Dihydropyrimidinones: efficient one-pot green synthesis using Montmorillonite-KSF and evaluation of their cytotoxic activity

A simple, efficient, cost-effective, recyclable and green approach has been developed for the synthesis of new dihydropyrimidinone analogs via the Biginelli reaction. The methodology involves a multicomponent reaction catalyzed by “HPA-Montmorillonite-KSF” as a reusable and heterogeneous catalyst. This method gives an efficient and much improved modification of the original Biginelli reaction, in terms of yield and short reaction times under solvent free conditions. All the derivatives were subjected to cytotoxicity screening against a panel of four different human cancer cell lines viz. colon (Colo-205), prostate (PC-3), leukemia (THP-1) and lung (A549) to check their effect on percentage growth. MTT [3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide] cytotoxicity assay was employed to check IC₅₀ values. Of the synthesized analogs, 16a showed the best activity with IC₅₀ of 7.1 ± 0.8, 13.1 ± 1.4, 13.8 ± 0.9 and 14.7 ± 1.1 μM against lung (A549), leukemia (THP-1), prostate (PC-3) and colon (Colo-205) cancer lines, respectively. The 16a analog was further checked for its effect on cancer cell properties through clonogenic (colony formation) and scratch motility (wound healing) assays and thereby was found that it reduced both the colony formation and migratory properties of the lung cancer cell line (A549). Further, molecular docking studies were performed with 16a to show its binding mode.

The general method for the preparation of DHPM analogs; cytotoxic activity and binding mode of the most active derivative against PI3Kγ and CDK2 targets.     

Microtensile bond strength of resin composite bonded to caries-affected dentin with three adhesives

This study evaluated the ability of two self-etching adhesives (a two-step and a one-step) and a conventional 3-step adhesive to bond composite to both intact and caries-affected dentin with and without thermocycling. Thirty extracted human teeth with occlusal caries were randomly assigned to three groups according to the adhesive used: Scotchbond Multi-purpose (3M) (SBMP), ClearfilSE Bond (Kuraray) (SE) and Xeno IV (Dentsply) (XEIV). The occlusal surfaces of the teeth were sectioned to expose dentin. The adhesives were applied according to manufacturers' instructions, and a composite material (Herculite XRV, Kerr) was applied and cured in increments to form a core 3 mm high. The teeth were stored in distilled water for 24 hours, then sectioned using a micro-slicing machine to obtain sections 1 mm thick. The sections were further cut to obtain rods 6 mm long and 1 x 1 mm in thickness, with dentin/composite interface located at the center. The specimens were examined microscopically to separate the caries-affected (AD) and sound dentin (SD) into two groups. Half the specimens from each group were subjected to 3,000 thermocycles (5 degrees C to 55 degrees C) prior to testing. All the specimens were then subjected to microtensile bond strength (microTBS) testing in a special apparatus. Mean microTBS was determined for each group, and data were statistically analyzed with ANOVA and Tukey's tests. Mean microTBS and standard deviation values in MPa were: SBMP-SD = 22.19 (4.6), SBMP-SD-thermocycled = 15.7 (5.55), SBMP-AD = 18.6 (2.89), SBMP-AD-thermocycled = 16.62 (6.23), SE-SD = 24.25 (5.7), SE-SD-thermocycled = 22.3 (6.7), SE-AD = 20.7 (5.55), SE-AD-thermocycled = 20.23 (6.1), XEIV-SD = 21.43 (7.6), XEIV-SD-thermocycled = 18.3 (7.11), XEIV-AD = 15.45 (6.62), XEIV-AD-thermocycled = 14.8 (3.89). ANOVA revealed a significant difference among the groups (p < .0001). The two-step self-etch adhesive resulted in highest mean microTBS values under all test conditions. However, these mean values were significantly higher than the mean values obtained with the other two adhesives under some, but not all test conditions.     

Which is Better for Patients with Breast Cancer: Totally Implanted Vascular Access Devices (TIVAD) or Peripherally Inserted Central Catheter (PICC)?

World Journal of Surgery -     

Effect of statin on semen quality characteristics

Statins are lipid-lowering medications widely used to reduce the risk of cardiovascular diseases. Biochemically, they act by decreasing synthesis of cholesterol via inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Since 1992, various research studies have investigated the effect of statins on semen quality characteristics; however, to date, there is no collective summary to such effect. Here, we have systematically discussed and abridged all research studies published in Scopus, PubMed and Web of Science databases that are directly linking statin to semen fertility characteristics using the keywords “statin” versus “sperm” and “semen”. In summary, considering the animal studies, statins, in general, were found to ameliorate semen quality characteristics in reproductive detrimental conditions, while, in human males or in in vivo systems with normal reproductive conditions, in general, statins showed negative to blunt effects against semen quality characteristics, mainly sperm motility. However, further research studies, in particular human studies, in this specific research setting is still needed to approve these effects.     

Effect of lansoprazole on DNA integrity of human spermatozoa and activity of seminal creatine kinase

Although lansoprazole (brand name Prevacid) is a commonly used dug to manage various acid-related gastrointestinal diseases, little is known about its effects on human semen quality and sperm parameters. Here, we aimed to investigate the effect of lansoprazole on DNA integrity of human spermatozoa and activity of seminal creatine kinase. DNA integrity of human spermatozoa was assessed by the Apo-Direct™ kit followed by flow cytometry. The activity of creatine kinase was measured by kinetic spectrophotometric method using commercially available kits following the International Federation of Clinical Chemistry recommendations. Lansoprazole at 3 µg/ml, after 1-hr incubation period, did not show any significant increase in fluorescein isothiocyanate fluorescence (p > .05) and hence on the content of DNA breaks of human spermatozoa. In addition, there was no significant change (p = .8113) in the activity of seminal creatine kinase by the effect of lansoprazole. In conclusion, lansoprazole at 3 µg/ml did not alter DNA integrity of human spermatozoa or activity of seminal creatine kinase after 1-hr incubation period.     

Planning of Plastic Surgery Practice to Say Sayonara

Having seen the retired life of our professors both in general and plastic surgery and how lonely and isolated they were toward the end of their lives prompted me to discuss the retirement plans. The retirement from active surgical practice is indeed difficult and more so in plastic surgery. I feel that it needs meticulous planning for setting up a successful practice and when to say sayonara , just like treatment planning of any surgical procedure for perfect execution! At the end of M.Ch training, one should analyze oneself about the goal of the professional life and commit oneself to either a solo/group practice as an independent institutional practice or in a corporate set-up or choose a state/central government set-up with some academic position. A successful plastic surgical practice is every plastic surgeon’s dream and it comprises professional and financial successes with a sense of personal achievement. The factors involved in the selection of practice are family obligations—if parents or spouse are in medical profession with an existing establishment—individual talent, willingness to learn newer techniques, and acceptance of help from the other professional colleagues. At the same time, life needs to be balanced between the professional and family commitments without ignoring either of them with a deep social and community responsibility. But what is the correct time to say sayonara ? The timing of retirement is difficult to get right, but the basic additional principle that guides one is “ Primum non-nocere ”—do no harm—to the receiver.     

Congenital massive hiatus hernia type IV; initial experience with laparoscopic repair in young infant

Congenital massive hiatus hernia (CMHH) is an uncommon disorder during childhood. It can be associated with grave complications especially if presented in the highest grade; type IV, when the hernia contains other intra-peritoneal organ beside the stomach through a large hiatus defect. The insidious form of clinical presentation can be deceptive in diagnosis and may mimic congenital diaphragmatic hernia or other chest pathologies. The basic principle of surgical repair is to reduce the herniated organs, excise the hernia sac, and repair the crural defect and to add anti-reflux procedure with or without gastropexy. Traditionally, this has been done by open approach. Nowadays, the minimally invasive approach is the preferred method of treatment. A sixteen-month-old boy with history of recurrent respiratory symptoms was diagnosed with CMHH type IV for which laparoscopic repair was performed. Few reports in using minimally invasive technique in the management of CMHH in the pediatric age group are present in the literature, to the best of our knowledge type IV had never been described in young infants. We present a new case repaired by laparoscope in a young infant with CMHH type IV from the Middle East.     

Interactions of antagonists with subtypes of inositol 1,4,5-trisphosphate (IP3) receptor

BACKGROUND AND PURPOSE

Inositol 1,4,5-trisphosphate receptors (IP₃Rs) are intracellular Ca²⁺ channels. Interactions of the commonly used antagonists of IP₃Rs with IP₃R subtypes are poorly understood.

EXPERIMENTAL APPROACH

IP₃-evoked Ca²⁺ release from permeabilized DT40 cells stably expressing single subtypes of mammalian IP₃R was measured using a luminal Ca²⁺ indicator. The effects of commonly used antagonists on IP₃-evoked Ca²⁺ release and ³H-IP₃ binding were characterized.

KEY RESULTS

Functional analyses showed that heparin was a competitive antagonist of all IP₃R subtypes with different affinities for each (IP₃R3 > IP₃R1 ≥ IP₃R2). This sequence did not match the affinities for heparin binding to the isolated N-terminal from each IP₃R subtype. 2-aminoethoxydiphenyl borate (2-APB) and high concentrations of caffeine selectively inhibited IP₃R1 without affecting IP₃ binding. Neither Xestospongin C nor Xestospongin D effectively inhibited IP₃-evoked Ca²⁺ release via any IP₃R subtype.

CONCLUSIONS AND IMPLICATIONS

Heparin competes with IP₃, but its access to the IP₃-binding core is substantially hindered by additional IP₃R residues. These interactions may contribute to its modest selectivity for IP₃R3. Practicable concentrations of caffeine and 2-APB inhibit only IP₃R1. Xestospongins do not appear to be effective antagonists of IP₃Rs.     

An In Vitro Stereomicroscopic Evaluation of Bioactivity between Neo MTA Plus,Pro Root MTA,BIODENTINE & Glass Ionomer Cement Using Dye Penetration Method

The ideal root end filling material should form a tight seal in the root canal by adhering to the cavity walls. Several materials have been used for root end filling. The present study aims to find out and compare the bioactivity of Neo MTA Plus, Pro Root MTA White, BIODENTINE & glass ionomer cement as root end filling materials using 1% methylene blue as tracer. Materials and methods: 80 extracted human permanent maxillary anterior teeth were used in the study. They were divided into four groups. Specimens were sectioned transversely in the cervical area to separate the crown from the root. The root canal was obturated with gutta percha and zinc oxide eugenol sealers. Thereafter, each sample was resected apically by removing 3 mm of the apex and filled with different materials. Samples were kept in buffering solution at 37 °C until the recommended evaluation periods. The specimens were then suspended in 1% methylene blue for 24 h, prior to the analysis. The teeth were then sectioned, and dye penetration was examined, photographed, and evaluated under a stereomicroscope. Results: Vertical dye penetration showed significant differences across different groups. The minimum dye penetration was seen in Neo MTA plus followed by BIODENTINE, Pro Root MTA and maximum in GIC. There was no significant difference in dye penetration between Neo MTA plus and BIODENTINE both at fifteen days and one-month intervals. Conclusion: The present study suggests Neo MTA plus and BIODENTINE should be the preferred material for root end filling.