Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus

Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans. We present the molecular basis for resistance transmission by the nicking enzyme in S. aureus (NES), which is essential for conjugative transfer. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin, gentamicin, and mupirocin. The NES N-terminal relaxase–DNA complex crystal structure reveals unique protein–DNA contacts essential in vitro and for conjugation in S. aureus. Using this structural information, we designed a DNA minor groove-targeted polyamide that inhibits NES with low micromolar efficacy. The crystal structure of the 341-residue C-terminal region outlines a unique architecture; in vitro and cell-based studies further establish that it is essential for conjugation and regulates the activity of the N-terminal relaxase. This conclusion is supported by a small-angle X-ray scattering structure of a full-length, 665-residue NES–DNA complex. Together, these data reveal the structural basis for antibiotic multiresistance acquisition by S. aureus and suggest novel strategies for therapeutic intervention.     

Coffee: good, bad, or just fun? A critical review of coffee's effects on liver enzymes

Coffee consumption is a regular part of daily life throughout the world. Research into the effects of coffee on human health is ongoing, but a recent study suggests that coffee and caffeine consumption can reduce the risk of elevated alanine aminotransferase activity in individuals at high risk for liver disease. This review will analyze the results of that study in light of the current literature.     

Surgical management of carotid body tumours: a 24-year surgical experience

BACKGROUND: Carotid body tumours (CBT) are rare tumours, best treated by complete surgical resection. However, there is no uniform agreement on the method of resection. The aim of this study was to review our 24 years' experience of meticulous subadventitial excision of CBT. METHODS: A retrospective study, from March 1980 to September 2004 of patients with CBT was undertaken, detailing presentation, diagnosis and treatment and postoperative complications. RESULTS: Twenty-five patients (six men and 19 women) with an age range of 23-72 years had been operated on, and all were treated by surgical excision. All patients had neck mass. No patient had a positive family history. Angiography was the main method of diagnosis. All of the patients had unilateral tumours. There was no postoperative permanent neurological deficit. Temporary neurological problems developed in only four patients. External carotid artery was ligated in three patients to facilitate excision of the tumour. Surgical care limited blood loss to an average of 480 mL. CONCLUSIONS: Subadventitial excision, carried out meticulously, allowed complete resection to be achieved in all of the patients with minimal morbidity and no surgical mortalities. This method is therefore recommended. Facilities for shunting and arterial repair should always be available.     

Surgical fixation of pathologic fractures: an evaluation of evolving treatment methods

The surgical techniques for the fixation of pathologic fractures continue to evolve. The present study examines clinical outcomes and complications associated with the use of newer generation interlocked intramedullary nails compared with open reduction and internal fixation with plates and screws for pathologic fractures in long bones. Fifty operative procedures performed on 37 patients by five community orthopaedic surgeons were retrospectively reviewed. The operative procedures were separated into two groups based upon the method of fracture fixation; the groups were compared for differences in hardware or fixation failure. The use of intramedullary devices was associated with a significantly lower number of hardware or fixation failures (p < 0.02). This data, in addition to several additional advantages of indirect reduction and intramedullary fixation of pathologic fractures, supports this method of fracture care over open reduction and internal fixation in appropriate cases.     

Anticonvulsant activity of Heracleum persicum seed

The anticonvulsant activity of acetone extract of the seeds of Heracleum persicum (Umbelliferae) was examined against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures in mice. The extract showed a dose-dependent protective effect in both seizure models. However, the sedative dose of the extract, examined by rotarod test, was close to the anticonvulsant doses. Preliminary phytochemical analysis showed the presence of alkaloids, terpenoids, triterpenes and steroids in the extract. The observed pharmacological effects could be due to alkaloids, terpenoids and triterpenes present in the plant.     

Modified retro-tubercle opening-wedge versus conventional high tibial osteotomy

Despite the fact that common surgical techniques for the treatment of genu varum usually correct the malalignment in the affected knee, these methods have significant complications and cause problems in the long term. Retro-tubercle opening-wedge high tibial osteotomy is among the newer techniques for the treatment of genu varum. The goal of this study was to compare the results of retro-tubercle opening-wedge high tibial osteotomy with those of medial opening-wedge osteotomy. In a randomized, controlled trial, 72 patients with varus knees who were scheduled for surgery were assigned into either the retro-tubercle opening-wedge high tibial osteotomy (n=34) or medial opening-wedge osteotomy groups (n=38). Groups were matched for age and sex. The position of the patella was compared with respect to the tuberosity and the upper tibial slope pre- and postoperatively. Patients were followed for an average of 13 months (range, 10-21 months). In the retro-tubercle opening-wedge high tibial osteotomy group, the length of the patellar tendon did not significantly differ pre- and postoperatively (P≥.5); however, in the medial opening-wedge osteotomy group, a statistically significant shortening was noted in patellar tendon postoperatively (P≤.05). Similarly, the tibial plateau inclination showed a statistically significant difference postoperatively in the medial opening-wedge osteotomy group, while the difference in the retro-tubercle opening-wedge high tibial osteotomy group did not reach statistical significance.     

Antimicrobial and cytotoxic constituents from leaves of Sapium baccatum

Six compounds, namely, Lupeol (1), Betulin (2), β-Taraxerol (3), Taraxerone (4), Stigmasterol (5) and β-Sitosterol (6) were isolated from the petroleum ether extract of the leaves of Sapium baccatum based on spectroscopic evidence. Lupeol (1), Betulin (2) and Stigmasterol (5) were isolated for the first time from this plant. The cytotoxic potential of the different solvent extracts (methanol, petroleum ether, carbon-tetrachloride and dichloromethane); six column fractions (F-4, F-7, F-10, F-12, F-18 and F-22) of petroleum ether extract and three pure compounds 1, 4 and 6 were determined by using brine shrimp lethality bioassay. The LC₅₀ of all the tested samples were showed to be lethal to brine shrimp nauplii. However, petroleum ether, carbon-tetrachloride extract, column fractions F-4 and F-18 of petroleum ether extract and pure compound 6 showed quite potent activity in brine shrimp lethality bioassay with LC₅₀ 1.33, 1.35, 1.40, 1.58 and 1.58 μg/ml, respectively. These result suggested that they might be contain antitumor or pesticidal activity. Further, the methanol extract and four column fractions (F-7, F-12, F-18 and F-22) of petroleum ether showed significant activity against the tested microorganisms.     

Interaction of adenosine and naloxone on regional cerebral blood flow in morphine-dependent rats

The present research aimed at investigating the opioid-adenosine interaction on regional cerebral blood flow (rCBF). Therefore rCBF in the sensory cortex of morphine-naive and -dependent rats was measured using the laser-Doppler flowmetry technique. The results showed that adenosine (10(-5), 10(-4), 10(-3) M) significantly increased rCBF in morphine-dependent rats (MDR) (P < 0.01). This effect was inhibited by theophylline (5 x 10(-5) M). Also systemic naloxone (0.5, 1.5 and 3 mg/kg, s.c.) significantly increased rCBF in MDR and it was accompanied by elevated blood pressure and heart rate. Local adenosine (10(-4) M) significantly augmented naloxone (0.5 mg/kg)-induced increase in rCBF of MDR but had no significant effect on naloxone's (1.5 and 3 mg/kg) increasing effect on rCBF. Theophylline also has no effect on naloxone increasing effect on rCBF. These data suggest that adenosine receptors responsiveness increase in sensory cortex of MDR. Naloxone also highly increased rCBF of MDR that probably not interfere with adenosine receptors. Also, it seems that adenosine acts as a modulator in rCBF regulation of morphine-dependent and morphine withdrawal rats.