Synthesis of novel 3-butyl-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents

A variety of novel 3-butyl-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 3-butyl-2-hydrazino-3H-quinazolin-4-one with various aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 3-butyl-2-(1-methylbutylidene-hydrazino)-3H-quinazolin-4-one (AS3) emerged as the most active analgesic agent. Compound 3-butyl-2-(1-ethylpropylidene-hydrazino)-3H-quinazolin-4-one (AS2) emerged as the most active anti-inflammatory agent and is moderately more potent when compared to the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to aspirin.     

Additive Effect of Plasma Rich in Growth Factors With Guided Tissue Regeneration in Treatment of Intrabony Defects in Patients With Chronic Periodontitis: A Split‐Mouth Randomized Controlled Clinical Trial

Background: Periodontal regeneration can be defined as complete restoration of lost periodontal tissues to their original architecture and function. A variety of treatment modalities have been proposed to achieve it. Plasma rich in growth factors (PRGF) is a concentrated suspension of growth factors that promotes restoration of lost periodontal tissues. The objective of the present study is to assess the effect of PRGF associated with guided tissue regeneration (GTR) versus GTR only in the treatment of intrabony defects (IBDs) in patients with chronic periodontitis (CP). Methods: Patients with CP (n = 14) with 42 contralateral 2‐ and 3‐walled defects were randomly assigned to test (PRGF+GTR) and control (GTR alone) treatment groups. Clinical and radiographic assessments performed at baseline and after 6 months were: 1) gingival index (GI), 2) probing depth (PD), 3) clinical attachment level (CAL), 4) radiologic defect depth, and 5) bone fill. Results: Comparison of parameters measured at baseline and after 6 months showed mean PD reduction of 3.37 ± 1.62 mm in the control group (P <0.001) and 4.13 ± 1.59 mm in the test group (P <0.001). There was a significant difference in mean change in CAL (P <0.001) in the control group (5.42 ± 1.99) and the test group (5.99 ± 1.77). Mean change in GI was 1.89 ± 0.32 and 1.68 ± 0.58 in the control group and test group, respectively, and the difference was statistically significant (P <0.001). When compared between groups, clinical parameters did not show any statistically significant variations. Mean radiographic bone fill was 1.06 ± 0.81 and 1.0 ± 0.97 in the control group and test group, respectively. However, the difference was not statistically significant. Conclusions: PRGF with GTR, as well as GTR alone, was effective in improving clinical and radiographic parameters of patients with CP at the 6‐month follow‐up. There was no additive effect of PRGF when used along with GTR in the treatment of IBDs in patients with CP in terms of both clinical and radiologic outcomes.     

Effects of growth hormone and testosterone on cortical bone formation and bone density in aged orchiectomized rats.

Osteoporosis in men is a disease that is increasing in incidence, and with an increasing elderly population it poses a serious health problem. Since both testosterone (T) and growth hormone (GH) have an anabolic effect on bone and both decrease with aging, we were prompted to test whether the administration of these hormones in combination would increase bone mass in orchiectomized (orx) senile rats more than administration of either agent alone. Twenty-month-old male Wistar rats were divided into five groups with seven animals each: (a) age-matched intact control, (b) orx, (c) orx+GH (2.5 mg/kg/day), (d) orx+T [10 mg/kg, subcutaneous (s.c.), injection given twice a week], and (e) orx+GH+T. Testosterone and GH were given subcutaneously for 4 weeks. Bone histomorphometry of the tibial shaft showed that the orx group had lower cortical bone area than the intact control group. The decrease in cortical bone area was due to increased intracortical porosis as well as decreased periosteal bone formation rate (BFR). Administration of T to the orx animals prevented the development of the porosis and the decrease in periosteal BFR. The bone mineral content (BMC) and bone mineral density (BMD) of the femur as tested by dual-energy X-ray absorptiometry were significantly higher in the orx+T than in the orx group and were not significantly different from that of the intact control group. Administration of GH to the orx rats increased periosteal BFR significantly; however, the BMC and BMD measured were not increased significantly in comparison to the orx group. When GH and T were combined in treatment, the cortical bone area, periosteal BFR, and femoral BMD were all significantly higher than that of the orx and even higher than the intact control rats. Two-way analysis of variance shows that the individual effect of GH and T treatment on the periosteal BFR and cortical bone area was significant. The effect of T, but not GH, on femoral BMC and BMD was also significant; however, there is no synergistic interaction between the two treatments. Four weeks of orx with or without GH or T administration had no significant effect on tibial metaphyseal cancellous bone volume. In conclusion, this short-term study suggests that the combined intervention of GH and T in androgen-deficient aged male rats may have an independent effect in preventing osteopenia. The significant effect of GH+T may be attributed to the prevention of intracortical porosis, and an increase in periosteal bone formation and cortical bone mass.     

Survivin deficiency leads to imparalization of cytokinesis in cancer cells

Background: Survivin has been implicated in cancer progression and is known to be over-expressed in a variety of human malignancies. Positive regulation of survivin expression provides a connecting link between cell cycle and tumorigenesis or perhaps tumour maintenance. Methods: An experiment was designed to analyse survivin expression in cell lines (MCF 7, Zr751, A549, HepG2) using SDS-PAGE, Western blots, RT-PCR, AGE and heamatoxylin-eosin staining were done. Results: SDS-PAGE revealed the presence of 16.5 kDa protein. Subsequent western Blot and cytological analysis showed down-regulation of survivin expression in cancer cells. Conclusion: Therefore, the study allows the conclusion that survivin is essential for proper chromosome segregation and cytokinesis. It seems reasonable to suspect that abnormal expression or function of survivin might contribute to multinucleated and apoptotic conditions.     

High Pressure (HP) in Spark Plasma Sintering (SPS) Processes: Application to the Polycrystalline Diamond

High-Pressure (HP) technology allows new possibilities of processing by Spark Plasma Synthesis (SPS). This process is mainly involved in the sintering process and for bonding, growing and reaction. High-Pressure tools combined with SPS is applied for processing polycrystalline diamond without binder (binderless PCD) in this current work. Our described innovative Ultra High Pressure Spark Plasma Sintering (UHP-SPS) equipment shows the combination of our high-pressure apparatus (Belt-type) with conventional pulse electric current generator (Fuji). Our UHP-SPS equipment allows the processing up to 6 GPa, higher pressure than HP-SPS equipment, based on a conventional SPS equipment in which a non-graphite mold (metals, ceramics, composite and hybrid) with better mechanical properties (capable of 1 GPa) than graphite. The equipment of UHP-SPS and HP-SPS elements (pistons + die) conductivity of the non-graphite mold define a Hot-Pressing process. This study presents the results showing the ability of sintering diamond powder without additives at 4–5 GPa and 1300–1400 °C for duration between 5 and 30 min. Our described UHP-SPS innovative cell design allows the consolidation of diamond particles validated by the formation of grain boundaries on two different grain size powders, i.e., 0.75–1.25 μm and 8–12 μm. The phenomena explanation is proposed by comparison with the High Pressure High Temperature (HP-HT) (Belt, toroidal-Bridgman, multi-anvils (cubic)) process conventionally used for processing binderless polycrystalline diamond (binderless PCD). It is shown that using UHP-SPS, binderless diamond can be sintered at very unexpected P-T conditions, typically ~10 GPa and 500–1000 °C lower in typical HP-HT setups. This makes UHP-SPS a promising tool for the sintering of other high-pressure materials at non-equilibrium conditions and a potential industrial transfer with low environmental fingerprints could be considered.     

A Modified Temporal Incision: An Alternative Approach to the Zygomatic Arch

Zygomatic arch fractures occur due to a direct injury to the lateral aspect of the head. When there are multiple fractures of the arch, open reduction and internal fixation is indicated. Conventionally hemi-coronal and pre-auricular incisions are placed to approach the arch. A modified temporal incision has been described. Open reduction and internal fixation of zygomatic arch fractures has been done.     

Synthesis, analgesic, anti-inflammatory, ulcerogenic index and antibacterial activities of novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-4(3H)-ones

A variety of novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-4(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)dithiocarbamic acid methyl ester (5) with a variety of amines. The starting material dithiocarbamate (5) was synthesized from 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzo (b) thiophene (1) by a novel innovative route. The title compounds were investigated for analgesic, anti-inflammatory, ulcerogenicity index and antibacterial activities. While the test compounds exhibited significant activity, the compounds 1-methyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A1), 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A4) showed more potent analgesic activity and the compounds 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno-[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d] pyrimidin-3-yl)thiourea (A4) showed more potent anti-inflammatory activity than the reference standard diclofenac sodium.     

Synthesis,analgesic, anti‐inflammatory and ulcerogenic index activities of novel 2‐methylthio‐3‐substituted‐5,6‐dimethyl thieno [2,3‐d] pyrimidin‐4(3H)‐ones

A variety of novel 2‐methylthio‐3‐substituted amino‐5,6‐dimethyl thieno [2,3‐d] pyrimidin‐4(3H)‐ones were synthesized by reacting 3‐amino‐2‐methylthio‐5,6‐dimethyl thieno [2,3‐d] pyrimidin‐4(3H)‐one with different aldehydes and ketones. The starting material 3‐amino‐2‐methylthio‐5,6‐dimethyl thieno [2,3‐d] pyrimidin‐4(3H)‐one was synthesized from 2‐amino‐3‐carbethoxy‐4,5‐dimethyl thiophene. The compounds were investigated for their analgesic activity in albino mice, and for their anti‐inflammatory and ulcerogenic index activities in Wistar rats. The compound 2‐(1‐ethylpropylideneamino)‐2‐methylthio‐5,6‐dimethyl thieno [2,3‐d] pyrimidin‐4(3H)‐one (AS2) showed the most potent analgesic activity of the series. It also showed more potent anti‐inflammatory activity when compared to the reference standard, diclofenac sodium. The test compounds showed only mild ulcerogenic potential when compared to aspirin. Drug Dev Res 68:134–142, 2007. © 2007 Wiley‐Liss, Inc.