Alpha 1-adrenoceptors and calcium sources in adrenergic neurogenic contractions of rat vas deferens

1. The involvement of alpha 1-adrenoceptor subtypes in adrenergic neurogenic contractions of different type was studied in epididymal and prostatic portions of the rat vas deferens. 2. The adrenergic component of neurogenic contractions was isolated by suramin (300 microM). Twitch-like and tonic contractions were elicited by appropriate pulse patterns of electrical field stimulation, and contractions relying on intracellular calcium mobilization and calcium entry were isolated by means of nifedipine (10 microM) and ryanodine (20 microM), respectively. Increasing concentrations of 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)- amino)-propyl)benzeneacetonitrile (HV 723), prazosin and 5-methylurapidil progressively, monophasically and with potency decreasing in that order reduced and finally abolished all types of contraction, with one exception: concentration-effect curves of 5-methylurapidil in epididymal segments in the presence of ryanodine levelled off at about 75% inhibition. In the presence of both nifedipine (10 microM) and ryanodine (20 microM), contractions were abolished. 3. Contractions elicited by exogenous noradrenaline were also studied in the presence of either nifedipine 10 microM (prostatic segments) or ryanodine 20 microM (epididymal segments). Increasing concentrations of tamsulosin, WB 4101, benoxathian, HV 723, prazosin, 5-methylurapidil and urapidil progressively, monophasically and with potency decreasing in that order reduced and eventually abolished both kinds of contraction, with two exceptions: in epididymal segments in the presence of ryanodine, the concentration-effect curve of 5-methylurapidil was biphasic and the curve of urapidil levelled off at only partial inhibition. 4. In slices prepared from the prostatic end and preincubated with [3H]-noradrenaline, WB 4101, HV 723, prazosin and 5-methylurapidil, at the highest concentrations tested against neurogenic contractions, increased only slightly the overflow of tritium elicited by trains of 50 pulses at 5 Hz. 5. It is concluded that two alpha l-adrenoceptor subtypes mediate adrenergic neurogenic contractions of rat vas deferens. The main one, pharmacologically alpha 1A, activates both calcium mobilization and entry. In addition there is a second receptor, not previously detected in the vas deferens and not corresponding to any named alpha l subtype, characterized by high and similar affinity for tamsulosin, WB 4101, benoxathian,HV 723 and prazosin and very low affinity for 5-methylurapidil and urapidil, and linked exclusively to calcium entry. Both subtypes and their respective transduction pathways also contribute to contractions elicited by exogenous noradrenaline. An alpha 1B-adrenoceptor-mediated contraction was not found under any experimental conditions.     

Hypocalcemic-induced tetany that causes triceps and bilateral quadriceps tendon ruptures

Small-cell carcinoma (also known as oat-cell carcinoma) is a rare tumor that previously concerns the lung; small-cell carcinoma of the bladder is extremely rare (0.5% of all bladder malignancies). The Authors report here the case of a 78th years old man. Fourteen months before our observation he was submitted to a partial cystectomy for a small-cell carcinoma of the bladder cupola. There was no evidence of extra-vesical location at that moment and the patient was not submitted to any adjuvant therapy. At the moment of our observation the disease was very advanced and the patient died in a few time. The Authors discuss about the therapy of bladder small-cell carcinoma in the few cases described by the literature and about the survival of those patients. A radical surgical treatment in association with an adjuvant chemo- or radiotherapy appears as a better way to treat these patients. On account of this case the Authors agree with this choice and conclude that only a combined treatment can allow a better survival.     

ERICE, a novel FLICE-activatable caspase

Programmed cell death, or apoptosis, is a process of fundamental importance to cellular homeostasis in metazoan organisms (Ellis, R. E., Yuan, J., and Horvitz, H. R. (1991) Annu. Rev. Cell Biol. 7, 663-698). The caspase family of mammalian proteases, related to the nematode death protein CED-3, plays a crucial role in apoptosis and inflammation. We report here the isolation and characterization of a new caspase, tentatively termed ERICE (Evolutionarily Related Interleukin-1beta Converting Enzyme). Based on phylogenetic analysis, ERICE (caspase-13) is a member of the ICE subfamily of caspases which includes caspase-1 (ICE), caspase-4 (ICErel-II, TX, ICH-2), and caspase-5 (ICErel-III, TY). Overexpression of ERICE induces apoptosis of 293 human embryonic kidney cells and MCF7 breast carcinoma cells. Like other members of the subfamily, ERICE is not activated by the serine protease granzyme B, a caspase-activating component of cytotoxic T cell granules. Therefore, ERICE most likely does not play a role in granzyme B-induced cell death. ERICE, however, was activated by caspase-8 (FLICE, MACH, Mch-5), the apical caspase activated upon engagement of death receptors belonging to the tumor necrosis factor family. This is consistent with a potential role for ERICE in this receptor-initiated death pathway.     

Effect of various lipid-bile salt mixed micelles on the intestinal absorption of amphotericin-B in rat

We investigated the effect of the somatosensory functions to the outcomes of motor functions in 28 patients with thalamic hemorrhage. The disturbance of the pyramidal tracts was assessed by the destruction of the internal capsule found in computed tomography (CT). The disturbance of the somatosensory function was analyzed by the N20 component of short-latency somatosensory evoked potentials (SSEP). The outcomes of motor function was evaluated after 3 months of ictus. Correlations between the outcomes of motor function, disturbance of the pyramidal tract, and disturbance of the somatosensory function were discussed. The result indicated that functional outcomes statistically correlated with neither disturbance of the internal capsule alone nor disturbance of N20 alone. But, there was statistically significant between functional outcomes and the combination of disturbance of the internal capsule with disturbance of N20 (p < 0.05, Wilcoxon signed-rank). There was not statistical difference in hematoma volume or consciousness. The implications of these results suggest that somatosensory function may affect the recovery of motor functions.     

Specific substitutions at amino acid 256 of the sarcoplasmic/endoplasmic reticulum Ca2+ transport ATPase mediate resistance to thapsigargin in thapsigargin-resistant hamster cells

High levels of resistance to thapsigargin (TG), a specific inhibitor of intracellular Ca2+ transport ATPases (SERCAs), can be developed in culture by stepwise exposure of mammalian cells to increasing concentrations of TG. We have identified, in two independently selected TG-resistant hamster cell lines of different lineages, mutant forms of SERCA. In the TG-resistant Chinese hamster lung fibroblast cell line DC-3F/TG, a T --> C change at nucleotide 766 introduces a Phe256 --> Leu alteration within the first cytosolic loop of the SERCA. In contrast, in the TG-resistant Syrian hamster smooth muscle cell line DDT/TG 4 microM, a T --> C change at nucleotide 767 introduces a Phe256 --> Ser mutation at that position. When these specific mutations are introduced into a wild-type full-length avian SERCA1 cDNA, transfection experiments reveal that Ca2+ transport function and ATP hydrolytic activity are not altered by such mutations. However, a 4-5-fold resistance to TG inhibition of Ca2+ transport function occurs upon the introduction of either the Phe256 --> Leu or the Phe256 --> Ser mutation into wild-type SERCA1. These specific mutations also render the hydrolytic activity of the ATPase resistant to inhibition by TG. Our results not only implicate amino acid 256 in TG-SERCA interactions, but also demonstrate that specific mutations within SERCA can mediate resistance to TG.     

A study of the diagnostic accuracy and reliability of the Scoliometer and Adam's forward bend test

STUDY DESIGN: Study of the diagnostic accuracy and interexaminer reliability of scoliosis diagnostic tests. OBJECTIVES: To estimate the sensitivity, specificity, and predictive value of the Scoliometer (National Scoliosis Foundation, Watertown, MA) and Adam's forward bend test in diagnosing scoliosis, and to determine the interexaminer reliability of the Scoliometer and Adam's forward bend test. SUMMARY OF BACKGROUND DATA: Exposure to diagnostic radiation in patients with adolescent idiopathic scoliosis may result in a small but significant increase in cancer rates. The full-spine radiographic examination remains the standard procedure for the assessment of scoliosis. There is a need for a valid and reliable noinvasive test to assess scoliosis. METHODS: Two examiners independently assessed 105 patients presenting to a scoliosis clinic for trunk asymmetry with Adam's forward bend test and axial trunk rotation with the Scoliometer. The Cobb method served as the gold standard. RESULTS: The interexaminer agreement for the Scoliometer is excellent in the thoracic spine and substantial in the lumbar spine. The interexaminer measurement error shows poor precision for thoracic and lumbar Scoliometer measurements. The interexaminer agreement for Adam's forward bend test is substantial in the thoracic spine and poor in the lumbar spine. Adam's forward bend test is more sensitive than the Scoliometer in detecting thoracic curves measuring 20 degrees or more by the Cobb method. Receiver operating characteristic curve analysis suggests that the use of the Scoliometer marginally improves the ability of diagnosing a scoliosis in the thoracic spine. CONCLUSIONS: The Scoliometer and Adam's forward bend tests have adequate interexaminer reliability for the assessment of thoracic curves. The Scoliometer has better interexaminer agreement in the lumbar spine. However, the Scoliometer has a high level of interexaminer measurement error that limits its use as an outcome instrument. Because Adam's forward bend test is more sensitive than the Scoliometer, the authors believe that it remains the best noninvasive clinical test to evaluate scoliosis.     

Influence of fibrinolytic factors on scar formation after lumbar discectomy. A magnetic resonance imaging follow-up study with clinical correlation performed 7 years after surgery

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To assess the amount of scar tissue by viewing magnetic resonance images, and to evaluate the correlation between the amount of scar tissue and clinical outcome, surgical technique, and fibrinolytic factors. SUMMARY OF BACKGROUND DATA: The influence of fibrinolytic factors on magnetic resonance images has not been investigated previously. The relation between clinical outcome and findings on magnetic resonance imaging remains uncertain. METHODS: Magnetic resonance imaging at 0.5 Tesla was performed to produce sagittal and axial spin-echo T1-weighted images before and after contrast enhancement on 78 patients 7 years after traditional lumbar discectomy with partial or full laminectomy. Before surgery all patients had been tested for fibrinolytic factors. RESULTS: The overall clinical success rate of the surgery was 73%. No evidence of scar formation was seen in 19 patients, a small amount was seen in 36 patients, a moderate amount in 17 patients, and a large amount was observed in 6 patients. Ten patients who had undergone surgery at two disc levels and 18 who had been treated with full laminectomy exhibited more scar tissue than those patients who had undergone surgery on a single level (P = 0.033) and those who had undergone a partial laminectomy, respectively (P = 0.017). The amount of scar formation also was associated with a poor outcome (P = 0.017) and with low preoperative values of tissue plasminogen activator antigen (P = 0.003) and tissue plasminogen activity (P = 0.048) in samples collected after venous occlusion. The intensity of contrast enhancement, however, was not influenced by these or any other parameters. CONCLUSION: The amount of scar formation after lumbar discectomy seems to be related to the clinical outcome, the size of the surgical exposure, and some fibrinolytic factors.     

Evaluation of biologic gastrin activity of compound CI-988 in the isolated, vascularly perfused rat stomach

BACKGROUND: The peptoid CI-988 has previously been shown to have high affinity for the cholecystokinin (CCK)-B/gastrin receptor and has been reported to be a powerful CCK antagonist in many systems, although it has agonist activity on histidine decarboxylase in the rat. METHODS: In the present study the effect of CI-988 on acid secretion and histamine release in the totally isolated, vascularly perfused rat stomach was assessed. RESULTS: CI-988 was found to be a gastrin agonist with regard to the stimulation of both histamine release and acid secretion. CONCLUSION: Thus, in this stomach model CI-988 behaved as a CCKB/gastrin agonist. The present study underlines the importance of testing the biologic activity of ligands in models with sufficient sensitivity.