Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP

Vasoactive intestinal peptide (VIP), the structurally homologous pituitary adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of PRL gene expression and release in the pituitary gland. Little is known about PRL regulation in the brain although it is hypothesized that the REMS-promoting activity of i.c.v. administered VIP may be mediated via the activation of cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA, the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic mRNA. Standardized amounts were analysed for PRL using the polymerase chain reaction followed by Southern blotting and hybridization. Compared with β-actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose-dependent fashion though VIP was more effective on a molar basis. The previously reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The data support the hypothesis that the REMS-promoting activity of central VIP and PACAP might be mediated by cerebral PRL.     

常温与低温体外循环心脏直视手术对细胞因子及补体的影响

目的探讨常温及低温体外循环心脏直视手术对细胞因子及补体的影响。方法选择先天性和风湿性心脏病患者40例,随机分为常温组及低温组各20例,分别于术晨、体外循环结束时及术后1、4、7、14 d抽取患者静脉血标本,测定血浆TNF、IL-2、C3、C4值。结果两组术前各项检查指标无显著差异。(1)两组术后1~4 d的IL-2水平较术前显著下降,至术后7 d恢复正常。体外循环结束至术后4 d,低温组IL-2显著低于常温组。(2)体外循环结束时以及术后1、4、7 d,常温组TNF水平显著低于低温组。两组体外循环结束时及术后1、4 d均高于术前,常温组至术后7 d、低温组术后14 d恢复正常。(3)体外循环结束时及术后1、7 d,常温组C3水平高于低温组,术后4 d两组无差别;常温组及低温组于体外循环结束时、术后1、4 d均低于术前,至术后7 d常温组恢复正常,低温组至术后14 d恢复至术前水平。(4)两组体外循环结束时及术后1、4 d C4水平均低于术前。体外循环结束时、术后1 d,常温组C4水平高于低温组。结论常温体外循环心脏直视手术对细胞因子及补体的影响显著轻于低温组,因而对术后机体的恢复优于低温方法。     

The adverse effect of treatment prolongation in cervical cancer by high-dose-rate intracavitary brachytherapy.

BACKGROUND AND PURPOSE: The potential risk of prolongation of treatment time in cervical cancer has been reported for many low-dose rate (LDR) studies, with an estimated loss of local control ranging from 0.3 to 1.6% per day of treatment prolongation. Since the treatment schedule for fractionated high-dose rate intracavitary brachytherapy (HDRICB) is not directly comparable with that for low-dose rate studies, this report aims to evaluate the adverse effect of treatment prolongation specifically for cervical cancer treated with HDRICB. MATERIAL AND METHODS: From September 1992 to December 1997, 257 patients diagnosed with uterine cervical cancer (35 Ib, 26 IIa, 122 IIb, 10 IIIa, 57 IIIb, 7 IVa), who underwent external radiotherapy combined with between two and four courses of HDRICB and a minimum of 3 years of follow-up (median 57 months), were analyzed. Treatment consisted of irradiation of the whole pelvis with 44-45 Gy consisting of 22-25 fractions by 5 weeks, with the dose boosted to 54-58 Gy (with central shielding) for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease. HDRICB was performed using an Ir-192 remote afterloading technique at 1-week intervals. The standard prescribed dose for each course of HDRICB was 7.2 Gy to point A for three insertions (before July 1995), or 6.0 Gy to point A for four insertions (after July 1995). Total prescribed point A doses (external beam radiotherapy+HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while analogous dosage for larger lesions (stage IIb-IVa) ranged from 59 to 75.6 Gy (median, 65.6 Gy). Kaplan-Meier and multivariate analyses were used to test the effect of treatment time on pelvic control rate (PCR) and cause-specific survival (CSS) at 5 years. RESULTS: Median treatment time was 63 days. For all stages of disease, the 5-year CSS and PCR were significantly different comparing treatment times of less than and greater than or equal to 63 days [83% and 65% (P=0.004], 93% and 83% (P=0.02), respectively]. These associations were also significant for stage Ib/IIa [97% and 79% (P=0.01), and 100% and 87% (P=0.02), respectively), but not for stage IIb [75% and 72% (P=0.79), and 93% and 87% (P=0.83), respectively] or stage III [66% and 49% (P=0.2), and 83% and 72% (P=0.21), respectively]. Multivariate analysis identified three prognostic factors for CSS, stage (P<0.001), tumor response to external RT (P=0.001), and overall treatment time (OTT; P=0.006). Prognostic factors for pelvic failure were stage (P<0.001), tumor response to external RT (P=0.001), and OTT (P=0.03). Prolongation of treatment time resulted in a daily decrease in pelvic control rate of 0.67% overall, and 0.43% for stage Ib-IIa, 0.57% for stage IIb, and 0.73% for stage III patients. CONCLUSION: Analysis of the data from the current study demonstrates that the adverse effect of treatment prolongation was observed later in the treatment course for the high-dose rate (HDR) series compared to the LDR analog, however, treatment-time prolongation still negatively influenced the cause-specific survival and pelvic control rate for both dosage groups.     

Long-term application of diethylstilbestrol upregulates expressions of μ- and m-calpains in pituitary intermediate lobe of female Wistar rats

BACKGROUND: During formation of prolactin neoplasia, how cells and its structure in adenohypophysis affect prolactin cells should be further studied. Intermediate lobe can be regarded as a driving region to release prolactin (PRL) and may promote formation of prolactin neoplasia in pituitary anterior lobe. OBJECTIVE: To observe the effect of diethylstilbestrol (DES) on the expressions of μ and m-calpains in pituitary intermediate lobe of female Wistar rats. DESIGN: Observational contrast animal study. SETTING: Beijing Neurosurgical Institute. MATERIALS: A total of 21 female Wistar rats, 3 weeks old weighing 70–80 g were housed with free access to tap water and standard pellet food. They were kept in a CL-grade condition, at (24±1)℃ and a humidity of (55±5)%, and with a 12 hours day-night cycle. Caprine anti-μ- and m-calpains antibodies were provided by Santa Cruz Biotechnology, CA, USA; rabbit-anti-PRL antibodies by Dako, Denmark; rabbit-anti-ACTH antibody by Boster Company, Wuhan. METHODS: The experiment was carried out in Pathophysiological Department and Animal Laboratory, Beijing Neurosurgical Institute from August 2006 to January 2007. ① Rats were randomly divided into groups with 7 in each group, including vehicle control group, in which rats were injected intraperitoneally with sun-flower seed oil (1 mL/kg, twice a week) for 16 weeks; DES group, where animals were administered with DES (5 mg/kg, twice a week) for 16 weeks; DES + vehicle control group, in which DES was administered for 12 weeks at the same dose with those in DES group, and then was discontinued and replaced by sun-flower seed oil (1 mL/kg, twice a week) for the following 4 weeks. ② At 16 weeks later, pituitary tissue was dealt with HE staining and PRL immunohistochemical examination to observe evoke of tumor; meanwhile, immunohistochemical examination was used to observe expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. MAIN OUTCOME MEASURES: ① Expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. ② Morphological observation of pituitary tissue. RESULTS: All 21 rats were involved in the final analysis. ① Results of immunohistochemical examination: Morphological changes of neoplasia in DES group were strongly positive to PRL, and this suggested that formation of prolactin adenoma was observed in pituitary tissue. As compared with vehicle control group, expression of adrenoeorticotropic hormone (ACTH) was increased in both DES group and DES + vehicle control group. In addition, expressions of μ- and m-calpains in pituitary intermediate lobe were higher in DES group than that in vehicle control group. Otherwise, expressions of m-calpains in pituitary intermediate lobe was decreased in DES + vehicle control group, but expression of μ-calpains was still increased. ② Morphological observation of pituitary tissue: Gland tubes were orderly arranged in rats in vehicle control group. Anterior pituitary gland in rats of DES group demonstrated an apparent disappearance of gland tubes and a relatively large-scaled vasculature formation, namely the vascular lake lined by tightly arranged endothelial cells. Local integrated tumor cell arrangements were also detected. In addition, the border between the IL and the anterior lobe was locally blurred. The definite tumor-like changes in pituitary tissues were confirmed in 6 of 7 female Wistar rats in DES group, and one spontaneous occurrence of tumor formation was found in vehicle control group. In DES + vehicle control group, DES withdrawal led to the subtile emergence of gland tube cavity, although tumor-like cells still existed in 4 of 7 rats, suggesting occurrence of the tumor regression due to the withdrawal of DES. CONCLUSION: A long-term application of DES can enhance the expressions of ubiquitours neutral cysteine protease in pituitary intermediate lobe and this suggests that both of them play a key role in release of hormone and formation of prolactin neoplasia through directly promoting PRL expression and release of neighboring pituitary intermediate lobe.     

AN-132 block of cardiac sodium channels: A gate-related receptor analysis

Summary Based on the gate-related receptor hypothesis, an analysis of kinetics of AN-132, a new antiarrhythmic agent, blockade of cardiac sodium channels and the gate-related receptor which is bound by the drug was performed by computer simulation. Model-predicted apparent rates of onset of AN-132 (30 μmol/L) blocking were 0.051, 0.038, and 0.034 AF⁻¹ at stimulation frequencies of 1.0, 2.0 and 3.0 Hz, respectively. The time constant of recovery from block by AN-132 at resting potential -90 mV was 39.5 s. These findings are in agreement with those experimental data documented. The analysis of gate-related receptor shows that AN-132 binds the inactivation gate-related receptor, and the binding and unbinding are modulated by the inactivation process.     

Spinal cholinergic and monoamine receptors mediate the antinociceptive effect of morphine microinjected in the periaqueductal gray on the rat tail, but not the feet

The antinociceptive effects of morphine (5 μg) microinjected into the ventrolateral periaqueductal gray were determined using both the tail flick and the foot withdrawal responses to noxious radiant heating in lightly anesthetized rats. Intrathecal injection of appropriate antagonists was used to determine whether the antinociceptive effects of morphine were mediated byα₂-noradrenergic, serotonergic, opioid, or cholinergic muscarinic receptors. The increase in the foot withdrawal response latency produced by microinjection of morphine in the ventrolateral periaqueductal gray was reversed by intrathecal injection of the cholinergic muscarinic receptor antagonist atropine, but was not affected by the a2-adrenoceptor antagonist yohimbine, the serotonergic receptor antagonist methysergide, or the opioid receptor antagonist naloxone. In contrast, the increase in the tail flick response latency produced by morphine was reduced by either yohimbine, methysergide or atropine. These results indicate that microinjection of morphine in the ventrolateral periaqueductal gray inhibits nociceptive responses to noxious heating of the tail by activating descending neuronal systems that are different from those that inhibit the nociceptive responses to noxious heating of the feet. More specifically, serotonergic, muscarinic cholinergic andα₂-noradrenergic receptors appear to mediate the antinociception produced by morphine using the tail flick test. In contrast, muscarinic cholinergic, but not monoamine receptors appear to mediate the antinociceptive effects of morphine using the foot withdrawal response.     

Comparative study of three fluorescent dyes for angiography: sodium fluorescein, carboxyfluorescein, and calcein

To compare the characteristics of carboxyfluorescein (CF) and calcein (Calc) with those of sodium fluorescein (Naf), the only fluorescent dye currently in clinical use, we performed angiography in rabbits and primates using these three dyes. The circulation decay time of all dyes was longer in primates than in rabbits. In primates, CF and Calc had longer decay times than Naf. Calc produced the greatest contrast between the choroidal and retinal vasculature. Tissue staining and dye leakage into the vitreous immediately after retinal photocoagulation were minimal with Calc, moderate with CF, and marked with Naf. The limited leakage and longer circulation time of Calc may permit simultaneous angiography and photocoagulation therapy without obscuring the fundus view with leaking dye from the photocoagulated structure.     

手术治疗胫腓骨远端骨折36例

目的 :探讨胫腓骨远端骨折治疗术式的选择、术中术后应注意的问题及其疗效。方法 :对不同类型的胫腓骨远端骨折 36例进行 8～ 18个月的随访 ,并结合临床及影像学资料 ,对其诊断、手术方法及治疗效果进行分析总结。结果 :本组术后 2 5～ 3 5个月骨折均愈合。踝关节功能优良率 77 7%。结论 :熟悉骨折的分型及相应内固定术式的选择 ;注重踝穴骨折的解剖复位及固定和踝关节的功能位固定及早期功能锻炼。     

直视下经尿道内切开术治疗尿道狭窄

目的：探讨直视下经尿道内次切开术治疗尿道狭窄的有效性和安全性。方法：总结直视下经尿道内切开术治疗68例尿道狭窄和闭锁患者的疗效和经验，63例1次手术成功；3例行2次、2例行3次成功。结果：68例中，57例术后随访3～71个月，平均28．3个月，43例(75％)均排尿通畅；2例暂时性尿失禁者分别于术后3～6月内恢复。结论：直视下经尿道内切开术创伤小，并发症少，疗效确切，是尿道狭窄和闭锁的首选治疗方法。