Fibroblast growth factor expression during skeletal fracture healing in mice

Fibroblast growth factors (FGFs) are important signaling molecules that regulate many stages of endochondral bone development. During the healing of a skeletal fracture, several features of endochondral bone development are reactivated. To better understand the role of FGFs in skeletal fracture healing, we quantitatively evaluated the temporal expression patterns of Fgfs, Fgf receptors (Fgfrs), and molecular markers of bone development over a 14‐day period following long bone fracture in a mouse model. These studies identify distinct groups of FGFs that are differentially expressed and suggest active stage‐specific roles for FGF signaling during the fracture repair process. Developmental Dynamics 238:766–774, 2009. © 2009 Wiley‐Liss, Inc.     

Functional Changes in Nonadrenergic, Noncholinergic Inhibitory Neurons in Ileal Circular Smooth Muscle After Small Bowel Transplantation in Rats

This experiment was designed to determinemechanisms of change in nonadrenergic, noncholinergic(NANC) inhibitory neurons in the ileum after small boweltransplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANCinhibitory neurotransmitter in the rat ileum. Eightgroups of rats (N 8 rats/group) were studied:neurally intact unoperated controls; rats one week afteranesthesia and sham celiotomy; and separate groups one andeight weeks after either 40 min of cold ischemia of thejejunoileum, combined jejunal and ileal intestinaltransection/reanastomosis, or orthotopic SBT of the entire jejunoileum. Contractile activitywas evaluated in full-thickness ileal circular musclestrips under isometric conditions. Spontaneous activitydid not differ among groups. In all groups, exogenous NO, N^G-monomethyl-L-arginine(L-NMMA, an NO synthase inhibitor), and methylene blue(soluble guanylate cyclase inhibitor) had no effect onspontaneous activity, while 8-bromocyclic guanosinemonophosphate (8Br-cGMP) inhibited contractile activity inall groups. Low frequency (2-10 Hz) electrical fieldstimulation (EFS) inhibited contractile activity only incontrol and SBT groups; L-NMMA and methylene blue did not alter the response to EFS in any group.These results suggest that each aspect of the SBTprocedure, ischemia/reperfusion injury, disruption ofenteric neural continuity by intestinal transection, and extrinsic denervation, alter function ofenteric ileal inhibitory neurons separately early (oneweek) after operation. NO, a known inhibitoryneurotransmitter in other gut regions, does not affectileal circular muscle in neurally intact tissue normediate functional changes in inhibitory nerve functionnor smooth muscle contractility after SBT.     

Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects

Summary A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO₂ max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO₂ max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.     

Diagnosis and management of acute obstetrical DIC

Obstetrical disseminated intravascular coagulation (DIC) is usually a very acute, serious complication of pregnancy. The DIC diagnostic criteria in obstetrics (the obstetrical DIC score) help with making a prompt diagnosis and starting treatment early. These DIC diagnostic criteria, in which higher scores are given for clinical parameters than for laboratory parameters, have three components: (1) the underlying disease, (2) clinical symptoms, and (3) laboratory findings. It is justified that it is appropriate to initiate therapy for DIC when the obstetrical DIC score reaches 8 points or more before obtaining the results of coagulation tests. Management: (1) Control of the underlying disease: because prolongation of exposure to the triggering factors worsens DIC, it is important to eliminate the etiologic factors as rapidly as possible. Elimination of the cause of DIC can be easily performed in obstetrics, for example, by cesarean section. (2) Antithrombin (AT) therapy: AT monotherapy (1,500 to 3,000 units/day, 2 days) is preferably employed instead of heparin monotherapy or heparin-AT therapy because of the hemorrhagic side effects of heparin. (3) Synthetic serine protease inhibitors: continuous infusion ofgabexate mesilate (FOY) or nafamostat mesilate (FUT) is effective for DIC. Controlled multicenter trials showed a significant improvement not only in clinical response but also in platelet counts and prothrombin time (PT) in the AT group compared with the FOY group. (4) Activated protein C (APC) can inhibit thrombin generation and accelerate fibrinolytic activity. APC (5,000 to 10,000 units) is administered for 2 days in patients with placental abruption complicated by DIC. APC is a very safe, effective, and useful agent for the treatment of DIC.     

Plasma level of homocysteine is correlated to extracranial carotid-artery atherosclerosis in non-hypertensive Japanese

BACKGROUND: Results of some epidemiologic studies in Western countries have clarified that hyperhomocysteinemia is a plausible risk factor for atherosclerotic vascular disease, but its role in Japanese communities is not known. DESIGN: A community-based cross-sectional design. METHODS: We performed a cross-sectional study of 474 elderly men aged 60-74 years in two Japanese rural communities (Noichi in southwestern Japan and Ikawa in northeastern Japan). We examined the association between plasma concentrations of homocysteine and the maximum intima-media thickness (assessed by ultrasonography). RESULTS: The prevalence of thickening was 10.7% for the lowest tertile of homocysteine level and 21.1% for the highest tertile. For the subjects without hypertension, the odds ratio for having carotid intima-media thickening was 5.8; it was significantly higher for the highest tertile of homocysteine level than it was for the lowest after adjusting for age, hypercholesterolemia, hypoalphalipoproteinemia, diabetes, and smoking by using a multiple logistic regression model. However, its correlation was not evident for those with hypertension. CONCLUSIONS: High levels of plasma homocysteine are correlated to extracranial carotid artery atherosclerosis in elderly men without hypertension in Japanese rural communities.     

New Reconstructive Procedure After Intestinal Resection for Crohn’s Disease: Modified Side-to-Side Isoperistaltic Anastomosis With Double Heineke-Mikulicz Procedure

Although side-to-side isoperistaltic anastomosis is a useful strictureplasty technique when long segments of intestinal stenosis complicate Crohns disease, concerns have been raised regarding disease recurrence adjacent to the anastomosis. We performed side-to-side isoperistaltic anastomosis without spatulated intestinal ends as a method of reconstruction after intestinal resection for Crohns disease; both intestinal ends were transversely closed like a Heineke-Mikulicz-type strictureplasty. With this procedure, the luminal diameter proximal and distal to the anastomosis became wider than the original diameter of the intestine. This new procedure, which we refer to as the modified side-to-side isoperistaltic anastomosis with double Heineke-Mikulicz procedure could become an alternative operation after intestinal resection in persons with Crohns disease, although long-term outcome analysis is necessary.     

G‐cell hyperplasia of the stomach induces ECL‐cell proliferation in the pyloric glands in a paracrinal manner

An inhibitory mechanism toward gastrin hypersecretion is significantly different between G‐cell hyperplasia and gastrinoma despite the common clinical manifestations; hypergastrinemia and its related persistent gastric ulcers. We recenlty studied the G‐cell, d ‐cell and ECL‐cell density in a case of G‐cell hyperplasia. The 70‐year‐old patient has been treated for persistent gastric ulcers with a markedly increased plasma gastrin (5600 pg/mL). The stomach was surgically resected because of the obstruction associated with ulcer scars. The number of G‐cells in the pyloric glands was quantified on the surgical specimens and G‐cell hyperplasia was histolopathologically identified. Immunostainig of histidine decarboxylate revealed the presence of ECL‐cell hyperplasia in the pyloric glands and its density was significantly and positively correlated with G‐cell density. Somatostatin immunoreactive cells (d ‐cells) increased in their number in the oxyntic glands. These results all indicated that hypersecretion of gastrin in G‐cell hyperplasia could induce ECL‐cell proliferation in a paracrinal manner. In addition, relatively non‐prominent endocrinological features in the G‐cell hyperplasia compared to gastrinoma could be also related to the paracrinal somatostatin inhibitory effects upon ECL‐cells in the pyloric glands.