nonetheless, no specific review articles on bergaptol have been published. Compiling updated information on bergaptol is crucial in guiding future research direction and application. The present review focuses on the research evidence related to the pharmacological properties and toxicity of bergaptol. Bergaptol has anti-inflammatory, antioxidant, anti-cancer, anti-osteoporosis, anti-microbial, and anti-lipidemic effects. It can inhibit the activities of cytochrome P450s (CYP), especially CYP2C9 and CYP3A4, thereby affecting the metabolism and concentrations of some drugs and toxins. Compared with other coumarins, bergaptol has the least potency to inhibit CYP3A4 in cancer cells. Instead, it can suppress drug efflux transporters, such as P-glycoprotein, thereby overcoming chemotherapeutic drug resistance. Furthermore, bergaptol has antimicrobial effects with a high potential for inhibition of quorum sensing. In vivo, bergaptol can be retained in plasma for longer than other coumarins. Nevertheless, its toxicity has not been clearly reported. In vitro study suggests that, unlike most furocoumarins, bergaptol is not phototoxic or photomutagenic. Existing research on bergaptol has mostly been conducted in vitro. Further in vivo and clinical studies are warranted to identify the safe and effective doses of bergaptol for its multimodal application. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is one of the main pathogens in community and hospital infections that could cause mild skin infections to severe life-threatening bacteremia. Piper betle has shown antibacterial activities against S. aureus but its pharmacodynamics remains unclear despite its widespread availability in many over-the-counter preparations. This study aimed to describe the time-kill kinetics of P. betle extract against methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA). Time-kill kinetics were conducted to describe the killing rate of P. betle extract by its effects on MSSA lag time duration, growth rate, and maximum optical density. The surviving colonies at different time-points after exposure to P. betle extract at minimum bactericidal concentration were also determined. Subinhibitory concentrations elucidated its concentration-dependent antibacterial activity by maintaining a trend of increasing lag time, decreasing growth rate, and decreasing maximum optical density as the concentration increases. In particular, concentration at 1250 μg/mL or 0.5 x minimum inhibitory concentration (MIC) showed consistent significant findings across these parameters. Concentrations at MIC and above did not show growth, indicating MSSA growth inhibition or death. P. betle extract’s bactericidal effect started immediately within two (2) hours and was sustained until no growth was observed from the eighth hour and beyond. P. betle extract maintained antibacterial activities against MSSA at subinhibitory concentrations and has also exhibited immediate and sustained bactericidal effect at minimum bactericidal concentration (MBC).

Objective: On the basis of data mining, systematic pharmacology, molecular docking, and experiment validation, the oxidative-inflammatory molecular targets of Coicis Semen in the therapy of osteoarthritis (OA) were explored. Methods: The association rule analysis was effectively applied to highlight the correlation between Coicis Semen and oxidative inflammation indices. The random walk model was subsequently used to evaluate the clinical efficacy of Coicis Semen. Network pharmacology was used to predict network targets. The binding affinity of the active ingredient in Coicis Semen to the key target of OA was also successfully predicted. Results: Coicis Semen showed a significant reduction in oxidative-inflammatory indicators of OA. A total of 108 promising targets were predicted for the 24 bioactive compounds in Coicis Semen. Eight target genes were considered core target genes. The enrichment analysis predicts that Coicis Semen may activate the interleukin (IL)-17, mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-kappa B) signaling pathways. Molecular docking demonstrated that stigmasterol, 2-monoolein, sitosterol, and sitosterol alpha1 had free binding energies to oxidative and inflammatory targets (MAPK1, Estrogen Receptor 1 [ESR1], and Peroxisome Proliferator-Activated Receptor Alpha [PPARA]). Both clinical trials and in vitro cell experiments revealed that Coicis Semen could increase ESR1 and PPAR-a levels while decreasing MAPK1 levels. Conclusions: Coicis Semen has a remarkable anti-OA effect. Precisely, the major components of Coicis Semen, including stigmasterol, sitosterol alpha1, sitosterol, and 2-monoolein, specifically inhibit MAPK1, ESR1, and PPARA to reduce the inflammatory response and oxidative damage in OA. [ABSTRACT FROM AUTHOR]

Background: Hyoscine butylbromide (HBB) has been available for use as an antispasmodic since 1951 and is indicated for the treatment of abdominal pain associated with cramps. A previous review in 2007 summarized the evidence on the mode of action of HBB in vitro and in vivo in both animal and human studies. However, since then, novel publications have appeared within the literature and also our knowledge of what represents normal motility in humans has evolved. Purpose: This review is the result of the collaboration between a basic scientist and clinicians with the aim of providing an updated overview of the mechanisms of action of HBB and its clinical efficacy to guide not only use in clinical practice, but also future research. [ABSTRACT FROM AUTHOR]

Background: Lawsonia inermis L., is a branched, glabrous shrub or small tree belonging to the Lythraceae family. A perennial plant commonly known as henna, it is native to North Africa and Southeast Asia. In this review, we highlighted previous information on the botanical description, and pharmacologic activities of Lawsonia inermis L. Methods: To collect the data on Lawsonia inermis L., we reviewed publications indexed in PubMed, Scopus, and Web of Science databases. The main judgment criterion was to mention ''Lawsonia inermis L.,'' or ''henna'' in the title, abstract or keywords, and the secondary judgment criterion was to mention ''pharmacological actions'', ''pharmacological activities,'' or ''pharmacological activity'' in the full text. Results: One hundred and eleven papers were identified after the initial database search from PubMed, Scopus, and the Web of Science. After abstract and title screening and deleting duplicates 84 articles were retained to be treated, and analyzed in this review. The information presented in this paper summarizes the phytochemicals and pharmacologic actions of Lawsonia inermis L., and their extracts. Conclusion: The reviewed articles approved different therapeutic powers and different biological actions of Lawsonia inermis L., in various in vitro and in vivo test models. Different parts of henna have been shown to have biological, pharmacological, and chemical activities, including Antibacterial, Antifungal, Antitumor and antiproliferative, Antiangiogenic, Larvicidal, Antileishmanial, Lousicide, Antimalarial, Hepatoprotective, Wound healing, Anti-inflammatory, Analgesic, Antipyretic, Memory enhancement, Enzyme inhibitor, and Antioxidant. This review provides direction for future studies on the composition and isolation of the active ingredients of Lawsonia inermis L., and references for the clinical use of prescriptions containing parts of this plant for the treatment of different diseases.

Bergaptol (5-hydroxypsoralen or 5-hydroxyfuranocoumarin) is a naturally occurring furanocoumarin widely found in citrus fruits, which has multiple health benefits. Nonetheless, no specific review articles on bergaptol have been published. Compiling updated information on bergaptol is crucial in guiding future research direction and application. The present review focuses on the research evidence related to the pharmacological properties and toxicity of bergaptol. Bergaptol has anti-inflammatory, antioxidant, anti-cancer, anti-osteoporosis, anti-microbial, and anti-lipidemic effects. It can inhibit the activities of cytochrome P450s (CYP), especially CYP2C9 and CYP3A4, thereby affecting the metabolism and concentrations of some drugs and toxins. Compared with other coumarins, bergaptol has the least potency to inhibit CYP3A4 in cancer cells. Instead, it can suppress drug efflux transporters, such as P-glycoprotein, thereby overcoming chemotherapeutic drug resistance. Furthermore, bergaptol has antimicrobial effects with a high potential for inhibition of quorum sensing. In vivo, bergaptol can be retained in plasma for longer than other coumarins. Nevertheless, its toxicity has not been clearly reported. In vitro study suggests that, unlike most furocoumarins, bergaptol is not phototoxic or photomutagenic. Existing research on bergaptol has mostly been conducted in vitro. Further in vivo and clinical studies are warranted to identify the safe and effective doses of bergaptol for its multimodal application.

Background: Gabapentin is a recommended first‐line agent for treating neuropathic pain; however, its efficacy rate is reportedly low, and the risk of adverse events is high. A plausible explanation for this lies with its wide range of actions, the entirety of which have yet to be fully elucidated. Methods: A review of the literature was conducted on gabapentin's known and proposed analgesic mechanisms of action, as well as potentially opposing or detrimental actions. Results: Gabapentin's classical analgesic mechanisms involve direct attenuation of excitatory neurotransmission in the spinal cord via inhibition of neuronal ion channels, while indirect mechanisms include descending inhibition and block of injury‐evoked synaptogenesis. Glial effects have also been reported; however, whether they are neuroprotective or detrimental is unknown. Furthermore, data from animal models do not reflect clinical outcomes. Conclusions: Gabapentin's clinical use should be reconsidered according to the net effects of its numerous assumed actions, including the tripartite synapse and oligodendrocyte effects. Whether it is doing more harm than good, especially in the scenarios of incomplete or loss of response, warrants consideration when prescribing gabapentin. [ABSTRACT FROM AUTHOR]

Objective: The Indian pharmaceutical market is flooded with different fixed drug combinations (FDCs), many of which lack a rational justification. The study aimed to assess the knowledge, attitude, and practice (KAP) regarding FDCs among the physicians of a tertiary-care teaching center. Method: The target sample size for this cross-sectional study was calculated as 75, and the study was conducted between February and August 2020 by using a content-validated questionnaire. Descriptive statistics had been utilized for data analysis, and Chi-square test had been applied for intergroup comparison (with P < 0.05 considered to be significant). Results: The mean age of the physicians who participated in this survey was 33.2 years. While 44% of them could identify all the potential advantages of using FDCs, only 09% could correctly recognize all the disadvantages associated with the same. Among the list of rational and irrational FDCs, only 49% could single out the irrational ones. And though the majority (83%) of the respondents do check for the rationality of FDCs before prescribing them, still out of 25 most commonly prescribed FDCs, 16 lacked any scientific justification for combination, and 09 (out of 16) had been banned by the Government of India. Conclusion: The outcome of this cross-sectional questionnaire-based study reflects the deficit in the knowledge regarding FDCs, as well as incoherence among the knowledge, attitude, and prescription practice. Though the physicians have cultivated a healthy attitude towards prescribing FDCs, the same is not reflected in their practice. In order to rectify these disparities, the authors have proposed certain recommendations within this article.

Perinatal derivatives or PnDs refer to tissues, cells and secretomes from perinatal, or birth-associated tissues. In the past 2 decades PnDs have been highly investigated for their multimodal mechanisms of action that have been exploited in various disease settings, including in different cancers and infections. Indeed, there is growing evidence that PnDs possess anticancer and antimicrobial activities, but an urgent issue that needs to be addressed is the reproducible evaluation of efficacy, both in vitro and in vivo. Herein we present the most commonly used functional assays for the assessment of antitumor and antimicrobial properties of PnDs, and we discuss their advantages and disadvantages in assessing the functionality. This review is part of a quadrinomial series on functional assays for the validation of PnDs spanning biological functions such as immunomodulation, anticancer and antimicrobial, wound healing, and regeneration.

Objective: The Indian pharmaceutical market is flooded with different fixed drug combinations (FDCs), many of which lack a rational justification. The study aimed to assess the knowledge, attitude, and practice (KAP) regarding FDCs among the physicians of a tertiary-care teaching center. Method: The target sample size for this cross-sectional study was calculated as 75, and the study was conducted between February and August 2020 by using a content-validated questionnaire. Descriptive statistics had been utilized for data analysis, and Chi-square test had been applied for intergroup comparison (with P < 0.05 considered to be significant). Results: The mean age of the physicians who participated in this survey was 33.2 years. While 44% of them could identify all the potential advantages of using FDCs, only 09% could correctly recognize all the disadvantages associated with the same. Among the list of rational and irrational FDCs, only 49% could single out the irrational ones. And though the majority (83%) of the respondents do check for the rationality of FDCs before prescribing them, still out of 25 most commonly prescribed FDCs, 16 lacked any scientific justification for combination, and 09 (out of 16) had been banned by the Government of India. Conclusion: The outcome of this cross-sectional questionnaire-based study reflects the deficit in the knowledge regarding FDCs, as well as incoherence among the knowledge, attitude, and prescription practice. Though the physicians have cultivated a healthy attitude towards prescribing FDCs, the same is not reflected in their practice. In order to rectify these disparities, the authors have proposed certain recommendations within this article. [ABSTRACT FROM AUTHOR]

Keywords: cardiomyopathy, hypertrophic; cardiac myosins; drug therapy; pharmacologic actions EN cardiomyopathy, hypertrophic cardiac myosins drug therapy pharmacologic actions 700 702 3 03/02/23 20230228 NES 230228 It has been 30 years since the identification of a I MYH7 i ( -myosin heavy chain mutation) as a cause of hypertrophic cardiomyopathy (HCM) in humans. How does mavacamten fit into the current treatment paradigm for obstructive HCM patients who are still symptomatic on standard medical therapy?. [Extracted from the article]

Objective: The causes of “delayed-on” and “no-on” phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. Case Description: A 69-year-old man with PD presented with “delayed-on” and “no-on” phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an “off” state. Videofluoroscopic examination of swallowing in an “off” state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of “delayed-on” and “no-on” phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of “no-on” phenomena decreased. Conclusion: In PD patients, the “no-on” phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

Objective: To investigate the vancomycin effectiveness against grampositive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio > 400. Methods: A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G1 < 7 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage. Results: There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients. Conclusion: A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial. [ABSTRACT FROM AUTHOR]

Background/Aim. Data on phytochemical and pharmacological investigations of genus Cirsium Mill. (Asteraceae) are scarce. Some data suggest that decoctions or infusions prepared from these plants are used in folk medicine as tonics, particularly in inflammatory, liver and stomach diseases. So far there have been no pharmacological investigations related to Cirsium ligulare (C. ligulare) Boiss. Accordingly, the aim of this study was to estimate antioxidative, anti-inflammatory and gastroprotective activities of aqueous extracts of C. ligulare herb prepared as 5% and 10% decoctions. Methods. Antioxidative activity was determined using the method of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. Investigations of anti-inflammatory (a model of systemic inflammatory response induced by endotoxin of Escherichia coli and carrageenan-induced rat paw oedema model for local inflammatory response), as well as gastroprotective effects (a model of stress-ulcer induced by absolute ethanol), were conducted in adult female Wistar rats that were given the aqueous extracts of C. ligulare herb per os. Indomethacin and ranitidine were used as reference drugs for evaluation of local anti-inflammatory and gastroprotective effects, respectively. Results. The results demonstrated that aqueous extracts of C. ligulare herb produced strong antioxidative activity, diminished body weight loss induced by endotoxin, significantly reduced carrageenan-induced paw oedema, and prevented the ulcerogenic action of absolute ethanol. Both anti-inflammatory and gastroprotective activities of the extract tested were comparable to those of the reference drugs. Conclusion. Presented results justify the traditional use of C. ligulare herb decoctions and further phytochemical and pharmacological investigations are warranted. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173021]

The gut microbiome is emerging as an important contributor to both cardiovascular disease risk and metabolism of xenobiotics. Alterations in the intestinal microbiota are associated with atherosclerosis, dyslipidemia, hypertension, and heart failure. The microbiota have the ability to metabolize medications, which can results in altered drug pharmacokinetics and pharmacodynamics or formation of toxic metabolites which can interfere with drug response. Early evidence suggests that the gut microbiome modulates response to statins and antihypertensive medications. In this review, we will highlight mechanisms by which the gut microbiome facilitates the biotransformation of drugs and impacts pharmacological efficacy. A better understanding of the complex interactions of the gut microbiome, host factors, and response to medications will be important for the development of novel precision therapeutics for targeting CVD. [ABSTRACT FROM AUTHOR]

Objective: Analyze the microbiological effectiveness, based on the pharmacokinetics/ pharmacodynamics correlation of vancomycin in pediatric patients, and to propose dose adjustment. Methods: This is an observational, cross-sectional study, conducted in a pediatric hospital, over a 1-year period (2016 to 2017). Children of both sexes, aged 2 to 12 years, were included in the study; burn children, and children in renal replacement therapy were excluded. For the pharmacokinetic analysis, two samples of 2mL of whole blood were collected, respecting the 2-hour interval between each withdrawal. Results: Ten pediatric patients with median age of 5.5 years and interquartile range (IQR) of 3.2-9.0 years, median weight of 21kg (IQR: 15.5-24.0kg) and median height of 112.5cm (IQR: 95-133cm), were included. Only one child achieved trough concentrations between 10μg/mL and 15μg/mL. Conclusion: The empirical use of vancomycin in the children studied did not achieve the therapeutic pharmacokinetic/ pharmacodynamic target for minimum inhibitory concentration of 1μg/mL. [ABSTRACT FROM AUTHOR]

• Endogenous cannabinoid and opioid systems have multi-level cross-talks. • Exposure to exogenous opioids dysregulates the endocannabinoid system. • Alterations of the endocannabinoid system are region-specific in the brain. Rates of opioid-related deaths and overdoses in the United States are at record-high levels. Thus, novel neurobiological targets for the treatment of OUD are greatly needed. Given the close interaction between the endogenous opioid system and the endocannabinoid system (ECS), targeting the ECS may have therapeutic potential in OUD. The various components of the ECS, including cannabinoid receptors, their lipid-derived endogenous ligands (endocannabinoids [eCBs]), and the related enzymes, present potential targets for developing new medications in OUD treatment. The purpose of this paper is to review the clinical and preclinical literature on the dysregulation of the ECS after exposure to opioids. We review the evidence of ECS dysregulation across various study types, exposure protocols, and measurement protocols and summarize the evidence for dysregulation of ECS components at specific brain regions. Preclinical research has shown that opioids disrupt various ECS components that are region-specific. However, the results in the literature are highly heterogenous and sometimes contradictory, possibly due to variety of different methods used. Further research is needed before a confident conclusion could be made on how exposure to opioids can affect ECS components in various brain regions. [ABSTRACT FROM AUTHOR]

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Copyright of Der Diabetologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

From its isolation and its beginning to the present day, vancomycin occupies a prominent role as an important antimicrobial reserved for the treatment of serious infections caused by microorganisms of relevance in the nosocomial environment. Thus, the objective of this study was to gather information about this antimicrobial. It is a version of the literature that uses electronic databases to cross the descriptors' vancomycin, glycopeptide, Streptomyces as well as their respective correspondents in the English language. Vancomycin belongs to the class of glycopeptides and is considered to be bactericidal by preventing cell wall synthesis having as its target structure a D-alanine, D-alanine portion of the bacterial cell wall. Vancomycin is an antimicrobial available especially for parenteral use and should be administered intravenously and due to observed adverse reactions monitoring of its use is necessary and is reserved for the treatment of serious infections. However, vancomycin-resistant microorganisms are a challenge for a medical clinic, where inadequate therapeutic practices on the part of health professionals lead to the emergence of resistant microorganisms. In addition, antimicrobial resistant bacteria are common not only in the nosocomial environment, but also in communities. [ABSTRACT FROM AUTHOR]

Objective: To develop a novel pharmacovigilance inferential framework to infer mechanistic explanations for asserted drug-drug interactions (DDIs) and deduce potential DDIs.Materials and Methods: A mechanism-based DDI knowledge base was constructed by integrating knowledge from several existing sources at the pharmacokinetic, pharmacodynamic, pharmacogenetic, and multipathway interaction levels. A query-based framework was then created to utilize this integrated knowledge base in conjunction with 9 inference rules to infer mechanistic explanations for asserted DDIs and deduce potential DDIs.Results: The drug-drug interactions discovery and demystification (D3) system achieved an overall 85% recall rate in terms of inferring mechanistic explanations for the DDIs integrated into its knowledge base, while demonstrating a 61% precision rate in terms of the inference or lack of inference of mechanistic explanations for a balanced, randomly selected collection of interacting and noninteracting drug pairs.Discussion: The successful demonstration of the D3 system's ability to confirm interactions involving well-studied drugs enhances confidence in its ability to deduce interactions involving less-studied drugs. In its demonstration, the D3 system infers putative explanations for most of its integrated DDIs. Further enhancements to this work in the future might include ranking interaction mechanisms based on likelihood of applicability, determining the likelihood of deduced DDIs, and making the framework publicly available.Conclusion: The D3 system provides an early-warning framework for augmenting knowledge of known DDIs and deducing unknown DDIs. It shows promise in suggesting interaction pathways of research and evaluation interest and aiding clinicians in evaluating and adjusting courses of drug therapy. [ABSTRACT FROM AUTHOR]

Os objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Revisamos sucintamente o novo tratamento farmacológico da tuberculose introduzido pelo Ministério da Saúde do Brasil em 2009 e mostramos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no esquema básico. Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos) assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal. Também descrevemos os mecanismos pelos quais as interações das drogas antituberculose do esquema básico podem causar hepatite medicamentosa e as possíveis alternativas nessa situação.The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We briefly review the new guidelines for the pharmacological treatment of tuberculosis, introduced by the Brazilian National Ministry of Health in 2009, and describe the general mechanism of action, absorption, metabolization, and excretion of the first-line drugs used in the basic regimen. We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure. We also describe the mechanisms by which the interactions among the antituberculosis drugs used in the basic regimen can cause druginduced hepatitis, and we discuss the alternatives in this situation.

Os objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Descrevemos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no tratamento da tuberculose multidroga resistente (aminoglicosídeos, fluoroquinolonas, cicloserina/terizidona, etionamida, capreomicina e ácido para-aminossalicílico). Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos) assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal.The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We describe the general mechanism of action, absorption, metabolization, and excretion of the drugs used to treat multidrug resistant tuberculosis (aminoglycosides, fluoroquinolones, cycloserine/terizidone, ethionamide, capreomycin, and para-aminosalicylic acid). We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure.

Background--Although primary percutaneous coronary intervention (pPCI) is the preferred reperfusion method for ST-segment--elevation myocardial infarction, it remains difficult to implement in many areas, and fibrinolytic therapy is still widely used. Methods and Results--We assessed 5-year mortality in patients with ST-segment-elevation myocardial infarction from the French Registry of Acute ST-Elevation or Non-ST Elevation Myocardial Infarction (FAST-MI) 2005 according to use and type of reperfusion therapy. Of 1492 patients with ST-segment-elevation myocardial infarction with a first call ≤12 hours from onset, 447 (30%) received fibrinolysis (66% prehospital; 97% with subsequent angiography, 84% with subsequent PCI), 583 (39%) had pPCI, and 462 (31%) received no reperfusion. Crude 5-year survival was 88% for the fibrinolytic-based strategy, 83% for pPCI, and 59% for no reperfusion. Adjusted hazard ratios for 5-year death were 0.73 (95% confidence interval, 0.50-1.06) for fibrinolysis versus pPCI, 0.57 (95% confidence interval, 0.36-0.88) for prehospital fibrinolysis versus pPCI, and 0.63 (95% confidence interval, 0.34-0.91) for fibrinolysis versus pPCI beyond 90 minutes of call in patients having called ≤180 minutes from onset. In propensity score-matched populations, however, survival rates were not significantly different for fibrinolysis and pPCI, both in the whole population (88% lysis, 85% pPCI) and in the population seen early (87% fibrinolysis, 85% pPCI beyond 90 minutes from call). Conclusions--In a real-world setting, on a nationwide scale, a pharmaco-invasive strategy constitutes a valid alternative to pPCI, with 5-year survival at least equivalent to that of the reference reperfusion method. [ABSTRACT FROM AUTHOR]

To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography ( EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials ( EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms 'analgesics', 'electroencephalography' and 'evoked potentials' for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl- D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients. [ABSTRACT FROM AUTHOR]

Perinatal derivatives or PnDs refer to tissues, cells and secretomes from perinatal, or birth-associated tissues. In the past 2 decades PnDs have been highly investigated for their multimodal mechanisms of action that have been exploited in various disease settings, including in different cancers and infections. Indeed, there is growing evidence that PnDs possess anticancer and antimicrobial activities, but an urgent issue that needs to be addressed is the reproducible evaluation of efficacy, both in vitro and in vivo . Herein we present the most commonly used functional assays for the assessment of antitumor and antimicrobial properties of PnDs, and we discuss their advantages and disadvantages in assessing the functionality. This review is part of a quadrinomial series on functional assays for the validation of PnDs spanning biological functions such as immunomodulation, anticancer and antimicrobial, wound healing, and regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Silini, Ramuta, Pires, Banerjee, Dubus, Gindraux, Kerdjoudj, Maciulatis, Weidinger, Wolbank, Eissner, Giebel, Pozzobon, Parolini and Kreft.)

OBJETIVO: O propósito deste artigo é o de revisar vários aspectos da esquizofrenia refratária levando em conta questões relacionadas à definição, aspectos clínicos, correlatos psicobiológicos, tratamentos farmacológicos e não farmacológicos, assim como preditores de resposta terapêutica. MÉTODO: Pesquisa no Medline, assim como artigos dos autores. RESULTADOS E CONCLUSÕES: Pelo menos um terço dos pacientes com esquizofrenia são refratários a tratamento com antipsicóticos e as evidências apontam a clozapina em monoterapia como a principal opção nesses casos. A politerapia com antipsicóticos não tem apoio em evidências. Ensaios clínicos recentes mostraram que a potencialização da clozapina com outros antipsicóticos não é superior ao placebo.OBJECTIVE: The aim of the present paper is to review the various aspects of refractory schizophrenia regarding issues such as definitions, clinical aspects, psychobiological correlates, pharmacological and non-pharmacological treatment options and predictors of treatment response. METHOD: Medline search as well as articles of the authors. RESULTS AND CONCLUSIONS: Refractory schizophrenia affects at least one third of patients with schizophrenia and the best evidence shows that is monotherapy with clozapine remains the mainstay for the treatment of such condition. Antipsychotic polipharmacy is not supported by current evidence and recent clinical trials have shown that clozapine augmentation with antipsychotics has no benefit over placebo.

Objective: The aim of the present paper is to review the various aspects of refractory schizophrenia regarding issues such as definitions, clinical aspects, psychobiological correlates, pharmacological and non-pharmacological treatment options and predictors of treatment response. Method: Medline search as well as articles of the authors. Results and Conclusions: Refractory schizophrenia affects at least one third of patients with schizophrenia and the best evidence shows that is monotherapy with clozapine remains the mainstay for the treatment of such condition. Antipsychotic polipharmacy is not supported by current evidence and recent clinical trials have shown that clozapine augmentation with antipsychotics has no benefit over placebo. [ABSTRACT FROM AUTHOR]