Correlation among the toxicity profiling (28-days repeated oral dose toxicity), toxicokinetics and tissue distribution data of ulifloxacin, the active metabolite of prulifloxacin in Wistar albino rats

This experiment was designed to investigate correlation among 28-days repeated oral dose toxicity, toxicokinetics and tissue distribution data of ulifloxacin (active metabolite of prulifloxacin) in Wistar albino rats. Prulifloxacin was administered for 28-days in rats at 0, 100, 200, 400mg/kg/day followed by 14-days recovery period. Simultaneously different toxicokinetic parameters and tissue distributions of ulifloxacin was examined by LC-MS/MS method. Plasma levels and tissue concentrations of ulifloxacin were increased with dose-related manner. Ulifloxacin was also distributed to many tissues, and concentration in lungs nearly equivalent to the plasma concentration. Based on these results it was concluded that long-term repeated dose of prulifloxacin may produce different blood parameters abnormality, liver damage, stomach ulcer, joint damage and dysfunction of lungs in rats which relates to high tissue distribution and accumulation of ulifloxacin in these tissues. These findings help in management of prulifloxacin induced adverse effects by appropriate dose selection in clinical practice.     

Dapsone-induced photosensitivity: a rare clinical presentation

Dapsone is an efficient anti-inflammatory and antimycobacterial agent. It is one of the main constituents of multidrug therapy (MDT). It acts by interference with folate metabolism. Dapsone-induced photosensitivity is a rare, non-dose-related adverse effect of the sulfone and can occur in patients with inflammatory skin disorders treated with dapsone. So far, only 12 cases seem to have been reported in the literature. We report a case of dapsone-induced photosensitivity in an Indian patient with leprosy.     

Optic disc tuberculoma in a patient with miliary tuberculosis

A 27-year-old female, on anti-tubercular therapy for miliary tuberculosis for 1 week, presented with gradual diminution of right eye vision for 4 months. Right eye visual acuity was counting fingers at 15 cm. Right fundus showed a yellowish-white vascularized lesion, 4 disc diameters in size, overlying the optic disc and associated neurosensory macular detachment. The left eye was normal. A Mantoux test was negative. The authors diagnosed presumed optic disc tuberculoma in the right eye. Oral prednisolone in tapering doses was added to the anti-tubercular therapy. The optic disc lesion regressed with residual scarring and vision became 20/30 at 7 months.     

Maculosin,a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18

ContextStreptomyces species are prolific sources of bioactive secondary metabolites known especially for their antimicrobial and anticancer activities.ObjectiveThis study sought to isolate and characterize antioxidant molecules biosynthesized by Streptomyces sp. KTM18. The antioxidant potential of an isolated compound and its toxicity were accessed.Materials and methodsThe compound was purified using bioassay-guided chromatography techniques. Nuclear magnetic resonance (NMR) experiments were carried out for structure elucidation. The antioxidant potential of the isolated compound was determined using DPPH free radical scavenging assay. The toxicity of the isolated compound was measured using a brine shrimp lethality (BSL) assay.ResultsEthyl acetate extract of Streptomyces sp. KTM18 showed more than 90% inhibition of DPPH free radical at 50 µg/mL of the test concentration. These data were the strongest among 13 Streptomyces isolates (KTM12–KTM24). The active molecule was isolated and characterized as maculosin (molecular formula, C₁₄H₁₆N₂O₃ as determined by the [M + H]⁺ peak at 261.1259). The DPPH free radical scavenging activity of pure maculosin was higher (IC₅₀, 2.16 ± 0.05 µg/mL) than that of commercial butylated hydroxyanisole (BHA) (IC₅₀, 4.8 ± 0.05 µg/mL). No toxicity was observed for maculosin (LD₅₀, <128 µg/mL) in brine shrimp lethality assay (BSLA) up to the compound’s antioxidant activity (IC₅₀) concentration range. The commercial standard, berberine chloride, showed toxicity in BSLA with an LD₅₀ value of 8.63 ± 0.15 µg/mL.ConclusionsMaculosin may be a leading drug candidate in various cosmetic and therapeutic applications owing to its strong antioxidant and non-toxic properties.     

经口机器人手术治疗口咽癌的初步经验北大核心CSCD

目的探讨经口机器人手术(transoral robotic surgery,TORS)治疗口咽癌的肿瘤学及功能学效果,以及该方法的安全性。方法回顾性分析2017年6月1日至2020年12月31日北京和睦家医院行TORS治疗的口咽癌患者26例,其中男性22例,女性4例,年龄39~76岁。T1-2期患者占88.5%(23/26)。收集相关临床病理学及随访资料,记录患者拔除胃管及气管插管的时间,采用SPSS软件包进行生存分析,计算总生存率及无病生存率。结果26例口咽癌患者均接受TORS治疗,无中转开放手术,其中20例行同期颈淋巴清扫术。TORS手术时间为65~360 min,平均215 min。术中出血量5~600 ml,平均70 ml。术后4例患者(15.4%)行气管切开,其中3例术后1个月内拔除气管套管,1例至随访结束未能拔除。12例患者(46.2%)行胃管置入,其中11例术后1个月内拔除胃管,1例患者术后13 d因口咽部出血死亡,死亡时胃管尚未拔除。术后1例患者(3.8%)切缘阳性,余患者切缘阴性。16例患者(61.5%)行术后放疗,其中11例患者(42.3%)进行以铂类为主的同步化疗。中位随访时间21.5个月(0.4~45.0个月)。3年总生存率为83.0%,3年无病生存率为75.8%。结论选择合适的口咽癌患者,TORS可取得良好的肿瘤学及功能学效果,手术并发症较少,治疗安全可行。     

Spontaneous fecal fistula in a neonate

A 19-day-old male neonate was brought to us with a left upper quadrant abdominal wall defect through which bowel was prolapsing, with a double intussusception appearance typical of a patent omphalomesenteric duct. However, the history showed that the defect was not congenital, the child had a normal umbilicus, and at surgery the lesion was shown to be a mid jejunal perforation with prolapse of bowel along both the ascending and descending limbs. Histology revealed presence of inflammation and no heterotopic tissue. We believe this is the first ever report of such a fecal fistula and we speculate on the cause of this entity.     

Plausible role of bacterial toxin–antitoxin system in persister cell formation and elimination

Although, a large proportion of pathogenic bacteria gets eliminated from hosts after antibiotic treatment, a fraction of population confronts against such effects and undergoes growth arrest to form persisters. Persistence in bacteria is a dormant physiological state where cells escape the effects of antimicrobials as well as other host immune defences without any genetic mutations. The state of dormancy is achieved through various complex phenomena and it is known that a gene pair named as toxin–antitoxin (TA) acts as a key player of persister cell formation where the toxin is activated either stochastically or after an environmental insult, thereby silencing the physiological processes. However, the controversial role of TA modules in persister cell formation has also been documented with reasonable clarity. Persisters may revert back from state of quiescence and regrow when conditions become favourable for their propagation. Therefore, the elimination of dormant bacteria is crucial, and currently, research interest is highly focussed on developing several antipersister strategies that may kill persister bacteria by targeting different molecules . It is worth examining these targets to develop appropriate therapeutic interventions against bacterial infections and it is believed that earmarking TA system can be a novel approach for resuscitation of persisters. In this review, we discussed the role of TA modules in mediating persistence with highlighting on the debatable issues regarding contribution of these modules in dormant bacteria formation. Furthermore, we discussed if these modules in bacteria can be targeted for successful elimination of dormant persister cells.