Capsaicin-like effect of (6)-shogaol on substance P-containing primary afferents of rats: a possible mechanism of its analgesic action.

The effects of (6)-shogaol, a pungent component of dried ginger with a capsaicin-like chemical structure, on the release of immunoreactive substance P from the spinal dorsal horn were examined by in vitro superfusion of the dorsal-half slices of the spinal cord of the rat. (6)-Shogaol (30 microM to 1 mM) increased dose-dependently the release of immunoreactive substance P. The maximum effect of (6)-shogaol was observed at a concentration of 100 microM and less than a half of the effect of 10 microM capsaicin. The effect of (6)-shogaol (100 microM) was attenuated in slices from rats with dorsal rhizotomy and abolished by elimination of calcium ions from the perfusion medium. Pretreatment with (6)-shogaol in vitro inhibited the capsaicin-evoked release of immunoreactive substance P. On the other hand, systemic administration of (6)-shogaol (160 mg/kg) produced antinociception in rats, with a peak effect between 15 and 30 min and a smaller dose of 80 mg/kg was without effect. Treatment of rats with (6)-shogaol, at a dose of 160 mg/kg but not at 80 mg/kg, for 20 min significantly decreased release of immunoreactive substance P, evoked by capsaicin (10 microM), from the slices of cord. These data suggest that (6)-shogaol shares the sites of action with capsaicin, on the terminals of substance P-containing primary afferents, to release of the neuropeptide and inhibit the release of substance P, by subsequent stimulation of the primary afferents. The latter action of (6)-shogaol might be relevant to its analgesic effect.     

Primary pulmonary valve papillary fibroelastoma

Papillary fibroelastoma (PFE) is a rare and benign cardiac tumor typically found on the valvular endocardium. In most cases, PFE is identified incidentally on echocardiography or during cardiac surgery. The patient was a 73-year-old man who had been treated for hepatocellular carcinoma for 5 years. On echocardiography, a 2.5-cm diameter mass was detected in the pulmonary trunk just above the pulmonary valve. Through a transpulmonary arterial approach with cardiopulmonary bypass, the mass identified on the commissure of the right and posterior pulmonary cusp was surgically excised together with the attached endocardium. Despite the benign histology of PFE, lethal embolic events such as stroke, myocardial infarction, and pulmonary embolism are reported in some cases. To prevent such complications, tumor identification and surgical excision are essential.     

Delayed onset massive oedema and deterioration in traumatic brain injury.

A 52-year-old man fell from standing and a computed tomography (CT) scan revealed traumatic intracerebral haematoma and subarachnoid haemorrhage in the temporal cortex. He was treated without surgery and discharged. On day 30 after the accident, he had no neurological deficit. On day 37 he complained of headache and urinary incontinence, and on day 39 he was hospitalized due to progressive neurological deterioration (reduced conciousness, dilated pupils, and left hemiplegia). A CT scan revealed a diffuse low-density in the right cerebral hemisphere with marked midline shift. Emergency decompressive craniectomy and right temporal lobectomy were performed. Angiography after surgery revealed moderate vasospasm in the right middle and anterior cerebral arteries. The patient remained severely disabled. Delayed onset neurological deterioration can be caused by brain oedema and vasospasm after traumatic brain injury, despite an intervening period of improvement.     

Heart Transplantation in a 68-Year-Old Patient with Senile Systemic Amyloidosis

Senile systemic amyloidosis (SSA) results from deposition, predominantly in the heart, of amyloid fibrils derived from wild-type transthyretin (T TR) molecules. Cardiac autopsies indicate that SSA progressively increases in subjects 80 years of age and older. However, only a few cases of patients with SSA and cardiac failure have been recognized by cardiac biopsies during life. Here, we report a case of heart transplantation in a 68-year-old male patient with SSA. After cardiopulmonary resuscitation in October 1998, he underwent complete evaluation. Myocardial biopsies revealed the presence of amyloid deposition. Immunohistochemical staining of the amyloid indicated T TR. Genomic DNA analysis of the T TR exons did not result in any identification of a mutation. In 2001, heart transplantation was performed because progressive heart failure occurred. At the 1-year follow-up, no amyloid deposits were found in the donor heart. At the 2-year follow-up, the patient's physical and mental health was excellent. We conclude that heart transplantation can be an effective treatment in progressive heart failure due to SSA.     

Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.     

Force-time parameters during explosive isometric grip correlate with muscle power

Although explosive isometric contraction provides little work toward the outside, force-time parameters of the rising phase of the force-time curve may be able to predict muscle power. The purpose of this study was to examine the relationship between muscle power with work (power grip) and force-time parameters during the rising phase in explosive isometric grip. Fifteen healthy young adult males participated in this study. Power grip was measured using loads of 20%–50% of maximal voluntary contraction (MVC) (peak isometric force). Subjects pulled explosively on a grip bar held with the second digital joints without the thumb. Peak power was calculated from peak velocity and load. Explosive isometric grip was measured using a hand dynamometer. Time-series data of both tests were sampled by an analog-to-digital interface. Both tests were performed with the subjects seated with a sagittal and horizontal position of the arm supported by an armrest. Peak power in the power grip test tended to be larger with an increase of the load, but there was no significant difference between 40% and 50% MVC. Only the peak power in 50% MVC significantly correlated with peak grip force (r=0.52, p<0.05). The force-time parameters related to the peak rate of the rising force phase in explosive isometric grip significantly correlated with the peak powers (30%–50% MVC, r=|0.58−0.78|). Peak rate of the rising force phase in explosive isometric grip may be useful for predicting muscle power with loads between 30%–50% MVC.