Scope and limitation of propylene carbonate as a sustainable solvent in the Suzuki–Miyaura reaction

The Suzuki–Miyaura reaction is one of the most used transformations in drug research. Thus making this reaction more sustainable is of considerable current interest. Here we show that propylene carbonate (PC) can be used as a solvent for the Suzuki–Miyaura reaction. PC is one of the greenest solvents since it is synthesized under green conditions by the use of carbon dioxide in the air. All reactions proceeded well and good or excellent yields were observed for the biaryl products. Nonetheless in the case of pyridazinones, 2-hydroxypropyl- chain containing side-products were observed. Importantly, this fact allowed the isolation of several novel compounds which were generated under prominently green conditions.

The Suzuki–Miyaura reaction was carried out in propylene carbonate yielding an interesting side-product besides the biphenyl derivative.     

Impact of maternal obesity on the fetal electrocardiogram during labor

Objective: Maternal obesity affects one in every five women giving birth worldwide. This condition is associated with adverse perinatal outcomes, as well as increased morbidity and mortality for mother and offspring.

Methods: We carried out a prospective study at the University of Pecs Medical Center, Pecs, Hungary, between 1 January 2013 and 1 January 2014. We enrolled 60 obese (body mass index >30?kg/m²) low-risk pregnant women and 108 age-, ethnicity-, and parity-matched nonobese pregnant control subjects. The ST segment of the fetal electrocardiogram was assessed by STAN® monitoring. Neonatal outcomes and cord gas analysis of the umbilical vessels were evaluated after birth.

Results: No infant with definitive metabolic acidosis was delivered in either group. We observed 32 and 106 ST events in the obese and control group, respectively, but this difference was not statistically significant. To date, none of the infants delivered as part of this study have demonstrated developmental insufficiency.

Conclusions: Obesity might not influence the fetal electrocardiogram during labor as an independent risk factor for adverse pregnancy outcomes. Studies with larger cohort sizes are needed to confirm our findings.     

Modification of tooth development by heat shock protein 60

Although several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 (Hsp 60). To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot (EK) and stratum intermedium (SI). Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2- deoxyuridine (BrdU) incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes.     

Rapid in silico selection of an MCHR1 antagonists’ focused library from multi-million compounds’ repositories: biological evaluation

Target-focused libraries can be rapidly selected by 2D virtual screening methods from multimillion compounds’ databases if structures of active compounds are available. In the present study, a multi-step virtual and in vitro screening cascade is used to select melanin-concentrating hormone receptor-1 antagonists. The 2D similarity search combined with physico-chemical parameter filtering is suitable for selecting candidates from multimillion compounds’ repository. The seeds of the first round of virtual screening were collected from literature commercial databases, whereas the seeds of the second round were the hits the first round of biological testing In vitro screening underlined the efficiency of our approach, as in the second screening round the hit rate (8.6 %) significantly improved compared to the first round (1.9 %), applying a strict requirement for hit selection, and also this cascade-like screening method was appropriate for selecting several compounds reaching efficacies even below 10 nM.     

Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes

Adrenergic activation of L-type Ca²⁺ and various K⁺ currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca²⁺ and K⁺ currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I _Ca, I _Ks, and I _Kr, while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I _Ca and I _Ks and moderate stimulation of I _Kr. The ISO-induced plateau shift and I _Ca increase developed faster than the shortening of APD and stimulation of I _Ks and I _Kr. Blockade of β₁-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β₂-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I _Ca is turned on faster than the stimulation of I _Ks and I _Kr in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.     

Cost-of-illness in patients with moderate to severe psoriasis: a cross-sectional survey in Hungarian dermatological centres

Background

Despite the widespread availability of biological drugs in psoriasis, there is a shortage of disease burden studies.

Objectives

To assess the cost-of-illness and quality of life of patients with moderate to severe psoriasis in Hungary.

Methods

Consecutive patients with Psoriasis Area and Severity Index (PASI) > 10 and Dermatology Life Quality Index (DLQI) > 10, or treated with traditional systemic (TST) or biological systemic treatment (BST) were included. Demographic data, clinical characteristics, psoriasis related medication, health care utilizations and employment status in the previous 12 months were recorded. Costing was performed from the societal perspective applying the human capital approach. Quality of life was assessed using DLQI and EQ-5D measures.

Results

Two-hundred patients were involved (females 32 %) with a mean age of 51 (SD 13) years, 103 (52 %) patients were on BST. Mean PASI, DLQI and EQ-5D scores were 8 (SD 10), 6 (SD 7) and 0.69 (SD 0.3), respectively. The mean total cost was €9,254/patient/year (SD 8,502) with direct costs accounting for 86 %. The main cost driver was BST (mean €7,339/patient/year). Total costs differed significantly across treatment subgroups, mean (SD): no systemic therapy €2,186 (4,165), TST €2,388 (4,106) and BST €15,790 (6,016) (p < 0,001). Patients with BST had better PASI and DLQI scores (p < 0.01) than the other two subgroups.

Conclusions

Patients with biological treatment have a significantly better quality of life and higher total costs than patients with or without traditional systemic treatment. Our study is the largest in Europe and the first in the CEE region that provides cost-of-illness data in psoriasis involving patients with BST.

     

Spiritualität in der psychodramatischen Praxis

The relationships of Hungarian psychotherapists and their praxis to spirituality are examined in a comprehensive qualitative research based on Grounded Theory. The study demonstrates what surplus originates according to the experience of psychotherapists from the means of psychodrama in psychotherapy applied to cases involving spiritual content.     

Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes

Diabetic nephropathy is the leading cause of end-stage renal failure and accounts for 30–40 % of patients entering renal transplant programmes. The nephroprotective effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) against diabetes have been shown previously, but the molecular mechanisms responsible for these effects remain unknown. In the present study, we showed that PACAP treatment counteracted the diabetes-induced increase in the level of the proapoptotic pp38MAPK and cleaved caspase-3 and also decreased the p60 subunit of NFκB. The examined antiapoptotic factors, including pAkt and pERK1/2, showed a slight increase in the diabetic kidneys, while PACAP treatment resulted in a notable elevation of these proteins. PCR and Western blot revealed the downregulation of fibrotic markers, like collagen IV and TGF-β1 in the kidney. PACAP treatment resulted in increased expression of the antioxidant glutathione. We conclude that the nephroprotective effect of PACAP in diabetes is, at least partly, due to its antiapoptotic, antifibrotic and antioxidative effect in addition to the previously described antiinflammatory effect.     

Disc‐like lesions in the intestinal tract after renal transplantation

We report a case of intestinal lesions in a patient with a history of lupus nephritis and renal transplantation. Biopsy revealed an EBV‐driven post‐transplant lymphoproliferative disease (PTLD). An EBV‐driven PTLD is a major complication after renal transplantation and is an important differential diagnostic consideration in the follow‐up of renal transplant recipients.