Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine

Previously, we have shown that repeated administration of d-fenfluramine (D-F) to rats is associated with development of tolerance to the initial anorexia, but that in mice no such tolerance seems to occur. In the first study, we show that chronic administration of neither d-norfenfluramine (D-NF; the principal metabolite of D-F) nor the serotonin (5-HT) 2C receptor agonist m-chlorophenyl-piperazine (mCPP) is associated with the development of anorectic tolerance tested using a dessert protocol. However, compared with mice receiving these drugs for the first time, both of these chronic treatments were associated with a significant attenuation of Fos immunoreactivity (Fos-ir) in several brain regions, including bed nucleus of the stria terminalis, paraventricular hypothalamus, and central nucleus of amygdala. This attenuation is similar to that described previously in rats. Because loss of efficacy of these agents could be related to loss of 5-HT transporter (5-HTT) sites, their presumptive primary mode of action, in the final study we determined the effect of various, low-dose regimens of D-F and D-NF on 5-HT uptake in frontal cortex of mice and rats. We show in mice that D-F causes a greater loss of 5-HT uptake than D-NF, and that at the lowest dose regimen used uptake was unaffected in rats but was reduced in mice. The data are discussed in terms of the species difference in behavioral tolerance and differences in neurochemical profile of D-F and D-NF.     

Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy

To study the role of one of the most potent motoneuron (MN) survival factors, glial cell line-derived neurotrophic factor (GDNF) derived from the CNS, we generated transgenic animals overexpressing GDNF under the control of an astrocyte-specific GFAP promoter. In situ hybridization revealed that GDNF was expressed at high levels in astrocytes throughout the brain and spinal cord. We analyzed the effects of CNS-derived GDNF on MN survival during the period of programmed cell death (PCD) and after nerve axotomy. In GFAP-GDNF mice at E15, E18, and P1, the survival of brachial MNs was increased on average by 30%, lumbar MNs by 20%, and thoracic MNs at P1 by 33%. GDNF also prevented MN PCD in several cranial motor nuclei. We demonstrated for the first time that the number of MNs in the mouse abducens nucleus was also increased by 40%, thus extending known MN populations that are responsive to GDNF. Next, we tested if GDNF could support complete and relatively long-term survival of MNs following neonatal facial nerve axotomy. We found that virtually all MNs (91%) in GFAP-GDNF mice survived for up to 18 weeks post-axotomy. This is the longest GDNF-mediated survival of neonatal MNs reported following axotomy. Most of surviving MNs were not atrophic, and MN-specific ChAT and neurofilament immunoreactivity (IR) were preserved. Furthermore, GDNF attenuated axotomy-induced astroglial activation. These data demonstrate that overexpression of GDNF in the CNS has very profound effects on MN survival both during the PCD period and after neuronal injury. GFAP-GDNF mice will be valuable to study the effects of CNS-derived GDNF in mouse models of MN degenerative diseases and axonal regeneration in vivo.     

Do women read poster displays on breast cancer in waiting rooms?

BACKGROUND: This study reports data from a survey carried out in the Iranian Center for Breast Cancer (ICBC) to examine whether women read poster displays in waiting rooms and whether they would have any suggestions to improve posters and thus meet their informational needs. METHODS: Five specially designed posters were displayed in waiting rooms in the ICBC. The content of posters was related to risk factors, early detection, signs and symptoms, and prevention of breast cancer. During a 3 month period a self-administered questionnaire was distributed to all attendees and they were asked to complete the questionnaire. RESULTS: Overall, 850 women were given the questionnaire and 777 completed questionnaires (91 per cent) were returned. The mean age of the women was 37.0 years (SD = 10.7) and they mostly had secondary education (47 per cent). In all, 691 women (86 per cent) reported that they had seen the posters and 620 (80 per cent) said that they had read the displays. The vast majority of the women reported that posters were readable (89 per cent) and understandable (80 per cent). However, 25 per cent of the respondents indicated that materials on the displays created more questions rather than answering their questions and some reported that they became upset (26 per cent) or felt anxiety (42 per cent) while reading the posters. Finally, 218 women (28 per cent) had suggestions to improve posters, of whom 110 (50 per cent) believed that the posters should be simpler. CONCLUSION: The study findings suggest that despite the limitations of posters as a means of health communication, their use in public places may be useful but consideration should be given to the content of the poster displays to prevent anxiety.     

Skp2 overexpression is a p27Kip1-independent predictor of poor prognosis in patients with biliary tract cancers

To better understand the pathogenesis of biliary tract carcinoma (BTC) and to increase the accuracy of predicting outcomes for patients with this disease, we performed molecular cytogenetic analyses of BTC cell lines and tumors to identify non-random amplification(s) and target gene(s) within the amplicons. Among several non random chromosomal aberrations detected in BTC cell lines by comparative genomic hybridization, gain/ampli-fication of DNA at 5p was the most frequently observed alteration. We assessed the copy number and expression status of the possible target gene SKP2 for 5p amplification in cell lines and 33 primary stage II or III tumors of BTC. SKP2 was amplified, and subsequently overexpressed in both cell lines and primary tumors of BTC. However, levels of Skp2 and p27Kip1 proteins were not correlated inversely. Heightened expression of Skp2 and reduced expression of p27Kip1 were both associated with a shorter disease-free and/or overall survival in univariate analyses. In multivariate regression analyses, Skp2 and p27Kip1 were independent predictive factors. Those results suggest that (a) overexpression of Skp2 through an amplification mechanism may contribute to the progression of BTC, (b) not only each molecule, but also the combination of Skp2 and p27Kip1, might be a useful predictor of the prognosis of BTC, and (c) molecular targets of Skp2 other than p27Kip1 may also be important factors in the pathogenesis of this disease.     

Low Helicobacter pylori eradication rates with 4- and 7-day regimens in an Iranian population

BACKGROUND: In Iran, there is insufficient information on the efficacy of Helicobacter pylori eradication regimens shorter than 10 days. This study aims at assessing the efficacy of 4- and 7-day H. pylori eradication regimens in a high-incidence area of gastric cancer in Iran. METHODS: Subjects with an endoscopic diagnosis of gastritis, positive urease test, and a histological diagnosis of chronic gastritis were enrolled. Patients were randomly assigned to one of three groups: AOC7 (1000 mg amoxicillin, 20 mg omeprazole, and 500 mg clarithromycin twice daily for 7 days), FOT4 (200 mg furazolidone, 20 mg omeprazole, and 500 mg tetracycline twice daily for 4 days) and FOT7 (the same treatment as the FOT4 group but for 7 days). Sensitivity to these antibiotics was determined in all isolates recovered from culture. The efficacy of eradication was assessed 8 weeks after the end-of-treatment by the 14C-urea breath test. RESULTS: One hundred and twenty-eight patients were enrolled in the study. Culture was positive for 84 patients and none of these were resistant to amoxicillin, tetracycline or furazolidone, 1.2% were resistant to clarithromycin and 32.1% to metronidazole. Forty-five, 41 and 42 patients were randomly allocated to the AOC7, FOT4, and FOT7 groups, respectively. The intention-to-treat eradication rates were 35.5, 17.1, and 23.8% for the AOC7, FOT4, and FOT7 groups, respectively. CONCLUSION: Treatment regimens of 4 or 7 days are unacceptable for H. pylori infection in Iran, even in the presence of a favorable sensitivity profile.     

Correlates of death anxiety in Pakistan

To ascertain the effect of gender, age, and religiosity on death anxiety, 132 participants were interviewed using Templer Death Anxiety Scale and Collett-Lester Fear of Death Scale (CLS). Women, older participants, and less religious participants were found to be more scared of their impending death. Gender effect was more pronounced, however, on the CLS. Women and less religious people reported to experience greater anxiety than their respective counterparts about different dimensions of death, for example, the shortness of life, total isolation of death, fear of not being, and disintegration of body after dying. The findings of the current work indicate that the general predictors of death anxiety, gender, age, and religiosity reported in Western, predominantly Christian samples also hold in an Eastern, Muslim sample.     

Effect of Short-term Administration of Prostaglandin E<Subscript>1 </Subscript>on Viability after Ischemia/Reperfusion Injury with Extended Hepatectomy in Cirrhotic Rat Liver

The cytoprotective effect of prostaglandin E₁ (PGE₁) has been demonstrated experimentally and clinically against hepatic ischemia and reperfusion injury and against the effects of partial hepatectomy in both individual and combined models of noncirrhotic livers. Cirrhotic livers are more vulnerable to ischemia/reperfusion injury during hepatectomy than are noncirrhotic livers, and postoperative malfunctioning complicates life with multiple organ failure. Cirrhotic livers with tumors have mostly been treated conservatively because extended hepatectomy with induced ischemia during surgery is impossible. The purpose of our study was to document postoperative surgical adaptation in inoperable cases with improved survival after extended hepatectomy in a rat model of cirrhosis treated by PGE₁. Cirrhosis was induced by intraperitoneal injections of 1% dimethylnitrosamine. The liver was subjected to 15 minutes of total ischemia by occluding the hepatoduodenal ligament. Hepatectomy was performed during ischemia. Pretreatment with PGE₁ (0.4 g/kg/min) (or without it in the controls) was given for 15 minutes by intravenous infusion prior to inducing ischemia and during reperfusion. Portal venous flow (PVF) and liver tissue blood flow (LTBF) were measured during reperfusion. At the end of 60 minutes of reperfusion, venous blood was collected for liver function tests. The animals were followed up regarding survival for 48 hours. The PVF and LTBF were significantly improved in the PGE₁ group. The blood chemical analysis indicated that PGE₁ significantly suppressed posthepatectomy liver dysfunction. Most importantly, PGE₁ treatment markedly improved the survival rate, from 42% in the controls to 75% in the test animals at 24 hours after hepatectomy and from 17% in the controls to 58% in the test animals at 48 hours. We concluded that short-term administration of PGE₁ makes extensive hepatectomy possible under ischemic conditions in cirrhotic livers.     

MRI of failed total hip replacement caused by abductor muscle avulsion

OBJECTIVE: Our purpose is to describe the use of MRI and associated metal artifact reduction techniques to detect abductor muscle avulsion from the greater trochanter, a complication unusual to the anterolateral approach for total hip replacement. CONCLUSION: MRI facilitates the detection of abductor muscle avulsion in patients who have undergone the anterolateral approach during total hip replacement. MRI is considered a valuable diagnostic tool when this condition is suspected.