IGFBP-3 Mediates Metabolic Homeostasis During Hyperosmolar Stress in the Corneal Epithelium

PurposeThe insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional secretory protein with well-known roles in cell growth and survival. Data in our laboratory suggest that IGFBP-3 may be functioning as a stress response protein in the corneal epithelium. The purpose of this study is to determine the role of IGFBP-3 in mediating the corneal epithelial cell stress response to hyperosmolarity, a well-known pathophysiological event in the development of dry eye disease.MethodsTelomerase-immortalized human corneal epithelial (hTCEpi) cells were used in this study. Cells were cultured in serum-free media with (growth) or without (basal) supplements. Hyperosmolarity was achieved by increasing salt concentrations to 450 and 500 mOsM. Metabolic and mitochondrial changes were assessed using Seahorse metabolic flux analysis and assays for mitochondrial calcium, polarization and mtDNA. Levels of IGFBP-3 and inflammatory mediators were quantified using ELISA. Cytotoxicity was evaluated using a lactate dehydrogenase assay. In select experiments, cells were cotreated with 500 ng/mL recombinant human (rh)IGFBP-3.ResultsHyperosmolar stress altered metabolic activity, shifting cells towards a respiratory phenotype. Hyperosmolar stress further altered mitochondrial calcium levels, depolarized mitochondria, decreased levels of ATP, mtDNA, and expression of IGFBP-3. In contrast, hyperosmolar stress increased production of the proinflammatory cytokines IL-6 and IL-8. Supplementation with rhIGFBP-3 abrogated metabolic and mitochondrial changes with only marginal effects on IL-8.ConclusionsThese findings indicate that IGFBP-3 is a critical protein involved in hyperosmolar stress responses in the corneal epithelium. These data further support a new role for IGFBP-3 in the control of cellular metabolism.     

Vitamin D deficiency in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder affecting, among others, the endocrine system, with derangement of steroid hormones functions. Vitamin D is a steroid recognized for its role in calcium homeostasis. In addition, vitamin D influences muscle metabolism by genomic and non-genomic actions, including stimulation of the insulin-like-growth-factor 1 (IGF1), a major regulator of muscle trophism. To verify the presence of vitamin D deficit in DM1 and its possible consequences, serum 25-hydroxyvitamin D (25(OH)D), calcium, parathormone (PTH), and IGF1 levels were measured in 32 DM1 patients and in 32 age-matched controls. Bone mineral density (BMD) and proximal muscle strength were also measured by DXA and a handheld dynamometer, respectively. In DM1 patients, 25(OH)D levels were reduced compared to controls, and a significant decrease of IGF1 was also found. 25(OH)D levels inversely correlated with CTG expansion size, while IGF1 levels and muscle strength directly correlated with levels of 25(OH)D lower than 20 and 10 ng/ml, respectively. A significantly higher percentage of DM1 patients presented hyperparathyroidism as compared to controls. Calcium levels and BMD were comparable between the two groups. Oral administration of cholecalciferol in 11 DM1 patients with severe vitamin D deficiency induced a normal increase of circulating 25(OH)D, ruling out defects in intestinal absorption or hepatic hydroxylation. DM1 patients show a reduction of circulating 25(OH)D, which correlates with genotype and may influence IGF1 levels and proximal muscle strength. Oral supplementation with vitamin D should be considered in DM1 and might mitigate muscle weakness.     

Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians

Objectives: The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options.

Methods: We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits.

Results: The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach.

Conclusions: Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices.     

Different diagnostic tools for the localization of impacted maxillary canines: clinical considerations

In this study we evaluated different radiographic exams for the localization of impacted maxillary canines (orthopantomography (OPT), laterolateral and posteroanterior teleradiography, parallax method, laterolateral, occlusal radiography, computerized axial tomography, cone beam CT) highlighting the advantages and disadvantages of each. Four patients with impacted maxillary canines underwent selected radiographic investigations which allowed us to discuss their potential in identifying the position relative to the impacted teeth in the upper jaw. It was not possible to carry out all methods on the same patient as the level of radiation exposure experienced by each patient would too high and therefore unethical. Each method revealed the position of the canine with respect to the adjacent structures and the inclination of the major axis of the impacted tooth with respect to the plane of reference. We then evaluated the ease of use, the dosage of radiation emitted, the significance of the localization of the impacted canine, the immediacy of availability of the information required and the cost of each method. Each technique presented intrinsic advantages and limitations; however CBCT provides elements which escape during traditional radiographic analysis and is therefore indicated in case of impacted teeth or cranio-facial structural anomalies.     

Monocyte to HDL ratio: a novel marker of resistant hypertension in CKD patients

International Urology and Nephrology - Inflammation, oxidative stress (OS), atherosclerosis and resistant hypertension (RH) are common features of chronic kidney disease (CKD) leading to a higher...     

Microsurgical reconstruction of the isolated columellar defect with a prelaminated radial forearm free flap. A case report and a review of the literature

The columella is one of the smallest subunits of the nose, but the loss of this structure has important aesthetic and structural implications. Few papers in literature present microsurgical techniques for the reconstruction of an isolated columellar defect. This report describes the use of a prelaminated radial forearm free flap (RFFF) for the reconstruction of an isolated columellar defect and reviews the current literature. A 45-year-old woman presented to our Unit with a history of palate squamous cell carcinoma and severe nasal deformity with an almost complete loss of the columella. A prelaminated RFFF with the fifth rib was used for a two-staged reconstruction of the isolated columellar defect. The radial pedicle was anastomosed to the facial vessels and the postoperative course was uneventful. Complete survival of the flap was achieved and, 10 months postoperatively, the patient had bilateral nasal patency, with an increased tip projection and a good aesthetic result. A prelaminated RFFF can be considered a valuable reconstructive option in cases of a large composite defect of the columella and limited availability of adjacent tissues.     

Continuous subcutaneous insulin infusion: A long-term study

Summary The authors report data obtained from a 3-year study of CSII and humanized insulin (semi-synthetic human insulin) administered to 18 insulin-dependent subjects in the outpatient clinic. The aim of this study was to evaluate the validity of insulin pumps in long-term treatment. Metabolic parameters were significantly improved (p<0.001) in the first month and remained so with only slight alterations throughout treatment. The authors underline some metabolic problems (ketosis) caused by malfunctioning of the insulin pumps, by the difficulties with the infusion sytem or by nodular skin lesions at the infusion site. Only these lesions called for treatment to be discontinued in 4 patients. The highest incidence of nodular skin lesions was seen after one year’s uninterrupted treatment and they seem connected to the duration of treatment rather than to the patients’ negligence (inadequate hygiene, delayed needle substitution). The authors conclude that CSII treatment is valid over short-term periods, whereas it presents drawbacks over long-term administration.