To the Editor： Deep brain stimulation （DBS） is widely used in Parkinson＇s disease. Here, we report a bilateral hemorrhage case Figure 1： Postoperative computed tomography data indicating the disease ...evolution in this case. （a） A computed tomography scan 8 h after the first operation; （b） A computed tomography scan 8 h after the second operation; （c） A computed tomography scan 13 day after the second operation.
Aim： The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle ...dogs.
Methods： The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry （LC/MS/MS）. The pharmacokinetic parameters were calculated using the Topfit 2.0 program. Results： The pharmacokinetic results showed that AUC0-t （23.9±8.26 pg·h·mL^-1） in plasma after oral administration was significantly higher than after transdermal delivery （1.00±0.43 pg·h·mL^-1）. In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration.
Conclusion： The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.
The aim of this study was to establish a clinically relevant model for gene transfer to liver with an adenoviral vector encoding wild-type p53 as a first step toward use of this class of gene ...products in the treatment of primary and metastatic liver tumors.
Full-size or 50% hepatectomized rat livers were subjected to asanguineous portal perfusion with a replication-defective adenoviral vector encoding wild-type p53 (Ad5p53), whereas control animals received adenoviral vector encoding Escherichia coli beta-galactosidase (beta-gal) (Ad5LacZ) or Ringer's lactate only. Liver biopsy specimens, blood samples, and liver weight were serially obtained. Gene transfer and expression were confirmed by X-Gal staining for gamma-gal, DNA/RNA polymerase chain reaction, (PCR) and Western blots for p53 and beta-gal. Liver integrity was assessed by histologic findings, serum transaminase levels, and synthetic function.
The gene transfer rate in whole liver and after hepatectomy ranged from 20% to 40%. DNA PCR showed Ad sequences in livers transduced with Ad5p53 and Ad5LacZ. RNA PCR and Western blot confirmed expression and production of recombinant wild-type p53. Liver regeneration was not affected by p53 gene transduction. Liver histologic findings and synthetic function were not different between transduced and control groups.
Ad5p53 gene transfer to full-size or hepatectomized livers is efficient. Liver regeneration and hepatocyte function are unaffected by overexpression of p53. Adenovirus-mediated tumor-suppressor transduction of the liver is a safe and promising adjuvant in cancer gene therapy.
Background Ahmed Glaucoma Valve implantation （AGVI） is blood-aqueous barrier （BAB） has been noted after some surgica BAB disruption afterAGVl. used to treat refractory glaucoma. Breakdown of the ...techniques. The current study was designed to assess Methods Anterior chamber protein content was measured by the laser flare cell photometry in 22 eyes of 22 patients with refractory glaucoma before AGVI and at each postoperative visit up to 1 month. Results Before AGVI the mean aqueous flare values in all eyes were （15.17＋9.84） photon counts/ms. After AGVI, the values significantly increased at day 1, day 3, and week I compared to those before AGVI （all P 〈0.05） with a peak at day 3. They returned to pre-operative levels at week 2, and were lower than preoperative level at month 1. Eyes with previous intraocular surgery history had greater aqueous flare values than those without previous intraocular surgery history, but there were no significant differences at all time points postoperatively （all P 〉0.05）. Furthermore, eyes with shallow anterior chambers had greater aqueous flare values at day 3 and week 1 （all P 〈0.05）. When comparing eyes with other refractory glaucoma conditions, neovascular glaucoma combined with intravitreal bevacizumab injection resulted in lower aqueous flare values after AGVI, but no significant differences were observed at all time points, postoperatively （all P 〉0.05）. Conclusions The BAB was impaired and inflammation was present in the anterior chamber in refractory glaucomatous eyes following AGVI. However, such conditions were resolved within 1 month postoperatively. Intravitreal bevacizumab treatment in neovascular glaucoma eyes before AGVI may prevent BAB breakdown.
Objective To explore the changes in spatial learning performance and long-term potentiation （LTP） which is recognized as a component of the cellular basis of learning and memory in normal and ...lead-exposed rats after administration of melatonin （MT） for two months. Methods Experiment was performed in adult male Wistar rats （12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment）. The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin （3 mg/kg） or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus （DG） area of the hippocampus in vivo. Results Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. Conclusion Melatonin is not suitable for normal and lead-exposed children.
Background The application of pulmonary valved conduit to reconstruct the continuity between right ventricles and pulmonary artery is one of the major surgeries.This study aimed to establish an in ...vivo model of in situ implantation using pulmonary valved conduit in large animals under off-pump condition to validate the long-term effects of artificial pulmonary valved conduit.Methods Domesticate juvenile male sheep and tissue-engineered poorine pulmonary valved conduit were used for the experiment：30 sheep,weighing （15±3） kg （range 13 to 17 kg） were randomly divided into two groups which were all operated under general anesthesia by off-pump surgery （group 1） and left thoracotomy （group 2）.Two different off-pump surgical methods were used to perform cannulation in sheep pulmonary artery to replace part of sheep pulmonary artery with pulmonary valved conduit which will work together with sheep pulmonary artery and valves.During the experiments,animal survival,complication rates,operating time and blood loss were recorded to compare the results between groups and to establish a surgical method with minimal invasion,simplicity,safety,and high success rates.Results In group 1,a total of 15 cases of surgeries were performed,in which two sheep died; the operative mortality was 13.3％ （2/15）.In group 2,a total of 15 cases of surgeries were performed,and the surgical mortality rate was 0 （0/15）.The operation time and blood loss in group 2 was significantly better than that in group 1.The postoperative echocardiograms showed that,after the surgeries by these two methods,the blood flows were normal,and the valves can open and close freely.Autopsy after 6 months showed that the inner wall and the valves of pulmonary valved conduit were smooth with no thrombus formation.Conclusion These two off-pump methods are feasible and safe with fewer traumas; but the second method is better and particularly suitable for the establishment of a juvenile animal model.
Background Neovascular glaucoma （NVG） is a refractory disease which is difficult to manage. This study aimed at evaluating the efficacy and safety of adjunctive intravitreal bevacizumab （IVB） ...injection in conjunction with Ahmed glaucoma valve implantation （AGVI） in the management of NVG. Methods This was a retrospective study of patients with NVG in whom AGVI was performed between October 2008 and May 2012. The sample was divided into two groups according to the pretreatment： with adjunctive IVB injection （the IVB group, n=25 eyes） and without adjunctive IVB injection （the control group, n=28 eyes）. The surgical success rate, number of antiglaucoma medications used, best-corrected visual acuity （BCVA）, postoperative complications, regression, and recurrence of iris neovascularization （NVI） were analyzed between the groups. Results The surgical outcomes of the two groups were compared. The complete success rates in the IVB and control groups were 84.0% and 64.3% at 12 months and 80.0% and 53.6% at 18 months, respectively. There was a significant difference between the two groups （P=0.041）. Mean postoperative intraocular pressures, mean number of postoperative antiglaucoma medications, and BCVA were not significant between the two groups. The NVI in 22 （88.0%） eyes had completely regressed within 2-8 days after IVB. However, NVI recurred in 10 eyes （40.0%） 2-9 months later after IVB. The IVB group had only 1 case （4.0%） of hyphema out of 25 eyes, while there were 8 （28.6%） cases of hyphema out of 28 eyes in the control group （P=0.026）.Conclusions This study showed that preoperative IVB injection reduced NVI remarkably, decreased hyphema, and led to higher surgical success rates. Pre-operative IVB injection may be an effective adjunct to AGVI in the management of NVG.
AIM:To evaluate changes of proinflammatory cytokines in aqueous humor of patients with acute primary angleclosure(APAC) and age-related cataracts. METHODS:Twenty eyes of 20 APAC patients and 15 eyes ...of 15 age-related cataract patients were included in this cross-sectional study. Aqueous humor samples were collected prospectively. The levels of 20 proinflammatory cytokines were evaluated in the aqueous humor of the APAC and cataract patients using the multiplex bead immunoassay technique. Clinical data were collected for correlation analysis.RESULTS:Seven of the 20 proinflammatory cytokines included in the magnetic bead panel were detectable in both APAC eyes and cataract eyes:interleukin(IL)-10, IL-12, IL-15, IL-21, IL-6, chemokine(C-C motif) ligand 20, and tumor necrosis factor alpha(TNF-α). IL-27 was only detectable in APAC eyes. Compared with the cataract eyes, the APAC eyes had significantly elevated concentrations of IL-12(P=0.036), IL-15(P=0.001), IL-6(P=0.012), and IL-27(only detectable in APAC eyes). Age was positively correlated with IL-12(P=0.022) and IL-6(P=0.037), and time elapsed between APAC onset and aqueous humor samples collection was positively correlated with IL-15(P=0.037), IL-27(P=0.040), and TNF-α(P=0.042).CONCLUSION:Several proinflammatory cytokines including IL-12,IL-15, IL-6 and IL-27, were elevated in the APAC eyes and may be implicated in its pathologic mechanism.
AIM：To evaluate changes of proinflammatory cytokines in aqueous humor of patients with acute primary angleclosure（APAC） and age-related cataracts. METHODS：Twenty eyes of 20 APAC patients and 15 eyes ...of 15 age-related cataract patients were included in this cross-sectional study. Aqueous humor samples were collected prospectively. The levels of 20 proinflammatory cytokines were evaluated in the aqueous humor of the APAC and cataract patients using the multiplex bead immunoassay technique. Clinical data were collected for correlation analysis.RESULTS：Seven of the 20 proinflammatory cytokines included in the magnetic bead panel were detectable in both APAC eyes and cataract eyes：interleukin（IL）-10, IL-12, IL-15, IL-21, IL-6, chemokine（C-C motif） ligand 20, and tumor necrosis factor alpha（TNF-α）. IL-27 was only detectable in APAC eyes. Compared with the cataract eyes, the APAC eyes had significantly elevated concentrations of IL-12（P=0.036）, IL-15（P=0.001）, IL-6（P=0.012）, and IL-27（only detectable in APAC eyes）. Age was positively correlated with IL-12（P=0.022） and IL-6（P=0.037）, and time elapsed between APAC onset and aqueous humor samples collection was positively correlated with IL-15（P=0.037）, IL-27（P=0.040）, and TNF-α（P=0.042）.CONCLUSION：Several proinflammatory cytokines including IL-12,IL-15, IL-6 and IL-27, were elevated in the APAC eyes and may be implicated in its pathologic mechanism.
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