Nicolae Constantin Paulescu: prvi eksplicitni opis unutarnjeg izlučivanja gušterače

The purpose of this article is to describe the research of Nicolae Constantin Paulescu and to emphasize his role in the discovery of insulin. Methods: We made a thorough review of the literature and research in the Romanian Academy Archive in order to find adequate references. Results: In 1912 N.C. Paulescu analysed the clinical and biochemical alterations in diabetic patients and in dogs after performing a pancreatectomy, that apart hyperglycemia and glycosuria (carbohydrate metabolism), had noted also changes in lipid and protein metabolism. In 1916 he started the experiments with a pancreas extract obtained by his original method, that was injected intravenously to the diabetic dogs. The results of his first experiments showed: “The pancreatic extract injected into a peripheral vein produce: 1) A diminution and even a temporary suppression of diabetic hyperglycemia, which may be replaced by hypoglycemia; 2) A diminution or even temporary suppression of glycosuria; 3) A diminution of blood urea; 4) A diminution of urinary urea. In other words, the intravenous injection of the pancreatic extract has as effect the disappearance of diabetic symptoms. The attenuation of the diabetic syndrome begins immediately after the injection. It reaches a maximum after 2 hours,- and it lasts for about 12 hours”. He concluded as such: “This discovery,- which sheds a bright light over the pathogenesis of diabetes gives us also the key for the treatment of this syndrome”. In 1921, Paulescu had published extensively his data in two outstanding French journals 8 months before the first publication of Banting and Best from February 1922. It is clear that insulin has been discovered in Europe. Conclusion: Paulescu thought that a new hormone – Pancreine, that he discovered is the key element in the treatment of diabetes, but his outstanding research was unfairly neglected.Svrha je ovog članka opisati istraživanje Nicolaea Constantina Paulescua i istaknuti njegovu ulogu u otkriću inzulina. Metode: Temeljito smo pregledali literaturu i istraživanja u rumunjskoj akademskoj arhivi kako bismo pronašli odgovarajuće reference. Rezultati: N. C. Paulescu je 1912. analizirao kliničke i biokemijske promjene kod pacijenata s dijabetesom i kod pasa nakon izvođenja pankreatektomije, koji su osim hiperglikemije i glikozurije (metabolizam ugljikohidrata) zabilježili i promjene u metabolizmu lipida i proteina. Godine 1916. Paulescu je započeo eksperiment s ekstraktom gušterače dobivenim njegovom izvornom metodom, koji je intravenski ubrizgan u pse koji su bolovali od dijabetesa. Rezultati njegovih prvih eksperimenata pokazali su: “Ekstrakt gušterače ubrizgan u perifernu venu proizvodi: 1. smanjenje, pa čak i privremenu supresiju dijabetičke hiperglikemije, koja može biti zamijenjena hipoglikemijom; 2. smanjenje ili čak privremenu supresiju glikozurije; 3. smanjenje uree u krvi; 4. smanjenje uree urina. Drugim riječima, intravenozna injekcija ekstrakta gušterače ima za posljedicu nestanak simptoma dijabetesa. Smanjenje dijabetičkog sindroma počinje odmah nakon ubrizgavanja, a maksimum doseže nakon dva sata – i traje oko 12 sati.” Zaključio je: “Ovo otkriće, koje baca novo svjetlo na patogenezu dijabetesa, daje nam i ključ za liječenje ovog sindroma.” Paulescu je 1921. objavio svoje podatke u dva izvanredna francuska časopisa i to osam mjeseci prije prve publikacije Bantinga i Besta u veljači 1922. Jasno je da je inzulin otkriven u Europi. Zaključak: Paulescu je smatrao da je novootkriveni hormon, nazvan pancrein, ključni element u liječenju dijabetesa, ali njegovo izvanredno istraživanje nepravedno je zanemareno

Eukaryotic genomes may exhibit up to 10 generic classes of gene promoters

Abstract Background The main function of gene promoters appears to be the integration of different gene products in their biological pathways in order to maintain homeostasis. Generally, promoters have been classified in two major classes, namely TATA and CpG. Nevertheless, many genes using the same combinatorial formation of transcription factors have different gene expression patterns. Accordingly, we tried to ask ourselves some fundamental questions: Why certain genes have an overall predisposition for higher gene expression levels than others? What causes such a predisposition? Is there a structural relationship of these sequences in different tissues? Is there a strong phylogenetic relationship between promoters of closely related species? Results In order to gain valuable insights into different promoter regions, we obtained a series of image-based patterns which allowed us to identify 10 generic classes of promoters. A comprehensive analysis was undertaken for promoter sequences from Arabidopsis thaliana, Drosophila melanogaster, Homo sapiens and Oryza sativa, and a more extensive analysis of tissue-specific promoters in humans. We observed a clear preference for these species to use certain classes of promoters for specific biological processes. Moreover, in humans, we found that different tissues use distinct classes of promoters, reflecting an emerging promoter network. Depending on the tissue type, comparisons made between these classes of promoters reveal a complementarity between their patterns whereas some other classes of promoters have been observed to occur in competition. Furthermore, we also noticed the existence of some transitional states between these classes of promoters that may explain certain evolutionary mechanisms, which suggest a possible predisposition for specific levels of gene expression and perhaps for a different number of factors responsible for triggering gene expression. Our conclusions are based on comprehensive data from three different databases and a new computer model whose core is using Kappa index of coincidence. Conclusions To fully understand the connections between gene promoters and gene expression, we analyzed thousands of promoter sequences using our Kappa Index of Coincidence method and a specialized Optical Character Recognition (OCR) neural network. Under our criteria, 10 classes of promoters were detected. In addition, the existence of “transitional” promoters suggests that there is an evolutionary weighted continuum between classes, depending perhaps upon changes in their gene products.</p

Gene promoters show chromosome-specificity and reveal chromosome territories in humans

BACKGROUND: Gene promoters have guided evolution processes for millions of years. It seems that they were the main engine responsible for the integration of different mutations favorable for the environmental conditions. In cooperation with different transcription factors and other biochemical components, these regulatory regions dictate the synthesis frequency of RNA molecules. Predominantly in the last decade, it has become clear that nuclear organization impacts upon gene regulation. To fully understand the connections between Homo sapiens chromosomes and their gene promoters, we analyzed 1200 promoter sequences using our Kappa Index of Coincidence method. RESULTS: In order to measure the structural similarity of gene promoters, we used two-dimensional image-based patterns obtained through Kappa Index of Coincidence (Kappa IC) and (C+G)% values. The center of weight of each promoter pattern indicated a structure similarity between promoters of each chromosome. Furthermore, the proximity of chromosomes seems to be in accordance to the structural similarity of their gene promoters. The arrangement of chromosomes according to Kappa IC values of promoters, shows a striking symmetry between the chromosome length and the structure of promoters located on them. High Kappa IC and (C+G)% values of gene promoters were also directly associated with the most frequent genetic diseases. Taking into consideration these observations, a general hypothesis for the evolutionary dynamics of the genome has been proposed. In this hypothesis, heterochromatin and euchromatin domains exchange DNA sequences according to a difference in the rate of Slipped Strand Mispairing and point mutations. CONCLUSIONS: In this paper we showed that gene promoters appear to be specific to each chromosome. Furthermore, the proximity between chromosomes seems to be in accordance to the structural similarity of their gene promoters. Our findings are based on comprehensive data from Transcriptional Regulatory Element Database and a new computer model whose core is using Kappa index of coincidence

Maps of electrical activity in diabetic patients and normal individuals

Here, data related to the electrical activity of the human skin are presented in detail. The 3D electrical activity maps in normal and diabetic individuals are shown and described using raw data obtained with Photon-Pixel coupling. Average electrical activity matrices are shown by subject, gender and group. Distributions of the electrical activity data are shown in connection with the ventral and dorsal side of the human torso. For a better understanding of the electrical activity data, critical parameters of the individuals that participated in the study are also presented

Competing risk analysis of site-specific cancer mortality for glargine exposure.

a<p>Although not shown here, the model also included age at first insulin prescription (FIP), gender, time between screening and FIP, treatment intensity level and all other available oral or insulin categories as both cumulative exposure and time-dependent ever exposed terms (see Methods).</p>b<p>SHR, subhazard ratios, similar to hazard ratios from the classic Cox regression.</p>c<p>Significant result rounded up to <0.05 due to very low estimated SHR.</p

Characteristics of ever and never glargine users.

a<p>Percent within ever and never users, respectively.</p><p>OGLD oral glucose lowering drugs,TIL treatment intensity level (see Methods), FIP first insulin prescription.</p>NS<p>not significant, *p<0.05, **p<0.01, ***p<0.001 vs. ever glargine users.</p

Cancer deaths cumulative incidence functions.

<p>Green line, females exposed to glargine; brown line, females unexposed to glargine; blue lines, males exposed to glargine; red line, males unexposed to glargine.</p

Negative association between paraoxonase 2, anthropometric markers and metabolic syndrome

Background Metabolic syndrome (MS) has a great impact on cardiovascular mortality and morbidity. Our aim was to investigate the association of MS with some oxidant and antioxidant markers, including pro-and antioxidant status of peripheral blood mononuclear cells (PBMC) in newly diagnosed type 2 diabetic mellitus patients (ND-T2D). Methods 219 ND-T2D and 88 healthy subjects were divided in two groups according to the absence or presence of MS. Anthropometric measurements, routine blood tests, total oxidant status (TOS), total antioxidant status (TAS) and ELISA measurements were included. The PBMC capacity to release free radicals and to neutralize them was also determined by measuring the respiratory burst (RB) together with the lactonase activity of the intracellular antioxidant enzyme paraoxonase 2 (PON2). Results Comparing ND-T2D MS+ with those MS- the RB of the PBMC was significantly higher (p<0.05) while lactonase PON2 enzymatic activity was decreased (p < 0.001). A negative correlation of RB was found with TAS (r = -0.416, p < 0.05). PON2 was also negatively correlated with glycaemia (r = -0.275, p < 0.001), HbA1c (r = -0.308, p < 0.001), weight (r = -0.183; p < 0.05), waist circumference (r = -0.353, p < 0.001) and body mass index (r = -0.290, p < 0.001). Conclusion PON2 lactonase activity is negatively associated with anthropometric markers in ND-T2D with MS

PATIENT EDUCATION: PREVENTING DIABETIC FOOT INFECTIONS

Diabetic foot infections are a common complication in people with diabetes. This article will discuss the foot-related complications that can happen in people with diabetes, as well as guidelines for good foot care. Patient education is a central component in the self management of diabetes infections in both prevention and treatment. Poor knowledge of foot care practices is an important risk factor for foot problems among diabetics. Studies have demonstrated deficiencies in knowledge and practices regarding foot care, particularly among rural populations with diabetes. Patients should be informed about the risk factors and their complications that could lead to amputation. The mainstay therapy for intervention of diabetic lower limb complications is prevention

Low frequency of HLA DRB1*03 - DQB1*02 and DQB1*0302 haplotypes in Romania is consistent with the country's low incidence of Type I diabetes

Aims/hypothesis. Our study aimed to determine the association of HLA class II HLA-DQB1 alleles with Type I (insulin-dependent) diabetes mellitus and the frequencies of these alleles in the Romanian population, which has one of the lowest incidences of Type I diabetes in children aged 0-14 years in Europe at 3-4 cases per 100 000 person-years. Methods. We used the sequence specific primer-polymerase chain reaction (PCR-SSP) technique to type HLA-DQB1 alleles, the HLA-DRB1 alleles DRB1*03 and one single nucleotide polymorphism (SNP) in the insulin gene (INS). We studied 204 Type I diabetic Romanian families, 196 of which were simplex with 70.3 % of subjects diagnosed under 14 years of age. Data was analysed using a modified version of the Transmission Disequilibrium Test, the Transmission Disequilibrium Test itself, and the affected family-based control method. Results. We found, as expected, the strong positive DQB1*02-DRB1*03 and DQB1*0302, and negative DQB1*0602, HLA class II allele associations with Type I diabetes in these Romanian families. However, using the affected family-based control method, we found relatively low population frequencies of DQB1*02-DRB1*03 and DQB1*0302 alleles in Romania (15.8%) compared with Sardinia (31.3%), a high incidence European region (35 cases per 100 000 person-years in children aged 0-14 years). The INS locus had a strong effect in this data set with 80.5 % transmission of the susceptible INS allele from parents to affected siblings (relative risk = 4.1). Conclusion/interpretation. Part of the explanation for the low incidence of Type I diabetes in Romania could be the lower frequency of the DRB1*03 - DQB1*02 and DQB1*0302 susceptibility haplotypes in this country