Interhemispheric visual competition after multisensory reversal of hemianopia

Unilateral lesions of visual cortex have the secondary consequence of suppressing visual circuits in the midbrain superior colliculus (SC), collectively producing blindness in contralesional space (“hemianopia”). Recent studies have demonstrated that SC visual responses and contralesional vision can be reinstated by a non‐invasive multisensory training procedure in which spatiotemporally concordant visual‐auditory pairs are repeatedly presented within the blind hemifield. Despite this recovery of visual responsiveness, the loss of visual cortex was expected to result in permanent deficits in that hemifield, especially when visual events in both hemifields compete for attention and access to the brain's visuomotor circuitry. This was evaluated in the present study in a visual choice paradigm in which the two visual hemifields of recovered cats were simultaneously stimulated with equally valent visual targets. Surprisingly, the expected disparity was not found, and some animals even preferred stimuli presented in the previously blind hemifield. This preference persisted across multiple stimulus intensity levels and there was no indication that animals were less aware of cues in the previously blind hemifield than in its spared counterpart. Furthermore, when auditory cues were combined with visual cues, the enhanced performance they produced on a visual task was no greater in the normal than in the previously blind hemifield. These observations suggest that the multisensory rehabilitation paradigm revealed greater inherent visual information processing potential in the previously blind hemifield than was believed possible given the loss of visual cortex.     

The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Clinical trials seen shifting overseas.

A Tufts University study released in mid-2003 indicates that increasing numbers of clinical trials for U.S.-produced pharmaceutical are being conducted outside the United States, mainly by contract research organizations. This process speeds up clinical trials, but raises ethical issues of the possible coercion or exploitation of more vulnerable and naive patient populations.     

Sustainability of pyrethroid-impregnated bednets for malaria control in Afghan communities.

Between 1992 and 1995 a series of studies was undertaken to assess the long-term suitability of pyrethroid-impregnated bednets (PIBs) for malaria control in Afghan refugee communities in two villages in North-West Frontier Province, Pakistan. During 1992, 86% of bednet owners volunteered to have their bednets re-impregnated, and a further 15% of families purchased nets at two-thirds of cost price. From 1992 onwards, 27% of the villagers returned to Afghanistan, and annual house spraying campaigns were introduced to protect those still resident but sleeping without bednets. Within 3 years, these campaigns, together with PIBs, reduced the annual incidence of malaria by 87%, from 597 to 78 cases per 1000 population. Nevertheless, 65% of resident families continued to re-impregnate their nets annually with permethrin. To assess whether PIBs were still being used and were still protective, in view of these reduced transmission rates, we carried out a case--control study in 1994 on febrile or otherwise symptomatic patients presenting at village health centres. Comparison of the slide-positivity rates of PIB users and those without bednets showed that regular usage reduced the odds of contracting falciparum and vivax malaria to 0.22 (95% confidence interval (CI): 0.09-0.55) and 0.31 (95% CI: 0.19-0.51), respectively. There was no evidence of a sex- or age-bias in bednet use or in protective effect. The results indicate that a community-based PIB programme is an appropriate malaria control measure in areas where management or security problems make traditional house-spraying campaigns impossible. A relevant finding for those involved in the monitoring of bednet distribution projects is that the local coverage of bednets and the local impact on malaria, even when introduced to remote areas, can be estimated very cheaply by health centre microscopists who simply catalogue blood film diagnoses according to patients'' bednet use practices.     

Effects of risk-associated human dietary macrocomponents on processes related to carcinogenesis in human-flora-associated (HFA) rats

Dietary fat, beef protein and fibre have been shown to modulatecancer risk in humans and the present study examined the biologicaleffects in human-flora-associated (HFA) rats of altering intakelevels within the normal human range. Two control groups, oneHFA and the other germfree (GF), consumed a human diet low infat, fibre and beef for 4 weeks; three other groups consumedhuman diets similar except for independent 3-fold increasesin fat, beef protein or fibre. After 2 weeks on the diets, magneticallyrecoverable microcapsules were given orally to the rats andsubsequently recovered from the faeces to assess endogenouscross-linking agents. After 4 weeks, measurements were madeof gut microfloral enzyme activities, hepatic activation ofdietary mutagens and hepatic DNA adducts by ³²P-postlabelling.Activation in vitro of the dietary mutagens 2-amino-3-methyl-3H-imidazo[4,5-f]quinolline (IQ) and 2-amino-l-methyl-6- phenytimidazo[4,5-b]pyridine(PhIP) by hepatic S9, formation of endogenous hepatic DNA adductsin vivo and the ß-glucuronidase activity of caecalcontents were all increased in the sequence high fat > highfibre > high beef = control. Of the two DNA adducts foundin all HFA rats, only one was present in GF controls, indicatingthat the human gut microflora (subject to human dietary modulation)either releases a DNA-adducting product able to act outsidethe gastrointestinal tract, or stimulates the generation ofsuch a product by mammalian processes. Caecal nitrate reductaseactivity was highest in rats fed the high beef diet, whilstentrapment of cross-linking agents was highest in those fedthe high fibre diet. These results show that risk-related componentsof human diets interact with human gut microflora to modulatethe production of endogenous DNA-adducting and cross-linkingsubstances.