盐酸米诺环素软膏辅助龈下刮治术及根面平整术对慢性牙周炎患者龈下牙周致病菌和龈沟液炎性因子的影响

目的:探讨盐酸米诺环素软膏辅助龈下刮治术及根面平整术(FM-SRP)对慢性牙周炎(CP)患者龈下牙周致病菌和龈沟液炎性因子的影响。方法:选择2015年10月到2019年10月期间我院收治的82例CP患者,根据随机数字表法分为对照组(n=41)和观察组(n=41),对照组给予FM-SRP,观察组在对照组基础上联合盐酸米诺环素软膏辅助治疗,比较两组疗效、牙周指标、龈下牙周致病菌和龈沟液炎性因子情况,统计两组不良反应情况。结果:与对照组总有效率70.73%(29/41)相比,观察组治疗后的总有效率90.24%(37/41)更高(P<0.05)。治疗后,两组龈沟出血指数(SBI)、附着水平(AL)、菌斑指数(PLI)、牙周袋深度(PD)均下降,且观察组低于对照组(P<0.05)。治疗后,两组转化生长因子-β(TGF-β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)均下降,且观察组低于对照组(P<0.05)。对比两组不良反应无差异(P>0.05)。治疗后,两组伴防线杆菌、牙龈卟啉单胞菌比例均下降,且观察组低于对照组(P<0.05)。结论:盐酸米诺环素软膏辅助FM-SRP治疗CP患者,可有效消除致病菌,缓解炎性反应,恢复牙周生态平衡,且不增加不良反应发生率,疗效确切。     

嗜麦芽窄食单胞菌对四环素类抗生素药敏试验评价

目的了解琼脂扩散法（K-B法）及肉汤稀释法检测嗜麦芽窄食单胞菌的耐药性,了解两种方法的差异及为临床分离的嗜麦芽窄食单胞菌提供药敏结果。方法对28株临床分离嗜麦芽窄食单胞菌进行K-B法及肉汤稀释法检测,了解扩散直径及每株菌的MIC值。结果多西环素、米诺环素对嗜麦芽窄食单胞菌的药敏结果较好;K-B法及肉汤稀释法所得结果相关性好。结论临床上可以选择多西环素、米诺环素治疗嗜麦芽窄食单胞菌感染;可以应用K-B法检测嗜麦芽窄食单胞菌对四环素类抗生素的药物敏感性。     

角膜新生血管的治疗新进展

角膜本身无血管,毛细血管网围绕角膜缘,如果血管超越角膜缘进入透明区即为病理性。角膜新生血管不是一种独立的角膜病,而是一种病理改变。由于维持角膜无血管的平衡因素被破坏,角膜缘的毛细血管侵入角膜周边部1-2 mm,即可视为角膜新生血管(CNV)形成1。随着它对感染的消除、创伤愈合、抑制免疫介导的角膜溶解有一定作用,但其结构和功能不完善,容易发生血浆渗漏,造成角膜水肿、脂质沉着以及激发的角膜瘢痕化,严重影响视力;也使角膜移植排斥反应的发生率大大增加。CNV的生长有利于病原微生物的清除和组织的修复,但严重影响了角膜的透明性,导致一系列的并发症,破坏眼球的完整性,目前国内外对治疗角膜新生血管的药物进行了大量的研究,希望通过不同的药物、不同的治疗方法解决这个大难题。     

Plasmodium berghei: Development of resistance to clindamycin and minocycline in mice

Strains of Plasmodium berghei resistant to clindamycin or minocycline were selected by a procedure in which groups of infected mice were treated with increasing doses of drug during each of a series of subpassages. Groups of five mice, each infected by intravenous inoculation with 10 million parasitized erythrocytes, were treated orally with different doses of drug for four consecutive days beginning on the day of infection. Subpassages were routinely made by Day 7, using donor mice from the group that had been treated with the highest dose of drug that allowed for some development of parasitemia during the preceding passage. Drug doses were increased in each passage as dictated by the development of parasitemia during the previous treated passage.The rate of development of resistance to clindamycin or minocycline was much slower than to conventional antimalarials such as chloroquine, quinine, or pyrimethamine. P. berghei developed total resistance to the latter compounds in nine to 12 treated passages in mice over a period of 60 to 85 days. In contrast, development of total resistance to clindamycin required 42 treated passages over a period of 300 days. Total resistance to minocycline was not attained during 86 successive minocycline-treated passages in mice over a period of 600 days, but a sixfold increase in resistance to minocycline was observed.The clindamycin-resistant strain was normally sensitive to minocycline, chloroquine, quinine, and pyrimethamine. The strain partially resistant to minocycline was normally sensitive to clindamycin, chloroquine, quinine, and pyrimethamine. Resistance to clindamycin was stable during 51 drug-free passages in mice over a period of 1 year. Resistance to minocycline was unstable. During 16 drug-free passages in mice the strain reverted towards normal sensitivity to minocycline. Strains resistant to clindamycin or minocycline showed no difference in rate of development in mice as compared to the parent strain. Likewise, only minor morphological modifications were seen in Giemsa-stained blood smears between the two resistant strains and the parent strain.These results suggest that other species of malaria may develop resistance to clindamycin or minocycline. Should resistance to one of these compounds appear, however, it should not invalidate the use of the other in the treatment of malaria.     

Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells

High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.     

Minocycline up-regulates BCL-2 levels in mitochondria and attenuates male germ cell apoptosis

In this study, we determined the efficacy of minocycline, a second generation tetracycline, in preventing male germ cell apoptosis after withdrawal of gonadotropins and intratesticular testosterone (T). Groups of 5 male rats received one of the following treatments daily for 5 days: (i) daily sc injection of GnRH-A (1.6 mg/kg BW), (ii) oral administration of 30% gum acacia as a vehicle control, and (iii) GnRH-A + oral administration of 50 or 100 mg/kg BW of minocycline. Minocycline at both 50 and 100 mg dose levels significantly (P < 0.05) prevented GnRH-A -induced germ cell apoptosis by 59.4% and 62.2%, respectively, and fully prevented PARP cleavage. Minocycline-mediated protection occurred at the mitochondria, involving the restoration of the BCL-2 levels and, in turn, suppression of cytochrome c and DIABLO release. Minocycline was also effective in preventing human male germ cell apoptosis induced by hormone free culture condition.     

High-performance liquid chromatographic assay for minocycline in human plasma and parotid saliva

A sensitive and specific high-performance liquid chromatographic (HPLC) method with UV detection was developed for the determination of minocycline in human plasma and parotid saliva samples. Samples were extracted using an Oasis™ HLB cartridge and were injected into a C₈ Nucleosil column. The HPLC eluent contained acetonitrile–methanol–distilled water–0.1% trifluoroacetic acid (25:2:72.9:0.1, v/v). Demeclocycline was used as internal standard. The assay showed linearity in the tested range of 0.1–25 μg/ml. The limit of quantitation was 100 ng/ml. Recovery from plasma or parotid saliva averaged 95%. Precision expressed as %CV was in the range 0.2–17% (limit of quantitation). Accuracy ranged from 93 to 111%. In the two matrices studied at 20 and 4°C, rapid degradation of the drug occurred. Frozen at −30°C, this drug was stable for at least 2 months, the percent recovery averaged 90%. The method’s ability to quantify minocycline with precision, accuracy and sensitivity makes it useful in pharmacokinetic studies.     

Effects of second generation tetracyclines on penicillin-epilepsy-induced hippocampal neuronal loss and motor incoordination in rats

Epileptic seizures cause pathological changes such as sclerosis and pyramidal neuronal loss in the hippocampus. Experimentally, epilepsy can be induced by application of various chemicals directly to the cerebral cortex. In this study, epilepsy was induced in rats by intracortical application of 500 IU penicillin G, and the effect of minocycline and doxycycline on the resulting motor incoordination (rotarod) and hippocampal neuronal loss in CA1, CA2 and CA3 fields (optical fractionator method) were investigated. The rotarod performance was reduced in the epilepsy group to 285.1+/-6.9 s (P<0.05 vs. sham-300 s). Minocycline and doxycycline increased this performance to 297.4+/-1.0 s and 296.9+/-1.2 s respectively. No significant difference was detected between minocycline and doxycycline. The present results also showed that the number of neurons (x10(3)) in the sham group was 150+/-9. In the penicillin-epileptic rats, the number was decreased to 105+/-7 (P<0.01). Minocycline, but not doxycycline (125+/-8), significantly increased the number to 131+/-3 (P<0.05). In conclusion, the second generation tetracycline minocycline decreased the loss of hippocampal neurons and motor incoordination in penicillin-epileptic rats. Minocycline could protect against a variety of neurological insults including epilepsy.     

Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4

Traumatic brain injury (TBI) is one of the main concerns worldwide as there is still no comprehensive therapeutic intervention. Astrocytic water channel aquaporin-4 (AQP-4) system is closely related to the brain edema, water transport at blood-brain barrier (BBB) and astrocyte function in the central nervous system (CNS). Minocycline, a broad-spectrum semisynthetic tetracycline antibiotic, has shown anti-inflammation, anti-apoptotic, vascular protection and neuroprotective effects on TBI models. Here, we tried to further explore the underlying mechanism of minocycline treatment for TBI, especially the relationship of minocycline and AQP4 during TBI treatment. In present study, we observed that minocycline efficaciously reduces the elevation of AQP4 in TBI mice. Furthermore, minocycline significantly reduced neuronal apoptosis, ameliorated brain edema and BBB disruption after TBI. In addition, the expressions of tight junction protein and astrocyte morphology alteration were optimized by minocycline administration. Similar results were found after treating with TGN-020 (an inhibitor of AQP4) in TBI mice. Moreover, these effects were reversed by cyanamide (CYA) treatment, which notably upregulated AQP4 expression level in vivo. In primary cultured astrocytes, small-interfering RNA (siRNA) AQP4 treatment prevented glutamate-induced astrocyte swelling. To sum up, our study suggests that minocycline improves the functional recovery of TBI through reducing AQP4 level to optimize BBB integrity and astrocyte function, and highlights that the AQP4 may be an important therapeutic target during minocycline treating for TBI.