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The purpose was to investigate the influence of zinc gluconate (ZnG) supplementation on liver and kidney toxicity induced with ethanol (E) and potentiated by rifampicin (R) addition in rats. Material and methods: The experiment was performed on 4 groups: group 1 – control, treated for 6 weeks with saline, 1mL/kg; group 2 – E, treated for 6 weeks with ethanol (E), 56%; group 3 – E+R, treated with E for 6 weeks and rifampicin 50mg /kg/day, only in the last 14 days of the experiment; group 4 – E+R+Zn (same treatment as group 3, but, in the last 14 days, zinc gluconate – ZnG,10 mg/kg/day was added). All administrations were performed by oral gavage. For groups 2, 3, and 4, the ethanol dose was 6g/kg/day on the first 3 days, then it was increased to 7g/kg/day in the following 3 days, and to 8g/kg/day until the end of the experiment. At the end of the experiment (6 weeks), rats were sacrificed and blood samples were collected for biochemistry determinations. Results: Treatment with E for 6 weeks determined significant increases in liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, gamma-glutamyl transferase and alkaline phosphatase, P < 0.001 group 2 vs. 1 for all mentioned parameters) and renal function impairment (increases in serum urea and creatinine, P < 0.001 and respectively P < 0.05, group 2 vs. 1). The antioxidant defense was also impaired in group 2 vs. 1 (superoxide dismutase and glutathione peroxidase activity decreased, P < 0.05). The addition of rifampicin, 50 mg/kg/day during the last 14 days resulted in further increases in alanine aminotransferase and alkaline phosphatase (P < 0.001, group 3 vs. control group 2), as well as aspartate aminotransferase, lactic dehydrogenase, creatinine and ureea (0.01 < P < 0.05, group 3 vs. group 2). ZnG provided a slight protection against the increase of some of the liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and alkaline phosphatase) and serum creatinine, as well as against the decrease of serum glutathione peroxidase and superoxide dismutase concentration. Conclusions: This study represents a furthermore proof for the beneficial effect of zinc salts against toxicity induced by different agents, including antibacterials added to the alcohol; the protection is proven mainly for liver function and the antioxidant profile improvement appears to have a key role in it. Supplements with zinc may be beneficial in patients undergoing long-term anti-biotherapy.

Introduction The patient satisfaction questionnaires in literature are according to the community pharmacies services in the authors’ countries and not all have psychometric reports to support the results. We designed a questionnaire specific to the services of community pharmacies in Romania to evaluate the level of patient satisfaction.Methods We carried out a cross-sectional study on voluntary patients. The questionnaire consisted of 22 items, grouped into three domains corresponding to patient satisfaction with pharmacies, pharmaceutical staff and medication availability, and four subdomains related to pharmaceutical staff skills. The 5-point Likert scale was used. Statistical analysis was done in SPSS 27.0.Results The Cronbach’s Alpha was 0.861. The Inter-rater Agreement was 72.0%, the Item Content Validity was 97.6% and the completeness index was 100%. The factor analysis indicated 6 factors (Eigen values >1.0). The 809 patients had a median of overall satisfaction score of 3.77; the median was 4.0 regarding satisfaction score with pharmaceutical staff skills. Respondents characteristics varied the patient’s satisfaction level (p ≤ 0.05).Conclusions The reliability and validity of the questionnaire have been demonstrated. Overall patient satisfaction with community pharmacy services had a moderate level, but the attitude and confidence in the pharmacist had a high level of satisfaction.

The topical therapy with rifampicin (RF)-based formulations is beneficial for treating postoperative wound infections and to accelerate healing. Despite recent research highlighting the antibiotic’s significant anti-inflammatory properties, limited topical wound healing products are currently available. The present study aimed to prove that the newly synthesized nanoparticles based on grafted alginate and poly(N-vinylcaprolactam) (pNVCL) and poly-lactic-co-glycolic acid (PLGA) contribute to the healing process of a wound. The methods used were at first the synthesis of the copolymer of alginate and pNVCL via grafting from technique and radical polymerization followed by water-in-oil-in water (W/O/W) emulsification; as oil phase PLGA dissolved in dichloromethane (DCM) was used. The formed nanoparticles were than characterized. The loaded RF was determined to be 160 µg/mL for a 20 mg formulation and within a four-hour time frame approximately 10% of the total loaded amount was released. The inhibitory concentrations (IC50) were 192.1 µg/mL for the nanoparticle, 208.8 µg/mL for pure rifampicin, and 718.1 µg/mL for the rifampicin-loaded nanoparticles. Considering the double role rifampicin was used for, the result was considered satisfactory in the way that these formulations could be used predominantly for postoperative wound irrigation in order to avoid infections and to improve healing.

Background/Objectives: The association between chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) is a common one, with long-term therapeutic and prognostic impact. In view of the high pulmonary and cardiovascular morbidity and mortality, self-management contributes to decreasing the risk of an acute cardiac event or pulmonary decompensation. Methods: We conducted a prospective cohort study on 100 patients admitted to Iasi Clinical Rehabilitation Hospital who were divided into two groups according to the presence (67 patients) or absence (33 patients) of MetS. All patients benefited from multidisciplinary counseling sessions on their active role in improving modifiable cardiovascular risk factors and thus increasing quality of life. The aim of this study was to examine the impact of metabolic syndrome on lung function and the role of self-management in a 6-month follow-up period. The demographic, anthropometric, cardiovascular risk factors, and respiratory function were analyzed at baseline and at 6 months. Results: The presence of MetS was associated with higher fasting blood glucose (p = 0.004) and triglycerides (p = 0.003) but not with higher levels of interleukins or TNF-alpha. At the 6-month follow-up, abdominal circumference, forced expiratory volume in one second (FEV1), dyspnea severity, and blood pressure values improved in male patients with COPD. Systolic and diastolic blood pressure decreased in the COPD group as a whole, but especially in male patients with and without associated MetS. BMI was positively correlated with FEV1 (r = 0.389, p = 0.001) and the FEV1/forced vital capacity (FVC) ratio (r = 0.508, p < 0.001) in all COPD patients and in the MetS subgroup. In the COPD group as a whole. the six-minute walk test (6MWT) results (m) were positively correlated with FEV1 and FVC. The correlation remained significant for FVC in COPD patients with and without MetS. An increase in BMI by one unit led to an increase in TG values by 3.358 mg/dL, and the presence of metabolic syndrome led to an increase in TG values by 17.433 mg/dL. Conclusions: In our study, MetS is a common comorbidity in patients with COPD and is associated with higher BMI, fasting glucose, and triglycerides but not with the inflammatory parameters. A mixed pulmonary–cardiovascular rehabilitation intervention leads to improvement in various parameters in both female and male COPD patients.

Background and Objectives: Although available therapies have changed the natural evolution of multiple sclerosis (MS), in time some patients assume a progressive course and no longer respond to treatment. There is no definitive clinical or laboratory parameter to certify MS progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS) in early phases of transition. Our study aims to evaluate the value of clinical parameters and serum neurofilament light chain levels (sNfLs) as early warning signs of conversion to SPMS. Materials and Methods: The Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), 25-foot walk test (25FWT) and Symbol Digit Modalities Test (SDMT) were evaluated at 12 months apart in a cohort of 83 RRMS treated patients. sNfLs were evaluated at the second time point. Results: sNfLs correlate with EDSS and SDMT, with EDSS change and disease duration. Clinical parameters correlate among themselves and perform well in supporting the diagnosis of SPMS in logistic regression and ROC curves analysis. Eighty percent of the RRMS patients in our study (of which 65% are treated with high-efficacy disease-modifying drugs) showed some type of progression independent of relapses (PIRA) after 12 months, with one in five patients experiencing isolated cognitive worsening and almost two-thirds some type of motor worsening. We found no differences in terms of progression between patients treated with platform drugs versus high-efficacy drugs. Conclusions: An elevated level of progression independent of relapses (PIRA) was found in our cohort, with high-efficacy drugs providing no supplementary protection. As sNfL levels were correlated with the progression of EDSS (the main clinical progression marker), they may be considered potential prognostic markers, but further studies are necessary to precisely define their role in this direction. The lack of early sensitive markers for risk of progression may contribute to therapeutic delay and failure.

Background and Objectives: Formaldehyde induces oxidative stress and is carcinogenic, particularly squamous cell carcinoma of the nasopharyngeal area. Around us, in exhaust gases, cigarette smoke, and various industrial products, FA primarily affects the respiratory tract and other organs like the cornea, liver, kidneys, brain, and cardiovascular system. This study aims to determine if antioxidants can mitigate FA’s harmful effects. Materials and Methods: Several databases, including PubMed, Science Direct, Springer, and Wiley, were systematically searched. Research publications on antioxidants mitigating FA-induced oxidative damage were included, but reviews and articles lacking complete texts were excluded. SYRCLE’s risk of bias tool for animal studies has been used. Tables were used for data synthesis. Out of 8790 articles, 35 publications detailing tissue homogenate for biochemical analysis, standard hematoxylin–eosin staining, and immunohistochemistry markers for histopathological and immunohistochemical diagnosis were selected. Most studies were case–control studies, utilizing rat or mouse models. Additionally, one cohort study on industrial workers was analyzed. Conclusions: Antioxidants, including plant extracts, vitamins, and pigments, can prevent or heal FA-induced lesions. However, human studies, particularly biopsies, remain challenging, and animal trials are limited. Further research is needed to confirm FA’s long-term effects and optimize antioxidant dosages.

We report a biocompatible hydrogel dressing based on sodium alginate-grafted poly(N-vinylcaprolactam) prepared by encapsulation of Rifampicin as an antimicrobial drug and stabilizing the matrix through the repeated freeze–thawing method. The hydrogel structure and polymer-drug compatibility were confirmed by FTIR, and a series of hydrogen-bond-based interactions between alginate and Rifampicin were identified. A concentration of 0.69% Rifampicin was found in the polymeric matrix using HPLC analysis and spectrophotometric UV–Vis methods. The hydrogel’s morphology was evaluated by scanning electron microscopy, and various sizes and shapes of pores, ranging from almost spherical geometries to irregular ones, with a smooth surface of the pore walls and high interconnectivity in the presence of the drug, were identified. The hydrogels are bioadhesive, and the adhesion strength increased after Rifampicin was encapsulated into the polymeric matrix, which suggests that these compositions are suitable for wound dressings. Antimicrobial activity against S. aureus and MRSA, with an increased effect in the presence of the drug, was also found in the newly prepared hydrogels. In vitro biological evaluation demonstrated the cytocompatibility of the hydrogels and their ability to stimulate cell multiplication and mutual cell communication. The in vitro scratch assay demonstrated the drug-loaded alginate-grafted poly(N-vinylcaprolactam) hydrogel’s ability to stimulate cell migration and wound closure. All of these results suggest that the prepared hydrogels can be used as antimicrobial materials for wound healing and care applications.

This study investigates the combined treatment of secukinumab (SECU) and magnolol (MAGN) in a mouse model of LPS-induced ALI overlapped with allergic pulmonary inflammation, aiming to better understand the mechanism behind this pathology and to assess the therapeutic potential of this novel approach in addressing the severity of ALI. The combined treatment reveals intricate immunomodulatory effects. Both treatments inhibit IL-17 and promote M2 macrophage polarization, which enhances anti-inflammatory cytokine production such as IL-4, IL-5, IL-10, and IL-13, crucial for lung repair and inflammation resolution. However, the combination treatment exacerbates allergic responses and increases OVA-specific IgE, potentially worsening ALI outcomes. MAGN pretreatment alone demonstrates higher potency in reducing neutrophils and enhancing IFN-γ, suggesting its potential in mitigating severe asthma symptoms and modulating immune responses. The study highlights the need for careful consideration in therapeutic applications due to the combination treatment’s inability to reduce IL-6 and its potential to exacerbate allergic inflammation. Elevated IL-6 levels correlate with worsened oxygenation and increased mortality in ALI patients, underscoring its critical role in disease severity. These findings offer valuable insights for the advancement of precision medicine within the realm of respiratory illnesses, emphasizing the importance of tailored therapeutic strategies.

Background and Objectives: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally induced with acetaminophen (AAPh) and potentiated by a ciprofloxacin addition in rats. Material and Methods: The experiment was performed on five animal groups: group 1—control, treated for 6 weeks with normal saline, 1 mL/kg; group 2—AAPh, treated for 6 weeks with AAPh, 100 mg/kg/day; group 3—AAPh + C, treated for 6 weeks with AAPh 100 mg/kg/day and ciprofloxacin 50 mg/kg/day, only in the last 14 days of the experiment; group 4—AAPh + C + Mg, with the same treatment as group 3, but in the last 14 days, MgCl2 10 mg/ kg/day was added; and group 5—AAPh + C + Zn, with the same treatment as group 3, but in the last 14 days, zinc gluconate (ZnG), 10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (p < 0.001 group 2 vs. group 1 for all mentioned parameters). Furthermore, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, at 0.001 < p < 0.01 and 0.01 < p < 0.05, respectively). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days, resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine (0.01 < p < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against the increase in liver enzymes, and a more pronounced protection against the increase in serum urea and creatinine (0.001 < p < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < p < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in the case of ZnG, to a higher extent, especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < p < 0.05 group 5 vs. group 4). Conclusions: This study presents further proof for the beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function, and the antioxidant profile improvement has a key role, especially in the case of zinc gluconate.

Neutrophils, known to be mobilized and activated in high amounts through Il-17 stimulation, are a key factor for clinical manifestation and imbalance of redox systems favoring a dominant oxidative state in both severe asthma and acute lung injury (f). The aim of this study was to evaluate in mice, the effect of Secukinumab (SECU) in a model of ovalbumin-induced asthma exacerbated with LPS administration to induce ALI, compared to dexamethasone (DEXA), already known for its benefit in both asthma and ALI. Results on cytokine levels for specific Th1, Th2 and Th17 revealed an interplay of immune responses. For Th1 effector cytokines in BALF, DEXA treatment increased TNF-α levels, but TNF-α was not modified by SECU; DEXA and SECU significantly decreased IFN-γ and IL-6 levels. For typical Th2 cytokines, DEXA significantly increased Il-4, Il-5 and Il-13 levels, while SECU significantly inhibited Il-5 levels. Both SECU and DEXA significantly decreased Il-17 levels. Cytokine level changes in lung tissue homogenate were partly similar to BALF cytokines. Conclusion: in addition to DEXA, SECU possesses the ability to modulate inflammatory cytokine release and to decrease Th17 responses in ALI overlapped on exacerbated asthma in mice.

Introduction: Medication non-adherence negatively affects the effectiveness of evidence-based therapies and sustainability of healthcare systems. Lack of agreed terminology of medication adherence enabling and supporting activities leads to underuse of the available tools. The ENABLE COST Action was aimed at proposing a new terminology for these activities in order to help both scientific research and its clinical application.Methods: Initial discussions within the ENABLE Working Groups allowed for the conceptualization of four interlinked terms related to adherence, i.e., “medication adherence technology”, “medication adherence enhancing intervention”, “best practice” and “reimbursement”. The iterative process of internal discussion was structured around two dedicated international workshops. Moreover, extensive stakeholder consultations have been organised, including an interactive online survey used to assess the level of agreement with, and the clarity of relevant terms and definitions proposed.Results: Detailed analysis of the results of this process allowed for fine-tuning of the items, and finally, for proposing the final set of definitions. Across all the three phases of this process, the definitions were substantially modified to better reflect the concepts, simplify the language, and assure completeness and cohesiveness of terminology. Feedback obtained from the stakeholders helped this process and confirmed that the final terms and definitions were well received by the experts active in the field of medication adherence.Discussion: Covering the gap in the existing terminology, this work proposes a cohesive set of terms and definitions applicable to medication adherence enabling and supporting activities. Promoting evidence-based approach to this field, this terminology may help research, clinical practice and policy.

Antibiotic administration commonly induces allergic reactions, dysmicrobism and microbial resistance, but longterm effects due to changes in gut microbiota composition are difficult to assess. This paper aims to identify in the literature adverse effects induced by changes in gut microbiota composition after perinatal administration of antibiotics. Antibiotic administration during pregnancy is a predisposing factor for the development of bronchial asthma, eczema, or allergic rhinitis in children, but does not support the hypothesis as being a risk factor for childhood obesity/overweight. The effect on the newborn’s microbiota of prophylactic administration of antibiotics during caesarean section is controversial. Postnatal treatments with antibiotics frequently causes intestinal dysmicrobism, the most severe form being necrotizing enterocolitis, especially among premature infants, but effects on the changes in body weight are controversial. Early administration of broad-spectrum antibiotics, particularly macrolides and cephalosporins, is strongly associated with the development of bronchial asthma at age 5 years. Recently, altered auditory processing and changes in recognition memory were described in newborn exposed to antibiotics in the absence of infection. More studies are needed to clarify the association between the type of antibiotic, the frequency, respectively period (both prenatal and intrapartum) of administration and long-term effects.

In intensive care units, the most prescribed drugs are antibiotics, as result of the high incidence of infections among patients admitted to these units. In medical practice, antibiotic resistance is a phenomenon with dramatic consequences, which has led to the development of new strategies to solve this public health problem, including the use of ”off-label” drugs. Classification as an off-label prescription of a drug mainly refers to: unapproved therapeutic indication, formulation, dose (including dose interval), age or unapproved route of administration. The aim of this paper is to present the categories of appropriate ”off-label” use of drugs with a detailed description of the principles of use in this regime of antibiotics as mono- or combo-therapy.

Background and Objectives: Oxidative stress is involved in the alterations at the level of salivary glands, being the cause of oral pathologies like xerostomia, periodontitis, gingivitis, leucoplakia, and cancer. It is known that antioxidants can reverse changes induced by drugs or other chemicals in some organs, but the question is whether these substances can reduce or revert the effects of oxidative stress at the salivary gland level. Our aim was to find histopathological data at the level of salivary glands supporting the hypothesis of the reversal of oxidative stress-induced changes after the treatment with substances with antioxidant effect. Materials and Methods: A systematic search was conducted in PubMed, Science Direct, and Springer databases, including research articles on oxidative stress histological aspects and oxidative stress biomarkers induced by drugs or other chemicals on salivary glands. Results: Out of 1756 articles, 25 articles were selected with data on tissue homogenate used for biochemical analysis of oxidative and antioxidative markers, along with routine hematoxylin eosin (HE) and immunohistochemical analysis used for histopathological and immunohistochemical diagnosis. Drugs (antineoplastic drugs, antibiotics, and analgesics), alcohol, heavy metals, and fluoride can cause oxidative stress, resulting in morphological changes in different tissues, including in salivary glands. There are many antioxidants but only a few were evaluated regarding the effects on salivary glands in animal studies, such as hesperidin and selenium, which can reverse the damage induced by cyclophosphamide; 10-dehydrogingerdione (10-DHGD), a compound extracted from ginger, which has a protective effect against the oxidative stress and apoptosis induced by tramadol; and glycyrrhizic acid, which may repair the injuries incurred after the administration of sodium nitrite. Conclusions: Substances such as hesperidin, selenium, 10-dehydrogingerdione, and glycyrrhizic acid are antioxidants with proven restorative effects on salivary glands for the damage induced by oxidative stress after exposure to drugs and other chemical substances; however, demonstrating their similar effects in human salivary glands is challenging.

Onychosis therapy is an ongoing challenge considering the diversity of nail pathology and the barrier function of the nail plate. Among the nail diseases, we identify the primary onychodystrophies, caused by tics or mental disorders, as well as severe onychoses, caused by bacterial and/or fungal infections, manifested by the degradation of the matrix and the nail bed. Onychosis treatment is complex, lasting 6-8 months, and is often frustrating for both patients and healthcare professionals. In this article we have described a series of common onychoses from the etiopathological point of view, briefly presenting the general therapeutic approach. We also highlighted the classic and modern pharmaceutical formulations used in local nail medication. From the perspective of recent approaches, there is the development of therapeutic systems for transungual administration that ensure the prolonged and controlled drug release to optimize the pharmacotechnical performance of medication used in local therapy of onychosis.

Coronavirus disease 2019 (COVID-19) is a complex infectious disease caused by the SARS-CoV-2 virus, and it currently represents a worldwide public health emergency. The pediatric population is less prone to develop severe COVID-19 infection, but children presenting underlying medical conditions, such as diabetes mellitus, are thought to be at increased risk of developing more severe forms of COVID-19. Diabetic children face new challenges when infected with SARS-CoV-2. On one hand, the glycemic values become substantially more difficult to manage as COVID-19 is a predisposing factor for hyperglycemia. On the other hand, alongside other risk factors, high glycemic values are incriminated in modulating immune and inflammatory responses, leading to potentially severe COVID-19 cases in the pediatric population. Also, there are hypotheses of SARS-CoV-2 being diabetogenic itself, but this information is still to be confirmed. Furthermore, it is reported that there was a noticeable increase in the number of cases of new-onset type 2 diabetes among the pediatric population, and the complications in these patients with COVID-19 include the risk of developing autoimmune diseases under the influence of stress. Additionally, children with diabetes mellitus are confronted with lifestyle changes dictated by the pandemic, which can potentially lead to the onset or exacerbation of a potential underlying anxiety disorder or depression. Since the literature contains a series of unknowns related to the impact of COVID-19 in both types of diabetes in children, the purpose of our work is to bring together the data obtained so far and to identify potential knowledge gaps and areas for future investigation regarding COVID-19 and the onset of diabetes type 1 or type 2 among the pediatric population.

Artificial intelligence (AI) plays a more and more important role in our everyday life due to the advantages that it brings when used, such as 24/7 availability, a very low percentage of errors, ability to provide real time insights, or performing a fast analysis. AI is increasingly being used in clinical medical and dental healthcare analyses, with valuable applications, which include disease diagnosis, risk assessment, treatment planning, and drug discovery. This paper presents a narrative literature review of AI use in healthcare from a multi-disciplinary perspective, specifically in the cardiology, allergology, endocrinology, and dental fields. The paper highlights data from recent research and development efforts in AI for healthcare, as well as challenges and limitations associated with AI implementation, such as data privacy and security considerations, along with ethical and legal concerns. The regulation of responsible design, development, and use of AI in healthcare is still in early stages due to the rapid evolution of the field. However, it is our duty to carefully consider the ethical implications of implementing AI and to respond appropriately. With the potential to reshape healthcare delivery and enhance patient outcomes, AI systems continue to reveal their capabilities.

Consumption of dietary supplements and over-the counter (OTC) medication is considered as a healthy promoting activity, therefore their use increased in the past decades. Material and methods. A cross-sectional self-filled questionnaire-based study was conducted on a group of at least 100 persons over 18 years old from Iasi city. The answers were based on Likert’s scales: “strongly agree / agree / neutral / disagree / strongly disagree”, “yes / no” or “yes/ no / I don’t know”. The questionnaire had 36 questions with closed or open answers that evaluated the practices, knowledge, perceptions and attitudes of the population under study. Results. A total of 109 questionnaires were fully filled. The median age was 43 years (min 18, max 80). Approximatively two-thirds of the group were females (63 females, 58%), similar to the users group (57 females, 63%). Vitamins and minerals were commonly used. One-third of the respondents of the user group (38.8%) consume dietary supplements after self-prescription and one-third use the dietary supplements after the recommendation of a physician (28%) or pharmacist (5%). Conclusions. Almost 82% of the studied population use dietary supplements, especially vitamins and minerals, most of the used by women. The findings of our study should be interpreted bearing in mind that the study population may differ from other regions. The results should be considered as being limited to a small sample of population and place of residence.

Abstract Background Dietary n− 3 polyunsaturated fatty acids (PUFAs) have a role in preventing cardiovascular and hepatic diseases. However, their effects might differ significantly depending on individual dietary patterns. The aim of the present study was to evaluate the effects of dietary supplementation with ω-3 fatty acids (FA), administered in different schedules, on hepatic and aortic histological structure, lipid profile, and body weight (BW) in male Wistar rats under standard (SD), high-fat diet (HFD) and mixed feeding conditions. Methods PUFA treatment consisted of the administration of 50 mg/kg fish oil (FO) daily by oral gavage. HFD was obtained by adding a suspension of 4% cholesterol, thiouracil and cholic acid to the animals’ drinking water. The rats were maintained on the diets for 6 weeks, and different schedules of PUFA administration were used. At 14, 28, and 42 days, the morphology of liver and aortic samples and the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) were assessed. Results The HFD groups exhibited significant hyperlipidemia and aortic inflammation, with progression to atherogenesis after 6 weeks. Administration of PUFAs slightly attenuated the aortic changes in these groups and reduced the liver’s tendency to steatosis. FO-induced metabolic improvement was more evident in SD than in HFD rats. For instance, after the first 2 weeks, SD animals that received PUFAs had significantly increased HDL levels vs. controls (62.375 ± 4.10 vs. 52.625 ± 8.38 mg/dL, P

Introduction. Chronic inflammation plays an essential role in the pathophysiology of both arterial hypertension (HTN) and coronary artery disease (CAD), and is more pronounced in individuals with a non-dipper circadian blood pressure (BP) pattern. A non-dipping BP pattern is in turn is associated with increased cardiovascular morbi-mortality, and a higher risk of atherosclerotic events. Neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) are readily available predictors of systemic inflammation and cardiovascular risk. The purpose of our study is to evaluate whether NLR, MLR and PLR can be used as cost-effective predictors of a non-dipping blood pressure pattern in hypertensive patients with stable CAD. Materials and Methods: We performed a cross-sectional retrospective analysis that included 80 patients with hypertension and stable CAD (mean age 55.51 ± 11.83 years, 71.3% male) referred to a cardiovascular rehabilitation center. All patients underwent clinical examination, 24 h ambulatory blood pressure monitoring (ABPM) and standard blood analysis. Results: Baseline demographic characteristics were similar in both groups. Patients with non-dipper pattern had significantly higher NLR (median = 2, IR (2–3), p < 0.001), MLR (median = 0.31, IR (0.23–0.39), p < 0.001) and PLR (median = 175, IR (144–215), p < 0.001) compared to dippers. Conclusion: Our results suggest that MLR and PLR are inexpensive and easily accessible biomarkers that predict a non-dipping pattern in hypertensive patients with stable CAD.

Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug–drug or drug–nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and/or PD results were included. Studies on patients

Medication non-adherence is associated with almost 200,000 deaths annually and €80–125 billion in the European Union. Novel technological advances (smart pill bottles, digital inhalers and spacers, electronic pill blisters, e-injection pens, e-Health applications, big data) could help managing non-adherence. Healthcare professionals seem however inadequately informed about non-adherence, availability of technological solutions in daily practice is limited, and collaborative efforts to push forward their implementation are scarce. The European Network to Advance Best practices and technoLogy on medication adherencE (ENABLE, COST Action 19132) aims to 1) raise awareness of adherence enhancing solutions, 2) foster knowledge on medication adherence, 3) accelerate clinical application of novel technologies and 4) work collaboratively towards economically viable policy, and implementation of adherence enhancing technology across healthcare systems.

The local anesthetics (LAs) immediate-type allergy is considered extremely rare by allergists. However, many health care practitioners and patients overestimate the risk of LA allergy and its potential of cross-reactivity. The aim of this paper was to identify the confounding factors for the diagnosis of an allergic reaction induced by a local anesthetics for a patient who needs local anesthesia during dental procedures. Material and methods. Studies selected from PubMED and from Web of Science (all databases) regarding the confounding factors for diagnostic of local anesthetics-induced allergic reactions during dental procedures were included. We recorded the confounding factors for diagnostic and management of allergic reactions during dental procedures. Results. From the 34 papers retrieved, there were selected only the clinical studies that mentioned the confounding factors for diagnostic of local anesthetics-induced allergic reactions during dental procedures (8 papers). The number of real LA-induced immediate-type allergy is very low (one retrospective study confirmed only 4 LAs-allergy cases: 1 to mepivacaine, 1 to prilocaine, 2 to articaine) within the past 20 years on 402 patients referred to allergist for diagnostic. The allergic reactions are due to vasopressors and bisulfites that are included as antioxidants. Conclusion. Most commonly the reactions have an underlying nonallergic mechanism such as vasovagal reactions, or are conditioned by simultaneous contact with other potential allergens such as chlorhexidine, antibiotics or latex.

Dentists are important antibiotic prescribers, therefore their therapeutic decisions should contribute to the rational use of antibiotics. Our study aim was to analyse the modalities to evaluate the prescription patterns among dental practitioners. Material and methods. Relevant studies from MEDLINE/PubMed database, published in English, in the interval 1980-2019, evaluating the patterns of prescription of antibiotics in dentistry were selected. We excluded the studies presenting only data about the knowledge regarding antibiotics in dental practice. We recorded the type of study, the modality of collection of data, the response rate, and the characteristics about the prescription behaviour. Results. The most frequently used modality for the evaluation of antibiotic prescribing patterns in dentists was realized through cross-sectional or longitudinal studies. Another modality to evaluate antibiotic prescribing patterns in dentistry was the analysis of prescriptions from dental practitioners. Conclusions. The study demonstrates need to for more research studies and for educational initiatives to prevent inappropriate recommendation of antibiotics in dentistry.

The success of pharmacovigilance is based on the adverse drug reaction (ADR) reports, this contributing to the identification of problematic drugs or dental materials. Our paper aim was to identify the factors influencing to the pharmacovigilance regarding knowledge, attitude, and behaviour among dental practitioners. Material and methods. Articles were selected from MEDLINE/PubMed and Web of Science all databases. Case reports, case series, reviews, abstracts to the meetings, studies presenting only data about the efficacy of the treatments and duplicate studies were excluded. We recorded the characteristics of the study, the evaluated parameters and the factors contributing to the attitude to report the adverse effects. Results. From the 82 papers retrieved, there were selected 7 papers. These were cross-sectional studies using self-administered questionnaires had a wide response rate (from 25% to 100%) and included groups from dental students to first year dentists or dental practitioners. Incomplete knowledge about ADR and lack of training of ADR reporting manifested through the difficulties in deciding the occurrence or not of an ADR and through concerns that the report may be wrong are the main factors contributing to the low reporting rate among dentists. Conclusions. Early recognition of an ADR, followed by its report to a pharmacovigilance centre contributes to the identification of problematic drugs or dental materials.

Background and Objectives: Functional capacity (FC) assessed via cardiopulmonary exercise testing (CPET) is a novel, independent prognostic marker for patients with coronary artery disease (CAD). Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are two readily available predictors of systemic inflammation and cardiovascular event risk, which could be used as cost-effective predictors of poor FC. The purpose of this study was to evaluate the utility of NLR and PLR in predicting poor FC in patients with CAD and recent elective percutaneous coronary intervention (PCI). Materials and Methods: Our cross-sectional retrospective analysis included 80 patients with stable CAD and recent elective PCI (mean age 55.51 ± 11.83 years, 71.3% male) who were referred to a cardiovascular rehabilitation center from January 2020 to June 2021. All patients underwent clinical examination, cardiopulmonary exercise testing on a cycle ergometer, transthoracic echocardiography and standard blood analysis. Results: Patients were classified according to percent predicted oxygen uptake (% VO2 max) in two groups—poor FC (≤70%, n = 35) and preserved FC (>70%, n = 45). There was no significant difference between groups regarding age, gender ratio, presence of associated comorbidities, left ventricular ejection fraction and NLR. PLR was higher in patients with poor FC (169.8 ± 59.3 vs. 137.4 ± 35.9, p = 0.003). A PLR cut-off point of 139 had 74% sensitivity and 60% specificity in predicting poor FC. After multivariate analysis, PLR remained a significant predictor of poor functional status. Conclusions: Although CPET is the gold standard test for assessing FC prior to cardiovascular rehabilitation, its availability remains limited. PLR, a cheap and simple test, could predict poor FC in patients with stable CAD and recent elective PCI and help prioritize referral for cardiovascular rehabilitation in high-risk patients.

Amiodarone low solubility and high permeability is the limiting step for its bioavailability, therefore new formulations are needed to improve the solubility of amiodarone either to increase its oral bioavailability or to reduce its toxic effects. Complexation of amiodarone with cyclodextrin results in improved dissolution rate, solubility, and allows for a more controlled drug release. We characterized the acute toxicity of a new amiodarone 2-hydroxypropyl-β-cyclodextrin complex (AMD/HP-β-CD) as powdered form and as a matrix based on Kollidon® and chitosan, administered intraperitoneally in laboratory animals. There were developed two formulations of matrix: one containing only pure AMD as a control sample (Fc) and one containing the inclusion complex with the optimal solubility (F). AMD was equitoxic with HP-β-CD after intraperitoneal administration (289.4 mg/kg for AMD and 298.3 mg/kg for AMD/HP-β-CD), with corresponding histopathological changes. The matrix based formulations presented higher LD50 values for acute toxicity, of 347.5 mg/kg for Fc and 455.6 mg/kg for F10, conducting to the idea of a safer administration because KOL and CHT matrix modified the solubility and controlled the AMD release. The LD50 is 1.5 higher for AMD/HP-β-CD included in a KOL and CHT based matrix compared to the pure AMD, administered intraperitoneally.

Scaling and root planing represent the gold standard in the treatment of periodontal disease, but these therapeutic methods cannot eliminate the remaining periodontopathogenic bacteria in cement, tubules, and periodontal soft tissue. Thus, a number of additional therapeutic means have been adopted, including local and systemic antibiotic therapy, as well as the use of photodynamic therapy techniques. Recently, special attention has been paid to potential phytotherapeutic means in the treatment of periodontal disease. In this review, we aim to present the effects generated by the extract of Curcuma longa, the various forms of application of turmeric as an additional therapeutic means, as well as the aspects related to its biotolerance.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global coronavirus (COVID-19) pandemic. Although initially viewed as an acute respiratory illness, COVID-19 is clearly a complex multisystemic disease with extensive cardiovascular involvement. Emerging evidence shows that the endothelium plays multiple roles in COVID-19 physiopathology, as both a target organ that can be directly infected by SARS-CoV-2 and a mediator in the subsequent inflammatory and thrombotic cascades. Arterial stiffness is an established marker of cardiovascular disease. The scope of this review is to summarize available data on the acute and long-term consequences of COVID-19 on vascular function. COVID-19 causes early vascular aging and arterial stiffness. Fast, noninvasive bedside assessment of arterial stiffness could optimize risk stratification in acute COVID-19, allowing for early escalation of treatment. Vascular physiology remains impaired at least 12 months after infection with SARS-CoV-2, even in otherwise healthy adults. This raises concerns regarding the extent of arterial remodeling in patients with preexisting vascular disease and the potential development of a persistent, chronic COVID-19 vasculopathy. Long-term follow up on larger cohorts is required to investigate the reversibility of COVID-19-induced vascular changes and their associated prognostic implications.

Guided tissue regeneration (GTR) and guided bone regeneration (GBR) became common procedures in the corrective phase of periodontal treatment. In order to obtain good quality tissue neo-formation, most techniques require the use of a membrane that will act as a barrier, having as a main purpose the blocking of cell invasion from the gingival epithelium and connective tissue into the newly formed bone structure. Different techniques and materials have been developed, aiming to obtain the perfect barrier membrane. The membranes can be divided according to the biodegradability of the base material into absorbable membranes and non-absorbable membranes. The use of absorbable membranes is extremely widespread due to their advantages, but in clinical situations of significant tissue loss, the use of non-absorbable membranes is often still preferred. This descriptive review presents a synthesis of the types of barrier membranes available and their characteristics, as well as future trends in the development of barrier membranes along with some allergological aspects of membrane use.

The role of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in neurosurgical practice is a secondary one, however they are still constantly involved in perioperative management of pain or in nonoperative management of acute radiculopathy. Beside the well-known adverse reactions (ADRs), the neurosurgeon practitioner should also take in account the drug hypersensitivity reactions (DHRs) of NSAIDs and be able to deal with it. The aim of this paper was to review the diagnostic and management steps for NSAIDs-induced Hypersensitivity Reactions. The actual stratification of NSAIDs-induced Hypersensitivity Reactions is based on understanding of the heterogeneity of immunological/non-immunological mechanisms of reactions and complexity of clinical manifestations. Practically, this stratification allows the physician to assess suspicion of DHR, based on anamnesis and clinical analysis, and to consider further practical steps to manage and eventually confirm the diagnosis. Drug allergies are considered only the DHRs for which a definite immunological mechanism (either drug-specific antibody or T cell) is demonstrated. In conclusion, clinical analysis and anamnesis of patient with NSAIDs-induced Hypersensitivity Reactions can be realized by any physician and could be enough to diagnose, but it is not sufficient to confirm the diagnosis. In vitro tests and oral provocation challenges may be necessary to be undertaken by an allergy specialist.

Meningiomas are the most common dural tumour, but there are also many other dural masses which mimic their appearances, such as neoplastic and non-neoplastic lesions. In this paper we report another mass which may mimic a dural lesion, namely a muscle graft harvested from the temporal site and left in situ, used to achieve haemostasis in a posttraumatic temporal extradural hematoma in a young male patient. Solid knowledge of differentiating neuroimaging characteristics of dural masses, as well as its corroboration with the patient’s medical history are extremely helpful in establishing an accurate diagnostic.

(1) Background: In the present pilot study, we examined the response of cortisol to a digital version of the Trier Social Stress Test (TSST) and corresponding eating preferences in non-overweight and overweight adolescents. (2) Methods: The experimental study group included 35 adolescents aged 15.7 ± 0.5 years (16 boys and 19 girls). The participants were split into two groups: non-overweight (N = 24) and overweight (N = 11), according to the Body Mass Index (BMI). We induced acute stress in all participants, using a digital version of the Trier Social Stress Test (TSST), with three different digital tasks. We measured salivary cortisol before the test (T0), during the stress induction by digital tasks (T5, T10, T15), and 25 min after the stress test (T40). The Health Behavior in School-Aged Children Questionnaire (HBSC) was administered to assess the influence of stress on eating behavior: the consumption of fruit, vegetables, sweets, and soft drinks and the frequency of snacks. (3) Results: Among the entire group of adolescents, we observed a significant difference between the sexes in terms of cortisol response, girls being predominantly hyperreactive (13 girls compared to 5 boys, p = 0.03). In overweight adolescents, the cortisol reactivity was lower in boys and higher in girls (p = 0.05). The overweight hyperreactive adolescents, as compared to the hyporeactive ones, had a higher frequency of daily consumption of sweets (25% vs. 0%) and soft drink (25% vs. 0). (4) Conclusions: The individual patterns of cortisol reactivity to laboratory-induced stress could be associated with an increased risk of unhealthy eating behavior in adolescents.

One of the challenges to the management of severe asthma is the poor therapeutic response to treatment with glucocorticosteroids. Compounds derived from marine sources have received increasing interest in recent years due to their prominent biologically active properties for biomedical applications, as well as their sustainability and safety for drug development. Based on the pathobiological features associated with glucocorticoid resistance in severe asthma, many studies have already described many glucocorticoid resistance mechanisms as potential therapeutic targets. On the other hand, in the last decade, many studies described the potentially anti-inflammatory effects of marine-derived biologically active compounds. Analyzing the underlying anti-inflammatory mechanisms of action for these marine-derived biologically active compounds, we observed some of the targeted pathogenic molecular mechanisms similar to those described in glucocorticoid (GC) resistant asthma. This article gathers the marine-derived compounds targeting pathogenic molecular mechanism involved in GC resistant asthma and provides a basis for the development of effective marine-derived drugs.

Objective. Our research aims to assess a possible connection between tumour localization and histological subtypes of grade II meningiomas. Material and methods. 143 patients with grade II WHO meningiomas underwent surgical resection in "Prof. Dr. N. Oblu" Emergency Clinical Hospital Iași between 1990 and 2015. The collected data included: patient age, gender, tumour localization and histopathological diagnosis (atypical, clear cells and chordoid meningioma). Results. 135 (94.4%) of all 143 patients with grade II meningiomas were atypical meningiomas, 6 (4.2%) were cell clear meningiomas and only 2 (1.4%) were chordoid meningiomas. As concerns their distribution by gender, 79 (55.2%) were female and 64 (44.8%) were male. Grade II meningiomas were most commonly located at convexity 49.7% (n=71), followed by skull base in 30.8% (n=44) of the cases and parasagittal/falcine in 14.7% (n=21) of the patients. Conclusions. The most common localization of grade II meningiomas was convexity, followed by skull base, parasagittal/falcine and intraventricular areas. We have also noticed that convexity meningiomas are more frequent in women, unlike the other anatomical localizations in which the male-female ratio is almost equal. Therefore, further research is necessary to determine the role of embryological, anatomopathological and genetic factors in underlying the connection between meningioma grade and anatomical localization.

Meningiomas are generally slow-growing extra-axial benign tumours and in rare cases they can metastasize both neural and extra-neural. Intracranial meningiomas with leptomeningeal dissemination are extremely rare and the exact pathogenesis still remains unknown. The aim of this review is to analyse the pathways of intracranial and spinal metastatic spread of intracranial meningiomas and to discuss their particular clinical and pathological features. We highlight the fact that there is a possibility of leptomeningeal dissemination, even if cerebrospinal fluid cytology is negative, in patients with a medical history of a resected meningioma. We identified three possible ways of dissemination: haematogenous, through the CSF, or during surgery. From a histopathological point of view, the more malignant the meningioma, the more likely its leptomeningeal dissemination.

The aim of this study was to improve the solubility of amiodarone hydrochloride (AMD) and the drug release using its inclusion complexes with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes were prepared by coprecipitation and freeze-drying. The solubility enhancement of AMD/HP-β-CD inclusion complexes by 4–22 times was evaluated by the phase solubility method. The inclusion complexes were studied both in solution and in solid state by spectroscopic methods, dynamic light scattering (DLS) and zeta potential analysis, SEM, and DSC. The formulations of AMD/HP-β-CD inclusion complexes both as powdered form and as matrix tablets showed superior pharmacokinetic performance in improving loading and release properties in respect of those of the insoluble AMD drug. In vitro kinetic study reveals a complex mechanism of release occurring in three steps: the first one being attributed to a burst effect and the other two to different bonding existing in inclusion complexes. An in vivo test on matrix tablets containing Kollidon® and chitosan also reveals a multiple (at least two) peaks release diagram because of both structures of the inclusion complexes and also of different sites of absorption in biological media (digestive tract).

The vestibular acute stress induces reversible alert-like reactions that involve the sympathetic adrenal-medullar system and hypothalamic-pituitary-adrenal axis responses. The present study aimed to evaluate salivary α-amylase and salivary cortisol production in relation with cardiovascular reactivity induced by acute stress in healthy subjects.Forty-eight young healthy male volunteers were examined under basal conditions and at various times after reaching the maximal nystagmic reaction following air caloric vestibular test. Heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were recorded at the same time as measurement of the salivary α-amylase and salivary cortisol. At the end of the caloric vestibular test session, perceived stress scale questionnaires were administered to measure the self-perceived stress impact induced by the task, and individual scores were compared with those measured on the enrollment day.Following caloric vestibular test-evoked vertigo, salivary α-amylase and cortisol showed distinct trends in their production after acute stress: Student's t-test was used to compare the α-amylase vs cortisol slopes of the respective interpolated regression lines, and the difference was significant (t = -3.283; p

Background Awareness about antibiotic resistance depends on the attitudes and information about antibiotic resistance of both patients and physicians. Persons who practice self-medication are at high risk of also self-medicating with antibiotics. The purpose of the present study was to evaluate the awareness about antibiotic resistance by investigating the practice in a group of self-medication users in a sample of adults in Romania and the variables associated with such practice. Material and Methods A cross-sectional self-filled questionnaire based study was conducted from December 2016 through January 2017 amongst 218 self-medication users (SMUG). The attitudes, the level of knowledge, the perceptions, about antibiotic use (ABU) and about antibiotic resistance (ABR) were compared to a reference group represented by medical residents group in their specialty training (MRG) considered to have a higher level of knowledge and awareness about ABU and ABR. Results The response rate was 87.2% in the SMUG group and 100% in the MRG group. The SMUG group reported self-medication practices for antibiotics with a high frequency at any time in life (72%), but with a very low frequency from the month previous to the date of the study (12%), comparative with the MRG group (75% and 7%, respectively). The multivariate logistic regression analysis showed that self-medication with antibiotics at any time in life in the SMUG group could be predicted by the answers to two questions regarding the practices and knowledge about ABU (Q13 and Q20). On the other hand, in the MRG group, a question about ABR perception (Q23), could be predictor for self-medication with antibiotics. Self-medication with antibiotics in the month previous to the date of the study in the SMUG group could be predicted with three questions: one about ABU practice (Q14), one about ABR perception (Q26) and one referring to ABR knowledge (Q28). On the other hand, in the MRG group, a question about ABR knowledge (Q32) could be predictor for self-medication with antibiotics. The reduced awareness about ABR in the SMUG group, is revealed by the reduced number of subjects (38%), who did not know that missing an antibiotic dose during a medical treatment contributes to ABR, comparative with the MRG group (84%). Indirectly, low ABR awareness in the SMUG group is revealed by the confusion about the appropriate use of antibiotics in bacterial or viral infections (that antibiotics are not used against viruses). Conclusions The findings from our study on the awareness about antibiotic resistance in the SMUG group might help the policy makers and regulatory authorities to develop educational programs directed to change the perceptions and attitudes about the appropriate use of antibiotics in order to diminish self-medication practices with antibiotics.

Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI) released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2) and cyclooxygenase 2 (cox-2) protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems).

ABSTRACT INTRODUCTION: The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE: The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS: Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION: The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.