Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload

Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene-targeted mice. Apelin mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure overload-induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin(-/y) and Apelin(+/y) mice showed concerted upregulation of genes involved in extracellular matrix remodeling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.     

Bispectral monitoring during vital capacity rapid inhalation induction with sevoflurane

STUDY OBJECTIVE: To evaluate the variables of bispectral index (BIS) values during vital capacity rapid inhalation induction (VCRII) with sevoflurane. DESIGN: Randomized, prospective study. SETTING: University hospital. PATIENTS: 40 ASA physical status I and II patients scheduled for elective orthopedic surgery with general anesthesia. INTERVENTIONS: Patients was divided into two groups, both of which received intravenous (IV) injection of propofol 2 mg/kg followed by inhalation of sevoflurane 3% (Group P), or vital capacity inhalation induction with sevoflurane 8% (Group S). After loss of consciousness, tracheal intubation was performed with vecuronium 0.1 mg/kg. MEASUREMENTS AND MAIN RESULTS: The induction times in Group P were significantly shorter than those in Group S (p < 0.01). In Group S, BIS values were gradually decreased and maintained the adequate hypnotic levels were maintained during induction. In Group P, although BIS values were rapidly decreased, the values remained higher compared with Group S. The BIS value before intubation in Group S was significantly lower than that in Group P (25 +/- 9 and 38 +/- 7, respectively; p < 0.01). Five of 20 Group P patients had BIS values exceeding 60 before tracheal intubation, but no patient in Group S had a BIS value as high. Mean arterial pressure immediately after intubation in Group S was significantly lower than that in Group P (p < 0.05). CONCLUSION: VCRII with a high concentration of sevoflurane provided adequate BIS values during induction, suggesting that it may allow smoother transition from anesthesia induction to maintenance, and also maintain an adequate hypnotic level in readiness for certain stimuli such as laryngoscopy and tracheal intubation.     

Dropped head syndrome in severe intractable epilepsies with mental retardation.

PURPOSE: Dropped head syndrome is characterized by a gradual forward sagging of the head due to the isolated weakness of the neck extensor muscles. The syndrome has a relatively benign clinical course. To date, there have been no reports of dropped head syndrome in epileptic patients. METHODS: Nine patients with intractable epilepsy (mean age, 33.6+/-9.91 years), each presenting with apparent dropped head, were evaluated. The duration of the drooping head symptom varied from 3 to 15 years (mean, 7.4+/-4.06 years), with a slowly progressing weakness in most of the patients. In all of the patients, extensive clinical, laboratory, electrophysiological, histopathological, and neuroimaging examinations were performed. RESULTS: The weakness in all of the subjects was strictly limited to the cervical paraspinal muscles. Laboratory studies produced normal results from all subjects. EMG and muscle biopsy were normal or revealed subtle nonspecific myopathic changes without inflammation in the cervical paraspinal muscles. Polymyographic investigation revealed that none of the patients had convincing dystonic spasms of the anterior neck muscles. No atrophy or fatty changes of the neck extensor muscles were observed on CT or MRI. In most of the patients (7/9), altered L-carnitine concentrations were observed (four patients displayed a marked decrease in plasma carnitine concentrations, and three other patients showed abnormalities in urinary excretion of carnitine). CONCLUSIONS: These findings seem to suggest that a secondary carnitine deficiency, induced by antiepileptic drugs (principally valproic acid), represents a plausible pathogenetic mechanism for the development of dropped head in some epileptic patients.     

Alterations of serum selenium concentrations in the acute phase of pathological conditions.

BACKGROUND: Selenium (Se), an essential trace element, is known to be a cofactor of antioxidative selenoenzymes such as glutathione peroxidase and thioredoxin reductase. METHODS: We assessed the pathophysiological significance of selenium (Se) by comparing the concentrations of serum Se and C-reactive protein (CRP) in healthy subjects (141; M=71, F=70) vs. patients with various pathological conditions. RESULTS: In normal males in their 40s, peak serum Se concentrations were observed (2.03+/-0.30 microg/g of serum protein, 128%, P<0.001) vs. males in their 20s (1.59+/-0.20), whereas a peak was observed in females in their 30s (1.87+/-0.31, 119%, P<0.025) vs. those in their 20s (1.57+/-0.22). The serum Se concentrations in the high CRP value group (n=40, 1.07+/-0.29 microg/g, 64.1%), the rheumatoid arthritis (RA) test positive group (n=24, 1.37+/-0.29, 82.0%), the lung cancer group (n=16, 1.38+/-0.30, 82.6%), and the adult T-cell leukemia (ATL) group (n=22, 1.26+/-0.35, 75.4%) were significantly lower (P<0.001) than those in the healthy subjects (1.67+/-0.29 microg/g). This finding was confirmed by inducing acute phase response (APR) in rats by injection of lipopolysaccharide (LPS), which produced a significant decrease of Se in plasma and liver (69.5% and 81.6% vs. untreated rats, P<0.05). In contrast, the Se content in muscle, kidney, lung, spleen, heart, and thymus showed increases of <10%. Se mobilized from liver after LPS-challenge appeared to be translocated to muscle, and Se concentrations recovered by 80 h after APR to the control concentrations in parallel with the subsidence of APR. CONCLUSIONS: The reduction of Se in the liver and plasma during APR may be associated with the increased CRP synthesis in the liver.     

Eosinophil infiltration in posttransurethral resection prostatitis and cystitis with special reference to sequential changes of eosinophilia

Posttransurethral resection (TUR) status in the prostate and urinary bladder has been infrequently documented. Furthermore, sequential changes in eosinophil count in peripheral blood (PB) after TUR have not been investigated in detail. In the present study, eosinophil counts and changes in eosinophils in PB were examined before to after TUR of the prostate (P) in 20 patients with benign prostatic hyperplasia. Among them, 14 patients exhibited increased numbers of eosinophils, the greatest increase being 17%. After TUR to treat bladder tumor (BT), massive infiltration of eosinophils into the resected areas, peaking 1 month later, was also detected in 8 of 15 cases of post-TUR cystitis. The PB eosinophil counts increased by more than 5% in two of five cases of post-TUR cystitis in which eosinophil counts were obtained before and after surgery. Most infiltrating eosinophils reacted positively to antibodies to eosinophil cationic proteins. These results indicated that, in patients with post-TUR prostatitis, the number of eosinophils in PB increased, and peaked 1 month later, with infiltration by eosinophils observed. Pathologists and urologists should be aware of the potential for increase in eosinophils not only in regions of TUR but also in PB.