Mapping the rat somatosensory pathway from the anterior cruciate ligament nerve endings to the cerebrum

The anterior cruciate ligament (ACL) serves as the primary restraint to anterior tibial translation. In addition to this biomechanical function, the ACL appears to have a function in neuromuscular control. This hypothesis was formulated after the discovery of mechanoreceptors within the ACL. The full somatosensory pathway from the ACL to the cerebrum has yet to be elucidated. In order to map this sensory pathway, we conducted a viral trans-synaptic tracing experiment using the neurotropic pseudorabies virus (PRV). The pseudorabies virus was injected into the ACL of rats and allowed to replicate and spread trans-synaptically for 6-7 days. The brain and spinal cord of each sacrificed rat was then removed and processed immunohistochemically to detect the presence of PRV. PRV-immunoreactive neurons were found to be localized in several different regions from the spinal cord to the cerebrum. Four nuclei in the reticular formation of the brain stem demonstrated strong positive labeling: the mesencephalic reticular nucleus, magnocellular reticular nucleus, paragigantocellular reticular nucleus, and gigantocellular reticular nucleus. This finding suggests that the nerve endings of the rat ACL project into the cerebrum and that the reticular formation may play an important role in the afferent pathway of those nerve endings.     

Hyperbaric oxygenation therapy enhances the protective effect of moderate hypothermia against forebrain ischemia in the gerbil hippocampus.

Moderate hypothermia may have a beneficial effect on the neurological outcome. However, ischemic deterioration such as brain swelling during rewarming has been reported as a notable complication after successful therapeutic cerebral hypothermia. In this study, we investigated the effects of hyperbaric oxygenation during rewarming. Forebrain ischemia was produced in 24 gerbils and sham ischemia in 8 animals. Then ischemia-treated animals were divided into 3 groups, whole-body moderate hypothermia (31 degrees C for 60 min) and hyperbaric oxygenation (HBO2) (2- atmosphere absolute for 60 min using 100% oxygen) during rewarming group (n = 8), moderate hypothermia without HBO2 group (n = 8), and sham treatment without hypothermia and without HBO2 group (n = 8). Both the hypothermia group (77.9 +/- 48.1 neurons per mm, mean +/- SD) and hypothermia + HBO2 group (127.6 +/- 29.7 neurons per mm,) showed significant preservation of CA1 pyramidal neurons in the hippocampus compared to that in the sham treatment group (6.4 +/- 2.7) (p < 0.01). Furthermore, the hypothermia + HBO2 group showed significantly greater preservation of CA1 pyramidal neurons than the hypothermia group (p < 0.05). These results suggest that HBO2 during rewarming preserves the protective effect of hypothermia against ischemic neuronal damage.     

Evaluation of 188 consecutive homografts implanted in pulmonary position after 20 years.

OBJECTIVE: Homografts are considered the gold standard for right ventricular outflow tract reconstruction. Their long-term durability is limited, and alternatives became available. We evaluate their long-term hemodynamic performance to permit comparisons with alternative devices. METHODS: Between 1985 and 2004, 188 homografts were implanted in pulmonary position at our institution. Mean patient age was 24.8 years (range 2 days-75 years); 56 were female and 132 male. Total follow-up time was 1073 years. Fifty-eight percent were Ross procedures (mean age 31.5 years) and 42% were different procedures (mean age 15.6 years); main diagnoses were tetralogy of Fallot (48%), truncus arteriosus (14%), transposition of the great arteries (11%). Twenty-six percent were redo implantations. We evaluated freedom from death, explantation, insufficiency, relevant gradient, degeneration, and the interval between diagnosis of degeneration and therapeutic procedure (therapeutic gap). Results were stratified by indication, age, history, homograft size, and origin. RESULTS: Ten-year-freedom-from explantation was 82% in homografts >19 mm and 45% in smaller ones. Ten-year freedom from degeneration was 68% after Ross procedure and 25% after other operations; it was 83% in patients older than 10 years at implantation and 51% in younger ones. 'Non-Ross-procedure' and 'implantation age below 10 years' were the only independent risk factors for degeneration. The observed trend towards therapeutical gap reduction was not statistically significant. CONCLUSIONS: Homograft implantation in the pulmonary position can be performed with good long-term freedom from explantation. However, freedom from degeneration is a matter of concern. Therefore, alternative valved conduits are required especially for pediatric patients.     

Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol)

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)_n (n = 1 to 11) and cyclo(RGDT)_n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)_n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)₁₁, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)₁₁ exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)_n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)₁₁ was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)₁₁ significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)_n, cyclo(RGDT)_n and PEG-(RGDT)₁₁ inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”).     

Thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat

The topical organization of thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat has been studied using the technique of retrograde axonal transport of horseradish peroxidase. The projections of the posterolateral and posteromedial ventral nuclei (VPL, VPM) to the second somesthetic area (SII) are organized somatotopically. The posterior portion of SII (hindlimb area) receives fibers mainly from the dorsolateral part of VPL, the middle portion of SII (forelimb area) from the ventromedial part of VPL, and the anterior portion of SII (face area) from VPM. These topical projections are more loosely organized and less densely arranged than those to the first somesthetic area. The SII receives a few fibers from the medial geniculate nucleus, particularly its magnocellular and dorsal principal parts, and from the suprageniculate nucleus. The posterior part of SII lying near the secondary auditory area receives many fibers from the medial geniculate and suprageniculate nuclei, and only a few fibers from the lateral central and paracentral nuclei. The fourth somesthetic area (SIV), located in the dorsal bank of the anterior ectosylvian sulcus, receives fibers mainly from the dorsal principal and magnocellular parts of the medial geniculate nucleus, and from the suprageniculate nucleus. The SIV receives a fair number of fibers from VPL and VPM roughly in a somatotopical manner. The posterior portion of SIV receives fibers chiefly from the dorsolateral part of VPL, the middle portion of SIV from the ventromedial part of VPL, and the anterior portion from VPM. In addition, SIV receives a few fibers from the lateral central, paracentral, ventral lateral and ventral medial nuclei. The SIV, together with the most posterior part of SII, forms an auditory area, receiving many fibers from the medial geniculate and suprageniculate nuclei, and a few fibers from the intralaminar nuclei.     

EMG myokymia as a cause of ptosis in hypothyroidism

Ptosis is known to be associated with thyroid disorders. We describe two biochemically corrected hypothyroid patients presenting with isolated bilateral ptosis. EMG of the orbicularis oculi showed continuous grouped motor unit potentials. In the absence of obvious aetiology, it is hypothesised that focal demyelination of terminal branches to the orbicularis oculi may play a role in the generation of the discharges.