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

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

Windborne spread of ergot disease (Claviceps africana) in sorghum A-lines in Zimbabwe

In field trials in Zimbabwe, C. africana spread rapidly through replicated plots of male-sterile sorghum A-lines, from a group of centrally situated, inoculated plants. Prominent secondary conidiation by the pathogen on the surface of exuded honeydew provided airborne spores which were trapped in a Burkard continuous spore trap and showed diurnal peaks in air close to the primary inoculum source. From the rate and pattern of disease spread it is concluded that the characteristic secondary conidia of C. africana were the principal disease agents within the experimental area, and that ergot spread by windborne secondary conidia has significant epidemiological and economic implications for sorghum hybrid breeding in southern Africa

Secondary conidiation of Sphacelia sorghi on sorghum, a novel factor in the epidemiology of ergot disease

Sphacelia sorghi, the ergot pathogen of sorghum in Zimbabwe, causes copious exudation of honeydew containing macroconidia. Within a few days the exudate develops a white crust consisting of a layer of secondary conidia borne above the honeydew surface on a palisade of sterigma-like projecting hyphae which arise from the macroconidia immediately below the honeydew surface. Secondary conidia are windborne, initiate infection and are recognized for the first time to have an important role in the epidemiology of ergot disease of sorghum in Southern Afric

Claviceps africana sp. nov.; the distinctive ergot pathogen of sorghum in Africa

Stromata arising from ergot sclerotia from sorghum in Zimbabwe were different in colour and texture from those of Claviceps sorghi from sorghum in India, compounding other differences in the dynamics of the early stages of parasitism, the sugar composition of honeydew, the quantitative expression of secondary conidiation and the morphology of sclerotia. The distinctive sexual stage forms the basis of describing the African material as a new Claviceps species which also uniquely elaborates a group of dihydrogenated ergot alkaloids that are biosynthetic intermediates leading to the principal product dihydroergosin

Relations Among Sorghum Ergot Isolates from the Americas, Africa, India, and Australia

Sorghum ergot, initially restricted to Asia and Africa, was recently found in the Americas and Australia. Three species causing the disease have been reported: Claviceps sorghi in India, C. sorghicola in Japan, and C. africana in all ergot-positive countries. The objective of our study was to study the intraspecific variation in C. africana isolates in the Americas, Africa, India, and Australia. We confirmed C. africana, C. sorghi, and C. sorghicola as different species using differences in nucleotide sequences of internal transcribed spacer 1 and 5.8S rDNA regions. Sequences of this region obtained from the representative American, Indian, and Australian isolates of C. africana were identical. In addition, random amplified polymorphic DNA (RAPD) banding patterns of sorghum ergot pathogen isolates from the United States, Mexico, Puerto Rico, Bolivia, Australia, and India were evaluated with nearly 100 primers. A total of 65 primers gave identical patterns for all isolates, which confirmed that all were C. africana. The identity of RAPD pattern and rDNA sequence of Indian isolates with those of C. africana confirmed that the species is now present in India. Only 20 primers gave small pattern differences and 7 of them were used for routine testing. All of the American isolates were identical and three isolates of the same type were also found in South Africa, suggesting Africa as the origin of the invasion clone in the Americas. Australian and Indian isolates were distinguishable by a single band difference; therefore, migration from the Asian region to Australia is suspected. Another distinct group was found in Africa. Cluster analysis of the informative bands revealed that the American and African group are on the same moderately (69%) supported clade. Isolates from Australia and India belonged to another clade

Use of hormonal contraceptives and occurrence of pregnancy-related pelvic pain: a prospective cohort study in Norway

BACKGROUND: Pregnancy-related pelvic pain is a common condition, and use of hormonal contraceptives before pregnancy has been proposed as a risk factor. We used data from a sub-sample of women participating in the "Norwegian Women and Cancer study" (NOWAC) to assess the association between hormonal contraceptive use and pelvic pain in pregnancy. METHODS: From a sub-group of 2078 parous women participating in the NOWAC study, information was collected from a self-instructive four-page questionnaire containing questions about lifestyle and medical conditions. We calculated odds ratios (OR) and 95% confidence intervals (CI), using unconditional logistic regression. RESULTS: In this study, the prevalence of pelvic pain in women was 26.5% during the first pregnancy and increased with parity. Use of hormonal contraceptives before a woman's first pregnancy was associated with an increased risk of pelvic pain in her first pregnancy (OR = 1.6; 95% confidence interval 1.2–2.2). There was no association between use of hormonal contraceptives and pelvic pain in the second or third pregnancy. Occurrence of pelvic pain in a previous pregnancy was the only factor associated with pelvic pain in subsequent pregnancies (OR = 51.1; 95% CI 32.9–79.5 in the second pregnancy and OR = 28.3; 95% CI 15.4–53.1 in the third pregnancy). CONCLUSION: Use of hormonal contraceptives was associated with an increased risk of pelvic pain in a woman's first pregnancy. The most important determinant of pelvic pain in the second or third pregnancy was the history of pelvic pain in the preceding pregnancy

Sunitinib and other targeted therapies for renal cell carcinoma

Targeted therapy has radically altered the way metastatic renal cancer is treated. Six drugs are now licensed in this setting, with several other agents under evaluation. Sunitinib is currently the most widely used in the first line setting with impressive efficacy and an established toxicity profile. However, as further randomised studies report and as newer drugs become available this may change. In this review, we address our current understanding of targeted therapy in renal cancer. We also discuss areas in which our knowledge is incomplete, including the identification of correlative biomarkers and mechanisms of drug resistance. Finally, we will describe the major areas of clinical research that will report over the next few years