Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 16, Issue 2, 2016

Anisakiasis is a zoonosis due to infection with the nematode Anisakis (A.) simplex. Humans represent an accidental host after ingesting raw fish infected with A. simplex. A. simplex larvae lead to a robust host immune response mostly at gastro-intestinal level and, usually, T helper (h)2 lymphocytes play a protective against this nematode. However, larvae can elude immunity triggering activation of T regulatory (Treg) cells, which, in turn, suppress Th2 responses via production of interleukin (IL)-10. According to our own experience in the area of Bari (south Italy) where anisakiasis is endemic, chronic urticaria (CU) is very often associated to A. simplex infection. The cytokine profile in CU patients with Anisakis infection is characterized by an elevated release of interferon-γ and IL-17, while IL-10 production is very low. This pattern of pro-inflammatory cytokine response was consistently detectable in patients who underwent a raw fish free diet regimen over a period of six months. In the light of the above considerations, we hypothesize that treating these patients with polyphenols it may be beneficial in terms of activation of Treg cell function. In fact, polyphenols have the capacity to expand Treg cell response in vitro. In this regard, activation of human Treg cells, by analogy to other helminthiasis, may lead to a reduction of allergic/inflammatory reaction in the course of human anisakiasis.

Immunoglobulin therapy represents a lifesaving intervention for many patients with primary immunodeficiency (PID). Antibody defects represent approximately half of the well-known PIDs requiring immunoglobulin replacement therapy. Following immunoglobulin therapy in PID patients, protection against serious upper and lower respiratory tract infections and pulmonary function improves which leads to an increase in the quality of life of these patients. Successful treatment of PID patients depends on the type of immunodeficiency, regular monitoring of the patient, comorbidities of the patient, and the availability of the products.

Inadequate functional beta cell mass seems to be the primary cause of type 2 diabetes. Increased oxidative stress and inflammation are the leading causes of betacell death. Preservation of functional beta-cell mass in type 2 diabetes is a critical target for type 2 diabetes management. Numerous studies have demonstrated beneficial effects of dietary components on beta cell management in type 2 diabetes, through multiple mechanisms. These dietary components modulate intercellular cascades that inhibit inflammatory molecule synthesis, the formation of free radicals, and nuclear damage, as well as induce antioxidant enzyme expression. The present review article focuses on dietary components and seeks to summarize their mechanism(s) in the prevention of diabetes initiation and progression through beta-cell management in type 2 diabetes.

Background: Beside the influence of nutritional habits and reduced physical activity, metabolic syndrome is associated with alterations in the structure of gut microbiota influencing the inflammatory immune responses. Gut microbiota and microbial metabolic activities are known to affect the lipid and glucose metabolism, satiety and chronic low-grade inflammation in the metabolic syndrome. The aim of the study was to identify genera or even species affecting host metabolism in obesity and type 2 diabetes beside the common used indicator: Firmicutes/ Bacteroidetes ratio. Methods: Differences in gut microbiota were investigated in three groups of subjects over a four month intervention period: type 2 diabetics under GLP1-Agonist therapy, obese individuals without established insulin resistance, both receiving nutritional counseling concerning weight reduction, and a lean control group. Collection of fecal samples was accomplished at two time points, before treatment, and after four months of treatment. For identification of bacteria at species-level we used 454 high-throughput sequencing and fragment length polymorphism analysis based on IS-pro (Intergenic-Spacer-profiling). Five bacterial species, two bacterial genera, total bacterial abundance, and the Firmicutes/Bacteroidetes ratio were determined. Results: Type 2 diabetics showed a higher Firmicutes/Bacteroidetes ratio even with an increase to the second time point (p=0.07). The abundance of B. thetaiotaomicron remained unaffected, whereas B. vulgatus significantly increased in type 2 diabetics (p=0.07) over the study period. Either Alistipes spp. showed an increase in type 2 diabetics between the time points (p=0.06). The abundance of F. prausnitzii (p=0.03) and A. muciniphila (p=0.03) also increased in type 2 diabetics over study period. In addition, the concentration of P. anaerobius (p=0.03) was significantly higher in type 2 diabetics after intervention compared to lean and obese controls. Conclusion: Our results clearly show a difference in the gut bacterial composition in type 2 diabetics compared to lean controls or obesity. Therefore, the ratio of Fimicutes/Bacteroidetes might only be an indicator, but a detailed view at species level is even more important in regard to distinction of their functions.

Background: The aim of this study was to assess serum levels of highly sensitive C-reactive protein (hs-CRP) and adiponectin in subjects with metabolic syndrome and control groups. Methods: There were 40 subjects with metabolic syndrome and 40 control groups. Mean serum level of adiponectin and high sensitive C reactive protein were lower and higher in subjects with metabolic syndrome than control groups, respectively. There were significant positive correlation between high sensitive C reactive protein and waist circumference, systolic and diastolic blood pressure, triglyceride and fasting blood glucose. There were significant negative correlation between adiponectin and waist circumference and triglyceride. Hs-CRP showed a stronger association with metabolic syndrome than adiponectin. Results: Our findings suggest that elevated hs-CRP and reduced adiponectin showed positive and negative association with some metabolic syndrome components. Hs-CRP showed a stronger association with the metabolic syndrome than adiponectin. Conclusion: It seems that hs-CRP may play a significant role as a risk factor for metabolic syndrome. In this study, in contrast with other findings it may suggest that hs-CRP is more important as a diagnostic biomarker for metabolic syndrome than adiponectin. These differences may be due to the changes in the lifestyle and dietary habits in subjects with metabolic syndrome in Gorgan inhabitants. It likes that these subjects do less physical activity and use more fatty nutrients. It seems that subjects with metabolic syndrome need to change their life style and dietary habits in this area to halt the burden of cardiovascular complications.

Background: Metabolic syndrome, described as one of the most common clustering metabolic risk factors in the world, combines minimum three of the following five risk factors: central obesity, elevated fasting glucose, lipid disorders, arterial hypertension and high serum triglycerides. International Diabetes Federation (IDF) in 2009 defined abdominal obesity as the waist circumference of ≥80 cm in women and ≥ 94 cm in men. The research goal of this study is to analyze the anthropometric risk factors for metabolic syndrome, their correlation and effects on metabolic indices related to metabolic syndrome in the analyzed population. Methods: The study population consisted of 90 patients (51 males and 39 females). Total cholesterol, triglycerides, glucose, body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure were measured in all patients. Results: In the complete study group, WC was found to be significantly correlated with BMI (R = 0. 67, P < 0. 001). Furthermore the correlation analysis significantly confirmed positive association between BMI and WC, where other cardiovascular risk factors significantly increased with increasing BMI. Conclusion: Our results show linear correlation between waist circumference and body mass index, suggesting that the presence of MetSy is seen in both healthy males and female in Sarajevo population.This research indicates and confirms that WC and BMI together are good indicators of health risks in both women and men.

Introduction: Diabetic Mellitus is the chronic metabolic illness characterised by hyperglycemia and various complications of heart, eyes, nerves, kidney etc. Diabetic Nephropathy is the leading causes of morbidity and mortality in diabetic patient. We hypothesized that decreased serum folic acid levels are associated with Diabetic Nephropathy. Materials and Method: Our study population consist of 100 subjects out of which 50 cases of Diabetes Mellitus are without Diabetic Nephropathy and 50 cases of Diabetes Mellitus with Diabetic Nephropathy. We measured various routine lab parameters, apart from that, we measured spot urinary albumin to creatinine ratio to assess diabetic nephropathy and we used chemiluminesence based immunoassay to measure serum folic acid. Result: Serum folic acid in the group with nephropathy was significantly lower than that of the group without nephropathy (4.9 ± 0.4 ng/dl) vs (6.8 ± 0.5 ng/dl) p = 0.05. We found that serum folic acid was negatively correlated with spot urinary albumin ratio and on multivariate logistic regression analysis we found that decrease in folic acid significantly (p < 0.05) increases the chances of diabetes with nephropathy by 19.9 %. Conclusion: Our study tilt toward the deficiency of serum folic acid levels in diabetes mellitus patient with nephropathy. So if we would correct folic acid deficiency in diabetic patient then we could prevent the development of various complication associated with diabetes and help in reducing the morbidity and mortality of diabetic patient.

Background: Beta thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia. RBCs hemolysis and repeated blood transfusions are the major causes of secondary iron overload which leads to deposition of iron in different endocrine glands. Delayed puberty and hypogonadism are the most obvious clinical consequences of iron overload. The aim of this study was to evaluate male sex hormone levels in male children with β- thalassemia major in correlation with iron overload. Material and Methods: The present study was conducted on 60 male children with β- thalassemia major with serum ferritin of more than 1000 ng/ml with their age ranging from 11-18 years and mean age value of 14.16±2.48 (Group I) and 60 male children with β- thalassemia major of matched age with no iron overload (Group II). For all children in both groups the following were done: Complete blood count, Hb electrophoresis, serum ferritin, serum iron, TIBC, serum testosterone levels and assessment of testicular volume by ultrasound and Orchidometer. Results: Serum iron and ferritin were significantly higher while TIBC, serum testosterone levels and testicular volume were significantly lower in Group I than Group II (Mean serum iron was 221.70 ± 46.76 in group I versus 122.45 ± 14.32 in group II with p value of 0.001, mean serum ferritin was 2595.06 ± 903.43 in group I versus 373.75 ± 6.82 in group II with p value of 0.001, mean serum TIBC was 210.93 ± 18.17 in group I versus 311.40 ± 13.57 in group II with p value of 0.001, mean serum testosterone was 1.01±1.61 in group I versus 2.73±2.66 in group II with p value of 0.006, mean testicular volume was 4.45± 4.92 in group I versus 8.66±7.08 in group II with p value of 0.016). There was significant negative correlation between serum ferritin and serum testosterone and between serum ferritin and testicular volume in studied patients in group I (r = -0.457 and p value = 0.011 for correlation between ferritin and testosterone and r = -0.908 and p value = 0.001 for correlation between ferritin and testicular volume). Conclusion: Male sex hormone and testicular volume were significantly lower in thalassemic patients with iron overload, significant negative correlation and serum ferritin. Recommendations: Regular follow up for thalassemia patients for early detection of iron overload with regular assessment of puberty as thalassemic patients are vulnerable to develop hypogonadism and may require sex hormone replacement therapy.

Background: Hashimoto’s thyroiditis (HT) is a common autoimmune disease. Vitamin D is an important regulator of immune system. It has been shown in several studies that vitamin D prevents the development of lots of autoimmune diseases. There are some studies that prove vitamin D receptor (VDR) gene polymorphism increases the risk of Hashimoto’s thyroiditis. In this study, we aimed to investigate the association between HT and level of 25(OH)D3, IL-2, IL-4, IL-5, TNF-α and IFN-γ and VDR FokI and TaqI gene polymorphism. Moreover, to find out whether low levels of vitamin D affect HT pathogenesis over inflammatory parameters. Methods: We performed a case-control study that included 136 cases with HT (49 euthyroid, 49 subclinical hypothyroid, 38 hypothyroid patients) and 50 healthy control. Serum levels of 25(OH)D3, glucose, insulin, parathyroid hormone, calcium, phosphorus, alkaline phosphatase were measured and IL-4, IL-5, TNF-α, IFN-γ analysis were performed with ELISA kits in all 186 subjects. Genetic analysis for VDR FokI and TaqI gene polymorphisms were done by RFLP in all subjects. Results: Mean serum 25(OH)D levels were 14.88±8.23 ng/ml in patient with HT and 15.52±1.34 ng/ml in healthy controls. There were no statically significant differences between the groups in terms of vitamin D levels (P=0.977). Prevalence of vitamin D insufficiency in HT cases was significantly higher than controls (p=0.02). Although serum IL-2, IL-4, TNF-α and IFN-γ were significantly higher in HT patients, there were no significant differences regarding IL-5 levels. Significant differences were observed between the groups regarding the genotype of TaqI but no differences regarding FokI genotype. Conclusion: Vitamin D insufficiency is associated with HT. There is a relationship between VDR TaqI gene polymorphism and HT. Although vitamin D levels are low in both patient and control group, detection of high level of inflammatory parameters in HT group makes us think that low level of vitamin D does not affect HT pathogenesis over these parameters.

Background: Activation of the nuclear factor-kappa β (NF-ΚB) signaling results in releasing of a variety of inflammatory cytokines that can induce skeletal muscle wasting (MW) in mammals. Curcumin is a natural product from spice turmeric that can block biological events in which NF-ΚB plays a critical role. Objective: The present study was conducted to evaluate the beneficial effects of curcumin on the NF-ΚB-dependent MW in rats. Methods: The MW rats were induced by lipopolysaccharide (LPS) injection and rats were fed 15 g curcumin per kg diet for 16 d. Results: LPS not only decreased the growth performance of rat, but significantly elevated its serum IL-1 concentration and muscle proteolysis rate. Interestingly, curcumin significantly prevented the muscle proteolysis rate and down-regulated expression levels of two critical muscle-specific ubiquitin ligases (Atrogin-1 and MuRF-1). When muscles from MW rats were incubated with curcumin in vitro, the calpain-, cathepsin L-, and proteasome-dependent muscle proteolysis were significantly decreased. Moreover, the nuclear NF-ΚB/p65 protein abundance were also decreased by curcumin. Conclusion: The results not only suggest a molecular mechanism by which curcumin modulates the inflammatory responses, but also offer a feasible avenue to ameliorate the NF-ΚB-dependent muscle proteolysis.

Background: Beta-thalassemia is ‘a hereditary blood disorder characterized by reduced or absent beta globin chain synthesis, resulting in reduced hemoglobin in red blood cells, decreased RBCs production and anemia’. Patients with thalassemia major require repeated blood transfusions which ‘lead to accumulation of iron in different tissues, including tissues of endocrine glands’. This study aims to evaluate serum gonadal hormones levels in adolescent females with β-thalassemia in relation to iron overload. Subjects and Methods: This study was conducted on 80 adolescent females with β-thalassemia having serum ferritin over 1000 ng/ml with range of their ages between 11 -15 years and mean age of 12. 42 ± 1.12 years (Group I) and 80 females with β-thalassemia of matched age having serum ferritin less than 500 ng/ml (Group II). For all patients the following were done: Complete blood count, hemoglobin electrophoresis, serum iron status including ‘serum ferritin, serum iron and total iron binding capacity and’ gonadal hormones including LH, FSH, and serum Estrogen. Results: ‘There were significantly higher serum ferritin and serum iron and significantly lower TIBC’, Follicular Stimulating Hormone, Luteinizing Hormone and Estrogen levels in Group I compared with Group II (Mean serum ferritin was 1839.5 ± 258.2 ng/ml in group I versus 336.2 ± 33.5 ng/ml in group II with p value of 0.001, mean serum iron was 201.3 ± 38.43 ug/dl in group I versus 124.47 ± 12.23 ug/dl in group II with p value of 0.001, mean serum total iron binding capacity was 252.56 ± 23.21 ug/dl in group I versus 353.6 ± 31.79 ug/dl in group II with p value of 0.001, mean FSH level was 1.17 ± 0.67 mIU/ml in group I versus 2.55 ± 1.92 mIU/ml group II with p value of 0.029, mean LH level was 0.98 ± 0.25 mIU/ml in group I versus 1.91 ± 0. 42 mIU /ml in group II with p value of 0.016, mean Estrogen level was 22.46 ± 6.36 pg/ml in group I versus 35 .63 ± 8.63 pg/ml in group II with p value of 0.010). There were significant negative correlations between gonadal hormones including serum Follicle-Stimulating Hormone, Luteinizing Hormone, Estrogen and serum ferritin (r = - 0. 835 and p value of 0.01 for FSH and serum ferritin, r = -0. 949 and p value of 0.01 for LH and serum ferritin and r= - 0. 900 and p value of p 0.01 for Estrogen and serum ferritin. Conclusion: Female patients with β-thalassemia with iron overload may have gonadal hormones deficiency with significant negative correlation between gonadal hormones and serum ferritin. Recommendations: Regular iron chelation to prevent iron overload with subsequent irreversible damage of the ovaries and also regular follow up for females with β-thalassemia with assessment of puberty as they are more vulnerable to develop hypogonadism and may require hormonal replacement therapy.

Context: An empty sella is a relatively common condition, often being an incidental finding at MRI or CT scan. It can develop because of the intrasellar herniation of Cerebro-spinal Fluid (CSF) and arachnoid membrane through an absent or rudimentary diaphragm sellae in concomitance of a sudden and even transient increment of intracranial pressure, leading to a picture in which the pituitary is flattened along the floor of the sella. Case Description: A young female with headache, nausea, dizziness, diplopia and visual impairment showed an empty sella on MRI and increased CSF pressure at the lumbar puncture. After an initial improvement, there was a progressive worsening of the headache, especially in orthostatic position, with transient relief after bed rest and hydration. At MRI the empty sella was no longer evident, cerebellar tonsils were displaced in the occipital foramen and there was an impregnation of the meninges after contrast medium, a picture of CSF hypotension, probably due to the previously performed lumbar puncture causing a fistula with leak of CSF and consequent disappearance of the empty sella. The patient gradually improved after being submitted to epidural blood patch. Conclusions: The case here reported demonstrates that an empty sella can be a reversible condition in rare cases. Its disappearance can be due to the reduction in intracranial pressure caused by the lumbar puncture itself. The changes in the characteristics of the headache, in particular its worsening in the orthostatic position, should lead to the suspicion of CSF leak through a fistula and consequent intracranial hypotension, a dangerous and sometimes life-threatening condition.