Pancreatic betacell function deteriorates continuously in type 2 diabetes patients despite optimal treatment, which has been attributed to hyperglycemia itself via formation of excess reactive oxygen species. Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet betacell destruction can be manipulated by the administration of cytokines, especially Th2 cytokines. Restoration of self tolerance at certain time period may facilitate islet cell regeneration and may enable complete recovery from diabetes. To overcome short halflives of cytokines, we would like to deliver genes which enable cytokine production in the body. We also induced antiapoptotic molecules in betacells, the protective effect of which we screened systematically, applying new gene/peptide delivery strategies. In this study, the effect of peptide delivery using specific carriers was evaluated both in vitro and in vivo. In view of the immunoregulatory activity of Th2 cytokines, we investigated whether systemic or local cytokine gene therapy stops islet destructive autoimmunity and regenerates betacells of the pancreas in NOD mice. In addition, treatment of betacells with the antioxidant metallothionein resulted in a significant reduction in pathological changes and restored GSIS. Specific inhibition of NF-kappaB activation by retroviral transduction of dominant negative inhibitor of NF-kappaB also protected betacells. Therefore, these results suggest the protective influence of these gene/ peptide delivery as an adjunctive measure to clinical islet transplantation may enable us to improve the results of the cell-based treatment to overcome the battle against the debilitating disease of diabetes mellitus.
Animals ; Autoimmunity ; Cytokines ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Genetic Therapy ; Humans ; Hyperglycemia ; Islets of Langerhans ; Islets of Langerhans Transplantation ; Metallothionein ; Mice ; Mice, Inbred NOD ; NF-kappa B ; Pancreas ; Reactive Oxygen Species ; Regeneration ; Self Tolerance ; T-Lymphocytes ; Zidovudine

The chronic, mainly vascular complications of diabetes mellitus involve many organs and are responsible for the majority of morbidity and mortality associated with the disease. The vascular complications of diabetes are divided into microvascular and macrovascular complications. Although some macrovascular complications may precede the development of diabetes, they frequently co-associate and present together. The increasing prevalence of diabetes and its association with macrovascular disease have become serious public health concerns. Patients with diabetes who have underlying coronary artery diseases have a different, more complex pathophysiology and a worse prognosis. Optimal management of these patients requires a comprehensive multifactorial approach to prevent microvascular and macrovascular events. In the setting of an acute myocardial infarction (aMI), immediate management should focus on limiting the infarct size using fibrinolytic agents, primary percutaneous intervention, or glycoprotein IIb/IIIa inhibitors. Drug-eluting stents may have an important role in patients with diabetes, who have a higher rate of post-intervention coronary restenosis than in nondiabetic individuals. All patients with aMI should be given aspirin, nitrates, beta-blockers, and angiotensin-converting enzyme inhibitors. Lipid-lowering agents as well as glycemic control have been shown to be effective in decreasing long-term mortality. Despite advances in the management of the vascular complications, the mortality rates of patients with diabetes remain 1.5-to 2-fold greater than those of individuals without diabetes. Maximizing the use of lifesaving therapies proved effective, and a tight metabolic control can further decrease mortality rates. However, many of these lifesaving therapies are underused in patients with diabetes because of the misconception that potential adverse effects may outweigh their benefits. New programs aimed at improving post-infarction quality of care in patients with diabetes, based on guidelines and expert recommendations, have shown promising. However, more efforts should be devoted to the improvement of outcomes related to these public health problems.
Angiotensin-Converting Enzyme Inhibitors ; Aspirin ; Coronary Artery Disease ; Coronary Restenosis ; Diabetes Complications ; Diabetes Mellitus* ; Drug-Eluting Stents ; Fibrinolytic Agents ; Glycoproteins ; Humans ; Mortality ; Myocardial Infarction ; Nitrates ; Prevalence ; Prognosis ; Public Health

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by selective destruction of pancreatic beta-cells resulting in insulin deficiency. The genetic determinants of T1D susceptibility have been linked to several loci, in particular to the human leukocyte antigen (HLA) region, which accounts for 50% of the genetic risk of developing T1D. Multiple genes in the HLA region, which are in strong linkage disequilibrium, are thought to be involved. Another important locus, with a smaller effect on genetic predisposition to T1D, is the insulin gene. The advent of numerous single nucleotide polymorphism markers and genome screening has enabled the identification of dozens of new T1D susceptibility loci. Some of them appear to predispose to T1D independently of the HLA and may be important in families with T1D who lack strong HLA susceptibility. Other loci may interact with each other to cause susceptibility. The autoimmune response against beta-cells can also be triggered by environmental factors in the presence of a predisposing genetic background. Deciphering the environmental and genetic factors involved should help to understand the origin of T1D and aid in the design of individualized prevention programs.
Autoimmune Diseases ; Autoimmunity ; Diabetes Mellitus, Type 1 ; Genetic Predisposition to Disease* ; Genetics ; Genome ; HLA Antigens ; Humans ; Insulin ; Leukocytes ; Linkage Disequilibrium ; Mass Screening ; Polymorphism, Single Nucleotide

No abstract available.

The endocrine pancreas secretes several hormones including insulin and glucagon and dysfunction of them may lead to diabetes mellitus. The integrated regulation of systemic glucose balance prevents the devastating consequences of hypoglycemia and hyperglycemia. This remarkable homeostatic feat is accomplished primarily by hormones, but also by neurotransmitters and substrate effects, and it reflects the interplay of plasma glucose-lowering and glucose-raising factors. Moreover, endocrine diseases frequently co-associate with diabetes mellitus. There have also been several reports on changes in growth hormone (GH) in nutrient excess or deprivation. GH is released into the general circulation where it interacts with multiple peripheral tissues through its receptor, GH receptor, to regulate growth and metabolic function. In humans, GH levels decrease in states of nutrient excess such as obesity, and increase in response to nutrient deprivation such as fasting. Considering that GH regulates metabolism of carbohydrate, lipid, and protein, clarifying the mechanisms by which metabolic changes alter GH synthesis and secretion will increase our knowledge on the pathophysiology and treatment of metabolic diseases. In this review, the effect of nutrient excess and nutrient deficiency on GH axis function in humans will be summarized, with particular emphasis on studies exploring the direct effects of systemic signals, including insulin-like growth factor 1 (IGF-1) and insulin, on somatotrope function. Moreover, there will be a discussion over the overlap syndrome consisting of multiple endocrine neoplasm (MEN) and polyglandular autoimmune diseases (PGA).
Autoimmune Diseases ; Diabetes Mellitus ; Endocrine System Diseases ; Fasting ; Glucagon ; Glucose ; Growth Hormone ; Humans ; Hyperglycemia ; Hypoglycemia ; Insulin ; Islets of Langerhans ; Metabolic Diseases ; Neurotransmitter Agents ; Nutritional Physiological Phenomena ; Obesity ; Plasma ; Axis, Cervical Vertebra

Diabetes among young patients in Korea is caused by a complex set of factors. In addition to the typical T1aD and T2D patients, there is a variable incidence of cases of non-autoimmune types of T1D associated with insulin deficiency (T1b), such as fulminant T1D (FT1D). Although T1a is the major type of childhood diabetes, FT1D exists as a hyper-acute subtype of T1D that affects older children, without causing autoimmunity. They showed a complete loss of beta-cell secretory capacity without evidence of recovery, necessitating long-term treatment with insulin. In addition, latent autoimmune diabetes in adults (LADA) is a form of autoimmune-mediated diabetes, usually diagnosed based on GAD autoantibody positivity. Although many epidemiological surveys of LADA have been conducted in Caucasian and Asian populations, their reported prevalence rates vary due to the use of different diagnostic criteria. In a recent study with a comparable design and valid methodology, the prevalence of LADA using GAD autoantibody positivity as the diagnostic criterion was higher (4.4%) than the previously reported prevalence of 1.7% in a population-based T2D survey. After 36 months of follow-up, only 3 of the 39 patients initially diagnosed with LADA had become insulin-dependent, and they were all positive for multiple autoantibodies (GAD, IA-2 and ZnT8 antibody). This demonstrates that true insulin dependency, which was initially indicated by multiple antibody positivity, has not increased in the Korean population. Therefore, despite etiological heterogeneity, in the clinical setting, early diagnosis and classification of patients with diabetes relying on clinical grounds without measuring autoantibodies could be a possible method to minimize complications.
Adult ; Asian Continental Ancestry Group ; Autoantibodies ; Autoimmunity ; Child ; Classification ; Diabetes Mellitus, Type 1 ; Early Diagnosis ; Follow-Up Studies ; Genetic Heterogeneity ; Humans ; Incidence ; Insulin ; Korea ; Population Characteristics* ; Prevalence

Chronic granulomatous infection of the skin and soft tissue by nontuberculous mycobacteria in patients with normal immune system is rarely reported. This case was about a child patient, with normal immune system, whose lower leg was lacerated after a slip down in the Philippines and it was previously treated at a hospital in the Philippines. After a couple of surgical debridement of the wound, the cause of the soft tissue infection was found to be a combined infection of nontuberculous mycobacteria and mycobacterium tuberculosis. We present a case that has been rare in Korea, but common overseas.
Child ; Debridement ; Humans ; Immune System ; Korea ; Leg ; Mycobacterium tuberculosis ; Nontuberculous Mycobacteria ; Philippines ; Skin ; Soft Tissue Infections

Objective: This study introduces a novel home-based dual-task platform incorporating augmented reality (AR), COGNIMO, aimed at simultaneously enhancing cognition and physical abilities. The purpose of this study was to assess the effectiveness of this intervention in enhancing cognitive and physical abilities in elderly individuals with subjective cognitive decline, mild cognitive impairment (MCI), and mild Alzheimer’s dementia. Methods: A 12-week observational study enrolled 57 participants aged 60–85 years. Primary outcomes included changes in cognitive scores (Korean Mini-Mental State Examination, 2nd edition [K-MMSE-2] and Korean-Montreal Cognitive Assessment [K-MoCA]), while secondary outcomes measured physical parameters and depression scores between baseline and week 12 in the active and the control groups. Results: Of 57 participants, 49 completed the study. The active group (≥12 sessions) exhibited significant improvement in K-MoCA compared to the control group (<12 sessions) (p=0.004), while K-MMSE-2 score changes showed no significant difference (p=0.579). Positive correlations between training sessions and K-MoCA changes were observed (r=0.31, p=0.038), emphasizing a dose-response relationship. Subgroup analyses revealed a distinction in cognitive changes, particularly in the MCI group. Conclusion The COGNIMO platform showed positive effects on cognitive function in MCI patients, suggesting potential benefits for this population. The study highlights the potential of AR-integrated home-based interventions for cognitive enhancement in elderly individuals, underlining the need for further trials in the future.

A case of a 36-yr-old woman with retroperitoneal synovial sarcoma is described. Her presenting symptom was epigastric pain that radiating to the back. On radiologic study, bulky retropancreatic soft tissue mass was detected which showed cystic and solid components. At operation, complete resection of the tumor was not possible because of the adhesion to the vena cava and the liver. During the follow-up, extensive tumor recurrence and liver metastasis were revealed. Primary retroperitoneal synovial sarcoma is a very rare malignant tumor with high mortality and recurrence rates. Retroperitoneal synovial sarcoma usually appears as a nonspecific soft tissue mass that do not have specific imaging features differentiating it from other mesenchymal tumors. However general radiologic findings and anatomic location of the tumor may help the diagnosis. In addition, synovial sarcoma should be included in the differential diagnosis of retroperitoneal soft tissue mass detected in young adults.
Adult ; Female ; Humans ; Retroperitoneal Neoplasms/*pathology/radiography/surgery ; Sarcoma, Synovial/*pathology/radiography/surgery ; Tomography, X-Ray Computed

Extramedullary plasmacytoma is a rare disease that is histopathologically defined as a solitary tumor composed of a monoclonal proliferation of cells with plasmacytic differentiation in an extramedullary site. Most of these tumors occur in the submucosa of the upper aerodigestive tract, and they rarely occur in the small bowel mesentery. We report here on a case of extramedullary plasmacytoma of the small bowel mesentery that was in association with a cecal cancer. Abdominal ultrasound and CT revealed a lobulated soft tissue mass with a cystic portion and peripheral calcification. In this case, the preoperative radiological diagnosis was difficult due to accompanying cecal cancer.
Cecal Neoplasms* ; Diagnosis ; Mesentery* ; Plasmacytoma* ; Rare Diseases ; Ultrasonography