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World Journal of Nuclear Medicine Jun 2024The biodistribution of gallium-68-dotatate (Ga-68-dotatate) and standardized uptake values (SUVs) using non-time-of-flight (TOF) positron emission...
The biodistribution of gallium-68-dotatate (Ga-68-dotatate) and standardized uptake values (SUVs) using non-time-of-flight (TOF) positron emission tomography/computed tomography (PET/CT) cameras is well established. However, with the eventual retirement of older PET cameras and their replacement with newer, highly sensitive TOF PET/CT cameras, where SUV measurements are reportedly higher, updated knowledge of normal SUV range is needed and, to our knowledge, not previously reported. Our objectives are as follows: To establish normal Ga-68-dotatate TOF SUV database for common structures and to aid the visual detection of abnormalities objectively. To compare SUV values using the TOF and non-TOF algorithms. Fifty consecutive patients referred routinely to our nuclear medicine service (20 men, 30 women; median age 55 years) with presumed neuroendocrine tumors underwent Ga-68-dotatate scans on a PET-CT camera having capability of reconstructing both TOF/non-TOF images. Region of interests (ROIs) were drawn around 24 normal structures as well as the primary lesion with abnormal radiotracer uptake and SUV was measured. The same ROI was analyzed using both algorithms simultaneously and both TOF and non-TOF SUV values were compared. Twelve hundred ROIs were evaluated. Non-TOF Ga-68-dotatate uptake in normal structures was in alignment with previously published studies. As compared to non-TOF, TOF images had better target to background ratios visually. TOF SUV was higher for all structures except for lung and brain. TOF SUV was more than double in adrenals/uncinate process of the pancreas; approximately 1.8 times in abnormal lesions, lymph nodes, pineal gland; and greater than 1.5 times in thyroid, breast, and pancreatic head. Normal database of Ga-68-dotatate TOF SUV is provided for common structures to aid visual detection of abnormalities objectively. Overall, TOF SUV measures higher in identical ROIs, with abnormal lesions measuring approximately 1.8 times higher versus non-TOF technology. These findings need to be taken in consideration when comparing patient scans imaged on different PET/CT technologies.
PubMed: 38933071
DOI: 10.1055/s-0044-1786529 -
Journal of Diabetes and Metabolic... Jun 2024This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence... (Review)
Review
OBJECTIVE
This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence specific genes in various cell types, including those involved in diabetes complications.
SIGNIFICANCE
Diabetes, a prevalent and severe condition, poses life-threatening risks due to elevated blood glucose levels. It results from inadequate insulin production by the pancreas or ineffective insulin utilization by the body. Recent research suggests siRNA could hold promise in addressing diabetes complications.
METHODS
In this review, we discussed several subjects, including diabetes; its function, and common treatment options. An in-depth analysis of gene silencing method for siRNA and role of siRNA in diabetes, focusing on its impact on glucose homeostasis, diabetic retinopathy, wound healing, diabetic nephropathy and peripheral neuropathy, diabetic foot ulcers, diabetic atherosclerosis, and diabetic cardiomyopathy.
RESULT
siRNA-based treatment has the potential to target specific genes without disrupting several other endogenous pathways, which decreases the risk of off-target effects. In addition, siRNA has the capability to provide long-term efficacy with a single dose which will reduce treatment options and enhance patient compliance.
CONCLUSION
In the context of diabetic complications, siRNA has been explored as a potential therapeutic tool to modulate the expression of genes involved in various processes associated with diabetes-related issues such as Diabetic Retinopathy, Neuropathy, Nephropathy, wound healing. The use of siRNA in these contexts is still largely experimental, and challenges such as delivery to specific tissues, potential off-target effects, and long-term safety need to be addressed. Additionally, the development of siRNA-based therapies for clinical use in diabetic complications is an active area of research.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01405-7.
PubMed: 38932822
DOI: 10.1007/s40200-024-01405-7 -
Journal of Diabetes and Metabolic... Jun 2024Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at...
Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial.
PURPOSE
Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group.
METHODS
A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7-25 years with T1D, a current HbA ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes.
CONCLUSION
This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden.
TRIAL REGISTRATION
This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452).
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01397-4.
PubMed: 38932805
DOI: 10.1007/s40200-024-01397-4 -
Journal of Medical Virology Jun 2024Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth...
Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long-term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also investigated the distribution, viral clearance, and pathology during the long-term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis-like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long-term infection.
Topics: Animals; Macaca mulatta; Hand, Foot and Mouth Disease; Disease Models, Animal; Viral Tropism; Viral Load; Enterovirus B, Human; Antibodies, Viral; Antibodies, Neutralizing; Animals, Newborn; Cytokines
PubMed: 38932451
DOI: 10.1002/jmv.29707 -
The American Journal of Case Reports Jun 2024BACKGROUND When people in their 60s experiences abdominal pain, vomiting, and unexplained weight loss without a history of abdominal surgery, the usual diagnosis is...
BACKGROUND When people in their 60s experiences abdominal pain, vomiting, and unexplained weight loss without a history of abdominal surgery, the usual diagnosis is obstruction caused by a neoplastic mass. Nevertheless, in exceptionally rare cases, these symptoms arise from complications linked to a visceral artery aneurysm. CASE REPORT We present a case of a 60-year-old man with immunodeficiency and Sneddon-Wilkinson disease (a rare subcorneal pustular dermatosis), who developed a pancreaticoduodenal aneurysm of uncertain origin, associated with pancreatic mass, retroperitoneal hematoma, and duodenal obstruction. The treatment approach included transcatheter arterial coil embolization with supportive measures such as parenteral nutrition, a nasogastric tube, octreotide administration, and antiemetics. Despite these interventions, persistence gastrointestinal symptoms prompted an endoscopic ultrasound fine-needle aspiration to rule out malignancy. The biopsy confirmed localized fibro-inflammation. Although he was initially considered for a gastro-jejunal bypass, conservative management effectively improved the pancreatic lesion and duodenal obstruction, leading to discontinuation of parenteral nutrition. The patient was able to resume a regular diet 4 weeks after embolization. CONCLUSIONS Pancreaticoduodenal artery aneurysm is a rare visceral aneurysm with multiple etiologies and potentially fatal consequences. We report an unusual case of a pancreaticoduodenal artery aneurysm associated with pancreatic mass and duodenal obstruction. This diagnosis warrants consideration when an immunodeficient patient presents symptoms of abdominal pain and vomiting. Early endovascular embolization, combined with conservative approaches, effectively alleviated the symptoms in our patient.
Topics: Humans; Male; Middle Aged; Aneurysm, False; Pancreas; Duodenal Obstruction; Duodenum; Embolization, Therapeutic
PubMed: 38932438
DOI: 10.12659/AJCR.943879 -
Viruses Jun 2024The study involved five ferrets from one household in Poland, comprising three sick 9-week-old juveniles, their healthy mother, and another clinically normal adult,...
The study involved five ferrets from one household in Poland, comprising three sick 9-week-old juveniles, their healthy mother, and another clinically normal adult, admitted to the veterinary clinic in June 2023. The juvenile ferrets displayed significant lethargy and a pronounced unwillingness to move with accompanying pulmonary distress. Prompted by concurrent outbreaks of A/H5N1 influenza virus infections in Polish cats, point-of-care tests were conducted that revealed type A influenza antigens in the throat swabs of all five ferrets. Despite treatment, one juvenile ferret exhibited dyspnea and neurological symptoms and eventually died. The two remaining ferrets recovered fully, including one severely affected showing persistent dyspnea and incoordination without fever that recovered after 11 days of treatment. In the RT-qPCR, the throat swabs collected from all surviving ferrets as well as the samples of lungs, trachea, heart, brain, pancreas, liver, and intestine of the succumbed ferret were found positive for A/H5N1 virus RNA. To our best knowledge, this is the first documented natural A/H5N1 avian influenza in domestic ferrets kept as pets. In addition, this outbreak suggests the possibility of asymptomatic A/H5N1 virus shedding by ferrets, highlighting their zoonotic potential and the advisability of excluding fresh or frozen poultry from their diet to reduce the A/H5N1 virus transmission risks.
Topics: Animals; Ferrets; Influenza A Virus, H5N1 Subtype; Orthomyxoviridae Infections; Pets; Female; Male; Poland; Disease Outbreaks; Virus Shedding; Cats
PubMed: 38932223
DOI: 10.3390/v16060931 -
Pharmaceutics May 2024Glucagon-like peptide-1 (GLP-1) is a multifunctional incretin hormone with various physiological effects beyond its well-characterized effect of stimulating... (Review)
Review
Glucagon-like peptide-1 (GLP-1) is a multifunctional incretin hormone with various physiological effects beyond its well-characterized effect of stimulating glucose-dependent insulin secretion in the pancreas. An emerging role for GLP-1 and its receptor, GLP-1R, in brain neuroprotection and in the suppression of inflammation, has been documented in recent years. GLP-1R is a G protein-coupled receptor (GPCR) that couples to Gs proteins that stimulate the production of the second messenger cyclic 3',5'-adenosine monophosphate (cAMP). cAMP, acting through its two main effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac), exerts several anti-inflammatory (and some pro-inflammatory) effects in cells, depending on the cell type. The present review discusses the cAMP-dependent molecular signaling pathways elicited by the GLP-1R in cardiomyocytes, cardiac fibroblasts, central neurons, and even in adrenal chromaffin cells, with a particular focus on those that lead to anti-inflammatory effects by the GLP-1R. Fully elucidating the role cAMP plays in GLP-1R's anti-inflammatory properties can lead to new and more precise targets for drug development and/or provide the foundation for novel therapeutic combinations of the GLP-1R agonist medications currently on the market with other classes of drugs for additive anti-inflammatory effect.
PubMed: 38931817
DOI: 10.3390/pharmaceutics16060693 -
Pharmaceuticals (Basel, Switzerland) May 2024Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high...
Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[F]fluoroethyl)-L-tryptophan (L-[F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[F]FETrp had a comparable tumor uptake with [⁸F]fluorodeoxyglucose (FDG). However, L-[F]FETrp showed a significantly higher tumor-to-brain ratio than FDG ( = 4, < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan-kynurenine pathway as a therapeutic target for treating NF1.
PubMed: 38931352
DOI: 10.3390/ph17060685 -
Nutrients Jun 2024Zinc deficiency has been associated with the worsening of diabetes while zinc supplementation has been proposed to ameliorate diabetes. This study examined the effects...
Zinc deficiency has been associated with the worsening of diabetes while zinc supplementation has been proposed to ameliorate diabetes. This study examined the effects of marginal zinc deficiency (MZD) and zinc supplementation (ZS) on obesity, glycemic control, pancreatic islets, hepatic steatosis and renal function of Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed an MZD, zinc control (ZC) or ZS diet (4, 30 and 300 mg Zn/kg diet, respectively), and lean Zucker rats were fed a ZC diet for 8 weeks. MZD and ZS did not alter body weight or whole-body composition in ZDF rats. MZD ZDF rats had reduced zinc concentrations in the femur and pancreas, a greater number of enlarged pancreatic islets and a diminished response to an oral glucose load based on a 1.8-fold greater incremental area-under-the-curve (AUC) for glucose compared to ZC ZDF. ZS ZDF rats had elevated serum, femur and pancreatic zinc concentrations, unchanged pancreatic parameters and a 50% reduction in the AUC for insulin compared to ZC ZDF rats, suggesting greater insulin sensitivity. Dietary zinc intake did not alter hepatic steatosis, creatinine clearance, or levels of proteins that contribute to insulin signaling, inflammation or zinc transport in epididymal fat. Potential adverse effects of ZS were suggested by reduced hepatic copper concentrations and elevated serum urea compared to ZC ZDF rats. In summary, ZS improved the pancreatic insulin response but not the glucose handling. In contrast, reduced zinc status in ZDF rats led to impaired glucose tolerance and a compensatory increase in the number and size of pancreatic islets which could lead to β-cell exhaustion.
Topics: Animals; Rats, Zucker; Zinc; Dietary Supplements; Male; Insulin; Islets of Langerhans; Rats; Blood Glucose; Obesity; Insulin Resistance; Pancreas; Liver; Diabetes Mellitus, Experimental
PubMed: 38931174
DOI: 10.3390/nu16121819 -
Simultaneous Pancreas and Kidney Transplantation from Donors after Circulatory Death in Switzerland.Journal of Clinical Medicine Jun 2024Simultaneous pancreas and kidney transplantation (SPK) remains the only curative treatment for type I diabetics with end-stage kidney disease. SPK using donors after...
Simultaneous pancreas and kidney transplantation (SPK) remains the only curative treatment for type I diabetics with end-stage kidney disease. SPK using donors after circulatory death (DCD) is one important measure to expand the organ pool for pancreas transplantation (PT). After initial doubts due to higher complications, DCD SPK is now considered safe and equivalent to donation after brain death in terms of survival and graft function. We assessed pancreas and kidney graft function, as well as complications of the first three patients who underwent a DCD SPK in Switzerland. Two transplantations were after rapid procurement, one following normothermic regional perfusion (NRP). Intra- and postoperative courses were uneventful and without major complications in all patients. In the two SPK after rapid procurement, pancreas graft function was excellent, with 100% insulin-free survival, and hemoglobin A1C dropped from 7.9 and 7.5 before SPK and to 5.1 and 4.3 after three years, respectively. Kidney graft function was excellent in the first year, followed by a gradual decline due to recurrent infections. The patient, after NRP SPK, experienced short-term delayed pancreatic graft function requiring low-dose insulin treatment for 5 days post-transplant, most likely due to increased peripheral insulin resistance in obesity. During follow-up, there was persistent euglycemia and excellent kidney function. We report on the first series of DCD SPK ever performed in Switzerland. Results were promising, with low complication rates and sustained graft survival. With almost half of all donors in Switzerland currently being DCD, we see great potential for the expansion of DCD PT.
PubMed: 38930054
DOI: 10.3390/jcm13123525