Can postoperative renal dysfunction be predicted by measuring intraoperative glomerular filtration rate in patients undergoing coronary artery bypass grafting without cardiopulmonary bypass? A pilot study

Objective

Currently, there is no effective paradigm to identify patients who are at risk for renal dysfunction following cardiac surgery. The specific mechanisms of renal injury during surgery are incompletely understood. The aim of the study was to evaluate whether postoperative renal dysfunction can be predicted from intraoperative glomerular filtration rate (GFR).

Design

This is a prospective study.

Setting

The study was conducted in a tertiary care multi-specialty hospital.

Participants and interventions

GFR was measured in 24 patients (mean age 56.6 ± 11.09 years, 20 male) undergoing elective off-pump coronary artery bypass grafting during preoperative period, intraoperative period, 24 h after surgery (ICU GFR), and on the fifth postoperative day (final GFR ).

Measurements and main results

Patients were divided into two groups depending upon changes in intraoperative GFR. Group 1 (n = 10): who had a rise in intraoperative GFR in comparison with preoperative baseline measurement. All these 10 (41.7 %) patients with a rise in intraoperative GFR had an uneventful hospital course and achieved an improvement in final GFR. Group 2 (n = 14): 14 (58.3 %) patients had a fall in intraoperative GFR (mean 36.4 %) in comparison with preoperative baseline value. Of these 14 patients, 1 patient required dialysis support and 3 patients required ionotropic support. Among these 14 patients in group two, 7 had deterioration in final GFR (mean 28.7 %), when compared to preoperative baseline value.

Conclusion

Postoperative renal dysfunction can be predicted from intraoperative GFR. Patients who have a rise in intraoperative GFR do not develop postoperative renal dysfunction, and only patients with intraoperative fall in GFR are at risk of postoperative renal dysfunction.

     

CT‐guided aspiration cytology of advanced silicosis and confirmation of the deposited zeolite nano particles through X ray diffraction: A novel approach

Silicosis is a common occupational lung disease, resulting in fibrotic nodular lesions in the upper lobes of the lung parenchyma. Most of the pneumoconioses are diagnosed on the basis of relevant history and clinico‐radiological correlation. Image‐guided aspiration cytology appears to be poorly yielding and is not usually considered as a diagnostic modality. However, silicosis may sometimes offer a diagnostic challenge because of its radiological resemblance and clinical overlap with pulmonary tuberculosis and neoplastic lesions. We present a unique situation where image‐guided fine needle aspiration cytology (FNAC) has been advised on the basis of nodular upper lobe opacities. The cytology smears revealed hypocellular granular material, while phase contrast and polarized light microscopy highlighted crystalline particles. History of silica dust exposure long back was available after the cytological evaluation, suggesting the diagnosis of pulmonary silicosis. X ray diffraction (XRD) crystallography was also possible on cytology smears, confirming zeolite nano particles of size as small as 40 ? 50 nm as the concerned agent for the first time. Cytological evaluation by phase contrast and polarized light microscopy may be useful for the confirmation of silicosis, supplemented by clinical history and radiological evaluation. XRD on smears may help in determination of chemical nature and particle size. Diagn. Cytopathol. 2016;44:246–249. © 2015 Wiley Periodicals, Inc.     

Leishmania donovani-induced ceramide as the key mediator of Akt dephosphorylation in murine macrophages: role of protein kinase Czeta and phosphatase

Leishmania donovani is an intracellular protozoan parasite that impairs the host macrophage immune response to render it suitable for its survival and establishment. L. donovani-induced immunosuppression and alteration of host cell signaling is mediated by ceramide, a pleiotropic second messenger playing an important role in regulation of several kinases, including mitogen-activated protein kinase and phosphatases. We observed that the endogenous ceramide generated during leishmanial infection led to the dephosphorylation of protein kinase B (PKB) (Akt) in infected cells. The study of ceramide-mediated Akt phosphorylation revealed that Akt was dephosphorylated at both Thr308 and Ser473 sites in infected cells. Further investigation demonstrated that ceramide was also responsible for the induction of PKCzeta, an atypical Ca-independent stress kinase, as well as the ceramide-activated protein phosphatases (e.g., protein phosphatase 2A [PP2A]). We found that Akt dephosphorylation was mediated by ceramide-induced PKCzeta-Akt association and PP2A activation. In addition, treatment of L. donovani-infected macrophages with PKCzeta-specific inhibitor peptide could restore the translocation of phosphorylated Akt to the cell membrane. This study also revealed that ceramide is involved in the inhibition of proinflammatory cytokine tumor necrosis factor alpha release by infected macrophages. These observations strongly suggest the importance of ceramide in the alteration of normal cellular functions, impairment of the kinase/phosphatase balance, and thereby establishment of leishmaniasis in the hostile macrophage environment.     

Involvement of caspase-3, lipid peroxidation and TNF-alpha in causing apoptosis of macrophages by coordinately expressed Salmonella phenotype under stress conditions

Invasive Salmonella has been reported to induce apoptosis of macrophages as a part of its infection process, which may allow it to avoid detection by the innate immune system. However, the bacterial components capable of inducing apoptosis, particularly under the environments offered by the host have not been fully identified. Therefore, in the present study, attempts were made to evaluate the apoptotic potential of Salmonella enterica serovar Typhi (S. typhi) outer membrane protein expressed under stress conditions like iron, oxidative and anaerobic simulating the in vivo situations encountered by the pathogen. Analysis of data revealed that a coordinately expressed 69kDa outer membrane protein (OMP) expressed with enhanced intensity under iron, oxidative and anaerobic stress conditions caused apoptotic cell death in 51% of macrophages, whereas OMPs of S. typhi extracted under normal conditions accounted for apoptotic cell death in only 31% of macrophages. A significantly enhanced activity of caspase-3 was observed during macrophage-apoptosis induced by this protein. A significant increase in the extent of lipid peroxidation (levels of oxidant) and decrease in the activities of antioxidants was also observed which correlated with the increased generation of tumor necrosis factor-alpha, interleukine-1alpha and interleukine-6. These results suggest that caspase-3 and tumor necrosis factor-alpha in conjunction with other cytokines may induce apoptotic cell death through the up-regulation of oxidants and down-regulation of antioxidants. These findings may be relevant for the better understanding of the disease pathophysiology and for the future developments of diagnostic and preventive strategies during the host-pathogen interactions.     

Induction of apoptosis by crambene protects mice against acute pancreatitis via anti-inflammatory pathways

Apoptosis is a teleologically beneficial form of cell death in acute pancreatitis. Our previous work has demonstrated that induction of pancreatic acinar cell apoptosis by crambene protects mice against acute pancreatitis. However, little is known about how the induction of apoptosis reduces the severity of acute pancreatitis. Because the clearance of apoptotic cells might suppress inflammation and critically regulate immune responses, we postulate that clearance of apoptotic cells stimulates an anti-inflammatory response, which has a protective action against acute pancreatitis. To test this hypothesis, induction of apoptosis in acute pancreatitis in vivo and co-cultures of peritoneal resident macrophages with apoptotic acinar cells in vitro were used as experimental systems, testing expression of phagocytic receptors and levels of inflammatory mediators. Moreover, neutralizing anti-interleukin (IL)-10 monoclonal antibody (2.5 mg/kg) was used before the induction of apoptosis in acute pancreatitis, testing whether the protection from apoptosis induction would be removed. Our study showed that clearance of apoptotic acinar cells, which may occur essentially through the CD36-positive macrophage, stimulates the release of anti-inflammatory mediators like IL-10. IL-10 plays an important role in crambene-induced protection in acute pancreatitis. Thus, induction of pancreatic acinar cell apoptosis by crambene protects mice against acute pancreatitis via induction of anti-inflammatory pathways.     

Formulation Development,Optimization, and In Vitro–In Vivo Characterization of Natamycin-Loaded PEGylated Nano-Lipid Carriers for Ocular Applications

The present study aimed at formulating and optimizing natamycin (NT)-loaded polyethylene glycosylated nano-lipid carriers (NT-PEG-NLCs) using Box-Behnken design and investigating their potential in ocular applications. Response surface methodology computations and plots for optimization were performed using Design-Expert^® software to obtain optimum values for response variables based on the criteria of desirability. Optimized NT-PEG-NLCs had predicted values for the dependent variables which are not significantly different from the experimental values. NT-PEG-NLCs were characterized for their physicochemical parameters; NT's rate of permeation and flux across rabbit cornea was evaluated, in vitro, and ocular tissue distribution was assessed in rabbits, in vivo. NT-PEG-NLCs were found to have optimum particle size (<300 nm), narrow polydispersity index, and high NT entrapment and NT content. In vitro transcorneal permeability and flux of NT from NT-PEG-NLCs was significantly higher than that of Natacyn^®. NT-PEG-NLC (0.3%) showed improved delivery of NT across the intact cornea and provided concentrations statistically similar to the marketed suspension (5%) in inner ocular tissues, in vivo, indicating that it could be a potential alternative to the conventional suspension during the course of fungal keratitis therapy.     

Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes

The tripeptide sequence asparagine‐glycine‐arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC‐c(NGR) and HYNIC‐PEG₂‐c(NGR), were synthesized, radiolabeled with ^99mTc, and evaluated in CD13‐positive human fibrosarcoma HT‐1080 tumor xenografts. The radiotracers, ^99mTc‐HYNIC‐c(NGR) and ^99mTc‐HYNIC‐PEG₂‐c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being ?2.33 ± 0.05 and ?2.61 ± 0.08. The uptake of 2 radiotracers ^99mTc‐HYNIC‐c(NGR) and ^99mTc‐HYNIC‐PEG₂‐c(NGR) was similar in nude mice bearing human fibrosarcoma HT‐1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of ^99mTc‐labeled HYNIC peptide could not be modulated through introduction of PEG₂ unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention.     

Using a microcantilever array for detecting phase transitions and stability of DNA

The authors report the extension of the microcantilever platform to study the thermal phase transition of biomolecules as they are heated. Microcantilever-based sensors directly translate changes in Gibbs free energy due to macromolecular interactions into mechanical responses. The authors observed surface stress changes in response to thermal dehybridization of double-stranded DNA oligonucleotides that are attached onto one side of a microcantilever. Once the cantilever is heated, the DNA undergoes a transition as the complementary strand melts, which results in changes in the cantilever deflection. This deflection is due to changes in the electrostatic, ionic, and hydration interaction forces between the remaining immobilized DNA strands. This new technique has allowed the authors to probe DNA melting dynamics and leads to a better understanding of the stability of DNA complexes on surfaces.     

Synthesis of water soluble copper(II) complexes: crystal structures,DNA binding,oxidative DNA cleavage,and in vitro anticancer studies

Two ternary copper(II) complexes of dl-threonine and polypyridyl ligands with formula of [Cu(Thr)(Byp)Cl]·H₂O (1) and [Cu(Thr)(Phen)H₂O]Cl·2H₂O (2) were synthesized. The complexes were characterized by spectral (NMR, FT-IR, and UV–Vis), CHN elemental analysis and have been structurally elucidated by X-ray crystallography. Both of the complexes formed slightly distorted square-pyramidal coordination geometry. The electronic absorption spectra of the complexes showed a very low intensity d–d electronic band in the range of 610–620 nm in Tris–HCl/NaCl (5:5 mM) pH 7.2 buffer solution. The DNA binding interaction with calf-thymus DNA (CT-DNA) was investigated by electronic absorption spectral titration and viscosity measurements. The results revealed that the phenanthroline complex (2) interact with CT-DNA through intercalation while bipyridyl complex (1) through the groove binding mode. The calculated intrinsic binding constant (K _b) of (1) and (2) were 0.5 and 4.4 × 10⁵ M^?1, respectively. Both the complexes were found to promote efficient DNA cleavage activities at low concentration in the presence of H₂O₂. The results showed that (2) has the highest DNA binding and nuclease activity. Furthermore, both the complexes were tested against human colon cancer (HCT 116) and breast cancer (MCF-7) cell lines and showed a dose-dependent antiproliferation effect.