Effect of siRNA-induced silencing of cellular prion protein on tyrosine hydroxylase expression in the substantia nigra of a rat model of Parkinson's disease.

The most significant pathological feature of Parkinson's disease (PD) is the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Currently, available treatments for PD cannot prevent the loss of DA neurons. Tyrosine hydroxylase (TH) expressed in substantia nigra neurons catalyzes the conversion of tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), which is the rate-limiting step of DA biosynthesis. Major reasons for PD occurrence include decreased TH activity in the substantia nigra and secondary DA suppression. Decreased TH activity and the resulting suppression of DA synthesis (or neurotransmission) in the substantia nigra are key factors underlying the development of PD. Cellular prion protein (PRP) is a membrane glycoprotein expressed in the central nervous system. Although the sequence of PRP is highly conserved, its physiological function is unclear. The purpose of this study was to investigate the effect of PRP-targeted small interfering RNA (siRNA) on TH expression in a rat model of PD. Thirty male Wistar rats were injected with 6-hydroxydopamine (6-OHDA) to generate a model of PD. The rats then received injections of PRP-siRNA or nonsense siRNA in the lateral ventricles. Substantia nigra samples were collected for quantification of PRP and TH expression using real-time polymerase chain reaction and western blotting. PRP-siRNA decreased PRP expression in the substantia nigra. TH expression was decreased in PD model rats but was increased after PRP silencing. We conclude that PRP-siRNA may increase TH expression in vivo and may therefore exert protective effects on neurons in a model of PD.

A comparative study of digital and anatomical techniques in skull base measurement.

This study compared the accuracy of measurements of the skull base made using computed tomography (CT) images and an image-guided surgery system with those made using scientific callipers in order to evaluate the practicability of replacing conventional direct anatomical measurements with digitized techniques in skull base surgery. Important bony landmarks and parameters were measured using the three different methods in 25 cadaver skull bases. No statistically significant differences were observed between the methods. Coefficient of variation calculations indicated that data obtained from CT images was the most stable. Digital methods of navigation have the potential to reflect individual skull base anatomical features more accurately than traditional group-based data, but it is important to assess their accuracy. This study demonstrated that CT imageology and image-guided surgery systems can provide accurate anatomical measurements. Digital methods are also more flexible and less variable, and may have wide applications in this field. Though not perfect, digital imaging is a promising tool for skull base surgery.

The classification of posterior petrous meningiomas and its clinical significance.

This retrospective analysis of the clinical records of 42 patients was used to study the clinical significance of a classification system for posterior petrous meningiomas. According to clinical manifestations and radiological images, posterior petrous meningiomas were classified into three types: type I (cerebella type; 12 patients), tumours involved and compressed the cerebellum; type II (cranial nerve type; 16 patients), tumours involved the cranial nerves; and type III (combined type; 14 patients), tumours involved more than one structure such as the cerebellum, cranial nerves and the brain stem. All patients underwent microneurosurgery and the total resection rate was 90%. It was more difficult totally to resect type II and III tumours than type I tumours and the post-operative functional outcomes were worse. Microneurosurgical techniques and skills are critical to increase the total resection rate of posterior petrous meningiomas in order to decrease the mortality and disability rates.

Relationship between a family history of malignancy and the incidence of laryngeal carcinoma in the Liaoning province of China.

OBJECTIVE: The purpose of this study was to determine the contribution of family history of malignancy to the incidence of laryngeal squamous cell carcinoma. DESIGN: We performed a retrospective review of classified statistics from the detailed information of cases and matched controls. SETTING: First Hospital of China Medical University in the Liaoning province of China, between October 2005 and November 2007. PARTICIPANTS: A total of 288 previously untreated patients with laryngeal cancer and 296 control subjects with non-malignant diseases were analysed by use of a hospital-based case-control study. MAIN OUTCOME MEASURES: Incidence rates and family history of malignancy. RESULTS: Single-factor logistic regression analysis indicated that the odds ratio value of a family history of malignancy was 2.0 (95% confidence interval: 1.3-3.2). Multiple logistic regression analysis confirmed this result, with an odds ratio value of 2.3 (95% confidence interval: 1.2-4.5). There was significant association between a family history of malignancy and the development of laryngeal squamous cell carcinoma. CONCLUSIONS: A family history of malignancy plays an important role in and is an independent risk factor for the incidence of laryngeal carcinoma.

[Clinical research about the consecutive pain and flubiprofen axetil analgesia following uvulopalatopharyngoplasty].

Objective:To evaluate the postoperative pain degree on OSAHS patients following UPPP, analyze the pain characteristic during seven consecutive days, and discuss the mechanism. To observe the analgesia effect by using flubiprofen axetil. Finally making a comprehensive understanding about UPPP perioperative period and providing more choices about analgesia treatment.Method:Fifty-five patients who underwent UPPP in the First Hospital of China Medical University were divided into analgesia group（n=30）and control group（n=25）.Normal saline 50 ml+ flubiprofen axetil 100 mg was used bid for pain relief in analgesia group during seven days following operation, and normal saline 50ml was used in control group.A visual analog scale(VAS) was used for measuring mean pain intensity each day during the period from operative day to the post-operative 7th day，scores were recorded. Continuous changes about pharynx pain were observed and VAS pain scores were compared betweenanalgesia groupand control group. Result:VAS pain scores were the highest on the operative day and the post-operative 1st day, median (interquartile range) was 7（5.5-8.25），7（6-8）respectively,then decreased gradually. The most significantly decrease happened on the post-operative 2nd and 5th day(P<0.01). Pain scores in analgesia group were most significantly lower than control group from the operative day to the post-operative 4th day(P<0.01), were lower during the post-operative 5th and 6th day(P<0.05),no difference on the post-operative 7th day. Conclusion:The most painful period following UPPP is from the operative day to the post-operative 1st day, then pain decreases gradually. The pain reduces significantly on the post-operative 2nd and 5,6th day.Surgical trauma, in flammatory reaction and suture pulling may be the reason of pain. Flubiprofen axetil effectively reduces pain and the suggested analgesia period is from the operative day to the post-operative 4th-6th day.

AnthracnoseTracer: A Spatiotemporal Model for Simulating the Spread of Anthracnose in a Lupin Field.

ABSTRACT A spatiotemporal model has been developed to simulate the spread of anthracnose, initiated by infected seed, in a lupin field. The model quantifies the loss of healthy growing points of lupin in all 1-m(2) subunits of a field throughout a growing season. The development of growing points is modeled as a function of temperature using a 1-day time step, and disease-induced compensatory growth is accounted for. Dispersal of spores is simulated explicitly using Monte Carlo techniques. Spread of spores occurs during rainfall events on a 1-h time step. The distance traveled by spores is partially dependent on wind speed and is generated by adding the values selected from half-Cauchy distributions. The direction of travel of the spores is influenced by wind direction. The model has been employed to produce a theoretical assessment of damage from disease in two environments at five levels of seed infection. It was calculated that in a susceptible lupin cultivar with a 0.01% initial seed infection, anthracnose would cause approximately 15% loss of healthy growing points in a high rainfall environment in Western Australia. In a low rainfall environment, similar damage would be unlikely even with a much higher (1%) level of seed infection.

[Clinical study on treatment of early glottic carcinoma with different cordectomy].

OBJECTIVE: To explore the advantage of KTP laser cordectomy in the treatment of early glottic carcinoma. METHOD: Follow-up observation on 30 patients who had KTP laser cordectomy and 18 patients who had laryneal split cordectomy was applied, then their postoperative laryngeal structure's change, the quality of voice and the quality of life (QOL) were compared and analyzed. RESULT: The patient group treated by KTP laser grew out a piece of new cord just at the place where it was excised after half a year, and the quality of voice was obviously improved near to norm, and they had higher QOL. On the contrary, the other group had no newly grown cord, their quality of voice was better in the first half year but was worse last out. Their QOL was lower than the laser group before decannulation and the same as the laser group after the decannulation. There are 2 cases recurrented in the laser group and 1 case recurrented in the laryneal split group, the two groups all had no metastasis and death in laryneal carcinoma by 2-4 years follow up postoperation. CONCLUSION: On the basis of effecting radical cure, the early glottic carcinoma treated with non-contact KTP laser with suspension laryngoscope can result in good recuperating in laryngeal structure, less injury and high QOL. So it makes micro-injury treatment in laryngeal carcinoma come true and better than the laryngeal split cordectomy.

Surface phosphorylation by ecto-protein kinase C in brain neurons: a target for Alzheimer's beta-amyloid peptides.

The powerful regulatory machinery of protein phosphorylation operates in the extracellular environment of the brain. Enzymatic activity with the catalytic specificity of protein kinase C (PKC) was detected on the surface of brain neurons, where it can serve as a direct target for neurotrophic and neurotoxic substances that control neuronal development and cause neurodegeneration. This activity fulfilled all the criteria required of an ecto-protein kinase (ecto-PK). Detailed analysis of surface protein phosphorylation in cultured brain neurons using specific exogenous substrates (casein, histones, and myelin basic protein), inhibitors (PKC-pseudosubstrate 19-36; K252b) and antibodies (anti-PKC catalytic region M.Ab.1.9, antibodies to the carboxy-terminus of eight PKC isozymes) revealed several types of ecto-PK activity, among them ecto-PKs with catalytic specificity of the PKC isozymes zeta and delta. The activity of the neuronal ecto-PKC is constitutive and not stimulated by phorbol esters. the phosphorylation of a 12K/13K surface protein duplex by ecto-PKC-delta was found to be developmentally regulated, with peak activity occurring during the onset of neuritogenesis. Alzheimer's amyloid peptides beta 1-40 and beta 25-35 applied at neurotrophic concentrations stimulated the phosphorylation of endogenous substrates of ecto-PKC activity in brain neurons but inhibited specifically this surface phosphorylation activity with the same dose-response relationships that cause neurodegeneration. As may be expected from a relevant pathophysiological activity, beta-amyloid peptide 1-28 did not inhibit this surface phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Surface protein phosphorylation by ecto-protein kinase is required for the maintenance of hippocampal long-term potentiation.

During the induction of long-term potentiation (LTP) in hippocampal slices adenosine triphosphate (ATP) is secreted into the synaptic cleft, and a 48 kDa/50 kDa protein duplex becomes phosphorylated by extracellular ATP. All the criteria required as evidence that these two proteins serve as principal substrates of ecto-protein kinase activity on the surface of hippocampal pyramidal neurons have been fulfilled. This phosphorylation activity was detected on the surface of pyramidal neurons assayed after synaptogenesis, but not in immature neurons nor in glial cells. Addition to the extracellular medium of a monoclonal antibody termed mAb 1.9, directed to the catalytic domain of protein kinase C (PKC), inhibited selectively this surface protein phosphorylation activity and blocked the stabilization of LTP induced by high frequency stimulation (HFS) in hippocampal slices. This antibody did not interfere with routine synaptic transmission nor prevent the initial enhancement of synaptic responses observed during the 1-5 min period immediately after the application of HFS (the induction phase of LTP). However, the initial increase in the slope of excitatory postsynaptic potentials, as well as the elevated amplitude of the population spike induced by HFS, both declined gradually and returned to prestimulus values within 30-40 min after HFS was applied in the presence of mAb 1.9. A control antibody that binds to PKC but does not inhibit its activity had no effect on LTP. The selective inhibitory effects observed with mAb 1.9 provide the first direct evidence of a causal role for ecto-PK in the maintenance of stable LTP, an event implicated in the process of learning and the formation of memory in the brain.