p38 MAPK inhibition alleviates experimental acute pancreatitis in mice.

BACKGROUND: The mitogen-activated protein kinases (MAPKs) signaling pathway is involved in inflammatory process. However, the mechanism is not clear. The present study was to investigate the role of p38 MAPK in acute pancreatitis in mice. METHODS: Mice were divided into 4 groups: saline control; acute pancreatitis induced with repeated injections of cerulein; control plus p38 MAPK inhibitor SB203580; and acute pancreatitis plus SB203580. The pancreatic histology, pancreatic enzymes, cytokines, myeloperoxidase activity, p38 MAPK and heat shock protein (HSP) 60 and 70 were evaluated. RESULTS: Repeated injections of cerulein resulted in acute pancreatitis in mice, accompanying with the activation of p38 MAPK and overexpression of HSP60 and HSP70 in the pancreatic tissues. Treatment with SB203580 significantly inhibited the activation of p38 MAPK, and furthermore, inhibited the expression of HSP60 and HSP70 in the pancreas, the inflammatory cytokines in the serum, and myeloperoxidase activity in the lung. CONCLUSION: The p38 MAPK signaling pathway is involved in the regulation of inflammatory response and the expression of HSP60 and HSP70 in acute pancreatitis.

[Neuroprotective effect of surround needling combined with acupoint injection on acute herpetic neuralgia].

OBJECTIVE: To explore the effect and mechanism of surround needling combined with acupoint injection on acute herpetic neuralgia (AHN). METHODS: Ninety-nine patients with T6-T10 segment AHN were randomly divided into 3 groups, 33 cases in each group, including 2 cases dropped off in the surround needling group, 4 cases dropped off in the acupoint injection group, and 3 cases dropped off in the combined group. Oral valacyclovir was given in each group, 0.3 g each time, 2 times a day for 10 days. Oblique insertion of needle used at ashi points around the herpes in the surround needling group, and continuous wave was stimulated to tolerance for 20 min; the same acupoints were selected as the surround needling group, stimulated with the mixture injection of mecobalamin and lidocaine in the acupoint injection group; After the surround needling, acupoint injection was performed in the combined group. The treatment was given once a day, 14 times for a course, and one course was needed in all groups. The skin healing conditions (blistering, crusting, and dislocation time) of each group were compared after treatment. The pain scores, pain area and quality of life scores in each group were observed before and after treatment. The levels of neuron specific enolase (NSE), substance P (SP) and calcitonin gene-related peptide (CGRP) in the local blister fluid were measured before and after treatment in all groups. RESULTS: The blistering, crusting and dislocation time in the combined group were earlier than the other two groups (all P<0.05). The pain score and pain area in the each group were significantly lower than those before treatment, and the quality of life score was significantly higher than that before treatment (all P<0.05). The improvements of pain score and quality of life score in the combined group were more obvious than the other two groups (all P<0.05). After treatment, the levels of NSE, SP and CGRP in the local blister fluid in each groups were significantly lower than those before treatment (all P<0.05). The indexes in the combined group were significantly lower than those in the other two groups (all P<0.05). CONCLUSION: Both surround needling and acupoint injection have an adjuvant effect on AHN. The combination of the two is better, the skin is healed quickly, the analgesia is significant, and the contents of local NSE, SP and CGRP are significantly decreased. The mechanism of action is to exert neuroprotective effects.

Pre-clinical evaluation of a new indirectly labeled 99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide with HYNIC as bifunctional chelator.

BACKGROUND: Technetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator. METHODS: The cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1. RESULTS: The molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl). CONCLUSION: The findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.