Ganglioside or sialic acid attenuates ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature.

1. This laboratory has previously reported that pretreatment with ganglioside, or even with its constituent, sialic acid (SA), can attenuate certain intoxicating effects of ethanol. It was important to see if these findings could be replicated, particularly by using other measures of ethanol effects. Herein we report that pretreatment with either gangliosides or SA attenuated ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature. 2. An ethanol dose of 4 gm/kg caused a temperature drop of about 3 degrees C, which was unaffected by any pretreatment. The onset to sleep, however, was delayed an average of 18 or 36 secs in mice pretreated with ganglioside or SA, respectively. Ethanol-only (4 gm/kg) depressed mean cumulative locomotor activity to 31% of normal, whereas the depression was 83% of normal with beef brain ganglioside pretreatment. At 2 gm/kg ethanol alone decreased nose poking in a hole-board test to 29% of normal, but the depression was only 55-63% of normal with SA or ganglioside pretreatment. In a staircase climbing anxiety test, this dose of ethanol had no effect by itself, but both ganglioside and SA pre-treatment increased climbing by 22%. Ethanol did depress rearing to only 11% of normal, whereas rearing was 51 and 99% of normal with SA and ganglioside pretreatment, respectively. In a dark-preference test, ethanol-only caused mice to spend 64% of the time in the light, compared to 31% for controls. Time in the light was only 39 and 46% with ganglioside and SA pretreatment, respectively. 3. Blood levels of ethanol were not significantly affected by pretreatment. 4. When given alone, gangliosides significantly stimulated locomotion and staircase climbing. SA significantly decreased rearing in the staircase test. Both gangliosides and SA tended to increase nose poking, number of crossings in the dark-preference test, and time in a lighted compartment. Thus, it is possible that some of the attenuation of intoxication is attributable to non-specific stimulant properties of gangliosides and SA.     

Hybrid procedures as a combined endovascular and open approach for pararenal and thoracoabdominal aortic pathologies

OBJECTIVES: to report our experience with hybrid vascular procedures in patients with pararenal and thoracoabdominal aortic pathologies. METHODS: 68 patients were treated for thoracoabdominal aortic pathologies between October 1999 and February 2004; 19 patients (16 men; mean age 68, range 40-79) with high risk for open thoracoabdominal repair were considered to be candidates for combined endovascular and open repair. Aortic pathologies included five thoracoabdominal Crawford I aneurysms, one postdissection expanding aneurysm, three symptomatic plaque ruptures (Crawford IV), five combined thoracic descending and infrarenal aneurysms with a healthy visceral segment, three juxtarenal or para-anastomotic aneurysms, and two patients with simultaneous open aortic arch replacement and a rendezvous maneuver for thoracic endografting. Commercially available endografts were implanted with standardized endovascular techniques after revascularization of visceral and renal arteries. RESULTS: Technical success was 95%. One patient developed a proximal type I endoleak after chronic expanding type B dissection and currently is waiting conversion. Nine patients underwent elective, five emergency and five urgent (within 24 h) repair. 17 operations were performed simultaneously, and 2 as a staged procedure. Postoperative complications include two retroperitoneal hemorrhages, and one patient required long-term ventilation with preexisting subglottic tracheal stenosis. Thirty-day mortality was 17% (one multiple organ failure, one secondary rupture after open aortic arch repair, one myocardial infarction). Paraplegia or acute renal failure were not observed. Total survival rate was to 83% with a mean follow-up of 30 months. CONCLUSIONS: Midterm results of combined endovascular and open procedures in the thoracoabdominal aorta are encouraging in selected high risk patients. Staged interventions may reduce morbidity.     

Radiofrequency-ablation of unresectable primary and secondary liver tumors: results in 88 patients

Background and aims Radiofrequency-ablation (RFA) is increasingly used for destruction of unresectable primary and secondary liver tumors. We report our experience in the use of RFA for the management of unresectable hepatic malignancies. Patients and methods Between February 2000 and December 2004 we have undertaken 120 RFA procedures to ablate 426 unresectable primary or metastatic liver tumors in 88 patients. RFA was performed via laparotomy (n=68), laparoscopy (n=9) or a percutaneous approach (n=43). Primary liver cancer was treated in seven patients (8%) and metastatic liver tumors were treated in 81 patients (92%). All patients were followed to assess complications, treatment response and recurrence of malignant disease. Results Procedure-related complication rate was low (3.4%). During a mean follow-up of 21.2 months, 15 patients had local tumor progression (17%), 21 patients (23,9%) had new malignant disease and 27 patients (30.7%) died from intervention-unrelated complications of their malignant disease. Additional liver lesions were identified in 27 (35%) of 77 cases by intraoperative ultrasound. Thirty-six patients received simultaneous resection and RFA. Conclusion RFA is a safe, well-tolerated and effective treatment for patients with unresectable primary and secondary liver malignancies.     

BIOCHEMICAL CORRECTION IN THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA BY SEVERE DIETARY SALT RESTRICTION SUGGESTS RENIN-ALDOSTERONE SUPPRESSION CRITICAL IN PATHOPHYSIOLOGY

1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities.     

RENIN GENE POLYMORPHISM ASSOCIATED WITH ALDOSTERONE RESPONSIVENESS TO THE RENINANGIOTENSIN SYSTEM IN PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMAS

1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.     

Influence of methylphenidate on brain development – an update of recent animal experiments

Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment.     

The pharmacokinetics and metabolism of bonnecor in rats

The pharmacokinetics of 14C-bonnecor after intravenous and oral administration was studied. The bioavailability was 70%. It was shown that administration of doses in the range of from 3 to 43 mg/kg as well as the repeated use of bonnecor failed to influence the pharmacokinetic parameters.