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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In focal segmental glomerulosclerosis (FSGS), a biphasic change in glomerular size is described in which glomeruli are enlarged with early glomerulosclerosis. Hyperperfusion of larger glomeruli is believed to contribute to progressive glomerular injury. This study was undertaken to investigate whether similar alterations in glomerular size can be found in other renal diseases. Volumes of sclerotic and nonsclerotic glomeruli were estimated in renal biopsy specimens using the Weibel and Gomez method (1962). Glomerulosclerosis was graded on individual glomeruli from 0 to 4, with 0 as no sclerosis and 4 as 76% to 100% sclerosis. Primary and secondary FSGS showed a biphasic change in which grade 2 glomeruli were 50% larger than grade 0 glomeruli and grades 3 and 4 glomeruli were solidified and smaller than grade 0 glomeruli. In essential hypertension, no increase in glomerular size was seen with early glomerulosclerosis, and the latter stages consisted of ischemic obsolescence in which collapsed tufts were 50% smaller than solidified glomeruli of FSGS. Grade 0 glomeruli of membranous glomerulonephritis (MGN) were significantly larger than grade 0 glomeruli of FSGS, and no significant difference in size was seen between grades 0 and 2 glomerulosclerosis. Solidified diabetic glomeruli maintained a large size with grades 3 and 4 sclerosis. Glomeruloscleroses of FSGS, hypertension, MGN, and diabetes have stereologically distinct features. A biphasic change in glomerular size is characteristic of primary and secondary FSGS, but not hypertension, in which tuft collapse supports reduced rather than increased perfusion in the pathogenesis of its glomerular obsolescence.
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PMID:Glomerular size and glomerulosclerosis: relationships to disease categories, glomerular solidification, and ischemic obsolescence. 1192 Mar 32

Tracheomalacia is a condition of the neonatal and infant airway, characterized by weakness of the supporting tracheal cartilage and widening of the posterior membranous wall. Together, these factors cause tracheal collapse, especially during times of increased airflow. The diagnosis of major airway collapse depends upon an accurate history combined with proper endoscopic evaluation. Tracheomalacia can be caused by a diffuse process of congenital origin or by a localized abnormality. The cases of acquired tracheomalacia occur with increasing frequency both in children and adults and are often not clearly recognized. These lesions may result from indwelling tracheostomy and endobronchial tube, chest trauma, chronic tracheobronchitis, inflammation (relapsing polychondritis), secondary to pulmonary resection, tracheal malignancy (cylindroma), and idiopathically. We present the case of a 59 years old male with acquired tracheobronchomalacia, associated with tracheopatia osteochondroplasica, secondary to COPD and a chronic parenchimal infection, on a diabetes mellitus type II background.
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PMID:[Tracheomalacia and secondary tracheopatia osteocondroplasica - a case report]. 1197 2

Alginate-polylysine-alginate capsules containing insulin-producing cells have been used as a bio-artificial pancreas in the treatment of diabetes mellitus. In a search for microcapsules with improved diffusion characteristics, a high voltage system was developed that produces 250,000 beads/min with a diameter of 160 microm +/- 3-5%. The diameter of the beads could be varied between 160-700 microm depending on the needle diameter and construction, the voltage, the distance between the electrodes and the flow of alginate solution. Ca-alginate beads with diameters of 200 and 500 microm were produced by the high voltage electrostatic system. The 200 microm beads were sensitive to poly-L-lysine (PLL) exposure and had to be washed in ion-free solution to avoid collapse. The 200 microm beads swelled more than the 500 microm beads in the washing and PLL treatment. Also, the porosity of the capsules changed with size, but capsules impermeable to tumour necrosis factor (TNF) could be made by exchanging PLL with poly-D-lysine (PDL) for the 500 microm beads. The 200 microm beads were impermeable to IgG after PLL exposure. Islets of Langerhans were encapsulated in alginate-PLL-alginate capsules and evaluated by measuring protruding islets and insulin production. Islets in microcapsules made by the high voltage electrostatic system did not function differently from islets in larger microcapsules made by an air jet system. In conclusion, alginate capsules made by a high voltage electrostatic system enable large-scale production of small capsules with a narrow size distribution that can meet the functional properties of larger capsules by small changes in the encapsulation procedure.
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PMID:Alginate-polylysine-alginate microcapsules: effect of size reduction on capsule properties. 1243 4

Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that is activated primarily by DNA damage. Upon activation, the enzyme hydrolyzes NAD(+) to nicotinamide and transfers ADP ribose units to a variety of nuclear proteins, including histones and PARP-1 itself. This process is important in facilitating DNA repair. However, excessive activation of PARP-1 can lead to significant decrements in NAD(+), and ATP depletion, and cell death (suicide hypothesis). In response to cellular damage by oxygen radicals or excitotoxicity, a rapid and strong activation of PARP-1 occurs in neurons. Excessive PARP-1 activation is implicated in a variety of insults, including cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes. The use of PARP inhibitors has, therefore, been proposed as a protective therapy in decreasing excitotoxic neuronal cell death, as well as ischemic and other tissue damage. Excitotoxic brain lesions initially result in the primary destruction of brain parenchyma and subsequently in secondary damage of neighboring neurons hours after the insult. This secondary damage of initially surviving neurons accounts for most of the volume of the infarcted area and the loss of brain function after a stroke. One major component of secondary neuronal damage is the migration of macrophages and microglial cells toward the sites of injury, where they produce large quantities of toxic cytokines and oxygen radicals. Recent evidence indicates that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may, therefore, be a promising strategy in protecting neurons from this secondary damage, as well. Studies demonstrating an important role for PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death. The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs is discussed with relation to nuclear factor kappaB and p53.
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PMID:Poly(ADP-Ribose) polymerase-1 in acute neuronal death and inflammation: a strategy for neuroprotection. 1285 16

Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity. Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death. The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation. Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes. The secondary damage of initially surviving neurons in brain stroke accounts for most of the volume of the infarcted area and the subsequent loss of brain function. Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well. As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death. PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.
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PMID:Poly(ADP-ribosyl)ation enzyme-1 as a target for neuroprotection in acute central nervous system injury. 1452 60

Troponins are highly sensitive and specific biochemical markers of myocardial injury that are released into the circulation during myocardial ischemia. We describe changes in cardiac troponin I (cTnI) prior to and following clinical evidence of severe myocardial dysfunction in a child with hemolytic uremic syndrome (HUS). A previously healthy, 22-month-old girl presented with typical HUS and stool cultures positive for Escherichia coli O157:H7. She required dialysis, blood and platelet transfusions, and insulin for HUS-related diabetes mellitus. On the 6th hospital day she had sudden circulatory collapse with a blood pressure of 70/40 mmHg and an oxygen saturation of 88%. She responded rapidly to emergency resuscitation but had diminished left ventricular function (ejection fraction 18%). Four days after the acute event an echocardiogram showed normal ventricular size and contractility. She underwent hemodialysis for 22 days, and renal function was normal after 33 days. cTnI levels were measured with a microparticle enzyme immunoassay. cTnI was normal (>0.4 microg/l) 32 h prior to cardiac collapse, mildly increased (2.1 microg/l) 8 h before the cardiac collapse, severely elevated shortly after the cardiac event (43.1 microg/l), and peaked (140.6 microg/l) at 24 h. It then fell gradually and was normal at discharge. These results suggest that measurement of cTnI may be a useful predictor of cardiac involvement in severely affected children with HUS.
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PMID:Troponin I levels in a hemolytic uremic syndrome patient with severe cardiac failure. 1468 41

Prostaglandin D(2) (PGD(2)) and its metabolites bind to the intracellular PPARs to regulate vasoactive substances involved in vascular remodeling through regulation of mRNAs transcription as well as through receptor-mediated mechanisms. PGD(2) decreases inducible NO, PAI-1, endothelin, and VCAM expression through inhibition to NF kappa B, STAT, or AP-1 transcription factors, which are regulated by cytokines/immune system. Moreover, transfer of L-PGDS (PGD(2) synthase) into the intracellular space of EC or SMC increases intracellular PGD(2), thereby decreasing these substances. PGD(2) attenuates in vivo organ injury mediated by cytokines and the immune system. The pretreatment with PGD(2) attenuates the liver damage and hemodynamic collapse following LPS. Dahl salt-sensitive rats, with decreased PGD(2) in the outer medulla of the kidney, are prone to hypertensive kidney injury. Serum L-PGDS level is increased in renal dysfunction through a decrease in glomerular filtration. L-PGDS in urine may be derived from a failure of tubular reabsorption or from in situ synthesis. Urinary L-PGDS excretion markedly increases in the early stage of kidney injury, and urinary L-PGDS is a useful predictor of the forthcoming renal injury. Indeed, urinary L-PGDS precedes clinically overt proteinuria or other parameters indicating renal dysfunction in hypertension, primary renal diseases, and diabetes in humans. PGD(2)/L-PGDS system is a Cinderella of vascular biology.
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PMID:[PGD(2)/L-PGDS system in hypertension and renal injury]. 1469 55

Mitochondria play a central role in cell life and cell death. An increasing number of studies place mitochondrial dysfunction at the heart of disease, most notably in the heart and the central nervous system. In this article, I review some of the key features of mitochondrial biology and focus on the pathways of mitochondrial calcium accumulation. Substantial evidence now suggests that the accumulation of calcium into mitochondria may play a key role as a trigger to mitochondrial pathology, especially when that calcium uptake is accompanied by another stressor, in particular nitrosative or oxidative stress. The major process involved is the opening of the mitochondrial permeability transition pore, a large conductance pore that causes a collapse of the mitochondrial membrane potential, leading to ATP depletion and necrotic cell death or to cytochrome c release and apoptosis, depending on the rate of ATP consumption. I discuss two models in particular in which these processes have been characterized. The first is a model of oxidative stress in cardiomyocytes, in which reperfusion after ischemia causes mitochondrial calcium overload, and oxidative stress. Recent experiments suggest that cardioprotection by hypoxic preconditioning or exposure to the ATP-dependent K(+) channel opener diazoxide increases mitochondrial resistance to oxidative injury. In a second model, of calcium overload in neurons, the neurotoxicity of glutamate depends on mitochondrial calcium uptake, but the toxicity to mitochondria also requires the generation of nitric oxide. Glutamate toxicity after activation of N-methyl-D-aspartate (NMDA) receptors results from the colocalization of NMDA receptors with neuronal nitric oxide synthase (nNOS). The calcium increase mediated by NMDA receptor activation is thus associated with nitric oxide generation, and the combination leads to the collapse of mitochondrial membrane potential followed by cell death.
Diabetes 2004 Feb
PMID:Roles of mitochondria in health and disease. 1474 73

Vaccinations protect to a high degree against infectious diseases, but may cause side effects. In the Netherlands since 1962 the adverse events following immunizations are registered and analysed by the National Institute of Health and Environment (RIVM). Since 1983 a permanent Committee of the Dutch Health Council reviews adverse events reported to the RIVM. With the so-called killed vaccines the side effects are mainly local (redness, swelling, pain) or general (fever, listlessness, irritability, sleep and eating problems). They are seen mainly after DPT-IPV vaccination against diphtheria, pertussis, tetanus and poliomyelitis. Some side effects occur rarely (collapse reactions, discoloured legs, persistent screaming and convulsions) and very rarely serious neurological events are reported. After MMR vaccination against measles, mumps and rubella, cases of arthritis, thrombocytopenia and ataxia are reported sporadically. Usually, they have a spontaneous recovery. During recent years a scala of diseases or symptoms have been associated with vaccination (presumed side effects). Careful and extensive investigations have shown that such hypotheses could not be supported. Examples are allergic diseases as asthma, diabetes mellitus, multiple sclerosis (after hepatitis B vaccination), autism and inflammatory bowel disease (after MMR vaccination) and sudden infant death syndrome. The total number of cases where at least a possible relation between side effects and vaccination is observed--apart from local reactions and moderate general symptoms--is very rare (about 0.25 per 1000 vaccinations) and does not balance the benefits from vaccination. There appears increasing doubt about the use and safety of vaccinations. More research is needed about the motives of people to choose for and against vaccination. The education about vaccination for parents and professionals who are involved with vaccination has to be improved. Internet can play an important role.
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PMID:[Childhood vaccinations anno 2004. II. The real and presumed side effects of vaccination]. 1503 89

A 29-year-old man developed diabetes mellitus in 1983 and diabetic nephropathy which gradually worsened from 1998. He was admitted to our hospital for initiation of peritoneal dialysis in May 2002. However, the efficiency of dialysis was not sufficient to improve elevated levels of blood urea nitrogen and serum creatinine. His body weight and cardiothoracic index by chest roentgenography gradually increased starting 9 days after admission. To improve the efficiency of dialysis, we tried to increase the dialysis fluid. Nevertheless, the efficiency of peritoneal dialysis remained low, and the patient complained of nausea 14 days after admission. Hypotension suddenly occurred 16 days after admission. Echocardiography showed massive pericardial effusion and collapse of the right ventricle. The diagnosis was cardiac tamponade. We performed cardiac centesis and pericardial drainage which revealed bloody pericardial effusion. Urgent hemodialysis was performed. The differential diagnosis of cardiac tamponade was established. After hemodialysis, the amount of pericardial effusion decreased, the gastro-intestinal symptoms disappeared, and the blood urea nitrogen and serum creatinine levels decreased. We speculated that the cause of cardiac tamponade was uremic pericarditis after ruling out infectious disease, collagen disease, malignant disease, and aortic dissection. Cardiac tamponade due to uremic pericarditis has become very rare since hemodialysis was developed.
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PMID:[Uremic pericarditis complicating cardiac tamponade: a case report]. 1563 26


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