Generalized neighbor-interaction models induced by nonlinear lattices

It is shown that the tight-binding approximation of the nonlinear Schrodinger equation with a periodic linear potential and periodic in space nonlinearity coefficient gives rise to a number of nonlinear lattices with complex, both linear and nonlinear, neighbor interactions. The obtained lattices present nonstandard possibilities, among which we mention a quasilinear regime, where the pulse dynamics obeys essentially the linear Schrodinger equation. We analyze the properties of such models both in connection to their modulational stability, as well as in regard to the existence and stability of their localized solitary wave solutions.

Evaluation of Brazilian ethanol production yeasts for maltose fermentation in media containing structurally complex nitrogen sources

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sexual behavior and fertility of male rats submitted to prolonged immobilization-induced stress

In order to investigate whether prolonged stress interferes with the onset of sexual behavior at puberty and with fertility at adulthood, prepubertal male Wistar rats (40 days of age) were immobilized 6 h a day for 15 days (up to early puberty) or for 60 days (until sexual maturity). Pubertal stressed rats showed a two-fold increase in the latency for the first mount (probably due to repeated aversive experience in which a change of environment was always followed by immobilization) and a 2.5-fold increase in the frequency of thrusting (indicative of enhanced sexual performance). The apparently stimulatory effect of prolonged stress on the onset of sexual behavior is discussed in terms of increased testosterone level and interference with the complex interchanges between the neurotransmitters/neuropeptides involved in the central control of male sexual activity. Adult stressed animals were mated with normal females, which became pregnant but exhibited a more than two-fold increase in both pre-implantation and post-implantation loss, probably due to a smaller rate of fertilization and/or fertilization with damaged spermatozoa.

Effect of acute heat stress on heat shock protein 70 messenger RNA and on heat shock protein expression in the liver of broilers

1. The synthesis of heat shock protein 70 (Hsp70) mRNA and the expression of Hsp70 in the liver of broiler chickens submitted to acute heat stress (35 degrees C for 5 h) was investigated.2. Hsp70 expression was detected by SDS-PAGE and Western blot analysis using a polyclonal antiserum against Hsp70 of Blastocladiella emersonii. The specific signal of Hsp70 mRNA was analysed by Northern blot using as probe a Hsp70 cDNA of B. emersonii.3. An increase in the amount of Hsp70 was detected from the first up to the fifth hour of acute heat exposure. This increase in the amount of Hsp70 was accompanied by an increase in Hsp70 mRNA which peaked at 3 h.4. This study shows that the heat induced increase in Hsp70 mRNA and protein in broiler liver, in vivo, are time dependent, similar to that in mammals.

Water regulation of actinomycin-D binding to DNA: the interplay among drug affinity, DNA long-range conformation, and hydration

Actiaomycin-D (actD) binds to natural DNA at two different classes of binding sites, weak and strong. The affinity for these sites is highly dependent on DNA se(sequence and solution conditions, and the interaction appears to be purely entropic driven Although the entropic character of this reaction has been attributed to the release of water molecules upon drug to DNA complex formation, the mechanism by which hydration regulates actD binding and discrimination between different classes of binding sites on natural DNA is still unknown. In this work, we investigate the role of hydration on this reaction using the osmotic stress method. We skew that the decrease of solution water activity, due to the addition of sucrose, glycerol ethylene glycol, and betaine, favors drug binding to the strong binding sites on DNA by increasing both the apparent binding affinity Delta G, and the number of DNA base pairs apparently occupied by the bound drug n(bp/actD). These binding parameters vary linearly with the logarithm of the molar fraction of water in solution log(X-w), which indicates the contribution of water binding to the energetic of the reaction. It is demonstrated that the hydration change measured upon binding increases proportionally to the apparent size of the binding site n(bp/uctD). This indicates that n(bp/actD) measured from the Scatchard plod is a measure of the size of the DNA molecule changing conformation due to ligand binding. We also find that the contribution of DNA deformation, gauged by n(bp/act) to the total free energy of binding Delta G, is given by Delta G = Delta G(local) + n(bp/actD) x delta G(DNA), where Delta G(local), = -8020 +/- 51 cal/mol of actD bound and delta G(DNa) = -24.1 +/- 1.7cal/mol of base pair at 25 degrees C. We interpret Delta G(local), as the energetic contribution due to the direct interactions of actD with the actual tetranucleotide binding site, and it n(bp/actB) X delta G(DNA) as that due to change inconformation, induced by binding, of it n(bp/actD) DNA base pairs flanking the local site. This interpretation is supported by the agreement found between the value of delta G(DNA) and the torsional free energy change measured independently. We conclude suggesting an allosteric model for ligand binding to DNA, such that the increase in binding affinity is achieved by increasing the relaxation of the unfavorable free energy of binding storage at the local site through a larger number of DNA base pairs. The new aspect on this model is that the size of the complex is not fixed but determined by solutions conditions, such as water activity, which modulate the energetic barrier to change helix conformation. These results may suggest that long-range allosteric transitions of duplex DNA are involved in the inhibition of RNA synthesis by actD, and more generally, in the regulation of transcription. (C) 2000 John Wiley & Sons, Inc.

Sufentanil-2-hydroxypropyl-beta-cyclodextrin inclusion complex for pain treatment: Physicochemical, cytotoxicity, and pharmacological evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Rat nephrotoxic nephritis. The relation between the type and intensity of induced histological lesions and the content of antiglomerular basement membrane antibodies of the inoculated serum

Six groups of 6 rats received equal doses (0.8 ml/100 g of body weight) of different rabbit anti rat kidney sera. The titer of anti GBM antibodies in the sera was evaluated by indirect immunofluorescent test in isolated GBM (IIT GBM). Rats of groups 1, 2, 3, 5, 6 received anti rat GBM sera with titers of 1/320, 1/240, 1/160, 1/60, 1/30 respectively. Group 4 received anti rat kidney serum with a titer of 1/80. The rats of group 1 died from 1 to 5 minutes after inoculation and their kidney were congested, with hialine trombi occluding arterioles and glomerular capillaries. The rats of group 2 and one of group 3 died from 2 to 15 days after inoculation and diffuse cortical necrosis was found. The remaining rats were sacrificed 2 months after inoculation. The kidneys were normal in control group; chronic membranoproliferative glomerulonephritis was observed in group 3 and 4, membranoproliferative glomerulonephritis in group 5 and minimal changes in group 6. By immunofluorescence rabbit gammaglobulin was seen in GBM of group 3, 4, 5 and 6. The IIT GBM performed in the eluates of the kidneys revealed the presence of heterologous antibody in groups 1, 2, 3, 4, 5 and 6 and autologous antibody in groups 3, 4 and 5. One concludes that the IIT GBM identifies and quantifies antibodies which have the property of damaging the kidney.

Effect of adrenergic stimulation of the amygdaloid complex on water intake

The effect of noradrenaline, isoproterenol, phentolamine and propranolol, injected into the basolateral nuclei of the amygdala on water intake, was investigated in male Holtzman rats. The injection of noradrenaline (40 nmol) into the amygdaloid complex (AC) of satiated rats produced no change in water intake (0.05 ± 0.03 ml/1 hour). The injection of isoproterenol (40 nmol) produced an increase in water intake in sedated rats (1.93 ± 0.23 ml/1 hour). Noradrenaline injected into the AC produced a decrease in water intake in deprived rats (0.40 ± 0.19 ml/1 hour). The injection of isoproterenol into the AC of deprived rats produced no change in water intake in comparison with control (11.65 ± 1.02 and 10.92 ± 0.88 ml/1 hour, respectively). When compared with control values, phentolamine injected prior to noradrenaline blocked the inhibitory effect of noradrenaline on water intake in deprived rats (10.40 ± 1.31 ml/1 hour). Propranolol blocked the effect of isoproterenol in satiated rats (0.85 ± 0.49 ml/1 hour) and also blocked the water intake induced by deprivation (0.53 ± 0.38 ml/1 hour). In satiated and deprived animals the injection of phentolamine before hexamethonium blocked the inhibitory effect of hexamethonium on water intake. In satiated animals, when hexamethonium was injected alone, water intake was 0.39 ± 0.25 ml/1 hour and when hexamethonium was injected with phentolamine, water intake was 1.04 ± 0.3 ml/1 hour. In deprived animals, hexamethonium alone blocked water intake (0.40 ± 0.17 ml/1 hour) and when injected with phentolamine it elicited an intake of 9.7 ± 1.8 ml/1 hour. these results clearly demonstrate the participation of catecholaminergic receptors of the AC in the regulation of water intake.

Hepatic bleeding induced by streptokinase and heparin in a patient with acute myocardial infarction

Although rare, major bleeding is the most important side effect of thrombolytic therapy in acute myocardial infarction (AMI) (Levine et al., 1995). Spontaneous hepatic bleeding in normal liver after thrombolytic administration has rarely been reported in literature. To our knowledge, there are only three cases of hepatic bleeding related to thrombolytic therapy in AMI. In these, the used drugs were anisolylated plasminogen streptokinase activator complex (APSAC) (Garcia-Jiménez et al., 1997; Fox et al., 1991) and rt-PA (Garcia-Jiménez et al., 1997). We report a case of hepatic bleeding after streptokinase followed by units over 60 minutes). The next day, the patient developed third-degree atrioventricular block and a temporary pacemaker was inserted. Twenty-seven hours after streptokinase infusion, the patient complained of refractory chest pain that was interpreted as post-myocardial infarction angina; clotting screen was normal and intravenous heparin was started (80 U/kg followed by 18 U/kg/hour). After four hours of heparin administration, the patient presented abdominal pain and distension, and his blood pressure and hematocrit level dropped. Abdominal ultrasonography revealed free fluid in the peritoneal cavity (about 3,000 mL). A laparotomy disclosed blood in the abdominal cavity with bleeding from the right lateral hepatic segment, which was removed. The remaining abdominal viscera were normal and there was no other evidence of hemorrhage. The partial liver resection presented subcapsular hemorrhage with small parenchymal hemorrhage. Histopathological examination also revealed focal areas of ischemic centrilobular necrosis. The patient died of multiple organ system failure 21 days after admission. Copyright © 2002 By PJD Publications Limited.

Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast tissue

Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at increased risk of the disease in the Breast Cancer Prevention Trial. In order to identify potential candidates to explain the preventive effect induced by tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern blot membranes were generated by the Human Cancer Genome Project funded by the Ludwig Institute for Cancer Research and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil). Total RNA was obtained from normal breast tissue from patients with clinical, cytological and ultrasound diagnosis of fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or placebo, normal breast tissue adjacent to the tumor was collected during lumpectomy with local anesthesia. One differentially expressed gene, Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down-regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein kinase that has been implicated in the diverse effects of hormones utilizing Ca2+ as a second messenger as well as in c-fos activation. These results indicate that the down-regulation of CaMKII induced by TAM might represent alternative or additional mechanisms of the action of this drug on cell cycle control and response to hormones in normal human breast tissue.

Synthesis, characterization, and biological activity of a new palladium(II) complex with deoxyalliin

Synthesis, characterization, and biological activity of a new water-soluble Pd(II)-deoxyalliin (S-allyl-L-cysteine) complex are described in this article. Elemental and thermal analysis for the complex are consistent with the formula [Pd(C6H10NO2S)2]. 13C NMR, 1H NMR, and IR spectroscopy show coordination of the ligand to Pd(II) through S and N atoms in a square planar geometry. Final residue of the thermal treatment was identified as a mixture of PdO and metallic Pd. Antiproliferative assays using aqueous solutions of the complex against HeLa and TM5 tumor cells showed a pronounced activity of the complex even at low concentrations. After incubation for 24 h, the complex induced cytotoxic effect over HeLa cells when used at concentrations higher than 0.40 mmol/L. At lower concentrations, the complex was nontoxic, indicating its action is probably due to cell cycle arrest, rather than cell death. In agreement with these results, the flow cytometric analysis indicated that after incubation for 24 h at low concentrations of the complex cells are arrested in G0/G1. © 2005 NRC Canada.

Acute and short-term insulin-induced molecular adaptations of GLUT2 gene expression in the renal cortex of diabetic rats

Increased GLUT2 gene expression in the renal proximal tubule of diabetic rats is an adaptive condition, which may be important in the diabetic nephropathy development. We investigated the effects of insulin treatment upon the renal GLUT2 overexpression of diabetic rats. Acute treatment, surprisingly, induced a rapid further increase in GLUT2 mRNA content. Twelve hours after insulin injection, GLUT2 mRNA was twice the value of saline-injected rats (P < 0.001), when GLUT2 protein remained unchanged. In response to short-term treatment, both GLUT2 mRNA and protein were increased in 1-day treated rats (P < 0.05 versus saline-injected), decreasing after that, and reaching, within 6 days, values close to those of non-diabetic rats. Concluding, insulin treatment induced: initially, an additional upregulation of GLUT2 gene expression, involving posttranscriptional modulation; thereafter, downregulation of GLUT2 expression, which returns to non-diabetic levels. The former may be related to increased insulin concentration, the latter may be due to glycemic control. © 2005 Elsevier B.V. All rights reserved.

The post-transcriptional gene silencing pathway in Eucalyptus

Post-transcriptional gene silencing (PTGS) is a conserved surveillance mechanism that identifies and cleaves double-stranded RNA molecules and their cellular cognate transcripts. The RNA silencing response is actually used as a powerful technique (named RNA interference) for potent and specific inhibition of gene expression in several organisms. To identify gene products in Eucalyptus sharing similarities with enzymes involved in the PTGS pathway, we queried the expressed sequence tag database of the Brazilian Eucalyptus Genome Sequence Project Consortium (FORESTs) with the amino acid sequences of known PTGS-related proteins. Among twenty-six prospected genes, our search detected fifteen assembled sequences encoding products presenting high level of similarity (E value < 10 -40) to proteins involved in PTGS in plants and other organisms. We conclude that most of the genes known to be involved in the PTGS pathway are represented in the FORESTs database. Copyright by the Brazilian Society of Genetics.

Age related obesity-induced shortening of GLUT4 mRNA poly(A) tail length in rat gastrocnemius skeletal muscle

Obese insulin resistant animals and humans have shown reduced GLUT4 gene expression. Yet, in skeletal muscle, discrepancy between mRNA and protein regulation has been frequently observed, suggesting a post-transcriptional modulation. We investigated the GLUT4 expression in adipose tissue and muscle of obese 12-month-old (12-mo) rats, comparing with lean 2-month-old (2-mo) animals. Obesity was accompanied by insulin resistance, and 65% reduction (P < 0.01) in GLUT4 mRNA and protein in adipose tissue. However, in muscle, despite increased (P < 0.05) mRNA content, GLUT4 protein was unchanged. RNase H and poly(A) test assays showed a reduction (P < 0.01) of ∼80 adenines in the GLUT4 mRNA poly(A) tail of muscle from 12-mo rats, recognizing that the poly(A) tail length correlates with translation efficiency. Concluding, age related obesity of 12-mo rats involves suppression of GLUT4 expression in adipose tissue; however, in muscle, GLUT4 mRNA content increases, but with a shorter poly(A) tail, thus unchanging the protein content. © 2007 Elsevier B.V. All rights reserved.

Anthracycline-induced cardiotoxicity

The anthracyclines constitute a group of drugs widely used for the treatment of a variety of human tumors. However, the development of irreversible cardiotoxicity has limited their use. Anthracycline-induced cardiotoxicity can persist for years with no clinical symptoms. However, its prognosis becomes poor after the development of overt heart failure, possibly even worse than ischemic or idiopathic dilated cardiomyopathies. Due to the successful action of anthracyclines as chemotherapic agents, several strategies have been tried to prevent/ attenuate their side effects. Although anthracycline-induced injury appears to be multifactorial, a common denominator among most of the proposed mechanisms is cellular damage mediated by reactive oxygen species. However, it remains controversial as to whether antioxidants can prevent such side effects given that different mechanisms may be involved in acute versus chronic toxicity. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade on the role of oxidative stress in cardiotoxicity induced by doxorubicin, the most used anthracycline agent. The clinical diagnosis and treatment is also discussed. © 2008 Bentham Science Publishers Ltd.