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  1. Type 1 diabetes and viral infections: What is the relationship?

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    Type 1 diabetes and viral infections: What is the relationship?

    J Clin Virol. 2017 Sep 08;96:26-31

    Authors: Principi N, Berioli MG, Bianchini S, Esposito S

    Type 1 diabetes (T1D) is the most common chronic metabolic disorder in children. Epigenetic and environmental factors capable of altering the penetrance of major susceptibility genes or capable of increasing the penetrance of low-risk genes are currently thought to play a role in triggering autoimmunity and T1D development. This paper discusses the current knowledge of the role of viruses in T1D. Most studies that have evaluated the potential association between viral infections and T1D have indicated that it is highly likely that some of these infectious agents play a role in T1D development. However, most T1D cases are immune-mediated, and it is supposed that the initial viral infection is capable of creating, in genetically predisposed subjects, a particular condition in which chronic local inflammation occurs through the persistence of the infecting virus in pancreatic tissue and the activation of autoimmunity by means of molecular mimicry, bystander activation, or both. Theoretically, this knowledge could lead to possible prophylaxis and therapy for T1D. Further studies devoted to evaluating which infectious agents are linked to T1D and which immune mechanisms induce or protect against the disease are needed before adequate prophylactic and therapeutic measures can be developed.

    PMID: 28934695 [PubMed - as supplied by publisher]

  2. Mitochondrial Dynamics in Mitochondrial Diseases.

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    Mitochondrial Dynamics in Mitochondrial Diseases.

    Diseases. 2016 Dec 23;5(1):

    Authors: Suárez-Rivero JM, Villanueva-Paz M, de la Cruz-Ojeda P, de la Mata M, Cotán D, Oropesa-Ávila M, de Lavera I, Álvarez-Córdoba M, Luzón-Hidalgo R, Sánchez-Alcázar JA

    Mitochondria are very versatile organelles in continuous fusion and fission processes in response to various cellular signals. Mitochondrial dynamics, including mitochondrial fission/fusion, movements and turnover, are essential for the mitochondrial network quality control. Alterations in mitochondrial dynamics can cause neuropathies such as Charcot-Marie-Tooth disease in which mitochondrial fusion and transport are impaired, or dominant optic atrophy which is caused by a reduced mitochondrial fusion. On the other hand, mitochondrial dysfunction in primary mitochondrial diseases promotes reactive oxygen species production that impairs its own function and dynamics, causing a continuous vicious cycle that aggravates the pathological phenotype. Mitochondrial dynamics provides a new way to understand the pathophysiology of mitochondrial disorders and other diseases related to mitochondria dysfunction such as diabetes, heart failure, or Hungtinton's disease. The knowledge about mitochondrial dynamics also offers new therapeutics targets in mitochondrial diseases.

    PMID: 28933354 [PubMed]

  3. Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species.

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    Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species.

    Curr Transplant Rep. 2017;4(3):193-200

    Authors: Mourad NI, Gianello P

    PURPOSE OF REVIEW: Cell xenotransplantation has the potential to provide a safe, ethically acceptable, unlimited source for cell replacement therapies. This review focuses on genetic modification strategies aimed to overcome remaining hurdles standing in the way of clinical porcine islet transplantation and to develop neural cell xenotransplantation.
    RECENT FINDINGS: In addition to previously described genetic modifications aimed to mitigate hyperacute rejection, instant blood-mediated inflammatory reaction, and cell-mediated rejection, new data showing the possibility of increasing porcine islet insulin secretion by transgenesis is an interesting addition to the array of genetically modified pigs available for xenotransplantation. Moreover, combining multiple modifications is possible today thanks to new, improved genomic editing tools.
    SUMMARY: Genetic modification of large animals, pigs in particular, has come a long way during the last decade. These modifications can help minimize immunological and physiological incompatibilities between porcine and human cells, thus allowing for better tolerance and function of xenocells.

    PMID: 28932650 [PubMed]

  4. Management of chronic constipation in patients with diabetes mellitus.

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    Management of chronic constipation in patients with diabetes mellitus.

    Indian J Gastroenterol. 2017 Jan;36(1):11-22

    Authors: Prasad VG, Abraham P

    AIM: The aim of this review is to provide an overview of the clinical assessment and evidence-based treatment options for managing diabetes-associated chronic constipation.
    METHODS: A literature search of published medical reports in English language was performed using the OVID Portal, from PUBMED and the Cochrane Database of Systematic Reviews, from inception to October 2015. A total of 145 abstracts were identified; duplicate publications were removed and 95 relevant full-text articles were retrieved for potential inclusion.
    RESULTS: Chronic constipation is one of the most common gastrointestinal symptoms in patients with diabetes, and occurs more frequently than in healthy individuals. Treatment goals include improving symptoms and restoring bowel function by accelerating colonic transit and facilitating defecation. Based on guidelines and data from published literature, food and dietary change with exercise and lifestyle change should be the first step in management. For patients recalcitrant to these changes, laxatives should be the next step of treatment. Treatment should begin with bulking agents such as psyllium, bran or methylcellulose followed by osmotic laxatives if response is poor. Lactulose, polyethylene glycol and lactitol are the most frequently prescribed osmotic agents. Lactulose has a prebiotic effect and a carry-over effect (continued laxative effect for at least 6 to 7 days, post cessation of treatment). Stimulants such as bisacodyl, sodium picosulphate and senna are indicated if osmotic laxatives are not effective. Newer agents such as chloride-channel activators and 5-HT4 agonist can be considered for severe or resistant cases.
    CONCLUSION: The primary aim of intervention in diabetic patients with chronic constipation is to better manage the diabetes along with management of constipation. The physician should explain the rationale for prescribing laxatives and educate patients about the potential drawbacks of long-term use of laxatives. They should contact their physician if short-term use of prescribed laxative fails to provide relief.

    PMID: 27987136 [PubMed - indexed for MEDLINE]

  5. Endoscopic Endonasal Management of Rare Sellar Lesions: Clinical and Surgical Experience of 78 Cases and Review of the Literature.

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    Endoscopic Endonasal Management of Rare Sellar Lesions: Clinical and Surgical Experience of 78 Cases and Review of the Literature.

    World Neurosurg. 2017 Apr;100:369-380

    Authors: Somma T, Solari D, Beer-Furlan A, Guida L, Otto B, Prevedello D, Cavallo LM, Carrau R, Cappabianca P

    OBJECTIVE: In the present study we aim to provide further definition of a group of rare sellar diseases treated by the endoscopic endonasal approach.
    METHODS: The study was a retrospective analysis of data obtained from a series of 1729 patients who underwent endoscopic endonasal surgery at 2 academic institutions (Università degli Studi di Napoli Federico II, Naples, Italy between January 1997 and December 2013 and the Wexner Medical Center at The Ohio State University between July 2010 and September 2015). Clinical charts, operative notes, and pathology reports were examined.
    RESULTS: A total of 346 cases were identified to have nonadenomatous diseases. Applying the Rosner test for outliers assisted in excluding relatively frequent lesions. The final cohort of rare sellar diseases comprised 78 patients. Arachnoid cysts were the most frequently encountered sellar lesion (12 patients, 15%), followed by metastasis (11 cases, 14%), followed by hypophysitis (8 cases, 10%), oncocytoma, and glioma (6 cases, 8% each). The most frequent clinical findings were headache (28%) and visual disorders (80%). A standard endoscopic endonasal approach was performed in 44 patients (56%), and an extended approach was carried out in 34 patients (44%). Tumor removal was gross total in 53% of patients, subtotal in 19%, and partial in 21%. Postoperative endocrinologic and visual deficit evaluation showed improvements in endocrine function in 8 patients (10%) and in visual disorders in 13 (16%). Postoperative complications arose in 28% of cases, mostly represented by diabetes insipidus (10%).
    CONCLUSIONS: Endoscopic endonasal approaches offer some specific benefits in the treatment of these patients.

    PMID: 27888088 [PubMed - indexed for MEDLINE]

  6. Diabetes in pregnancy and lung health in offspring: developmental origins of respiratory disease.

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    Diabetes in pregnancy and lung health in offspring: developmental origins of respiratory disease.

    Paediatr Respir Rev. 2017 Jan;21:19-26

    Authors: Azad MB, Moyce BL, Guillemette L, Pascoe CD, Wicklow B, McGavock JM, Halayko AJ, Dolinsky VW

    Diabetes is an increasingly common complication of pregnancy. In parallel with this trend, a rise in chronic lung disease in children has been observed in recent decades. While several adverse health outcomes associated with exposure to diabetes in utero have been documented in epidemiological and experimental studies, few have examined the impact of diabetes in pregnancy on offspring lung health and respiratory disease. We provide a comprehensive overview of current literature on this topic, finding suggestive evidence that exposure to diabetes in utero may have adverse effects on lung development. Delayed lung maturation and increased risk of respiratory distress syndrome have been consistently observed among infants born to mothers with diabetes and these findings are also observed in some rodent models of diabetes in pregnancy. Further research is needed to confirm and characterize epidemiologic observations that diabetes in pregnancy may predispose offspring to childhood wheezing illness and asthma. Parallel translational studies in human pregnancy cohorts and experimental models are needed to explore the role of fetal programming and other potential biological mechanisms in this context.

    PMID: 27665512 [PubMed - indexed for MEDLINE]

  7. Nephrogenic Adenoma: Clinical Features, Management, and Diagnostic Pitfalls.

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    Nephrogenic Adenoma: Clinical Features, Management, and Diagnostic Pitfalls.

    Urology. 2016 Sep;95:29-33

    Authors: Gordetsky J, Gennaro KH, Selph JP, Rais-Bahrami S

    OBJECTIVE: To review the diagnosis and management of nephrogenic adenoma (NA), an uncommon benign lesion found in the urinary tract. This lesion arises from a proliferation of implanted renal tubular cells. Although more common in adults, it can occur in all ages. NAs can recur and cause significant morbidity in patients. NAs are also a potential diagnostic pitfall as they can clinically and histologically mimic malignancy in the urinary tract.
    MATERIALS AND METHODS: We performed an Institutional Board Review approved search of our surgical pathology database from 2005 to 2015 for cases of NA. A retrospective chart review was performed with a focus on the clinical, pathologic, and radiographic findings in these patients.
    RESULTS: We identified 32 cases of NA in 31 patients. Lesions were most common in Caucasian males (male-to-female ratio of 2:1) with an average age at diagnosis of 55 years (range 25-77). Bladder was the most common site of occurrence (81.2%), followed by ureter (9.4%), urethra (6.3%), and intrarenal collecting system (3.1%). Most patients (72%) were symptomatic and presented with hematuria (41%), lower urinary tract symptoms (28%), pelvic or flank pain (6%), hydronephrosis (19%), or urinary incontinence (13%). NA was asymptomatic and identified incidentally in 9 (28%) patients. One patient (3%) had a renal transplant and 8 (26%) patients had diabetes mellitus. Twenty-six (84%) patients were managed with endoscopic resection of their tumors.
    CONCLUSION: NAs are benign lesions that may cause significant morbidity and mimic malignant tumors. There should be increased suspicion in patients with predisposing factors.

    PMID: 27138263 [PubMed - indexed for MEDLINE]

  8. A Comprehensive Review of Novel Drug-Disease Models in Diabetes Drug Development.

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    A Comprehensive Review of Novel Drug-Disease Models in Diabetes Drug Development.

    Clin Pharmacokinet. 2016 Jul;55(7):769-88

    Authors: Gaitonde P, Garhyan P, Link C, Chien JY, Trame MN, Schmidt S

    Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, which affects millions of people worldwide. The disease is characterized by chronically elevated blood glucose concentrations (hyperglycaemia), which result in comorbidities and multi-organ dysfunction. This is due to a gradual loss of glycaemic control as a result of increasing insulin resistance, as well as decreasing β-cell function. The objective of T2DM drug interventions is, therefore, to reduce fasting and postprandial blood glucose concentrations to normal, healthy levels without hypoglycaemia. Several classes of novel antihyperglycaemic drugs with various mechanisms of action have been developed over the past decades or are currently under clinical development. The development of these drugs is routinely supported by the application of pharmacokinetic/pharmacodynamic modelling and simulation approaches. They integrate information on the drug's pharmacokinetics, clinically relevant biomarker information and disease progression into a single, unifying approach, which can be used to inform clinical study design, dose selection and drug labelling. The objective of this review is to provide a comprehensive overview of the quantitative approaches that have been reported since the 2008 review by Landersdorfer and Jusko in an increasing order of complexity, starting with glucose homeostasis models. Each of the presented approaches is discussed with respect to its strengths and limitations, and respective knowledge gaps are highlighted as potential opportunities for future drug-disease model development in the area of T2DM.

    PMID: 26798033 [PubMed - indexed for MEDLINE]