In late 1986, several vials of Humulin N (NPH human insulin, recombinant DNA origin) came to our attention because of a clumped, white coating on the inside of the vials. To determine the frequency ...of this phenomenon, we surveyed 100 consecutive patients who used Humulin N. Ten patients had encountered 21 vials of flocculated insulin in the previous 12 mo, reflecting an incidence of 1 per 72 vials. Insulin drawn from affected vials was markedly reduced in potency: 20.9 +/- 3.4 U/ml vs. the labeled potency of 100 U/ml. Several patients reporting flocculated insulin, including one hospitalized with ketoacidosis, experienced unusual and unexplained elevation in blood glucose concentration for several days before flocculation was observed. Patients who use NPH human insulin should be aware of this phenomenon and carefully inspect their vials for evidence of insulin precipitation before each injection.
The influence of extracellular potassium concentration on adrenal sensitivity to angiotensin II and ACTH was studied in isolated canine adrenal glomerulosa cells. When potassium was absent from the ...incubation medium, the aldosterone response to angiotensin II or ACTH was completely abolished. At physiologic angiotensin II concentrations (2.5 x 10(-11) M), aldosterone formation increased 4-fold when potassium concentration was increased from 2.5 to 5.0 mM, and rose 6-fold as potassium was increased from 2.5 to 7.5 mM. In the absence of angiotensin II, the same changes in potassium concentration increased aldosterone production only to 2-fold and 3.5-fold, respectively. The effect of potassium concentration upon the aldosterone response to ACTH was similar but less marked. The concentration and binding affinity of angiotensin II receptor sites in glomerulosa cells were not changed by increasing potassium concentrations from 0 to 7.5 mM. These observations demonstrate that the aldosterone response to the glomerulosa cell to angiotensin II is potassium-dependent within the physiological range for each of these stimuli. Such an interaction suggests that the in vivo effect of potassium upon aldosterone secretion includes a significant modulating action upon adrenal sensitivity to angiotensin II, as well as a direct action of potassium upon the adrenal glomerulosa cell.
Flocculated humulin N insulin Benson, E A; Webster, B; Becker, N ...
The New England journal of medicine,
1987-Apr-16, Letnik:
316, Številka:
16
Journal Article
Exacerbation of a variety of symptoms during the menstrual cycle is a well-described phenomenon. The exact causes of these changes are poorly understood, and no specific and efficacious therapy has ...been described. We successfully treated a patient with severe catamenial insulin reactions with a long-acting gonadotropin releasing hormone agonist to suppress menstrual function and added a combination of estrogen and progestin to offset any adverse effect of the resultant hypoestrogenemia for 1 year.
The complete repertoire of endothelial functions elicited by FGD5, a guanine nucleotide exchange factor activating the Rho GTPase Cdc42, has yet to be elucidated. Here we explore FGD5's importance ...during vascular endothelial growth factor A (VEGFA) signaling via VEGF receptor 2 (VEGFR2) in human endothelial cells. In microvascular endothelial cells, FGD5 is located at the inner surface of the cell membrane as well as at the outer surface of EEA1-positive endosomes carrying VEGFR2. The latter finding prompted us to explore if FGD5 regulates VEGFR2 dynamics. We found that depletion of FGD5 in microvascular cells inhibited their migration towards a stable VEGFA gradient. Furthermore, depletion of FGD5 resulted in accelerated VEGFR2 degradation, which was reverted by lactacystin-mediated proteasomal inhibition. Our results thus suggest a mechanism whereby FGD5 sustains VEGFA signaling and endothelial cell chemotaxis via inhibition of proteasome-dependent VEGFR2 degradation.
•FGD5 co-localizes with VEGFR2 in early endosomes.•FGD5 silencing inhibits VEGFA-induced chemotaxis.•VEGFR2 signaling is impaired in response to FGD5 silencing.•FGD5 silencing promotes VEGFR2 proteasomal degradation.
Heparan sulfate (HS) proteoglycans, present at the plasma membrane of vascular endothelial cells, bind to the angiogenic growth factor VEGFA to modulate its signaling through VEGFR2. The interactions ...between VEGFA and proteoglycan co-receptors require sulfated domains in the HS chains. To date, it is essentially unknown how the formation of sulfated protein-binding domains in HS can be regulated by microRNAs. In the present study, we show that microRNA-24 (miR-24) targets NDST1 to reduce HS sulfation and thereby the binding affinity of HS for VEGFA. Elevated levels of miR-24 also resulted in reduced levels of VEGFR2 and blunted VEGFA signaling. Similarly, suppression of NDST1 using siRNA led to a reduction in VEGFR2 expression. Consequently, not only VEGFA binding, but also VEGFR2 protein expression is dependent on NDST1 function. Furthermore, overexpression of miR-24, or siRNA-mediated reduction of NDST1, reduced endothelial cell chemotaxis in response to VEGFA. These findings establish NDST1 as a target of miR-24 and demonstrate how such NDST1 suppression in endothelial cells results in reduced responsiveness to VEGFA.
Background: Heparan sulfate proteoglycan (HSPG) co-receptors modulate VEGFA signaling.
Results: MicroRNA-24 targets NDST1 to reduce HS sulfation and HS affinity for VEGFA, suppressing VEGFA signaling and endothelial cell migration.
Conclusion: MicroRNAs targeting HS biosynthesis can regulate VEGFA-induced chemotaxis, essential during angiogenesis.
Significance: HSPG-dependent signaling of pathophysiological importance can be targeted via microRNA interference with HS biosynthesis.
The resilient modulus of a soil is an important parameter needed for pavement design. However, this parameter experiences post-compaction seasonal changes during the service life of the pavement as a ...result of wetting or drying of the soil during dry or rainy periods. Variations in the resilient modulus should be introduced into pavement design methodologies. Research literature shows resilient modulus results from other countries; however, the information is scarce for Mexican soils. In this paper, the authors show results of a research carried out in the laboratory to evaluate a model for the prediction of the effect of wetting and drying on the resilient modulus of soils classified as clays, silt, and sand. Several samples were prepared at optimum conditions using the Proctor standard test. Some specimens were then dried by allowing a loss of water through evaporation while others were allowed to gain water through capillarity (assumed to simulate post-compaction conditions). After the samples were conditioned to new water contents, resilient modulus tests were performed following the NCHRP 1-28A protocol. The results show that the resilient modulus can be predicted using a model which is a function of the deviator stress and confining pressure (i.e., (sd/s3) and the variation of water content from optimum water content conditions (i.e., the condition after field compaction). The R2 results when using the proposed resilient modulus model was 84.1%.
The authors present a series of compaction curves obtained in fine-grained soilsthrough use of a gyratory compactor. The effect on compaction curves of variables such as vertical pressure, angle of ...gyration, and speed of gyrationis shown. The curves obtained with the gyratory compactor were compared with those obtained using traditional methods of compaction (Proctor standard and modified compaction). It was observedthat the standard compaction curve can be obtained with 200 gyrations, 1.25 degrees of angle of gyration, and a vertical pressure of 200 kPa.On the other hand, with the combination of variables studied in this research, modified compaction curvescould not be reached. Tests were also performed to measure resilient modulus and unconfined compression strength onspecimens prepared at optimum compaction conditions, 2% below the optimum and 2% above the optimum (for Proctor standard tests) using two methodsof compaction.The results indicate that unconfined compressionstrengths and resilient modulus are related to the compaction method when samples are compacted at water content below optimum.
AbstractThe authors present a series of compaction curves obtained in fine-grained soils through use of a gyratory compactor. The effect on compaction curves of variables such as vertical pressure, ...angle of gyration, and speed of gyration is shown. The curves obtained with the gyratory compactor were compared with those obtained using traditional methods of compaction (Proctor standard and modified compaction). It was observed that the standard compaction curve can be obtained with 200 gyrations, 1.25 degrees of angle of gyration, and a vertical pressure of 200 kPa. On the other hand, with the combination of variables studied in this research, modified compaction curves could not be reached. Tests were also performed to measure resilient modulus and unconfined compression strength on specimens prepared at optimum compaction conditions, 2% below the optimum and 2% above the optimum (for Proctor standard tests) using two methodsofcompaction.The results indicate that unconfined compression strengths and resilient modulus are related to the compaction method when samples are compacted at water content below optimum.
AbstractThe resilient modulus of a soil is an important parameter needed for pavement design. However, this parameter experiences post-compaction seasonal changes during the service life of the ...pavement as a result of wetting or drying of the soil during dry or rainy periods. Variations in the resilient modulus should be introduced into pavement design methodologies. Research literature shows resilient modulus results from other countries; however, the information is scarce for Mexican soils. In this paper, the authors show results of a research carried out in the laboratory to evaluate a model for the prediction of the effect of wetting and drying on the resilient modulus of soils classified as clays, silt, and sand. Several samples were prepared at optimum conditions using the Proctor standard test. Some specimens were then dried by allowing a loss of water through evaporation while others were allowed to gain water through capillarity (assumed to simulate post-compaction conditions). After the samples were conditioned to new water contents, resilient modulus tests were performed following the NCHRP 1-28A protocol. The results show that the resilient modulus can be predicted using a model which is a function of the deviator stress and confining pressure (i.e., (σd/σ3)) and the variation of water content from optimum water content conditions (i.e., the condition after field compaction). The R2 between predicted and measured results was 84.1%.
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