Reclaimed

Reclaimed is a medical thriller with science fiction tendencies. The narrative follows Grace, a gardener for a wealthy mayor. Grace is a Reclaimed Human mutated by the vaccine for a population-crushing pandemic. She lives a ‘healthy’ life, reliant on medications to keep her from succumbing to the leftover ailments of her past mutation. Her work with the wealthy family provides her with free medication that Elencos, the genetics company, manufactures. Out of fear of illness, Elencos has become the central authority in society. Though Grace starts to doubt the genetics company when instances of vandalism are downplayed, it is not until a friend is arrested for such occurrences that she decides to leave her home in hopes of helping her friend. She quickly aligns with the rebel group Vega, and discovers the depths of the tyrannical genetics company’s abuse of power. Medical authority has created a rigid status quo and Grace enters into a quest for emancipation, not just for herself, but for all Reclaimed Humans, from this oppressive structure

Etiology and Treatment of Angiotensin Converting Enzyme Inhibitor-Induced Cough

ABSTRACTAngiotensin-converting enzyme inhibitors (ACEls) are widely used in the treatment of hypertension and congestive heart failure (CHF). They have also been shown to slow the progression of diabetic nephropathy. In addition, evidence suggests ACEls may be beneficial in angina and myocardial infarction. Although usually well tolerated, these agents may produce a bothersome cough. The mechanism of ACEI-induced cough remains unclear but has been associated with increased bradykinin and prostaglandin levels, bronchial hyperreactivity, increased sensitivity of the extrathoracic airways and genetic polymorphism. Management principles in ACEI-induced cough are not clear. Treatment often requires discontinuation of the offending agent. This may be relatively simple in the hypertensive patient as many equally efficacious alternative hypertensive agents are available. However, discontinuation of an ACEI may be more difficult in the heart failure patient as these agents decrease morbidity and mortality in this population to a greater extent than the limited number of alternative therapies available. Other options for treating the cough may include dosage reduction or substitution with fosinopril. The addition of a pharmacological agent may also play a role. Bupivacaine, sodium cromoglycate, theophylline, nifedipine, indomethacin, and sulindac have all been utilized with limited success. When adding a pharmacological agent to control the ACEI-induced cough, influence on underlying disease control must be considered. Until large, well designed studies are available, the addition of any agent for the treatment of ACEI-induced cough must be approached with caution.RÉSUMÉLes inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA) sont largement utilisés dans le traitement de l'hypertension et de l'insuffisance cardiaque (IC). On a pu également démontrer qu'ils pouvaient ralentir la progression des néphropathies diabétiques. De plus, certaines données laissent croire que les IECA seraient utiles dans l'angine et l'infarctus du myocarde. Bien qu'ils soient généralement bien tolérés, ces agents peuvent provoquer une toux incommodante. On connaît toutefois toujours mal les mécanismes déclencheurs de cette toux, mais on croit qu'ils seraient associés à des taux élevés de bradykinine et de prostaglandines, à une hyperréactivité bronchique, à une hypersensibilité des voies aériennes supérieures ou à un polymorphisme génétique. Malheureusement, il n'existe aucune démarche thérapeutique clairement définie pour le traitement de la toux causée par les IECA. Souvent, la démarche fera appel au retrait du médicament qui cause la toux, ce qui peut être relativement simple chez l'hypertendu, car il existe bon nombre d'autres agents antihypertenseurs tous aussi efficaces. Cependant, chez l'insuffisant cardiaque, le retrait de l'IECA pose une plus grande difficulté parce que ces médicaments diminuent, dans cette population, la morbidité et la mortalité dans une plus large mesure que ne le font les autres médicaments disponibles qui sont en nombre restreint. Parmi les autres mesures thérapeutiques pour traiter une telle toux, on compte la réduction de la dose d'IECA ou la substitution de ces derniers par le fosinopril. L'ajout d'un autre agent pharmacologique pourrait aussi s'avérer utile. En effet, on a eu recours avec un certain succès à la bupivacaïne, au cromoglycate sodique, à la théophylline, à la nifédipine, à l'indométhacine et au sulindac. Lorsqu'on ajoute un autre médicament pour soigner la toux provoquée par les IECA, il faut cependant tenir compte des effets que ces médicaments ont sur le traitement spécifique utilisé contre la maladie sous-jacente. Par conséquent, jusqu'à ce que de grandes études très rigoureuses aient été menées, il faudra user de beaucoup de prudence si l'on décide d'ajouter un autre médicament pour traiter la toux causée par les IECA

Acceleration of Petasis reactions of salicylaldehyde derivatives with molecular sieves

Mild reaction conditions for Petasis reactions of substituted salicylaldehydes with various amines and arylboronic acids in the presence of molecular sieves were developed. Molecular sieves (MS) significantly accelerated the reaction rates and drove the reactions to high conversions. The conditions were applied to the synthesis of the core structure of BIIB042, a γ-secretase modulator, without stereochemical erosion of a stereogenic center in the salicylaldehyde intermediate. © 2011 American Chemical Society

Lactate Dehydrogenase Kinetics and Inhibition using a Microplate Reader

A lactate dehydrogenase (LDH) enzyme kinetics lab. expt. has been developed in which students obtain kinetic data using a microplate spectrophotometer (reader). These instruments have the capability of reading absorbances of many samples in a very short time frame. In this expt. 12 samples are prepd. at a time and the absorbances read in less than 1 min. In a 3-h lab. period, students collect data at five different substrate concns. without inhibitor and also in the presence of two different concns. of inhibitor. Students have enough time to repeat each part if they obtain too much scatter in their data. The enzyme examd., LDH, correlates with the study of metab. and has particular relevance for students who are interested in medical careers. The LDH assay itself is not new, but the microplate format and the use of urea as a quench reagent are novel features. Students plot Michaelis-Menten and Lineweaver-Burk plots and calc. values for Vmax, apparent Vmax (Vappmax), Km, apparent Km (Kappm), kcat, and kl. Students typically obtain results correctly showing that oxalic acid is a competitive inhibitor and oxamic acid is a noncompetitive inhibitor when lactate is the substrate of the reaction

Process Development of an N‑Benzylated Chloropurine at the Kilogram Scale

A two-step pharmaceutical manufacturing process was developed for the large-scale preparation of 6-chloro-9-((4-methoxy-3,5-dimethylpyridin-2-yl)­methyl)-9<i>H</i>-purin-2-amine methanesulfonic acid salt (<b>4</b>) from commercially available starting materials. In the first step, the benzylpurine free base (<b>3</b>) was prepared by benzylation of 6-chloro-9<i>H</i>-purin-2-amine (<b>1</b>) with 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine hydrochloride (<b>2</b>). The benzylpurine free base was then directly converted into the methanesulfonic acid salt. It was necessary to charge the pyridine hydrochloride <b>2</b> in portions into the mixture of K₂CO₃ (−325 mesh) and the chloropurine compound <b>1</b> in dimethylacetamide (DMA). The major regioisomeric impurity (<b>6</b>), formed by <i>N</i>⁷ benzylation, and inorganic salts were removed by filtration. Treatment of the DMA filtrate with MsOH afforded the target salt with negligible degradation. In the second step, recrystallization of the crude salt from DMSO–EtOAc with seeding gave crystalline API in high yield and purity despite the hydrolytic instability of the product in solution