Can rodent models of diabetic kidney disease clarify the significance of early hyperfiltration?: recognizing clinical and experimental uncertainties

2007 ◽  
Vol 114 (2) ◽  
pp. 109-118 ◽  
Author(s):  
David Z. Levine
Keyword(s):  
Filtration Rate ◽  
Diabetic Kidney Disease ◽  
Basic Research ◽  
Experimental Models ◽  
Rodent Models ◽  
The Past ◽  
Single Nephron

In the past, hyperfiltration and increased glomerular capillary pressure have been identified as important determinants of the development of DN (diabetic nephropathy). Recently, some basic research and clinical reviews on DN have omitted identifying hyperfiltration as an important risk factor. At the same time, different rodent models of DN have been described without and with documented hyperfiltration. In the present review, the importance of hyperfiltration is reassessed, reviewing key clinical and research studies, including the first single nephron studies in a mouse model of DN. From clinical studies of Type 1 and Type 2 diabetes mellitus, it is clear that many patients do not have early hyperfiltration and, even when present, its contribution to subsequent DN remains uncertain. Key mechanisms underlying hyperfiltration in rodent models are reviewed. Findings on intrarenal NO metabolism and the control of single-nephron GFR (glomerular filtration rate) in rodent models of DN are also presented. Characterization of valid experimental models of DN should include a careful delineation of the absence or presence of early hyperfiltration, with special efforts made to establish the specific role hyperfiltration may play in the emergence of DN.

scholarly journals Challenge of diabetes mellitus and researchers’ contributions to its control

2021 ◽  
Vol 19 (1) ◽  
pp. 614-634
Author(s):  
Ayodele T. Odularu ◽  
Peter A. Ajibade
Keyword(s):  
Diabetes Mellitus ◽  
Medical Records ◽  
Diabetes Type ◽  
Future Studies ◽  
The Past ◽  
Significant Events ◽  
Review Study ◽  
Type 3

Abstract The aim of this review study was to assess the past significant events on diabetes mellitus, transformations that took place over the years in the medical records of treatment, countries involved, and the researchers who brought about the revolutions. This study used the content analysis to report the existence of diabetes mellitus and the treatments provided by researchers to control it. The focus was mainly on three main types of diabetes (type 1, type 2, and type 3 diabetes). Ethical consideration has also helped to boost diabetic studies globally. The research has a history path from pharmaceuticals of organic-based drugs to metal-based drugs with their nanoparticles in addition to the impacts of nanomedicine, biosensors, and telemedicine. Ongoing and future studies in alternative medicine such as vanadium nanoparticles (metal nanoparticles) are promising.

scholarly journals Imaginary Worlds: The Status of Simulation Modeling in Claims for Cost-Effectiveness In Diabetes Mellitus

2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Paul C Langley ◽  
Taeho Greg Rhee
Keyword(s):  
Diabetes Mellitus ◽  
Cost Effectiveness ◽  
Simulation Modeling ◽  
Decision Makers ◽  
The Past ◽  
The Status ◽  
The Impact

Over the past 20 years a number of simulations or models have been developed as a basis for tracking and evaluating the impact of pharmacological and other interventions in type 1 and type 2 diabetes mellitus. These models have typically tracked the natural course of these diseases generating long-term composite claims for cost-effectiveness. These claims can extend over the lifetime of the modeled patient cohort. Set against the standards of normal science, however, these claims lack credibility. The claims presented are all too often either immune to failure or are presented in a form that is non-testable. As such they fail to meet the key experimental requirements of falsification and replication. Unfortunately, there is a continuing belief that long-term or lifetime models are essential to decision-making. This is misplaced. The purpose of this review is to argue that there is a pressing need to reconsider the needs of health system decision makers and focus on modeled or simulated claims that are meaningful, testable, reportable and replicable in evaluating interventions in diabetes mellitus.   Type: Commentary

Characterization of damage and biotic factors associated with the decline of Eucalyptus wandoo in southwest Western Australia

2005 ◽  
Vol 35 (11) ◽  
pp. 2589-2602 ◽  
Author(s):  
Ryan J Hooper ◽  
K Sivasithamparam
Keyword(s):  
Western Australia ◽  
Partial Harvest ◽  
Foliage Density ◽  
Density Ratios ◽  
The Relationship ◽  
Mixed Age ◽  
Eucalyptus Wandoo

Crown decline of wandoo, Eucalyptus wandoo, in southwest Western Australia has escalated over the last 10 years, so very few unaffected stands remain. To assess the canopy-damage characteristics of trees in decline a destructive, partial-harvest method was used to sample branches in natural mixed-age stands. Necrosis of common cankers was closely associated with type-1 borer damage, characterized by "longitudinal" gallery structure on declining trees only. Cankers were found to be consistently more severe on declining trees, with decay regions affecting a greater proportion of sapwood tissue. Several infestations causing type-1 borer damage that varied in age were found on declining branches, providing evidence of cyclical damage events. Type-2 borer damage characterized by "ring-barking" gallery structure caused extensive damage in canopies, but was not always associated with decline. Interactions between foliage density and canker score showed that 17.8% and 63.1% of the variability in foliage-density ratios was accounted for in declining intermediate-health and unhealthy classes, respectively. The relationship was negligible for the healthy class (9.9%), providing strong evidence that cankers are causing foliage loss in declining canopies. Evidence suggests that an interaction between type-1 borer infestations and decay-causing fungi is responsible for the decline in E. wandoo wandoo canopies.

Diabetic Retinopathy In Patients With Type 2 Diabetes: Aspects Of Early Diagnosis, Treatment And Prediction Of The Outcome Of The Disease

2021 ◽  
Vol 03 (07) ◽  
pp. 53-65
Author(s):  
Fazilat Arifovna Bakhritdinova ◽  
◽  
Urmanova Firuza Makhkamovna ◽  
Nabiyeva Iroda Fayzullayevna ◽  
◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Hong Kong ◽  
Early Diagnosis ◽  
Research Group ◽  
Black Population ◽  
The Past ◽  
Number Of Patients

In this review, the authors performed an overview of the literature on early diagnosis, treatment and methods for predicting the outcomes of the disease. According to regional endocrinological dispensaries, for 2020 registered SD for RUZ 277 926., Of these, type 1 type 18178, SD 2 type 259,748 patients. At the same time, the number of patients with DR was 2020 g of 83,632 persons, of which 73690 persons with di type 2. The real number of patients exceeds a registered 10 times, over the past 18 years, the number of patients with a rope in Uzbekistan increased by 2.4 times (according to the Ministry of Health of RUZ). The prevalence of others among patients of the CD is 10-90%, according to some specialists, up to 97-98.5%. For example, the frequency of development dr in India is lower than among Europeans and Americans, and among the black population more frequent than among the white. According to the WHO research group, it was revealed that the highest frequency of DR was detected in Oklahoma (76.4%), Zagreb (73.1%) and Hong Kong (58.1%). The lowest frequency was observed in Tokyo (29.7%). The prevalence of DR in patients in China amounted to 47.4%, and the frequency of DR in Poland was 31.4%.

scholarly journals The Blue Copper-Containing Nitrite Reductase fromAlcaligenes xylosoxidans: Cloning of the nirAGene and Characterization of the Recombinant Enzyme

1999 ◽  
Vol 181 (8) ◽  
pp. 2323-2329 ◽  
Author(s):  
Miguel Prudêncio ◽  
Robert R. Eady ◽  
Gary Sawers
Keyword(s):  
Amino Acid ◽  
Nitrite Reductase ◽  
Recombinant Enzyme ◽  
Leader Peptide ◽  
Resonance Spectroscopy ◽  
Gene Encoding ◽  
Blue Copper

ABSTRACT The nirA gene encoding the blue dissimilatory nitrite reductase from Alcaligenes xylosoxidans has been cloned and sequenced. To our knowledge, this is the first report of the characterization of a gene encoding a blue copper-containing nitrite reductase. The deduced amino acid sequence exhibits a high degree of similarity to other copper-containing nitrite reductases from various bacterial sources. The full-length protein included a 24-amino-acid leader peptide. The nirA gene was overexpressed inEscherichia coli and was shown to be exported to the periplasm. Purification was achieved in a single step, and analysis of the recombinant Nir enzyme revealed that cleavage of the signal peptide occurred at a position identical to that for the native enzyme isolated from A. xylosoxidans. The recombinant Nir isolated directly was blue and trimeric and, on the basis of electron paramagnetic resonance spectroscopy and metal analysis, possessed only type 1 copper centers. This type 2-depleted enzyme preparation also had a low nitrite reductase enzyme activity. Incubation of the periplasmic fraction with copper sulfate prior to purification resulted in the isolation of an enzyme with a full complement of type 1 and type 2 copper centers and a high specific activity. The kinetic properties of the recombinant enzyme were indistinguishable from those of the native nitrite reductase isolated from A. xylosoxidans. This rapid isolation procedure will greatly facilitate genetic and biochemical characterization of both wild-type and mutant derivatives of this protein.

scholarly journals Genetic Risk Scores for Diabetes Diagnosis and Precision Medicine

2019 ◽  
Vol 40 (6) ◽  
pp. 1500-1520 ◽  
Author(s):  
Miriam S Udler ◽  
Mark I McCarthy ◽  
Jose C Florez ◽  
Anubha Mahajan
Keyword(s):  
Risk Scores ◽  
Diabetes Diagnosis ◽  
Physiological Mechanisms ◽  
Risk Variants ◽  
Polygenic Scores ◽  
Disease Predisposition ◽  
Dna Sequence Variants

Abstract During the last decade, there have been substantial advances in the identification and characterization of DNA sequence variants associated with individual predisposition to type 1 and type 2 diabetes. As well as providing insights into the molecular, cellular, and physiological mechanisms involved in disease pathogenesis, these risk variants, when combined into a polygenic score, capture information on individual patterns of disease predisposition that have the potential to influence clinical management. In this review, we describe the various opportunities that polygenic scores provide: to predict diabetes risk, to support differential diagnosis, and to understand phenotypic and clinical heterogeneity. We also describe the challenges that will need to be overcome if this potential is to be fully realized.

scholarly journals Detection and Partial Characterization of Simian Immunodeficiency Virus SIVsm Strains from Bush Meat Samples from Rural Sierra Leone

2005 ◽  
Vol 79 (4) ◽  
pp. 2631-2636 ◽  
Author(s):  
Cristian Apetrei ◽  
Michael J. Metzger ◽  
David Richardson ◽  
Binhua Ling ◽  
Paul T. Telfer ◽  
...  
Keyword(s):  
Sierra Leone ◽  
Phylogenetic Trees ◽  
The Past ◽  
Immunodeficiency Virus ◽  
Bush Meat ◽  
Cercocebus Atys ◽  
Meat Samples ◽  
The Relationship

ABSTRACT Human immunodeficiency virus type 2 (HIV-2) originated from simian immunodeficiency viruses (SIVs) that naturally infect sooty mangabeys (SMs; Cercocebus atys). In order to further investigate the relationship between HIV-2 and SIVsm, the SIV specific to the SM, we characterized seven new SIVsm strains from SMs sold in Sierra Leone markets as bush meat. The gag, pol, and env sequences showed that, while the viruses of all seven SMs belonged to the SIVsm-HIV-2 lineage, they were highly divergent viruses, in spite of the fact that most of the samples originated from the same geographical region. They clustered in three lineages, two of which have been previously reported. Two of the new SIVsm strains clustered differently in gag and env phylogenetic trees, suggesting SIVsm recombination that had occurred in the past. In spite of the fact that our study doubles the number of known SIVsm strains from wild SMs, none of the simian strains were close to the groups in which HIV-2 was epidemic (groups A and B).

scholarly journals Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

2020 ◽  
Vol 21 (20) ◽  
pp. 7693
Author(s):  
Dhanush Haspula ◽  
Michelle A. Clark
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Inflammatory Diseases ◽  
Endocannabinoid System ◽  
Future Directions ◽  
The Past ◽  
Health And Disease ◽  
Made In

The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

The TUDID Study – Background and Design of a Prospective Cohort

2020 ◽  
Author(s):  
Benjamin Assad Jaghutriz ◽  
Robert Wagner ◽  
Stephanie Kullmann ◽  
Louise Fritsche ◽  
Sabine S. Eckstein ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Laboratory Tests ◽  
Diabetes Complications ◽  
Treatment Options ◽  
University Hospital ◽  
Tailored Treatment ◽  
The Individual

AbstractPrevalence of both type 1 and type 2 diabetes mellitus is growing worldwide and one major cause for morbidity and mortality. However, not every patient develops diabetes-related complications, but causes for the individual susceptibility are still not fully understood. As a platform to address this, we initiated the TUDID (TUebingen DIabetes Database) study, a prospective, monocentric, observational study that includes adults with diabetes mellitus who are treated in the inpatient clinic of a University Hospital in southern Germany. Besides a thorough clinical examination and extensive laboratory tests (with integrated biobanking), major study focuses are the kidneys, the eyes, the vasculature as well as cognition and mood where standardized investigations for early stages for diabetes complications are performed. Analyses of the data generated by this precise characterization of diabetes-related complications will contribute to our understanding of the development and course of such complications, and thus facilitate the implementation of tailored treatment options that can reduce the risk and severity of diabetes-related complications.

scholarly journals Characterization of cDNAs encoding isoforms of hamster 3 beta-hydroxysteroid dehydrogenase/delta 5-->4 isomerase

1998 ◽  
Vol 20 (1) ◽  
pp. 99-110 ◽  
Author(s):  
FM Rogerson ◽  
J Courtemanche ◽  
A Fleury ◽  
JG LeHoux ◽  
JI Mason ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Cdna Libraries ◽  
Sexually Dimorphic ◽  
High Affinity ◽  
Liver And Kidney ◽  
Low Levels ◽  
Type 3

Western blot analyses of various hamster tissues reveal high levels of expression of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in adrenal and liver, and moderate levels of expression in kidney. The expression in liver is sexually dimorphic; very high levels of protein are observed in adult male liver but very low levels are seen in the female liver. Three distinct cDNAs encoding isoforms of 3 beta-HSD were isolated from hamster cDNA libraries. The type 1 isoform is a high-affinity dehydrogenase/isomerase expressed in adrenal and male kidney. The type 2 isoform is also a high-affinity dehydrogenase/isomerase expressed in kidney and male liver. The type 3 enzyme is a 3-ketosteroid reductase expressed predominantly in kidney. Sequencing of the clones showed that all three are structurally very similar, although types 1 and 2 share the greatest degree of similarity. Immunohistochemical staining for 3 beta-HSD in the adrenal was found throughout the adrenal cortex. In the kidney staining was confined to tubules, and in the liver, heavy staining was found in hepatocytes. The cloning of cDNAs for 3 beta-HSD from the liver and kidney should help in elucidating the function of this enzyme in these tissues.

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