Appearance Of Adverse Effects Research Articles

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice

Background and purposeThe aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. MethodsWe conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. ResultsClinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. ConclusionsOur real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

Evidence for the use of atropine to control myopia in children

To describe the effectiveness of using atropine as a method of controlling the progression of myopia in children. This is a systematic review study of literature, which search strategies in the Biblioteca Virtual em Saúde (BVS) and PubMed, through different combinations of the descriptors “Myopia”, “Control”, “Children” and “Atropine ” in the 2020-2023 timeframe. After selecting the inclusion and exclusion criteria, 30 articles compose the sample corpus. Atropine concentration is directly related to efficacy, with higher doses being more effective, however, also is associated with the appearance of adverse effects, especially photophobia. The most used dose is 0.01%, which presents positive results in control and fewer side effects; most of these studies involve the Asian population. There is a variation in results between populations, due to the different level of pigment in the iris, in addition to sociocultural differences between ethnicities. The lack of intervention can result in complications, with an increased risk related to the degree among children, and is not reduced with optical correction alone. The use of atropine is promising for controlling myopia in children, however it must be tested in association with other control methods and in different populations, so that the treatment is individualized and carried out in a way that presents results, in addition to reducing complications related to refractive disorder.

Kidney toxicity and transcriptome analyses of male ICR mice acutely exposed to the mushroom toxin α-amanitin

Amatoxins are responsible for most fatal mushroom poisoning cases, as it causes both hepatotoxicity and nephrotoxicity. However, studies on amatoxin nephrotoxicity are limited. Here, we investigated nephrotoxicity over 4 days and nephrotoxicity/hepatotoxicity over 14 days in mice. The organ weight ratio, serological indices, and tissue histology results indicated that a nephrotoxicity mouse model was established with two stages: (1) no apparent effects within 24 h; and (2) the appearance of adverse effects, with gradual worsening within 2–14 days. For each stage, the kidney transcriptome revealed patterns of differential mRNA expression and significant pathway changes, and Western blot analysis verified the expression of key proteins. Amanitin-induced nephrotoxicity was directly related to RNA polymerase II because mRNA levels decreased, RNA polymerase II-related pathways were significantly enriched at the transcription level, and RNA polymerase II protein was degraded in the early poisoning stage. In the late stage, nephrotoxicity was more severe than hepatotoxicity. This is likely associated with inflammation because inflammation-related pathways were significantly enriched and NF-κB activation was increased in the kidney.

Repositioning VU-0365114 as a novel microtubule-destabilizing agent for treating cancer and overcoming drug resistance.

Microtubule-targeting agents represent one of the most successful classes of anticancer agents. However, the development of drug resistance and the appearance of adverse effects hamper their clinical implementation. Novel microtubule-targeting agents without such limitations are urgently needed. By employing a gene expression-based drug repositioning strategy, this study identifies VU-0365114, originally synthesized as a positive allosteric modulator of human muscarinic acetylcholine receptor M5 (M5 mAChR), as a novel type of tubulin inhibitor by destabilizing microtubules. VU-0365114 exhibits a broad-spectrum in vitro anticancer activity, especially in colorectal cancer cells. A tumor xenograft study in nude mice shows that VU-0365114 slowed the in vivo colorectal tumor growth. The anticancer activity of VU-0365114 is not related to its original target, M5 mAChR. In addition, VU-0365114 does not serve as a substrate of multidrug resistance (MDR) proteins, and thus, it can overcome MDR. Furthermore, a kinome analysis shows that VU-0365114 did not exhibit other significant off-target effects. Taken together, our study suggests that VU-0365114 primarily targets microtubules, offering potential for repurposing in cancer treatment, although more studies are needed before further drug development.

Sex-dependent differences in behavioral and immunological responses to antibiotic and bacteriophage administration in mice.

The problem of antibiotic resistance is a global one, involving many industries and entailing huge financial outlays. Therefore, the search for alternative methods to combat drug-resistant bacteria has a priority status. Great potential is seen in bacteriophages which have the natural ability to kill bacterial cells. Bacteriophages also have several advantages over antibiotics. Firstly, they are considered ecologically safe (harmless to humans, plants and animals). Secondly, bacteriophages preparations are readily producible and easy to apply. However, before bacteriophages can be authorized for medical and veterinary use, they must be accurately characterized in vitro and in vivo to determinate safety. Therefore, the aim of this study was to verify for the first time the behavioral and immunological responses of both male and female mice (C57BL/6J) to bacteriophage cocktail, composed of two bacteriophages, and to two commonly used antibiotics, enrofloxacin and tetracycline. Animal behavior, the percentage of lymphocyte populations and subpopulations, cytokine concentrations, blood hematological parameters, gastrointestinal microbiome analysis and the size of internal organs, were evaluated. Unexpectedly, we observed a sex-dependent, negative effect of antibiotic therapy, which not only involved the functioning of the immune system, but could also significantly impaired the activity of the central nervous system, as manifested by disruption of the behavioral pattern, especially exacerbated in females. In contrast to antibiotics, complex behavioral and immunological analyses confirmed the lack of adverse effects during the bacteriophage cocktail administration. The mechanism of the differences between males and females in appearance of adverse effects, related to the behavioral and immune functions, in the response to antibiotic treatment remains to be elucidated. One might imagine that differences in hormones and/or different permeability of the blood-brain barrier can be important factors, however, extensive studies are required to find the real reason(s).

Toxicity and Outcomes of Ibrutinib in Chronic Lymphatic Leukemia-Real-World Results from the Study of 215 Patients in Argentina

Different pivotal works allowed the approval of ibrutinib as a CLL treatment, both in the first line and in relapsed/refractory patients, the adverse effects differ from conventional chemotherapy, the discontinuation rate was 10%, but in different real-life studies, showed a higher number of complications and medication suspension rates of 40 to 50%. To know the reality of the use of ibrutinib in CLL in our environment, we designed this work with the objectives of evaluating the safety profile of the drug with the description of the adverse effects, their incidence, and their severity. The clinical efficacy will also be studied with the determination of the response achieved, calculation of overall survival (OS) and progression-free survival. Also as an additional objective, the discontinuation rate and its causes will be obtained. A total of 215 patients in 26 centers throughout the country were retrospectively analyzed. 189 patients (88%) had a global response, and the majority 58% achieved a partial response. The 5-year overall survival was 60%, with no difference between patients with different numbers of previous lines. The progression-free survival of the entire group was 5.06 years. 44.7% of the population, presented at least 1 adverse effect. The most frequent ones were: bleeding, thrombocytopenia, pneumonia and diarrhea. Others presented: anemia, neutropenia, infections, AF, HTA, arthralgia, rash, opportunistic infections. Most adverse events were mild to moderate in grade and generally occurred within the first 6 months. The main cause of treatment suspension was the appearance of adverse effects, 37 patients had to suspend it, 27 due to adverse effects (72.97%). In our work, we found that ibrutinib, as a single agent, has outstanding activity in CLL, with a significant percentage of overall responses, even in patients with several lines of prior treatment. Most of the adverse effects were of a mild to moderate degree. The cardiovascular effects of TKI, HBP, and AF, are in percentages similar to those reported in other studies. If we analyze the percentage of treatment discontinuation, which is 17%, mostly due to adverse effects, this finding is similar to pivotal studies. In conclusion, our real-life study confirms the important activity of ibrutinib in patients with CLL, in the first line and relapses, highlighting the low percentage of treatment discontinuation in our environment. We believe our work reflects the real life and daily care of patients with CLL, under treatment with ibrutinib in our environment.

Arterial blood gases in newborn infants: Early extraction without prior clamping versus extraction after delayed clamping

ObjectivesTo compare the postpartum arterial blood gas parameters recorded early before cord clamping and after delayed cord clamping (DCC). To explore adverse effects and complications of the cord blood gas collection technique without clamping. DesignRandomised controlled trial. SettingBirthing room of La Ribera University Hospital (Valencia, Spain). Participants122 full-term infants born between February 2020 and January 2021. Two groups were established: the experimental group (early sampling prior to clamping and sampling again after DCC) and the non-experimental group (sampling only after DCC). Measurements and findingsThe comparison of arterial blood gas parameters was made using the Student t-test, while the Fisher's exact test was used to compare the proportion of the adverse effects recorded. The pH and base excess values in the experimental group were significantly greater when the sampling was performed without prior clamping. No statistically significant differences were observed in relation to pCO2 or the appearance of adverse effects between the two groups. No complications were recorded. Key conclusions and implications for practiceThe pH and base excess values were higher when the arterial blood gas measurements were made prior to performing the umbilical cord clamping than when the sampling was performed after the DCC. Arterial blood gas sampling without prior clamping was found to be safe, since no complications or increased adverse effects were observed. The use of this technique is therefore advised in normal births of full-term infants.

Aspirin desensitization in nonsteroidal anti-inflammatory exacerbated respiratory disease: The first prospective cohort in Chile.

Nonsteroidal anti-inflammatory exacerbated respiratory disease (N-ERD) is characterized by the Samter triad: chronic rhinosinusitis with nasal polyps, asthma, and nonallergic hypersensitivity to NSAIDs. Its diagnosis is based on a complete clinical history and an aspirin (ASA) challenge test. Medical treatments include biological drugs and ASA desensitization. This study aims to evaluate the clinical response of patients with N-ERD undergoing functional endoscopic surgery (FES), followed by ASA desensitization and maintenance treatment, being the first prospective cohort study carried out in Chile. We conducted 1-year follow-up of 12 patients with N-ERD treated with FES, desensitization, and maintenance with ASA. For each control, the medication score, sinonasal symptomatology (SNOT-22), PEF (peak expiratory flow), nasal polyposis (Lildholdt score), and the appearance of adverse effects were recorded. Computed tomography (CT) of the paranasal cavities was performed at baseline and at the 12-month follow-up to calculate the Lund-Mackay score. Patients presented a reduction of SNOT-22 after the FES, which was maintained at 12 months (p = 0.002); the symptoms that showed the greatest reduction were feeling embarrassed and nasal obstruction. The Lildholdt score was also significantly reduced (p = 0.001); in only three patients, the nasal polyps recurred, and all were small. The PEF showed a slight nonsignificant increase of 3.3%. In total, 75% of patients had an adverse effect, the most frequent being abdominal pain (66.7%), but none of the 12 patients required discontinuation of aspirin treatment in 1-year follow-up. The Lund-Mackay score had a significant reduction of 6.6 points (p < 0.001). ASA desensitization is safe and effective in reducing upper and lower respiratory symptoms in patients with N-ERD and delays the reappearance of nasal polyps, although it is not exempt from adverse effects, with the vast majority being mild.

Off-label use of fixed-dose combination of tramadol and dexketoprofen in primary health care. Evidence-based or cause for concern?

Introduction: The use of the fixed-dose combination of tramadol/dexketoprofen in Spain and in other countries has increased considerably. The authorized therapeutic indication for this medicinal product is the short-term symptomatic treatment of moderate to severe acute pain in adult patients. The objective of this study was to describe the pattern of use of tramadol/dexketoprofen in the field of primary health care. Method: A cross-sectional, descriptive and multicenter study was carried out. The study population included all patients from a Primary Care Department (53 Primary Care teams) with an active prescription of tramadol/dexketoprofen on March 28, 2018. The target population was those patients who were prescribed tramadol/dexketoprofen. dexketoprofen for &gt;20 days. Results: A total of 176 patients had an active prescription for tramadol/dexketoprofen. All patients (100%) had a duration of treatment greater than 5 days and 72.7% (N=128) greater than 20 days. The mean duration of treatment was 14±160.9 days in patients who had less than 20 days of treatment and 224±160.8 days in patients who had more than 20 days of treatment. 35.1% of the patients were treated with &gt;2 pain medications and concomitantly with tramadol/dexketoprofen. The general practitioner initiated 65.6% of the prescriptions. Conclusions: The fixed-dose combination of tramadol/dexketoprofen was frequently used off-label, according to the product characteristics and the available scientific evidence. This study warns about the potential risks associated with the use of this drug in clinical practice, such as lack of effectiveness and/or the appearance of adverse effects.

Management of Pharmacologic Adverse Effects in Advanced Liver Disease

As a consequence of the altered hepatic architecture in advanced liver disease, drug metabolism is modified by changes in pharmacokinetic and pharmacodynamic properties, leading to the appearance of adverse effects and drug interactions and increasing the risk of over- or underdosing of medications. However, there are no tests that accurately determine the degree of impairment of liver metabolic function; therefore, general recommendations are established based on the degree of hepatic extraction, degree of hepatic metabolism, and degree of protein binding. Although the hepatic toxicity of some frequently used drugs, such as acetaminophen, is well known, many health care professionals are unaware or not fully aware of the deleterious effects that other drugs can have on patients with advanced liver injury, as is the case for nonsteroidal anti-inflammatory drugs. It is very important to increase awareness among both health care professionals and patients with advanced liver disease to limit the use of inappropriate drugs and prevent drug-induced liver injury.

Intestinal Dysbiosis in Patients with Histamine Intolerance.

An underlying cause of histamine intolerance is diamine oxidase (DAO) deficiency, which leads to defective homeostasis and a higher systemic absorption of histamine. Impaired DAO activity may have a genetic, pharmacological or pathological origin. A recent proposal also suggests it can arise from an alteration in the gut microbiota, although only one study has explored this hypothesis to date. A greater abundance of histamine-secreting bacteria in the gut could lead to the development of histamine intolerance. Thus, the aim of this study was to characterize the composition of the intestinal microbiota of patients with histamine intolerance symptoms and compare it with that of healthy individuals. The study was performed by sequencing bacterial 16S rRNA genes (V3-V4 region) and analyzing the data using the EzBioCloud Database. Dysbiosis of the gut microbiota was observed in the histamine intolerance group who, in comparison with the healthy individuals, had a significantly lower proportion of Prevotellaceae, Ruminococcus, Faecalibacterium and Faecablibacterium prausnitzii, which are bacteria related to gut health. They also had a significantly higher abundance of histamine-secreting bacteria, including the genera Staphylococcus and Proteus, several unidentified genera belonging to the family Enterobacteriaceae and the species Clostridium perfringens and Enterococcus faecalis. A greater abundance of histaminogenic bacteria would favor the accumulation of high levels of histamine in the gut, its subsequent absorption in plasma and the appearance of adverse effects, even in individuals without DAO deficiency.

Major radiological threats and emergencies requiring public health preparedness (the example of Greece)

Radiological emergencies carry the potential for major disruptions to public health care provision, due to their infrequency, unpredicted nature, delay in appearance of adverse effects and the grave psychological impact on sufferers and society. This study aims to describe and analyze the main categories of radiological hazards and emergencies that require hospital response and preparedness at a nation-wide level, taking into specific account the example of Greece. These radiological threats are either accidental, like reactor emergencies and accidents in hospital or industrial units implementing radiological sources of high activities, or deliberate, like detonation of nuclear devices and malicious use of various radionuclides.

Disruptive Behavior at Hospitals and Factors Associated to Safer Care: A Systematic Review

Disruptive behavior creates a dysfunctional culture that has a negative impact on work relations and influences the quality of care and safety of the patient. The objective of the present work is to provide the best methodological quality scientific evidence available on disruptive behavior at a hospital, the aspect associated with the safety of the patient, and its impact on quality of care. For this, we included studies that addressed the prevalence of disruptive behaviors observed in the area of hospital health and its professionals. The selection, eligibility, data extraction and evaluation of the risk of bias stages were conducted by two researchers, and any discrepancies were solved by a third researcher. The data presented show that disruptive behaviors are frequently observed in the daily life of health professionals, and compromise the quality of care, the safety of the patient, and can lead to adverse effects. The results presented indicate that the appearance of disruptive behaviors compromises the quality of care, the safety of the patient, and the appearance of adverse effects, and can also affect the physical and mental health of the health professionals. PROSPERO registration number: CRD42021248798.

The health risks of dysphagia for patients with head and neck cancer: a multicentre prospective observational study

It is well known that malnutrition is a frequent co-morbidity in cancer patients, especially in those with head and neck neoplasms. This may be due both to the presence of dysphagia symptoms and to the appearance of adverse effects on chemotherapy and / or radiotherapy. The aim of this retrospective observational multicentric study is to evaluate the nutritional status between dysphagia cancer patients and non-dysphagia cancer patients. Data from 60 patients were analysed, 31 of which without dysphagia and 29 with dysphagia. Results highlight that patients with dysphagia had higher involuntary body weight loss than non-dysphagia ones (p < 0.001). By analysing the entire population, it stands out a weight loss rate of 12 ± 9% compared to the usual weight was observed and a prevalence of moderate / severe malnutrition diagnosis of 53%. Furthermore, 76% of the population who manifested the symptom of dysphagia presented severe malnutrition already at the first visit, compared to 32% of non-dysphagia subjects.

Assessment of Knowledge, Attitude, and Practice of Pharmacists towards Drug Interactions in Saudi Arabia

Background: Drug interactions, which are generally encountered in medical prescriptions, may lead to severe health issues. Pharmacists in both the public and private pharmacy setting are by profession in a unique position to gain and use their competencies to find and prohibit drug interactions.&#x0D; Aim of the Study: To assess knowledge, attitude and practice of pharmacists toward drug interactions in Saudi Arabia.&#x0D; Materials and Methods: A cross-sectional study was conducted using a self- administered questionnaire.&#x0D; Results: Two hundred sixty-three pharmacists participated in the survey and results were expressed in frequencies and percentages. The mean age of participant pharmacists was (31.7) years showing a relatively young participant’s population. Males were (75.3%), while females were (24.7%). Majority of pharmacists (67.3%) were working in public sector. Half of them had a bachelor’s degree in pharmacy as their latest academic degree.&#x0D; Participants’ averages of awareness, attitude and practice regarding drug interactions, correct knowledge of drug-drug, drug-food, drug-disease interactions were, (90.7%), (65.3%), (67.7%), (61.7%) respectively. Most (79.8%) of the participants asserted that the notified doctors usually agree with pharmacists’ opinion and decision. This percentage indicates a good cooperation when compared to other studies.&#x0D; Conclusion: Pharmacists’ knowledge about drug interactions was inadequate. Lack of knowledge of drug interactions may lead to improper patient counseling and the appearance of adverse effects. There is a need to improve the knowledge and to uplift the level of awareness of pharmacists about the potential drug interactions that are clinically related.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice

Background and purposeThe aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. MethodsWe conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. ResultsClinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. ConclusionsOur real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

TT genotype of the MMP-9-1562C/T polymorphism may be a risk factor for thrombolytic therapy-induced hemorrhagic complications after acute ischemic stroke.

Levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) influence recombinant tissue plasminogen activator (rtPA) therapy response in patients with acute ischemic stroke (AIS). Serum levels of MMPs and TIMPs along with the expression of genes coding these proteins are related to the recovery and appearance of adverse effects (AE) after AIS. Consequently, it is important to explore whether polymorphisms in regulatory sequences of MMPs and TIMPs are associated with rtPA response in AIS patients. To determine whether selected polymorphic variants within MMP-2, MMP-9, and TIMP-2 genes may influence rtPA therapy response with regard to outcomes in patients with AIS and the occurrence of AE. Our study included 166 patients suffering AIS, treated with rtPA. Patients' recovery was estimated using the Modified Rankin Scale (mRS) 3months after the AIS occurred. Favorable outcome was defined with scores 0-1 and poor outcome with scores 2-6. Genotyping was performed using real-time PCR (rs243866, rs243865, rs243864, rs2277698, and rs8179090) and PCR-RFLP (rs2285053, rs3918242) methods. Additionally, rtPA AE were followed during the hospitalization. There was no significant association between genotypes and alleles of selected polymorphisms and rtPA therapy response measured through the decrease of the mRS score in patients with AIS. Intracranial hemorrhage, as well as parenchymal hematoma type 2, was significantly more frequent in patients with TT genotype of the MMP-9-1562C/T polymorphism (p=0.047, p=0.011, respectively). Patients with intracranial hemorrhages after rtPA were significantly more likely to have the TT genotype of TIMP-2-303C/T polymorphism and the TT genotype of MMP-9-1562C/T polymorphism (p<0.001). TT genotype of the MMP-9-1562C/T polymorphism may be a risk factor for rtPA-induced hemorrhagic complications after AIS.

Treating with esketamine nasal, will increase blood pressure?

IntroductionEsketamine had been rised as a potential treatment for Resistant Depression, becoming an alternative for the use of Electroconvulsive Therapy. In Spain since 2020, it has been applied for compassionate use but is not widely used. Although Esketamine is defined safe and effective in preliminary studies, there are common side effects which could reduce it use.ObjectivesIncreasing blood pressure has been found commonly in ederly population treated with Esketamine Nasal. Studies showed as very common side effect (10% or more) increasing systolic and diastolic blood pressure which is higher in elderly people. Our aim is to show that esketamine is well tolerated and safe in ederly people without increasing blood pressure, although is combinate with oral antidepressant therapy.MethodsPresenting female 65-year-old with 4 years of treatment maintaining a moderate-severe symptoms. Althougt numerous pharmacological strategies have been attempted, with optimal time and maximum doses, which have been progressively withdrawing showing lack of efficacy or appearance of adverse effects. Among the drugs used we find; 11 antidepressants, 3 antipsychotics, benzodiazepines and even lithium, without response after 6 weeks of treatment. Futhermore, patient refusal to receive Electro-Convulsive Therapy. Treating with Esketamine nasal and applying the established guidelines.ResultsAssess the response to Esketamine Nasal with Montgomery-Asberg depression scale (MADRS) we found that decrease the initial score in 26 points. Evaluating blood pressure before and after each time with no increased value.ConclusionsConcluding esketamine is well tolerated and safe in ederly people without increasing blood pressure. These findings and results should be confirmed with futher studies.

Organ-on-a-Chip systems for new drugs development.

Research on alternatives to the use of animal models and cell cultures has led to the creation of organ-on-a-chip systems, in which organs and their physiological reactions to the presence of external stimuli are simulated. These systems could even replace the use of human beings as subjects for the study of drugs in clinical phases and have an impact on personalized therapies. Organ-on-a-chip technology present higher potential than traditional cell cultures for an appropriate prediction of functional impairments, appearance of adverse effects, the pharmacokinetic and toxicological profile and the efficacy of a drug. This potential is given by the possibility of placing different cell lines in a three-dimensional-arranged polymer piece and simulating and controlling specific conditions. Thus, the normal functioning of an organ, tissue, barrier, or physiological phenomenon can be simulated, as well as the interrelation between different systems. Furthermore, this alternative allows the study of physiological and pathophysiological processes. Its design combines different disciplines such as materials engineering, cell cultures, microfluidics and physiology, among others. This work presents the main considerations of OoC systems, the materials, methods and cell lines used for their design, and the conditions required for their proper functioning. Examples of applications and main challenges for the development of more robust systems are shown. This non-systematic review is intended to be a reference framework that facilitates research focused on the development of new OoC systems, as well as their use as alternatives in pharmacological, pharmacokinetic and toxicological studies.

Reduced Trypanosoma cruzi-specific humoral response and enhanced T cell immunity after treatment interruption with benznidazole in chronic Chagas disease.

Interruption of benznidazole therapy due to the appearance of adverse effects, which is presumed to lead to treatment failure, is a major drawback in the treatment of chronic Chagas disease. Trypanosoma cruzi-specific humoral and T cell responses, T cell phenotype and parasite load were measured to compare the outcome in 33 subjects with chronic Chagas disease treated with an incomplete benznidazole regimen and 58 subjects treated with the complete regimen, during a median follow-up period of 48 months. Both treatment regimens induced a reduction in the T. cruzi-specific antibody levels and similar rates of treatment failure when evaluated using quantitative PCR. Regardless of the regimen, polyfunctional CD4+ T cells increased in the subjects, with successful treatment outcome defined as a decrease of T. cruzi-specific antibodies. Regardless of the serological outcome, naive and central memory T cells increased after both regimens. A decrease in CD4+ HLA-DR+ T cells was associated with successful treatment in both regimens. The cytokine profiles of subjects with successful treatment showed fewer inflammatory mediators than those of the untreated T. cruzi-infected subjects. High levels of T cells expressing IL-7 receptor and low levels of CD8+ T cells expressing the programmed cell death protein 1 at baseline were associated with successful treatment following benznidazole interruption. These findings challenge the notion that treatment failure is the sole potential outcome of an incomplete benznidazole regimen and support the need for further assessment of the treatment protocols for chronic Chagas disease.