ABSTRACT
Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.
Subject(s)
Hypertriglyceridemia , Insulin Resistance , Lipodystrophy, Familial Partial , Lipodystrophy , Pancreatitis , Acute Disease , Female , Humans , Hypertriglyceridemia/complications , Lipodystrophy, Familial Partial/diagnosis , Lipodystrophy, Familial Partial/genetics , Lipodystrophy, Familial Partial/therapySubject(s)
Diabetes Mellitus, Type 1/diagnosis , Diabetic Ketoacidosis/diagnosis , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Aged , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/immunology , Diabetic Ketoacidosis/drug therapy , Diabetic Ketoacidosis/immunology , Humans , Male , Treatment OutcomeABSTRACT
EM66 is a conserved 66-amino acid peptide derived from secretogranin II (SgII), a member of the granin protein family. EM66 is widely distributed in secretory granules of endocrine and neuroendocrine cells, as well as in hypothalamic neurones. Although EM66 is abundant in the hypothalamus, its physiological function remains to be determined. The present study aimed to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behaviour. We show that i.c.v. administration of EM66 induces a drastic dose-dependent inhibition of food intake in mice deprived of food for 18 hours, which is associated with an increase of hypothalamic pro-opiomelanocortin (POMC) and melanocortin-3 receptor mRNA levels and c-Fos immunoreactivity in the POMC neurones of the arcuate nucleus. By contrast, i.c.v. injection of EM66 does not alter the hypothalamic expression of neuropeptide Y (NPY), or that of its Y1 and Y5 receptors. A 3-month high-fat diet (HFD) leads to an important decrease of POMC and SgII mRNA levels in the hypothalamus, whereas NPY gene expression is not affected. Finally, we show that a 48 hours of fasting in HFD mice decreases the expression of POMC and SgII mRNA, which is not observed in mice fed a standard chow. Taken together, the present findings support the view that EM66 is a novel anorexigenic neuropeptide regulating hypothalamic feeding behaviour, at least in part, by activating the POMC neurones of the arcuate nucleus.
Subject(s)
Appetite Regulation/drug effects , Feeding Behavior/drug effects , Hypothalamus/drug effects , Peptide Fragments/pharmacology , Secretogranin II/pharmacology , Animals , Caloric Restriction , Food Preferences/drug effects , Hypothalamus/metabolism , Infusions, Intraventricular , Male , Mice , Mice, Inbred C57BL , Peptide Fragments/administration & dosage , Secretogranin II/administration & dosage , Secretogranin II/chemistryABSTRACT
OBJECTIVE: Staphylococcus lugdunensis is a coagulase-negative staphylococcus that displays an unusually high virulence rate close to that of Staphylococcus aureus. It also shares phenotypic properties with S. aureus and several studies found putative virulence factors. The objective of the study was to describe the clinical manifestations of S. lugdunensis infections and investigate putative virulence factors. METHOD: We conducted a prospective study from November 2013 to March 2016 at the University Hospital of Strasbourg. Putative virulence factors were investigated by clumping factor detection, screening for proteolytic activity, and sequence analysis using tandem nano-liquid chromatography-mass spectrometry. RESULTS: In total, 347 positive samples for S. lugdunensis were collected, of which 129 (37.2%) were from confirmed cases of S. lugdunensis infection. Eighty-one of these 129 patients were included in the study. Bone and prosthetic joints (PJI) were the most frequent sites of infection (n=28; 34.6%) followed by skin and soft tissues (n=23; 28.4%). We identified and purified a novel protease secreted by 50 samples (61.7%), most frequently associated with samples from deep infections and PJI (pr 0.97 and pr 0.91, respectively). Protease peptide sequencing by nano-liquid chromatography-mass spectrometry revealed a novel protease bearing 62.42% identity with ShpI, a metalloprotease secreted by Staphylococcus hyicus. CONCLUSION: This study confirms the pathogenicity of S. lugdunensis, particularly in bone and PJI. We also identified a novel metalloprotease called lugdulysin that may contribute to virulence.
Subject(s)
Metalloproteases/genetics , Staphylococcus lugdunensis/enzymology , Virulence Factors/genetics , Adult , Aged , Aged, 80 and over , Amino Acid Sequence , Aminoglycosides/therapeutic use , Base Sequence , DNA, Bacterial/genetics , Drug Resistance, Multiple, Bacterial , Erythromycin/therapeutic use , Female , Fluoroquinolones/therapeutic use , Follow-Up Studies , Fosfomycin/therapeutic use , Fusidic Acid/therapeutic use , Humans , Male , Metalloproteases/metabolism , Methicillin/therapeutic use , Middle Aged , Phosphonoacetic Acid/therapeutic use , Prospective Studies , Sequence Analysis, DNA , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcus lugdunensis/genetics , Staphylococcus lugdunensis/pathogenicity , Vancomycin/therapeutic useSubject(s)
Arthritis, Infectious/microbiology , Bone Diseases, Infectious/microbiology , Staphylococcal Infections/microbiology , Staphylococcus lugdunensis , Arthritis, Infectious/diagnosis , Arthritis, Infectious/epidemiology , Biomarkers , Bone Diseases, Infectious/diagnosis , Bone Diseases, Infectious/epidemiology , Comorbidity , Female , Humans , Male , Mortality , Risk Factors , Staphylococcal Infections/diagnosis , Staphylococcal Infections/epidemiology , Staphylococcus lugdunensis/classification , Staphylococcus lugdunensis/pathogenicity , VirulenceABSTRACT
UNLABELLED: α-Defensins produced by neutrophils are important effector molecules of the innate immune system. In addition to their microbicidal effects, α-defensins have the ability to neutralize bacterial toxins. Panton-Valentine leukocidin (PVL) is the hallmark of community-acquired methicillin-resistant Staphylococcus aureus. Staphylococcus aureus that produce PVL are responsible for severe diseases, including necrotizing pneumonia. Polymorphonuclear neutrophils (PMNs) are the target cells of PVL action. The goal of this study was to elucidate the effect of a group of α-defensins known as the human neutrophil peptides (HNPs) on the interactions between LukS-PV and LukF-PV, which compose PVL, and human PMNs. We observed that HNPs bound to both subunits of PVL and significantly decreased PVL pore formation in PMNs, with a maximum inhibition of 27%. When various HNP molecules were tested individually under the same conditions, we observed that HNP3, but not HNP1 or 2, decreased pore formation. Similarly, HNP3 significantly decreased PVL-induced PMN lysis, with a maximum inhibition of 31%. Interestingly, HNPs did not affect LukS-PV LukF-PV oligomerization, LukS-PV LukF-PV binding to PMNs or calcium influx induced by PVL in PMNs. Our results suggest that HNP3 partially protects neutrophils against PVL by interfering with the conformational changes of PVL required to form a functional pore. SIGNIFICANCE AND IMPACT OF THE STUDY: Panton-Valentine leukocidin (PVL) is a pore-forming toxin produced by Staphylococcus aureus, responsible for neutrophil damage and key player of severe staphylococcal diseases. Antimicrobial peptides produced by neutrophils (HNP1-3) neutralize several other bacterial cytotoxins. We examined the impact of human neutrophil peptides (HNPs) on PVL cytotoxicity against human neutrophils and we found that HNPs bind to both LukS and LukF components of PVL, thereby inhibiting pore formation and neutrophil lysis. Our results suggest that HNP3 may impair PVL conformational changes required to form a functional pore and provide insight into the pathogenesis of PVL-related staphylococcal infection, with potential impact on the disease outcome.
Subject(s)
Bacterial Toxins/toxicity , Exotoxins/toxicity , Leukocidins/toxicity , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Neutrophils/enzymology , Staphylococcal Infections/immunology , alpha-Defensins/metabolism , Bacterial Proteins/metabolism , Humans , Leukocidins/metabolism , Neutrophils/immunologyABSTRACT
OBJECTIVE: A calcium load to suppress parathyroid hormone (PTH) secretion can help to perform the diagnosis in some case of primary hyperparathyroidism (PHPT) with atypical presentation. A similar test with calcimimetic, which avoids hypercalcaemia, would be of interest. Our proof of concept study was conducted to compare firstly the results of a single-dose cinacalcet testing with those of the standardized short-time calcium load in healthy control (HC) and secondly the results of the single-dose cinacalcet testing in HC and in PHPT. METHODS: Twelve HCs received in a random order, at a 2-week interval, either 0·33 mmol/kg calcium gluconate intravenously for 3 h, or a single oral dose of 30 mg or 60 mg cinacalcet. Twelve PHPTs received 30 mg cinacalcet and twelve other PHPTs 60 mg cinacalcet orally. Calcaemia and serum PTH levels were measured basally and then hourly for 6 h. RESULTS: In HC, plasma calcium did not significantly change after cinacalcet intake, whereas calcaemia rose up to 3·47 ± 0·05 mmol/l (mean ± SEM) at the end of the calcium load. PTH dropped from basal level to a similar extend (≥80%) with 60 mg cinacalcet and calcium load, whereas the decrease was significantly lesser (P < 0·01) with 30 mg cinacalcet. In PHPT, serum PTH levels dropped by 44·8 ± 6·9% and 58·2 ± 5·3% 1 h after the respective intake of 30 and 60 mg cinacalcet. One hour after the oral intake of 60 mg cinacalcet, serum PTH levels were <8 ng/l in HC and ≥8 ng/l in PHPT. CONCLUSION: Sixty milligrams of cinacalcet provides similar results as the standardized calcium load test; PHPT patients have a lower response to 60 mg cinacalcet than HC.
Subject(s)
Calcium/blood , Calcium/chemistry , Cinacalcet/administration & dosage , Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/diagnosis , Administration, Oral , Adult , Calcium Gluconate/administration & dosage , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Parathyroid Hormone/metabolism , Pilot Projects , Random Allocation , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Pyloric pressure and compliance have never been investigated in health nor gastroparesis. AIM: We hypothesised that pyloric pressure and/or compliance may be altered in gastroparesis. METHODS: Fasting pyloric pressure and compliance were investigated in 21 healthy volunteers (HV), 27 gastroparetic patients (GP) and 5 patients who had undergone oesophagectomy without pyloroplasty as positive controls. Under videofluoroscopic control, pyloric compliance and pressure were measured by the EndoFLIP technique. Gastric emptying half time (T1/2 ) using (13) C-octanoic acid breath test, as well as symptoms and quality of life (GIQLI score) were also monitored. RESULTS: Mean fasting pyloric compliance was measured at 25.2 ± 2.4 mm²/mmHg in HV, and was lower both in GP (16.9 ± 2.1 mm²/mmHg; P < 0.05) and patients with oesophagectomy (10.9 ± 2.9 mm²/mmHg; P < 0.05). By contrast, fasting pyloric pressure was not different among groups. Fasting pyloric compliance and pressure correlated with T1/2 in GP (R = -0.43; P = 0.04). Fasting pyloric compliance, but not pressure, correlated with symptoms and GIQLI score. Pyloric dilation in 10 GP with low fasting pyloric compliance (<10 mm²/mmHg) increased compliance from 7.4 ± 0.4 to 20.1 ± 4.9 mm²/mmHg (P < 0.01) and improved the GIQLI score from 72.5 ± 5.5 to 89.3 ± 6.1 (P = 0.04). CONCLUSION: This prospective study assessed pyloric compliance for the first time, and showed that fasting pyloric compliance is decreased in gastroparetic patients and is associated with T1/2 , symptoms and quality of life. This suggests that pyloric compliance may be a new relevant metric in gastroparetic patients, and may be useful to target patients for pyloric dilation or botulinum toxin injection.
Subject(s)
Dilatation/methods , Fasting/physiology , Gastric Emptying/physiology , Gastroparesis/physiopathology , Pylorus/physiopathology , Adult , Breath Tests , Caprylates/analysis , Esophagectomy , Female , Gastroparesis/surgery , Humans , Male , Middle Aged , Prospective Studies , Quality of LifeABSTRACT
Serotonin (5-hydroxytryptamine; 5-HT) is able to activate the hypothalamo-pituitary-adrenal axis via multiple actions at different levels. In the human adrenal gland, 5-HT, released by subcapsular mast cells, stimulates corticosteroid production through a paracrine mode of communication which involves 5-HT receptor type 4 (5-HT4) primarily located in zona glomerulosa. As a result, 5-HT is much more efficient to stimulate aldosterone secretion than cortisol release in vitro and administration of 5-HT4 receptor agonists to healthy individuals is followed by an increase in plasma aldosterone levels without any change in plasma cortisol concentrations. Interestingly, adrenocortical hyperplasias and tumors responsible for corticosteroid hypersecretion exhibit various cellular and molecular defects which tend to reinforce the intraadrenal serotonergic tone. These pathophysiological mechanisms, which are summarized in the present review, include an increase in adrenal 5-HT production and overexpression of 5-HT receptors in adrenal neoplastic tissues. Altogether, these data support the concept of adrenal serotonergic paracrinopathy and suggest that 5-HT and its receptors may constitute valuable targets for pharmacological treatments of primary adrenal diseases.
Subject(s)
Adrenal Cortex Neoplasms/drug therapy , Paracrine Communication/drug effects , Serotonin/pharmacology , Serotonin/therapeutic use , Steroids/biosynthesis , Animals , Humans , Hyperplasia , Models, BiologicalABSTRACT
Illegitimate G-protein coupled receptors are known to control cortisol secretion in adrenal adenomas and bilateral macronodular adrenal hyperplasias (BMAHs) causing Cushing's syndrome. In the present study, we have evaluated the role of glucagon in the regulation of cortisol secretion in 13 patients with BMAH or adrenocortical adenoma causing subclinical or overt Cushing's syndrome. Injection of glucagon provoked an increase in plasma cortisol in 2 patients. After surgery, immunohistochemical studies showed the presence of glucagon receptor-like immunoreactivity in clusters of spongiocytic cells in adrenal tissues from patients who were sensitive in vivo to glucagon. We also observed an in vitro cortisol response to vasoactive intestinal peptide from an adenoma, which was insensitive to glucagon and pituitary adenylate cyclase-activating peptide. Altogether, our data show that ectopic glucagon receptors are expressed in some adrenal cortisol-producing benign lesions. Our results also indicate that circulating glucagon may influence cortisol release under fasting conditions.
Subject(s)
Adrenal Glands/pathology , Cushing Syndrome/pathology , Glucagon/pharmacology , Peptides/pharmacology , Adrenal Glands/drug effects , Adrenocortical Adenoma/blood , Adult , Aged , Cushing Syndrome/blood , Female , Humans , Hydrocortisone/blood , Hydrocortisone/metabolism , Hyperplasia , Immunohistochemistry , Kinetics , Male , Middle Aged , Receptors, Glucagon/metabolism , Young AdultABSTRACT
Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/surgery , Glycated Hemoglobin/metabolism , Immunosuppressive Agents/therapeutic use , Insulin-Secreting Cells/metabolism , Islets of Langerhans Transplantation , C-Reactive Protein/metabolism , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/physiopathology , Female , Humans , Insulin-Secreting Cells/immunology , Islets of Langerhans Transplantation/adverse effects , Islets of Langerhans Transplantation/methods , Male , Patient Selection , Practice Guidelines as Topic , Prognosis , Quality of Life , Reproducibility of Results , Risk Assessment , Treatment OutcomeABSTRACT
A wide variety of autocrine/paracrine bioactive signals are able to modulate corticosteroid secretion in the human adrenal gland. These regulatory factors, released in the vicinity of adrenocortical cells by diverse cell types comprising chromaffin cells, nerve terminals, cells of the immune system, endothelial cells, and adipocytes, include neuropeptides, biogenic amines, and cytokines. A growing body of evidence now suggests that paracrine mechanisms may also play an important role in the physiopathology of adrenocortical hyperplasias and tumors responsible for primary adrenal steroid excess. These intra-adrenal regulatory systems, although globally involving the same actors as those observed in the normal gland, display alterations at different levels, which reinforce the capacity of paracrine factors to stimulate the activity of adrenocortical cells. The main modifications in the adrenal local control systems reported by now include hyperplasia of cells producing the paracrine factors and abnormal expression of the latter and their receptors. Because steroid-secreting adrenal neoplasms are independent of the classical endocrine regulatory factors angiotensin II and ACTH, which are respectively suppressed by hyperaldosteronism and hypercortisolism, these lesions have long been considered as autonomous tissues. However, the presence of stimulatory substances within the neoplastic tissues suggests that steroid hypersecretion is driven by autocrine/paracrine loops that should be regarded as promising targets for pharmacological treatments of primary adrenal disorders. This new potential therapeutic approach may constitute an alternative to surgical removal of the lesions that is classically recommended in order to cure steroid excess.
Subject(s)
Adrenal Cortex Neoplasms/physiopathology , Adrenocortical Hyperfunction/physiopathology , Autocrine Communication/physiology , Paracrine Communication/physiology , Adrenal Cortex Hormones/biosynthesis , Adrenal Cortex Neoplasms/complications , Adrenal Glands/physiology , Adrenal Glands/physiopathology , Adrenocortical Hyperfunction/etiology , Humans , Renin-Angiotensin System/physiologyABSTRACT
BACKGROUND: Incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)] released by the gut modulate gastrointestinal motility and influence gastric emptying (GE). Abnormal secretion or sensitivity to these hormones could contribute to the pathogenesis of gastroparesis. The aim of this study was to investigate incretin hormone secretion during a prolonged oral glucose load in non-diabetic patients with documented idiopathic gastroparesis. METHODS: Fifteen patients referred for digestive postprandial discomfort with delayed GE demonstrated by a (13) C-labeled octanoate breath test were included and compared with 10 healthy controls. A 75 g oral glucose load was performed, with blood samplings every 30 min for 5 h, to determine glucose, insulin, GIP, and GLP-1 blood levels. KEY RESULTS: Fasting GIP concentration was significantly higher in the patient group (56.1 ± 5.8 pg mL(-1) vs 29.9 ± 7.7 pg mL(-1), P =0.012). Postglucose load GIP concentrations were also significantly elevated in patients with gastroparesis, whereas GLP-1 concentrations during fasting and postglucose load conditions were not different to those of healthy controls. Moreover, glucose tolerance during glucose load was abnormal in patients, combining hyperglycemic insulin resistance and hyperinsulinism patterns, while fasting values for glycemia, insulin sensitivity, and insulin concentrations were normal. CONCLUSIONS & INFERENCES: Patients with idiopathic gastroparesis exhibit abnormal GIP levels associated with impaired insulin sensitivity during oral glucose load. Further studies are needed to establish the involvement of these defects in the pathophysiology of gastroparesis.
Subject(s)
Gastric Inhibitory Polypeptide/metabolism , Gastroparesis/blood , Glucagon-Like Peptide 1/blood , Glucose/administration & dosage , Insulin Resistance/physiology , Administration, Oral , Adult , Blood Glucose/drug effects , Blood Glucose/metabolism , Female , Gastric Emptying/drug effects , Gastric Emptying/physiology , Gastric Inhibitory Polypeptide/blood , Gastroparesis/diagnosis , Humans , Incretins/blood , Male , Middle Aged , Pilot Projects , Postprandial Period/drug effects , Postprandial Period/physiologyABSTRACT
We establish the presence of Vibrio parahaemolyticus and deepen the comparison of isolates using MALDI-TOF MS for the typing of isolates originating from the Khnifiss lagoon (Morocco). Amongst 48 samples from sea water, sediment and shellfish isolated from different sites of Khnifiss lagoon, Morocco, we obtained 22 isolates of V. parahaemolyticus identified by Vitek 2™ System (bioMérieux) and MALDI Biotyper™ (Bruker Daltonics). All isolates were highly resistant to ampicillin and ticarcillin, moderately resistant to cefalotin, but sensitive to 16 other antimicrobials tested. MALDI-TOF MS was used to discriminate between closely related environmental strains of V. parahaemolyticus. A clustering and distribution based on MALDI-TOF spectra were generated using the BioTyper 1.1™ software. Despite low diversity in regard to the biochemical characteristics and antimicrobial resistance, the isolates evoke a larger biodiversity when analysed through mass spectra of abundant proteins. Different evaluations of a cut-off value showed that, when placed at a 10% threshold of the whole diversity, isolates differed by at least three mass peaks.
Subject(s)
Bacterial Typing Techniques , Geologic Sediments/microbiology , Seawater/microbiology , Shellfish/microbiology , Vibrio parahaemolyticus/classification , Vibrio parahaemolyticus/isolation & purification , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/analysis , Morocco , Peptide Mapping , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Vibrio parahaemolyticus/chemistry , Vibrio parahaemolyticus/physiologyABSTRACT
Pancreastatin, derived from chromogranin A, inhibits insulin and stimulates glucagon secretion in rodents. Immunohistochemistry localised pancreastatin in human pancreatic islet cells and gonadotroph pituitary cells. Nonsecreting pituitary adenomas, frequently associated with diabetes mellitus, arise quasi-constantly from gonadotroph cells. We evaluated the possible involvement of pancreastatin in the physiopathology of diabetes mellitus associated with nonsecreting pituitary adenomas. Plasma pancreastatin levels were measured by radioimmunoassay in 5 groups of subjects: 10 patients with nonsecreting pituitary adenomas associated with diabetes mellitus (group I), 10 patients with nonsecreting pituitary adenomas without diabetes (Group II), 10 patients with ACTH or GH-secreting pituitary adenomas and diabetes mellitus (Group III), 10 diabetic patients without pituitary adenomas (Group IV), and 10 healthy controls (Group V). Kidney and liver functions were normal in all of them and no patient was treated with a proton pump inhibitor. All pituitary adenomas were trans-sphenoidally removed. Immunohistochemistry against pancreastatin was performed in 5 patients of each of the 3 groups of pituitary adenomas. Plasma pancreastatin levels were not different between the different groups: 182±46 pg/ml (Group I), 195±57 pg/ml (Group II), 239±42 pg/ml (Group III), 134±31 pg/ml, (Group IV), and 122±29 pg/ml (Group V). In contrast, they were significantly (p<0.05) higher before (391±65 pg/ml) than after trans-sphenoidal surgery (149±18 pg/ml) without post-surgical change in diabetes. An immunostaining against pancreastatin was found in a majority of pituitary adenomas, associated or not with diabetes mellitus. These results argue against a role of pancreastatin in the pathogenesis of diabetes mellitus associated with nonsecreting pituitary adenomas.
Subject(s)
Diabetes Complications/blood , Pancreatic Hormones/blood , Pituitary Neoplasms/blood , Pituitary Neoplasms/complications , Aged , Aged, 80 and over , Chromogranin A , Diabetes Complications/physiopathology , Female , Humans , Male , Middle AgedABSTRACT
AIM: Vascular accelerated aging represents the major cause of morbidity and mortality in subjects with diabetes mellitus. In the present study, our aim was to compare premature functional and morphological changes in the arterial wall resulting from streptozotocin (STZ)-induced diabetes mellitus in mice over a short-term period with those that develop during physiological aging. The effect of aminoguanidine (AG) on the prevention of these alterations in the diabetic group was also analyzed. METHODS: The vascular relaxation response to acetylcholine (ACh) in the mouse was tested in isolated segments of phenylephrine (Phe)-precontracted aorta at 2, 4 and 8 weeks (wk) of STZ-induced diabetes and compare to 12- and 84-wk-old mice. Aortic structural changes were investigated, and receptor for AGE (RAGE) aortic expression was quantified by western blot. RESULTS: Compared to the 12-wk control group (76 ± 5%), significant endothelium-dependant relaxation (EDR) impairment was found in the group of 12-wk-old mice, which underwent a 4-wk diabetes-inducing STZ treatment (12wk-4WD) (52 ± 4%; P < 0.01) and was yet more apparent in the group of 16-wk-old mice, which underwent an 8-wk diabetes-inducing STZ treatment (16wk-8WD) (34 ± 4%; P < 0.001). The alteration in EDR was relatively comparable between the diabetic 12wk-4WD group and the 84-wk-old group (52.7 ± 4 vs. 48 ± 4%). Intima/media aortic thickening and aortic structural changes were significantly increased in the diabetic 12wk-4WD group and were even more apparent in the 84-wk group compared to the 12-wk controls. AG treatment in the 12wk-4WD+AG diabetic group significantly improved EDR, decreased RAGE expression and showed an aging preventive effect on the structural changes of the arterial wall. CONCLUSION: Our study compared EDR linked to physiological aging with that observed in the case of STZ-induced diabetes over a short-term period, and demonstrated the beneficial effect of AG.
Subject(s)
Aging/physiology , Arteries/pathology , Arteries/physiopathology , Diabetes Mellitus, Experimental/pathology , Acetylcholine/pharmacology , Animals , Aorta/chemistry , Aorta/pathology , Aorta/physiopathology , Diabetes Mellitus, Experimental/physiopathology , Endothelium, Vascular/physiopathology , Male , Mice , Mice, Inbred C57BL , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/physiopathology , Phenylephrine/pharmacology , Receptor for Advanced Glycation End Products , Receptors, Immunologic/analysisABSTRACT
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is now widely used for marker/multi-biomarker detection in medical diagnosis. We tested a new protocol for bacterial identification from blood culture broths in hospital routine by using collection tubes with separator gels on 503 included samples examined over 3 months, where 1.5 mL was injected by a syringe into BD Vacutainer tubes from BACTEC-positive bottles, before processing for bacterial protein extraction. Samples were loaded in duplicate onto the MALDI MS target, allowing a series of 12 samples to be processed in duplicate within 80 min by using Biflex III and BioTyper 2.0 software (Bruker). Including polymicrobial samples, 193 of 213 of Gram-negative bacteria (91.08%) and 284 of 319 of Gram-positive bacteria (89.02%) were correctly identified at the species level. Enterobacteriaceae constituted 35.15% of all species found, Staphylococaceae 37.96%, Streptococaceae and Enterococaceae 20.85%, Pseudomonadaceae 1.69%, and anaerobes 2.44%. In most of the polymicrobial samples, one of the species present was identified (80.9%). Seven isolates remained misidentified as Streptococcus pneumoniae, all belonging to Streptococcus mitis. Staphylococcus aureus was identified better when grown on anaero-aerobic medium, and MALDI BioTyper identification scores as low as 1.4 were pertinent, provided that four successive proposals of the same species were given. This new protocol correlates with conventional microbiology procedures by up to 90%, and by >95% for only monomicrobial samples, and provides a decreased turn-around time for identification of bacteria isolated from blood cultures, making this technology suitable also for blood cultures, with less delay and cost decreases in bacterial diagnostics, and favouring better care of patients.