The historic evolution of intracranial pressure and cerebrospinal fluid pulse pressure concepts: Two centuries of challenges.

BACKGROUND: There is a consensus on the importance of monitoring intracranial pressure (ICP) during neurosurgery, and this monitoring reduces mortality during procedures. Current knowledge of ICP and cerebrospinal fluid pulse pressure has been built thanks to more than two centuries of research on brain dynamics. METHODS: Articles and books were selected using the descriptors "ICP," "cerebrospinal fluid pulse," "monitoring," "Monro-Kellie doctrine," and "ICP waveform" in electronic databases PubMed, Lilacs, Science Direct, and EMBASE. RESULTS: Several anatomists and physiologists have helped clarify the patterns of intracranial volumes under normal and pathological conditions. Monro-Kellie doctrine was an important step in a story that is reconstructed in this article. Through documentary research, we report the contribution of important medical figures, such as Monro, Kellie, Abercrombie, Burrows, Cushing, Langfitt, Marmarou, and other physiologists and anatomists who left their marks on the history of Medicine. CONCLUSION: Understanding intracranial dynamics is an unfinished historical construction. Current knowledge is the result of two centuries of research that began with the investigations of Alexander Monro secundus.

Tranexamic acid in Neurosurgery: a controversy indication-review.

Tranexamic acid (TXA) is one of the measures indicated to reduce bleeding and the need for volume replacement. However, data on risks and benefits are controversial. This study analyzes the effectivity and risks of using tranexamic acid in neurosurgery. We selected articles, published from 1976 to 2019, on the PubMed, EMBASE, Science Direct, and The Cochrane Database using the descriptors: "tranexamic acid," "neurosurgery," "traumatic brain injury," "subdural hemorrhage," "brain aneurysm," and "subarachnoid hemorrhage." TXA can reduce blood loss and the need for blood transfusion in trauma and spinal surgery. Despite the benefits of TXA, moderate-to-high doses are potentially associated with neurological complications (seizures, transient ischemic attack, delirium) in adults and children. In a ruptured intracranial aneurysm, the use of TXA can considerably reduce the risk of rebleeding, but there is weak evidence regarding its influence on mortality reduction. The TXA use in brain surgery does not present benefit. However, this conclusion is limited because there are few studies. TXA in neurosurgeries is a promising method for the maintenance of hemostasis in affected patients, mainly in traumatic brain injury and spinal surgery; nevertheless, there is lack of evidence in brain and vascular surgeries. Many questions remain unanswered, such as how to determine the dosage that triggers the onset of associated complications, or how to adjust the dose for chronic kidney disease patients.

Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies.

Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.

4-aminoquinoline analogues and its platinum (II) complexes as antimalarial agents.

The high incidence of malaria and drug-resistant strains of Plasmodium have turned this disease into a problem of major health importance. One of the approaches used to control it is to search for new antimalarial agents, such as quinoline derivates. This class of compounds composes a broad group of antimalarial agents, which are largely employed, and inhibits the formation of ß-haematin (malaria pigment), which is lethal to the parasite. More specifically, 4-aminoquinoline derivates represent potential sources of antimalarials, as the example of chloroquine, the most used antimalarial worldwide. In order to assess antimalarial activity, 12 4-aminoquinoline derived drugs were obtained and some of these derivatives were used to obtain platinum complexes platinum (II). These compounds were tested in vivo in a murine model and revealed remarkable inhibition of parasite multiplication values, whose majority ranged from 50 to 80%. In addition they were not cytotoxic. Thus, they may be object of further research for new antimalarial agents.