Nasal decolonisation of MRSA

The recent demonstration for the first time of urinary monic acid A as a clinical urinary biomarker of exposure to intra-nasal mupirocin during medication for methicillin-resistant Staphylococcus aureus (MRSA) offers a way of verifying adherence to the regimen. However, absence of the biomarker in some patients needs explanation, to ensure that efficient decolonisation has not been compromised by confounding circumstances, and that additional resistance to mupirocin has not unwittingly been encouraged

Renal apoptosis in the mycotoxicology of Penicillium polonicum and ochratoxin A in rats

Penicillium polonicum K. M. Zaleski, which is common on foodstuffs in Balkan regions that are notable for their history of endemic nephropathy, has been shown experimentally to cause a striking histopathological renal change in rats that are given feed contaminated by this fungus. The nephrotoxic agent(s) are only partially characterized. The principal change seen in the cortico-medullary region is karyocytomegaly, but apoptosis, identified with the ApopTag® methodology, is the first response to a dietary extract of P. polonicum-molded wheat after a few days of exposure. Chromatin debris migrates along the nephrons into the medulla, but whether the damaged epithelial fate is via autophagy is unclear. In intermittent exposure experiments, renal apoptosis was resolved with the cessation of exposure and was restored with renewed exposure. Apoptosis became less evident after 3 months of chronic exposure. In contrast, a relatively high dose of dietary ochratoxin A, a potent nephrocarcinogen in male rats after many months of dietary exposure, gave no evidence of apoptosis in asymptomatic weanlings over a few days of dietary exposure. This was attributed to a masking effect by concomitant marked histological disruption in renal tissue. However, in young adults, renal apoptosis was a primary outcome of dietary exposure to either the P. polonicum extract or to ochratoxin A, but the histopathological response to the former was less distorted. The apparent conflicted use in the literature of P. polonicum as a descriptor is highlighted

Chromatographic fractionation of Penicillium polonicum fermentation metabolites in search of the nephrotoxin(s) for rats

Complex renal histopathological changes in rats, in silent response to dietary contamination with wheat moulded by a common Penicillium from the Balkans, have long eluded attribution of a causal toxin. So far, water-soluble amphoteric glyco-peptides seem responsible, at least for the nuclear pyknoses in nephron epithelia after several days of dietary exposure. Recently, refined histology analysis has diagnosed pyknosis as apoptosis, and followed the finding through application of medium-pressure liquid chromatography, anion exchange and silica layer chromatography to fractionate a water/alcohol-soluble extract of a fungal fermentation on wheat. Proline was revealed, with other amino acids, in acid hydrolysate of the fermentation extract. Application of mass spectrometry has recognized prominent ions (m/z 550 and 564) correlated with fragmentations consistent with a terminal proline moiety for the putative toxins, coupled with other structural fragments and correlated with apoptosis. Use of 14C-proline in probing Penicillium polonicum fermentation to aid isolation of the new potential toxins, along with application of gel electrophoresis, may further aid characterization of the apoptosis toxin(s). The present focus on proline peptides in mycotoxicosis fits easily with their increasingly recognised pharmacological activity associated with proline’s rigid secondary amine structure, which causes conformational contortion in peptides. Nevertheless, there remains the striking rat renal karyocytomegaly by P. polonicum, for which there is yet no causative mycotoxin

Immunohistochemical review of Leydig cell lesions in ochratoxin A-treated Fischer rats and controls

Ochratoxin A is best known as a potent renal carcinogen in male rats and mice after necessarily protracted ingestion, although valid extrapolation to any human disease has not been verified. The hypothesis that the toxin is a cause of human testicular cancer was proposed a decade ago and has proliferated since, partly through incomplete study of the scientific literature. Archived tumorous rat testes were available from Fischer F344 rats exposed to continuous dietary exposure for half of or the whole life in London in the 2000s. Renal cancer occurred in some of these cases and testicular tumours were observed frequently, as expected, in both treated and untreated animals. Application of clinical immunohistochemistry has for the first time consistently diagnosed the testicular hypertrophy in toxin-treated rats as Leydig cell tumours. Comparison is made with similar analysis of tumorous testes from control (untreated) rats from U.S. National Toxicology Program studies, both of ochratoxin A (1989) and the more recent one on Ginkgo biloba. All have been found to have identical pathology as being of sex cord-stromal origin. Such are rare in humans, most being of germinal cell origin. The absence of experimental evidence of any specific rat testicular cellular pathology attributable to long-term dietary ochratoxin A exposure discredits any experimental animal evidence of testicular tumorigenicity. Thus, no epidemiological connection between ochratoxin A and the incidence of human testicular cancer can be justified scientifically

1H NMR Spectroscopy-Based Metabolomic Assessment of Uremic Toxicity, with Toxicological Outcomes, in Male Rats Following an Acute, Mid-Life Insult from Ochratoxin A

Overt response to a single 6.25 mg dose of ochratoxin A (OTA) by oral gavage to 15 months male rats was progressive loss of weight during the following four days. Lost weight was restored within one month and animals had a normal life-span without OTA-related terminal disease. Decline in plasma OTA concentration only commenced four days after dosing, while urinary excretion of OTA and ochratoxin alpha was ongoing. During a temporary period of acute polyuria, a linear relationship between urine output and creatinine concentration persisted. Elimination of other common urinary solutes relative to creatinine was generally maintained during the polyuria phase, except that phosphate excretion increased temporarily. 1H NMR metabolomic analysis of urine revealed a progressive cyclic shift in the group principal components data cluster from before dosing, throughout the acute insult phase, and returning almost completely to normality when tested six months later. Renal insult by OTA was detected by 1H NMR within a day of dosing, as the most sensitive early indicator. Notable biomarkers were trimethylamine N-oxide and an aromatic urinary profile dominated by phenylacetylglycine. Tolerance of such a large acute insult by OTA, assessed by rat natural lifetime outcomes, adds a new dimension to toxicology of this xenobiotic

Changes in male rat urinary protein profile during puberty: a pilot study

BACKGROUND: Androgen-dependent proteins (lipocalins) circulate in blood of male rats and mice and, being small (~ 18 kDa), pass freely into glomerular filtrate. Some are salvaged in proximal nephrons but some escape in urine. Several organic molecules can bind to these proteins causing, where salvage occurs, nephropathy including malignancy in renal cortex. In urine, both free lipocalins and ligands contribute to an increasingly-recognised vital biological role in social communication between adults, especially in the dark where reliance is on smell and taste. Crystal structure of the first-characterised lipocalin of male rats, α2u-globulin, has been determined and peptide sequences for others are available, but no study of occurrence during early puberty has been made. We have followed temporal occurrence in urine of juveniles (n = 3) for non-invasive pilot study by high resolution gradient mini-gel electrophoresis, tryptic digest of excised protein bands, and LC-MS/MS of digest to identify peptide fragments and assign to specific lipocalins. Study objective refers directly to external availability for social communication but also indirectly to indicate kinetics of circulating lipocalins to which some xenobiotics may bind and constitute determinants of renal disease. RESULTS: Mini-gels revealed greater lipocalin complexity than hitherto recognised, possibly reflecting post-translational modifications. Earliest patterns comprised rat urinary protein 1, already evident in Sprague-Dawley and Wistar strains at 36 and 52 days, respectively. By 44 and 57 days major rat protein (α2u-globulin) occurred as the progressively more dominant protein, though as two forms with different electrophoretic mobility, characterised by seven peptide sequences. No significant change in urinary testosterone had occurred in Wistars when major rat protein became evident, but testosterone surged by 107 days concomitant with the marked abundance of excreted lipocalins. CONCLUSIONS: Qualitative temporal changes in the composition of excreted lipocalins early in puberty, and apparent increase in major urinary protein as two resolvable forms, should catalyse systematic non-invasive study of urinary lipocalin and testosterone dynamics from early age, to illuminate this aspect of laboratory rodent social physiology. It could also define the potential temporal onset of nephrotoxic ligand risk, applicable to young animals used as toxicological models

Effects of surface modifications on molecular diffusion in mesoporous catalytic materials

In this work, we use pulsed-field gradient (PFG) NMR to probe molecular diffusion of liquids inside mesoporous structures and assess the influence of surface modifications, namely, deposition of palladium (Pd) nanoparticles over alumina (Al2O3) surfaces and passivation of titania (TiO2) surfaces with alkyl chains, on the diffusion pattern

Pearl Millet as an Alternate Host of the Sorghum Ergot Pathogen, Claviceps africana

The infectivity of C. africana on pearl millet (Pennisetum glaucum) lines in Africa was studied. C. africana consistently gave 100% disease incidence on male-sterile sorghum in experiments undertaken in Zimbabwe. C. fusiformis established disease with moderate incidence on most but not all lines tested. In contrast, C. africana established a parasitic association with all the pearl millet lines tested, with incidence as high as 23% in ICMSR 260, the genotype that also supported the highest incidence with C. fusiformis. However, the disease severities were always low, between 1 and 5%. All infections on pearl millet were verified as the sphacelial stage by virtue of their conidial characteristics. After 1 passage through a pearl millet host, C. africana did not apparently become more infectious on this host

Quantitative characterization of machining-induced white layers in Ti–6Al–4V

Machining-induced white layers can affect the functional performance of engineered components, due to the resulting mechanical and microstructural properties. Destructive inspection methods such as cross-sectional microscopy are typically used to identify white layers, however, these methods are inherently costly and time-consuming. It is, therefore, desirable to detect this anomalous surface feature using non-destructive methods which requires improved knowledge around the characteristics of white layers. The present paper reports on the characterization of white layers formed during machining of Ti–6Al–4V, to aid future development of a reliable non-destructive assessment method. The microstructure of the material in the white layer was found to have a basal α-hexagonal close packed texture and there was no evidence of an α→β phase transformation during white layer formation. The white layer has a highly refined grain structure with an increased nanohardness of up to 15% compared with the bulk material. It is proposed that white layers in Ti–6Al–4V are formed by continuous dynamic recrystallization driven by severe plastic deformation during machining. According to the measured micro-mechanical properties of the white layer, suitable non-destructive testing methods are suggested for the detection of this surface feature