Microalbuminuria in children and adolescents with and without Type-I diabetes mellitus (IDDM)

In 73 healthy (group I) and 32 children and juveniles with insulin dependent diabetes mellitus (IDDM, group II) urinary albumin excretion is determined by radioimmunoassay (RIA). In both groups albumin excretion is observed in every urine sample when measured by RIA (mean +/- SD: group I: 7-19 h: 5.17 +/- 5.28 mg, 19-7 h: 3.86 +/- 4.00 mg, 24 h: 9.03 +/- 8.60 mg; group II: 7-19 h: 6.68 +/- 6.86 mg, 19-7 h: 3.46 +/- 2.82 mg, 24 h: 10.13 +/- 9.25 mg). No significant difference is detected between the values of the two groups. However in diabetic patients a significant difference is observed between diurnal and nocturnal urinary albumin excretion. Microalbuminuria is defined as an albumin excretion above 30 mg/d and is present in 6.9% of the values in group I and in 3.1% in group II. The physiological limits of microalbuminuria in children and juveniles compared to adults and several methods of urine sampling are discussed.     

Sensitivity and specificity of screening for Down syndrome with alpha-fetoprotein, hCG, unconjugated estriol, and maternal age.

The sensitivity and specificity of maternal serum screening for Down syndrome with different biochemical markers were evaluated. Detection rates with different combinations of maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (uE3) were established by retrieving and analyzing 54 serum specimens from women with confirmed Down syndrome pregnancies, compared with 657 specimens from women with normal outcomes. With a risk cutoff of 1:270 at the second trimester, the detection rate with MSAFP, hCG, and uE3 was two to three times higher than with MSAFP alone. With all three markers, the detection rate for Down syndrome increased from 50 to 77% as maternal age increased, and was 60% in a representative screened population. If uE3 was omitted, the detection rate decreased from 60 to 48%. One thousand women were screened prospectively, either with MSAFP or with all three markers prospectively, either with MSAFP or with all three markers and 4.1% with MSAFP. With the three markers, the positive predictive value for Down syndrome was 2.2% overall and as high as 5.9% in older women. Therefore, the addition of hCG and uE3 to the maternal serum screen increases the positive predictive value by 50-300%, depending on maternal age. These results confirm the efficacy of screening for Down syndrome using maternal age and three serum markers.     

Decreased sensitivity to experimental pain in adjustment disorder.

An altered perception of pain has been described for several psychiatric disorders. To date the influence of adjustment disorders (AD) on pain perception has not been described. Here, we investigated perception of experimentally induced pain in 15 patients suffering from AD (subtype with depressive symptoms) and controls matched for age and sex. Thresholds and tolerances were assessed for thermal and electrical pain on both sides of the body. We found an overall increase of pain thresholds and tolerances in AD patients as compared to controls, predominately on the right side of the body. Analogue findings have been reported for pain perception in major depressive disorder (MDD). Of the data obtained, only thermal pain threshold on the right arm correlated with the severity of depressive symptoms. Although the underlying pathology is elusive it is likely that the mechanisms for reduced pain sensitivity are comparable in MDD and AD.     

Effects of pinacidil upon penile erectile tissue, in vitro and in vivo

The effect of pinacidil, a new antihypertensive vasodilator, was studied in vitro upon human and porcine Corpus cavernosum and in vivo upon simian Corpus cavernosum. In vitro, pinacidil incubation (10(-5)-10(-3) M) was found to induce a concentration-dependent inhibition of the tissue response to norepinephrine (NE) and high potassium (K+). Likewise a concentration-related relaxation of the tissue, precontracted with either NE or K+, was seen using pinacidil 10(-5)-10(-3) M. Depending on the concentration applied, spontaneous activity as well as tone and amplitude of the contractions were reduced until total relaxation of the tissue was obtained with a pinacidil incubation of 10(-3) M. In vivo, 5 mg pinacidil in 0.3 ml solution was injected intracavernosally in 17 monkeys. Sixteen monkeys developed tumescence and 10, rigidity of the penis as well. Only one of 5 showed a decrease in the systemic blood pressure. Pinacidil might be of clinical interest as an agent facilitating erection when given intravernosally.     

Synthetic inhibitors of serine proteinases. 32. Inhibition of trypsin, plasmin and thrombin by amides of N-alpha-substituted 4-amidinophenylalanine. Effect of various amino acids and blocking groups of the n-alpha residue on inhibitory activity

Cyclic amides of N alpha-arylsulfonylated 4-amidinophenylalanine are specific, highly potent inhibitors of thrombin. Introduction of amino acids between the arylsulfonyl blocking group and amino nitrogen influence particularly the antithrombin activity. By the use of glycine as spacer the compounds become tight binding thrombin inhibitors, while introduction of other omega-amino acids, Gly-Gly, L-Pro, Gly-L-Pro or L-Pro-Gly, reduces the specificity and potency of thrombin inhibition. Substitution of the arylsulfonyl blocking group for a heteroarylsulfonyl residue or an aryl residue causes a decrease in antithrombin activity, while substitution for a benzoyloxycarbonyl blocking group has only slight influence. It is concluded that the N alpha-moiety is of decisive importance for the antithrombin activity of derivatives of 4-amidinophenylalanine.     

Reepithelialization of experimental scalds effected by topically applied superoxide dismutase: controlled animal studies

Highly reactive metabolites, such as oxygen free radicals, initiate a cascade of inflammatory processes in thermally damaged skin, leading to enhanced tissue loss and delayed wound healing. The extent of tissue necrosis in the zone of stasis is of prognostic significance in the wound healing process. In this study, the effect of oxygen free radical removal by recombinant human-Cu/Zn-superoxide dismutase, given in three different formulations during the inflammatory postburn phase and wound repair, was examined. Recombinant human superoxide dismutase was either injected directly into the lesions, spread as enzyme-containing gel onto the burned tissue, or encapsulated into liposomes consisting of 1,2 dipalmitoy-sn-glycero-3-phosphocholine, cholesterol and stearylamine, suspended into a hydrophilic gel and administered to burned animals immediately after trauma. Controls were treated with plain gel or kept untreated. Edema formation, size of lesions, deepening of necrosis, and reepithelialization were examined. Results indicate that superoxide dismutase treatment resulted in reduced and faster recruitment of edema formation, smaller wound sizes, and minor tissue necrosis compared to the controls, thus resulting in significantly faster reepithelialization after 3 weeks. These animal studies on the efficacy of liposomal oxygen free radical scavenger showed accelerated wound healing in all parameters tested.     

Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases.

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.     

Pharmacokinetics of moxonidine after single and repeated daily doses in healthy volunteers

The pharmacokinetics of the centrally acting alpha-2 agonist moxonidine were investigated in 12 healthy male subjects after single and repeated oral doses (q12h for five days) of moxonidine 0.2 mg. Plasma concentration-time data followed the general characteristics of a one-compartment model with first-order absorption. Peak plasma concentrations of 1.29 +/- 0.32 ng/mL were achieved 0.74 +/- 0.35 hours after ingestion of a 0.2-mg tablet. The terminal half-life of elimination was 2.12 +/- 0.58 hours. The oral clearance (CL/F) amounted to 830 +/- 171 mL/min with renal elimination being the major route of elimination. No significant differences in pharmacokinetic parameters could be observed following repeated dosing over five days.