Novel diarylated tacrine derivatives: Synthesis, characterization, anticancer, antiepileptic, antibacterial, and antifungal activities.

In this study, our goal was to synthesize novel aryl tacrine derivatives and assess their potential as anticancer, antibacterial agents, and enzyme inhibitors. We adopted a two-step approach, initiating with the synthesis of dibromotacrine derivatives 3 and 4 through the Friedlander reaction. These intermediates underwent further transformation into diarylated tacrine derivatives 3a-e and 4a-e using a Suzuki-Miyaura cross-coupling reaction. Thorough characterization of these novel diarylated tacrines was achieved using various spectroscopic techniques. Our findings highlighted the potent anticancer effects of these innovative compounds across a range of cancer cell lines, including lung, gynecologic, bone, colon, and breast cancers, while demonstrating low cytotoxicity against normal cells. Notably, these compounds surpassed the control drug, 5-Fluorouracil, in terms of antiproliferative activity in numerous cancer cell lines. Moreover, our investigation included an analysis of the inhibitory properties of these novel compounds against various microorganisms and cytosolic carbonic anhydrase enzymes. The results suggest their potential for further exploration as cancer-specific, enzyme inhibitory, and antibacterial therapeutic agents. Notably, four compounds, namely, 5,7-bis(4-(methylthio)phenyl)tacrine (3d), 5,7-bis(4-(trifluoromethoxy)phenyl)tacrine (3e), 2,4-bis(4-(trifluoromethoxy)phenyl)-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-amine (4e), and 6,8-dibromotacrine (3), emerged as the most promising candidates for preclinical studies.

Liquid chromatography-tandem mass spectrometry profile and antioxidant, antimicrobial, antiproliferative, and enzyme activities of Thymus pectinatus and Thymus convolutus: in vitro and in silico approach.

BACKGROUND: The objective of this study is to investigate the antiproliferative, antioxidant, antimicrobial, and enzyme activity capacities and phytochemical compositions of Thymus pectinatus (TP), Thymus convolutus (TC), which are endemic to Türkiye. Quantitative analysis of phenolic compounds in the extracts was conducted using liquid chromatography-tandem mass spectrometry, targeting 53 phenolic compounds. RESULTS: Rosmarinic acid, quinic acid, and cynaroside were identified as the major compounds, exhibiting quantitative variation in both extracts. The extracts had a high total phenolic content, with 113.57 ± 0.58 mg gallic acid equivalents (GAE)/g extract for TP and 130.52 ± 1.05 mg GAE/g extract for TC. Furthermore, although both extracts exhibited high total flavonoid content; the TP extract (75.12 ± 1.65 mg quercitin equivalents (QE)/g extract) displayed a higher flavonoid content than the TC extract (30.24 ± 0.74 mg QE/g extract) did. The extracts had a promising antiproliferative effect on C6, HeLa, and HT29 cancer cell lines with a less cytotoxic effect (10.5-14.2%) against normal cells. Both extracts exhibited very potent inhibitory activity against the xanthine oxidase enzyme, with half-maximal inhibitory concentration values of respectively 2.07 ± 0.03 µg mL-1 and 2.76 ± 0.06 µg mL-1 and moderate activity against tyrosinase and α-glucosidase. Docking simulations proved that rosmarinic acid and cynaroside, the major components of the extracts, were the most potent inhibitors of xanthine oxidase. According to antimicrobial activity results, the TC extract exhibited moderate activity against Staphylococcus aureus, and the TP extract had strong activity against both Enterococcus faecium and S. aureus. CONCLUSION: These findings emphasize the beneficial effects of the two endemic Thymus species on human health and suggest their potential use as plant-derived bioactive agents. © 2024 Society of Chemical Industry.

Phytochemical analysis and biological evaluation of Ferulago setifolia K. Koch.

BACKGROUND: Ferulago setifolia K. Koch (Apiaceae) has been the subject of this study, aiming to comprehensively determine its phenolic fingerprint and evaluate its various biological activities. The liquid chromatography-tandem mass spectrometry analysis of the 70% methanol extract of F. setifolia (FS) revealed the presence of 23 phytochemicals, among which chlorogenic acid, quinic acid, kaempferol-3-O-glucoside, and quercetin-3-O-glucoside were identified as the major phenolics in the extract. RESULTS: The biological screening included examinations of antioxidant, antibacterial, antiproliferative, and cytotoxic activities. The FS extract displayed moderate 2,2-diphenyl-1-picrylhydrazyl radical scavenging and ferric-reducing capacity, indicating moderate antioxidant activity. Furthermore, FS exhibited significant antiproliferative effects on cancer cells while showing low cytotoxicity on normal cells. The antibacterial activity findings revealed that FS demonstrated potent activity against Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus, and Escherichia coli. CONCLUSION: The findings of this study suggest that the methanolic extract of FS holds promise as a potential source of biologically active compounds. It can be utilized for the development of pharmaceutical formulations, thanks to its significant antiproliferative and antibacterial activities. Additionally, FS can serve as a valuable source of chlorogenic acid for industrial applications. © 2023 Society of Chemical Industry.

Ferruginoside†D: A Novel Phenylethanoid from Verbascum leiocarpum.

A novel phenylethanoid, ferruginoside D, together with fourteen known compounds were isolated from the Verbascum leiocarpum for the first time. Chemical structures of isolated compounds were determined by spectroscopic analysis including HR-ESI-MS and NMR spectra. The antioxidant, α-glucosidase inhibitory properties, and antiproliferative activities against multiple cell lines (A172, C6, HeLa, A2780, SW620, HT29, Beas2B, RPE, and HSF) of the isolated compounds were evaluated in vitro. According to the results, iridoids, flavonoids (luteolin and apigenin), and phenylethanoids (poliumoside and isoverbascoside) with strong antiproliferative potential were also found to have cytostatic effects. Furthermore, the investigation revealed that compounds luteolin, poliumoside, verbascoside, isoverbascoside, ferruginoside C, ferruginoside D, and ursolic acid show potent alpha-glucosidase inhibitory activity, while compounds luteolin, verbascoside, and isoverbascoside exhibit substantial antioxidant activity. The new compound (ferruginoside D) was found moderately active against cancer cell lines, with strong alpha-glucosidase inhibitory activity, and moderate antioxidant properties.

Neuroleptic Malignant Syndrome in Patients With Dementia: Experiences of A Single Memory Clinic.

OBJECTIVES: Neuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic and antiemetic agents or sudden withdrawal of dopaminergic medications. Given the metabolic and functional reserves and the comorbidities in older adults, NMS may show an atypical course. METHODS: The medical records of patients with neurodegenerative diseases leading to dementia between 2013 and 2020 were reviewed for the diagnosis of NMS. Demographic and clinical characteristics of the patients were obtained from the records of laboratory parameters, management, and length of stay. RESULTS: Fifteen older adults (19 episodes) diagnosed with NMS were included. The median age was 76 years, and 5 were female. Ten of 15 NMS patients were atypical. Most of them had an infection accompanying NMS. Neuroleptic malignant syndrome was caused by antidopaminergic agents (5 antipsychotics, 1 metoclopramide) in 6 episodes and discontinuation of a dopaminergic agent, l -DOPA, in 12 episodes. In 1 patient, it was associated with simultaneous use of domperidone and amantadine withdrawal. Rigidity in NMS due to l -DOPA discontinuation was higher than in those due to antipsychotic use ( P = 0.027). Two of our patients needed intensive care, and 1 died. CONCLUSIONS: This study highlights the high frequency of atypical NMS and the importance of early recognition of this potentially fatal syndrome, which can accompany neurodegenerative diseases and infections in older adults.

New pyrimidine-N-ß-D-glucosides: synthesis, biological evaluation, and molecular docking investigations.

In this study, syntheses of new pyrimidine-coupled N-ß-glucosides and tetra-O-acetyl derivatives were carried out. All glycoconjugates were investigated in comparison with known chemotherapeutic agents in terms of their antimicrobial and anticancer functions and DNA/protein binding affinities. Spectral data showed that all glycoside derivatives were obtained by diastereoselectivity as ß-anomers. Both tested groups exhibited strong antiproliferative activity (2.29-66.84 µg/mL), but some of them had sufficiently ideal % cytotoxicity values (10.01%-16.78%). And also all synthetic compounds exhibited remarkable antibacterial activity against human pathogenic bacteria. Binding of these compounds to CT-DNA resulted in significant changes in spectral properties, consistent with groove binding. Molecular docking studies of some compounds revealed that the docking score, complex energy, and MM-GBSA ΔGBind energy values were consistent with the experimental results, which showed that the new compounds were potent chemotherapeutic agents. Overall bioactivity results suggest that these compounds may be candidates as new chemotherapeutic agents and deserve further pharmacological evaluation.

Some Wild Mushrooms with High Antioxidant Capacity Exhibit Potent Anticancer Activity on Cancer Cells using the Apoptotic and Antimigration Cell Death Mechanisms.

AIM: This study aims to provide in vitro experimental evidence that wild mushrooms have the potential to be used as a pharmaceutical that could be effective against various types of cancer. BACKGROUND: Throughout human history, besides food, traditional medicine and natural poisons obtained from mushrooms have been used for the treatment of many diseases. Clearly, edible and medicinal mushroom preparations have beneficial health effects without the known severe adverse side effects. OBJECTIVES: This study was designed to reveal the cell growth inhibitory potential of five different edible mushrooms and the biological activity of Lactarius zonarius was shown here for the first time. METHODS: The mushrooms fruiting bodies were dried and powdered then extracted with hexane, ethyl acetate, and methanol. The mushroom extracts were screened for possible antioxidant activities by the free radical scavenging activity (DPPH) method. Antiproliferative activity and cytotoxicity of the extracts were investigated in vitro on A549 (human lung carcinoma), HeLa (human cervix carcinoma), HT29 (human colon carcinoma), Hep3B (human hepatoma), MCF7 (human breast cancer), FL (human amnion cells), and Beas2B (normal human cells) cells lines by using MTT cell proliferation assay, lactate dehydrogenase (LDH) assay, DNA degradation, TUNEL, and cell migration assay. RESULTS: Using proliferation, cytotoxicity, DNA degradation, TUNEL, and migration assay, we displayed that hexane, ethyl acetate, and methanol extracts of the Lactarius zonarius, Laetiporus sulphureus, Pholiota adiposa, Polyporus squamosus, and Ramaria flava were effective on the cells even so at low doses (< 45.0 - 99.6 µg/mL) by acting in a way that represses migration, as a negative inducer of apoptosis. It was also demonstrated that mushroom extracts with high antioxidant effect have within the acceptable cytotoxic activity of 20%-30% on the cell membrane at concentrations higher than 60 µg/mL. Overall, all of the mushroom extracts with high antioxidant effects had strong antiproliferative activity and low toxicity for cells. These findings, at least, highlight that these mushroom extracts can be used for the treatment of cancer disease, especially as a supportive therapy against colon, liver, and lung cancer.

Eco-friendly Synthesis and Characterization of Silver Nanoparticles using Juglans regia Extract and their Anti-Trichomonas vaginalis, Anticancer, and Antimicrobial Effects.

BACKGROUND: Green synthesis is an efficient and eco-friendly method that has been used frequently in silver nanoparticle production in recent years. This method facilitates the production of nanoparticles using various organisms, such as plants, and is also cheaper and easier to apply than the other techniques. AIMS: This study aims to find possible mechanisms and pharmacological effects of cubic silver nanoparticles (AgNPs). OBJECTIVES: This study characterizes cubic AgNPs and describes in detail their anticancer, antimicrobial, and anti- Trichomonas vaginalis abilities. METHODS: Silver nanoparticles were produced by green synthesis using Juglans regia (walnut) leaf aqueous extract. We validated the formation of AgNPs by UV-vis spectroscopy, FTIR analysis, and SEM micrographs. To determine the pharmacological effects of the AgNPs, we conducted anti-cancer, anti-bacterial, and anti-parasitic activity experiments. RESULTS: Cytotoxicity data revealed that AgNPs have cellular inhibitory properties on cancerous MCF7 (breast), HeLa (cervix), C6 (glioma), and HT29 (colorectal) cell lines. Similar results are also obtained with anti-bacterial and anti- Trichomonas vaginalis activity experiments. At certain concentrations, AgNPs displayed stronger anti-bacterial activities than the sulbactam/cefoperazone antibiotic combination in five bacteria species. Furthermore, the 12-h AgNPs treatment exhibited satisfactory anti-Trichomonas vaginalis activity similar to the FDA-approved metronidazole. CONCLUSION: Consequently, AgNPs produced by the green synthesis method by Juglans regia leaves showed remarkable anti-carcinogenic, anti-bacterial, and anti-trichomonas vaginalis activities. We propose the potential usefulness of green synthesized AgNPs as therapeutics.

Protective effect of fatty acid amide hydrolase inhibitor URB597 and monoacylglycerol lipase inhibitor KML29 on renal ischemia-reperfusion injury via toll-like receptor 4/nuclear factor-kappa B pathway.

BACKGROUND: Arachidonoyl ethanolamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) are the most studies endocannabinoids. AEA and 2-AG are degraded by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes, respectively. FAAH and MAGL enzymes are widely expressed in many tissues, including kidney. Recent works have depicted that AEA and 2-AG levels are associated with ischemia-reperfusion (IR) injury. In this study, we investigated the effects of MAGL inhibitor KML29 and FAAH inhibitor URB597 against kidney IR injury. METHODS: The kidneys of the rats underwent ischemia for 45 min and then reperfusion for 24 h. KML29 and URB597 were administered intraperitoneally with kidney IR to two different treatment groups. RESULTS: IR application increased serum blood urea nitrogen (BUN), creatinine (Cre), interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels, while these parameters were decreased following KML29 and URB597 administration. KML29 and URB597 administration also reduced the increased toll-like receptor-4 (TRL-4), phosphorylated-NF-κB, phosphorylated-IκB-α, tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), caspase-3 levels and histopathological damage in kidney tissue. CONCLUSIONS: Our results reveal that MAGL inhibitor KML29 and FAAH inhibitor URB597 have a protective effect on kidney IR injury by preventing apoptosis and inflammation. Inhibition of MAGL and FAAH may be a new therapeutic strategy to prevent kidney IR injury.

Complete Left-Atrial Lesion Set versus Pulmonary Vein Isolation Only in Patients with Paroxysmal AF Undergoing CABG or AVR.

Background and Objectives: In patients with paroxysmal atrial fibrillation (AF) undergoing CABG or aortic valve surgery, many surgeons are not willing to open the left atrium to perform a complete left-sided Cox-Maze lesion set. Pulmonary vein isolation (PVI) is often favored in those patients. We investigated the outcome of patients with isolated pulmonary vein isolation compared to those receiving an extended left atrial (LA) lesion set. Materials and Methods: Between 2003 and 2016, 817 patients received concomitant surgical AF ablation in our institution. A total of 268 patients with paroxysmal AF were treated by surgical ablation concomitant to AVR or CABG. Of those, 86 patients underwent a complete left-sided lesion set, while 182 patients were treated with an isolated pulmonary vein isolation. The primary endpoint was freedom from atrial fibrillation at 12 months' follow-up. Results: There were no statistically significant differences regarding baseline characteristics. No major ablation-related complications were observed in any of the groups. In the PVI group, three patients (1.6%) had an intraoperative stroke, while two (2.3%) patients experienced a stroke in the LA ablation group (p = 0.98). In-hospital mortality was 3.4% in the PVI group, and 2.8% in the extended LA group (p = 0.33). Freedom from AF at 12 months' follow-up was 76% in the extended LA ablation group and 70% in the PVI group, showing no statistically significant difference (p = 0.32). Conclusion: Surgical AF ablation concomitant to CABG or AVR in patients with paroxysmal AF is safe and effective. There was no statistically significant difference between the compared lesion sets in terms of freedom from AF, survival or stroke rate after 12 months.

Biogenic Nanocopper: Eco-Friendly Synthesis, Characterization, and Their Anti-Trichomonas vaginalis, Anticancer, and Antimicrobial Effects.

Biogenic nanocopper (BNC) agents exhibit strong anticancer, antimicrobial, and antiparasitic effects. Their fewer side effects to normal cells cause them to be preferred to treat various diseases. Metal nanoparticles, particularly copper nanoparticles, are attracting more significant interest as therapeutic agents with the improvement of green synthesis methods. Studies to reduce the side effects of copper nanoparticles to exhibit strong pharmacological properties are progressing intensively. Here, BNCs with reduced side effects were synthesized using L-ascorbic acid as the reducing agent and various concentrations of copper (II) chloride. BNCs exhibited significant pharmacological activity on cancer, bacteria, and Trichomonas vaginalis cells. The newly synthesized BNCs were characterized by scanning electron microscopy, UV-Vis spectrophotometry, Fourier transform infrared spectroscope, and Differential/Thermal Gravimetric Analysis. The pharmacological activity of BNCs was evaluated by obtaining their inhibitor concentration and minimum inhibitory concentrations against some cancer, bacteria, and T. vaginalis cells. Newly synthesized BNCs have various shapes such as cubic, spherical, or rod and particle size distribution between 70 and 100 nm. According to experiment results, the newly synthesized BNCs were a significantly antiproliferative, antibacterial, and anti-T. vaginalis effect on cells compared to the control drugs. These findings confirm newly synthesized BNCs and their in vitro pharmacological potential. Further research should be targeted on the preclinical study of absorption, distribution, metabolism, excretion/toxicity (ADME/Tox) and in vivo effects on cancer and microbial pathogens.

Antiproliferative and cytotoxic effects of bioactive compounds isolated from Onosma bourgaei.

Onosma species have been used commonly for traditional medicine for years due to their bioactive compounds content. Onosma bourgaei aerial part was extracted with hexane and methanol successively. The methanol extract was subjected to chromatographic techniques to isolate allantoin (1), 3,4-dihydroxybenzaldehyde (2), luteolin-7-O-glucoside (3), apigenin-7-O-ß-glucoside (4), diosmetin-7-O-ß-glucoside (5), rosmarinic acid (6), and globoidnan A (7). The structure of isolated compounds were identified by spectroscopic techniques such as 1D-NMR, 2D-NMR, FTIR, and LC-TOF/MS/MS. Antiproliferative activity of extract and natural compounds were carried out using HeLa (human epithelial cervix adenocarcinoma, ATCC® CCL-2™), HT29 (human colorectal adenocarcinoma, ATCC® HTB38™), MCF7 (human mammary gland adenocarcinoma, ATCC® HTB22™), and A549 (human lung carcinoma, ATCC® CCL185™) cancerous cells and normal cells, FL (human epithelial amnion cell, ATCC® CCL62™). Lactate dehydrogenase (LDH) was performed for cytotoxicity. The compounds, 4, 6, and 7 displayed the strong antiproliferative activity against corresponding cell lines. Apigenin-7-O-ß-glucoside (4) revealed the excellent activity on HeLa, HT29, A549, and MCF6 cancer cell lines with the values of (IC50, µM) 167.3, 196.8 181.1, and 203.5, respectively, compared standard compound, cisplatin.

Predictivity of the comorbidity indices for geriatric syndromes.

BACKGROUND: The aging population and increasing chronic diseases make a tremendous burden on the health care system. The study evaluated the relationship between comorbidity indices and common geriatric syndromes. METHODS: A total of 366 patients who were hospitalized in a university geriatric inpatient service were included in the study. Sociodemographic characteristics, laboratory findings, and comprehensive geriatric assessment(CGA) parameters were recorded. Malnutrition, urinary incontinence, frailty, polypharmacy, falls, orthostatic hypotension, depression, and cognitive performance were evaluated. Comorbidities were ranked using the Charlson Comorbidity Index(CCI), Elixhauser Comorbidity Index(ECM), Geriatric Index of Comorbidity(GIC), and Medicine Comorbidity Index(MCI). Because, the CCI is a valid and reliable tool used in different clinical settings and diseases, patients with CCI score higher than four was accepted as multimorbid. Additionally, the relationship between geriatric syndromes and comorbidity indices was assessed with regression analysis. RESULTS: Patients' mean age was 76.2 ± 7.25 years(67.8% female). The age and sex of multimorbid patients according to the CCI were not different compared to others. The multimorbid group had a higher rate of dementia and polypharmacy among geriatric syndromes. All four indices were associated with frailty and polypharmacy(p < 0.05). CCI and ECM scores were related to dementia, polypharmacy, and frailty. Moreover, CCI was also associated with separately slow walking speed and low muscle strength. On the other hand, unlike CCI, ECM was associated with malnutrition. CONCLUSIONS: In the study comparing the four comorbidity indices, it is revealed that none of the indices is sufficient to use alone in geriatric practice. New indices should be developed considering the complexity of the geriatric cases and the limitations of the existing indices.

A Novel Basic Training Laboratory Model on Live Subjects for Supermicrosurgery: Mouse Femoral Artery, Vein and Nerve.

BACKGROUND: Increasing success rates of supermicrosurgery operations have increased the importance of developing the ideal training model for super-microsurgery. Working on the model is very important for increasing and continuing microsurgery and supermicrosurgery skills. We aimed to present a standardized, simple and easy to access live training model for supermicrosurgery. METHODS: The experiment was performed in the University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, IDEA, Istanbul, Turkey in 2020. Twelve BALB/c male albino mice weighing 20-45 gr were used in the study. Unilateral femoral artery, vein and nerve diameters of mice were measured. Anastomosis was performed on the bilateral femoral vessels. The surgical procedure times were also recorded. RESULTS: The mean weight of the mice was 36.6 ± 6.09 gr, the length was 15.10 ± 1.10 cm. The mean external diameter of the femoral artery, vein and nerves were 0.31 ± 0.34 mm, 0.48 ± 0.70 mm, 0.38 ± 0.43 mm, respectively. The mean preparation time of neurovascular structures for anastomosis was 15.75 ± 1.54 min, mean femoral artery and vein anastomosis time was 24.91±1.72 and 33.16±1.74 min, respectively. Vascular patency was detected as 100% after all vascular anastomosis procedures. CONCLUSION: Mice femoral neurovascular structures are similar to rats in terms of basic morphology, and they are small enough for super-microsurgery education model. Dissection of mice femoral bundles are easy to perform. In terms of training models, anesthetic requirement and laboratory costs are less for mice, and handling them is much easier compared to rats; thus, making them especially suitable for basic supermicrosurgery training courses.

Transconjunctival Approach: A Safe and Effective Access to Mass Lesions in the Anterior Orbit.

BACKGROUND: The orbit is an eloquent organ of the body. Safe surgical access to the orbit could be challenging due to the dense network of critical structures confined to it. There are versatile approaches to different parts of the orbit that could be used by neurosurgeons without causing injury to critical neurovascular structures. In this study, we aimed to present our surgical experience with the transconjunctival approach through the bulbar conjunctiva to anterior intraorbital lesions caused by diverse pathologies. METHODS: We conducted a retrospective review of cases with intraorbital lesions operated via the transconjunctival approach by the same senior surgeon between 2015 and 2017. All patients were evaluated before the surgery by computed tomography, magnetic resonance imaging, and plain anteroposterior and lateral radiographs. RESULTS: Five patients underwent surgery by the transconjunctival approach through the medial or lateral routes for different pathologies: cavernoma, lymphoma, inflammatory reaction, meningocele, and foreign body. No complications were recorded, and all patients were satisfied with their clinical and esthetic results. CONCLUSIONS: The transconjunctival approach is a safe, effective, and time-sparing surgical approach to diverse pathologies in the anterior orbit. Navigation systems enhance the ability to maneuver in selected cases. The transconjunctival approach could be performed in collaboration with ophthalmologists since it provides better esthetic outcomes and higher satisfaction rates in operated patients.

The oxygen initial dip in the brain of anesthetized and awake mice.

An ongoing controversy in brain metabolism is whether increases in neural activity cause a local and rapid decrease in oxygen concentration (i.e., the "initial dip") preceding functional hyperemia. This initial dip has been suggested to cause a transient increase in vascular deoxyhemoglobin with several imaging techniques and stimulation paradigms, but not consistently. Here, we investigate contributors to this initial dip in a distinct neuronal network, an olfactory bulb (OB) glomerulus most sensitive to a specific odorant (ethyl tiglate [ET]) and a site of strong activation and energy consumption upon ET stimulation. Combining two-photon fluorescence and phosphorescence lifetime microscopy, and calcium, blood flow, and pO2 measurements, we characterized this initial dip in pO2 in mice chronically implanted with a glass cranial window, during both awake and anesthetized conditions. In anesthetized mice, a transient dip in vascular pO2 was detected in this glomerulus when functional hyperemia was slightly delayed, but its amplitude was minute (0.3 SD of resting baseline). This vascular pO2 dip was not observed in other glomeruli responding nonspecifically to ET, and it was poorly influenced by resting pO2. In awake mice, the dip in pO2 was absent in capillaries as well as, surprisingly, in the neuropil. These high-resolution pO2 measurements demonstrate that in awake mice recovered from brain surgery, neurovascular coupling was too fast and efficient to reveal an initial dip in pO2.

The protective effects of pomegranate juice on lead acetate-induced neurotoxicity in the male rat: A histomorphometric and biochemical study.

The purpose of this study was to investigate the potential side-effects of lead acetate (LA), which is toxic to the nerves, blood and muscles, in the rat brain. The neuroprotective effects of pomegranate juice (PJ) against LA exposure were also observed. The experiment involved 28 male Wistar albino rats aged 12 weeks. These were divided into four groups: Control, PJ, LA and LA+PJ. Stereological techniques were employed to determine hippocampal volume in each rat brain. Biochemical investigations and histopathological examinations were also performed. Analysis demonstrated a significant decrease in hippocampal volume in the LA group compared to the control group (p < .05). The stereology results also indicated that PJ has protective effects when compared with the LA and LA+PJ groups. A significant increase was also determined in malondialdehyde (MDA) levels and glutathione S-transferase (GST) activity in the LA group compared to the control group, in contrast to glutathione (GSH) levels and carboxylesterase (CaE) and acetylcholinesterase (AchE) activities. MDA and GST activity decreased significantly in the LA+PJ group compared to the LA group in contrast to GSH levels and CaE and AchE activities. Histopathological examination revealed a number of degenerative changes in the LA group. Exposure to LA adversely affects the hippocampus on the male rat brain. It might also be suggested that PJ may ameliorate these deleterious effects.

Intraperitoneal Ultrasound-Guided Safe Laparoscopic Fenestration of Lymphocele After Kidney Transplantation.

Background: Lymphocele is a common complication after kidney transplantation, which does not require treatment unless it is symptomatic. In this study, we aimed to evaluate the incidence, clinical symptoms, treatment choices, and success of different treatment methods of symptomatic lymphocele. Materials and Methods: We evaluated 168 patients who had kidney transplantation between January 2012 and January 2020. Patients with decreased kidney functions due to lymphocele formation during the clinical follow-up were included in the study. External drainage catheter was placed in all patients, except one. In case of treatment failure with external drainage, laparoscopic fenestration guided by intraperitoneal ultrasonography was performed. Clinical symptoms and success rates of treatments were evaluated. Results: Symptomatic lymphocele requiring interventional treatment was detected in 15 (8.9%) of 168 renal transplant patients. All of the symptomatic lymphocele cases had increased serum creatinine levels, whereas 10 had decreased urine volume, 4 had abdominal discomfort, and 2 had ipsilateral lower extremity edema. External drainage catheter was placed as the first-line treatment in 13 patients. In 6 cases, due to treatment failure with external drainage and in 2 patients as a first-choice treatment, laparoscopic fenestration was performed. No lymphocele recurrence was observed during follow-up. Conclusion: Among various methods defined in the treatment of lymphocele, use of laparoscopic fenestration is increasing because of its high success rate and advantages over other methods. Intraperitoneal ultrasound-guided laparoscopic fenestration is a useful and safe method that can be performed as a first-choice treatment since it eliminates the risk of organ injury or bleeding.

Novel amino acid Schiff base Zn(II) complexes as new therapeutic approaches in diabetes and Alzheimer's disease: Synthesis, characterization, biological evaluation, and molecular docking studies.

Schiff bases are compounds that have gained importance in the paint industry due to their colorful nature and in the field of chemistry and biochemistry due to their biological activities. Various biological applications of Schiff bases, such as antitumor, antifungal, antibacterial, antioxidant, antituberculosis, and anthelmintic, have been widely studied. Within the scope of the study, 5-bromo-2-hydroxybenzaldehyde and amino acid methyl esters (isoleucine, phenylalanine, and methionine) and amino acid Schiff bases were synthesized first. The synthesis of the new Zn(II) complexes of these Schiff bases was carried out by the reaction of synthesized Schiff bases and Zn(OAc)2 ·2H2 O. The structures of the synthesized complexes were elucidated using elemental analysis, Fourier transform infrared, nuclear magnetic resonance, UV-visible, and thermal analysis spectroscopy techniques. These synthesized salts were found to be effective inhibitor compounds for the α-glycosidase, and acetylcholinesterase enzyme with Ki values in the range of 30.50 ± 3.82-38.17 ± 6.26 µM for α-glycosidase, 3.68 ± 0.54-10.27 ± 1.68 µM for butyrylcholinesterase, and 6.26 ± 0.83-15.73 ± 4.73 µM for acetylcholinesterase, respectively.

Simultaneous versus staged surgeries for the treatment of bilateral developmental hip dysplasia in walking age: A comparison of complications and outcomes.

OBJECTIVES: This study aims to compare the radiological outcomes and rate of complication between single-stage and staged operation for the treatment of bilateral developmental dysplasia of the hip (DDH). PATIENTS AND METHODS: A total of 100 patients (13 males, 87 females; mean age: 18.1±2.1 months; range, 12 to 36 months) with bilateral DDH who were older than 15 months of age and treated with open reduction (OR) or Pemberton pericapsular osteotomy (PPO) were retrospectively analyzed. Of the patients, 48 were operated with OR and 52 were operated with PPO. Improvements in acetabular indices, presence of avascular necrosis, radiological results, and other complications were noted. RESULTS: There was no statistically significant difference in the preoperative acetabular indices, range of International Hip Dysplasia Institute (IHDI) classification, follow-up period, and age at the time of operation between the groups (p>0.05). There was no statistically significant difference in the acetabular indices, rate of avascular necrosis, and radiological results at the end of 24 months of follow-up between the groups (p>0.05). CONCLUSION: Our study results show no significant difference in the radiological outcomes and complications between simultaneous and staged surgeries for the treatment of bilateral DDH in children in the walking age.