Background: Clonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity.
Methods: Clonidine (30, 100, and 300 [mu]g/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity.
Results: In neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain. 相似文献
A conjugate of antisense oligodeoxynucleotide (AS ODN) covalently linked with deoxorubicin (DOX) was synthesized. Its properties and antitumour activity in human carcinoma DOX resistant cells (KB-A-1) were investigated in vitro. The results showed that the conjugate was strongly stable both in Dulbecco's Phosphate-Buffered Saline (PBS) and in culture medium. The intracellular concentration of the conjugate was higher than that of the AS DON by HPLC analysis. The conjugate showed potent dose-dependent inhibition to the growth of KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) and then exposed to DOX for 24 h, the IC50 value of DOX decreased from 21.5 to 2.2 microM. In contrast, when treated with the mixture of the same concentration of the AS ODN with equivalent DOX, the IC50 value of DOX was 16.8 microM. Intracellular DOX concentration was detected in KB-A-1 treatment with the conjugate in vitro by HPLC. The results showed that the intracellular DOX concentration was 6.4-fold increased in KB-A-1 cells treated with the conjugate compared to treatment with DOX alone. In contrast, 1.8-fold increasing was observed when treated with the AS ODN. Western blot analysis showed a significantly decrease in the amount of P-glycoprotein in KB-A-1 cells. These results suggest that the conjugate is effective in reversing multidrug resistance. Certainly, further studies are conducting to explore the antitumour effect of the conjugate in vivo. 相似文献
Objective: Two major changes have occurred in inguinal hernia repair during the last two decades: (i) the use of tension‐free mesh repair; and (ii) the application of laparoscopic technique for repair. The aims of the present study were to study: (i) how inguinal hernia repair was carried out; and (ii) the outcome of inguinal hernia repair in Hospital Authority (HA) hospitals. Methodology: This was a retrospective analysis on 8311 elective inguinal hernia repairs performed in 16 HA hospitals from January 2001 to December 2003. The mean age was 63.9 ± 14.2 years, and the male to female ratio was 22.0 : 1.0. Among these, 869 (10.5%) repairs were performed with the laparoscopic approach and 7442 (89.5%) repairs with the open approach. The proportion of laparoscopic hernia repair increased from 8.7% to 12.6%. Results: For open repair, 39% of cases were carried out with regional anaesthesia, 32% with general anaesthesia and 29% with local anaesthesia (LA). Furthermore, mesh repair was used in 88% of the patients. For laparosocpic repair, 98.4% of cases were carried out under general anaesthesia, and all patients had mesh repair using the totally extraperitoneal approach. A significantly higher proportion of bilateral repair and recurrent hernia repair was performed with the laparoscopic approach (P = 0.000). For primary unilateral repair, there was no significant difference in the postoperative length of stay (LOS) and the total LOS between the laparoscopic and the open surgery groups. No difference in LOS was found in recurrent hernia repair between the two groups. With respect to bilateral repair, both the preoperative LOS (P = 0.036) and total LOS (P = 0.039) were shorter in the laparoscopic group. Furthermore, a significantly higher proportion of day‐surgery patients was observed in the laparoscopic group than the open surgery group (21.3%vs 16.9%, P = 0.001). Nevertheless, when only the results of 2003 were analyzed, the postoperative LOS (P = 0.000) and total LOS (P = 0.000) were significantly shorter in the laparoscopic group than the open surgery group. The LOS parameters were significantly shorter in the open surgery LA subgroup compared with the non‐LA subgroup (P = 0.000), and they were not different from those in the laparoscopic group. Conclusions: The open mesh repair is the predominant approach for inguinal hernia repair in HA hospitals. The originally described local anaesthetic approach was under utilized, although it resulted in good outcome. The use of laparoscopic hernia repair is increasing and a learning curve was recently observed with improved outcome. 相似文献
Several neurodegenerative diseases, including motor neuron disease (MND), are characterized by formation of abnormal cytoskeleton-derived inclusions which contain ubiquitin (Ubq). We have studied the distribution of Ubq in 26 cases of MND with light and electron microscopic immunocytochemistry. Ubiquitin-positive inclusions were found in neurons of anterior horns in most cases of amyotrophic lateral sclerosis (ALS) but were not present in other forms of MND. Ubiquitin immunoreactivity was observed in 10-15 nm intraneuronal filaments, which were not stained by antibodies to neurofilaments, and on dense bodies of dystrophic neurites throughout the neuropil of anterior horns and pyramidal tracts. Data analysis showed a trend toward lower percentage of Ubq-positive neurons in cases with longer duration of illness or lower number of neurons. A high percentage of Ubq-positive inclusions occurred in cases with an aggressive clinical course, suggesting that ubiquitination takes place at early stages of the disease. 相似文献
Objective: To evaluate the effect and safety of clinical use of zoledronic acid in the treatment of malignant hypercalcemia. Methods: A multi-center, open phase II clinical trial was conducted in 15 cases with malignant hypercalcemia who received zoledronic acid intravenously for 15 min. The level of blood calcium and side effects were recorded regularly within 28 days after injection. Results: One case was dropped out due to bad compliance. The complete response rate (the corrected serum calcium was reduced to normal level) was 100.00% (14/14). The medium time of complete response rate was 5.07 days. The medium maintain time was 22.30 days. Slight, or moderate fever was observed. Conclusion: Zoledronic acid can effectively reduce the malignant hypercalcemia. The use of zoledronic acid appears to be safety and convenient. 相似文献