Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Immunology, Endocrine and Metabolic Agents) - Volume 14, Issue 1, 2014

As the Editor-in-Chief of Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (IEMAMC; formerly 'Current Medicinal Chemistry - Immunology, Endocrine and Metabolic Agents', online ISSN 1875-5844, print ISSN 1871- 5222), a quarterly peer-reviewed journal, I wish a warm welcome to all the readers. It is already known that, IEMAMC aims to cover all the latest and outstanding developments in the field of medicinal chemistry and rational drug design for the discovery of new immunology, endocrine & metabolic agents. This field is now rapidly growing due to the tremendous increase in the instances of the diabetes and obesity. The number of the submissions to the journal was 45 in 2013 from Italy, Portugal, England, USA, Japan, Spain and others. The number of the submissions is maintained in 2014, since it was 48 in 2013, and 32 in 2012. In 2014, the number of submission is expected to increase. Each issue contains a series of timely in-depth reviews and original research articles written by laureates in the field covering a range of current topics in immunology, endocrine & metabolic medicinal chemistry. It takes 8-10 weeks for IEMAMC to be reviewed. IEMAMC is now indexed in BIOSIS Previews, BIOSIS Reviews Reports and Meetings, Chemical Abstracts, EMBASE/ExcerptaMedica, Scopus, GenamicsJournalSeek, MediaFinder®-Standard Periodical Directory, PubsHub, J-Gate. Therefore, IEMAMC recognizes a space for any basic research and clinical experiences in immunology, endocrinology and metabolism.

INTRODUCTION TO EDITION The objective of this edition is to present hypothesis and the main evidence about areas of nutrition, immunology, cancer, diabetes and infectious diseases. The articles presented in this edition untitled “Nutrition and immunology in Diabetes, cancer and infectious diseases”, are result of three mini reviews that summarize the main studies that have addressed these issues and described with detail the mechanism of different nutrient over some pathologies. The first mini review, “The Role of the Healthy Dietary Intake in Women with Human Papilloma Virus”, is about the most common viral sexually transmitted infection in humans and the lesions caused by HPV are under the influence of immunological factors. Nutritional status and intake adequate amounts of macronutrients (protein, carbohydrates and fat) and micronutrients (mainly zinc, folic acid and vitamin A), facilitate appropriate functioning of the immune system [1, 2]. Several studies have reported beneficial associations with the intake of some micronutrients, among them being mainly vitamin A and C and folic acid. These compounds have a chemopreventive effect due to their antioxidant action [1]. This evidence reflect the importance of consider a dietary and nutritional approach in treating these infection disease. The second mini review “The Role of NO-cGMP Signaling Pathway in Pancreatic Beta-cell Function” highlights that in the last decades, there has been an increasing evidence on the role of nitric oxide (NO) on the function of pancreatic islet cells, but it has not been fully elucidated. There are many reports about the negative effects of NO on the beta-cell function and its survival [3, 4]. The study of the main mechanisms, and the role of NO in beta-cells, may lead to new aspects in insulin secretion modulation and therefore, to the establishment of novel therapeutic targets for diabetes treatment [4]. The third article, “Anti-inflammatory and Antitumor Properties of Eriobotrya Japonica Lindl: Mini-Review”, is about the anti-inflammatory and anti-tumor properties of Eriobotrya japónica extracts and isolated phytochemical compounds, where the Astringent leaves of loquat have been used to treat asthma, chronic bronchitis, coughs, phlegm, high fever, cancer, diabetes, and gastroenteric disorders [5] and are widely used as a herbal remedy in many countries. But it is important to continue to search their effects. The nutrition aspects are important for understanding the knowledge about inflammation, metabolic disorder, and damage in organs and systems [6]. This edition covers the main diseases that may have some form of prevention or healing coming from the nutrition area.

Human papillomavirus (HPV) is the most common sexually transmitted viral infection in humans. More than half of sexually active women and men are infected with HPV at some point in their lives. The behavior of lesions caused by HPV is under the influence of immunological factors; cell-mediated immunity is an important aspect. Some authors report that women with severe immunosuppression have an increased risk of cytological abnormalities in the presence of a high load of HPV due to persistent infection. When nutritional status is poor in macronutrients (proteins, carbohydrates and fats) and micronutrients (mainly zinc, folic acid and vitamin A), immune function is limited, which leaves the body unprotected against infectious pathogens like HPV. Several studies have reported beneficial associations with the intake of some micronutrients such as vitamins A and C, folic acid, etc. These compounds have a chemopreventive effect due to their antioxidant action. Analyzing the intake of some foods in patients with HPV will allow control of the injuries caused by the virus. A dietary and nutritional approach in treating these patients should be considered.

Insulin-secretion in pancreatic beta-cells is modulated by several second messengers and complex signaling pathways. Nitric oxide has been usually associated with beta-cell apoptosis, as part of the physiopathology of Type-2 diabetes. However there is increasing evidence that NO/cGMP signaling pathway is also involved in the secretory function through the activation of some target proteins such as the modulation of glucokinase activity, ionic channels, protein kinases, phosphodiesterases; and gene expression through the activation of transcription factors. These observations could be useful to establish new therapeutic strategies to maintain beta-cell optimal response before the development of islet dysfunction that leads to diabetes.

Eriobotrya japonica Lindl. (Rosaceae) is widely used as an herbal remedy in many countries. Astringent leaves of loquat have been used to treat asthma, chronic bronchitis, coughs, phlegm, high fever, cancer, diabetes, and gastroenteric disorders. Various phytochemical compounds, such as triterpenes, sesquiterpenes, flavonoids, tannins, and megastigmane glycosides, have been found in the leaves of this plant and some of these compounds have been reported to be biologically active, exhibiting anti-inflammatory, antiviral, antioxidant, cytotoxic, anti-mutagenic, anti-tumor, or hypoglycemic properties. In this review, we will present the anti-inflammatory and antitumor properties of Eriobotrya japonica extracts and isolated phytochemical compounds, highlighting the need for further evidence-based research.

Objectives: To evaluate the serum levels of common autoimmune parameters in women with polycystic ovary syndrome (PCOS) and compare with the control group. Design: prospective case-control study. Setting: Academic research institution. Patients: 102 women with PCOS and 100 healthy controls. Interventions: Questionnaire, physical examination, sonography, blood sampling. Main outcome measure(s): Serum levels of Anti Ds-DNA, Anti SS-A, Anti SS-B, Anti Sm, Anti RNP/sm, Anti Scl70and Anti jo-1 were evaluated in PCOS patients and control group by enzyme immunoassays. Results: No significant differences were detected between cases and controls in the level of antibodies and in the correlation between Biochemical markers (FSH, LH, TSH, Prolactin, Testosterone and DHEAS). Only higher scores of hirsutism showed a statistically significant correlation with Anti sm Ab. Conclusion: Our study showed that serologic markers of autoimmunity (Anti ds-DNA & ANAs) are not elevated in PCOS patients. However, severity of hirsutism was found to have a statistically significant correlation with anti sm Ab, so maybe with repeat to these tests in future trials, the exact relationship will be revealed.

During the preclinical study of the original functional peptide, SR-0379, a sensitive liquid chromatographytandem mass spectrometry method was newly developed to study the pharmacokinetics of SR-0379 in rat plasma and subcutaneous tissue samples. Although SR-0379 was unstable in the rat plasma and subcutaneous tissue samples, pretreatment with EDTA and phosphoric acid (4 %) inhibited its degradation. The lower limits of quantification (LLOQ) for SR- 0379 were fully validated as 5 ng/ml in plasma and 5 ng/g in tissue with acceptable linearity, intra- and inter-assay precisions, and accuracy. Measurement of SR-0379 concentration in plasma after intravenous injection via LC-MS/MS yields plasma concentration-time curves (AUC0-∞) with areas of 667 ng•min/ml and an elimination half-life (t1/2) of 4.8 min. The concentration of SR-0379 in the subcutaneous tissue samples was 13.1 µg/g tissue at 30 minutes after a single dermal application (1 mg/ml, 50 µl) to a full-thickness excisional wound. Here, a highly sensitive and specific LC-MS/MS assay with a lower limit of quantification of 5 ng/ml was developed and validated to quantify SR-0379 in rat plasma. This method is useful for pharmacokinetic studies of the peptide drugs in rats.

Peripheral artery disease (PAD) is caused by atherosclerosis, hardening and narrowing arteries over time due to buildup of fatty deposit in vascular bed called plaque. Severe blockage of an artery of the lower extremity markedly reduce blood flow, resulting in critical limb ischemia (CLI) manifested by a variety of clinical syndromes including rest pain in the feet or toes, ulcer and gangrene with infection. Despite significant advances in clinical care and interventions for revascularization, patients with CLI remain at high risk for amputation and cardiovascular death. To overcome this unmet need, therapeutic angiogenesis using angiogenic growth factors has evolved in an attempt to increase blood flow in ischemic limb. Initial animal studies and phase I clinical trials with vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) demonstrated promising results, inspiring scientists to progress forward. However, more rigorous phase II and III clinical trials have failed to demonstrate beneficial effects of these angiogenic growth factors to date. Recently, two multicenter, double-blind, placebo-controlled clinical trials in Japan (phase III) and US (phase II) demonstrated that hepatocyte growth factor (HGF) gene therapy for CLI significant improved primary end points and tissue oxygenation up to two years in comparison to placebo. These clinical results implicate a distinct action of HGF on cellular processes involved in vascular remodeling under pathological condition. This review presents data from phase I-III clinical trials of therapeutic angiogenesis by gene therapy in patients with PAD. Further, we discuss the potential explanation for the success or failure of clinical trials in the context of the biological mechanisms underlying angiogenesis and vascular remodeling, including cellular senescence, inflammation, and tissue fibrosis.

Urinary Tract Infections are the most common infections seen in medical practice and a frequent complication in pregnancy. Diet and nutritional status, especially regarding the consumption of certain antioxidants, has a particularly strong relationship with urinary function and health. The aim of this study was to describe the intake of vitamin C, probiotics and flavonoids, and assess the nutritional status of pregnant women with urinary tract infection. A descriptive transversal study was conducted with a pilot sample of 18 pregnant women over 18 years of age, with Urinary Tract Infection, presenting in any quarter of the pregnancy, and blood counts in their medical records. Body mass index and weight gain were measured. Intakes of vitamin C, flavonoids and probiotics were analyzed based on the frequency of consumption of respective food sources. Dietary quality and quantity were analyzed according to report of the frequency of food consumption and in a 24-hour recall (p<0.05). Most patients consumed foods rich in vitamin C. Consumption of flavonoids, probiotics and water was low. Energy and macronutrient intake was below the recommendations. Nutritional status decreased by 50% compared to pre-pregnancy nutritional status, and anemia was present in the 50% of cases. These findings may lead to defining programs for nutritional and dietary monitoring which could improve the health and nutritional prognosis for women and newborns, and prevent obstetric complications from Urinary Tract Infection.

Scope: FTO is now confirmed as the gene responsible for obesity but epidemiological studies showed various results based on different locations in the gene and in which ethnic group the polymorphism was found. The objective of this meta analysis was to contrast reports on FTO and obesity association among Asian and Caucasian ancestries. Methods and Results: This study was done by a literature search from PUBMED using a combination of terms of “FTO”, “obesity”, “BMI”, “weight” and “waist circumference” between January 2007 and February 2012. Observation studies were collected from several countries in Europe and North America reflecting Caucasian ethnic group and countries in South, East and South East Asia reflecting Asian ethnic group. FTO rs9939609 was the most studied loci. The minor allele frequency (MAF) of A allele of rs9939609 in Asians (es=24.77; 95%CI=20.91-28.63; I2=60.79%) was lower as compared to Caucasians (es=41.03; 95% CI=40.48-41.68; I2=0%). The OR for obesity of rs9939609 SNP was not different between Asians (es=1.31; 95%CI=1.12-1.49; I2=0%) and Caucasians (es=1.27; 95%CI=1.18 - 1.36; I2=31.65%). Conclusion: Although Caucasians have higher minor allele frequency (MAF) of FTO rs9939609 than Asians, the effect of this SNP on obesity is similar. This might explain higher prevalence of obesity in Caucasians.