Drug-induced handwriting changes: an empirical review.

Since handwriting is a highly complex, coordinated motor activity, handwrits of pharmacological agents. Its potential has been most evident in research involving therapeutic administrations of anti-psychotic an anti-Parkinsonian drugs, from which consistent and systematic handwriting changes have been observed. This relationship has been found to be particularly significant among the anti-psychotics, since the onset of these graphomotor alterations appear to mark the optmal dose of the drug. Consistent and systematic handwriting changes have not been as evident in inivestigations of drugs used in a nontherapeutic atmosphere. Psychiatric assessments of subjects in ths type of research provided data which indicated that psychological stability may be a factor influencing the susceptibility of one's handwriting to drug induced changes.     

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

Dyslipidemia is an important risk factor for cardiovascular disease (CVD) and atherosclerosis. When dyslipidemia coincides with other metabolic disorders such as obesity, hypertension, and glucose intolerance, defined as the metabolic syndrome (MS), individuals present an elevated risk to develop type 2 diabetes (T2D) as well as CVD. Because the MS epidemic represents a growing public health problem worldwide, the development of therapies remains a major challenge. Alterations of bile acid pool regulation in T2D have revealed a link between bile acid and metabolic homeostasis. The bile acid receptors farnesoid X receptor (FXR) and TGR5 both regulate lipid, glucose, and energy metabolism, rendering them potential pharmacological targets for MS therapy. This review discusses the mechanisms of metabolic regulation by FXR and TGR5 and the utility relevance of natural and synthetic modulators of FXR and TGR5 activity, including bile acid sequestrants, in the treatment of the MS.     

Prevention of the retained fetal membrane syndrome (retained placenta) during induced calving in dairy cattle

Sixty-six dairy cattle were induced to calve with dexamethasone treatment at 5 d prior to expected time of calving. Each animal was assigned randomly to one of two treatments, saline (2 ml) or PGF(2)alpha (10 mg), which were administered within 1 h postpartum. With the saline treatment, 90.5 % of the animals had placental retention, whereas only 8.8 % of the PGF(2)alpha-treated animals had placental retention. The PGF(2)alpha-treated cows released the fetal membranes in 7.4 +/- 1.35 h postpartum, whereas the saline-treated cows released the membranes in 98.3 +/- 10.93 h postpartum. These data demonstrate that treatment with PGF(2)alpha within the immediate postpartum period is effective (P < 0.001) in the prevention of placental retention in the dairy cow induced to calve with dexamethasone.     

RNA primary sequence or secondary structure in the translational initiation region controls expression of two variant interferon-beta genes in Escherichia coli

Efficient expression in Escherichia coli (E. coli) of the human interferon-beta gene (IFN-beta) gene and of a chemically synthesized IFN-beta gene variant (506 base pairs; synIFN-beta) adapted to the E. coli codon usage, both fused to the E. coli atpE ribosome-binding site, is controlled either by primary sequence or by mRNA secondary-structure in the translational initiation region. High level expression of the natural human atpE/IFN-beta gene fusion is governed by the nucleotide composition preceding the initiator codon AUG. A single U----C exchange in the -2 or -1 position preceding the initiator codon AUG reduces the translational efficiency from 18% of total cellular protein to only 8% or 4%, respectively, while both U----C substitutions reduce IFN-beta expression below 1%. These sequence alterations interfere with efficient ribosome binding as revealed by toeprinting. They provide further evidence for the influence of the anticodon-flanking regions of tRNA(fMet) upon the initiation rate of translation. In contrast, translation of the synthetic variant atpE/synIFN-beta gene fusion is controlled by a moderately stable stem-loop structure (delta G = -4 kcal/mol; 37 degrees C) located within the coding region and overlapping the 30 S ribosomal subunit attachment site. That the stability of the hairpin interferes with the initiation of translation is inferred from site-directed mutagenesis and toeprint analyses. mRNA half-life in these variants is positively correlated with the rate of translation and involves two major endonucleolytic cleavage site 5'-upstream of the Shine-Dalgarno region.