Alterations in epithelial glycocalyx of rabbit uteri during early pseudopregnancy and pregnancy,and following ovariectomy

Pseudopregnant, pregnant, and ovariectomized rabbits were utilized to study hormonal mediation of uterine epithelial surface negativity and glycocalyx morphology, and to seek local effects of blastocysts at sites of implantation. A loss of surface negativity [polycationic ferritin (PCF) binding] by day 6 of pregnancy or pseudopregnancy was noted, accompanied by alterations in epithelial glycocalyx. Uteri from estrous animals, or ovariectomized animals receiving oil or estradiol injections, bound PCF and exhibited a “globular” glycocalyx. Uteri from day 6 pseudopregnant or pregnant animals, or ovariectomized animals receiving progesterone injections, did not bind PCF or exhibit a globular glycocalyx. Both PCF binding and the globular character of the epithelial glycocalyx were sensitive to neuraminidase and trypsin treatment, suggesting sialoglycoprotein contribution to surface negativity. Implanting blastocysts had no detectable local effect on surface negativity, but did induce local reduction of epithelial glycocalyx at sites of implantation. Results of this study suggest that uterine epithelial glycocalyx alterations during the preimplantation period reflect a general response to prosgesterone stimulation, primarily qualtitative in nature, related to the acquisition of receptivity to ovo-implantation.     

Numerical simulation of aerosol particle transport by oscillating flow in respiratory airways

Particle transport by oscillating flow in a tapered channel or in a tapered tube was computed from the complete equations of motion. These geometries represent a simplified model of the divergent flow field of the mammalian bronchial tree. The computed deformation profile of a line of particles, transported by the oscillatory motion, was compared with prior experimental results and analytical calculations. All three methods agree that there is transport in the divergent direction of the tube by an axial stream of steady drift in the core for moderately high frequency of oscillation (Womersley parameter in the range of 1 to 10). Bidirectional flow is established by an annular stream in the convergent direction, with no net flow on integral cycles of the oscillating fluid. At higher frequency, however, the steady stream transforms to a different shape in the tapered tube, with transport in the divergent direction nearer the walls of the tube, rather than in the core. Transport by the continuing streams with oscillatory ventilation of the respiratory tract should deliver medicinal aerosols of low intrinsic particle mobility to the peripheral regions of the lungs.     

Role of Peripheral Adrenergic Responsiveness in the Development of DOCA/NaCl Hypertension in Rats

Alterations in - and -adrenergic responsiveness were investigated prior to and during the development of hypertension in rats treated with desoxycorticosterone acetate and NaCl (DOCA/ NaCl). The DOCA/NaCl rats became noticeably hypertensive (> 150 mm Hg) six weeks after the initiation of treatment. Prior to the development of hypertension, a reduced in vivo and in vitro - and an enhanced -adrenergic responsiveness of the DOCA/NaCl group resulted. At 2 and 12 weeks of the study, the dipsogenic response to isoproterenol was significantly attenuated in the DOCA/NaCl rats, whereas no difference in the dipsogenic response to 24 hour water deprivation was observed between control and DOCA/NaCl rats. Isoproterenol-induced relaxation of aortic smooth muscle from the DOCA/NaCl treated rats was significantly reduced at 4 weeks and further attenuated at 12 weeks of the study. However, aortic smooth muscle sensitivity to norepinephrine stimulation was significantly increased at 4 and 12 weeks of the study. These results suggest that alterations in both in vivo and in vitro - and -adrenergic responsiveness occur prior to establishment of hypertension of the DOCA/NaCl rats and that these alterations may have a role in the early stages of the development of this form of hypertension.     

Chemonucleolysis. A ten-year retrospective study

An 11.8-year median follow-up evaluation of 42 "ideal" patients who had chemonucleolysis was obtained by examination, questionnaire, and roentgenograms. The excellent and good rating of this group was 81%, as compared to the total of 135 patients previously evaluated at 42 months and showing 85.2%. No complications were noted. Disc space rewidening, after initial narrowing, was observed in eight patients and 26% of all discs injected. While all who showed rewidening had excellent results, widening was not necessary to achieve an excellent rating. Marked narrowing and sclerosis of intervertebral margins were seen in many excellent and good clinical results. Chemonucleolysis represents a viable option as definitive treatment for a herniated nucleus pulposus in carefully selected patients.     

急性心肌梗死早期QT间期JT间期离散度与近期严重心律失常的关系

目的 :探讨AMI早期QT间期离散度、JT间期离散度与严重心律失常的关系。方法 :测定 46例AMI患者心梗发生后第 3d的QT间期离散度 (QTd)和JT间期离度 (JTd)。并与30例正常人的对照组比较。结果 :AMI组QTd、JTd、QTcd较对照组显著增大 (P <0 0 1 )。住院期间严重室性心律失常发生组 (1 8例 )的QTd、JTd、QTcd较无严重室性心律失常组 (2 8例 )明显增大 (P <0 0 1 ) ,且发生室颤的 9例患者QTd、JTd、QTcd比无室颤的明显增大 (P <0 0 1 )。结论 :早期测定AMI患者QTd、JTd、QTcd对患者近期严重室性心律失常的发生有预测意义     

Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents

1. Gabapentin (neurontin) is a novel antiepileptic agent that binds to the α₂δ subunit of voltage-dependent calcium channels. The only other compound known to possess affinity for this recognition site is the (S)-(+)-enantiomer of 3-isobutylgaba. However, the corresponding (R)-(−)-enantiomer is 10 fold weaker. The present study evaluates the activity of gabapentin and the two enantiomers of 3-isobutylgaba in formalin and carrageenan-induced inflammatory pain models.
2. In the rat formalin test, S-(+)-3-isobutylgaba (1–100 mg kg⁻¹) and gabapentin (10–300 mg kg⁻¹) dose-dependently inhibited the late phase of the nociceptive response with respective minimum effective doses (MED) of 10 and 30 mg kg⁻¹, s.c. This antihyperalgesic action of gabapentin was insensitive to naloxone (0.1–10.0 mg kg⁻¹, s.c.). In contrast, the R-(−)-enantiomer of 3-isobutylgaba (1–100 mg kg⁻¹) produced a modest inhibition of the late phase at the highest dose of 100 mg kg⁻¹. However, none of the compounds showed any effect during the early phase of the response.
3. The s.c. administration of either S-(+)-3-isobutylgaba (1–30 mg kg⁻¹) or gabapentin (10–100 mg kg⁻¹), after the development of peak carrageenan-induced thermal hyperalgesia, dose-dependently antagonized the maintenance of this response with MED of 3 and 30 mg kg⁻¹, respectively. Similar administration of the two compounds also blocked maintenance of carrageenan-induced mechanical hyperalgesia with MED of 3 and 10 mg kg⁻¹, respectively. In contrast, R-(−)-3-isobutylgaba failed to show any effect in the two hyperalgesia models.
4. The intrathecal administration of gabapentin dose-dependently (1–100 μg/animal) blocked carrageenan-induced mechanical hyperalgesia. In contrast, administration of similar doses of gabapentin into the inflamed paw was ineffective at blocking this response.
5. Unlike morphine, the repeated administration of gabapentin (100 mg kg⁻¹ at start and culminating to 400 mg kg⁻¹) over 6 days did not lead to the induction of tolerance to its antihyperalgesic action in the formalin test. Furthermore, the morphine tolerance did not cross generalize to gabapentin. The s.c. administration of gabapentin (10–300 mg kg⁻¹), R-(−) (3–100 mg kg⁻¹) or S-(+)-3-isobutylgaba (3–100 mg kg⁻¹) failed to inhibit gastrointestinal motility, as measured by the charcoal meal test in the rat. Moreover, the three compounds (1–100 mg kg⁻¹, s.c.) did not generalize to the morphine discriminative stimulus. Gabapentin (30–300 mg kg⁻¹) and S-(+)-isobutylgaba (1–100 mg kg⁻¹) showed sedative/ataxic properties only at the highest dose tested in the rota-rod apparatus.
6. Gabapentin (30–300 mg kg⁻¹, s.c.) failed to show an antinociceptive action in transient pain models. It is concluded that gabapentin represents a novel class of antihyperalgesic agents.