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[Tubulo-interstitial nephritis (TIN) with no glomerular lesions, distal renal tubular acidosis and asteatosis cutis in a patient with systemic lupus erythematosus (SLE): a case report].

We report a 28-year-old woman with systemic lupus erythematosus (SLE) who showed tubulo-interstitial nephritis (TIN) without any glomerular changes. In 1990, she was admitted to our hospital, complaining of anorexia, vomiting and persistent high fever. Laboratory findings showed proteinuria, pancytopenia, hypocomplementemia and positive for antinuclear antibody, anti-DNA antibody, anti-Sm antibody, anti-SSA antibody and anti-SSB antibody. We made a diagnosis of SLE. Furthermore, distal renal tubular acidosis and asteatosis cutis were revealed. The diagnosis of Sjögren's syndrome was not made. We treated with high-dose prednisolone (60mg/day) and achieved improvement of symptoms and laboratory data. Open renal biopsy showed TIN without any glomerular changes. Predominant TIN is very rare in SLE. We discussed its pathogenesis and relation to the renal lesions of Sjögren's syndrome.

Acidosis, Renal Tubular↗

A comparison of cutaneous vascular responses to transient pressure loading in smokers and nonsmokers.

Smoking has been recognized as a risk factor for pressure ulcer development. This study investigated the hypothesis that smoking causes alterations in cutaneous vascular perfusion, which may contribute to this increased risk. With the use of the laser Doppler fluximetry (LDF), the adaptive vasodilatory response to a transient pressure load at the sacrum was measured in nine healthy female smokers and their age, sex, body mass index (BMI), and menstrual cycle matched nonsmoker controls. In all subjects, removal of the pressure load resulted in a reactive hyperaemic response. The total hyperaemic response was approximately 45% smaller in smokers compared to nonsmoker controls. The reduction was due to a shortening of the duration of the response predominantly through an increase in the rate of recovery from peak, which was twice as fast in the smokers (2.4 +/- 1.7 AU x seconds) compared with the nonsmoking controls (1.1 +/- 0.9 AU x seconds) (p < 0.005). We conclude that changes in the vascular responsiveness can be measured objectively at skin sites at risk of pressure ulcers. We have also shown that vascular responsiveness is altered in light smokers compared to control subjects. These preliminary data open the way for further investigation into the risk factors associated with pressure ulcer development.

Adult↗

Dydrogesterone (Duphaston) and its 20-dihydro-derivative as selective estrogen enzyme modulators in human breast cancer cell lines. Effect on sulfatase and on 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity.

Estradiol (E2) is one of the main factors which control the growth and evolution of breast cancer. Consequently, to block the formation of E2 inside cancer cells has been an important target in recent years. Breast cancer cells possess all the enzymatic systems (e.g. sulfatase, aromatase, 17beta-hydroxysteroid dehydrogenase [17beta-HSD]) involved in the conversion of estrogen precursors into E2. Sulfotransferase, which converts estrogen to its sulfate, is also present in this tumoral tissue. Duphaston is a synthetic progestogen with properties similar to the natural progesterone. In the present study we examined the effect of Duphaston and its 20-dihydro-metabolite on the sulfatase and 17beta-HSD activities in MCF-7 and T-47D breast cancer cells. The cells were incubated with estrone sulfate (E1S) (5x10(-9)M) in the absence or presence of Duphaston or its 20-dihydro-metabolite (5x10(-5) to 5x10(-9)M) for 24h at 37 degrees C. In another series of experiments, estrone (E1) (5x10(-9)M) was incubated with T-47D cells in the absence or presence of the two progestogens (5x10(-5) to 5x10(-9)M) for 24h at 37 degrees C. E1S, E1 and E2 were characterized by thin layer chromatography and quantified using the corresponding standard. Duphaston and its 20-dihydro-metabolite, at concentrations of 5x10(-7) and 5x10(-5)M, inhibited the conversion of E1S to E2 by 14% and 63%, 65% and 74%, respectively, in MCF-7 cells; the values were 15% and 48% and 31% and 51%, respectively, in T-47D cells. In another series of experiments it was observed that, after 24-h incubation, E1 (5x10(-9)M) was converted in a great proportion to E2 in the T-47D cells and that this transformation was significantly inhibited by Duphaston and its 20-dihydro-metabolite. The IC50 value, corresponding to 50% of the inhibition in the conversion of 1 to E2, was 9x10(-6)M for 20-dihydro-metabolite in this cell line. It was concluded that the progestogen Duphaston and its 20-dihydro-metabolite are potent inhibitory agents on sulfatase and 17beta-HSD activities in breast cancer cells. Duphaston is a progestogen with properties similar to the endogenous progesterone. The data open interesting perspectives to study the biological responses of these progestogens in clinical trials of patients with breast cancer.

17-Hydroxysteroid Dehydrogenases↗

[Control of the survival/apoptosis balance by E-cadherin: role in enterocyte anoikis].

Cadherins are transmembrane glycoproteins involved in cell-cell adherence. Recent developments indicate that classical cadherins may act as adherence-activated signaling receptors. Here, we review recent data from the literature concerning the role of classical cadherins in the control of cell survival and the signaling pathways involved. We focus on the fate and the role of E-cadherin, the main classical cadherin expressed in epithelial cells, in the cell death program triggered in enterocytes by loss of anchorage from the extracellular matrix (anoikis). These data open new perspectives on the key role of this protein, which is dysregulated in most carcinoma and is considered as a tumour-suppressor.

Animals↗

An assessment study of maternal mortality ratio databank in five districts of North Western Frontier Province Pakistan.

BACKGROUND: Maternal mortality ratio is an indicator to measure the summary of information about mother and child health. It is estimated that about 500 maternal deaths occur per 100,000 live births each year in Pakistan. It is a well known fact that all health statistics coming out of the developing countries are calculated "guesstimates" some are perhaps more close to the real figures than the others. There is a dire need to help generate information that can be used by health professionals, health care planners and managers to save women's lives by improving the quality of care provided to turn away maternal mortality. The maternal mortality ratio for Pakistan as well as for NWFP is projected as 533/100,000 live births for the year 1990-91 produced by National Institute of Population Studies, Pakistan. METHODS: This was a retrospective cross-sectional quantitative study for the period (2001-2002) conducted in five districts of (NWFP) North Western Frontier Province, Pakistan. RESULTS: National HMIS data opened the maternal mortality ratio for; Haripur as 0.168 and 0.173, Mansehra 00 and 00, Battagram 00 and 00, Swat 0.051. and 0.524 and Swabi 00 and 0.968 per/1000 live births, respectively. The small part exercise outcome (the study) endorsed more shadowy side of the actual maternal mortality ratio for the same period in the same districts. CONCLUSION: In our country there is a urgent need to institute an efficient mode of operation to get accurate maternal mortality database. Verbal Autopsy method is cost effective and feasible approach for implementation in a country like Pakistan.

Adult↗

[The neuroendocrinology of sleep].

It is now well established that some pituitary hormones have a pattern of secretion closely linked to the sleep-waking cycle. These data open a new approach to the problem of sleep disturbances and suppose a completely new evaluation of their meaning.

Adrenocorticotropic Hormone↗

The systematic study of drug therapy in rheumatoid arthritis.

Important advances in therapeutics for rheumatoid arthritis (RA) will probably require coordination of the experience with new developing agents with an ongoing program of systematically collected open data, and formal controlled clinical trials to address key problematic issues. Controlled trials, despite formidable obstacles, not the least of which is the lack of satisfactory end points, are necessary because randomized treatment assignment is the only valid way to obtain results with a defined degree of certainty. A formal test of whether early aggressive intervention can arrest disease appears feasible. On the other hand, it does not now seem desirable to pursue a controlled, blinded study of RA over the longterm.

Anti-Inflammatory Agents↗

[Contribution of immunology and molecular biology].

Recent technical advances in immunology and molecular genetics have allowed to better delineate Ewing sarcoma among other small round cell tumors of bone and soft tissues. Ewing cells present with a characteristic translocation t (11;22) (q23-24; q11-12) shared with neuroepithelioma. They express a series of cell-surface antigens associated with the neuroectodermal differentiation lineage. These data open new avenues for exploring the origin and the mechanism of transformation of these tumors and to conceive new therapeutical approaches.

Antigens, Surface↗

Mutagenesis induced by procarcinogens at the hypoxanthine-guanine phosphoribosyl transferase locus of human fibroblasts cocultured with rat hepatocytes.

The addition of diethylnitrosamine or cyclophosphamide in cultures of hepatocytes overlaid on confluent diploid human fibroblasts resulted in a dose-dependent increase in the frequency of hypoxanthine-guanine phosphoribosyl transferase human fibroblast mutants with both chemicals. Different toxicity patterns for the two cell types were seen. Diethylnitrosamine was more toxic to the hepatocytes, whereas cyclophosphamide was more toxic to the fibroblasts. These data open the possibility of using strains of human fibroblasts as in vitro screens for mutagenicity of procarcinogens.

Animals↗

[Mitotic index and kinetics of lymphocyte proliferation in biologic monitoring].

Xenobiotics exposure generates concern, mostly because the effects on DNA and cancer generation are not well known. Identification of dangerous agents are difficult due to the large latency period between exposure and clinic manifestations (from years to several generations). Biomarkers are proposed for human biomonitoring of individuals that due to natural, occupational, medical or accidental exposure are considered of "high risk". The present work evaluates the use of biomarkers of cell proliferation in lymphocyte cultures of individuals exposed to hydro-arsenicism, dangerous industrial products (DIP), neuro-cysticercosis patients under treatment with praziquantel and individuals treated with metronidazole. The slowing of cell proliferation in arsenic exposed individuals and in neuro-cysticercosis patients, in which higher cancer frequencies han been reported, evidence the usefulness of these parameters. We did not find lymphocyte proliferation changes due to DIP exposure although we did find an increased proliferation due to metronidazole treatment. The biological meaning of these data opens new research interests.

Adolescent↗

[Directed transpositions in the genome of the mobile hobo element in a long-term selected strain of Drosophila melanogaster].

The object of our investigation was an inbred LA strain of Drosophila melanogaster. This strain was selected during more than 700 generations for low male mating activity and was characterized by complex abnormalities and the remarkably high level of spontaneous mutability. The last property is determined by hobo system of hybrid dysgenesis. LA strain's hobo activity potential in H-E system of hybrid dysgenesis comprise 30-40%. It may be drastically increased up to 70-80% through LA-strain chromosome isogenization in dysgenic crosses. In genomes of independent isogenic LA substrains, numerous directional transpositions of hobo element take place. In spite of it, the retention of hobo element insertion sites inherent in original LA persist. The obtained data open up a new possibilities to study the genome instability mechanisms.

Animals↗

Microanalysis of serotonin by high pressure liquid chromatography with electrochemical detection.

Serotonin (5-HT) analysis by high pressure liquid chromatography with electrochemical detection (HPLC-ED) has been designed to perform micro assays below the picogram range. We demonstrated that the oxidation potential of 5-HT was tightly linked to the pH of the buffer used as eluent phase. The electrochemistry of 5-HT in pH 4.00 acetate buffer and in pH 6.80 phosphate buffer allowed quantification down to 2 x 10(-18) g. The oxidization current was linked to the 5-HT amount added. The electrochemical response of 5-HT was different for low amounts in the 10(-18) g range and for amounts above the picogram range. Two curves were obtained according to the electrochemical response of 5-HT: the first one was for the 10(-18) g range and the second one was for the picogram range and above. It thus appeared between concentration ranges that assays are not be feasible. This method has been used to analyse 20 microns frozen slices of rat spinal cord. These data open new insights into scarce quantification of 5-HT without the use of radio-elements.

Animals↗

[The high-frequency electroencephalogram: the results and outlook].

At present, the significance of high-frequency (HF) components in brain electrical activity (EA) is widely discussed in literature. In particular, the gamma range of human EEG is considered as one of the indices of cognitive activity. In the paper a review is presented of the author's own data concerning the functional estimation of low-voltage HF components of the neocortical EA recorded in the broad band (1-100, 1-256 Hz) in the course of instrumental conditioning in dogs. Three different techniques of EA analysis were used in the study: 1) fast Fourier transformation (FFT) of EA in a broad band, 2) developed by us alternative method of non-harmonic expansion of the EEG curves taking into account their shape, 3) factor analysis of the EA spectral densities. Combination of these techniques allowed us to obtain some novel evidence indicative of high informativity of the HF fluctuations. Spatial cortical localization of the HF components of the EA is much more expressed in comparison with the traditional 1-30 Hz range. Results of factor analysis suggest functional heterogeneity of the HF band. Obtained data open new ways for researches concerning the phenomena of the functional mosaics in the neocortex as one of fundamental mechanisms in brain activity organization.

Animals↗

Topiramate: a new antiepileptic drug.

OBJECTIVE: To review proposed mechanisms of action, clinical pharmacology, efficacy, safety, and tolerability of the antiepileptic drug (AED) topiramate. METHODS: All available data from the clinical development program--published and unpublished data (provided by investigators or the RW Johnson Pharmaceutical Research Institute)--were analyzed, with emphasis on the results of double-blind, placebo-controlled trials. Data from open-label studies provided information about long-term efficacy and tolerability. FINDINGS: Topiramate is highly effective in the control of previously therapy-resistant partial seizures, with or without secondary generalization. In the refractory adult patient population enrolled in controlled clinical trials, seizures were reduced by 50% or more in 27-47% of patients compared with 0-18% in placebo-treated patients and by 75% or more in 9-36% of the patients compared with 0-9% of those receiving placebo. The most common adverse effects involve the central nervous system and are mild to moderate in nature. Adverse effects include somnolence, fatigue, psychomotor slowing, and concentration problems. The currently recommended dosing is lower and titration slower than schedules used in the clinical trials; this may improve the tolerability of topiramate. Topiramate has few interactions with currently available AEDs, but phenytoin concentrations increased in some patients. Topiramate can be used initially as adjunctive therapy. Plasma topiramate concentrations are reduced substantially when used with enzyme-inducing AEDs. Open-label data and a single double-blind trial suggest that topiramate monotherapy may be effective. Open-label data also indicate that topiramate may be effective in generalized seizures of nonfocal origin, including those associated with Lennox-Gastaut syndrome. CONCLUSIONS: The robust clinical effects of topiramate expand the therapeutic options for patients with epilepsy. Controlled clinical trials are needed to verify initial observations that topiramate may be effective against a broad spectrum of seizure types and to directly compare efficacy and tolerability with other new and standard AEDs.

Adult↗

A numerical analysis of the combined open-top chamber data from the USA and Europe on ambient ozone and negative crop responses.

Statistical analysis was performed using selected sets of combined data from the US National Crop Loss Assessment Network and the European Open-Top Chambers Programme to examine the relationships between the occurrences of hourly ambient ozone (O3) concentrations and adverse crop yield responses. The results suggest that the frequency of occurrences of relatively low hourly O3 concentrations ( approximately <35 ppb) are not as important as moderate to higher concentrations in eliciting negative crop biomass responses. They also suggest that daily peak (highest) hourly O3 values ( approximately >90 ppb) may not be as critical, most likely because they frequently do not occur during time periods when conditions that promote atmospheric conductivity (O3 deposition) and plant uptake (O3 absorption) are in coherence.

Journal Article↗

Fertility estimation from open birth-interval data.

Censuses and surveys frequently collect information on period fertility through questions on the timing of last births. The standard approach to estimating fertility with open-interval data uses the proportion of women giving birth in the year before the interview. I propose a more efficient, maximum likelihood method for estimating fertility from open-interval data. I illustrate a mathematical derivation of the new method, perform sensitivity analyses, and conduct empirical tests with Brazilian census data. The new estimators have small biases and lower variance than standard estimators for open-interval data. Consequently, the new method is more likely to generate accurate results from small or moderately sized samples.

Adolescent↗