Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 17, Issue 4, 2017

Background and Objectives: Maternal prenatal stress (MPS) may result in a range of longterm consequences in the offspring among which there is susceptibility to allergic diseases. This review presents the current knowledge on the pathways through which MPS may affect the fetus, and the existing evidence regarding the association between MPS and development of allergy in the offspring. Result and Discussion: A pivotal mediator triggered in response to stress is the release of glucocorticoids (GC). GC may affect gene expression through binding to GC receptors, thus affecting fetal development in general, and allergic vulnerability in particular. A series of recent findings also indicate that MPS may affect the fetus programming of immune functions and lead to vulnerability of the immune system. MPS may hinder the gradual process in the offspring's cytokine production towards a Th1 type immune response. Prenatal factors may also influence the intrauterine microbiome and thereby the maternal bacteria transferred into the fetal gastrointestinal tract. The imbalances of intestinal microbiota in infancy could result in deviations in the development of systemic immune function, predisposing to allergic sensitization. Epidemiological studies in humans also suggest that there is an association of MPS and allergic vulnerability of the offspring. Conclusion: Although the existing evidence support a relationship of MPS with allergic predisposition of the offspring, further studies are needed to elucidate whether the association is dependent on the type of stress and whether it involves any type of allergic predisposition or not.

Background and Objective: Increasing evidence has demonstrated that dietary products and their active components are independently or jointly responsible for the apparent reduction of the cardiovascular diseases (CVDs) risk. Discussion: Nowadays, there is a growing attention in the use of nutraceuticals as a new approach for the prevention and management of many diseases, as well as for controlling rising of chronic illnesses with minimal side effects. Food-derived peptides, as well as peptide-rich protein hydrolysates, represent new and valuable tools for the prevention of metabolic and cardiovascular diseases, acting as modulators of oxidative stress, inflammation, and overactivity of the renin–angiotensin system (RAS). Conclusion: This review summarizes the recently published data on antioxidant, anti-inflammatory, and vascular protective properties of nutraceuticals, notably on the effects of food-derived bioactive peptides and protein hydrolysates, paying particular attention to those derived from fermented foods.

Background and Objective: Prostate cancer is the most prevalent non-cutaneous cancer in men, which causes significant mortality among the patients. Since prostate cancer cells are stimulated by androgen, effective androgen ablation in men is one of the essential strategies in the management of prostate cancer. Discussion: Several treatment options are available for different stages of prostate cancer. Hormone therapy known as androgen deprivation therapy (ADT) is the first line treatment used to treat advanced prostate cancer. Chemical castration by gonadotropin-releasing hormone agonists suppresses lutenizing hormone production, which in turn inhibits the production of testosterone and dihydrotestosterone. This will prevent the growth of prostate cancer cells. However, ADT causes deleterious effects on bone health because the androgens are essential in preserving optimal bone health in men. Conclusion: Various observational studies showed that long-term ADT for advanced or metastatic prostate cancer was associated with decreased bone mineral density, as well as altered body composition that might affect bone health. Considering the potential impact of osteoporotic fracture, interventions to mitigate these skeletal adverse effects should be considered by physicians when initiating ADT on their patients.

Background and Objective: The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficiency (GHD) and in compensated panhypopituitarism including GH deficit. Methods: Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was carried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heterogeneity test (Chi-square statistic). Results: Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global outcome D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85). Conclusion: Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months.

Background and Objectives: Personalized management of diabetes has become an imperative since majority of monotherapy fails within 3 years of its use. Identifying responders from nonresponders for a certain type of therapy would reduce a period of unsuccessful treatment and minimize health care costs. Incretin therapies, mainly glucagon-like peptide (GLP)-1 receptor agonists (GLP- 1RA) are relatively new glucose-lowering agents which increase insulin and lower glucagon response as well as slow down glucose absorption by acting on gastric emptying. However, problem with incretin- based therapy is distinguishing responders from non-responders and currently lack of specific predictors of treatment response. Discussion: Experimental data demonstrated that activation of GLP-1 and gastrin signaling induces beta cell neogenesis, leading to glucose-dependent insulin secretion. Several studies demonstrated better glycemic control in patients with type 2 diabetes (DMT2) co-treated with proton pump inhibitors (PPI) and incretin based therapy agents. Conclusion: Higher gastrin levels in patients with diabetes prior to initiation of treatment with incretin mimetics could suggest a better potential for reversible human β-cell reprogramming with concomitant incretin therapy. Therefore, baseline levels of endogenous gastrin could be used as a predictor of response to GLP-1 therapy. In addition, treatment with PPI could also raise gastrin levels and in patients treated with GLP-1RA, lead to better glycemic control by initiating β-cell neogenesis and proliferation of pancreatic β-cells.

Background: Fatty acid profile can be considered an appropriate biomarker for investigating the relations between the patterns of fatty acid metabolism and specific diseases, as cancer, cardiovascular and degenerative diseases. Objective: Aim of this study was to test the effects of diets enriched with olive oil and omega-3 Polyunsaturated Fatty Acids (PUFAs) on fatty acid profile in intestinal tissue of ApcMin/+ mice. Method: Three groups of animals were considered: control group, receiving a standard diet; olive oilgroup, receiving a standard diet enriched with olive oil; omega-3 group, receiving a standard diet enriched with salmon fish. Tissue fatty acid profile was evaluated by gas chromatography method. Results: Olive oil and omega-3 PUFAs in the diet differently affect the tissue fatty acid profile. Compared to control group, the levels of Saturated Fatty Acids (SFAs) were lower in olive oil group, while an increase of SFAs was found in omega-3 group. Monounsaturated Fatty Acids (MUFAs) levels were enhanced after olive oil treatment, and in particular, a significant increase of oleic acid levels was detected; MUFAs levels were instead reduced in omega-3 group in line with the decrease of oleic acid levels. The total PUFAs levels were lower in olive oil respect to control group. Moreover, a significant induction of Saturation Index (SI) levels was observed after omega-3 PUFAs treatment, while its levels were reduced in mice fed with olive oil. Conclusion: Our data demonstrated a different effect of olive oil and omega-3 PUFAs on tissue lipid profile in APCMin/+ mice.

Background: Universal reference values of penile length, circumferences and testicular volume in newborns and infants are inappropriate to be used in variable ethnic backgrounds. Objective: The aim of this prospective study was to establish normal reference values for stretched penile length, penile circumference and testicular volume for Egyptian newborn and infants. Subjects and Methods: This observational cross-sectional study included 1850 healthy male full term newborn and infants applied for routine check-up, aged 0 -24 months, the newborn and infants were recruited from Tanta University Hospital in the period from July 2015 to January 2017. Penile length, penile circumference, testicular volume, weight, length and occipito-frontal circumference were measured. Results: The studied infants were divided into five groups. Group I: 1-4 weeks, the mean penile length was 3.51 ± 0.49 cm, penile circumference was 3.95 ± 0.48 cm, and testicular size was (right 1.81 ± 0.44 cm and left 1.67 ± 0.47 cm). Group II: > 1-6 months age, the mean penile length was 3.99 ± 0.46 cm, penile circumference was 4.10 ± 0.38 cm, and testicular size was (right 2.10 ± 0.33 cm and left 2.04 ± 0.27 cm). Group III: >6-12 months age, the mean penile length was 4.45 ± 0.48 cm, penile circumference was 4.21 ± 0.33 cm, and testicular size was (right 2.13 ± 0.33 cm and left 2.06 ± 0.28 cm). Group IV: >12-18 months age, the mean penile length was 4.55 ± 0.54 cm, penile circumference was 4.28 ± 0.32 cm, and testicular size was (right 2.12 ± 0.33 cm and left 2.09 ± 0.32 cm). Group V: >18-24 months age, the mean penile length was 4.89 ± 0.63 cm, penile circumference was 4.45 ± 0.33 cm, and testicular size was (right 2.28 ± 0.45 cm and left 2.25 ± 0.45 cm). There were significant positive correlations between penile length, penile circumference, left and right testicular volumes with each other and also with all other anthropometric measures including: weight, height and head circumference. Conclusion and Recommendation: The age-related values of penile and testicular measurements must be known to be able to determine the abnormal sizes and to monitor treatment of underlying diseases. Our study is a step to achieve accurate reference values of penile and testicular measurements for Egyptian male newborns and infants. Therefore multicenter studies are recommended to establish Egyptian norms.

Objective: To investigate potential reproductive effects of Pterocarpus marsupium methanolic extract on testosterone propionate induced Polycystic Ovarian Syndrome (PCOS) in female albino rats. Methodology: PCOS was induced in female albino rats by daily injecting testosterone propionate for 15 days intraperitoneally. Animals are divided into five groups with six rats per group. Group 1: Control group received olive oil, Group 2: Testosterone propionate+natural recovery, Group 3: Testosterone propionate + a dose of clomiphene citrate (standard), Group 4 and 5: Testosterone propionate + low dose (200mg/kg) and high dose (400mg/kg) b.w respectively for 15 days. Various biochemical and histopathological investigations were assessed. Results: Methanol extract of Pterocarpus marsupium was able to exert its protective effect successfully by restoring all the parameters to normal and diminishing the cysts found in ovaries. Conclusion: Pterocarpus marsupium showed potential reproductive effects on testosterone propionate induced PCOS female albino rats and could be used as an alternative therapy in the treatment of PCOS.

Background: Nickel (Ni) is a metal largely present in the environment and prolonged exposure to it may lead to multiple pathological conditions in human subjects. Among these, the most frequent is allergic contact dermatitis. Methods: Peripheral blood mononuclear cells isolated from 25 patients with Ni-dependent contact dermatitis were evaluated in terms of cytokine release and nitric oxide (NO) production in the presence or absence of two doses (3 and 5 μg, respectively) of polyphenols. Results: Polyphenols were able to reduce the increased release of interferon-γ and interleukin (IL)-4, while maintaining the equilibrium between IL-10 and IL-17. At the same time, exaggerated release of NO was reduced by polyphenol supplementation. Conclusion: In view of their anti-inflammatory activities, polyphenols may represent a potential therapeutic tool to treat Ni-sensitized patients.

Background: Common variable immunodeficiency (CVID) is a heterogeneous immune deficiency characterized by hypogammaglobulinemia. Since B cell maturation and differentiation is defective in this disorder, we evaluated apoptosis in B cells of patients with CVID compared with healthy donors (HD). Methods: Determination of peripheral blood B-cell subsets in CVID and HDs, was performed using flow cytometry. We compared total apoptosis, early apoptosis and late apoptosis/necrosis in unstimulated and stimulated B-cells of patients with CVID and HDs. We also assessed the expression of the anti-apoptotic molecule BCL2 mRNA levels in B-cells by real-time PCR in CVID patients compared with HDs. Results: Total B-cell apoptosis was increased in both unstimulated and stimulated B-cells from CVID patients compared with HDs (p=0.02 and p=0.004). Early apoptosis in stimulated B-cells (p=0.04) and late apoptosis/necrosis of B-cells in both unstimulated and stimulated B-cells (p=0.04 and p=0.03, respectively) were significantly higher in CVID patients compared with HDs. There was a significant inverse correlation between the percentages of post germinal center B-cells in the peripheral blood of CVID patients compared with percentage of apoptotic B-cells. However, anti-apoptotic BCL2 expression was not significantly reduced in B-cells from CVID patients compared with HDs (p=0.16). Conclusion: Increased apoptosis of B-cells may be a factor in abnormality of differentiated B-cell subsets and the impaired endogenous immunoglobulin production in CVID patients. Further studies of the expression of pro/anti-apoptotic mediators in B-cells of CVID patients may shed light on the mechanism behind this increased B-cell apoptosis, and present potential therapeutic interventions in the future.