The N-formyl peptide receptors: contemporary roles in neuronal function and dysfunction

N-formyl peptide receptors(FPRs)were first identified upon phagocytic leukocytes,but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family.FPRs are expressed within neuronal tissues and markedly in the central nervous system,where FPR interactions with endogenous ligands have been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease,as well as neurological cancers such as neuroblastoma.Whilst the homeostatic function of FPRs in the nervous system is currently undefined,a variety of novel physiological roles for this receptor family in the neuronal context have been posited in both human and animal settings.Rapid developments in recent years have implicated FPRs in the process of neurogenesis and neuronal differentiation which,upon greater characterisation,could represent a novel pharmacological target for neuronal regeneration therapies that may be used in the treatment of brain/spinal cord injury,stroke and neurodegeneration.This review aims to summarize the recent progress made to determine the physiological role of FPRs in a neuronal setting,and to put forward a case for FPRs as a novel pharmacological target for conditions of the nervous system,and for their potential to open the door to novel neuronal regeneration therapies.     

Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy

Variants in RORB have been reported in eight individuals with epilepsy, with phenotypes ranging from eyelid myoclonia with absence epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and epilepsy syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of epilepsy syndromes.     

Paediatric dentistry in the new millennium: 3. Use of inhalation sedation in paediatric dentistry

Provision of General Anaesthesia is now limited and restricted to the hospital setting. Sedation for paediatric patients is an essential tool in anxiety management and is used as an adjunct to behaviour management. Inhalation sedation with nitrous oxide/oxygen sedation to reach a plane of relative analgesia may be administered easily and safely to children in general dental practice and is a potential alternative to general anaesthesia.     

The effect of a sodium lauryl sulfate-free dentifrice on patients with recurrent oral ulceration

OBJECTIVE: Sodium lauryl sulphate (SLS) is the most commonly used detergent in dentifrices. Recent reports have suggested that it may exacerbate conditions with compromised epithelial integrity. The aim of this study was to compare the effect of an SLS-free dentifrice and an SLS-containing dentifrice on recurrent oral ulceration (ROU). DESIGN: A double-blind crossover clinical trial was carried out during which subjects used an SLS dentifrice for 8 weeks and an SLS-free dentifrice for 8 weeks. Each phase was preceded by a 2-week washout period. SETTING: A UK dental teaching hospital. SUBJECTS AND METHODS: Forty-seven subjects completed the trial. They were all in the age range 10-62 years, had regularly recurrent oral ulceration reporting at least one to two ulcers per month and had normal levels of vitamin B12, ferritin and folate. MAIN OUTCOME MEASURES: The trial phases were compared for the following ulcer parameters--number of ulcer days, total pain scores, number of ulcer episodes, and number of ulcers. Additional parameters compared were the number of ulcers per episode, ulcer duration, total pain per episode and ulcer size. RESULTS: None of the ulcer parameters measured was significantly affected by the use of the SLS-free dentifrice as compared with the SLS dentifrice. CONCLUSION: SLS-free dentifrice had no significant effect on ulcer pattern in the ROU study group.     

Pulp response to Streptococcus mutans

The maxillary molar pulps of germ-free rats were mechanically exposed, and suspensions of a strain of freshly grown Streptococcus mutans were applied to the pulp wounds. The pulps were left open to the oral environment, and the animals were maintained in the isolator until they were killed in groups after 2, 7, and 28 days. After 2 days there was little evidence of any pulp response. In the 7-day group early pulp necrosis was present. No evidence of inflammatory infiltration was detected in either the 2- or 7-day animals. After 28 days there was extensive pulp necrosis in many specimens. Dentine bridges were present in fewer than one fourth of the teeth.     

组织工程化人形下颌骨髁状突的实验研究

目的　评价采用组织工程技术构建人下颌骨髁状突软骨复合组织的可行性。方法　以可降解生物材料聚羟基乙酸 (polyglycolicacid ,PGA) /聚乳酸 (polylacticacid ,PLA)预制人下颌骨髁状突模型 ,体外培养扩增牛骨膜成骨细胞和牛关节表面软骨。实验分 3组 :第 1组 ,模型内仅注入 1.5 %藻酸钙和 30 %氧化乙丙烯 ;第 2组 ,模型内分别注入成骨细胞和软骨细胞悬液 ,浓度为 5× 10 7/ml;第 3组 ,模型内接种成骨细胞藻酸钙悬液 ,同时在模型关节表面涂敷软骨细胞 PluronicF12 7悬液 ,浓度为 5× 10 7/ml。分别植入裸鼠皮下 ,12周后取材 ,作大体和组织学观察。结果　第 1组无骨和软骨形成 ,模型支架明显缩小 ,形态不规则 ;第 2组仅留残缺不全的组织结构 ,标本体积缩小变形 ;第 3组形态结构与原植入模型支架相同 ,组织学观察有骨和软骨组织结构 ,两者界面连接有序 ,骨组织内有大量新生骨板。结论　以人工合成生物材料预制人下颌骨髁状突支架 ,采用组织工程技术 ,可以在裸鼠体内构建具有骨软骨复合结构的正常形态的人形下颌骨髁状突 ,从而为进一步临床应用提供了理论依据