7-(5-Methyl­sulfanyl-β-d-erythrofuran­osyl)-7H-pyrrolo­[2,3-d]pyrimidin-4-amine monohydrate (MT-tubercidin·H2O)

The title compound, C12H16N4O3S·H2O, which has potential as a possible anti­malarial drug, was studied when small deviations in melting points, for two differently aged preparations, were observed. The unexpected existence of a water mol­ecule of crystallization is considered to be the cause of this variation. The 7H-pyrrolo­[2,3-d]pyrimidine unit is very slightly puckered with a total puckering amplitude of 0.035 (2) Å; its mean plane makes an angle of 88.40 (12)° with the mean plane through the ribofuranosyl unit. In the crystal, the mol­ecules are bound by strong O—H⋯N and N—H⋯O hydrogen bonds, utilizing all available protons and linking mainly through the water of crystallization

An expanded cavity hexaamine cage for copper(II)

The crystal structure of the bicyclic hexaamine complex [Cu(fac-Me-5-tricosane-N-6)](ClO4)(2) center dot H2O (fac-Me-5-tricosane-N-6 = facial-1,5,9,13,20-pentamethyl-3,7,11,15,18,22-hexaazabicyclo[7.7.7] tricosane) at 100 K defines an apparently tetragonally compressed octahedral geometry, which is attributed to a combination of dynamic interconversion and static disorder between two tetragonally elongated structures sharing a common short axis. This structure is fluxional at 60 K and above as shown by EPR spectroscopy. Aqueous cyclic voltammetry reveals that a remarkably stable Cu-I form of the complex is stabilised by the encapsulating nature of the expanded cage ligand

1,3-Bis(2-meth­oxy­phen­yl)thio­urea

In the title compound, C15H16N2O2S, the N–C(=S) bond lengths are indicative of the presence of amide-type resonance. The dihedral angles between the thio­urea unit and the attached aromatic rings are 59.80 (5) and 73.41 (4)° while the dihedral angle between the rings is 56.83 (4)°. In the crystal, inversion dimers linked by pairs of N—H⋯S hydrogen bonds occur. An N—H⋯π inter­action is observed for the second amino group. The shortest centroid–centroid distance between two aromatic systems is 4.0958 (8) Å

Treatment of gastroparesis: a multidisciplinary clinical review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75594/1/j.1365-2982.2006.00760.x.pd

Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity

BackgroundAutonomic dysfunction can be present in patients with idiopathic and diabetic gastroparesis. The role of autonomic dysfunction relating to gastric emptying and upper gastrointestinal symptoms in patients with gastroparesis and chronic unexplained nausea and vomiting (CUNV) remains unclear. The aim of our study is to evaluate autonomic function in patients with gastroparesis and CUNV with respect to etiology, gastric emptying and symptom severity.MethodsWe studied 242 patients with chronic gastroparetic symptoms recruited at eight centers. All patients had a gastric emptying scintigraphy within 6 months of the study. Symptom severity was assessed using the gastroparesis cardinal symptom index. Autonomic function testing was performed at baseline enrollment using the ANX 3.0 autonomic monitoring system which measures heart rate variability and respiratory activity measurements.Key ResultsLow sympathetic response to challenge (Valsalva or standing) was the most common abnormality seen impacting 89% diabetic and 74% idiopathic patients. Diabetics compared to idiopathics, exhibited greater global hypofunction with sympathetic (OR = 4.7, 95% CI 2.2‐10.3; P < .001) and parasympathetic (OR = 7.2, 95% CI 3.4‐15.0; P < .001) dysfunction. Patients with delayed gastric emptying were more likely to have paradoxic parasympathetic excessive during sympathetic challenge [(Valsalva or standing) 40% vs. 26%, P = .05]. Patients with more severe symptoms exhibited greater parasympathetic dysfunction compared to those with mild‐moderate symptoms: resting sympathovagal balance [LFa/RFa 1.8 (1.0‐3.1) vs. 1.2 (0.6‐2.3), P = .006)] and standing parasympathetic activity [0.4 (0.1‐0.8) vs. 0.6 (0.2‐1.7); P = .03].ConclusionsAutonomic dysfunction was common in patients with gastroparesis and CUNV. Parasympathetic dysfunction was associated with delayed gastric emptying and more severe upper gastrointestinal symptoms. Conversely, sympathetic hypofunction was associated with milder symptoms.InferencesGastroparesis and CUNV may be a manifestation of GI autonomic dysfunction or imbalance, such that sympathetic dysfunction occurs early on in the manifestation of chronic upper GI symptoms, while parasympathetic dysfunction results in more severe symptoms and delayed gastric emptying.Sympathetic withdrawal (low sympathetic activity in response to a sympathetic challenge) was the most common autonomic abnormality found among all patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156243/2/nmo13810_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156243/1/nmo13810.pd

Satiety testing in diabetic gastroparesis: Effects of insulin pump therapy with continuous glucose monitoring on upper gastrointestinal symptoms and gastric myoelectrical activity

BackgroundSymptoms induced by caloric or nonâ caloric satiety test meals and gastric myoelectrical activity (GMA) have not been studied in patients with diabetic gastroparesis (DGP) before and after intense glucose management.AimsWe determined the effects of continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM) on GI symptoms, volume consumed, and GMA induced by the caloric meal satiety test (CMST) and water load satiety test (WLST) in DGP.MethodsFortyâ five patients with DGP underwent CMST and WLST at baseline and 24 weeks after CSII with CGM. Subjects ingested the test meals until they were completely full. Visual analog scales were used to quantify preâ and postmeal symptoms, and GMA was recorded with cutaneous electrodes and analyzed visually and by computer.Key ResultsAt baseline and 24â week visits, nausea, bloating, abdominal discomfort, and fullness were immediately increased after CMST and WLST (Ps < 0.01). The meal volumes ingested were significantly less than normal controls at both visits in almost oneâ third of the subjects. After the CMST, the percentage 3 cycle per minute GMA increased and bradygastria decreased compared with WLST (Ps < 0.05). After treatment for 24 weeks meal volumes ingested, postmeal symptoms and GMA were no different than baseline.Conclusions and inferences(a) Satiety test meals elicited symptoms of nausea, bloating, and abdominal discomfort; (b) CMST stimulated more symptoms and changes in GMA than WLST; and (c) CSII with CGM for 24 weeks did not improve symptoms, volumes ingested, or GMA elicited by the two satiety test meals in these patients with diabetic GP. Satiety tests in diabetic gastropresis are useful to study acute postprandial symptoms and GMA, but these measures were not improved by intensive insulin therapy.Water load and caloric load satiety tests immediately increase symptoms associated with gastroparesis. Normal 3 cpm gastric myoelctrical activity increased more after caloric load than water load tests. After 24 weeks of insulin therapy there were no differences in volumes ingested, symptoms or gastric myooelectrical activity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152474/1/nmo13720_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152474/2/nmo13720.pd

Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis

Abstract Background Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are still unclear. Methods Diabetic gastroparetics, diabetic non-gastroparetic controls, idiopathic gastroparetics and non-diabetic non-gastroparetic controls underwent full-thickness gastric body biopsies. Deep RNA sequencing was performed and pathway analysis of differentially expressed transcripts was done using Ingenuity®. A subset of differentially expressed genes in diabetic gastroparesis was validated in a separate cohort using QT-PCR. Results 111 genes were differentially expressed in diabetic gastroparesis and 181 in idiopathic gastroparesis with a log2fold difference of | ≥ 2| and false detection rate (FDR) < 5%. Top canonical pathways in diabetic gastroparesis included genes involved with macrophages, fibroblasts and endothelial cells in rheumatoid arthritis, osteoarthritis pathway and differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F. Top canonical pathways in idiopathic gastroparesis included genes involved in granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Sixty-five differentially expressed genes (log2fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonical pathways associated with immune signaling. 4/5 highly differentially expressed genes (SGK1, APOLD1, CXCR4, CXCL2, and FOS) in diabetic gastroparesis were validated in a separate cohort of patients using RT-PCR. Immune profile analysis revealed that genes associated with M1 (pro inflammatory) macrophages were enriched in tissues from idiopathic gastroparesis tissues compared to controls (p < 0.05). Conclusions Diabetic and idiopathic gastroparesis have both unique and overlapping transcriptomic signatures. Innate immune signaling likely plays a central role in pathogenesis of human gastroparesis.https://deepblue.lib.umich.edu/bitstream/2027.42/145193/1/12920_2018_Article_379.pd

Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis

Abstract Background Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are still unclear. Methods Diabetic gastroparetics, diabetic non-gastroparetic controls, idiopathic gastroparetics and non-diabetic non-gastroparetic controls underwent full-thickness gastric body biopsies. Deep RNA sequencing was performed and pathway analysis of differentially expressed transcripts was done using Ingenuity®. A subset of differentially expressed genes in diabetic gastroparesis was validated in a separate cohort using QT-PCR. Results 111 genes were differentially expressed in diabetic gastroparesis and 181 in idiopathic gastroparesis with a log2fold difference of | ≥ 2| and false detection rate (FDR) < 5%. Top canonical pathways in diabetic gastroparesis included genes involved with macrophages, fibroblasts and endothelial cells in rheumatoid arthritis, osteoarthritis pathway and differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F. Top canonical pathways in idiopathic gastroparesis included genes involved in granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Sixty-five differentially expressed genes (log2fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonical pathways associated with immune signaling. 4/5 highly differentially expressed genes (SGK1, APOLD1, CXCR4, CXCL2, and FOS) in diabetic gastroparesis were validated in a separate cohort of patients using RT-PCR. Immune profile analysis revealed that genes associated with M1 (pro inflammatory) macrophages were enriched in tissues from idiopathic gastroparesis tissues compared to controls (p < 0.05). Conclusions Diabetic and idiopathic gastroparesis have both unique and overlapping transcriptomic signatures. Innate immune signaling likely plays a central role in pathogenesis of human gastroparesis.https://deepblue.lib.umich.edu/bitstream/2027.42/145193/1/12920_2018_Article_379.pd