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Background: Thesis is an important part of specialisation and doctorate education and requires intense work. The aim of this study was to investigate the publication rates of Turkish Public Health Doctorate Theses (PHDT) and Public Health Specialization (PHST) theses in international and Turkish national peer-review journals and to analyze the distribution of research areas. Methods: List of all theses upto 30 September 2009 were retrieved from theses database of the Council of Higher Education of the Republic of Turkey. The publication rates of these theses were found by searching PubMed, Science Citation Index-Expanded, Turkish Academic Network and Information Center (ULAKBIM) Turkish Medical Database, and Turkish Medline databases for the names of thesis author and mentor. The theses which were published in journals indexed either in PubMed or SCI-E were considered as international publications. Results: Our search yielded a total of 538 theses (243 PHDT, 295 PHST). It was found that the overall publication rate in Turkish national journals was 18%. The overall publication rate in international journals was 11.9%. Overall the most common research area was occupational health. Conclusion: Publication rates of Turkish PHDT and PHST are low. A better understanding of factors affecting this publication rate is important for public health issues where national data is vital for better intervention programs and develop better public health policies.

Background: Thesis is an important part of specialisation and doctorate education and requires intense work. The aim of this study was to investigate the publication rates of Turkish Public Health Doctorate Theses (PHDT) and Public Health Specialization (PHST) theses in international and Turkish national peer-review journals and to analyze the distribution of research areas. Methods: List of all theses upto 30 September 2009 were retrieved from theses database of the Council of Higher Education of the Republic of Turkey. The publication rates of these theses were found by searching PubMed, Science Citation Index-Expanded, Turkish Academic Network and Information Center (ULAKBIM) Turkish Medical Database, and Turkish Medline databases for the names of thesis author and mentor. The theses which were published in journals indexed either in PubMed or SCI-E were considered as international publications. Results: Our search yielded a total of 538 theses (243 PHDT, 295 PHST). It was found that the overall publication rate in Turkish national journals was 18%. The overall publication rate in international journals was 11.9%. Overall the most common research area was occupational health. Conclusion: Publication rates of Turkish PHDT and PHST are low. A better understanding of factors affecting this publication rate is important for public health issues where national data is vital for better intervention programs and develop better public health policies.

Objectives: Third-hand smoke (THS) is residual smoke after extinguishing a cigarette and adhering to surfaces. Re-emission into the air also makes THS a health concern for those who suffer from respiratory diseases. The present study aimed to elucidate the mechanistic pathways involved in THS-induced respiratory toxicity and the accelerative potential of THS in an H 2 O 2 -induced oxidative stress model of human airway epithelia in vitro ., Materials and Methods: THS extracted from terrycloth exposed to 3R4F cigarettes was assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to identify cytotoxicity. The reactive oxygen species (ROS) level was determined via 2,7-dichlorofluorescein diacetate (DCFDA) fluorescence intensity in a flow cytometer, and glutathione (GSH), malondialdehyde (MDA), and catalase (CAT) activity were assessed spectrophotometrically. Interleukin-6 (IL-6) level was measured via enzyme-linked immunosorbent assay., Results: THS 50% ( v/v ) with significant cytotoxicity in A549 cells upregulated intracellular ROS levels via a right-shifted fluorescence intensity of DCFDA compared with the control ( p < 0.05), which was also amplified with H 2 O 2 co-treatment. MDA levels remarkably increased with THS ( p < 0.05). Both THS and THS + H 2 O 2 led to notable GSH depletion, increased CAT activity, and increased IL-6 levels, which were attenuated by the negative control (N-acetylcysteine, 1 mM) ( p < 0.05)., Conclusion: The induction of oxidative stress may be an important event in THS-induced airway toxicity that may contribute to the progression of respiratory diseases., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright© 2024 The Author. Published by Galenos Publishing House on behalf of Turkish Pharmacists’ Association.)

Two novel ibuprofen cystamine salts (IBU-CYS 1 and IBU-CYS 2) are synthesized by coupling the anion of ibuprofen with cystamine dihydrochloride in 1 : 1 and 2 : 1 ratio to improve the solubility and bioavailability of ibuprofen. The salts are characterized by 1 H NMR, FT-IR and UV-Vis spectroscopy, differential scanning calorimetry (DSC), thermogravimetry (TGA, DTA) and X-ray diffraction measurements. IBU-CYS 1 and IBU-CYS 2 show higher solubility (6.11 and 7.81 mg/mL) compared to ibuprofen (0.04 mg/mL) in water. IBU-CYS2 was encapsulated into 2-hydroxyethyl methacrylate: poly (ethylene glycol) acrylate hydrogels for enhanced delivery. The in vitro studies in PBS (pH 7.4) indicate that the salts are effective in relieving inflammatory responses induced by lipopolysaccharide in RAW264.7 macrophage cells (nitrite inhibition percentages of IBU-CYS 1, IBU-CYS 2 and ibuprofen: approximately 34.29, 27.03 and 31.50 respectively) while indicating no cytotoxicity. Therefore, these salts may be promising candidates for the development of effective formulations of this drug., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

Due to the serious gastrointestinal side effects associated with prolonged use of current anti-inflammatory therapies, various strategies such as the regulation of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) production have been explored in the field of anti-inflammatory drug development. In this study, a series of disubstituted 1,3,4-oxadiazoles (3a-f and 4a-f) and their cyclized 1,2,4-triazole derivatives (5a-e and 6a-e) were synthesized and tested for their NO, PGE 2 , and interleukin-6 (IL-6) releasing inhibition ability. All of the compounds were observed to reduce lipopolysaccharide (LPS)-induced nitrite production in a concentration-dependent manner. Moreover, compounds 3b (50 μM) and 6d (1 μM) exhibited 63% and 49% inhibition, respectively, while indomethacin showed 52% at 100 μM. Based on a preliminary NO inhibition assay, 10 of the compounds (3a, 3b, 3e, 4b, 4d, 6a-e) were selected to be evaluated for in vitro PGE 2 , IL-6, and inducible nitric oxide synthase (iNOS) inhibition. Notably, compound 6d proved to be the most active of the series with the lowest dose (1 µM), in comparison to the other further tested compounds (5-100 µM) and the reference drug indomethacin (100 µM). The inhibitory activity of the compounds was supported by docking simulations into the binding site of the iNOS protein receptor (Protein Data Bank [PDB]ID: 3E7G). The data showing that 4d reduced iNOS levels the most can be explained by the H-bond with Tyr347 through oxadiazole and π-halogen interactions through the p-bromo, in addition to aromatic interactions with protoporphyrin IX., (© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Background: Iron chelators; deferasirox, deferiprone, and deferoxamine; used to treat iron toxicities due to excessive ingestions or blood transfusions, may cause serious adverse reactions., Research Design and Methods: This study investigates pharmacovigilance data to uncover unknown safety information. Disproportionality analysis was conducted using VigiBase, the WHO global database of individual case safety reports, to known safety profile of products and the FDA Adverse Event Reporting System, reviewing over 117.000 iron chelator cases between 2010 and 2020., Results: Commonly reported adverse events for iron chelators are general disorders and administration site conditions and GI-related disorders. Reporting Odds Ratio was calculated for iron chelator associations to headache (common), blurred vision (rare) and sepsis (serious). Strong association between deferoxamine and blurred vision (ROR: 2.47 in VigiBase and 3.04 in FAERS), deferiprone and sepsis (ROR; 5.95 in VigiBase and 1.24 in FAERS) were identified. However, results showed some inconsistent associations, such as headache and deferiprone, blurred vision and deferasirox association as per FAERS data; sepsis and deferasirox and deferoxamine association as per VigiBase data. Forty-five new potential signals with different associative values were suggested., Conclusion: The study identified strong associations between specific iron chelators and adverse events, though some inconsistencies were observed in the data. These findings, including the 45 new potential signals, suggest areas for further review and validation with additional data.

Background: This study aimed to evaluate the epidemiology of septic shock (SS) associated with intraabdominal infections (IAI) as well as associated mortality and efficacy of early source control in a tertiary-care educational hospital., Methods: Patients who had SS with IAI and consulted by Infectious Diseases consultants between December 2013 and October 2022 during night shifts in our centre were analyzed retrospectively., Results: A total number of 390 patients were included. Overall, 30-day mortality was 42.5% on day 3, while day 14 and 30 mortality rates were 63.3% and 71.3%, respectively. Source control by surgical or percutaneous operation was performed in 123 of 390 cases (31.5%), and the mortality rate was significantly lower in cases that were performed source control at any time during SS (65/123-52.8% vs 213/267-79.8%, p<0.001). In 44 of 123 cases (35.7%), source control was performed during the first 12 hours, and mortality was significantly lower in this group versus others (24/44-54.5% vs 254/346-73.4%, p=0.009). On the other hand, female gender (p<0.001, odds ratio(OR)= 2.943, 95%CI=1.714-5.054), diabetes mellitus (p= 0.014, OR=2.284, 95%CI=1.179-4.424), carbapenem-resistant Gram-negative etiology (p=0.011, OR=4.386, 95%CI=1.398-13.759), SOFA≥10 (p<0.001, OR=3.036, 95%CI=1.802-5.114), lactate >3 mg/dl (p<0.001, OR=2.764, 95%CI=1.562-4.891) and lack of source control (p=0.001, OR=2.796, 95%CI=1.523-5.133) were significantly associated with 30-day mortality in logistic regression analysis., Conclusion: Source control has a vital importance in terms of mortality rates for IAI-related septic shock patients. Our study underscores the need for additional research, as the present analysis indicates that early source control does not manifest as a protective factor in logistic regression., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Background/aim: Although seasonal human coronaviruses (HCoVs) have long been recognized as respiratory tract viruses, the newly identified SARS-CoV-2 caused a pandemic associated with severe respiratory failure. We aimed to evaluate the incidence of COVID-19 infection in patients diagnosed in three tertiary teaching hospitals, both with and without prior confirmed HCoV infection, and to compare these cohorts in terms of COVID-19 contraction., Materials and Methods: In our study, we examined HCoV PCR-positive cases obtained retrospectively between January 2014 and March 2020 from three University Hospital Microbiology Laboratories (Cohort 1), as well as PCR-negative patients detected in the same PCR cycle as the positive cases (Cohort 2). We also evaluated subgroups of HCoV-positive cases., Results: There was no difference in COVID-19 contraction rates between Cohort 1 and Cohort 2 (p = 0.724). When previous HCoV subgroups of COVID-19-positive patients were examined, no significant difference was found between the betacoronavirus and alphacoronavirus subgroups (p = 0.822), among the four groups (NL63, 229E, OC43, HKU-1) (p = 0.207), or between the OC43 subgroup and the other groups (p = 0.295)., Conclusion: Being previously infected with HCoV did not provide protection against COVID-19 in our study group. We suggest evaluating the possible effect of previous OC43 infection on COVID-19 contraction in larger cohorts., Competing Interests: Conflict of interest: The authors declare that they have no competing interests., (© TÜBİTAK.)

Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion formulations for wound healing that contained both fusidic acid (FA), an antibacterial agent, and benzocaine (BNZ), a local anesthetic. Studies on characterization were carried out, including viscosity, droplet size, and zeta potential. The drug-loaded microemulsion had a stable structure with -3.014 ± 1.265 mV of zeta potential and 19.388 ± 0.480 nm of droplet size. In both in vitro release and ex vivo permeability studies, the microemulsion was compared with Fucidin cream and oily BNZ solution. According to the drug release studies, BNZ release from the microemulsion and the BNZ solution showed a similar profile (p > 0.05), while FA release from the microemulsion had a higher drug release compared to Fucidin cream (p < 0.001). The microemulsion presented lower drug permeation (p > 0.05) for both active ingredients, on the other hand, provided higher drug accumulation compared to the control preparations. Moreover, according to the results of in vitro wound healing activity, the microemulsion indicated a dose-dependent wound healing potential with the highest wound healing activity at the highest concentrations. To the best of our knowledge, this developed BNZ- and FA-loaded microemulsion would be a promising candidate to create new opportunities for wound healing thanks to present the active ingredients, which have low water solubility, in a single formulation and achieved higher accumulation than control preparations., (© 2024. The Author(s).)

This multicentre (22 centres in Turkey) retrospective cohort study aimed to assess the clinical outcomes of patients with neutropenic fever and SARS-CoV-2 positivity. Study period was 15 March 2020-15 August 2021. A total of 170 cases (58 female, aged 59 ± 15.5 years) that fulfilled the inclusion criteria were included in the study. One-month mortality rate (OMM) was 44.8%. The logistic regression analysis showed the following significant variables for the mentioned dependent variables: (i) achieving PCR negativity: receiving a maximum of 5 days of favipiravir (p = 0.005, OR 5.166, 95% CI 1.639-16.280); (ii) need for ICU: receiving glycopeptide therapy at any time during the COVID-19/FEN episode (p = 0.001, OR 6.566, 95% CI 2.137-20.172), the need for mechanical ventilation (p < 0.001, OR 62.042, 95% CI 9.528-404.011); (iii) need for mechanical ventilation: failure to recover from neutropenia (p < 0.001, OR 17.869, 95% CI 3.592-88.907), receiving tocilizumab therapy (p = 0.028, OR 32.227, 95% CI 1.469-707.053), septic shock (p = 0.001, OR 15.4 96% CI 3.164-75.897), and the need for ICU (p < 0.001, OR 91.818, 95% CI 15.360-548.873), (iv) OMM: [mechanical ventilation (p = 0.001, OR 19.041, 95% CI 3.229-112.286) and septic shock (p = 0.010, OR 5.589,95% CI 1.509-20.700)]. Although it includes a relatively limited number of patients, our findings suggest that COVID-19 and FEN are associated with significant mortality and morbidity., (© 2024. The Author(s).)

Aim: To evaluate the effect of timing of antimicrobial therapy on clinical progress of patients with septic shock., Materials and Method: We included 204 adult patients diagnosed with septic shock according to Sepsis-3 criteria between March 2016 and April 2021. One-month survival was evaluated using univariate and logistic regression analysis., Results: Antibiotic treatment was initiated within 1 h of the vasopressors in 26.4 % of patients. One-month mortality did not differ significantly between patients with and without empirical therapy coverage on etiological agents. Univariate factors that significantly affected one-month survival were starting antibiotics at the first hour, the unit where the case was diagnosed with septic shock, SOFA scores, qSOFA scores, and lactate level. In multivariate analysis, diagnosis of septic shock in the Emergency Service, SOFA score ≥11, qSOFA score of three and lactate level ≥4 were significantly associated with one-month mortality., Conclusion: Training programs should be designed to increase the awareness of septic shock diagnosis and treatment in the Emergency Service and other hospital units. Additionally, electronic patient files should have warning systems for earlier diagnosis and consultation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Nosocomial meningitis may occur after procedures affecting the central nervous system or following traumatic injury. The causative infectious organism is commonly Staphylococcus aureus, a Gram-positive bacterium. The aim of the present study was to compare the effectiveness of two antibacterial agents, ceftobiprole and vancomycin, in an animal model of methicillin-resistant S. aureus (MRSA) meningitis., Method: The strain of MRSA used was ATCC 43300. The animals were divided into three groups and infected intracisternally with MRSA. Controls received no antibiotherapy while the ceftobiprole group received 25 mg/kg and the vancomycin group received 20 mg/kg intravenously. Blood and cerebrospinal fluid (CSF) samples were collected at three time points. All animals were euthanized at 73 h after start of treatment., Results: There was a significant difference (p &lt; 0.05) between both treatment groups and the control animals at 24 h (drug trough) and 73 h (1 h after third dose) after start of treatment in terms of CSF bacterial levels. At 73 h, there was a significant difference in survival between the control group and the two treatment groups but no difference between the treated animal survival rates., Conclusion: Intravenous treatment with ceftobiprole and vancomycin appears to be equally effective in a rabbit model of MRSA meningitis., (© 2024 S. Karger AG, Basel.)

Background: Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM)., Materials/methods: This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018., Results: Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3-5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34)., Conclusions: Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Crataegus turcicus is a plant endemic to Türkiye. For the first time, this study aimed to comparatively assess its flower-bearing branches, leaves, and fruits with other well-known Crataegus species ( C. monogyna , C. pentagyna , and C. orientalis ) in terms of chemical composition and bioactivity studies to evaluate its potential use as a food supplement. Firstly, the contents of total phenolics (TPC), flavonoids (TFC), proanthocyanidin (TPAC), and anthocyanin (TAC) in different plant parts of Crataegus species were evaluated. The highest TPAC was found in the hydroalcoholic extract of C. turcicus flower-bearing branches. Moreover, all plant parts had comparatively higher amounts of TPC, TFC, and TAC compared to other Crataegus species. The chemical screening by high-performance thin-layer chromatography (HPTLC) resulted that C. turcicus parts were rich with chlorogenic acid, neochlorogenic acid, quercetin and vitexin derivatives, epicatechin, procyanidin, etc., and their quantities were evaluated by high-performance liquid chromatography (HPLC). In terms of several in vitro antioxidant activity outcomes, the flower-bearing branches of C. turcicus showed the highest antioxidant activity by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) test among the assessed antioxidant assays. Additionally, hydroalcoholic extracts of C. turcicus significantly decreased LPS-induced nitric oxide, tumor necrosis factor-alpha, and interleukin-6 production more potently than indomethacin (positive control). In addition to its remarkable anti-inflammatory activity, C. turcicus showed analgesic activity by reducing prostaglandin E 2 levels.

A previously unreported secoiridoid glycoside, cruciatoside ( 1 ) was isolated from the aerial parts of Gentiana cruciata L. along with ten known compounds eustomoside ( 2 ), eustomorusside ( 3 ), gentiopicroside ( 4 ), 6'- O -β-D-glucopyranosyl gentiopicroside ( 5 ), loganic acid ( 6 ), isoorientin ( 7 ), isovitexin ( 8 ), isovitexin 2'' -(E)- ferulate ( 9 ), mangiferin ( 10 ), and 2-methyl-inositol ( 11 ). The chemical structures of the isolates were elucidated based on extensive 1 D and 2 D NMR experiments as well as HRMS analysis. All isolates were evaluated for their in vitro anti-inflammatory and analgesic activities. Compounds 9 , 4 , and 7 (200 µM) showed moderate anti-inflammatory activity by inhibiting nitrite production from LPS-induced RAW 264.7 macrophage cells, with the inhibition rates of 39.5%, 25.8% and 22.9% respectively without exhibiting substantial cytotoxicity. Besides, 1 , 2 , 4 , and 7 exerted the highest decrease in IL-6 levels. Moreover, compound 4 showed in vitro analgesic activity by decreasing the PGE 2 level comparable to the reference drugs.

Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds 7a , 7d , and 7f were promising. Among these, 7f (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds 7a , 7d and 7f were also tested for their cytotoxic effects on healthy cell line but only compound 7d showed selectivity. Compounds 7a , 7d , and 7f showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC 50 value was observed for 7c (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds 7a (3.78 µM), 7c (2.60 µM), 7e (3.3 µM), and 7f (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds 7c , 7e , and 7f to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, 7a and 7f were identified as the most promising compounds.

Propolis is mainly composed of plant resins, and its type is named according to the primary plant origin in its composition. Identification of propolis botanical origin is essential for predicting and repeating its pharmacological activity because of the variations in chemical composition. This study aimed to compare chemical composition of black poplar (Populus nigra L.) type-propolis (PR1 and PR2) and Eurasian aspen (P. tremula L.)-type propolis (PR3) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique and to evaluate their biological activity profiles. According to LC-MS/MS results, in addition to marked caffeic acid phenethyl ester content in PR1 and PR2, flavonoid aglycones such as pinocembrin, chrysin, pinobanksin, and galangin were found to be dominant in these samples. On the other hand, PR3 contained relatively high concentrations of phenolic acids such as ferulic acid, p-coumaric acid, and trans-cinnamic acid. The anti-estrogenic activity test showed that PR2 exerted the highest anti-estrogenic activity by inhibiting cell proliferation by 44.6%. All propolis extracts showed anticancer activity, which was justified by decreasing activity on the 3D spheroid size in a concentration-dependent manner. Besides, all extracts showed moderate or potent antimutagenic activity in Salmonella typhimurium TA98 and TA100 strains with and without metabolic activation, respectively. In addition, the Comet assay results revealed that propolis extracts have a geno-protective effect against H 2 O 2 -induced DNA damage in CHO-K1 cells at 0.625 and 1.25 μg/mL concentrations. Overall, the result of this study may help in preparing standardized propolis extracts and developing products with defined pharmacological benefits in the food supplements industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Smoking has been associated with NAFLD recently, thus might be a contributing factor for liver disease progression. In this study, we identified the modulative action of α-lipoic acid (α-LA), an organosulphur compound, towards heated tobacco product (HTP) and cigarette smoke extract (CSE)-induced oxidative stress and inflammation in human liver HepG2 cells. The cells were pre-treated with α-LA and exposed to tobacco extracts, and cytotoxicity, oxidative response (SOD, CAT activities and GSH, MDA levels), inflammation (nitrite, IL-6, AhR levels), and liver function (AST/ALT) were assessed. According to the results, a notable increase in oxidative response was observed with CSE, whereas GSH depletion and decreased SOD activity were the key toxicological events induced by HTP (p<0.05). The oxidative and inflammatory responses were ameliorated with α-LA treatment, particularly through GSH restoration and IL-6 modulation. To conclude, these findings on α-LA might contribute to the design of novel adjuvant therapies for people exposed to tobacco smoke., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

The prevalence of depression has increased dramatically over the past few decades. Although depression is categorized as a brain disorder, its symptomatology includes some behaviors that also occur during chronic inflammatory stress. According to research, cytokine production and immune system activation may have a role in depression, so this relationship has received much attention. Moreover, there is a bidirectional relationship between oxidative stress and inflammation. Oxidative stress plays a pathogenic role in chronic inflammatory diseases; depressive disorder is being suggested as one of them. Recent research using several oxidative stress indicators demonstrates that antioxidant defenses are diminished and oxidative stress is elevated in depression. Another cytokine- related mechanism widely known for its association with inflammatory illnesses is the kynurenine pathway (KP). KP is responsible for maintaining the balance between neuroprotective and neurogenerative processes in the brain. Therefore, KP plays a role in the pathophysiology of depression. It is thought to impact neurological processes that stem the depression, making it one of the mainstays in explaining oxidative stress-depression-inflammation interrelation. The mechanism is thought to be driven by increasing the expression of proinflammatory cytokines, IDO, and thus the KYN/TRP ratio. This review aims to evaluate the relationship between oxidative stress, depression, and inflammation through the kynurenine pathway through the current studies in the literature., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study aimed to evaluate the influencing variables for outcomes in patients with septic shock having culture-proven carbapenem-resistant Gram-negative pathogens. It included 120 patients (mean age 64.29 ± 1.35 years and 58.3% female). The mean Sequential Organ Failure Assessment score during septic shock diagnosis was found to be 11.22 ± 0.43 and 9 ± 0.79 among the patients with mortality and among the survivors, respectively (P = 0.017). The logistic regression analysis showed that empirical treatment as mono Gram-negative bacteria-oriented antibiotic therapy (P = 0.016, odds ratio (OR) = 17.730, 95% confidence interval (CI): 1.728-182.691), Charlson Comorbidity Index >2 (P = 0.032, OR = 7.312, 95% CI: 5.7-18.3), and systemic inflammatory response syndrome score 3 or 4 during septic shock diagnosis (P = 0.014, OR = 5.675, 95% CI: 1.424-22.619) were found as independent risk factors for day 30 mortality. Despite early diagnosis and effective management of patients with septic shock, the mortality rates are quite high in CRGNP-infected patients.

Wall-associated kinases (WAKs) are receptors that bind pectin or small pectic fragments in the cell wall and play roles in cell elongation and pathogen response. In the Cannabis sativa (Cs) genome, 53 CsWAK/CsWAKL (WAK-like) protein family members were identified and characterized; their amino acid lengths and molecular weights varied from 582 to 983, and from 65.6 to 108.8 kDa, respectively. They were classified into four main groups by a phylogenetic tree. Out of the 53 identified CsWAK/CsWAKL genes, 23 CsWAK/CsWAKL genes were unevenly distributed among six chromosomes. Two pairs of genes on chromosomes 4 and 7 have undergone duplication. The number of introns and exons among CsWAK/CsWAKL genes ranged from 1 to 6 and from 2 to 7, respectively. The promoter regions of 23 CsWAKs / CsWAKLs possessed diverse cis-regulatory elements that are involved in light, development, environmental stress, and hormone responsiveness. The expression profiles indicated that our candidate genes ( CsWAK1, CsWAK4, CsWAK7, CsWAKL1, and CsWAKL7 ) are expressed in leaf tissue. These genes exhibit different expression patterns than their homologs in other plant species. These initial findings are useful resources for further research work on the potential roles of CsWAK/CsWAKL in cellular signalling during development, environmental stress conditions, and hormone treatments.

A broad range of evidence has confirmed that natural products and essential oils might have the potential to suppress COVID-19 infection. Therefore, this study aimed to develop an oral/throat spray formulation for prophylactic use in the oral cavity or help treatment modalities. Based on a reference survey, several essential oils, a cold-pressed oil, and propolis were selected, and cytotoxicity and antiviral activity of each component and the developed spray formulation were examined against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using Vero E6 cells. Anti-inflammatory, antimicrobial, and analgesic activities as well as mutagenicity and anti-mutagenicity of the formulation were analysed. Forty-three phenolics were identified in both propolis extract and oral/throat spray. The spray with 1:640-fold dilution provided the highest efficacy and the cytopathic effect was delayed for 54 h at this dilution, and the antiviral activity rate was 85.3%. A combination of natural products with essential oils at the right concentrations can be used as a supplement for the prevention of SARS-CoV-2 infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd.)

Drug development efforts that focused on single targets failed to provide effective treatment for Alzheimer's disease (AD). Therefore, we designed cholinesterase inhibition (ChEI)-based multi-target-directed ligands (MTDLs) to simultaneously target AD-related receptors. We built a library of 70 compounds, sequentially screened for ChEI, and determined σ 1 R, σ 2 R, NMDAR-GluN2B binding affinities, and P2X7R antagonistic activities. Nine fulfilled in silico drug-likeness criteria and did not display toxicity in three cell lines. Seven displayed cytoprotective activity in two stress-induced cellular models. Compared to donepezil, six showed equal/better synaptic protection in a zebrafish model of acute amyloidosis-induced synaptic degeneration. Two P2X7R antagonists alleviated the activation state of microglia in vivo . Permeability studies were performed, and four did not inhibit CYP450 3A4, 2D6, and 2C9. Therefore, four ChEI-based lead MTDLs are promising drug candidates for synaptic integrity protection and could serve as disease-modifying AD treatment. Our study also proposes zebrafish as a useful preclinical tool for drug discovery and development.

Ethnopharmacological Relevance: Okra fruit (Abelmoschus esculentus (L.) Moench) has been extensively used for the treatment of skin damage and subcutaneous tissue abscess for many years in Turkish folk medicine., Aim of Study: In this study, we aimed to investigate the wound healing potential of okra fruit by in vitro and in vivo experimental models in detail. Furthermore, based on the results of experiments, a wound healing formulation was developed and its activity profile was studied., Materials and Methods: For this purpose, the phenolic, flavonoid and proanthocyanidin contents and chemical profile of aqueous and ethanolic extracts prepared from okra fruits cultivated in two different locations of Turkey, i.e. Aegean and Kilis regions, were comparatively determined and the tryptophan levels, which is known to be an influential factor in wound healing, were measured. Antioxidant activity of the okra fruit extracts was determined by DPPH test, ABTS radical scavenger activity, iron-binding capacity, total antioxidant capacity and copper reduction capacity assays. Moreover, antibacterial activity potentials of the aqueous and ethanolic extracts of okra fruits were determined. The protective effect of the extracts against H 2 O 2 -induced oxidative stress and anti-inflammatory activity were assessed in HDF (human dermal fibroblast) cells and in RAW 264.7 murine macrophages, respectively. The biocompatibility of the gel formulations prepared with the best performing extract were evaluated by human Epiderm™ reconstituted skin irritation test model. Wound-healing activity was investigated in rats by in vivo excision model and, histopathological examination of tissues and gene expression levels of inflammation markers were also determined., Results: According to our findings, the aqueous and ethanolic extracts of okra fruits were found to possess a rich in phenolic content. Besides, isoquercitrin was found to be a marker component in ethanolic extracts of okra fruits. Both extracts exhibited antioxidant activity with significant protective effect against H 2 O 2 -induced damage in HDF cells by diminishing the MDA level. Also, the highest dose of ethanolic extracts has displayed a potent anti-inflammatory activity on LPS-induced RAW264.7 cells. Besides, both water and ethanolic extracts were shown to possess antimicrobial activity. On the other hand, the formulations prepared from the extracts were found non-irritant on in vitro Epiderm™-SIT. In vivo excision assay showed that tissue TGF-β and IL-1β levels were significantly decreased by the 5% okra ethanolic gel formulation. The histopathological analysis also demonstrated that collagenisation and granulation tissue maturation were found higher in 5% (w/v) okra ethanolic extract-treated group., Conclusion: 5% of okra ethanolic extract might be suggested as a potent wound healing agent based on the antimicrobial, antioxidant and anti-inflammatory tests. The proposed activity was also confirmed by the histopathological findings and gene expression analysis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with α-hydroxy aldehyde or α-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by 1 H NMR, 13 C NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0 μM and 8.0 μM IC 50 , respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 μM IC 50 . Rest of the compounds ( 1 , 3 - 9 ) showed 10.4-28.1 μM IC 50 on COX-2 and 17.0-35.6 μM IC 50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds ( 1-9 ) showed activity on NO production. Only compound was the 4 , which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100 μM for all compounds ( 1 - 9 ) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: 4-(2-fluorophenoxy) quinoline derivatives constitute one of the chemical classes of hepatocyte growth factor receptor (c-MET) inhibitors, a promising treatment against various human tumors. There are three aims of the present study: (1) To develop a robust and validated quantitative structure-activity relationship model to predict the c-Met kinase inhibition; (2) to examine the toxicity profiles of these compounds; (3) to design new quinoline derivatives and apply the developed model on these compounds to observe its pertinence., Materials and Methods: A multiple linear regression method was used to develop the model with calculated descriptors. State-of-the-art internal and external validation parameters were calculated. The in silico toxicity profiles including structural alerts and the lowest observed adverse effect level (LOAEL) values were evaluated using online tools. New derivatives were designed and tested on the developed model., Results: A series of 4-(2-fluorophenoxy) quinoline derivatives was linearly modeled and vigorously validated to predict the molecules' c-MET kinase inhibition potential. Statistical metrics of the developed model showed that it was robust and able to make successful predictions for this chemical class. The mass, electronegativity, partial charges, and the structure of the molecules had an effect on the activity. Moreover, the toxicity profiles of the studied compounds were found to be adequate., Conclusion: Five of the synthesized compounds were observed to be auspicious for the toxicity/activity ratio. The developed model is useful in the virtual screening and in the design of new anti-tumor compounds.

Propolis shows a great variation in its chemical content depending on the vegetation around the beehive. Determination of its botanical origin and the chemical characterization are the most important issues for the standardization and the quality evaluation for propolis samples that are intended to be used in the pharmaceutical industry. This study has focused on the identification of the botanical origin of 47 propolis samples collected from different locations in the Black Sea Region of Turkey. Firstly, palynological and chromatographic analyses were carried out. Then, the major distinguishing components were identified by high-performance thin-layer chromatography (HPTLC), or by nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS) after isolation of the components. Based on the results, the samples were categorized into three main groups as black poplar-type, Euroasian aspen-type, and non-phenolic-type. Key markers of black poplar-type were assigned as phenolic acids and flavonoids, whereas lasiocarpin B and C (phenolic glycerides) were determined as markers for Euroasian aspen-type propolis. The total phenolics and flavonoid contents (TPC and TFC) and antioxidant capacities of the samples were comparatively assessed by free radical-scavenging activity (DPPH) and metal-reducing activity (CUPRAC and FRAP) methods. Additionally, HPTLC-direct bioautography was applied to determine the contribution of components to antioxidant activity. Hierarchical clustering analysis revealed similarities in TFC, TPC values, and antioxidant activity related to the sample origins' geographic proximity. The anti-inflammatory activities of the black poplar sub-type and Euroasian aspen-type propolis samples were comparatively investigated on RAW 264.7 macrophage cells. The black poplar-type propolis extract dominated by caffeic acid, caffeic acid phenethyl ester, apigenin, quercetin, kaempferol, pinocembrin, and galangin exhibited the highest anti-inflammatory and antioxidant activities. Therefore, chemically characterized black poplar-type propolis may be suggested as a good candidate to develop pharmaceutical products., Competing Interests: Declaration of Competing Interest There is no conflict of interest to declare regarding the publication of this article., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of intraocular pressure in patients suffering from glaucoma. Currently, the marketed product of brinzolamide is in the form of ocular drops; nonetheless, the conventional drops provide decreased therapeutic efficacy owing to their low bioavailability and pulsed drug release. Thus, the development of novel ocular formulations such as topical microemulsions is of high importance. In this work, the preparation of new microemulsions containing brinzolamide (0.2, 0.5 and 1% w/w) and comprised from isopropyl myristate, tween 80 and span 20 and Cremophor EL was performed. The obtained microemulsions were further characterized for their physicochemical properties. In addition, Fourier Transformed-Infrared spectroscopy was used touate the compatibility of active ingredients and components. In vitro release studies along with kinetic modeling were performed using the dialysis membrane method in simulated tear fluid. Bioadhesion studies were performed using Texture analysis. Finally, in vitro ocular irritation based on EpiOcular™ Eye Irritation Test and cytocompatibility studies was performed to examine any possible harm on ocular cells and predict in vivo safety profile.

Smoking is one of the most important leading death cause worldwide. From a toxicological perspective, cigarette smoke serves hazards especially for the human being exposed to passive smoke. Over the last decades, the effects of natural compounds on smoking-mediated respiratory diseases such as COPD, asthma, and lung cancer have been under investigation, as well as the mechanistic aspects of disease progression. In the present study, the protective mechanism of eucalyptol (EUC), curcumin (CUR), and their combination on BEAS-2B cells were investigated in vitro to understand their impact on cell death, oxidative cell injury, and inflammatory response induced by 3R4F reference cigarette extract (CSE). According to the present findings, EUC, CUR, and their combination improved cell viability, attenuated CSE-induced apoptosis, and LC3B expression. Further, CSE-induced oxidative damage and inflammatory response in human bronchial epithelial cells were remarkably reduced by the combination treatment through modification of enzymatic antioxidant activity, GSH, MDA, and intracellular ROS levels as well as nitrite and IL-6 levels. In addition, nuclear translocation of Nrf2, a regulatory protein involved in the indirect antioxidant response, was remarkably up-regulated with the combination pre-treatment. In conclusion, EUC and CUR in combination might be a potential therapeutic against smoking-induced lung diseases through antioxidant and inflammatory pathways and results represent valuable background for future in vivo pulmonary toxicity studies.

To obtain new anti-inflammatory agents, recent studies have aimed to replace the carboxylate functionality of nonsteroidal anti-inflammatory drugs with less acidic heterocyclic bioisosteres like 1,3,4-oxadiazole to protect the gastric mucosa from free carboxylate moieties. In view of these observations, we designed and synthesized a series of 3,5-disubstituted-1,3,4-oxadiazole derivatives as inhibitors of prostaglandin E 2 (PGE 2 ) and NO production with an improved activity profile. As initial screening, and to examine the anti-inflammatory activities of the compounds, the inhibitions of the productions of lipopolysaccharide-induced NO and PGE 2 in RAW 264.7 macrophages were evaluated. The biological assays showed that, compared with indomethacin, compounds 5a, 5g, and 5h significantly inhibited NO production with 12.61 ± 1.16, 12.61 ± 1.16, and 18.95 ± 3.57 µM, respectively. Consequently, the three compounds were evaluated for their in vivo anti-inflammatory activities. Compounds 5a, 5g, and 5h showed a potent anti-inflammatory activity profile almost equivalent to indomethacin at the same dose in the carrageenan-induced paw edema test. Moreover, the treatment with 40 mg/kg of 5h produced significant anti-inflammatory activity data. Furthermore, docking studies were performed to reveal possible interactions with the inducible nitric oxide synthase enzyme. Docking results were able to rationalize the biological activity data of the studied inhibitors. In summary, our data suggest that compound 5h is identified as a promising candidate for further anti-inflammatory drug development with an extended safety profile., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Coumarins (2H-1-benzopyran-2-one), derivatives that can be isolated from several plants, have been reported for their anticoagulant, antimicrobial, anti-inflammatory, or anticancer activity. Some of these structures are currently approved for the treatment of cardiovascular diseases, as antibiotics or as an anticancer drug. Given the great potential of this structure and the limited number of studies that focus on molecules derived from carbon 8 of the benzopyranone heterocycle, we synthesized in this project 38 coumarin derivatives by substituting carbon 8 of the benzopyran ring with some aromatic and aliphatically substituted piperidines and piperazines. As a few of these structures were already shown to exhibit some carbonic anhydrase (CA) inhibition and as CA enzymes are reported to be closely related to inflammation, the synthesized derivatives were evaluated for their anti-inflammatory activity in vitro. The results indicated that compounds 20 and 31 revealed promising anti-inflammatory activity, as they demonstrated better activity than the reference drugs., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Objectives: Daptomycin is highly effective against Gram-positive multidrug-resistant bacteria. Publications on daptomycin in osteomyelitis treatment are limited., Patients and Methods: In this multicenter retrospective cohort study, the aim was to evaluate the outcomes of osteomyelitis cases having received daptomycin or teicoplanin. This multicenter retrospective cohort study gathered data from seven centers located in five cities of Turkey. Study inclusion criteria were as follows: (a) magnetic resonance imaging and/or direct X-ray revealed osteomyelitis or biopsy pathologic examination results concomitant with osteomyelitis. Chi-squareand Student t-tests were used for statistical comparison., Results: A total of 72 patients, 38 cases in the daptomycin group and 34 cases in the teicoplanin group diagnosed with osteomyelitis fulfilling the study inclusion criteria, were included in the study. Clinical success at the end of induction therapy was achieved in 32/38 cases in the daptomycin cohort vs. 30/34 cases in the teicoplanin cohort (p: 0.73)., Conclusion: Although this is a limited experience in a small but well-defined cohort, our data suggest that daptomycin may be a safe alternative to glycopeptides in osteomyelitis treatment. A randomized controlled clinical study involving larger cohorts may increase the available evidence., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Over the last decade, electrolyzed water (EW) produced by salt and tap water has gained importance due to its antimicrobial effects. Regarding to chlorine-based compounds, EW also used in post-harvest safety of food processing and sterilization of surfaces. The latest studies suggested that EW might act as wound healing agent due to anti-infective and cell proliferative properties. In this study, we evaluated acute contact cytotoxicity in L929 mice fibroblast cells and wound healing activity of EWs in vitro. In addition, mutagenic activity was evaluated by Ames test with and without metabolic activation by S9 fraction and the stability profile of freshly prepared EWs has been followed up. According to the results, strong acid (StAEW) and mixed EW (MEW) showed dose-dependent cytotoxicity due to possible high HOCl concentration, while slightly acidic and catholyte EW (CEW) were not cytotoxic even applied directly for 30 sec. Further, StAEW and CEW showed a significant increase in L929 cell migration in scratch assay. Likewise, with/ without metabolic activation, neither of EWs had shown mutagenic profile in TA 98 and TA100 strains of Salmonella typhimurium. Follow-up of ORP (oxidation-reduction potential), pH and FCC (free chlorine concentration) showed that temperature and light were important storage conditions to maintain a stable profile particularly for ORP and FCC, which are the most important indicators for biological activity of EW. According to the present findings, it can be suggested that particularly StAEW, may represent a valuable wound healing agent with an achievable, economical and easy production system when stored under proper conditions.

Thiouracil and thiocytosine are important heterocyclic pharmacophores having pharmacological diversity. Antitumor and antiviral activity is commonly associated with thiouracil and thiocytosine derivatives, which are well known fragments for adenosine receptor affinity with many associated pharmacological properties. In this respect, 33 novel compounds have been synthesized in two groups: 24 thiouracil derivatives (4a-x) and 9 thiocytosine derivatives (5a-i). Antitumor activity of all the compounds was determined in the U87 MG glioblastoma cell line. Compound 5e showed an anti-proliferative IC 50 of 1.56 μM, which is slightly higher activity than cisplatin (1.67 μM). The 11 most active compounds showed no signficant binding to adenosine A 1 , A 2A or A 2B receptors at 1 μM. Brain tumors express high amounts of phosphodiesterases. Compounds were tested for PDE4 inhibition, and 5e and 5f showed the best potency (5e: 3.42 μM; 5f: 0.97 μM). Remakably, those compounds were also the most active against U87MG. However, the compounds lacked a cytotoxic effect on the HEK293 healthy cell line, which encourages further investigation., Competing Interests: Declaration of competing interest There is not any conflict of interest by the authors., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: The preparations of Phlomis aerial parts are used traditionally in Anatolia for wound healing and in inflammatory disorders., Methods: For the identification of the active fraction, the air dried aerial parts of Phlomis rigida Labill. were extracted by methanol and fractionated successively by n-hexane, dichloromethane and ethyl acetate, respectively. The phenolic constituents were characterized by the Folin-Ciocaltheu method; the antioxidant activity was performed by ABTS and DPPH radical scavenging assays. In vitro anti-inflammatory activity was evaluated by LOX enzyme inhibition, spectrophotometrically as well as cell cultures. The wound healing properties of P. rigida extract gels were studied via in vitro cell culture methods and in vivo by excisional wound model using Balb-c mice. The P. rigida extract was analyzed and characterized by GC-FID, GC-MS, and LC-MS., Results: The P. rigida methanol extract showed moderate LOX inhibitory at IC 50  = 19.5 ± 2.8 μg/mL whereas the antioxidant activity was by DPPH • IC 50  = 0.89 mg/mL, and by ABTS • IC 50  = 0.99 mg/mL, respectively. In addition, a remarkable P. rigida extracts anti-inflammatory activity was observed in the cell culture assay, which was then confirmed by the in vitro wound healing activity applied at 0.125-0.5 mg/mL concentrations, resulting in a dose-dependent increase in wound closure at the final stage. The P. rigida gel formulation was prepared to evaluate the extract in vivo, whereas the experimental results of the new gel formulation supported the findings of the in vitro wound healing activity., Conclusion: The findings of this in vitro and in vivo study suggest that the wound healing and anti-inflammatory properties provide a scientific evidence of the ethnopharmacological application of Phlomis species., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The objective of the present research was to examine the possible usage of terbinafine loaded hydrogels for vaginal application as part of vaginal candidiasis treatment. Vaginal candidiasis belongs to the most frequent gynecological disorders. Various antifungal drugs are used for its treatment, with Terbinafine being one of them. In this study, new gel formulations were prepared for Terbinafine vaginal delivery. Natural polymers such as chitosan, sodium carboxymethylcellulose, and Carbopol were used for the development of Terbinafine vaginal gels. The developed gels were examined for their viscosity and spreadability, pH and mechanical properties. The most optimal formulations were further evaluated for their in vitro release behavior and antifungal activities. In further, the cytotoxicity and irritation inducing capacity of optimum gel formulations were evaluated. In vitro drug release studies demonstrated that terbinafine release was prolonged whereas anti-candida activity in several species showed the superiority of the gels compared to the marketed product. G-5 and G-8 gels did not cause lysis, hemorrhage and coagulation, therefore, classified as non-irritant. The optimal formulations were also studied for their stability, demonstrating that they were stable for 3 months.

Psoriasis is a chronic autoinflammatory disorder characterized by patches of abnormal skin. For psoriasis management, the application of topical retinoids as Tazarotene is recommended. However, Tazarotene could induce skin irritation limiting its use. Herein, it is evaluated the possible usage of in situ gels for tazarotene skin delivery. The topical in situ gels were developed using thermosensitive poloxamers via cold method. They were examined for their appearance, sol-gel temperature, clarity, pH, viscosity, in vitro release, and stability. Their biocompatibility was evaluated by investigating their cytotoxicity and irritation inducing capacity. The possible anti-inflammatory and analgesic activities were determined by measuring the nitric oxide and prostaglandin E 2 levels production in LPS-stimulated RAW264.7 murine macrophage cells. It was revealed that the in situ gels had no cytotoxic effect (∼95-100% cell viability) and nor irritation potential (∼97% cell viability), according to the in vitro EpiDerm™ reconstituted skin irritation test. Additionally, the 10% tazarotene- in situ gels showed possible analgesic activity since the production of prostaglandin E 2 (PGE 2 ) was decreased. In further, both concentrations of 5% and 10% tazarotene- in situ gels inhibited significantly the nitrite oxide production at 16% and 19%, respectively. Finally, the prepared in situ gels can act as a potential non-irritant alternative option for tazarotene topical skin delivery.

Objectives: The aim of this study was to compare the antibacterial activity of ceftaroline versus vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in an experimental rabbit meningitis model., Methods: The antibacterial activity of ceftaroline was compared with vancomycin in the treatment of meningitis induced by MRSA strain ATCC 43300 in an experimental rabbit meningitis model. Quantitative cerebrospinal fluid (CSF) cultures were performed at the beginning of antibiotic treatment and 24h and 73h after the first antibiotic dose. Furthermore, in vitro time-kill data were investigated at 0, 2, 4, 6, 8, 12 and 24h in sterile human serum., Results: The difference between the control group versus both treatment groups was significant when comparing the decrease in colony counts in CSF both at 24h and 73h after the first antibiotic dose (P<0.05). At the end of the experiment, there was a significant difference in survival between both the ceftaroline-treated group and the vancomycin-treated group versus the control group, but not between the two treatment groups., Conclusion: These results suggest that the antibacterial activity of both ceftaroline and vancomycin are similar in the treatment of MRSA meningitis in an experimental rabbit meningitis model., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A series of novel ibuprofen and salicylic acid-based 3,5-disubstituted-1,3,4-oxadiazole-2(3H)-thione derivatives was synthesized, and they were evaluated as potential anti-inflammatory agents. Following the structure identification studies employing IR, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and elemental analysis, the title compounds were tested by cyclooxygenase (COX)-1 and COX-2 inhibition assays concomitant to lipopolysaccharide (LPS)-induced nitric oxide and prostaglandin production prevention experiments. The results indicated that the majority of the compounds displayed either a superior or comparable activity in preventing both LPS-induced NO production and COX-1 activity in comparison to the activities of the reference molecules. Furthermore, docking studies were also performed to reveal possible interactions with the COX enzymes., (© 2020 Deutsche Pharmazeutische Gesellschaft.)