Coumarin-modified ruthenium complexes: Synthesis, characterization, and antiproliferative activity against human cancer cells.

Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs. Considering the advantages of ruthenium-based anticancer drugs and the cytostatic activity of organometallic complexes with triazole- and coumarin-derived ligands, we set out to synthesize Ru(II) complexes of coumarin-1,2,3,-triazole hybrids (L) with the general formula [Ru(L)(p-cymene)(Cl)]ClO4. The molecular structure of the complex [Ru(2a)(p-cymene)(Cl)]ClO4 (2aRu) was determined by single-crystal X-ray diffraction, which confirmed the coordination of the ligand to the central ruthenium(II) cation by bidentate mode of coordination. Coordination with Ru(II) resulted in the enhancement of cytostatic activity in HepG2 hepatocellular carcinoma cells and PANC-1 pancreatic cancer cells. Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.

Comparison of Tooth Size Measurements in Orthodontics Using Conventional and 3D Digital Study Models.

(1) Background: The objective of this study was to assess which digitization method produces the biggest deviation in the 3D images of tooth size from plaster models made using alginate impressions, which are considered the gold standard in orthodontics. (2) Methods: The sample used in this study included 30 subjects (10 males and 20 females). Measurements were made on four types of models: (1) digital models obtained through intraoral scanning and digitized models of plaster cast made from (2) alginate impressions, (3) silicone impressions, and (4) conventional plaster models. Mesio-distal (MD) and buccal/labial-lingual/palatal (BL) dimensions were measured on the reference teeth of the right side of the jaw (central incisor, canine, first premolar, and first molar). Comparisons of tooth size between the methods were conducted using a repeated measurement analysis of variance and the Friedman test, while the intraclass correlation coefficient was used to determine agreement between the different methods. (3) Results: The results showed a similar level of agreement between the conventional and digital models in both jaws and the anterior, middle, and posterior segments. Better agreement was found for the MD measurements (r = 0.337-0.798; p ≤ 0.05) compared to the BL measurements (r = 0.016-0.542), with a smaller mean difference for MD (0.001-0.50 mm) compared to BL (0.02-1.48 mm) and a smaller measurement error for MD (0.20-0.39) compared to BL (0.38-0.89). There was more frequently a better level of agreement between 3D images than measurements made using a digital caliper on the plaster models with 3D images. (4) Conclusions: The differences in measurements between the digital models and conventional plaster models were small and clinically acceptable.

Synthesis, characterisation and biological evaluation of monometallic Re(I) and heterobimetallic Re(I)/Fe(II) complexes with a 1,2,3-triazolyl pyridine chelating moiety.

Bioorganometallic complexes have attracted considerable interest and have shown promise for potential application in the treatment and diagnosis of cancer, as well as bioimaging agents, some acting as theranostic agents. The series of novel ferrocene, benzimidazo[1,2-a]quinoline and fluorescein derivatives with bidentate pyridyl-1,2,3-triazole and 2,2'-dipyridylamine and their tricarbonylrhenium(I) complexes was prepared and fully characterised by NMR, single-crystal X-ray diffraction, UV-Vis and fluorescence spectroscopy in biorelevant conditions. The fluorescein and benzimidazo[1,2-a]quinoline ligands and their complexes with Re(I) showed interactions with ds-DNA/RNA and HSA, characterised by thermal denaturation measurements, fluorimetric and circular dichroism titrations. The binding constants revealed that addition of Re(I) increases the affinity of fluorescein but decreases the affinity of benzimidazo[1,2-a]quinoline. The complexation of Re(I) had the opposite effect on fluorescein and benzimidazo[1,2-a]quinoline ligands' fluorimetric sensitivity upon biomacromolecule binding, Re(I) fluorescein complex emission being strongly quenched by DNA/RNA or HSA, while emission of Re(I) benzimidazo[1,2-a]quinolone complex was enhanced, particularly for HSA, making it a promising fluorescent probe. Some mono- and heterobimetallic complexes showed considerable antiproliferative activity on colon cancer cells (CT26 and HT29), with ferrocene dipyridylamine complexes exhibiting the best inhibitory activity, comparable to cisplatin. The correlation of the cytotoxicity data with the linker type between the ferrocene and the 1,2,3-triazole ring suggests that direct binding of the metallocene to the 1,2,3-triazole is favourable for antitumor activity. The Re(I) benzimidazo[1,2-a]quinolone complex showed moderate antiproliferative activity, in contrast to the Re(I) fluorescein complex, which exhibited weak activity on CT26 cells and no activity on HT29 cells. The accumulation of the Re(I) benzimidazo[1,2-a]quinolone complex in the lysosomes of CT26 cells indicates the site of its bioactivity, thus making this complex a potential theranostic agent.

Megalin Expression in Primary Oral Squamous Cell Carcinoma Is Associated with the Presence of Lymph Node Metastases, Vascular Invasion, and Lower Overall Survival.

Megalin (LRP2) is a rapidly recycling multiligand endocytic receptor primarily expressed in polarized epithelial cells. Although megalin might be involved in tumor growth and invasiveness through several mechanisms, its role has been understudied in the field of molecular oncology so far. The present study aimed to evaluate the impact of megalin expression in oral squamous cell carcinoma (OSCC) on disease progression. Megalin expression was evaluated immunohistochemically in 63 OSCC specimens. Data obtained were retrospectively compared with patient clinicopathological features and their survival. The proportion of megalin-expressing cells in the primary OSCC tissue was significantly associated with metastatic spreading to lymph nodes, vascular invasion and lower overall survival rate. Results obtained by the study suggest that megalin can be considered as a novel molecule involved in OSCC pathogenesis, but also useful as a potential biomarker for cancer progression.

Tuning the coordination properties of chiral pseudopeptide bis(2-picolyl)amine and iminodiacetamide ligands in Zn(II) and Cu(II) complexes.

Seven bis(2-picolyl)amine (bpa) and five iminodiacetamide (imda) ligands were prepared with different modifications in their side chain structure. The coordination properties of the ligands (L) were influenced by changes in the aliphatic linker length (C1, C2, or C3), amide group isomers and type of chiral terminal group. Complexation with Cu(II) afforded two polymorphs of a ML complex which features tetradentate coordination of a ligand with C2 linkers, while crystal structures of three trans-fac ML2 complexes with Cu(II) and Ni(II) show tridentate coordination of ligands with a C3 linker. The stoichiometry and stereochemistry of Zn(II) and Cu(II) complexes was further studied in solution by NMR and UV-Vis spectroscopy. DFT calculations gave an insight into the relative stability of isomers, as well as potential hydrogen bonding between two ligands in a ML2 complex. Furthermore, ML complexes of Cu(II) exhibited DNA cleavage activity.

Oligomicrodontia in a Pediatric Cancer Survivor after Chemotherapy: A Case Report.

Chemotherapy used on pediatric patients especially those below 3 years of age causes disturbances in dental development. The aim of this case report was to present the late dental effects of chemotherapy in a patient treated for anaplastic ependymoma (WHO III) at an early age. Radiographic findings at the age of 9 years showed oligomicrodontia of six teeth, maxillary lateral incisors, and maxillary and mandibular first premolars. Pediatric cancer survivors after chemotherapy have an increased risk of one or more dental development disorders. To ensure proper dental care and to assess the long-term effects on oral health, tooth development, and occlusion, the involvement of a dentist is crucial. Adequate diagnosis and well-planned treatment of the dental defect can significantly improve patient oral health-related quality of life.

Induction of Λ-helicity in a zinc complex with an alanine-appended aminopyridine ligand.

The crystal structure of tris[dimethyl 5-({1-[(pyridin-2-yl-κN)carbamoyl-κO]ethyl}carbamoyl)benzene-1,3-dicarboxylate]zinc(II) dinitrate acetonitrile trisolvate, [Zn(C19H19N3O6)3](NO3)2·3CH3CN or [Zn(L)3](NO3)2·3CH3CN, (1), has been determined by single-crystal X-ray diffraction. The neutral ligand L coordinates to the Zn2+ cation in a bidentate fashion via the pyridine N atom and an amide O atom, forming a six-membered chelate ring. The Λ-helical chirality of the Zn2+ coordination sphere is induced by pendant L-alanine residues through stacking interactions between the arene groups of two coordinated ligands, assisted by a hydrogen bond between amide groups bonded to the stacked arene rings. The third ligand is coordinated to the Zn2+ cation by the same six-membered chelate ring, but in the opposite direction with respect to the analogous chelate rings of the first two coordinated ligands. Besides ionic interactions between [ZnL3]2+ complexes and NO3- anions, several types of hydrogen bonds and intermolecular stacking interactions contribute to the stability of the solid-state phase.

Comparison of Nonheme Manganese- and Iron-Containing Flavone Synthase Mimics.

Heme and nonheme-type flavone synthase enzymes, FS I and FS II are responsible for the synthesis of flavones, which play an important role in various biological processes, and have a wide range of biomedicinal properties including antitumor, antimalarial, and antioxidant activities. To get more insight into the mechanism of this curious enzyme reaction, nonheme structural and functional models were carried out by the use of mononuclear iron, [FeII(CDA-BPA*)]2+ (6) [CDA-BPA = N,N,N',N'-tetrakis-(2-pyridylmethyl)-cyclohexanediamine], [FeII(CDA-BQA*)]2+ (5) [CDA-BQA = N,N,N',N'-tetrakis-(2-quinolilmethyl)-cyclohexanediamine], [FeII(Bn-TPEN)(CH3CN)]2+ (3) [Bn-TPEN = N-benzyl-N,N',N'-tris(2-pyridylmethyl)-1,2-diaminoethane], [FeIV(O)(Bn-TPEN)]2+ (9), and manganese, [MnII(N4Py*)(CH3CN)]2+ (2) [N4Py* = N,N-bis(2-pyridylmethyl)-1,2-di(2-pyridyl)ethylamine)], [MnII(Bn-TPEN)(CH3CN)]2+ (4) complexes as catalysts, where the possible reactive intermediates, high-valent FeIV(O) and MnIV(O) are known and well characterised. The results of the catalytic and stoichiometric reactions showed that the ligand framework and the nature of the metal cofactor significantly influenced the reactivity of the catalyst and its intermediate. Comparing the reactions of [FeIV(O)(Bn-TPEN)]2+ (9) and [MnIV(O)(Bn-TPEN)]2+ (10) towards flavanone under the same conditions, a 3.5-fold difference in reaction rate was observed in favor of iron, and this value is three orders of magnitude higher than was observed for the previously published [FeIV(O)(N2Py2Q*)]2+ [N,N-bis(2-quinolylmethyl)-1,2-di(2-pyridyl)ethylamine] species.

A ferrocene-based pseudopeptide chiroptical switch.

We present a double-stranded ferrocene pseudopeptide 2b which exhibits stimuli responsive chirality inversion triggered by solvent exchange or acid addition. Compound 2b exists as a mixture of self-assembled fast exchanging oligomers which macroscopically behave as a chiroptical switch with two stable states. The ferrocene group inversion results in a distinct CD signal in the visible part of the spectrum. The inversion is accomplished through a conformational change due to a rearrangement of hydrogen bonding forcing the rotation of ferrocene rings.

Comparison of different surgical procedures on the stability of dental implants in posterior maxilla: A randomized clinical study.

BACKGROUND: Stability of a dental implant is very important when planning immediate loading and design of a final restoration. The aim of this study was to compare the primary and the secondary stability of dental implants inserted by three different surgical techniques: conventional (standard) technique using a sequence of drills for implant bed preparation, osteotome technique using tapered hand instruments for creating implant sites by condensing the bone and guided flapless implant surgery with surgical templates. MATERIAL AND METHODS: The study included 150 patients (80 males and 70 females), 46-71 years old, who required implant supported fixed partial dentures in the posterior maxilla of D3 or D4 bone density. Patients were randomly assigned into one of the three surgical insertion technique groups. All patients received tapered implants of the same manufacturer of the same length and two different widths (3.3 × 11.5 mm or 4.2 × 11.5 mm). Primary and secondary implant stability were measured by means of resonance frequency analysis (RFA) at the time of implant placement and 5 months after surgery using the Ostell ISQ device (Osstell AB, Sampgatan, Goteborg, Sweden). Statistical analysis included one-sample Kolmogorov Smirnov test, descriptive statistics, multivariate analysis (Bonferoni post-hoc tests) and paired t-tests. RESULTS: Patients in the osteotome group exhibited higher primary stability (P < 0.01) than in the conventional and surgically guided flapless groups. There were no significant differences in the secondary stability (p > 0.05). Wider implants presented higher ISQ values (P<0.01). CONCLUSION: The osteotome technique led to the highest implant primary stability, therefore it can be recommended when immediate loading is planned or for one-piece implant insertion.

Copper(ii) and zinc(ii) complexes of mono- and bis-1,2,3-triazole-substituted heterocyclic ligands.

Chelating 1,4-disubstituted mono- (8a-8d) and bis-1,2,3-triazole-based (9a-11a) ligands were prepared by regioselective copper(i)-catalysed 1,3-dipolar cycloaddition of terminal alkynes with aromatic azides, together with bioconjugate 13a synthesized by amide coupling of l-phenylalanine methyl ester to 11a. Cu(ii) and Zn(ii) complexes were prepared and single crystal structures were determined for complexes 8aCu, 8dCu, 9cCu and 10cCu, as well as the free ligands 10a and 10c. The in situ prepared Zn(ii) complexes were studied by NMR spectroscopy, while the stoichiometry of the Cu(ii) complexes in solution was determined by UV-Vis titrations and confirmed by the electronic structure DFT calculations at the (SMD)/M05-2X/6-31+G(d)/LanL2DZ+ECP level of theory.

Stereochemistry of Hexacoordinated Zn(II), Cu(II), Ni(II), and Co(II) Complexes with Iminodiacetamide Ligands.

Metal complexes of iminodiacetamide (imda) ligands and metal ions Zn(II), Cu(II), Ni(II), and Co(II) were prepared using eight imda ligands (L1-L8) substituted with groups of different steric and electronic properties on the central amine N atom (H atom, methyl, isopropyl, and benzyl) and the para position of the phenyl rings (nitro and dimethylamino). The effect of these substituents on the stoichiometry (ML and ML2), geometry, and stereochemistry (mer, trans-fac, cis-fac) of the complexes was studied in the solid state, in solution, and by density functional theory calculations. Single-crystal and powder X-ray diffraction, thermogravimetry, and IR spectroscopy showed that in the solid state imda ligands preferentially form trans-fac ML2 complexes, with the exception of the cis-fac complex 7Zn. NMR spectroscopy of diamagnetic Zn(II) and paramagnetic Co(II) complexes revealed the formation of both ML and ML2 complexes in solution, which was also confirmed by UV-vis titrations. Variable-temperature NMR was used to study the effect of the substituent on the central amine N atom on the Zn-N bond strength and nitrogen inversion. The relative stabilities of the isomers were rationalized by computations and the optimized structures used for geometry analysis.

ANGIOMYOMA OF THE UPPER LIP - CASE REPORT AND REVIEW OF THE LITERATURE.

A case is presented of upper lip angiomyoma in a 36-year-old man. The tumor was painless, palpable and clinically visible. The operation was performed under local anesthesia in the Outpatient Department. There were no complications during the postoperative course. Current literature on the subject is listed in the introduction, followed by presentation of the case and histologic characteristics of the tumor. This case is described as one of the differential diagnostic possibilities in the diagnosis of soft tissue tumors of the lip. Also, through review of the literature, different clinical appearances of angiomyoma, histologic variations and immunohistochemical characteristics are discussed that can help identify this tumor.

A Large Cheek Hematoma as a Complication of Local Anesthesia: Case Report.

Hematoma is among less frequent complications which occur following local anesthesia. The posterior superior alveolar nerve block and inferior alveolar nerve block are known to be accompanied with a higher incidence of positive aspiration compared to all infiltration and block anesthesia techniques in oral surgery. We present the case of an otherwise healthy 8-year-old boy who experienced a large cheek hematoma after a routine infiltration anesthesia in the maxilla. Firstly, he was mistakenly treated under the diagnosis of type1 allergic reaction. Subsequently, the topical therapy for an evident, large hematoma was unsuccessful. Ultimately, incision of the infected hematoma and antibiotic therapy were crucial for its resolution. Early recognition of clinical signs of hematoma is of utmost importance for the surgeon in order to treat the patient adequately.

Metal-induced supramolecular chirality inversion of small self-assembled molecules in solution.

A non-covalent self-assembled chiral alanyl aminopyridine ligand exhibits supramolecular chirality in solution, independent of the organic solvent used. The supramolecular chirality of the assemblies is completely inverted by complexation to zinc ions. To date, such a supramolecular metal-ligand system has not been reported in the literature.

Myofascial pain of the head and neck among Croatian war veterans treated for depression and posttraumatic stress disorder.

BACKGROUND: During the Croatian War of Independence, 1991-1995, Croatian soldiers were exposed to traumatic and stressful events. Certain number of soldiers who took part in the war, developed depression and posttraumatic stress disorder (PTSD). Stress is one of the etiological factors in the development of myofascial pain (MPS), although the mechanism of these processes is not entirely understood. The aims of this study were to determine the frequency of myofascial pain among Croatian war veterans with depression and PTSD, association between MPS and severity of depression, to describe the most common locations of trigger points in the region of head and neck, and to find out if there is any association in frequency between MPS and endotracheal intubation. SUBJECTS AND METHODS: A total of 101 Croatian war veterans suffering from PTSD and depression participated in the current study. Diagnosis of myofascial pain was based on detailed anamnestic history and careful clinical examination. RESULTS: Our findings showed a high rate of myofascial pain among Croatian war veterans, with occipital region and right temporal region as the most common places of trigger points. Higher severity of depression was accompanied by a higher percentage of subjects with MPS. Finally, there was no significant association between endotracheal intubation and development of MPS among the war veterans. CONCLUSIONS: It can be concluded that the rate of myofascial pain among Croatian war veterans is high and therefore it must be considered in patients with depression and PTSD. Moreover, the severity of depressive symptomatology seems to be related to the presence of myofascial pain.

Botryoid Cyst, a Rare Type of Odontogenic Cyst

Botryoid cyst, a rare type of odontogenic cyst, is usually considered a multilocular variant of lateral periodontal cyst. It was first described in 1973, and up to the present less than a hundred cases have been reported in the literature. Botryoid cysts are characterized by a multilocular histologic finding and a higher risk of recurrence than lateral periodontal cysts. In this article, we present a case of botryoid cyst from our clinical practice, accompanied by literature review of previous cases reported in the literature so far. Study results showed that botryoid cysts mostly affected population in their fifties, with a slight female (53.5%) predominance over males (46.5%). The mandible was the most frequently affected region, accounting for 70 (83.3%) cases. Maxilla was only sporadically affected accounting for 14 (16.7%) cases. Radiographic appearance of botryoid cysts can be multilocular or unilocular. It is concluded that the recurrence rate is relatively high (30.1%), therefore long term follow up is needed.

Colorectal Adenocarcinoma Metastasizing to the Oral Mucosa of the Upper Jaw.

INTRODUCTION: Metastases to the oral cavity are uncommon, accounting for only 1% of all oral malignant tumors. When they occur they mostly originate from primary tumors of the lungs, kidney, breast and prostate. Oral metastases from the primary colorectal carcinoma are much more infrequent. CASE OUTLINE: We present an unusual case of a 78-year-old man with a soft tissue oral metastasis originating from the primary colorectal carcinoma.The patient was referred to the Department of Otorhinolaryngology, Head and Neck Surgery with an intraoral mass on the right side of the maxilla. The diagnosis was confirmed by histopathologic examination and immunohistochemical analysis. CONCLUSION: Oral metastases occur rarely and often can mimic much more common benign lesions, therefore they should be considered as a possibility in a differential diagnosis.

Actinomycosis of the cheek.

INTRODUCTION: Actinomycosis is an uncommon chronic granulomatous infection first described by Bollinger in 1 877.The infection is caused by actinomyces species and it is characterized by slow contiguous spread and suppurative inflammation, formation of multiple abscesses and sinus tracts with possible drainage of "sulfur granules". CASE OUTLINE: We report an unusual case of actinomycosis of the cheek that occurred 6 years after buccal odontogenic abscess. A 56-year-old male was referred to the Department of Oral Surgery because of a painless swelling of the left cheek, which initiated three weeks prior to the referral. The diagnosis of actinomycosis was confirmed by histopathologic examination. In accordance with the diagnosis oral penicillin was prescribed for four months with complete resolution. CONCLUSION: This case of actinomycosis is presented as a rarity. For proper diagnosis, careful examination and a high degree of clinical suspicion are necessary.

Trigeminal neuralgia--case and treatment analysis at the Department of Oral Surgery of the University Hospital Dubrava.

The aim of the study was to explore certain risk factors for trigeminal neuralgia (TN), assess the prevalence of misdiagnoses of TN made by primary care dentists, compare the treatment practice for TN at the Department of Oral Surgery with the guidelines, and the importance of interdisciplinary approach in TN treatment. The study included 237 patient records (70 men and 167 women, aged 5-91 years) referred to the Department under the diagnosis of TN. From their medical records, demographic data, referral diagnose, clinical diagnose, additional diagnostic procedures and treatment were analysed. Neuralgia of the trigeminal nerve affects predominantly elderly female population, while the impact of the season on the incidence of the disease has not been determined. The most common therapy used at the Department were blockades, carbamazepine or their combination. 63.3% patients were referred for further diagnostic tests following the first examination. The number of misdiagnosed cases referred by primary care dentists (33.6%) points that better training in diagnosing TN is needed for the dental practitioners. The treatment methods at the Department need to be harmonized with the latest guidelines on neuralgia treatment. Due to the complexity of etiological factors, an interdisciplinary approach is necessary.