Losartan but not verapamil inhibits angiotensin II-induced tissue endothelin-1 increase: role of blood pressure and endothelial function

Endothelin partially mediates angiotensin (Ang) II-induced vascular changes in vivo. This study investigated the effects of the angiotensin type 1 receptor antagonist losartan and the calcium channel blocker verapamil on vascular reactivity and tissue endothelin-1 levels in aortas of Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng x kg(-1) x min(-1)). Ang II increased systolic blood pressure (39+/-4 mm Hg, P<0.05). Concomitant treatment with losartan abolished the Ang II-induced pressure increase (P<0.05), whereas verapamil reduced it only partially (P<0.05). In the aortas of rats with Ang II-induced hypertension, tissue endothelin-1 content was increased threefold and contractions to endothelin-1 were impaired (P<0.05). Interestingly, these alterations were normalized by losartan (P<0.05) but not by verapamil. Hence, there was a strong, negative correlation between contractions to endothelin-1 and tissue endothelin-1 content (r=-0.733, P<0.0001). In contrast, both antihypertensive drugs normalized impaired endothelium-dependent relaxations to acetylcholine and reduced the sensitivity of vascular smooth muscle to sodium nitroprusside compared with Ang II-treated rats (P<0.05). Ang II-induced hypertension enhanced endothelium-dependent contractions to acetylcholine, and these were normalized by either drug. In conclusion, these findings suggest that long-term treatment with Ang II modulates endothelin-1 protein expression in the rat aorta. Although both antihypertensive agents lowered blood pressure and normalized endothelial function, only losartan prevented the increase in tissue endothelin-1 content, suggesting that angiotensin type 1 receptor antagonists but not calcium antagonists modulate tissue endothelin-1 in vivo.     

Delivery of salbutamol to nonventilated preterm infants by metered-dose inhaler, jet nebulizer, and ultrasonic nebulizer

An isocratic reversed-phase high-performance liquid chromatographic method with ultraviolet detection at 230 nm has been developed for the determination of paclitaxel in human plasma. Plasma samples were prepared by a selective one-step liquid-liquid extraction involving a mixture of acetonitrile-n-butyl chloride (1:4, v/v). Paclitaxel and the internal standard docetaxel were separated using a column packed with ODS-80A material, and a mobile phase consisting of water-methanol-tetrahydrofuran-ammonium hydroxide (37.5:60:2.5:0.1, v/v). The calibration graph for paclitaxel was linear in the range 10-500 ng/ml, with a lower limit of quantitation of 10 ng/ml, using 1 ml plasma samples. The extraction recoveries of spiked paclitaxel and docetaxel to drug-free human plasma were 89.6+/-8.52 and 93.7+/-5.0%, respectively. Validation data showed that the assay for paclitaxel is sensitive, selective, accurate and reproducible. The assay has been used in a single pharmacokinetic experiment in a patient to investigate the applicability of the method in vivo.     

Identification and characterization of the KlCMD1 gene encoding Kluyveromyces lactis calmodulin

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of morbidity and death after lung transplantation. Therapy has focused on augmented immunosuppression with a variety of agents. Although transient responses are often achieved, sustained remission has been unusual. The outcome of cytolytic therapy for BOS at our center has been analyzed and is reported. METHODS: Between July 1988 and July 1994, 233 patients underwent lung transplantation at Barnes-Jewish Hospital. Among 207 recipients (88.8%) who survived more than 3 months, 81 recipients (39%) had development of BOS; 48 of these patients underwent 64 courses of treatment with a cytolytic agent (antilymphocyte globulin, antithymocyte globulin, or OKT3 monoclonal antibody). The cases of BOS were retrospectively analyzed to determine the impact of cytolytic therapy. RESULTS: The 4-year survival rate was significantly greater in recipients without BOS than in those with BOS (82.8% vs 46.0%; p < .05). Various clinical factors, including diagnosis, forced expiratory volume in 1 second at onset of BOS, presence or absence of pathologically proven bronchiolitis obliterans, type of transplant operation, cytomegalovirus serologic status, and cytomegalovirus pneumonia, were examined, but no significant predictor of survival after the development of BOS was discerned. The mean decrement in forced expiratory volume in 1 second was significantly reduced by cytolytic therapy (-23.5% +/- 2.3% in the 3 months before therapy vs -9.9% +/- 3.5% in the 3 months after the therapy; p < .002). Nevertheless, the stage of BOS progressed over time in spite of therapy in most cases, and only 4 recipients (4.9%) with BOS remained in a lower BOS stage 2 years after treatment. CONCLUSIONS: Recipients with BOS had a significantly lower survival rate than recipients without BOS. No predictor of survival after the onset of BOS was identified. Although cytolytic therapy decreased the rate of decline in pulmonary function in the 3 months after treatment, the stage of BOS ultimately progressed in most patients.     

Ruminal degradation of tannin‐treated legume meals

The inefficiency of protein utilisation by ruminants fed protein concentrates (based on legume meals) causes serious economic loss and environmental damage owing to their rapid hydrolysis and deamination in the rumen. Thus efforts aimed at slowing the ruminal fermentation of such feeds are needed, and recent studies have observed potentially positive effects of tannins on ruminant nutrition under certain circumstances. Tannins are a complex group of naturally occurring plant polyphenols characterised by their ability to bind with proteins. This property of tannins is considered responsible for the decreased ruminal digestibility of forages both in vivo and in vitro. Under that perspective, commercial tannic acid was added at three proportions (10, 25 and 50 g kg^?1 on a dry matter basis) to four different legume meals (horse bean, kidney bean, soybean and pea), and the effect on in situ dry matter and crude protein ruminal disappearance was assessed. The results confirmed the dose‐dependent (although not persistent after 48 h) slowing of in situ digestibility, this effect being significant at the highest tannin treatment when compared with untreated samples. Scanning electron microscopy revealed that soybean seed endosperm cell walls were protected from digestion by the ruminal microbiota, while the digestion of starch granules was relatively unaffected by tannic acid. Electrophoresis of the protein fractions confirmed the lower digestibility of tannin‐treated seeds as well as the relative lack of alteration of the electrophoretic profile of individual proteins. Implications for the digestion of concentrates in ruminants are discussed. Copyright © 2004 Society of Chemical Industry     

Isotropic isotopy and symplectic null sets

Capacity is an important numerical invariant of symplectic manifolds. This paper studies when a subset of a symplectic manifold is null, i.e., can be removed without affecting the ambient capacity. After examples of open null sets and codimension-2 non-null sets, geometric techniques are developed to perturb any isotopy of a loop to a hamiltonian flow; it follows that sets of dimension 0 and 1 are null. For isotropic sets of higher dimensions, obstructions to the perturbation are found in homotopy groups of the orthogonal groups.     

Pancreatic pseudocysts associated with chronic pancreatitis--early and late results of 1367 operations

The authors hereby review the data of 1367 operations for pancreatic pseudocysts. The surgical procedures of choice in particular pancreatic pathologies are analysed in the light of early morbidity and mortality, as well as long term follow-up results. The best operations for pancreatic pseudocysts have been the internal drainage procedures, which resolve the pathological alterations without the necessity of pancreatic resection. The treatment of chronic pancreatitis may require combined surgical procedure, such as cysto-Wirsungo-gastrostomy. The pancreatic resections performed for the treatment of small pseudocysts in the pancreatic head have been superseded by the less invasive blunt, forced cysto-duodenostomies, representing better results secondary to the smaller perioperative risk for the patient. The cyst-to-stomach and cyst-to-duodenum internal drainage techniques are just as effective, but with shorter operation time, than the Roux-en-Y cysto-jejunostomies.     

CD19 expression levels regulate B lymphocyte development: human CD19 restores normal function in mice lacking endogenous CD19

Establishing signal transduction thresholds that regulate B lymphocyte responses to foreign Ags and tolerance to self Ags is critical for humoral immune responses. The effects of altered signaling thresholds in B lymphocytes were examined in CD19-deficient mice and transgenic mice that expressed human CD19 at varying densities. Human CD19 restored normal B cell function and development to CD19-deficient mice when expressed at levels comparable to those of circulating human B cells. While CD19 expression levels were found to be developmentally regulated and tightly controlled in normal mice, two- or threefold changes in cell surface CD19 expression in transgenic mice dramatically affected B cell development, mitogen responses, serum Ig levels, humoral immune responses, and germinal center formation. B cells from mice that overexpressed CD19 also had decreased levels of surface IgM and a cell surface phenotype consistent with increased signaling in these cells. These results suggest that CD19 may serve similar functions in humans and mice and that CD19 defines signaling thresholds in vivo for the Ag receptor as well as other cell surface receptors that regulate B lymphocyte selection, activation, and differentiation.     

Children's perception of faces of varied immaturity

This research examined the relationship between facial immaturity and the perception of youthfulness, helplessness, and cuteness. In the first study, college students rated 16 faces for youthfulness. Faces varied within four dimensions (eye position, eye size, nose length, and shape of chin) representing either a mature or immature feature. College students rated faces conserving immature features as more youthful than those without those features. In the second study, three groups of children (5 to 8, 9 to 12, and 13 to 16 years old) rated the same 16 faces with respect to cuteness, helplessness, and youthfulness. Children were similar with respect to their attention to immature features when evaluating faces for youthful qualities, although older children were more sensitive to eye position than younger children when rating faces for youthfulness and helplessness. Older children were more consistent in their attention to immature features when rating faces.