Quinine

Gurmarin (Gur) is a peptide that selectively suppresses responses of the chorda tympani nerve to sweet substances in rats and mice. In the present study, we examined the effect of Gur on behavioral responses to sweet substances in C57BL mice. To accomplish this, we developed a new short-term lick test and measured numbers of licks for 10 s for sweet substances mixed with quinine hydrochloride (QHCl) in water-deprived mice. Numbers of licks for sucrose mixed with 1 or 3 mM QHCl increased with increasing concentration of sucrose from 0.01 to 1.0 M. Oral infusion with 30 micro g/ml Gur produced significant decreases in responses to concentration series for sucrose mixed with 3 mM QHCl, whereas no such effect by Gur was observed in responses to QHCl alone or QHCl-mixed HCl, NaCl or monosodium glutamate. The Gur suppression of QHCl-mixed sucrose responses, which otherwise lasted for 2-3 h, rapidly returned to approximately 80% of control levels after oral infusion with beta-cyclodextrin. These results are comparable to neural data previously found in chorda tympani responses, and thereby provide further evidence for Gur as a sweet response inhibitor in C57BL mice. In the other aspect, our newly developed short-term test can also provide a tool for measurements of taste-guided behavioral responses to sweeteners.

IntroductionTo assure drug safety, the investigation of the relationship between plasma concentration and drug-induced prolongation of the QT interval of the ECG is a challenge in drug discovery. For this purpose, dofetilide was utilized to demonstrate the benefits of characterizing the complete time course of concentrations and effect in conscious beagle dogs in the assessment of drug safety.

The parasite dynamics in severe malaria (SM) varies with malaria endemicity. This study was conducted in eastern Sudan, an area of seasonal and unstable malaria transmission. From the beginning of October to the end of December (malaria season) in the years 2000, 2001, and 2003, 99 patients with severe malarial anemia (SMA) and 54 patients with cerebral malaria (CM) were identified. There was marked variation in the incidence of SMA and CM (up to six folds) and in the CM/SMA incidence ratio, over 3 years. In the heavy season of 2003, CM peaked at the beginning of the season and declined within a month at a time that the SMA reached the peak. At diagnosis, the rate of gametocytemia had inclined from ∼10% to 100% from the beginning to the end of the season. During follow-up, gametocytemia was more associated with SMA than with CM. Paradoxically, the late occurring SMA was associated with early gametocytemia (day 7) and the opposite was true in CM. In conclusion, within the season the transmission of CM and SMA was bimodal, the prevalence of the asexual and sexual parasitemia was reciprocal, and the peaks of transmission and gametocytemia were paradoxical.

The cinchona alkaloids are the longest standing antimalarial drugs in clinical use, but their mode of action is still incompletely understood. This is the first study to provide comprehensive physico-chemical information regarding these alkaloids.The results strikingly demonstrate that ...

Background Plasmodium vivax accounts for about 40% of all malaria infection in Ethiopia. Chloroquine (CQ) is the first line treatment for confirmed P. vivax malaria in the country. The first report of CQ treatment failure in P. vivax was from Debre Zeit, which suggested the presence of chloroquine resistance. Methods An in vivo drug efficacy study was conducted in Debre Zeit from June to August 2006. Eighty-seven patients with microscopically confirmed P. vivax malaria, aged between 8 months and 52 years, were recruited and treated under supervision with CQ (25 mg/kg over three days). Clinical and parasitological parameters were assessed during the 28 day follow-up period. CQ and desethylchloroquine (DCQ) blood and serum concentrations were determined with high performance liquid chromatography (HPLC) in patients who showed recurrent parasitaemia. Results Of the 87 patients recruited in the study, one was lost to follow-up and three were excluded due to P. falciparum infection during follow-up. A total of 83 (95%) of the study participants completed the follow-up. On enrolment, 39.8% had documented fever and 60.2% had a history of fever. The geometric mean parasite density of the patients was 7045 parasites/μl. Among these, four patients had recurrent parasitaemia on Day 28. The blood CQ plus DCQ concentrations of these four patients were all above the minimal effective concentration (> 100 ng/ml). Conclusion Chloroquine-resistant P. vivax parasites are emerging in Debre Zeit, Ethiopia. A multi-centre national survey is needed to better understand the extent of P. vivax resistance to CQ in Ethiopia.

The present study investigated a subpopulation of neurons in the mouse parabrachial nucleus (PbN), a gustatory and visceral relay area in the brainstem, that project to the lateral hypothalamus (LH). We made injections of the retrograde tracer Fluorogold (FG) into LH, resulting in fluorescent labeling of neurons located in different regions of the PbN. Mice were stimulated through an intraoral cannula with one of seven different taste stimuli, and PbN sections were processed for immunohistochemical detection of the immediate early gene c-Fos, which labels activated neurons. LH projection neurons were found in all PbN subnuclei, but in greater concentration in lateral subnuclei, including the dorsal lateral subnucleus (dl). Fos-like immunoreactivity (FLI) was observed in the PbN in a stimulus-dependent pattern, with the greatest differentiation between intraoral stimulation with sweet (0.5 M sucrose) and bitter (0.003 M quinine) compounds. In particular, sweet and umami-tasting stimu...

During the first decades of the 20th century, the lives of ordinary Indonesians were changed dramatically as part of larger global transformations. The great advances in tropical medicine and public health beginning in the late 19th century and intensifying in the 20th century are particularly striking, including groundbreaking work on malaria and mosquito varieties. This same-time frame witnessed an explosive growth of publishing in Indonesia. In an effort to better understand the dynamics of malaria research and treatment in the final years before WWII, this article focuses on advertisements about Malaria in a medical journal, the Geneeskundig Tijdschrift voor Nederlandsch-Indië [Medical Journal for the Netherlands Indies] and in more “popular” publications of the government publisher Balai Poestaka during the final five years of Dutch colonial rule (c.1937-1941). The differences in audiences were reflected both in the medicines advertised and in advertising strategies, as one might expect with the professionalization of advertising. Wartime years presented major changes, including a major drop in quinine advertising and an absence of Atabrine and Plasmochin.

The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71-50% inhibitory concentration (IC50) values for doxycycline ranged from 0.7 to 108.0 microM and the geometric mean IC50 for the 71 isolates was 11.3 microM (95% confidence interval = 9.5-13.4 microM). The activity of doxycycline did not differ significantly (P = 0.0858) between the chloroquine-susceptible isolates and the chloroquine-resistant isolates. There was no in vitro correlation between the responses to doxycycline and those to artemether, chloroquine, quinine, amodiaquine, pyrimethamine, and cycloguanil, suggesting no in vitro cross-resistance among these drugs. Potency was increased by prolonged exposure. In 96-hr incubations, the activity of doxycycline was 4-5-fold more increased than in 48-hr incubations. The in...