Objective To explore the relationship between the genesis of dyskinesia and the degree of substantia nigra lesion in Parkinson disease(PD).Methods The hemi-parkinsonian rat model was established by injecting 6-OHDA stereotaxically to right medial forebrain bundle(MFB). Then the hemi-parkinsonian rat was injected intraperitoneally with levodopa methylester(25 mg?kg~(-1)?d~(-1),twice a day)for 21 days,the abnormal involuntary movements were estimated.After being sacrificed,the midbrain was removed,and the injured degree of dopaminergic neurons at substantia nigra was observed by tyrosine hydroxylase immunohistochemistry staining.The relationship between the abnormal involuntary movement scores and dopaminergic neurons loss at substantia nigra was evaluated by sigmoid equation analysis by using Excel software.Results The apomorphine-induced rotation rate above 7 r/min was found in 10 of 25 rats,those rats were regarded as successful hemi-parkinsonian model rats.After the treatment with levodopa methylester,8 of 10 rats displayed abnormal involuntary movements,including stereotype and contralateral rotation,the types of movements varied.Abnormal involuntary movements were appeared in the rats with dopaminergic neurons loss above 90%.The positive relationship was observed between the degree of lesion in substantia nigra and the severity of abnormal involuntary movements.Conclusions The severe loss of dopaminergic neurons at substantia nigra probably plays a role in the development of levodopa-induced dyskinesia in patient with Parkinson disease.

Objective To investigate cellular and behavioural effects of 5-HT1A receptor agonist 8- OH-DPAT in a rat model of levodopa-induced motor complications.Methods The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to right medial forebrain bundle(MFB).Two sets of experiments were performed.First,rats were intrapefitoneally treated with levodopa 50 mg/kg plus benserazide 12.5 mg/kg twice a day for 22 days.On day 23,rats intraperitoneally received either 8-OH- DPAT(1 mg/kg)or 8-OH-DPAT plus WAY-100635(0.1 mg/kg)or dissolvent with each levodopa dose as controls.In the second set,rats were intraperitoneally treated either with levodopa(50 mg/kg)plus 8-OH- DPAT(1 mg/kg)or levodopa 50 mg/kg plus dissolvent,administered twice daily for 22 consecutive days. Rotational duration and frequency of off period were estimated.After sacrificed,subcellualr distribution of GluR1 and GluR1Ser845 phosphorylation was observed by Western blot.Results 8-OH-DPAT,reversing the shortened rotational duration induced by levodopa,prolonged the rotational duration by 27.8%?6.1% and reduced the frequency of failures to levodopa by 7.2%?1.7%.Co-administration of WAY-100635,a 5-HT1A receptor antagonist,with 8-OH-DPAT eliminated the effect of 8-OH-DPAT on motor complications, indicating that the observed 8-OH-DPAT responses were probably mediated via the 5-HT1A autoreceptor. Moreover,8-OH-DPAT could regulate subcellular distribution of GluR1 and reduce hyperphosphorylation of GluR1 Ser845 by 22.1%?3.5%,which was closely associated with levodopa-induced motor complications. Conclusions These results suggest that pharmaceuticals stimulating 5-HT1A receptors could be useful in the treatment and prevention of the motor complications in parkinsonian patients.

To establish a method for detecting microdialysis recovery of tetramethylpyrazine (TMP) and ferulic acid (FA) and investigating the influencing factors, providing the basis for further in vivo microdialysis experiments. The concentration of FA and TMP in dialysates were determined by high pressure liquid chromatography ( HPLC) and probe recovery were calculated respectively. The influence of the flow rates, medium concentration, temperature and in vivo probe stability on the recovery of FA and TMP were investigated by using concentration difference method (incremental method and decrement method). The recovery obtained by incremental method were similar to by decrement method. The in vitro recovery rate of FA and TMP decreased with the increase of 1-2.5 μL min(-1), and increased obviously with the temperature of 25-42 degrees C under the same conditions. The concentration of FA and TMP had no obvious effect on the probe recovery under the same flow rate. In addition, the recovery of TMP and FA remained stable and showed similar trends under the condition of four concentration cycles, indicating that the intra day reproducibility of the concentration difference method was good. The recovery of brain microdialysis probes in vivo 8 h maintained a relatively stable, but certain differences existed between different brain microdialysis probes, demonstrating that each probe was required for recovery correction in vivo experiment. Microdialysis sampling can be used for the local brain pharmacokinetic study of FA and TMP, and retrodialysis method can be used in probe recovery of FA and TMP in vivo.
Animals ; Brain ; metabolism ; Chromatography, High Pressure Liquid ; Coumaric Acids ; analysis ; isolation & purification ; pharmacokinetics ; Drugs, Chinese Herbal ; Humans ; Microdialysis ; methods ; Pyrazines ; analysis ; isolation & purification ; pharmacokinetics ; Rats

OBJECTIVETo evaluated the safety and efficacy of hyperthermic intraperitoneal perfusion chemotherapy(HIPC) in the prevention and treatment of pseudomyxoma peritonei (PMP) recurrence after cytoreductive surgery(CRS).

METHODSStudies published in English before 2010 on HIPC after CRS for PMP were searched in PubMed database. Each study was carefully evaluated based on pre-determined criteria. Study results were comprehensively displayed in a form. A descriptive systematic review was performed.

RESULTSA total of 11 studies were included. The median survival time of patients in these studies ranged from 25.6 months to 156 months. The ranges of 1-year, 2-year, 3-year, 5-year, and 10-year survival rates were 72%-100%, 55%-96%, 59%-96%, 52%-96%, and 55%-96%, respectively. The overall complication rate ranged from 2%-15%, and the total perioperative mortality were from 0 to 7%.

CONCLUSIONHIPC after CRS is effective and safe for patients with PMP.

Chemotherapy, Cancer, Regional Perfusion ; methods ; Humans ; Peritoneal Neoplasms ; drug therapy ; surgery ; Postoperative Care ; Pseudomyxoma Peritonei ; drug therapy ; surgery ; Treatment Outcome

The aim of this study was to investigate the effect of integripetal rhodiola herb on pulmonary arterial remodeling and expression of vascular endothelial growth factor (VEGF) in high altitude pulmonary hypertension in rats. Fifty healthy male Wistar rats were divided into five groups randomly: Plain control group (LC group), 10-day plateau group (H(10) group), 30-day plateau group (H(30) group), 10-day rhodiola-treated plateau group (R(10) group), and 30-day rhodiola-treated plateau group (R(30) group). Each group included 10 rats. The rats in LC group were kept in Chengdu (500 meters above sea level), and rats in H and R groups were kept in Lhasa (3 700 meters above sea level). The rats in R group were daily treated with integripetal rhodiola herb extract (24%, 10 mL/kg) intragastrically for 10 d or 30 d, while rats in LC and H groups were treated with the same volume of saline. Mean pulmonary arterial pressure (mPAP) was detected via a catheter in the pulmonary artery by pressure waveform monitoring. The ratio value of right ventricle weight to left ventricle plus septum weight [RV/(LV + S)] was measured. The microstructure of pulmonary arterioles was examined by electron microscopy. The expression of VEGF in the lung was investigated using immunohistochemistry. The results showed that mPAP and [RV/(LV + S)] in H(10) group and H(30) group were higher than those in LC group (P < 0.05); but there was no significant difference between H(10) group and R(10) group (P < 0.05); and mPAP and [RV/(LV + S)] in H(30) group were lower than those in H(30) group (P < 0.05). Electron microscopy showed that compared to LC group, arteriolar endothelial cells were arranged in a columnar or palisading form, protruding into the lumen, accompanied with luminal stenosis, irregular internal elastic membrane, and proliferation of vascular smooth muscle cells in H groups, which was more obvious in H(30) group than in H(10) group; while these pathological changes were attenuated in the R groups compared to H groups. The levels of VEGF protein in H groups were also higher than those in LC group (P < 0.05); while the expression of VEGF in R(30) group was lower than that in H(30) group. In summary, the results show that the integripetal rhodiola herb can attenuate high altitude-induced pulmonary arterial remodeling in rats, and the inhibition of VEGF protein expression by rhodiola may be one of the mechanisms.
Altitude ; Altitude Sickness ; prevention & control ; Animals ; Arterioles ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Hypertension, Pulmonary ; metabolism ; pathology ; physiopathology ; Male ; Pulmonary Artery ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Rhodiola ; Vascular Endothelial Growth Factor A ; metabolism