Objective: Nearby the specific therapeutic action, ASMs, like other types of pharmacotherapy, can produce various side effects. In this review, we shall analyze the different pharmaceutical classes of ASMs, their mechanism of action, and their interaction with the respiratory system.

Methods: This manuscript is based on a retrospective review of English publications indexed by Pubmed, UpToDate and datasheets published by the European Medicines Agency and the Food and Drug Administration (FDA), using various terms reminiscent of ASMs and pulmonary function.

Results: ASMs act on organism homeostasis in different ways, acting on lung function directly and indirectly and playing a protective or damaging role. A damaging direct lung involvement ranged from infections, hypersensitivity reactions, and respiratory depression to other structured pulmonary diseases. Meanwhile, a damaging indirect effect, might be constituted by pulmonary artery hypertension. On the other hand, a protective effect might be the expression of developmental processing, decreasing airway remodelling in asthma patients, vascular remodelling in pulmonary hypertension and, nonetheless, anti-inflammatory and immunomodulatory actions.

Conclusion: An adequate awareness of ASMs effects on the respiratory system seems essential for better managing frail individuals or/and those predisposed to respiratory disorders to improve our patients' clinical outcomes.

Methods: To achieve this, a comprehensive search was conducted in Persian medicine references and scientific databases to gather information on the traditional uses, chemical composition, and pharmacological effects of spinach. Studies that met the inclusion criteria were meticulously categorized, and relevant data were analyzed to draw insightful comparisons.

Results: Persian medicine describes spinach as a nutrient-rich, laxative, and fast-digesting agent with therapeutic effects on inflammation, lung diseases, back pain, sore throats, jaundice, urinary disorders, joint pain, eye inflammation, insomnia, dementia, and more. Modern studies have substantially corroborated these traditional uses, revealing that spinach possesses antioxidant, anti-inflammatory, anti-cancer, blood sugar-lowering, lipid-lowering, anti-obesity, neurological, ocular, and musculoskeletal effects.

Conclusion: Spinach exhibits a wide range of beneficial effects on various health conditions. Its widespread availability, low cost, and exceptional nutritional richness position it as a promising candidate for further investigation. Future studies should explore the clinical effectiveness of spinach in various diseases, while taking into consideration the principles emphasized in Persian medicine to guide research and inform therapeutic strategies.

Methods: The study is a narrative review conducted by collecting the most relevant and up-todate data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles.

Results: Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDsexacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDsinduced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed.

Conclusion: HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.

Objective: To reduce drug attrition rates, drug metabolism and pharmacokinetics studies are fully integrated into modern drug discovery research, and the structure-property relationship illustrates how the modification of the chemical structure influences the pharmacokinetic and toxicological properties of drug compounds. Understanding the structure- property relationships of clinically approved protease inhibitor drugs and their analogues could provide useful information on the lead-to-candidate optimization strategies.

Methods: About 70 inhibitors against human or pathogenic viral proteases have been approved until the end of 2021. In this review, 17 inhibitors are chosen for the structure- property relationship analysis because detailed pharmacological and/or physicochemical data have been disclosed in the medicinal chemistry literature for these inhibitors and their close analogues.

Results: The compiled data are analyzed primarily focusing on the pharmacokinetic or toxicological deficiencies found in lead compounds and the structural modification strategies used to generate candidate compounds.

Conclusion: The structure-property relationships hereby summarized how the overall druglike properties could be successfully improved by modifying the structure of protease inhibitors. These specific examples are expected to serve as useful references and guidance for developing new protease inhibitor drugs in the future.

IgE-mediated fish allergy differs substantially from other forms of immunological adverse reactions to fish, such as Food Protein-Induced Enterocolitis Syndrome and eosinophilic esophagitis. In addition, fish ingestion can cause non-immunological adverse reactions, such as in the case of scombroid poisoning, anisakiasis and toxic poisoning.

This review aims to summarize the characteristics of the main immunological and non-immunological fish reactions, analyzing the epidemiology, clinical manifestations, diagnosis and therapy, with a particular focus on clinical management.

Objective: This review article focuses on SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes associated with the use of paracetamol or paracetamol-containing products.

Methods: To find published articles relevant to paracetamol-associated SJS, TEN, AGEP, and DRESS, we searched the online databases Medline/Pubmed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists using keywords like Stevens-Johnson Syndrome, Acetaminophen, Paracetamol, Toxic epidermal necrolysis, Acute generalized exanthematous pustulosis, Drug reaction with eosinophilia and systemic symptoms.

Results: The paracetamol-associated SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes have been identified by a number of publications.

Conclusion: When evaluating drug-induced hypersensitivity skin reactions, healthcare professionals, including prescribers, pharmacists, and others, should be aware of this rare risk. Patients who exhibit signs and symptoms of paracetamol-associated hypersensitivity should be referred to physicians by pharmacists for further treatment. At the first sign of a skin rash or other hypersensitivity reaction while taking paracetamol, patients should be told to stop taking it and see a doctor right away.

Methods: We propose a compilation and analysis of around 100 medications, including small new molecular entities (NMEs), approved by the US Food and Drug Administration for the years 2020 and 2021. Novel drug discovery is crucial for pharmaceutical research and development as well as patient care. The only possible way to achieve this crucial goal is to repurpose current medications that may have anticipated effects as possible candidates. The availability of new drugs and biological products often means new treatment options for patients and advances in health care.

Results: Around 40% of the drugs were approved for various types of cancers. Other major therapeutic areas that were focused on were neurological products (around 17%), infectious diseases (13-15%), and cardiovascular disorders (7-8%). Various new products were approved for rare diseases (58-60%). This study aimed to discover a pattern in FDA medicine approvals during the last two decades.

Conclusion: This data shows that anticancer medicines and biologics are receiving increased attention in research. With a bigger number of biologically derived medications being produced, the price could rise much higher. FDA should embrace innovative techniques that will stimulate the industry to enhance research and development of novel compounds or medications that can deliver considerable improvements over existing ones. To put it briefly, FDA had to update our approach to regulation as a whole in order to effectively develop the types of technologies that are becoming available. Modernizing medical product review programmes is a part of this. These initiatives are part of the Medical Innovation Access Plan.

Case Report: We report a case of 35-year-old woman, known asthmatic with history of chronic urticaria, allergic rhinoconjunctivitis and angioedema after taking NSAIDs. The patient was presented 10 minutes after administrating Pfizer-BioNTech vaccine, an immediate allergic reaction complicated 12 hours followed by angioedema.

Discussion: During the first wave of COVID-19, and after the initiation of the vaccination program in Morocco, vaccinating people with severe allergies was not recommended. This reality was changed after the second wave of SARS-CoV-2 Delta, on condition of doing it under medical monitoring. We should propose to all risky persons to take premedication if needed to avoid such reactions considering the benefits incurred. The use of anti-histamines seems to be necessary. But as in our patient’s case, anti-histamines alone were not sufficient to avoid this local reaction. They probably reduced the intensity of the reaction but did not avoid it. Therefore, we proposed a combination of drugs made by corticosteroids and anti-histamines as a premedication may be a safe alternative for the patients with risks and last but not least a, close monitoring was proposed.

Conclusion: The main purpose of this case is to raise awareness of this side effect among practitioners and make them capable to manage it correctly.

Objective: To analyze pathophysiological characteristics/co-morbidities precipitating myocardial ischemia in patients with HTN LVH and provide a rationale for recommending beta-blockers (BBs) to prevent/treat ischemia in LVH.

Methods: We searched PubMed, SCOPUS, PubMed, Elsevier, Springer Verlag, and Google Scholar for review articles and guidelines on hypertension from 01/01/2000 until 01/05/2022. The search was limited to publications written in English.

Results: HTN LVH worsens ischemia in coronary artery disease (CAD) patients. Even without obstructive CAD, several pathophysiological mechanisms in HTN LVH can lead to myocardial ischemia. In the same guidelines that recommend BBs for patients with HTN and CAD, we could not find a single recommendation for BBs in patients with HTN LVH but without proven CAD. There are several reasons for the proposal of using some BBs to control ischemia in patients with HTN and LVH (even in the absence of obstructive CAD).

Conclusion: Some BBs ought to be considered to prevent/treat ischemia in patients with HTN LVH (even in the absence of obstructive CAD). Furthermore, LVH and ischemic events are important causes of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death; these events are another reason for recommending certain BBs for HTN LVH.

Objective: The primary objective of this narrative review is to critically summarize existing evidence regarding the use of Angiotensin Receptor-Neprilysin Inhibitor (ARNI), spironolactone, pirfenidone and empagliflozin in HFpEF.

Methods: Medline (via PubMed) and Scopus were searched - from inception up to May 2022- using adequately selected keywords. Additional hand-search was also performed using the references of the articles identified as relevant (snowball strategy).

Results: Angiotensin Receptor-Neprilysin Inhibitor (ARNI) and spironolactone, despite being very successful in HFrEF, did not do well in clinical trials of HFpEF, although there appear to be certain subsets of patients who may derive benefit. Data regarding pirfenidone are limited and come from small trials; as a result, it would be premature to draw firm conclusions, although it seems improbable that this agent will ever become a mainstay in the general population of HFpEF patients, while there may be a niche for the drug in individuals with comorbidities associated with an intense fibrotic activity. Finally, empagliflozin, largely welcomed as the first agent to have a “positive” randomized clinical trial in HFpEF, does not seem to evade the general pattern of reduced hospitalizations for HF with no substantial effect on mortality, seen in ARNI and spironolactone HFpEF trials.

Conclusion: Recent research in drug treatment for HFpEF has resulted in an overall mixed picture, with trials showing potential benefits from certain classes of drugs, such as sodium-glucose co-transporter 2 inhibitors, and no benefit from other drugs, which have shown to be effective in patients with reduced ejection fraction. However, small steps may be the way to go in HFpEF, and success is sometimes just a series of small victories.

Materials and Methods: In the present case-control study, for the study population, patients with chronic idiopathic urticaria were referred to the Asthma and Allergy Clinic, and their caregivers were selected as the case and control groups, respectively. In this study, the mean platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and Total IgE values were simultaneously measured in the case and control groups. After taking 5CCs of venous blood, a blood sample was sent to the laboratory for platelet and IgE marker measurements.

Results: 100 patients and 100 healthy persons were evaluated in this study. The mean age in the case group was 34.95, and in the control group was 35.78 years. The results showed that the mean values of PLT, MPV, PDW, and Total IgE in the case group were 12.86, 9.83, 252190, and 147.05, respectively. The mean values of PLT, MPV, PDW, and Total IgE in the control group were 16.93, 7.53, 231410, and 15.29, respectively, which was statistically significant (P = 0.001). Moreover, total IgE in the Autologous Serum Skin Test (ASST) positive group was higher than ASST negative group and was statistically significant (P = 0.001).

Conclusion: The study results indicate the possible role of platelets in urticaria and inflammation. MPV in patients with chronic urticaria was higher than in the control group. The present study showed no significant relationship between the severity of urticaria and platelet markers, but there was a significant relationship between the severity of urticaria and ASST. Moreover, the severity of urticaria was higher in the positive skin test group.

Materials and Methods: The electronic databases, such as Medline/PubMed Central/PubMed, Google Scholar, ScienceDirect, Cochrane Library, Directory of Open Access Journals (DOAJ), Embase, and reference lists were searched to identify relevant articles.

Results: The risk of hyperkalemia may be enhanced potentially in patients receiving a RAS blocker and potassium-sparing diuretics, potassium supplements, trimethoprim, adrenergic betablockers, antifungal agents, calcineurin inhibitors, pentamidine, heparins or an NSAID, concomitantly. The patients taking ACE inhibitors and mTOR inhibitors, DPP4 inhibitors, alteplase, or sacubitril/valsartan concurrently may be at increased risk of developing angioedema.

Conclusion: Clinicians, pharmacists, and other healthcare practitioners should be accountable for medication safety. To avoid adverse implications, prescribers and pharmacists must be aware of the drugs that interact with RAAS blockers.

Case Presentation: Here we describe a case of maculopapular rash induced by pregabalin in an older man, which resolved with withdrawal of the offending drug and conservative management.

Conclusion: We have also conducted a literature review of similar cases and highlighted the clinical patterns and management strategies for pregabalin-induced skin rashes.]]> https://www.benthamscience.comarticle/118143Background: Iodinated contrast media (ICM) are responsible for multiple side effects, especially hypersensitivity reactions. These reactions can either be authentic allergies or non-allergic hypersensitivity reactions. Skin tests (prick and intradermal tests) are simple to perform and can be of great help, especially if the ICM needs to be re-used. The aim of the study was to assess the characteristics of the patients in whom skin tests were performed and the results of these tests.

Methods: This is a retrospective study from June 2014 to June 2019. All included patients had at least one episode of hypersensitivity reaction to ICM and underwent skin tests.

Results: We included 35 patients aged 18 to 85 years. The iopromide was the most implicated ICM. The reactions were mainly cutaneous (n=30) and immediate (n=27). The skin tests were negative, except for two patients. The re-use of ICM occurred in 11 patients: 9 with an ICM other than the one suspected and two patients with the same ICM. Among these patients, 5 did not have any premedication. Two of them had a second hypersensitivity reaction, the first with another ICM and the second with the same ICM.

Conclusion: One of the main pillars of allergic exploration is ICM skin testing, not only to prevent a recurrence, but also to allow patients to benefit from ICM re-use, which are sometimes essential.

Objective: In this review, answers to two questions above and the safety of treatments, toxicities of agents involving chloroquine, hydroxychloroquine, remdesivir, favipiravir, lopiravir/ritonavir, sarilumab, tocilizumab, siltuximab, corticosteroids and bromhexine which are the most frequently used in Turkey and all over the world will be summarized.

Conclusion: Among these drugs, favipiravir seems the most promising drug due to more tolerable adverse effects. More clinical trials with large sample sizes are needed to find the most effective and safe drug for COVID-19 treatment.

Objective: The general aim of this comparative overview is to highlight the most significant effects of COVID-19 pandemic on the main healthcare systems. Also, we critically analyzed the macroeconomic variables and the most promising solutions to improve both healthcare system and its related risk management, taking into specific consideration the most industrialized countries.

Methods: The main strategy has been built on a renewed concept of the hospital, rebuilding the old concepts of “triage” and “intensive care”. Recently, COVID-19 hospitals have allowed to cater the patients affected by COVID-19.

Results: The reshaping of several healthcare policies and requirements has led to several positive effects, such as the recruitment of a huge number of human resources in the healthcare systems. Nevertheless, several negative effects have also impacted the communities mostly subjected to infections.

Conclusion: Undoubtedly, the national healthcare systems have somehow addressed the people’s needs, trying not to neglect the social, healthcare, economic and political aspects. In our overview, we have reported how the different actions taken in the last months, have resulted in different outcomes.

Methods: A comprehensive search of the PubMed database was performed, and relevant articles on the topic were included in this review.

Results: Extensive study of diabetic animal models has shown that the etiology of diabetic peripheral neuropathy is complex, with multiple mechanisms affecting neurons, Schwann cells, and the microvasculature, which contribute to the phenotypic nature of this most common complication of diabetes. Moreover, animal studies have demonstrated that the mechanisms related to peripheral neuropathy occurring in type 1 and type 2 diabetes are likely different, with hyperglycemia being the primary factor for neuropathology in type 1 diabetes, which contributes to a lesser extent in type 2 diabetes, whereas insulin resistance, hyperlipidemia, and other factors may have a greater role. Two of the earliest mechanisms described from animal studies as a cause for diabetic peripheral neuropathy were the activation of the aldose reductase pathway and increased non-enzymatic glycation. However, continuing research has identified numerous other potential factors that may contribute to diabetic peripheral neuropathy, including oxidative and inflammatory stress, dysregulation of protein kinase C and hexosamine pathways, and decreased neurotrophic support. In addition, recent studies have demonstrated that peripheral neuropathy-like symptoms are present in animal models, representing pre-diabetes in the absence of hyperglycemia.

Conclusion: This complexity complicates the successful treatment of diabetic peripheral neuropathy, and results in the poor outcome of translating successful treatments from animal studies to human clinical trials.

Objective: We report the case of a patient with acute ischemic stroke who, after treatment of alteplase, developed angioedema.

Methods: We report the case of an 81-year-old woman who presented to our observation with acute ischemic stroke. The patient was on therapy with 100 mg acetylsalicylic acid and a triple combination antihypertensive drug (perindopril 10 mg + 2.5 mg indapamide + 5 mg amlodipine). The patient was treated with alteplase infusion.

Results: Five minutes after the end of the alteplase infusion (0.9 mg/kg for 1 hour), the patient developed isolated angioedema of the lips and tongue.

Conclusion: Although the incidence of alteplase-induced angioedema in these patients is rare, this case report suggests the need for a routine inspection of the tongue in an acute ischemic patient in treatment with alteplase infusion, especially in female patients in treatment with ACE inhibitors.

Materials and Methods: 321 ADRs were obtained with the keywords “Adverse Drug Reaction”. Out of those, 158 were independently extracted by two investigators, observed and categorized according to classes of the drugs, geographic location, severity, hospitalization, Completeness of ADR, whether reported to the regulatory authority (Vigibase), or listed in the package insert. Literature review articles were excluded.

Results: Out of the 158 ADRs, antibiotics accounted for 12.65%, CNS drugs and monoclonal antibodies11.39%, anticancer drugs 9.49%, CVS drugs 4.43%, anti-viral 3.79%, others 45.56%, respectively. According to geographic region, 26 ADRs published were from USA, Australia 4, Italy 3, India 17, Turkey 9, Singapore and UK 1, China 20, Denmark and Canada 2, Japan 10, France 9, Austria 1, Korea 5, South America 3, Switzerland 2, respectively. Depending upon the severity, causality assessment was done only for 45 ADRs, and not done for 113 ADRs. 41.13% patients (from 65 case reports) were hospitalized. Among the 158 ADRs, 14 ADRs were not found in Vigibase. 32 ADRs were not mentioned in the Drug package inserts. When categorized according to the completeness of case reports, weight accounted for1.89%, lab values and procedure for diagnosis, 96.8%, risk factors, 95.56%, prior exposure, 88.60%, Post ADR status, 60.12%, start-stop medication, route of administration, first dose, last dose, duration of illness accounted for 100%, respectively.

Conclusion: Depending upon our observation, we have noticed that there is deficiency in reporting of suspected ADRs to regulatory authorities. Reporting can be included as mandatory criteria for ADR case reports. Also, there is an increased need to aware various healthcare workers for reporting ADR.

Methods: PubMed, Web of Science, Scopus, Cochrane Library databases, Science Direct, and Google Scholar were searched using specific keywords. The reference lists of relevant articles were searched for additional studies related to HF and VAs among seniors as well as associated outcomes.

Results: The prevalence of VAs increases with worsening HF. A 24-hour Holter electrocardiogram may be useful in risk stratifying patients for device therapy if they do not meet the criterion of low ventricular ejection fraction. Implantable Cardiac Defibrillators (ICDs) are superior to anti-arrhythmic drugs in reducing mortality in patients with HF. Guideline-Directed Medical Therapy (GDMT) together with device therapy may be required to reduce symptoms. In general, the proportion of seniors on GDMT is low. A combination of ICDs and cardiac resynchronization therapy may improve outcomes in selected patients.

Conclusion: Seniors with HF and VAs have high mortality even with the use of device therapy and GDMT. The holistic effect of device therapy on outcomes among seniors with HF is equivocal. More studies focused on seniors with advanced HF as well as therapeutic options are, therefore, required.

Methods: This was retrospective study conducted on snakebites patients referred to the Rahimi Hospital in Khorramabad. The files of these patients were accessed for demographic data, snakebite-related data, treatment provided, clinical presentation and allergic reaction status as a result of antivenom treatment.

Results: 141 cases were investigated, including 73.8% male and 26.2% female patients. The mean age of the patients was 38.1±17.1 years. Age group 30-39 years accounted for the highest number of snakebite cases (24.1%). A majority of victims (89.4%) were from rural areas. Most of the patients (51.8%) were bitten in the spring and highest number of snakebite were reported in May (39.1%). The most common site of snakebite was lower extremities (50.4%) and upper extremities (44.7%). Among clinical feature of snakebite, pain was the most prevalent in 135 cases (95.7%) followed by swelling (83.7%). The mean antivenom vials used were 6.5±3.7 vials. Allergic reactions occurred in 6 patients (4.26%); reactions were mild in 5 patients and severe in 1 patient. The commonest presentation was maculopapular rash (1.4%) and the least common were headache (0.71%), nausea (0.71%), fever (0.71) and hypotension (0.71%).

Conclusion: Snakebite is one of the significant life-threatening environmental events. Immediate antivenom treatment can reduce mortality however, patients should be carefully monitored for adverse allergic reactions]]> https://www.benthamscience.comarticle/111400 https://www.benthamscience.comarticle/115727Background: Allergic diseases are turning into an expanding occurrence around the globe, imposing a socioeconomic burden, causing grimness and even death. Allergen encounter initiates the influx of TH2 cells, triggering the production of T_H2 associated cytokines (IL-4, IL-5, and IL-13), which in turn promotes the detrimental allergic inflammation associated with asthma, allergic rhinitis, food allergy, urticaria, atopic eczema, and anaphylaxis. Cytokine alarmins (TSLP and IL-33) produced by epithelial cells play important roles in the promotion of T_H2 cell development and the initiation of allergic pathogenesis.

Objective: To target cytokine alarmins (TSLP and IL-33) as novel therapeutic proteins, using natural compounds as a potential cure at an early stage of allergic diseases.

Methods: Structure-based virtual screening of two large natural compounds databases (Universal Natural product Database (UNPD) and ZINC natural product database) was conducted for the identification of TSLP and IL-33 inhibitors using Autodock Vina followed by rescoring of the hit compounds. using Autodock 4.2 software. In silico physicochemical, pharmacokinetic, and toxicity analyses were conducted to assess the drug-like properties of the hit compounds. The binding mode stability of UNPD116849, ZINC01448143, and ZINC04096134 in the binding pocket of TSLP and IL-33 was probed by all-atom 50 ns molecular dynamics simulation.

Results: Five natural compounds (UNPD111, UNPD116849, ZINC01448143, ZINC15957528, and ZINC04096134) containing different structural moieties (steroidal, chromone, benzodioxole, and indole) were identified to inhibit TSLP and IL-33, with limonin (ZINC04096134) found to demonstrate dual inhibitory activity potential. These compounds were found to be drug-like and toxicity-free using in silico Absorption, Distribution, Metabolism, Elimination, and Toxicity (ADME-T) prediction methods. Taken together, this study suggests the dual inhibition potential of limonin (ZINC04096134) against the cytokine alarmins.

Conclusion: Five natural compounds with diverse structural moieties (steroidal, chromone, benzodioxole, and indole) were virtually identified as hit compounds against cytokine alarmins (TSLP and IL-33), with limonin showing dual inhibitory potential.

Methods: Nine Corriedale sheep that had been monitored for 10 minutes during a basal stage underwent 5-minute myocardial ischemia, followed by 60-minute reperfusion. Seven of them were subjected to an induced heart failure through an overdose of halothane, two of which were treated with intra-aortic counterpulsation during the reperfusion stage. The remaining two animals were monitored during their ischemia-reperfusion stage.

Results: Data obtained in the 5 animals suffering from heart failure followed by myocardial ischemia showed that: a) heart failure induction determined decrease in cardiac output, cardiac index and systolic and diastolic aortic pressure (AoP) with respect to their basal values (p<0.05), b) myocardial ischemia decreased the WTF compared with basal and induced heart failure values (p<0.05), c) during the reperfusion stage accompanied by induced heart failure, WTF increased with respect to values observed during the ischemia induction stage (p<0.05); nevertheless, basal values were not recovered after reperfusion (p<0.05). During this 60-minute stage, systolic and diastolic AoP values were lower (p<0.05) than those at the basal stage.

Conclusion: AIx and WTF values calculated from synchronically recorded values of aortic pressure and left ventricular wall thickness during the reperfusion stage in all animals (n = 9) showed a negative correlation (p<0.05). Analysed data provided evidence of a negative relationship between a left ventricular index of myocardial function and an arterial index obtained from AoP waves.

Methods: An overview of DM pathogenesis and its associated micro- and macro-vascular complications is presented. Possible underlying mechanisms of herbal remedies in DM management are provided, highlighting some key therapeutic targets. The review also appraises the recent progress of herbal products in treating DM through regulating inflammation and gut microbiota. Finally, currently available pharmacological treatments are discussed.

Results: The results show that numerous plants have proven to be promising sources of insulin secreting agents, α-glucosidase and α-amylase inhibitors. Among the non- conventional targets, inhibition of key enzymes such as lipase, cholinesterases and angiotensin converting enzyme has been directly and/or indirectly linked to DM and DM complications. For instance, hypericin, pseudohypericin and I3,II8-biapigenin isolated from Hypericum perforatum L., and palmatine and columbamine isolated from Dichocarpum auriculatum (Franch.) W. T. Wang & P. K have been found to be powerful lipase and cholinesterase inhibitors, respectively. Moreover, a number of plant-derived compounds such as feruloylated oligosaccharides from maize bran, baicalein and berberine are reported to mediate anti-diabetic property via modulation of gut microbiota.

Conclusion: The information amassed in this review is anticipated to provide useful scientific baseline information to support advanced research in natural antidiabetic drug development.

Objective: This review aimed to describe the particularities of the RAS and the immune system profile of particular subgroups of patients.

Methods: This non-systematic review summarizes evidence on SARS-CoV-2 infection in specific subgroups of patients and possible relationships between immune system, RAS and the pathophysiology of COVID-19.

Results: The RAS and the immune system exert a role in the pathogenesis and prognosis of COVID-19, mainly in cases of hypertension, diabetes, obesity and other chronic diseases. The overactivation of the ACE/Ang II/AT1R axis and the enhancement of inflammation contribute to deleterious effects of COVID-19. Likewise, pregnant women and elderly patients usually display immune responses that are less effective in withstanding exposition to viruses, while children are relatively protected against severe complications of COVID-19. Women, conversely, exhibit stronger antiviral responses and are less sensitive to the effects of increased Ang II.

Future Perspectives: The recognition of vulnerable subgroups and risk factors for disease severity is essential to better understand the pandemic. Precision medicine tools, including proteomics and metabolomics approaches, identified metabolic patterns of the severe form of disease and might be the alternative to diagnose, evaluate and predict the prognosis and the efficiency of therapies.

Conclusion: The pathogenesis of SSR is not well known. The patients after reinfusion can develop immediate reactions suggesting involvement of IgE hypersensitivity. Nevertheless, there are patients who tolerated reinfusion. Further studies and assays are needed for a better understanding of these reactions and to lead to a safer re-administration if needed.]]> https://www.benthamscience.comarticle/116069 https://www.benthamscience.comarticle/111215 https://www.benthamscience.comarticle/107842Background: Burns induce a boost in local and systemic complement levels as well as immune cell infiltration in the burn wound, which may negatively affect wound healing.

Objective: In this study, the effects of long-term treatment with complement inhibitor C1 esterase inhibitor (C1inh) on post-burn inflammation and wound healing parameters were analyzed in time up to 60 days post-burn.

Methods: Burned pigs were treated either with or without C1inh up to 15 days post-burn. Burn wound biopsies and blood were collected at different time points up to 60 days post-burn. Thereafter, complement in blood as well as complement and immune cells in the wound, capillary leakage, necrosis, reepithelialization and wound contraction were quantified.

Results: No significant differences in complement C3 blood levels were observed at any time point between C1inh-treated and control pigs. In the wound, complement C4 levels were significantly lower in the C1inh group than in controls at day 3-6 and 21-30 post-burn. Similarly, C3 levels, neutrophil and macrophage infiltration in the wound were, although not statistically significant, reduced in C1inh-treated pigs at day 9-14 post-burn. No differences in lymphocyte infiltration in the wound were found between C1inh and control pigs. C1inh-treated pigs also showed reduced capillary leakage. Despite these effects, no significant differences in the long-term wound healing parameters necrosis, reepithelialization and wound contraction were observed between C1inh and control pigs.

Conclusion: In pigs, 15 days of C1inh treatment after burn, leads to a reduction in local inflammation and capillary leakage in the burn wound without affecting long-term wound healing parameters.

Methods: Solvent emulsification and evaporation method were employed to prepare Ramiprilloaded solid lipid nanoparticles containing stearic acid and phosphatidylcholine as a lipid and surfactant, respectively. The prepared formulations were studied for particle size analysis, % entrapment efficiency, Zeta Potential, SEM, X-ray diffraction study, FTIR, NMR spectroscopy, in vitro release study and stability study.

Results: The obtained results were noted to be within the standard limits. No interaction between Ramipril and other excipients, was confirmed with the FT-IR study of the formulations. Particle size analysis confirmed that the size of the prepared formulations ranged between 200-350 nm. The percent entrapment efficiency was observed in the range of 70.61-91.60%. The result of entrapment and particle size of the nanoparticles from the R5 batch was adjudged. The designed formulation noted a 70.50% cumulative drug release within a period of 7 h. The designed batch showed a mean zeta potential of -29.4 mV, exhibiting good stability of the formulation.

Conclusion: The developed formulation was found to be stable and it represents a promising system for the sustained and controlled delivery of Ramipril.]]> https://www.benthamscience.comarticle/111532 https://www.benthamscience.comarticle/110421 Methods: 362 adult CSU patients seen over a 10-year period at a University Allergy/Asthma clinic were identified. Patients reported no drug allergies or any drug allergy. Multiple drug allergies were defined as allergies to ≥ 2 chemically unrelated drugs. Using Chi-square or Wilcoxon analysis, we compared demographic features of CSU with and without drug allergy and with multiple vs. single drug allergy.

Results and Discussion: Overall, 202 CSU patients (56%) reported drug allergy. Drug allergic CSU patients were older, with a greater proportion of whites and higher BMI vs. CSU without drug allergy (p=0.002, p=0.047, p=0.004, respectively). Penicillin was the most common drug allergy, with urticaria the most frequently reported reaction. Female sex, white race, older age at the visit, and co-existing asthma were more common in multiple drug allergy (n=115) vs. single drug allergy (p=0.002, p=0.02, p=0.03, p=0.0002, respectively).

Conclusion: In CSU, the prevalence of self-reported drug allergies was higher than the general population. Drug allergy is associated with older age, white race and higher BMI, while multiple drug allergy was also associated with asthma. These CSU sub-populations should be studied to avoid the potential for morbidity associated with less efficacious and more costly drugs.]]> https://www.benthamscience.comarticle/109640 Objective: The objective of this article is to examine existing data on the reduction of cardiovascular morbidity and mortality in diabetes. Control of glycemia, lipid levels, and blood pressure are described in brief. The main scope of this article is, however, to review the glucose-independent cardiovascular effect of antidiabetic pharmacological agents (mainly other than insulin).

Methods: The article is a narrative review based on recently published reviews and meta-analyses complemented with data from individual trials, when relevant.

Results and Discussion: Older data suggest a cardioprotective role of metformin (an inexpensive and safe drug); a role to date not convincingly challenged. The cardiovascular effects of thiazolidinediones, sulphonylurea, and glinides are debatable. Recent large-scale cardiovascular outcome trials suggest a neutral profile of dipeptidyl peptidase 4 inhibitors, yet provide compelling evidence of cardioprotective effects of glucagon-like 1 receptor antagonists and sodium-glucose transporter 2 inhibitors.

Conclusion: Metformin may have a role in primary and secondary prevention of cardiovascular disease; glucagon-like 1 receptor antagonists and sodium-glucose co-transporter 2 inhibitors play a role in secondary prevention of atherosclerotic cardiovascular disease. Sodium-glucose transporter 2 inhibitors have a role to play in both primary and secondary prevention of heart failure; yet, they carry a small risk of the potentially dangerous adverse effect, euglycemic diabetic ketoacidosis.]]> https://www.benthamscience.comarticle/104174Background: Chronic Spontaneous Urticaria (CSU) is a disease presenting typical wheals characterized by itching, angioedema or both. Although CU is, by appearance, a relatively “simple” disease, yet it has a devastating effect on those suffering due to its immense social implications.

Aims: The aim of the present study was to investigate the effect of omalizumab in the treatment of CSU. In particular, gender, co-administration of drugs and comorbidities were taken into account.

Materials and Methods: 108 patients (25 Males/83 Females) admitted to our department were diagnosed with CSU and were treated for 30 months. CSU was estimated on a score basis, which was used in order to define disease severity. The mean total CSU score and the mean CSU score of the first trimester, as well as the first semester, were calculated. Patients were treated with omalizumab, and in several cases, with co-administration of dapsone, cyclosporine and anti-histamines.

Results: Females manifested significantly higher scores as compared to males. Further on, patients who relapsed manifested significantly higher scores during the whole time course, as well as at the end of the first semester.

Conclusion: Females are more prone to CSU. Although CSU scores in patients with remission, relapse and poor response manifested no significant difference at diagnosis, relapsed patients manifested higher CSU scores in the first semester. Therefore, the first semester of treatment is probably critical for the final patient outcome. Further studies are necessary in order to understand the mechanisms of CSU for better treatment and prognosis.

Methods: Reports published in PubMed that covered Pharmacological and Non-Pharmacological Approaches in subjects taking hypertension management were reviewed by the group independently and collectively. Practical recommendations for hypertension management were established by the panel.

Results: Pharmacological mechanism, action characteristics, and main adverse reactions varied across different pharmacological agents, and patients with hypertension often require a combination of antihypertensive medications to achieve the target BP range. Non-pharmacological treatment provides an additional effective method for improving therapy adherence and long-term BP control, thus reducing the risk of cardiovascular diseases, and slowing down the progression of the disease.

Conclusion: This review summarizes the available literature on the most convincing guideline principles, pharmacological treatment, biotechnology interference, interventional surgical treatment, managing hypertension with technical means of big data, Artificial Intelligence and Behavioral Intervention, as well as providing future directions, for facilitating Current and Developing knowledge into clinical implementation.

Objective: In this review, we aimed to describe the intimate connections between the RAS components, the immune system and COVID-19 pathophysiology.

Methods: This non-systematic review article summarizes recent evidence on the relationship between COVID-19 and the RAS.

Results: Several studies have indicated that the downregulation of membrane-bound ACE2 may exert a key role for the impairment of immune functions and for COVID-19 patients’ outcomes. The downregulation may occur by distinct mechanisms, particularly: (1) the shedding process induced by the SARS-CoV-2 fusion pathway, which reduces the amount of membrane-bound ACE2, stimulating more shedding by the high levels of Angiotensin II; (2) the endocytosis of ACE2 receptor with the virus itself and (3) by the interferon inhibition caused by SARS-CoV-2 effects on the immune system, which leads to a reduction of ACE2 receptor expression.

Conclusion: Recent research provides evidence of a reduction of the components of the alternative RAS axis, including ACE2 and Angiotensin-(1-7). In contrast, increased levels of Angiotensin II can activate the AT1 receptor in several organs. Consequently, increased inflammation, thrombosis and angiogenesis occur in patients infected with SARS-COV-2. Attention should be paid to the interactions of the RAS and COVID-19, mainly in the context of novel vaccines and proposed medications.

Materials and Methods: Current antiretroviral therapy can prevent viral replication but cannot cure the disease completely. HAART-Highly active antiretroviral therapy is used for the treatment of HIV infection. Challenges in neuro-AIDS therapy are as shown in the graphical abstract. One of the challenges is latent viral reservoirs like the brain; which act as a sanctuary site for viruses. Nearly ~50% of HIV patients show neuropathological signs. Nervous system related disorders, including AIDS dementia, sensory neuropathy, and myelopathy have a 25% of prevalence in patients having access to a highly active combination of antiretroviral therapy.

Results and Conclusions: Brain is one of the viral sanctuary sites for HIV. The current need of neuro-AIDS therapy is to target the brain as a viral reservoir. Drugs should cross or bypass the blood-brain barrier to reach the brain with effective concentrations. Current research on novel drug delivery approaches may prove helpful in treating neuro-AIDS and related disorders effectively.

Objective: This article aimed to provide an update on the evaluation, diagnosis, and treatment of nummular eczema.

Methods: A PubMed search was performed in using the key terms “nummular eczema”, “discoid eczema”, OR “nummular dermatitis”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key terms “nummular eczema”, “discoid eczema”, OR “nummular dermatitis” in www.google.com/patents and www.freepatentsonline.com.

Results: Nummular eczema is characterized by sharply defined, oval or coin-shaped, erythematous, eczematous plaques. Typically, the size of the lesion varies from 1 to 10cm in diameter. The lesions are usually multiple and symmetrically distributed. Sites of predilection include the lower limbs followed by the upper limbs. The lesions are usually intensely pruritic. The diagnosis is mainly clinical based on the characteristic round to oval erythematous plaques in a patient with diffusely dry skin. Nummular eczema should be distinguished from other annular lesions. Dermoscopy can reveal additional features that can be valuable for correct diagnosis. Biopsy or laboratory tests are generally not necessary. However, a potassium hydroxide wet-mount examination of skin scrapings should be performed if tinea corporis is suspected. Because contact allergy is common with nummular eczema, patch testing should be considered in patients with chronic, recalcitrant nummular eczema. Avoidance of precipitating factors, optimal skin care, and high or ultra-high potency topical corticosteroids are the mainstay of therapy. Recent patents related to the management of nummular eczema are also discussed.

Conclusion: With proper treatment, nummular eczema can be cleared over a few weeks, although the course can be chronic and characterized by relapses and remissions. Moisturizing of the skin and avoidance of identifiable exacerbating factors, such as hot water baths and harsh soaps may reduce the frequency of recurrence. Diseases that present with annular lesions may mimic nummular eczema and the differential diagnosis is broad. As such, physicians must be familiar with this condition so that an accurate diagnosis can be made, and appropriate treatment initiated.

Aim: The present study aims at analyzing CU score concerning time, as a time-series. The authors have attempted to model the investigated time-series to unravel possible causative relationships.

Methods: 108 patients (25Males/83Females) admitted to our department were diagnosed with CU. CU was estimated on a score basis, which was used to define disease severity. Urticaria score was assessed on the basis of Urticaria Activity Score 7 (UAS7). The mean CU score, the mean CU score rate concerning the first month at diagnosis as well as the monthly CU score rate were calculated.

Results: Gender is a factor that influences CU score with time. In addition, there was a significant finding that time-series differ with the administration of monotherapy or complementary therapy.

Conclusion: We have found that females are more prone to CU, while omalizumab monotherapy has more beneficial results as compared to the application of concurrent and maintenance therapies. Further, patients with co-morbidities were more likely to interrupt treatment. Finally, and most significantly, it was shown that monthly CU score rate manifested an oscillatory pattern, which was modelled with the sum of sines functions, highlighting a relative immunological pattern.

Methods: Sprague Dawley rats' heart and myocardial cells I/R model were established in vivo and vitro, then 100 mg/kg and 10 μmol/l baicalin were administrated, respectively. The experiment was randomly divided into 4 groups (n=10): Control; I/R; IR+DMEM; and I/R+baicalin groups. Postoperation, the Left Ventricular (LV) End-Diastolic Pressure (LVEDP), the maximum velocity of LV contraction (dP/dtmax) and the maximum velocity of LV diastole (dP/dtmin) were recorded by the transthoracic echocardiography; the myocardial apoptosis percentage was analyzed by Annexin VFITC/ PI and TUNEL staining, and the apoptosis gene and protein were detected by RT-PCR and western blot. Furthermore, the protein expression of the calcium-sensing receptor (CaSR) and ERK1/2 phosphorylation were observed by western blot and Fura-2-acetoxymethyl ester. Moreover, primary rats’ cardiomyocytes were cultured and ERK1/2 specific inhibitor PD98059 was added to the culture medium. The cell survival rate, vitality and apoptosis were detected by MTT, lactate dehydrogenase (LDH) and TUNEL staining assay Kit, respectively.

Results: Our present study showed that baicalin significantly improved LV hemodynamic parameters and myocardial apoptosis in myocardial I/R injury rats. Furthermore, we found that baicalin could down-regulate the protein expression of CaSR, but up-regulate the protein expression of ERK1/2. Furthermore, when the cells were pretreated with ERK1/2 inhibitor PD98059, the cells survival rate significantly decreased, but LDH activity and apoptosis significantly increased. The results indicated that the effect of baicalin on myocardial I/R injury could be inhibited by ERK1/2 inhibitor.

Conclusion: In conclusion, our data suggests that baicalin attenuates I/R-induced myocardial injury maybe through the suppression of the CaSR/ERK1/2 signaling pathway.

Objectives: To review the published data for leukotriene inhibitors of plant origin and the recent patents for leukotriene inhibitors, as well as their role in the management of inflammatory diseases.

Methods: Published data for leukotrienes antagonists of plant origin were searched from 1938 to 2019, without language restrictions using relevant keywords in both free text and Medical Subject Headings (MeSH terms) format. Literature and patent searches in the field of leukotriene inhibitors were carried out by using numerous scientific databases including Science Direct, PubMed, MEDLINE, Google Patents, US Patents, US Patent Applications, Abstract of Japan, German Patents, European Patents, WIPO and NAPRALERT. Finally, data from these information resources were analyzed and reported in the present study.

Results: Currently, numerous anti-histaminic medicines are available including chloropheneremine, brompheniramine, cetirizine, and clementine. Furthermore, specific leukotriene antagonists from allopathic medicines are also available including zileuton, montelukast, pranlukast and zafirlukast and are considered effective and safe medicines as compared to the first generation medicines. The present study reports leukotrienes antagonistic agents of natural products and certain recent patents that could be an alternative medicine in the management of inflammation in respiratory diseases.

Conclusion: The present study highlights recent updates on the pharmacology and patents on leukotriene antagonists in the management of inflammation respiratory diseases.

Better understanding of the underlying mechanisms of DHRs will help us to identify the drugs likely to induce DHRs and to manage patients at risk.

Objective: The study aims to provide an update on the evaluation and diagnosis of skin allergy to azole antifungal agents.

Methods: This is a systematic review performed on PubMed and Google Schoolbarusing using the key terms “allergy, hypersensitivity, anaphylaxis, immediate-type reaction, delayed-type reaction, ketoconazole, fluconazole, posaconazole, voriconazole, itraconazole, triazoles, imidazoles, antifungals, antimycotics”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, reviews and case reports.

Results: One hundred twenty-four articles matched our search terms. The most common adverse events reported were T-cell mediated delayed-type hypersensitivity reactions, fixed drug eruptions, exanthematous dermatitis, Steven-Johnson syndrome, toxic epidermal necrolysis and acute generalized exhanthematous pustulosis. Rarely a drug rash with eosinophilia systemic symptoms, has been described. Also, immediate-type reactions such as urticaria-angioedema or anaphylaxis have been reported following the administration of antifungal imidazoles, although not so frequently.

Conclusion: Despite their widespread use, triazoles seem to induce rare cutaneous hypersensitivity reactions, but the pathomechanisms, risk factors, diagnostic and management strategies, including skin tests and challenge tests, are little known and poorly investigated.

Methods: A review was conducted to search for the causes, mechanism, clinical features, and management of MDIS.

Results: The most common cause of MDIS is antibiotics followed by non-steroidal antiinflammatory drugs (NSAIDs). Although some non-specific immunological mechanisms are involved, the immunological tests for MDIS are negative. Rashes, gastrointestinal reflux, headache, cough, muscle ache, fever, dermatitis, hypertension, and psychiatric symptoms are the usual manifestations. Treatment is mostly symptomatic with the withdrawal of the offending drug. Drug rechallenges and desensitization may be required for the management of this syndrome.

Conclusion: MDIS occurs by a nonimmune mechanism which requires a prompt withdrawal of the offending drug(s), and in some cases may require drug re-challenge and desensitization.

Methods: Male C57BL/6J mice were fed with a normal diet (10% kcal as fat, lean group) or a high-fat diet (60kcal as fat, obese group) for 12 consecutive weeks. To detect the MIF expression and AMPK activation in response to I/R in isolated hearts from lean and obese mice, myocardial samples were collected from left ventricular areas at different time points. To determine whether MIF supplementation is protective against I/R injury, recombined MIF (10 ng/mL) was applied before ischemia. Myocardial infarct size was estimated by triphenyltetrazolium staining. Western blot was used to detect myocardial MIF expression, AMPK activation and membrane glucose transporter 4 (Glut4) expression.

Results: The expression of MIF was remarkably higher in obese group compared to lean group. Ischemia increased myocardial MIF expression and phosphorylation of AMPK in lean mice, whereas it had no significant effect on obese mice. Furthermore, administration of recombinant MIF increased ischemic AMPK activation and membrane Glut4 expression in both lean and obese mice, while it reduced the infarct size in lean mice only.

Conclusion: An impaired MIF/AMPK activation response and consequent reduced membrane Glut4 expression may play an important role in increasing myocardial susceptibility to I/R in obesity.

Objective: This study aims to provide an update on the epidemiology, pathogenesis, clinical manifestations, diagnosis, aggravating factors, complications, treatment and prognosis of CU.

Methods: The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term "chronic urticaria" at the following links: www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com.

Results: CU is a clinical diagnosis, based on the episodic appearance of characteristic urticarial lesions that wax and wane rapidly, with or without angioedema, on most days of the week, for a period of six weeks or longer. Triggers such as medications, physical stimuli, and stress can be identified in 10 to 20% of cases. C-reactive protein/erythrocyte sedimentation rate, and complete blood cell count with differential are the screening tests that may be used to rule out an underlying disorder. The mainstay of therapy is reassurance, patient education, avoidance of known triggers, and pharmacotherapy. Secondgeneration H1 antihistamines are the drugs of choice for initial therapy because of their safety and efficacy profile. If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms are intolerable, the dose of second-generation H1 antihistamines can be increased up to fourfold the manufacturer’s recommended dose (all be it off license). If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms are intolerable after the fourfold increase in the dosage of second-generation H1 antihistamines, omalizumab should be added. If satisfactory improvement does not occur after 6 months or earlier if the symptoms are intolerable after omalizumab has been added, treatment with cyclosporine and second-generation H1 antihistamines is recommended. Short-term use of systemic corticosteroids may be considered for acute exacerbation of CU and in refractory cases. Recent patents for the management of chronic urticaria are also discussed. Complications of CU may include skin excoriations, adverse effect on quality of life, anxiety, depression, and considerable humanistic and economic impacts. On average, the duration of CU is around two to five years. Disease severity has an association with disease duration.

Conclusion: CU is idiopathic in the majority of cases. On average, the duration of CU is around two to five years. Treatment is primarily symptomatic with second generation antihistamines being the first line. Omalizumab has been a remarkable advancement in the management of CU and improves the quality of life beyond symptom control.

Objective: An 80-year-old man with a history of allergy to pyrazolones, with good tolerance to other NSAIDs was referred to our allergy department because he presented a generalized urticaria after the administration of Intravenous (IV) paracetamol.

Methods: We performed an Intradermal Test (IDT) with paracetamol (0.02mg/ml) and later a Single Blind Oral Challenge Test (SBOCT) with oral paracetamol.

Results: IDT reading at 15min showed negative result so an SBOCT was performed with oral paracetamol. With an accumulative dose of 250mg, after 20min, he developed discomfort, nausea and dizziness, urticarial, hypotension (BP 80/40) as well as flare-up phenomenon was observed in the site of the IDT with paracetamol. Tryptase levels during the reaction and 2hrs later were increased.

Conclusion: We present an anaphylactic shock due to sensitization to paracetamol because of a type I hypersensitivity mechanism, diagnosed by SBOCT and a positive IDT because of flare-up phenomenon, in a patient with previous pyrazolones allergy and with tolerance to other NSAIDs. Some relevant patents are also summarized in this paper.

Clopidogrel is a thienopyridine antiplatelet drug widely used for treatment and also employed for secondary prevention regarding a range of cardiovascular diseases. However, it has been reported to cause hypersensitivity reactions. Ticlopidine is an alternative medication that can be considered when patients have an allergic reaction to clopidogrel. Additionally, ticlopidine is associated with increased risk causing potentially life-threatening adverse reactions to include: Aplastic anemia, reversible neutropenia, and thrombotic thrombocytopenia purpura vs. clopidogrel. Thus, clopidogrel desensitization offers an attractive alternative.

Drug desensitization is defined as causing a temporary state of tolerance to a specific medication responsible for a hypersensitivity reaction. Furthermore, drug desensitization can only be maintained by continuous administration of this drug.

Discussion: The exact immunologically mediated mechanism of how rapid oral desensitization works is not fully understood and yet to be defined. Ultimately desensitization results in causing antigen-specific mast cell tolerance. Various protocols have been published. The length of desensitization ranged from 2 h using 9 doses to 7 h using 15 doses.

Recommendations: Taking the above into account, we recommend using a modification to the protocol that has the largest number of patients to undergo a standardized clopidogrel desensitization. This approach is shorter, as time has immense importance for these patients. Dosing starts at 10 mg dose and with 60 min intervals between doses, this now becomes a 4 h desensitization protocol.]]> https://www.benthamscience.comarticle/94163 https://www.benthamscience.comarticle/91943

Case Report: Here, we report a rare occurrence of non-pigmenting fixed drug eruption after the use of aceclofenac in a 19 year old female.]]> https://www.benthamscience.comarticle/85344

Methods and Results: Data was analysed from 2,683 consecutive patients admitted with AHF and Left Ventricular Ejection Fraction (LVEF) (<40%) from 47 hospitals from February to November 2012. Analyses were evaluated using univariate and multivariate statistics. The overall mean age of the cohort was 58±15, 72% (n=1,937) were males, 62% (n=1,651) had coronary artery disease, 57% (n=1,539) were hypertensives and 47% (n=1,268) had diabetes. Overall cumulative mortality at inhospital, 3- and 12-month follow-up was 5.8% (n=155), 12.6% (n=338) and 20.4% (n=548), respectively. Adjusting for demographic and clinical characteristics as well as medication in a multivariate logistic regression model, ACEIs were associated with lower risk of in-hospital mortality (adjusted odds ratio (aOR), 0.48; 95% Confidence Interval (CI): 0.25 to 0.94; p=0.031). At 3-month follow-up, both ACEIs (aOR, 0.64; 95% CI: 0.43 to 0.95; p=0.025) and ARBs (aOR, 0.34; 95% CI: 0.18 to 0.62; p<0.001) were associated with lower risk of mortality. Additionally, at 12-month follow-up, those prescribed ACEIs (aOR, 0.71; 95% CI: 0.53 to 0.96; p=0.027) and ARBs (aOR, 0.47; 95% CI: 0.31 to 0.71; p<0.001) were still associated with lower risk of mortality.

Conclusion: ACEIs and ARBs treatments were associated with lower mortality risk during admission and up to 12-month of follow-up in Middle East AHF patients with left ventricular systolic dysfunction.]]> https://www.benthamscience.comarticle/87931

Objective: To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patients regardless of their background on equality basis.

Results: Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogenactivated protein, nuclear factor, etc. Considering all the above-mentioned factors, further research from molecular to cellular level will enable a better understanding of the mechanisms. Common antiinflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppresants used for controlling and suppressing inflammatory crisis. A proper phytochemical, pharmacological and physiological evaluation will enable their safe and effective use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal preparations have been patented with some under consideration.

Conclusion: Natural herbs are safe, effective and better options as anti-inflammatory agents than synthetic ones. The phytoconstituents are as effective with the comparable mechanism of action as synthetic molecules. Future research should focus on molecular mechanisms of different beneficial applications of these herbal plants in various diseases. Recent patents on anti-inflammatory drugs and herbal plants have been covered which provide insight into the current status and future prospects in this field.]]> https://www.benthamscience.comarticle/90528 https://www.benthamscience.comarticle/90572