High prevalence of hepatitis G virus infection in Hodgkin's disease and B-cell lymphoproliferative disorders: absence of correlation with hepatitis C virus infection

BACKGROUND AND OBJECTIVES: During the last decade an epidemiological association between hepatitis C virus (HCV) and B-cell lymphoproliferative disorders (B-LPD) has been reported; the same association has not been observed for Hodgkin's disease (HD). Hepatitis G virus (HGV) shares genetic and biological features with HCV, thus it might also be involved in lymphomagenesis. DESIGN AND METHODS: The aim of this study was to compare the prevalence of HCV and HGV infection in patients at diagnosis of B-LPD or HD. RESULTS: We tested 227 consecutive untransfused patients (127 with B-LPD and 100 with HD) and 110 healthy controls. The prevalence of HCV infection was significantly higher in B-LPD patients than in controls (17.3% vs. 1.8%, p<0.002 ), whereas it was the same in HD patients as in controls. In contrast, the prevalence of HGV was significantly higher in patients, both those with B-LPD (7.8% vs. 0.9%, p<0.03) and those with HD (13% vs. 0.9%, p<0.002), than in controls. Among the various B-LPD tested, HGV infection was more frequent in B-NHL (11.5%). INTERPRETATION AND CONCLUSIONS: Our data support the hypothesis that HGV infection may play a role in lymphomagenesis and that this role is different and separate from that of HCV.     

Methyl psilalate: a new antimicrobial metabolite from Psila boliviensis

Psila boliviensis (Wedd.) Cabr. yielded a new phenylpropanoid, named methyl psilalate. The structure was established by means of standard spectroscopic techniques. The microbiological evaluation of the compound revealed antibacterial activity against Gram-positive and Gram-negative bacteria.     

Glucocorticoids interfere with mycophenolate mofetil bioavailability in kidney transplantation

BACKGROUND: Steroids have been shown to induce the hepatic glucuronyltransferase (GT) expression enhancing the activity of uridine diphosphate-GT, the enzyme responsible for mycophenolic acid (MPA) metabolism. The impact of steroids on MPA pharmacokinetics, however, has not been investigated to date. METHODS: As a part of a steroid-sparing clinical trial, we studied the effect of steroids on MPA bioavailability in 26 kidney transplant recipients. RESULTS: Despite that the MMF dose did not change significantly with time, dose-normalized MPA AUC0-12h was lower during the first month (triple therapy, high doses of steroids) than at month 6 post-surgery (triple therapy, low maintenance dose of steroids (32.94 +/- 10.98 vs. 50.87 +/- 22.37 microg/mL. h; P < 0.01). During the steroid tapering and withdrawal phase (from month 6 to 21 post-Tx), plasma MPA trough and peak concentration as well as AUC0-12h progressively increased, while plasma MPA clearance and MPAG (the major MPA metabolite) trough levels declined. Renal function was stable throughout. Since cyclosporine A (CsA) may interfere with MPA pharmacokinetics, MPA and CsA also were measured in an additional control group of 12 kidney transplant patients at month 21 post-Tx who were still on triple therapy (MMF, CsA and steroids). Despite a similar CsA exposure, the control group had a significantly lower MPA AUC0-12h and higher MPAG trough concentration than patients on dual therapy at month 21 post-Tx. CONCLUSION: These findings indicate that steroids interfere with MPA bioavailability, and that discontinuation of the drug results in higher MPA exposure, which may compensate at least in part for the lower immunosuppressive level achieved with the remaining dual therapy with CsA and MMF.     

Eye-hand preference dissociation in obsessive-compulsive disorder and dyslexia

Dyslexia may be a development disturbance in which there are alterations in visual-spatial and visual-motor processing, while obsessive-compulsive disorder (OCD) is a psychiatric disease in which there are alterations in memory, executive function, and visual-spatial processing. Our hypothesis is that these disturbances may be, at least partially, the result of a crossed eye and hand preference. In the present study 16 controls, 20 OCD (DSM-IV criteria) and 13 dyslexic adults (Brazilian Dyslexia Association criteria) were included. All had a neurological examination, the Yale-Brown scale for obsessive-compulsive symptoms application and the Zazzó evaluation for laterality, abridged by Granjon. Results showed a right hand preference for 100% of controls, 84.6% of dyslexics, and 75% of OCD patients and a right eye preference for 73.3% of controls, 69.2% of dyslexics, and 35% of OCD patients. The left eye preference was significantly higher in OCD when compared with the two other groups (p = 0.01) and the left hand preference of OCD patients (25%) was also significant when compared to Brazilian population (4%) or British population (4.5%). It is possible that this crossed preference may be partially the reason for visual-spatial and constructive disturbances observed in OCD.     

Extended use of a progesterone-releasing vaginal ring in nursing women: a phase II clinical trial

AIM: This study evaluates the performance of extended use of a progesterone (P)-releasing vaginal ring (PVR) in nursing women. METHOD: An open-label, noncomparative study on the safety and contraceptive efficacy of PVR replaced every 4 months of use (instead of 3 months) in 192 PVR acceptors. PVR use was initiated at day 59+/-2 (mean+/-SD) postpartum and continued until weaning or completing the use of three PVRs. RESULTS: Plasma P levels attained with the ring decreased from 17+/-1 to 14+/-1 nmol/L (mean+/-SE) from the third to the fourth month of use. These levels are still over the critical level of 10 nmol/L required for contraceptive protection. One pregnancy occurred in the third month of use of the second ring in 1998 woman-months of exposure. Extended use of the ring did not appear to affect breast-feeding performance or the rate of infant growth, and lactational amenorrhea was prolonged. No differences in the characteristics of bleeding between the third and fourth month of ring use were observed. CONCLUSION: The results indicate that use of the PVR for 4 months represents a safe and effective contraceptive for nursing women.     

Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3beta

BACKGROUND: Postischemic administration of volatile anesthetics activates reperfusion injury salvage kinases and decreases myocardial damage. However, the mechanisms underlying anesthetic postconditioning are unclear. METHODS: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane (1.5 minimum alveolar concentration) administered at the onset of reperfusion. In some experiments, atractyloside (10 microm), a mitochondrial permeability transition pore (mPTP) opener, and LY294002 (15 microm), a phosphatidylinositol 3-kinase inhibitor, were coadministered with isoflurane. Western blot analysis was used to determine phosphorylation of protein kinase B/Akt and its downstream target glycogen synthase kinase 3beta after 15 min of reperfusion. Myocardial tissue content of nicotinamide adenine dinucleotide served as a marker for mPTP opening. Accumulation of MitoTracker Red 580 (Molecular Probes, Invitrogen, Basel, Switzerland) was used to visualize mitochondrial function. RESULTS: Anesthetic postconditioning significantly improved functional recovery and decreased infarct size (36 +/- 1% in unprotected hearts vs. 3 +/- 2% in anesthetic postconditioning; P < 0.05). Isoflurane-mediated protection was abolished by atractyloside and LY294002. LY294002 inhibited isoflurane-induced phosphorylation of protein kinase B/Akt and glycogen synthase kinase 3beta and opened mPTP as determined by nicotinamide adenine dinucleotide measurements. Atractyloside, a direct opener of the mPTP, did not inhibit phosphorylation of protein kinase B/Akt and glycogen synthase kinase 3beta by isoflurane but reversed isoflurane-mediated cytoprotection. Microscopy showed accumulation of the mitochondrial tracker in isoflurane-protected functional mitochondria but no staining in mitochondria of unprotected hearts. CONCLUSIONS: Anesthetic postconditioning by isoflurane effectively protects against reperfusion damage by preventing opening of the mPTP through inhibition of glycogen synthase kinase 3beta.     

Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications

BACKGROUND: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. METHODS: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. RESULTS: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. CONCLUSIONS: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic factor.     

Headaches during pregnancy in women with a prior history of menstrual headaches

OBJECTIVE: To evaluate the presence of menstrual headaches prior to pregnancy according to the International Headache Society (IHS) classification criteria, 2004, and also study the outcome (frequency and intensity) of these pre-existing headaches during the gestational trimesters. METHOD: This study involved 1,101 pregnant women (12 to 45 years old). A semi-structured questionnaire was used to interview the women during the first, second and third gestational trimesters as well as after delivery. All the interviews were conducted by one of the researchers by applying the IHS Classification (IHSC-2004). RESULTS: A 1,029 women out of the 1,101 women interviewed presented headaches prior to gestation, which made it possible to study headaches in 993 women during the gestational trimesters. Menstrually related headaches were presented by 360 of the 993 women. Migraine was reported by 332/360 women (92.22%) with menstrual headaches and 516/633 women (81.51%) without menstrual headaches, respectively, prior to gestation. The majority of the women with menstrual migraine presented a headache improvement or disappearance during gestation (62.22% during the first trimester; 74.17% during the second trimester; 77.78% during the third trimester). CONCLUSION: Most of the pregnant women with menstrual or non-menstrual headaches prior to gestation presented migraine, which either improved or disappeared during pregnancy. Women who suffered from non-menstrual headaches improved during pregnancy but not as much as women with menstrual headaches.