Combined surgery and embolization to treat ruptured cerebral aneurysms with cerebral hematoma and intracranial hypertension: a retrospective analysis and review of the literature. / Tratamiento combinado, mediante embolización y cirugía, de los aneurismas cerebrales rotos con hematoma cerebral e hipertensión intracraneal: Análisis retrospectivo y revisión de la bibliografía.

OBJECTIVE: To determine whether the urgent embolization of a cerebral aneurysms and posterior surgery on cerebral hematomas is safe and efficacious in patients with hematomas and signs of intracranial hypertension due to the rupture of cerebral aneurysms. METHODS: We included 23 consecutive patients in poor clinical condition due to an intracranial hematoma caused by a ruptured cerebral aneurysm who were treated with both embolization and surgery within 4hours of the onset of symptoms. All patients had clinical signs of intracranial hypertension and / or altered levels of consciousness, including coma due to rostrocaudal deterioration. We evaluated the efficacy of the combined technique by determining the degree of closure of the aneurysms and the patients' prognosis one month after the procedures; we evaluated safety by analyzing the complications of the treatments. RESULTS: All but two of the patients (21/23; 91.3%) had an aneurysm of the middle cerebral artery. All patients scored 4 on the Fisher scale and were classified as Hunt and Hess IV or V. The mean time from the identification of the aneurysm on computed tomography to embolization was 115minutes. A balloon remodeling technique was used in 18 (78%) patients; embolization achieved adequate closure in 19 (82.6%) patients. During surgery, a ventricular drain was placed in 9 (39.1%) patients. One month after treatment, 13 (56.5%) patients were functionally independent and 3 (13%) had died. No episodes of rebleeding were observed. CONCLUSION: In our experience, combined treatment including embolization of the aneurysm and surgical decompression with evacuation of the hematoma is a safe and effective alternative to surgical treatment alone.

Amino acid profiles of young adults differ by sex, body mass index and insulin resistance.

BACKGROUND AND AIMS: An increase in plasma branched-chain amino acids is associated with a higher risk of developing type 2 diabetes and cardiovascular diseases. However, little is known about the basal plasma amino acid concentrations in young adults. Our aim was to determine the plasma amino acid profiles of young adults and to evaluate how these profiles were modified by sex, body mass index (BMI) and insulin resistance (IR). METHODS AND RESULTS: We performed a transversal study with 608 Mexican young adults aged 19.9 ± 2.4 years who were applicants to the Universidad Autónoma de San Luis Potosí. The subjects underwent a physical examination and provided a clinical history and a blood sample for biochemical, hormonal and amino acid analyses. The women had higher levels of arginine, aspartate and serine and lower levels of α-aminoadipic acid, cysteine, isoleucine, leucine, methionine, proline, tryptophan, tyrosine, urea and valine than the men. The obese subjects had higher levels of alanine, aspartate, cysteine, ornithine, phenylalanine, proline and tyrosine and lower levels of glycine, ornithine and serine than the normal weight subjects. Subjects with IR (defined as HOMA > 2.5) had higher levels of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine than the subjects without IR. Furthermore, we identified two main groups in the subjects with obesity and/or IR; one group was composed of amino acids that positively correlated with the clinical, biochemical and hormonal parameters, whereas the second group exhibited negative correlations. CONCLUSION: This study demonstrates that young adults with obesity or IR have altered amino acid profiles characterized by an increase in alanine, aspartate, proline and tyrosine and a decrease in glycine.

Histopathologic, immunohistochemical and ultrastructural features of a granular cell tumour in an Australian parakeet (Melopsittacus undulatus).

An adult male Australian parakeet (Melopsittacus undulatus) presented a firm nodular lesion in the lateral metacarpal region of the right wing. Microscopically, there were neoplastic cells, round and polyhedral in shape, with abundant, slightly eosinophilic granular cytoplasm; they were strongly periodic-acid Schiff-positive and resistant to diastase digestion. Some groups of neoplastic cells were immunopositive for smooth muscle actin and desmin. There was no immunopositivity for S-100 protein, CD68 and cytokeratin. Ultrastructurally, the neoplastic cells were round and polygonal in shape, and they were characterized by abundant cytoplasm with numerous homogeneous osmophilic bodies covered by an electron-dense membrane (lysosomes). The histopathologic, immunohistochemical and ultrastructural features of the neoplastic tissue are consistent with a granular cell tumour, which has been described in different animal species and anatomic locations; however, this seems to be an infrequent neoplasm in Australian parakeets. The immunopositivity of the neoplastic cells for smooth muscle actin and desmin, as well as slight positivity for muscle with Masson's trichrome, suggest that this is a tumour of myogenic origin.

ATM-dependent IGF-1 induction regulates secretory clusterin expression after DNA damage and in genetic instability.

Secretory clusterin (sCLU) is a stress-induced, pro-survival glycoprotein elevated in early-stage cancers, in particular in APC/Min-defective colon cancers. sCLU is upregulated after exposure to various cytotoxic agents, including ionizing radiation (IR), leading to a survival advantage. We found that stimulation of insulin-like growth factor-1 (IGF-1) and IGF-1R protein kinase signaling was required for sCLU induction after IR exposure. Here, we show that activation of Ataxia telangiectasia-mutated kinase (ATM) by endogenous or exogenous forms of DNA damage was required to relieve basal repression of IGF-1 transcription by the p53/NF-YA complex, leading to sCLU expression. Although p53 levels were stabilized and elevated after DNA damage, dissociation of NF-YA, and thereby p53, from the IGF-1 promoter resulted in IGF-1 induction, indicating that NF-YA was rate limiting. Cells with elevated endogenous DNA damage (deficient in H2AX, MDC1, NBS1, mTR or hMLH1) or cells exposed to DNA-damaging agents had elevated IGF-1 expression, resulting in activation of IGF-1R signaling and sCLU induction. In contrast, ATM-deficient cells were unable to induce sCLU after DNA damage. Our results integrate DNA damage resulting from genetic instability, IR, or chemotherapeutic agents, to ATM activation and abrogation of p53/NF-YA-mediated IGF-1 transcriptional repression, that induces IGF-1-sCLU expression. Elucidation of this pathway should uncover new mechanisms for cancer progression and reveal new targets for drug development to overcome resistance to therapy.

HDAC inhibitors with different gene regulation activities depend on the mitochondrial pathway for the sensitization of leukemic T cells to TRAIL-induced apoptosis.

Epigenetic modifications commonly associated with tumor development, such as histone deacetylation, may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating gene transcription of components of the TRAIL signalling pathway. In the present study we have analyzed the effect of six different histone deacetylase inhibitors (HDACi), belonging to the four classic structural families, on TRAIL-induced apoptosis in leukemic T cell lines. Non-toxic and functional doses of all HDACi but apicidin, similarly sensitized different leukemic T cell lines to TRAIL-induced apoptosis, while they showed no effect on the resistance of normal T lymphocytes. Sensitizing doses of vorinostat, valproic acid, sodium butyrate and MS-275 regulated the expression of TRAIL-R2, c-FLIP and Apaf-1 in leukemic cells while TSA modulated only the expression of Apaf-1. The synergistic effect of all HDACi and TRAIL was inhibited in Bcl-2-overexpressing leukemic T cells. Thus, different HDACi may affect the expression of different TRAIL-related genes, but regulation of the mitochondrial pathway seems to be essential for the TRAIL sensitizing effect of HDACi in leukemic T cells. Overall, HDACi represent a promising and safe strategy in combination with TRAIL for treatment of T-cell leukaemia.

Effect of lipophilization of hydroxytyrosol on its antioxidant activity in fish oils and fish oil-in-water emulsions.

The effect of lipophilization of the antioxidant efficiency of hydroxytyrosol on fish oil enriched systems was studied. Hydroxytyrosol fatty acid esters with increasing size of the alkyl chain and different lipophilicity were tested in bulk fish oils and fish oil-in-water emulsions. Results showed a significant antioxidant activity of hydroxytyrosol esters in both systems especially in emulsions. The introduction of a lipophilic chain decreased the antioxidant effectiveness of hydroxytyrosol in homogeneous systems as fish oils. In emulsion systems, the presence of a short-medium lipophilic chain (acetate, butyrate or octanoate) improved the antioxidant efficiency of hydroxytyrosol favoring the physical location of the antioxidant in the interface, but longer alkyl chain (laurate) maintained or even decreased their antioxidant activity. A maximum of antioxidant efficiency seems to appear when the chain length of the hydroxytyrosol derivative is that of eight carbons which is probably associated with a preferential location of the diorthophenolic moiety in the right geometry. These results are of high importance for the optimum design of effective antioxidants for omega 3 enriched foods, which are very susceptible to suffer oxidation and, then, rancidity.

Human decidual stromal cells protect lymphocytes from apoptosis.

Human decidual stromal cells (DSC) have been shown to be involved in different immune functions that may be relevant for the relationship between the mother and fetus and hence for successful pregnancy. The expression of death ligands by fetal trophoblast and maternal decidual cells has been proposed as a mechanism for the establishment of materno-fetal immunotolerance. This study intended to elucidate the interrelations between DSC and lymphocytes. We analyzed the expression and function of death receptors and ligands in DSC maintained in culture. These DSC lines expressed CD95 and TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2), although they were resistant to death receptor-mediated apoptosis. Regarding the expression of CD95L and TRAIL, it was variable among DSC lines although none of them induced apoptosis in death ligand-sensitive Jurkat T cells. Interestingly, most of the DSC lines, as well as fresh DSC, reduced apoptosis in Jurkat cells induced by anti-CD95 antibody and recombinant TRAIL. The protective effect of DSC was observed when they were co-cultured with Jurkat cells in Transwell plates, indicating that DSC may produce soluble factors of importance for lymphocyte survival. Moreover, the viability of peripheral blood lymphocytes and decidual lymphocytes was improved when co-cultured with DSC. Our results suggest that DSC, far from inducing apoptosis, may be relevant in the regulation of lymphocyte survival at the materno-fetal interface.

The effect of diabetes and centrally administered insulin on anterior hypothalamic estrogen receptor alpha immunoreactivity.

Diabetic rats have characteristic reproductive deficits. Peripheral and central (intra-cerebro-ventricular [ICV]) insulin restores the reproductive phenotype to control levels. In this experiment, we evaluated a possible defect in steroid feedback by evaluating hypothalamic estrogen receptor (ER) alpha availability using ERalpha immunocytochemistry. Animals were ovariectomised and given estradiol and progesterone. Diabetic and control animals were given ICV insulin or saline. Nuclear and/or cytoplasmic ERalpha immunoreactivity was evaluated in the paraventricular nucleus (PVN) and the organum vasculosum laminae terminalis (OVLT). In the PVN, nuclear immunoreactivity was increased among diabetic, ICV insulin-treated animals. Diabetic saline-treated and nondiabetic animals had similar ERalpha immunoreactivity. The OVLT had lower numbers of immunoreactive neurons compared to the PVN; no differences among the treatment groups were found in the OVLT. Central insulin treatment increased the number of PVN nuclear ERalpha immunoreactive neurons among diabetic animals. However, there was no reduction in ERalpha when comparing saline-treated diabetic animals to non-diabetic rats, suggesting that decreases in hypothalamic ERalpha in the regions studied do not account for diabetes-induced reproductive deficits.

Properties of triple helices formed by oligonucleotides containing 8-aminopurines.

The synthesis of parallel hairpins carrying 8-aminopurines is described. These hairpins have a high affinity for specific polypyrimidine sequences resulting in the formation of very stable triplexes.

Parallel-stranded hairpins containing 8-aminopurines. Novel efficient probes for triple-helix formation.

We describe novel oligomers with a greater propensity to form triplexes than oligomers containing only natural bases. They consist of a polypyrimidine sequence linked head-to-head with a polypurine sequence carrying one or several 8-aminoadenine or 8-aminoguanines. The presence of 8-aminopurines also stabilised the parallel-stranded duplex structure.

Negative cell cycle regulation and DNA damage-inducible phosphorylation of the BRCT protein 53BP1.

In a screen designed to discover suppressors of mitotic catastrophe, we identified the Xenopus ortholog of 53BP1 (X53BP1), a BRCT protein previously identified in humans through its ability to bind the p53 tumor suppressor. X53BP1 transcripts are highly expressed in ovaries, and the protein interacts with Xp53 throughout the cell cycle in embryonic extracts. However, no interaction between X53BP1 and Xp53 can be detected in somatic cells, suggesting that the association between the two proteins may be developmentally regulated. X53BP1 is modified via phosphorylation in a DNA damage-dependent manner that correlates with the dispersal of X53BP1 into multiple foci throughout the nucleus in somatic cells. Thus, X53BP1 can be classified as a novel participant in the DNA damage response pathway. We demonstrate that X53BP1 and its human ortholog can serve as good substrates in vitro as well as in vivo for the ATM kinase. Collectively, our results reveal that 53BP1 plays an important role in the checkpoint response to DNA damage, possibly in collaboration with ATM.

Cyclic GMP may potentiate lordosis behaviour by progesterone receptor activation.

The purpose of this study was to test the hypothesis that cGMP acts as a progesterone substitute to facilitate lordosis in oestrogen-primed rats. Female Sprague-Dawley rats underwent stereotaxic surgery to place a 26-gauge guide cannula into the third ventricle. Bilateral ovariectomy was done at the same time as stereotaxic surgery. Five days later ovariectomized rats were primed with 2 microg estradiol benzoate 24 and 48 h prior to behaviour testing. Some animals were further injected with 200 microg progesterone 4 h before behaviour testing. A nitric oxide synthase inhibitor infused into the third ventricle before progesterone administration significantly reduced lordosis performance. 8-Bromo-cGMP, a cell permeable cGMP analogue, or saline vehicle was infused into the third ventricle of hormone-primed animals approximately 4 h prior to the first of 3-h behaviour tests. This cGMP analogue facilitated lordosis behaviour. We next used KT5823, a highly specific inhibitor of protein kinase G (PKG), to test the hypothesis that cGMP action is mediated by this kinase. In this experiment, KT5823 was infused 15 min before progesterone. KT5823 significantly decreased lordosis behaviour. RU486, a progesterone receptor antagonist, was used to assess whether the stimulatory effects of cGMP are mediated through the progesterone receptor. Oestrogen-primed animals were injected with 5 mg of RU486 or vehicle 60 min before infusion with 8-bromo-cGMP. RU486 significantly attenuated cGMP-facilitated lordosis behaviour. These data show that cGMP facilitates lordosis through activation of PKG and the progesterone receptor.

Efficient replication between non-hydrogen-bonded nucleoside shape analogs.

DNA polymerase enzymes make an error only once per 10(4)-10(5) initial nucleotide insertions during DNA replication. Most currently held models of this high fidelity cite the hydrogen bonds between complementary pyrimidines and purines as a critical controlling factor. Testing this has been difficult, however, since standard molecular strategies for blocking or removing polar hydrogen-bonding groups cause changes to size and shape as well as hydrogen bonding ability. One answer to this problem is the use of nonpolar molecules that mimic the shape of natural DNA bases. Here we show that a non-hydrogen-bonding shape mimic for adenine is replicated efficiently and selectively against a nonpolar shape mimic for thymine. The results establish that hydrogen bonds in a base pair are not absolutely required for efficient nucleotide insertion. This adds support to the idea that shape complementarity may play as important a role in replication as base-base hydrogen bonds.

Effects of diabetes and estradiol on norepinephrine release in female rat hypothalamus, preoptic area and cortex.

These studies determined whether diabetes and estradiol treatment altered norepinephrine (NE) release from hypothalamus, preoptic area (POA), and cortical slices from ovariectomized (OVX) female rats. Animals were sacrificed 12 days after the onset of streptozotocin-induced diabetes and 48 h following vehicle or estradiol injection. Brain slices were preloaded with 3H-NE, and release was evoked twice (S and S2) by electrical stimulation. Diabetes increased hypothalamic NE release during S1 regardless of the administration of vehicle or estradiol. Neither estradiol treatment nor diabetes alone affected NE release during S2 in the hypothalamus or POA. Estradiol treatment elevated NE release in the POA during S2 but only in diabetic animals. Moreover, estradiol elevated cortical NE release during S2 regardless of the presence or absence of disease. We also examined whether alpha2-adrenoceptor regulation of NE release was influenced by diabetes or hormone treatment. Enhancement of NE release by alpha2-adrenoceptor antagonism was evident in all 3 brain regions. However, alpha2-adrenoceptor regulation of NE release was unaffected by diabetes and hormone treatment. These findings suggest that diabetes alters NE release in the hypothalamus/POA of female rats. Additionally, this work identifies a novel action of estradiol to enhance stimulated NE release in the cortex of female rats.

Fulminant amebic colitis: analysis of 55 cases.

UNLABELLED: Fulminant amebic colitis is a rare disease with high morbidity and mortality. PURPOSE: This study was designed to identify the most frequent clinical and histopathologic features of fulminant amebic colitis and to analyze results of surgical treatment and the existence of risk factors for mortality. MATERIALS AND METHODS: A retrospective analysis was conducted of clinical and histopathologic data of 55 patients with fulminant amebic colitis. Data were obtained from the files of autopsies and surgical operations that had been performed at a referral center in Mexico from 1943 through 1994. RESULTS: Median age was 52 (range, 18-79) years. There were 34 men (62 percent) and 21 women (38 percent). Diabetes mellitus and chronic alcoholism were the most frequent diseases in association with fulminant amebic colitis (40 and 31 percent, respectively). The most frequent clinical manifestations were abdominal pain, diarrhea, rectal bleeding, and fever. There was a coexistent amebic liver abscess in 54 percent of patients. The main histopathologic characteristics were necrosis, presence of trophozoites, and acute and/or chronic inflammation. Of 25 patients who underwent surgery, only six survived (operative mortality, 76 percent; overall mortality, 89 percent). The variables that correlated with mortality were longer duration of symptoms, lower count of leukocytes, nonsurgical treatment, nonresective surgical procedure, hospital admission before 1971, and invasion of trophozoites into or through the muscularis. CONCLUSIONS: The results may help to obtain an earlier diagnosis and establish proper treatment of fulminant amebic colitis.

Nifedipina en pre-eclampsia severa / Nifedipine in severe preeclampsia

Se estudiaron 12 pacientes con pre-eclampsia severa (PES) a las cuales se les administró nifedipina por vía sublingual para el manejo de la tensión arterial. Los valores tensionales pre y post-tratamiento fueron: T. A. Sistólica 178,5 ñ 12.1 / 147,3 ñ 15,2 mm Hg, T. A. Diastólica 115,8 ñ 8,4 / 96,1 ñ 9,4 mm Hg, T. A. Media 136,6 ñ 6,5 /113,2 ñ 9,9 mm Hg. Estas diferencias resultaron estadísticamente significativas. Ningún caso desarrolló eclampsia. El control tensional alcanzado permitió adecuar la duración del embarazo a la madurez fetal. No hubo efectos colaterales materno-fetales ni en los recién nacidos. Nuestros datos sugieren que la nifedipina es efectiva y segura para el manejo de la hipertensión arterial en la PES. Sin embargo es necesaria una mayor experiencia para asegurar la inocuidad de la droga durante la gestación