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Gordon Memorial Lecture. An egg ist ein ei, es un huevo, est un oeuf.

1. Many of the mechanical tests devised to measure shell quality are inadequate because they fail to recognise the complex interaction between the organic and inorganic aspects of the eggshell. 2. Twelve structural modifications have been observed at the level of the mammillary layer and their presence correlated with a variety of environmental stress events. Occurring as they do in the basal layers of the shell, these morphological variants influence its mechanical properties. 3. The organic matrix proteins which complex with the calcium carbonate derive from a variety of sites within the oviduct and vary in their location within the fully formed shell. In vitro mineralisation reveals the significance of these proteins in the crystal growth mechanism. 4. The isolation and identification of the protein moiety in well-structured eggshells is an essential prerequisite to understanding the abnormalities in crystal growth observed in the shells of older birds challenged by disease and other undesirable 'on farm' events. 5. The eggshell is the daily indicator of the bird's harmony with its environment and as such provides a readily accessible and non invasive measure of welfare. The integration of these data with those derived from behavioural and biochemical testing should provide industry with a reliable numerical welfare index.

Animal Feed↗

Calcium-activated chloride channels: (un)known, (un)loved?

Calcium-activated chloride channels (CaCCs) participate in many different physiologic processes such as transepithelial transport, excitability of neurons and muscle cells, and oocyte fertilization. Within the airways, they contribute to epithelial fluid secretion. This review focuses on three outstanding questions about CaCCs. First, although their biophysical fingerprint (anion selectivity, Ca2+ and voltage dependence, kinetics) is fairly well established, the molecular identity of CaCCs is still unresolved. CLCA, a family of proteins of which four members have so far been identified in humans, has been proposed to mediate calcium-activated chloride currents. However, the biophysical profile and expression pattern of endogenous CaCCs differ from those of the CLCA proteins. Another family of membrane proteins, the bestrophins, has recently been shown in transfected HEK293 cells to confer anion-selective currents that are activated by submicromolar Ca2+ concentrations. Second, pharmacologic tools to manipulate CaCCs are poorly selective. This lack of specificity not only hampers the structural and functional characterization of these channels but also restricts therapeutic options for altering CaCC function. Finally, potential pitfalls with respect to CaCCs as molecular targets for cystic fibrosis therapy are discussed.

Animals↗

[Un analysis of present situation of medical specialties un Chile].

During the fifties and sixties, physicians were mostly prepared as general practitioners. However, the progress in scientific knowledge and the introduction of complex technologies required the training of specialists. A number of sub specialties have been progressively added to the four basic specialties, namely Internal Medicine, Pediatrics, Obstetrics and Gynecology and General Surgery. The Post Graduate Schools of the traditional universities devised courses and training periods to teach these sub specialties. The Association of Medicine Schools has been in charge of the accreditation of the new training centers. Since the training of new specialists required the collaboration of hospitals of the public National Health Service, there is a special commission that coordinates the relationships between teaching requirements and medical attention in these hospitals. There is still a controversy on the exact proportion of general practitioners and specialists that the country needs, the role of Family Practice and the role of prevention and health promotion.

Accreditation↗

Comparison of indoor air quality in electrified and un-electrified dwellings in rural South African villages.

UNLABELLED: A feasibility study was undertaken to assess the suitability of South African rural villages due to be electrified, for the purposes of undertaking a large-scale study of the impact of reductions in indoor air pollution on acute lower respiratory infections. As part of the feasibility study, quantitative assessments of indoor air pollution in non-electrified and electrified dwellings were performed. Concurrent measurements were made of levels of respirable particulate matter (RSP-stationary), and carbon monoxide (CO) (personal on children <18 months), as well as a stationary co-located with RSP) over a 24-h period in 52 un-electrified and 53 electrified dwellings. The proportion of dwellings with a detectable 24-h concentration of RSP was significantly higher in un-electrified (48.1%) than electrified dwellings (24.5%) (chi(2) = 6.30 on 1 d.f., P = 0.012). In addition a Kruskal-Wallis test (adjusted for ties) showed that the distribution of RSP differed between un-electrified and electrified areas (Kruskal-Wallis chi(2) = 8.20 on 1 d.f., P = 0.014). In those dwellings where some RSP was detected, the amount was on average higher in the un-electrified areas (mean 162 microg/m(3), median 107 microg/m(3)) than in the electrified areas (mean 77 microg/m(3), median 37.5 microg/m(3)). Stationary (kitchen CO) levels in un-electrified dwellings ranged from 0.36 to 20.95 p.p.m. However, in electrified dwellings, kitchen levels ranged from 0 to 11.8 p.p.m. When mean concentrations of CO were compared between electrified and un-electrified dwellings using a two-sample t-test (on log-transformed data), there was overwhelming evidence (P = 0.0004) that the mean level of log (CO) in the kitchen was higher in the un-electrified areas (1.25 vs. 0.69) and also overwhelming evidence (P < 0.0001) that the mean level of log (CO) on the child was higher in the un-electrified areas (0.83 vs. 0.34). Of importance in terms of both policy and for a potential future large-scale study, is that measurable significant differences in indoor pollutants between electrified and un-electrified dwellings during summer were found in spite of only partial transition to electricity use for cooking in electrified villages. PRACTICAL IMPLICATIONS: It is estimated that at least two-thirds of all households in the developing world are still primary dependent on biomass fuels and coal. This situation applies to 59% of rural households in South Africa. In the last decade a program of providing electricity to three million homes has been underway in South Africa. Among others this intervention aims to reduce exposure to pollutants from burning biomass fuels and reduce detrimental health effects, especially in young children. This study provides scientific evidence that electrified homes in South African villages have lower levels of air pollution (RSP and CO) relative to their non-electrified counterparts.

Air Pollution, Indoor↗

North American opossum Didelphis virginiana as a fetal nephrotoxicity model: histologic and ultrastructural assessment of uranyl nitrate (UN)-induced damage.

We have used our opossum model of fetal nephrotoxicity to investigate uranyl nitrate-induced morphologic changes in the developing kidney. The present study establishes a renal dose response curve for the uranyl nitrate (UN). We find that pups treated with nonlethal doses of UN do not demonstrate growth retardation compared to saline-treated controls. The kidneys of UN-treated pups are heavier than the control animals, an effect less apparent the longer the pups are followed. A low dose of 60 mg/kg of UN administered to small pups causes slight histologic derangement but nevertheless more change than the same dose administered to larger more mature pups. Using a dose of 100 mg/kg of UN that effectively causes nonfatal renal disruption, we examined the kidneys from 4 to 42 days following injection. We find that tubular dilation and epithelial necrosis starts soon after treatment (day 4) and reaches its maximum during the second and third week (11 and 22 days). Architectural restoration appears complete by the end of the third week. By electron microscopy, UN induces sequential structural damage with loss of proximal tubule brush border, epithelial necrosis with intact basement membranes and regeneration at 4, 11, and 22 days. Residual tubular mitochondrial damage is present at 42 days in spite of histologically normal tubules. No apparent lesions are seen in glomeruli. Fibroblastic interstitial proliferation in UN-treated kidneys at 11 days is not followed by appreciable fibrosis when assessed at 22 and 42 days. As the structural changes caused by 100 mg/ml UN administration in fetal opossum kidneys are reversible, this is a useful model to study the molecular mediators responsible for this form of renal damage and repair.

Animals↗

Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20.

Because the ionized species is more polar than its un-ionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination of pH control and complexation to pH control and micellization and to pH control and cosolvency. The total aqueous solubility is expressed as the addition of the concentration of all contributing species: free un-ionized drug [Du], free ionized drug [Di], un-ionized drug micelle [DuM], and ionized drug micelle [DiM] for surfactant, and free un-ionized drug [Dcu] and free ionized drug [Dci] for cosolvent. The equations indicate that under certain conditions the ionized species can be more important in determining the drug total solubility than the un-ionized species. Flavopiridol, a weak base, is used to test these newly generated equations. As expected, the micellar partition coefficient and solubilization power for ionized flavopiridol are both less than those of the un-ionized species. However, at acidic pH, the solubilities of the ionized drug in surfactant micelles [DiM] and in cosolvent-water [Dci] are both much greater than that of the un-ionized drug. This difference is because the solubilization of the ionized drug is proportional to its aqueous solubility, and its solubility [Di] can be as much as 24-fold greater than that of the free un-ionized species [Du].

Antineoplastic Agents↗

Determination of renal porphyrin handling in rats suffering from different kinds of chronic renal failure (CRF): uranyl nitrate (UN) induced fibrosis or 5/6-nephrectomy (5/6NX).

The renal handling of porphyrins is reported to be a sensitive marker for chronic renal failure (CRF) for two reasons: heme is synthesised in proximal tubules and porphyrins are reabsorbed in the renal proximal tubule by apical peptide transporter PEPT 2. Two different models of CRF in female Wistar rats have been used for investigation of renal porphyrin handling: (1) single administration of uranyl nitrate (UN; 0.5 mg/100 g b.wt.) and (2) 5/6 nephrectomy (5/6NX). Renal clearance experiments were performed at weeks 2 and 10 after the onset of CRF. The concentrations of porphyrin intermediates (uroporphyrin I and III, coproporphyrin I and II, heptaporphyrin, and pentaporphyrin) were measured by HPLC with fluorescence detection. Both after UN and 5/6NX a significant reduction of body weight occurred. The kidney weight was enhanced 2 weeks after UN compared to controls (+31%). After 5/6NX, the weight of the remnant kidney was 44% (2nd week) and 140% (10th week) higher compared to one control kidney. Urine volumes and GFR were significantly reduced at week 2 and 10 after 5/6NX, but at week 10 after UN values were comparable to controls. Two weeks after UN and 5/6NX the concentrations of heptaporphyrin was moderately decreased in renal tissue whereas after 10 weeks the concentrations of most porphyrins were increased in the kidney. The plasma levels of free porphyrins were only slightly enhanced (week 2). The renal excretion of porphyrins was initially slightly reduced in both models, whereas it increases 10 weeks after UN, but it remained reduced 10 weeks after 5/6NX. UN induces tubulointerstitial fibrosis including atrophic glomeruli, whereas 5/6NX was characterized by distinct proteinuria, dilated tubules containing hyaline casts. A modulation of porphyrin metabolism in the kidney seems first of all to be responsible for UN effect on renal porphyrin handling. Summing up the 5/6NX results, both reduction in intact renal tissue mass and a modification of enzymes involved in heme biosynthesis by uraemic toxins are responsible for accumulation of porphyrins in renal tissue. After 5/6NX reduced excretion of porphyrins into urine and enhanced porphyrin concentrations in the kidney indicate more a damage of renal porphyrin biosynthesis than changes in their reabsorption.

Animals↗

UN system machinery for coordinating follow-up to the World Food Summit.

FAO [UN Food and Agriculture Organization] does not stand alone in implementing and monitoring the Summit Plan of Action. Commitments 7.2 and 7.3 give responsibility to the UN's Administrative Committee on Coordination (ACC) for coordinating interagency follow-up and to the Economic and Social Committee (ECOSOC) for receiving progress reports from FAO and other agencies. The UN General Assembly in December 1996 welcomed the outcome of the Summit and received FAO's first report on it at its 1997 session. The ACC has launched interagency follow-up by establishing the ACC Network on Rural Development and Food Security, as proposed jointly by FAO and the International Fund for Agricultural Development (IFAD). More than 16 UN agencies have joined and the UN Secretary-General has welcomed the intention to involve civil society and the emphasis placed on country-level action in the two-tiered network. All FAO country representatives and UN resident coordinators have been asked to help in setting up interagency thematic groups on rural development and food security at the country level. FAO has introduced a website for the network within SD Dimensions (http://www.fao.org/waicent/faoinfo/sustdev). ECOSOC has welcomed the ACC's decision to include follow-up to the World Food Summit within the context of the integrated follow-up process of all major UN conferences and summits. With these decisions, the machinery has been set in motion for early and sustained support from both interagency and intergovernmental bodies to national efforts to implement the Plan of Action.

Agriculture↗

Postnatal ocular expression of tyrosinase and related proteins: disruption by the pink-eyed unstable (p(un)) mutation.

Ocular pigmentation in the mouse occurs primarily postnatally as a result of the melanization of neural crest-derived melanocytes. Using immunologic and biochemical techniques, we demonstrate that in normal mice the expression of tyrosinase and the related proteins TRP-1 and TRP-2, rises during the first week of life, remains elevated for a week, and then steadily declines to low levels by adulthood. Sucrose gradient density centrifugation demonstrates that tyrosinase, TRP-1 and TRP-2 are present in high molecular weight forms in the eyes of wild-type mice. The normal time course is disrupted in mice carrying the pink-eyed unstable (p(un)) mutation at the P-locus, a model for tyrosinase-positive albinism in man. Tyrosinase and TRP-2 are present at wild-type levels in the eyes of p(un)/p(un) mice at birth, but, rather than rising, their levels rapidly decline over the first week of life. TRP-1 is almost undetectable, even at birth. High molecular weight complexes could not be detected in eyes of p(un)/p(un) mice. Our results suggest that postnatal ocular melanogenesis in the mouse presents an attractive model for the study of the orderly expression and action of the proteins involved in eumelanin synthesis, and that the p(un) mutation disrupts this temporally controlled process.

Albinism↗