Sediment contamination and toxic effects on Violet Goby fish (Gobioides broussonnetii - Gobiidae) from a marine protected area in South Atlantic.

The Estuarine-Lagoon Complex of Iguape-Cananéia (ELCIC), a Marine Protected Area (MPA) in Brazil, was the focus of this study that aimed to relate external levels of exposure to contaminants to toxic effects on Gobioides broussonnetii fish. Different anthropogenic contaminants such as metals, polycyclic aromatic hydrocarbons (PAHs) and pharmaceuticals and personal care products (PPCPs) were analyzed in the sediments; and biochemical, histopathological and genotoxicity biomarkers evaluated in fish; in two different seasons at three sites of the estuarine region. Higher contamination of the sediments was observed near the main urban center (Iguape city - IG). Metal concentrations were considered low to moderate, while PAHs concentrations were considered low. The concentrations of PPCPs increased due to the anthropogenic presence and were higher near IG and the Cananéia Island (CI). Contributions from historical mining, agriculture, nautical activities, oil, sewage and waste disposal, biomass and fossil fuels combustion were identified. Higher concentrations of metals and PPCPs were observed during the cold-dry season, suggesting influences of the lower hydrodynamics during the season of lower precipitation. Higher PAHs concentrations occurred in the hot-rainy season, indicating influences of greater human presence in summer. In fish, biological responses followed the same spatial and seasonal pattern. More pronounced changes in antioxidant, biotransformation, histopathological and genotoxic biomarkers were observed in IG and CI. The multivariate analysis and the integrated biomarkers response index (IBR) also evidenced worse environmental conditions in these sites. This result can indicate a negative influence of anthropogenic activities on the contamination of sediments and on the biological responses of fish. This study presented the first ecotoxicological data for the species and suggested that these chronic exposures can cause adverse effects on this fish population. The data contribute to the understanding of local environmental quality and can be applied in the future to the environmental and social management of marine protected areas.

Clinical investigation of gustatory and neurosensory alterations following mandibular third molar surgery: an observational prospective study.

OBJECTIVE: This study aimed to prospectively observe gustatory and neurosensory alterations following surgical removal of mandibular third molars. MATERIAL AND METHODS: A prospective clinical study was conducted with patients who required mandibular third molar extraction, recruited from the Division of Oral and Maxillofacial Surgery at the Federal University of Ceará (Brazil). Age, sex, and radiographic signs were recorded. The outcome variables were the presence or absence of gustatory and neurosensory alterations. The patients were observed preoperatively and at 7, 30, 90, and 180 days postoperatively by using gustatory and neurosensory tests. RESULTS: The response to sweet (p = 0.509) and sour (p = 0.078) stimulus did not alter significantly over time. The salty threshold significantly increased from the preoperative to 7- and 30-day postoperative periods, returning to baseline values at 90 days postoperatively (p = 0.038). The bitter threshold increased significantly from the preoperative to 7-day postoperative period, returning to baseline values at 30 days after surgery (p < 0.001). Regarding neurosensory evaluation, there was an altered response to stimulus at 7 days postoperatively in specific studied areas, returning to baseline values 30 days after surgery (p < 0.05). CONCLUSION: The present study shows that mandibular third molar removal was associated with slight sensory disturbances related to mechanical, tactile, and gustatory perception. Regarding the recovery period, all patients returned to normal function without intervention, over a period ranging from 30 to 90 days. CLINICAL RELEVANCE: This study highlighted the importance of a sensory evaluation following removal of third molars, notably regarding mechanical perception and gustatory threshold assessment.

Antimicrobial potential of Alpinia purpurata lectin (ApuL): Growth inhibitory action, synergistic effects in combination with antibiotics, and antibiofilm activity.

The Alpinia purpurata inflorescence contains a lectin (ApuL), which has immunomodulatory activities on human cells. In the present work, it was evaluated the antibacterial and antifungal effects of ApuL against human pathogens. ApuL showed bacteriostatic activity against non-resistant (UFPEDA-02) and an oxacillin-resistant isolate (UFPEDA-672) of Staphylococcus aureus with minimal inhibitory concentrations (MIC50) of 50 and 400 µg/mL, respectively. In addition, it showed bactericidal effect on the non-resistant isolate (minimal bactericidal concentration: 200 µg/mL). For Candida albicans and Candida parapsilosis, ApuL showed fungistatic effect (MIC50: 200 and 400 µg/mL, respectively). The lectin was able to impair the viability of the microorganism cells, as indicated by propidium iodide (PI) staining. Analysis of growth curves, protein leakage, and ultrastructural changes supported that ApuL acts through distinct mechanisms on S. aureus isolates. Ultrastructural analysis of ApuL-treated Candida cells revealed malformations with elongations and bulges. ApuL-oxacillin combination showed synergistic effect on the oxacillin-resistant isolates UFPEDA-670 and 671, which were not sensitive to lectin alone. Synergism was also detected for ApuL-ceftazidime against a multidrug-resistant isolate of Pseudomonas aeruginosa. Synergistic action of ApuL-fluconazole was detected for C. parapsilosis, which was insensitive to the drug alone. Biofilm formation by S. aureus non-resistant isolate and C. albicans was remarkably inhibited by ApuL at sub-inhibitory concentrations. In conclusion, ApuL showed differential effects on non-resistant and resistant bacterial isolates, was active against Candida species, and showed synergistic action in combination with antibiotics.

Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 µM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers ßIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection.

The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid.

Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24h incubation with 100 µM QUIN, cells were exposed to (32)P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca(2+)/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 µM), KN93 (10 µM) and staurosporin (10nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca(2+) quelators (1mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca(2+) influx through voltage-dependent Ca(2+) channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders.

Cytoskeleton of cortical astrocytes as a target to proline through oxidative stress mechanisms.

Hyperprolinemia is an inherited disorder of proline (Pro) metabolism and patients affected by this disease may present neurological manifestations. However, the mechanisms of neural excitotoxicity elicited by hyperprolinemia are far from being understood. Considering the pivotal role of cytoskeletal remodeling in several neurodegenerative pathologies and the potential links between cytoskeleton, reactive oxygen species production and cell death, the aim of the present work was to study the effects of Pro on astrocyte and neuron cytoskeletal remodeling and the possible oxidative stress involvement. Pro induced a shift of actin cytoskeleton in stress fibers together with increased RhoA immunocontent and ERK1/2 phosphorylation/activation in cortical astrocytes. Unlike astrocytes, results evidenced little susceptibility of neuron cytoskeleton remodeling, since Pro-treated neurons presented unaltered neuritogenesis. We observed increased hydrogen peroxide production characterizing oxidative stress together with decreased superoxide dismutase (SOD) and catalase (CAT) activities in cortical astrocytes after Pro treatment, while glutathione peroxidase (GSHPx) activity remained unaltered. However, coincubation with Pro and Trolox/melatonin prevented decreased SOD and CAT activities in Pro-treated astrocytes. Accordingly, these antioxidants were able to prevent the remodeling of the actin cytoskeleton, RhoA increased levels and ERK1/2 phosphorylation in response to high Pro exposure. Taken together, these findings indicated that the cytoskeleton of cortical astrocytes, but not of neurons in culture, is a target to Pro and such effects could be mediated, at least in part, by redox imbalance, RhoA and ERK1/2 signaling pathways. The vulnerability of astrocyte cytoskeleton may have important implications for understanding the effects of Pro in the neurotoxicity linked to inborn errors of Pro metabolism.

Correction: Pontes do Nascimento et al. Synthesis of Mesoporous Zn1-xMxAl2O4 Substituted by Co2+ and Ni2+ Ions and Application in the Photodegradation of Rhodamine B. Materials 2020, 13, 2150.

In the original publication [...].

Prognosis of programmed ventricular stimulation in adult patients with syncope of unexplained origin: A historical cohort.

Background: Programmed ventricular stimulation (PVS) during electrophysiological study (EPS), is a globally accepted tool for risk stratification of sudden cardiac death (SCD) in some specific clinical situations. The aim of this study was to evaluate the prognosis of ventricular arrhythmia induction in a cohort of patients with syncope of undetermined origin (SUO). Methods: This is a historical cohort study in a population of patients with SUO referred for EPS between the years 2008-2021. In this interval, 575 patients underwent the procedure. Results: Patients with induced ventricular arrhythmias had a higher occurrence of structural heart disease (36.7% vs. 76.5%), ischemic heart disease (28.2 vs. 57.1%), heart failure (15.5% vs. 34.4%), and lower left ventricular ejection fraction (59.16% vs. 47.51%), when compared to the outcome with a negative study. PVS triggered ventricular arrhythmias in 98 patients, 62 monomorphic and 36 polymorphic. During a median follow-up of 37.6 months, 100 deaths occurred. Only the induction of sustained ventricular arrhythmias showed a significant association with the primary outcome (all-cause mortality) with a p value <.001. After the performance of EPS, 142 patients underwent cardioverter-defibrillator (ICD) implantation. At study follow-up, 30 patients had therapies by the device. Only the induction of sustained monomorphic ventricular arrhythmia showed statistically significant association with appropriate therapies by the device (p = .012). Conclusion: In patients with SUO, the induction of sustained monomorphic ventricular arrhythmia after programmed ventricular pacing is related to a worse prognosis, with a higher incidence of mortality and appropriate therapies by the ICD.

Methylglyoxal-induced cytotoxicity in neonatal rat brain: a role for oxidative stress and MAP kinases.

Carbonyl compounds such as methylglyoxal (MGO) seem to play an important role in complications resulting from diabetes mellitus, in aging and neurodegenerative disorders. In this study, we are showing, that MGO is able to suppress cell viability and induce apoptosis in the cerebral cortex and hippocampus of neonatal rats ex-vivo. These effects are partially related with ROS production, evaluated by DCFH-DA assay. Coincubation of MGO and reduced glutathione (GSH) or Trolox (vitamin E) totally prevented ROS production but only partially prevented the MGO-induced decreased cell viability in the two brain structures, as evaluated by the MTT assay. Otherwise, L-NAME, a nitric oxide (NO) inhibitor, partially prevented ROS production in the two structures but partially prevented cytotoxicity in the hippocampus. Pharmacological inhibition of Erk, has totally attenuated MGO-induced ROS production and cytotoxicity, suggesting that MEK/Erk pathway could be upstream of ROS generation and cell survival. Otherwise, p38MAPK and JNK failed to prevent ROS generation but induced decreased cell survival consistent with ROS-independent mechanisms. We can propose that Erk, p38MAPK and JNK are involved in the cytotoxicity induced by MGO through different signaling pathways. While Erk could be an upstream effector of ROS generation, p38MAPK and JNK seem to be associated with ROS-independent cytotoxicity in neonatal rat brain. The cytotoxic damage progressed to apoptotic cell death at MGO concentration higher than those described for adult brain, suggesting that the neonatal brain is resistant to MGO-induced cell death. The consequences of MGO-induced brain damage early in life, remains to be clarified. However, it is feasible that high MGO levels during cortical and hippocampal development could be, at least in part, responsible for the impairment of cognitive functions in adulthood.

The lectin from Schinus terebinthifolia leaf (SteLL) reduces immobility of mice on the tail suspension test dependent on the monoaminergic and nitric oxide signaling.

Depression underlies a common psychiatric disorder that has been rising in the diagnosis of long-term disabilities worldwide. Natural products have been studied as an antidepressant and anxiolytic agents aiming to make available new options for the daily basis treatment of those psychological disorders. SteLL is a lectin extracted from Schinus terebinthifolia leaf that has been revealed as an antimicrobial, immunomodulatory, antitumor, and antinociceptive agent. Nonetheless, the efficacy of SteLL in the treatment of depression has not yet been explored. In view of this, the aim of this study was to investigate the effect of SteLL in an acute protocol for symptoms of depression using the tail suspension test (TST) to assess despair. Administration of SteLL (1, 2 e 4 mg/kg) significantly diminished the immobility time of animals in the TST and this anti-immobility action was dependent on the carbohydrate-recognizing domain (CRD) since the prior incubation with casein (an inhibitor of SteLL carbohydrate-binding property) blocked the effect. SteLL effect was also reversed by pre-treatment with pharmacological antagonists of α2-adrenoceptor, 5-HT2A/2C serotonin receptor, and D1 dopamine receptor as well as by a selective inhibitor of iNOS (aminoguanidine). l-arginine, a precursor of NO, potentiated SteLL anti-immobility effect. In a subacute evaluation, the anti-immobility effect of SteLL persisted after seven days of treatment. Our findings suggest a role of SteLL in the modulation of depression mostly through monoaminergic and nitric oxide signaling.

Water-soluble Moringa oleifera Seed Lectin Exhibits Monoaminergic Pathway-linked Anti-depressive-like Effects in Mice.

OBJECTIVES: The present study investigated the anti-depressive-like (anti-immobility) effect of a lectin from Moringa oleifera seeds (WSMoL) in mice. METHODS: To evaluate an acute effect, the animals were treated with WSMoL (1, 2, and 4 mg/kg, i.p.) 30 min before the tail suspension test (TST). To investigate the involvement of monoaminergic and nitrergic signaling, the mice were pre-treated with selective antagonists. The role of the WSMoL carbohydrate-recognizing domain (CRD) was verified using previous blockage with casein (0.5 mg/mL). The subacute anti-immobility effect was also evaluated by administering WSMoL (1, 2, and 4 mg/kg, i.p.) once a day for 7 d. Finally, an open field test (OFT) was performed to identify possible interferences of WSMoL on animal locomotory behavior. RESULTS: WSMoL reduced the immobility time of mice in the TST at all doses, and combined treatment with fluoxetine (5 mg/kg, i.p.) and WSMoL (1 mg/kg) was also effective. The CRD appeared to be involved in the anti-immobility effect since the solution of WSMoL (4 mg/kg) pre-incubated with casein showed no activity. The lectin effect was prevented by the pre-treatment of mice with ketanserin, yohimbine, and SCH 23390, thereby demonstrating the involvement of monoaminergic pathways. In contrast, pre-treatment with L-NAME, aminoguanidine, and L-arginine did not interfere with lectin action. WSMoL exhibited a subacute effect in the TST, thereby reducing immobility time and increasing agitation time even on the seventh day. OFT data revealed that the anti-immobility effect was not caused by interference with locomotor behavior. CONCLUSION: WSMoL elicits an anti-depressant-like effect that is dependent on monoaminergic signaling.

Diphenyl ditelluride induces hypophosphorylation of intermediate filaments through modulation of DARPP-32-dependent pathways in cerebral cortex of young rats.

We studied the effect of different concentrations of diphenyl ditelluride (PhTe)(2) on the in vitro phosphorylation of glial fibrillary acidic protein (GFAP) and neurofilament (NF) subunits from cerebral cortex and hippocampus of rats during development. (PhTe)(2)-induced hypophosphorylation of GFAP and NF subunits only in cerebral cortex of 9- and 15-day-old animals but not in hippocampus. Hypophosphorylation was dependent on ionotropic glutamate receptors, as demonstrated by the specific inhibitors 10 µM DL-AP5 and 50 µM MK801, 100 µM CNQX and 100 µM DNQX. Also, 10 µM verapamil and 10 µM nifedipine, two L-voltage-dependent Ca(2+) channels (L-VDCC) blockers; 50 µM dantrolene, a ryanodine channel blocker, and the intracellular Ca(2+) chelator Bapta-AM (50 µM) totally prevented this effect. Results obtained with 0.2 µM calyculin A (PP1 and PP2A inhibitor), 1 µM Fostriecin a potent protein phosphatase 2A (PP2A) inhibitor, 100 µM FK-506 or 100 µM cyclosporine A, specific protein phosphatase 2B inhibitors, pointed to PP1 as the protein phosphatase directly involved in the hypophosphorylating effect of (PhTe)(2). Finally, we examined the activity of DARPP-32, an important endogenous Ca(2+)-mediated inhibitor of PP1 activity. Western blot assay using anti-DARPP-32, anti-pThr34DARPP-32, and anti-pThr75DARPP-32 antibodies showed a decreased phosphorylation level of the inhibitor at Thr34, compatible with inactivation of protein kinase A (PKA) by pThr75 DARPP-32. Decreased cAMP and catalytic subunit of PKA support that (PhTe)(2) acted on neuron and astrocyte cytoskeletal proteins through PKA-mediated inactivation of DARPP-32, promoting PP1 release and hypophosphorylation of IF proteins of those neural cells. Moreover, in the presence of Bapta, the level of the PKA catalytic subunit was not decreased by (PhTe)(2), suggesting that intracellular Ca(2+) levels could be upstream the signaling pathway elicited by this neurotoxicant and targeting the cytoskeleton.

A Case of Varicella-Zoster Virus Meningomyelitis in an HIV-1-Infected Patient: Facing the Challenges Related to Its Management and Prognosis.

Varicella-zoster virus (VZV) myelitis is a rare complication of herpes zoster. Diagnosing and treating this entity may be challenging. Clinical outcomes vary and neurological sequelae may be seen despite treatment. We report a case of a 43-year-old woman with human immunodeficiency virus type 1 (HIV-1) infection (CD4 cell count 191 cells/µL - 14%; undetectable viral load) who was started on antiretroviral treatment eight months before. She presented with VZV meningitis and transverse myelitis and concomitant thoracic vesicular rash at the dermatomal level T6. Neurological examination revealed neck stiffness, paraplegia, sensory level below T4, and autonomic dysfunction. Magnetic resonance imaging (MRI) revealed signs of myelitis from C4 to T10 and VZV DNA by polymerase chain reaction (PCR) was positive (20,00,000 cp/mL) in the cerebrospinal fluid (CSF). The patient completed four weeks of intravenous acyclovir and systemic corticosteroids. Repeat lumbar puncture returned negative for VZV PCR and MRI showed spinal cord improvement. However, only partial neurological improvement was observed after six months. Some features of the present case may be associated with an unfavorable outcome, including high VZV viral load in the CSF and rapid progression of neurological deficits to paraplegia and sphincter dysfunction. Moreover, the recovery of CD4+ cells from 4% to 14% after starting antiretroviral treatment might also have contributed to the extension of myelopathy. Further studies are needed to improve the understanding of VZV myelitis course and optimize its treatment.

Effects of 5-ALA mediated photodynamic therapy in oral cancer stem cells.

The aim of the present study was to investigate the effects of PDT using the photosensitizer 5-aminoulevulinic acid (5-ALA) in oral squamous cell carcinoma (OSCC) behavior, mainly regarding its role on the cancer stem cell (CSC) phenotypes and in maintenance of the stem cell properties. Two OSCC cell lines were used and divided in the groups: Control, 5-ALA, LED 6 J/cm2 and PDT. MTT and Neutral red assays were used to access cellular viability, cell migration was evaluated by the wound healing assay. The stem cell phenotype was analyzed by flow cytometry to evaluate the CD44high/ESAhigh, CD44high/ESAlow and CD44low populations, by the clonogenic and tumor sphere formation assays as well as by RT-qPCR. The presence of Protoporphyrin IX in each CSC fraction was evaluated by flow cytometry. The OSCC cell lines showed a significant decrease in cell viability and migration after PDT. The percentage of CD44high/ESAhigh cells decreased after PDT, which was associated with an increase in the CD44low cells and with a functional decrease in the colony and sphere formation capacity. CD44high/ESAhigh cells showed increased PpIX, which contributed for their greater sensitivity to PDT. INV gene increased significantly after PDT, indicating cellular differentiation. Altogether, our results demonstrate that 5-ALA mediated PDT decreases not only the fraction of oral CSC but also their functional capabilities, inducing their differentiation.

Cross-talk among intracellular signaling pathways mediates the diphenyl ditelluride actions on the hippocampal cytoskeleton of young rats.

In the present report, we showed that diphenyl ditelluride (PhTe)(2) induced in vitro hyperphosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament (NF) subunits in hippocampus of 21 day-old rats. Hyperphosphorylation was dependent on L-voltage dependent Ca(2+) channels (L-VDCC), N-methyl-d-aspartate (NMDA) and metabotropic glutamate receptors, as demonstrated by the specific inhibitors verapamil, DL-AP5 and MCPG, respectively. Also, dantrolene, a ryanodine channel blocker, EGTA and Bapta-AM, extra and intracellular Ca(2+) chelators respectively, totally prevented this effect. Activation of metabotropic glutamate receptors by (PhTe)(2) upregulates phospholipase C (PLC), producing inositol 1, 4, 5-trisphosphate (IP(3)) and diacylglycerol (DAG). Therefore, high Ca(2+) levels and DAG directly activate Ca(2+)/calmodulin-dependent protein kinase (PKCaMII) and protein kinase C (PCK), resulting in the hyperphosphorylation of Ser-57 in the carboxyl-terminal tail domain of the low molecular weight NF subunit (NF-L). Also, the activation of Erk1/2, and p38MAPK resulted in hyperphosphorylation of KSP repeats of the medium molecular weight NF subunit (NF-M). It is noteworthy that PKCaMII and PKC inhibitors prevented (PhTe)(2)-induced Erk1/2MAPK and p38MAPK activation as well as hyperphosphorylation of KSP repeats on NF-M, suggesting that PKCaMII and PKC could be upstream of this activation. Taken together, our results highlight the role of Ca(2+) as a mediator of the (PhTe)(2)-elicited signaling targeting specific phosphorylation sites on IF proteins of neural cells of rat hippocampus. Interestingly, this action shows a significant cross-talk among signaling pathways elicited by (PhTe)(2), connecting glutamate metabotropic cascade with activation of Ca(2+) channels. The extensively phosphorylated amino- and carboxyl- terminal sites could explain, at least in part, the neural dysfunction associated with (PhTe)(2) exposure.

Super aggregated amphotericin B with a thermoreversible in situ gelling ophthalmic system for amoebic keratitis treatment.

Acanthamoeba spp. are the causative agents of a sight-threatening infection of the cornea known as Acanthamoeba keratitis (AK). Amphotericin B - deoxycholate (AB) is used in the treatment of infectious keratitis, however, its topical administration has side effects as blepharitis, iritis, and painful instillation. In this context, the preheating of AB can decrease its toxicity by the formation of super aggregates (hAB). hAB associated with a thermoreversible in situ gelling ophthalmic system is a promising option due to the latter biocompatibility, low toxicity, and high residence time on the ocular surface. Our objective was to develop a topical ocular formulation of hAB for the treatment of AK. After heating at 70°C for 20 min, hAB was incorporated into a thermoreversible gelling system. The amebicidal activity of AB and hAB was evaluated against trophozoites and cysts of A. castellanii (ATCC 50492) and a regional clinical isolate (IC01). The results showed that the preheating of AB did not change the pharmacological action of the drug, with the amebicidal effect of AB and hAB under trophozoites and cysts of Acanthamoeba spp. The thermoreversible system remained stable, allowing the increase of drug retention time. For assessment of cytotoxicity, HUVEC (ATCC® CRL-1730) cells were challenged with AB and hAB for 48h. Cell viability was assessed, and hAB did not show cytotoxicity for HUVEC cells. As far as we know this was the first study that showed the preheated AB associated with a thermoreversible in situ gelling ophthalmic system as a promising system for topical ocular topical administration of hAB for AK therapy.

Artemether/Lumefantrine for the Treatment of P. malariae in a Patient on Hemodialysis.

The combination of artemether/lumefantrine is indicated for the treatment of acute uncomplicated Plasmodium falciparum malaria. There have been no clinical trials to assess the efficacy of this medication in patients with renal impairment. While it is unlikely that artemether/lumefantrine would be removed during dialysis, clinical experience regarding drug use in this setting is limited. In this article, the authors report successful treatment of Plasmodium malariae malaria on a patient with end-stage kidney disease undergoing hemodialysis.

Risk factors for extensively drug-resistant tuberculosis: a review.

INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) is emerging as a global public health problem. Its treatment is more expensive and difficult, and the outcomes much severe. The identification of risk factors for XDR-TB is of paramount importance to design effective TB control strategies. OBJECTIVE: To review published articles on risk factors for XDR-TB. METHODS: We identified 249 English articles on PubMed, and 182 were excluded by the abstract. The remaining articles were retrieved for full-text detailed evaluation by authors, and 27 relevant articles were selected for final review. RESULTS: Some risk factors were consistently present, mainly previous TB treatment and its length. Other conditions often associated were immigration, alcoholism and HIV coinfection. Pre-XDR-TB points to an increased risk of XDR-TB. CONCLUSION: The information regarding determinants of XDR-TB is relatively weak. However, special emphasis should be given to minimize the risks of TB retreatment to prevent the emergence of highly resistant TB.

Biochemical, histopathological and behavioral alterations caused by intrastriatal administration of quinolic acid to young rats.

Quinolinic acid (QUIN) is a neuroactive metabolite of the kinurenine pathway, and is considered to be involved in aging and some neurodegenerative disorders, including Huntington's disease. QUIN was injected intrastriatally into adolescent rats, and biochemical and histopathological analyses in the striatum, cortex, and hippocampus, as well as behavioral tests, were carried out in the rats over a period of 21 days after drug injection. Decreased [(3)H]glutamate uptake and increased (45)Ca(2+) uptake were detected shortly after injection in the striatum and cerebral cortex. In the hippocampus, increased (45)Ca(2+) uptake preceded the decreased [(3)H]glutamate uptake, without histopathological alterations. Also, corticostriatal astrogliosis was observed 7 days later, progressing to neuronal death at day 14. QUIN-treated rats also showed cognitive deficits 24 h after injection, concurrently with striatal astrogliosis. Motor deficits appeared later, after corticostriatal neurodegeneration. We assume that glutamate excitotoxicity could represent, at least in part, a molecular mechanism associated with the cognitive and motor impairments, corticostriatal astrogliosis and neuronal death observed in the QUIN-treated rats. We propose that our findings could be relevant for understanding the pathophysiology of human neurodegenerative diseases affecting young people, such as the juvenile form of Huntington's disease, and for the design of potential therapeutic strategies to slow down the progression of the disease.

Hand, foot, and mouth syndrome in an immunocompetent adult: a case report.

BACKGROUND: Hand, foot, and mouth syndrome (HFMS) is a common acute illness. It is characterized by mild clinical symptoms including fever, blisters, and sores in the mouth and on the palms and soles following a 3- to 7-day incubation period. This syndrome is rarely seen in adults. CASE PRESENTATION: A 35-year-old male Caucasian patient had a history of multiple episodes of acute pharyngitis, hypertension, hypercholesterolemia, and occasional abdominal pain. He presented with polyarthralgia in the knees and hands and odynophagia, followed by fever, oral mucosal aphthous lesions, and vesicles on the palms and soles. Three weeks after presentation, he was admitted to the emergency room with acute myocarditis. The in-hospital evaluation revealed positive serology for coxsackie A9 (1:160), positive anti-transglutaminase and anti-gliadin antibodies, normal immunoglobulins, and human immunodeficiency virus negativity. CONCLUSION: We herein describe a case of HFMS that was associated with coxsackie A9 infection complicated by acute myocarditis. Although an association between celiac disease and HFMS has not been described, this patient's immunologic disruption could have favored the development of infection and ultimately HFMS.