Increased Lymphocyte Concentration in the Semen of Patients with Reduced Testicular Volume

Low testicular volume (TV) is associated with a decreased testicular function. Several studies explored the conventional sperm parameters and the endocrine function in patients with low TV. No other parameters have been examined. On the basis of these premises, the aim of this study was to evaluate a non-conventional seminal parameter: seminal lymphocyte characterisation in men with low TV compared with that of subjects with normal TV. A further comparison was made between fertile men and infertile patients with low or normal TV (78 patients). The testis was considered normal in size when it had a volume between 15 and 25 cm 3 , low-normal with a volume between 10 and 12 cm 3 and hypotrophic when the volume was <10 cm 3 . Statistically significant differences were observed in the following sperm parameters: percentage of immature germ elements, peroxidase-positive leukocyte concentration and CD45 pos leukocytes (p<0.05). A correlation analysis showed the presence of a positive linear relationship between CD45 pos leukocytes and the percentage of immature germ elements (r=0.88; p<0.05) and between CD45 pos leukocytes and the percentage of spermatozoa with phosphatidylserine externalisation (r=0.90; p<0.05) as well as a negative linear relationship between the percentage of spermatozoa with normal morphology and the seminal CD45 pos leukocyte concentration (r=-0.75; p<0.05). The results of this study showed that patients with low testicular volume (<10 cm 3 ) have a significantly increased CD45 pos concentration that is associated with increased percentages of immature germ elements, spermatozoa with signs of early apoptosis, and spermatozoa with abnormal morphology

Arterial erectile dysfunction: Different severities of endothelial apoptosis between diabetic patients &quot;responders&quot; and &quot;non responders&quot; to sildenafil

Background: The low pharmacological response to phosphodiesterase type 5 inhibitors represents an expression of higher endothelial damage in certain categories of patients with erectile dysfunction and high cardiovascular risk. The present study evaluated this objective in type 2 diabetic patients with erectile dysfunction, classified as &quot;non responders&quot; to Sildenafil. Methods: Eighteen &quot;responder&quot; and twelve &quot;non responder&quot; type 2 diabetic patients were evaluated, relatively to different levels of endothelial damage, through the diagnostic use of a new immunophenotype of circulating endothelial progenitor cells (CD45neg/CD34pos/CD144pos) and endothelial microparticles (CD45neg/CD144pos/Annexin Vpos), recently developed and published by our group. Results &quot;Non responder&quot; patients showed a significant higher severity [8.0 ± 3.0 (International Index of Erectile Function-abbreviated version with 5 questions) vs 14.0 ± 3.0] and duration (10.0 ± 2.0 vs 7.0 ± 2.0 years) of erectile dysfunction, higher level of penile arterial insufficiency (peak systolic velocity = 13.0 ± 16.0 vs 28.0 ± 26.0 cm/s; acceleration time = 153 ± 148 vs 125 ± 128 mm/s) and finally a significant higher level of endothelial apoptosis [0.15 ± 0.13 vs 0.05 ±.0.03% (serum concentrations of endothelial microparticles)] associated with higher serum concentrations of circulating late immunophenotype of endothelial progenitor cells (0.40 ± 0.35 vs 0.12 ±.0.10%). Conclusions: The results of this study corroborate the clinical value of the low clinical response to phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction in the patients with high cardiovascular risk profile, such as diabetics. In addition, the markers used in this study confirm their potential application in clinical practice as useful indicators of endothelial alteration. However, in the future we will have to assess a larger number of patients and for a longer period of observation in order to better understand the causal and temporal relations. © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved

Fish and human health: an umbrella review of observational studies

Fish represents one of the most important dietary sources of omega-3 polyunsaturated fatty acids, which are known to be associated with various health benefits. This study aimed to systematically review existing meta-analyses of observational studies exploring the association between fish intake and various health outcomes. A systematic search of electronic databases was conducted to retrieve a total of 63 studies. Evidence was deemed as possible for the association between higher fish intake and decreased risk of the acute coronary syndrome, liver cancer, and depression, and limited for other outcomes (including age-related macular degeneration, Alzheimer's disease, heart failure, all-cause and coronary heart disease mortality, total and ischaemic stroke) due to heterogeneity between results and potential otherwise inexplicable confounding factors. In conclusion, results from epidemiological studies support the mechanistic effects associated with omega-3 fatty acids from high fish consumption, but evidence needs to be further corroborated with more reliable results

Histone deacetylase inhibitors cause TP53-dependent induction of p21/Waf1 in tumor cells with TP53 mutations

The p21/Waf1 protein is one of the main regulators of cell cycle arrest and one of the best-known transcriptional targets of the TP53 protein. Here, we demonstrated that there is activation of expression of the p21/Waf1 gene when the cells were treated with sodium butyrate (NaBu), which is a natural histone deacetylase inhibitor, and investigated whether this phenomenon depends on the presence of a functionally active TP53 protein. For this purpose, we compared the effect of NaBu treatment of human cell lines with different TP53 mutation profiles, including wild-type TP53, single nucleotide substitutions, and the complete absence of the TP53 gene. NaBu activated the TP53 protein via hyperacetylation at the lysine residue K382, without significant changes in the level of protein expression. Western blotting showed that the addition of NaBu triggers a significant increase in the p21/Waf1 protein level in both TP53 wild-type cells and in cells with single nucleotide substitutions in the central DNA-binding core domain (DBD) of the TP53 protein. At the same time, no p21/Waf1 protein induction was observed in cells with complete deletion of the TP53 gene. However, NaBu was not able to induce p21/Waf1 production when the expression of TP53 was transiently knocked down by the p53 siRNA. Overall, our results suggest that NaBu-dependent induction of p21/Waf1 does require the presence of TP53 protein, but, unexpectedly, it can occur regardless of mutational changes in the domain responsible for the TP53 binding to DNA. One possible explanations is that NaBu increases the level of TP53 acetylation and the modified protein is able to establish a new network of protein–protein interactions or trigger conformational changes affecting the TP53-dependent transcriptional machinery even when its DNA binding ability is impaired

Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE)

Background: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. Purpose: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life

Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE)

Background: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. Purpose: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life