Search

Egy ország biztonsági környezeti leírásának, értékelésének feladatát végezve fényképszerű képet kaphatunk az országot érintő legkomolyabb vagy épp csak legjellemzőbb kihívásokról. Bizonyos időközönként ugyanezt a feladatot elvégezve pedig folyamatokat láthatunk, vagy akár tehetünk kísérletet előrejelzésekre is. Akárhogy is legyen, egy ilyen vizsgálat elvégzése kulcsfontosságú az ország kül- és biztonságpolitikájának értelmezéséhez. Olaszország biztonsági környezetének legjelentősebb kihívásait keresem a buzani biztonsági szektorok (kiegészítve az információs technológia kihívásaival) alkalmazásával, az analízis különböző szintjein. A mátrixban az általam azonosított legjelentősebb kihívások közé tartozik természetesen a koronavírus-világjárvány, demográfiai trendek, alacsony védettség a koronavírussal szemben, vagy éppen a kritikus infrastruktúra elleni kibertámadások. Ezzel szemben a katonai és politikai biztonság szektora tekintetében egyéni és állami szinten jelenleg nincs ok aggodalomra, miközben a gazdasági biztonság e két szintjén régóta fennálló, de létbiztonságot nem fenyegető kihívásokat találunk.

It is beyond doubt that in today’s security environment Italy is one of the major stakeholders when it comes to participation in missions and operations. The aim of this essay is to examine if the often used expression presenzialismo is also applicable to Hungary’s participation. With the method of overviewing the contributions to the missions and operations of the main international organisations, the goal is to prove whether Hungary’s participation is or is not comparable to Italy’s actions in proportion to their respective power and opportunities. One of the main findings is that the two countries’ areas of interest are almost identical. They also share a common view that they consider NATO as the main partner in safeguarding the security of the transatlantic region. There is a kind of reform ongoing in the armed forces of both nations, but these shall not result in the weakening of the participation in missions and operations. Nevertheless, Italy’s participation is way too more conspicuous; we found that Hungary does not fall short significantly of Italy’s contribution proportionately.

In March 2020, a group of experts was appointed by secretary General Jens Stoltenberg to examine the situation of the Alliance in these uncertain times and to provide a proposition for the principles of the Alliance for the coming decade. After the completion, the Report mostly stayed under the radar. My goal is to identify those fields in which Italy can take a leading role, or on the contrary: the fields in which Italy has more to do. During my research, my method was to find the Report’s most significant recommendations and to assess Italy’s position on the issue, trying to find the main implications for Italy. I identified four major fields in which the changing NATO goes lack consensus, and causes intra-Alliance frictions. One of these is the question of Russia. Italy has a good relationship with the old rival, but NATO – not excluding the possibility for cooperation – has a way more negative perspective about Russia. Almost the same stands for China. Italy’s and several other Member States’ relationship with China causes some controversy among the Allied States. Among other factors, these cause strategic divergencies in the Alliance. Different friends and adversaries, different interests and values sometimes make the cooperation hard. Because of this, it is of utmost importance to improve political coordination and cooperation. The most important field, in which Italy can take a leading role is the Southern Strategic Direction. Italy is already a very active player in the Mediterranean region, as it is a vital area in Italy’s security. I believe Italy will have the military and political power, and most likely also the willingness to be among the leading nations in implementing the findings of NATO 2030, if it can maintain or strengthen its position in the Alliance.

Skin bacterial colonization/infection is a frequent cause of morbidity in patients with chronic wounds and allergic/inflammatory skin diseases. This study aimed to develop a novel approach to eradicate meticillin-resistant Staphylococcus aureus (MRSA) from human skin. To achieve this, the stability and antibacterial activity of the novel LL-37-derived peptide P10 in four ointments was compared. Results indicate that P10 is chemically stable and antibacterial in hypromellose gel and Softisan-containing cream, but not in Cetomacrogol cream (with or without Vaseline), at 4 degrees C for 16 months. Reduction in MRSA counts on Leiden human epidermal models (LEMs) by P10 in hypromellose gel was greater than that of the peptide in Cetomacrogol cream or phosphate buffered saline. P10 did not show adverse effects on LEMs irrespective of the ointment used, while Cetomacrogol with Vaseline and Softisan cream, but not hypromellose gel or Cetomacrogol cream, destroyed MRSA-colonized LEMs. Taking all this into account, P10 in hypromellose gel dose-dependently reduced MRSA colonizing the stratum corneum of the epidermis as well as biofilms of this bacterial strain on LEMs. Moreover, P10 dose-dependently reduced MRSA counts on ex-vivo human skin, with P10 in hypromellose gel being more effective than P10 in Cetomacrogol and Softisan creams. P10 in hypromellose gel is a strong candidate for eradication of MRSA from human skin. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

We previously found the LL-37-derived peptide P60.4Ac to be effective against methicillin-resistant Staphylococcus aureus (MRSA) on human epidermal models (EMs). The goal of this study was to identify the preferred carrier for this peptide for topical application on skin and mucosal surfaces. We prepared P60.4Ac in three formulations, i.e., a water-in-oil cream with lanolin (Softisan 649), an oil-in-water cream with polyethylene glycol hexadecyl ether (Cetomacrogol), and a hydroxypropyl methylcellulose (hypromellose) 4000 gel. We tested the antimicrobial efficacy of the peptide in these formulations against mupirocin-resistant and -sensitive MRSA strains on EMs and bronchial epithelial models (BEMs). The cytotoxic effects of formulated P60.4Ac on these models were determined using histology and WST-1 and lactate dehydrogenase assays. Moreover, we assessed the stability of the peptide in these formulations with storage for up to 3 months. Killing of MRSA by P60.4Ac in the two creams was less effective than that by P60.4Ac in the hypromellose gel. In agreement with those findings, P60.4Ac in the hypromellose gel was highly effective in eradicating the two MRSA strains from EMs. We found that even 0.1% (wt/wt) P60.4Ac in the hypromellose gel killed >99% of the viable planktonic bacteria and >85% of the biofilm-associated bacteria on EMs. Hypromellose gels containing 0.1% and 0.5% (wt/wt) P60.4Ac effectively reduced the numbers of viable MRSA cells from BEMs by >90%. No cytotoxic effects of P60.4Ac in the hypromellose gel with up to 2% (wt/wt) P60.4Ac on keratinocytes in EMs and in the hypromellose gel with up to 0.5% (wt/wt) P60.4Ac on epithelial cells in BEMs were observed. High-performance liquid chromatography analysis showed that P60.4Ac was stable in the Softisan cream and the hypromellose gel but not in the Cetomacrogol cream. We conclude that P60.4Ac formulated in hypromellose gel is both stable and highly effective in eradicating MRSA from colonized EMs and BEMs.

1H-Imidazo[4,5-c]quinolin-4-amine derivatives have been synthesized as allosteric modulators of the human A3 adenosine receptor (AR). Structural modifications were made at the 4-amino and 2 positions. The compounds were tested in both binding and functional assays, and many were found to be allosteric enhancers of the action of A3AR agonists by several different criteria. First, a potentiation of the maximum efficacy of the agonist Cl-IB-MECA was observed for numerous derivatives. Also, a number of these compounds decreased the rate of dissociation of the agonist [125I]I-AB-MECA from the A3AR. Most prominently, compound 43 (LUF6000) was found to enhance agonist efficacy in a functional assay by 45% and decrease dissociation rate similarly without influencing agonist potency. The structural requirements for allosteric enhancement at the A3AR were distinct from the requirements to inhibit equilibrium binding. Thus, we have prepared allosteric enhancers of the human A3AR that have an improved allosteric effect in comparison to the inhibition of equilibrium binding at the orthosteric site.

We synthesized two series (7a-i and 8a-i) of 2,3,5-substituted [1,2,4]-thiadiazole analogues of SCH-202676 (7a, 2,3-diphenyl-5-N-methylimino-2H-[1,2,4]-thiadiazole) with emphasis on the N-imino substituent. Compounds 7a-g,i and 8a-g at a final concentration of 1 microM significantly inhibited [(3)H]CCPA (2-chloro-N(6)- cyclopentyladenosine) agonist binding to human A(1) adenosine receptors. At the same concentration, all compounds appeared to increase [(3)H]DPCPX (1,3-dipropyl-8-cyclopentylxanthine) antagonist binding. Compound 7a and LUF5855 (7g) were selected for further characterization and studied in both equilibrium and kinetic radioligand binding experiments. The results suggest a nonstoichiometric interaction with the receptor. Further bioanalytical procedures (HPLC and MS) provided proof for an unusual receptor interaction in which 7a and 7g upon incubation were transformed into their corresponding thioureas 5a and 5g. We suggest that the thiadiazoles are sulfhydryl modifying agents rather than allosteric modulators, as they appear to reversibly modify the sulfhydryl groups of cysteine residues in cell membrane preparations.

N-Methyl-, N-ethyl-, N-(n-propyl)-, N-(iso-propyl)- and N-phenyl-2-arylimidazolidines proved to be ring-chain tautomeric mixtures in CDCl3. The ratios of the open and ring forms in the tautomeric equilibria of these compounds is described by the equation log Kx = ϱσ + log KX−H, used earlier for the ring-chain equilibria of saturated 2-aryl-1,3-O,N-heterocycles. These are the first examples among 2-arylimidazolidines of ring-chain tautomeric processes characterized by a Hammett-type correlation.

Among the purine and pyrimidine receptors, the discovery of small molecular allosteric modulators has been most highly advanced for the A(1) and A(3) adenosine receptors (ARs). These AR modulators have allosteric effects that are structurally separated from the orthosteric effects in SAR studies. The benzoylthiophene derivatives tend to act as allosteric agonists as well as selective positive allosteric modulators (PAMs) of the A(1) AR. A 2-amino-3-aroylthiophene derivative T-62 has been under development as a PAM of the A(1) AR for the treatment of chronic pain. Several structurally distinct classes of allosteric modulators of the human A(3) AR have been reported: 3-(2-pyridinyl)isoquinolines, 2,4-disubstituted quinolines, 1H-imidazo-[4,5-c]quinolin-4-amines, endocannabinoid 2-arachidonylglycerol, and the food dye Brilliant Black BN. Site-directed mutagenesis of A(1) and A(3) ARs has identified residues associated with the allosteric effect, distinct from those that affect orthosteric binding. A few small molecular allosteric modulators have been reported for several of the P2X ligand-gated ion channels and the G protein-coupled P2Y receptor nucleotides. Metal ion modulation of the P2X receptors has been extensively explored. The allosteric approach to modulation of purine and pyrimidine receptors looks promising for development of drugs that are event and site specific in action.

Allosteric modulators for the G(i)-coupled A(3) adenosine receptor (AR) are of considerable interest as therapeutic agents and as pharmacological tools to probe various signaling pathways. In this study, we initially characterized the effects of several imidazoquinolinamine allosteric modulators (LUF5999, LUF6000 and LUF6001) on the human A(3) AR stably expressed in CHO cells using a cyclic AMP functional assay. These modulators were found to affect efficacy and potency of the agonist Cl-IB-MECA differently. LUF5999 (2-cyclobutyl derivative) enhanced efficacy but decreased potency. LUF6000 (2-cyclohexyl derivative) enhanced efficacy without affecting potency. LUF6001 (2-H derivative) decreased both efficacy and potency. We further compared the agonist enhancing effects of LUF6000 in several other A(3) AR-mediated events. It was shown that although LUF6000 behaved somewhat differently in various signaling pathways, it was more effective in enhancing the effects of low-efficacy than of high-efficacy agonists. In an assay of cyclic AMP accumulation, LUF6000 enhanced the efficacy of all agonists examined, but in the membrane hyperpolarization assay, it only enhanced the efficacy of partial agonists. In calcium mobilization, LUF6000 did not affect the efficacy of the full agonist NECA but was able to switch the nucleoside antagonist MRS542 into a partial agonist. In translocation of β-arrestin2, the agonist-enhancing effect LUF6000 was not pronounced. In an assay of ERK1/2 phosphorylation LUF6000 did not show any effect on the efficacy of Cl-IB-MECA. The differential effects of LUF6000 on the efficacy and potency of the agonist Cl-IB-MECA in various signaling pathway were interpreted quantitatively using a mathematical model.

The adenosine receptor subfamily consists of the adenosine A(1), A(2A), A(2B), and A(3) receptors, which are localized in a variety of tissues throughout the human body. It is, therefore, a challenge to develop receptor specific ligands with improved tissue selectivity. Allosteric modulators could have these therapeutic advantages over orthosteric ligands. In the present study, a series of 2,4-disubstituted quinolines were synthesized on the basis of the structure of LUF6000 (34). Compound 27 (LUF6096) was able to allosterically enhance agonist binding to a similar extent as 34. In addition, this new compound showed low, if any, orthosteric affinity for any of the adenosine receptors. In a functional assay, compound 27 showed improved activity in comparison to 34, as it increased both the intrinsic efficacy and the potency of the reference agonist Cl-IB-MECA at the human adenosine A(3) receptor.

A 2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A 2A antagonists, we synthesized a new class of compounds having a 2-amino nicotinonitrile core moiety. From our data, we conclude that the presence of at least one furan group rather than phenyl is beneficial for high affinity on the A 2A adenosine receptor. Compounds 39 (LUF6050) and 44 (LUF6080) of the series had K i values of 1.4 and 1.0 nM, respectively, with reasonable selectivity toward the other adenosine receptor subtypes, A 1, A 2B, and A 3. The high affinity of 44 was corroborated in a cAMP second messenger assay, yielding subnanomolar potency for this compound.

Our results show that the different cultivation methods have higher effect on the yield than on the grape quality. In 2007 the weather was extreme dry (from May to August only 195 mm precipitation was recorded) the straw mulch proved to be the best solution regarding the yield and the grape quality. Although no significant differences were observed in the sugar- and titratable acidity content of the must, the ratio of noble rotted berries was higher on the straw mulched plots. Straw mulch could conserve the moisture content of the soil and it seems to be contributed to the conformation of suitable microclimate for Botrytis infection, but for long distance conclusions further examinations need to be investigated. The less yield and ratio of rot was observed in case of barely covered vines and the vegetative growth of the grape was less intensive in case of these vines.

The authors review knowledge of the clinical, imaging and pathological diagnosis of mastopathy syndrome and the issues of its therapy and care. They observe that no unified nomenclature exists, all the disciplines judge the idea of mastopathy differently. Clinical and imaging diagnosis is uncertain, the correct diagnosis can be established only by the pathologist. The role of surgery is minimal. The precancerous nature of mastopathy is also discussed, the rate of malignant transformation is low. Malignant transformation of benign lesions is very rare. The most important tools are close observation, systematic care of patients by a team of professionals, possibly by the same persons, in the same institute. Further research, and more exact definitions are necessary.

A number of 2-aminothiazoles (2a–e) and their amide derivatives (4–10) were prepared. The 2-aminothiazoles themselves were tested as allosteric enhancers of agonist binding to human adenosine A1 receptors. In a variety of experimental set-ups the compounds did not show any such effect, in contrast to earlier findings by another research group. Subsequently the 2-aminothiazoles were used as intermediates in the synthesis of a number of amide derivatives of either aromatic (4–6) or aliphatic nature (7–10). Some of the compounds emerged as moderately active antagonists on human adenosine A1 and/or A2A receptors with lower or negligible potency at adenosine A3 receptors.

The literature of breast-screening is vastly large, and enlarges by newer publications permanently. This summary can only be confined to publish data, with arbitrary selection. The mass-screening of complaintless and symptomless persons for early recognition of certain illnesses is to be completed according to district-principles, and to preliminarily agreed criteria. The breast-screening started in 1963 with the HIP-study, since then it is underway in a number of countries of the world. In Hungary, this activity started relatively early, in 1969. Circumstances of breast-screening are different in the individual countries. Standpoints of organisation: information, recruiting with the help of family-doctors. With respect to rates of occurrence of the breast-cancer, women between 45-65 years of age are mostly to be screened. The most suitable is the screening in every two years. Data are to be put in computer. The most important method for examination is mammography. About its complementary methods is the most important the ultrasonography. Certificating is always to be made by two physicians. Oncologists are to be in the closest cooperation with cytologists and pathologists. It is suitable, when an interdisciplinary team decides about the fate of patients. The quality-control and product-control of screening is obligatory based on international guidelines. An important idea of screening is the interval-carcinome, a cancer developing between two screening examinations. Mammology is to be performed only by personal trained accordingly for this. Advantage of screening: reducing of mortality by approximately. 30%--with certain differences in countries, with older, then 50 years of age, but it becomes evident after 10 years. The contrary opinions are scientifical, ethical and financial. The cancer-patients are to be observed and followed in their whole life. In this activity everybody may have some role. In the struggle against breast-cancer there is no better solution, than the breast-screening.

A healthy, non-consanguineous couple had a son with complete situs inversus viscerum (including dextrocardia but without other cardiac defects), broad thumbs and big toes, postaxial polydactyly, average intelligence and length proportion of the extremities, and a normal face. The common cause of these defects may have a role in the origin of sidedness and symmetry in morphogenesis.

To diagnose premature or prepubertal breast development or breast diseases.Harmless, non-invasive examinations were conducted on young girls by the use of ultrasound and liquid crystal thermography with discs of various sensitivity.The study was conducted at the Radiological Department of the Postgraduate Medical University in Budapest, Hungary.The study entailed examination of 283 patients, all under age 14, of the paediatric gynaecological ward and the outpatient service who had breast problems.Aspiration cytology or surgical intervention were used only in rare cases.The outcome was measured based on the accuracy and expediency of the diagnostic procedures.The most frequent problems observed were precocious breast development, precocious pubertal development and asymmetric breasts. Precocious thelarche was observed in 117 patients, four patients were found to have cysts, and there were 59 cases of inflammation or abscess.Liquid crystal thermography and ultrasound proved to be sufficient and accurate means of diagnosis breast problems.