(Me2NH2)10[H2-Dodecatungstate] polymorphs: dodecatungstate cages embedded in a variable dimethylammonium cation + water of crystallization matrix

Two polymorphs and a solvatomorph of a new dimethylammonium polytungstate—decakis(dimethylammonium) dihydrogendodecatungstate, (Me₂NH₂)₁₀(W₁₂O₄₂)·nH₂O (n = 10 or 11)—have been synthesized. Their structures were characterized by single-crystal X-ray diffraction and solid-phase NMR methods. The shape of the dodecatungstate anions is essentially the same in all three structures, their interaction with the cations and water of crystallization, however, is remarkably variable, because the latter forms different hydrogen-bonded networks, and provides a highly versatile matrix. Accordingly, the N–H⋯O and C–H⋯O hydrogen bonds are positioned in each crystal lattice in a variety of environments, characteristic to the structure, which can be distinguished by solid-state ¹H-CRAMPS, ¹³C, ¹⁵N CP MAS and ¹H–¹³C heteronuclear correlation NMR. Thermogravimetry of the solvatomorphs also reflect the difference and multiformity of the environment of the water molecules in the different crystal lattices. The major factors behind the variability of the matrix are the ability of ammonium cations to form two hydrogen bonds and the rigidity of the polyoxometalate anion cage. The positions of the oxygen atoms in the latter are favourable for the formation of bifurcated and trifurcated cation–anion hydrogen bonds, some which are so durable that they persist after the crystals are dissolved in water, forming ion associates even in dilute solutions. The H atom involved in furcated hydrogen bonds cannot be exchanged by deuterium when the compound is dissolved in D₂O. An obvious consequence of the versatility of the matrix is the propensity of these compounds to form multiple polymorphs.

Two polymorphs and a solvatomorph of a new dimethylammonium polytungstate—decakis(dimethylammonium) dihydrogendodecatungstate, (Me₂NH₂)₁₀(W₁₂O₄₂)·nH₂O (n = 10 or 11)—have been synthesized.     

Specific expression of PAD4 and citrullinated proteins in lung cancer is not associated with anti-CCP antibody production

Anti-citrullinated protein antibodies (ACPAs), produced against citrullinated proteins, are diagnostic and prognostic markers of rheumatoid arthritis (RA). The underlying mechanism that explains the connection of smoking, citrullination [catalyzed by peptidyl arginine deiminases (PADs)] and ACPAs is still unclarified in RA. Thus, we searched for a non-arthritic model in which an increased cell death allows the formation of autoantibodies. Data supporting that lung cancer might be a good candidate are as follows: (i) smoking plays a role in its pathogenesis, (ii) the disease is frequently accompanied by paraneoplastic syndrome, (iii) smoking increases citrullination in the lung, (iv) various types of malignancies are associated with increased citrullination and (v) lung cancer tissue shows similarities with RA synovium. Serum PAD4, rheumatoid factor (RF) and ACPA levels were measured in 42 lung cancer patients; expression of cytokeratin 7 (CK7), PAD4 and citrullinated proteins was visualized in 113 lung cancer tissues. All parameters were analyzed in correlation with smoking history. None of the patients had polyarthritis or autoimmune disease. Significantly increased RF levels were associated with higher PAD4 levels in smoker lung cancer patients compared with non-smokers. Both PAD4 and citrullination immunostaining strongly correlated with that of CK7 in lung cancer, however, did not differ according to smoking history. Two of 30 smoker lung cancer patients had high anti-cyclic citrullinated peptide levels. In conclusion, PAD4 and citrullination may be helpful in distinguishing lung cancer from healthy tissue. Smoking, abnormal serum PAD4 and RF levels may not be sufficient for the production of ACPAs and development of autoimmunity.     

Strong HIV and hepatitis disclosure norms and frequent risk behaviors among Hungarian drug injectors

Ethnographic interviews and focus groups were conducted between May 2003 and January 2004 among injection drug users (IDUs; n=29) in Budapest, Hungary, to assess knowledge related to HIV, hepatitis B (HBV), and hepatitis C (HCV) and norms, attitudes, and behaviors. Participants perceived themselves at low risk for infection with HIV but at high risk for hepatitis through injection but not sexual exposure. They reported strong disclosure norms for HIV and hepatitis infections, while sexual and injection risk behaviors were influenced by trust about partners' self-report of infection status. Injection networks were small, with infrequent syringe sharing among a few close friends. Cookers and drug filters often were shared, and filters were reused as a backup drug supply. Most sexual relationships were monogamous, and condoms were used rarely. Although participant norms supported HIV/HBV/HCV testing, the lack of available behaviors with injection and sex partners who are close friends. Network interventions among IDUs in Hungary should build on disclosure norms and trust to reduce injection and sex risk. Testing services should be expanded and access increased so that IDUs can act on and reinforce their norms for testing.     

Effect of PACAP on MAP kinases,Akt and cytokine expressions in rat retinal hypoperfusion

Pituitary adenylate cyclase activating polypeptide (PACAP) is known for its potent neuroprotective effects, including the retinoprotective actions in several types of retinal injuries. We have shown earlier that PACAP treatment causes activation of protective pathways and inhibition of pro-apoptotic signaling in excitotoxic retinal lesions. The aim of the present study was to gain insight into the in vivo protective mechanism of PACAP in retinal hypoperfusion injury induced by bilateral common carotid artery occlusion (BCCAO). Rats underwent BCCAO and received intravitreal PACAP (PACAP38) treatment. We investigated the activation level of the protective Akt pathway as well as the different mitogen activated protein kinases (MAPKs) by Western blot analysis and the expression of cytokines using a cytokine array kit. We found that PACAP treatment alone did not influence the phosphorylation of Akt or the MAPKs, but decreased the hypoperfusion-induced activation of both p38MAPK and JNK and increased the activation of the protective Akt and ERK1/2 in hypoperfused retinas. The cytokine profile was dramatically changed after BCCAO, with most cytokines and chemokines showing an increase, which was attenuated by PACAP (such as CINC, CNTF, fractalkine, sICAM, IL-1, LIX, Selectin, MIP-1, RANTES and TIMP-1). In addition, PACAP increased the expression of VEGF and thymus chemokine. The present results provide further insight into the neuroprotective mechanism induced by PACAP in ischemic retinal injuries, showing that PACAP ameliorates hypoperfusion injury involving Akt, MAPK pathways and anti-inflammatory actions.     

Ipsilateral Alteration of Resting State Activity Suggests That Cortical Dysfunction Contributes to the Pathogenesis of Cluster Headache

The pathomechanism of cluster headache (CH) is not entirely understood, but central and peripheral components were suggested. A recent report showed that transcranial magnetic stimulation measured cortical excitability was increased in the hemisphere ipsilalteral to the pain. In the current study we set out to investigate the amplitude of resting brain fMRI activity to find signatures of the increased excitability. High resolution T1 weighted and resting state functional MRI images were acquired from seventeen patients with CH in pain free period and from twenty-six healthy volunteers. Patients’ data were normalized (e.g. inverted along the midsagittal axis) according to the headache side. Independent component analysis and a modified dual regression approach were used to reveal the differences between the resting state networks. Furthermore, the timecourses were decomposed into five frequency bands by discrete wavelet decomposition and were also re-regressed to the original data to reveal frequency specific resting activity maps. Two of the identified resting state networks showed alterations in CH. When the data were inverted to have patients’ headaches on the left, the ipsilateral attention network showed increased connectivity in 0.08–0.04 Hz frequency band in the in CH group. In the same dataset, cerebellar network showed higher functional connectivity in 0.02–0.01 Hz range in the ipsilateral cerebellum. When the data of patients having headache on the left were inverted to the right, similar increased signal was found in the ipsilateral attention network in 0.08–0.04 Hz band. The cerebellar network showed increased connectivity in the cerebellum in 0.02–0.01 Hz band in patients. The Fourier analysis of these area revealed increased power in CH at all cases. Our results showed alterations of brain functional networks in CH. The alterations of resting state activity were found in the hemisphere ipsilateral to the pain, signifying the altered cortical processing in the pathomechanism of CH.     

Association of Exercise Capacity with Physical Functionality and Various Aspects of Fatigue in Patients with Coronary Artery Disease

The aim of this study was to examine associations between exercise capacity—indexed as the metabolic equivalent of the task—and various aspects of subjective fatigue, physical functionality, and depression in patients with coronary artery disease. A cross-sectional design was used. Patients with stable coronary artery disease (N = 240) underwent an exercise stress test and completed self-report assessments of depression, subjective physical limitations, vital exhaustion, and the impact of fatigue on physical, social, and cognitive functions. Associations between exercise capacity and these self-report variables were assessed using bivariate correlations and a series of multivariate regressions. Exercise capacity was negatively associated with vital exhaustion, physical limitations, and impact of fatigue on physical and social functioning but not on cognitive functioning. There was a marginal association between exercise capacity and depression. The associations between exercise capacity and fatigue remained significant even after controlling for effects of age, body mass index, gender, education, and comorbid diabetes mellitus. The main conclusion of the study is that in patients with coronary artery disease, exercise capacity has the strongest predictability for physical fatigue, but, importantly, it also independently predicts the feeling of loss of energy and malaise.