GDNF and NGF released by synthetic guidance channels support sciatic nerve regeneration across a long gap

The present work was performed to determine the ability of neurotrophic factors to allow axonal regeneration across a 15-mm-long gap in the rat sciatic nerve. Synthetic nerve guidance channels slowly releasing NGF and GDNF were fabricated and sutured to the cut ends of the nerve to bridge the gap. After 7 weeks, nerve cables had formed in nine out of ten channels in both the NGF and GDNF groups, while no neuronal cables were present in the control group. The average number of myelinated axons at the midpoint of the regenerated nerves was significantly greater in the presence of GDNF than NGF (4942 +/-1627 vs. 1199 +/-431, P < or = 0.04). A significantly greater number of neuronal cells in the GDNF group, when compared to the NGF group, retrogradely transported FluoroGold injected distal to the injury site before explantation. The total number of labelled motoneurons observed in the ventral horn of the spinal cord was 98.1 +/-23.4 vs. 20.0 +/-8.5 (P < or = 0.001) in the presence of GDNF and NGF, respectively. In the dorsal root ganglia, 22.7% +/- 4.9% vs. 3.2% +/-1.9% (P +/-0.005) of sensory neurons were labelled retrogradely in the GDNF and NGF treatment groups, respectively. The present study demonstrates that, sustained delivery of GDNF and NGF to the injury site, by synthetic nerve guidance channels, allows regeneration of both sensory and motor axons over long gaps; GDNF leads to better overall regeneration in the sciatic nerve.     

Relationship of baseline ovarian volume to ovarian response in World Health Organization II anovulatory patients who underwent ovulation induction with gonadotropins

OBJECTIVE: To assess whether ovarian volume of World Health Organization II anovulatory patients in the early follicular phase predicts the response to ovulation induction with gonadotropins. DESIGN: Retrospective data analysis of two prospective, randomized, multicenter studies. SETTING: Clinical development unit of biotechnology company. PATIENT(S): Four hundred sixty-five World Health Organization II anovulatory patients undergoing ovulation induction. MAIN OUTCOME MEASURE(S): Ovarian response to stimulation, ovulation (mid-luteal serum progesterone > 30 nmol/L), cancellation rate, pregnancy rate, and incidence of the ovarian hyperstimulation syndrome (OHSS) according to baseline ovarian volume (day 2-5) before stimulation. RESULT(S): Mean ovarian volume was 11.55 +/- 6.0 cm(3) (range, 0.8-49.3 cm(3)). Small ovarian volume was associated with lower rates of cycle cancellation owing to risk for OHSS (3 vs. 29 patients [2.8% vs. 9%]). Patients with small ovarian volume (<7.25 cm(3)) required fewer ampules of FSH (1373 IU vs. 1629 IU) and shorter duration of stimulation (16 vs. 18.1 days) and had higher ovulation rate than did patients with mid-range and larger ovarian volume (84.3% vs. 69.1% and 68.8%, respectively). The clinical pregnancy rate per cycle of hCG administration was similar in the three groups (25.8%, 28.1%, and 27.5%). CONCLUSIONS: World Health Organization II anovulatory women with medium-sized or large ovaries who are undergoing low-dose gonadotropin stimulation for ovulation induction may have higher risk for OHSS than do women with small ovaries. Women with small ovaries who meet criteria for administration of hCG respond better to ovulation induction and have a similar likelihood of conceiving compared with women with larger ovaries.     

Differential analgesic sensitivity of two distinct neuropathic pain models

Progressive tactile hypersensitivity (PTH) manifesting after sciatic nerve crush and spared nerve injury (SNI) are two distinct rodent experimental models of neuropathic pain. PTH develops months after recovery from the nerve crush in response to repeated intermittent low-threshold mechanical stimulation of the reinnervated sciatic nerve skin territory and represents a model of stimulus-induced pain. SNI is characterized by an early and sustained increase in stimulus-evoked pain sensitivity in the intact skin territory of the spared sural nerve after sectioning of the two other terminal branches of the sciatic nerve. We examined the effects of morphine (0.5-10 mg/kg), gabapentin (30-200 mg/kg), MK801 (0.01-0.02 mg/kg), amitriptyline (10-25 mg/kg), and carbamazepine (5-7.5 mg/kg) in both models. Morphine, gabapentin, and carbamazepine both reversed and prevented stimulus-induced PTH, whereas MK801 and amitriptyline reduced but did not prevent stimulus-induced PTH. In contrast, the stimulus-evoked behavioral hypersensitivity in the SNI model was poorly modified by these drugs. Independent neuropathic pain models show differential sensitivity to analgesic drug treatment. We suggest that this is due to the different mechanisms responsible for the neuropathic pain-related behavior. Multiple models are required, therefore, to study the mechanisms that contribute to neuropathic pain and to predict analgesic efficacy for different components of the neuropathic pain syndrome.     

The epidemiology of female genital tract cancers

Endometrial, ovarian and cervical cancer are among the leading causes of death in women. The role of unopposed estrogens in endometrial carcinogenesis is well established. Any factor that increases the exposure of the endometrium to unopposed estrogen, such as menopausal replacement treatment, obesity, or irregular menstrual cycles tends to raise the risk of the disease, while factors that lower exposure to estrogens or increase progesterone levels, such as oral contraceptives (OC) or smoking, decrease the risk. These well-established risk factors can have different effects at different ages, particularly in pre- and postmenopausal women: more generally, the interaction between various factors is still not totally defined. With reference to ovarian cancer, OC and parity, late menopause and lifelong regular menstrual periods increase the risk of the disease. In terms of biologic mechanisms, these factors are thought to act on ovarian cancer risk by affecting lifetime number of ovulations. Along this line, 'incessant ovulation' could be the relevant exposure that defines the incidence of the neoplasm. Among the factors other than reproductive or hormonal, diet is likely to be the most relevant, but it is still. however, poorly quantified. There is now consistent evidence that Human Papillomavirus (HPV) has a causal role in the ethiology of cervical cancer and that sexual habits and reproductive/hormonal factors are associated with the risk of invasive cervical cancer. Less clear is the role of smoking and dietary habits, but recent studies have shown a direct relationship between smoking and the risk of invasive cervical cancer and an inverse one between selected vitamin intake and risk of the disease. In this paper we review and discuss these evidences.     

Aromatic DNA adducts in foundry workers in relation to exposure, life style and CYP1A1 and glutathione transferase M1 genotype

Levels of aromatic DNA adducts in foundry workers and controls were followed at four annual samplings. During this time exposure to polycyclic aromatic hydrocarbons (PAH) decreased and the level of DNA adducts decreased accordingly. In the total group exposure was related to the level of adducts. Adduct levels correlated with urinary 1- hydroxypyrene (LOGU1OH), air benzo[a]pyrene, weekly working hours and daily cigarette consumption. In a multivariate model 1-hydroxypyrene had a consistent effect. Neither glutathione transferase M1 (GSTM1) nor cytochrome P450 1A1 (CYP1A1) genotypes had clear effects. Yet the individuals lacking GSTM1 had a stronger effect of LOGU1OH and some effect by other sources of PAH, such as charcoal broiled food, although all these variables were not significant in the multivariate model. The rare individuals with a CYP1A1 polymorphism MspI containing an amino acid change at isoleucine had an increased level of adducts. The results showed that the postlabelling method used was able to detect an increase in aromatic DNA adducts in leukocytes when exposure to benzo[a]pyrene in air was approximately 5 ng/m3. At such low levels smoking and charcoal broiled food may be important contributors to adducts.      

妊娠肝内胆汁淤积症患者脂质过氧化作用的变化与雌激素水平及受体的关系

目的　探讨妊娠肝内胆汁淤积症 (intrahepatic cholestasis of pregnancy,ICP)患者血清丙二醛 (MDA)和超氧化物岐化酶 (SOD)含量的变化与游离雌三醇 (E3 )和胎盘雌激素受体 (ER)水平之间的关系。　方法　取 ICP患者 33例为研究组 ,另选同期入院的正常产妇 30例作为对照组 ,两组均在分娩前 30 min内取肘静脉血 3ml,测定 MDA、SOD、E3 及 β- h CG。随机选择 ICP组和正常对照组2 0例测定胎盘组织中 ER和 HCG水平。　结果　 ICP组中 MDA为 (6 .4± 2 .1) m ol/L、E3 为 (19± 9)ng/m l高于对照组 (5 .2± 1.4) m ol/L,14± 6 ) ng/ml(P<0 .0 1)。 SOD、β- h CG与对照组相比无显著差异 (P>0 .0 5 )。ICP组中胎盘组织 ER的阳性表达百分比 70 %高于对照组 2 5 % (P<0 .0 5 ) ,而 HCG的阳性百分比在两组间无显著差异 (P>0 .0 5 )。 ICP组 E3 与胎盘 ER水平之间有正相关关系 r=0 .6 3。而 β- h CG与胎盘 HCG水平则无显著相关 (P>0 .0 5 )。　结论　妊娠期 ICP患者体内氧化和抗氧化失衡及雌激素水平升高与胎盘 ER表达增强 ,对 ICP的发生可能起重要的作用     

Pubertal linear growth of Indian girls adopted in Sweden

Pubertal linear growth in 66 adopted Indian girls was studied. The infancy-childhood-puberty standard was used, since it is applicable to Indian girls, and enables determination of the onset and height gain of the pubertal growth phase in an individual. At arrival in Sweden, mean height was —2.8 SDS. Despite rapid catch-up growth, the girls were still below the reference mean (—0.8 SDS) at the onset of the pubertal growth spurt, which occurred approximately 1.5 years earlier than in Swedish girls and also earlier than in Indian girls. The pubertal height gain, however, was equivalent to that in Swedish girls with similar timing of puberty. The short final height found in some of these girls appears to be related to shortness prior to puberty and to very early onset of an otherwise normal pubertal growth component.