Acoustic startle response in the opossum Monodelphis domestica in comparison with the Wistar albino rat

The acoustic startle response (ASR) was studied in 20 gray short-tailed opossums (Monodelphis domestica) and its characteristics were compared with those obtained from responses of 20 Wistar albino rats. The animals were exposed to 10 ms, 110 dB white noise acoustic pulses in the Coulbourn apparatus. Amplitude of ASR was normalized to the weight of animals and then analyzed. The results show that probability of a freezing response is much higher in the opossums that generally respond with lower startle amplitudes in comparison to rats. These differences may reflect different emotional characteristics of the two species, different reactions to fear in opossum and/or different ecological specializations of the two species.     

Proliferative response of T lymphocytes to a proline-rich polypeptide (PRP): PRP mimics mitogenic activity of Il-1

Mitogenic properties of a proline-rich polypeptide were investigated. The mitogenic action of PRP was compared with the mitogenic action of Il-1. PRP was not mitogenic for thymocytes at doses 0.01-50 micrograms/ml. PRP, at doses 0.1-50 micrograms/ml, augmented the proliferative response of thymocytes to Con A in a similar fashion as Il-1. At doses higher than 10 micrograms/ml, PRP induced proliferation of lymph node cells and splenocytes as well as T cells from the lymph nodes. It did not, however, cause significant proliferation of B cells from the lymph nodes, at the doses used. PRP did not induce proliferation of an antigen specific Lyt 1+ T cell clone. Il-1 behaved in a similar way as PRP in all the tests described. We consider a possibility that under physiological conditions, at a very early stage of postneonatal life, PRP may replace some functions of Il-1.     

Design, synthesis, and biological evaluation of matrix metalloproteinase inhibitors derived from a modified proline scaffold

The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.     

Inhibition of aminophylline-induced convulsions in mice by antiepileptic drugs and other agents

Common antiepileptic drugs and agents affecting different neurotransmitter systems were studied against aminophylline (280 mg/kg i.p.)-induced convulsions in mice. All drugs and agents were administered i.p. Diazepam and phenobarbital antagonized the whole seizure pattern and the respective ED50 values for the clonic phase were 3.5 and 62 mg/kg. Valproate at 500 mg/kg protected fewer than 50% of mice against the clonic phase. The remaining antiepileptics (acetazolamide, up to 1,000 mg/kg; carbamazepine and diphenylhydantoin, up to 50 mg/kg; ethosuximide, 500 mg/kg and trimethadione, 400 mg/kg) were totally ineffective in this respect. Propranolol (up to 20 mg/kg), baclofen (20 mg/kg), gamma-hydroxybutyric acid (300 mg/kg), aminooxyacetic acid (20 mg/kg), clonidine (up to 0.2 mg/kg), ketamine (30 mg/kg), atropine (20 mg/kg), papaverine (50 mg/kg) and L-phenylisopropyladenosine (2 mg/kg) did not affect the clonic phase either. Only antagonists of N-methyl-D-aspartic acid excitation, 2-amino-5-phosphonopentanoic acid and 2-amino-7-phosphonoheptanoic acid afforded protection against aminophylline-induced clonic seizure activity. The results show that aminophylline convulsions are relatively resistant to antiepileptic drugs and suggest that antagonists of excitatory transmission are potential antiaminophylline drugs.     

Krukenberg tumor--8 years after surgical treatment of gastric carcinoma

The aim of the study was to discuss the case of Krukenberg tumor in a patient, eight years after the diagnosis and surgical treatment of gastric carcinoma. We have concluded that there was no safe period after which distant metastases may be excluded. In case of gastric carcinoma diagnosed in women, a regular gynecological examination is necessary due to a high propability of metastases into ovaries, even if the clinical stage of gastric carcinoma is low.     

Postpartum depression: Identifying associations with bipolarity and personality traits. Preliminary results from a cross-sectional study in Poland

The goals of this study have been to determine the prevalence of the bipolar spectrum features in the population of women with postpartum depression (PPD) symptoms, as well as to analyze the personality differences between putative ‘unipolar’ and ‘bipolar’ PPD subjects. The sample enrolled into the cross-sectional study consisted of 344 women at 6–12 weeks postpartum. The authors used the Edinburgh Postnatal Depression Scale (EPDS; cut-off score: 13 pts.) for the assessment of the PPD symptoms, the Mood Disorder Questionnaire (MDQ; cut-off scores: 7 or 8 pts.) for diagnosing the bipolar features, and the NEO-Five Factor Inventory (NEO-FFI) for the assessment of personality traits. The EPDS-positive subjects were more likely to score positively on the MDQ, as compared to the EPDS-negative ones. The EPDS-positive subjects who also scored ≥8 pts. on the MDQ were characterized by higher index of neuroticism, as compared to those who scored positively on the EPDS only. The results suggest that the presence of PPD symptoms is related to significantly higher scores of bipolarity and neuroticism. The more robust trait of neuroticism might be a marker of the ‘bipolar’ PPD, as compared to the ‘unipolar’ form of the disorder.     

Angiopoietin-2 as a biomarker of non-ST-segment elevation myocardial infarction in patients with or without type 2 diabetes

IntroductionAngiopoietin-2 (Ang-2) is a novel marker of coronary artery disease (CAD) and diabetes (DM). The aim was to evaluate Ang-2 as a potential new biomarker of non-ST elevation myocardial infarction (NSTEMI) in patients with or without type 2 DM (T2DM).Material and methodsThis was a multi-center, prospective study that included 138 (males: 91/66%) consecutive patients hospitalized due to NSTEMI, T2DM, or different cardiac disorders. The subjects were divided into four study groups: group A: 28 patients with NSTEMI and T2DM; group B: 47 patients with NSTEMI without T2DM; group C: 31 patients with T2DM, without a history of CAD; group D: 32 patients as a control group. Patients with NSTEMI underwent urgent coronarography. Clinical characteristics including biomarkers (hs-CRP, hsTnT, NT-proBNP, VEGF, HbA_1c), SYNTAX SCORE, type of intervention (PCI vs. CABG), and number of implanted stents were taken into account in the analysis.ResultsSerum Ang-2 concentrations were significantly higher in patients with NSTEMI (group A: 1769 pg/ml; group B: 1757 pg/ml) and patients with T2DM (group C: 1993 pg/ml) as compared to the patients without CAD and without T2DM (group D: 866.8 pg/ml; p < 0.05). The prognostic accuracy of Ang-2 in NSTEMI diagnosis was determined with the area under the ROC curve (area under curve (AUC) = 0.63).ConclusionsAngiopoietin-2 serum concentration is elevated in the presence of NSTEMI in patients with and without T2DM and does not correspond to the degree of myocardial injury and hemodynamic status. Ang-2 remains elevated also in patients with T2DM without a history of CAD.     

Synthetic immunostimulatory oligonucleotides in experimental and clinical practice

BackgroundOligonucleotides belong to a class of macromolecules with great potential for research and various therapeutic applications. Their mechanisms of action are extremely diverse, although they are rather homogeneous in composition. Single-stranded oligodeoxynucleotides are not only inhibitors of gene expression, but their CpG sequence motifs may activate the innate immune response. Recent progress made in preclinical and clinical testing, as well as the case of the most recently discovered RNA interference technology, will help to overcome efficacy problems of the previous approaches of the ‘standard therapy’ of such diseases as tumors and various infections.MethodsThe aim of this article is to present various therapeutic aspects of oligonucleotides, and to review the most significant therapeutic applications of synthetic oligonucleotides. This paper presents a comprehensive review of current literature on various therapeutic properties of synthetic oligonucleotides.ConclusionsThe available results gathered from preclinical and clinical studies suggest that TLR9-targeted therapy of oligonucleotides can stimulate both innate and adaptive immunity. It also appears that CpG ODNs are generally safe, although moderate adverse effects, based on a backbone-related mechanism have been reported. The presented studies demonstrate that adjuvant CpG ODN can unify an immune response that leads to enhanced antigen-specific Ab formation. CpG ODN may therefore provide a unique approach to enhancing the efficacy of immunization, including the strengthening of antitumor immunity.     

The conventional versus automated measurement of blood pressure in the office (CAMBO) trial: masked hypertension sub-study

OBJECTIVES:: To determine the prevalence of masked hypertension [normal office blood pressure (BP) with high awake ambulatory BP] using automated office BP (AOBP) or conventional manual office BP (MOBP) measurement in routine clinical practice. METHODS:: The prevalence of masked hypertension was evaluated on three consecutive visits during a median 6 months period in patients with systolic hypertension randomized to management with AOBP (n?=?140) or continued conventional MOBP (n?=?112) in routine primary care practice. AOBP was recorded using the automated BpTRU device with the patient resting alone in a quiet examining room. All patients underwent 24-h ambulatory BP monitoring. RESULTS:: The prevalence of masked hypertension on any one of three visits calculated using only SBP varied between 12 and 17% in the AOBP group compared with 19 and 22 % in the MOBP group. Masked hypertension was present on both of the first two visits in 7 and 12% and on all three visits in 6 and 7% of AOBP and MOBP patients, respectively. The prevalence for masked hypertension based upon both SBP and DBP was similar being 11-15% for AOBP and 19-20% for MOBP patients on single visits, but decreased to 6 and 10% when readings from the first two visits were used and to 4 and 6% when all three visits were used for the AOBP and MOBP groups, respectively. CONCLUSION:: The prevalence of masked hypertension is lower with AOBP compared with MOBP. The number of patients with masked hypertension decreases if the criteria for having this condition need to be met on multiple visits.