Heme oxygenase (HO) is the rate-limiting enzyme for heme degradation, and elevated levels of HO may be associated with a variety of pathologic disturbances. A limited number of HO inhibitors such as the metalloporphyrins have been proposed as possible chemotherapeutic agents for the treatment of hyperbilirubinemia. We undertook the study of various natural newly synthesized heme analogues as possible inhibitors of HO in human adult and fetal liver microsomes. We investigated two compounds with substitutions at the 2 and 4 position of the porphyrin ring, iron deuteroporphyrin 2,4 disulfonic (1a) and iron deuteroporphyrin 2,4 bis glycol (1b), and two compounds with substitutions of aromatic groups on the methene bridges of the porphyrin molecule, meso-tetra-4-carboxyphenyl-porphine (2a) and meso-tetra-4-sulfonatophenyl-porphine (2b). When these heme analogues were incubated in the reaction media in the presence of heme, two of the analogues (1a) and (1b) inhibited the conversion of heme to bilirubin. This inhibition was 97% and 65% respectively for (1a) and (1b) when both were present in 30 microM concentrations. Both of these compounds exhibited competitive type inhibition. The kI for the more potent inhibitor, (1b), was determined to be 0.30 microM. Porphyrins with aromatic substitutions at the methene bridges (2a, 2b) did not inhibit the conversion of heme to bilirubin, even at relatively high concentrations. Furthermore, the specific activity of HO was significantly greater (5X) in fetal microsomes as contrasted with adult microsomes as contrasted with adult microsomes. Even though fetal microsomes had greater HO activity, 5 microM of compound (1b) caused a similar degree of inhibition in both adult and fetal preparations.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
Serum, lymphocyte and erythrocyte potassium, magnesium and calcium concentrations were measured in 31 patients with congestive cardiac failure and 14 patients with mild noncomplicated hypertension, who had been receiving either furosemide or chlorothiazide (with or without potassium supplementation) or a combination of hydrochlorothiazide and amiloride for more than 6 months. Lymphocyte potassium concentrations (pmol/100 cells +/- SE) were as follows: controls 18.1 +/- 1.5, furosemide 14.1 +/- 0.9 (p less than 0.001), furosemide + potassium 12.3 +/- 0.7 (p less than 0.001), chlorothiazide 13.1 +/- 1.0 (p less than 0.001) and hydrochlorothiazide + amiloride 18.6 +/- 0.7 (p = NS). There was a statistically significant relationship between the number of months the patients had been on diuretics and their lymphocyte potassium concentrations. Serum electrolytes, apart from the group receiving chlorothiazide who showed a significant fall in serum K, were unchanged. 相似文献
Reports of accessory soleus muscle are rare, perhaps as a result of it often remaining unrecognized. It presents as a swelling behind the ankle and may be mistaken for a tumour or inflammatory lesion, as occurred in the first of a series of three cases. The other two were incidental findings, one in a 30 year old man with an open tibial fracture and the other in a 9 month old child with a club foot. Patients present with either pain or a diagnostic problem. When large, it may make wearing of footwear difficult. Computerized tomography with electromyography enables confirmation of the diagnosis. Pain is relieved by epimysiotomy and when encountered incidentally during surgery, incision of the epimysium is all that is needed. Excision of the muscle may be considered only if wearing of footwear is difficult. The significance of its presence in a case of club foot is unknown. Disinsertion of its insertion was all that was required to obtain surgical correction of the deformity in the present case. Awareness of the condition will prevent unnecessary surgery in asymptomatic cases. 相似文献
Small single-institutional studies performed prior to the introduction of organ allocation using the Model for End-Stage Liver Disease (MELD) suggest that early airway extubation of liver transplant recipients is a safe practice. We designed a multicenter study to examine adverse events associated with early extubation in patients selected for liver transplantation using MELD score. A total of 7 institutions extubated all patients meeting study criteria and reported adverse events that occurred within 72 hours following surgery. Adverse events were uncommon: occurring in only 7.7% of 391 patients studied. Most adverse events were pulmonary or surgically related. Pulmonary complications were usually minor, requiring only an increase in ambient oxygen concentration. The majority of surgical adverse events required additional surgery. Analysis of a limited set of perioperative variables suggest that blood transfusions and technical factors were associated with an increased risk of adverse events. In conclusion, while early extubation appears to be safe under specified circumstances, there are performance differences between institutions that remain to be explained. 相似文献
Background: The authors explored the database of the first International Study of Postoperative Cognitive Dysfunction study to specify the domains of cognitive function that were most vulnerable and to determine the pattern of deterioration in patients with preoperative cognitive impairment.
Methods: One thousand two hundred eighteen patients were included in the first International Study of Postoperative Cognitive Dysfunction, where neuropsychological testing was performed at entry to the study, at 1 week, and at 3 months after surgery. The authors' analyses determined the extent to which seven neuropsychological measures changed after surgery with focus on the relation with preoperative cognitive impairment, defined as a preoperative score 1.5 SD below healthy controls in the memory test.
Results: Preoperative cognitive impairment was found in 74 patients at baseline. At 1 week, cognitive deterioration was seen in all tests, but in particular in the Letter Digit Coding and the time of the Stroop interference test, with 14% and 16% of the total sample (n = 1,016) exceeding 2 SD, respectively. At 3 months, deterioration was more uniform. Significantly fewer in the preoperative cognitive impairment group had deterioration in the memory test, both at 1 week and at 3 months, with no patient displaying a deterioration exceeding 2 SD. 相似文献
We have previously demonstrated that in pentylenetetrazole (PTZ)-kindled rats, cysteamine causes prolonged depression of the kindled state. We now report that administration of cysteamine before or during the kindling process prevents attainment of the kindled state. This effect lasts long after cysteamine administration has ceased, suggesting that depletion or somatostatin may not be the only mechanism underlying cysteamine's effect on kindling. The results also support the likelihood that PTZ kindling primarily effects neocortical rather than limbic structures. 相似文献
The purpose of this study was to determine the effects of superior displacement of the hip center and changes in three prosthetic parameters (neck length, neck-stem angle, and anteversion angle) on the capacity of muscles to generate force and moment about the hip. A three-dimensional model that calculates the maximum isometric forces and moments generated by 25 muscles crossing the hip over a wide range of body positions was used to evaluate the effects of a 2 cm elevation of the hip center and changes in the prosthetic parameters. After superior displacement of the hip center, the neck length was increased from 0 to 3 cm, the neck-stem angle was varied between 110 and 150°, and the anteversion angle was varied between 0 and 40°. Our analysis showed that a 2 cm superior displacement of the hip center would decrease the moment-generating capacity of the four muscle groups studied (abductors, adductors, flexors, and extensors) if neck length were not increased to compensate for decreased muscle length. In the computer model of an adult man that we used, a 2 cm increase in neck length restored the moment-generating capacity of the muscles by increasing muscle length and force-generating capacity. However, a 3 cm increase in neck length increased passive muscle forces substantially, which potentially could limit joint motion. An increased neck-stem angle (i.e., a valgus neck) decreased the abduction moment arm but increased the moment-generating capacity of the other muscle groups. A change in the anteversion angle from 0 to 40° had a relatively small effect on the isometric moment-generating capacity of the muscles studied. 相似文献
Background: Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS‐B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Methods: Saliva samples were collected from 20 patients and 20 age‐, race‐, and gender‐matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Results: Higher number of salivary CaMBPs was observed among patients than controls. Conclusions: The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease. 相似文献
A 26-year-old female was on continuous ambulatory peritoneal dialysis (CAPD) because of diabetic end-stage renal failure. She developed an acute peritonitis that relapsed repeatedly despite appropriate antibiotic treatment. Investigations showed the presence of a splenic abscess, and splenectomy and peritoneal cannula removal were required. The patient died of myocardial infarction two weeks postoperatively. This is the first recorded case of peritonitis secondary to splenic abscess in a CAPD patient. Autopsy findings suggest that the abscess developed from infection of a splenic infarct. 相似文献