Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.     

Independent determinants of second derivative of the finger photoplethysmogram among various cardiovascular risk factors in middle-aged men.

The second derivative of the finger photoplethysmogram (SDPTG) has been used as a non-invasive examination for arterial stiffness. The present study sought to elucidate independent determinants of the SDPTG among various cardiovascular risk factors in middle-aged Japanese men. The SDPTG was obtained from the cuticle of the left-hand forefinger in 973 male workers (mean age: 44+/-6 years) during a medical checkup at a company. The SDPTG indices (b/a and d/a) were calculated from the height of the wave components. Multiple logistic regression analyses revealed that the independent determinants of an increased b/a (highest quartile of the b/a) were age (odds ratio [OR]: 1.12 per 1-year increase, 95% confidence interval [CI]: 1.09-1.15), hypertension (OR: 1.65, 95% CI: 1.03-2.65), dyslipidemia (OR: 1.51, 95% CI: 1.09-2.09), impaired fasting glucose/diabetes mellitus (OR: 2.43, 95% CI: 1.16-5.07), and a lack of regular exercise (OR: 2.00, 95% CI: 1.29-3.08). Similarly, independent determinants of a decreased d/a (lowest quartile of the d/a) were age (OR: 1.11 per 1-year increase, 95% CI: 1.08-1.14), hypertension (OR: 3.44, 95% CI: 2.20-5.38), and alcohol intake 6 or 7 days per week (OR: 2.70, 95% CI: 1.80-4.06). No independent association was observed between the SDPTG indices and blood leukocyte count or serum C-reactive protein levels. In conclusion, the SDPTG indices reflect arterial properties affected by several cardiovascular risk factors in middle-aged Japanese men. The association between inflammation and the SDPTG should be evaluated in further studies.     

A case of aneurysm of the inferior left ventricular wall

Aneurysms of the inferior left ventricular wall represent only a small fraction of all aneurysms that have been reported in surgical series. And in comparison to anterior left ventricular aneurysms, a comparatively higher percentage of reported inferior wall aneurysms was classified as false. A 73-year-old male was admitted for acute inferior myocardial infarction. Three weeks after admission, cardiac catheterization was carried out. Coronary arteriography revealed triple vessel disease and left ventriculography showed an aneurysm of the inferior left ventricular wall, whose feature near the mitral annulus was multiple fenestrations. Left ventricular aneurysmectomy and aortocoronary bypass grafting to the left anterior descending artery were simultaneously performed under cardiopulmonary bypass with moderate hypothermia. The pathological feature was a true aneurysm. The postoperative course was uneventful.     

Ketamine infusion for control of pain in patients with advanced cancer

The effect of ketamine infusion to control the intractable pain which had not responded to ordinary procedures in 12 patients with advanced cancer were evaluated. Ketamine 250 mg or 500 mg in 500 ml of transfusion fluid with or without 10 to 20 mg of droperidol was administered intravenously at the rate of 3 to 20mg of ketamine per hour. The pain scores by VAS in most of the patients decreased significantly with an averaged value of 8.3 before the treatment to 1 during the procedure. The durations of this therapy lasted from over 6 hours to 48 days. Slight disorientation in one patient and drowsiness in 5 were seen during the infusion. No cardiovascular or respiratory complications were noted. These results indicate that ketamine infusion is a useful therapeutic procedure to treat cancer pain which resist ordinary pain therapies.     

Abnormalities in cough reflex]

Enzymes degrading peptides may participate in the regulation of the cough reflex. Thus, decreases in enzyme activities may enhance cough reflex and a decrease in cough reflex may lead to aspiration pneumonia. Down- and up-regulation of cough reflex is important for the understanding of cough reflex.     

Plasma carnitine concentrations in patients undergoing open heart surgery.

Carnitine is an essential cofactor for fatty acid (FA) metabolism, the predominant source of ATP in the normal aerobic heart. During myocardial ischemia, FA metabolism is impaired and tissue carnitine levels are depleted. Since the heart cannot synthesize carnitine, plasma carnitine could play an important role in maintaining myocardial carnitine levels during reperfusion. The purpose of this study was to determine the incidence of abnormal plasma carnitine concentrations in open heart surgery. Blood samples were obtained from eleven patients before, immediately after, and two hours after cardiopulmonary bypass (CPB). Total and free carnitine levels were significantly reduced immediately after CPB (p<0.01) and remained depressed until two hours after CPB (p<0.01 vs. pre CPB), while acyl carnitine levels were unchanged over the course of this study. These depressed free carnitine levels might affect cardiac metabolism in the heart after open heart surgery. Carnitine supplement might be a useful adjunct in the therapy after open heart surgery.     

Comparison between a new acceleration transducer and a conventional force transducer in the evaluation of twitch responses

An acceleration transducer elicits an output voltage proportional to the deformation of the piezo crystal, in accordance with the twitch responses of the applied fingers. The reliability of such a transducer was evaluated by comparing induced twitch responses with those from a force transducer applied on the contralateral arm of an individual during neuromuscular block with vecuronium. The results obtained from twitch responses with the acceleration transducer during neuromuscular block were almost identical to those obtained with the force transducer. Also, the twitch heights due to acceleration of the examined thumb correlated extremely well with the twitch height due to twitch tension with the force transducer. It is concluded that the acceleration transducer may be a useful and reliable device for monitoring neuromuscular block, although responses during tetanic stimulation such as tetanic fade cannot be determined by the transducer.     

Response of V beta 8.1+ T cell clones to self Mls-1a: implications for the origin of autoreactive T cells.

Clonal deletion and anergy are two major mechanisms of self-tolerance. However, the molecular mechanisms underlying clonal deletion and anergy, as well as the threshold of TCR affinity/avidity required for these processes, are not known. Expression of the V beta 8.1 TCR correlates with the reactivity of the T cells to the minor lymphocyte stimulating locus-1a (Mls-1a) and T cells expressing this TCR are deleted in the thymus of Mls-1a mice. Similarly, in TCR V beta 8.1 transgenic mice, the number of CD4+CD8-T cells is reduced in Mls-1a mice. However, small numbers of CD4+CD8-T cells remain in the periphery of adult Mls-1a transgenic mice. We have generated T cell clones from TCR V beta 8.1 transgenic mice by stimulation of lymph node T cells with C57BL/6 alloantigens. Interestingly, CD4+CD8-V beta 8.1+ clones isolated from the transgenic mice of Mls-1a background responded to the self-antigen Mls-1a, to which they did not respond in primary assay. Reactive patterns of the clones were compared with clones derived from Mls-1b mice. Proliferation and cytokine production of the clones from Mls-1a mice to the self-antigen Mls-1a were generally reduced when compared with clones from Mls-1b mice. More importantly, T cell clones from Mls-1a mice required more Mls-1a antigen for their activation, and were more susceptible to the inhibitory effects of anti-CD4 antibody on the proliferative responses to Mls-1a than those from Mls-1b mice. These results suggest that the T cell receptor on clones derived from Mls-1a mice have functional but reduced affinity/avidity for self-antigen Mls-1a.     

Serum Levels of Free Insulin-Like Growth Factor (IGF)-I in Normal Children

Serum levels of free insulin-like growth factor (IGF)-I were measured by immunoradiometric assay (IRMA) in fasting sera of 137 normal boys and 120 normal girls aged from 8 to 15 yr to study relationships between free IGF-I levels and ages, total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit (ALS) levels. In both sexes, serum free IGF-I levels and the ratios of free IGF-I to total IGF-I were significantly higher in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-I showed a significant positive correlation with those of total IGF-I, IGFBP-3 and ALS, while they showed a significant negative correlation with those of IGFBP-1. These observations suggest that increase in serum free IGF-I levels during puberty is caused by a dramatic increase in total IGF-I, rather than IGFBP-3, and a decrease in IGFBP-1. Also, high free IGF-I levels may play an important role in pubertal growth spurt.     

Effects of sodium nitroprusside (MR7S1) and nitroglycerin on the systemic,renal, cerebral,and coronary circulation of dogs anesthetized with enflurane

Summary In beagle dogs anesthetized with enfluranenitrous oxide, effects of sodium nitroprusside (SNP; MR7S1) and nitroglycerin (NTG) on hemodynamics and main organ circulation were studied to evaluate their effectiveness and safety as hypotensive agents during anesthesia. SNP (MR7S1) infusion (1–10 g/kg/min) decreased arterial blood pressure in a dose-dependent manner. The hypotension was stable during the infusion. After discontinuation of infusion, the blood pressure rapidly returned to the initial level. The hypotension was associated with decreases in cardiac output and total peripheral resistance. NTG infusion (3–10 g/kg/min) decreased arterial blood pressure, too, but the hypotension was less marked and not dose dependent, and the recovery was slower. Neither drug changed the heart rate. Infusion of SNP (MR7S1) and NTG did not change the hypotension induced by the injection of adenosine, SNP, and NTG. Furthermore, cerebral blood flow, cerebral oxygen consumption, and renal blood flow were unchanged during the hypotension produced by either drug. Coronary blood flow was decreased, but this was due to decreases in cardiac oxygen consumption. In conclusion, SNP (MR7S1) is superior to NTG as a hypotensive agent during anesthesia in efficacy, clear dose dependency, and rapid recovery. The hypotension induced by NTG as well as SNP (MR7S1) seems to have no undesirable effects on the circulation of important organs.