Adrenergic influences on the control of blood-brain barrier permeabilit

Summary The central adrenergic innervation of the cerebral microvessels may play a role in the control of blood-brain barrier permeability. To pursue the study of this hypothesis we investigated the effect of noradrenaline on both the permeability of the blood-brain barrier to sodium fluorescein and on the pinocytotic activity of cerebral endothelial cells in the rat. Noradrenaline, stereotactically injected in the right lateral cerebral ventricle, significantly increased the cerebral extraction ratio of sodium fluorescein in a dose-dependent way. The same effect was induced by phenylephrine. Prostaglandin F₂ had no significant effect on the passage of sodium fluorescein through the blood-brain barrier.The effect of noradrenaline (150 µg) on the cerebral extraction ratio of sodium fluorescein was totally blocked by phenoxybenzamine (25 mg/kg i.p., 24 h before noradrenaline). Noradrenaline (150 µg) significantly increased the pinocytotic activity of cerebral endothelial cells. Phenoxybenzamine (as above) reduced the effect of noradrenaline on pinocytosis.It is concluded that noradrenaline increases the blood-brain barrier's permeability to sodium fluorescein, most probably through an effect on alpha adrenoceptors. The increase induced in the blood-brain barrier's permeability by noradrenaline seems to be due, at least in part, to an increase in the pinocytotic activity of endothelial cells. Send offprint requests to A. Sarmento at the above address     

Survival after first recurrence of breast cancer. The Miami experience.

BACKGROUND. Four hundred thirty-three patients with recurrent breast cancer were treated by the authors at a large medical breast oncology facility from 1976-1982. The median survival time from first relapse (MSFR) for the 193 patients whose survival experience was not confounded by lead-time bias was 26 months. This MSFR is similar to that of most series published in the 1970s and 1980s and is approximately double that of series published in the 1960s. METHODS. In this series, regression analysis identified disease-free interval (DFI), estrogen receptor (ER) status, and dominant disease site as significant prognostic variables, similar to other published series. RESULTS. In 113 patients with known ER values, DFI, and dominant metastatic sites, a prognostic spectrum of MSFR patterns was identified among combinations of these three variables. The MSFR ranged from 15 months for poor risk patients with negative ER values, visceral dominant sites, and DFI of less than 24 months, to more than 90 months for good risk patients with positive ER values, soft tissue dominant sites, and DFI of more than 24 months. Although menopausal status alone was not a significant prognostic variable in regression analysis, 66% of premenopausal patients had a constellation of "poor" prognostic variables. CONCLUSIONS. This type of prognostic factor analysis at first relapse could help identify subsets of patients who might be considered for aggressive investigational therapies such as high-dose chemotherapy with autologous bone marrow reconstitution.     

Microcystin production by Radiocystis fernandoi (Chroococcales, Cyanobacteria) isolated from a drinking water reservoir in the city of Belém, PA, Brazilian Amazonia region.

During the monitoring of toxic cyanobacteria in the Utinga Reservoir, which is the main drinking water supply for the city of Belém, PA, Brazil, a Radiocystis fernandoi strain (SPC714) was isolated. This non-axenic strain was submitted to a toxicity bioassay with mice and microcystin production analyzed by HPLC-DAD. The species was identified based on cultured and natural preserved material. Morphometric, developmental and reproductive characteristics were analyzed. The strain was cultured in liquid ASM-1 medium, at 25+/-1 degrees C, at an incident irradiance of 20 micromol photon m(-2)s(-1) and constant aeration. At the end of the exponential growth phase, cells were lyophilized and submitted to toxicity tests. The strain showed high toxicity to mice, by intraperitoneal route, with an approximate LD100 of 60 mg kg(-1) of body weight, producing characteristic symptoms of hepatotoxicity. Analyses performed by HPLC-DAD confirmed the production of microcystins, in a concentration of 3.83 microg mg(-1) of lyophilized cells. This is the first reference related to the toxicity of the genus Radiocystis.     

Induction of partial protection in mice after oral administration of Lactococcus lactis producing Brucella abortus L7/L12 antigen.

The Brucella abortus ribosomal protein L7/L12 is an immunodominant antigen and an interesting candidate for the development of oral live vaccines against brucellosis. Here, a recombinant Lactococcus lactis strain producing L7/L12 under the control of nisin inducible promoter was orally administered to BALB/c mice. Significant levels of anti-L7/L12 specific IgA detected in feces revealed an induced local humoral immune response. However, serum analysis did not reveal any anti-L7/L12 antibodies suggesting the absence of a systemic response. Nevertheless, the vaccinated mice showed a partial protective immunity against B. abortus virulent strain (S2308) challenged by intraperitoneal inoculation.     

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol -blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.     

SIMULTANEOUS OCCURRENCE OF ADVANCED NEUROBLASTOMA AND ACUTE MYELOID LEUKEMIA

The authors report the case of a 4-year-old boy with a diagnosis of stage IV neuroblastoma (NB), who had been treated with 6 cycles of cyclophosphamide, doxorubicin, cisplatin, and etoposide for 12 months. The patient reached partial remission and presented a diagnosis of acute myelomonocytic leukemia (M4 AML), confirmed by immunophenotyping. After 2 months of therapy for leukemia, the child died with both malignancies in activity. A necropsy histologically confirmed the simultaneity of the two diseases. The authors review the possibilities of this association. The review leads to the conclusion that AML can occur as a secondary malignancy after the onset of the neuroblastoma, or be suggested by a misdiagnosis. The simultaneous occurrence of both as described here is not, however, found in the literature, to the best of the authors' knowledge.     

Fair Play Game: a group contingency strategy to increase students' active behaviours in physical education

A dependent group contingency strategy called Fair Play Game was applied to promote increase in number of steps during physical education classes for sixth-grade students. Results from a multiple baseline design across three classes showed that the mean number of steps for baseline vs. intervention were: Class 1: 43 vs. 64 steps/minute; Class 2: 49 vs. 81 steps/minute; Class 3: 50 vs. 87 steps/minute. Visual inspection of the graphs showed that Class 1 had an upward trend of number of steps (baseline vs. intervention) without a change in level. Classes 2 and 3 demonstrated clearer change in level of number of steps between these two phases. Social validity data showed that students increased their engagement in class and Fair Play Game is a feasible and acceptable strategy. Therefore, it can be concluded that Fair Play Game appeared to be associated with students' increase in active behaviours in physical education lessons.