The innate immune response of triatomines against Trypanosoma cruzi and Trypanosoma rangeli with an unresolved question: Do triatomines have immune memory?

The present work aimed to review the immune response from different triatomines against Trypanosoma cruzi and Trypanosoma rangeli and propose the study of immune memory in such insects. Trypanosoma use triatomines as vectors to reach and infect mammals. A key question to be answered about vector-parasite interaction is why the immune defense and resistance of the insect against the parasites vary. Up to date data shows that the defense of triatomines against parasites includes cellular (phagocytosis, nodulation and encapsulation) and humoral (antimicrobial peptides, phenoloxidase and reactive oxygen and nitrogen species) responses. The immune response varies depending on the triatomine species, the trypanosome strain and species, and the insect intestinal microbiota. Despite significant advances to understand parasite-insect interaction, it is still unknown if triatomines have immune memory against parasites and if this memory may derive from tolerance to parasites attack. Therefore, a closer study of such interaction could contribute and establish new proposals to control the parasite at the vector level to reduce parasite transmission to mammals, including men. For instance, if immune memory exists in the triatomines, it would be interesting to induce weak infections in insects to find out if subsequent infections are less intense and if the insects succeed in eliminating the parasites.

Screening for Resistance to Meloidogyne enterolobii in Capsicum annuum Landraces From Mexico.

Meloidogyne enterolobii has become an economically important plant parasitic nematode worldwide because of its high aggressiveness, increasing geographic distribution, wide host range, and pathogenicity in pepper (Capsicum annuum) cultivars carrying resistance genes to Meloidogyne incognita, Meloidogyne arenaria, and Meloidogyne javanica. The objectives of this study were to identify landraces of peppers resistant to M. enterolobii and analyze the relationship between resistance indicators and the phenotype parameters of plant height, stem width, leaf length, leaf width, relative chlorophyll, and number of flowers. Ninety landraces of C. annuum were collected from several states of Mexico and were inoculated with 2,000 eggs of M. enterolobii. Eleven resistant landraces were selected and confirmed with a second inoculation experiment. Seventy-five days after inoculation, in both experiments, the resistance of landraces UTC66, UTC90, UTC67, UTC88, and UTC81 to M. enterolobii was consistent. Although genotypes UTC24, UTC79, UTC65, UTC68, UTC69, and UTC25 were susceptible, these landraces had a significantly higher proportion of resistant plants, less root galling, and a lower reproductive index, in comparison with the rest of the 79 genotypes and the susceptible control, which were highly susceptible in both experiments. There was no correlation between resistant indicators and phenotypic parameters, although plant height, relative chlorophyll, and number of flowers were in general significantly affected compared with noninoculated controls, indicating that the nematodes reduce the growth and yield of peppers. Results indicate that all resistant plants from these landraces are promising sources of resistance for the development of pepper cultivars resistant to M. enterolobii.

Activation of adenosine receptors modulates the efflux transporters in brain capillaries and restores the anticonvulsant effect of carbamazepine in carbamazepine resistant rats developed by window-pentylenetetrazole kindling.

Up-regulation of efflux transporters in brain capillaries may lead to the decreased therapeutic efficacy of antiepileptic drugs in patients with Drug Resistant Epilepsy. Adenosine receptor activation in brain capillaries can modulate blood-brain barrier permeability by decreasing the protein levels and function of efflux transporters. Therefore, we aimed to investigate whether the activation of adenosine receptors improves convulsions outcome in carbamazepine (CBZ) resistant animals and modulates the protein levels of efflux transporters (P-GP, MRP1, MRP2) in brain capillaries. We employed the window-pentylenetetrazol (PTZ) kindling model to develop CBZ resistant rats by CBZ administration during the post-kindling phase, and tested if these animals displayed subsequent resistance to other antiepileptic drugs. Crucially, we investigated if the administration of a broad-spectrum adenosine agonist (NECA) improves convulsions control in CBZ resistant rats. Of potential therapeutic relevance, in CBZ resistant rats NECA restored the anticonvulsant effect of CBZ. We also evaluated how the resistance to CBZ and the activation of adenosine receptors with NECA affect protein levels of efflux transporters in brain capillaries, as quantified by western blot. While CBZ resistance was associated with the up-regulation of both P-GP/MRP2 in brain capillaries, with the administration of NECA in CBZ resistant rats, we observed a decrease of P-GP and an increase of MRP2 levels, in brain capillaries. Since the activation of adenosine receptors improves the outcome of convulsions probably through the modulation of the efflux transporters protein levels in brain capillaries, adenosine agonists could be useful as an adjunct therapy for the control of Drug Resistant Epilepsy.

Catalytic nanomedicine: a new field in antitumor treatment using supported platinum nanoparticles. In vitro DNA degradation and in vivo tests with C6 animal model on Wistar rats.

Novel nanostructured TiO2 and SiO2 based biocatalysts, with 3-4 wt. % of Pt have been developed. The obtained materials exhibit a high surface area together with a broad pore size distribution. The method of synthesis allowed obtaining high dispersed platinum metal nanoparticles. In vitro DNA reactivity test of the biocatalysts were carried out by electrophoresis and formation of DNA adducts was observed. The most active biocatalyst was H2PtCl6/SiO2. These biocatalysts were also tested in an experimental model of C6 brain tumours in Wistar rats. Administration of the material was made by stereotactic brain surgery to place it directly in the malignant tissue. A significant decrease in tumour size and weight as well as morphologic changes in cancer cells were observed.

Growth of hydroxyapatite in a biocompatible mesoporous ordered silica.

A novel biomaterial (HA-SBA-15) has been developed based on the growth of calcium phosphate hydroxyapatite (HA) nanoparticles within an organized silica structure (SBA-15). Characterization of the material was carried out using a combination of X-ray diffraction, X-ray fluorescence, transmission electron microscopy, N2 adsorption-desorption isotherms and nuclear magnetic resonance. Transmission electron microscopy observations and N2 porosimetry revealed the crystallization of hydroxyapatite nanoparticles inside the mesopore cavities of the silica structure. Specific surface areas of 760 m2 g(-1) and 260 m2 g(-1) were measured for the SBA-15 and the HA-SBA-15 material, respectively. The hydroxyl groups present in the silica nanostructure surface have brought about cationic defects in the silicium sites, mainly with those of tetrahedral symmetry, and promoted the formation of siloxanes. 29Si MAS-NMR analysis shows a significant reduction of the silanol groups concentration with HA growing within the base (SBA-15) material. Studies and brain tissue biocompatibility tests were carried out. Histopathological studies on the SBA-15 implant material showed no changes to the tissue nearby. The results confirmed the synthesis of a silica-based composite containing HA nanoparticles with the potential for biomedical applications.

Molecular vibrational analysis and MAS-NMR spectroscopy study of epilepsy drugs encapsulated in TiO2-sol-gel reservoirs.

A nanostructured matrix, consisting of titania, was designed in such a way that an antiepileptic drug could be encapsulated and released according to a well-defined time release schedule. The titania was synthesized by a sol-gel method in which titanium n-butoxide was used as the precursor for the formation of the sol. The synthesis was optimized to yield a homogeneous particle size with a high porosity and an anatase crystal structure. The antiepilectic drugs, phenytoine or valproic acid, were added during the gelation stage in order to obtain a homogeneous gel phase. The resulting nanostructured matrix including the drug showed only weak attractive forces, such as London forces, dipole-dipole coupling, and in some cases hydrogen bonds. The resulting assembly, referred to as a reservoir, was characterized using conventional FTIR and NMR spectroscopic techniques. Theoretical simulation studies were performed so as to obtain an understanding of the equilibrium electrostatic potential distribution and the relative charges on the titania and the anticonvulsants.

Effect of electrical stimulation of the baso-lateral amygdala nucleus on defensive burying shock probe test and elevated plus maze in rats.

In the present report, the putative effect of a single electrical stimulation (75, 150 or 300 microA) to the baso-lateral amygdala (BLA) nucleus was assessed in shock probe defensive burying behavior test (DB) and elevated plus maze (EPM). These models have been used for measuring anxiety levels and screening putative anxiolytic compounds. A group of 28 rats were randomly divided for the following experimental conditions: Control-control, sham-operated, BLA stimulated groups: 75, 150 and 300 microA tested for DB. The cumulative defensive burying in a 15 min-test, the latency of burying, the number of shock received and the height of the bedding material in the probe were recorded. Another group of 28 individuals was also randomly distributed for the following experimental conditions: Control-control, sham-operated, BLA stimulated animals: 75, 150, 300 microA and tested in the EPM. The time the subjects spent in the open arms, the crosses and the faeces number excreted during the test were recorded. Decreased levels of defensive burying were observed in 75, 150 and 300 microA stimulated groups. The 150 and 300 microA groups reached statistical significance. The fact that 300 microA stimulated group showed statistically significant increase in the latency of defensive burying, in the number of shock received and decreased amount in bedding material suggests a sedative action of electrical stimulation. Increased time in the open arms and augmented number of crossings in 150 microA group was observed. No changes in the number of faeces were observed in any group. The evidence supported the notion of an inhibitory amygdaline mechanism triggered by sub-threshold electrical stimulation.

Differential effects of NMDA antagonists microinjections into the nucleus reticularis pontis caudalis on seizures induced by pentylenetetrazol in the rat.

It has been shown that NMDA antagonists block the tonic but not the clonic component of seizures when they are injected in the oral region of the rat pontine reticular formation (PRF). The participation of the caudal PRF in the effects of NMDA antagonists upon the tonic and the clonic components of generalized seizures induced by pentylenetetrazol (PTZ) is unknown. The aim of the present study was to evaluate the effects of unilateral microinjections of competitive and non-competitive NMDA antagonists, 2-amino-7-phosphonoheptanoic acid (AP-7) and dizocilpine (MK-801), respectively, into the nucleus reticularis pontis caudalis of the rat PRF upon seizures induced by PTZ (70 mg/kg i.p.). MK-801 induced a dose-related decrease both in the incidence of generalized tonic-clonic seizures (GTCS) and in the presence of spikes in the EEG. MK-801 also increased GTCS latency. On the contrary, AP-7 did not have effects on GTCS. Interestingly, it induced ipsilateral circling behavior. These results suggest that in the caudal region of the rat PRF only non-competitive NMDA antagonists should block the generation of tonic and clonic components of generalized seizures.

Infusion of 3alpha,5alpha-THP to the pontine reticular formation attenuates PTZ-induced seizures.

Whether progesterone (P(4)) and its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) have anti-seizure effects through actions in the pontine reticular formation (PRF) was investigated. Concentrations of P(4) and 3alpha, 5alpha-THP in the PRF were greater in proestrous and hormone-primed rats, that are typically more resistant to seizure-induction, than diestrous and males rats. Ovx, Long-Evans rats with unilateral microinjections into the PRF of 3alpha,5alpha-THP (5 microg/0.2 microl), but not P(4) (11 microg/0.2 microl) or vehicle (beta-cyclodextrin), had a greater latency and lower incidence of tonic-clonic seizures induced by pentylenetetrazol (PTZ; 70 mg/kg, IP) administration. Infusions that missed the PRF were not effective. These data suggest 3alpha,5alpha-THP has anti-seizure effects in part through actions in the PRF.

Progesterone microinjections into the pontine reticular formation modify sleep in male and female rats.

It has been reported that progesterone (P4) induces changes in sleep, but the brain regions involved in these actions are unknown. We studied the effects of P4 microinjections into the pontine reticular formation (PRF) upon rat sleep. Intact adult male and ovariectomized female rats were unilaterally injected with P4 into the PRF and the sleep-waking cycle was recorded for 6 h. P4 (1.0 and 5.0 microg/0.2 microl) did not modify sleep, but at a higher dose (7.5 microg/0.2 microl) it produced a marked decrease in rapid eye movement sleep (REM) latency in both male (55%) and female (63%) rats. A non-significant increase in the number of REM episodes was observed after P4 administration. These findings suggest that P4 should participate in the mechanisms related to REM initiation in the rat through its effects in the PRF.

Microinjections of muscimol and bicuculline into the pontine reticular formation modify the sleep-waking cycle in the rat.

The role of gamma-aminobutyric acid (GABA) in the sleep-waking cycle was evaluated by means of microinjections of muscimol and bicuculline into the rat pontine reticular formation (PRF). Muscimol (20 ng) produced a marked increase in wakefulness (70%), a decrease in slow-wave sleep (SWS) (35%) and a remarkable delay in the onset of both SWS and paradoxical sleep, without modifying the percentage of the latter. Bicuculline (4 ng) shortened SWS latency by about 70%. These results suggest that GABAergic transmission in the PRF is involved in the regulation of sleep-waking cycle in the rat.

Repetitive electrical stimulation of X-area and parabrachial lateral nucleus: effects upon ponto-geniculo-occipital activity in the reserpinized cat.

The ponto-geniculo-occipital (PGO) activity is a characteristic field potential of paradoxical sleep, that can be continually induced by reserpine administration. It has been postulated that the X area (XA) and parabrachial lateral nucleus (Pbl) contain the generator cells for the PGO activity. In this study, repetitive electrical stimulation in the XA and Pbl was applied, with the aim of inducing progressive plastic changes in PGO activity, which was recorded from the lateral geniculate nucleus (LGN). Reserpinized cats were used; they were curarized and maintained with artificial respiration. We analyzed the PGO spike frequency at one, five and sixty minutes after stimulation, which was given every 30 minutes for at least 8 consecutive hours. Stimulation of the XA did not produce changes, while that of the Pbl induced a relatively poor progressive increment in the PGO spike frequency. The findings obtained with XA stimulation discard the possibility of inducing functional plastic changes in this region. On the other hand, the response to Pbl stimulation indicates an activation of the PGO spike generator system. These differences suggest that these nuclei have different influence on PGO activity, although it is possible that the responses found in the Pbl were indirect effects, given its anatomical relationships.