[A drink with an unexpected ending... Adverse reaction by tonic water: A case report]. / Una copa con final inesperado... Reacción adversa por agua tónica: reporte de un caso.

BACKGROUND: Quinine is an alkaloid with antipyretic and anti-infective properties, and also an ingredient in tonic waters. Adverse reactions have been reported with this product, such as photosensitivity, vasculitis, and contact dermatitis. CASE REPORT: A 31-year-old male patient who, after 3-4 hours of consuming "Schweppes®" gin with tonic water, manifested ulcers on the lips and oral cavity, and a fixed erythematous lesion on the second phalanx of the hand, 24 hours later. Skin tests with aeroallergens and food were negative, and 48-hour patch tests were positive (quinine [++] and "Schweppes®" [++]). Based on the test findings, the diagnosis of an adverse reaction to quinine, contained in the tonic water, will be established. CONCLUSIONS: Quinine can be found in other types of foods or medications, so it is important to establish an accurate diagnosis and offer adequate recommendations to the patient with the consumption of this product.

ANTECEDENTES: La quinina es un alcaloide con propiedades antipiréticas, antiinfecciosas y, además, un ingrediente del agua tónica. Se han descrito reacciones adversas con este producto, como fotosensibilidad, vasculitis y dermatitis de contacto. REPORTE DE CASO: Paciente masculino de 31 años, que luego de 3-4 horas de consumir ginebra con agua tónica "Schweppes®" manifestó úlceras en los labios y la cavidad bucal, y una lesión eritematosa fija en la segunda falange de la mano, 24 horas después. Las pruebas cutáneas con aeroalérgenos y alimentos resultaron negativas, y las pruebas epicutáneas de 48 horas positivas (quinina [++] y "Schweppes®" [++]). Con base en los hallazgos de las pruebas, se estableció el diagnóstico de reacción adversa por quinina, contenida en el agua tónica. CONCLUSIÓN: La quinina puede encontrarse en diferentes alimentos o medicamentos, por lo que es importante establecer el diagnóstico preciso y ofrecer recomendaciones adecuadas por el consumo de este producto.

Palatability profile in spontaneously hypertensive rats.

The spontaneously hypertensive rats (SHRs) have enhanced palatability for NaCl taste as measured by the increased number of hedonic versus aversive responses to intraoral infusion (1 mL/1 min) of 0.3 M NaCl, in a taste reactivity test in euhydrated condition or after 24 h of water deprivation + 2 h of partial rehydration (WD-PR). SHRs also ingested more sucrose than normotensive rats, without differences in quinine hydrochloride intake. Here, we investigated the palatability of SHRs (n = 8-10) and normotensive Holtzman rats (n = 8-10) to sucrose and quinine sulphate infused intraorally in the same conditions that NaCl palatability was increased in SHRs. SHRs had similar number of hedonic responses to 2% sucrose in euhydrated condition (95 ± 19) or after WD-PR (142 ± 25), responses increased when compared with normotensive rats in euhydrated condition (13 ± 3) or after WD-PR (21 ± 6). SHRs also showed increased number of aversive responses to 1.4 mM quinine sulphate compared with normotensive rats, whether in euhydrated condition (86 ± 6, vs. normotensive: 54 ± 7) or after WD-PR (89 ± 9, vs. normotensive: 40 ± 9). The results suggest that similar to NaCl taste, sweet taste responses are increased in SHRs and resistant to challenges in bodily fluid balance. They also showed a more intense aversive response in SHRs to bitter taste compared with normotensives. This suggests that the enhanced response of SHRs to taste rewards does not correspond to a decreased response to a typical aversive taste.

A Novel Morphine Drinking Model of Opioid Dependence in Rats.

An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants' presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg/mL) solutions for two weeks. Then, quinine was removed, and the preference for morphine against water was evaluated. Using this paradigm, we show that rats highly preferred the consumption of morphine over water, reaching a voluntary morphine intake of 15 mg/kg/day. Morphine consumption led to significant analgesia and hyperlocomotion, and to a marked deprivation syndrome following the administration of the opioid antagonist naloxone. Voluntary morphine consumption was also shown to generate brain oxidative stress and neuroinflammation, signs associated with opioid dependence development. We present a robust two-bottle choice animal model of oral morphine self-administration for the evaluation of therapeutic interventions for the treatment of morphine dependence.

Physiology of Taste Processing in the Tongue, Gut, and Brain.

The gustatory system detects and informs us about the nature of various chemicals we put in our mouth. Some of these have nutritive value (sugars, amino acids, salts, and fats) and are appetitive and avidly ingested, whereas others (atropine, quinine, nicotine) are aversive and rapidly rejected. However, the gustatory system is mainly responsible for evoking the perception of a limited number of qualities that humans taste as sweet, umami, bitter, sour, salty, and perhaps fat [free fatty acids (FFA)] and starch (malto-oligosaccharides). The complex flavors and mouthfeel that we experience while eating food result from the integration of taste, odor, texture, pungency, and temperature. The latter three arise primarily from the somatosensory (trigeminal) system. The sensory organs used for detecting and transducing many chemicals are found in taste buds (TBs) located throughout the tongue, soft palate esophagus, and epiglottis. In parallel with the taste system, the trigeminal nerve innervates the peri-gemmal epithelium to transmit temperature, mechanical stimuli, and painful or cooling sensations such as those produced by changes in temperature as well as from chemicals like capsaicin and menthol, respectively. This article gives an overview of the current knowledge about these TB cells' anatomy and physiology and their trigeminal induced sensations. We then discuss how taste is represented across gustatory cortices using an intermingled and spatially distributed population code. Finally, we review postingestion processing (interoception) and central integration of the tongue-gut-brain interaction, ultimately determining our sensations as well as preferences toward the wholesomeness of nutritious foods. © 2021 American Physiological Society. Compr Physiol 11:1-35, 2021.

Description of optochin-resistant Streptococcus pneumoniae due to an uncommon mutation in the atpA gene and comparison with previously identified atpC mutants from Brazil.

Optochin susceptibility testing is a major assay used for presumptive identification of Streptococcus pneumoniae. Still, atypical optochin-resistant (Optr) pneumococci have been reported and this phenotype has been attributed to nucleotide substitutions in the genes coding for the F0F1ATPase. While substitutions in the atpC gene (c-subunit of ATPase) are more common and better characterized, data on mutations in the atpA (a-subunit) are still limited. We have characterized five Optr isolates presenting alterations in the atpA (Trp206Cys in four isolates and Trp206Ser in one isolate), constituting the first report of such mutations in Brazil. Most of the Optr isolates consisted of heterogeneous populations. Except for Opt MICs and the nucleotide changes in the atpA gene, Optr and Opts subpopulations originating from the same culture had identical characteristics. In addition, we compared phenotypic and genetic characteristics of these atpA mutants with those of atpC mutants previously identified in Brazil. No structural alterations were detected among predicted proteins, regardless of mutations in the coding gene, suggesting that, despite the occurrence of mutations, protein structures tend to be highly conserved, ensuring their functionalities. Phylogenetic analysis revealed that atypical Optr strains are true pneumococci and Opt resistance does not represent any apparent selective advantage for clinical isolates.

QSAR-Based Virtual Screening of Natural Products Database for Identification of Potent Antimalarial Hits.

With about 400,000 annual deaths worldwide, malaria remains a public health burden in tropical and subtropical areas, especially in low-income countries. Selection of drug-resistant Plasmodium strains has driven the need to explore novel antimalarial compounds with diverse modes of action. In this context, biodiversity has been widely exploited as a resourceful channel of biologically active compounds, as exemplified by antimalarial drugs such as quinine and artemisinin, derived from natural products. Thus, combining a natural product library and quantitative structure-activity relationship (QSAR)-based virtual screening, we have prioritized genuine and derivative natural compounds with potential antimalarial activity prior to in vitro testing. Experimental validation against cultured chloroquine-sensitive and multi-drug-resistant P. falciparum strains confirmed the potent and selective activity of two sesquiterpene lactones (LDT-597 and LDT-598) identified in silico. Quantitative structure-property relationship (QSPR) models predicted absorption, distribution, metabolism, and excretion (ADME) and physiologically based pharmacokinetic (PBPK) parameters for the most promising compound, showing that it presents good physiologically based pharmacokinetic properties both in rats and humans. Altogether, the in vitro parasite growth inhibition results obtained from in silico screened compounds encourage the use of virtual screening campaigns for identification of promising natural compound-based antimalarial molecules.

Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum.

Neospora caninum is an apicomplexan parasite that causes abortion in cattle, resulting in significant economic losses. There is no commercial treatment for neosporosis, and drug repositioning is a fast strategy to test possible candidates against N. caninum. In this article, we describe the effects of atovaquone, chloroquine, quinine, primaquine and tetracycline on N. caninum proliferation. The IC50 concentrations in N. caninum were compared to the current information based on previous studies for Plasmodium and Toxoplasma gondii, correlating to the described mechanisms of action of each tested drug. The inhibitory patterns indicate similarities and differences among N. caninum, Plasmodium and T. gondii. For example, atovaquone demonstrates high antiparasitic activity in all the analyzed models, while chloroquine does not inhibit N. caninum. On the other hand, tetracycline is effective against Plasmodium and N. caninum, despite its low activity in T. gondii models. The repurposing of antimalarial drugs in N. caninum is a fast and inexpensive way to develop novel formulations using well-established compounds.

Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum / Atovaquona, cloroquina, primaquina, quinino e tetraciclina: efeitos antiproliferativos de antimaláricos relevantes em Neospora caninum

Neospora caninum is an apicomplexan parasite that causes abortion in cattle, resulting in significant economic losses. There is no commercial treatment for neosporosis, and drug repositioning is a fast strategy to test possible candidates against N. caninum. In this article, we describe the effects of atovaquone, chloroquine, quinine, primaquine and tetracycline on N. caninum proliferation. The IC50 concentrations in N. caninum were compared to the current information based on previous studies for Plasmodium and Toxoplasma gondii, correlating to the described mechanisms of action of each tested drug. The inhibitory patterns indicate similarities and differences among N. caninum, Plasmodium and T. gondii. For example, atovaquone demonstrates high antiparasitic activity in all the analyzed models, while chloroquine does not inhibit N. caninum. On the other hand, tetracycline is effective against Plasmodium and N. caninum, despite its low activity in T. gondii models. The repurposing of antimalarial drugs in N. caninum is a fast and inexpensive way to develop novel formulations using well-established compounds.(AU)

Neospora caninum é um parasita Apicomplexa relacionado a abortos no gado bovino, que resultam em impactos econômicos. Não há tratamento comercial para neosporosis e o reposicionamento de drogas indica uma estratégia rápida para testar candidatos anti-N. caninum. Neste artigo, são descritos os efeitos da atovaquona, cloroquina, quinino, primaquine e tetraciclina na proliferação de N. caninum. As concentrações IC50 em N. caninum foram comparadas com a informação disponível, baseada em estudos publicados previamente para Plasmodium e Toxoplasma gondii, incluindo a correlação com os mecanismos de ação descritos para cada droga testada. Os padrões de inibição indicam pontos de similaridades e diferenças entre N. caninum, Plasmodium e T. gondii. Por exemplo, a atovaquona demonstra uma alta atividade antiparasitária em todos os modelos testados, enquanto a cloroquina não inibe N. caninum. Por outro lado, a tetraciclina é efetiva contra Plasmodium e N. caninum, em contraste com a baixa atividade em modelos de T. gondii. O reposicionamento de drogas antimaláricas em N. caninum é uma forma rápida e de baixo custo para o desenvolvimento de novas formulações que usam compostos bem estabelecidos.(AU)

Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum / Atovaquona, cloroquina, primaquina, quinino e tetraciclina: efeitos antiproliferativos de antimaláricos relevantes em Neospora caninum

Abstract Neospora caninum is an apicomplexan parasite that causes abortion in cattle, resulting in significant economic losses. There is no commercial treatment for neosporosis, and drug repositioning is a fast strategy to test possible candidates against N. caninum. In this article, we describe the effects of atovaquone, chloroquine, quinine, primaquine and tetracycline on N. caninum proliferation. The IC50 concentrations in N. caninum were compared to the current information based on previous studies for Plasmodium and Toxoplasma gondii, correlating to the described mechanisms of action of each tested drug. The inhibitory patterns indicate similarities and differences among N. caninum, Plasmodium and T. gondii. For example, atovaquone demonstrates high antiparasitic activity in all the analyzed models, while chloroquine does not inhibit N. caninum. On the other hand, tetracycline is effective against Plasmodium and N. caninum, despite its low activity in T. gondii models. The repurposing of antimalarial drugs in N. caninum is a fast and inexpensive way to develop novel formulations using well-established compounds.

Resumo Neospora caninum é um parasita Apicomplexa relacionado a abortos no gado bovino, que resultam em impactos econômicos. Não há tratamento comercial para neosporosis e o reposicionamento de drogas indica uma estratégia rápida para testar candidatos anti-N. caninum. Neste artigo, são descritos os efeitos da atovaquona, cloroquina, quinino, primaquine e tetraciclina na proliferação de N. caninum. As concentrações IC50 em N. caninum foram comparadas com a informação disponível, baseada em estudos publicados previamente para Plasmodium e Toxoplasma gondii, incluindo a correlação com os mecanismos de ação descritos para cada droga testada. Os padrões de inibição indicam pontos de similaridades e diferenças entre N. caninum, Plasmodium e T. gondii. Por exemplo, a atovaquona demonstra uma alta atividade antiparasitária em todos os modelos testados, enquanto a cloroquina não inibe N. caninum. Por outro lado, a tetraciclina é efetiva contra Plasmodium e N. caninum, em contraste com a baixa atividade em modelos de T. gondii. O reposicionamento de drogas antimaláricas em N. caninum é uma forma rápida e de baixo custo para o desenvolvimento de novas formulações que usam compostos bem estabelecidos.

Cryptic Plasmodium chronic infections: was Maurizio Ascoli right?

Cryptic Plasmodium niches outside the liver possibly represent a major source of hypnozoite-unrelated recrudescences in malaria. Maurizio Ascoli, an Italian physician and scientist, suggested that infection was maintained as a result of the persistence of endoerythrocytic parasites in the circulatory bed of some internal organs, mainly the spleen. This would explain a proportion of the recurrences in patients, regardless of the Plasmodium species. Ascoli proposed a method that included the co-administration of adrenaline, in order to induce splenic contraction, and quinine to clear expelled forms in major vessels. Driven by controversy regarding safety and effectiveness, along with the introduction of new drugs, the Ascoli method was abandoned and mostly forgotten by the malaria research community. To date, however, the existence of cryptic parasites outside the liver is gaining supportive data. This work is a historical retrospective of cryptic malaria infections and the Ascoli method, highlighting key knowledge gaps regarding these possible parasite reservoirs.

Alcohol intake in Carioca High- and Low-conditioned Freezing rats.

Evidence from clinical and epidemiological studies point towards an association between generalized anxiety disorder (GAD) and alcohol abuse. In the present study we investigated whether a similar relationship could be observed in an animal model of GAD. Specifically, we evaluated the alcohol intake of Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively). Sex differences in alcohol drinking behavior were also studied. Male and female rats from randomized crossbreeding populations served as controls (CTL). Free- and forced-choice protocols were used to measure alcohol consumption, and quinine and saccharin were used as taste control solutions. Our results indicate that CHF rats consumed more alcohol than CLF and CTL ones in both the free-choice (6 and 10% concentrations) and the forced-choice (10% concentration) conditions. CHF female rats exhibited the highest amount of alcohol intake in the forced-choice condition. CHF females also consumed more quinine than CHF male rats. Finally, CHF rats exhibited lower saccharin consumption compared to CLF and CTL animals. Altogether, these results support the hypothesis that there is a positive relationship between anxiety and alcohol intake, and provide further evidence for the use of CHF rats as a model of GAD.

Impact of alkaloids in food consumption, metabolism and survival in a blood-sucking insect.

The sense of taste provides information about the "good" or "bad" quality of a food source, which may be potentially nutritious or toxic. Most alkaloids taste bitter to humans, and because bitter taste is synonymous of noxious food, they are generally rejected. This response may be due to an innate low palatability or due to a malaise that occurs after food ingestion, which could even lead to death. We investigated in the kissing bug Rhodnius prolixus, whether alkaloids such as quinine, caffeine and theophylline, are merely distasteful, or if anti-appetitive responses are caused by a post-ingestion physiological effect, or both of these options. Although anti-appetitive responses were observed for the three alkaloids, only caffeine and theophylline affect metabolic and respiratory parameters that reflected an underlying physiological stress following their ingestion. Furthermore, caffeine caused the highest mortality. In contrast, quinine appears to be a merely unpalatable compound. The sense of taste helps insects to avoid making wrong feeding decisions, such as the intake of bitter/toxic foods, and thus avoid potentially harmful effects on health, a mechanism preserved in obligate hematophagous insects.

Hidroxicloroquina: Del fármaco de herencia Inca hasta la inmunología moderna / Hydroxychloroquine: Inca inheritance drug to modern immunology

Resumen La hidroxicloroquina es un antiguo fármaco proveniente del árbol de quino (Cinchona pubescens), a partir del componente químico alcaloide llamado quinina. Sus primeros usos se documentaron en el Imperio Inca del Perú. Se caracteriza por distintos efectos beneficiosos en enfermedades inmunológicas, al disminuir los procesos de autoinflamación y autoinmunidad persistente. Esta revisión se enfoca en describir los mecanismos inmunomoduladores de la hidroxicloroquina, así como los efectos del fármaco en algunas de las enfermedades autoinmunes más prevalentes: lupus eritematoso sistémico, artritis reumatoide, síndrome de Sjögren, vasculitis sistémicas, nefropatía por IgA, síndrome antifosfolípido, distintas enfermedades inmunológicas de la piel. También se revisarán los efectos adversos descritos para este fármaco, especialmente la toxicidad de retina, que es el más temido.

Abstract Hydroxychloroquine is an old drug derived from the quino tree (Cinchona pubescens), from the alkaloid chemical component called quinine. Its first uses trace back to the Inca empire of Peru. It is characterized by different beneficial effects in immunological diseases, decreasing the processes of autoinflammation and persistent autoimmunity. This review focuses on describing the immunomodulatory mechanisms of hydroxychloroquine as well as the effects of the drug on some of the most prevalent autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, systemic vasculitis, IgA nephropathy, antiphospholipid syndrome, different skin-related autoimmune disorders. The main adverse effects will be revised, focusing in the retinal toxicity.

Exposure to maternal odor enhances intake of a taste that mimicks the sensory attributes of ethanol.

Early exposure to ethanol increases subsequent acceptance of this drug. Little attention, however, has been devoted to the interaction of the taste of the drug with other, familiar or non-familiar, odors contingent with ethanol access, particularly early in ontogeny. This study assessed the influence of exposure to maternal odor on intake and grasp responses to an artificial nipple providing a solution (a sucrose-quinine mix) that emulates the taste of alcohol, in 4-day-old rat pups. The results showed that the mother's odor enhanced intake from and seeking responses to an artificial nipple that provided the solution that mimicked the taste of alcohol (Experiment 1). This pattern of results was not evoked by the odor of an unrelated dam (Experiment 2), nor was it observed when the nipple delivered water. The main new finding of the present study is that 4-day-old rats tested in the presence of the mother (and hence exposed to her odor cues) exhibited enhanced seeking and intake of a solution that mimics the chemosensory properties of ethanol.

Effects of Surface Characteristics of Polymeric Nanocapsules on the Pharmacokinetics and Efficacy of Antimalarial Quinine.

INTRODUCTION: The surface charge of nanoparticles, such as nanospheres (NS) and nanocapsules (NC), has been studied with the purpose of improving the in vivo performance of drugs. The aim of this study was to develop, characterize, and evaluate the in vitro antimalarial efficacy of NCP80 and NSP80 (polysorbate coated) or NCEUD and NSEUD (prepared with Eudragit RS 100) loading quinine (QN). METHODS: Formulations were prepared by the nanoprecipitation method, followed by wide physicochemical characterization. Antimalarial activity in Plasmodium berghei-infected mice and populational pharmacokinetics (PopPK) in rats were evaluated. RESULTS: The formulations showed a nanometric range (between 138 ± 3.8 to 201 ± 23.0 nm), zeta potential (mV) of -33.1 ± 0.7 (NCP80), -30.5 ± 1 (UNCP80), -25.5 ± 1 (NSP80), -20 ± 0.3 (UNSP80), 4.61 ± 1 (NCEUD), 14.1 ± 0.9 (UNCEUD), 2.86 ± 0.3 (NSEUD) and 2.84 ± 0.6 (UNSEUD), content close to 100%, and good QN protection against UVA light. There was a twofold increase in the penetration of QN into infected erythrocytes with NC compared to that with NS. There was a significant increase in t1/2 for all NC evaluated compared to that of Free-QN, due to changes in Vdss. PopPK analysis showed that NCP80 acted as a covariate to Q (intercompartmental clearance) and V2 (volume of distribution in the peripheral compartment). For NCEUD, V1 and Q were modified after QN nanoencapsulation. Regarding in vivo efficacy, NCEUD increased the survival of mice unlike Free-QN. CONCLUSION: Cationic nanocapsules modified the pharmacology of QN, presenting a potential alternative for malaria treatment.

Absence of Plasmodium falciparum K13 Propeller Domain Polymorphisms among Field Isolates Collected from the Brazilian Amazon Basin between 1984 and 2011.

Artemisinin resistance, presently confined to Southeast Asia and associated with mutations in the Plasmodium falciparum K13 (PfK13) propeller domain, represents a serious threat to global malaria control. This study aimed to provide baseline information for future artemisinin resistance surveillance, by analyzing the PfK13 propeller domain in P. falciparum field isolates collected from the Brazilian Amazon Basin between 1984 and 2011. A total of 152 P. falciparum mono-infections were assessed, of which 118 (78%) were collected before and 34 (22%) after the introduction of artemisinin-based combination therapy (ACT) in 2006. An 849-base pair fragment encoding the PfK13 propeller was amplified by nested polymerase chain reaction and sequenced in both directions. The sequences were compared with the reference sequence of P. falciparum 3D7. All samples showed wild-type sequences, thus, no mutations were observed. The results are in agreement with other recent reports and do not provide evidence for presence of PfK13 propeller domain polymorphisms associated with artemisinin resistance among P. falciparum field isolates in the Brazilian Amazon Basin neither before nor after the implementation of ACT.

Co-nanoencapsulation of antimalarial drugs increases their in vitro efficacy against Plasmodium falciparum and decreases their toxicity to Caenorhabditis elegans.

Drugs used for the treatment and prevention of malaria have resistance-related problems, making them ineffective for monotherapy. If properly associated, many of these antimalarial drugs may find their way back to the treatment regimen. Among the therapeutic arsenal, quinine (QN) is a second-line treatment for uncomplicated malaria but has side effects that limit its use. Curcumin (CR) is a natural compound with anti-plasmodial activities and low bioavailability. In this context, the aim of this work was to develop and characterize co-encapsulated QN + CR-loaded polysorbate-coated polymeric nanocapsules (NC-QC) to evaluate their activity on Plasmodium falciparum and the safety of the nanoformulations for Caenorhabditis elegans. NC-QC displayed a diameter of approximately 200 nm, a negative zeta potential and a slightly basic pH. The drugs are homogeneously distributed in the NCs in the amorphous form. Co-encapsulated NCs exhibited a significant reduction in P. falciparum parasitemia, better than QN/CR. The worms exposed to NC-QC showed higher survival and longevity and no decrease in their reproductive capacity compared to free and associated drugs. It was possible to prove that the NCs were absorbed orally by the worms using fluorescence microscopy. Co-encapsulation of QN and CR was effective against P. falciparum, minimizing the toxic effects caused by chronic exposure of the free drugs in C. elegans.

Influence of prenatal pre-exposure to an odor on intake behavior of an aversive solution in newborn rats.

Early pre- or postnatal sensory experiences significantly influence flavor preference and food intake, and can induce liking for innately unpalatable flavors. Previous work found that newborn rats stimulated with an odor experienced shortly after birth exhibited heightened intake and seeking towards an artificial nipple containing quinine. This result suggests that odors made familiar trough early postnatal pre-exposure can shift the motivational value of unconditional stimuli. The objective of the current study was to assess the effect of an odor (lemon) experienced in-utero on the first intake responses towards an artificial nipple supplying quinine. The hypothesis, which was corroborated, was that stimulation with the olfactory stimulus experienced in-utero would increase the newborn's intake and grasp responses to the artificial nipple containing quinine. Exposure to the odor that had been pre-exposed in utero increased quinine intake and seeking (i.e., latency to grasp and total time in contact with the nipple, as well as number of and mean duration of nipple grasps) in 3-h-old pups. These results replicate those previously found with postnatal odor pre-exposure, and extend the phase for pre-exposure to the prenatal stage.

Synthesis of novel quinine analogs and evaluation of their effects on Trypanosoma cruzi.

AIM: Chagas disease is a tropical disease caused by the hemoflagellate protozoan Trypanosoma cruzi. There is no vaccine for Chagas disease and available drugs (e.g., benznidazole) are effective only during the acute phase, displaying a variable curative activity in the established chronic form of the disease. New leads with high efficacy and better toxicity profiles are urgently required. Materials & methods: A library of novel quinine derivatives was synthesized using Heck chemistry and evaluated against the various developmental forms of T. cruzi. RESULTS AND CONCLUSION: Several novel quinine analogs with trypanocidal activity have been identified with the para-nitro-substituted derivative displaying a submicromolar IC50, which is 83-times lower than quinine and three-times lower than benznidazole. Transmission electron microscopy analysis demonstrated that these compounds induced a marked vacuolization of the kinetoplast of intracellular amastigotes and cell-derived trypomastigotes.

[One hundred years later, recalling how BMJ and JAMA reported the 1918-1919 influenza pandemic]. / Cien años después, recordando cómo BMJ y JAMA comunicaron la pandemia de gripe de 1918-1919.

The influenza pandemic that ravaged the planet in 1918-1919 is, undoubtedly, the most virulent and lethal infectious disease that the human species has ever overcome. This essay was to evaluate the medical interpretation of this phenomenon and the response given by doctors in terms of diagnostic and therapeutic technology based on the data published in the medical literature of two of the most important journals of the time, BMJ (The British Medical Journal) and JAMA (The Journal of the American Medical Association). It was found that the arsenal of knowledge, diagnosis and therapeutics of the time offered very few tools to address clinical management and curb contagion and mortality. However, the difficulties that clinicians and health authorities had to overcome were a solid incentive to make significant progress in the understanding and management of infectious diseases, particularly of viral etiology, in a short period of time.

La pandemia de gripa que en 1918-1919 asoló el planeta, es sin duda el evento de enfermedad masivo de mayor virulencia y letalidad que la especie humana ha sorteado a lo largo de la historia. Este ensayo se centró en evaluar, a partir de lo publicado en la literatura médica de dos de las más importantes revistas de la época, (BMJ) The British Medical Journal y (JAMA)The Journal of the American Medical Association, la interpretación que desde la medicina se hizo de este fenómeno y de la respuesta que en términos de tecnología diagnóstica y terapéutica se dio por parte de los médicos. Se encontró que el arsenal de conocimientos, diagnóstico y terapéutica de la época ofrecía muy pocas herramientas para abordar el manejo clínico y frenar los contagios y mortalidad. No obstante, las dificultades que debieron sortear los clínicos y autoridades sanitarias de la época se constituyeron en un sólido aliciente para que en poco tiempo se avanzara significativamente en la comprensión y manejo de las enfermedades infecciosas, particularmente de etiología viral.