Evaluation of intracoronary blood from obstructive vessel in patients of ST-elevation myocardial infarction undergoing PPCI

ObjectiveInformation available on acid–base imbalance in ST-elevation myocardial infarction (STEMI) submitted to primary percutaneous intervention is limited and no data were present on intracoronary blood analysis, extracted from obstructed artery.MethodsThis was a prospective study conducted over 12 months in which STEMI patients presenting in emergency and undergoing primary percutaneous coronary intervention were included. Blood gas analysis of intracoronary arterial blood from obstructed vessel and peripheral arterial blood was performed. Patients in whom adequate intracoronary sample could not be obtained were excluded. Intracoronary and peripheral arterial blood gas measurements were correlated and relationship of intracoronary parameters were compared with clinical parameters, investigational markers and short-term outcome.ResultsThe mean age of study population was 54.8 years and average symptom onset to door time was 162 min. On comparing intracoronary blood with peripheral blood arterial obtained, pH (95% confidence interval [CI] ?0.01 to 0.02;p = 0.44), lactate (95% CI 0.03–0.1;p = 0.28), bicarbonate (95% CI 0.6–1.5;p = 0.64), pCO₂ (95% CI 1.1–2.4;p = 0.79) and pO₂ (95% CI 3.2–47.5; p = 0.06) were all found to be statistically insignificant. Intracoronary hyperlactatemia was present in patients presenting with higher symptom onset to door time (p = 0.025). Systolic blood pressure (SBP) (p = 0.03) was also significantly lower in patients who had high intracoronary lactate levels.ConclusionThe evaluation of intracoronary blood provides no additional information regarding the prognosis and short-term (30-day) outcome of the patients when compared with peripheral blood. However, there was a significant intracoronary hyperlactatemia in patients presenting late after symptom onset. SBP was also significantly less in patients with high intracoronary lactate, which signifies that predominant cause of hyperlactatemia was systemic hypoperfusion rather than local increase in lactate levels.     

Age-related learning and memory deficits in rats: role of altered brain neurotransmitters,acetylcholinesterase activity and changes in antioxidant defense system

Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino–Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.     

Albumin mediates the transcytosis of myeloperoxidase by means of caveolae in endothelial cells

Myeloperoxidase (MPO), the phagocyte hemoprotein involved in neutrophil host defense and consuming nitric oxide (*NO), induces the nitration of extracellular matrix proteins and tissue remodeling subsequent to its transcytosis across the endothelial barrier. We addressed the role of an interaction of MPO with albumin as a requirement for MPO transport across the endothelium. Matrix-assisted laser desorption/ionization MS analysis of 80- and 60-kDa proteins purified from human lung tissue [with a human serum albumin (HSA)-affinity column] identified these albumin-binding proteins as MPO and MPO-heavy chain. A peptide corresponding to the MPO-heavy chain residues 425-454 demonstrated high-affinity binding to HSA. Replacement of the positively charged residues, R and K with G, prevented the binding of HSA to the peptide. We observed that albumin increased the binding of (125)I-MPO to lung microvascular endothelial cells by 2-fold and the rate of transendothelial flux of (125)I-MPO in cultured monolayers and intact vessels. Disruption of caveolae with cyclodextrin prevented the albumin-induced increase in transendothelial flux of (125)I-MPO. We also observed by confocal imaging that albumin induced the rapid internalization of MPO and its colocalization with albumin-labeled vesicles. MPO colocalized with the caveolae markers cholera toxin subunit B and caveolin 1 in the endocytosed vesicles. Thus, transcytosis of MPO by caveolae induced by its charge-dependent interaction with albumin is an important means of delivering MPO to the subendothelial space. Albumin-mediated transport of MPO may thereby regulate NO bioavailability and formation of NO-derived oxidants in the vessel wall.     

The role of risk stratification in the decision to provide upstream versus selective glycoprotein IIb/IIIa inhibitors for acute coronary syndromes: a cost-effectiveness analysis.

OBJECTIVES: We endeavored to determine under what conditions a strategy of upstream use of small molecule platelet glycoprotein (GP) IIb/IIIa inhibitors for all acute coronary syndromes (ACS) patients is cost effective compared to that of selective use of abciximab in only those patients requiring percutaneous coronary intervention (PCI). BACKGROUND: Small molecule GP IIb/IIIa inhibitors have shown benefit in ACS, but abciximab, the more expensive GP IIb/IIIa inhibitor, may be more effective during PCI. However, abciximab does not have proven efficacy in medical management. No prior study has attempted to balance these competing benefits. METHODS: A decision analysis was performed to examine two strategies: 1) treat all ACS patients upstream with a small molecule GP IIb/IIIa inhibitor and continue through medical management and PCI, if performed; or 2) wait, and selectively use abciximab only in patients who ultimately undergo PCI. Applicable randomized controlled trial data were used for the principal analysis. RESULTS: The strategy of upstream use of a small molecule GP IIb/IIIa inhibitor was superior to selective use, and economically acceptable, with a cost-effectiveness ratio of 18,000 dollars per year of life gained. The superiority of the upstream use strategy persisted over the majority of sensitivity analyses. When stratified by risk according to Thrombolysis in Myocardial Infarction risk score, a strategy of upstream use was only cost effective in those patients with moderate or high risk. CONCLUSIONS: Upstream use of small molecule GP IIb/IIIa inhibition in ACS patients with moderate or high risk for cardiovascular events is a cost-effective approach that should be considered in this subset of patients.     

Direct N-heterocyclization of hydrazines to access styrylated pyrazoles: synthesis of 1,3,5-trisubstituted pyrazoles and dihydropyrazoles

A microwave-assisted method has been developed for the synthesis of tri-substituted pyrazoles via direct N-heterocyclization of hydrazines with metal-acetylacetonate and -dibenzylideneacetonate without using any base or additives. Most importantly, the synthesis of 1-aryl-5-phenyl-3-styryl-1H-pyrazoles was achieved in a single step using hydrochloride salt of various phenylhydrazines and this is the first report for direct construction of these molecules. The reaction medium and microwave conditions play a critical role for their selective product formation during the reaction. The present reaction explored the usage of metal-diketonic complexes as reaction substrates providing acetylacetone and dibenzylideneacetone moieties to directly participate in cyclization with hydrazines to form the corresponding pyrazoles in excellent yields. The present protocol introduces the important N-heterocyclic moieties in the final structures, giving the reaction great applications from a medicinal chemistry perspective, particularly in the late stage modification strategies in drug discovery.

The synthesis of tri-substituted pyrazoles was achieved via direct N-heterocyclization of hydrazines with metal-acetylacetonate and -dibenzylideneacetonate without using any base or additives under microwave irradiation in a single step.     

Bioactive Compounds from Carissa spinarum

In our continuing efforts to find new antiherpetic agents from plants, an extract prepared from the stems of Carissa spinarum L. was found to possess appreciable activity against herpes simplex viruses (HSV I and II). A chemical study of this plant was then initiated, and this led to the isolation of 12 compounds, including a coumarin, two cardiac glycosides and nine lignans. These isolated compounds were evaluated for several biological activities, including antiherpetic, cytotoxic, antioxidant and antibacterial effects. The cardiac glycoside evomonoside was found to be the only antiherpetic principle, showing moderate activity against herpes simplex virus types I and II in the inactivation method. The lignans (?)‐carinol, (?)‐carissanol and (?)‐nortrachelogenin exhibited cytotoxicity against breast (MCF7) and lung (A549) cancer cells. Moderate anti‐DPPH free radical activity was observed for all the lignans. None of the isolates showed antibacterial activity. Copyright © 2012 John Wiley & Sons, Ltd.     

Robot-assisted resection of choledochal cysts and hepaticojejunostomy in children less than 10 kg

Background/Purpose

Laparoscopic resection of choledochal cysts and hepaticojejunostomy have been described in children since 1995, but these can be technically demanding procedures. Robotic surgical systems can facilitate complex minimal-access procedures. In 2009, we made the transition from conventional laparoscopic to robotic-assisted choledochal cyst excision with hepaticojejunostomy. We present our experience in children weighing less than 10 kg.

Methods

During 2009, 5 children weighing less than 10 kg underwent robotic resections of choledochal cysts and hepaticojejunostomy using the da Vinci surgical system. The Roux loop was fashioned extracorporeally. Mean age was 1 year (range, 0.5-1.4), and mean weight was 8.5 kg (range, 7.6-9.5). All 5 had type 1c cysts, and 3 were very large.

Results

All 5 cases were treated successfully by robotic resection of the cyst and hepaticojejunostomy. Feeding was established by a median of 4 days (range, 3-6), and patients were discharged after a median of 6 days (range, 5-7) with no postoperative complications.

Conclusion

The technique is safe and effective in children weighing less than 10 kg. The authors found ergonomic advantages in using robotic-assisted surgery for this complex minimal-access procedure.     

Brain metastases from breast cancer: management approach

Brain metastases are a significant cause of morbidity and mortality in patients with breast cancer. HER-2 positivity is an increasingly recognized risk factor for the development of brain metastases. Although considerable progress has been made in the treatment of this complication, supportive measures like steroids, anti-seizure medication and whole-brain radiation remain the cornerstones of management in the majority of patients. The current review discusses the above and other issues like surgical excision, stereotactic radiotherapy, adjuvant radiation, radiosensitization and chemotherapy. A brief discussion of the recent evidence for the use of 'HER-1/ HER-2'-targeted therapy is also present.