Resistin, visfatin, leptin and omentin are differently related to hormonal and metabolic parameters in growth hormone-deficient children.

PURPOSE: The effect of growth hormone (GH) on adipose tissue and the role of adipokines in modulating metabolism are documented, but with discordant data. Our aim was to evaluate the impact of GH treatment on a series of selected adipokines known to have a metabolic role and poorly investigated in this setting. METHODS: This is a prospective study. Thirty-one prepubertal children (25 M, 6 F; aged 8.5 ± 1.6 years) with isolated GH deficiency treated with GH for at least 12 months and 30 matched controls were evaluated. Auxological and metabolic parameters, insulin sensitivity indexes, leptin, soluble leptin receptor, adiponectin, visfatin, resistin, omentin, adipocyte fatty acid-binding protein and retinol-binding protein-4 were evaluated before and after 12 months of treatment. RESULTS: At baseline, no significant difference in metabolic parameters was found between GHD children and controls, except for higher LDL cholesterol (p = 0.004) in the first group. At multivariate analysis, LDL cholesterol was independently associated with resistin (B 0.531; p = 0.002), while IGF-I was the only variable independently associated with visfatin (B 0.688; p < 0.001). After 12 months, a significant increase in fasting insulin (p = 0.008), Homa-IR (p = 0.007) and visfatin (p < 0.001) was found, with a concomitant decrease in LDL cholesterol (p = 0.015), QUICKI (p = 0.001), ISI Matsuda (p = 0.006), leptin (p = 0.015) and omentin (p = 0.003)]. At multivariate analysis, BMI was the only variable independently associated with leptin (B 0.485; p = 0.040). CONCLUSIONS: GH treatment modifies adipokine secretion and the perturbation of some adipokine levels could contribute to the clinical and metabolic changes observed during the follow-up.

miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1.

MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells.

Migrainous infarction: association with vascular risk factors in a male subject.

Migraine with aura (MA) is associated with an increased risk of ischemic stroke, especially in young women with vascular risk factors (smoke, contraceptive pill). Patent foramen ovale (PFO) has also been associated with MA. We describe a 41-year-old man, in good health, with MA since 16, familiar history of diabetes, heavy smoker (30 cigarettes/day). Frequency (1-2 attacks/year) and clinical features of migraine have been unchanged since the onset. A few days before our examination he suffered a typical migraine attack. In the following hours, however, the headache became more and more throbbing and the aura symptoms (regressed as usual in 30 min) reappeared and persisted, so he went to an Emergency Department. The CT-scan (without contrast) was normal. The following days he had visual disturbances and spatial disorientation. We found a normal neurological examination and fundus oculi. He referred persisting visual troubles. We prescribed MR + angioMR which confirmed a migrainous infarction and ruled out others pathological conditions. Further tests found out dyslipidemia, hyperhomocysteinemia, impaired glucose tolerance. Transcranial Doppler showed right to left shunting. We also prescribed the screening tests for vasculitis (normal). In our opinion this case highlights the relevance of vascular risk factors in MA complications also in male subjects.

Bilateral adrenal non-Hodgkin lymphoma type B.

The adrenal localization of a primary non-Hodgkin lymphoma (NHL) is rare. We report a case of a 66-yr-old woman who had severe asthenia, diffuse skin hitching and abdominal pain. The physical examination revealed poor general conditions, irritability, pallor, dehydration and diffuse skin scratching lesions. The abdomen was painful at left hypochondrium and the Giordano's maneuvre was positive on both sides. A peripheral blood smear showed the presence of big rare lymphocytes with dyshomogeneous chromatin and granulated and hyperbasophil cytoplasm. She underwent abdominal ultrasonography which showed the presence of a hypoechogenic ovoidal mass (major diameter 8.4 cm) within the splenorenal left region. The presence of the suprarenal mass was confirmed by computed tomography (CT) scan which showed an enlarged left adrenal gland (8.1 x 6.2 cm) of solid structure. The right adrenal gland was also enlarged and of round shape (4.5 cm). CT scan-guided fine needle aspiration biopsy was then carried out on the left adrenal mass. It revealed the presence of NHL type B with large cells and modest T-lymphocyte reactive component. The patient was treated with three cycles of cyclophosphamide, adriamycin, vincristine and prednisolone. At the end of the third cycle, there was a transient clinical improvement and the hitching disappeared, but the patient worsened rapidly and she died few weeks later.

Recurrence of ibuprofen-induced aseptic meningitis in an otherwise healthy patient.

We report the case of a 74-year-old woman who had three episodes of aseptic meningitis in a period of 20 years. These episodes always occurred a few hours after the assumption of a non-steroidal anti-inflammatory drug (NSAID) per os. Nevertheless, the pharmacological anamnesis did not receive proper attention, neither the first nor the second time, and the meningeal syndrome with aseptic liquor was attributed to a viral aggression. However, when the third episode occurred, due to the strict time correlation between the assumption of the drug and the occurrence of symptoms, both the results of the liquoral analysis and the anamnestic records allowed recognition of ibuprofen as the cause of acute meningitis.

Do child welfare clinics influence growth?

Child welfare clinics established in a rural Jamaican community for research purposes are described. These special clinics were able to devote more resources to the care of their children than is usual, yet the growth and health of these children were very similar to those in another group to whom this service was not available and who attended routine Government Welfare Clinics only infrequently.(AU)