Idiopathic myointimal hyperplasia of mesenteric veins: Rare case of ischemic colitis mimicking inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76‐year‐old Japanese man presented to our hospital with a 1‐year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C‐reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.     

Changes in HRCT findings in patients with respiratory bronchiolitis-associated interstitial lung disease after smoking cessation.

High-resolution computed tomography (HRCT) findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are varied and nonspecific. There is no known report of changes in HRCT findings and respiratory function test results for RB-ILD patients following the cessation of smoking. Five patients with RB-ILD, confirmed by surgical lung biopsy, were retrospectively studied. Each stopped cigarette smoking and did not receive corticosteroid therapy after diagnosis. The clinical symptoms, respiratory function test results and HRCT findings obtained at the final observation were compared with those from the time of diagnosis. Ground-glass opacity and centrilobular nodules corresponding to pathological respiratory bronchiolitis, as well as intralobular fine linear-reticular opacity corresponding to fibrosis involving the subpleural alveolar septa, showed computed tomography-pathological correlations. Both clinical symptoms and the diffusing capacity of the lungs for carbon monoxide improved significantly following smoking cessation, as did ground-glass opacity and centrilobular nodules seen during the initial HRCT examination. Centrilobular nodules and ground-glass opacity, which are the main features of high-resolution computed tomography of respiratory bronchiolitis-associated interstitial lung disease patients and represent pathological respiratory bronchiolitis, can be improved by smoking cessation. The diffusing capacity of the lung for carbon monoxide in respiratory function tests can be also improved.     

Immunohistochemical detection of imidazolone, a novel advanced glycation end product, in kidneys and aortas of diabetic patients.

To investigate the role of the Maillard reaction in the pathogenesis of diabetic complications, we produced several clones of monoclonal antibodies against advanced glycation end products (AGEs) by immunizing mice with AGE-modified keyhole limpet hemocyanin, and found that one clone (AG-1) of the anti-AGE antibodies reacted specifically with imidazolones A and B, novel AGEs. Thus, the imidazolones, which are the reaction products of the guanidino group of arginine with 3-deoxyglucosone (3-DG), a reactive intermediate of the Maillard reaction, were found to be common epitopes of AGE-modified proteins produced in vitro. We determined the erythrocyte levels of imidazolone in diabetic patients using ELISA with the monoclonal anti-imidazolone antibody. The imidazolone levels in the erythrocytes of diabetic patients were found to be significantly increased as compared with those of healthy subjects. Then we studied the localization of imidazolone in the kidneys and aortas obtained from diabetic patients by immunohistochemistry using the antibody. Specific imidazolone immunoreactivity was detected in nodular lesions and expanded mesangial matrix of glomeruli, and renal arteries in an advanced stage of diabetic nephropathy, as well as in atherosclerotic lesions of aortas. This study first demonstrates the localization of imidazolone in the characteristic lesions of diabetic nephropathy and atherosclerosis. These results, taken together with a recent demonstration of increased serum 3-DG levels in diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term diabetic complications such as nephropathy and atherosclerosis.     

Action of Isoflurane on the Substantia Gelatinosa Neurons of the Adult Rat Spinal Cord

Background: Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immobility and analgesia) and suppress autonomic responsiveness, how it exerts these effects at the neuronal level in the spinal cord is not fully understood.

Methods: The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the [gamma]-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined.

Results: Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature [gamma]-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity.     

Insulinoma: Selective arterial calcium injection performed to confirm localization and complete resection

A case of insulinoma is reported in a patient in whom selective arterial calcium injection (SACI) tests were performed both to confirm tumor localization before surgery and to confirm complete tumor removal during surgery. An 18-year-old woman with hypoglycemic episodes was diagnosed with an insulinoma in the pancreatic body demonstrated by celiac arteriography. In a preoperative SACI test, calcium was injected into the splenic artery (SpA), gastroduodenal artery (GDA), and superior mesenteric artery (SMA). Serum immunoreactive insulin (IRI) and proinsulin levels were measured in hepatic venous samples. IRI was markedly increased after the injection of calcium into the GDA and SMA, while there was no response in IRI levels when calcium was injected into the SpA. Therefore, no occult insulinoma was revealed in the distal area fed by the SpA, although the presence of insulinoma was uncertain in the proximal pancreas. In the intraoperative SACI test, calcium was injected into the celiac artery. Insulin (determined by enzyme immunoassay) and proinsulin levels were measured in portal venous samples before and after resection of the tumor. After resection, these levels decreased in response to the calcium stimuli, confirming complete removal of the insulinoma. The SACI test was helpful to localize the insulinoma and was useful to confirm the complete removal of the tumor.     

Spontaneous subcapsular hepatic hemorrhage associated with pregnancy: Report of a case

We report herein a case of spontaneous subcapsular hepatic hemorrhage which occurred in a 33-year-old woman 1 day after she had been delivered of her second child by cesarean section following an uneventful pregnancy. She complained of right upper quadrant pain on the 1st postoperative day, and computed tomography (CT) showed subcapsular low-density masses in both liver lobes, while extravasation was demonstrated by CO₂ intraarterial digital subtraction angiography (IADSA). The hemorrhage was successfully controlled by transcatheter arterial embolization (TAE). However, on the 3rd day after TAE, an exploratory laparotomy was performed to establish an exact diagnosis to explain the persistent abdominal pain and abnormal liver function tests. Subcapsular hematomas in both lobes were confirmed and no visible laceration was present. The patient recovered gradually by spontaneous absorption of the hematomas and was discharged on the 22nd postoperative day. Spontaneous hepatic hemorrhage associated with pregnancy is a very rare complication, and establishing a correct diagnosis and initiating appropriate therapy are essential for this life-threatening disease.     

Electron microscopic study of monkey retina after photodynamic treatment

The purpose of this histological study was to determine the effects of photodynamic treatment, using a hematoporphyrin derivative and argon laser, on normal retinas of monkeys. Ten cynomolgus monkeys were treated with a hematoporphyrin derivative, given intravenously at a dose of 2.5 mg/kg. Forty minutes or 1 or 3 days after the injection, argon laser photoradiation was given over a 2.0-mm-diameter with a 10-min exposure and at an intensity of 40, 100, or 200 mW. The eyes were enucleated 1, 3, 4, 15, 18, 21, 35, or 38 days after the photoradiation and tissue samples were observed under a transmission electron microscope. The most fragile regions in the retina were the retinal nerve fibers, the outer segments of the visual cells, and the retinal pigment epithelium. Vascular endothelial cells were also fragile. The retinal capillary was easily obstructed, and the choriocapillaris was also occluded in an animal with severe retinal damage. The Mueller cells had the highest tolerance to the photodynamic treatment. Thus, exposing the normal part of the retina to light during photodynamic therapy should be avoided.     

Effect of carbon dioxide and oxygen on endothelin production by cultured porcine cerebral endothelial cells

We have previously reported the production of endothelin, a potent vasoconstrictor peptide, by porcine cerebral microvessel endothelia and suggested its important role in the regulation of local blood flow within the brain. In our present study, radioimmunoassay with anti-porcine endothelin antiserum revealed that endothelin, produced by cerebral microvessel endothelia grown on a filter, is released mainly to the basement membrane side, not the vascular lumen side. This finding suggests that endothelin constricts arterioles locally where it is produced by endothelia. We also found that cerebral microvessel endothelia produce less endothelin under low oxygen pressure and more endothelin under low carbon dioxide pressure. Our results suggest that endothelin has a role in the regulation of cerebral blood flow in response to oxygen and carbon dioxide pressure.     

Intrathecal administration of N-methyl-D-aspartate receptor antagonist reduces the minimum alveolar anaesthetic concentration of isoflurane in rats

We have studied the effect of intrathecal administration of N-methyl-D- aspartate (NMDA) receptor antagonists on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats. In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after administration of a competitive NMDA receptor antagonist, APV (0.01, 0.1, 1.0, 10, 30 micrograms), a non-competitive NMDA receptor antagonist, MK801 (0.1, 1.0, 10, 30 micrograms). NMDA (0.01, 0.1, 1.0, 10, 30 micrograms) and saline. APV at all doses except 0.01 micrograms decreased MAC by 17.1-32% (P < 0.001 and P < 0.0001). Although MK801 at 10 and 30 micrograms reduced MAC by 24.3-31.7% (P < 0.001 and P < 0.0001), lower doses did not affect MAC. Intrathecal administration of NMDA reversed these decreases in MAC, but not to control values with APV 10 and 30 micrograms and MK801 30 micrograms. We suspect that NMDA and NMDA receptor antagonists play important roles in the spinal cord in determining the MAC of isoflurane.      

Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats.

Recent studies have revealed that the phosphatidylinositol 3-kinase (PI3-K) pathway is involved in apoptotic cell death after experimental cerebral ischemia. The serine-threonine kinase, Akt, functions in the PI3-K pathway and prevents apoptosis by phosphorylation at Ser473 after a variety of cell death stimuli. After phosphorylation, activated Akt inactivates other apoptogenic factors, including glycogen synthase kinase-3beta (GSK3beta), thereby inhibiting cell death. However, the role of Akt/GSK3beta signaling in the delayed death of hippocampal neurons in the CA1 subregion after transient global cerebral ischemia (tGCI) has not been clarified. Transient global cerebral ischemia for 5 mins was induced by bilateral common carotid artery occlusion combined with hypotension. Western blot analysis showed a significant increase in phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) in the hippocampal CA1 subregion after tGCI. Immunohistochemistry showed that expression of phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) was markedly increased in the vulnerable CA1 subregion, but not in the ischemic-tolerant CA3 subregion. Double staining with phospho-GSK3beta (Ser9) and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed different cellular distributions in the CA1 subregion 3 days after tGCI. Phosphorylation of Akt and GSK3beta was prevented by LY294002, a PI3-K inhibitor, which facilitated subsequent DNA fragmentation 3 days after tGCI. Moreover, transgenic rats that overexpress copper/zinc-superoxide dismutase, which is known to be neuroprotective against delayed hippocampal CA1 injury after tGCI, had enhanced and persistent phosphorylation of both Akt and GSK3beta after tGCI. These findings suggest that activation of the Akt/GSK3beta signaling pathway may mediate survival of vulnerable hippocampal CA1 neurons after tGCI.