Short-term and long-term stimulation of Na+−H+ exchange in cortical brush-border membranes during compensatory growth of the rat kidney

The effect of unilateral nephrectomy on Na⁺–H⁺ exchange in rat renal cortical brush-border membrane vesicles (BBMV) was studied by the method of acridine orange fluorescence quenching. The exchanger activity in BBMV from remnant kidney increased rapidly by 70–75% within first 30 min following uninephrectomy. Only a slight further increase was found in later stages of renal growth, i.e. 30 min to 7 days following uninephrectomy. The changes in antiporter activity were restricted toV _max, whereas theK _m for Na⁺ was similar in control and compensatory growing kidney. The increase of Na⁺–H⁺ exchange at 15 min was not affected by actinomycin D in vivo, whereas the increase at 48 h was completely abolished indicating that protein synthesis could be involved in the late, but not in the initial stimulation of renal Na⁺–H⁺ exchange. The late, but not the initial stimulations of Na⁺–H⁺ exchange were associated with elevated activities of cortical (Na⁺+K⁺)-ATPase indicating that changes in antiporter activity precede those in the (Na⁺+K⁺)-pump. The early stimulation of Na⁺–H⁺ exchange in BBMV in one kidney was induced also by the occlusion of blood flow through the contralateral kidney for 15 min, without removing it. Thirty min after the occlusion was removed and the reflow established, the Na⁺–H⁺ exchange in BBMV from the intact kidney decreased to the control values. The observed modulations in renal Na⁺–H⁺ exchanger may be regulated by phosphorylation-dephosphorylation events. In support, the concentration of a well known protein kinase C activator, 1,2-diacylglycerol, in the cortical tissue of the remnant kidney increased up to 100% within 5 min following unilateral nephrectomy and preceded the increase in Na⁺–H⁺ exchange. The early stimulation of Na⁺–H⁺ exchange may be a trigger in initiating the kidney growth.     

Genetic correction of PSA values using sequence variants associated with PSA levels

Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.     

The prognosis of highly active antiretroviral therapy (HAART) treated HIV infected patients in Serbia,related to the time of treatment initiation

BackgroundWith the introduction of highly active antiretroviral treatment (HAART) an impressive improvement in patient survival and quality of life has bee observed. However, the optimal timing of initial HAART is still under consideration.ObjectiveTo investigate the prognosis of HAART treated patients in Serbia, related to the timing of HAART initiation.Study designA series of 563 patients on HAART was retrospectively analyzed to investigate treatment response and survival.ResultsAfter a mean of 6 years (range 1–14) of treatment with PI-based and/or NNRTI-based regimens, a favorable response was achieved in 72.4%, treatment failure occurred in 7.9%, while 19.7% had a dissociative immunological/virological response. If treatment was initiated during primary HIV infection it took a shorter time to achieve a favorable response than in patients who began HAART in chronic HIV infection (2.7 ± 2.2 years vs. 6.9 ± 2.7 years, P < 0.01). A higher proportion of patients with primary HIV infection then those treated in the chronic phase achieved a favorable response to HAART (88.4% vs. 71.9%, P = 0.045). Patients who initiated HAART when their CD4 cell counts were below 200 cells/μL needed longer treatment for favorable response (8 years vs. 6 years, log rank P < 0.01). Forty-seven (8.3%) patients died. The overall estimated survival was 13 years. Patients older then 40 and IVDU were more likely to die during HAART (OR 2.6, 95% CI 1.1–5.9, P = 0.016, and OR 2.0, 95% CI 1.0–3.7, P = 0.02, respectively). However, reaching and maintaining undetectable viremia was an independent predictor of longer survival (OR 11.3, 95% CI 4.6–27.7, P < 0.01).ConclusionReaching and maintaining undetectable viremia during HAART predicted longer survival, even if sub-clinical immunodeficiency remained.     

Expression of tumor associated antigens CA 15-3 and CA 19-9 in trophoblast of the normal human placenta

Mucin 1 (MUC1) is abundantly expressed by various organs, including human placenta and endometrium. Since glycan modifications of MUC1 are potentially relevant for physiological as well as pathological processes, this study was aimed at establishing an expression profile of two MUC1 glycoepitopes, CA 15-3 and CA 19-9, in trophoblast throughout pregnancy. Immunohistochemical analysis of normal placenta demonstrated that trophoblast cells express both mucin antigens throughout gestation with a distinct staining pattern. The staining of villous trophoblast was non-uniform for both antigens, and stronger for CA 15-3. Only a proportion of extravillous trophoblast of the cell column, in decidual stroma or lining blood vessels was also stained. Whether the studied MUC 1 glycoforms can be linked to trophoblast cells invasion remains to be established.     

BONE MARROW FINDINGS IN JUVENILE IDIOPATHIC ARTHRITIS

The diagnosis of juvenile idiopathic arthritis (JIA) is an exclusion one due to heterogeneous clinical presentation and lack of specific laboratory tests. The authors investigated bone marrow of 25 untreated children with JIA at the onset of the disease. Bone marrow smears were evaluated for cell populations as well as myelodysplastic features and compared to two control groups. The characteristic of bone marrow in JIA was myeloid hyperplasia and elevated plasmocyte count. There was no difference between JIA patients and control groups in terms of myelodysplastic features. These findings can be helpful in explaining hematological alterations in JIA.     

Increased central adiposity is associated with pro-inflammatory immunoglobulin G N-glycans

Background

Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans.

Rapid diagnosis of parasitic diseases: current scenario and future needs

Background

Parasitic diseases are one of the world's most devastating and prevalent infections, causing millions of morbidities and mortalities annually. In the past, many of these infections have been linked predominantly to tropical or subtropical areas. Nowadays, however, climatic and vector ecology changes, a significant increase in international travel, armed conflicts, and migration of humans and animals have influenced the transmission of some parasitic diseases from ‘book pages’ to reality in developed countries. It has also been noted that many patients who have never travelled to endemic areas suffer from blood-borne infections caused by protozoa. In the light of existing knowledge, this new trend can be explained by the fact that in the process of migration a large number of asymptomatic carriers become a part of the blood bank donor and transplant donor populations. Accurate and rapid diagnosis represents the crucial weapon in the fight against parasitic infections.

Propriétés mécaniques des parois de l'orbite et de leurs structures de supports

Conclusion En fonction des résultats de notre expérimentation, les fractures « blow-out » de l'orbite paraissent dépendre de plusieurs facteurs extrinsèques et intrinsèques: lesfacteurs extrinsèques sont tout d'abord les forces agissant sur le globe: intensité, direction, point d'application, durée de l'impact, énergie cinétique résultante transmise ou partiellement absorbée par le globe et les structures rétro-bulbaires; l'absorption et la transmission de l'énergie cinétique par les structures orbitaires dépendent des variations anatomiques du contenu orbitaire.Les facteurs intrinsèques sont les variations des structures intra-orbitaires, leur volume et leur masse absolue, leur distribution relative, les variations des parois de l'orbite (qualité de l'os, dépendant de l'âge, du sexe, de la nutrition, des fonctions endocrines, etc). La structure et l'épaisseur des parois peuvent être visualisées in vivo au moyen de méthodes radiographiques ou de la tomodensitométrie.La rigidité et la résistance à la fracture des parois de l'orbite sont directement dépendantes des structures anatomiques qui supportent et renforcent ces parois sur leur face extra-orbitaire. De ce fait la paroi médiale voit sa solidité liée à la présence de cellules ethmoïdales. Le plancher est d'autant plus solide que sa surface est plus faible et qu'il existe des trabéculations et des septa au niveau du sinus maxillaire. La résistance des parois supérieures et latérales est proportionnelles à leur épaisseur. En moyenne, la paroi inférieure est la plus. faible, suivie par la paroi médiale, la paroi supérieure, tandis que la paroi latérale est la plus résistante, car elle est renforcée par la surface temporale de la grande aile du sphénoïde.     

The influence of demographic and behavioral factors on the risk of human papillomavirus infection

OBJECTIVES: The aim of this work was the assessment of correlation between different types of HPV and chosen factors: the number of pregnancies, childbirths and smoking habits. MATERIALS AND METHODS: Patients were examined in the Gynaecology Clinic, Silesian Medical Academy in Zabrze from 1998 until 2000. They were either hospital patients or women subjected to routine cytological examination. The smears were simultaneously collected for both cytooncologic examination and PCR identification of HPV viruses. Cytological smears were classified according to the Bethesda system. RESULTS: A relationship between the presence of HPV and number of pregnancies or childbirths was confirmed as well as the relationship between smoking and the presence of HPV genome. The higher number of pregnancies or childbirths the higher frequency of HPV presence is. HPV presence was more frequent in the group of smoking women. CONCLUSIONS: A relationship between the presence of HPV and the number of past childbirth or pregnancies was found. The statistically significant correlation between smoking and the risk of HPV infection was also confirmed.