Interaction between cytokines and ammonia in the mitochondrial permeability transition in cultured astrocytes

Hepatic encephalopathy (HE) is the major neurological complication occurring in patients with acute and chronic liver failure. Elevated levels of blood and brain ammonia are characteristic of HE, and astrocytes are the primary target of ammonia toxicity. In addition to ammonia, recent studies suggest that inflammation and associated cytokines (CKs) also contribute to the pathogenesis of HE. It was previously established that ammonia induces the mitochondrial permeability transition (mPT) in cultured astrocytes. As CKs have been shown to cause mitochondrial dysfunction in other conditions, we examined whether CKs induce the mPT in cultured astrocytes. Cultures treated with tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon-γ, individually or in a mixture, resulted in the induction of the mPT in a time-dependent manner. Simultaneous treatment of cultures with a mixture of CKs and ammonia showed a marked additive effect on the mPT. As oxidative stress (OS) is known to induce the mPT, so we examined the effect of CKs and ammonia on hemeoxygenase-1 (HO-1) protein expression, a marker of OS. Such treatment displayed a synergistic effect in the upregulation of HO-1. Antioxidants significantly blocked the additive effects on the mPT by CKs and ammonia, suggesting that OS represents a major mechanism in the induction of the mPT. Treatment of cultures with minocycline, an antiinflammatory agent, which is known to inhibit OS, also diminished the additive effects on the mPT caused by CKs and ammonia. Induction of the mPT in astrocytes appears to represent a major pathogenetic factor in HE, in which CKs and ammonia are critically involved.     

National Practice Patterns in Preoperative and Postoperative Antibiotic Prophylaxis in Breast Procedures Requiring Drains: Survey of the American Society of Breast Surgeons

Background

To assess national practice patterns regarding use of perioperative antibiotics by surgeons performing breast operations requiring drainage tubes.

Methods

The members of the American Society of Breast Surgeons (ASBrS) were surveyed regarding use of perioperative antibiotics for breast operations requiring drains, with or without immediate tissue expander or implant reconstruction.

Results

Of 2,857 ASBrS members contacted, 917 (32?%) responded; all self-identified as surgeons. Of 905 evaluable respondents, most described themselves as general surgeons (46?%) or breast surgeons (46?%). For cases in which drains are anticipated, most respondents (86?%) reported routine use of preoperative prophylactic antibiotics, with 99?% selecting cephalosporins. Use of antibiotic >24?h postoperatively varied by whether or not reconstruction was performed. In nonreconstruction cases, the majority (76?%) reported ??never/almost never?? prescribing antibiotics beyond the 24-h postoperative period, but 16?% reported ??always/almost always.?? In reconstruction cases, the majority (58?%) reported routine antibiotic use beyond 24?h, and the primary driver of the decision to use antibiotics was reported to be the plastic surgeon (83?%). Among those reporting use at >24?h, the duration recommended for nonreconstruction cases was ??up to 1?week?? in 38?% and ??until drains removed?? in 39?%; this was similar for reconstruction cases.

Conclusions

Cephalosporins are utilized uniformly as preoperative antibiotic prophylaxis in breast operations requiring drains. However, use of postoperative antibiotic prophylaxis is strongly dependent on the presence of immediate breast reconstruction. Consensus is lacking on the role of postoperative antibiotic prophylaxis in breast operations utilizing drains.     

Advancing the strategic use of HIV operations research to strengthen local policies and programmes: the Research to Prevention Project

In the field of HIV prevention, there is renewed interest in operations research (OR) within an implementation science framework. The ultimate goal of such studies is to generate new knowledge that can inform local programmes and policies, thus improving access, quality, efficiency and effectiveness. Using four case studies from the USAID-funded Research to Prevention (R2P) project, we highlight the strategic use of OR and the impact it can have on shaping the focus and content of HIV prevention programming across geographic and epidemic settings and populations. These case studies, which include experiences from several sub-Saharan African countries and the Caribbean, emphasize four unique ways that R2P projects utilized OR to stimulate change in a given context, including: (1) translating findings from clinical trials to real-world settings; (2) adapting promising structural interventions to a new context; (3) tailoring effective interventions to underserved populations; and (4) prioritizing key populations within a national response to HIV. Carefully crafted OR can bridge the common gap that exists between research-generated knowledge and field-based practice, lead to substantial, real-world changes in national policies and programmes, and strengthen local organizations and the use of data to be more responsive to a given topic or population, ultimately supporting a locally tailored HIV response.     

One pot synthesis of some novel coumarins containing 5-(substituted-2-hydroxybenzoyl) pyridine as a new class of antimicrobial and antituberculosis agents

A novel class of substituted pyridyl coumarin derivatives has been synthesized starting from 3-acetyl coumarin and chromone-3-carbaldehyde via one pot reaction and fully characterized by spectral and elemental analysis. All these derivatives 3a–l were screened in vitro for antimicrobial activity against a representative panel of pathogenic strains. Compounds demonstrated good to excellent antibacterial activity, while some compounds exhibited equipotent antifungal activity as compared to that of first line standard drug. As a part of investigation of new antitubercular agents, in vitro screening of synthesized compounds against Mycobacterium tuberculosis H₃₇Rv has been done. Among the designed molecules, three compounds showed relatively better activity. From the entire study, it has been revealed that compounds appear to be better antimicrobials but relatively poor antituberculars.     

Rheolytic thrombectomy in patient with massive pulmonary embolism: a case report and review of literature.

OBJECTIVE: Despite advances in management with thrombolytic therapy or open embolectomy, the mortality rate remains high in patients with massive pulmonary embolism (MPE). BACKGROUND: We present a case of 51-year-female patient who collapsed while jogging and was brought to the Emergency Department. Upon arrival, she was found to have marked hypotension and hypoxia. EKG showed marked ST T abnormalities suggestive of anterior and lateral ischemia. Blood was drawn for labs. Patient received aspirin, heparin, and was transferred to cardiac catheterization laboratory. METHODS: Coronary angiogram revealed normal epicardial coronaries. A pigtail catheter was inserted through right femoral vein and pulmonary angiogram was performed. It revealed bilateral MPE. Tissue plasminogen activator was initiated as per standard protocol. A 7-French aspiration catheter (Export, Medtronic Vascular, Santa Rosa, CA) was used without any success. Rheolytic thrombectomy (RT) (AngioJet, Possis, Minneapolis, MN) was performed successfully with adjunctive local and systemic thrombolytic therapy. Immediate pulmonary angiogram showed increased perfusion through right pulmonary artery. Her hemodynamic status improved significantly. Patient was discharged home after 8 days of hospitalization. Patient remains on lifelong anticoagulation therapy and she continues to remain stable at 20 months follow up. CONCLUSIONS: RT with adjunctive localized and systematic thrombolytic therapy was performed successfully in this patient with MPE and significant hemodynamic compromise. In our patient who was very unstable from cardio-respiratory perspective with maximized hemodynamic support, RT device use was life saving. RT has an advantage of not dispersing emboli particles to the distal pulmonary circulation.