Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation.

STUDY QUESTION: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy? SUMMARY ANSWER: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC. STUDY DESIGN, SIZE, DURATION: This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density). MAIN RESULTS AND ROLE OF CHANCE: The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients. LIMITATIONS, REASONS FOR CAUTION: The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report. TRIAL REGISTRATION NUMBER: NCT02184806.

Brucellosis in West and Central Africa: A review of the current situation in a changing landscape of dairy cattle systems.

Brucellosis is a neglected endemic zoonosis in West and Central Africa. In this narrative review, evidence of livestock and human infection is presented along with details of past and current control strategies in 14 selected countries. Data from available literature is combined with expert opinion elicited during a regional workshop on brucellosis diagnostics. Demographic changes that affect both the epidemiology of brucellosis and the success of control or surveillance are also considered. The evidence suggests that brucellosis prevalence in emerging peri-urban dairy cattle systems may be higher than that found in traditional transhumant extensive systems. Accurate microbiological and epidemiological evidence across the region is lacking but it appears there is inherent interest in controlling the disease. There are many data gaps which require collaborative future research to evaluate fully the social and economic impact of the disease in an evolving livestock sector heavily influenced by high rates of urbanisation and regional population growth.

4-Methylpyrazole protects against acetaminophen hepatotoxicity in mice and in primary human hepatocytes.

Liver injury due to acetaminophen (APAP) overdose is the major cause of acute liver failure in the United States. While treatment with N-acetylcysteine is the current standard of care for APAP overdose, anecdotal evidence suggests that administration of 4-methylpyrazole (4MP) may be beneficial in the clinic. The objective of the current study was to examine the protective effect of 4MP and its mechanism of action. Male C57BL/6J mice were co-treated with 300 mg/kg of APAP and 50 mg/kg of 4MP. The severe liver injury induced by APAP at 6 h as indicated by elevated plasma alanine aminotransferase activities, centrilobular necrosis, and nuclear DNA fragmentation was almost completely eliminated by 4MP. In addition, 4MP largely prevented APAP-induced activation of c-Jun N-terminal kinase (JNK), mitochondrial translocation of phospho-JNK and Bax, and the release of mitochondrial intermembrane proteins. Importantly, 4MP inhibited the generation of APAP protein adducts and formation of APAP-glutathione (GSH) conjugates and attenuated the depletion of the hepatic GSH content. These findings are relevant to humans because 4MP also prevented APAP-induced cell death in primary human hepatocytes. In conclusion, early treatment with 4MP can completely prevent liver injury after APAP overdose by inhibiting cytochrome P450 and preventing generation of the reactive metabolite.

Glucose Tolerance in Non-Diabetic Adult Subjects of an Urban West-African Population.

The present study was carried out to determine glucose tolerance and insulin sensitivity in adult subjects of a west African population. 103 subjects recruited in the town of Cotonou were included in the study. After anthropometric measurement, they were subjected to an oral glucose tolerance test (OGTT). Serum glucose and insulin levels were determined throughout the OGTT. Homeostatic model of assessment of insulin resistance (HOMA-IR), MATSUDA insulin sensitivity index (MATSUDA-ISI) and insulinogenic index (IGI) have been determined to evaluate insulin sensitivity and beta cells function. Normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined glucose intolerance (CGI) were observed in respectively 53.40%, 1.94%, 35.92% and 8.74% of subjects. The prevalence of IFG and or IGT (IFG/IGT) was higher in obese subjects (66.67%) than in subjects with normal BMI (41.17%). Fasting hyperinsulinemia was observed in 82% of subjects. Mean values of HOMA-IR were not significantly different in NGT (6.86 ± 0.7) and in IFG/IGT subjects (7.47 ± 0.57). In contrast to HOMA-IR, mean value of Matsuda-ISI was significantly lower in IFG/IGT than in NGT subjects (1.47 ± 0.1 versus 1.96 ± 0.13, p<0.01). Matsuda-ISI values were also significantly lower in obese subjects (1.33 ± 0.12) than in subjects with normal BMI (1.93 ± 0.13). The mean insulinogenic index value in IFG/IGT subjects (42.5 ± 4.36) was not significantly different of that in NGT subjects (50.3 ± 5.21). These data show that the glucose tolerance disorders observed in subjects of the present study are more related to a decrease in insulin sensitivity than to an alteration of the beta cells function.

Serological evidence in sheep suggesting phlebovirus circulation in a Rift Valley fever enzootic area in Burkina Faso.

Within the Phlebovirus serogroup, Rift Valley fever (RVF) virus is endemo-enzootic in the African sahelian zone. Recently an RVF epizootic in West Africa prompted a serosurvey in the major sheep and cattle raising areas. Because of the close antigenic relationship between the phleboviruses it appeared of interest to evaluate the prevalence of the other phleboviruses also. In 1987, 482 sheep serum samples were collected in 2 different ecological zones of Burkina Faso and tested for the presence of phlebovirus antibodies. A sensitive but non-specific immunofluorescent antibody test and a specific enzyme-linked immunosorbent assay (ELISA) were used, with the following African phlebovirus antigens: Rift Valley fever (RVF), Arumowot, Gabek Forest, Gordil, Saint Floris and Odrenisrou. A total of 15.8% of the sera sampled had anti-RVF antibody in the ELISA. RVF virus appeared to be more active in drier areas such as the sahelian region, known to be an enzootic area for the disease. Antibodies to other phleboviruses were found in 11.8% of the samples, independent of RVF virus activity. It is assumed that sheep can be infected by different phleboviruses.

Treatment of bovine dermatophilosis with Senna alata, Lantana camara and Mitracarpus scaber leaf extracts.

This study describes interesting preliminary results on the therapeutic effects of ointments prepared with extracts of medicinal plants on bovine dermatophilosis. Our results show that the use of ointments made with ethanolic extracts of leaves of Senna alata, Lantana camara and Mitracarpus scaber, as topical treatments on chronic crusty or acute lesions of dermatophilosis, induces healing of the disease in the nine infected animals treated without recurrence. This is opposed to what is observed by using oxytetracycline, terramycin long-acting (TLA), or procaine-penicillin, antibiotics commonly used parenterally for the treatment of dermatophilosis in the Republic of Benin which could not prevent the recurrence of the disease. These ointments, when applied once a day for 8-15 days, provoked the falling off of the crusts after 3-4 days of treatment. Hair grows on the treated areas, which heal without scarring, within 3-4 weeks after the end of the treatment. The healed animals became free of dermatophilosis without recurrence for more than 3 years and were in good health.

[Decrease of natural immunity against Rift Valley fever in domestic ruminants of the Senegal River basin after the epizootic outbreak of 1987]. / Baisse de l'immunité naturelle vis-à-vis de la fièvre de la Vallée du Rift chez les ruminants domestiques du Bassin versant du fleuve Sénégal après l'épizootie de 1987.

A domestic ruminants serosurvey of Rift valley fever (RVF) neutralizing antibodies has been carried out during three years after the 1987 epidemic in the Senegal River Basin. Authors present results from the 1990 serosurvey that are matched with the preview surveys. Out of 1,225 ongulate tested, 17.2% had RVF virus antibodies. There is a global decrease in the herds immunity since the epizootic manifestation associated with the 1987 epidemic. Significant differences in seroprevalence are observed from the delta (28.5%) to the lower (17.9%) and middle valley (6.1%) of the Senegal river. Cattle are more likely to be with an higher seroprevalence than goat and sheep.

Changes in Rift Valley fever neutralizing antibody prevalence among small domestic ruminants following the 1987 outbreak in the Senegal River basin.

Following the Rift Valley fever (RVF) epizootic of 1987 in the Senegal River basin, 2 series of serosurveys were carried out. In 1988 and 1989, respectively, 303 and 331 randomly selected sheep and goats were investigated and sera tested for the presence of specific RVF-virus-neutralizing antibodies. In 1988, 24.4% of the sera was found to have anti-RVF neutralizing antibodies and in 1989, 19.3% was found. In 1988, we observed in the Dagana district, including the 1987 epizootic area, a significantly higher prevalence (71.1%) than in the two other more distant districts of Podor (21.5%) and Matam (9.7%). From 1988 to 1989, the antibody seroprevalence dropped significantly from 71.7 to 23.9% within the Dagana district. Young animals showed a significantly lower antibody prevalence (7.9%, N = 114) than adults (25.3%, N = 217). RVF virus circulated at a low level in 1988-89 without any epizootic manifestation. The population turnover generated an important non-immune population potentially at risk.

Characteristics of Togo strains of Brucella abortus from cattle.

Thirty Togolese strains of Brucella from cattle were classified as members of B. abortus biotype 3 by the recommended methods of the Subcommittee on Taxonomy of this genus. However two unusual characteristics distinguish the Togolese strains from the main group of B. abortus: their mean oxidative profile altered on four of the conventional substrates (L-asparagine, L-arabinose, D-galactose and D-xylose) and their very slow growth on usual media. These two original characteristics are discussed from an epidemiological and taxonomical point of view.

Alveolar lymphocytosis in patients with chronic uveitis: relationship to sarcoidosis.

Bronchoalveolar lavage (BAL) is frequently performed in patients with suspected ocular sarcoidosis. This study describes the immunogenetical, immunological, radiological, and functional features of a subclinical alveolar lymphocytosis unrelated to sarcoidosis in patients with chronic uveitis. Two hundred and ten patients with chronic uveitis of unknown origin, who underwent fiber-optic bronchoscopy with BAL as part of a prospective protocol over a three-year period, were evaluable for retrospective analysis. Sixty-five patients had alveolar lymphocytosis: Sarcoidosis was diagnosed in 13 (6%) patients, whereas alveolar lymphocytosis was considered unrelated to sarcoidosis in 52 (25%). Alveolar lymphocytosis unrelated to sarcoidosis was not associated with radiologically detectable interstitial lung disease or pulmonary function impairment. CD4/CD8 lymphocyte ratio was 3.7 +/- 3.0. Total cell count, total lymphocyte, and CD4 lymphocyte percentage were significantly lower when compared with sarcoidosis-related alveolitis (129,000 +/- 80,000 vs. 218,000 +/- 117,000, p <0.05; 33.1% +/- 13.2 vs. 39.7% +/- 13.2, p <0.05; and 54.3% +/- 18.2 vs. 65.4% +/- 10.1, p <0.05, respectively). Patients with alveolar lymphocytosis unrelated to sarcoidosis were older (47.8 +/- 17.7 years vs. 42.7 +/- 14.2 years, p <0.05) and more likely to carry the HLA-B51 allele (19.7% vs. 7.1%, p <0.01) than patients with chronic uveitis without alveolar lymphocytosis. They did not appear to be at risk of developing clinically apparent interstitial lung disease on followup. We conclude that alveolar lymphocytosis is frequently observed in patients with chronic uveitis. It is generally unrelated to sarcoidosis and may then be associated with a distinctive immunogenetic phenotype.