Toward better probing for hypomania of bipolar-II disorder by using Angst's checklist

The reliability of the diagnosis of bipolar-II disorder (BP-II) is still a problem. Semi-structured interviews by clinicians might partly overcome this problem. The aims of this study were to find the degree of agreement in the diagnosis of BP-II between the Structured Clinical Interview for DSM-IV (SCID) and a semi-structured interview based on Angst's hypomania checklist (Angst et al., 2003), and to assess the priority among hypomanic symptoms for the diagnosis of BP-II. Remitted depression outpatients (N = 102) were interviewed during a follow-up visit using th Structured Clinical Interview for DSM-IV (SCID), and then with Angst's semi-structured interview, following DSMIV criteria. Bipolar I (BP-I) patients were excluded. Using the SCID, 29 patients were diagnosed BP-II, 26 BP-I, and 47 major depressive disorder (MDD). By the semi-structured interview 69 patients were diagnosed BP-II, 33 MDD, and none BP-I. Agreement for the diagnosis of BP-II between the two interviews was 53.9% (k = 0.18). Re-analysis, after deleting the SCID question on the impact on functioning (DSM-IV unclear boundary between BP-I and BP-II), increased agreement to 78.4% (k = 0.55). Elevated mood and overactivity (increased goal-directed activity) had th lowest agreement (k = 0.46 0.49). For predicting BP-II, overactivity had the highest sensitivity (94.2%), whil elevated mood had a sensitivity of 84.0%. Multivariate analysis for predicting BP-II (diagnosed by semi-structured interview), including all DSM-IV hypomanic symptoms, found that mood change and overactivity were the only independent predictors. Overactivity plus at least three symptoms (as suggested by Angst and Gamma, 2002) were present in 71 patients, of whom 91.5% also met DSM-IV criteria for hypomania. Overactivity and elevated mood were strongly associated (but not overactivity and irritability). Findings may support a diagnosis of BP-II based on Angst's semi-structured interview versus the fully structured SCID interview. While DSM-IV always requires mood change for the diagnosis of hypomania, the present findings may suggest that overactivity could have the same priority, as suggested by Angst et al. (2003) and by Akiskal et al. (1977, 2001, 2003).     

Phase I and Pharmacokinetic Study of Fostriecin given as an Intravenous Bolus Daily for Five Consecutive Days

Fostriecin (CI-920) is a potent inhibitor of protein phosphatase 2A (PP2A) and protein phosphatase 4(PP4) found to have anticancer activity in preclinical testing. A phase I study was conducted to evaluate the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of this drug. Forty-six patients were treated with escalating doses of fostriecin (2-47 mg/m2) administered as a daily bolus infusion for five consecutive days. PK studies were performed at different time points following administration of fostriecin. Dose-limiting toxicities included: elevation of creatinine, bilirubin, and hepatic transaminases; nausea, anorexia, lethargy, and hypotension. PK studies were compatible with a two-compartment model. Regression analysis revealed a significant relationship between dose and clearance; however, the r2 value was only 0.168 indicating a low predictive value for the model. No significant difference was seen in PK parameters with repeated dosing during the same cycle. Although no tumor responses were seen, 16 patients had stable disease with a median duration response of 2.6 months. The study was closed before reaching MTD due to problems with the supply of fostriecin from the National Cancer Institute of the United States (NCI US). New methods for synthesizing fostriecin have recently been described and therefore further development of this unique anticancer agent may be warranted.     

Cytotoxicity and dna topoisomerases inhibitory activity of constituents from the sclerotium of<Emphasis Type="Italic">Poria cocos</Emphasis>

The bioactivity-guided fractionation of the methylene chloride extract of the sclerotium of Poria cocos led to the isolation of (S)-(+)-turmerone (1), ergosterol peroxide (2), polyporenic acid C (3), dehydropachymic acid (4), pachymic acid (5), and tumulosic acid (6). Compounds 4-6 exhibited moderate cytotoxicities, with IC50 values of 20.5, 29.1, and 10.4 microM, respectively, against a human colon carcinoma cell line. However, 3-6 not only showed inhibitory activities as potent as etoposide used as a positive control on DNA topoisomerase II (36.1, 36.2, 43.9 and 66.7% inhibition at a concentration of 20 microM, respectively), but also inhibition of DNA topoisomerase I (55.8, 60.7, 43.5, and 83.3% inhibition at a concentration of 100 microM, respectively).     

The ophthalmic wound of Philip II of Macedonia (360-336 BCE)

The aim of this report is to present the ophthalmic wound of King Philip II of Macedonia, father of Alexander the Great. From a series of ancient literary and historical sources, a number of archaeological finds, and the paleopathological remains in the supposed tomb of Philip in Vergina, it can be deduced that the king was seriously wounded in his right eye during the siege of Methoni. The renowned physician Critobulos undertook the removal of the arrow that had injured the eye and the postoperative follow-up. He was already experienced and belonged to the official medical family of Asclepiades of Cos Island. It seems that an ugly scar remained in the area of Philip's right eye, possibly causing him psychological problems.     

Inhibitory effect of resveratrol on angiotensin II-induced cardiomyocyte hypertrophy

Resveratrol is proposed to account in part for the protective effect of red wine on the cardiovascular system. Angiotensin II (Ang II) is a potent hypertrophic stimulus in cardiomyocytes. In this study, we determined the effect of resveratrol on Ang II-induced cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were stimulated with Ang II, and [³H]leucine incorporation and -myosin heavy chain (-MyHC) promoter activity were examined. Intracellular reactive oxygen species (ROS) were measured by a redox-sensitive fluorescent dye, 2 7-dichlorofluorescin diacetate, and the extracellular signal-regulated kinase (ERK) phosphorylation was examined by Western blotting. Resveratrol inhibited Ang II-increased intracellular ROS levels. Furthermore, resveratrol, as well as the antioxidant N-acetyl-cysteine, decreased Ang II- or H₂O₂-increased protein synthesis, -MyHC promoter activity, and ERK phosphorylation. In summary, we demonstrate for the first time that resveratrol inhibits Ang II-induced cardiomyocyte hypertrophy via attenuation of ROS generation.Abbreviations Ang II Angiotensin II - MAPKs Mitogen-activated protein kinases - ERK Extracellular signal-regulated kinase - JNK c-Jun N-terminal kinase - p38 MAPK p38 mitogen-activated protein kinases - MEK MAPK or ERK kinase - NAC N-acetylcysteine - DCF-DA Dichlorodihydrofluorescein diacetate - DCF Dichlorofluorescein     

A pharmacological differentiation between postjunctional (AT<Subscript>1A</Subscript>) and prejunctional (AT<Subscript>1B</Subscript>) angiotensin II receptors in the rabbit aorta

The effects of angiotensin II and angiotensin III were compared at prejunctional and postjunctional AT₁ receptors of the rabbit thoracic aorta. Furthermore, the influence of PD123319, losartan and eprosartan on these effects was also compared. To study prejunctional effects, the tissues were preincubated with (³H)-noradrenaline, superfused and electrically stimulated (1 Hz, 2 ms, 50 mA, 5 min). To study postjunctional effects, non-cumulative concentration–response curves were determined. Both angiotensin II and angiotensin III were more potent prejunctionally than postjunctionally. In the case of angiotensin II, the EC₅₀ was 12 times lower at the prejunctional than at the postjunctional level, while that of angiotensin III was 30 times lower prejunctionally. Furthermore, whereas angiotensin II was about 33 times more potent than angiotensin III postjunctionally, it was only 12 times more potent than angiotensin III prejunctionally. Eprosartan did not differentiate between prejunctional and postjunctional effects of both angiotensins. In contrast, PD123319 and losartan did differentiate; however, whereas PD123319 concentration-dependently antagonised the facilitation of tritium release caused by angiotensin II and angiotensin III and had no influence on the contraction of the aortic rings elicited by the peptides, losartan did the opposite: it concentration-dependently antagonised the contractions caused by the peptides on the aortic rings and exerted no influence on the facilitatory effect of angiotensin II and angiotensin III. These results show that prejunctional and postjunctional receptors for angiotensin II and angiotensin III are different and underline the hypothesis that postjunctional AT₁ receptors belong to the AT_1A subtype, while prejunctional AT₁ receptors belong to the AT_1B subtype.     

An NMDAR-independent LTP mediated by group II metabotropic glutamate receptors and p42/44 MAP kinase in the dentate gyrus in vitro

The induction of long-term potentiation (LTP) under conditions of blockade of the N-methyl-D-aspartate receptor (NMDAR) was studied in the medial perforant path to granule cell synapse in the dentate gyrus. A small amplitude NMDAR-independent potentiation was induced by a single brief high frequency stimulation (HFS), and a summated larger LTP was induced by repeated spaced HFS. The NMDAR-independent LTP was mediated by activation of group II mGluR as it was inhibited by the group II antagonists EGLU and also low concentrations of LY341495, but not the group I mGluR antagonist MPEP. Perfusion of the group II mGluR agonist DCG-IV induced NMDAR-independent LTP in media containing an NMDAR antagonist. The NMDAR-independent LTP induced by HFS was mediated via activation of p42/44 MAP kinase as it was blocked by the selective inhibitor PD98059.     

Cardiac failure caused by severe pre-eclampsia with placental abruption, and its treatment with anti-hypertensive drugs

Pre-eclampsia is the abnormality of blood circulation in late pregnancy, often caused by renal failure, hemolysis, elevated liver enzyme, low platelet syndrome, and eclampsia. We present a case of severe pre-eclampsia with placental abruption in a 24-year-old woman, pregnant for the first time. The patient was diagnosed with congestive heart failure, which came as a result of pre-eclampsia. Anti-hypertensive drugs were used for its treatment.     

Different immunogenicity of H-2 Kb-restricted epitopes in natural variants of the hepatitis B surface antigen

The small hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV) has limited variability, but some serotypes and genotypes have been defined. Although no biological or pathogenetic differences could be traced to HBV serotypes, the clinical picture, response to treatment and long-term prognosis of HBV infection may vary with the HBV genotype, possibly due to differences in specific T cell recognition of HBV antigens from different genotypes. We analyzed murine CD8(+) T cell responses to two K(b)-restricted HBsAg epitopes primed by four different HBsAg variants using protein- and DNA-based vaccination protocols. The K(b)-binding S(208-215) epitope 1 is processed from exogenous but not endogenous HBsAg. Variants of epitope 1 differing at two positions within the epitope (ILSPFLPL in ayw/adr versus IVSPFIPL in adw2) efficiently primed cross-reactive CD8(+) T cell responses. In contrast, the exchange of an N-terminal flanking residue (S to N) completely eliminated the immunogenicity of epitope 1. The K(b)-binding S(190-197) epitope 2 is processed from endogenous but not exogenous HBsAg. A single-residue exchange within the epitope (VWLSVIWM in ayw/adr versus VWLSAIWM in adw2) completely eliminated the immunogenicity of epitope 2. Single, conservative residue exchanges can thus give rise to diverging CD8(+) T cell repertoires, suggesting an impressive complexity and flexibility of the CD8(+) T cell repertoire to antigen variants from viruses with limited diversity.