insulino-resistenza e disfunzione vascolare

L’insulino-resistenza e le alterazioni metaboliche ed emodinamiche ad essa associate sono indiscusse caratteristiche del diabete tipo 2 (DM2) e delle sue complicanze macrovascolari. Numerosi studi epidemiologici hanno dimostrato che il diabete conferisce un aumentato rischio di coronaropatia e mortalità cardiovascolare. Nell’ambito delle complicanze microvascolari del DM2 già 20 anni fa il Framingham Heart and Eye Study dimostrava che la retinopatia diabetica era la manifestazione di processi microangiopatici e la spia di una disfunzione microvascolare multiorgano. Il dilemma di come l’insulino-resistenza si correli al tipo di danno cardiovascolare è più che attuale. Assumendo che l’insulino-resistenza si associa all’iperglicemia, alla dislipidemia e all’ipertensione arteriosa, non sorprende che essa possa avere un ruolo sicuramente importante nello sviluppo e nella progressione del danno microcircolatorio, ma il legame causale è lungi dall’esser chiarito. Scopo dello studio è stato quello di valutare le correlazioni esistenti nel DM2 fra insulino-resistenza e disfunzione micro- e macrocircolatoria, e di valutare le correlazioni fra i fattori di rischio cardiovascolare classici e non e la retinopatia. Per tale motivo sono stati studiati 28 pazienti con DM2, di cui 14 pazienti con retinopatia diabetica (9M/5F, con età 63±4 anni) e 14 pazienti non affetti da tale complicanza (9M/5F, con età 60±8 anni), ben appaiati per indice di massa corporea (BMI). Dei 14 pazienti con retinopatia diabetica 9 presentavano retinopatia proliferativa/laser trattata e 5 presentavano retinopatia “background”. I metodi utilizzati per lo studio di tutti i pazienti sono stati: clamp euglicemico iperinsulinemico, per la valutazione della sensibilità insulinica, fluorangiografia retinica, per la valutazione del microcircolo retinico, iontoforesi laser Doppler, per la valutazione del microcircolo cutaneo, ecocardiografia bidimensionale-CD, eco-CD dei vasi cerebro-afferenti, valutazione di alcuni parametri di rigidità arteriosa, come indicativi della funzionalità macrovascolare. I risultati ottenuti hanno rilevato che i retinopatici mostrano una più bassa sensibilità all’insulina rispetto ai diabetici non affetti da tale complicanza. Non ci sono sostanziali differenze nei valori di insulinemia a digiuno e nel profilo lipidico, fuorché un più basso valore di colesterolo HDL. I diabetici retinopatici inoltre presentano più elevati livelli glicemia a digiuno, di emoglobina glicata e maggior durata di malattia. I diabetici affetti da retinopatia presentano inoltre valori più alti di alcuni indici infiammatori, quali il fibrinogeno, la velocità di eritrosedimentazione (VES), il numero dei globuli bianchi, e un più basso valore di albumina sierica. Il nostro studio ha dimostrato che il grado di retinopatia è indipendente dall’età, dal sesso e dal BMI mentre è significativamente associato al fibrinogeno, alla VES, alla durata della malattia diabetica, al colesterolo HDL, all’insulino-resistenza. L’insulino-resistenza si correla invece al colesterolo HDL, alla circonferenza addominale, alla glicemia a digiuno e alla presenza di retinopatia. La presenza di retinopatia è associata a precoce disfunzione diastolica e ad alterazioni del microcircolo cutaneo. In conclusione, insulino-resistenza e retinopatia sembrano essere entrambe parte integrante di una malattia diabetica in cattivo controllo glicemico; è si presente insulino-resistenza nei retinopatici, ma maggiore enfasi viene data alla possibilità che tale aspetto faccia parte di una fenomenologia più complessa, comprendente diverse alterazioni che concertano insieme a produrre un più avverso fenotipo cardiovascolare nel soggetto diabetico

Evaluasi Pengawasan Kredit Modal Kerja Sebagai Upaya Menekan Tunggakan Kredit (Studi Pada Perusahaan Daerah Bank Perkreditan Rakyat Tugu Artha Kota Malang Periode 2009-2011)

Penelitian ini bertujuan untuk mendeskripsikan hasil evaluasi pengawasan kredit modal kerja pada PD. BPR Tugu Artha dalam upaya menekan tunggakan kredit selama tahun 2009-2011. Berdasarkan hasil evaluasi pengawasan kredit modal kerja pada PD. BPR Tugu Artha Malang periode 2009-2011, terdapat beberapa kelemahan pada bagian pengawasan kredit. Kelemahan-kelemahan tersebut yaitu jumlah pemberian kredit yang melampaui batas kemampuan bank, rasio kredit terhadap simpanan atau Loan to Deposit Ratio (LDR) yang harus tetap diperhatikan agar tidak melampaui batas maksimum, bank terlalu mudah untuk memberikan fasilitas kredit, bank kurang teliti dalam mengecek kebenaran dan keaslian berkas-berkas yang ada seperti bukti diri (KTP) calon debitur, jaminan kredit yang kurang diperhatikan oleh pihak bank, debitur tidak menyampaikan laporan secara berkala atas jenis-jenis laporan yang telah disepakati dan dituangkan dalam perjanjian kredit dikarenakan debitur tidak memiliki kemampuan untuk membuat laporan-laporan tersebut, dan kunjungan yang dilakukan pihak bank ke tempat USAha debitur tidak dilakukan secara baik dan benar. Kelemahan-kelemahan tersebut yang mengakibatkan tingkat NPL pada bank jauh melampaui batas maksimum yang diberikan oleh Bank Indonesia yaitu sebesar 5%. Tingkat NPL kredit modal kerja pada PD. BPR Tugu Artha Malang pada tahun 2009 sebesar 22,13%, tahun 2010 sebesar 21,59%, dan pada tahun 2011 sebesar 26,10%. Berdasarkan hasil evaluasi pengawasan kredit modal kerja tersebut, maka pengawasan kredit modal kerja perlu lebih ditingkatkan lagi, bank yang bersangkutan harus lebih memperhatikan ketentuan-ketentuan dari Bank Indonesia khususnya yang berkenaan dengan prinsip kehati-hatian, dan pihak bank lebih mengaktifkan penagihan kepada debitur yang bersangkutan agar membayar angsuran tepat waktu sehingga dapat menekan tunggakan kredit. Kata kunci : kredit, modal kerja This study aimed to describe the results of the evaluation of working capital credit control in PD. BPR Artha monument in an effort to suppress loan arrears during the year 2009-2011. Based on the evaluation of working capital credit control in PD. BPR Tugu Malang Artha period 2009-2011, there are some weaknesses in the credit conrol. The weaknesses of the amount of credit that exceed the limits the ability of banks, loan-to-deposit ratio or Loan to Deposit Ratio (LDR) must be attented so that not more than the maximum limit, the bank is too easy to give the credit facility, the bank is less rigorous in checking the correctness and authenticity of the files that no such proof of identity (ID) of borrowers, loan guarantees are not considered by the bank, the debtor does not submit periodic reports on the types of reports that have been agreed upon and set forth in the credit agreement because the debtor does not have the ability to make these reports , and visits made by the bank to the debtor's place of business was not done properly and correctly. Weaknesses that resulted in the bank NPL levels far exceeding the maximum limit provided by Bank Indonesia at 5%. NPL level of working capital at the PD. BPR Artha Tugu Malang in 2009 amounted to 22.13%, in 2010 amounted to 21.59%, and in 2011 was 26.10%. Based on the evaluation results of the monitoring of working capital loans, working capital loans, supervision needs to be improved, the bank should pay more attention to the provisions of Bank Indonesia in particular with regard to the precautionary principle, and enable the bank over billing to the debtor in question in order to pay the installments on time so as to reduce delinquent loans

Calcium Inhibits Promotion by Hot Dog of 1,2-Dimethylhydrazine-Induced Mucin-Depleted Foci in Rat Colon

Epidemiology suggests that processed meat is associated with colorectal cancer risk, but few experimental studies support this association. We have shown that a model of cured meat made in a pilot workshop promotes preneoplastic lesions, mucin-depleted foci (MDF) in the colon of rats. This study had two aims: to check if real store-bought processed meats also promote MDF, and to test if calcium carbonate, which suppresses heme-induced promotion, can suppress promotion by processed meat. A 14-day study was done to test the effect of nine purchased cured meats on fecal and urinary biomarkers associated with heme-induced carcinogenesis promotion. Fecal water from rats given hot dog or fermented raw dry sausage was particularly cytotoxic. These two cured meats were thus given to rats pretreated with 1,2-dimethylhydrazine, to evaluate their effect on colorectal carcinogenesis. After a 100-d feeding period, fecal apparent total N-nitroso compounds (ATNC) were assayed and colons were scored for MDF. Hot dog diet increased fecal ATNC and the number of MDF per colon compared with the no-meat control diet (3.0±1.7 vs. 1.2±1.4, P<0.05). In a third study, addition of calcium carbonate (150 µmol/g) to the hot dog diet decreased the number of MDF/colon and fecal ATNC compared with the hot dog diet without calcium carbonate (1.2 ± 1.1 vs. 2.3 ± 1.4, respectively, P<0.05). This is the first experimental evidence that a widely consumed processed meat promotes colon carcinogenesis in rats. It also shows that dietary prevention of this detrimental effect is possible

Estudi comparatiu de les proves eliminatòries i finals de 100 metres en nedadors andalusos de grups d’edat

L’estudi va tenir com a objectiu analitzar les possibles diferències en els resultats de les sèries eliminatòries i finals en les proves de 100 m, obtinguts durant els campionats Infantils d’Andalusia de Natació. Els nedadors pertanyien a la categoria de 13-14 anys femenina i 15-16 anys masculina. Van ser recollides diferents variables temporals i cinemàtiques: velocitat (V), freqüència de cicle (Fc), longitud de cicle (Lc) i índex de cicle (Ic) dels diferents estils: crol (C), esquena (E), braça (B) i papallona (P); es va realitzar una anàlisi comparativa segons gènere, estil de natació i eliminatòries o finals. Els resultats mostren que en aquestes  edats de competició s’obtenen diferències significatives entre gèneres i entre sèries eliminatòries i finals en les variables analitzades; les diferències entre l’edat i la variable Lc són les principals conseqüències de les diferències trobades entre ambdós gèneres

Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution

Metaiodobenzylguanidine (MIBG) is an enzymatically stable synthetic analog of norepinephrine that when radiolabled with diagnostic ((123)I) or therapeutic ((131)I) isotopes has been shown to concentrate highly in sympathetically innervated tissues such as the heart and neuroendocrine tumors that possesses high levels of norepinephrine transporter (NET). As the transport of MIBG by NET is a saturable event, the specific activity of the preparation may have dramatic effects on both the efficacy and safety of the radiodiagnostic/radiotherapeutic. Using a solid labeling approach (Ultratrace), noncarrier-added radiolabeled MIBG can be efficiently produced. In this study, specific activities of >1200 mCi/micromol for (123)I and >1600 mCi/micromol for (131)I have been achieved. A series of studies were performed to assess the impact of cold carrier MIBG on the tissue distribution of (123/131)I-MIBG in the conscious rat and on cardiovascular parameters in the conscious instrumented dog. The present series of studies demonstrated that the carrier-free Ultratrace MIBG radiolabeled with either (123)I or (131)I exhibited similar tissue distribution to the carrier-added radiolabeled MIBG in all nontarget tissues. In tissues that express NETs, the higher the specific activity of the preparation the greater will be the radiopharmaceutical uptake. This was reflected by greater efficacy in the mouse neuroblastoma SK-N-BE(2c) xenograft model and less appreciable cardiovascular side-effects in dogs when the high-specific-activity radiopharmaceutical was used. The increased uptake and retention of Ultratrace (123/131)I-MIBG may translate into a superior diagnostic and therapeutic potential. Lastly, care must be taken when administering therapeutic doses of the current carrier-added (131)I-MIBG because of its potential to cause adverse cardiovascular side-effects, nausea, and vomiting

An enhanced model for small-signal analysis of the phase-shifted full-bridge converter

This paper presents an in-depth critical discussion and derivation of a detailed small-signal analysis of the Phase-Shifted Full-Bridge (PSFB) converter. Circuit parasitics, resonant inductance and transformer turns ratio have all been taken into account in the evaluation of this topology’s open-loop control-to-output, line-to-output and load-to-output transfer functions. Accordingly, the significant impact of losses and resonant inductance on the converter’s transfer functions is highlighted. The enhanced dynamic model proposed in this paper enables the correct design of the converter compensator, including the effect of parasitics on the dynamic behavior of the PSFB converter. Detailed experimental results for a real-life 36V-to-14V/10A PSFB industrial application show excellent agreement with the predictions from the model proposed herein.

Education and articulation: Laclau and Mouffe’s radical democracy in school

This paper outlines a theory of radical democratic education by addressing a key concept in Laclau and Mouffe’s Hegemony and Socialist Strategy: articulation. Through their concept of articulation, Laclau and Mouffe attempt to liberate Gramsci’s theory of hegemony from Marxist economism, and adapt it to a political sphere inhabited by a plurality of struggles and agents none of which is predominant. However, while for Gramsci the political process of hegemony formation has an explicit educational dimension, Laclau and Mouffe ignore this dimension altogether. My discussion starts with elaborating the concept of articulation and analysing it in terms of three dimensions: performance, connection and transformation. I then address the role of education in Gramsci’s politics, in which the figure of the intellectual is central, and argue that radical democratic education requires renouncing that figure. In the final section, I offer a theory of such education, in which both teacher and students articulate their political differences and identities

Influence of a Concurrent Exercise Training Intervention during Pregnancy on Maternal and Arterial and Venous Cord Serum Cytokines: The GESTAFIT Project

The aim of the present study was to analyze the influence of a supervised concurrent exercise-training program, from the 17th gestational week until delivery, on cytokines in maternal (at 17th and 35th gestational week, and at delivery) and arterial and venous cord serum. Fifty-eight Caucasian pregnant women (age: 33.5 +/- 4.7 years old, body mass index: 23.6 +/- 4.1kg/m(2)) from the GESTAFIT Project (exercise (n = 37) and control (n = 21) groups) participated in this quasi-experimental study (per-protocol basis). The exercise group followed a 60-min 3 days/week concurrent (aerobic-resistance) exercise-training from the 17th gestational week to delivery. Maternal and arterial and venous cord serum cytokines (fractalkine, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha) were assessed using Luminex xMAP technology. In maternal serum (after adjusting for the baseline values of cytokines), the exercise group decreased TNF-alpha (from baseline to 35th week, p = 0.02), and increased less IL-1 beta (from baseline to delivery, p = 0.03) concentrations than controls. When adjusting for other potential confounders, these differences became non-significant. In cord blood, the exercise group showed reduced arterial IL-6 and venous TNF-alpha (p = 0.03 and p = 0.001, respectively) and higher concentrations of arterial IL-1 beta (p = 0.03) compared to controls. The application of concurrent exercise-training programs could be a strategy to modulate immune responses in pregnant women and their fetuses. However, future research is needed to better understand the origin and clearance of these cytokines, their role in the maternal-placental-fetus crosstalk, and the influence of exercise interventions on them

Reduction of colonic inflammation in HLA-B27 transgenic rats by feeding Marie Ménard apples, rich in polyphenols

Inflammatory bowel diseases (IBD) are immunomediated ailments affecting millions of individuals. Although diet is regarded as an important factor influencing IBD, there are no accepted dietary recommendations presently available. We administered 7.6 % lyophilised apples obtained from two cultivars (Golden Delicious and Marie Ménard, low and high in polyphenols, respectively) to HLA-B27 transgenic rats which develop spontaneous IBD. After 3 months feeding, rats fed Marie Ménard apples had reduced myeloperoxidase activity (3.6 (sem 0.3) v. 2.2 (sem 0.2) U/g tissue; P <0.05) and reduced cyclo-oxygenase-2 (P <0.05) and inducible NO synthase gene expression (P <0.01) in the colon mucosa and significantly less diarrhoea (P <0.05), compared with control rats. Cell proliferation in the colon mucosa was reduced significantly by feeding Golden Delicious apples, with a borderline effect of Marie Ménard apples. Gene expression profiling of the colon mucosa, analysed using the Whole Rat Genome 4 x 44 K Agilent Arrays, revealed a down-regulation of the pathways of PG synthesis, mitogen-activated protein kinase (MAPK) signalling and TNFalpha-NF-kappaB in Marie Ménard-fed rats. In the stools of the animals of this group we also measured a significant reduction of bacteria of the Bacteriodes fragilis group. In conclusion, the administration of Marie Ménard apples, rich in polyphenols and used at present only in the manufacturing of cider, ameliorates colon inflammation in transgenic rats developing spontaneous intestinal inflammation, suggesting the possible use of these and other apple varieties to control inflammation in IBD patient