Synthesis of New 6-[4-(2-Fluorophenylpiperazine-1-YL)]-3(2H)-Pyridazinone-2-Acethyl-2- (Substitutedbenzal)Hydrazone Derivatives and Evulation of Their Cytotoxic Effects in Liver and Colon Cancer Cell Lines

Pharmaceutical Chemistry Journal - In this study, seven new 3(2H)-pyridazinone derivatives expected to show cytotoxic activity in liver and colon cancer cell lines were synthesized. Their...     

Structural and Mechanical Repair of Diffuse Damage in Cortical Bone In Vivo

Physiological wear and tear causes bone microdamage at several hierarchical levels, and these have different biological consequences. Bone remodeling is widely held to be the mechanism by which bone microdamage is repaired. However, recent studies showed that unlike typical linear microcracks, small crack damage, the clusters of submicron‐sized matrix cracks also known as diffuse damage (Dif.Dx), does not activate remodeling. Thus, the fate of diffuse damage in vivo is not known. To examine this, we induced selectively Dif.Dx in rat ulnae in vivo by using end‐load ulnar bending creep model. Changes in damage content were assessed by histomorphometry and mechanical testing immediately after loading (ie, acute loaded) or at 14 days after damage induction (ie, survival ulnae). Dif.Dx area was markedly reduced over the 14‐day survival period after loading (p < 0.02). We did not observe any intracortical resorption, and there was no increase in cortical bone area in survival ulnae. The reduction in whole bone stiffness in acute loaded ulnae was restored to baseline levels in survival ulnae (p > 0.6). Microindentation studies showed that Dif.Dx caused a highly localized reduction in elastic modulus in diffuse damage regions of the ulnar cortex. Moduli in these previously damaged bone areas were restored to control values by 14 days after loading. Our current findings indicate that small crack damage in bone can be repaired without bone remodeling, and they suggest that alternative repair mechanisms exist in bone to deal with submicron‐sized matrix cracks. Those mechanisms are currently unknown and further investigations are needed to elucidate the mechanisms by which this direct repair occurs. © 2014 American Society for Bone and Mineral Research     

Results of intravitreal triamcinolone acetonide in patients with macular edema secondary to branch retinal vein occlusion

Background Macular edema is one of the most common causes of visual loss in patients with retinal vein oclusions. Intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factors are modalities of treatment for macular edema secondary to branch retinal vein occlusion (BRVO). Objective To present the results of intravitreal triamcinolone acetonide therapy in patients with macular edema secondary to BRVO. Setting A retrospective clinical interventional study included 32 patients with macular edema secondary to BRVO. Method The records of 32 eyes of 32 patients who received 4 mg/0.1 mL injection of intravitreal triamcinlone for macular edema secondary to BRVO were evaluated. Patients with visual acuity <0.40 logMAR (logarithm of the minimum angle of resolution), central macular thickness (CMT) >260 μm and no neovascularization at baseline were included. Patients with diabetes mellitus, a history of intravitreal anti vascular endothelial growth factor injection, grid laser photocoagulation and ischemic BRVO were excluded. The re-injections were performed in cases with increased CMT >100 μm or vision loss of five or more letters. Results The mean follow-up was 12 ± 1.9 months. The visual acuity increased from 0.58 ± 0.16 at baseline to 0.25 ± 0.11 logMAR (P < 0.001). The CMT decreased from 490 ± 107 μm at baseline to 266 ± 90 μm at 12 months (P < 0.001). Both cataract and glaucoma developed in 18.75 % patients. Conclusion Intravitreal triamcinolone, due to absence of systemic side effects, can be used with confidence for treatment macular edema secondary to BRVO. However the main disadvantages of intravitreal triamcinolone injection are elevation of intraocular pressure and formation of cataract.     

A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders

Genetic ataxias are associated with mutations in hundreds of genes with high phenotypic overlap complicating the clinical diagnosis. Whole‐exome sequencing (WES) has increased the overall diagnostic rate considerably. However, the upper limit of this method remains ill‐defined, hindering efforts to address the remaining diagnostic gap. To further assess the role of rare coding variation in ataxic disorders, we reanalyzed our previously published exome cohort of 76 predominantly adult and sporadic‐onset patients, expanded the total number of cases to 260, and introduced analyses for copy number variation and repeat expansion in a representative subset. For new cases (n = 184), our resulting clinically relevant detection rate remained stable at 47% with 24% classified as pathogenic. Reanalysis of the previously sequenced 76 patients modestly improved the pathogenic rate by 7%. For the combined cohort (n = 260), the total observed clinical detection rate was 52% with 25% classified as pathogenic. Published studies of similar neurological phenotypes report comparable rates. This consistency across multiple cohorts suggests that, despite continued technical and analytical advancements, an approximately 50% diagnostic rate marks a relative ceiling for current WES‐based methods and a more comprehensive genome‐wide assessment is needed to identify the missing causative genetic etiologies for cerebellar ataxia and related neurodegenerative diseases.     

Spontaneous external jugular vein pseudoaneurysm treated by thrombin injection: Case report and literature review

Although external jugular vein (EJV) aneurysms are infrequent, regardless of etiology, spontaneous pseudoaneurysms (PAs) are extremely rare and generally require surgery. We describe a case of spontaneous PA of the EJV, which was successfully treated by percutaneous thrombin injection.     

In situ reduction of chloroauric acid (HAuCl4) for generation of catalytic Au nanoparticle embedded triazine based covalent organic polymer networks

Covalent-organic polymer networks (COPNs) have been used as catalyst supports due to their stable and favorable structure. Herein, a simple synthetic route was applied to generate Au@COPN-1 hybrids via in situ reduction of gold ions with no additional reducing agent. Synthesized novel COPN-1 was mixed with different concentrations of HAuCl₄ which resulted in Au@COPN-1 with varying sizes of Au nanoparticles in a controlled manner. The microstructural and morphological features of COPN-1 and Au@COPN-1 were characterized in detail using FT-IR, C-NMR, elemental analysis, UV-Vis, XRD, TEM, BET, and TGA. It is noteworthy that the red-shifted LSPR peaks of Au nanoparticles produced with increasing concentrations of HAuCl₄ indicated an increase in the particle size of the Au nanoparticles as justified by TEM images. The optimum catalytic activity of Au@COPN-1 was obtained when 4.6 × 10⁻³ mM HAuCl₄ was used, which led to the complete reduction of 4-nitrophenol within 16 minutes with excellent recyclability for more than 5 catalytic cycles, giving yields over 94%. Moreover, the non-aggregation of nanoparticles in the reused catalyst further confirmed the stability of the prepared catalysts. Consequently, these results indicated that in situ synthesis of AuNPs inside the COPN-1 matrix produces a promising catalyst platform for the reduction of aromatic nitro compounds, for example, for the degradation of one of the most common persistent organic pollutants 4-nitrophenol, as shown here. In addition, the Au@COPN-1 hybrid system showed good biocompatibility at appropriate doses confirmed by a dynamic real-time cell analysis system which can be used in various medical applications, such as drug delivery, in the future.

A facile synthetic route was applied to generate Au@COPN-1 hybrids via in situ reduction of Au³⁺ with no additional reducing agent. Au@COPN-1 is a promising catalyst platform and good biocompatibility confirmed by dynamic real-time cell analysis.     

Effect of the bracket types on microbial colonization and periodontal status

Objective:To evaluate the effect of different bracket types on the levels of Streptococcus mutans (SM) and Lactobacillus (LB) in saliva, in plaque, and on the periodontal condition.Materials and Methods:Forty patients aged 14 to 16 years, who had Angle Class I malocclusion with minimal crowding, were nonsmokers, were without systematic disease, and did not use antibiotics or oral mouth rinses during the 3-month period before the study were randomly selected. The patients were subdivided into two groups with random allocation of bracket type: conventional brackets (CB; Avex Mx, OPAL orth.) with steel wire ligature or self-ligating brackets (SLB; F1000, Leone S.p.A.). Microbial and periodontal records were obtained before bonding (T₁) and 1 month after bonding (T₂). Microbial samples were collected from the stimulated saliva and the plaque from the labial surfaces of the upper and lower lateral incisors. To estimate the number of colony-forming units of SM and LB, Dentocult SM and LB kits were used. The plaque index (PI), gingival index (GI), and pocket depth (PD) values were recorded to evaluate the periodontal condition. Paired t-test and Mann-Whitney U-test were used to compare the groups statistically.Results:No significant differences occurred in SM or LB colonization between the groups. In the SLB group, PI, GI, and PD values increased significantly (P < .05). A greater increase was found in PD value in the SLB group (0.98 mm) compared with the CB group (0.04 mm; P < .05).Conclusions:The F1000 SLB do not have an advantage over Avex Mx CB with respect to periodontal status and colonization of SM and LB.