Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brachial endothelial function in subjects with familial combined hyperlipidemia and its relationships to carotid artery intima-media thickness.

AIM: The aim of this study was to quantify the flow-mediated dilatation (FMD) of brachial artery in asymptomatic members of families with familial combined hyperlipidemia (FCH) and to determine the relation between FMD and risk factors accompanying FCH. We also investigated the association between FMD and the intima-media thickness (IMT) of the common carotid artery. METHODS: Eighty-two members of 29 FCH families were divided into two groups: probands and hyperlipidemic first-degree relatives (HL) (n=47) and normolipidemic first-degree relatives (NL) (n=35). The control (C) groups, C-HL (n=20) and C-NL (n=20), consisted of sex- and age-matched healthy individuals. FMD was assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia. RESULTS: Both hyperlipidemic subjects and their NL had significantly lower FMD (3.4+/-3% vs 6.3+/-2.8%, P<0.001, 5.2+/-2.3% vs 7.8+/-2.8%, P<0.01, respectively) compared to controls. In multivariate backward stepwise regression analysis, FMD in members of FCH families was independently associated with sex (P<0.001), age (P<0.01), C-peptide (P<0.05) and borderline with glycemia (P=0.052). FMD correlated inversely with IMT in all subjects of FCH families and in hyperlipidemic members. In multivariate backward stepwise regression analysis this relation remained independent (P<0.001, P<0.01, respectively). CONCLUSIONS: Members of FCH families showed impaired FMD, which was independently associated with markers of insulin resistance. FMD and IMT were independently associated in hyperlipidemic, but not in normolipidemic members of FCH families.     

Surgical treatment of cavernous haemangiomas of the liver

Cavernous haemangiomas of the liver were surgically treated in 36 women and 14 men over a 10-year period. The tumours were solitary in 42 cases and multiple in 8. Locations were the right lobe in 39 cases, the left one in 5 and both lobes in 6. The size of the tumours ranged from 0.4 to 14 cm in diameter. Enucleation of tumours was carried out in 29 cases, an atypical liver resection in 19 cases, anatomical lobectomy in 2 cases and a right trisegmentectomy in 1 case. There was no mortality. Morbidity rate seems to be lower in patients who underwent enucleation. The authors indicate the importance of enucleation for removal of liver haemangiomas of various sizes.

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Chirurgische Behandlung kavernöser Hämangiome der Leber

Zusammenfassung Über einen Zeitraum von 10 Jahren wurden kavernöse Hämangiome der Leber bei 36 Frauen und 14 Männern chirurgisch behandelt. Bei 42 Patienten waren die Tumoren solitär, bei 8 multipel. Sie waren in 39 Fällen im rechten, bei 5 Patienten im linken und bei 6 in beiden Leberlappen lokalisiert, ihr Durchmesser betrug 0,4 bis 14 cm. In 29 Fällen wurde eine Enukleation, in 19 eine atypische Leberresektion, in 2 eine anatomische Lobektomie und in einem Falle eine rechtsseitige Trisegmentektomie durchgeführt. Die Mortalität war gleich Null; die Morbiditätsrate scheint bei den Patienten geringer, die mit Enukleation behandelt wurden. Der Beitrag hebt die Bedeutung der Enukleation zur Beseitigung von Leberhämangiomen unterschiedlicher Größe hervor.

     

Tumor necrosis factor production in septic conditions following pancreatitis (preliminary report)]

Detectable TNF levels in sera 33% of patients with sepsis following pancreatitis have been found. No correlation was observed between serum TNF concentration and the severity of illness. However, monocytes and granulocytes of septic patients exerted higher TNF-mediated cytotoxicity than leukocytes of normal blood donors. The in vitro TNF-producing capacity was also higher in the patients in the study group, and it decreased only before fatal outcoming of sepsis. Our results suggest that determination of the TNF-producing capacity of leukocytes might be more informative than measurement of the serum TNF level in the evaluation of the severity or prognosis of sepsis.     

Observation on serum prolactin in hepatic cirrhosis.

Serum prolactin assays in patients of hepatic cirrhosis were analysed. Patients with cirrhosis had higher values of serum prolactin (27.2 +/- 5.1 ng/ml in males and 38.4 +/- 4.1 ng/ml in females) as compared to control subjects (p less than 0.05). Majority of patients of cirrhosis with suspected portal-systemic encephalopathy had significantly higher serum prolactin than those without encephalopathy (p less than 0.05). Significantly higher values of serum prolactin on admission had positive correlation with mortality (p less than 0.01). Clinico-biochemical severity of hepatic dysfunction was directly correlated with level of serum prolactin. The present study reveals the possibility of diagnostic and prognostic values of serum prolactin in cirrhosis, specially in clinical/sub-clinical subsets of portal-systemic encephalopathy.     

Combined high-efficiency hemodialysis and charcoal hemoperfusion in severe N-acetylprocainamide intoxication.

Several extracorporeal techniques have been used to remove N-acetylprocainamide (NAPA), the major metabolite of procainamide, in patients intoxicated with this substance. We report a patient with life-threatening NAPA intoxication who was rapidly and successfully treated with combined high-efficiency hemodialysis and charcoal hemoperfusion. The hemodialyzer and hemoperfusion cartridge were placed in series such that the patient's blood was dialyzed before reaching the cartridge. Overall clearance of NAPA was 153 mL/min, with clearance due to hemodialysis averaging 102 mL/min and that due to hemoperfusion averaging 88 mL/min. Thus, addition of the hemoperfusion cartridge into the extracorporeal circuit resulted in a 50% increase in clearance over that obtainable by high-efficiency hemodialysis alone. In comparison to other modalities, this technique is more effective than either hemodialysis or charcoal hemoperfusion alone and can achieve a more rapid reduction of serum NAPA levels than that observed with slow continuous hemofiltration or hemodiafiltration.