Age-dependent effect of cholinergic lesion on dendritic morphology in rat frontal cortex

Previously, we demonstrated that plasticity of frontal cortex is altered in aging rats: 3 months after surgery, excitotoxic lesions of the nucleus basalis magnocellularis (NBM) produce larger declines in dendritic morphology in frontal cortex of aged rats relative to young adults. To determine whether the differential effect of the lesion was due specifically to loss of cholinergic input from the NBM, we assessed dendritic morphology in frontal cortex after specific cholinergic depletion in young adult, middle-aged, and aged male rats. Rats received unilateral sham or 192-IgG-saporin lesions of the NBM. Two weeks after surgery, brains were stained using a Golgi-Cox procedure. Dendritic morphology was quantified in pyramidal neurons in layers II-III of frontal cortex. Although lesions altered apical dendrites at all ages, these effects were most pronounced in aged rats. In addition, lesions produced marked atrophy of basilar dendrites in middle-aged and aged rats only. Thus, the differential dendritic atrophy resulting from NBM lesions in aged rats occurs within 2 weeks after lesion, and results specifically from loss of cholinergic innervation.     

Sociotropic cognition moderates stress-induced cardiovascular responsiveness in women through effects on total peripheral resistance, but not cardiac output.

Although cardiovascular disease (CVD) remains the leading cause of mortality in women, few studies have examined the role of psychosocial factors in its development. This study examined the moderating effects of sociotropic cognition (SC), a need for social acceptance and approval, on psychosocial stress-induced cardiovascular responsiveness (CVR) and affect reactivity in women. Sixty-eight normotensive, college-aged females were randomly assigned to a low or high social threat condition. Measures of systolic, diastolic and mean arterial blood pressures (SBP, DBP and MAP, respectively), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR) and negative affect were collected during rest, and under conditions of high vs. low interpersonal threat. A two-step hierarchical regression analysis was performed to predict all response variables (BPs, HR, CO, TPR and affect). Increases in SBP, DBP, MAP, TPR and negative affect were greater in the high threat than low threat condition. Changes in SBP, MAP and TPR positively covaried with SC under conditions of high interpersonal threat, but showed no significant covariation in the low threat condition. The data suggest that an excessive need for social acceptance may contribute to rises in BP through an increase in TPR, but not CO under conditions of high social threat.     

Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of leukocytes by indomethacin and compound BW755C

Arachidonic acid is metabolized via two pathways in leukocytes: cyclo-oxygenase, leading to the stable prostaglandins, and lipoxygenase, leading to hydroxyacids. Indomethacin inhibits the cyclo-oxygenase selectively, whereas compound BW755C (3-amino-1-(m-(trifluoromethyl)phenyl)-2-pyrazoline) inhibits both pathways equally. This offers a possible explanation for the differing activities of these two compounds in inflammatory models in vivo. The patterns of product inhibition by the two compounds support the suggestion that 11-HETE (hydroxy-eicosatetraenoic acid) and 15-HETE can arise by incomplete operation of the cyclo-oxygenase pathway.     

MR imaging with surface coils

The use of specialized coils to improve signal-to-noise ratios in magnetic resonance (MR) imaging is an important innovation. The role of surface coils has not yet been well defined, but it seems likely that they will be routinely used for clinical imaging of the orbit, neck, and spine. Surface coils have important limitations that make other designs, such as "closely coupled" volume coils, attractive for some applications, especially for limb imaging. With improvement in our ability to visualize anatomy with MR imaging, specialized radio frequency coils may provide new imaging capabilities for clinical problems that were not previously considered to be indications for diagnostic imaging.     

Benzodiazepine ligands,nociception and ‘defeat’ analgesia in male mice

Recent studies have indicated that defeat experience induces acute non-opioid analgesia in intruder mice. To investigate the potential involvement of benzodiazepine receptors in this biologically-relevant form of environmentally-induced antinociception, we initially assessed the effects of some benzodiazepine ligands on basal nociception (tail-flick assay). Chlordiazepoxide (5–30 mg/kg), midazolam (0.625–5 mg/kg), diazepam (0.5–4 mg/kg), Ro15-1788 (5–80 mg/kg) and CGS8216 (5 mg/kg) were found to be ineffective in altering basal nociception. However, higher doses of CGS8216 (10–20 mg/kg) induced significant analgesia, an effect also observed with the -carboline derivatives FG7142 (5–20 mg/kg) and DMCM (1–2 mg/kg). Time-course analyses revealed that the onset of CGS8216 analgesia was slower than for FG7142 and DMCM, but that all three drugs produced long-lasting elevations in tailflick latencies. The analgesic effects of FG7142 and DMCM were completely reversed by Ro15-1788 (20 mg/kg) and by chlordiazepoxide (20 mg/kg), suggesting mediation by benzodiazepine receptor mechanisms. Although CGS8216 analgesia was also reversed by Ro15-1788, it was unaffected by chlordiazepoxide; however, diazepam (5 mg/kg) did significantly attenuate the reaction. Further studies indicated that the antinociceptive consequences of defeat experience were dose-dependently blocked by Ro15-1788 (10–40 mg/kg) and by diazepam (0.5–2 mg/kg). Surprisingly, however, neither chlordiazepoxide (5–20 mg/kg) nor midazolam (1.25–2.5 mg/kg) blocked defeat analgesia under present test conditions. Although several issues remain unresolved, present findings would not be inconsistent with the proposal that stimuli associated with the acute stress of defeat experience release an endogenous ligand which acts in an inverse agonist-like manner at benzodiazepine sites.     

L-654,284 a new potent and selective α2-adrenoceptor antagonist

Summary L-654,284 ((2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizine-2-yl)-N-methyl-2-hydroxyethanesulfonamide) was tested in several in vitro and in vivo models for ₂-adrenoceptor antagonist activity and compared to several reference agents. In vitro L-654,284 competed for the binding of ³H-clonidine or ³H-rauwolscine (K _i's 0.8 nM, 1.1 nM) and blocked the presynaptic effects of clonidine in the rat isolated vas deferens (pA₂, 9.1). L-654,284 exhibited marked ₂- vs. ₁-adrenoceptor selectivity in vitro, inhibiting ³H-prazosin binding with a K _i of 110 nM and blocking the effects of methoxamine on the vas deferens with a pA₂ of 7.5. In vivo L-654,284 at 22 nmoles/kg i.v. doubled the ED₅₀ of clonidine to produce mydriasis in rats. Given orally, the potency of L-654,284 in this test was reduced by a factor of 5.5. L-654,284 also potently increased cerebrocortical NE turnover in the rat, another in vivo index of ₂-adrenoceptor blockade in the central nervous system. In the periphery, L-654,284 demonstrated ₂-adrenoceptor selectivity by preferentially blocking the pressor effects of UK 14304 versus those of methoxamine in the pithed rat. Overall, L-654,284 was generally a more potent ₂-adrenoceptor antagonist than RX 781094 with comparable ₂/₁ selectivity and was several times more potent and ₂-selective than WY 26703 or yohimbine. In addition, L-654,284 had better (5–6 times) oral bioavailability than RX 781094 or WY 26703.     

Evaluation of knee extensor mechanism disorders: clinical presentation of 1 12 patients*

Results of physical therapy evaluation of 112 patients with extensor mechanism disorders (chondromalacia patella, infrapatellar tendinitis, and peripatellar pain) are presented. An equal number of male and female patients were evaluated and of the 73 patients with unilateral involvement (65%) there were equal numbers of right and left involved knees. Running was the activity most commonly associated with pain, followed by basketball and tennis. Stairclimbing was painful in 79% of the patients, with ascending being more painful than descending in patients reporting a clear-cut difference. Hamstring and quadriceps tightness was statistically significant relative to the uninvolved limb although clinically, negligible differences were measured. The inferior pole of the patella was the most tender site to palpation, followed by medial peripatellar structures, then lateral sites. Biomechanical malalignment was not detected by the attending therapist in the majority of patients. The authors emphasize careful assessment of flexibility, quadriceps (VMOIVL) imbalance, and biomechanical alignment in performing a thorough evaluation of patients with extensor mechanism disorders. J Orthop Sports Phys Ther 1986;8(5):248-254.     

Physical therapy treatment of knee extensor mechanism disorders: comparison of four treatment modalities*

Fifty-three patients diagnosed as having one of several types of extensor mechanism disorders of the knee were randomly assigned to one of four treatment groups to assess the effects of one of four different modalities (ice, phonophoresis, iontophoresis, and ultrasound/ice contrast). Following four physical therapy treatments over a 10-day period, the group treated with the ultrasound/ice contrast demonstrated the greatest subjective improvement (47%). The pre- to post-treatment isometric strength resulted in a 28% improvement in knee extension strength and a 34% improvement in knee flexion strength. The authors emphasize that evaluation should include assessment of quadriceps tone and strength as well as careful palpation to determine the irritable structures. Ultrasound/ice is advocated as the most effective choice of the modalities tested for treatment of pain associated with extensor mechanism disorders. J Orthop Sports Phys Ther 1986;8(5):255-259.     

Variation in acute fluid resuscitation among pediatric burn centers

BackgroundAccurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates.MethodsFive pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received.ResultsDifferences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers’ resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35 ml/kg/% TBSA, p < 0.001), (4.90 versus 6.35 ml/kg/TBSA, p = 0.002) and (3.38 versus 6.35 ml/kg/TBSA, p < 0.0001).ConclusionsThis variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.