Evidence for the formation of supplementary corpora lutea in the pregnant and pseudopregnant rat

In a series of experiments investigating a possible post-coitum contraceptive, it was observed that the numbers of corpora lutea (CL) of pregnant Sprague-Dawley (CD) rats were greater than in cyclic, unmated control females (p<0.001). The ontogeny of these supplementary CL (SCL) was established by the recording the mean number of CL in pregnant Sprague-Dawley rats on days 1 to 9 post-coitum (day 1 being the first day post-coitum) using the gross phological dissection of the ovary. Compared to cyclic controls, an initial significant increase in mean CL numbers was recorded on day 1 post-coitum (p<0.05) with a further significant increase between days 5 and 7 (p<0.001). This phenomena was neither Sprague-Dawley strain, nor pregnancy specific, as a similar increase was also recorded for Wistar rats between days 4 and 7 postcoitum and identical increases in mean CL numbers were recorded in pseudopregnant rats of both strains. Histological studies of ovarian tissue confirmed the presence of newly formed CL on day 5 and 6 post-coitum and an absence of entrapped ova; follicular development was also present in early pregnancy with Graafian follicles evident on day 4 post-coitum. Plasma progesterone determinations revealed no increase in circulating progesterone as a result of SCL formation in either pregnant or pseudopregnant rats. Supplementary ovulations may be initiated by the preimplantation surge of oestrogen, on day 4 post-coitum, as treatment with the anti-oestrogen. Tamoxifen, inhibits their formation. Investigations into the presence of an appropriately-timed preovulatory surge of gonadotrophins in the early stages of pregnancy however, proved inconclusive. Supplementary ovulation occurs therefore between day 4 and 7 post-coitum in both pregnant and pseudopregnant Wistar and Sprague-Dawley rats, probably initiated by a consistent physiological event. This phenomena therefore obviously has an impact on the estimation of embryo mortality studies in this species

An update on the potential for male contraception : emerging options

The human population continues to grow and is estimated to rise to 10.1 billion by the end of the century. Therefore, there is still an unmet need for safe and highly effective contraceptive options for both men and women. Current options available to men include withdrawal, condoms, and vasectomy. Methods in development fall into two categories: hormonal and nonhormonal. This review will provide an overview of the testosterone combinations and immunocontraception of hormonal targets. Nonhormonal immunocontraception of sperm proteins will also be examined, together with the use of agents to disrupt other sperm-associated targets and pathways. The categories focused on include epididymal proteins, testicular kinases, epigenetic reader proteins, opioids, lonidamine derivatives, retinoic acid, microRNAs associated with spermatogenesis, and plant extracts. Considering these developments, the number of options available to men is likely to increase in the near future

Hepatitis B: The view from West Africa

The Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) study began in 2011 in The Gambia, Sénégal and Nigeria. The study aims to reduce the risk of hepatocellular carcinoma (HCC) in West Africa through the suppression of the Hepatitis B virus (HBV). The biological samples collected allow for the detection of novel liver cancer biomarkers in the hope of improving the diagnostic ability of early disease states. The PROLIFICA platform hopes to improve cancer diagnostics whilst simultaneously providing the training, skills and infrastructure necessary to develop the quality of liver cancer care in West Africa

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Reproductive component vaccine developments for contraceptive and non-contraceptive uses

Introduction: There has been no novel contraceptive development since 'the Pill', 50 years ago. Despite the subsequent steady increase in the use of contraceptives, the contraceptive needs of a significant proportion of the world population have not yet been met. The key need is for novel, effective, practical, long-lasting, affordable, non-steroidal contraceptives. Immunocontraception, based on vaccination against components of the reproductive system that do not affect other physiological systems, fulfils most of the criteria of such a contraceptive. To date, immunocontraceptives have been developed for animal use and the application to human contraception is an exciting proposition. In addition, immunocontraceptive research has provided a greater understanding of the vaccination against 'self-antigens' and has led to non-contraceptive developments for these vaccines. Areas covered: This review provides an understanding of the historic context of immunocontraceptives and the progress that has been made. In some cases, the contraceptive aspect has been abandoned, but the knowledge gained has enabled other therapeutic advances. Expert opinion: Reproductive research is still an important area and innovations continue to arise, which offer hope for new therapeutics in reproduction and related fields

An update on developments in female hormonal contraception

The human population continues to grow in some parts of the world, which has severe impact on resources, health and the environment. Individually, contraception enables women to choose their optimal family size and birth spacing, while in resource-poor countries it can help lift families out of poverty. While the oral contraceptive pill revolutionised female contraceptive options, there was a price to pay in terms of increased health risks. Today, improved formulations have been developed, together with non-oral hormonal technologies. This review will examine the history of female contraceptive research and provide an update on the status and future direction of new products

Hepatitis B: The view from West Africa

The Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) study began in 2011 in The Gambia, Sénégal and Nigeria. The study aims to reduce the risk of hepatocellular carcinoma (HCC) in West Africa through the suppression of the Hepatitis B virus (HBV). The biological samples collected allow for the detection of novel liver cancer biomarkers in the hope of improving the diagnostic ability of early disease states. The PROLIFICA platform hopes to improve cancer diagnostics whilst simultaneously providing the training, skills and infrastructure necessary to develop the quality of liver cancer care in West Africa

Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans

There is no clinically applicable biomarker for surveillance of hepatocellular carcinoma (HCC), because the sensitivity of serum alpha-fetoprotein (AFP) is too low for this purpose. Here, we determined the diagnostic performance of a panel of urinary metabolites of HCC patients from West Africa. Urine samples were collected from Nigerian and Gambian patients recruited on the case-control platform of the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) program. Urinary proton nuclear magnetic resonance (1H-NMR) spectroscopy was used to metabolically phenotype 290 subjects: 63 with HCC; 32 with cirrhosis (Cir); 107 with noncirrhotic liver disease (DC); and 88 normal control (NC) healthy volunteers. Urine samples from a further cohort of 463 subjects (141 HCC, 56 Cir, 178 DC, and 88 NC) were analyzed, the results of which validated the initial cohort. The urinary metabotype of patients with HCC was distinct from those with Cir, DC, and NC with areas under the receiver operating characteristic (AUROC) curves of 0.86 (0.78-0.94), 0.93 (0.89-0.97), and 0.89 (0.80-0.98) in the training set and 0.81 (0.73-0.89), 0.96 (0.94-0.99), and 0.90 (0.85-0.96), respectively, in the validation cohort. A urinary metabolite panel, comprising inosine, indole-3-acetate, galactose, and an N-acetylated amino acid (NAA), showed a high sensitivity (86.9% [75.8-94.2]) and specificity (90.3% [74.2-98.0]) in the discrimination of HCC from cirrhosis, a finding that was corroborated in a validation cohort (AUROC: urinary panel = 0.72; AFP = 0.58). Metabolites that were significantly increased in urine of HCC patients, and which correlated with clinical stage of HCC, were NAA, dimethylglycine, 1-methylnicotinamide, methionine, acetylcarnitine, 2-oxoglutarate, choline, and creatine. Conclusion: The urinary metabotyping of this West African cohort identified and validated a metabolite panel that diagnostically outperforms serum AFP