Is arterial hypertension an underlying factor in the increased serum Lp(a) levels in ESRD dialyzed patients?

Except for the disorders in lipoprotein metabolism several other factors have been involved in the development of atherosclerotic changes in ESRD patients, including arterial hypertension. Serum lipid profile (total cholesterol (TC), triglycerides (TG), apolipoproteins (AI,AII,B,E) and Lp(a)) was evaluated in 109 ESRD dialyzed patients, 46 in HD and 63 in CAPD and 45 hyperlipidemic patients without renal failure (HL-group). According to the presence of arterial hypertension the dialyzed patients were divided in two groups: group A of 42 hypertensive patients, (mean age 62.3 +/- 15.5 years), which were satisfactorily controlled with anti-hypertensive medication, and group B of 67 non-hypertensive patients, (mean age 66.6 +/- 11.9 years). Lp(a) levels were statistically significantly higher than HL group in both HD (p = 0.001) and PD (p < 0.05) patients. Besides, by dividing HD and PD group in hypertensive and non-hypertensive patients, Lp(a) levels were statistically significantly higher in hypertensive patients, while such a difference was not observed among non-renal failure patients. These results indicate that arterial hypertension may play an important role in Lp(a) serum titles, in ESRD patients undergoing either HD or PD.     

Multifocal soft-tissue metastases of gastric leiomyosarcoma

Distant soft-tissue metastases in gastric leiomyosarcoma (LMS) are extremely rare. In a 65-year-old woman, a large, low-grade LMS originating from the stomach wall was treated by partial gastrectomy. Eight years later, the patient developed multifocal, soft-tissue, high-grade LMS. These tumors were presumably metastases of the gastric LMS. However, due to the demonstration of mutations in some cases of leiomyosarcoma, the possibility of multifocal sarcoma should be kept in mind.     

Development and validation of a highly sensitive RIA for zoledronic acid,a new potent heterocyclic bisphosphonate,in human serum,plasma and urine

Zoledronic acid is a new, highly potent bisphosphonate drug under clinical evaluation. A radioimmunoassay has been developed to determine zoledronic acid concentration in human serum, plasma, and urine. The assay utilizes rabbit polyclonal antisera against a zoledronic acid-BSA conjugate and a [125I]zoledronic acid derivative as tracer in a competitive format adapted to microtiter plates. The assay shows a LLOQ 0.4 ng/ml in serum or plasma (interassay%CV=17%, accuracy 97%), 5 ng/ml in urine (21%, 98%). In 23 patients receiving 4, 8 or 16 mg of zoledronic acid, drug concentrations in plasma were dose proportional and showed a multiphasic profile, followed by a prolonged gradual decline to concentrations near the LLOQ. Zoledronic acid disposition in plasma and the recovery of only 40-50% of the dose in urine are consistent with the rapid and extensive uptake by and slow release from bone in parallel with renal clearance, typically shown by bisphosphonates.     

Unweaving the Web: an exploratory study of low-literate adults' navigation skills on the World Wide Web

For traditionally underserved populations, the Web can potentially unlock resources that could fundamentally improve health and wellbeing. However, there are many barriers to using Web-based content. While physical access issues are well documented, there is little understanding of how nonmainstream populations use or will use the Web. Based on an ethnographic study of a group of low-literate adults, we have identified specific navigational and content issues that present barriers to this population. We discuss preliminary assumptions that can be used to inform the development of Web tools for this target audience, and directions for future applied research.     

G protein-coupled receptor for nicotinic acid in mouse macrophages

The use of the HDL-elevating drug nicotinic acid in the treatment and prevention of atherosclerotic disease is limited by the frequent induction of skin flushing. The therapeutic effects of nicotinic acid are attributed to inhibition of lipolysis in adipose tissue via a G protein-coupled receptor, whereas the mechanism of flush induction by release of prostaglandin D(2) from macrophages is not understood. In this study, we investigated if macrophages contain nicotinic acid receptors. Specific guanine nucleotide sensitive binding sites for [(3)H]nicotinic acid were detected in membranes from mouse RAW 264.7 macrophages. Nicotinic acid and related heterocycles stimulated activation of pertussis toxin-sensitive G proteins. The rank orders of potency in macrophage membranes were identical for inhibition of [(3)H]nicotinic acid binding and G protein activation, and were pharmacologically indistinguishable from that of the G protein-coupled nicotinic acid receptor in spleen membranes. These results indicate that the effects of nicotinic acid on macrophages, spleen and probably adipocytes are mediated via an identical, unique G protein-coupled receptor.     

Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport

1. Neuronal cholinergic input is an important regulator of epithelial electrolyte transport and hence water movement in the gut. 2. In this study, colitis was induced by treating mice with 4% (w v(-1)) dextran sodium-sulphate (DSS)-water for 5 days followed by 3 days of normal water. Mid-colonic segments were mounted in Ussing chambers and short-circuit current (Isc, indicates net ion movement) responses to the cholinergic agonist, carbachol (CCh; 10(-4) M)+/-tetrodotoxin, atropine (ATR), hexamethonium (HEX), naloxone or phenoxybenzamine were assessed. 3. Tissues from mice with DSS-induced colitis displayed a drop in Isc in response to CCh (-11.3+/-3.3 microA/cm(2)), while those from control mice showed a transient increase in Isc (76.3+/-13.0 microA/cm(2)). The DeltaIsc in colon from DSS-treated mice was tetrodotoxin-sensitive, atropine-insensitive and was reversed by hexamethonium (HEX+CCh=16.7+/-7.8 microA/cm(2)), indicating involvement of a nicotinic receptor. 4. CCh induced a drop in Isc in tissues from controls only when they were pretreated with the cholinergic muscarinic receptor blocker, atropine: ATR+CCh=-21.3+/-7.0 microA/cm(2). Nicotine elicited a drop in Isc in Ussing-chambered colon from both control and DSS-treated mice that was TTX-sensitive. 5. The drop in Isc evoked by CCh challenge of colonic tissue from DSS-treated mice or ATR+CCh challenge of control tissue was not significantly affected by blockade of opiate or alpha-adrenergic receptors by naloxone or phenoxybenzamine, respectively. 6. The data indicate that DSS-colitis reveals a nicotinic receptor that becomes important in cholinergic regulation of ion transport.