Estrogens affect endothelin-1 mRNA expression in LNCaP human prostate carcinoma cells

OBJECTIVE: To study effects of estrogens on endothelin-1 (ET-1) mRNA expression in the androgen-sensitive LNCaP-FGC cell line and its androgen-resistant derivative LNCaP-r. Further, if effects of estrone sulfate (E1S) are mediated via conversion to estradiol-17beta (E2). Estrogens have been shown to down-regulate ET-1, a mediator of the osteoblastic response of bone to metastatic prostate cancer.METHODS: Cells were grown in steroid-depleted medium and incubated for 2-4 and 48 hours with 0, 1, 10, and 100 nM of either E1S or E2. mRNA levels were measured with an RT-PCR technique. Estrogen metabolism by LNCaP-FGC cells was studied by incubation with estrone (E1) and E1S at the same conditions, followed by determination of E1 and E2.RESULTS: ET-1 mRNA expression in LNCaP-FGC cells was significantly suppressed by E2 and E1S following incubation for 2-4h but after 48 h only by E2 at 1 and 10nM and in LNCaP-r cells only by E2 at 100 nM following 2-4h of incubation. ET-1 mRNA expression was significantly higher in untreated LNCaP-r than in untreated LNCaP-FGC cells. E1 was efficiently transformed into E2 by LNCaP-FGC cells but very little to E1 and no E2 was formed from E1S.CONCLUSION: ET-1 mRNA expression in LNCaP-FGC can be inhibited by E2, but also by its prehormone E1S. The lack of formation of E2 from E1S suggests a mode of action not related to classical steroid receptors. The higher level of ET-1 mRNA expression found in LNCaP-r cells may reflect the capability of a hormone refractory tumor to maintain activity on its own, independently of known regulatory mechanisms such as sex steroids.     

Stimulation of spinal 5-HT(2A/2C) receptors potentiates the capsaicin-induced in vivo release of substance P-like immunoreactivity in the rat dorsal horn

Stimulation of spinal serotonin (5-HT)_2A/2C receptors has previously been reported to lead to either a pro-nociceptive or an anti-nociceptive response. Behavioral data have indicated that the pro-nociceptive effect is related to the release of substance P (SP). The aim of this in vivo microdialysis study was to investigate if stimulation of spinal 5-HT_2A/2C receptors by the selective agonist (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) induces spontaneous or capsaicin-evoked increase in the release of SP-like immunoreactivity (SP-LI) in the rat dorsal horn. A dose of capsaicin (25 μM in the perfusion medium administered for 30 min), which did not lead to a significant release of SP-LI on its own, induced a significant increase of greater than 4-fold of the SP-LI level following spinal application of 50 nmol DOI. Higher (500 nmol) or lower (5 nmol) doses of DOI failed to induce a similar effect. In rats with a peripheral inflammation, induced by carrageenan, capsaicin (25 μM) induced a non-significant increase of SP-LI. A significant 8-fold increase of the SP-LI level was detected following administration of 50 nmol DOI in combination with capsaicin. The effect of DOI, which was completely prevented by co-administration of the 5-HT_2A receptor antagonist ketanserin in control animals without peripheral inflammation, was only partly blocked in animals with carrageenan induced peripheral inflammation. In conclusion, stimulation of 5-HT_2A/2C receptors facilitates the capsaicin-evoked release of SP-LI in the dorsal horn in both animals with and without carrageenan-induced unilateral inflammation. The observation that the highest dose of DOI failed to induce SP-LI release may be due to an inhibitory postsynaptic action at this dose.     

Progression of cardiomyopathy after liver transplantation in patients with familial amyloidotic polyneuropathy, Portuguese type

BACKGROUND: Transthyretin amyloidosis is today an accepted indication for orthotopic liver transplantation (OLT). For several mutations progression of the cardiomyopathy has been observed after OLT. The aim of this study was to assess the course of cardiac involvement in Swedish familial amyloidotic polyneuropathy (FAP), Portuguese type, after OLT. By comparison of the echocardiographic findings before OLT with those obtained after, the course of the heart involvement was followed. METHODS: Twenty-three patients, who had undergone OLT and were examined with echocardiography 1-12 months before OLT, were available for the study. Twenty-one patients were examined 12-27 months after OLT, and 12 were re-examined 52-71 months after OLT. Two-dimensional and M-mode echocardiography were performed in accordance with the standards of the American Society of Echocardiography. RESULTS: A significantly increased septal and left ventricular posterior wall thickness and a significantly increased left atrial dimension was observed at the post-OLT examinations, indicating a progression of the amyloid heart disease. This increase of the cardiac involvement was neither correlated to waiting time for OLT or to pre-operative signs of cardiomyopathy. CONCLUSIONS: Even though the production of the amyloidogenic-mutated transthyretin is stopped by OLT, the cardiomyopathy may progress after the operation even for the Portuguese type of FAP. The increase of the septal and left ventricular posterior wall thickness after OLT is not restricted to patients with signs of left ventricular hypertrophy before the transplantation. The findings have important implications for the follow-up of FAP patients after OLT.     

Postoperative pain relief using intermittent injections of 0.5% ropivacaine through a catheter after laparoscopic cholecystectomy

Postoperative pain has been an important limiting factor for ambulatory laparoscopic cholecystectomy. We anesthetized 40 ASA physical status I-II patients using propofol for the induction and sevoflurane in oxygen and air for the maintenance of anesthesia. At the end of the anesthesia, the patients were randomized into one of two groups: Group P (Placebo) and Group R (0.5% Ropivacaine). Twenty milliliters of normal saline or ropivacaine, respectively, were injected intraperitoneally at the end of surgery via a catheter placed in the bed of the gall bladder. Postoperatively, intermittent injections (10 mL) of the study solution were given when required for pain. Ketobemidone 1-2 mg was given IV as rescue medication. Pain was assessed using a visual analog scale at 1, 2, 3, 4, 8, 12, 16, and 20 h after surgery and once each day for 1 wk at rest (deep pain), shoulder and incision sites, and pain during coughing. Recovery was assessed by the time to transfer from Phase 1 to 2, the ability to walk, drink, and eat, and the ability to void. Plasma concentrations of ropivacaine were measured in eight patients. Time to ability to walk, defecation, driving a car, and return to normal activities were also recorded through a questionnaire sent home with the patient. During the first 4 postoperative h, patients in Group R had lower scores for deep pain and during coughing compared with Group P (P < 0.05). No differences were found in the postoperative consumption of ketobemidone. Median times to recovery at home were similar between the groups. By the seventh day, 93% of the patients had returned to normal activities of daily living. We conclude that the early postoperative pain after ambulatory laparoscopic cholecystectomy could be relieved using intermittent injections of ropivacaine 0.5% into the bed of the gall bladder. IMPLICATIONS: Early postoperative pain can be relieved by intermittent injections of ropivacaine 0.5% through a catheter placed in the bed of the gall bladder after ambulatory laparoscopic cholecystectomy.     

Cognitive functioning in Alzheimer's disease and vascular dementia: further evidence for similar patterns of deficits

The purpose of the present study was to examine possible differences in patterns of cognitive performance between population-based samples of Alzheimer's disease (AD; n = 51) and vascular dementia (AD; n = 14) patients between 75 and 96 years of age. The two demented groups were comparable in age, years of education, gender distribution, and severity of dementia. The selection of cognitive tasks (letter and category fluency, Block design, Clock reading and setting, and episodic face recognition) was thought to address some of the inconsistencies in previous research. The main finding was that AD and AD patients were comparable on most tasks, although robust dementia-related deficiencies were found when comparing the results of the demented participants with those of the control participants. These findings suggest that AD and AD may affect several basic cognitive functions in an equal manner.     

Neurotensin-induced modulation of dopamine D2 receptors and their function in rat striatum: counteraction by a NTR1-like receptor antagonist

The present study investigated the neurotensin (NT) receptor subtype (NTR) involved in the antagonistic neurotensin modulation of striatal dopamine D2 receptors observed in vitro and in vivo. The NT induced increase of the IC50 values of dopamine (DA) competition for [125I]iodosulpiride binding sites was counteracted by the NTR1-like antagonist SR48692 in rat striatal slices. Intrastriatal perfusion of pergolide induced in the awake rat an inhibition of striatal DA release that was antagonized by NT. This action of NT was counteracted by co-perfusion with the NTR1 like antagonist SR48692. These data indicate that there exists in the striatum at the prejunctional level an intramembrane antagonistic NT receptor/DA D2 receptor-receptor interaction where NTR1 like receptor activation reduces the DA D2 autoreceptor function.     

Gliomas among men employed in the Swedish pulp and paper industry

OBJECTIVES: This study investigated whether previous findings of an increased risk of gliomas among workers in some pulp and paper mills could be confirmed for all Swedish pulp and paper mill workers and whether the increase could be attributed to certain occupational groups. METHODS: The study was based on the Swedish Cancer Environment Register, which links the incidence of cancer from 1971 to 1990 and the 1960 and 1970 census data on codes of occupation and industry for the whole population. Standardized incidence ratios (SIR) were used to estimate the risks for men in different occupations in pulp (N = 28,142) and paper (N = 39,169) mills in 1960, 1970 or both years as compared with those of all gainfully employed men in Sweden. RESULTS: Maintenance workers employed in pulp or paper mills in 1960, 1970 or both years, as well aspulp workers, showed an increased incidence of gliomas in 1971-1990 [SIR 1.5, 95% confidence interval (95% CI) 1.1-2.1 and SIR 1.5,95% CI 1.0-2.2, respectively], whereas the incidence among process workers in paper mills was lower than expected (SIR 0.6, 95% CI 0.3-0.9). Taken together, all employed men in the pulp mill industry had an increased incidence of gliomas (SIR 1.3, 95% CI 1.0-1.7). CONCLUSIONS: Pulp mill workers, but not paper mill workers, were found to have more gliomas in 1971-1990 than expected. There was an increased risk of gliomas among maintenance workers in both pulp and paper mills. Few risk factors for brain tumors are recognized, and the causes of the increase are not obvious.