Impairment of acid-neutralizing capacity and lesion formation in the rat duodenum during hemorrhagic shock: comparative study with indomethacin

The effects of hemorrhagic shock (HE) on duodenal pH, acid-neutralizing capacity and mucosal tolerance to acid were investigated in anesthetized rats, and they were compared with those of indomethacin. HE was performed by bleeding from the carotid artery to reduce arterial blood pressure to about 55 mmHg (3 ml of bleeding per 200 g of body weight), and indomethacin was given s.c. in a dose of 5 mg/kg. Duodenal pH was determined in the outflow from the proximal duodenum (1.7 cm) which was perfused with 10(-4) M HCl, and acid-neutralizing capacity was measured by back-titration of the perfusate to pH 4.0 with 10 mM HCl. Under these conditions, duodenal pH was kept at around 6.0 as the result of neutralization in the loop (approximately 8 microEq/hr). Both HE and indomethacin significantly decreased the pH and acid-neutralizing capacity. Administration of 16,16-dimethyl prostaglandin E2 (16-dmPGE2: 30 micrograms/kg, s.c.) significantly increased both pH and acid-neutralizing capacity in normal and indomethacin-treated rats, but failed to affect these parameters in rats under HE conditions. When the duodenal loop was perfused with 50 mM HCl for 1.5 hr, both HE and indomethacin induced extensive damage in the mucosa. Pretreatment with 16-dmPGE2 significantly reduced the formation of duodenal lesions induced by indomethacin but not by HE. These results suggest that HE as well as indomethacin impaired duodenal acid-neutralizing capacity to reduce the tolerance to acid of the mucosa. The deleterious effects of HE on the mucosa may be mainly due to a decreased mucosal blood flow, but not due to a deficiency of endogenous prostaglandins.     

Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes

The association of bone with the metabolic syndrome and its features, visceral fat accumulation or insulin resistance, remains unclear. We determined visceral and subcutaneous fat areas (V and S) by computed tomography on 187 men (28–83 years) and 125 postmenopausal women (46–82 years) with type 2 diabetes. Men whose V was 100 cm² or more had significantly lower urinary N-terminal cross-linked telopeptide of type-I collagen (p = 0.005), higher femoral neck bone mineral density (FN-BMD) (p = 0.004), and lower prevalence of vertebral fractures (VFs) (p = 0.04) than controls. Fat mass, V, S, and lean body mass positively correlated with FN-BMD in men and with lumbar (L) and FN-BMD in women. When adjusted for weight, these correlations became negative. Urinary C-peptide positively correlated with FN-BMD in both genders. Multivariate logistic regression analysis adjusted for age, height, weight, L-BMD, duration of diabetes, and diabetes therapies identified V in men and urinary C-peptide in women as factors inversely associated with the presence of VFs [odds ratio (OR) = 0.61 per SD increase, p = 0.04, and OR = 0.32, p = 0.01, respectively]. These findings suggest that, of the components of the metabolic syndrome, body fat in gravity and hyperinsulinemia could increase FN-BMD in diabetic subjects. Visceral fat in men and hyperinsulinemia in women may protect against VFs independent of weight, L-BMD, diabetes duration, or therapies.     

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.     

Vasovagal syncope with asystole associated with intravenous access.

Two cases of vasovagal syncope (VVS) during venous access are reported. Both patients had a history of fainting episodes and experienced bradycardia with asystole, hypotension, and fainting. Pain and phobic stress during venous access triggered an increase in parasympathetic tone, resulting in bradycardia with asystole and hypotension in both cases. Hypotension and bradycardia likely caused cerebral hypoperfusion, leading to fainting. The intense parasympathetic tone triggered by somatic or emotional stress was likely responsible for directly depressing the sinus node, leading to asystole and bradycardia. Bradycardia with asystole progressing to syncope is a potentially fatal dysrhythmia in patients with cardiovascular disease or older patients with decreased cardiac function. Appropriate treatment for VVS includes the administration of intravenous fluids, vagolytics, ephedrine, and the rapid use of the Trendelenburg position. Intravenous fluids and atropine were used to treat the present patients.     

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.     

AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Dopamine agonists and valvular heart disease in Japanese patients with Parkinson's disease

Journal of Neurology - A high incidence of valvular heart disease in Parkinson's disease (PD) patients treated with ergot-derived dopamine agonists, such as cabergoline and pergolide, has been...