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PubMed1985

Histological, ultrastructural and mitochondrial oxidative phosphorylation studies in liver of rats chronically treated with oral valproic acid.

The effects of oral administration of valproic acid (VPA) have been studied on the liver of female adult Wistar rats, at doses of 60 and 120 mg/kg/day during 4 and 18 weeks (periods I and II). Other groups received the same doses of VPA with phenobarbital (PB). The animals developed periportal steatosis, more intense at the end of period II and in groups non-induced by PB, and also some degree of mitochondrial swelling. An uncoupling of the oxidative phosphorylation was also evident with both doses in the non-induced groups, and only with the high dose of VPA in the induced group. An in vitro study on isolated liver mitochondria showed uncoupling only with very high concentration of VPA (10 mM). We comment on these findings and propose a chronic model of experimental hepatotoxicity of oral VPA in the rat.

Administration, Oral↗
PubMed2002

Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer.

Natural killer (NK) cells have been implied in the resistance against certain tumors and virally-infected cells. The prognostic significance of tumor infiltrating NK cells in primary squamous cell lung carcinoma (SqCLC) has not been fully studied. Fifty patients with primary SqCLC were evaluated for the presence of tumor infiltrating natural killer cells subset CD57 (TINK) after surgery. None of them received adjuvant therapy. Immunohistochemical studies of surgery pieces were performed by using the monoclonal antibody CD57. The number of TINK cells was counted by using a MICRON image analyzer. The total area studied for each tumor was of 1 cm(2). In this area, 50 intratumoral fields of 0.173 mm(2) were selected. The reference value used was the median (five TINK cells/field) of all tumors analyzed. After a minimum follow-up of 2 years the Kaplan-Meier method was used to obtain survival curves. Multivariate analysis were performed by using the Cox regression model. The survival was significantly better in patients with more than five TINK cells/field (Logrank P=0.0317). According to TNM classification, in those patients screened as stage IB (37 patients) the differences in survival were significantly higher (Logrank P=0.0016). In the multivariate analysis including TNM (surgical-pathologic stage), age, and endoscopy localization, the risk of death in patients with less than five TINK cells/field was 2.50 fold higher (CI 95%; range 1.07-5.85) than in those patients with more than five TINK cells/field. These results show that TINK cells appear to be a prognostic factor in the survival of patients with SqCLC. The possible antitumoral role of these cells in SqCLC is discussed.

Aged↗
PubMed2002

[Effects of oxytetracycline on rat liver].

OBJECTIVES: This experimental project was designed to evaluate: a) the capacity of oxytetracycline to induce microvesicle steatosis in rat liver when administered over long time periods; b) whether female rats are more susceptible to this substance, and c) the possible ultrastructural alterations and their relation to the mechanisms of steatosis. METHODS: Sixty-two Wistar rats (31 males and 31 females) were distributed into six groups, two control groups and four experimental groups. The experiment lasted three months. Blood and hepatic tissue samples were extracted under anesthesia for morphologic study (optical and electron microscopy). RESULTS: Steatosis was of the microvesicular type with mainly periportal distribution. Steatosis developed in the treated groups and the degree was significantly greater in the females (p = 0.004). No relationship was found with dose. Ultrastructural study revealed microsome dilation in all experimental groups, with no differences according to sex. Despite the steatosis, no proliferation of peroxisomes or mitochondrial alterations were observed. CONCLUSIONS: Oxytetracycline produced predominantly periportal microvesicular hepatic steatosis, appearing mostly in the females. As a possible mechanism for tetracycline-induced steatosis, we postulate a decrease in mitochondrial, peroxisome and microsome function as a result of protein synthesis inhibition in these cell compartments.

Animals↗
PubMed2001

[Accuracy and precision in blood pressure measurement. Comparative study of home self-measurement with measurement in the clinic and out-patient monitoring].

OBJECTIVE: To compare accuracy and precision of self-measurement blood pressure (SMBP) at home, as a diagnosis method of hypertension, with mercury measurement in office and ambulatory blood pressure monitoring (ABPM). DESIGN: A comparison study of diagnosis methods.Setting.Hypertension Unit in the Hospital General de Albacete. PATIENTS: By means of a non-probabilistic sample, selected from consecutive cases that went to the unit, a 64 pharmacologically untreated hypertensive sample older than 18 has been selected. METHODS: All subjects were taken 3 measurements with mercury from a validated nurse in office, and were also taught to make 20 self-measurements of blood pressure in the morning at the office and 20 self-measurements in the evening at home with an automatic device Omron 705-CP, during the same day they were set a Takeda TM-2420 device programmed to measure their blood pressure for 24 hours. All proceedings were repeated 4 weeks later. Mean blood pressure values have been compared with every diagnosis method and sensitivity, specificity, positive and negative predictive value have been studied in every method reproducibility in every method has been analyzed. RESULTS: Subjects were 29 men and 35 women with a mean of 53 years old. The mean values of office blood pressure (OBP) have been higher than SMBP and ABPM in the two periods of the study. SMBP has had a higher specificity and predictive value than OBP. Reproducibility of repeated SMBP in standardized conditions is similar to ABPM. CONCLUSIONS: With a minimum program self-measurements at home, in standardized conditions, they can be considered as an accurate technique in the diagnosis of hypertension.

Adult↗
PubMed2006

[Different uses of home blood pressure measurement in the diagnosis and monitoring of hypertension].

OBJECTIVE: To find differences between measurements of clinical blood pressure and self-monitored home blood pressure measurement (HBPM). DESIGN: Descriptive study developed in a general population census. SETTING: Primary care. SUBJECTS: A total of 1411 subjects > or =18 years old were selected by stratified randomized sampling. METHODS: A skilled nurse made 3 clinical blood pressure (CBP) measurements, and trained patients or their relatives in HBPM, doing 12 in one day. CBP and HBPM employed an electronic device (OMRON 705CP). RESULTS: A total of 12 HBPM from 1184 subjects (52% women) were completed, with a mean age of 47.6 (SD, 17.2); 195 subjects were known to have hypertension. White-coat effect was diagnosed in 14.9% of subjects with normal pressure, 22.3% of hypertense patients treated and 57.6% of subjects with suspicion of isolated clinical hypertension. Possible isolated clinical hypertension was diagnosed in 10% of subjects without hypertension. White Coat normal pressure was found in 2.3% of untreated subjects and 4.7% of subjects with treated hypertension. 20.7% of subjects with hypertension poorly controlled in the clinic were considered pseudo-refractory (11.4% at the end of dosage interval). 77% of subjects conducted HBPM on their own and 89% thought it easy to do so. CONCLUSION: Incorporation of HBPM into daily medical practice could avoid 20%-30% of possible mistakes in diagnosis and monitoring of hypertense patients.

Adult↗
PubMed1999

[Repercussions in clinical practice of the results of the HOT (Hypertension Optimal Treatment) study].

The HOT study (Hypertension Optimal Treatment) was designed to answer three questions: What is the optimum target diastolic blood pressure (DBP) level that treatment should reach for the greatest reduction in cardiovascular mortality risk; whether there are additional benefits with a progressive reduction of diastolic blood pressure from 90 to below 80 mmHg; and whether low-dose acetylsalicylic acid is of any additional benefit in the primary prevention of myocardial infarction in treated hypertensive patients? To resolve this posing, more than 19,000 essential hypertensives were recruited in 26 countries worldwide by 1,904 investigators with a follow-up period of almost 4 years. Patients were randomly assigned to three different diastolic blood pressure targets: < or = 90 mmHg, < or = 85 mmHg or < or = 80 mmHg respectively. Additionally, in each group, patients were randomly assigned to acetylsalicylic acid or placebo. The follow-up period was about 4 years. Although the HOT trial failed to demonstrate the primary objective for which it was designed, of defining optimum target diastolic blood pressure to be achieved by antihypertensive treatment, this HOT study has helped to clarify very important issues related to blood pressure lowering such as the nonexistence of the J-shaped curve concept in hypertension, the possibility of achieving substantial improvement in blood pressure control by the use of antihypertensive combination therapy, the additional benefit of low-dose aspirin in primary prevention of myocardial infarction among treated hypertensives, and the demonstration of the necessity of reducing diastolic blood pressure below 80 mmHg in diabetic hypertensive patients. For all these reasons, the HOT study is destined to become among the most relevant hypertension intervention studies of this century.

Aged↗
PubMed1998

Expression of vascular endothelial growth factor in cerebellar hemangioblastomas does not correlate with tumor angiogenesis.

The relation between angiogenesis and tissue expression of vascular endothelial growth factor (VEGF) was studied in a series of 14 capillary cerebellar hemangioblastomas. In the present series, the number of intratumoral microvessels, identified by the endothelial marker CD34, does not correlate with the degree of VEGF expression. This finding suggests that endothelial growth factors other than VEGF may regulate tumor angiogenesis in these neoplasms.

Antigens, CD34↗
PubMed2002

Differential regulation of gene expression of neurotensin and prohormone convertases PC1 and PC2 in the bovine ocular ciliary epithelium: possible implications on neurotensin processing.

Prohormone convertases PC1 and PC2 are enzymes involved in the intracellular processing of pro-neurotensin/neuromedin N (pro-NT/NN) through the regulated secretory pathway. In this study, we present evidence of the differential gene expression of pro-NT/NN, pro-PC1 and pro-PC2 in two cell lines established from the neuroendocrine ocular ciliary epithelium. Dexamethasone and forskolin were found to synergistically up-regulate NT/NN mRNA expression in both cell types. The pigmented cells released NT, and this release was enhanced by agents that induced its biosynthesis. In contrast, nonpigmented cells exhibited a significantly reduced neurotensin secretion in response to inducers, leading to an accumulation of the peptide. PC1 and PC2 mRNA expression was induced in a cell-specific manner by the same agents that enhanced pro-NT/NN biosynthesis. These results demonstrate cell-specific processing of pro-NT/NN by the ciliary epithelium.

Animals↗
PubMed1996

Primary malignant lymphoma of the bladder. Report of three cases.

Primary malignant lymphoma of the bladder is a rare tumour. In a recent literature search only 70 cases have been found since 1885. Most of these tumours were low grade B-cell non Hodgkin's lymphomas and only 20% were high grade neoplasms. This tumour usually appears in women between 20 and 85 years (median 64 yr.) of age. 20% of them have antecedents of chronic cystitic. Some authors have considered that some of the primary malignant lymphomas of the bladder arise from the mucosa-associated lymphoid tissue (MALT), therefore acting like MALT lymphomas which affect the gastrointestinal tract, the salivary glands or the thyroid. We report three additional cases of primary malignant lymphoma of the bladder, two of high grade, and discuss the histological criteria that support their MALT nature.

Aged↗
PubMed1999

Identification, expression and chromosome localization of a human gene encoding a novel protein with similarity to the pilB family of transcriptional factors (pilin) and to bacterial peptide methionine sulfoxide reductases.

Here we report the isolation, characterization and chromosome localization of a subtracted cDNA (CBS-1) isolated from the human ocular ciliary body which encodes a novel protein. As is deduced from the nucleotide sequence of the cDNA, CBS-1 contains an open reading frame consisting of 182 amino acids, with a molecular weight of 19.5kDa. CBS-1 shares significant nucleotide and amino acid sequence identities (residues 51 to 182) with a hypothetical 15.5kDa protein in the ANSA-GAP intergenic region (yeaA) of Escherichia coli, and the carboxyl terminal region of pilB, a transcription factor involved in the regulation of expression of pili, from Neisseria gonorrhoeae. Interestingly, CBS-1 also shares significant identity with the carboxyl terminus of the peptide-methionine sulfoxide reductase (MsrA), a repair enzyme, from Helicobacter pylori and Streptococcus pneumoniae. However, the amino terminal of CBS-1 (residues 23 to 43), which lacks homology to the amino terminal region of gonococcal pilB or pneumococcal MsrA, exhibits significant identity in a stretch of 20 amino acids, with glycine-rich proteins. By Northern blot, CBS-1, hybridized to a 0.6 to 0.7kb transcript in size, is expressed ubiquitously in many tissues, but most abundantly in the retina and ocular ciliary body, skeletal muscle and heart. An epitope-directed antibody to an amino acid sequence at the carboxyl terminus of CBS-1 recognized a main protein of 19.5kDa in ocular ciliary body extracts, and a 23kDa protein in total extracts from E. coli MC1061 cells, which expresses high levels of MsrA. The CBS-1 gene was mapped to human chromosome 10p12 between markers WI-8535 and WI-4724, and is tightly linked to the two STRP markers of D10S1789 and D10S550. We suggest that the CBS-1 gene encodes a mammalian transcription factor related to the bacterial pilB and certain bacterial MsrA homologues.

Amino Acid Sequence↗
PubMed2005

[A urachus cyst revealing a torpid Crohn's disease in a young adult with chronic fever].

INTRODUCTION: This case report describes a rare situation in which a superinfected cyst of the urachus complicated initially unknown and inactive Crohn's disease. CASE: A 21-year-old man presented a chronic fever finally attributed to a superinfected urachal cyst. Six months after ablation of the cyst, progressive Crohn's disease was diagnosed. DISCUSSION: The association of Crohn's disease and a superinfected urachal cyst is extremely rare. The case reported here is original in two aspects: the slowly progressive Crohn's disease was diagnosed after its complication; the superinfection developed through local bacterial translocation (ileal loop adjacent to the urachal cyst).

Adult↗
PubMed2002

ACE inhibition and cardiovascular mortality and morbidity in essential hypertension: the end of the search or a need for further investigations?

Scientific evidence currently available supports the concept that renin-angiotensin blockade with angiotensin converting enzyme inhibitors as a first-line treatment exhibits in arterial hypertension beneficial effects in the prevention of mortality and morbidity comparable to those achieved with diuretics and beta-blockers. In addition, the renin-angiotensin blockade has also proved to be beneficial in the secondary prevention of several complications of hypertensive disease such as after myocardial infarction and congestive heart failure, as well as in the prevention of the incidence of type 2 diabetes, and the progression of diabetic and nondiabetic nephropathy. In this later regard, recent evidence with angiotensin II receptor antagonists in reducing the progression of nephropathy in type 2 diabetes strongly confirms that antagonism of the renin-angiotensin system is an effective approach to cardiovascular and renal disease. Finally, the renin-angiotensin blockade in high-risk patients may reduce cardiovascular mortality independently of the effect on blood pressure (BP). The effect of other antihypertensive drugs on cardiovascular risk in patients with high-normal BP should be investigated to establish whether they exhibit a comparable effect or whether there is a class-related benefit of drugs blocking the renin-angiotensin system. Such a strategy could also be encouraged to design future interventional studies with the newer classes of compounds (angiotensin II AT1-receptor antagonists, vasopeptidase inhibitors, endothelin antagonists), which would have the additional potential advantage of providing information more easily transferable to large-scale clinical practice.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Correlation between silent cerebral white matter lesions and left ventricular mass and geometry in essential hypertension.

BACKGROUND: It has been proposed that concentric left ventricular hypertrophy (LVH) is related to a worse degree of target organ damage in hypertensives with this feature than in those without. Moreover, the presence of cerebral white matter lesions (WMLs) is considered to be an early marker of brain damage in essential hypertension. The aim of this study was to assess the association between the presence of silent WMLs and left ventricular mass and geometry in middle-aged individuals with hypertension that had never been treated. METHODS: A total of 62 patients (39 men, 23 women, aged 50 to 60 years, mean age 54.4 +/- 3.2 years) with never-treated essential hypertension and without clinical evidence of target organ damage were studied. All patients underwent brain magnetic resonance imaging and were classified into two groups according to the presence or absence of WMLs. Echocardiography measuring posterior wall thickness (PWT), interventricular septum thickness (IVST) and left ventricular end-diastolic diameter (LVEDD) was also performed. Left ventricular mass index (LVMI) was calculated using the Penn convention criteria, and relative wall thickness ratio (RWT) was estimated by the standard formula: 2 x PWT/LVEDD. RESULTS: Hypertensive patients with WMLs exhibited significantly higher PWT, IVST, LVMI, and RWT when compared with hypertensive patients without WMLs. In addition, 23 of 26 hypertensive patients with WMLs showed echocardiographic criteria for LVH that was significantly higher than that observed in hypertensive patients without WMLs (21 of 36; P = .01). Concentric hypertrophy (LVH and RWT > or = 0.45) was present in 14 hypertensive patients with WMLs and in only four patients without WMLs (P = .002). CONCLUSION: There is a close association between cerebral WMLs and concentric LVH in asymptomatic middle-aged hypertensive patients, independent of blood pressure values.

Blood Pressure↗
PubMed2000

Genetic variation of the gamma subunit of the epithelial Na+ channel and essential hypertension. Relationship with salt sensitivity.

We evaluated the association of a common polymorphism in gammaENaC, consisting in a C to G transversion in codon 649, with essential hypertension and to the pressor response to salt in whites. Two hundred fifteen essential hypertensive patients, and 137 normotensive controls were genotyped for the gamma649 ENaC polymorphism by polymerase chain reaction method and diagnostic restriction enzyme digestion. The genotype distribution of the gamma649 ENaC polymorphism in the hypertensives, 129 CC (60%) and 86 CG/GG (40%) was not significantly different from that of the control group, 84 CC (61%) and 53 CG/GG (39%) (P = .81). Salt sensitivity was assessed in a group of 48 patients by 24-h mean blood pressure response to changes in salt intake. Nineteen patients were diagnosed as salt sensitive, whereas 29 had salt-resistant hypertension. The gamma649 ENaC genotype distribution in salt-sensitive patients was 12 CC (63%) and 7 CG/GG (37%), not significantly different from the distribution in the salt-resistant group, 19 CC (65%) and 10 CG/GG (35%), P = .87. The changes in systolic, diastolic, and mean blood pressure as measured by ambulatory blood pressure monitoring, and in plasma renin activity and plasma aldosterone induced by high salt diet were not different among the gamma649 ENaC genotypes. In the present study we found no association between the gamma649 ENaC polymorphism and essential hypertension or salt sensitivity. Although these data do not support a major causative role for this polymorphism, we cannot exclude that a functional mutation elsewhere in ENaC might be associated with essential hypertension.

Adult↗
PubMed1997

Is management of anesthesia in achondroplastic dwarfs really a challenge?

STUDY OBJECTIVE: To review our eight-year anesthetic experience with achondroplastic patients. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: 15 achondroplastic patients who underwent 53 surgical procedures of orthopedic surgery between 1987 and 1994. INTERVENTIONS: Anesthetic technique, drugs, number of incidents, and complications in the intraoperative and postoperative period were recorded. MEASUREMENTS AND MAIN RESULTS: Adequate premedication before the transfer to the operating room was very useful to reduce anxiety and increase cooperation. Inhalation induction was well tolerated and allowed easy peripheral venous cannulation. Only one patient presented difficulties during intubation (on two occasions). In the other patients, we found small difficulties only during ventilation with a face mask, which was easily corrected by modifying the position of the patient and/or inserting an oropharyngeal airway. No adverse effect was identified for any particular anesthetic drug or technique used. CONCLUSIONS: Although the characteristic deformities of achondroplastic patients can impede the management of anesthesia, in our study we found no special difficulties. Airway complications did not occur. Thus, no specific optimal anesthetic regimen can be recommended.

Achondroplasia↗
PubMed1998

Osmotin, a plant antifungal protein, subverts signal transduction to enhance fungal cell susceptibility.

The plant pathogenesis-related protein osmotin is an antifungal cytotoxic agent that causes rapid cell death in the yeast S. cerevisiae. We show here that osmotin uses a signal transduction pathway to weaken defensive cell wall barriers and increase its cytotoxic efficacy. The pathway activated by osmotin includes the regulatory elements of the mating pheromone response STE4, STE18, STE20, STE5, STE11, STE7, FUS3, KSS1, and STE12. Neither the pheromone receptor nor its associated G protein alpha subunit GPA1 are required for osmotin action. However, mutation of SST2, a negative regulator of G alpha proteins, resulted in supersensitivity to osmotin. Phosphorylation of STE7 was rapidly stimulated by osmotin preceding any changes in cell vitality or morphology. These results demonstrate that osmotin subverts target cell signal transduction as part of its mechanism of action.

Antifungal Agents↗