Meningeal cells influence cerebellar development over a critical period

Summary We have investigated the influence of meningeal cells on the development of the cerebellum by destroying these cells with 6-hydroxydopamine in hamsters of different ages. The ensuing foliation and lamination disruption in the cerebellar vermis is attributed to a disintegration of the cerebellar surface and a disorganization of the glial scaf-fold of the cerebellar cortex due to a loss of meningeal-glial interaction in stabilizing the extracellular matrix at the glia limitans superficialis (v. Knebel Doeberitz et al. 1986, Neuroscience 17:409–426). The severity of these cerebellar defects is correlated with the ontogenetic stage at which meningeal cells are destroyed, being greatest after treatment at postnatal day 1 and decreasing thereafter until day 5 and beyond, when no abnormalities occur, although all meningeal cells are destroyed throughout. The absence of cerebellar defects after destruction of meningeal cells at day 5 or later is associated firstly with the end of the period of branching morphogenesis of the cerebellum when all folial primordia are established, and, secondly, with the maturation of the glia limitans superficialis. These findings indicate that meningeal cells stabilize the cerebellar surface and glial scaffold over a critical period that ends, when the pattern of cerebellar foliation is established, and when the glia limitans superficialis has reached a mature state. Beyond this stage glial end-feet alone are sufficient to maintain the epithelial integrity of the cerebellum.     

Drinking to intracellular dehydration following vagotomy in rats

Abdominally vagotomized rats maintained on a solid diet drank less and had longer latencies to drink than sham vagotomized rats following IP injection of an osmotic load (0.75 M NaCl, 1% BW). However, these two groups did not differ in latency or water intake following injection of isotonic saline. Since both vagotomized and control rats drank more water and had shorter latencies following injection of hypertonic saline than after isotonic saline, vagotomy apparently attenuated but did not abolish osmotic drinking. Maintenance on a liquid diet and a brief fast prior to testing (to ensure an empty stomach) did not alter these results, indicating that the impairment of gastric emptying of solid food that accompanies total abdominal vagotomy cannot account for the attenuation of osmotically induced drinking. Furthermore, this deficit was seen even when intracellular dehydration was produced at different times during the circadian cycle and when water presentation was delayed 0.5 hr postinjection. In addition, vagotomized rats drank less than control rats following 16-hr water deprivation and exhibited a lower water-food ratio on ad lib regimen. However, vagotomized and sham vagotomized rats exhibited the same relative day-night difference in water consumption as well as short latency response to thermal pain, which with other results indicates that vagotomy did not result in a general impairment of behavior. These findings suggest that osmotic perturbations are detected by the viscera and the information conveyed to the brain via afferent vagus nerves.     

IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis

The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2 cytokine production and eosinophilia. The scope of the present study was to directly elucidate the role of interleukin-5 (IL-5) and eosinophils in controlling the development of L. sigmodontis after vaccination and in primary infection. BALB/c mice immunized with irradiated third-stage larvae (L3) were confirmed to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppressed both blood and tissue eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive filarial infection, that IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected mice, anti-IL-5 treatment did not modify filarial infection within the 1st month, most likely because during primary infection IL-5-dependent mechanisms such as subcutaneous eosinophilia are induced too late to disturb worm establishment. However, there is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsulation is also under the control of IL-5. Received: 30 March 2000     

HIV protease inhibitors and dyslipidemia

Highly active antiretroviral therapy (HAART) significantly prolongs the lives of HIV-infected patients. Current regimens may consist of a protease inhibitor (PI) combined with at least two or more other antiretroviral drugs. PI administration has been shown to be associated with alterations in plasma lipids (i.e. prompt and sustained increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides) and insulin levels that place PI-treated patients at risk for coronary heart disease (CHD). Because PI-associated dyslipidemia is generally asymptomatic and occurs in patients who are often younger than those traditionally at risk for CHD, the need for primary prevention of acute coronary events in these patients is often unappreciated. Statins form a significant component of pharmacotherapy for PI-associated dyslipidemia. However, because PIs and all statins except pravastatin are metabolized by the cytochrome P450 (CYP) system, co-administration of these agents produces a significant risk of drug interactions and statin-induced hepatotoxicity and myopathy. This risk can be greatly reduced by administering a statin not metabolized by CYP. The need for lipid reduction therapy may be minimized with the use of new PIs that are comparable in efficacy to current PIs but do not negatively affect lipid levels.     

The effect of erroneous responses on response monitoring in patients with major depressive disorder: a study with event-related potentials

Perceived failure is reported to have detrimental effects on subsequent performance in patients with major depressive disorder. We investigated the error-related negativity (ERN)/error negativity (Ne), an electrophysiological correlate of response monitoring, using a 64-channel EEG. Sixteen patients with DSM-IV major depressive disorder and 16 matched controls participated in an Eriksen flanker task with continuous performance feedback that signaled monetary reward. Compared to controls, patients with major depressive disorder showed a less negative ERN/Ne in error trials following error trials. This result might reflect impaired response monitoring processes in major depressive disorder resulting from an underactivity in a central reward pathway and/or a deficit in strategic reasoning.     

In vivo autofluorescence imaging of early cancers in the human tracheobronchial tree with a spectrally optimized system

The changes in the autofluorescence characteristics of the bronchial tissue is of crucial interest as a cancer diagnostic tool. Evidence exists that this native fluorescence or autofluorescence of bronchial tissues changes when they turn dysplastic and to carcinoma in situ. There is good agreement that the lesions display a decrease of autofluorescence in the green region of the spectrum under illumination with violet-light, and a relative increase in the red region of the spectrum is often reported. Imaging devices rely on this principle to detect early cancerous lesions in the bronchi. Based on a spectroscopic study, an industrial imaging prototype is developed to detect early cancerous lesions in collaboration with the firm Richard Wolf Endoskope GmbH, Germany. A preliminary clinical trial involving 20 patients with this spectrally optimized system shows that the autofluorescence can help to detect most lesions that would otherwise have remained invisible to an experienced endoscopist under white light illumination. A systematic off line analysis of the autofluorescence images pointed out that real-time decisional functions can be defined to reduce the number of false positive results. Using this method, a positive predictive value (PPV) of 75% is reached using autofluorescence only. Moreover, a PPV of 100% is obtained, when combining the white light (WL) mode and the autofluorescence (AF) mode, at the applied conditions. Furthermore, the sensitivity is estimated to be twice higher in the AF mode than in WL mode.     

Maternal behavior is related to prepartum urinary estradiol levels in red-bellied tamarin monkeys

This is the first study in a primate, the red-bellied tamarin (Saguinus labiatus), to demonstrate a correlation between urinary estradiol during late pregnancy and postpartum infant-directed behavior. Females were defined as good (N = 6) or poor (N = 6) mothers, and were selected so that both groups contained 3 females with and 3 without prepubertal experience with infants. Females with prepubertal experience of infants were defined as good or poor mothers if 2 or less than 2 infants survived one week, respectively; females without such experience were defined as good or poor mothers if at least 1, or 0 infants survived one week, respectively. Five of the six good mothers had 2 surviving infants; 10 of the 13 infants of poor mothers died at day 0. Prepartum urinary total estradiol concentrations were constant in good mothers (5-4 weeks prepartum: 32.29 +/- 3.65 micrograms/mg creatinine; 1 week prepartum: 33.76 +/- 5.02 micrograms/mg CR.; p greater than 0.98), but declined significantly in poor mothers (5-4 weeks prepartum: 38.34 +/- 7.07 micrograms/mg Cr.; 1 week prepartum: 18.35 +/- 4.72 micrograms/mg Cr.; p less than 0.0004). At 1 week prepartum, estradiol was significantly higher in good mothers (p less than 0.03). When analysed separately, only good and poor mothers without prepubertal experience of infants had significantly different urinary estradiol concentrations. In the 2-hour postpartum period, good mothers spent more time lick-cleaning (p less than 0.02), carrying and nursing infants; poor mothers rubbed off clinging infants more, their infants spent less time being carried (p less than 0.03), and apparently starved because they had no opportunity to suckle.     

Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest

The automatic external defibrillator is a simple device that can be used by nonprofessional rescuers to treat cardiac arrest. In 1287 consecutive patients with out-of-hospital cardiac arrest, we assessed the results of initial treatment with this device by firefighters who arrived first at the scene, as compared with the results of standard defibrillation administered by paramedics who arrived slightly after the firefighters. Of 276 patients who were initially treated by firefighters using the automatic defibrillator, 84 (30 percent) survived to hospital discharge (expected rate according to a logistic model, 17 percent; P less than 0.001), as compared with 44 (19 percent) of 228 patients when fire-fighters delivered only basic cardiopulmonary resuscitation and the first defibrillation was performed after the arrival of the paramedic team. Few patients with conditions other than ventricular fibrillation survived. In a multivariate analysis of characteristics that influenced survival after ventricular fibrillation, a better survival rate was related to a witnessed collapse (odds ratio, 3.9; 95 percent confidence interval, 2.0 to 7.6), younger age (odds ratio, 1.2; 95 percent confidence interval, 1.0 to 1.4), the presence of "coarse" (higher-amplitude) fibrillation (odds ratio, 4.2; 95 percent confidence interval, 1.6 to 11.0), a shorter response time for paramedics (odds ratio, 1.4; 95 percent confidence interval, 1.0 to 2.1), and initial treatment by firefighters using an automatic external defibrillator (odds ratio, 1.8; 95 percent confidence interval, 1.1 to 2.9). These findings support the widespread use of the automatic external defibrillator as an important part of the treatment of out-of-hospital cardiac arrest, although the overall impact of the use of this device on community survival rates is still uncertain.     

Effects of Behavioral Control and Type A Behavior on Cardiovascular Responses

The purpose of this study was twofold: (a) to examine the relationship between degree of behavioral control and cardiovascular changes in 60 adult males performing an anagram solution task, and (b) to assess the interaction between behavioral control and type of subject (A vs. B). Three conditions were used, differing from each other in the percentage of solvable anagrams (100, 50, and 30%). Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured before, during, and after the anagram task. In all conditions, during-task SBP, DBP, and HR were significantly elevated above baseline. Blood pressure (BP) elevations appeared to be curvilinearly related to degree of behavioral control, i.e., more elevated in the 50% than in the 100% and 30% conditions. HR changes did not differ among conditions. Concerning the Type A behavior pattern, the results revealed significantly greater BP elevations for Type A than for Type B subjects, especially in the 50% condition, thereby confirming that the physiologic correlates of Type A behavior are predominantly evoked in challenging circumstances. Findings were discussed in the light of results of cardiovascular and endocrinological research. Consideration was given to the possible role of disengagement in the 30% condition and to differences in the pattern of responding between As and Bs.