Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: search for anticancer agent

The synthesis of some 2-furano-4(3H)-quinazolinones, diamides (open ring quinazolines), quinoxalines and their biological evaluation as antitumor agents using National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Among the synthesize compounds, seventeen compounds were granted NSC code and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10(-5) M) in full NCI 60 cell panel. Among the selected compounds, 3-(2-chloro benzylideneamine)-2-(furan-2-yl) quinazoline-4(3h)-one 21 was found to be the most active candidate of the series at five dose level screening against Ovarian OVCAR-4 and Non-small cell lung cancer NCI-H522 with GI50 1.82 & 2.14 μM respectively. Rational approach and QSAR techniques enabled the understanding of the pharmacophoric requirement for quinazoline, diamides and quinoxaline derivatives.     

Optimal use of platelet glycoprotein IIb/IIIa receptor antagonists in patients undergoing percutaneous coronary interventions

Discovery of the central role of platelets in the pathogenesis of acute coronary syndromes (ACS) and ischaemic complications of percutaneous coronary interventions (PCI) has led to the widespread use of oral and parenteral platelet inhibitors to treat these conditions. Glycoprotein (GP) IIb/IIIa (also known as α(IIb)β(3)) receptors on the surface of platelets play an essential role in platelet aggregation and serve as a key mediator in the formation of arterial thrombus. When activated, GP IIb/IIIa receptors bind to fibrinogen, which serves as the 'final common pathway' in platelet aggregation. Of the numerous agents developed for modulating platelet activity, intravenous platelet GP IIb/IIIa receptor antagonists are the most potent. There are four agents in clinical use, including abciximab, eptifibatide, tirofiban and lamifiban, although lamifiban is not approved for use in the US. While all agents block fibrinogen binding to GP IIb/IIIa, they do so by different mechanisms. Abciximab is a humanized form of a murine monoclonal antibody directed against GP IIb/IIIa, eptifibatide is a synthetic, cyclic heptapeptide that contains a lysine-glycine-aspartic acid (KGD) sequence that mimics the arginine-glycine-aspartic acid (RGD) sequence found on GP IIb/IIIa, tirofiban is a non-peptide antagonist derived by optimization of the tyrosine analogue that structurally mimicks the RGD-containing loop of the disintegrin echistatin, and lamifiban is a synthetic, non-cyclic, non-peptide, low-molecular-weight compound. In clinical trials, use of these agents reduces ischaemic adverse cardiovascular events in patients with ACS undergoing PCI, but at a cost of increased bleeding.     

Outcomes of kidney transplantation in patients with hepatitis B virus infection: A systematic review and meta-analysis

AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus(HBV) infection, and the trends of patient's outcomes overtime.METHODS A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through October 2017. Studies that reported odds ratios(OR) of mortality or renal allograft failure after kidney transplantation in patients with HBV [defined as hepatitis B surface antigen(HBs Ag) positive] were included. The comparison group consisted of HBs Agnegative kidney transplant recipients. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of Der Simonian and Laird. The protocol for this metaanalysis is registered with PROSPERO(International Prospective Register of Systematic Reviews; no. CRD42017080657).RESULTS Ten observational studies with a total of 87623 kidney transplant patients were enrolled. Compared to HBs Ag-negative recipients, HBs Ag-positive status was significantly associated with increased risk of mortality after kidney transplantation(pooled OR = 2.48; 95%CI: 1.61-3.83). Meta-regression showed significant negative correlations between mortality risk after kidney transplantation in HBs Ag-positive recipients and year of study(slopes =-0.062, P = 0.001). HBs Agpositive status was also associated with increased risk of renal allograft failure with pooled OR of 1.46(95%CI: 1.08-1.96). There was also a significant negative correlation between year of study and risk of allograft failure(slopes =-0.018, P = 0.002). These associations existed in overall analysis as well as in limited cohort of hepatitis C virus-negative patients. We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test with P = 0.18 and 0.13 for the risks of mortality and allograft failure after kidney transplantation in HBs Ag-positive recipients, respectively.CONCLUSION Among kidney transplant patients, there are significant associations between HBs Ag-positive status and poor outcomes including mortality and allograft failure. However, there are potential improvements in patient and graft survivals in HBs Ag-positive recipients overtime.     

Nausea and vomiting after ENT surgeries: A comparison between ondansetron, metoclopramide and small dose of propofol

Aims

To evaluate the antiemetic efficacy of ondansetron, metoclopramide or small dose of propofol following ear, nose and throat (ENT) surgery.

Materials and methods

A prospective randomized study involving 60 patients, both children and adults undergoing elective ENT surgery under standard general anesthesia. At the completion of surgery the patients received either 0.1 mg/kg of ondansetron or 0.2 mg/kg of metoclopramide or 0.5 mg/kg of propofol intravenously. The patients were observed for 24 hrs after operation for any occurrence of nausea and vomiting.

Results

The incidence of postoperative nausea and vomiting (PONV) during first 24 hrs was recorded in 20%, 70%, 50% of patients who had received ondansetron, metoclopr-amide or propofol respectively (p < 0.05). Fewer patients given ondansetron needed rescue antiemetic. The incidence of PONV was higher following middle year surgery.

Conclusion

It was concluded that ondansetron was most effective in preventing occurrence of PONV while metoclopramide was least effective. Propofol was effective only in 50% of patients, thus not recommended for routine use.     

Dysphagia,reflux and related sequelae due to altered physiology in scleroderma

Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement, commonly in the esophagus. Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility. However, there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia. The oral phase of swallowing may be disrupted by poor mastication due to microstomia and poor dentition, as well as by xerostomia. In the pharyngeal phase of swallowing, pharyngeal muscle weakness due to concurrent myositis or cricopharyngeal muscle tightening due to acid reflux can cause disturbance. The esophageal phase of swallowing is most commonly disturbed by decreased peristalsis and esophageal dysmotility. However, it can also be affected by obstruction from chronic reflux changes, pill-induced esophagitis, or Candida esophagitis. Other contributing factors to dysphagia include difficulties in food preparation and gastroparesis. Understanding the anatomy and physiology of swallowing and evaluating systemic sclerosis patients presenting with dysphagia for disturbances in each step can allow for development of better treatment plans to improve dysphagia and overall quality of life.