Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from Entamoeba histolytica and Giardia lamblia Identifies Inhibitors of Their Trophozoite Growth Phase

Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure-based virtual screening of FDA-approved drugs was performed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL).     

Aciduric, pH-Elevating Bacillus which Cause Noneffervescent Spoilage of Underprocessed Tomatoes

In the preliminary phase of this study, a selective isolation medium was developed. Using the new medium, 24 strains of Bacillus Spp. that elevate tomato juice pH were isolated from garden soil or natural vegetative materials. Two jars of home-canned, water-bathed tomatoes contained sporeformers which produced noneffervescent spoilage. All strains were morphologically and physiologically different from 2 flat-sour strains of B. coagulans and B. licheniformis strains, but similar to a previous isolate from home-canned, spoiled green beans that elevated pH. The new medium may have future applications in isolation and enumeration of other acidurics including yeast-like microorganisms.     

Inhibiting Left-Handed Wave Propagation by a Band Gap of Stacked Cut-Off Metallic Hole Arrays

In this letter, the behavior of a recently reported left-handed metamaterial working at millimeter-wave frequencies is analyzed. The metamaterial is built by the periodic stacking of metallic plates with sub-wavelength hole arrays that show extraordinary optical transmission. If the longitudinal period of the stacked structure is chosen adequately, it is possible to mold the electromagnetic wave propagation inside the structure from right-handed to left-handed. The transmission response of the fabricated prototype has been measured with a millimeter wave quasioptical vector network analyzer in the range between 40 GHz and 110 GHz confirming the possibility to tune the left-handed or right handed characteristics of the waves propagating there. These results can give rise to interesting applications such as novel lenses and other quasioptical structures     

Composite gel-filled giant vesicles: Membrane homogeneity and mechanical properties

We further investigate the properties of composite Poly(NIPAM) (poly(N-isopropylacrylamide)) gel-filled giant vesicles, focusing here on i) the homogeneity of the membrane, ii) its coupling to the inner gel under strong suction pressures, and iii) the relation between the final elastic modulus of the vesicles and the amount of crosslinker in the pre-gel medium. We show that whereas the photo-polymerization process induces a decrease of the membrane homogeneity at the micrometer size range, the membrane still remains strongly coupled to the internal gel network. The vesicles studied here display average moduli in the range [0.5–25] kPa, confirming their potential as biomimetic mechanical systems.     

Fluorimetric Nerve Gas Sensing Based on Pyrene Imines Incorporated into Films and Sub‐Micrometer Fibers

The chemical sensing of nerve gas agents has become an increasingly important goal due to the 1995 terrorist attack in a Tokyo subway as well as national security concerns in regard to world affairs. Chemical detection needs to be sensitive and selective while being facile, portable, and timely. In this paper, a sensing approach using a pyrene imine molecule is presented that is fluorimetric in response. The detection of a chloro‐Sarin surrogate is measured at 5 ppmv in less than 1 second and is highly selective towards halogenated organophosphates. The pyrene imine molecule is incorporated into polystyrene films as well as micrometer and sub‐micrometer fibers. Using both a direct drawing approach and electrospinning, micrometer and nanofibers can be easily manufactured. Applications for functional sensing micrometer and nanofibers are envisioned for optical devices and photonics in addition to solution and airflow sensing devices.     

Evolution of the arthropod prophenoloxidase/hexamerin protein family

PURPOSE: Because intraperitoneal (i.p.) therapy may provide a therapeutic advantage and because hyperthermia enhances carboplatin (CBDCA) cytotoxicity, we evaluated the feasibility, toxicity, and pharmacokinetics of CBDCA given via continuous hyperthermic peritoneal perfusion (CHPP) in patients with small-volume residual ovarian cancer. Patients and METHODS: Six patients underwent optimal cytoreductive procedures (residual disease < or =5 mm) as initial treatment of stages II and III epithelial ovarian adenocarcinoma. All patients received a 90-min CHPP at a CBDCA dose of 800-1200 mg/m2, with the perfusate being recirculated rapidly from a reservoir through a heat exchanger, resulting in i.p. temperatures of 41-43 degrees C. Plasma, perfusate, and urine samples were collected and platinum was quantified by flameless atomic absorption spectrophotometry. RESULTS: At no time did any patient's core temperature exceed 40 degrees C. Peak perfusate platinum concentrations were 8- to 15-fold higher than peak ultrafilterable plasma concentrations. The permeability-area product was extremely high and variable (14-90 ml/min), resulting in a regional advantage of 1.9-5.3. The percentage of the dose absorbed ranged widely from 27% to 77%. Dose-limiting hematologic toxicity was observed at a dose of 1200 mg/m2 and this was associated with a CBDCA AUC in plasma of 11 mg min ml(-1). CONCLUSION: CHPP with CBDCA was safely given to three patients at a dose of 800 mg/m2, and dose-limiting hematologic toxicities observed at 1200 mg/m2, correlated with the plasma CBDCA exposure established when lower doses of CBDCA are given systemically. The pharmacokinetic data are consistent with the expected effect of vigorous mixing on the exposed peritoneal surface area. Variable drug absorption and clearance make the prediction of systemic exposure highly uncertain. These findings may have important implications for novel therapies given i.p.     

Transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding in portal hypertension: comparison of emergency and elective interventions

Nonsurgical reduction of portal hypertension by transjugular intrahepatic portosystemic shunt (TIPS) is widely used for prevention of variceal rebleeding (elective TIPS). Information is limited about the value of emergency TIPS for acute variceal bleeding unresponsive to endoscopic and drug therapy. The aim of the present study was therefore to determine whether the effects and complications differ between emergency and elective TIPS in patients with cirrhosis of the liver. TIPS was performed in 11 patients with acute variceal bleeding unresponsive to endoscopic treatment and 22 patients in stable condition after an episode of variceal bleeding. Clinical examination, blood sampling, Doppler sonography of TIPS flow, and upper gastrointestinal endoscopy were performed at days 1, 7, and 30 and at three-month intervals after TIPS. Mean follow-up was 549 (1-987) days. Bleeding was controlled by emergency TIPS in 10/11 patients. Probability of survival was not different after emergency and elective TIPS (0.73 vs 0.84 at one year). Early rebleeding (< or =2 weeks) occurred more often after emergency TIPS (3/11 vs 0/22 patients; P = 0.03), but there was no significant difference in late rebleeding. Occlusion of TIPS was more frequent after emergency TIPS. Occurrence of TIPS stenoses was identical in both groups (4/11 vs 8/22). De novo or deterioration of preexisting hepatic encephalopathy was similar (18% vs 24%; NS). It is concluded that TIPS is effective for control of acute variceal bleeding unresponsive to endoscopic and drug treatment. Early rebleeding and stent occlusion occurred more often after emergency TIPS. Late rebleeding, complications, and long-term survival did not differ from elective TIPS.     

The effect of a pressure garment on post-surgical drainage and seroma formation in breast cancer patients

BACKGROUND: The treatment of choice for cancer of the breast are mastectomy and axillary clearance or wide excision with axillary clearance. The most common complication following such a procedure is seroma formation. Various methods have been used to prevent it. However, the use of a pressure garment in this context has not been fully evaluated in the current literature. RESULTS: In a randomised trial comparing patients with a pressure garment with those without one, we have found no improvement in post-operative drainage with the use of a pressure garment. There were more complications in the group without the pressure garment (19%) compared with those with the garment (15.7%). The only seroma occurred in those patients not using the garment. The use of the pressure garment appeared to increase the duration of use of the drain (6.8 vs 6.1 days), these differences in the two groups was not significant. One of the patients in the pressure garment group was unable to tolerate the warmth and discontinued wearing the garment in the third post-operative day. This gave a rejection rate of 5%. CONCLUSION: The use of a pressure garment does not reduce the post-operative drainage, however, the complication rate appears to be higher when the pressure garment is not being used.