The virulence of Plasmodia depends partly on the strain of parasite and partly on the host. In this study, Plasmodium berghei N/13/1A/4/203 caused the death of mice, whereas Plasmodium chabaudi chabaudi AS was not lethal. Current opinion is that nitric oxide (NO) and other reactive nitrogen intermediates (RNI) are produced in several host organs during malaria to resist infection or produce tissue damage. NO and RNI production in blood or plasma, brain, liver and spleen in MF1 mice was investigated during P. berghei and P. c. chabaudi infection, in order to help determine whether changes in NO production are beneficial or detrimental to the host in vivo. NO production was measured both directly and indirectly as nitrites and nitrates, to represent RNI. No changes in blood NO were detected in P. berghei infected mice, but increases were observed in brain, liver and spleen. In P. c. chabaudi infected mice, rises in NO concentration were observed in blood and spleen, whereas a decline in liver NO was seen, but there were no changes in brain. Liver contained the highest concentration of RNI, but increasing concentrations were seen in both plasma and spleen in both P. berghei and P. c. chabaudi infected mice. These results show that NO and RNI production alters during murine malaria. The changes depend upon the tissue, the day of infection, the degree of parasitaemia, the strain of Plasmodia and the method of measuring NO biosynthesis. Lethal P. berghei induced NO production in the mid and late stages of infection in mice when parasitaemia was high, whereas in nonlethal P. c. chabaudi infection, NO production was increased in the early and late stages when parasitaemia was low. These data are consistent with a role for NO in the protection of the MF1 mouse against Plasmodia. Failure to clear the parasite is associated with evidence of increased NO production in brain and liver, which may contribute to the pathology of malaria, but this hypothesis requires confirmation from other experimental approaches.

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INTRODUCTION:Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO) in learning and memory has been widely investigated.METHODS:This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03% methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3.DISCUSSION:Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01). In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001), and the time spent by this group in the target quadrant (Q1) during the probe trial was significantly lower (P<0.001). There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05).CONCLUSION:These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s) remains to be elucidated.

Nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions and signaling pathways. The NO synthase (NOS) enzyme family consists of three major isoforms, which convey variety of messages between cells, including signals for vasorelaxation, neurotransmission and cytotoxicity. This family of enzymes are generally classified as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Increased levels of NO are induced from iNOS during infection; while eNOS and nNOS may be produced at the baseline in normal conditions. An association of some key cytokines appears to be essential for NOS gene regulation in the immunity of infections. Accumulating evidence indicates that parasitic diseases are commonly associated with elevated production of NO. NO plays a role in the immunoregulation and it is implicated in the host non-specific defence in a variety of infections. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial. In the present review, the role of parasitic infections will be discussed in the controversy related to the NO production and iNOS gene expression in different parasites and a variety of experimental models.

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Nitric oxide (NO) is thought to be an important mediator and critical signaling molecule for malaria immunopathology; it is also a target for therapy and for vaccine. Inducible nitric oxide synthase (iNOS) is synthesized by a number of cell types under inflammatory conditions. The most relevant known triggers for its expression are endotoxins and cytokines. To date, there have been conflicting reports concerning the clinical significance of NO in malaria. Some researchers have proposed that NO contributes to the development of severe and complicated malaria, while others have argued that NO has a protective role. Infection with parasites resistant to the microbicidal action of NO may result in high levels of NO being generated, which could then damage the host, instead of controlling parasitemia. Consequently, the host-parasite interaction is a determining factor for whether the parasite is capable of stimulating NO production; the role of NO in resistance to malaria appears to be strain specific. It is known that NO and/or its related molecules are involved in malaria, but their involvement is not independent of other immune events. NO is an important, but possibly not an essential contributor to the control of acute-phase malaria infection. The protective immune responses against malaria parasite are multifactorial; however, they necessarily involve final effector molecules, including NO, iNOS and RNI.

The aim of this study is pharmacochemistry of Iranian floraArtemisia sieberiand its antimalarial effects onPlasmodium berghei in vivo. This is the first application ofA. sieberifor treatment of murine malaria.A. sieberiwere collected at flowering stage from the Khorassan and Semnan provinces of Iran; the aerial parts were air-dried at room temperature and then powdered. The powder was macerated in methanol, filtered with Bokhner hopper and solvent was separated in rotary evaporator. Total herbal extract was subsequently processed for ether and chloroform extracts preparation. The toxicity of herbal extract was assessed on naive NMRI mice with high, average and low doses; then pathophysiological signs were assessed. Finally, the antimalarial efficacy was investigated on two groups ofPlasmodium bergheiinfected mice. Percentage of parasitaemia and pathophysiology were also evaluated. The results of this assessment showed no toxicity even by high concentration of herbal extract. A significant reduction in percentage of parasitaemia was observed; no alterations of hepatosplenomegaly and body weight were indicated in study group.A. sieberiextracts showed antimalarial effects against murine malaria with some efficacies on reducing pathophysiology. However, there is requirement to find the major component of this herbal extract by further studies.