[Effects of tibial second toe free flap bridged with blood flow and nerve in the treatment of severe flexion contracture of the proximal interphalangeal joint].

Objective: To investigate the effects of tibial second toe free flap bridged with blood flow and nerve in the treatment of severe flexion contracture of the proximal interphalangeal joint. Methods: A retrospective observational study was conducted. From March 2013 to October 2019, 9 patients with severe flexion contracture (type Ⅲ) of the proximal interphalangeal joint after trauma operation, conforming to the inclusion criteria, were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 5 males and 4 females, aged from 17 to 62 years. After the contracture tissue affecting the extension of the proximal interphalangeal joint was cut off, and the scar tissue was resected, the size of the volar wound near the proximal interphalangeal joint in extended position was 2.0 cm×1.0 cm-2.5 cm×1.5 cm, with the length of proper digital artery and nerve defect being 1.0-1.5 cm. A free flap of the same size as the wound was cut from the tibial side of the second toe and transplanted to repair the wound, and the defective proper digital artery and nerve was repaired by bridging with the tibial proper plantar digital artery and nerve of about 1.5 cm in length. The full-thickness skin graft was taken from the proximal tibial side of the lower leg to repair the wound at flap donor site. The wound at skin graft donor site was sutured directly. The survival of flap and skin graft was observed after operation. The patients were followed up, and at the last follow-up, the recovery of the affected finger and the second toe, including the donor and recipient areas were observed, the two-point discrimination distances of the flap repaired site and the pulp of the affected finger were observed and measured at the same time, the blood flow patency of bridged vessel of the affected finger was examined by Allen test, and the function of the proximal interphalangeal joint of the affected finger was evaluated according to Chinese Medical Association's standard for the range of motion of proximal interphalangeal joint. Results: The flaps and skin grafts survived smoothly after operation. The follow-up after operation lasted for 5 to 22 months, with a mean of 10 months. At the last follow-up, the flap repaired site had good shape, good color and texture, with the two-point discrimination distance being 9-12 mm, and the two-point discrimination distance of the pulp of the affected finger was 6-10 mm; the Allen test results of the affected fingers were all negative (i.e., the bridged vessels had good blood flow patency), with no recurrence of flexion contracture, and the function of the proximal interphalangeal joint was evaluated as excellent; the skin graft area of the second toe was not ruptured but was a little pigmented, and the flexion and extension activities of toe were good. Conclusions: The tibial second toe free flap bridged with blood flow and nerve has reliable therapeutic effect in the treatment of severe flexion contracture of the proximal interphalangeal joint, and the color and texture of the flap repaired area are good. Bridging to repair the severely contracted proper digital artery and nerve is beneficial to improve the blood supply of the finger body and rebuild the sensation.

[Comparative study of the effects between second toe tibial dorsal artery flap and second toe tibial plantar proper artery flap in repairing finger skin and soft tissue defects].

Objective: To compare the effects between second toe tibial dorsal artery flap (2-TDAF) and second toe tibial plantar proper artery flap (2-TPPAF) in repairing finger skin and soft tissue defects. Methods: A retrospective cohort study was conducted. From January 2019 to June 2020, 27 patients with skin and soft tissue defects at the fingertips with area of 1.5 cm×1.2 cm-2.6 cm×1.8 cm after debridement who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 21 males and 6 females, aged 19-59 (37±10) years. According to flap repair methods used in the defective fingers, the patients were divided into 2-TDAF group (12 cases) and 2-TPPAF group (15 cases). The area of 2-TDAF ranged from 1.5 cm×1.2 cm to 2.5 cm×1.6 cm, and the area of 2-TPPAF ranged from 1.7 cm×1.3 cm to 2.6 cm×1.8 cm. Full-thickness skin grafts from the medial side of the ipsilateral leg were grafted to the wounds in donor sites, and the wounds in donor sites of skin grafts were directly sutured. Flap arterial diameter, flap excision time, flap survival situation of patients in 2 weeks after operation, and follow-up time were recorded. At the last follow-up, the two-point discrimination distance of flap graft site, total action motion (TAM) of the finger joints, and wound healing of the flap donor site were recorded; the Vancouver scar scale (VSS) was used to score the scar in donor area of the second toe and the recipient area of fingers; the appearance and self-satisfaction subscales of the Michigan hand outcomes questionnaire (MHQ) were used to evaluate the affected finger. Data were statistically analyzed with independent sample t test or Fisher's exact probability test. Results: The flap artery diameter of patients in 2-TDAF group was 0.35-0.80 (0.56±0.14) mm and the flap cutting time was (14.0±2.7) min, which were significantly shorter than 0.80-1.35 (1.02±0.16) mm and (19.7±3.4) min in 2-TPPAF group (with t values of 7.81 and 4.79, respectively, P<0.01). The flaps of patients in the 2 groups in recipient areas survived well in 2 weeks after operation, and the wounds in donor areas of flaps of patients in the 2 groups healed well at the last follow-up. There was no statistically significant difference in the postoperative follow-up time, and two-point discrimination distance of flap graft site, TAM of the finger joints, VSS score of scar in the second toe donor site and the finger recipient site, and the appearance and self-satisfaction of MHQ scores of the affected finger at the last follow-up (P>0.05). Conclusions: Compared with 2-TPPAF, 2-TDAF has a shallower anatomical layer and shorter time for surgical flap removal, which can preserve the proper arteries and nerves at the base of the toes and reduce the damage to the donor site.

[Multiple free homologous superficial peroneal artery perforator flaps of crus for repair of multiple hand wounds].

Objective: To explore the effects of multiple free homologous superficial peroneal artery perforator flaps of crus for repair of multiple hand wounds. Methods: From November 2017 to December 2018, eight cases with eighteen hand wounds were hospitalized in our unit. Among them, wounds were distributed in the forefinger and middle finger in four cases, wounds were distributed in the middle finger and ring finger in two cases, wounds were distributed in the forefinger, middle finger, and ring finger in one case, and wounds were distributed in the middle finger, ring finger, and little finger in one case. The area of skin defect ranged from 1.5 cm×0.8 cm to 4.0 cm×3.0 cm. There were 4 males and 4 females, aged 34-62 years. Wounds of six cases were repaired by two free superficial peroneal artery perforator flaps from homolateral crus, and those of two cases were repaired by three free superficial peroneal artery perforator flaps from homolateral crus. Superficial peroneal artery and its accompanying vein of flap were anastomosed by end to end with digital artery and palmar or dorsal subcutaneous vein of recipient site during the operation. The area of flap ranged from 2.5 cm×1.2 cm to 5.0 cm×4.0 cm. No nerve was harvested during the operation, and donor site was sutured directly. The survival of the flaps and the healing of donor sites were recorded. During follow-up, the recovery of donor and recipient sites was observed. Results: All flaps survived well, donor site healed well. No vascular crisis occurred. Follow-up for 4 to 12 months showed that the appearance of flap was satisfactory with good color, texture, elasticity, and function. Protective sensation of recipient site was recovered. Five months after operation, flap of finger pulp in one case was swollen slightly with two-points discrimination of 10 mm, which received the thinning surgery. Obvious scar formation was not observed in donor site of crus. The appearance of the donor site was good without functional damage. Conclusions: The application of multiple free homologous superficial peroneal artery perforator flaps of crus to repair the multiple hand wounds has advantages of easy acquisition, easy operation, little effect on donor sites, and satisfactory clinical effects.

[Clinical effects of extra-long lateral femoral supercharged perforator flaps in repair of foot and ankle wounds].

Objective: To investigate the clinical effects of extra-long lateral femoral supercharged perforator flaps in repair of ankle and foot wounds. Methods: From March 2014 to October 2018, 16 patients with foot and ankle injuries were admitted to our hospital and left large area of wounds on foot and ankle after emergency treatment. There were 13 males and 3 females, with age of 27 to 60 years. The area of the wounds ranged from 14 cm×10 cm to 40 cm×17 cm. The wounds were repaired with extra-long lateral femoral supercharged perforator flaps. The widths of flaps in 8 patients were longer than 8 cm, and the bilobed flaps were designed to repair the wounds. The area of the flaps ranged from 12 cm×5 cm to 40 cm×9 cm. During the operation, 54 perforators were detected, with an average of 3.2 perforators in each flap, and 36 source arteries of perforators were detected. The blood vessel trunk of 15 patients was descending branch of the lateral femoral circumflex artery, and their supercharged mode was anastomosis of the bulky perforator of descending branch of the lateral femoral circumflex artery with the oblique branch of the lateral femoral circumflex artery and/or medial femoral circumflex artery or the descending branch of superficial illiac circumflex artery. The blood vessel trunk of 1 patient was oblique branch of the lateral femoral circumflex artery, and the supercharged mode of the patient was anastomosis of the oblique branch of the lateral femoral circumflex artery with the bulky perforator of the descending branch of the lateral femoral circumflex artery. The wounds were covered with the flaps after supercharged blood vessel anastomosis, and blood vessels in the donor sites were anastomosed with those in the recipient sites. The donor site was sutured directly. The survival of the flap after the operation and healing time of the wound, and the flap condition, the two-point discrimination distance of flap in patients who were reconstructed with sensation, the recovery of the ankle function, and the appearance of the donor site during follow-up were recorded. Results: A total of 17 flaps in 16 patients were designed, including 8 bilobed flaps and 9 non-lobulated flaps. Sixteen flaps in 15 patients survived. Vascular crisis occurred in the flap of one patient, and the flap survived when the vascular crisis was relieved by the second operation. The healing time of foot and ankle wounds ranged from 12 to 90 days. All the lateral femoral donor sites healed completely. During follow-up of 8 to 48 months, flaps in 2 patients were slightly bloated and were trimmed in 6 months after the operation. The other flaps were with good appearance, soft texture, good elasticity, and no rupture or ulceration. The two-point discrimination distances of flaps ranged from 7 to 16 mm in 8 patients who were reconstructed with sensation, and the other flaps recovered protective sensation. The flexion and extension function of ankle joint recovered well, and the walking function was not affected significantly. All donor sites formed linear scar, with no deep tissue infection such as osteomyelitis. Conclusions: The application of extra-long lateral femoral supercharged perforator flaps to repair the large area of wounds in foot and ankle can significantly reduce damage to donor sites and has advantages of rich blood supply and good safety, thus it has satisfactory clinical effects.

[The relationship between fragmented QRS complex and coronary collateral circulation in patients with chronic total occlusion lesion without prior myocardial infarction].

Objective: To explore the relationship between fragmented QRS complex(fQRS) and coronary collateral circulation(CCC) in patients with chronic total occlusion(CTO)lesion without prior myocardial infarction. Methods: This retrospective study analyzed 238 consecutive patients with CTO lesion in one of the major coronary arteries from May 2014 to October 2015 in our department. Patients were divided into poor CCC group (grade 0 and 1, 58 cases) and good CCC group(grade 2 and 3, 180 cases) based on Rentrop's classification of CCC. The fQRS was defined as the presence of an additional R wave or notching of R or S wave or the presence of fragmentation in two contiguous electrocardiogram leads corresponding to a major coronary artery territory. Multivariate logistic regression was used to analyze the relationship between CCC and fQRS on electrocardiogram. Results: Compared with good CCC group, patients in poor CCC group had older age((65.2±8.9)years old vs. (60.3±10.1) years old, P=0.03), higher plasma glucose ((7.22±3.00) mmol/L vs.(6.31±1.83)mmol/L, P=0.04), and lower left ventricular ejection fraction ((45.2±11.4)% vs. (51.2±13.5)%, P=0.02). None of patients had Rentrop grade 0, the presence of fQRS on ECG in patients with Rentrop grade 1, grade 2, and grade 3 CCC was 69.0% (40/58), 48.6% (35/72) , and 19.4% (21/108), respectively (P<0.01). The presence of fQRS were higher in poor CCC group than in good CCC group (69.0%(40/58)vs. 31.1%(56/180), P<0.01), and number of leads with fQRS were higher in poor CCC group than in good CCC group (3(0, 4)vs.0(0, 3), P<0.01). Multivariate logistic regression analysis demonstrated that poor CCC growth in patients with CTO lesion without prior myocardial infarction was independently related to the presence of fQRS (OR=3.659, 95%CI 1.619-8.217, P<0.01). Conclusion: Poor CCC in patients with CTO lesion without prior myocardial infarction is independently related to the presence of fQRS on electrocardiogram.

Effect of dopamine depletion on DARPP-32 protein in ischemic rat striatum.

AIM: To study the effects of dopamine depletion on the phosphorylation level, intracellular distribution, and mRNA expression of DARPP-32 in the ischemic striatum and to elucidate the mechanisms underlying the ischemic injury. METHODS: A complex model of SN lesioning with 6-OHDA to deplete dopamine and four vessels occlusion for inducing forebrain ischemia was constructed in rats. DARPP-32 was investigated with autoradiogram, immunohistochemistry and in situ hybridization. RESULTS: The [32P]phosphate incorporation of DARPP-32 was reduced in vitro following ischemia. However, the [32P]phosphate incorporation, the numbers of positive neurons, and mRNA expression of DARPP-32 were increased in SN lesioning plus ischemic rats with denervated striatum. CONCLUSION: Dopamine depletion reduced the DARPP-32 phosphorylation in vivo following ischemia, and protected DARPP-32 immunoreactivity and mRNA expression level against the reduction induced by ischemia.

Esters of chlorambucil with 2-substituted 1,4-dihydroxy-9,10-anthraquinones as multifunctional anticancer agents.

Novel twelve esters of chlorambucil with 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone were synthesized and tested for their antitumor activity in mice bearing S-180 ascitic cells as well as cytotoxic activity against L1210 cells. Eight of them were highly cytotoxic on L1210 cells (ED(50), <6 microg mL(-1)) and derivatives 1 and 12 (T/C, 200 and 205%) appeared more active in vivo than chlorambucil (T/C, 168%).

[Changes in the state of phosphorylation of DARPP-32 of gerbil striatum during ischemia].

Using the mongolian gerbil model of transient forebrain ischemia by bilateral carotid arteries occlusion, the levels of phosphorylation and the amount of DARPP-32 in striatum were measured by back-phosphorylation and Western-blotting assay in vitro. Transient forebrain ischemia had no effect on the immunoreaction of DARPP-32 in striatum, but the state of phosphorylation of DARPP-32 showed a significant change. The [32P] phosphate incorporation in DARPP-32 decreased after 2, 7 or 10 min of ischemia, but increased after a 5-min ischemia. In contrast, the result of back-phosphorylation in vivo was opposite to that obtained in vitro.

Modulation of medical prefrontal cortical D1 receptors on the excitatory firing activity of nucleus accumbens neurons elicited by (-)-Stepholidine.

(-)-Stepholidine (SPD), with D1 agonistic action, elicited an excitatory firing activity of nucleus accumbens (NAc) neurons by intravenous administration, but this effect was hardly observed by iontophoresis of SPD into the NAc. The present study intends to determine whether D1 receptors in the medial prefrontal cortex (mPFC) are involved in the action of SPD on the firing activity of NAc neurons in the chloral hydrate-anesthetized male rats. The results showed that the intra-mPFC microinjected SCH-23390 (D1 antagonist, 30 mM), but not the D2 antagonist spiperone (30 mM), significantly attenuated the enhanced firing activity induced by intravenous injection of SPD (2 mg/kg). Similarly, the excitatory firing of NAc neurons was also exhibited by the microinjection of either SPD or D1 agonist SKF-38393 into the mPFC. The SPD-induced excitatory effect was in a dose-dependent way from 277.8 +/- 51.3% (10 mM) to 1105.4 +/- 283.5% (30 mM) of NAc basal firing, which was completely reversed by SCH-23390 (i.v.). Furthermore, the direct D1 agonistic action of SPD on the mPFC neuron was observed with microiontophoresis. These results indicate that SPD possesses a direct agonistic action on the mPFC D1 receptors, by which it modulates the firing activity of NAc neurons.

2-(1 -hydroxyiminoalkyl)-1 ,4-dimethoxy-9,10-anthraquinones: synthesis and evaluation of cytotoxicity.

A series of 2-(1-hydroxyiminoalkyl)-1,4-dimethoxy-9,10-anthraquinones (oximes) was synthesized and evaluated for cytotoxicity against L1210 cells and A549 cells. These oximes showed a greater cytotoxic activity compared to those of 2-(1-hydroxyalkyl)-1,4-dimethoxy-9,10-anthraquinones as the hydroxyalkyl bioisosteres. The enhanced cytotoxicity assumed to be due to the improved water solubility of the hydroxyimino group. Moreover, it was found that the cytotoxicity of the oximes decreased with elongation of alkyl groups at the side chain. All of the synthesized compounds showed higher cytotoxicity against L1210 cells than A549 cells.

Synthesis and evaluation of the antitumor activity of 2-substituted 1,4-dihydroxy-9,10-anthraquinones.

2-(1-Hydroxyiminoalkyl)-1,4-dimethoxy-9,10-anthraquinones were demethylated to produce 2-(1-hydroxyiminoalkyl)-1,4-dihydroxy-9,10-anthraquinones (1,4-dihydroxy-9,10-anthraquinone, DHAQ), oxime hydroxyl groups were in turn acylated to give the corresponding 2-(1-acyloxyiminoalkyl)-DHAQ derivatives. The anti-proliferative activity of 2-(1-hydroxyiminoalkyl)-DHAQ derivatives was found to be dependent on the size of an alkyl chain. Thus, DHAQ analogues with alkyl chains longer than heptyl had negligible anti-proliferative activity, whilst those compounds possessing shorter chains demonstrated moderate anti-proliferative activity (ED50, 2.73-19.21 microM). However, the antitumor activity as expressed by T/C values did not correlate with the anti-proliferative activity; 2-(1-hydroxyiminononyl)-DHAQ with an ED50 value of more than 20 microM exhibited potent antitumor activity (T/C, 166%). Only four of the 2-(1-hydroxyiminoalkyl)-DHAQ analogues showed good antitumor activity (T/C, > 150%); 2-(1-hydroxyiminobutyl)-DHAQ (T/C, 163%), 2-(1-hydroxyiminopentyl)-DHAQ (T/C, 180%) and 2-(1-hydroxyiminononyl)-DHAQ (T/C, 166%). Acylation of the hydroxyl group of these oximes enhanced the anti-proliferative activity and antitumor effects; 2-(1-propanoyloxyiminopropyl)-DHAQ (ED50, 4.41 microM; T/C, 221%) vs. 2-(1-hydroxyiminopropyl)-DHAQ (ED50, 14.64 microM; T/C, 100%) and 2-(1-propanoyloxyiminobutyl)-DHAQ (ED50, 2.65 microM; T/C, 202%) vs. 2-(1-hydroxyiminobutyl)-DHAQ (ED50, 16.43 microM; T/C, 163%).

Naphthazarin derivatives (V): formation of glutathione conjugate and cytotoxic activity of 2-or 6-substituted 5,8-dimethoxy-1,4-napthoquinones in the presence of glutathione-S-transferase, in rat liver S-9 fraction and mouse liver perfusate.

Formation of glutathione (GSH) conjugates with 2- or 6-(1-hydroxymethyl)- and 2-(1-hydroxyethyl)-DMNQ derivatives (DMNQ, 5,8-dimethoxy-1,4-naphthoquone) was carried out in phosphate buffer (pH 7.4), in the presence of glutathione-S-transferase (GST), in rat liver S-9 fraction and by perfusion, and the rates of conjugates formation were compared and correlated to cytotoxicity. The GSH conjugates of 6-(1-hydroxyalkyl)-DMNQ derivatives were formed faster than 2-(1-hydroxyalkyl)-DMNQ derivatives under all of the media, implying that steric hindrance was the cause of lowering the rate of conjugate formation of 2-substituted derivatives. For both isomers, addition of GST did not improve the reaction rate, compared with that in buffer, while the reaction in the S-9 fraction and the perfusate was accelerated to a great extent. The catalytic effect of the S-9 fraction and the perfusion on 2-isomers was greater than on 6-substituted ones, suggesting that S-9 fraction and the perfusate contain an effective system relaxing the steric hindrance of 2-(1-hydroxyalkyl)-DMNQ derivatives. Furthermore, a good correlation between the formation of the GSH conjugates and the cytotoxic activity of both naphthazarin isomers suggests that the steric hindrance is a cause of lowering the cytotoxicity of 2-isomers.

Dopamine-glutamate interaction in rat striatal slices: changes of CCDPK II, PKA, and LDH activity by receptor-mediated mechanisms.

AIM: To study the effects of dopamine (DA) and glutamate (Glu) and their receptor agonists/antagonists on Ca2+/calmodulin-dependent protein kinase II (CCDPK II), cyclic AMP-dependent protein kinase A (PKA) activities and the LDH release in rat striatal slices, and to examine the interaction between DA and Glu transmitter systems in striatum. METHODS: The activities of CCDPK II, PKA, and the release of LDH were determined with the 32P-incorporation and colorimetry respectively in rat striatal slices. RESULTS: (1) Exogenous DA, D1 receptor agonist SKF 38393 and D2 receptor agonist LY 171555 reduced CCDPK II activity in striatal slices; Glu also inhibited CCPPK II activity in a concentration-dependent manner. NMDA receptor antagonist MK-801 could antagonize the inhibitory effect of SKF 38393 and LY 171555 on the CCDPK II activity. D1 and D2 receptor antagonists SCH 23390 and spiperone could also antagonize the decrease of CCDPK II activity induced by Glu; (2) DA and SKF 38393 markedly increased PKA activity in striatal slices, which was reduced by MK-801; (3) DA and Glu increased the release of LDH from the striatal neurons in a concentration-dependent manner. MK-801 antagonized the increase of LDH induced by DA. Spiperone, rather than SCH 23390, could reduce the release of LDH from striatal neuron in the presence of Glu. CONCLUSION: The interaction between DA and Glu transmitter systems is found in the regulation of the CCDPK II and PKA activities and cell function in the striatum.

Electrophysiological study on biphasic firing activity elicited by D(1) agonistic-D(2) antagonistic action of (-)-stepholidine in nucleus accumbens.

Our previous work has demonstrated that (-)-stepholidine (SPD) has dual action, ie D(1) agonistic-D(2) antagonistic action on DA receptors in the nigra-striatal dopamine (DA) system. The present study attempted to ascertain its dual action on the mesolimbic DA system. The firing activities of the nucleus accumbens (NAc) neurons were extracellularly recorded with intravenous and iontophoretic administration of the drug in 6-hydroxydopamine (6-OHDA)-lesioned and intact rats. The results showed that SPD produced a consistently biphasic firing of NAc neurons during the cumulative doses of 0.02 2 mg/kg, iv. When the rats were pretreated with D(2) antagonist spiperone, SPD only exerted an increasing effect, which was subsequently reversed by the D(1) antagonist SCH-23390. Moreover, SCH-23390 could prevent the rate of increase elicited by SPD at high doses, presumably due to the D(1) agonistic action of SPD on the activity of NAc neuron. On the other hand, the inhibition of NAc firing elicited by either D(2) agonist LY171555 or D(1)/D(2) agonists apomorphine was completely reversed by SPD, suggesting an antagonistic action of SPD to D(2) receptors. In 6-OHDA-lesioned rats, iontophoresis of SPD also had an inhibitory effect in the majority of NAc neurons (91%) as SKF-38393 did. This inhibition could be completely blocked by the ejection of SCH-23390, but not by spiperone. These results indicate that SPD also has a D(1) agonistic-D(2) antagonistic dual action on NAc neuron activity, which may be beneficial to the treatment of schizophrenia.

[Effects of tetrahydroberberine on peripheral vascular dopamine DA1 and DA2 receptor subtypes].

OBJECTIVE: To study the effect of tetrahydroberberine (THB) on the peripheral vascular dopamine DA1 and DA2 receptors. METHOD: Using isolated vascular rings method. RESULT: THB(0.1-10 mumol.L-1) shifted the dose-response curves to the right in a nonparallel fashion and decreased the maximal response (Emax) of both the fenoldopam(FODA, a selective DA1 agonist)-induced and the propyl-butyl-dopamine(PBDA, a selective DA2 agonist)-induced vasorelaxation, showing a non-competitive antagonistic action. The pD'2 values of THB for FODA in the renal, pulmonary and mesenteric arteries were 5.29, 5.37 and 5.46, respectively, while for PBDA in the mesenteric and femoral arteries were 5.53 and 5.48, respectively. The potencies of this antagonistic action were weaker than those of SCH23390, a selective DA1 antagonist, domperidone, a selective DA2 antagonist and l-SPD, a mixed DA1/DA2 antagonist, domperidone, a selective DA2 antagonist and l-SPD, a mixed DA1/DA2 antagonist. CONCLUSION: THB is a mixed peripheral DA, and DA2 receptor antagonist similar to l-SPD.

Arcuate nucleus of hypothalamus involved in analgesic action of l-THP.

AIM: To study the role of the arcuate nucleus of hypothalamus in analgesic action of l-tetrahydropalmatine (l-THP). METHODS: The horseradish peroxidase (HRP) retrograde tracing, HRP retrograde tracing combined with immunohistochemistry, lesion of nucleus, tail-flick test, and intra-PAG injection were used in the present study. RESULTS: HRP retrograde tracing results showed that the striatum or accumbens nucleus connect with PAG by two pathways: 1) striatum or accumbens nucleus-->arcuate nucleus-->PAG; 2) striatum or accumbens nucleus-->habenula-->PAG. It was found that neurons in the arcuate nucleus projecting to PAG were mainly beta-endorphin neurons as observed by HRP retrograde tracing combined with immuno-histochemistry. After lesion of the arcuate nucleus, the analgesic action of l-THP (40 mg.kg-1, i.p.) was abolished, while lesion of the habenula had no such effect. Moreover, intra-PAG injection of naloxone (2, 3 micrograms) could markedly attenuate the analgesic action of l-THP (40 mg.kg-1, i.p.) in a dose-dependent manner. CONCLUSION: beta-Endorphin neurons in the arcuate nucleus play an important role in the analgesic action of l-THP.

Tetrahydroprotoberberines inhibit lipid peroxidation and scavenge hydroxyl free radicals.

AIM: To study the effects of tetrahydroprotoberberines (THPB) on rat liver and brain lipid peroxidation (LPO) and oxygen free radicals generation. METHODS: The malondialdehyde (MDA) levels in rat brain and liver homogenates, induction of MDA by Fe(2+)-Vit C in mitochondria, OH. generation by Fenton reaction, and O2.- generation by pyrogallol oxidation were observed in vitro. RESULTS: (1) THPB lowered the MDA contents in the liver homogenate and mitochondria, and the IC50 values of l-THPB-18 and l-stepholidine (SPD) in the liver mitochondria were 3.1 and 12.7 mumol.L-1 respectively. SPD decreased the MDA contents in the brain homogenate and mitochondria with IC50 values of 102 and 35.0 mumol.L-1 respectively. (2) THPB scavenged OH., and the IC50 values of l-THPB-18 and SPD were 0.21 and 3.8 mumol.L-1 respectively, but no effect on O2.- was observed. CONCLUSION: THPB could reduce the MDA contents and scavenge OH. and THPB-18 was the most potent amongst them.

Behavioral characteristics of olanzapine: an atypical neuroleptic.

AIM: To assess the atypical neuroleptic properties of a novel antipsychotic agent, olanzapine (Ola). METHODS: The action of Ola on apomorpine (Apo)-induced climbing behavior, 5-hydroxy-dl-tryptophan (5-HTP)-induced head twitch response, oxotremorine-induced tremor, and the conditioned avoidance behavior in mice were observed. The catalepsy of mice induced by Ola was also investigated. The single unit extracellular recording technique was used to compare the spontaneous firing rate changes of dopamine (DA) cells in the ventral tegmental area (VTA, A10) and the substantia nigra pars compact (SNC, A9) in rats after i.v. Ola. RESULTS: Ola antagonized the climbing behavior (ED50 1.8 mg.kg-1, p.o.), head twitch behavior (ED50 0.3 mg.kg-1, p.o.), and tremor (ED50 5.2 mg.kg-1, p.o.) in mice. In a conditioned avoidance paradigm in mice, Ola inhibited the avoidance response with an ED50 of 2.72 mg.kg-1 (p.o.). However, the catalepsy was not induced by Ola in mice even under a very high dose of 100 mg.kg-1 (p.o.). Ola selectively increased the firing rate of DA cells in the VTA, but failed to affect that of SNC DA cells. CONCLUSION: Ola distinguished itself from the typical neuroleptic (e.g. haloperidol, Hal) and took resemblance of the atypical neuroleptic (e.g. clozapine, Clo) in 3 aspects: 1) the multiple receptor pharmacodynamics involving D1/D2, 5-HT2 and M-ACh receptors; 2) dose-response separation between the block of conditioned avoidance response and catalepsy induction; and 3) the specificity of action sites of firing rates upon acute drug challenge.

I-stepholidine facilitates inhibition of mPFC DA receptors on subcortical NAc DA release.

AIM: To determine whether the D1 agonistic action of (-)-stepholidine (SPD) on the medial prefrontal cortex (mPFC) neuron is involved in the modulation of evoked subcortical dopamine (DA) release from nucleus accumbens (NAc) of rats. METHODS: With the microinjection of SPD into the mPFC, the ventral tegmental area (VTA)-stimulated or amphetamine (AMP)-evoked DA efflux in the NAc was detected by microdialysis + HPLC-ECD in the 6-hydroxydopamine (6-OHDA)-lesioned and intact rats. RESULTS: The depletion of DA in the mPFC did not modify both the basal level and the VTA-stimulated DA efflux in the NAc, but significantly facilitated the AMP (20 mumol.L-1)-evoked DA efflux within the NAc. It indicates that the mPFC DA system is involved in the regulation of evoked DA release in the NAc. Besides, the AMP-evoked increase of the extracellular DA release in the NAc was significantly attenuated by SPD (10, 30 mmol.L-1) microinjection into the mPFC, though this injection of SPD could not alter the response of DA release by the stimulation of the VTA. Furthermore, the inhibitory effect of SPD on the AMP-evoked DA efflux could be partially reversed by intravenous administration of D1 antagonist Sch-23390 (1 mg.kg-1), but not by D2 antagonist spiperone. CONCLUSION: SPD is capable of enhancing the function of D1 receptors in the mPFC, by which it facilitates the inhibition of DA release in the NAc.

Relevance between striatal expression of Fos, proenkephalin mRNA, prodynorphin mRNA and rotation induced by l-stepholidine in 6-hydroxydopamine-lesioned rats.

AIM: To study that l-stepholidine (SPD) regulates the expression of proenkephalin (PENK) and prodynorphin (PDYN) mRNA and Fos in the striatum after rotational test in the 6-hydroxydopamine (6-OHDA)-lesioned rats. METHODS: PENK and PDYN mRNA levels were examined with in situ hybridization, and Fos expression was detected with immunocytochemistry. The data were semi-quantified with image analyzer. RESULTS: (1) Following repeated SPD treatment, the rotation was kept on high activity in the 6-OHDA-lesioned rats. (2) SPD significantly elicited Fos expression in both sides of striatum, particularly in the denervated one. Repeated administration of SPD, Fos expression declined on both sides, particularly in the intact one. (3) In the denervated striatum of 6-OHDA-lesioned rats, the PENK mRNA level was extremely increased vs that in the intact striatum. This high level of PENK mRNA was significantly reduced by 7-d treatments of SPD. SPD also reduced the level of PENK mRNA in the intact striatum. However, the level of PDYN mRNA did not show significant change in both sides of striatum after denervation or SPD treatment. CONCLUSION: In the 6-OHDA-lesioned rats, the rotation induced by SPD was kept on a high activity, which was in pace with the inducement of Fos expression and the reduction of expression of PENK mRNA in the denervated striatum. But then the lesion and SPD treatment had no remarkable effect on the expression of PDYN mRNA.