Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis C.

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.     

Postoperative pain management—clinical practice is still not optimal

Major progress in clinical pain assessment and management has been achieved in the last decade. More effective analgesic drugs and improved techniques for pain management have been introduced. However, medical reports published during the last few years on postoperative pain management (POPM) indicate that moderate or even severe pain is still rather commonly experienced by surgical patients in the early postoperative period and that worst-pain-episodes may occur even in the late postoperative phase. Insufficient relief of postoperative pain seems a more common problem on surgical wards than on a postanaesthesia care unit (PACU). The aims of POPM are to inhibit autonomic trauma-induced nociceptive impulses that may result in functional disturbances of vital organs and thereby affect the incidence of potentially severe complications influencing clinical outcome. Considering that recent studies continue to show sub-optimal pain management despite the availability of effective drugs and analgesic techniques it must be considered essential to identify possible barriers to effective pain management in clinical practice so that necessary improvements in POPM routines can be carried out.     

Plasma levels and vascular effects of vasopressin in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies have suggested that endogenous vasopressin (AVP) acts as a spasmogen during coronary artery bypass grafting (CABG). Given that AVP could induce vasospasm in the grafted vessel, we assessed the release of this peptide during and after CABG, and explored ways of counteracting its contractile effect on the internal mammary artery (IMA). METHODS: Plasma levels of AVP were determined by radioimmunoassay in 16 patients before, during and after CABG. Using isometric force recording techniques, we also investigated the mechanisms involved in the contractile effect of AVP in ring preparations of IMA specimens taken from 95 patients. RESULTS: Plasma AVP levels peaked after the start of cardiopulmonary bypass (CPB) and correlated well with serum osmolality (Pearson's r=0.9490; P<0.0001; n=16). An inverse correlation was observed between plasma AVP levels recorded at this stage and the maximal contraction induced in vitro by AVP in vascular rings from the same patients (Pearson's r=-0.6968; P<0.01; n=16). No change in the AVP response was produced by endothelium removal, exposure to the NO precursor (3 x 10(-4)M L-arginine), inhibition of nitric oxide (NO) synthase (3 x 10(-5) M L-NAME) or soluble guanylate cyclase (3 x 10(-6) M 1H-[1,2,4]oxadiazol [4,3,-alpha]quinoxalin-1-one (ODQ)), removal of the superoxide anion (100 U/ml superoxide dismutase (SOD) plus 1200 U/ml catalase) or hydroxyl radical (10(-4) M deferoxamine), or specific alpha1 - (10(-6) M prazosin) or endothelin (10(-5) M bosentan) receptor antagonism. In contrast, adenylate cyclase activation (3 x 10(-8) M forskolin) reduced the contractile response to AVP, while prostanoid synthesis (3 x 10(-6) M indomethacin) inhibition and blockade of Ca2+ -activated potassium channels (KCa) (10(-3) M tetraethylammonium (TEA)) enhanced AVP contraction. Age, gender and smoking also modified the AVP response. CONCLUSION: Our findings suggest a role for AVP as a modulator of vascular tone in human IMA. The effect of AVP is dependent on prostanoids and Ca2+ -activated K+ channels, so its dysfunction in pathophysiological cardiovascular processes could mean that AVP, among other factors, produces vasospasm in IMA grafts.     

Increased glucose excursion in cystic fibrosis and its association with a worse clinical status

BACKGROUND: Abnormal glucose tolerance is a frequent co-morbidity in cystic fibrosis patients (CF), and is associated with a worse prognosis. The objectives are to investigate (a) the relative contribution of insulinopenia and insulin resistance (IR) for glucose tolerance and (b) the association between various glucose parameters and CF clinical status. METHODS: Oral glucose tolerance tests were performed in 114 consecutive CF patients not known to be diabetic as well as 14 controls similar for age and BMI. RESULTS: Abnormal glucose tolerance was found in 40% of patients with CF: 28% had impaired glucose tolerance (IGT) and 12% had new cystic fibrosis related diabetes (CFRD). Compared to control subjects, all CF patients were characterized by an increased glucose excursion (AUC). While reduced early insulin release characterised CF, IGT and CFRD patients also present IR thus both mechanisms significantly contribute to glucose tolerance abnormalities. Increased glucose AUC and reduced early insulin release but not glucose tolerance categories were associated with a reduced pulmonary function (FEV(1)). CONCLUSION: In CF, early insulin secretion defect but also IR contribute to glucose intolerance. Early in the course of the disease, increased glucose AUC and reduced early insulin secretion are more closely associated with a worse clinical status than conventional glucose tolerance categories.     

Vitamin K in colostrum and mature human milk over the lactation period--a cross-sectional study

Vitamin K was quantitated in the milk of four groups of 15 mothers from 1 d to 6 mo postpartum in a cross-sectional study. Concentrations were 7.52 +/- 5.90 and 6.36 +/- 5.32 nmol/L (3.39 +/- 2.66 and 2.87 +/- 2.40 micrograms/L) in colostrum and mature milk, respectively. Differences between colostrum and mature milk or among samples of mature milk collected at 1, 3, and 6 mo were not statistically significant. Because of significantly increased volumes of milk over the lactation period, approximately twice as much vitamin K was delivered in mature milk as in colostrum. Within normal ranges, concentrations of vitamin K in milk were not predicted by dietary intake of vegetables or fat. Vitamin K was correlated with fat in colostrum and was localized in the lipid core of the milk fat globule but was not associated with membranes. Vitamin K in human milk is insufficient to meet recommended intakes for infants aged less than 6 mo. Population and clinical studies are needed to assess the vitamin K status of exclusively breast-fed infants and to evaluate current recommendations.     

Rotavirus serology and breast-feeding in young children in rural Guinea-Bissau

One hundred and forty-four children aged 9-20 months living in 14 villages in a rural area of Guinea-Bissau were examined for circulating rotavirus antibodies twice in a 15-month period. An immunofluorescence technique was used. About 3/4 of the children seroconverted, independent of age on entering the study. The age-specific proportion of seropositivity increased from 4/40 (10%) at 9-11 months to 26/29 (90%) at 33-35 months of age. All the initially seropositive children retained detectable antibodies to rotavirus. The relative risk of seroconversion was 1.4 times (95% confidence interval 1.0-2.0) more common among children living in villages by the mainroad as compared to those living off the road. Contact rate is probably dependent on population density and mobility but not on age. Breast-feeding, decreasing sharply through the age interval covered by the follow-up (9-35 months), had no apparent influence on seroconversion at the ages concerned.     

Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba.

We report here the antiproteolytic and antihemorrhagic properties of triterpenoid saponin inhibitors, named macrolobin-A and B, from Pentaclethra macroloba, against Bothrops snake venoms. The inhibitors were able to neutralize the hemorrhagic, fibrin(ogen)olytic, and proteolytic activities of class P-I and P-III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. Clotting and fibrinogenolytic activities induced by snake venoms and isolated thrombin-like enzymes were partially inhibited. Furthermore, the potential use of these inhibitors to complement antivenom therapy as an alternative treatment and/or used as molecular models for development of new therapeutical agents in the treatment of snake bite envenomations needs to be evaluated in future studies.