[Meta-analysis of the effects of triamcinolone acetonide alone and in combination with 5-fluorouracil for treating keloids].

Objective: To compare the efficacy and safety of triamcinolone acetonide (TA) alone and in combination with 5-fluorouracil (5-FU) for treating keloids using meta-analysis. Methods: Databases including PubMed, Embase, and Cochrane Library were retrieved with the search terms of " triamcinolone acetonide, 5-fluorouracil, glucocorticoid, fluorouracil, keloid, scar, TAC, 5-FU, hypertrophic scar " and databases including Chinese Journal Full-Text Database, Chinese Biomedical Database, and Wanfang Data were retrieved with the search terms of ",, 5-,," in Chinese to obtain the publicly published randomized controlled trials about the effects of TA alone and in combination with 5-fluorouracil for treating keloids from the establishment of each database to august 2019. The outcome indexes included effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion of keloids. RevMan 5.3 and Stata 14.0 statistical software were used to conduct a meta-analysis of eligible studies. Results: A total of 1 326 patients with keloids were included in 14 studies, including 668 patients in TA+ 5-fluorouracil group whose keloids were injected with TA and 5-fluorouracil and 658 patients in TA alone group whose keloids were injected with TA alone. A total of 7 articles achieved 1 to 3 points in modified Jadad score, while 7 articles achieved 4 to 7 points in modified Jadad score. Patients in TA+ 5-fluorouracil group had a higher effective proportion of treatment than that of TA alone group (relative risk=1.28, 95% confidence interval=1.16-1.41, P<0.01). Subgroup analysis showed that the quality of the included literature and ethnic factors might be the source of heterogeneity in effective proportion of treatment. Patients in TA+ 5-fluorouracil group had a lower incidence proportion of adverse reactions than that of TA alone group (relative risk=0.44, 95% confidence interval=0.25-0.75, P<0.01). Patients in TA+ 5-fluorouracil group had a lower recurrence proportion of keloids than that of TA alone group (relative risk=0.25, 95% confidence interval=0.14-0.44, P<0.01). There was no publication bias in incidence proportion of adverse reactions (P>0.05), while the effective proportion of treatment and recurrence proportion of keloids had publication bias (P<0.05). Conclusions: TA combined with 5-fluorouracil is more effective than TA alone for treating keloids, with less incidence of adverse reactions and recurrence.

[Effects of perforator flaps combined with muscle flaps for repairing grade â £ pressure ulcers in ischial tuberosity of elderly patients].

Objective: To explore effects of perforator flaps combined with muscle flaps for repairing grade Ⅳ pressure ulcers in ischial tuberosity of elderly patients. Methods: Nine elderly patients with grade Ⅳ pressure ulcers in ischial tuberosity were hospitalized in our burn ward from April 2014 to April 2017. Size of wounds ranged from 5 cm×3 cm to 12 cm×7 cm, and depth of sinus ranged from 6 to 22 cm. After admission, emergency debridement or debridement in selective time was performed. After debridement, the wounds were treated with continuous vacuum assisted closure therapy. After the treatment for 1 to 2 weeks, tissue flaps repair operations were performed. Four patients were repaired with inferior gluteal artery perforator flaps combined with long head of biceps femoris muscle flaps. Three patients were repaired with inferior gluteal artery perforator flaps combined with semimembranous muscle flaps. One patient was repaired with inferior gluteal artery perforator flap combined with gracilis muscle flap. One patient was repaired with femoral profound artery perforator flap combined with gluteus maximus muscle flap, and the distal area of femoral profound artery perforator flap of the patient which showed intraoperative cyanosis of 6 cm×4 cm was thinned to medium thickness skin to cover the muscle flap. The other eight patients showed no abnormality during operation. Size of perforator flaps ranged from 7 cm×5 cm to 14 cm×12 cm, and size of muscle flaps ranged from 11 cm×4 cm to 24 cm×6 cm. The donor sites of flaps were all sutured directly. Results: The tissue flaps and skin graft of all patients survived well after operation. During follow-up of 8 to 35 weeks, operative area of all patients showed good shape and texture, with no local diabrosis or recurrence of pressure ulcers. Conclusions: The combination of perforator flaps and muscle flaps is effective in repairing and reducing recurrence of grade Ⅳ pressure ulcers in ischial tuberosity of elderly patients.

Recent developments on ketolides and macrolides.

Recent semi-synthetic studies of erythromycin A culminated in the discovery of two ketolide drug candidates, HMR-3647 and ABT-773, for the treatment of community-acquired bacterial infections caused by both macrolide- and beta-lactam-susceptible and -resistant S. pneumoniae, gram negative bacteria, and intracellular atypical pathogens. The discovery of ketolides has rekindled interest in macrolides, and recent efforts have also led to a novel class of 4''-carbamates with activity against macrolide-resistant organisms. This review is an account of recent developments on ketolides and macrolides in terms of both chemistry and antibacterial activity.

Glycylcyclines bind to the high-affinity tetracycline ribosomal binding site and evade Tet(M)- and Tet(O)-mediated ribosomal protection.

N,N-dimethylglycylamido (DMG) derivatives of 6-demethyl-6-deoxytetracycline and doxycycline bind 5-fold more effectively than tetracycline to the tetracycline high-affinity binding site on the Escherichia coli 70S ribosome, which correlates with a 10-fold increase in potency for inhibition of E. coli cell-free translation. The potencies of DMG-doxycycline and DMG-6-demethyl-6-deoxytetracycline were unaffected by the ribosomal tetracycline resistance factors Tet(M) and Tet(O) in cell-free translation assays and whole-cell bioassays with a conditional Tet(M)-producing E. coli strain.

A glutathione conjugate of hepoxilin A3: formation and action in the rat central nervous system.

Incubation of (8R)- and (8S)-[1-14C]hepoxilin A3 [where hepoxilin A3 is 8-hydroxy-11,12-epoxyeicosa-(5Z,9E,14Z)-trienoic acid] and glutathione with homogenates of rat brain hippocampus resulted in a product that was identified as the (8R) and (8S) diastereomers of 11-glutathionyl hepoxilin A3 by reversed-phase high performance liquid chromatographic comparison with the authentic standard made by total synthesis. Identity was further confirmed by cleavage of the isolated product with gamma-glutamyltranspeptidase to yield the corresponding cysteinylglycinyl conjugate that was identical by reversed-phase high performance liquid chromatographic analysis with the enzymic cleavage product derived from the synthetic glutathionyl conjugate. The glutathionyl and cysteinylglycinyl conjugate are referred to as hepoxilin A3-C and hepoxilin A3-D, respectively, by analogy with the established leukotriene nomenclature. Formation of hepoxilin A3-C was greatly enhanced with a concomitant decrease in formation of the epoxide hydrolase product, trioxilin A3, when the epoxide hydrolase inhibitor trichloropropene oxide was added to the incubation mixture demonstrating the presence of a dual metabolic pathway in this tissue involving hepoxilin epoxide hydrolase and glutathione S-transferase processes. Hepoxilin A3-C was tested using intracellular electrophysiological techniques on hippocampal CA1 neurons and found to be active at concentrations as low as 16 nM in causing membrane hyperpolarization, enhanced amplitude and duration of the post-spike train afterhyperpolarization, a marked increase in the inhibitory postsynaptic potential, and a decrease in the spike threshold. These findings suggest that these products in the hepoxilin pathway of arachidonic acid metabolism formed by the rat brain may function as neuromodulators.

Hepoxilin A3 induces changes in cytosolic calcium, intracellular pH and membrane potential in human neutrophils.

The effects of hepoxilin A3 (HxA3), a 12-lipoxygenase metabolite of arachidonic acid, on cytosolic calcium ([Ca2+]i), intracellular pH (pHi), transmembrane potential and right-angle light scattering in human neutrophils were investigated. A rapid, transient elevation of [Ca2+]i was observed with HxA3 which was dependent on the concentration used. The effect of HxA3 on [Ca2+]i was blocked by pertussis toxin, suggesting involvement of receptors coupled to GTP-binding proteins. Experiments in Ca2(+)-free medium and using intracellular Ca2+ chelators indicated that HxA3 mobilized Ca2+ from intracellular stores. At similar concentrations, HxA3 altered pHi, producing an initial acidification followed by an alkalinization. The initial acidification was decreased in cells loaded with a Ca2+ chelator. In the presence of N-ethyl-N-(1-methylethyl)amino amiloride, an inhibitor of the Na+/H+ antiport, HxA3 induced a greater acidification but failed to elicit the recovery phase, suggesting that the latter is due to activation of the antiport. HxA3 also depolarized the membrane potential, although this effect was small. A decrease in right-angle light scattering, qualitatively similar to that observed with chemotactic peptides, was seen with HxA3, indicating that the 12-lipoxygenase metabolite can induce shape changes in neutrophils. At the concentrations used for the above effects, HxA3 was unable to generate a respiratory burst. These findings suggest that hepoxilins, which are formed by stimulated neutrophils, may have a role as messengers in neutrophil activation.

New products in the hepoxilin pathway: isolation of 11-glutathionyl hepoxilin A3 through reaction of hepoxilin A3 with glutathione S-transferase.

We describe herein the metabolism of hepoxilin A3 (HxA3) by glutathione S-transferase (GST) into a glutathione conjugate. The reaction was carried out with HxA3 (unlabelled and 14C-labelled) and glutathione (unlabelled and tritium labelled). When two isomers of HxA3 were reacted with GST, two products were formed. Only one product was formed when a single isomer of HxA3 was used. The isomeric product HxB3 was marginally active indicating considerable specificity in the reaction with GST. The products were characterized by retention of tritium from glutathione and by comparison of their migration on high performance liquid chromatography with authentic reference compounds. The products bear the structure, 11-glutathionyl HxA3.

Actions of arachidonic acid and hepoxilin A3 on mammalian hippocampal CA1 neurons.

The effects of arachidonic acid and its lipoxygenase metabolites, the hepoxilins, were investigated in rat hippocampal CA1 neurons in vitro by intracellular electrophysiological recordings. Both arachidonic acid and the hepoxilins cause a hyperpolarization which is sometimes followed by a later depolarization, augment the postspike train long-lasting afterhyperpolarization (AHP) and increase orthodromic inhibitory postsynaptic potentials (IPSPs). These data show that this arachidonic acid metabolic pathway has significant actions on mammalian central neurons, and may represent an important mechanism of neuromodulation.

Endogenous release of hepoxilin A3 from isolated perifused pancreatic islets of Langerhans.

Pancreatic islets of Langerhans were perifused with Krebs-bicarbonate solution containing glucose (5 and 10 mM). The perifusate was spiked with tetradeuterated hepoxilin A3 and was extracted and analysed by gas chromatography-mass spectrometry using NICI detection. Evidence is presented showing the presence of hepoxilin A3 as the hydrolysis product trioxilin A3. These results demonstrate for the first time that this pathway is active in intact cells; this finding, taken together with our previous evidence that hepoxilins possess insulin secretagogue properties further supports our hypothesis that these products could play a role as endogenous mediators of insulin release.