Generation of long-range curved-surface plasmonic modes and their propagation through thin metal films in a tandem array.

We describe the generation of plasmonic modes that propagate in a curved trajectory. This is performed by masking a metal surface with two screens containing a randomly distributed set of holes that follow a Gaussian statistic. The diameter of the holes is less than the wavelength of the illuminating plane wave. By implementing scaling and rotations on each screen, we control the correlation trajectory and generate long-range curved plasmonic modes. The study is generalized for the transmission of a plasmonic mode propagating in a tandem array of thin metal films using the evanescent character of the electric field.

Topological properties of the interaction between focusing regions kind cusped.

We study here the cusped-cusped interaction between two kinds of Pearcey optical fields by analyzing its topological structure. We do it in two steps; the first one is an irradiance interaction that allows us to identify organization regions. The second one is an amplitude interaction, where it is shown that the interference fringes are organized around the irradiance distribution. The topological behavior of the optical field is analyzed identifying regions with different phase functions, one of them, corresponds with a catastrophe function which has associated a focusing region, the other region can be approximated by a quadratic function. The main consequence heritage from the phase structure is interference fringes emerge from focusing regions having similar features like a topological charges. We show computational and experimental results which are in very well agreement with the theoretical model.

New insights on the mechanism of oxidation of D-galacturonic acid by hypervalent chromium.

The pollutant Cr(VI) is known to be very carcinogenic. In conditions of excess of Cr(VI), oxidation of D-galacturonic acid (Galur), the major metabolite of pectin, yields d-galactaric acid (Galar) and Cr(III). The redox reaction takes place through a multistep mechanism involving formation of intermediate Cr(II/IV) and Cr(V) species. The mechanism combines one- and two-electron pathways for the reduction of Cr(IV) by the organic substrate: Cr(VI)→ Cr(IV)→ Cr(II) and Cr(VI)→ Cr(IV)→ Cr(III). This is supported by the observation of the optical absorption spectra of Cr(VI) esters, free radicals, CrO(2)(2+) (superoxoCr(III) ion) and oxo-Cr(V) complexes. Cr(IV) cannot be directly detected; however, formation of CrO(2)(2+) provides indirect evidence for the intermediacy of Cr(II/IV). Cr(IV) reacts with Galur much faster than Cr(V) and Cr(VI) do. The analysis of the reaction kinetics via optical absorption spectroscopy shows that the Cr(IV)-Galur reaction rate inversely depends on [H(+)]. Nevertheless, high [H(+)] still does not facilitate accumulation of Cr(IV) in the Cr(VI)-Galur mixture. Cr(VI) and the intermediate Cr(V) react with Galur at comparable rates; therefore the build-up and decay of Cr(V) accompany the decay of Cr(VI). The complete rate laws for the Cr(VI), Cr(V) and Cr(IV)-Galur redox reaction are here derived in detail. Furthermore, the nature of the five-co-ordinated oxo-Cr(V) bischelate complexes formed in Cr(VI)-Galur mixtures at pH 1-5 is investigated using continuous-wave and pulsed electron paramagnetic resonance (EPR) and density functional theory (DFT).

Short communication: oral lesions in HIV/AIDS patients undergoing HAART including efavirenz.

Oral lesions (OL) have an important prognostic value for HIV/AIDS patients. However, the behavior of OL in HIV/AIDS patients undergoing highly active antiretroviral therapy including efavirenz (HAART/EFV) has not been documented. Our objective was to establish the prevalence of OL in HIV/AIDS patients undergoing HAART/EFV and to compare it with the prevalence of OL in patients undergoing antiretroviral therapy including a protease inhibitor (HAART/PI). Seventy-three HIV/AIDS patients undergoing antiretroviral treatment for at least for 6 months at "La Raza" Medical Center's Internal Medicine Unit (IMSS, Mexico City) were included. To detect OL, a detailed examination of oral soft tissues was performed in each patient. Patient records recorded gender, seropositivity time, route of contagion, antiretroviral therapy type and duration, CD4 lymphocyte count/ml, and viral load. Two groups were formed: 38 patients receiving HAART/EFV [two nucleoside analogue reverse transcriptase inhibitors (NARTI) plus efavirenz] and 35 patients receiving HAART/PI (two NARTIs plus one PI). OL prevalence was established in each study group. The Chi-square test was applied (p < 0.05(IC95%)). OL prevalence in the HAART/EFV group (32%) was lower (p < 0.007) than in the HAART/PI group (63%). Candidosis was the most prevalent OL in both groups. Herpes labialis, HIV-associated necrotizing periodontitis, xerostomia, hairy leukoplakia, and nonspecific oral sores were identified. The highest prevalence for all OL was found in the HAART/PI group. These findings suggest that HIV/AIDS patients undergoing HAART/EFV show a lower prevalence of oral lesions than patients undergoing HAART/PI.

Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents.

Our objective was to search for differences in genotypes of peroxisome proliferator-activated receptor gamma (PPARgamma) (Pro12 Ala) and its coactivator PGC-1alpha (Gly482 Ser) in adolescents harboring features of metabolic syndrome. In a population-based study, we determined medical history, anthropometric variables, biochemical measurements and arterial blood pressures of 934 high-school students of Caucasian origin. We selected 220 adolescents who had systolic or diastolic blood pressures more than the 80th or less than the 20th percentiles based on the previous single set of measurements. One hundred and seventy-five adolescents completed the study and underwent two additional blood pressure measurements on different days, as well as biochemical analysis and genotyping. We found no association between insulin resistance, body mass index (BMI) and leptin levels and PPARgamma and PGC-1alpha genotypes. The 12 Ala PPARgamma allele was associated with increased waist-to-hip ratio (WHR) and carriers seemed to have higher diastolic blood pressure and lower pulse pressure than non-carriers, particularly in the hypertensive and overweight group. Although Ser482 Ser PGC-1alpha homozygotes had lower WHRs than other PGC-1alpha genotypes, they were more frequent in the hypertensive group than in the normotensive (44.4 vs 24.5%, P<0.03), so the 482 Ser PGC-1 allele was in our population a risk factor for hypertension independently of WHR, homeostasis model assessment of insulin resistance, BMI and Pro12 Ala PPARgamma variant (odds ratio=4.0, 95% confidence interval 1.5-10.6, P<0.01). Multiple regression analysis showed that age- and sex-adjusted systolic blood pressure correlated with the 482 Ser PGC-1 allele regardless of those covariates. In conclusion, the Gly482 Ser variant of the PGC-1alpha gene may be an independent genetic risk factor for young-onset hypertension.

Thyrotropin-releasing hormone receptor (TRHR) gene is associated with essential hypertension.

In essential hypertension, a polygenic and multifactorial syndrome, several genes interact with the environment to produce high blood pressure. Thyrotropin-releasing hormone (TRH) plays an important role in central cardiovascular regulation. We have described that TRH overexpression induces hypertension in a normal rat, which was reversed by TRH antisense treatment. This treatment also reduces the central TRH hyperactivity in spontaneously hypertensive rats and normalizes blood pressure. Human TRH receptor (TRHR) belongs to the G protein-coupled seven-transmembrane domain receptor superfamily. Mutations of these receptors may result in constitutive activation. As it has been demonstrated that hypertensive patients have a blunted TSH response to TRH injection, suggesting a defect in the TRHR, we postulate that the TRHR gene is involved in human hypertension. We studied 2 independent populations from different geographic regions of our country: a sample of adult subjects from a referral clinic and a population-based sample of high school students. In search of molecular variants of TRHR, we disclosed that a polymorphic TG dinucleotide repeat (STR) at -68 bp and a novel single nucleotide polymorphism, a G-->C conversion at -221 located in the promoter of the TRHR are associated with essential hypertension. As STRs detected in gene promoters are potential Z-DNA-forming sequences and seem to affect gene expression, we studied the potentially different transcriptional activity of these TRHR promoter variants and found that the S/-221C allele has a higher affinity than does the L/G-221 allele to nuclear protein factor(s). Our findings support the hypothesis that the TRHR gene participates in the etiopathogenesis of essential hypertension.

Antisense inhibition of thyrotropin-releasing hormone reduces arterial blood pressure in spontaneously hypertensive rats.

Thyrotropin-releasing hormone (TRH) plays an important role in central cardiovascular regulation. Recently, we described that the TRH precursor gene overexpression induces hypertension in the normal rat. In addition, we published that spontaneously hypertensive rats (SHR) have central extrahypothalamic TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number. In the present study, we report that intracerebroventricular antisense (AS) treatment with a phosphorothioate oligonucleotide against the TRH precursor gene significantly diminished up to 72 hours and in a dose-dependent manner the increased diencephalic TRH content, whereas normalized systolic blood pressure (SABP) was present in the SHR compared with Wistar-Kyoto (WKY) rats. Although basal thyrotropin was higher in SHR compared with WKY rats and this difference disappeared after antisense treatment, no differences were observed in plasma T4 or T3 between strains with or without AS treatment, indicating that the effect of the AS on SABP was independent of the thyroid status. Because the encephalic renin-angiotensin system seems to be crucial in the development and/or maintenance of hypertension in SHR, we investigated the effect of antisense inhibition of TRH on that system and found that TRH antisense treatment significantly diminished the elevated diencephalic angiotensin II (Ang II) content in the SHR without any effect in control animals, suggesting that the Ang II system is involved in the TRH cardiovascular effects. To summarize, the central TRH system seems to be involved in the etiopathogenesis of hypertension in this model of essential hypertension.

Expression of TRH and TRH-like peptides in a human glioblastoma-astrocytoma cell line (U-373-MG).

The human glioblastoma-astrocytoma cell line U-373-MG shows morphological features typical of its neuroectodermal origin. Cells showed positive immunostaining for the glial fibrillary acidic protein. We used this cell culture for studying the putative production of TRH and TRH-related peptides. In a cell extract and conditioned medium, cation and anion exchange chromatography and HPLC revealed the presence of TRH and acidic TRH-like peptides which were identified, at least in part, as pGlu-Glu-ProNH(2). These findings demonstrated that U-373-MG cells are able to produce and release these peptides. Further evidence of TRH synthesis was obtained by amplification using RT-PCR of a 396 bp fragment that corresponds to the TRH precursor mRNA. Our results therefore suggest that the U-373-MG cell line may be a useful model for studying the regulation of TRH and TRH-related peptide production and the interaction of these peptides with other classical neurotransmitter systems. In fact, pilocarpine (a muscarinic cholinergic agonist) enhanced and nicotine (a nicotinic cholinergic agonist) decreased TRH and TRH-related compound production by this cell line. These data also point out that glia may produce substances with neuromodulatory action.

Parathyroid hormone-related protein expression in vascular smooth muscle of spontaneously hypertensive rats: evidence for lack of response to angiotensin II.

OBJECTIVE: We studied the expression of parathyroid hormone (PTH)-related protein in vascular smooth muscle cells of spontaneously hypertensive rats (SHR) using Wistar-Kyoto (WKY) and Sprague-Dawley rats as normotensive controls. METHODS: Aortae from 4- and 18-week-old SHR versus age-matched WKY and Sprague-Dawley rats were excised to obtain total RNA or smooth muscle cells. The cells were subcultured in Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum, then serum-deprived for 72 h and stimulated with 0.1 micromol/I angiotensin II. PTH-related protein, c-myc and angiotensin II type qa receptor (AT1aR) messenger (m)RNA levels were measured by Northern blot, using total RNA extracted by phenol/chloroform. The effects of PTH-related protein(1-34)NH2 intravenous injections on arterial blood pressure and the heart rate were studied in anesthetized SHR and WKY rats. RESULTS: The Northern blots showed a significantly higher abundance of PTH-related protein mRNA in aortae of SHR versus WKY rats in the prehypertensive state but no significant difference in adult animals. In cultured aortic smooth muscle cells, angiotensin II induced a four- to sixfold increase in PTH-related protein mRNA levels in smooth muscle cells from normotensive animals, but failed to elicit a significant response in smooth muscle cells derived from SHR in either the prehypertensive or the hypertensive state. This lack of response to angiotensin II in SHR smooth muscle cells was not due to decreased expression or responsiveness of the AT1aR, since SHR smooth muscle cells had more AT1aR mRNA than Sprague-Dawley smooth muscle cells, and angiotensin II-induced activation of c-myc was faster and greater in smooth muscle cells derived from 4- or 18-week-old SHR than in Sprague-Dawley smooth muscle cells. In contrast, PTH-related protein(1-34)NH2 induced a long-lasting dose-dependent hypotensive and tachycardic response in both SHR and WKY rats, indicating that SHR retained responsiveness to the vasodilator. CONCLUSIONS: PTH-related protein gene expression in response to angiotensin II is impaired in SHR arteries. A deficiency in this potent local vasodilator may contribute to the development and/or maintenance of arterial hypertension in this model.

Increased expression of magnocellular vasopressin mRNA in rats with deoxycorticosterone-acetate induced salt appetite.

The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) have been implicated in the genesis of hypertension due to deoxycorticosterone acetate (DOCA)-salt treatment of uninephrectomized rats. In this work, we studied if DOCA treatment of intact rats in doses arousing a salt appetite (a prehypertensive state), modulated mRNA for AVP and OT in the hypothalamus. Male Sprague-Dawley rats were offered both tap water and 3% NaCl in separate bottles and received vehicle or subcutaneous injections of 10 mg DOCA on alternate days for 7 days (4 injections) or 17 days (9 injections). They developed a preference for 3% NaCl solutions 24-48 h after treatment. Brain slices from rats killed on the 8th or 18th day were exposed to 35S-labeled probes encoding prepro-AVP mRNA or OT mRNA, respectively. Expression of these mRNAs was measured in the magnocellular and parvocellular divisions of the paraventricular nucleus (PVN) and magnocellular cells of the supraoptic nucleus (SON). No changes were obtained in neuropeptide mRNA levels in the parvocellular division of the PVN between control and the two groups of DOCA-treated rats. However, DOCA-treated animals presented an increased number of grains per cell for AVP mRNA in the magnocellular division of the PVN and in magnocellular cells of the SON, as shown by group mean comparisons and frequency histograms. No changes were detected for OT mRNA. In a second series of studies, control or DOCA-treated rats were offered 3% NaCl or water as the only choice. Animals drinking 3% NaCl showed increased AVP and OT mRNA levels, whether they received DOCA or not. However, AVP mRNA levels in both nuclei were higher in DOCA-treated rats drinking 3% NaCl than in controls drinking salt solution. In comparison, control and DOCA-treated rats drinking water showed lower levels of AVP mRNA. OT mRNA levels in the SON remained unchanged in the same groups. The results suggest that in the magnocellular cells of the PVN and SON, increments in AVP mRNA are obtained following increments in salt intake produced by either mineralocorticoid treatment or exclusive salt drinking. In rats offered salt solution and water to drink, DOCA effects on AVP mRNA developed before changes occurred in serum sodium levels. Because combined DOCA + salt treatment induced a higher response in terms of AVP mRNA expression, we suggest that AVP could be a target of the central effects of the mineralocorticoid.

Central overexpression of the TRH precursor gene induces hypertension in rats: antisense reversal.

Extrahypothalamic TRH participates in cardiovascular regulation and spontaneous hypertension of the rat. To investigate whether an increase in central TRH activity produces hypertension we studied the effect of the preTRH overproduction induced by I.C.V. transfection with a naked eukaryotic expression plasmid vector which encodes preTRH (pCMV-TRH). Northern blot analysis and RT-PCR showed that pCMV-TRH was transcribed in vitro and in vivo. At 24, 48, and 72 hours, pCMV-TRH (100 microg) in a significant and dose-dependent manner increased 37%, 84%, and 49%, respectively, the diencephalic TRH content and SABP (42+/-3, 50+/-2, and 22+/-2 mm Hg, respectively) with respect to the vector without the preTRH cDNA insert (V[TRH(-)]) as measured by RIA and the plethysmographic method, respectively, in awake animals. In addition, using immunohistochemistry we found that the increase of TRH was produced in circumventricular areas where the tripeptide is normally located. To further analyze the specificity of these effects we studied the actions of 23-mer sense (S), antisense (AS), and 3'self-stabilized sense (Ss) and antisense (ASs) phosphorothioate oligonucleotides against the initiation codon region. Only ASs inhibited the increase of TRH content and SABP induced by pCMV-TRH treatment. In addition, pCMV-TRH-induced hypertension seems not to be mediated by central Ang II or serum TSH. To summarize, central TRH overproduction in periventricular areas induced by I.C.V. transfection produces hypertension in rats which is reversed by specific antisense treatment. This model may help in testing effective antisense oligodeoxynucleotides against other candidate genes.

Angiotensin II enhances long-term memory in the crab Chasmagnathus.

An opaque screen moving overhead provokes an escape response in the crab Chasmagnathus granulatus that habituates after a few presentations of the eliciting stimulus. Fifteen trials with a 180-s intertrial interval or 30 trials with a 90-s interval (strong training protocol) ensures long-term habituation (LTH) of the response for 24 h, whereas 10 trials (weak training protocol) fail to induce it. However, robust LTH is obtained when crabs are injected with human angiotensin (All; 50 pmol) immediately after a weak training protocol. This memory-enhancing effect of All is dose-dependent, reversible by saralasin (5 pmol), and vanishes either when the weak training protocol is reduced to only five trials, or when the peptide is given before training or 1 h after. LTH is impaired by saralasin (5 pmol) administered before or after the strong training protocol, but no amnestic effect is disclosed when the antagonist is given 1 h after. On the other hand, both All-like immunoreactivity and angiotensin-converting enzyme-like activity are described in diverse tissues of Chasmagnathus, namely, in gills and in both thoracic and supraesophageal ganglia. Results support the view that some components of the renin-angiotensin system and their influence on memory might have emerged early in evolution.

Thyrotropin-releasing hormone hyperactivity in the preoptic area of spontaneously hypertensive rats.

Thyrotropin-releasing hormone (TRH) plays an important role in central cardiovascular regulation through the activation of different neurotransmitter systems at distinct extrahypothalamic sites. To study possible alterations in the TRH system in the hypertensive state, we measured TRH concentration in cerebrospinal fluid and TRH content of the preoptic area in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) by radioimmunoassay. In addition, we also measured the density of the TRH receptor in this area by a rapid filtration technique using [3H]methyl-TRH. We found a significant increase in both the TRH content (634 +/- 61 versus 350 +/- 26 pg/mg protein, SHR versus WKY; P < .01, n = 5) and density of TRH receptors without changes in affinity (Bmax, 5.0 +/- 0.1 versus 3.3 +/- 0.1 fmol/mg protein, P < .01, n = 4). An increase in TRH concentration was also found in the cerebrospinal fluid of SHR (30 +/- 3 versus 21 +/- 2 pg/mL, P < .01, n = 5), suggesting increased TRH release in the central nervous system. Northern blot analysis indicated a threefold augmented abundance of TRH precursor mRNA in the preoptic area of SHR. A polyclonal antibody raised against TRH injected peripherally or intracerebroventricularly lowered arterial blood pressure in SHR but not in WKY. In addition, long-term treatment with enalapril (5 mg/kg twice daily), which was effective in inhibiting serum angiotensin-converting enzyme activity by more than 50%, decreased arterial blood pressure and preoptic area TRH content of SHR, whereas another vasodilator, diltiazem (10 mg/kg every 8 hours), failed to produce a similar change.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction between thyrotrophin-releasing hormone and the muscarinic cholinergic system in rat brain.

TRH increases the pressor response to acetylcholine through an increment in muscarinic receptors. As chronic atropinization produces a similar effect, we hypothesized that both phenomena may be related. The effect of chronic atropine treatment on the TRH content of several brain areas in Wistar rats was studied. Atropine produced significant increases in TRH content in the preoptic and septal areas, while decreases were observed in the hypothalamus and hypophysis. The concentration of TRH in cerebrospinal fluid rose significantly in atropine-treated rats compared with controls. A similar effect was observed with eserine, an acetylcholinesterase inhibitor. Finally, perfusion of brain preoptic area slices from normal rats with Krebs-Ringer solution in the presence of pilocarpine increased basal TRH release significantly and this effect was blocked by atropine. These results are compatible with a muscarinic control on the activity of the central TRH system.

The cholinergic system participates in thyrotropin-releasing hormone (TRH) regulation.

The effect of chronic atropine treatment was studied on thyrotropin releasing hormone (TRH) content of several brain areas in Wistar rats. Atropine produced TRH increases in the septal area, preoptic area and the hypophysis; this was observed when rats were killed immediately after the last dose, while a decrease was observed only in the hypophysis 48 h after the last atropine dose. TRH concentration in cerebrospinal fluid rose significantly after atropine withdrawal with respect to controls. Treatment with eserine, an acetylcholinesterase inhibitor, produced the same effect. These results indicate cholinergic participation in central TRH regulation.

Brain amines in glucocorticoid-induced hypertension in the rat.

A two week administration of the glucocorticoid betametasone to male Wistar rats produced a mild hypertensive state. The brain of these rats showed some significant changes in amine and metabolite content with respect to normotensive controls. Epinephrine and metanephrine were increased in the rostral ventrolateral medulla and in the preoptic area. Epinephrine also increased in the septal area. Normetanephrine decreased in the rostral ventrolateral medulla. Dopamine and homovanillic acid increased in septal and preoptic areas. Dopamine alone increased in rostral ventrolateral medulla. Serotonin and 5-hydroxyindole-3-acetic acid increased in the septal area and dorsal medulla. These changes suggest significant alterations in the aminergic activity of the brain circuitry known to regulate cardiovascular functions; the changes may play a basic role in the development and maintenance of glucocorticoid-induced hypertension.