Common cold and influenza symptom management: the use of pharmacokinetic considerations to predict the efficacy of a twice-daily treatment for colds and flu

SUMMARY

Objective: The objective of the two pharmacokinetic studies reported here was to compare the relative bioavailability of an ibuprofen/pseudoephedrine modified-release capsule with each of the active ingredients given alone as standard formulations.

Study design: Evaluation of two open, randomised, cross-over studies, one single dose and one multiple dose, in healthy male volunteers.

Methods: Healthy volunteers were randomised in a cross-over design to single or multiple doses of a combination of ibuprofen (600 mg) plus pseudoephedrine (90 mg) in a slow-release formulation and the individual active products alone as standard formulations; ibuprofen 400mg, pseudoephedrine 60 mg.

Results: The single-dose study demonstrated that the bioavailabilities of ibuprofen and pseudoephedrine achieved with the slow-release formulation were not significantly different from those with standard tablets of each ingredient alone. In addition, mean plasma levels of ibuprofen predictive of clinical efficacy were achieved within 0.5-1 h and lasted for 10-12 h thereafter. The time required to reach clinically effective blood levels of pseudoephedrine was longer, starting at approximately 2 h. However, the plasma levels predicted that the clinical effect would then last for at least a further 12 h. Trough levels from the multiple-dose study showed that clinically relevant analgesic and decongestant plasma levels were maintained for 24 h during twice-daily dosing. The slow-release formulation was well tolerated with only mild adverse events.

Conclusion: Blood levels would predict that the present slow-release fo rmulation of ibuprofen plus pseudoephedrine should offer reliable day and night control of cold and flu and sinus symptoms and be associated with a favourable safety profile.     

Simultaneous epicardial–endocardial mapping of the sinus node in humans with structural heart disease: Impact of overdrive suppression on sinoatrial exits

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慢性鼻窦炎伴鼻息肉患者嗅觉障碍的影响因素分析

目的分析慢性鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyps,CRSwNP)患者嗅觉障碍的影响因素。方法回顾性分析2014—2018年就诊于北京安贞医院行内镜鼻窦手术治疗的CRSwNP患者88例,男性22例,女性66例,年龄(48.1±11.3)岁(±s,下同)。所有入选患者均于术前行Sniffin′Sticks嗅觉测试、Lund-Mackay评分及改良鼻窦CT嗅区评分、鼻阻力及声反射检查、血常规及血生化等实验室检测、血清特异性IgE检测;术中取鼻息肉组织进行嗜酸粒细胞计数。根据Sniffin′Sticks嗅觉测试结果将患者分成嗅觉功能正常组和嗅觉功能障碍组,两组之间进行临床基线资料比较,根据单因素分析结果,结合临床有意义的指标进一步行多因素Logistic回归模型分析,并初步建立CRSwNP嗅觉障碍的预测模型。设P<0.05为差异有统计学意义。结果88例CRSwNP患者中,嗅觉正常32例(36.4%),嗅觉障碍56例(63.6%),其中嗅觉下降40例(45.5%)、失嗅16例(18.2%)。单因素分析发现,两组间组织嗜酸粒细胞数、血嗜酸粒细胞百分比、血尿素的差异存在统计学意义[12.7[2.0,52.3]个/高倍视野(M[P25,P75],下同)比38.6[16.2,87.0]个/高倍视野、2.75[1.60,4.80]%比4.35[2.50,6.60]%、(5.56±1.15)mmol/L比(4.98±1.33)mmol/L,P值均<0.05];改良鼻窦CT嗅区评分、除窦口鼻道复合体评分外的Lund-Mackay评分的差异均存在统计学意义(P值均<0.05)。多因素Logistic回归模型分析发现,改良鼻窦CT双侧嗅区总分和血尿素的差异具有统计学意义,其中双侧嗅区总分是嗅觉功能的危险因素(OR=2.108,95%CI:1.407~3.159,P<0.001);一定浓度的血尿素是嗅觉功能的保护因素(OR=0.461,95%CI:0.240~0.884,P=0.020)。进一步研究发现,由组织嗜酸粒细胞计数、血嗜酸粒细胞百分比、改良鼻窦CT双侧嗅区总分、总吸气、血尿素组成的预测模型受试者工作特征(ROC)曲线下面积(AUC)的值为0.888(P<0.01),对CRSwNP嗅觉障碍预测效果较好。结论改良鼻窦CT嗅区评分与CRSwNP患者的嗅觉障碍密切相关,一定程度的血尿素升高可能对CRSwNP患者的嗅觉功能有保护作用。     

Hormonal and synaptic influences of serotonin on adult neurogenesis

New neurons are incorporated into the adult brains of a variety of organisms, from humans and higher vertebrates, to non-vertebrates such as crustaceans. In virtually all of these systems serotonergic pathways appear to provide important regulatory influences over the machinery producing the new neurons. We have developed an in vitro preparation where adult neurogenesis can be maintained under highly controlled conditions, and are using this to test the influence of hormones on the production of neurons in the crustacean (Homarus americanus) brain. Serotonin levels have been manipulated in this in vitro preparation, and the resulting effects on the rate of neurogenesis have been documented. In addition we have compared in vitro influences of serotonin with results acquired from in vivo exposure of whole animals to serotonin. These experiments suggest that there are multiple mechanisms and pathways by which serotonin may regulate neurogenesis in the crustacean brain: (1) serotonin is effective in regulating neurogenesis at levels as low as 10⁻¹⁰ M, suggesting that circulating serotonin may have hormonal influences on neuronal precursor cells residing in a vascular niche or the proliferation zones; (2) contrasting effects of serotonin on neurogenesis (up- vs. down-regulation) at high concentrations (10⁻⁴ M), dependent upon whether eyestalk tissue is present or absent, indicate that serotonin elicits the release of substances from the sinus glands that are capable of suppressing neurogenesis; (3) previously demonstrated (Beltz, B.S., Benton, J.L., Sullivan, J.M., 2001. Transient uptake of serotonin by newborn olfactory projection neurons. Proc. Natl. Acad. Sci. USA 98, 12730-12735) serotonergic fibers from the dorsal giant neuron project directly into the proliferation zone in Cluster 10, suggest synaptic or local influences on neurogenesis in the proliferation zones where the final cell divisions and neuronal differentiation occur. Serotonin therefore regulates neurogenesis by multiple pathways, and the specific mode of influence is concentration-dependent.     

Lamb’s head: The model for novice education in endoscopic sinus surgery

Structured training in endonasal endoscopic sinus surgery (EESS) and skull base surgery is essential considering serious potential complications. We have developed a detailed concept on training these surgical skills on the lamb’s head. This simple and extremely cheap model offers the possibility of training even more demanding and advanced procedures in human endonasal endoscopic surgery such as: frontal sinus surgery, orbital decompression, cerebrospinal fluid-leak repair followed also by the naso-septal flap, etc. Unfortunately, the sphenoid sinus surgery cannot be practiced since quadrupeds do not have this sinus. Still, despite this anatomical limitation, it seems that the lamb’s head can be very useful even for the surgeons already practicing EESS, but in a limited edition because of a lack of the experience and dexterity. Only after gaining the essential surgical skills of this demanding field it makes sense to go for the expensive trainings on the human cadaveric model.     

Septic arthritis due to bacteroides fragilis after pilonidal sinus resection in a patient with rheumatoid arthritis

Summary Bacteroides fragilis is a rare cause of septic arthritis. Most patients with B.fragilis septic arthritis have a chronic joint disease, particularly rheumatoid arthritis, and sources of infection are lesions of the gastrointestinal tract and the skin. We report a 69-year-old male, who developed B.fragilis septic arthritis after pilonidal sinus resection. High level of suspicion of development B.fragilis septic arthritis must be present in patients with chronic joint disease in whom gastrointestinal or skin surgery was previously performed.