Screening for Gastric Sensory Motor Abnormalities in Pediatric Patients With Type 1 Diabetes

ObjectiveTo determine the frequency of gastric sensory motor symptoms in youth with type 1 diabetes.MethodsA prospective cross-sectional study was performed to evaluate symptoms of delayed gastric emptying in participants with type 1 diabetes, aged 12 to 25 years, using the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire. In addition, a 5-year (January 2015 to December 2019), a retrospective study was completed on all gastric emptying scans performed in youth at our institution.ResultsA total of 359 participants (mean age, 17.7 ± 3.33 years) with type 1 diabetes completed the GCSI questionnaire. Compared with nonresponders, responders were more likely to be non-Hispanic White (90% vs 86%; P =.003) and female patients (58% vs 44%; P <.0001), with a lower HbA1c (8.1 ± 1.8 vs 9.0 ± 2.1; P <.0001). At least 1 gastrointestinal symptom was reported in 270 (75%) of responders, of which nausea was the most common (71%). A GCSI score of ≥1.9 suggestive of more severe gastrointestinal symptoms was reported in 17% of responders. Participants with scores ≥1.9 were older (19.1 ± 3.0 vs 17.8 ± 3.3 years; P =.01). In the retrospective study, 778 underwent gastric emptying scan, 29 participants had type 1 diabetes and 11 (38%) showed delayed gastric emptying.ConclusionGastrointestinal symptoms related to gastric sensory motor abnormalities are seen in youth and young adults with type 1 diabetes. In particular, for those with higher GCSI scores, earlier recognition and referral may be warranted.     

Personalized Medical Treatment of Patients With Acromegaly: A Review

Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone normalization as well as tumor shrinkage, the treatment goals include relieving symptoms, managing complications, and improving patients’ quality of life. Surgical resection is a first-line treatment option for most patients, with few being pretreated preoperatively with medications. Somatostatin receptor ligands (SRLs), injectable and, more recently, oral capsules, have been the cornerstone of first-line medical therapy for persistent disease. However, several factors, including sparsely granulated adenomas, absent or low somatostatin receptor status, T2-hyperintensity imaging, young age, and aryl hydrocarbon receptor-interacting protein mutations, can predict first-generation SRL resistance. Patients with these characteristics may be better candidates for the growth hormone receptor antagonist pegvisomant, or in cases of large tumors, the second-generation SRL pasireotide. Combination therapy should be further pursued in patients who remain biochemically uncontrolled or have a high remnant tumor after monotherapy. An efficacious and cost-effective pegvisomant dose-sparing effect of SRLs when used in combination has been demonstrated. With such a wide array of medical treatment options, it is becoming increasingly important to tailor treatment to patients’ unique characteristics and preferences, with a goal of personalizing management to achieve high-quality outcomes.     

Binge-Eating Disorder and Type 2 Diabetes: A Review

ObjectiveTo familiarize health care providers with diagnosis and treatment of binge-eating disorder (BED), a common comorbidity of type 2 diabetes (T2DM).MethodsLiterature review of binge eating and T2DM. Key words used in search include BED, T2DM, obesity, and treatment.ResultsThe prevalence of BED in patients with T2DM appears to be much higher than the 2% to 3.5% prevalence seen in the general population. Studies suggest that up to 20% of patients with T2DM have an underlying eating disorder, the most common of which is binge eating. BED is probably underdiagnosed, even though there are multiple simple tools that providers can use to improve screening for the disorder. Though the relationship between BED and hemoglobin A1c control can vary, it appears that binge-eating behaviors can worsen metabolic markers, including glycemic control. Various medications used by patients with diabetes have been associated with new-onset BED, and treatment may be as simple as removing or replacing such agents. Several medications have been found to significantly reduce binge-eating frequency, and potentially, weight. Patients with BED generally benefit from psychotherapy, including cognitive behavioral therapy.ConclusionBED, only recently added to the International Classification of Disease-10 diagnostic list, is very common in patients with obesity and T2DM. The diagnosis is important to establish, as treatment or referral for treatment, could potentially improve many of the comorbidities and metrics of T2DM.     

Genetic investigations and pedigree analysis in captive barbary sheep (Ammotragus lervia pallas 1777)

The electrophoretic variation of blood proteins (hemoglobin, transferrin, adenylatekinase, and phosphoglucomutase) was studied in a population of 21 barbary sheep (Ammotragus lervia) living at Frankfurt Zoological Gardens. A polymorphism in hemoglobin was sufficient for pedigree analysis in most cases. It could be demonstrated that one female Barbary sheep cared for a lamb that genetically was not its own descendant. “Mismothering” has also been reported from domestic sheep. We suggest this to be critical when basing pedigree assumptions for stud-book purposes merely on behavioral evidence. Biochemical pedigree control is recommended for the genetic management of endangered social caprines during bottleneck phases of population recovery.     

Cloning of chicken globin cDNA in bacterial plasmids

Chicken globin cDNA was prepared from mRNA isolated from phenylhydrazine-treated chicken reticulocytes, and cloned into the tetracycline-resistance gene of plasmid pMB9. Restriction enzyme analysis indicates that there are at least two classes of clones isolated. Nucleotide sequence data have shown that these classes corresponded to the chicken α- and β-globin genes.     

Potential of isoquercitrin as antisickling agent: a multi-spectroscopic,thermophoresis and molecular modeling approach

Abstract

Sickle cell disease is an inherited disease caused by point mutation in hemoglobin (β-globin gene). Under oxygen saturation, sickle hemoglobin form polymers, leading to rigid erythrocytes. The transition of the blood vessels is altered and initiated by the adhesion of erythrocytes, neutrophils and endothelial cells. Sickle Hemoglobin (HbS) polymerization is a major cause in red blood cells (RBC), promoting sickling and destruction of RBCs. Isoquercitrin, a medicinal bioactive compound found in various medicinal plants, has multiple health benefits. The present study examines the potential of isoquercitrin as an anti-sickle agent, showing a significant decrease in the rate of polymerization as well as sickling of RBCs. Isoquercitrin-induced graded alteration in absorbance and fluorescence of HbS, confirmed their interaction. A negative value of ΔG° strongly suggests that it is a spontaneous exothermic reaction induced by entropy. Negative ΔH° and positive ΔS° predicted that hydrogen and hydrophobic binding forces interfered with a hydrophobic microenvironment of β6Val leading to polymerization inhibition of HbS. HbS-Isoquercitrin complex exhibits helical structural changes leading to destabilization of the HbS polymer as confirmed by CD spectroscopy. MST and DSC results indicate greater changes in thermophoretic mobility and thermal stability of sickle hemoglobin in the presence of isoquercitrin, respectively. These findings were also supported by molecular simulation studies using DOCK6 and GROMACS. Hence, we can conclude that isoquercitrin interacts with HbS through hydrogen bonding, which leads to polymerization inhibition. Consequently, isoquercitrin could potentially be used as a medication for the treatment of sickle cell disease.

Communicated by Ramaswamy H. Sarma     

Complete nucleotide sequence of a chicken α-globin cDNA

The entire sequence of a 541 bp insert in recombinant plasmid pHb1003 has been determined. This plasmid, which was shown to carry a cloned cDNA copy of the chicken α-globin mRNA, contains the complete structural gene as well as 19 bp of the 5'-untranslated region and 99 bp of the 3'-untranslated region. This sequence may encode a non-adult α-globin gene, especially since the cDNA clones were generated from phenylhydrazine-induced, globin-specific mRNA extracted from anemic white leghorns. The possibility that this α-globin might represent a stress globin is considered.     

Hemoglobin autofluorescence as potential long-term glycemic marker in the rat animal model

Diabetes is a serious disease whose patients often require long-term care. Blood glucose and intermediate glycation product of glycated hemoglobin (HbA1c) are, at best, surrogate biomarkers of disease progression. There is indication that advanced glycation end products (AGEs) better reflect diabetic risks. In this study, we explored the use of red blood cells (RBCs) and lysed hemoglobin (Hb) autofluorescence (AF) as potential biomarkers of diabetic complication. AF spectra measured under 370 nm excitation reveals that both RBC and Hb fluorescence in the 420 to 600 nm region. At early time points following diabetic induction in rats, AF increase in lysed Hb is more dramatic compared to that of RBCs. Moreover, we found significance variance of Hb autofluorescence despite relatively constant HbA1c levels. Furthermore, we found that although a correlation exists between AGE autofluorescence and HbA1c levels, the lack of complete correspondence suggests that the rate of AGE production differs significantly among different rats. Our results suggest that with additional development, both RBC and Hb autofluorescence from lysed RBCs may be used act long-term glycemic markers for diabetic complications in patients.      

Molecular dynamics simulations indicate that deoxyhemoglobin,oxyhemoglobin, carboxyhemoglobin,and glycated hemoglobin under compression and shear exhibit an anisotropic mechanical behavior

We developed a new mechanical model for determining the compression and shear mechanical behavior of four different hemoglobin structures. Previous studies on hemoglobin structures have focused primarily on overall mechanical behavior; however, this study investigates the mechanical behavior of hemoglobin, a major constituent of red blood cells, using steered molecular dynamics (SMD) simulations to obtain anisotropic mechanical behavior under compression and shear loading conditions. Four different configurations of hemoglobin molecules were considered: deoxyhemoglobin (deoxyHb), oxyhemoglobin (HbO₂), carboxyhemoglobin (HbCO), and glycated hemoglobin (HbA_1C). The SMD simulations were performed on the hemoglobin variants to estimate their unidirectional stiffness and shear stiffness. Although hemoglobin is structurally denoted as a globular protein due to its spherical shape and secondary structure, our simulation results show a significant variation in the mechanical strength in different directions (anisotropy) and also a strength variation among the four different hemoglobin configurations studied. The glycated hemoglobin molecule possesses an overall higher compressive mechanical stiffness and shear stiffness when compared to deoxyhemoglobin, oxyhemoglobin, and carboxyhemoglobin molecules. Further results from the models indicate that the hemoglobin structures studied possess a soft outer shell and a stiff core based on stiffness.