Clinical studies with the potassium channel activator cromakalim in normotensive and hypertensive subjects.

Eight normotensive subjects received single and multiple doses of cromakalim (1 mg) and placebo in a randomised double-blind cross-over study to examine general tolerance to cromakalim and its effects on blood pressure (BP), heart rate (HR), and pressor responses to norepinephrine (NE) and angiotensin II (AII). In a second study, 10 hypertensive patients whose BP control was unsatisfactory with atenolol 50-100 mg received additional treatment with placebo followed by cromakalim 1 mg daily for 4 weeks. Assessments were made of BP, HR, apparent hepatic blood flow and renal blood flow (RBF), pulmonary function, and the pharmacokinetics of atenolol. Cromakalim was generally well tolerated in both normotensive and hypertensive subjects. In the normotensive group, cromakalim produced a reflex increase in HR without any detectable decrease in BP: average (placebo-subtracted) increases in HR at 4 h were 16 beats/min with subjects in an erect position after the single dose and 14 beats/min after 7 days. Cromakalim had no effect on pressor responses to NE and AII. Addition of cromakalim to atenolol was associated with modest further reductions in BP between 0.5 and 3 h after drug administration, with maximal reductions of 21/14 mm Hg (subjects in supine position) 2 h after the first dose. Cromakalim had no effect on apparent liver blood flow and RBF, pulmonary function, and the steady-state pharmacokinetics of atenolol. Single and multiple 1-mg doses of cromakalim are well tolerated but are associated with only modest vasodilator activity.     

Interaction between bovine collagen and glycolic acid peeling: A proposal of a new protocol

For the past 10 years the alfa-hydroxyacids and the bovine collagen injection have been used for peeling and the correction of multiple skin diseases. Until now, such progressive achievement has occurred in separate parallels just like the indications that have been held distinct. However, the studies carried out in order to clarify the mechanical action of the two substances have shown a common and fundamental denominator: the stimulation of synthesis of the new collagen in the patient's skin. On the basis of these results and the existence of common clinical indications of the use of glycolic acid and collagen, the authors have worked out a protocol involving a combined and contemporary application in progressive steps. They developed the rationales of such protocol and analyzed the results of its application on a number of carefully selected patients for a clinical comparison and on a sample of rats for a histological comparison. They have concluded that the contemporary use of glycolic acid and bovine collagen is a simple and safe method whose synergy action leads to more intense and long-lasting effects than the ones observed in the isolated application of the two substances. The authors have also obtained interesting and significant histological results.     

Hereditary gastrointestinal polyposis syndromes

Hereditary gastrointestinal polyposis syndromes can be divided into adenomatous and hamartomatous types. Familial adenomatous polyposis coli (FAPC) is the prototype adenomatous polyposis syndrome and is defined by the autosomal dominant transmission of multiple (more than 100) colorectal adenomas. Virtually all affected patients develop colorectal carcinoma if untreated. Adenomas may develop also in the stomach and small bowel in FAPC patients, but the incidence of carcinoma in these sites is low. A variety of extracolonic manifestations has been reported in FAPC, with the name Gardner's syndrome applied to kindreds with osteomas of the skull and mandible, multiple epidermal cysts, and other skin and soft-tissue lesions. In Turcot's syndrome, brain tumors are present. The distinction between Gardner's and Turcot's syndromes and classical FAPC has become blurred because of marked overlap between them; some authorities consider them to be varying manifestations of a single genetic defect. The hamartomatous polyposes include Peutz-Jeghers syndrome, familial juvenile polyposis, Cowden's disease, intestinal ganglioneuromatosis, and the Ruvalcaba-Myrhe-Smith syndrome. The incidence of gastrointestinal cancer in patients with Peutz-Jeghers syndrome and familial juvenile polyposis exceeds that in the normal population, but is relatively low. In Cowden's disease, the gastrointestinal tract may be the site of multiple hamartomas, but there is no associated increase in the incidence of gastrointestinal cancers; instead, there is an increased incidence of carcinoma of the breast and thyroid. Intestinal ganglioneuromatosis occurs in von Recklinghausen's disease, in association with multiple endocrine neoplasia, type 2b, or as an isolated abnormality. Patients with ganglioneuromatosis do not appear to have an increased risk of developing gastrointestinal cancer. Ruvalcaba-Myrhe-Smith syndrome comprises macrocephaly, mental deficiency, an unusual craniofacial appearance, hamartomatous intestinal polyposis, and pigmented macules on the penis. No increased risk of developing cancer has been identified in the few reported cases.     

Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects.

Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter- and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray-matter to white-matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray-matter perfusion, which was found to decrease by 0.45% per year (P = 0.04). Regional analysis suggested that the gray-matter age-related changes were predominantly localized in the frontal cortex. Whole-brain perfusion was 13% higher (P = 0.02) in females compared to males.     

Sphingolipid metabolites in neural signalling and function

Sphingolipid metabolites, such as ceramide, sphingosine, sphingosine-1-phosphate (S1P) and complex sphingolipids (gangliosides), are recognized as molecules capable of regulating a variety of cellular processes. The role of sphingolipid metabolites has been studied mainly in non-neuronal tissues. These studies have underscored their importance as signals transducers, involved in control of proliferation, survival, differentiation and apoptosis. In this review, we will focus on studies performed over the last years in the nervous system, discussing the recent developments and the current perspectives in sphingolipid metabolism and functions.