Advanced Glycation end products (AGEs) in food: focusing on Mediterranean pasta

5Advanced glycation end products, also known as glycotoxins, are a diverse group of highly oxidant compounds with pathogenic significance in aged-chronic disease, including diabetes, cardiovascular disease and neurodegenerative disease. They are produced physiologically in the body when reducing sugar binds to a free amino acid group of macromolecules. Thus conditions such as hyperglycemia and/or oxidative stress can favor AGE product formation, contributing to ageing processes and the exacerbation of pathological states. Beside endogenous AGEs, dietary AGE intake contributes significantly to the body AGE pool. It assumes that if dietary AGE intake gets lower, any chronic disease, such as diabetes and cardiovascular disease can be ameliorated, and even cured. For this reason, recently great attention has been made on the identification and quantification of AGE products in the consumed foods. Here we reviewed some knowledge, found in literature, concerning the formation of AGEs in food, their gastrointestinal absorption, and their toxic effects. In addition original data on AGE content in the Mediterranean pasta was discussed in relation to their production processes and cooking time.openopenAbate, G.; Delbarba, A.; Marziano, M.; Memo, M.; Uberti, D.Abate, Giulia; Delbarba, Andrea; Marziano, Mariagrazia; Memo, Maurizio; Uberti, Daniela Letizi

Gonadal Function in Male Patients With Metastatic Renal Cell Cancer Treated With Sunitinib

Background/aim: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. Patients and methods: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. Results: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. Conclusion: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib

Liquid levothyroxine formulations in patients taking drugs interfering with L-T4 absorption

PurposeTo describe the current knowledge on thyroid hormonal profile in patients on liquid L-T4 therapy and drugs known to interfere with L-T4 absorption. MethodsA PubMed/MEDLINE, Web of Science, and Scopus research was performed. Case reports, case series, original studies and reviews written in English and published online up to 31 August 2022 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. ResultsThe available data showed that novel levothyroxine formulations circumvent gastric pH impairment due to multiple interfering drugs such as proton pump inhibitors, calcium or iron supplements, sevelamer, aluminum/magnesium hydroxide and sodium alginate. ConclusionNew formulations can be taken simultaneously with drugs interfering with L-T4 absorption, in particular liquid formulations. Softgel capsules need more studies to support these data

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study

ObjectiveHypogonadism is common in male patients with adrenocortical carcinoma (ACC) who are under treatment with mitotane, but the phenomenon is underestimated, and its prevalence has been poorly studied. This single-center retrospective longitudinal study was undertaken to assess the frequency of testosterone deficiency before and after mitotane therapy, the possible mechanism involved, and the relationship between hypogonadism with serum mitotane levels and prognosis.Research design and methodsConsecutive male ACC patients followed at the Medical Oncology of Spedali Civili Hospital in Brescia underwent hormonal assessment to detect testosterone deficiency at baseline and during mitotane therapy.ResultsA total of 24 patients entered the study. Of these patients, 10 (41.7%) already had testosterone deficiency at baseline. During follow-up, total testosterone (TT) showed a biphasic evolution over time with an increase in the first 6 months followed by a subsequent progressive decrease until 36 months. Sex hormone binding globulin (SHBG) progressively increased, and calculated free testosterone (cFT) progressively decreased. Based on cFT evaluation, the proportion of hypogonadic patients progressively increased with a cumulative prevalence of 87.5% over the study course. A negative correlation was observed between serum mitotane levels >14 mg/L and TT and cFT.ConclusionTestosterone deficiency is common in men with ACC prior to mitotane treatment. In addition, this therapy exposes these patients to further elevated risk of hypogonadism that should be promptly detected and counteracted, since it might have a negative impact on quality of life

Autoimmune polyglandular syndrome type 4: experience from a single reference center

Purpose: To characterize patients with APS type 4 among those affected by APS diagnosed and monitored at our local Reference Center for Autoimmune Polyglandular Syndromes. Methods: Monocentric observational retrospective study enrolling patients affected by APS diagnosed and monitored in a Reference Center. Clinical records were retrieved and analyzed. Results: 111 subjects (51 males) were affected by APS type 4, mean age at the onset was 23.1 ± 15.1 years. In 15 patients the diagnosis of APS was performed during the first clinical evaluation, in the other 96 after a latency of 11 years (range 1-46). The most frequent diseases were type I diabetes mellitus and celiac disease, equally distributed among sexes. Conclusions: The prevalence of APS type 4 is 9:100,000 people. Type I diabetes mellitus was the leading indicator of APS type 4 in 78% subjects and in 9% permitted the diagnosis occurring as second manifestation of the syndrome. Our data, showing that 50% of patients developed APS type 4 within the first ten years, don't suggest any particular follow-up time and, more importantly, don't specify any particular disease. It is important to emphasize that 5% of women developed premature ovarian failure

An Integrated Approach for a Structural and Functional Evaluation of Biosimilars: Implications for Erythropoietin

BACKGROUND: Authorization to market a biosimilar product by the appropriate institutions is expected based on biosimilarity with its originator product. The analogy between the originator and its biosimilar(s) is assessed through safety, purity, and potency analyses. OBJECTIVE: In this study, we proposed a useful quality control system for rapid and economic primary screening of potential biosimilar drugs. For this purpose, chemical and functional characterization of the originator rhEPO alfa and two of its biosimilars was discussed. METHODS: Qualitative and quantitative analyses of the originator rhEPO alfa and its biosimilars were performed using reversed-phase high-performance liquid chromatography (RP-HPLC). The identification of proteins and the separation of isoforms were studied using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF–MS) and two-dimensional gel electrophoresis (2D-PAGE), respectively. Furthermore, the biological activity of these drugs was measured both in vitro, evaluating the TF-1 cell proliferation rate, and in vivo, using the innovative experimental animal model of the zebrafish embryos. RESULTS: Chemical analyses showed that the quantitative concentrations of rhEPO alfa were in agreement with the labeled claims by the corresponding manufacturers. The qualitative analyses performed demonstrated that the three drugs were pure and that they had the same amino acid sequence. Chemical differences were found only at the level of isoforms containing N-glycosylation; however, functional in vitro and in vivo studies did not show any significant differences from a biosimilar point of view. CONCLUSION: These rapid and economic structural and functional analyses were effective in the evaluation of the biosimilarity between the originator rhEPO alfa and the biosimilars analyzed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40259-015-0136-3) contains supplementary material, which is available to authorized users

INSL3: a marker of Leydig cell function and testis-bone-skeletal muscle network

This article reviews the role of INSL3 as biomarker of Leydig cell function and its systemic action in testis-boneskeletal muscle crosstalk in adult men. Insulin-like factor 3 (INSL3) is a peptide hormone secreted constitutively in a differentiation-dependent mode by testicular Leydig cells. Besides the role for the testicular descent, this hormone has endocrine anabolic functions on the bone-skeletal muscle unit. INSL3 levels are low in many conditions of undifferentiated or altered Leydig cell status, however the potential clinical utility of INSL3 measurement is not yet well defined. INSL3 levels are modulated by the long-term cytotropic effect of the hypothalamic- pituitary-gonadal axis, unlike testosterone that is acutely sensitive to the stimulus by luteinizing hormone (LH). INSL3 directly depend on the number and differentiation state of Leydig cells and therefore it represents the ideal marker of Leydig cell function. This hormone is more sensitive than testosterone to Leydig cell impairment, and the reduction of INSL3 in adult men can precociously detect an endocrine testicular dysfunction. Low INSL3 levels could cause or contribute to some symptoms and signs of male hypogonadism, above all sarcopenia and osteoporosis. The evidence provided, suggested that the measurement of INSL3 levels should be considered in the clinical management of male hypogonadism and in the evaluation of testicular endocrine function. The monitoring of INSL3 levels could allow an early detection of Leydig cell damage, even when testosterone levels are still in the normal range

Positive effect of nutraceuticals on sperm DNA damage in selected infertile patients with idiopathic high sperm DNA fragmentation

The use of nutraceuticals to improve sperm parameters and male fertility is debatable, even if evidence suggests that selected infertile patients might benefit from their use. In particular, oxidative stress might play a role in idiopathic male infertility, leading to sperm membrane damage and high sperm DNA fragmentation (SDF). The aim of this study was to evaluate, in selected idiopathic infertile men with high SDF, the effect on sperm DNA damage and on standard semen parameters of a nutraceutical formulation containing myoinositol, alpha lipoic acid, coenzyme Q10, selenium, zinc and B vitamins

Osteoporosis in men with hypogonadism because of ApoA-I Leu75Pro amyloidosis under long-term testosterone therapy

Background: Apo A-I Leu75Pro amyloidosis is a rare systemic hereditary disease, whose hallmark and earliest involvement is testicular impairment, characterized by hypogonadism and macrorchidism; renal and hepatic involvement are the other characteristics. Objective: To evaluate for the first time the prevalence of osteopenia, osteoporosis and vertebral fractures (VFs) in men with this form of amyloidosis affected by hypogonadism and under long-term testosterone replacement therapy (TRT). Materials and methods: Retrospective study on 50 men >50 years (median age 64.5) with dual-energy X-ray absorptiometry (DXA), hormonal, and biochemical data available at least 3 years after the start of TRT. Serum gonadal hormones and bone markers, lumbar and femoral DXA-scan with morphometric assay for evaluation of VFs were assessed. Results: At 7.5 years from start of TRT, lumbar and/or femoral osteopenia and osteoporosis were found in 54% and 10% of patients, respectively. Of the men who had the morphometric assay performed, five of 34 (14.7%) had VFs. Compared to patients with normal bone mineral density, men with osteopenia and osteoporosis were older, had lower body mass index, higher sex hormone binding globulin and showed more frequently renal involvement. Multiorgan involvement, without different TRT dosage, was associated with lower testosterone levels. Discussion and conclusion: Men with hypogonadism because of Apo A-I Leu75Pro amyloidosis under long-term TRT had a high burden of low bone mass (64%) and VFs (almost 15%). Osteopenia-osteoporosis was more frequently observed in older patients with multi-organ disease, which might contribute to impair bone health beyond hypogonadism

Wpływ suplementacji selenu na przywrócenie eutyreozy u chorych na subkliniczną niedoczynność tarczycy w wyniku autoimmunologicznego zapalenia tarczycy

  Intriduction: The thyroid is an organ with one of the highest selenium concentrations, containing many selenoproteins implicated in thyroid hormone metabolism. Treatment with levothyroxine has been recommended for all subclinical hypothyroid patients with TSH levels > 10 mU/L, whereas for those with TSH< 10 mU/L treatment remains controversial. Aim: A randomised controlled prospective study was performed to investigate the effects of Se treatment on patients with autoimmune thyroiditis and mild sub-clinical hypothyroidism (TSH < 10 mU/L). Material and methods: A total of 196 patients with autoimmune thyroiditis were recruited in the study. Patients were assigned to receive (case) or not receive (control) an oral selenomethionine treatment. Cases received 83 mcg selenomethionine/day orally for four months. All the patient’s charts were submitted to thyroid hormonal profile (TSH, fT4) and TPOAb evaluation upon enrolment and at the end of the study. Results: In total 192 patients completed the study. Cases and controls were superimposable for age, gender, thyroid hormonal profile, and TPOAb levels. At the end of the study, 33/192 (17.2%) participants restored euthyroidism (Responders). Responders were significantly more frequent among Cases than Controls (30/96 [31.3%] vs. 3/96 [3.1%], p < 0.0001). Conclusion: Selenium supplementation could restore euthyroidism in one third of subclinical hypothyroidism patients with autoimmune thyroiditis. (Endokrynol Pol 2016; 67 (6): 567–571)    Wstęp: Tarczyca jest narządem, w którym występuję jedno z najwyższych stężeń selenu, zawierającym wiele selenoprotein biorących udział w metabolizmie hormonów tarczycy. Leczenie lewotyroksyną jest zalecane u wszystkich chorych z subkliniczną niedoczynnością tarczycy, u których stężenia TSH wynoszą > 10 mj./l, natomiast u osób ze stężeniem TSH < 10 mj./l takie leczenie pozostaje kontrowersyjne. Cel: Randomizowane prospektywne badanie z grupą kontrolną przeprowadzono w celu oceny wpływu leczenia selenem u chorych z autoimmunologicznym zapaleniem tarczycy i łagodną subkliniczną niedoczynnością tarczycy (TSH < 10 mj./l). Materiał i metody: Do badania włączono 196 chorych z autoimmunologicznym zapaleniem wątroby. Chorych podzielono na dwie grupy: badaną i kontrolną, którym doustnie podawano preparat selenometioniny. Osobom z grupy badanej podawano doustnie 83 mcg selenometioniny/dobę przez 4 miesiące. U wszystkich chorych oznaczono stężenia hormonów tarczycy (TSH, fT4) przeciwciał przeciw TPO na początku i na końcu badania. Wyniki: Badanie ukończyło 192 chorych. Grupa badana i grupa kontrolna były porównywalne pod względem wieku, płci oraz stężeń hormonów tarczycy i przeciwciał przeciw TPO. W momencie zakończenia badania przywrócenie eutyreozy stwierdzono u 33/192 (17,2%) uczestników (odpowiedź na leczenie). Odpowiedź na leczenie występowała istotnie częściej w grupie badanej niż w grupie kontrolnej (30/96 [31,3%] vs. 3/96 [3,1%]; p < 0,0001). Wnioski: Suplementacja selenem spowodowała przywrócenie eutyreozy u jednej trzeciej chorych z subkliniczną niedoczynnością tarczycy w wyniku autoimmunologicznego zapalenia tarczycy. (Endokrynol Pol 2016; 67 (6): 567–571)