Antimicrobial diazanaphthalenes are indispensable in the treatment of various infections. The quinoxaline scaffold possesses unique physicochemical properties and provides a possibility of a great number of targeted modifications. Quinoxaline-based compounds have a wide range of promising biological properties; therefore a special attention is paid to them for research and designing of new drugs. In fact, quinoxaline can be considered as a privileged structure. The scaffold can be easily and rapidly constructed, which emphasizes the significance of this favourable structure. The review is focused on recently reported potential antibacterial, antimycobacterial, antifungal and antiprotozoal agents derived from the quinoxaline scaffold, their mechanism of action and structure-activity relationships. A brief classification of synthetic pathways of quinoxaline derivatives is provided too.

• MeSH
• Anti-Infective Agents chemical synthesis   chemistry   pharmacology   MeSH
• Quinoxalines chemical synthesis   chemistry   pharmacology   MeSH
• Gram-Negative Bacteria drug effects   MeSH
• Gram-Positive Bacteria drug effects   MeSH
• Fungi drug effects   MeSH
• Microbial Sensitivity Tests MeSH
• Drug Resistance, Multiple, Bacterial drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Plasmodium drug effects   MeSH
• Drug Design * MeSH
• Trypanosoma drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Anti-Infective Agents MeSH
• Quinoxalines MeSH

The aim of this article is to introduce the topic of newly designed peptides as well as their biological activity. We designed nine encoded peptides composed of six amino acids. All these peptides were synthesized with C-terminal amidation. To investigate the importance of increased hydrophobicity at the amino end of the peptides, all of them were subsequently synthesized with palmitic or lithocholic acid at the N-terminus. Antimicrobial activity was tested on Gram-positive and Gram-negative bacteria and fungi. Cytotoxicity was measured on HepG2 and HEK 293 T cell cultures. Peptides bearing a hydrophobic group exhibited the best antimicrobial activity. Lipopeptides with palmitic or lithocholic acid (PAL or LCA peptides) at the N-terminus and with C-terminal amidation were highly active against Gram-positive bacteria, especially against strains of Staphylococcus aureus and Candida tropicalis. The LCA peptide SHP 1.3 with the sequence LCA-LVKRAG-NH2, had high efficiency on HepG2 human liver hepatocellular carcinoma cells (97%).

• Keywords
• Antimicrobial peptides, De novo design, Mechanism of action, Solid phase peptide synthesis, Structure–activity relationship,
• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Gram-Negative Bacteria MeSH
• Gram-Positive Bacteria MeSH
• HEK293 Cells MeSH
• Lithocholic Acid MeSH
• Humans MeSH
• Lipopeptides * pharmacology   MeSH
• Microbial Sensitivity Tests MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Lithocholic Acid MeSH
• Lipopeptides * MeSH

The increase in the number of bacterial strains resistant to known antibiotics is alarming. In this study we report the synthesis of novel compounds termed Lipophosphonoxins II (LPPO II). We show that LPPO II display excellent activities against Gram-positive and -negative bacteria, including pathogens and multiresistant strains. We describe their mechanism of action-plasmatic membrane pore-forming activity selective for bacteria. Importantly, LPPO II neither damage nor cross the eukaryotic plasmatic membrane at their bactericidal concentrations. Further, we demonstrate LPPO II have low propensity for resistance development, likely due to their rapid membrane-targeting mode of action. Finally, we reveal that LPPO II are not toxic to either eukaryotic cells or model animals when administered orally or topically. Collectively, these results suggest that LPPO II are highly promising compounds for development into pharmaceuticals.

• MeSH
• Anti-Bacterial Agents chemical synthesis   chemistry   pharmacology   MeSH
• Apoptosis drug effects   MeSH
• Cell Membrane metabolism   MeSH
• Cell Line MeSH
• Phospholipids chemistry   MeSH
• Gram-Negative Bacteria drug effects   MeSH
• Gram-Positive Bacteria drug effects   MeSH
• Rabbits MeSH
• Humans MeSH
• Lipid Bilayers chemistry   MeSH
• Microbial Sensitivity Tests MeSH
• Drug Resistance, Multiple, Bacterial MeSH
• Mice, Inbred ICR MeSH
• Cell Line, Tumor MeSH
• Pyrazoles chemical synthesis   chemistry   pharmacology   MeSH
• Drug Design MeSH
• Stereoisomerism MeSH
• Skin Irritancy Tests MeSH
• Uridine Monophosphate analogs & derivatives   chemical synthesis   chemistry   pharmacology   MeSH
• Cell Survival drug effects   MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Phospholipids MeSH
• Lipid Bilayers MeSH
• Pyrazoles MeSH
• Uridine Monophosphate MeSH

A series of benzaldehyde and salicylaldehyde-S-benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram-positive and Gram-negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty-eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron-chelating properties were investigated. Two derivatives, 5-bromosalicylaldehyde-S-(4-fluorobenzyl)-isothiosemicarbazone and salicylaldehyde-S-(4-bromobenzyl)-isothiosemicarbazone, influenced the isocitrate lyase activity and caused a better inhibition at 10 μmol/L than 3-nitropropionic acid, a standard inhibitor. The compounds were also found to act as exogenous chelators of iron, which is an obligate cofactor for many mycobacterial enzymes. Due to their low cytotoxicity, together with the activity against isocitrate lyase and the ability to sequester iron ions, the compounds belong to potential antibiotics with the main effect on mycobacteria.

• Keywords
• Biological activity, Cytotoxicity, Isocitrate lyase, Isothiosemicarbazone, Tuberculosis,
• MeSH
• Anti-Bacterial Agents chemical synthesis   chemistry   pharmacology   MeSH
• Antitubercular Agents chemical synthesis   chemistry   pharmacology   MeSH
• Gram-Negative Bacteria drug effects   MeSH
• Gram-Positive Bacteria drug effects   MeSH
• Enzyme Inhibitors chemical synthesis   chemistry   pharmacology   MeSH
• Isocitrate Lyase antagonists & inhibitors   MeSH
• Mycobacterium drug effects   MeSH
• Drug Design MeSH
• Thiosemicarbazones chemical synthesis   chemistry   pharmacology   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Antitubercular Agents MeSH
• Enzyme Inhibitors MeSH
• Isocitrate Lyase MeSH
• Thiosemicarbazones MeSH

A new thiourea ligand (HL), namely N-(4-chlorophenyl)morpholine-4-carbothioamide and its Co(III), Ni(II) and Ag(I) complexes (1a, 1b and 1c) were synthesized and investigated by Fourier-transform infrared, 1H NMR and UV-visible spectroscopies. The compounds HL and 1c were characterized by single-crystal X-ray crystallography revealing the triclinic space group P[Formula: see text] for both compounds. The inhibitory effect of HL ligand, 1a, 1b, and 1c complexes was investigated with in vitro tests on Gram-positive and Gram-negative bacteria. For the 1c complex, the results showed that the coordination of the HL to Ag(I) ion increased its antibacterial effect especially against E. coli. The assays also indicated that for the same bacteria strains, the new complexes showed higher activity than the ligand, with the relative activity 1c > 1b > 1a > HL. Moreover, all samples were more suitable antimicrobial agents against the Gram-negative than those of the Gram-positive bacteria. Eventually, the relationship between the structure and bactericidal activities of these specimens was examined by calculating frontier molecular orbital (HOMO and LUMO) energies using density functional theory method at the 6-31 G*/LANL2DZ level of theory.

• MeSH
• Anti-Bacterial Agents chemical synthesis   chemistry   pharmacology   MeSH
• Gram-Negative Bacteria drug effects   MeSH
• Gram-Positive Bacteria drug effects   MeSH
• Coordination Complexes chemical synthesis   chemistry   pharmacology   MeSH
• Crystallography, X-Ray MeSH
• Magnetic Resonance Spectroscopy MeSH
• Microbial Sensitivity Tests MeSH
• Molecular Structure MeSH
• Morpholines chemical synthesis   chemistry   pharmacology   MeSH
• Spectrophotometry, Ultraviolet MeSH
• Spectroscopy, Fourier Transform Infrared MeSH
• Thioamides chemical synthesis   chemistry   pharmacology   MeSH
• Thiourea metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Coordination Complexes MeSH
• Morpholines MeSH
• Thioamides MeSH
• Thiourea MeSH

AIM: Ankle brachial index (ABI) is a diagnostic tool for peripheral arterial disease (PAD) and a cardiovascular risk stratification tool. Despite this evidence and guidelines recommending its use in everyday practice, ABI is not widely used. Automatic ABI measurement may lower the barrier to incorporate ABI measurement into everyday practice. The aim of this study was to validate a novel automatic oscillometric ABI device (BOSO ABI) against a gold standard-Doppler device in an epidemiological setting. METHODS: In 839 patients from the Czech post-MONICA study (a randomly selected representative population sample aged over 25 years), mean age 54.3±13.8 years (47% of men), ABI measurement was performed using the BOSO ABI device and a handheld Doppler device in a random fashion. The two techniques were carried out by different investigators each blinded to the findings of the other. Analyses were conducted as proposed by Bland and Altman. RESULTS: The mean ABI difference between the two methods was 0.1±0.11, with 95% limits of agreement ranging from -0.11 to 0.30. The difference between Doppler and oscillometric ABI increased significantly with increasing mean ABI (r=0.29; P<0.001). When considering Doppler the gold standard, automated oscillometric measurement had a 76.9% sensitivity, 97.9% specificity, and 37% positive and 99.6% negative predictive values in diagnosing ABI <0.9. CONCLUSION: The BOSO ABI device cannot be used interchangeably for standard Doppler ABI measurement in diagnosing PAD. However, its high negative predictive value allows using it as a screening tool for PAD.

• MeSH
• Analysis of Variance MeSH
• Equipment Design MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Peripheral Arterial Disease diagnosis   diagnostic imaging   physiopathology   MeSH
• Oscillometry instrumentation   MeSH
• Mass Screening instrumentation   MeSH
• General Practice * MeSH
• Predictive Value of Tests MeSH
• Reproducibility of Results MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Ankle Brachial Index instrumentation   MeSH
• Ultrasonography, Doppler instrumentation   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Validation Study MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: The aim of the study was to verify the correct anchoring location for the tip of the right ventricular lead using cardiac computed tomography and to assess the best fluoroscopic and ECG criteria associated with the correct location of the electrode into the midseptum. METHODS AND RESULTS: Patients indicated to pacemaker implantation were prospectively enrolled. The right ventricular lead was implanted into the midseptum according to standard criteria in left anterior oblique 40 view. The cardiac shadow on the right anterior oblique 30 was divided into 4 quadrants perpendicular to the lateral cardiac silhouette and the position of the lead tip was analyzed. The exact position of the lead tip was assessed using computed tomography. Of 51 patients, the right ventricular lead was anchored midseptum in 21 (41.2%; MS group). In 30 patients (58.8%; non-MS group), the lead was anchored in the adjacent anterior wall. The angle between the lead and horizontal axis on the left anterior oblique was similar in both groups. The non-MS group was associated with shorter distances between the tip and the cardiac contours in the right anterior oblique 30 (96.7% of leads in the non-MS group were in the outer quadrant versus 9.6% in the MS group; P<0.001). The presence of the lead in the middle or inferior quadrants was independently associated with correct midseptum placement with positive predictive value of 94.7%. CONCLUSIONS: Despite the optimal shape of the left anterior oblique, substantial numbers of leads were not anchored in the midseptum. Knowing the right anterior oblique 30 lead position can ensure proper midseptal placement.

• Keywords
• cardiac pacing, fluoroscopy, pacemaker implantation, right ventricular apex, ventricular septum,
• MeSH
• Equipment Design MeSH
• Electrocardiography MeSH
• Fluoroscopy MeSH
• Cardiac Pacing, Artificial * MeSH
• Humans MeSH
• Logistic Models MeSH
• Ventricular Septum diagnostic imaging   MeSH
• Multidetector Computed Tomography * MeSH
• Multivariate Analysis MeSH
• Predictive Value of Tests MeSH
• Prospective Studies MeSH
• Radiographic Image Interpretation, Computer-Assisted * MeSH
• Chi-Square Distribution MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Heart Ventricles diagnostic imaging   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Because of their obvious advantages, active and passive optoelectronic sensor concepts are being investigated by biomedical research groups worldwide, particularly their camera-based variants. Such methods work noninvasively and contactless, and they provide spatially resolved parameter detection. We present 2 techniques: the active photoplethysmography imaging (PPGI) method for detecting dermal blood perfusion dynamics and the passive infrared thermography imaging (IRTI) method for detecting skin temperature distribution. PPGI is an enhancement of classical pulse oximetry. Approved algorithms from pulse oximetry for the detection of heart rate, heart rate variability, blood pressure-dependent pulse wave velocity, pulse waveform-related stress/pain indicators, respiration rate, respiratory variability, and vasomotional activity can easily be adapted to PPGI. Although the IRTI method primarily records temperature distribution of the observed object, information on respiration rate and respiratory variability can also be derived by analyzing temperature change over time, for example, in the nasal region, or through respiratory movement. Combined with current research areas and novel biomedical engineering applications (eg, telemedicine, tele-emergency, and telemedical diagnostics), PPGI and IRTI may offer new data for diagnostic purposes, including assessment of peripheral arterial and venous oxygen saturation (as well as their differences). Moreover, facial expressions and stress and/or pain-related variables can be derived, for example, during anesthesia, in the recovery room/intensive care unit and during daily activities. The main advantages of both monitoring methods are unobtrusive data acquisition and the possibility to assess vital variables for different body regions. These methods supplement each other to enable long-term monitoring of physiological effects and of effects with special local characteristics. They also offer diagnostic advantages for intensive care patients and for high-risk patients in a homecare/outdoor setting. Selected applications have been validated at our laboratory using optical PPGI and IRTI techniques in a stand-alone or hybrid configuration. Additional research and validation is required before these preliminary results can be introduced for clinical applications.

• MeSH
• Monitoring, Ambulatory instrumentation   methods   MeSH
• Time Factors MeSH
• Equipment Design MeSH
• Photoplethysmography * instrumentation   MeSH
• Hemodynamics * MeSH
• Infrared Rays MeSH
• Skin blood supply   MeSH
• Humans MeSH
• Respiratory Mechanics * MeSH
• Transducers MeSH
• Optical Imaging * instrumentation   MeSH
• Oximetry * instrumentation   MeSH
• Predictive Value of Tests MeSH
• Regional Blood Flow MeSH
• Reproducibility of Results MeSH
• Blood Flow Velocity MeSH
• Thermometers MeSH
• Skin Temperature * MeSH
• Thermography * instrumentation   MeSH
• Facial Expression * MeSH
• Health Status MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

AIM: To evaluate single balloon enteroscopy in diagnostic and therapeutic endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y hepaticojejunoanastomosis (HJA). METHODS: The study took place from January 2009 to December 2011 and we retrospectively assessed 15 patients with Roux-en-Y HJA who had signs of biliary obstruction. In total, 23 ERC procedures were performed in these patients and a single balloon videoenteroscope (Olympus SIF Q 180) was used in all of the cases. A transparent overtube was drawn over the videoenteroscope and it freely moved on the working part of the enteroscope. Its distal end was equipped with a silicone balloon that was inflated by air from an external pump at a pressure of ≤ 5.4 kPa. The technical limitations or rather the parameters of the single balloon enteroscope (working length - 200 cm, diameter of the working channel - 2.8 mm, absence of Albarran bridge) showed the need for special endoscopic instrumentation. RESULTS: Cannulation success was reached in diagnostic ERC in 12 of 15 patients. ERC findings were normal in 1 of 12 patients. ERC in the remaining 11 patients showed some pathological changes. One of these (cystic bile duct dilation) was subsequently resolved surgically. Endoscopic treatment was initialized in the remaining 10 patients (5 with HJA stenosis, 2 with choledocholithiasis, and 3 with both). This treatment was successful in 9 of 10 patients. The endoscopic therapeutic procedures included: balloon dilatation of HJA stenosis - 11 times (7 patients); choledocholitiasis extraction - five times (5 patients); biliary plastic stent placement - six times (4 patients); and removal of biliary stents placed by us - six times (4 patients). The mean time of performing a single ERC was 72 min. The longest procedure took 110 min and the shortest took 34 min. This shows that it is necessary to allow for more time in individual procedures. Furthermore, these procedures require the presence of an anesthesiologist. We did not observe any complications in these 15 patients. CONCLUSION: This method is more demanding than standard endoscopic retrograde cholangiopancreatography due to altered postsurgical anatomy. However, it is effective, safe, and widens the possibilities of resolving biliary pathology.

• Keywords
• Endoscopic diagnosis, Endoscopic retrograde cholangiography, Endoscopic treatment, Roux-Y hepaticojejunoanastomosis, Single balloon enteroscopy,
• MeSH
• Time Factors MeSH
• Cholangiopancreatography, Endoscopic Retrograde adverse effects   instrumentation   methods   MeSH
• Cholestasis diagnosis   etiology   therapy   MeSH
• Equipment Design MeSH
• Adult MeSH
• Endoscopes, Gastrointestinal MeSH
• Jejunostomy adverse effects   methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Device Removal MeSH
• Predictive Value of Tests MeSH
• Retrospective Studies MeSH
• Anastomosis, Roux-en-Y * adverse effects   MeSH
• Aged MeSH
• Stents MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Case Reports MeSH

BACKGROUND: There are several types of LPC (long peripheral catheters) that vary in length, size, insertion method, and cost. The aim of the study was to evaluate whether ultrasonography can be useful for the selection of the suitable LPC in DIVA (difficult intravenous access) patients. METHODS: Based on the ultrasonographic examination, a long peripheral catheter was selected. A 6.4 cm LPC into a vein at a depth of up to 0.5 cm, a 8.5 cm LPC into a vein at a depth up to 1.5 cm, and a 9.8 cm catheter at a depth up to 2 cm using the cannula over needle method. A 12 cm catheter was inserted into the deeper veins using the direct Seldinger method. The catheter diameter was no more than 33% vein diameter. Dwell time and the number of complications of four vascular devices were recorded and compared. RESULTS: One thousand one hundred fifty-six patients, average age 76 years (19-102), 501 men and 655 women, were included in the study. Average dwelling time was 10 days (1-30), there were 136 complications (11.7%). A catheter 6.4 cm long was inserted in 346 (29.8%), 8.5 cm in 140 (12.1%), 9.8 cm in 320 (27, 5%), and 12 cm in 356 (30.6%) patients. There were no significant differences in dwelling time, rate, and type of complications among the four catheters used. CONCLUSION: Our results confirm that ultrasound examination can be useful for the selection of the suitable long peripheral catheter in DIVA patients.

• Keywords
• DIVA patient, Long peripheral catheter, complications, indwelling time, ultrasonography,
• MeSH
• Time Factors MeSH
• Vascular Access Devices MeSH
• Equipment Design * MeSH
• Adult MeSH
• Ultrasonography, Interventional * MeSH
• Clinical Decision-Making MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Catheterization, Peripheral * instrumentation   adverse effects   MeSH
• Predictive Value of Tests * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Catheters, Indwelling * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH