A Comparison of Oral and Rectal Absorption of L-Dopa Esters in Rats and Mice

Short-chain alkyl esters of L-dopa were administered to rats and mice via oral and rectal routes. Plasma L-dopa esters and L-dopa were determined in the systemic and portal circulation by HPLC. A comparison of isopropyl, butyl, and 4-hydroxybutyl esters of L-dopa demonstrated significantly higher levels of the esters in both systemic and portal blood samples following rectal administration than following oral administration. In most cases, oral administration resulted in nondetectable (<0.01 µg/ml) levels of the esters in plasma. Correspondingly, the plasma levels of L-dopa itself were consistently higher following rectal administration. At very high oral doses (500 mg L-dopa equivalents/kg body weight), systemic plasma levels of the butyl ester could be detected (1.25 µg/ml at 10 min), which might indicate saturation of the esterase activity of the small intestine. These studies indicate that the systemic availability of L-dopa from short-chain alkyl esters of L-dopa may be best optimized by rectal administration, which avoids the relatively high esterase activity characteristic of the small intestine.     

Pleiotropy in Coffin-Lowry syndrome: Sensorineural hearing deficit and premature tooth loss as early manifestations

We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin-Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These “;new”; clinical manifestations expand the phenotype of Coffin-Lowry syndrome and constitute an additional indication of pleiotropy. © 1993 Wiley-Liss, Inc.     

Effect of epidural anesthesia on colorectal anastomosis

PURPOSE: Epidural anesthesia is believed to benefit colorectal anastomotic blood flow because of the sympathetic blockade it produces. Our purpose is to measure with tonometry the effect of epidural anesthesia on colorectal anastomotic oxygenation. PATIENTS AND METHODS: Fifteen patients operated on for rectal cancer (radical anterior resection) were monitored postoperatively using tonometers placed in the stomach (celiac trunk), transverse colon (superior mesenteric artery), and the anastomotic area during the operation. An epidural catheter was placed at L1-2, and on the first postoperative day, 8 ml of bupivacaine (0.25 percent) was administered. The anesthetic effect extended up to T-4. Intramucosal pH (pHi) at the three locations was measured before, during, and after the epidural blockade. RESULTS: Gastric and transverse colon pHi increased during the epidural blockade from 7.35±0.01 to 7.41±0.01 and from 7.34±0.02 to 7.40±0.02, respectively. The anastomotic pHi decreased from 7.3±0.02 to 7.24±0.03 under the epidural and increased up to 7.34±0.02 after withdrawal of the effect on the following day. All pHi variations were statistically significant (P<0.05, paired Student'st-test and Wilcoxon's test), because it was the comparison between gastric and transverse colon pHi with the anastomotic pHi during the epidural (P<0.05, one-way analysis of variance and Kruskal-Wallis tests). None of the patients developed anastomotic or other complications. CONCLUSIONS: Epidural anesthesia with bupivacaine causes a significant decrease in the oxygenation-perfusion state of colorectal anastomosis in comparison with the increase in other areas of the digestive tract. Further studies need to be done to see if other epidural anesthetic-analgesic protocols also worsen colorectal anastomotic blood flow.Supported in part by a grant from the Spanish Society of Digestive Diseases, Madrid, Spain. All tonometric catheters and drugs were donated by the Clinic University Hospital of Valencia, Spain.Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

Cementoblastoma related to a primary tooth: a case report

Cementoblastomas are benign lesions of the odontogenic ectomesenchyme that rarely occur related to the primary dentition, especially on the left side of the mandible. This study describes a case of a true cementoblastoma related to the left second primary mandibular molar in a 7-year-old child (the largest one seen in the left side of the mandible). Additionally, the radiographic and histologic findings of the lesion are described in details.     

Reelin expression is upregulated following ocular tissue injury

Purpose Reelin is important in the guidance of neuronal stem cells in the central nervous system during normal development. We wished to determine whether reelin is expressed in the retina and cornea after injury. Methods Mice underwent laceration of their retina as well as corneal epithelial debridement. The mice were sacrificed at 3 days, and eyes were fixed and stained for reelin expression and reelin messenger ribonucleic acid (mRNA). Results In normal eyes, reelin was expressed only at very low levels in the ganglion cell layer of the retina and the endothelial cell layer of the cornea. In injured eyes, there was marked expression in reelin immunoreactivity in the retina and cornea. Reelin gene expression was seen in the retina and cornea. Conclusions Reelin is expressed during normal retinogenesis. This study shows that reelin is also upregulated following injury to the retina and cornea. The expression of reelin following injury suggests that reelin may play an important role in regulating stem cell trafficking in neuronal and nonneuronal tissues following injury similar to its role in normal organogenesis. For consideration of publication in Graefe’s Archive for Clinical and Experimental Ophthalmology.     

Characterization of the effects of histamine on the transmembrane electrical activity of guinea-pig and rabbit SA- and AV-node cells

Summary The effects of histamine on the transmembrane electrical activity of cells of small preparations (0.5 × 0.5 mm) of guinea-pig and rabbit sinoatrial- and atrioventricular-nodes were studied. Histamine at concentrations above 10^–7 mol/l increased the firing rate, the rate of diastolic depolarization, the maximum diastolic potential, the amplitude and the maximum rate of depolarization of the action potential of pacemaker cells of rabbit and guineapig sinoatrial cells and rabbit atrioventricular cells. These effects were antagonized by the HZ-receptor blocker cimetidine (2.5 × 10^–6 mol/1) but they were not modified by the H₁-receptor blocker chlorphenamine (2.5 and 5×10^–6 mol/1). Small preparations of guinea-pig atrioventricular node did not exhibit spontaneous activity, but it was induced by histamine and blocked by cimetidine. Histamine increased the maximum upstroke velocity of propagated action potential of cells of the central part of complete atrioventricular node in both species studied. These effects were blocked by cimetidine, but not by chlorphenamine. It is concluded that the increase in automaticity induced by histamine in guinea-pig and rabbit sinoatrial and atrioventricular nodes was due to stimulation of H₂receptors. Histamine did not depress electrical activity of atrioventricular node cells, but rather increased it. This effect was due to H₂-receptor stimulation. Send offprint requests to: J. Sanchez-Chapula at the above address