Blood-brain barrier penetration of 3-aminopropyl-n-butylphosphinic acid (CGP 36742) in rat brain by microdialysis/mass spectrometry.

The detection and quantitation of the novel drug 3-aminopropyl-n-butylphosphinic acid (APBP), also known as CGP 36742, was performed in vivo using microdialysis and tandem mass spectrometry. This drug is a GABA-B antagonist with high specificity for GABA-B receptors. Animals received doses of 100, 200, 500 and 1000 mg kg-1 of the drug either intravenously or per os (p.

Molecular analysis of the human vitamin D binding protein (group specific component, Gc) in tuberous sclerosis complex (TSC).

Group specific component (Gc) is an abundant plasma protein whose functional role is not clearly established. Gc protein is synthesised in the liver and is known to bind vitamin D, vitamin D metabolites, and G actin; Gc protein is also implicated in macrophage activation. Several polymorphic electrophoretic variants of Gc protein are found in all human populations; the most common alleles are Gc-1f, Gc-1s, and Gc-2.

Long duration-mild whole body hyperthermia of up to 12 hours in rats: feasibility, and efficacy on primary tumour and axillary lymph node metastases of a mammary adenocarcinoma: implications for adjuvant therapy.

The feasibility and efficacy of low temperature (40 degrees C) long duration whole body hyperthermia (LL-WBH) was investigated in rats bearing a highly metastatic mammary adenocarcinoma (MTLn3). We compared the treatment effects of various durations of LL-WBH (40 degrees C for 2-12 h) to that of conventional short duration-high temperature WBH (SH-WBH, 41.5 degrees C for 2 h).

Resistance to antifungal agents in the critical care setting: problems and perspectives.

As is the case with antibacterial agents, the increasing use of antifungal agents has led to development of antifungal resistance, the most clinically important of which is the resistance of Candida to fluconazole. While mutation to high-level fluconazole resistance is possible, the most important aspect of fluconazole resistance for patients in the ICU is the possibility of an epidemiologic shift away from such susceptible species as C. albicans and C.

Regulation of synaptic facilitation by postsynaptic Ca2+/CaM pathways in hippocampal CA1 neurons.

1. Current- and voltage-clamp recordings with simultaneous field potential recordings were used to study the cellular and molecular mechanisms that contribute to synaptic facilitation at CA1 synapses in rat hippocampal slices. Microelectrodes used for intracellular recordings were also used to inject modulators of intracellular signal pathways into postsynaptic CA1 neurons.

Report of a critical recombination further narrowing the TSC1 region.

A large tuberous sclerosis multigenerational family segregating with markers on chromosome 9q from the TSC1 region was studied with a new highly polymorphic marker (designated A6) from the region. A critical affected person showed recombination with the marker, eliminating approximately 100 kilobases from the telomeric end of the critical region, which contains three genes and three to four additional exons for which the associated genes have not been delineated. This information serves to further the search for the TSC1 gene.

Behavioral outcomes after pediatric closed head injury: relationships with age, severity, and lesion size.

This study investigated the behavioral outcomes and adaptive functioning of 138 children with mild to severe closed head injury in the 6- to 16-year age range. Each child was evaluated with the Personality Inventory for Children-Revised. A subset of this sample (n = 77) received the Vineland Adaptive Behavior Scales.

Role of H(+)-K(+)-ATPase in pHi regulation in inner medullary collecting duct cells in culture.

Studies in inner medullary collecting duct (IMCD) cells in primary culture have proposed two mechanisms for Na(+)-independent hydrogen ion transport: an H(+)-adenosinetriphosphatase (H(+)-ATPase) and an H(+)-K(+)-ATPase. In the present study, we have employed two sources of IMCD cells, cells in primary culture derived from the terminal papilla of the Munich-Wistar rat (IMCDp) and an established murine cell line (mIMCD-3), to define the predominant mechanism(s) of Na(+)-independent intracellular pH (pHi) recovery in the IMCD. In confluent monolayers of IMCDp and mIMCD-3 cells, pHi was measured using the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) following addition and withdrawal of NH4Cl.

En bloc transplantation of kidneys from pediatric donors.

Purpose: Cadaveric kidneys from pediatric donors represent an important resource for human allotransplantation. We report 7 cases in which a new technique was used for en bloc transplantation of pediatric cadaver kidneys into adult recipients.

Materials And Methods: Paired cadaveric kidneys obtained from donors younger than 6 years (mean age 26 months) were transplanted en bloc into 2 children (mean age 12.

Hypoxia-induced alterations in cytoskeleton coincide with collagenase expression in cultured neonatal rat cardiomyocytes.

Incubation of cultured neonatal rat cardiomyocytes in hypoxic conditions, mimicking the deprivation of O2 which occurs during in situ myocardial ischemia, leads to a progressive change in cardiomyocytes cytoskeletal components. Confocal scanning laser immunofluorescence microscopy (CSLIM) reveals that the typical striated costameric distribution of vinculin gradually disappears to be replaced by circular, vinculin-containing sarcolemmal rosettes. There is little change in distribution of vinculin in the focal adhesions or in the intercalated disks.

Potential applications of therapeutic drug monitoring of sirolimus immunosuppression in clinical renal transplantation.

Sirolimus is a potent immunosuppressive agent with a novel mechanism of action. It inhibits the transduction of cytokine signals necessary for the proliferation and maturation of T cells. Because sirolimus blocks a broad spectrum of cytokine signals, it seems logical to use it as an adjunct to CsA-based immunosuppression.

Membrane-bound or soluble truncated RT1.Aa rat class I major histocompatibility antigens induce specific alloimmunity.

Transfectants that express membrane-bound (MB) or secrete soluble truncated (TR) rat class I RT1.Aa major histocompatibility (MHC) antigens induce alloimmunity in vivo. The MB-RT1.

Mitogenic effect of serotonin on vascular endothelial cells.

Background: Recent studies indicate that serotonin (5-HT) has a growth-promoting effect on several different cell types, including smooth muscle cells. After percutaneous transluminal coronary angioplasty, there is damage and denudation of vascular endothelial cells, which promotes platelet aggregation at the site of injury. Aggregating platelets release 5-HT; thus, a high concentration of the amine may be present at sites of endothelial damage, which may act as a mitogen to endothelial cells.

Variability of expression in tuberous sclerosis.

We present three families in whom a diagnosis of tuberous sclerosis is difficult to secure and we review published reports about similar cases. Tuberous sclerosis has been reported to affect as many as 1 in 9400 subjects in the population. The manifestations of this disease vary not only between but also within families.

Tuberous sclerosis complex: genetic aspects.

Much has been learned about tuberous sclerosis complex (TSC) since it was described at the end of the nineteenth century. TSC was recognized to be a genetic disease with autosomal dominant inheritance in the early twentieth century. The prevalence in the general population is at least 1 in 10,000 with two-thirds of cases occurring sporadically and one-third of cases being familial.

Evidence for genetic heterogeneity in tuberous sclerosis: one locus on chromosome 9 and at least one locus elsewhere.

Linkage of tuberous sclerosis complex (TSC), an autosomal dominant disorder, to markers on chromosome 9 was reported first in 1987. This assignment was confirmed by an international collaborative study that suggested more than one locus may be responsible for the phenotype. We studied 14 multigenerational TSC families (13 previously unreported) with markers for nine loci in the linked region of chromosome 9q32-q34.

Musculoskeletal injuries caused by weight training. Guidelines for prevention.

Tens of thousands of U.S. children, adolescents, and young adults are using weights either recreationally, to train for sports, or to compete in weight lifting, power lifting, or body building contests.

Analysis of the interactions of immunosuppressive drugs with cyclosporine in inhibiting DNA proliferation.

Though the high immunosuppressive efficacy of cyclosporine has revolutionized clinical transplantation, renal, hepatic, and neural toxicities limit its therapeutic potential. One approach to this problem is to combine CsA therapy with immunosuppressive agents that act synergistically with it, thereby permitting lower doses and mitigating drug-induced toxicity. The present study examines the in vitro interactions of various immunosuppressive agents--namely, 6-mercaptopurine (6MP), dexamethasone (Dexa), FK506, and Enisoprost (EP)--with CsA.

A transaxial compression technique (TACT) for localized pulse-echo estimation of sound speed in biological tissues.

We describe a new method for the estimation of the speed of sound in soft tissues in the pulse-echo mode. A transducer imparts an accurate transaxial compression to the tissue, and the corresponding change in the arrival time of an echo feature is measured. The ratio between the compressed depth and the difference in arrival time is taken as the estimate of the speed of sound.

Treacher Collins syndrome: an otologic challenge.

Patients with Treacher Collins syndrome have severe middle ear malformations that render operation difficult. We have evaluated 43 patients with Treacher Collins syndrome, on whom only 11 were operated. Computed tomography, the single most important study done preoperatively, routinely showed an underdeveloped temporal bone with islands of bone marrow and absent mastoid pneumatization.

Sphenoidotomy.

Because of the complex anatomic relations of the sphenoid, the surgical approach to this sinus was only introduced 100 years ago. There are three approaches to the sphenoid sinus: transethmoidal, transseptal, and transpalatal. We present a case report, and discuss surgical anatomy, with attention to the important anatomic relationship of the cavernous sinus and its contents.