Administration of tibolone decreases 24 h heart rate but not blood pressure of post-menopausal women

OBJECTIVE: Elevation of blood pressure and heart rate increase the risk of cardiovascular disease. Administration of estrogens does not affect heart rate but may decrease 24 h blood pressure. In this study, we tested the effect of the estro-progestogenic compound tibolone. METHODS: Thirty healthy, post-menopausal women were randomized to receive placebo (n = 15) or tibolone, at the commonly prescribed dose of 2.5 mg per day (n = 15). Before and after 6 months of treatment, in each woman blood pressure and heart rate were monitored every 30 min for 41 h by an ambulatory device. Valuable readings were those collected from 8:00 a.m. of the second day to 8:00 a.m. of third day. Analyses were performed of 24 h, day-time (7:00 a.m.-11:00 p.m.) and night-time (11:00 p.m.-7:00 a.m.) values. Day to night difference was also calculated. Results: Placebo did not modify 24h, day-time, and night-time blood pressure or heart rate values. Day-night differences were also not affected by placebo. Similarly to placebo, tibolone administration did not modify any of the blood pressure parameters taken into consideration. By contrast, a significant decline of 24 h heart rate (73.2 +/- 2.3 beats/min versus 69.3 +/- 1.7 beats/min; P < 0.0008) was observed. The effect was significant both at day (76.6 +/- 2.4 beats/min versus 72.1 +/- 1.9 beats/min; P < 0.0001) and night (65.8 +/ 2.6 beats/min versus 62.4 +/- 1.9 beats/min; P < 0.05). Day-night blood pressure and heart rate differences were not affected by tibolone. CONCLUSIONS: In post-menopausal women, administration of tibolone does not influence 24 h blood pressure but reduces heart rate.     

Cellular and subcellular localization of the small G protein RhoA in the human and rat embryonic and adult kidney

Rho proteins, a subgroup of the Ras GTPase superfamily, control many cellular processes and morphogenetic events by acting as signaling molecules in the transduction pathways of various receptors. Among the "Rho-dependent" receptors are the extracellular matrix- and growth factor-binding sites; these are particularly involved in the modulation of renal development since they control the epithelial-mesenchymal interactions that drive kidney organogenesis. The present study has addressed the immunohistochemical localization of RhoA in developing and adult kidneys of rats and humans because: a) Rho proteins are known to have a morphogenetic role, b) data in the literature on expression of Rho GTPases during mammalian histogenesis and organogenesis are scarce, and c) their involvement in the transduction pathways of receptors is implicated in kidney development. In particular, RhoA peptide was found to be localized in the mesonephric duct and vesicles in both rats and humans; metanephric anlagen were mainly stained in ampullar-derived cells. Periglomerular tubules of fetal and adult kidneys as well as collecting ducts of adult kidneys showed intense staining. Therefore, the present study provides new information on the distribution patterns of RhoA during early stages of mammalian kidney development suggesting that this signaling molecule may take part in epithelial-mesenchymal induction processes that control kidney organogenesis. RhoA expression in adult structures may be linked with renewal of renal epithelial cells and the maintenance of their morphology and polarity.     

Colorectal polyposis with mixed juvenile and adenomatous patterns

Summary An unusual form of colorectal polyposis is described displaying juvenile, adenomatous and mixed patterns in a 17-year-old girl. Although juvenile polyposis is generally considered to be non-neoplastic in nature, in both the present and in other case reports histological findings support a neoplastic nature. Since an increase in the incidence of large bowel carcinomas has been found in subjects with a previous diagnosis of juvenile polyposis, these patients should be considered to be at risk, and submitted to follow up.     

Walking modality affects respiratory muscle action and contribution to respiratory effort

We hypothesized that walking at increased speed or increasing gradient might have different effects on chest wall kinematics and respiratory muscle power components, and contribute differently to respiratory effort sensation. We measured the volumes of chest wall compartments by optoelectronic plethysmography, esophageal, gastric and transdiaphragmatic (P _di) pressures, and the sensation of the respiratory effort by a Borg scale in five normal subjects walking both at ascending gradient with constant speed (AG) and at ascending speed with constant gradient (AS). Chest wall kinematics, evaluated by displacement of chest wall compartments, did not show any significant difference between AS and AG. Muscle power, calculated as the product of mean flow and mean pressure, increased similarly, but its partitioning into pressure and velocity of shortening differed in the two modes. A greater increase in the pressure developed by the abdominal muscles (P _abm) (4.06-fold), and in the velocity of shortening of both rib cage inspiratory muscles (v _rcm,i) (2.01-fold) and the diaphragm (v _di) (1.90-fold) was associated with a lower increase in the pressure developed by the rib cage inspiratory muscles (P _rcm,i) (1.24-fold) and P _di (0.99-fold) with AG. Instead, with AS, a lower increase in P _abm (2.12-fold), v _rcm,i (1.66-fold) and v _di (1.54-fold) was associated with a greater increase in P _rcm,i (1.56-fold) and P _di (1.97-fold). A combination of P _abm and v _di during AG (Wald ²=23.19, P<0.0000), with the addition of P _rcm,i during AS (Wald ²=29.46, P<0.0000), was the best predictor of Borg score. In conclusion, the general strategy adopted by respiratory centers during different walking modes does not differ in terms of ventilation, chest wall kinematics, and respiratory muscle power production, whereas it does in terms of partitioning of power into pressure and velocity of shortening, and respiratory muscle contribution to respiratory effort sensation. Combinations of different patterns of flow and pressure generation made the respiratory effort sensation similar during AS and AG modes.     

Detection and identification ofMycobacterium avium in the blood of AIDS patients by the polymerase chain reaction

One hundred fifty-three blood samples from patients positive for the human immunodeficiency virus (HIV) were analyzed by polymerase chain reaction (PCR) to detect the presence ofMycobacterium avium. Samples were collected from patients who also had blood cultures performed by a radiometric method. Blood samples were centrifuged on a Ficoll-Hypaque gradient to purify peripheral blood mononuclear cells. The purified cells were washed and incubated with a resin, boiled to release mycobacterial DNA, and then amplified. Polymerase chain reaction products were detected by a nonisotopic method. A 123 base-pair (bp) insertion sequence, namely IS6110, fromMycobacterium tuberculosis complex was also included in the reaction as an internal control ofTaq polymerase activity to exclude the presence of enzyme inhibitors. This IS6110 fragment can be distinguished from the 383 bp target product on ethidium bromide-stained agarose gel and may also be used in a colorimetric assay. Such results were compared with the results of culture and indicated that the assay is as sensitive as bacteriological methods, though faster.     

The dual role of IL-10

Classification of cytokines as pro-versus anti-inflammatory might not apply to the pleiotropic effects of interleukin-10 (IL-10). Several reports suggest that IL-10 enhances the function of natural killer cells, which leads, through pathogen destruction, to increased antigen availability. In addition, by inhibiting the maturation of antigen-presenting cells (APCs), IL-10 preserves their ability for antigen uptake while simultaneously hampering their migration to draining lymph nodes. This review suggests that this "antigen-loading" phase might constitute an important component of the innate immune reaction to a pathogen. Additional proinflammatory stimuli might subsequently lead to maturation of "loaded" APCs that could migrate to draining lymph nodes or recruit and activate adaptive immune effectors locally.     

Identifying recent HIV infections using the avidity index and an automated enzyme immunoassay

We evaluated a procedure for identifying recent HIV infections, using sequential serum samples from 47 HIV-positive persons for whom the seroconversion date could be accurately estimated. Each serum sample was divided into two aliquots: one diluted with phosphate-buffered saline and the other diluted with 1 M guanidine. We assayed the aliquots with the automated AxSYM HIV1/2gO test (Abbott Diagnostics Division), without modifying the manufacturer's protocol. We then calculated the avidity index (AI): the ratio of the sample/cutoff value for the guanidine aliquot to that of the phosphate-buffered saline aliquot. We analyzed 216 serum samples: 34 samples were collected within 6 months of seroconversion (recent seroconversions), and 182 were collected after 6 months. The mean AIs, by time from seroconversion, were 0.68 +/- 0.16 (within 6 months) and 0.98 +/- 0.10 (after 6 months) (P < 0.0001). AI of <0.90 correctly identified 88.2% of recent infections but misclassified as recent infections 13.2% of serum samples collected afterward. The probability of an infection being classified as recent and having AI of > or = 0.90 would be 0.7% in a population with 5% recent infections. AI can identify with a certain degree of accuracy recent HIV infections, and being a quantitative index, it provides different levels of sensitivity and specificity, depending on the selected cutoff value. The standard assay procedure is not modified. This test is simple and inexpensive and could be used for surveillance, decision-making in treatment, and prevention.