Budd-Chiari syndrome secondary to toxic pyrrolizidine alkaloid exposure.

In this report, we describe a case of pyrrolizidine alkaloid-related Budd-Chiari syndrome in Hong Kong. A 10-month-old boy presented with ascites, right pleural effusion, and hepatomegaly after consumption of herbal drinks for 3 months. His clinical (including imaging) features were compatible with Budd-Chiari syndrome. Budd-Chiari syndrome is a rare disease entity in paediatric patients. In our case, extensive workup performed to look for the underlying cause of Budd-Chiari syndrome was unrevealing, except for toxic pyrrolizidine alkaloid exposure in his herbal drinks.

High-dose glucose-insulin-potassium treatment reduces myocardial apoptosis in patients with acute myocardial infarction.

BACKGROUND: Several clinical trials have suggested that a metabolic cocktail of glucose-insulin-potassium (GIK) decreases mortality rates in patients with acute myocardial infarction (AMI). It has also been reported that Fas-mediated apoptosis plays an important role in ischaemic/reperfusion injury in the rat model. This study was designed to evaluate the interaction of ischaemic/reperfusion and reperfusion therapy coadministered with high-dose GIK treatment on soluble Fas/APO-1 (sFas) and Fas ligand (sFasL) plasma concentration in patients with AMI. MATERIALS AND METHODS: Seventy-four patients presenting with AMI who underwent reperfusion therapy were randomized into a GIK group (n = 35) receiving high-dose GIK for 24 h or a vehicle group (n = 39). Thirty-four control subjects were also enrolled in the present study. Strepavidin-biotin ELISA was used to determine the soluble sFas and sFasL plasma concentration at baseline, 24 h (h), 3 day (d), 7 d and 14 d. RESULTS: Soluble Fas and sFas-L serum concentrations ([sFas] and [sFas-L]) of patients with AMI were significantly elevated at baseline as compared with normal controls (NCs; P < 0.01 vs. NC). The sFas in the GIK and vehicle groups markedly decreased 24 h after the GIK infusion (10.7-->5.9 ng mL(-1) and 9.7-->6.5 ng mL(-1); P < 0.01 vs. baseline) and then increased during the 3-7-d period (5.9-->12.1 ng mL(-1) and 6.5-->11.1 ng mL(-1); P < 0.01 vs. 24 h). The GIK group demonstrated reduced sFas (12.1-->5.9 ng mL(-1)) at 14 d (P < 0.01 vs. 7 d), with no concomitant changes in the vehicle group. The sFas-L in the GIK and vehicle groups was not significant different during the 14-d period. CONCLUSIONS: These results indicate that the sFas and sFasL in patients with AMI increased significantly compared with NC. Owing to the cardioprotective effects reported here and by others, a high-dose GIK infusion co-administered with the timely re-establishment of nutritive perfusion should be strongly considered as a treatment of choice for AMI. Additionally, sFas may be a valuable marker of the physiological response to ischaemic/reperfusion injury and reperfusion associated with high-dose GIK treatment.

Oral fusidic acid fails to eradicate methicillin-resistant Staphylococcus aureus colonization and results in emergence of fusidic acid-resistant strains.

Carriers of methicillin-resistant Staphylococcus aureus (MRSA) in hospital constitute a reservoir of infections and increase the risk of bacteremia and wound infection. In this prospective randomized trial, we tested the effectiveness of oral fusidic acid for eradication of MRSA colonization. From March 1997 through February 1998, patients with MRSA colonization in medical intensive care units in a large urban teaching hospital were randomly assigned to receive fusidic acid 500 mg q8h orally for 7 days or no anti-staphylococcal treatment. Twenty-three MRSA carriers were found during the study period and 16 were eligible for evaluation; six of them received fusidic acid. MRSA colonization was cleared in only two of the six patients with fusidic acid treatment, and later recurred in one of them. MRSA disappeared for 1, 2, 7, 7, and 8 weeks, respectively, in five of the 10 patients without treatment. MRSA persisted in the other five cases. Although all MRSA isolates found in the initial surveillance culture were susceptible to fusidic acid (MIC /= 256 microg/mL). Pulsed-field gel electrophoresis pattern analysis showed that the resistant strains were genetically identical to the susceptible strains isolated from the same patient before fusidic acid treatment, in both cases. However, genetically distinct strains colonized in the same individual during follow-up were found in four out of 16 cases. We conclude that oral fusidic acid alone is not suitable for eradication of MRSA colonization, and may lead to the emergence of resistant strains.

The effectiveness of acupressure in improving the quality of sleep of institutionalized residents.

BACKGROUND: Elderly people often suffer from disturbed sleep. Because traditional Chinese medicine indicates that acupressure therapy may induce sedation, testing the effectiveness of acupressure in enhancing the quality of sleep of institutionalized residents with a well-designed scientific study is needed. METHODS: A randomized block experimental design was used. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used as a screening tool to select subjects with sleep disturbance. By matching the effects of hypertension, hypnosis, naps, and exercise, subjects were randomly assigned to an acupressure group, a sham acupressure group, and a control group. Each group had 28 subjects for a total of 84 subjects. The same massage routine was used in the acupressure group and the sham acupressure group, whereas only conversation was employed in the control group. RESULTS: There were significant differences in PSQI subscale scores of the quality, latency, duration, efficiency, disturbances of sleep, and global PSQI scores among subjects in the three groups before and after interventions. Furthermore, there was a significant reduction in the frequencies of nocturnal awakening and night wakeful time in the acupressure group compared to the other two groups. CONCLUSIONS: This study confirmed the effectiveness of acupressure in improving the quality of sleep of elderly people and offered a nonpharmacological therapy method for sleep-disturbed elderly people.

The antiproliferative and differentiative activities of 1,25-dihydroxyvitamin D3 are potentiated by epidermal growth factor and attenuated by insulin in cultured human keratinocytes.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a potent inhibitor of keratinocyte proliferation, as well as a stimulator of epidermal terminal differentiation. In the present studies, we investigated the influence of epidermal growth factor (EGF) and insulin on the antiproliferative and differentiation activities of 1,25(OH)2D3. Our results indicate the following: (1) EGF caused a dramatic potentiation of the 1,25(OH)2 D3-induced inhibition of 3H-thymidine incorporation into keratinocytes in a dose-dependent manner; (2) insulin acted antagonistically on the EGF-dependent potentiation of the 1,25(OH)2D3-induced antiproliferative activity; (3) transforming growth factor-alpha potentiated 1,25(OH)2D3-induced antiproliferative activity similar to EGF; (4) the EGF effect was not dependent upon 1,25(OH)2D3 receptor mRNA up-regulation; and (5) removal of insulin from medium supplemented with growth factors significantly potentiated the 1,25(OH)2D3-induced inhibition on the number of basal cells and the 1,25(OH)2D3-dependent cornified envelope formation. In conclusion, the antiproliferative activity of 1,25(OH)2D3 in cultured normal human keratinocytes is greatly enhanced by EGF or transforming growth factor-alpha and reduced by insulin. Insulin also inhibits 1,25(OH)2D3-induced terminal differentiation of cultured normal human keratinocytes.

Effects of 1,25-dihydroxyvitamin D3 and phorbol ester on 25-hydroxyvitamin D3 24-hydroxylase cytochrome P450 messenger ribonucleic acid levels in primary cultures of rat renal cells.

The renal 25-hydroxyvitamin D3 24-hydroxylase enzyme, which may be the starting point in the catabolic pathway for vitamin D metabolism, is markedly induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the hormonal form of vitamin D. The purpose of this study was to investigate the regulation of the cytochrome P450 component of this enzyme (P450cc24) by 1,25-(OH)2D3 and phorbol 12-myristate 13-acetate (TPA). P450cc24 messenger RNA (mRNA) levels were measured using the full-length rat complementary DNA probe (p108). In primary cultures of rat renal tubular cells, 1,25-(OH)2D3 produced a 26-fold increase in P450cc24 mRNA which was detectable at 4 h, maximal at 24 h, and returned almost to baseline by 48 h. The induction was inhibited by actinomycin D, 5,6-dichloro-1-b-D-ribofuranosyl benzimidazole (DRB), and cycloheximide, and it was specific for vitamin D compounds containing a 1-hydroxyl group. TPA alone had no effect, but TPA in the presence of 1,25-(OH)2D3 produced an increase in P450cc24 mRNA within 30 min, and this increase peaked at 2 h. TPA also shifted the dose-response curve of 1,25-(OH)2D3 to the left, so that 1,25-(OH)2D3 was effective at a concentration as low as 1 nM. In the same experiments, TPA increased c-fos mRNA levels, and this increase was accelerated by 1,25-(OH)2D3. These studies suggest that the induction of P450cc24 mRNA by 1,25-(OH)2D3 is a receptor-mediated genomic event and that this induction may account for the stimulation of 24-hydroxylase enzyme activity by 1,25-(OH)2D3. In addition, TPA accelerates the effect of 1,25-(OH)2D3 by a mechanism which may involve protein kinase C.

Effects of dietary polyunsaturated fatty acid on platelet aggregation in rats.

In the present study, we changed the fatty acid profile in blood and platelet membranes by dietary manipulation, and examined the effect on platelet aggregation in rats. Fifty-five rats were divided into five groups and fed for 56 days with 1% cholesterol and different types of fatty acid-rich diets: basal, lard, lard + fish oil, soybean oil, and soybean oil + fish oil. a decrease in serum arachidonic acid (20:4, omega-6, AA) and an increase in serum eicosapentaenoic acid (20:5, omega-3, EPA) were found in all experimental dietary groups fed with refined fish oil. Similar changes in the polyunsaturated fatty acids were also found in the platelet membrane phospholipids. Platelet aggregation, quantitated by the slope and height of the aggregation curve induced by different concentrations of ADP in a platelet aggregometer, was inhibited in all groups fed with refined fish oil. This inhibition of platelet aggregation may be related to an increase in the ratio of EPA and AA in the platelet membrane phospholipids after dietary manipulation. The differences in the platelet aggregation and thromboxane B2 (TXB2) concentration between the lard and the lard + fish oil groups were more profound than that between the soybean oil and the soybean oil + fish oil group. However, the malondialdehyde (MDA) concentration revealed no significant differences between the five groups.

Iron metabolism in genetically obese (ob/ob) mice.

Several reports in the clinical literature suggest that obese children may be at risk for developing iron deficiency. Here the absorption, retention, tissue distribution and tissue levels of iron were compared in lean (+/?) and obese (ob/ob) C57BL/6J mice to examine the impact of obesity on the iron status of this animal model. Obese mice absorbed and retained approximately twice as much 59Fe as lean mice after receiving a solution containing 1 mumol iron per os. This difference was independent of age, severity of obesity and mass of the gastrointestinal tract. Obese mice fed ad libitum had higher levels of 59Fe in blood and fat pads, but lower amounts of 59Fe in the skeletal-muscular system, than lean mice 6 d after subcutaneous injection of 1 mumol of the metal. At least 30% of carcass 59Fe was present in the liver of obese and lean mice 6 d after injection. Despite significantly lower concentrations of iron in liver and bone, blood hemoglobin and hematocrit were significantly higher in obese mice fed ad libitum than in lean mice at 10 wk of age. Plasma iron and transferrin were not affected by chronic obesity. Although several characteristics of iron metabolism differed in obese and lean mice, the results indicate that ob/ob mice were not iron deficient when fed a diet containing an adequate level of this micronutrient. The increased absorption of iron by obese mice probably represents an adaptive response that is required to supply additional micronutrient for the expanded blood volume in these animals.

Effect of dietary vegetable (water convolvulus) on cholesterol metabolism in rats.

Male rats were fed diets containing 0.5% cholesterol with or without vegetable (water convolvulus) or neutral detergent fiber supplementation. After 2 weeks, rats were given [4-14C]cholesterol i.p. Feces were collected for 1 week. Three hours prior to necropsy, [3H]acetate was administered i.p. Samples of serum, liver, adipose tissue, muscle and brain were obtained for analysis. Concentrations of total lipids and cholesterol and synthesis and recovery of labeled steroids are reported. Results showed that the growth of animals and food utilization were not significantly affected by different dietary treatments. The notable effect of vegetable was that the elevated liver and serum cholesterol levels due to increased intake can be nearly offset by increasing the fecal excretion. The high rate of excretion of 14C-labeled steroids shown in vegetable-fed rats indicated that both decreased absorption and increased endogenous excretion occurred in these animals. The synthesis of total lipids as demonstrated by [3H]acetate incorporation was not affected appreciably by diet. In liver, however, cholesterol synthesis appeared to be lower in rats receiving cholesterol-supplemented diet, but higher in rats fed vegetable diets. The ratio of 3H:14C of liver cholesterol was significantly higher in rats fed the vegetable diet. In brain cholesterol we also found consistently high 3H:14C ratios, which were not affected by dietary intake. It appears that brain cholesterol level is maintained mainly by synthesis in situ and not by uptake from dietary or other sources.