An overview on the correlation between blood zinc, zinc intake, zinc supplementation and bone mineral density in humans.

INTRODUCTION: In case of zinc (Zn) deficiency, this mineral becomes a nutrient limiting muscle and bone synthesis. The study in humans on zinc and bone health are few and no reviews have been published on this topic. So, the aim of this narrative review was to consider the state of the art on the correlation between blood zinc, daily zinc intake, zinc supplementation and bone mineral density. MATERIAL AND METHODS: A narrative review was performed. RESULTS: This review included 16 eligible studies: eight studies concern Zn blood; three studies concern Zn intake and five studies concern Zn supplementation. CONCLUSION: Blood zinc levels seem to be lower in subjects with pathology related to bone metabolism. Regarding daily zinc intake, a high proportion of the population, more than 20%, seems to be at risk of having inadequate zinc intake. The literature suggests that an insufficient zinc intake (less than 3 mg/day) could be a risk factor for fractures and for development of osteopenia and osteoporosis. Zinc supplementation (40-50 g/day) could have beneficial effects on bone health in terms of maintaining bone mineral density and faster healing in the event of fractures, with even better results in situations of reduced intake zinc through food.

INTRODUCCIÓN: En caso de deficiencia de zinc, se limitará la síntesis muscular y ósea. Los estudios en humanos sobre zinc y salud ósea son pocos y no se han publicado comentarios sobre este tema. Por lo tanto, el objetivo de esta revisión narrativa es considerar el estado de la técnica sobre la correlación entre el zinc en la sangre, la ingesta diaria de zinc, la suplementación de zinc y la densidad mineral ósea. MATERIAL Y MÉTODOS: Se realizó una revisión narrativa. RESULTADOS: Esta revisión incluyó 16 estudios elegibles: ocho se refieren al zinc en sangre; tres estudios se refieren a la ingesta de Zn y cinco estudios se refieren a la suplementación de Zn. CONCLUSIÓN: Los niveles de zinc en sangre parecen ser más bajos en sujetos con patología relacionada con el metabolismo óseo. En cuanto a la ingesta diaria de zinc, una alta proporción de la población, más de 20%, parece estar en riesgo de tener una ingesta inadecuada de zinc. La literatura sugiere que una ingesta insuficiente de zinc (menos de 3 mg/día) podría ser un factor de riesgo de fracturas y para el desarrollo de osteopenia y osteoporosis. La suplementación con zinc (40-50 g/día) podría tener efectos beneficiosos sobre la salud ósea para mantener la densidad mineral ósea y una curación más rápida en caso de fracturas, con resultados aún mejores en situaciones de reducción de la ingesta de zinc a través de los alimentos.

An overview on the correlation between blood zinc, zinc intake, zinc supplementation and bone mineral density in humans / Una visión general sobre la correlación entre el zinc en la sangre, la ingesta de zinc, la suplementación de zinc y la densidad mineral ósea en los seres humanos

Abstract: Introduction: In case of zinc (Zn) deficiency, this mineral becomes a nutrient limiting muscle and bone synthesis. The study in humans on zinc and bone health are few and no reviews have been published on this topic. So, the aim of this narrative review was to consider the state of the art on the correlation between blood zinc, daily zinc intake, zinc supplementation and bone mineral density. Material and methods: A narrative review was performed. Results: This review included 16 eligible studies: eight studies concern Zn blood; three studies concern Zn intake and five studies concern Zn supplementation. Conclusion: Blood zinc levels seem to be lower in subjects with pathology related to bone metabolism. Regarding daily zinc intake, a high proportion of the population, more than 20%, seems to be at risk of having inadequate zinc intake. The literature suggests that an insufficient zinc intake (less than 3 mg/day) could be a risk factor for fractures and for development of osteopenia and osteoporosis. Zinc supplementation (40-50 g/day) could have beneficial effects on bone health in terms of maintaining bone mineral density and faster healing in the event of fractures, with even better results in situations of reduced intake zinc through food.

Resumen: Introducción: En caso de deficiencia de zinc, se limitará la síntesis muscular y ósea. Los estudios en humanos sobre zinc y salud ósea son pocos y no se han publicado comentarios sobre este tema. Por lo tanto, el objetivo de esta revisión narrativa es considerar el estado de la técnica sobre la correlación entre el zinc en la sangre, la ingesta diaria de zinc, la suplementación de zinc y la densidad mineral ósea. Material y métodos: Se realizó una revisión narrativa. Resultados: Esta revisión incluyó 16 estudios elegibles: ocho se refieren al zinc en sangre; tres estudios se refieren a la ingesta de Zn y cinco estudios se refieren a la suplementación de Zn. Conclusión: Los niveles de zinc en sangre parecen ser más bajos en sujetos con patología relacionada con el metabolismo óseo. En cuanto a la ingesta diaria de zinc, una alta proporción de la población, más de 20%, parece estar en riesgo de tener una ingesta inadecuada de zinc. La literatura sugiere que una ingesta insuficiente de zinc (menos de 3 mg/día) podría ser un factor de riesgo de fracturas y para el desarrollo de osteopenia y osteoporosis. La suplementación con zinc (40-50 g/día) podría tener efectos beneficiosos sobre la salud ósea para mantener la densidad mineral ósea y una curación más rápida en caso de fracturas, con resultados aún mejores en situaciones de reducción de la ingesta de zinc a través de los alimentos.

Polycystic ovary syndrome management: a review of the possible amazing role of berberine.

PURPOSE: The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment. METHODS: The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management. RESULTS: This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates. CONCLUSIONS: Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy.

Natural Killer Response and Lipo-Metabolic Profile in Adults with Low HDL-Cholesterol and Mild Hypercholesterolemia: Beneficial Effects of Artichoke Leaf Extract Supplementation.

The aim of the present study is to evaluate the effects of 60-day artichoke leaf extract (ALE) supplementation (250mg, twice daily) on cytokines levels, natural killer cell (NK) response, and lipo-metabolic profile (HDL, LDL, and total-cholesterol, triglycerides (TG), ApoB, ApoA, lipid accumulation product (LAP), glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR)) in twenty adults (9/11 males/females, age=49.10 ± 13.74 years, and BMI=33.12 ± 5.14 kg/m2) with low HDL-C and mild hypercholesterolemia. Hierarchical generalized linear model, adjusted for sex, BMI, and age, has been used to evaluate pre-post treatment changes. A significant increase for HDL-C (ß=0.14, p=0.0008) and MCP-1 (ß=144.77, p=0.004) and a significant decrease for ApoB/ApoA (ß=-0.07, p=0.03), total-C/HDL-C ratio (ß=-0.58, p<0.001), and NK response at stimulus low (ß=0.43, p=0.04), medium (ß=0.40, p<0.001), and high (ß=0.42, p=0.001) have been found. These results support the benefits of ALE supplementation on metabolic profile.

Does endogenous GLP-1 affect resting energy expenditure and fuel selection in overweight and obese adults?

PURPOSE: To investigate the association between fasting glucagon-like peptide 1 (GLP-1) levels and resting energy expenditure (REE), and respiratory quotient (RQ) in overweight and obese adults. METHOD: Study participants were enrolled at the Dietetic and Metabolic Unit, University of Pavia, Italy. Inclusion criteria were age ≥ 25 and ≤ 45 years, and body mass index (BMI) ≥ 25 and ≤ 35 kg/m2. Diabetic subjects were excluded. Body composition was measured by dual-energy X-ray absorptiometry. REE was evaluated using indirect calorimetry, and RQ was calculated from respiratory gas exchanges. Fasting GLP-1, glucose, insulin and free fatty acid (FFA) levels, and 24-h norepinephrine urinary excretion were measured. Homeostasis model assessments of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß) were calculated. RESULTS: Thirty-seven participants were included (age 43.4 ± 1.6 years; BMI 30.6 ± 0.5 kg/m2). REE was not associated with fasting GLP-1 levels (p = 0.98) after adjustment for age, sex, fat-free mass (FFM), and fat mass (FM). Similarly, no association was observed between RQ and GLP-1 levels (p = 0.95), after adjustment for age, sex, and body fat. CONCLUSION: In adults subjects with increased adiposity fasting, GLP-1 levels do not seem to play a role in the regulation of energy metabolism and in fuel selection.

Application of excess activated sludge ozonation in an SBR Plant. Effects on substrate fractioning and solids production.

This paper provides new insights on the application of the ozonation process for the reduction of the activated sludge production in a sequencing batch reactor (SBR). The study was performed in two identical lab-scale SBRs plant, one for experimental activities (Exp SBR) and one used as control (Control SBR), both fed with domestic sewage. A fraction of the activated sludge collected from the Exp SBR at the end of the aerobic react phase was periodically subjected to ozonation for 30 minutes at three different specific dosages (0.05, 0.07 and 0.37 g O(3)/gSS) and then recirculated before the beginning of the following cycle.Recirculation of the ozonated sludge to the Exp SBR did not appreciably affect the efficiency of the biological nitrogen and carbon removal processes. Nonetheless, an improvement of the denitrification kinetic was observed. Mixed liquor volatile and suspended solids (MLSS and MLVSS, respectively) concentrations in the reactor decreased significantly with time for long term application of the ozonation treatment. Kinetic batch tests on unstressed sludge taken from Control SBR indicated that the different oxidant dosages (0.05, 0.07 and 0.37 g O(3)/gSS) and durations of the ozonation process (10, 20 and 30 minutes) used remarkably affected chemical oxygen demand (COD) and organic nitrogen fractioning. In particular, soluble and biodegradable fractions seemed to be higher at lower dosage and longer contact time.

Effect of ozonation on sludge reduction in a SBR plant.

This paper provides new insights on the application of the ozonation process for the reduction of activated sludge production in a Sequencing Batch Reactor. The study was performed on two identical lab-scale SBRs plant, fed with domestic sewage: a fraction (1/3 of the working volume) of the activated sludge from one reactor (Exp SBR) was periodically subjected to ozonation for 30 minutes at 0.05 g O(3)/gSS and then recirculated before the beginning of the cycle; the other reactor was used as control and therefore managed at the same sludge retention time but without the application of ozonation. The effects of the recirculation of the ozonated sludge to the Exp SBR were evaluated in terms of biological nitrogen and carbon removal efficiencies, Mixed Liquor Volatile and Suspended Solids (MLSS and MLVSS, respectively) concentrations, effluent quality and sludge settleability. Besides, characterization of the ozonated sludge was carried out for different oxidant dosages (0.05, 0.07 and 0.37 g O(3)/gSS) and durations of the ozonation process (10, 20 and 30 minutes). The results show that at 0.05 g O(3)/gSS and 30 minutes contact time MLVSS as well as MLVSS/MLSS ratio do not change appreciably. Ozone dosage must be increased much further to obtain a relevant effect.

Molecular cloning of a gene from 'chromosome 3 specific' genomic library that encodes a novel CC-chemokine receptor like isotype.

CC-chemokine receptors form a closely linked locus in the p21-23 region on the short arm of human chromosome 3. We report the isolation of a novel chemokine receptor like gene from a 'human chromosome 3 specific' genomic library, screened by cross-hybridization with cDNA probes derived from known chemokine receptors. The gene, CKR-SKG2 contains an open reading frame that encodes a 359-377 amino acid protein, with two potential in frame start codons. However, comparative Southern blot analysis of human, mouse and hamster genomic DNA, revealed that CKR-SKG2 is the hamster ortholog of a novel chemokine receptor. This presumably occurred because chromosome 3 used for construction of the genomic library were purified from a human-hamster somatic cell hybrid. Further studies are underway to identify and clone the putative human homolog of this novel chemokine receptor.

Expression pattern and mapping of the murine versican gene (Cspg2) to chromosome 13.

Versican is a modular proteoglycan harboring a hyaluronan-binding domain at its amino-terminal end and a selectin-like domain at its carboxyl-terminal end, separated by a large intervening region containing the attachment sites for the glycosaminoglycan side chains. By virtue of its modular nature, versican may play a role in cellular attachment, migration, and proliferation by interacting with cell surfaces and extracellular matrix molecules. To discern the function of versican through the analysis of spontaneous and targeted genetic mutations, we have isolated a mouse versican cDNA encoding part of the hyaluronan-binding region, analyzed its mRNA expression in various adult mouse tissues and embryos, and determined the chromosomal location of the gene. Murine versican was 89% identical to human versican at the amino acid level and was highly expressed in mouse embryos at Days 13, 14, and 18. Expression was also detected in adult mouse brain, heart, lung, spleen, skeletal muscle, skin, tail, kidney, and testis. Using interspecific backcross analysis, we assigned the versican gene (Cspg2) to mouse chromosome 13, in a region that is syntenic with the long arm of human chromosome 5 where the human CSPG2 gene is located.

Characterization of the complete genomic structure of the human versican gene and functional analysis of its promoter.

Versican is a modular proteoglycan involved in the control of cellular growth and differentiation. To understand versican gene regulation and transcriptional control, we have isolated genomic clones spanning the entire gene locus including 5'- and 3'-flanking sequences. Versican was encoded by 15 exons encompassing over 90 kilobase pairs of continuous DNA. The exon organization corresponded to the protein subdomains encoded by homologous proteins, with a remarkable conservation of exon size and intron phase. We discovered an additional exon just proximal to the glycosaminoglycan-binding region that was identical to a recently identified splice variant of versican (Dours-Zimmermann, M.T., and Zimmermann, D.R. (1994) J. Biol. Chem. 269, 32992-32998). The versican promoter harbored a typical TATA box located approximately 16 base pairs upstream of the transcription start site and binding sites for a number of transcription factors involved in regulated gene expression. This promoter was shown to be highly functional in transiently transfected cells of both mesenchymal and epithelial origin. Stepwise 5' deletions identified a strong enhancer element between -209 and -445 base pairs and a strong negative element between -445 and -632 base pairs. This study provides the molecular basis for discerning the transcriptional control of the versican gene and offers the opportunity to investigate genetic disorders linked to this important human gene.

Abnormal expression of perlecan proteoglycan in metastatic melanomas.

Abnormal expression of proteoglycans has been implicated in cancer and metastasis primarily because these macromolecules are involved in the control of cell growth and matrix assembly. In this report, we have investigated the expression and immunolocalization of perlecan, a major heparan sulfate proteoglycan of basement membranes and pericellular matrices, in human metastatic melanomas. Twenty-six of the 27 tumor samples showed a significant increase (up to 15-fold) in the perlecan mRNA levels when compared with normal tissue. This change correlated with a vast deposition of perlecan protein core in the pericellular matrix of metastatic melanomas. Furthermore, we have established a relationship between perlecan expression in clonal melanoma cells (70W) stimulated with neurotrophins and their increased invasiveness. Interestingly, perlecan mRNA levels were up-regulated within 10 min of neurotrophin stimulation, indicating that perlecan is an early response gene. This upregulation also occurred prior to heparanase production, suggesting that perlecan expression and its regulation might play a pivotal role in the initial onset of invasion.

Mapping of the versican proteoglycan gene (CSPG2) to the long arm of human chromosome 5 (5q12-5q14).

Versican is a major chondroitin sulfate proteoglycan of vascularized connective tissues whose eponym reflects its functional versatility in macromolecular affinity and interactions. In this report we have localized the versican gene (CSPG2) to the long arm of human chromosome 5 by utilizing a combination of somatic cell hybrids, Southern blotting, polymerase chain reaction, and chromosomal in situ hybridization. The proteoglycan gene segregated concordantly with hybrid cell lines containing the long arm of chromosome 5, comprising the 5q12-q14 band regions. To refine this locus further, we screened a chromosome 5-specific library and isolated several genomic clones encoding a portion of the 5' end of versican. One of these genomic clones was used as a probe for in situ hybridization of human chromosome metaphases. The results corroborated the data obtained using somatic cell hybrids and further refined the assignment of the versican gene to the narrow band region of 5q12-5q14, with the primary site likely to be 5q13.2. The availability of novel genomic clones and the mapping data presented here will make possible the identification of any defect genetically linked to this proteoglycan gene.