Use Of Inositol Research Articles

Know your Enemy: The Rationale of Using Inositol in the Treatment of Polycystic Ovary Syndrome

The Polycystic Ovary Syndrome (PCOS) is defined, according to Rotterdam’s criteria proposed by the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine [1,2], by the identification of two out of following parameters: oligo-anovulation; hyperandrogenism (clinical or biochemical); the presence of 12 or more follicles in each ovary measuring 2÷9 mm in diameter, and/or an increased ovarian volume (>10 ml). PCOS affects about 4÷8% of the women in reproductive age [3], causing anovulatory cycles in the 74% of the cases, insulinresistance in the 42% and hyperandrogenism in the 48% [4]. PCOS in our opinion could be considered as the result of concurrent endocrinological alterations, which affects each other. First of all, obesity affects the 35% of PCOS patients [5] and provoke multiple metabolic and endocrine dysfunctions: fatty tissue, in fact, behaves as non-classical endocrine organs and secretes specific cytokines and chemokines [6] which stimulate the androgens production by adrenal cortex and ovaries [7]; on the other hands, adipocytes’ mediators seems to alter thehypothalamus-hypophisis-gonads regulation system, causing high and constant production of Luteinizing Hormone (LH). This may accounts, at least in part, for the typical inhibition of the ovarian follicular maturation in PCOS patients [8]. Moreover, metabolic profile is strictly connected to gonadal function [9]: in PCOS patient’s insulinresistance is commonly associated with hyperinsulinemia [10], and the latter acts synergistically with LH to enhance the androgen production of theca cells [11]. Furthermore, it is able to reduce circulating levels of Sex Hormone Binding Globulin (SHBG), leading to increased levels of free testosterone [12]. Considered altogether, these evidences led to the use of insulin sensitizing drugs to stem the symptoms of this pathology. To date, different Inositol isoforms seems to increase insulin action on various tissues and, in this way to improve the ovulatory function and to inhibit or limit the production of testosterone [13]. Moreover, the use of Inositol may improve the possibility of spontaneous ovulation and regular menstrual cycles, as well as to increase the production of progesterone in the luteal phase of female infertile patients with PCOS [14]. Inositol is a polyalcohol classified as insulin sensitizer and existing as nine stereoisomers, two of which, D-Chiro-inositol [15-18] and Myo-Inositol [14,19-22], are currently used in PCOS treatment. Myo-Inositol, which is the most abundant form of inositol in humans, is converted to D-Chiro-inositol by an insulin-dependent epimerase [23]. These two stereoisomer showed an insulin-like action in vivo exerting the function of insulin mediators as inositolphosphoglycans (IPGs) [24]. In our experience, both Inositol isoforms are effective in improving ovarian function and metabolism of patients with PCOS, although Myo-Inositol shows the most marked effect on the metabolic profile, whereas D-Chiro-Inositol reduces more hyperandrogenism [25].

Stereotypies in Captive Primates and the Use of Inositol: Lessons from Obsessive–Compulsive Disorder in Humans

Animal stereotypies have long been used in the study of obsessive–compulsive disorder (OCD) in humans. These studies have led to the understanding of some of the molecular pathways in the disorder and the use of selective serotonin reuptake inhibitors and myo-inositol in the treatment of these conditions. If animal models, especially nonhuman primate models, were used to study human disorders and if the resulting treatments were successful, then conversely one should be able to treat nonhuman primate stereotypies with similar methods. We here summarize animal models of OCD (including nonhuman primate models) and human OCD treatments, and using successful human treatment by myo-inositol as models, recommend the use of myo-inositol in good captive management practice and the treatment of nonhuman primate stereotypies. We believe that this would be particularly useful in the treatment of stereotypies in nonhuman primates because they are physiologically so similar to humans.

Misdiagnosis of Mycobacterium brumae Infection

We read with interest the paper “Catheter-Related Bloodstream Infection Caused by Mycobacterium brumae” by Lee and colleagues (4) because we had described this species in 1993 and no other isolates had been reported from this first description (5). So we contacted the corresponding author, Dr. Han, who gently sent us the M. brumae strain causing the bloodstream infection (MDA0695 strain). In order to confirm the identification of the MDA0695 strain, we performed a total of 24 biochemical tests and growing characteristics by following standard procedures (8). In vitro antibiotic susceptibility was performed in Middlebrook 7H10 agar by the proportion method (8). The M. brumae type strain and the MDA0695 strain were in disagreement in the following eight phenotypic characteristics: colony pigmentation (Fig. 1), growth at 42°C, growth in the presence of 5% NaCl, nitrate reductase (2 h), arylsulfatase (3 days), iron uptake, use of inositol as a sole carbon source, and sensitivity to streptomycin (4 μg/ml) (Table 1). Fig. 1. The MDA0695 strain displays yellow colonies that are very different from the nonpigmented colonies of the M. brumae type strain (CIP103465). Colonies of the M. brumae type strain (A) and the MDA0695 strain (B) on Middlebrook 7H10 medium. Table 1. Properties of the M. brumae type strain and the MDA0695 strain For mycolic acid analyses, the two strains were grown on Middlebrook 7H10 agar at 30°C for 2 weeks. Mycolic acids were liberated by saponification, methylated with diazomethane, and analyzed by thin-layer chromatography as previously described (2). All the M. brumae strains contain only α-mycolates (5); nevertheless, the MDA0695 strain showed small amounts of α-mycolates and large amounts of dicarboxymycolates with their corresponding long-chain alcohols. The pattern of mycolic acids is widely used in taxonomy and identification of mycobacterial species. With few exceptions (1, 6), all the strains that belong to the same species share the same pattern of mycolic acids. So a different pattern of mycolic acids must arouse suspicions on whether the strains compared really belong to the same species. The sequencing of the 16S rRNA gene was performed with PCR amplicons (7) and analyzed using EditSeq and MegAlign software (DNAStar). By comparing the species-specific hypervariable regions A (39 bp) and B (45 bp) of the 16S rRNA gene (3), we found mismatches in 5 and 3 nucleotides, respectively. The MDA0695 isolate showed only 85% and 93% similarity for both regions with the M. brumae type strain (GenBank/EMBL/DDBJ accession number {type:entrez-nucleotide,attrs:{text:AF547907,term_id:27733731,term_text:AF547907}}AF547907). Thus, the nucleotide sequence of the MDA0695 strain shows substantial differences from the corresponding sequence of the type strain. The sequences of hypervariable regions are very much conserved within species. The homology should be 100%, or very close to it, in strains of the same species. However, we found significant differences in both of the hypervariable regions. The results of the genotype study show that the MDA0695 strain is not an M. brumae strain. Hypervariable A or B 16S rRNA region's sequence alignments of the MDA0695 strain revealed it to be closer to noncultivable mycobacteria species and other known rapid-grower mycobacteria than to M. brumae (see Fig. S1 in the supplemental material). An unrooted neighbor-joining tree based on the concatenated hypervariable A and B sequences of MDA0695 and concatenated sequences of other related Mycobacterium species indicated a close relationship between MDA0695 and Mycobacterium flavescens, Mycobacterium monacense, Mycobacterium novocastrense, Mycobacterium smegmatis, and Mycobacterium goodii (see Fig. S2 in the supplemental material). Therefore, the genotypic differences found between the M. brumae type strain and the MDA0695 strain, together with differences found in mycolic acid patterns and the other phenotypic characteristics, allow us to conclude that the MDA0695 strain cannot be considered a strain of the M. brumae species. As a result of the misidentification of the MDA0695 strain, the species M. brumae is now considered a bacterial pathogen and has been classified as biosafety level 2 by the ATCC. Except for the MDA0695 strain, no other M. brumae strains have been associated with infections up to the present; thus, M. brumae must recover its nonpathogenic species status.

Carbohydrate-Based Mimics of D-myo-Inositol 1,4,5-Trisphosphate

Many cellular events such as secretion or proliferation require activation of proteins by calcium ions. Intracellular calcium is mobilized by the formation of the second messenger D-myo-inositol 1,4,5-trisphosphate (InsP3) and subsequent binding to a receptor located on the endoplasmic reticulum. Pharmacological studies of these biological processes have stimulated the search for new ligands of the InsP3 receptor (InsP3R) able to promote or to block the calcium-signaling pathway. As a result, many analogs of InsP3 itself have been prepared by modification of the inositol structure and or modification of the trisphosphate pattern and have been tested for their ability to mobilize calcium. Many weak to full agonists of InsP3R have been disclosed but a synthetic antagonist of InsP3R yet to be discovered. One disadvantage of the use of inositol as starting material is its meso structure and the number of protecting groups manipulation needed to put in place the appropriate phosphate decoration. Some years ago, we reasoned that carbohydrates might be used as scaffolds mimicking the inositol ring to properly present the trisphosphate pattern. During the course of our preliminary investigations the discovery of the adenophostins shed light on a new way to design highly potent calcium mobilizing agents. This review will summarize on advances in the field of the use of carbohydrates as surrogates for inositol and the use of adenophostins as a model.

Observations in the Use of Inositol in Advanced Malignancy of the Genito-Urinary Tract ,

Observations in the Use of Inositol in Advanced Malignancy of the Genito-Urinary Tract ,