Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.     

Relation of left ventricular shape to volume and mass in patients with minimally symptomatic chronic aortic regurgitation

In 19 male patients with significant but minimally symptomatic or asymptomatic chronic aortic regurgitation, measurements of left ventricular shape, volume, and mass were assessed by cross-sectional echocardiography. End-diastolic volume and mass were significantly larger than normal values. There was a significant negative correlation between the volume-to-mass ratio (V/M) and both the end-diastolic (r = -0.70, p less than 0.01) and end-systolic (r = -0.73, p less than 0.001) long axis-to-minor diameter ratios (L/D), suggesting that maintenance of the normal geometry of the left ventricle is in part dependent on the adequacy of hypertrophy, as expressed by a normal V/M. Since preoperative volume-to-mass indices have been shown to be important predictors of postoperative course, the L/D ratio should be a useful and simple parameter to follow in asymptomatic patients.     

Myelinated and nonmyelinated nerves: comparison of proton MR properties

The magnetic resonance (MR) relaxation rates of protons were compared in the myelinated and nonmyelinated nerves of the garfish. The long, large olfactory nerve of the garfish, as an easily accessible source of nonmyelinated axons, is uniquely suited for such a comparison. The T1 and T2 measurements revealed distinct and consistent differences between nonmyelinated olfactory nerves and myelinated optic and oculomotor nerves. Comparisons between water content, lipid content, and relaxation rates indicated that the differences in MR properties represent complex differences in the distribution and physical environment of the constituent lipid and water protons.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Failure of two-dimensional echocardiography to detect aspergillus endocarditis

Two-dimensional echocardiography has been shown to be a reliable diagnostic procedure in patients with valvular lesions due to fungal endocarditis. We describe a patient with four-chamber Aspergillus endocarditis localized to the nonvalvular endocardium. In this case, two-dimensional echocardiography failed to demonstrate cardiac abnormalities despite the presence of extensive endomyocardial disease at autopsy. The case emphasizes the diagnostic limitations of two-dimensional echocardiography in the absence of valvular vegetations.     

Clinical value of determining C-reactive protein in the maternal serum in pregnancies with threatened premature labor

In this article, because of the importance of subclinical infections for triggering premature labor, we have investigated the maternal serum levels of C-reactive protein (CRP) in 88 pregnancies with comparable gestational ages at the onset of premature birth symptoms. We found certain associations between possible prolongation of gestation by tocolysis and absence or presence of pathologic values of this acute-phase-protein. Positive CRP-values are associated with significantly lowered prolongation of pregnancy by tocolysis and subsequently lowered gestational age at birth. Though there are no correlations to maternal temperature and white blood cell counts, antenatal CTG-results, amniotic fluid properties and parameters of the neonate, we found probable relations to the detection of Ureaplasmas in the vaginal swabs. Once more we point out to possible associations between mycoplasmas and premature birth.     

Synthesis and biological activities of cyclic lanthionine enkephalin analogues: delta-opioid receptor selective ligands

The synthesis and biological test results of a series of enkephalin analogues incorporating the lanthionine modification are presented. The syntheses of four monosulfide-bridged analogues of enkephalins, Tyr-c[D-Ala(L)-Gly-Phe-D-Ala(L)]-OH (1a), Tyr-c[D-Val(L)-Gly-Phe-D-Ala(L)]-OH (1b), Tyr-c[D-Ala(L)-Gly-Phe-Ala(L)]-OH (1c), and Tyr-c[D-Val(L)-Gly-Phe-Ala(L)]-OH (1d), where Ala(L) and Val(L) denote the lanthionine amino acid ends linked by a monosulfide bridge to form the lanthionine structure, were successfully carried out via preparation of the linear peptide on solid support and cyclization in solution. In vitro binding assays against mu-, delta-, and kappa-opioid receptors and in vitro tests using GPI and MVD assays revealed that the dimethyl lanthionine analogues 1b and 1d, denoted as D-Val(L) in position 2, show substantial selectivity toward the delta-opioid receptor, while the unsubstituted analogues 1a and 1c, denoted as D-Ala(L) in position 2, bind to both mu- and delta-opioid receptors. The in vivo thermal escape assay by intrathecal administration showed that the analogues 1b and 1d are among the most potent ligands at producing antinociception through the delta-opioid receptor. The picomolar potencies of analogues 1a and 1c in the intrathecal (it.) assay strongly indicate that mu- and delta-opioid receptors interact synergistically to modulate the antinociceptive responses.     

Differential sensitivities of mouse strains to morphine and [Dmt1]DALDA analgesia

[Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)), is a highly potent and selective mu-opioid agonist. Nevertheless, systemic [Dmt(1)]DALDA retained its analgesic actions in MOR-1 knockout animals and CXBK mice despite the inactivity of morphine in these mice. [Dmt(1)]DALDA was 6-fold less potent in C57BL/6J mice than in CD-1 mice, whereas morphine potency did not differ between the two strains. Thus, [Dmt(1)]DALDA is a highly selective mu-opioid analgesic with significant pharmacological differences with the prototypic mu-opioid morphine.