Hypoactive sexual desire disorder: can we treat it with drugs?

Hypoactive sexual desire disorder (HSDD) is a common multidimensional condition which is characterized by a decrease in sexual desire that causes marked personal distress and/or interpersonal difficulty. There are a number of potential causes and contributing factors to HSDD and a balanced approach comprising both biological and psycho-relational factors is mandatory for accurate diagnosis and tailored management in clinical practice. It is clearly evident that sex hormones play a crucial role in modulating sexual response during the entire reproductive life span of women. On the other hand, a better understanding of the neurobiological basis of sexual desire supports the idea that selective psychoactive agents may be proposed as non-hormonal treatments to restore the balance between excitatory and inhibitory stimuli leading to a normal sexual response cycle. However, there are currently no approved pharmacological treatments for premenopausal women with HSDD, while transdermal testosterone is approved in Europe for post-menopausal women who experience HSDD as a result of a bilateral oophorectomy. That being so, the ideal clinical approach remains to be established in term of efficacy and safety and further research is needed to develop specific pharmacotherapies for individualized care of women with sexual dysfunction of any age.     

An unusual case of fatty liver in a patient with desmoid tumor

A desmoid tumor, also known as aggressive fibromatosis, is a rare benign neoplasm that arises from fascial or musculoaponeurotic tissues. It can occur in any anatomical location, most commonly the abdominal wall, shoulder girdle and retroperitoneum. The typical clinical presentation is a painless mass with a slow and progressive invasion of contiguous structures. It is associated with a high local recurrence rate after resection. Many issues regarding the optimal treatment of desmoid tumors remain controversial. Aggressive surgical resection with a wide margin (2-3 cm) remains the gold standard treatment with regard to preserving quality of life. Radiotherapy alone has been shown to be effective for the control of unresectable or recurrent lesions. Desmoid tumors tend to be locally infiltrative, therefore, the fields must be generous to prevent marginal recurrence. The radiation dose appropriate for treating desmoid tumors remains controversial. We present a 25-year-old Caucasian man with local recurrence of a desmoid tumor after repeated surgical resection, treated with radiotherapy. The patient achieved complete tumor regression at 4 mo after radiotherapy, and he is clinically free of disease at 12 mo after the end of treatment, with an acceptable quality of life. The patient developed short bowel syndrome as a complication of second surgical resection. Consequently, radiotherapy might have worsened an already present malabsorption and so led to steatohepatitis.     

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.