Oral supplementation with gamma-linolenic acid extracted from Mucor circinelloides improves the deformability of red blood cells in hemodialysis patients

BACKGROUND: The development of abnormalities in red blood cell (RBC) deformability in patients undergoing hemodialysis remains a major problem, because it is related to peripheral microcirculation, oxygen supply, and various complications in such patients. gamma-Linolenic acid (GLA; 18:3n-6), one of the polyunsaturated fatty acids and a precursor of prostaglandin E(1), is reported to have a favorable effect on the deformability of circulating blood cells in diabetic patients. METHODS: In order to clarify the efficacy of GLA on RBC deformability in 7 patients undergoing maintenance hemodialysis, we examined in a pilot study the changes in the deformability of RBC and the changes in the phospholipid fatty acid composition in both plasma and RBC membrane before and after high-dose oral supplementation with GLA derived from Mucor circinelloides for 12 weeks. RESULTS: Before supplementation, the micropore passage time of RBC suspension, which is an indicator of RBC deformability, in these patients was markedly longer than that in healthy control subjects. After administering GLA, the prolonged passage time of the patients both rapidly and steadily decreased and nearly reached control levels. Light microscopic observations of RBCs using Giemsa stain revealed a decreased number of poikilocytes after supplementation. An analysis of the fatty acid composition before treatment and 8 weeks after starting the treatment showed the dihomo-gamma-linolenic acid (DGLA; 20:3n-6) level in the plasma to have increased (p < 0.05), while the arachidonic acid (AA; 20:4n-6) concentration in the RBC membrane decreased (p < 0.05). The level of DGLA in the RBC membrane, the level of GLA, and the ratio of GLA + DGLA/AA in plasma and RBC membrane did not change significantly; however, these all tended to increase. CONCLUSION: The results of this pilot study indicate that the oral supplementation of GLA extracted from M. circinelloides improves the poor RBC deformability in hemodialysis patients, partly by inducing changes in the composition of fatty acids in plasma and RBC membrane.     

Successful catheter ablation of ventricular tachycardia originating from the idiopathic saccular apical left ventricular aneurysm

Left ventricular (LV) aneurysm has been recognized to frequently become a substrate of ventricular tachyarrhythmias. We report a case of a 66-year-old woman with symptomatic sustained monomorphic ventricular tachycardia (SMVT) originating from saccular apical LV aneurysm without definite underlying diseases. We performed catheter ablation using electroanatomical and conventional bipolar potential mapping. During SMVT, we found an area of fragmented potential -40 ms preceding the earliest wide QRS complex in the area of the apical LV aneurysm. Radiofrequency applications were delivered to this area. Since then, SMVT was no longer inducible by programmed electrical stimulation. The patient has remained free of VT recurrences during a subsequent 12-month follow-up period.     

The physical activity patterns of cardiac rehabilitation program participants

PURPOSE: This investigation aimed to examine the physical activity patterns of cardiac rehabilitation program (CRP) participants. METHODS: The investigation enrolled 53 male and 24 female CRP participants between 46 and 88 years of age. By means of a uniaxial accelerometer (Life-Corder), the amount of physical activity (in kilocalories) and the time spent in physical activity at light (<3 metabolic equivalents [METs]), moderate (3 to 6 METs), and vigorous (>6 METs) intensity were evaluated. In addition to these variables, the MET levels for the CRP and non-CRP periods were calculated. RESULTS: The weekly amount of physical activity energy expenditure averaged 1597 +/- 846 kcal/week, and the time spent in light, moderate, and vigorous physical activity averaged, respectively, 375.5 +/- 124.5 minutes, 125.2 +/- 109.4 minutes, and 5.7 +/- 12.8 minutes per week. These levels were significantly lower on non-CRP days than on CRP days: 177 +/- 113 versus 299 +/- 161 kcal/day and, respectively, 49.3 +/- 19.3 versus 59.7 +/- 19.8 minutes, 10.5 +/- 14.6 versus 26.4 +/- 20.4 minutes, and 0.4 +/- 1.7 versus 1.4 +/- 3.0 minutes per day. CONCLUSIONS: These results indicate that the amount of physical activity was generally adequate on CRP days, but failed to reach target levels on non-CRP days. Thus CRP participants, when it is medically appropriate, should be encouraged to incorporate lifestyle physical activity, additional exercise, or both on non-CRP days to supplement their caloric expenditure from CRP exercise sessions.     

Infection mechanism of biofilm‐forming Staphylococcus aureus on indwelling foreign materials in mice

Indwelling foreign‐body infections are a critical medical problem, especially in immunocompromised patients. To examine the pathogenicity of biofilm‐forming bacteria settling on foreign materials, mice implanted with plastic discs were infected with Staphylococcus aureus. After opening a wide subcutaneous pocket on the dorsal side of mice with or without temporal leukocytopenia, a plastic sheet was placed in the left subcutaneous space; subsequently, bacteria in a planktonic state were dispersed over the subcutaneous space. Bacterial numbers were examined 7 days after inoculation. In subcutaneous tissue on the right, S. aureus was found only in leukocytopenic mice. Meanwhile, bacteria were detected on the plastic and neighbouring tissue in both leukocytopenic and normal mice; however, colony‐forming analysis indicated that leukocytopenic mice possessed significantly more bacteria. Tissue reaction against bacteria was pathologically examined. Invading S. aureus induced severe inflammation. In transient leukocytopenic mice, bacterial microcolonies formed on the plastic as well as in the developed necrotic tissue – both of which were shielded from inflammatory cell infiltration – result in bacteraemia. These results indicate that biofilm‐forming S. aureus settling on indwelling foreign material are tolerant against host immunity and assault neighbouring tissue, which may lead to chronic wound infection.     

The mitochondrial protein frataxin is downregulated in hemodialysis patients

Background

The mitochondrial protein frataxin regulates iron metabolism for heme and iron sulfur cluster synthesis in the mitochondria and could be associated with the regulation of oxidative stress. To clarify the expression of frataxin and its association with uremia, we evaluated the mRNA and protein levels of frataxin in the polymorphonuclear leukocytes (PMNLs) of patients on hemodialysis (HD).

Methods

Uremic patients on HD (n = 18) and healthy control subjects (n = 18) were investigated. PMNLs were isolated by differential centrifugation. The mRNA levels of frataxin in isolated leukocytes were quantified by TaqMan real-time polymerase chain reaction. Frataxin protein expression in the cell lysate was evaluated using SDS-polyacrylamide gel electrophoresis and Western blotting.

Results

The frataxin/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in PMNLs from uremic patients was significantly lower than that in control subjects. Frataxin protein expression in uremic patients was also significantly lower than that in controls. Multiple regression analysis showed that frataxin mRNA levels were independently associated with the serum levels of both the oxidative stress marker malondialdehyde and the proinflammatory cytokine tumor necrosis factor-α.

Conclusion

The downregulation of frataxin seems to be linked with uremic status, which is usually associated with chronic inflammation and the acceleration of oxidative stress. Mitochondrial iron regulation may play a role in several comorbidities and in the poor prognosis in uremic patients. Further investigation is needed to elucidate whether reduced frataxin levels are linked to the pathological status of uremic patients and whether uremic substances affect frataxin expression.     

Endovascular therapy for massive haemothorax caused by ruptured extracranial vertebral artery aneurysm with neurofibromatosis Type 1

Extracranial vertebral artery aneurysm is uncommon, and the common cause is penetrating trauma. Rupture of extracranial vertebral artery aneurysm into the thoracic cavity is extremely rare and fatal due to haemorrhagic shock by massive haemothorax. We report an intrathoracic rupture of the extracranial vertebral artery aneurysm with neurofibromatosis Type 1, successfully treated by coil and liquid embolisation.     

Amenorrhea in Olympic marathon runners

Women who exercise heavily may develop secondary amenorrhea. Since the mechanism of so-called "runner's amenorrhea" has not been conclusively established, the authors examined the occurrence of amenorrhea in one of the most intensively exercising groups of female runners in the United States (average, 70 miles/week): those women participating in the marathon trials for the 1984 Olympics. Nineteen percent of these Olympic runners were amenorrheic. When compared with eumenorrheic marathon runners, these amenorrheic runners were significantly (P less than 0.05) younger (24.8 +/- 1.2 [standard error of the mean] versus 30.8 +/- 0.8 years), lighter (108.4 +/- 2.5 versus 114.6 +/- 1.7 lb), and leaner (11.2 +/- 0.5 versus 12.5 +/- 0.3% body fat). There were no differences between the two groups in weekly training mileage, proportion completing the marathon trial, finishing time, basal serum prolactin, or postmarathon serum prolactin. Although basal serum cortisol was slightly higher in the amenorrheic group (26.6 +/- 0.8 versus 22.3 +/- 0.7 micrograms/dl; P less than 0.05), postmarathon serum cortisol was similar in the two groups. This study supports the concept that training intensity above a certain threshold seems to have little effect on the development of runner's amenorrhea, and vigorously training national caliber marathon runners have a lower incidence of amenorrhea than previously predicted.     

Chymase inhibitor improves survival in hamsters with myocardial infarction

The purpose of the present study was to assess the effects of chronic treatment with an orally active chymase inhibitor, 4-[1-(naphthylmethyl)benzimidazol-2-ylthio]butanoic acid (TEI-E548), in a hamster myocardial infarction model. In the first experiment, after confirming the biochemical inhibitory action of TEI-E548 on human and hamster chymases (Ki = 6.2 and 30.6 nM, respectively), the biological action of TEI-E548 in vivo was assessed by the inhibition of hamster chymase-induced microvascular leakage. In the second experiment, myocardial infarction was produced by coronary artery ligation in male Syrian hamsters. TEI-E548 (0.1% containing chow) was given 24 h after surgery and continued for 3 or 5 weeks, while the control and sham-operated groups were fed a standard chow. The survival rate was assessed in each group. At the end of each study period, blood pressure was measured at the left hind-limb, the heart rate and cardiac function were measured by echocardiography, the end-diastolic pressure by a direct catheterization, and organ weights and biochemical parameters, including plasma renin and angiotensin-converting enzyme activities and plasma angiotensin I and angiotensin II concentrations, were measured. In the first experiment, a standard chow containing 0.1% TEI-E548 completely inhibited the hamster chymase-induced microvascular leakage. In the second experiment, TEI-E548 treatment significantly increased the survival rate (37% versus control), and attenuated cardiac hypertrophy (13% versus control) and end-diastolic left ventricular pressure (34% versus control), but it did not decrease the infarction size nor improve the ejection fraction. The plasma angiotensin II concentration post-myocardial infarction was significantly suppressed by TEI-E548 throughout the study period. We conclude that TEI-E548 is an orally active useful chymase inhibitor and improves survival and cardiac hypertrophy of the post-myocardial infarction hamster.     

Mediastinal ultrasonography for the assessment of mediastinal lymph node metastases in lung cancer patients

Using an ultrasonic probe inserted into the mediastinum during cervical mediastinoscopy, mediastinal ultrasonography (USM) was performed on 63 patients with lung cancer. The patients with a small peripheral mass of less than 2 cm in diameter, according to the chest X-ray results, and with mediastinal lymph nodes smaller than 1 cm in their short axes as determined by computed tomography (CT), were excluded from this study. An analysis of the areas under the receiver operating characteristic curves derived from CT and USM showed that USM was superior (P=0.043) to CT in terms of the diagnosis for mediastinal lymph node metastases, when the short axis dimension of mediastinal lymph nodes was employed for the diagnosis of metastases. The reason for this is that 97% of the mediastinal lymph nodes imaged by USM were located vertically along the body axis of the patient, and hence USM imaged the true short axis of the node in many cases. Our results indicate that USM is useful for performing a safe biopsy of lymph nodes during mediastinoscopy as well as for obtaining a clear imaging of the subcarinal nodes, which are inaccessible by normal cervical mediastinoscopy.