Search PubMed⌕ Search

Biomedical subjects

D M Ferguson

Publications and source records attributed to D M Ferguson.

49 records · Page 3Linked to original sources
PubMed1977

Toxicological evaluation of Norpace after intravenous administration to rat and dog.

Norpace (disopyramide phosphate) is a drug for treating cardiac arrhythmias. It has been evaluated for potential toxicological effects in albino rats and Beagle dogs, to provide safety support for clinical studies involving intravenous infusion. The compound was dissolved in Sodium Chloride for Injection, U.S.P. and administered daily by continuous intravenous infusion to groups of rats and dogs. Dose levels to 4.95 mg/kg/h for 14 and 28 consecutive days, respectively were employed. Rats received the formulation for 6--12 h daily; dogs were infused for 6 h daily. Conventional physical, cardiovascular, hematology, clinical chemistry and postmortem gross and microscopic examinations were performed. No compound-related changes were observed in the physical examinations (including ophthalmic), blood pressure (rat), ECG (dog), body weight, or clinical lab parameters evaluated; Food consumption was unontinuous restraining procedure employed during infusions reduced food consumption in all dogs, however, Postmortem examination did not reveal any lesions unique to treated animals. Some dogs exhibited intravenous fibrin thrombi at the site of injection. Organizing blood clots were occasionally present in the thoracic cavity of the rat. These findings were considered related to the infusion technique employed, rather than the drug administered. It was concluded that daily intravenous infusions of Norpace at doses up to 4.65 mg/kg/h to rats and dogs for 14 and 28 consecutive rays respectively, cause no biologically meaningful detrimental effects.

Animals↗
PubMedDate not supplied

An analysis of the conserved residues between halobacterial retinal proteins and G-protein coupled receptors: implications for GPCR modeling.

An alignment of the transmembrane domains of halobacterial retinal proteins (including bacteriorhodopsin) and G-protein coupled receptors (GPCRs) is presented based on the commonality of conserved residues between families. Due to the limited sequence homology displayed by these proteins, an alternative strategy is proposed for sequence alignment that correlates residues within secondary structure elements. The nonsequential alignment developed identifies three proline and two aspartates residues that share common positions and, in the former case, similar functions in the transmembrane domain. The alignment is further applied to model the packing of transmembrane helices 5 and 6 of the beta-adrenergic receptor based on the backbone coordinates of bacteriorhodopsin helices 3 and 2, respectively. Unlike models derived from standard sequential alignments, the approach developed here allows the key structural features conferred by the proline residues to be captured during model building. The structure described is also compared with available site directed mutagenesis results as well as existing GPCR models. In addition to the implications to model building, the commonality observed suggests a potential relationship among the GPCRs and retinal proteins.

Amino Acid Sequence↗
PubMedDate not supplied

Oral phentolamine and female sexual arousal disorder: a pilot study.

Female sexual arousal disorder (FSAD) is a highly prevalent problem, although little is known about pathophysiology or treatment of the disorder. Given the potential role of vascular mechanisms, a small pilot study was conducted on the effects of oral phentolamine in menopausal women with FSAD. Six postmenopausal women with a lack of lubrication and with sexual arousal difficulties of at least 6 months duration participated in the study. All subjects received a single dose of oral phentolamine (40 mg) and placebo in a single-blind, dose-escalation design. Dependent variables for the study included vaginal pulse amplitude (VPA), as measured by vaginal photoplethysmography, self-report measures of sexual response, and patient- and physician-based assessments of adverse events. Results indicated a mild, positive effect of phentolamine across all measures of arousal, with significant changes (p < .05) in self-reported lubrication and pleasurable sensations in the vagina. The drug was well tolerated, overall, with few reports of adverse side effects. Further studies are needed to assess the potential value of phentolamine and other vasoactive agents in the treatment of female sexual dysfunction.

Administration, Oral↗
PubMedDate not supplied

Quantitation of Cryptosporidium parvum infection in cell culture using a colorimetric in situ hybridization assay.

A quantitative colorimetric in situ hybridization assay was developed for detecting Cryptosporidium parvum infection in cell cultures using a digoxigenin-labeled probe targeting 18S rRNA. Intra-cellular developmental stages of C. parvum such as trophozoites and meronts were clearly discerned by light microscopy as localized areas of dark purple/black precipitate against a colorless background. Infections developed focally and the term infectious focus was applied to each cluster of developmental stages. There were no significant differences in the number of infectious foci following 24 h or 48 h incubation. However, 24 h and 48 h dose response curves were significantly different when infectivity was measured as the number of developmental stages per monolayer, with an average of 5.3-fold more stages following 48 h incubation. When infectivity was expressed as the number of infectious foci per inoculum oocyst converted to a percentage, it was demonstrated that the rate of infection decreased with increasing oocyst age. Oocysts of the Iowa isolate that were 7-10 days old demonstrated 7.8+/-2.4% infectivity (mean +/- standard deviation) compared to 4.2+/-0.8% for 21-28 day-old oocysts and 1.4+/-1.3% for 42-70 day-old oocysts. The assay also detected infection with other genotype 2 oocysts and a genoptye 1 isolate. This assay provides a direct quantitative approach for measuring C. parvum infectivity in cell culture.

Adenocarcinoma↗
PubMedDate not supplied

Pharmacodynamic differentiation of chronotropic and inotropic beta-adrenergic receptors in rabbit heart.

Isolated, perfused rabbit hearts were used to identify substituted phenylethylamines selective for either chronotropic or inotropic stimulation relative to norepinephrine. Heart rate and dF/dtmax were measured; the difference in their normalized values was used as an index of selectivity. p-Octopamine (OA) showed chronotropic preference, while phenylephrine (PE) showed a significant inotropic preference. Their effects were not prevented by reserpine pretreatment, cocaine, butoxamine, or phenoxybenzamine, but were antagonized by propranolol, which suggests that OA and PE exert their selective actions directly at beta 1-receptors. These findings provide further evidence for the existence of separate chronotropic and inotropic beta-adrenergic receptors in the heart.

Animals↗
PubMedDate not supplied

Antiviral activity in vitro of Kutapressin against human herpesvirus-6.

The recently discovered human herpesvirus-6 (HHV-6) is being associated with an increasing number of conditions in which there is evidence of immunologic dysfunction. A number of widely available antiviral agents have shown little or no activity against the virus. We found that Kutapressin (KU), a drug that has been available to practicing physicians for over 50 years, has potent, previously unexpected antiviral effects. Cells known to allow replication of HHV-6 were infected with the virus, under various conditions. Either pretreatment of the cells prior to infection or treatment shortly after infection, inhibited viral replication by > 90%. Indirect evidence suggests that KU may inhibit viral attachment to cellular receptors, and inhibit intracellular maturation of the virus. Given these in vitro findings, and the low frequency of toxicity reported with the use of KU, clinical trials of this drug in patients with evidence of reactivated HHV-6 infection would seem to be warranted.

Animals↗