Template synthesis of multifunctional nanotubes for controlled release.

In the past few decades, nanoscale materials have been widely used for controlled release applications. Importantly, many researches have focused on multifunctional nanoparticles for targeted delivery of bioactive and imaging agents as therapeutics and diagnostics. Recent advances in nanotechnology have made possible the design and development of tubular nanoscale particles called nanotubes. The tubular shape of such particles is highly attractive since it is possible to differentially functionalize the inner and outer surfaces to facilitate drug loading, biocompatibility and biorecognition. Novel synthetic strategies allow the fabrication of tubular structures with well-defined diameters and lengths. This can have important implications in biodistribution, subcellular trafficking and drug release. In this article the biomedical applications of nanotubes will be discussed with emphasis on the template synthesis of composite nanotubes containing silica and iron oxide that have potential use in drug delivery, magnetic resonance imaging (MRI), and chemical and biochemical separations.     

Targetable water-soluble polymer-drug conjugates for the treatment of visceral leishmaniasis.

The present work describes the synthesis, characterization, and biological evaluation of targetable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-anti-leishmanial drug conjugates for the treatment of visceral leishmaniasis (VL). Conjugates of HPMA copolymer with NPC1161, an 8-aminoquinoline analog with anti-leishmanial activity, containing N-acetylmannosamine (ManN) in the side chains were synthesized and characterized. In vitro anti-leishmanial efficacy of the conjugates was determined in mouse peritoneal macrophages infected with Leishmania donovani amastigotes. The conjugates were tested against mammalian KB cells for cytotoxicity. The effect of ManN content on uptake was evaluated in RAW 264 murine macrophages. In vivo anti-leishmanial efficacy was evaluated at 1 mg/kg intravenous dose in BALB/c mice. HPMA copolymer-NPC1161 conjugates with 5 mole% or higher ManN content were significantly (p<0.0001) more active (ED50<15 microg/ml) than nontargeted conjugates (ED50>30 microg/ml). All conjugates were relatively nontoxic towards the mammalian cells. Significantly (p<0.003) higher uptake was observed for targeted conjugates compared to nontargeted conjugates. The targeted conjugates were significantly more effective in vivo (67-80% inhibition, p<0.0001) than nontargeted conjugate (47% inhibition). HPMA copolymers containing ManN in the side chains can potentially reduce the toxicity and increase efficacy of anti-leishmanial drugs for the treatment of VL.     

Detection of VEB-1, OXA-10 and PER-1 genotypes in extended-spectrum β-lactamase-producing Pseudomonas aeruginosa strains isolated from burn patients

Resistance of Pseudomonas aeruginosa strains to the broad-spectrum cephalosporins may be mediated by the extended-spectrum β-lactamases (ESBLs). These enzymes are encoded by different genes located on either chromosomes or plasmids. This study aimed to investigate the prevalence of ESBLs and antimicrobial susceptibilities of P. aeruginosa isolated from burn patients in Tehran, Iran. Antimicrobial susceptibility of 170 isolates to cefpodoxime, aztreonam, ciprofloxacin, ofloxacin, ceftazidime, cefepime, imipenem, meropenem, cefotaxime, levofloxacin, piperacillin–tazobactam and ceftriaxone was determined by disc agar diffusion test. Polymerase chain reaction (PCR) amplification of the genes encoding OXA-10, PER-1 and VEB-1 was also performed. All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime and aztreonam. Imipenem and meropenem were the most effective anti-pseudomonal agents. The results revealed that 148 (87.05%) of the isolates were multidrug resistant and 67 (39.41%) of the isolates were ESBL positive. Fifty (74.62%), 33 (49.25%) and 21 (31.34%) strains among 67 ESBL-producing strains amplified bla_OXA-10, bla_PER-1 and bla_VEB-1 respectively.     

Gold nanorod mediated plasmonic photothermal therapy: a tool to enhance macromolecular delivery

Plasmonic photothermal therapy (PPTT) with gold nanostructures has been used to generate significant heat within tumors to ablate vasculature. Here we report the use of gold nanorod (GNR) mediated PPTT to induce moderate hyperthermia as a tool to enhance the delivery of macromolecules. GNRs were injected intravenously in a mouse sarcoma (S-180) tumor model. After 24h Evans blue dye (EBD) was injected and the right tumor was radiated with a laser diode for 10 min. EBD content in the right and left tumors were extracted in formamide, measured spectrophotometrically and expressed as a thermal enhancement ratio (TER). Enhanced delivery of EBD was observed (up to 1.8-fold) when tumor temperatures reached 43°C or 46°C. No statistical difference was observed between tumors at these two temperatures, though significant hemorrhage was observed in tumors and surrounding areas receiving the higher thermal dose (46°C). These results indicate that tumor directed PPTT may be used to induce moderate hyperthermia and therefore selectively increase the delivery of macromolecules with therapeutic anticancer drugs.     

Crush syndrome due to drug-induced compartment syndrome: A rare condition not to be overlooked

Purpose  The crush syndrome caused by drug-induced compartment syndrome (DCS) is a challenge for surgeons because it is regularly associated with potentially fatal complications. Drug-induced compartment syndrome can often be distinguished from other forms of compartment syndrome by the presence of severe rhabdomyolysis with kidney crush and severe postoperative complications such as local and generalized infection, persistent nerve damage, coagulopathy, and multiorgan failure. Methods  In the past 15 years, eight prospectively documented, operatively managed, DCS with subsequent crush syndrome cases were recorded. Results  All of the patients required renal replacement therapy. The creatine kinase (CK) values in the context of rhabdomyolysis reached an average of 86 (range 47–144) kU/l. The renal function recovered in all surviving patients. The analysis showed that the diagnosis of a DCS is usually made after an average of 13 h. It then took an average of an additional 7 h before a fasciotomy was performed. Six operational revisions were necessary. In three out of eight patients the extremities had to be amputated. Conclusions  In DCS the decision to open the compartment should be made immediately upon the clinical diagnosis. A protracted intensive phase is expected. The benefit to patients is closely associated with surgical wound debridement along with rigorous intensive therapy. M. Golling and H. Fonouni contributed equally to this work.     

Transplantation of a severely lacerated liver – a case report with review of the literature

Abstract:  Using lacerated livers for liver transplantation (LTx) can add an option to the extended donor criteria. We present an LTx case using a severely lacerated liver and review of the literature for reported cases. We used a high-grade lacerated liver from a 19-yr-old brain-dead patient caused by traffic accident. The liver had grade IV and II lacerations in the right and left lobe, respectively. Lacerations were managed by sealants, stitching and perihepatic packing. The liver was transplanted to a 49-yr-old man suffering from hepatocellular carcinoma on hepatitis C-induced liver cirrhosis. The two-yr follow-up was uneventful. All published LTx cases using traumatized livers (n = 18) were analyzed. The liver injury ranged from subcapsular hematoma to deep ruptures. Most reported lacerations were in the right lobe, which were managed by digital compression, suturing, electrocautery, and perihepatic packing. The reported complications were primary non- (18%), or poor function, liver abscess, bilioma, and subhepatic hematoma each in one case (5.5%). Six-month graft and patient survival were 71% and 88%, respectively. With meticulous management lacerated livers can be transplanted successfully. Because of complexity of the management, procurement and transplantation should be done by experienced liver surgeons. These organs are marginal grafts and should be offered to selected patients.     

Estrogen pretreatment modulates morphine-induced conditioned place preference in ovariectomized mice

Estrogen is known to modulate the neurotransmission in the brain. The main aim of this study was to investigate the effects of estrogen on the rewarding properties of morphine using conditioned place preference (CPP) paradigm in adult female mice. The possible rewarding effect of estrogen was also examined in ovariectomized mice. Following a 6-day conditioning procedure, sham operated animals showed a significant preference towards the side previously paired with a range of morphine doses (2, 5 and 10—but not 20—mg/kg, SC). However, ovariectomized mice showed decreased CPP compared to gonadally intact mice with a right shift in their morphine dose-response curve. These effects were reversed by chronic daily administration of estradiol benzoate (EB; 20 µg/kg, SC). Furthermore, in ovariectomized mice, EB per se was able to induce CPP. In conclusion, our findings indicate that estradiol has a facilitating effect on morphine reward while its deficiency increases the threshold dose of morphine to induce CPP.