Comparison of angiotensin II-induced blood pressure and structural changes in Fischer 344 and Wistar Kyoto rats

1. The purpose of the present study was to evaluate the blood pressure (BP) response, the BP and heart rate (HR) components of the startle reaction and the structure of the carotid artery and the aorta during chronic infusion of angiotensin (Ang) II in Fischer 344 (F344) compared with Wistar Kyoto (WKY) rats, two in-bred normotensive contrasted strains. 2. Osmotic mini-pumps filled with saline vehicle or AngII (120 ng/kg per min) were implanted subcutaneously in 8-week-old normotensive rats and infused for 4 weeks in F344 rats (saline, n = 10; AngII, n = 10) and WKY rats (saline, n = 10; AngII, n = 9). Basal BP, HR and the responses to an acoustic startle stimulus (duration 0.7 s, 115 dB) were recorded in conscious rats. The structure of the carotid artery and aorta was determined in 4% formaldehyde-fixed arteries. 3. Compared with WKY rats, vehicle-treated F344 rats had lower bodyweight (BW; 266 +/- 7 vs 299 +/- 9 g; P < 0.05) and heart weight (0.80 +/- 0.02 vs 0.98 +/- 0.04 g; P < 0.05) and higher aortic systolic BP (SBP; 131 +/- 1 vs 123 +/- 5 mmHg; P < 0.001) and diastolic BP (98 +/- 3 vs 89 +/- 2 mmHg; P < 0.001). In F344 rats, compared with the WKY rats, the wall thickness/BW ratio was increased in the carotid artery (156 +/- 9 vs 131 +/- 6 nm/g; P < 0.05) and abdominal aorta (264 +/- 13 vs 217 +/- 12 nm/g; P < 0.05) and decreased in the thoracic aorta (246 +/- 13 vs 275 +/- 8 nm/g; P < 0.05). There was no difference in elastin and collagen density. Angiotensin II differentially enhanced BP in both strains: (SBP: 163 +/- 5 and 132 +/- 4 mmHg in F344 and WKY rats, respectively; P(strain x treatment) < 0.05). Circumferential wall stress was increased in the aorta of F344 rats compared with WKY rats (1176 +/- 39 vs 956 +/- 12 kPa (P < 0.001) and 1107 +/- 42 vs 813 +/- 12 kPa (P < 0.001) in thoracic and abdominal aortas, respectively). The startle response was amplified in F344 rats, with enhanced increases in SBP and pulse pressure (PP) and bradycardia compared with responses of WKY rats (+44 +/- 9 mmHg, +10 +/- 2 mmHg and -40 +/- 17 b.p.m., respectively, in F344 rats vs+28 +/- 4 mmHg, + 4 +/- 2 mmHg and -19 +/- 10 b.p.m. in WKY rats, respectively; P(strain) < 0.05 for BP and PP). The startle response was not affected by AngII. 4. These results indicate a higher BP producing an increase in wall thickness in F344 rats compared with WKY rats. We propose that an increase in sympathetic nervous activity causes these haemodynamic differences, as suggested by the excessive increase in BP during an acoustic startle stimulus. Angiotensin II increased BP in F344 rats, but did not exaggerate the increase in BP during the startle reaction.     

Non-human primate models of childhood psychopathology: the promise and the limitations

Although non-human primate models have been used previously to investigate the neurobiology of several sensory and cognitive developmental pathologies, they have been employed only sparingly to study the etiology of childhood psychopathologies for which deficits in social behavior and emotion regulation are major symptoms. Previous investigations of both adult human and non-human primates have indicated that primate social behavior and emotion are regulated by a complex neural network, in which the amygdala and orbital frontal cortex play major roles. Therefore, this review will provide information generated from the study of macaque monkeys regarding the timing of normal social and emotional behavior development, the normal pattern of anatomical and functional maturation of the amygdala and orbital frontal cortex, as well as information regarding the neural and behavioral effects of early perturbations of these two neural structures. We will also highlight 'critical periods' of macaque development, during which major refinements in the behavioral repertoire appear to coincide with significant neural maturation of the amygdala and/or orbital frontal cortex. The identification of these 'critical periods' may allow one to better predict the specific behavioral impairments likely to appear after neonatal damage to one or both of these neural areas at different time points during development. This experimental approach may provide a new and important way to inform and stimulate research on childhood psychopathologies, such as autism, schizophrenia and Williams syndrome, in which the development of normal social skills and emotional regulation is severely perturbed. Finally, the promise and limitations inherent to the use of non-human primate models of childhood psychopathology will be discussed.     

Posterior tibial tendon and subtalar joint complex in rheumatoid arthritis: magnetic resonance imaging study

OBJECTIVE: To observe by magnetic resonance imaging (MRI) the pathologic changes in the posterior tibial tendon (PTT), subtalar joint complex (STJC), and sinus tarsi in patients with rheumatoid arthritis (RA), and if possible to determine their involvement in the course of the disease. METHODS: Sixty-seven rheumatoid feet with mid and hindfoot pain underwent MRI with gadolinium injection. Localized enhancement and anatomic lesions were assessed in the 3 sites. RESULTS: On MRI, PTT involvement was seen to be more frequent than STJC or sinus tarsi. When there was gadolinium enhancement of the PTT there was no sinus tarsi enhancement (p = 0.014). Interosseous talocalcaneal ligament rupture was correlated with disability (p = 0.031). CONCLUSION: In RA patients with hindfoot pain, PTT synovitis is observed when there is no sinus tarsi synovitis.     

Observations on the function of the female urethra: I: relation between maximum urethral closure pressure at rest and urethral hypermobility

AIMS: To study the relation between maximum urethral closure pressure at rest and urethral hypermobility in female patients. PATIENTS AND METHODS: We selected 255 patients aged 20 years and older, with a stable bladder on multichannel urodynamics, without known neurological pathology, and without a history of pelvic or anti-incontinence surgery. A resting urethral pressure profile and the degree of urethral hypermobility were registered. Two-tailed analyses of variance (ANOVA) with Fisher's post-hoc tests were used to detect any statistically significant difference (P < 0.05) in urethral closure pressure between groups with varying degrees of urethral hypermobility. RESULTS: Mean age was 45.6 +/- 12.7 (range 20-77) years. Mean maximum urethral closure pressure for the entire group was 62.7 +/- 29 (range 10-150) cm of water. A statistically significant inverse relationship was found between age and maximum urethral closure pressure (r = 0.489, P < 0.0001) when both analyzed as continuous variables, and with age categorized in 10-year increments (P < 0.0001). When comparing mean urethral closure pressure in each group examined for urethral hypermobility, a statistically significant difference was noted when grades I, II, and III were compared to grade 0 hypermobility. No significant difference was observed when grades I, II, and III were compared to each other. Even if statistically non-significant, there exists an inverse relationship between the degree of urethral hypermobility and the maximum urethral closure pressure: a higher hypermobility is associated with a lesser urethral closure pressure. CONCLUSIONS: Urethral closure pressure falls significantly when urethral hypermobility is present. This decrease is not related to patient's age or parity. Our observations demonstrate an inverse relation between urethral closure pressure and the degree of cysto-urethrocele. As hypermobility increases, closure pressure decreases, even if this decrease does not reach the level of statistical significance.     

Availability of 11-cis retinal and opsins without chromophore as revealed by small bleaches of rhodopsin in excised albino mouse eyes

Small bleaches were used to study the rhodopsin regeneration process. At bleaches from 5.2% to 24.7%, the rhodopsin regenerations were consistent with a one-for-one recovery of bleached molecules. At response saturation rod photoreceptors exhibit a bleach level of only 5%. Major increases in rhodopsin regeneration were observed at bleach levels between 1.3% and 5.2%. The rhodopsin regenerations exhibited a linear relationship that was 4-times the bleach (dark adaptations of 0.75 and 1.5 h). The data show that the bleach initiates the availability, and possibly production, of 11-cis retinal in amounts that are 4-times the number of bleached molecules within the functional range of the rod photoreceptors. Rhodopsin regeneration also requires the presence of opsins without chromophore. Regenerations beyond the bleach indicate the presence of such opsins prior to the bleach. The opsin amounts were 8.1%, 8.6%, 3.1% and 0% of the total visual pigment at dark adaptation times of 0.75, 1.5, 24 and 48 h, respectively. Those opsins, as well as the ones produced by the bleach, may be regenerated to rhodopsin following a small bleach or with additional time in the dark.     

Clinical and economic choices in anaesthesia for day surgery: a prospective randomised controlled trial

We compared the cost-effectiveness of general anaesthetic agents in adult and paediatric day surgery populations. We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups. Total costs were calculated from individual patient resource use to 7 days post discharge. Incremental cost-effectiveness ratios were expressed as cost per episode of postoperative nausea and vomiting (PONV) avoided. In adults, variable secondary care costs were higher for propofol induction and propofol maintenance (propofol/propofol; p < 0.01) than other groups and lower in propofol induction and isoflurane maintenance (propofol/isoflurane; p < 0.01). In both studies, predischarge PONV was higher if sevoflurane/sevoflurane (p < 0.01) was used compared with use of propofol for induction. In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane).     

Prevalence of mutations in AGPAT2 among human lipodystrophies

Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous genetic disease characterized by near absence of adipose tissue and severe insulin resistance. We have previously identified mutations in the seipin gene in a subset of our patients' cohort. Recently, disease-causing mutations in AGPAT2 have been reported in BSCL patients. In this study, we have performed mutation screening in AGPAT2 and the related AGPAT1 in patients with BSCL or other forms of lipodystrophy who have no detectable mutation in the seipin gene. We found 38 BSCL patients from 30 families with mutations in AGPAT2. Three of the known mutations were frequently found in our families. Of the eight new alterations, six are null mutations and two are missense mutations (Glu172Lys and Ala238Gly). All the patients harboring AGPAT2 mutations presented with typical features of BSCL. We did not find mutations in patients with other forms of lipodystrophies, including the syndromes of Lawrence, Dunnigan, and Barraquer-Simons, or with type A insulin resistance. In conclusion, mutations in the seipin gene and AGPAT2 are confined to the BSCL phenotype. Because we found mutations in 92 of the 94 BSCL patients studied, the seipin gene and AGPAT2 are the two major genes involved in the etiology of BSCL.     

Myelin basic protein-reactive T cells induce conduction failure in vivo but not in vitro

The ability of myelin basic protein (MBP)-reactive T cells to induce conduction failure was investigated and. With the model, somatosensory evoked potentials (SEP) were recorded before and during adoptively transferred experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Maximum amplitude SEP were reached within 15 min of anesthesia. During EAE, the SEP decreased considerably and their onset was delayed. However, the compound action potentials (CAPs) recorded from Lewis rat optic nerves incubated with encephalitogenic T cells were not affected, emphasizing the importance of environmental factors. This study shows that the model described here is an useful means of investigating the neurological disorders associated with EAE.     

Reactions to familiar and novel objects in infant monkeys with neonatal temporal lesions

Adult monkeys with late temporal lobe damage are known to touch and mouth objects compulsively, even unknown objects. To determine whether infants with early temporal damage display this symptom as well, 9-month-old rhesus monkeys with neonatal ablations of either the medial temporal lobe or inferior temporal cortex were exposed to four objects, two familiar and two novel. All operated infants were less active/more withdrawn than controls and showed neither exaggerated object manipulation nor hyperorality. Furthermore, like controls, they touched novel objects less than they touched familiar ones. Thus, infants with neonatal medial or inferior temporal ablations did not display the compulsive exploration evidenced after similar lesions in adulthood and retained some ability to detect novelty despite their known memory impairments.