Analysis of new imidazoline derivative-induced increase in the maximum response to norepinephrine in the rat vas deferens

The effects of newly synthesized 5-imidazoline derivatives on the dose-response relationship to norepinephrine were investigated in the normal and denervated vasa deferentia of the rat. Three derivatives (K-3827, K-4011 and K-4300) exerted alpha-antagonistic action, the potency of which was similar to that of tolazoline. The pA2 values of these derivatives and currently known alpha-antagonists (tolazoline, phentolamine and prazosin, but not yohimbine) in the denervated tissue were slightly but significantly larger than those in the normal tissue. All imidazoline derivatives and alpha-antagonists produced an increase in the maximum response to norepinephrine in the normal vas deferens. In the denervated tissue, however, K-3827, K-4011 and alpha-antagonists caused only a rightward shift of the dose-response curve to norepinephrine, but not an increase in the maximum response, i.e., relatively pure alpha-antagonism. In contrast, the other 3 imidazoline derivatives, K-4299 and K-6342 which exhibited neither alpha-agonistic nor antagonistic action and K-4300, increased the maximum response to norepinephrine even after denervation. Their effects were nonspecific in that they also potentiated acetylcholine-induced contractions in both normal and denervated tissues. These 3 imidazoline derivatives antagonized the action of diltiazem. The effects of imidazoline derivatives and alpha-antagonists were discussed in relation to those of denervation, and the drug enhancement by 3 imidazoline derivatives was analyzed from the viewpoint of calcium movement.     

The evaluation of cystoscopy in the screening of asymptomatic microhematuria

As a prospective study on asymptomatic microhematuria, complete urological examinations including cystoscopy, IVP, ultrasound and urinary cytology were performed on 422 patients over 40 years old between January 1987 and December 1988 (group A). The results of group A was compared with that of retrospective study on 266 patients, who had incomplete urological examination between January 1984 and December 1985 (group B). Cystoscopy was performed on 321 patients (87.2%) in group A and on 108 patients (40.6%) in group B. Bladder tumor was found in 10 cases (2.4%) in group A, including 7 cases of male patients (5.7%), but in only 1 case (0.4%) in group B. Since the negative rate of abnormal urinary cytology was 50% and that of abnormal IVP was 90% in 10 cases of bladder tumor in group A, cystoscopy was considered to be an essential examination for the screening of patients with asymptomatic microhematuria over 40 years old patients.     

Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal.

Recently an essential role of interstitial cells of Cajal (ICC) within myenteric plexus (ICC-MY) was suggested in ascending contraction and descending relaxation in the mouse ileum. The role of ICC in these neural reflexes was examined in the distal colonic segments prepared from the wild type and c-kit mutant, W/W(V) mice, in the present study. Localized distension of the segments from the wild type mice by using a small balloon resulted in ascending contraction and descending relaxation. In the segments from the mutant mice, localized distension also induced these neural reflexes similar to those observed in the wild type mice. Immunohistochemical examination demonstrated that ICC-MY and ICC present in muscle layers (ICC-IM) were severely disrupted in the mutant mouse, but only ICC, present within submucosal plexus (ICC-SMP), remained unchanged. In the small strips with ICC-SMP absent prepared from the mutant mouse, electrical field stimulation induced contraction or relaxation in the absence or presence of atropine, respectively. It was suggested that ICC have no important role in the ascending and descending neural reflexes in the mouse distal colon, this is in direct contrast to the role of ICC-MY in the ileum.     

Study on extensive lymph node dissection: metastatic lymph nodes in papillary carcinoma of the thyroid

Bilateral cervical lymph node dissection was performed in 71 cases of papillary thyroid carcinoma, considered to be relatively early cases because of mobility, irrespective of the size of tumor or presence of node enlargement. Of these, 33 cases received additional node dissection of the anterosuperior mediastinum through longitudinal sternotomy. The number of lymph nodes examined per subject averaged 89.9, the number of metastatic nodes was 13.8, and metastasis was noted in 88.7% of all cases. Lymph node metastasis tended to be more frequent on the affected side, but was simultaneously scattered over the whole cervical area. As to sites, metastasis of paratracheal nodes on the affected side occurred at a frequency of 66.2%, inferior and superior jugular nodes at 62.0% and 59.0% respectively, pretracheal nodes at 50.7%, and tracheoesophageal nodes at 47.9%. The high incidence of para- and pretracheal nodes suggests that the lymph flow in this direction is of great importance in metastasis. In fact, lymph nodes in the mediastinum, which were directly continuous with these nodes, showed as high as 39.4% metastasis in cases of anterosuperior mediastinal extirpation. This extensive node dissection is considered to be very preferable as at least the agony of survival with carcinoma can be lessened.     

Observations in simultaneous microencapsulation of 5-fluorouracil and leucovorin for combined pH-dependent release.

5-Fluorouracil (5-FU) in combination with leucovorin (LV) is nowadays the standard treatment in colon cancer and would be a candidate to be delivered orally to the colon. Eudragit P-4135F or Eudragit RS100 were used separately to prepare microspheres by an oil/oil emulsification process trapping 5-FU and LV simultaneously. Scanning electron microscopy permitted a structural analysis, process parameters were analyzed and drug loading and release profiles were recorded. Particle size varied between 123 (RS100) and 146 microm (P-4135F). Generally, higher encapsulation rates were found with RS100 (5-FU, 60.3+/-9.7%; LV, 81.4+/-8.6%) compared to P-4135F (5-FU, 48.3+/-2.0%; LV, 55.4+/-2.7%). Microparticles made from Eudragit RS100 released the incorporated drug combination within 8 h not exhibiting general differences between the kinetics of both drugs. P-4135F was found to maintain the undesired 5-FU release at pH 6.8 lower than 25% within 4 h while at pH 7.4, a nearly immediate release (within 15 min) was observed. Although the release was similar at pH 7.4, at pH 6.8 LV showed a distinct initial drug loss of about 60% and a complete release within 2 h. SEM analyses revealed a substantial presence of LV crystals on the particle surface provoking a distinct burst effect of LV. These observations were concluded to be related to the high lipophilicity of P-4135F provoking a separation between P-4135F and LV during the preparation process.     

Isolated rupture of radial collateral ligament of the small finger dip joint repaired with a bone suture anchor: a case report.

Isolated rupture of radial collateral ligament of the small finger DIP joint is a rare injury. We treated this lesion using a bone suture anchor with excellent results.     

Lithium and haloperidol differentially alter the dynorphin A (1-8) and enkephalin levels in the neurointermediate lobe of rat pituitary

Repeated administration of the antimanic drug lithium (4 mEq/kg/day for 2, 4 or 6 days, i.p.) to rats produced a progressive decline and eventual depletion of dynorphin-A (1-8) (DYN) concentration whereas Met5-enkephalin (ENK) was only marginally decreased in the neurointermediate lobe of the pituitary (NIL). Administration of a neuroleptic haloperidol neither affected ENK and DYN levels nor influenced lithium-induced changes. The study reveals that lithium produces a preferential perturbation in the dynorphin system relative to the enkephalin system. These results taken together with other evidence, indicate that dynorphin is possibly coreleased with vasopressin following lithium administration and provide a pharmacological support to the previously described colocalization and corelease of these endogenous peptides in the NIL.