Fatty acid profiles in Leishmania spp. isolates with natural resistance to nitric oxide and trivalent antimony

Fatty acids, especially those from phospholipids (PLFA), are essential membrane components that are present in relatively constant proportions in biological membranes under natural conditions. However, under harmful growth conditions, such as diseases, environmental changes, and chemical exposure, the fatty acid proportions might vary. If such changes could be identified and revealed to be specific for adverse situations, they could be used as biomarkers. Such biomarkers could facilitate the identification of virulence and resistance mechanisms to particular chemotherapeutic agents. Therefore, specific biomarkers could lead to better therapeutic decisions that would, in turn, enhance treatment effectiveness. The objective of this study was to compare the fatty acid profiles of trivalent antimony and nitric oxide (NO)-resistant and -sensitive Leishmania chagasi and Leishmania amazonensis isolates. Fatty acid methyl esters (FAMEs) were obtained from total lipids (MIDI), ester-linked lipids (ELFA), and ester-linked phospholipids (PLFA). FAMEs were analyzed by chromatography and mass spectrometry. Species- or resistance-associated differences in FAME profiles were assessed by nonmetric multidimensional scaling, multiresponse permutation procedures, and indicator species analyses. The isolate groups had different MIDI-FAME profiles. However, neither the ELFA nor PLFA profiles differed between the sensitive and resistant isolates. Levels of the fatty acid 18:1 Δ9c were increased in sensitive isolates (p?<?0,001), whereas the fatty acid 20:4 Δ5,8,11,14 showed the opposite trend (p?<?0.01). We conclude that these two fatty acids are potential biomarkers for NO and antimony resistance in L. chagasi and L. amazonensis and that they could be helpful in therapeutic diagnoses.     

Glycine Intracerebroventricular Administration Disrupts Mitochondrial Energy Homeostasis in Cerebral Cortex and Striatum of Young Rats

High tissue levels of glycine (GLY) are the biochemical hallmark of nonketotic hyperglycinemia (NKH), an inherited metabolic disease clinically characterized by severe neurological symptoms and brain abnormalities. Considering that the mechanisms underlying the neuropathology of this disease are not fully established, the present work investigated the in vivo effects of intracerebroventricular administration of GLY on important parameters of energy metabolism in cerebral cortex and striatum from young rats. Our results show that GLY reduced CO₂ production using glucose as substrate and inhibited the activities of citrate synthase and isocitrate dehydrogenase in striatum, whereas no alterations of these parameters were verified in cerebral cortex 30 min after GLY injection. We also observed that GLY diminished the activities of complex IV in cerebral cortex and complex I–III in striatum at 30 min and inhibited complex I–III activity in striatum at 24 h after its injection. Furthermore, GLY reduced the activity of total and mitochondrial creatine kinase in both brain structures 30 min and 24 h after its administration. In contrast, the activity of Na⁺, K⁺-ATPase was not altered by GLY. Finally, the antioxidants N-acetylcysteine and creatine, and the NMDA receptor antagonist MK-801 attenuated or fully prevented the inhibitory effects of GLY on creatine kinase and respiratory complexes in cerebral cortex and striatum. Our data indicate that crucial pathways for energy production and intracellular energy transfer are severely compromised by GLY. It is proposed that bioenergetic impairment induced by GLY in vivo may contribute to the neurological dysfunction found in patients affected by NKH.     

Visual scene processing in familiar and unfamiliar environments

Humans and animals use information obtained from the local visual scene to orient themselves in the wider world. Although neural systems involved in scene perception have been identified, the extent to which processing in these systems is affected by previous experience is unclear. We addressed this issue by scanning subjects with functional magnetic resonance imaging (fMRI) while they viewed photographs of familiar and unfamiliar locations. Scene-selective regions in parahippocampal cortex (the parahippocampal place area, or PPA), retrosplenial cortex (RSC), and the transverse occipital sulcus (TOS) responded more strongly to images of familiar locations than to images of unfamiliar locations with the strongest effects (>50% increase) in RSC. Examination of fMRI repetition suppression (RS) effects indicated that images of familiar and unfamiliar locations were processed with the same degree of viewpoint specificity; however, increased viewpoint invariance was observed as individual scenes became more familiar over the course of a scan session. Surprisingly, these within-scan-session viewpoint-invariant RS effects were only observed when scenes were repeated across different trials but not when scenes were repeated within a trial, suggesting that within- and between-trial RS effects may index different aspects of visual scene processing. The sensitivity to environmental familiarity observed in the PPA, RSC, and TOS supports earlier claims that these regions mediate the extraction of navigationally relevant spatial information from visual scenes. As locations become familiar, the neural representations of these locations become enriched, but the viewpoint invariance of these representations does not change.     

Adverse effects of perioperative paracetamol,NSAIDs, glucocorticoids,gabapentinoids and their combinations: a topical review

Post‐operative pain affects millions of patients worldwide and the post‐operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non‐opioid analgesics: paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta‐analyses of analgesic efficacy and/or adverse effects of perioperative non‐opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post‐operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single‐dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non‐opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.