Effects of a new dihydropyridine calcium antagonist on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding

The effects of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2- yl)-1,4- dihydropyridine 3-carboxylate (DHP-218), a new dihydropyridine calcium antagonist, on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding to the cardiac muscle and brain membranes were investigated in vitro. Vascular smooth muscles: Calcium-induced contraction of the rat aorta in high K+ solution was inhibited by DHP-218 with the pA2 value of 9.11. The IC50 value for the inhibitory effects of this compound in high K+-induced and phenylephrine-induced contraction was 6.3 nmol/l and 66 nmol/l, respectively. Vasodilatory effects of this drug on various blood vessels of rabbits contracted by high K+ appeared to a similar extent. The onset of the vasodilatory effect was very slow and the recovery rate of vasodilatory response after washout with the bathing solution containing high K+ or phenylephrine was also very slow. Cardiac muscles: Negative chronotropic and inotropic actions were observed at concentrations more than 30 and 100 nmol/l, respectively. Duration of the plateau phase of normal action potential was shortened and the amplitude and duration of slow action potential were reduced at concentrations more than 1 mumol/l. Very high vasculoselectivity was observed. Displacement of [3H]-nitrendipine binding: The pattern of displacement of [3H]-nitrendipine binding by DHP-218 was very similar to that of other 1,4-dihydropyridines but this compound was about 70 times less potent than nifedipine in [3H]-nitrendipine displacement capacity. These results indicate that DHP-218 has specific vasodilatory action due to calcium antagonism, but association and dissociation rates with tissue and receptors were different from those of nifedipine.     

Met-RANTES ameliorates fibrous airway obliteration and decreases ERK expression in a murine model of bronchiolitis obliterans.

OBJECTIVES: Bronchiolitis obliterans (BO) is the main cause of late mortality among long-term survivors of lung transplantation. Chemokine-chemokine receptor (CCR) interaction and subsequent recruitment of infiltrating cells to the graft are early events in the development of chronic rejection of transplanted lungs. The present study investigated whether blockade of chemokine receptors CCR1 and CCR5 with Met-regulated-on-activation, normal T cells expressed and secreted (RANTES), an amino-terminal modified derivative of RANTES/CCL5, affects the development of BO in murine model and we sought to determine the expression of RANTES/CCL5 and their relationship with extracellular signal-regulated kinase (ERK). Materials and Methods: BALB/c mouse tracheas were heterotopically transplanted into C57Black6 recipients and treated for 21 days with either Met-RANTES at 20 microg/day or vehicle. Animals were killed at 21 days after transplantation for histologic examination of ERK expression. RESULTS: RANTES/CCL5 was highly expressed in allografts compare to isografts. Met-RANTES treatment ameliorated fibrous airway obliteration in a mouse model of BO and decreased ERK expression. CONCLUSION: Blockade of chemokine receptors by Met-RANTES ameliorated airway obliteration and decreased ERK expression. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and ERK may be a new molecular target for chronic rejection.     

Double congenital bronchoesophageal fistulae in an adult

We report adult congenital bronchoesophageal fistula with both symptomatic fistula and asymptomatic one. A 56-year-old woman with a history of cough after drinking fluids was diagnosed as bronchoesophageal fistula by upper gastrointestinal series that showed a diverticulum in the middle portion of the esophagus with a fistula between the esophagus and right lower lung. Esophagoscopy revealed an orifice of the fistula located 27 cm from the incisors. Computed tomography showed chronic inflammatory change with bronchiectasis in the S6 segment of the right lung. The patient underwent video assisted thoracic surgery that identified two fistulae without missing a symptomatic one, and both were successfully resected. The fistulae were lined by squamous epithelium and smooth muscle without evidence of malignancy, infection or chronic inflammation that were histologically compatible with congenital fistulae.     

A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy]

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.     

Neuroradiological analysis of small infarcts in deep subcortical structure detected by CT

We studied angiographic findings of 56 patients who were diagnosed as lacunar infarcts in the basal ganglia or deep subcortical white matter based on clinical symptomatology and brain computed tomography. In 26 patients with CT lesions less than 15 mm in diameter, only eight (31%) showed minor angiographic findings. In 30 patients with lesion of 15 mm or more, however, 22 (73%) had abnormal angiographic findings. Fourteen of the 22 patients had minor irregularities, three had 25-75% stenosis, five had 75% less than stenosis at the bifurcation of the common carotid artery or the horizontal portion of the middle cerebral artery. Our findings support the notion that a small lesion on CT can result from an occlusion of the perforating artery itself and a larger lesion is much related to the major vessel or heart diseases, i.e., emboli from the parent artery or heart, obstruction of perforators at their origin by an atheromatous plaque of the horizontal portion of the middle cerebral artery, or terminal zone infarct due to hemodynamically significant stenotic lesion. In patients with a larger deep infarct on CT, further investigation of the arteries in the carotid-axis and heart is important for determination of therapeutic indication.     

Recovery functions of somatosensory vertex potentials in man: interaction of evoked responses from right and left fingers.

Somatosensory vertex potentials (SVPs) were examined in 12 healthy subjects in response to painful electrical stimulation of the finger. SVPs consisted of N1, P1, and N2. The average latencies of the 3 peaks were 150, 225, and 350 msec, respectively. The latency and amplitude of each potential were reproducible for each subject. Recovery functions of the SVPs were analyzed in 10 subjects. A pair of stimuli were delivered to the right or left finger with interstimulus intervals (ISIs) of 50, 100, 150, 200, 350, 500 and 650 msec. SVPs partially recovered with the shortest ISI (50 msec). Full recovery could not be obtained even with the longest ISI (650 msec). Differences in recoveries within 650 msec of ISI were not observed between right and left stimulations. To examine the interaction between SVPs evoked by right and left finger stimulation, recovery functions from prior contralateral finger stimulation were analyzed with the same ISIs. SVP recoveries for right after left or left after right patterns of stimulus delivery were nearly the same as those for ipsilateral ones. It is suggested that SVPs are generated at nearly the same site in the sensory pathway regardless of the side stimulated.     

Treatment of a malignant esophageal fistula with a Gore-Tex-covered flexible nitinol stent

In order to treat fistulated esophageal cancer using a flexible stent, a covered flexible stent was constructed by wrapping a nitinol stent with a thin sheet of Gore-Tex, preserving the stents original advantages of flexibility and a low-profile introducer system. This stent was used to perform standard radiotherapy in a case of fistulated esophageal cancer.