Progress in treatment and diagnosis of renal diseases. I. Primary glomerular diseases. 2. Chronic glomerulonephritis]

The formation of dinitrophenylglutathione (DNP-SG) in human colon adenocarcinoma cells was identified and quantified by an HPLC-UV method, following exposure to 1-chloro-2,4-dinitrobenzene (CDNB) at 10 degrees for 40 min. The rate of efflux of DNP-SG at 37 degrees likewise, was measured by monitoring the DNP-SG content in the extracellular medium. Among the polyphenols examined for their action on DNP-SG export, butein was the most potent inhibitor with an IC50 value of 15 microM. The others, in order of decreasing potencies, were quercetin, tannic acid, 2'-hydroxychalcone, 2-hydroxychalcone anIIC50 values in the micromolar range. These polyphenols did not affect the ATP or the glutathione content of the cells. Mg(2+)-ATPase extracted from the plasma membrane of the cells was activated by DNP-SG in a concentration-dependent manner, and the reaction showed saturation kinetics with K(m) and Vmax values of 110 microM and 12.3 nmol/min/mg protein, respectively. However, the six polyphenols mentioned above had negligible effects on the Mg(2+)-ATPase activity, suggesting that this was probably not the target of their inhibitory action. Probenecid, p-trifluoromethoxy-phenylhydrazone (FCCP) and chlorambucil also showed varying degrees of inhibition of the export of DNP-SG.     

Primary socialization theory. The role played by personal traits in the etiology of drug use and deviance. II

Primary socialization theory proposes that drug use and deviant behaviors emerge from interactions with the primary socialization sources--the family, the school, and peer clusters. The theory further postulates that the individual's personal characteristics and personality traits do not directly relate to drug use and deviance, but, in nearly all cases, influence those outcomes only when they affect the interactions between the individual and the primary socialization sources. Interpretation of research results from the point of view of primary socialization theory suggests the following: 1) Characteristics such as depression, anxiety, and low self-esteem are related to drug use and deviance only when they have strong effects on the primary socialization process, i.e., among younger children; 2) Traits such as anger, aggression, and sensation seeking are related to drug use and deviance because these traits are more likely to influence the primary socialization process at all ages; 3) The psychopathologies that are least likely to interfere with bonding with prosocial socialization sources, the anxieties and most of the affective disorders, are less likely to have comorbidity drug dependence; and 4) Psychopathologies such as oppositional disorder, conduct disorder, attention deficit disorder, and antisocial personality are more likely to interfere with primary socialization, and the literature shows that these syndromes are also most likely to have a dual diagnosis with drug dependency.     

Obesity and diseases. 4. Molecular mechanism involved in the onset of arteriosclerosis in obesity]

BACKGROUND AND PURPOSE: The frequency of recurrent primary cerebral hemorrhage (RPCH), mainly in cases related to hypertension, has been considered low. This study investigated the frequency, mechanisms, and prognosis of RPCH. METHODS: We evaluated 359 patients with neuroimaging evidence of cerebral hemorrhage and selected 22 with RPCH. RESULTS: Five patients (23%) were older than 70 years at the first cerebral hemorrhage. Mean ages at the first and second hemorrhages were 60 and 63 years, respectively. Risk factors included hypertension (86%), diabetes (27%), and tobacco and alcohol use (each 14%). Hypocholesterolemia was demonstrated in 35% of the patients. The most common pattern of recurrent bleeding was ganglionic-ganglionic, mainly related to hypertension. Overall mortality was 32%. Forty-one percent and 27% of patients, respectively, had incapacitating and nonincapacitating sequelae; 2 of the latter had RPCH with a lobar location. Ganglionic-ganglionic hemorrhage was associated with a poor prognosis; otherwise, this pattern was uncommon in patients with nonincapacitating sequelae. Analysis of the control of risk factors, primarily hypertension after the first cerebral hemorrhage, disclosed that 56% of patients did not gain subsequent control. CONCLUSIONS: Rebleeding after a first primary intracerebral hemorrhage is not uncommon. The main topographic pattern of bleeding, ganglionic-ganglionic, is likely the result of hypertension; the less common lobar-lobar pattern probably results from amyloid angiopathy.     

Nonpeptide angiotensin II receptor antagonists. 1. Synthesis and in vitro structure-activity relationships of 4-[[[(1H-pyrrol-1-ylacetyl)amino]phenyl]methyl]imidazole derivatives as angiotensin II receptor antagonists

A novel series of non-biphenylyltetrazole angiotensin II receptor antagonists which contain a 1H-pyrrol-1-ylacetyl residue in place of the benzoyl residue in EXP 6803 have been developed. The receptor binding activity of several members of this new series was in the 10(-8) M range, which was better than that of EXP 6803. Introduction of a carboxylic acid moiety at the 2-position of the pyrrole ring enhanced the in vitro binding affinity at the receptor by 10-fold. Compounds containing an acetic acid (18) or a propionic acid residue (20) at the 5-position of the imidazole were more potent than the carboxylic acid analogue (24). The binding IC50 of the most potent compound 20 was 22 nM. Compounds 18, 20, and 24 in their best fit conformations were manually overlayed on that of the template conformation of EXP 6803 and EXP 8623, respectively. The synthesis and structure-activity relationship data are described.     

Different periods of feed restriction before compensatory growth in Belgian Blue bulls: II. Plasma metabolites and hormones

Plasma metabolites and hormones were studied in 16 double-muscled Belgian Blue bulls maintained at low growth (.5 kg/d) for 114 (G2), 243 (G3), or 419 (G4) d (low growth period, LGP) before fattening (rapid growth period, RGP). Animals from the control group (CG) were fed a diet high in energy and protein. The animals from G2, G3, and G4 were fed a restricted amount of a diet low in energy and protein during LGP and the same diet as CG during RGP. Plasma glucose, alpha-amino nitrogen (AAN), NEFA, urea, creatinine, thyroxine (T4), 3,3',5'-triiodothyronine (T3), and IGF-I were measured in blood samples taken fortnightly. Plasma GH and insulin (I) profiles were measured in serial blood samples obtained at three times during growth. The RGP was characterized by an initial compensatory growth, by higher plasma glucose, AAN, and urea levels, and by lower plasma NEFA and creatinine levels. Plasma GH concentration decreased after refeeding. Plasma T4 increased linearly during refeeding, as opposed to T3, which showed a different profile in each group. Plasma IGF-I showed a curvilinear increase during RGP and reached a plateau after 3 mo in each compensating group. In G4, changes of plasma metabolites and hormones differed often distinctly from G2 or G3. During refeeding, higher nutrient supply improved the functionality of the somatotropic axis and increased the concentration of anabolic hormones, allowing rapid muscle deposition. However, animals underfed the longest period behaved differently from the other groups, possibly because they reached a more complete sexual maturity.     

Quality of life in chronic inflammatory bowel diseases. Validation of a questionnaire and first French data]

One hundred and seventy patients with Graves' disease underwent thyroidectomy between 1987 and 1994 (10.5% of all thyroidectomies performed in the same period). Female/male ratio was 9/1; mean age 55.2 years and average period between diagnosis and surgical treatment 5.3 years. The average thyroid weight was 230 g (range 90-950 g). Thyroidectomy was subtotal in 110 and total in 60 patients, 5 of which had been previously treated elsewhere from 5 to 33 years before. Malignancy was incidentally found in 2.35% of patients. The complication rate resulted higher in total thyroidectomies than in subtotal procedures (bleeding 0.9% vs 5.4%, transient hypoparathyroidism 4.5% vs 12.7%, recurrent nerve lesion 0.45% vs 2.72%) however the differences were not statistically significant; this probably because both the procedures were carried out with the same technique for parathyroid gland and recurrent nerve safety. The need of repeated surgery increased the risk. In opposition to total thyroidectomy, subtotal thyroidectomy does not doom to complete and permanent replacement therapy (96.4% of hypothyroidism at 2 months, 72.6% at 4 years), but in this series it failed to achieve remission in 2 patients who maintained a mild hyperthyroidism and in one more patient who developed a relapse 4 years later. Serum TSI meaning is not clear, but preoperative positivity suggests a wider resection and postoperative persistence a closer follow-up by functional assessment. In conclusion surgical procedures for Graves' disease range from subtotal to total thyroidectomy but for a safe outcome the choice depends more on the intraoperative troubles of each single case than on theoretic advantages.     

Lymphocyte nucleolar activation as a marker of autoimmune disorders. II. Observations in patients with systemic lupus erythematosus and other connective tissue diseases

An increased number of lymphocytes with active nucleoli was found in the peripheral blood of most patients suffering from connective tissue diseases associated with autoimmunity.     

Cytogenetic analysis of sister chromosome sets in the second polar body and in pronuclei of unicellular mouse embryos. I. Frequency and origin of aneuploidy in embryos heterozygous for the reciprocal chromosome translocation T[14;15]6Ca]

Matrix metalloproteinases have been implicated to play a vital role in glioma invasion as they degrade extracellular matrix to facilitate the subsequent migration of tumor cells into the surrounding brain tissue. The cytokine Interleukin-10 (IL-10) was detected recently in glial tumors in vivo. Expression of specific IL-10 mRNA as well as blood serum levels of IL-10 in glioma patients increased with malignancy suggesting a functional role of IL-10 in glioma progression. Moreover, glioma cell migration in vitro was enhanced in the presence of IL-10. We therefore investigated the expression of the matrix metalloproteinases (MMPs) stromelysin-1 (MMP-3), 72-kDa collagenase (MMP-2), 92-kDa collagenase (MMP-9), matrilysin (MMP-7) and the human macrophage metalloelastase (MMP-12). In addition, a possible relation between exposure of glioma cells to IL-10 and invasiveness of these cells due to MMP expression was analyzed. Experiments with Matrigel coated Boyden chambers revealed a pronounced dose dependent effect of IL-10 on glioma invasiveness. The synthetic MMP-inhibitor Marimastat markedly reduced cell invasion in the Boyden chambers confirming the significance of MMPs in the process of invasion. Subsequently, the expression level of MMPs and the serine protease uPA was investigated in 7 glioma cell lines (U373, GaMG, U251, GHE, SNB19, U138 and D54) by RT-PCR. In all but one cell line no enhancement of MMP expression by IL-10 was detected. Matrilysin in U373 cells was the only protease found to be upregulated in the presence of IL-10 dependent on cell density. The present data suggest that IL-10 related effects on the invasive properties of the cell lines are not directly mediated by an upregulation of matrix metalloproteinase expression.     

Insulin kinetics after portal and peripheral injection of [125I] insulin: II. Experiments in the intact dog

Insulin metabolism in man is usually investigated by peripheral injection of the hormone, whereas native insulin undergoes hepatic extraction prior to mixing in the general circulation. To quantify this difference, in 10 dogs [125I] insulin was injected into a peripheral vein, and the initial distribution volume (IDV), the metabolic clearance rate (MCR), and the mean transit time (t) were computed from the plasma disappearance curve of the immunoprecipitable activity. The splenic vein was then cannulated under pentobarbital anesthesia, and the parameters were again computed from the peripheral activity after portal introduction of the tracer. The MCR after portal injection [15.1 +/- (SE) 1.1 ml/min per kg] was greater (P is less than 0.001) than the MCR after peripheral administration (13.4 +/- 0.9 ml/min per kg). Also, IDV was larger (P is less than 0.01) after portal injection (167 +/- 12 vs. 138 +/- 10 ml/kg). Mean transit times did not change significantly. Insulin secretion rate (0.29 +/-0.04 mU/min per kg) and body insulin mass (7.03 +/- 1.5 mU/kg) were also measured. An estimate of hepatic extraction was obtained from the difference between the clearance rate values calculated following portal and peripheral injection. Under our experimental conditions, hepatic retention of insulin was found to be 19.6% (range 9.6-36.2%). The method is recommended for investigations in man.     

The USFAM Study: the prevalence of allergic diseases in the school-age population of the province of Cádiz. I. Ubrique, San Fernando, Algeciras and Medina Sidonia]

The purpose of this study was to determine the prevalence of allergic diseases in the school population of the province of Cádiz in order to confirm the hypothesis that these diseases are more frequent there than in the rest of the Spanish provinces. Four cities of our province were chosen (Ubrique, San Fernando, Algeciras and Medina Sidonia, whose initials form the acrostic USFAM) with clear differential characteristics (climatological, orographical, environmental, etc). In each city, schools, both public and private, were chosen at random. Complete classes were used, and the age-limit was that established in each school. A questionnaire was given to all of the parents who, together with the teachers, were given instructions for its completion. Of the 4,000 questionnaires distributed, 2,572 were correctly completed. Of these, 1,988 answered that their child was non-allergic and 584 as allergic (22.7%). The ratio male/female was almost 2/1 (64.4%/35.6%) and the largest prevalence of these allergic diseases was in the group of children between 10 and 13 years of age. We have found that the prevalence of this pathology in the province of Cádiz is higher than the national mean.     

Effect of the parameters of dynamic hot pressing on the structure and properties of the powder material ZhGr0.8D2N3G3CaF214. II. Heating temperature and time before dynamic hot pressing,protective atmosphere in sintering and dispersity of solid lubricant

Conclusions With heating temperature before DHP equal to 1000°C and heating time of 1200 sec, the specimens have the best antifriction characteristics. On the other hand, an increase of DHP impairs the physicomechanical properties (except impact toughness), and a change of the temperature has an ambiguous effect on them.Comparatively good physicomechanical properties and the smallest linear wear were found in specimens sintered in dissociated ammonia, in vacuum, and in a container with fusible seal. Specimens sintered in dissociated ammonia and dried hydrogen have a low friction coefficient.The effect of the dispersity of inclusions of solid lubricant on the mechanical properties is imperceptible, but on the friction coefficient and on linear wear it is substantial. Optimal is the use of particles of the fraction +100 m: thanks to their spongy shape they adhere more strongly to particles of the matrix, and that has a favorable effect on the antifriction properties.Translated from Poroshkovaya Metallurgiya, No. 9(333), pp. 53–58, September, 1990.     

Orally active cephalosporins. II. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-cephalospori ns with 1,2,3-triazole in C-3 side chain

The synthesis, antibacterial activity and oral absorbability of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3 -(1H-1,2, 3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid (1g) and related compounds are described. Their oral absorbability was influenced by the spacer length between C-3 of a cephem nucleus and C-4' of 1,2,3-triazole. The SCH2S structure was also found to contribute to their good oral absorption. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a-1n) is discussed.