Glucose metabolism in injured tissue: a longitudinal study

Injured tissue is characterized by increased glucose uptake and increased lactate production as compared to normal tissue. These metabolic changes have been attributed to the presence of inflammatory cells in injured tissues. To correlate these metabolic changes with changes in the inflammatory cell population at various times after injury, we studied the lambda-carrageenan hindlimb wound model in anesthetized rats. Perfusion studies demonstrated that at 3 and 5 days after injury glucose uptake was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. At 3, 5, and 10 days after injury, lactate production from glucose was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. These metabolic changes were not related to differences in body weight or food intake. There was no difference in glucose oxidation or in oxygen consumption in injured hindlimbs, compared with hindlimbs from pair-fed control animals. The increased glucose uptake and increased lactate production from glucose was coincident with the presence of inflammatory cells--predominantly macrophages--at the site of injury. It is suggested that the glucose metabolism in injured tissue reflects the metabolism of the inflammatory cells at the site of injury.     

Expressed emotion in children: associations with sibling relationships

Objective   To investigate the reliability and validity of the expressed emotion (EE) measure, the Pre-school Five Minute Speech Sample (PFMSS), in child-to-child sibling relationships.
Method   A total of 106 boys aged 7–11 were recruited from 12 mainstream primary schools in North Wales. The children completed the PFMSS regarding their sibling and two self-report measures of sibling relationship: the Sibling Relationship Questionnaire (SRQ) and a Child Visual Analogue Scale (CVAS). The parents of 60 participants completed the Strengths and Difficulties Questionnaire regarding the behavioural problems of the participating child and his younger sibling.
Results   The PFMSS demonstrated good inter-rater and code–recode reliability. The significant associations between EE dimensions such as relationship, positive comments and critical comments with various components of the SRQ and CVAS provided support for the concurrent validity of the PFMSS. Significantly higher levels of Conflict and Rivalry and significantly lower levels of Warmth/Closeness on the SRQ were reported by children with high EE, demonstrating good discriminant validity for the PFMSS. There was no significant association between the child's EE profile and the behavioural difficulties of both siblings as reported by parents.
Conclusions   The study found that the PFMSS is a valid and reliable measure of child EE. Future research is needed to clarify the concurrent validity of the warmth and initial statement components of the measure as well as the association between EE dimensions and behaviour.     

Cutaneous postural vasoconstriction is modified by exogenous but not endogenous female hormones in young women

Previously reported attenuation of skin postural vasoconstriction in women during the luteal menstrual cycle phase may be due to a progesterone-mediated decrease in myogenic or veno-arteriolar (VAR) mechanisms. Skin perfusion was measured in the shin and foot dorsum by Laser Doppler Fluxometry during leg dependency that increased vascular transmural pressure below (myogenic constriction only) and above (myogenic and VAR) the 25 mmHg threshold for activation of the VAR, and during venous distension to activate the VAR alone (cuff inflation to 50 mmHg). In six young women with normal menstrual cycles, vasoconstrictor responses to all interventions did not differ between days 7–13 (follicular) and 18–23 (luteal) of the normal menstrual cycle when progesterone levels were low and at their peak respectively. In eight women taking combined oral contraceptives (OC) and tested during pill consumption days, reductions in foot skin perfusion were smaller (P = 0.05) than in the luteal phase of the normal cycle for leg dependency below (−36.9 ± 5.2% OC vs. −52.5 ± 7.8% luteal, mean ± S.E.M.) and above (−43.7 ± 3.4% OC vs. −55.1 ± 4.8% luteal) the VAR threshold, and for venous distension (−53.1 ± 2.6% OC vs. 66.4 ± 5.5% luteal). In women with normal menstrual cycles, impaired postural vasoconstriction may be confined to those who experience pre-menstrual symptoms rather than a direct effect of endogenous hormones. Reduced vasoconstriction in the dependent foot during OC use is consistent with the known vasodilator action of exogenous hormones and its long-term effects     

Substance abuse and schizophrenia: impediments to optimal care

With lifetime prevalence estimates of substance abuse among schizophrenics as high as 47.01%, there is an increasing awareness of the importance of this dual diagnosis and the global deficiencies in our knowledge about this comorbid condition. Patients with substance abuse disorders and schizophrenia are problematic from a clinical, economic, and health care systems perspective. The lack of systematic research into phenomenology, etiology, and treatment approaches (both psychotherapeutic and psychopharmacologic) has hindered the development of an adequate strategy to care for the needs of these patients. Thus, these patients place a significant burden on the mental health delivery system through chronic disability, social dysfunction, frequent rehospitalizations, and poor overall treatment compliance. The authors critically review the contemporary literature relevant to concurrent substance abuse and schizophrenia, highlight major deficiencies in our knowledge, and call for research to reduce the individual, economic, and social costs of this condition.     

Pharmacology of the AC AT Inhibitor Avasimibe (CI‐1011)

Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration‐dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B‐containing lipoproteins into plasma. Avasimibe induced cholesterol 7α‐hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol‐fed as well as in non‐cholesterol‐fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non‐HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50–500 mg/day, significantly reduced plasma total triglyceride and VLDL‐cholesterol. Although total cholesterol, LDL‐cholesterol, and HDL‐cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol‐lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol.