Human papillomavirus: emerging trends in detection and management

Cervical cancer continues to be a major epidemiologic problem in developed and underdeveloped nations alike. Current screening practices rely on cervical cytology for the early detection of cervical neoplasms. It has now been demonstrated that over 99% of cervical carcinomas are positive for human papillomavirus (HPV) DNA. This article reviews the currently available methods of HPV detection as well as emerging strategies for the implementation of HPV testing into clinical practice.     

Actions of intrathecal omega-conotoxins CVID,GVIA, MVIIA,and morphine in acute and neuropathic pain in the rat

Agents which decrease conductance of N-type voltage-gated Ca(2+) channels have been shown to attenuate measures of neuropathic pain in animal models and to provide symptom relief in humans. The omega-conotoxins have demonstrated efficacy but have a low therapeutic index. We have investigated the effects of a new omega-conotoxin, CVID (AM-336), and compared them with omega-conotoxin GVIA (SNX-124), omega-conotoxin MVIIA (SNX-111) and morphine in a spinal nerve ligation model of neuropathic pain in the rat. The ED(50) (and 95% CI) for attenuation of tactile allodynia by intrathecal administration for omega-conotoxin CVID, GVIA, MVIIA and morphine was 0.36 (0.27-0.48), 0.12 (0.06-0.24), 0.32 (0.23-0.45) and 4.4 (2.9-6.5) microg/kg, respectively. Only morphine significantly prolonged acute tail flick responses (ED(50) 2.3 (1.1-4.9) microg/kg). Of the omega-conotoxins, omega-conotoxin CVID showed the highest ratio of efficacy to behavioural toxicity. These observations show that intrathecal omega-conotoxins are effective in attenuating tactile allodynia in the rat without significantly affecting acute nociceptive responses. Omega-conotoxin CVID had similar potency to omega-conotoxin MVIIA but showed less toxicity in the therapeutic range.     

Rare sesquiterpenes from the algicolous fungus Drechslera dematioidea

From the inner tissue of the marine red alga Liagora viscida the fungus Drechslera dematioidea was isolated. After mass cultivation, the fungus was investigated for its secondary metabolite content, and 10 new sesquiterpenoids [isosativenetriol (1), drechslerines A (2) and B (3), 9-hydroxyhelminthosporol (5), drechslerines C-G (6-10), and sativene epoxide (12)] were isolated. Compounds 8 and 10 exhibited antiplasmodial activity against Plasmodium falciparum strains K1 and NF54. The known compounds helminthosporol (4), cis-sativenediol (11), isocochlioquinone A (14), isocochlioquinone C (15), and cochlioquinone B (16) were also isolated. All structures were elucidated using spectroscopic methods, mainly 1D and 2D NMR and MS.     

Behavioral training increases local astrocytic metabolic activity but does not alter outcome of mild transient ischemia

Functional neurological outcome after transient ischemia might be improved by timely therapeutic intervention. To determine if restorative behavioral therapy influences damage, improves task learning, or alters astrocyte metabolic activity after ischemia, rats (food-restricted to 85% of free-feeding weight) were (a) first trained to respond on one of two levers under a fixed-ratio 20 schedule of food presentation (FR20), then (b) subjected to sham manipulation of carotid arteries or 10 min ischemia by four-vessel occlusion, followed by (c) 4 days of operant testing or inactivity, (d) then all rats were tested under a FR20 lever reversal task for 4 weeks, and (e) 3 days after the last behavioral session astrocyte metabolism was assayed by local uptake of [2-14C]acetate. Mild loss of hippocampal neurons occurred in ischemic rats with or without training after ischemia. Glial fibrillary acidic protein-positive astrocytes were present in similar numbers throughout brains of sham control and ischemic rats. Mild ischemia did not impair learning, and no changes in FR20 reversal learning were detected in sham vs. ischemic rats. Net [14C]acetate uptake was unaffected by ischemia but [14C]acetate uptake increased 15-24% (P<0.05; n=12-15/group) in specific structures (caudate, primary motor and sensorimotor cortex, CA1 hippocampus, subcortical white matter) in the pooled groups of rats that had 4 days FR20 testing vs. inactivity before reversal learning. 'Behavioral therapy' (operant testing on the 4 days immediately following either sham manipulation or ischemia) did not alter ischemic outcome, but was associated with higher acetate utilization in regions involved in motor activities.     

The G protein-coupled receptor repertoires of human and mouse

Diverse members of the G protein-coupled receptor (GPCR) superfamily participate in a variety of physiological functions and are major targets of pharmaceutical drugs. Here we report that the repertoire of GPCRs for endogenous ligands consists of 367 receptors in humans and 392 in mice. Included here are 26 human and 83 mouse GPCRs not previously identified. A direct comparison of GPCRs in the two species reveals an unexpected level of orthology. The evolutionary preservation of these molecules argues against functional redundancy among highly related receptors. Phylogenetic analyses cluster 60% of GPCRs according to ligand preference, allowing prediction of ligand types for dozens of orphan receptors. Expression profiling of 100 GPCRs demonstrates that most are expressed in multiple tissues and that individual tissues express multiple GPCRs. Over 90% of GPCRs are expressed in the brain. Strikingly, however, the profiles of most GPCRs are unique, yielding thousands of tissue- and cell-specific receptor combinations for the modulation of physiological processes.     

Intestinal absorption in health and disease--sugars

Carbohydrates are mostly digested to glucose, fructose and galactose before absorption by the small intestine. Absorption across the brush border and basolateral membranes of enterocytes is mediated by sodium-dependent and -independent membrane proteins. Glucose and galactose transport across the brush border occurs by a Na(+)/glucose (galactose) co-transporter (SGLT1), whereas passive fructose transport is mediated by a uniporter (GLUT5). The passive exit of all three sugars out of the cell across the basolateral membrane occurs through two uniporters (GLUT2 and GLUT5). Mutations in SGLT1 cause a major defect in glucose and galactose absorption (glucose-galactose Malabsorption), but mutations in GLUT2 do not appear to disrupt glucose and galactose absorption. Studies on GLUT1 null mice and Fanconi-Bickel patients suggest that there is another exit pathway for glucose and galactose that may involve exocytosis. There are no known defects of fructose absorption.