PVI in analyzing pressure volume relationship--effect of a bolus mannitol administration

It has been considered that mannitol reduces a raised intracranial pressure effectively by improving pressure volume relationship. The objective of this study is to determine how the pressure volume status is changed by a bolus mannitol administration with using several biomechanical parameters (intracranial pressure, pressure volume index, and intracranial elastance). Our data indicated that mannitol changed the PVI more sensitively than ICP and elastance. "Estimated Intracranial Volume Change (EICVC)" has been newly defined during mannitol infusion on the basis of PVI and ICP change. EICVC for first 30 minutes-period at which the intracranial pressure most vigorously decreased was only about 5 ml in volume. The temporal course of EICVC and ICP were not different, thus, it could account for the change of ICP properly. However, the temporal course of PVI indicating the intracranial venous blood pooling, can not be explained only by EICVC since the PVI has been changed more rapidly than any other parameters. Therefore, we speculated that the ratio of intracranial components could be more largely altered by mannitol than the net of intracranial volume change. The fundamental mechanism of ICP reduction by mannitol is possibly the brain water movement into venous circulation.     

Adult Growth Hormone Deficiency: Current Concepts

The clinical syndrome of adult growth hormone deficiency (AGHD) was widely recognized in the 1980s. In this review, we first describe the clinical features and diagnosis of AGHD and then state the effects of growth hormone (GH) therapy for these patients. The main characteristics of AGHD are abnormal body composition, dyslipidemia, insulin resistance, and an impaired quality of life (QoL) due to decreased psychological well-being. For diagnosing AGHD, the international consensus guidelines have suggested that an insulin tolerance test (ITT) is the gold standard, but in Japan, the growth hormone releasing peptide-2 (GHRP-2) test is available and is recommended as a convenient and safe GH stimulating test. The cut-off for diagnosing severe AGHD is a peak GH concentration of 9 g/L during the GHRP-2 test. Since 2006, GH therapy has been approved for Japanese patients with severe AGHD. For adults, GH replacement therapy should be initiated at a low dose (3 g/kg body weight/day), followed by individualized dose titration while monitoring patients'' clinical status and serum insulin-like growth factor-I (IGF-I) concentrations. A variety of favorable effects of GH replacement have been indicated; however, it has not yet been established fully whether there is a direct effect of GH treatment on reducing mortality.     

Lactone-rich fraction from Vernonia blumeoides: antitrypanosomal activity and alleviation of the parasite-induced anemia and organ damage

The anti-Trypanosoma brucei brucei activity in vitro and in vivo of a lactone-rich fraction of Vernonia blumeoides leaves (VBLF) and its potential in alleviating trypanosome-induced anemia and organ damage were investigated. Gas chromatography–mass spectrometry (GC–MS) analysis of VBLF revealed the presence of a number of lactone-containing compounds. In an in vitro study, VBLF showed concentration-dependent activity and was further used to treat T. brucei brucei-infected rats. The VBLF treatments, especially at 300 mg/kg body weight (BW), significantly (P < 0.05) kept the parasites reduced during the entire experimental period compared with the infected untreated group. At the end of the experiment, the trypanosome-induced anemia and hepatic damage were significantly (P < 0.05) alleviated in all the VBLF treatment groups, but renal damage was only prevented in the 200 and 300 mg/kg BW treatment groups. Furthermore, the trypanosome-induced increase in the relative weights of liver, spleen and kidney were significantly (P < 0.05) alleviated by the 300 mg/kg BW VBLF treatment. It was concluded that orally administered VBLF, especially at 300 mg/kg BW, possessed antitrypanosomal activity and could alleviate parasite-induced anemia and organ damage.     

Caregiver Practices of Families of Children with and Without Physical Disability

Reports suggest children with physical disability are at greater risk than peers for negative caregiver interactions. The environmental, parental, and child characteristics associated with variation in caregiver practices among families of children with (n?=?450) and without physical disability (n?=?450) in a nationally representative sample from the U.S. Agreement and variation about the shared meaning of “caregiver practices” were measured using consensus analysis. Associated parent, child, and family characteristics were identified using regression analysis. Parents did not spank, hit back, yell, ignore, put to work, or make fun of their children as a punishment. Parents maintained rules set about eating, bedtime, chores, and watching television. They reported playing with children, preparing food for them, going to religious services, reading, singing songs, and telling stories with their children. They reported not being involved in organized exercise and art classes. Child’s socio-emotional skills and behaviors (β?=??.331), socio-economic status (β?=??.223), the influence of religion on raising child (β?=??.180), race/ethnicity of the parent (β?=??.071), and physical disability (β?=??.104) explained 24 % of the variance in caregiver practices (F?=?32.34, p?<?.000). More negative caregiver practices are associated with families of children with lower levels of socio-emotional skills and behaviors, lower socio-economic status, less religious influence on child rearing practices, who are not Euro-American, or whose children have physical disability. Children’s socio-emotional skills and behaviors explained the largest amount of variance in caregiver practices, not disability status. Health professionals working with children with physical disability should target developing socio-emotional skills to support positive child-parent interactions and promote positive outcomes.     

Therapeutic action of 5-HT3 receptor antagonists targeting peritoneal macrophages in post-operative ileus

Background and Purpose

Post-operative ileus (POI) is induced by intestinal inflammation. Here, we aimed to clarify the effects of 5-HT₃ receptor antagonists against POI.

Experimental Approach

We administered three 5-HT₃ receptor antagonists, ondansetron, tropisetron and palonosetron, to a mouse model of POI induced by surgical intestinal manipulation (IM). Immunohistochemistry, intestinal transit, inflammatory mediator mRNA expression and 5-HT content were measured. In some experiments, 5-HT₃A receptor null mice were used.

Key Results

Three 5-HT₃ receptor antagonists reduced IM-induced infiltration of inflammatory CD68-positive macrophages and myeloperoxidase-stained neutrophils. Ondansetron exhibited no anti-inflammatory actions in 5-HT₃A receptor null mice. Ondansetron inhibited expression of the chemokine CCL2, IL-1β, IL-6, TNF-α and iNOS mRNAs up-regulated by IM, and also ameliorated the delayed gastrointestinal transit. Peritoneal macrophages, but not most infiltrating monocyte-derived macrophages, expressed 5-HT₃ receptors. IM stimulation increased the 5-HT content of peritoneal lavage fluid, which up-regulated mRNA expression of proinflammatory cytokines in peritoneal macrophages. Immunohistochemical localization of 5-HT₃ receptors suggests that ondansetron suppressed expression of these mRNAs in activated peritoneal macrophages, adhering to the serosal region of the inflamed intestinal wall.

Conclusion and Implications

5-HT₃ receptor antagonists were anti-inflammatory, mainly targeting peritoneal macrophages expressing these receptors. They also restored the delayed gastrointestinal transit by IM. 5-HT₃ receptor antagonists should be therapeutically useful agents against POI.     

Angiotensin II type 1a receptor signals are involved in the progression of heart failure in MLP-deficient mice.

BACKGROUND: Angiotensin II (AT) is implicated in the development of cardiac remodeling, which leads to heart failure, and pharmacological inhibition of the AT type 1 (AT1) receptor has improved mortality and morbidity in patients of heart failure. The aim of this study was to elucidate the role of the AT1 receptor in disease progression in muscle LIM protein (MLP)-deficient mice, which are susceptible to heart failure because of defective function of mechanosensors in cardiomyocytes. METHOD AND RESULTS: Hearts from MLP knockout (MLPKO) mice and MLP-AT1a receptor double knockout (DKO) mice were analyzed. MLPKO hearts showed marked chamber dilatation with cardiac fibrosis and reactivation of the fetal gene program. All of these changes were significantly milder in the DKO hearts. Impaired left ventricular (LV) contractility and filling were alleviated in DKO hearts. However, the impaired relaxation and downregulated expression of sarcoplasmic reticulum calcium-ATPase 2 were unchanged in DKO hearts. CONCLUSIONS: The AT1a receptor is involved in progression of LV remodeling and deterioration of cardiac function in the hearts of MLPKO mice. These results suggest that blockade of the receptor is effective in preventing progression of heart failure in dilated cardiomyopathy.