Artemisinin drug resistance and monitoring: a narrative review

Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.

Lowering Pulmonary Wedge Pressure after Heart Transplant: Pulmonary Compliance and Resistance Effect / Redução da Pressão Capilar Pulmonar após Transplante Cardíaco: Complacência Pulmonar e Efeito Resistência

AbstractBackground:Right ventricular (RV) afterload is an important risk factor for post-heart transplantation (HTx) mortality, and it results from the interaction between pulmonary vascular resistance (PVR) and pulmonary compliance (CPA). Their product, the RC time, is believed to be constant. An exception is observed in pulmonary hypertension because of elevated left ventricular (LV) filling pressures.Objective:Using HTx as a model for chronic lowering of LV filling pressures, our aim was to assess the variations in RV afterload components after transplantation.Methods:We retrospectively studied 159 patients with right heart catheterization before and after HTx. The effect of Htx on hemodynamic variables was assessed.Results:Most of the patients were male (76%), and the mean age was 53 ± 12 years. HTx had a significant effect on the hemodynamics, with normalization of the LV and RV filling pressures and a significant increase in cardiac output and heart rate (HR). The PVR decreased by 56% and CPA increased by 86%. The RC time did not change significantly, instead of increasing secondary to pulmonary wedge pressure (PWP) normalization after HTx as expected. The expected increase in RC time with PWP lowering was offset by the increase in HR (because of autonomic denervation of the heart). This effect was independent from the decrease of PWP.Conclusion:The RC time remained unchanged after HTx, notwithstanding the fact that pulmonary capillary wedge pressure significantly decreased. An increased HR may have an important effect on RC time and RV afterload. Studying these interactions may be of value to the assessment of HTx candidates and explaining early RV failure after HTx.

ResumoFundamento:A pós-carga do ventrículo direito (VD) é um fator de risco importante para avaliar a mortalidade decorrente de transplante cardíaco (HTx) e resulta da interação entre a resistência vascular pulmonar (RVP) e a complacência pulmonar (CPA). Acredita-se que o produto da interação, o RC-time, seja constante. Entretanto, é exceção a hipertensão pulmonar devido às elevadas pressões de preenchimento do ventrículo esquerdo (VE).Objetivos:Ao utilizar o HTx como modelo para redução crônica das pressões de preenchimento do VE, nosso objetivo foi avaliar as variações nos componentes pós-carga do VD após o transplante.Métodos:Foram estudados, retrospectivamente, 159 pacientes com cateterismo cardíaco direito realizado antes e após o HTx. O impacto do HTx nas variáveis hemodinâmicas foi avaliado.Resultados:A maioria dos pacientes foi do sexo masculino (76%) e a média de idade foi 53 ± 12 anos. O HTx teve um efeito significativo na hemodinâmica, com normalização do VE e das pressões de preenchimento de VD e no aumento significativo do débito cardíaco e da freqüência cardíaca (FC). A RVP diminuiu 56% e a CPA aumentou 86%. Em vez de aumentar como era esperado, o RC-time não alterou significativamente e teve papel secundário em relação à normalização da pressão capilar pulmonar (PECP) após o HTx. O aumento esperado no RC timecom PWP reduzido foi atenuado pelo aumento da FC (devido à denervação autonômica do coração). Esse efeito ocorreu independentemente da diminuição da PCPConclusões:O RC-time permaneceu inalterado após HTx, entretanto a PECP diminuiu significativamente. O aumento da FC pode ter impacto importante no RC-time e na pós-carga do VD. O estudo dessas interações pode ser de grande valor para avaliar os candidatos HTx e explicar a falência do VD ocorrida logo após o HTx.

The Effet of Nifedipine on the Blood Pressure, Water and Cation Balance of the Lens in Spontaneous Hypertensive Rats

In systemic hypertension, capillary resistance is highly elevated and' contractility of vascular smooth muscle is elevated. This is due to increased calcium uptake into the sarcoplasmic reticulum of the vascular smooth muscle. Recently, nifedipine, an antihypertensive medication which inhibits calcium uptake into the vascular smooth muscle is commonly used. It decreases the contractility of the vascular smooth muscle and causes the vessels to relax, which in turn lowers the blood pressure. In 1987, according to Rodriguez-Sargent et al. the increased incidence of cataract in Dahl-salt sensitive rats(DSR) was due to increasd water and sodium contents and decreased potassium content. In this investigative study on hypertension, the water, Sodium and potassium contents in Spontaneous Hypertensive Rats(SHR) were measured. After treatment with nifedipine in SHR, we observed decreased blood pressure along with the changes in water, sodium and potassium contents of the lenses. The following results were obtained from our experiments. 1. In normal SDR, The blood pressure did not decrease with nifedipine injection. 2. After 3-7 days of nifedipine injection bidaily, the blood pressure of SHR did not decrease. 3. After 2 weeks of nifedipine injection bidaily, the blood pressure of the SHR decreased slightly and after 4 weeks of nifedipine injection bidaily, the blood pressure of SHR decreased significantly. 4. Water and sodium contents of SHR were higher than that of SDR and the potassium content was similar to that of SDR. 5. The elevated water and sodium contents of SHR decreased along with decrease of blood pressure, and after 2 weeks of nifedipine injection, showed similar level as the contents of SDR lenses. 6. Potassium contents of SHR lenses showed no change were similar to SDR lines except the 4 weeks nifedipine injection group which showed higher potasslum contents.