Influence of the hypothalamic-pituitary-adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism.

BACKGROUND AND AIMS: Functional hypercortisolism (FH) is generated by clinical states able to chronically activate the hypothalamic-pituitary-adrenal (HPA) axis [e.g. diabetes mellitus (DM)]. No study has evaluated FH influence in worsening the metabolic profile of male patients affected by DM-associated hypogonadism. In this retrospective work, we assess the possible association between HPA axis-dysregulation and cardiovascular risk factors in men simultaneously affected by DM and late-onset hypogonadism (LOH). METHODS AND RESULTS: Fourteen DM and LOH subjects affected by FH (Hypercort-DM-LOH) and fourteen DM and LOH subjects who were not suffering from FH (Normocort-DM-LOH) were retrospectively considered. Clinical, hormonal and metabolic parameters were retrieved. All metabolic parameters, except for systolic blood pressure, were significantly worse in Hypercort-DM-LOH than in Normocort-DM-LOH. After adjustment for body mass index, waist and total testosterone, Hypercort-DM-LOH subjects showed significantly worse metabolic parameters than Normocort-DM-LOH ones. In Normocort-DM-LOH, no significant correlation between general/hormonal parameters and metabolic variables was present. In Hypercort-DM-LOH, positive and significant correlations of cortisol area under the curve (AUC) after corticotropin releasing hormone with glycemia, triglycerides and blood pressure were evident; on the other hand, negative and significant correlation was present between cortisol AUC and high density lipoprotein (HDL) cholesterol. The associations of AUC cortisol with glycemia, HDL cholesterol and diastolic blood pressure (DBP) were further confirmed at quantile regression after adjustment for therapy. CONCLUSIONS: FH may determine a worsening of the metabolic profile in DM-associated hypogonadism.

Level of macroautophagy drives senescent keratinocytes into cell death or neoplastic evasion.

Senescence is a non-proliferative state reached by normal cells in response to various stresses, including telomere uncapping, oxidative stress or oncogene activation. In previous reports, we have highlighted that senescent human epidermal keratinocytes have two opposite outcomes: either they die by autophagic programmed cell death or they evade in the form of neoplastic postsenescence emergent (PSNE) cells. Herein, we show that partially reducing macroautophagy in senescent keratinocytes using 3-methyl adenine or anti-Atg5 siRNAs increases the PSNE frequency, suggesting that senescent keratinocytes have to escape autophagic cell death to generate PSNE cells. However, totally inhibiting macroautophagy impairs PSNE and leads to a huge accumulation of oxidative damages, indicating that senescent keratinocytes need to achieve quality-control macroautophagy for PSNE to occur. In accordance, we demonstrate that the progenitors of PSNE cells display a level of macroautophagy slightly lower than that of the average senescent population, which is directly dictated by their level of reactive oxygen species, their level of upregulation of MnSOD, their level of activation of NF-κB transcription factors and their level of dysfunctional mitochondria. Macroautophagy thus has antagonistic roles during senescence, inducing cell death or promoting neoplastic transformation, depending on its level of activation. Taken together, these data suggest that levels of oxidative damages and ensuing macroautophagic activity could be two main determinants of the very initial phases of neoplastic transformation by senescence evasion.

Changes in the excitability of soleus muscle short latency stretch reflexes during human hopping after 4 weeks of hopping training.

Changes in the excitability of the human triceps surae muscle short latency stretch reflexes were investigated in six male subjects before and after 4 weeks of progressive two-legged hopping training. During the measurements the subjects performed 2-Hz hopping with: preferred contact time (PCT) and short contact time. The following reflex parameters were examined before and after the training period: the soleus muscle (SOL) Hoffmann-reflex (H-reflex) at rest and during hopping, the short latency electromyogram (EMG) components of the movement induced stretch reflex (MSR) in SOL and medial gastrocnemius muscle (MG), and the EMG amplitude of the SOL and MG tendon reflexes (T-reflexes) elicited at rest. The main results can be summarized as follows: the SOL T-reflex had increased by about 28% (P < 0.05) after training while the MG T-reflex was unchanged; the SOL MSR (always evident) and the MG MSR (when observable) did not change in amplitude with training, and before training the SOL H-reflex in both hopping situations was significantly depressed to about 40% of the reference value at standing rest (P < 0.05). After training the H-reflex during PCT hopping was no longer depressed. As the value of the measured mechanical parameters (the total work rate, joint angular velocity and the ankle joint work rate) was unchanged after training in both hopping situations, the reflex changes observed could not be ascribed to changes in the movement pattern. To explain the observed changes, hypotheses of changes in the excitability of the stretch reflex caused by the training were taken into consideration and discussed.

The therapeutic role of naltrexone in negative symptom schizophrenia.

1. Naltrexone (50 mg bid, p.o.) was administered in a double-blind fashion (with placebo control) to chronic schizophrenic patients who maintained their routine neuroleptic and anxiolytic therapy. 2. Both positive and negative symptom patients who received naltrexone improved with regard to symptoms involving deterioration and social withdrawal. No significant amelioration was recorded in subjects assuming placebo relative to the same psychopathological areas. 3. Favourable results were obtained mainly from patients affected by negative symptom schizophrenia. 4. Naltrexone may have acted by direct or indirect neurochemical mechanisms related to negative symptom schizophrenia.

Fish-oil fatty acid supplementation in mixed cryoglobulinemia: a preliminary report.

OBJECTIVE: Since fish oils seem to play a potential role in the treatment of inflammatory disorders by inhibiting arachidonic acid metabolism, the purpose of this study was to determine their therapeutic efficacy in mixed cryoglobulinemia (MC), an inflammatory condition caused by the deposition of immune complexes in vessel walls. METHODS: In an 8-week double-blind randomized trial, ten MC patients received a daily dietary supplement of 3 gm of eicosapentaenoic acid (EPA) and 2 gm of docosahexenoic acid (DHA), while 10 other MC patients received placebo (olive oil). The severity of purpura, arthralgias, paresthesias, asthenia and Raynaud's phenomenon were monitored daily, and serological assays were performed at the beginning of the study, at the end of the treatment period, and after 4 weeks of wash-out. RESULTS: No significant differences were found between the two groups with regard to the clinical symptoms, although the percentage of patients who reported a clinical improvement was higher in the group treated with fish oils. As for the serological parameters, no variation was found in the placebo group, while in the group receiving fish oils a significant decrease in cryocrit and rheumatoid factor levels was observed, which in the case of rheumatoid factor persisted at the end of the wash-out period. CONCLUSIONS: Under the experimental conditions employed in this study, we could not demonstrate a significant improvement in clinical symptoms in patients with mixed cryoglobulinemia treated with fish oils. However, since our results indicated some improvement in the serological parameters potentially involved in the pathogenesis of the disorder, further studies are warranted to establish the optimal dose and duration of fish oil supplementation in the treatment of MC.