Novel Tricyclo[4.2.1]nonane and Bicyclo[2.2.1]heptane Derivatives: Synthesis, in vitro Biological Activities and in Silico Studies.

The target compounds benzothiazole derivatives (8a-g) were synthesized starting from the norbornene. The antiproliferative activities of the compounds 6a-g and 8a-g were determined against C6 (rat brain tumor) and HeLa (human cervical carcinoma cells) cell lines using BrdU cell proliferation ELISA assay using 5-fluorouracil (5-FU) as standard. In both series, when compared with 5-FU (IC50=<5 µM for C6 and 16.33µM for HeLa), the most active compounds against C6 cells were 6a and 8g with IC50 values of 14.13 µM and 29.99 µM, respectively, while 6a, 6e, 6f and 8b were the most active compounds against HeLa cells with IC50 values of <5, <5, 19.33 and 1813 µM, respectively. Addition, to predict the physicochemical and AMDE properties of the tested compounds, SwissADME online web tool was used. The results showed that all compounds possess promising predicted physiochemical and pharmacokinetic properties, and they complied with Lipinski's rule of 5 indicating that they are predicted to be orally bioavailable, and they possess a predicted bioavailability score of 0.55. Furthermore, in SwissADME Boiled-Egg chart, all compounds showed high predicted GIT absorption, and while compounds 6a-g showed blood brain barrier (BBB) permeation, the compounds 8a-g did not. Moreover, all compounds are not p-glycoprotein (P-gp) substrates.

Deep Brain Stimulation with Double Targeting of the VIM and PSA for the Treatment of Rare Tremor Syndromes.

INTRODUCTION: In tremor syndromes, pharmacological therapy is the primary treatment, but deep brain stimulation (DBS) is used when it is insufficient. We explore the use of DBS, focusing on the globus pallidus internus for dystonia and the ventral intermediate nucleus (VIM) for tremor conditions. We introduce the posterior subthalamic area (PSA) as a potential target, suggesting its efficacy in tremor reduction, particularly in rare tremor syndromes. We aim to evaluate the efficacy and safety of double targeting the VIM and PSA in rare tremor conditions, highlighting the limited existing data on this. METHODS: Between 2019 and 2023, 22 patients with rare tremor syndromes were treated with bilateral DBS of the VIM and PSA. This case series consisted of 7 isolated head tremor, 1 hepatic encephalopathic tremor due to Abernethy syndrome, 2 voice tremor, 4 dystonic tremor, and 8 Holmes tremor (2 multiple sclerosis, 2 cerebellar insult, and 4 posttraumatic) patients. Patients' preoperative and 12-month postoperative tremor scores were compared, and the optimum VIM and PSA stimulation areas were investigated. RESULTS: There was a significant reduction in the mean TRS score from 3.70 (±0.57) to 0.45 (±0.68) after 12 months of surgery. Specific outcomes for different indications were observed: for head tremor, 6 of 7 patients showed a reduction in TRS scores to 0 points; the vocal tremor patients demonstrated improvement; this change was not statistically significant, which is likely to be due to the low number of patients in this subgroup; the dystonic tremor patients showed either complete tremor abolition or a reduction in TRS scores; the Holmes tremor patients showed an 80% reduction in TRS scores; and the hepatic encephalopathy tremor and Abernethy syndrome patients showed a 75% improvement in TRS scores. The stimulation parameters converged on the VIM and dorsal PSA. Complications included the need for electrode repositioning, infections requiring electrode removal and re-implantation, dysarthria, and stimulation-induced ataxia, which was resolved by adjusting the stimulation parameters. DISCUSSION: The literature on DBS for rare tremors is limited. Double targeting of the VIM and PSA appears to produce promising improvements on the outcomes reported in the existing literature on VIM-only DBS. The proximity of the VIM and PSA allows for flexible electrode placement, contributing to the potential success of the dual-target approach. We also discuss the theoretical advantages of targeting the PSA based on the distribution of tremor circuits, emphasizing the need for further research and electrophysiological studies.

1,3-Diaryl Triazenes Incorporating Disulfonamides Show Both Antiproliferative Activity and Effective Inhibition of Tumor-associated Carbonic Anhydrases IX and XII.

AIM: The aim of this study was to synthesize a library of novel di-sulfa drugs containing 1,3- diaryltriazene derivatives TS (1-13) by conjugation of diazonium salts of primary sulfonamides with sulfa drugs to investigate the cytotoxic effect of these new compounds in different cancer types and to determine their inhibitory activity against tumor-associated carbonic anhydrases IX and XII. MATERIALS AND METHODS: A carbonic anhydrase inhibitory activity of the obtained compounds was evaluated against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX and hCA XII) by a stoppedflow CO2 hydrase assay. In addition, in vitro, cytotoxicity studies were applied by using A549 (lung cancer), BEAS-2B (normal lung), MCF-7 (breast cancer), MDA-MB-231 (breast cancer), CRL-4010 (normal breast epithelium), HT-29 (colon cancer), and HCT -116 (colon cancer) cell lines. RESULTS: As a result of the inhibition data, the 4-aminobenzenesulfonamide derivatives were more active than their 3-aminobenzenesulfonamide counterparts. More specifically, compounds TS-1 and TS-2, both of which have primary sulfonamides on both sides of the triazene linker, showed the best inhibitory activity against hCA IX with Ki values of 19.5 and 13.7 nM and also against hCA XII with Ki values of 6.6 and 8.3 nM, respectively. In addition, in vitro cytotoxic activity on the human breast cancer cell line MCF-7 showed that some derivatives of di-sulfa triazenes, such as TS-5 and TS-13, were more active than SLC-0111. CONCLUSION: With the aim of developing more potent and isoform-selective CA inhibitors, these novel hybrid molecules containing sulfa drugs, triazene linkers, and the classical primary sulfonamide chemotype may be considered an interesting example of effective enzyme inhibitors and important anticancer agents.

Effectiveness of Mesenchymal Stem Cell Therapy for COVID-19 Patients in the Intensive Care Unit: A Case-Control Study

Objective: Many methods are used in the treatment of coronavirus disease 2019 (COVID-19), which causes acute respiratory distress syndrome (ARDS), and there are conflicting reports in the literature regarding the results of mesenchymal stem cell (MSC) therapy, which is one of those methods. The aim of our study is to evaluate the effect of MSC treatment applied together with standard treatments on survival. Materials and Methods: This retrospective case-control study evaluates the survival effect of MSC treatment administered to patients treated in intensive care after the development of ARDS due to COVID-19 between March 2020 and March 2021. The age, gender, comorbid disease status, APACHE II score, and overall and comorbidity-based survival rates were compared between patients who received standard medical treatment (SMT) and patients who received MSC treatment together with SMT. Results: There were 62 patients in the group receiving only SMT and 81 patients in the group receiving SMT and MSC. No difference was observed between the groups in terms of age, gender, presence of comorbid diseases, or APACHE II scores. There were also no differences according to Kaplan-Maier analysis for the survival statuses of the groups. There was no serious adverse effect due to MSC treatment among these patients. Conclusion: Our study presents the largest case series in the literature, and it was observed that MSC treatment may not significantly affect overall survival or comorbid disease-based survival, in contrast to many other studies in the literature.

Synthesis and biological evaluation of thiosemicarbazone derivatives.

In this study, firstly, 22 thiosemicarbazone derivatives (3a-y) were synthesized. Then, ADME parameters, pharmacokinetic properties, drug-like structures, and suitability for medicinal chemistry of these molecules were studied theoretically by using SwissADME and admetSAR programs. According to the results of these theoretical studies, it can be said that the bioavailability and bioactivity of these compounds may be high. In silico molecular docking between ligands (thiosemicarbazone derivatives) and targeted proteins (protein-78 (GRP78) for C6 and quinone reductase-2 (4ZVM for MCF 7) was analyzed using Hex 8.0.0 docking software. According to the docking data, almost all molecules had higher negative E values than Imatinib (already used as a drug). For this, in vitro anticancer studies of these molecules were done. The cytotoxic activities of thiosemicarbazone derivatives (3a-y) were evaluated on C6 glioma and MCF7 breast cancer cell lines at 24 h, and Imatinib was used as the positive control. According to the results of the cytotoxicity assay, it can be said that the five compounds (3b, c, f, g, and m with IC50 = 10.59-9.08 µg/mL; Imatinib IC50 = 11.68 µg/mL) showed more potent cytotoxic activity than Imatinib on C6 cell line. Together with to these results ten compounds (3b, d, f, g, I, k, l, m, n, and r with IC50 = 7.02-9.08 µg/mL; Imatinib IC50 = 9.24 µg/mL) had a more effective cytotoxic activity against MCF7 cell line than Imatinib. Compound 3 m showed the highest antiproliferative effect against C6 and MCF7 cell lines.

Antiproliferative and Antimigratory Effects of Isoeugenol-Based Polyphenolic Compounds.

In this research, the effect of synthesized polyphenolic compounds 4 and 5 at the cellular and molecular levels was examined. Within this framework, related substances effects on prostate cell (PC3) viability were evaluated by MTT analysis, and their effects on migration were examined by in vitro scratch analysis. Additionally, mRNA expression levels of gene regions known to be associated with metastasis and apoptosis were determined by real-time quantitative PCR. DNA binding researches have also been carried out to determine the DNA compound interactions. As a consequence, it was determined that 4 and 5 obstructed the PC3 cell viability in a manner that is dose- and time-dependent. The IC50 dose of 4 and 5 in PC3 cell was found to be 60.14 µM, 15.51 µM for 48 h, respectively. 4 and 5 substances showed suppressive effect on migration of PC3 cancer cells in the in vitro scratch model created at IC50 concentrations. Compared to the negative control, PC3 cancer cells treated with 4 and 5 showed 24 % and 46 % closure, respectively, at the wound site at 48 h. 4 and 5 compounds were treated at IC50 concentrations with PC3 cancer cells for 48 h, and then the effects of both compounds on the gene expression, that have been linked to metastasis and apoptosis, at the mRNA level were evaluated. It was determined that 4 decreased the expression of the HIF1-α gene 294 times and 5 decreased the expression of the said gene 30 times. In addition, both 4 and 5 were able to significantly increase the Bax/Bcl-2 mRNA expression ratio (32.65 and 10.46 fold, P<0.0001) in PC3 cells as compared to untreated cells after 48 h. Finally, when DNA binding analysis results were evaluated, it was determined that both polyphenolic compounds did not bind to DNA at the tested time and concentrations and did not cause DNA breaks.

Synthesis, Antiproliferative and Cytotoxic Activities, DNA Binding Features and Molecular Docking Study of Novel Enamine Derivatives.

Novel enamine derivatives were synthesized from the reaction of lactone and chalcones and their antiproliferative and cytotoxic activities against six cancer cell lines (e. g., HeLa, HT29, A549, MCF7, PC3 and Hep3B) and one normal cell lines (e. g., FL) were investigated along with their mode of interactions with CT-DNA. Most of the enamine derivatives with IC50 values of 86-168 µM demonstrated much stronger antiproliferative activity than the starting molecules against the cancer cells. While, among the enamine derivatives, four compounds displayed higher cytotoxic potency than the control drugs (5-fluorouracil and cisplatin) against the Hep3B cell lines, these compounds did not exhibit any significant toxicity against normal cells, FL. The UV/VIS spectral data suggest that eight compounds cause hypochromism with a slight bathochromic shift (∼6 nm), indicating that they bind to the DNA by way of an intercalative or minor groove binding mode. The binding constants of the compounds are in the range of 0.1×103 M-1 -2.3×104 M-1 . The antiproliferative activity of studied enamine derivatives could possibly be due to their DNA binding as well as their cytotoxic properties. In addition to these assays, the chalcones and enamine derivatives were investigated by molecular docking to calculate the synergistic effect of antiproliferative activities against six human cancer cell lines.

Antiproliferative Evaluation of Some 2-[2-(2-Phenylethenyl)-cyclopent-3-en-1-yl]-1,3-benzothiazoles: DFT and Molecular Docking Study.

The 2-[2-(2-phenylethenyl)cyclopent-3-en-1-yl]-1,3-benzothiazoles were synthesized from the reactions of 7-benzylidenebicyclo[3.2.0]hept-2-en-6-ones with 2-aminobenzenethiol. The antiproliferative activities of 2-[2-(2-phenylethenyl)cyclopent-3-en-1-yl]-1,3-benzothiazoles were determined against C6 (rat brain tumor) and HeLa (human cervical carcinoma cells) cell lines using BrdU cell proliferation ELISA assay. Cisplatin and 5-fluorouracil (5-FU) were used as standards. The most active compound was 2-{(1S,2S)-2-[(E)-2-(4-methylphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole against C6 cell lines with IC50 =5.89 µm value (cisplatin, IC50 =14.46 µm and 5-FU, IC50 =76.74 µm). Furthermore, the most active compound was 2-{(1S,2S)-2-[(E)-2-(2-methoxyphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole against HeLa cell lines with IC50 =3.98 µm (cisplatin, IC50 =37.95 µm and 5-FU, IC50 =46.32 µm). Additionally, computational studies of related molecules were performed by using B3LYP/6-31G+(d,p) level in the gas phase. Experimental IR and NMR data were compared with the calculated results and were found to be compatible with each other. Molecular electrostatic potential (MEP) maps of the most active 2-{(1S,2S)-2-[(E)-2-(2-methoxyphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole against HeLa and the most active 2-{(1S,2S)-2-[(E)-2-(4-methylphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole against C6 were investigated, aiming to determine the region that the molecule is biologically active. Biological activities of mentioned molecules were investigated with molecular docking analyses. The appropriate target protein (PDB codes: 1 M17 for the HeLa cells and 1JQH for the C6 cells) was used for 2-{(1S,2S)-2-[(E)-2-(2-methoxyphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole and 2-{(1S,2S)-2-[(E)-2-(4-methylphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole molecules exhibiting the highest biological activity against HeLa and C6 cells in the docking studies. As a result, it was determined that these molecules are the best candidates for the anticancer drug.

A new method in robotic-assisted laparoscopic radical prostatectomy: personalised neuroprotective surgery with neuromonitoring system-randomised controlled study.

PURPOSE: Erectile dysfunction is one of the important morbidities following the radical prostatectomy (RP) surgeries. The goal of this research is to investigate the contribution of intraoperative neuromonitorisation method (IONM) on postoperative erectile function in patients who underwent robotic-assisted laparoscopic radical prostatectomy (RALP) with the localise prostate cancer (LPCa). MATERIALS AND METHODS: In this randomised controlled study contains 88 patients with LPCa were classified based on D'Amico Risk Classification. 61 patients who met the necessary criteria were divided into two groups as neuromonitorisation group (n = 30) and control group (n = 31). All patients were operated under general anaesthesia. All patients included in the study underwent RALP by robotic-assisted system. For the neuromonitorisation, IONM electromyography electrodes were placed to the right and left cavernous bodies in neuromonitorisation group. Impulses in the corpora cavernosa were considered significant. Postoperative erectile functions were determined according to the 3th and 6th month IIEF-5 scores. Demographic data, operative procedures, Gleason scores, final pathology, surgery border, PSA, and IIEF-5 score of patients were recorded. RESULTS: No statistically difference was found between the groups in terms of demographic data, operative procedures, Gleason scores, final pathology, surgery border, and third-month PSA levels (p > 0.05). There was statistically difference between the postoperative third and 6-month IIEF-5 score in neuromonitorisation group (p < 0.05). CONCLUSION: In the IONM technique, high rate of improvement in erectile function was observed in the early period thanks to personalised neuroprotective surgery applied to patients.

Synthesis and biological evaluation of novel indenopyrazole derivatives.

A series of novel indenopyrazole derivatives 2a-j and 3a-j were synthesized from the reaction of 1-(4-(hydroxy(1-oxo-1,3-dihydro-2 H-inden-2-ylidene)methyl)phenyl)-3-phenylurea derivatives 1a-j with hydrazine and phenylhydrazine, respectively. The obtained novel indenopyrazoles ( 2a-j and 3a-j) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay; 2a, 2b, 2d, 2h, and 3h were found to be the most active compounds. The compounds were also screened for antimicrobial activity, and all compounds showed moderate activity against used microorganisms.

Synthesis of chalcone-imide derivatives and investigation of their anticancer and antimicrobial activities, carbonic anhydrase and acetylcholinesterase enzymes inhibition profiles.

The new 1-(4-(3-(aryl)acryloyl)phenyl)-1H-pyrrole-2,5-diones (5a-g) were prepared from 4'-aminchalcones (3a-g) and screened for biological activities. All compounds (3a-g and 5a-g), except 3d and 3e displayed good cytotoxic activities with IC50 values in the range of 7.06-67.46 µM. IC50 value of 5-fluorouracil (5-FU) was 90.36 µM. Moreover, most of compounds 5a-g showed high antibacterial activity with 8-20 mm of inhibition zone (19-25 mm of Sulbactam-Cefoperazone (SCF)). In addition, they showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase I, and II (hCA I and hCA II) isoforms. Also, these compounds demonstrated effective inhibition profiles with Ki values of 426.47-699.58 nM against hCA I, 214.92-532.21 nM against hCA II, and 70.470-229.42 nM against AChE. On the other hand, acetazolamide, clinically used drug, showed a Ki value of 977.77 ± 227.4 nM against CA I, and 904.47 ± 106.3 nM against CA II, respectively. Also, tacrine inhibited AChE showed a Ki value of 446.56 ± 58.33 nM.

Synthesis of 2-Substituted Benzothiazole Derivatives and Their In Vitro Anticancer Effects and Antioxidant Activities Against Pancreatic Cancer Cells.

Pancreatic cancer is one of the deadliest malignancies characterized by strong resistance to almost all chemotherapeutic agents and radiotherapy. In this study, we aimed to investigate the anticancer effect, enzymatic antioxidant activity [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and total antioxidant capacity (TAC) of synthesized benzothiazole compounds against adenocarcinoma cancer cells (PANC-1). 2-((1S,2S)-2-((E)-4-nitrostyryl)cyclopent-3-en-1-yl)benzo[d]thiazole and 2-((1S,2S)-2-((E)-4-fluorostyryl) cyclopent-3-en-1-yl)benzo[d]thiazole containing 2-substituted benzothiazole group were synthesized in two steps. PANC-1 cells were treated with different concentrations of benzothiazole compounds (5, 25, 50. 75 and 100 µM) for 48 h and their cytotoxicity effects were determined by the MTT assay. To determine whether these compounds induced apoptosis, PANC-1 cells were treated with increasing concentrations of the synthetic products. Our study showed that the synthesized compounds have antiproliferative effects against PANC-1 cells and reduced cell viability. These compounds induced apoptosis of pancreatic cancer cells and at the same time reduced the activity of SOD and GPx and reduced TAC. On the basis of these findings, these synthesized benzothiazole compounds may be considered as a potential therapeutic drug against human PANC-1 cancer cells.

Synthesis and Biological Evaluation of Novel 1-(4-(Hydroxy(1-oxo-1,3-dihydro-2H-inden-2-ylidene)methyl)phenyl)-3-phenylurea Derivatives.

A series of novel phenylurea containing 2-benzoylindan-1-one derivatives 3a - 3j were synthesized from the reaction of phenylurea-substituted acetophenones 1a - 1j with phthalaldehyde 2 under mild reaction conditions in good yields. All synthesized compounds were characterized by spectroscopic methods. The obtained compounds (3a - 3j) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay, 3f and 3g were found to be most active compounds. The compounds were also screened for antimicrobial activity and all compounds showed remarkable activity against used microorganisms.

Synthesis, characterization, anticancer, antimicrobial and carbonic anhydrase inhibition profiles of novel (3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives.

In the present study, a series of new hybrid compounds containing chalcone and methanoisoindole units 7a-n ((3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione) were synthesized, characterized and investigated for their anticancer activity against C6 gliocarcinoma cell in rats, and antimicrobial activity against some human pathogen microorganisms. The compounds 7e, 7h, 7j, 7k, 7L and 7n showed very high anticancer activity with the inhibition range of 80.51-97.02% compared to 5-FU. Some of the compounds exhibited anti-microbial activity. Also, they evaluated for inhibition effects against human carbonic anhydrase I, and II isoenzymes (hCA I and II) with Ki values in the range of 405.26-635.68pM for hCA I, and 245.40-489.60pM for hCA II, respectively. These results demonstrated that 3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives could be used in different biomedical applications.

Synthesis, carbonic anhydrase I and II isoenzymes inhibition properties, and antibacterial activities of novel tetralone-based 1,4-benzothiazepine derivatives.

Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti-HIV agents. In this study, the synthesis of novel tetralone-based benzothiazepine derivatives (1-16) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography from fresh human red blood cells. All compounds demonstrated the low nanomolar inhibitory effects on both isoenzymes using esterase activity. Benzothiazepine derivative 2 demonstrated the best hCA I inhibitory effect with Ki value of 18.19 nM. Also, benzothiazepine derivative 7 showed the best hCA II inhibitory effect with Ki value of 11.31 nM. On the other hand, acetazolamide clinically used as CA inhibitor, showed Ki value of 19.92 nM against hCA I and 33.60 nM against hCA II, respectively.

Age and gender related prevalence of intracranial calcifications in CT imaging; data from 12,000 healthy subjects.

PURPOSE: Location and extent of intracranial calcifications have been detected accurately with the use of CT technology and since, many clinical or pathological entities have been linked to these calcifications. Our purpose is to provide data regarding the prevalence of calcifications in various locations in brain. MATERIAL AND METHODS: We retrospectively examined 11,941 subjects who underwent non-contrast enhanced brain CT examination. We determined the prevalence of choroid plexus, pineal gland, habenula, dura mater, basal ganglia and vascular calcifications. RESULTS: Of 11,941 subjects, 70.2% had choroid plexus calcifications. Calcifications were most frequently seen in pineal gland and 71.6% of the study population had pineal calcifications. Habeluna and dural calcifications were present in 19.2% and 12.5% of the population respectively. Basal ganglia calcifications and vascular calcifications only constituted 1.3% and 3.5% of the study population respectively. Male dominance was present in all calcification types except basal ganglia calcifications. CONCLUSIONS: Showing associations and dissociations from the literature, our study provides a baseline data regarding the prevalence of various types of intracranial calcifications.

Serum Prolidase Activity as a Biomarker for Choroid Plexus Calcification.

The choroid plexus (CP) performs multiple functions such as secretion and reabsorption. CP also acts as the blood-cerebrospinal fluid barrier. Prolidase plays an important role in collagen metabolism by degrading imidodipeptides, in which proline or hydroxyproline residue is located at the C-terminal end. Serum prolidase activity (SPA) may reflect the degree of fibrosis and inflammation. Choroid plexus calcification (CPC) is considered as the physiological calcification of the brain, and CPC is diagnosed by the presence of calcification in the anatomical region on computed tomography (CT). Here, CPC and non-calcified CP were defined by Hounsfield Units (HU) values of > 150 and < 50, respectively. We aimed to measure SPA in subjects with CPC and those with non-calcified CP. This study included 89 subjects who were admitted to the neurology clinic and underwent CT: 44 subjects with CPC and 45 subjects with non-calcified CP. The neurological examination of all subjects was normal; namely, the subjects with CPC were asymptomatic. The SPA level was significantly higher in the CPC group than that in the non-calcified CP group (p < 0.002), and there was a significant positive correlation between vitamin D and SPA levels in the CPC group. In contrast, the vitamin D and parathyroid hormone levels were higher in the CPC group, but the difference was not statically significant (p > 0.05). These findings indicate that SPA is a biomarker for CPC that may be predictive of future brain disease.

Serum fetuin-A levels in subjects with and without choroid plexus calcification.

Choroid plexus is an intraventricular plexus of tissue which is responsible for secretion of cerebrospinal fluid. Calcification of choroid plexus is found to be associated with age and gender. One of novel and popular glycoprotein that involves in inhibition of mineralization is human fetuin-A. In our study, we investigated plasma levels of fetuin-A in subjects with and without choroid plexus calcification. For this purpose, 41 subjects with choroid plexus calcification and 41 age and gender matched subjects with normal appearing choroid plexus were recruited. Calcified and normal choroid plexus tissue identified on computed tomography images. Overnight fasting venous blood samples were collected to measure serum fetuin-A levels using a human fetuin-A enzyme-linked immunosorbent assay kit. Statistically significant difference concerning the median concentration of fetuin-A was found between subjects with and without choroid plexus calcification (p: 0.040). Significance was also present between male subgroups (p: 0.017) and 18-27 years age subgroups (p: 0.025). Our results suggest that fetuin-A has an potent role in calcification process of choroid plexus.

Evaluation of new chalcone derivatives as polyphenol oxidase inhibitors.

A newly series of 4-(phenylurenyl)chalcone (4a-j) and 4'-(phenylurenyl/thiourenyl)chalcone (9a-l) derivatives were synthesized and their inhibitory effects on the diphenolase activity of banana tyrosinase were evaluated. Tyrosinase has been purified from banana on an affinity gel comprised of Sepharose 4B-l-tyrosine-p-aminobenzoic acid. The result showed that 4a-j inhibited the PPO enzyme activity. Conversely, 9a-h and 9i-l showed activator effect on tyrosinase enzyme activity.