National and International Policies and Policy Instruments in the Development of Agroforestry in Chad

The potential of agroforestry to improve livelihoods and mitigate climate change and environmental degradation has been widely recognized, especially within the context of climate-smart agriculture. However, agroforestry opportunities have not been fully exploited because of several reasons, among which are adverse policies and legislations. However, many countries do not have a full understanding of how their policy and institutional environment may affect agroforestry development. We aim to fill this gap by looking at the particular case of Chad. The method used included examining data from: (i) literature reviews of important national and international polices, strategies, and legislation governing access to land and trees, among which are ‘La Loi 14’, Chad’s 2010 poverty reduction strategy paper, draft zero of the National Environmental Policy, (ii) interviews and focus group discussions with NGOs, government officials, and farmers, and (iii) surveys with 100 households. Results show that Chad has no specific agroforestry policy but opportunities for agroforestry can be found in some of the above-mentioned policy documents and government strategies. Most stakeholders interviewed had positive attitudes towards agroforestry, but uptake of the practice is handicapped by poor understanding of the forestry law by farmers and forestry officials. Gaps in existing laws give room for rent-seekers to collect individual (USD 272–909) and collective (USD 36–1818) access fees to trees on both forest and farmland. We propose that the government of Chad should unmask elements of agroforestry in existing policies and policy instruments to demonstrate its importance in responding to livelihood and environmental challenges in the country

Pharmacogenetic Study on Risperidone Long-Acting Injection: Influence of Cytochrome P450 2D6 and Pregnane X Receptor on Risperidone Exposure and Drug-Induced Side-Effects.

Risperidone is metabolized by polymorphic enzymes, and a large variability in plasma concentration and therapeutic response is observed. Risperidone long-acting injection (RLAI) avoids the first-pass effect, and little is known about the influence of gene polymorphisms involved in its pharmacokinetics. The influence on plasma concentrations of risperidone (RIS), its metabolite 9-hydroxy-risperidone, and on adverse effects were investigated for polymorphisms of cytochrome P450 2D6 (CYP2D6) (*3, *4, *5, *6), CYP3A (CYP3A4*1B, CYP3A4 rs4646437, CYP3A5*3, CYP3A7*1C), ABCB1 (1236C>T, 2677G>T, 3435C>T), NR1/2 coding for pregnane X receptor (rs1523130, rs2472677, rs7643645), and for CYP3A activity measured by a phenotyping test. Forty-two patients with at least 4 consecutive unchanged doses of RLAI were included in a multicenter cross-sectional study. A 55% lower dose-adjusted plasma levels of RIS were observed for CYP2D6 ultrarapid metabolizers (n = 5) as compared with CYP2D6 intermediate metabolizers (P < 0.007). NR1/2 polymorphism (rs7643645A>G) influenced RIS exposure with a 2.8-fold lower active moiety (P = 0.031) in GG compared with the AA genotype. This was confirmed in a second independent cohort (n = 16). Furthermore, high-density lipoprotein cholesterol was positively correlated with CYP3A activity (P = 0.01), and the NR1/2 (rs2472677) polymorphism was associated with different adverse effects including prolactin plasma levels adjusted for age and sex. In conclusion, our results confirmed the influence of CYP2D6 genotype on plasma levels of RIS. This is the first report on the influence of NR1/2 polymorphisms on RLAI exposure and on drug-induced adverse effects. These results should be validated in larger cohorts

Evidence of CYP3A Allosterism In Vivo: Analysis of Interaction Between Fluconazole and Midazolam

The allosteric effect of fluconazole (effector) on the formation of 1’-hydroxymidazolam (1’-OH-MDZ) and 4-hydroxymidazolam (4-OH-MDZ) from the CYP3A4/5 substrate, midazolam (MDZ), was examined in healthy volunteers. Following pre-treatment of fluconazole, AUC(4-OH)/AUC(MDZ) increased 35–62%, while AUC(1’-OH)/AUC(MDZ) decreased 5–37%; AUC(1’-OH)/AUC(4-OH) ratio decreased 46–58% by fluconazole and had no association with CYP3A5 genotype. 1’-OH-MDZ formation in vitro was more susceptible than 4-OH-MDZ formation to inhibition by fluconazole. Fluconazole decreased the intrinsic formation clearance ratio of 1’-OH-MDZ/4-OH-MDZ to an extent that was quantitatively comparable to in vivo observations. The elimination clearance of midazolam metabolites appeared unaffected by fluconazole. This study demonstrated that fluconazole alters midazolam product formation both in vivo and in vitro in a manner consistent with an allosteric interaction. The 1'-OH-MDZ/4-OH-MDZ ratio may serve as a biomarker of such interactions between midazolam, CYP3A4/5 and other putative effectors