Immunolocalization of CCK1R in rat brain using a new anti-peptide antibody

An antibody directed at the carboxy tail of the cholecystokinin-1 receptor (CCK1R) was characterized by ELISA and Western blotting. Immunohistochemistry established that CCK1R-like immunoreactivity (CCK1R-LI) was widely and topographically distributed through the neuroaxis, appearing relatively higher in rhi- and diencephalon, and intense in both neuronal somata (cytoplasmic) and processes. CCK1R-LI was found in new loci, but also in areas previously identified by receptor autoradiography, electrophysiology and in situ hybridization of CCK1R mRNA. The widespread distribution of CCK1R has implications for the functional roles of these receptors in brain. The high titre and low background seen with this new antiserum makes it of great value for cell and tissue research.     

Indoor gardening older adults: effects on socialization, activities of daily living, and loneliness

This study examined the effects of indoor gardening on socialization, activities of daily living (ADLs), and perceptions of loneliness in elderly nursing home residents. A total of 66 residents from two nursing homes participated in this two-phase study. In phase one, experimental group 1 participated once a week for 5 weeks in gardening activities while a control group received a 20-minute visit. While no significant differences were found between groups in socialization or perceptions of loneliness, there were significant pretest-posttest differences within groups on loneliness and guidance, reassurance of worth, social integration, and reliable alliance. The results also demonstrated gardening interventions had a significant effect on three ADLs (transfer, eating, and toileting). Phase two examined differences in the effects of a 5-week versus a 2-week intervention program. Although no significant within-group differences were noted in socialization, loneliness, or ADLs, the 5-week program was more effective in increasing socialization and physical functioning.     

PACAP promotes neural stem cell proliferation in adult mouse brain

In recent years, it has become evident that neural stem cells in the adult mammalian brain continuously generate new neurons, mainly in the hippocampus and olfactory bulb. Although different growth factors have been shown to stimulate neurogenesis in the adult brain, very little is known about the role of neuropeptides in this process. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic effects acting through three receptors to which it has high affinity, namely, PACAP receptor 1 (PAC1), vasoactive intestinal peptide (VIP) receptor 1, and VIP receptor 2. We show that PAC1 is expressed in the neurogenic regions of the adult mouse brain, namely the ventricular zone of the lateral ventricle and the hippocampal dentate gyrus. Cultured neural stem cells isolated from the lateral ventricle wall of adult mice express PAC1 and proliferate in vitro in response to two PAC1 agonists, PACAP and Maxadilan, but not VIP at physiologic concentrations, indicating PAC1 as a mediator of neural stem cell proliferation. Pharmacologic and biochemical characterization of PACAP-induced neural stem cell proliferation revealed the protein kinase C pathway as the principal signaling pathway, whereas addition of epidermal growth factor synergistically enhanced the proliferating effect of PACAP. Further in vitro characterization of the effect of PACAP on neural stem cells showed PACAP capable of stimulating ex novo in vitro formation of multipotent neurospheres with the capacity to generate both neuronal and glial cells. Finally, intracerebroventricular infusion of PACAP increases cell proliferation in the ventricular zone of the lateral ventricle and the dentate gyrus of the hippocampus. We conclude that PACAP, through PAC1, is a potent mediator of adult neural stem cell proliferation.     

Circulating ghrelin levels and central ghrelin receptor expression are elevated in response to food deprivation in a seasonal mammal (Phodopus sungorus)

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHSR). However, the functional interaction of ligand and receptor is not very well understood. We demonstrate that GHSR mRNA is up-regulated after food deprivation (48 h) in the hypothalamic arcuate nucleus and ventromedial nucleus of the seasonal Siberian hamster, Phodopus sungorus. This increase is accompanied by a two-fold elevation of circulating ghrelin concentration. Chronic changes in feeding state imposed by food restriction over a period of 12 weeks during long day-length induced increased GHSR gene expression, whereas food restriction for 6 weeks had no effect. Phodopus sungorus reveals remarkable seasonal changes in body weight, fat mass and circulating leptin levels. Ghrelin is generally regarded as having opposing effects on appetite and body weight with respect to those exhibited by leptin. However, our study revealed that seasonal adaptations were not accompanied by changes in either GHSR gene expression or circulating ghrelin concentration. Therefore, we suggest that ghrelin only plays a minor role in modulating long-term seasonal body weight cycles. Our findings imply that ghrelin predominantly acts as a short-term regulator of feeding.     

Ex vivo reversal of chemoresistance by tariquidar (XR9576)

The expression of P-glycoprotein (P-gp) has been demonstrated to confer resistance to several anticancer drugs, including anthracyclines, taxanes and vinca alkaloids. Tariquidar is a novel inhibitor of P-gp that has been shown to reverse resistance to cytotoxic drugs in tumor cell lines and mouse xenografts. We have used an ATP-based chemosensitivity assay (ATP-TCA) to compare the activity of cytotoxic drugs in combination with tariquidar against a variety of solid tumors (n = 37). The expression of P-gp was determined in a subset of solid tumor samples by immunohistochemistry (n = 16). Resistance was seen in 20 of 37 (54%) tumors tested with doxorubicin, in 27 of 34 (79%) samples tested with paclitaxel and 17 of 31 (55%) with vinorelbine. Tariquidar alone showed no activity over a wide range of concentrations up to 2 microM (n = 14). The median IC90s for doxorubicin, paclitaxel and vinorelbine, alone were 2.57, 27.4 and 15.5 microM. These decreased to 1.67 (p<0.0005), 20.6 (p<0.05) and 9.5 microM (p<0.001), respectively, in combination with tariquidar. Tariquidar also significantly decreased resistance in 14 of 20 (70%), six of 27 (22%) and six of 17 (35%) samples tested with doxorubicin, paclitaxel and vinorelbine, respectively. Immunohistochemical staining for P-gp was positive in nine of 16 (56%) samples and in all of these cases addition of tariquidar improved the activity of the cytotoxic. The results show that tariquidar is able to decrease resistance in a number of solid tumors resistant to cytotoxic drugs known to be P-gp substrates. These data support the introduction of tariquidar in combination with chemotherapy to clinical trials of patients expressing P-gp.     

What we have learned about the predictors of preterm birth

The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 1996 studied a large number of risk factors for preterm birth in more than 3,000 women at 10 centers. The goals of the study were to better understand the strength of one risk factor versus another and to explore interactions among the predictors looking for combinations of factors that were more predictive of preterm birth than any single factor used alone. The most potent factors that were associated with spontaneous preterm birth at < 32 weeks were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and < l0th percentile cervical length (odds ratio, 5.8), and in serum, > 90th percentiles of alpha-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and > 75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at < 35 weeks were generally similar but not as strong. The overlap among the strongest biologic markers for predicting spontaneous preterm birth was small. This suggests that the use of tests such as maternal alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.     

Pregnancy in a spinal cord-injured bilateral total leg amputee: management and considerations

A 35-year-old woman, gravida 2, para 0, was seen at 20 weeks' gestation with complete T10 spinal cord transection at age 15 years, subsequent bilateral total leg amputation, urinary diversion, colostomy, and lumbar spine resection. Pregnancy complications included recurrent urinary tract infections, preterm contractions without cervical change, lumbosacral abscesses, and fetal malpresentation. Delivery was through cesarean section near term.     

Relationship of prenatal care and perinatal morbidity in low-birth-weight infants

OBJECTIVE: Lack of or no prenatal care (NPC) is associated with preterm birth (PTB) and low birth weight (LBW). Our purpose was to determine whether LBW infants delivered after NPC have worse outcomes than LBW infants with prenatal care (PC). STUDY DESIGN: Eight thousand sixty-five consecutive women delivered at six hospitals in Shelby County, Tenn, were evaluated regarding clinical characteristics and perinatal outcomes depending on the occurrence of PC. Infant and LBW infant outcomes were evaluated on the basis of the occurrence of PC. Multivariate analysis was performed for neonatal outcomes adjusting for race, plurality, antenatal steroids, amnionitis, and ponderal index. A P value less than .05 was considered significant. RESULTS: NPC women were more likely multiparous (80% vs 65%), African American (70% vs 61%), and uninsured (25% vs 4%), P<.0001 for each. PTB (36% vs 15%) and LBW (22% vs 12%) were more common with NPC, P<.0001 for each. Women with NPC had more advanced cervical dilation (ACD) greater than 4 cm (ACD: 63% vs 39%) and more amnionitis on admission (2% vs 1%), P相似文献   

Low maternal weight, failure to thrive in pregnancy, and adverse pregnancy outcomes

OBJECTIVE: The purpose of this study was to correlate low maternal pregravid weight, delivery weight, and poor gestational weight gain with perinatal outcomes. STUDY DESIGN: Maternal and perinatal data from January 1997 to June 2001 were obtained from a perinatal database at MetroHealth Medical Center. Low maternal weight (LMW) was defined as pregravid or delivery weight <100 pounds or body mass index (BMI) < or =19.8 kg/m(2). Low maternal weight gain was defined as <0.27 kg per week. Perinatal complication rates in these subjects were compared with those with weights of 100 to 200 pounds, normal BMI (>19.8, <26 kg/m(2)), and normal gestational weight gain (0.27-0.52 kg/wk). Chi-square and t tests were used where appropriate. P<.05 was significant. RESULTS: A percentage (2.6%) of 15,196 subjects began pregnancy weighing < or =100 pounds; 0.15% weighed <100 pounds at delivery and 13.2% had a pregravid BMI < or =19.8 kg/m(2). Pregravid LMW was highly correlated with ethnicity (Asians, 8.6%; Hispanics, 4.3%; Caucasians, 2.5%; African Americans, 1.9%; P<.001). Subjects with pregravid LMW were at increased risk for intrauterine growth restriction (IUGR) (relative risk [RR], 2.3, 95% CI, 1.3-4.05), and perineal tears (3rd-degree lacerations; RR, 1.8, 95% CI, 1.1-2.9), and low birth weight ([LBW] <2500 g; RR, 1.8, 95% CI, 1.1-2.9). They had a lower risk of cesarean section (RR, 0.72, 95% CI, 0.56-0.92) and preterm delivery (PTD) (RR, 1.1, 95% CI, 0.97-1.06). Pregravid BMI <19.8 kg/m(2) was associated with preterm labor (PTL) (RR, 1.22, 95% CI, 1.02-1.46), IUGR (RR, 1.67, 95% CI, 1.2-2.39), and LBW (<2500 g; RR, 1.13, 95% CI, 1.0-1.27) and was protective against cesarean delivery (RR, 0.8, 95% CI, 0.71-0.91). Delivery LMW was associated with LBW (<2500 g; RR, 2.81, 95% CI, 1.62-4.84), active-phase arrest (RR, 5.07, 95% CI, 1.85-13.9), PTL and PTD (RR, 2.5, 95% CI, 1.02-6.33, and RR, 2.45, 95% CI, 1.4-4.4, respectively), a lower gestational age at delivery (36.8 vs 38.3 wks, P<.05), and mediolateral episiotomy (RR, 9.6, 95% CI, 1.9-48.0). A percentage (0.8%) of subjects had BMI <19.8 kg/m(2) at delivery. Low delivery BMI was associated with birth weight <2500 g (RR, 1.74, 95% CI, 1.3-2.32), PTL (RR, 2.16, 95% CI, 1.45-3.19), and PTD (RR, 1.57, 95% CI, 1.18-2.11). Failure to thrive in pregnancy (weight gain <0.27 kg/wk) was associated with LBW (<1500 g; RR, 1.23, 95% CI, 1.03-1.45), <2500 g; RR, 1.22, 95% CI, 1.13-1.33), and PTL and PTD (RR, 1.2, 95% CI, 1.05-1.37, and RR, 1.11, 95% CI, 1.02-1.2, respectively). CONCLUSION: Low weight and BMI at conception or delivery, as well as poor weight gain during pregnancy, are associated with LBW, prematurity, and maternal delivery complications.