Effects of neurotransmitters or drugs on the in vivo release of dopamine and its metabolites

The effects of neurotransmitters or drugs on the release of endogenous dopamine (DA) and extracellular levels of its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were examined in vivo by intracerebral dialysis. A dialysis tube was implanted stereotaxically through bilateral caudate nuclei of rats and perfused with the Ringer solution. Amounts of DA, DOPAC and HVA in the perfusates were measured by high performance liquid chromatography (HPLC) with electrochemical detection. The basal level of DA was 2.76 +/- 0.64 pg/min, whereas the levels of DOPAC and HVA were 218.7 +/- 20.7 and 142.4 +/- 10.6 pg/min, respectively. Apomorphine (4 mg/kg, i.v.) reduced the efflux of DA and its metabolites. Haloperidol (0.4 mg/kg, i.v.) did not change DA release and produced only a minor increase of its metabolites. This increase of metabolites was inhibited by pargyline. Met-enkephalin (10(-4) M), substance P (10(-4) M) and acetylcholine chloride (10(-4) M) added to the perfusing medium increased the release of DA. Met-enkephalin also increased the release of DOPAC. gamma-Amino-n-butyric acid (GABA, 10(-4) M) reduced the release of DOPAC and HVA when added to the perfusing medium. Thyrotropin releasing hormone (TRH, 5 mg/kg, i.v.) increased the release of HVA. These findings indicated that different mechanisms mediated effects of neurotransmitters or drugs on the release and metabolism of DA in the rat striatum.     

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.     

Three-dimensional identification of hemangiomas and feeding arteries in the head and neck region using combined phase-contrast MR angiography and fast asymmetric spin-echo sequences.

OBJECTIVE: To evaluate a proposed technique for the 3-dimensional (3D) detection of hemangiomas, including vascular malformation and their feeding arteries, in the head and neck. The new technique combines phase-contrast magnetic resonance angiography (PCMRA) without contrast medium and 3D fast asymmetric spin-echo (FASE) sequences. METHODS: The technique was applied to 3 patients having hemangiomas in the head and neck region. In 1 patient the image obtained with the proposed technique was compared to that obtained by standard contrast angiography. RESULTS: In all 3 patients, the 3D presence of the hemangiomas and the feeding arteries were well defined in images created by the proposed technique. Additionally, the characterization of the hemangioma's 3D structure and distribution of the feeding arteries coincided with those observed using contrast angiography in the case for which contrast angiography was also performed. CONCLUSIONS: Preliminary experience shows that the proposed technique combining 3D-FASE and 3D-PCMRA is useful to visualize both the 3D structure of hemangiomas and to identify the 3D distribution of the feeding arteries without using contrast medium.     

Two cases of acute disseminated encephalomyelitis with lesions in the thalamus or basal ganglia on MRI]

Lesions in the thalamus or basal ganglia have rarely been reported in acute disseminated encephalomyelitis (ADEM). We experienced 2 cases of ADEM, in which MRI showed lesions in the thalamus or basal ganglia. Case 1, a 4-year-old boy, had gait disturbance, hyperesthesia and hyperreflexia. MRI (T2 weighted image) showed multiple high intensity areas in the right frontal lobe, bilateral parietal lobes and bilateral thalami. Case 2, a 4-year-old girl, complained of gait disturbance following a febrile episode, and displayed hyperreflexia. Several days later, she had visual disturbance of the left eye. MRI (T2 weighted image) revealed multiple high intensity areas in the dentate nucleus of left cerebellum, left occipital lobe, bilateral caudate nuclei, and the anterior part of bilateral lenticular nuclei. In both cases, CT could not demonstrate these lesions. Both of them were treated with corticosteroid and recovered rapidly. They had no recurrence. MRI is useful in diagnosis and follow-up of ADEM and may reveal lesions other than cerebral or cerebellar white matters.     

Recent Advances in Molecular Genetics of Colorectal Cancer

APC gene and mismatch repair genes. The role of these genes in colorectal carcinogenesis has been studied intensively. The adenoma–carcinoma sequence was initially proposed by Vogelstein, and the multistep carcinogenesis theory is now well accepted. The various functions of the APC gene have been elucidated. APC genes are considered to play a role in shedding of the epithelial cells into the lumen. The mechanism behind formation of a unicryptal adenoma is now better understood. Adenoma formation is a monoclonal event with two hits of the APC gene. There is no zonal extension of the proliferative zone in the background colonic mucosa of FAP patients. In addition to the adenoma–carcinoma sequence, there seem to be various carcinogenetic pathways in the development of colorectal cancer. A depressed type of early cancer was recently found by the use of magnifying endoscopy. The incidence of K- ras mutation was extremely low in this group of early cancers. Some of the minute cancers show the p53 mutation before the occurrence of APC mutation. Cancers of microsatellite mutator phenotype show exaggerated genomic instability at simple repeat sequences, such as TGFβRII. These genes may play a suppressor role in a p53 independent pathway of colorectal carcinogenesis. We are now in an exciting era of this progressing field of science. This genetic information may be more widely applicable clinically in the near future (e.g., for presymptomatic diagnosis, selection of patients for the most appropriate treatments, and assessment of malignant potential).     

A case report of spinal epidural hematoma complicated after open heart surgery]

The authors reported the first case of acute spinal epidural hematoma (SEH) developed after open heart surgery. The patient was noticed that her legs felt weak and numb on the first postoperative day evening. On the next day morning, neurological examination revealed that flaccid paralysis of both legs and also loss of all sensory perception below the level of Th-6 spine bilaterally. The prolonged effect of anesthesia and painless onset made delayed recognition of the lesion. SEH (Th5-7) was diagnosed with MRI and decompressive surgery was immediately done, sixty hours after the beginning of cardiac operation. But in this case neurological deficits were not changed. We concluded that a routine diagnostic approach was very important procedure to find out this serious complication for all patients underwent open heart surgery in early period of its onset.     

Sodium Valproate-lnduced Cardiovascular Abnormalities in the JchlCR Mouse Fetus

Sodium valproate was administered to Jcl:ICR mice in order to evaluate teratogenicity in the cardiovascular system. A single dose of 600mg/kg of sodium valproate was injected intraperitoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized to observe incidence and type of cardiovascular abnormality in live fetuses. Cardiovascular abnormalities were found most frequently in the group treated on day 7, being recognized in 86% of litters (19/22) and in 29% of live fetuses (70/238). Among these, there were 28 cases of transposition of the great arteries, 13 of double outlet right ventricle, 11 of endocardial cushion defect, 9 of ventricular septal defect, 5 of tricuspid atresia, and 4 of hypoplastic left heart syndrome.     

Pharmacokinetic analysis of antibody localization in human colon cancer: Comparison with immunoscintigraphy

The biodistribution and imaging characteristics of the 111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of 111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of 111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8 +/- 8.7 h and 69.5 +/- 21.8 h for t1/2 alpha and t1/2 beta, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of 111In-ZCE-025 in tumors resected by surgery could be found. How 111In-labeled antibody is accumulated into tumors as well as into some nontumor tissues needs further study.