Protonation-induced red-coloured circularly polarized luminescence of [5]carbohelicene fused by benzimidazole.

Benzimidazole-fused [5]carbohelicene ([5]HeliBI) was newly synthesized to examine the spectroscopic and chiroptical properties. The reversible protonation and deprotonation processes of [5]HeliBI were successfully investigated using (1)H NMR, absorption and fluorescence spectral measurements. We also confirmed the circularly polarized luminescence of protonated [5]HeliBI (H(+)-[5]HeliBI). This is the first observation of red-coloured CPL of a helicene derivative.

The use of the 300 microsecond 1064 nm Nd:YAG laser in the treatment of keloids.

BACKGROUND: Keloids can be quite resistant to conventional methods of treatment. A wide range of treatment modalities exists, often with suboptimal results, recurrences, and adverse events occurring. Laser therapy with the carbon dioxide, erbium:YAG, Q switched frequency doubled neodymium-doped yttrium aluminium garnet (Nd:YAG), and 585/595 nm pulsed dye lasers have all be purported as potential treatment modalities however with limited efficacy and data especially in the skin of color population is limited. We report the successful use of the 300 microsecond 1064 nm Nd:YAG laser in treating keloids in patients with skin types ranging from Fitzpatrick I through VI with special attention in treating skin of color patients. OBJECTIVE: We examined the use of the 300 microsecond 1064 nanometer (nm) Nd:YAG laser for the treatment keloids in patients with skin types ranging from Fitzpatrick I through VI. METHODS & MATERIALS: A retrospective analysis of treatment efficacy was conducted on 44 patients with keloids. Three separate treatment groups were compared. The groups consisted of: a "control group" in which the whole keloid was only treated with intralesional corticosteroid (triamcinolone 10 mg/cc) (16 patients); a "laser only" group in which the patient's keloid was only treated with the 1064 nm Nd:YAG laser at a fluency of 13 to 18 Joules / centimeter2 (J/cm2), a fixed pulse duration of 300 microseconds, 5 mm spot size, and a total of 2000 pulses (14 patients); and a "combination group" that received both the aforementioned laser therapy and adjuvant intralesional triamcinolone (14 patients). RESULTS: Patients in the "combination group" treated with the 300 microsecond 1064 nm Nd:YAG laser therapy plus intralesional corticosteroid and the "laser only" group both were observed to have durable clinical reduction in the thickness and erythema of the keloids. These results were shown to be superior to the "control group" whom were only treated with intralesional corticosteroids. Only mild and transient post treatment erythema was noted as an adverse effect. STATISTICAL ANALYSIS: Data analysis was performed using IBM SPSS Statistics 19.0.0 (Armonk, NY). In order to assess the statistical significance of differences in keloid improvement among the three treatment groups, The Kruskal-Wallis test (non-parametric ANOVA test) was applied. The level of statistical significance was set at P< 0.05. A statistically significant difference in keloid improvement was appreciated between treatment groups (P<0.0001). LIMITATIONS: A small sample size and the retrospective nature of the analysis are limitations to the study.
CONCLUSION: The 300 microsecond 1064 nm Nd:YAG laser proved effective in improving the clinical appearance of keloids. We recommended this laser protocol in conjunction with intralesional corticosteroids as a treatment option for patients with keloids, especially in the skin of color population. The 1064 nm Nd:YAG laser did not show post inflammatory hyperpigmentation nor hypopigmenatation, which are concerns for skin types IV to VI, and therefore is a suitable option for such patients.

Failure of ethanol and acetaldehyde to alter in vivo norepinephrine release in the striatum and hippocampus of rats.

The effect of ethanol (EtOH) and acetaldehyde (AcH) on norepinephrine (NE) release was examined in the striatum and hippocampus of freely moving rats by means of in vivo microdialysis coupled with high-performance liquid chromatography and an electrochemical detector. Rats were treated intraperitoneally with EtOH (1 g/kg) or cyanamide (CY, 50 mg/kg, a potent aldehyde dehydrogenase inhibitor) plus EtOH (1 g/kg). No significant difference in NE levels in the dialysates was observed in the striatum and hippocampus in either the EtOH or CY+EtOH groups. NE levels in the hippocampal dialysates were about fivefolds higher than those in the striatum. The concentration of EtOH and AcH in the striatal dialysate reached a peak at 30 min after EtOH dosing and then gradually decreased in the CY+EtOH group. In the EtOH group the striatal concentration of EtOH also reached a peak at 30 min after EtOH dosing, and then gradually decreased while AcH was not detected. The present study suggests that there is no in vivo effect of brain EtOH or AcH on NE release in the striatum and hippocampus of awake rats.

Molecular characterization of a cephamycin-hydrolyzing and inhibitor-resistant class A beta-lactamase, GES-4, possessing a single G170S substitution in the omega-loop.

The nosocomial spread of six genetically related Klebsiella pneumoniae strains producing GES-type beta-lactamases was found in a neonatal intensive care unit, and we previously reported that one of the six strains, strain KG525, produced a new beta-lactamase, GES-3. In the present study, the molecular mechanism of cephamycin resistance observed in strain KG502, one of the six strains described above, was investigated. This strain was found to produce a variant of GES-3, namely, GES-4, which was responsible for resistance to both cephamycins (cefoxitin MIC, >128 microg/ml) and beta-lactamase inhibitors (50% inhibitory concentration of clavulanic acid, 15.2 +/- 1.7 microM). The GES-4 enzyme had a single G170S substitution in the Omega-loop region compared with the GES-3 sequence. This single amino acid substitution was closely involved with the augmented hydrolysis of cephamycins and carbapenems and the decreased affinities of beta-lactamase inhibitors to GES-4. A cloning experiment and sequencing analysis revealed that strain KG502 possesses duplicate bla(GES-4) genes mediated by two distinct class 1 integrons with similar gene cassette configurations. Moreover, the genetic environments of the bla(GES-4) genes found in strain KG502 were almost identical to that of bla(GES-3) in strain KG525. From these findings, these two phenotypically different strains were suggested to belong to a clonal lineage. The bla(GES-4) gene found in strain KG502 might well emerge from a point mutation in the bla(GES-3) gene harbored by its ancestor strains, such as strain KG525, under heavy antibiotic stress in order to acquire extended properties of resistance to cephamycins and carbapenems.

Nosocomial spread of ceftazidime-resistant Klebsiella pneumoniae strains producing a novel class a beta-lactamase, GES-3, in a neonatal intensive care unit in Japan.

Klebsiella pneumoniae strain KG525, which showed high-level resistance to broad-spectrum cephalosporins, was isolated from the neonatal intensive care unit (NICU) of a Japanese hospital in March 2002. The ceftazidime resistance of strain KG525 was transferable to Escherichia coli CSH-2 by conjugation. Cloning and sequence analysis revealed that production of a novel extended-spectrum class A beta-lactamase (pI 7.0), designated GES-3, which had two amino acid substitutions of M62T and E104K on the basis of the sequence of GES-1, was responsible for resistance in strain KG525 and its transconjugant. The bla(GES-3) gene was located as the first gene cassette in a class 1 integron that also contained an aacA1-orfG fused gene cassette and one unique cassette that has not been described in other class 1 integrons and ended with a truncated 3' conserved segment by insertion of IS26. Another five ceftazidime-resistant K. pneumoniae strains, strains KG914, KG1116, KG545, KG502, and KG827, which were isolated from different neonates during a 1-year period in the same NICU where strain KG525 had been isolated, were also positive for GES-type beta-lactamase genes by PCR. Pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus-PCR analyses displayed genetic relatedness among the six K. pneumoniae strains. Southern hybridization analysis with a GES-type beta-lactamase gene-specific probe showed that the locations of bla(GES) were multiple and diverse among the six strains. These findings suggest that within the NICU setting genetically related K. pneumoniae strains carrying the bla(GES) gene were ambushed with genetic rearrangements that caused the multiplication and translocation of the bla(GES) gene.

Microdialysis for the determination of acetaldehyde and ethanol concentrations in the striatum of freely moving rats.

The subject of the present paper is the simultaneous determination of ethanol (EtOH) and acetaldehyde (AcH) concentrations in the striatum of freely moving rats using an in vivo microdialysis followed by head-space gas chromatography (GC). Major operation conditions of GC were as follows: column, injector and detector temperatures 90, 110 and 200 degrees C, respectively; Supelcowax wide bore capillary column (60 m length, 0.53 mm i.d., 2 microm film thickness); carrier gas, nitrogen; flow rate, 20 ml/min. The recovery of EtOH and AcH at a concentration 40 mM and 250 microM, respectively, by microdialysis showed a maximum of 83.8+/-12.2 and 51.2+/-6.5%, respectively, at a flow rate of 0.8 microl/min. A good linear calibration curve in the concentration range of 5-50 mM for EtOH (r=0.998), and 10-250 microM for AcH (r=0.988) was observed. Microdialysates were collected for 10 min each after insertion of probe into the striatum. Rats were treated with cyanamide (100mg/kg, a potent aldehyde dehydrogenase inhibitor) and 60 min later with EtOH (1g/kg) intraperitoneally. A 10 min sample was about 8 microl. This volume was mixed with 40 microl of 0.002% t-butanol as an internal standard in 0.6N perchloric acid, and then analyzed by head-space GC method. The peak EtOH and AcH concentrations in the striatal dialysates reached maximum at 30 min, and then gradually decreased. This method represents a reasonable tool to quantify in vivo both AcH and EtOH levels simultaneously in rat brain.

In vivo formation of salsolinol induced by high acetaldehyde concentration in rat striatum employing microdialysis.

AIMS: The in vivo formation of salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquionoline), an endogeneous condensation product of dopamine (DA) with acetaldehyde (AcH), was examined following the administration of cyanamide (CY) plus ethanol (EtOH) using microdialysis-high-performance liquid chromatography with electrochemical detection. METHODS: After the insertion of a microdialysis probe into the striatum, rats were treated with CY (a potent inhibitor of aldehyde dehydrogenase, 50 mg/kg), 4-methylpyrazole (4-MP, a strong inhibitor of alcohol dehydrogenase, 82 mg/kg), and CY + 4-MP, followed 1 h later by EtOH (1 g/kg), CY and 4-MP only by intraperitoneal administration. RESULTS: In the CY + EtOH group, salsolinol was detected in striatal dialysates and high AcH concentrations were found in the blood. The time course of changes in salsolinol concentrations correlated with blood AcH concentrations. In the other experimental groups, salsolinol in the dialysates and high AcH concentrations in the blood were not detected. CONCLUSIONS: These observations indicate that: (1) high AcH concentrations induce the formation of salsolinol in the rat striatum; (2) there is no effect of EtOH or AcH on striatal dialysate concentrations of DA and 5-hydroxytryptamine.