Cytochrome P450 3A4 Activity in Premenopausal and Postmenopausal Women,Based on 6-β-Hydroxycortisol:Cortisol Ratios

Study Objective . To characterize cytochrome P450 (CYP) 3A4 activity in premenopausal and postmenopausal women by evaluating the urinary 6-β-hydroxycortisokcortisol ratio. Design . Prospective study. Subjects . Thirteen premenopausal and 13 postmenopausal women who were healthy and not receiving drugs known to affect CYP3A4 activity. Interventions . Beginning on day 2 of menses, premenopausal women collected first morning urine samples every other day for a complete menstrual cycle. Postmenopausal women collected first morning urine every other day for 28 days. Measurements and Main Results . Mean weekly 6-β-hydroxycortisol:cortisol ratios did not differ during the phase (week) of the menstrual cycle. Daily ratios did not differ in postmenopausal women. No difference between premenopausal and postmenopausal women was found on comparing overall median ratios. Conclusion . Cytochrome P450 3A4 activity as measured by 6-β-hydroxy cortisol:cortisol ratio did not differ by week of menstrual cycle, suggesting no menstrual cycle-related changes. Menopause does not appear to be associated with differences in CYP3A4 activity, compared with premenopause.     

SPECT gallium scanning for lymphoma and infection

Thirty gallium scans, using currently acceptable dosage levels (5-6 mCi) and a conventional rotating gamma camera, were performed on 20 patients with lymphoma or infection. Compared to planar scans, SPECT increased sensitivity and lesion detection from 48% to 89% in lymphoma, and from 50% to 80% in infection. The predictive value of a negative site was 81% in lymphoma and 67% in infection. Gallium utility is markedly increased by SPECT imaging. A normal gallium SPECT scan is highly accurate in ruling out disease.     

Progress toward re‐engineering non‐ribosomal peptide synthetase proteins: a potential new source of pharmacological agents

Many important pharmaceutical agents, including vancomycin, bleomycin, cyclosporin, and several antibiotics, are produced by non‐ribosomal peptide synthetase (NRPS) enzymes in microorganisms. The NRPS pathway produces an extensive library of products using multienzyme complexes acting in an assembly‐line fashion. Engineering an NRPS system to produce an even greater variety of products, some of which may also have beneficial therapeutic value, would be an enormous advantage. Several approaches have been successful in generating novel NRPS products: mutational biosynthesis during which nonnatural substrates are fed to an organism; domain and module swapping between different species to generate hybrid enzymes; and rational site‐directed mutagenesis, based either on phylogeny or computational prediction, intended to switch substrate specificity and produce altered products. This review will highlight the progress in these areas and describe research in the future that will extend the capacity for re‐engineering NRPS systems. Drug Dev. Res. 66:9–18, 2006. © 2006 Wiley‐Liss, Inc.     

A comparison of the effects of climbing fiber deafferentation in adult and weanling rats

The climbing fiber input to the cerebellar cortex was destroyed using both electrolytic and chemical (3-acetylpyridine) lesions. The long-term effects of climbing fiber deafferentation on the ansiform lobule of weanling and adult rats were examined at both the light and electron microscopic levels. Image analysis of Golgi-impregnated Purkinje cells indicated a significantly lower number of smooth branches and spiny branchlets following climbing fiber deafferentation of both adult and weanling rats. The results suggest that the lower number of smooth branches and spiny branchlets following climbing fiber deafferentation of the weanling rat is the result of a loss of postnatal growth rather than transneuronal degeneration. Ultrastructural evidence is provided in confirmation of these quantitative findings. Formation of ectopic dendritic spines was found following climbing fiber deafferentation of the weanling rat, but not the adult. It is shown that ectopic spines and the denervated dendritic thorns of these animals were synaptically innervated by the parallel fiber system and basket axons. The formation of ectopic spines on climbing fiber deafferentated Purkinje cells may represent a form of dendritic plasticity. Ultrastructurally, the dendritic arborizations of weanling deafferentated Purkinje cells showed no signs of transneuronal degeneration. However, the primary response to climbing fiber deafferentation in the adult rat was marked transneuronal degeneration of the Purkinje cell dendrites. It is suggested that the inability of the adult Purkinje cell to form ectopic spines and to replace the excitatory postsynaptic potential of the climbing fiber varicosity is directly related to the Purkinje cell's subsequent transneuronal degeneration.     

The impact of percutaneous transluminal angioplasty on the management of peripheral vascular disease

Percutaneous transluminal angioplasty is a well established technique with wide application, but its place in the overall management of peripheral vascular disease is not well defined. This study compares similar groups of patients with peripheral vascular disease in 1981 and 1984, before and after the introduction of the technique to a district general hospital. More patients are now being investigated and treated and this is almost entirely due to the availability of angioplasty. The rates for surgery have not changed. Percutaneous transluminal angioplasty should therefore be seen as a new and separate form of treatment for peripheral vascular disease, not necessarily influencing or replacing surgery, and requiring its own allocation of resources in accordance with the increase in the level of care afforded by the technique.     

A review of lacrimal drainage surgery

The advent of improved silicone intubation sets, increased understanding of lacrimal and nasal anatomy and physiology, and refinements in surgical instrumentation and technique have led to higher success rates in lacrimal surgery. Recent clinical studies, combined with new techniques in canalicular reconstruction, have helped identify which patients will benefit from surgical intervention and which techniques are indicated. Fortunately, this has greatly reduced the number of CDCRs necessary.