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Biomedical subjects

S Ruiz

Publications and source records attributed to S Ruiz.

At least 37 records · Page 2Linked to original sources
PubMed2001

Inhibition of protein kinase B (PKB) and PKCzeta mediates keratin K10-induced cell cycle arrest.

The intermediate filament cytoskeleton is composed of keratins in all epithelial cells and imparts mechanical integrity to these cells. However, beyond this shared function, the functional significance of the carefully regulated tissue- and differentiation-specific expression of the large keratin family of cytoskeletal proteins remains unclear. We recently demonstrated that expression of keratin K10 or K16 may regulate the phosphorylation of the retinoblastoma protein (pRb), inhibiting (K10) or stimulating (K16) cell proliferation (J. M. Paramio, M. L. Casanova, C. Segrelles, S. Mittnacht, E. B. Lane, and J. L. Jorcano, Mol. Cell. Biol. 19:3086-3094, 1999). Here we show that keratin K10 function as a negative modulator of cell cycle progression involves changes in the phosphoinositide 3-kinase (PI-3K) signal transduction pathway. Physical interaction of K10 with Akt (protein kinase B [PKB]) and atypical PKCzeta causes sequestration of these kinases within the cytoskeleton and inhibits their intracellular translocation. As a consequence, the expression of K10 impairs the activation of PKB and PKCzeta. We also demonstrate that this inhibition impedes pRb phosphorylation and reduces the expression of cyclins D1 and E. Functional and biochemical data also demonstrate that the interaction between K10 and these kinases involves the non-alpha-helical amino domain of K10 (NTerm). Together, these results suggest new and essential roles for the keratins as modulators of specific signal transduction pathways.

Animals↗
PubMed2000

Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia.

The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21; complete remission, n = 20). Microvessels were scored in at least 3 areas (x500 field, 0.126 mm(2)) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin. Microvessel counts were significantly higher in patients with AML (n = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/x500 field vs 11.2 (10. 0-12.0)/x500 field, respectively (P <.001). On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P <. 001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with >/= 5% residual blasts (P <.001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML. Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML. (Blood. 2000;95:2637-2644)

Acute Disease↗
PubMed2000

Combined effects of okadaic acid and cadmium on lipid peroxidation and DNA bases modifications (m5dC and 8-(OH)-dG) in Caco-2 cells.

Okadaic acid (OA) is a marine toxin, a tumour promoter and an inducer of apoptosis. It mainly inhibits protein-phosphatases, protein synthesis and enhances lipid peroxidation. Cadmium (Cd) is known to be carcinogenic in animals and humans (group 1 according to the International Agency for Research on Cancer (IARC) classification). Cd also induces oxidative stress in living organisms. Since they are sometimes found simultaneously in mussels, we have evaluated in the present investigation, the lipid peroxidation, as malondialdehyde (MDA) production, in the variation of the ratios of 8-(OH)-dG/10(5)dG and m5dC/(dC + m5dC) induced by OA and/or Cd in Caco-2 cells. When cells were treated exclusively by OA (15 ng/ml) or Cd (0.625 and 5 microg/ml) for 24 h, protein synthesis was inhibited (by 42 +/- 5%, 18 +/- 13%, and 90 +/- 4% respectively) while MDA production was 2,235 +/- 129, 1710 +/- 20, and 11,496 +/-1,624 pmol/mg protein respectively. In addition, each toxicant induced modified bases in DNA; increases in oxidised bases and methylated dC. The combination of OA and cadmium was more cytotoxic and caused more DNA base modifications; the ratio m(5)dC/(m(5)dC + dC) was increased from 3 +/- 0.15 to 9 +/- 0.15 and the ratio 8-(OH)-dG/10(5) dG also (from 36 +/- 2 to 76 +/- 6). The combination of OA and Cd also increased the level of MDA (1,6874 +/- 2,189 pmole/mg protein). The present results strongly suggest that DNA damage resulting from the oxidative stress induced by these two toxicants may significantly contribute to increasing their carcinogenicity via epigenetic processes.

5-Methylcytosine↗
PubMed2000

[Prognostic relevance of proliferation marker Ki-67 (MIB 1), PCNA and p53 in combined surgically and radiologically treated cancers of the oropharynx and mouth cavity].

STUDY DESIGN: A matched-pair study on the relationship between proliferation associated markers Ki-67, PCNA, and p53 and treatment failure in carcinomas of the oropharynx and oral cavity. MATERIAL AND METHOD: Fifty-six T1-T3 carcinomas of the oropharynx or oral cavity, treated uniformly with primary surgery and postoperative irradiation, were investigated. Twenty-eight patients had recurrent disease and were matched with 28 patients with nonrecurrent disease regarding stage and location of tumor as well as age and therapy. MIB1 staining was used to determine the Ki-67 labeling index. Immunohistochemical studies determined the p53 status and PCNA labeling index. RESULTS: Where treatment failed, the Ki-67 labeling index was significantly (p = 0.032) higher (mean = 59.1%) than in patients without recurrence (mean = 50.5%). Mean time to relapse was 45 months (n = 25) for carcinomas with a Ki-67 (MIB1) labeling index above the median (53.7%) of the general study population, compared to 61.7 months for those cases (n = 31) below this median (p = 0.029). The PCNA labeling index did not correlate significantly with tumor recurrence, nor with time to relapse. In 46% of all tumors, p53 overexpression was present. No significant correlation could be found between p53 overexpression and tumor recurrence or time to relapse. CONCLUSION: Examination of Ki-67 is thought to provide useful prognostic information concerning squamous cell carcinomas of the oropharynx and oral cavity. Overexpression of p53 or PCNA status is not of prognostic value, which is consistent with earlier results. We conclude that the detection of Ki-67 is an unfavorable prognostic factor for squamous cell carcinoma of the oropharynx and oral cavity, at least if treated with a combination of surgery and postoperative irradiation.

Adult↗
PubMed2000

[Vitreus incarceration after using iris retractors].

PURPOSE/METHODS: Biomicroscopic and ophthalmoscopic evaluation of an aphakic patient treated for a retmal detachment with scleral surgery and iris retractors. To describe a complication of the use of iris retractors in retinal surgery in aphakic patients. RESULTS/CONCLUSIONS: On physical examination, a vitreus incarceration in the paracentesis performed for the iris retractors was observed. Nevertheless retinal application and good visual acuity was achieved. We conclude that the use of flexible iris retractors during scleral surgery in aphakic patients is not exempt from complications.

Aged↗
PubMed1999

Effects of mild protein prenatal malnutrition and subsequent postnatal nutritional rehabilitation on noradrenaline release and neuronal density in the rat occipital cortex.

There is evidence that severe malnutrition started during gestation and continued through lactation affects adversely the morphologic development of the neocortex leading to increased neuronal cell packing density and decreased dendritic branching. Nevertheless, the effect of purely mild protein prenatal malnutrition on neocortical development remains rather unexplored. This study evaluates the effects of mild protein prenatal malnutrition (8% casein diet, calorically compensated by carbohydrates) and subsequent postnatal nutritional rehabilitation (25% casein diet) on: (i) the potassium-induced release of [(3)H]-noradrenaline (NA) in occipital cortex slices obtained from 1- and 22-day-old pups; and (ii) the packing density of neurons in lateral, dorso-lateral and dorsal regions of the occipital cortex of 22-day-old pups by using the optical dissector method. The experiments were performed in rats normally fed during gestation and lactation (G(+)L(+)), malnourished during gestation but rehabilitated during lactation (G(-)L(+)) and malnourished during gestation and lactation (G(-)L(-)). At day 1 of age, no significant differences in body and brain weights were observed between prenatally well-nourished and malnourished pups. Nevertheless, at this early age, pups born from mothers submitted to the 8% casein diet had significantly higher cortical net percent NA release than pups born from mothers receiving the 25% casein diet. At weaning (22 days of age) G(-)L(+) rats had, compared to the G(+)L(+) group, similar body weight, brain weight and [(3)H]-NA release values, but significantly higher neuron density scores in the lateral region of the occipital cortex. In contrast, at 22 days of age, G(-)L(-) rats exhibited, compared to G(+)L(+) animals, significant deficits in body and brain weights as well as significant increases in cortical net percent NA release together with enhanced packing density of neurons in the lateral, dorso-lateral and dorsal regions of the occipital cortex. Moreover, in G(-)L(-) animals was not found the laterodorsal histogenetic gradient of neuronal cell packing density observed in G(+)L(+)rats. Results suggest that mild prenatal malnutrition per se is able to induce deleterious effects on cortical neuronal density, in spite of nutritional rehabilitation during lactation, through a mechanism involving central NA hyperactivity during gestation. Prosecution of malnutrition after birth magnifies both neurochemical and morphometric disorders.

Analysis of Variance↗
PubMed1999

C1qRP is a heavily O-glycosylated cell surface protein involved in the regulation of phagocytic activity.

C1q, mannose-binding lectin (MBL), and pulmonary surfactant protein A (SPA) interact with human monocytes and macrophages, resulting in the enhancement of phagocytosis of suboptimally opsonized targets. mAbs that recognize a cell surface molecule of 126,000 Mr, designated C1qRP, have been shown to inhibit C1q- and MBL-mediated enhancement of phagocytosis. Similar inhibition of the SPA-mediated enhancement of phagocytosis by these mAbs now suggests that C1qRP is a common component of a receptor for these macromolecules. Ligation of human monocytes with immobilized R3, a IgM mAb recognizing C1qRP, also triggers enhanced phagocytic capacity of these cells in the absence of ligand, verifying the direct involvement of this polypeptide in the regulation of phagocytosis. While the cDNA for C1qRP encodes a 631 amino acid membrane protein, Chinese hamster ovary cells transfected with the cDNA of the C1qRP coding region express a surface glycoprotein with the identical 126,000 Mr in SDS-PAGE as the native C1qRP. Use of glycosylation inhibitors, cleavage of the mature C1qRP with specific glycosidases, and in vitro translation of C1qRP cDNA demonstrated that both posttranslational glycosylation and the nature of the amino acid sequence of the protein contribute to the difference between its predicted m.w. and its migration on SDS-PAGE. These results verify that the cDNA cloned codes for the mature C1qRP, that C1qRP contains a relatively high degree of O-linked glycoslyation, and that C1qRP cross-linked directly by monoclonal anti-C1qRP or engaged as a result of cell surface ligation of SPA, as well as C1q and MBL, enhances phagocytosis.

Animals↗
PubMed1999

Digestion of C1q collagen-like domain with MMPs-1,-2,-3, and -9 further defines the sequence involved in the stimulation of neutrophil superoxide production.

C1q, a subunit of the first component (C1) of the classical complement pathway, binds to neutrophils via its collagen-like region (C1q-CLR) stimulating superoxide production. We previously identified a region of C1q-CLR, defined by fragments generated by trypsin and endoLys-C digestion, that was required for triggering this respiratory burst. To further localize that critical site, purified human C1q was digested with pepsin to generate C1q-CLR, and subsequently cleaved with the matrix metalloproteinases, MMP-1, MMP-2, MMP-3, and MMP-9. Digestion of C1q-CLR with any of these MMPs did not alter the circular dichroism spectra, demonstrating that the fragments generated had maintained the secondary structure observed in the native molecule. All fragments retained the ability to trigger superoxide production by neutrophils. Analysis of the amino acid sequences of the purified cleavage products (none of which are identical to the published cleavage site specificities for these enzymes) demonstrated that it is the C-chain, but not the A-chain of C1q, that is critical for stimulating this activity, and thus may be a target for future therapeutic intervention.

Amino Acid Sequence↗
PubMed1999

Maturation, fertilization and complete development of porcine oocytes matured under different systems.

This study was designed 1) to determine the effectiveness of 2 in vitro maturation systems commonly employed to produce nuclear and cytoplasmically mature pig oocytes, 2) to assess the effects of boar, sperm concentration and maturation system on oocyte penetrability and male pronucleus formation and 3) to determine the ability of the in vitro matured oocytes to be fertilized in vivo by artificial insemination (AI) of sows. The differences examined between the 2 maturation systems included the culture medium (Waymouth vs TCM199), hormones, additives, culture conditions (static vs gentle agitation) presence or absence of porcine follicular fluid (PFF) and presence or absence of follicular shells. The results showed that nuclear maturation rate was similar in both systems (83.3 +/- 3.5 vs 86.4 +/- 2.5%), and intracellular content of glutathione was 5.21 +/- 0.73 vs 3.5 +/- 0.39 pmol/oocyte, although no correlation between these parameters was observed. The penetration rate and number of sperm cells per oocyte were dependent on the boar, maturation system and sperm concentration, but the rate of male pronuclear formation seemed to be influenced only by the boar and the maturation system but not by sperm concentration. In vivo fertilization of in vitro matured oocytes showed that both maturation systems could yield viable oocytes since 3 of 4 gilts and 2 of 4 gilts, respectively, became pregnant. Failure to become pregnant was not associated with inadequate oocyte maturation since control gilts, which received their own ovulated oocytes rather than in vitro matured oocytes at transfer, also did not become pregnant. We conclude that polyspermy may be an inherent problem in the IVF but not in the IVM systems.

Animals↗
PubMed1999

Prognostic significance of Ki-67 (MIB1), PCNA and p53 in cancer of the oropharynx and oral cavity.

Up to now results concerning the prognostic value of tumor proliferation markers in squamous cell head and neck carcinoma have been equivocal. Beside biological reasons, different treatment modalities are hypothetically responsible for contradictory findings. The aim of this study was to investigate the relationship between proliferative capacity, represented by the immunohistochemical labeling index of proliferation markers Ki-67, PCNA and p53 status, and treatment failure in a matched-pair study design of recurrent and non-recurrent carcinoma initially treated with primary surgery combined with curative post-operative radiation. From a group of 239 patients with T1-T3 carcinoma of the oropharynx or oral cavity, 28 patients with recurrent disease were selected and matched with 28 patients with non-recurrent disease regarding stage and location of tumor as well as age and therapy. All patients received primary surgery combined with post-operative radiation. Immunohistochemistry determined the p53 status and the PCNA and MIB1 (Ki-67) labeling index. The Ki-67 labeling index was significantly (p=0.032) higher in tumors from patients suffering from treatment failure (mean=59. 1%) than in non-failures (mean=50.5%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (53.7%) of the general study population showed a mean time to relapse of 45 months (n=25), whereas mean time-to-relapse was 61.7 months for those cases (n=31) below the median of the general study population (p=0.029). The PCNA labeling index did not correlate significantly with tumor recurrence (mean=50.2% for treatment failures, 45% for non-failures, p=0.31), nor with time-to-relapse (p=0.26). Forty-six percent of tumors showed p53 over-expression. However, there was no significant correlation between p53 over-expression and tumor recurrence or time-to-relapse. We present the largest series of oropharyngeal and oral cavity carcinoma investigated by immunohistochemistry in a controlled study. We conclude that a high Ki-67 labeling index is an indicator for treatment failure in these patients. Like other investigations for different head and neck subsites, we found no relationship between p53 or PCNA status and tumor prognosis. Our data, obtained from a group of patients treated with a combination of surgery and post-operative irradiation, show that for squamous cell carcinoma of the oropharynx and oral cavity the detection of Ki-67 is an unfavorable prognostic factor.

Adult↗
PubMed1999

Fatal haemorrhagic infarct in an infant with homocystinuria.

Thrombotic and thromboembolic complications are the main causes of morbidity and mortality in patients with homocystinuria. However, it is unusual for thrombosis and infarction to be the presenting feature leading to investigation for homocystinuria and cerebrovascular lesions in the first year of life. We describe a previously healthy 6-month-old infant who presented with a large middle-cerebral-artery territory infarction and died of massive brain swelling. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency was diagnosed by metabolite analysis and confirmed by enzymatic activity measurement in a postmortem liver biopsy. Homocystinuria should be considered in the differential diagnosis of venous or arterial thrombosis, regardless of age, even in the absence of other common features of the disease. We recommend systematic metabolic screening for hyperhomocysteinemia in any child presenting with vascular lesions or premature thromboembolism.

Brain Edema↗
PubMed1999

Radioprotection of DNA by spermine: a molecular modelling approach.

PURPOSE: To observe and explain the sequence-dependence of DNA radioprotection by spermine. MATERIALS AND METHODS: Sequencing gel electrophoresis was used to analyse the probability of frank strand break (FSB) induction at each nucleotide site. Molecular modelling of complexes of DNA with spermine molecules and of a curved electrically null DNA has been performed. RESULTS: The effect of spermine on radiation-induced strand breakage varied significantly along the studied fragment. At low spermine concentration, some sequences were protected while others were unprotected. Molecular modelling calculations show that the most electro-negative sites are located in the minor or in the major groove of DNA. The positively charged spermine (Z=+4) should preferentially bind to such sites. When bound in the minor groove, spermine triggers a reduction of the accessibility of radiolytic attack sites to OH* radicals. This is due to induced structural modifications and to the masking of attack sites. In the case of major groove binding, no reduction of accessibility occurs. This type of binding can explain the lack of protection of sequences with electro-negative sites in the major groove. At high spermine concentration, the fragment is strongly protected. A nucleosome-like pattern of breakage with periodically distributed regions of protection was observed. Molecular modelling calculations show that the accessibility of the attack sites in a curved electrically null DNA is also periodically reduced. CONCLUSIONS: Molecular modelling of DNA-spermine complexes that takes into account the electrostatic properties of DNA, allows an explanation of the experimentally observed effects of spermine on DNA radiosensitivity.

Base Sequence↗
PubMed1999

[Acute effects of the breathing of industrial waste and of sulfur dioxide on the respiratory health of children living in the industrial area of Puchuncaví, Chile].

This study investigated the acute effect of air pollution on the respiratory health of children living in the industrial area of Puchuncaví, in Region V of Chile. The 114 children studied were from 6 to 12 years old; 57 of them had chronic respiratory symptoms and 57 did not. Each day for 66 days the air was checked for levels of sulfur dioxide (SO2) and of breathable particles that were < 10 microns (PM10). The children were selected and classified according to their susceptibility to chronic respiratory disease by means of a questionnaire used with 882 children living within the area of the emissions from a copper foundry and a thermoelectric plant. Each day, each studied child's peak expiratory flow (PEF) and incidence of respiratory symptoms were checked and recorded. Using regression models (generalized estimation equations), estimates were made of the association of SO2 and PM10 levels with PEF and the incidence of cough, expectoration, episodes of wheezing, dyspnea, and use of bronchodilators. Among the children who were initially symptomatic, an increase of 50 micrograms/m3 in the daily mean level of SO2 caused a reduction of -1.42 L/min (95% confidence interval (95% CI): -2.84 to -0.71) in the PEF of the following day. An increase of 30 micrograms/m3 in the cumulative concentration of PM10 over three days produced a PEF reduction of -2.84 L/min (95% CI: -4.26 to 0.00). With respect to symptoms, an increase of 30 micrograms/m3 in the weekly mean level of PM10 was related with a 26% increase (odds ratio (OR) = 1.26; 95% CI: 1.01 to 1.57) in the incidence of cough and of 23% (OR = 1.23; 95% CI: 1.00 to 1.50) in the incidence of expectoration. An increase of 50 micrograms/m3 in the mean level of SO2 for three days was associated with a 5% increase (OR = 1.05; 95% CI: 1.00 to 1.10) in the incidence of expectoration. An increase of 30 micrograms/m3 in the daily average of PM10 increased the use of bronchodilators two days later by 10% (OR = 1.10; 95% CI: 1.03 to 1.18). Among the initially asymptomatic children, a significant effect from PM10 exposure was found after an increase of 30 micrograms/m3 in the mean daily PM10 level, with a reduction of -1.34 L/min (95% CI: -2.68 to -0.67) in the PEF of the following day. A similar increase in the cumulative exposure over three days was associated with an increase of 9% in the incidence of episodes of wheezing (OR = 1.09; 95% CI: 1.01 to 1.31). It is concluded that high levels of PM10 and SO2 affect the respiratory health of children living in the industrial area of Puchuncaví.

Allergens↗
PubMed1999

Prevalence of asthma and other childhood allergies in Brazilian schoolchildren.

We determined the prevalence of asthma, rhinitis, and eczema among Brazilian children using the standardized protocol of the International Study on Asthma and Allergies in Childhood (ISAAC) to facilitate the comparison of our results with other studies using the ISAAC methodology. We conducted a cross-sectional study from June to October 1994 to determine the prevalence of asthma, rhinitis, and eczema in 5182 school children aged 7-8 years and 13-14 years residing in the Brazilian towns of Santa Maria and Itabira (iron-mining cities located in Minas Gerais). Parents completed questionnaires at their child's school in the presence of trained interviewers. The cumulative prevalence of doctor-diagnosed asthma was 4.6% for all ages with no significant difference between the age groups. In general, there was a higher prevalence of symptoms in the younger age group than the older. The prevalence of wheezing in the previous 12 months was 14.3% (7-8 years old) and 9.3% (13-14 years old) (p < 0.01), of chronic cough in the previous 12 months was 25.6% (7-8 years old) and 22.1% (13-14 years old) (p < 0.01), and of nighttime cough in the previous 12 months was 22.3% (7-8 years old) and 19.4% (13-14 years old) (p < 0.05). Overall the prevalences of asthma and wheezing symptoms in the previous 12 months were higher for boys than girls (5.2% vs. 3.9% for asthma, p < 0.01, and 13.2% vs. 10.6% for wheezing, p < 0.01, respectively). These results suggest that asthma-related respiratory illnesses affect a substantial part of the childhood population in Itabira and Santa Maria, Minas Gerais. Some factors such as male gender and younger age may be associated with an increase risk for chronic respiratory symptoms. Prevalences of asthma and allergic diseases in these Brazilian cities on the basis of self-reporting of symptoms and of one's medical history may more accurately portray the true prevalence of asthma than the use of medical records.

Adolescent↗
PubMed1999

[Metalloproteinase activity in myocardium of rats exposed to endotoxin and its inhibition with doxycycline].

BACKGROUND: The ventricular dysfunction of endotoxic shock could be secondary to the activity of myocardial metalloproteinases that degrade collagenous matrix. Metalloproteinase activity can be inhibited with doxycycline in some tissues. AIM: To study if the effect of endotoxemia on myocardial metalloproteinase activity can be inhibited with doxycycline. MATERIAL AND METHODS: Left ventricular metalloproteinase activity was studied in four groups of rats. Group 1 received intraperitoneal dextrose in water, group 2 received 8 mg/kg intraperitoneal E coli endotoxin, group 3 received 60 mg/kg/day doxycycline for three days and group 4 received doxycycline and E coli endotoxin. Enzymatic activity was measured by Western Blot and zymography. RESULTS: Zymography showed a higher metalloproteinase 2 (49%) and 9 (100%) activity in rats treated with endotoxin, when compared with control rats. In group 4, doxycycline reduced the activity of metalloproteinases 2 and 9 by 71% and 63% respectively, as compared with group 3. Western blot showed a 50% increase in the expression of metalloproteinase 1 in rats treated with endotoxin, that was reduced by 64% with the use of doxycycline. CONCLUSIONS: Endotoxin administration increases myocardial metalloproteinases and doxycyclin inhibits this activation. Therefore, doxycyclin could reduce the degradation of myocardial fibrillar collagen and ventricular dysfunction of endotoxic shock.

Animals↗
PubMed1998

Locus coeruleus-mediated inhibition of chemosensory responses in the rat nucleus tractus solitarius is mediated by alpha2-adrenoreceptors.

It is known that electrical and L-glutamate stimulation of the locus coeruleus (LC) reduce the multiunit activity evoked in the nucleus of the tractus solitarius (NTS) by cyanoboro-hydride. In the present study, rats anaesthetised with urethane were microinjected with noradrenergic antagonists into the NTS, to test whether the inhibitory effects of LC stimulation on cyanide-evoked discharge in the NTS were mediated by noradrenaline. Microinjection of yohimbine into the NTS (0.2, 0.6, 1.8, 5.4 nmol) induced dose-dependent reduction of the inhibitory effect of LC stimulation on NTS neurones, while prazosin produced no effect. The results indicate that LC-induced inhibition of the cyanide-evoked discharge in the NTS is mediated by endogenous noradrenaline release acting on alpha2-adrenoreceptors.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1998

Prenatal protein restriction alters synaptic mechanisms of callosal connections in the rat visual cortex.

Mild prenatal protein malnutrition, induced by reduction of the casein content of the maternal diet from 25 to 8%, calorically compensated by the addition of excess carbohydrates, leads to so-called "hidden" malnutrition in the rat. This form of malnutrition results in normal body and brain weights of pups at birth, but in significant alterations of their central nervous system neurochemical profiles. Since severe forms of prenatal malnutrition induce morpho-functional deficits on callosal interhemispheric communication together with brain neurochemical disturbances, we evaluated, in rats born from mothers submitted to an 8% casein diet, the potassium-induced release of [3H]-noradrenaline in visual cortex slices, as well as functional properties of callosal-cortical synapses by determining cerebral cortical excitability to callosal inputs and fatigability and temporal summation of transcallosal evoked responses. Rats born from mothers submitted to a 25% casein diet served as controls. At birth prenatally malnourished pups had significantly higher cortical percent net noradrenaline release (14.79 +/- 1.11) than controls (9.14 +/- 1.26). At 45-50 days of age, rehabilitated previously malnourished rats showed, when compared to controls; (i) significantly reduced percent net noradrenaline release in the visual cortex (4.50 +/- 0.52 vs 11.31 +/- 1.14); (ii) decreased cortical excitability to callosal inputs as revealed by significantly increased chronaxie (607.2 +/- 82.8 microseconds vs 351.3 +/- 47.7 microseconds); (iii) enhanced fatigability of transcallosal evoked responses as revealed by significantly decreased stimulus frequency required to fatigate the responses (4.9 +/- 0.8 Hz vs 9.2 +/- 1.3 Hz); and (iv) decreased ability of callosal-cortical synapses to perform temporal summation, as revealed by significantly reduced percent response increment to double-shock (54.2 +/- 6.2 vs 83.0 +/- 11.0, for a 3.2-ms interstimulus time interval). These changes, resulting from mild prenatal protein restriction, are discussed in relationship to developmental processes leading to the formation of synaptic contacts between callosal axons and their appropriate cortical target during perinatal age.

Animals↗