A pilot study of the effects of chromium picolinate supplementation on serum fetuin-A, metabolic and inflammatory factors in patients with nonalcoholic fatty liver disease: A double-blind, placebo-controlled trial.

BACKGROUND: Evaluating the impact of chromium picolinate supplementation on glycemic status, lipid profile, inflammatory markers and fetuin-A in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In present research, participants (N = 46) were randomized to (400 mcg/day, n = 23) chromium picolinate and placebo (n = 23) for 3 months. RESULTS: Glucose indices, and lipid profiles, inflammatory biomarker and fetuin-A were measured before and after the intervention. Chromium reduced triglyceride (TG), atherogenic index of plasma (AIP), very-low-density lipoprotein (VLDL), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL) -6, tumor necrosis factor-alpha (TNF-α) and fetuin-A significantly compared to placebo group (p < 0.05). Furthermore, chromium significantly increased the quantitative insulin sensitivity check index (QUICKI). There were no significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), fasting blood sugar (FBS), Hemoglobin A1c (HbA1C), interleukin (IL)-17 between the two groups (p < 0.05). CONCLUSION: Chromium picolinate significantly decreased TG, insulin, HOMA-IR, fetuin-A, the number of inflammatory factors, and increased QUICKI without changing FBS, HbA1C, TC, LDL, HDL, IL-17 levels and liver steatosis intensity in patients with NAFLD. Further studies by examining the effect of different doses of chromium and mechanisms of cellular action, would help further clarify the subject.

Ultrasensitive detection of malignant melanoma using PET molecular imaging probes.

Malignant melanoma has one of the highest mortality rates of any cancer because of its aggressive nature and high metastatic potential. Clinical staging of the disease at the time of diagnosis is very important for the prognosis and outcome of melanoma treatment. In this study, we designed and synthesized the 18F-labeled pyridine-based benzamide derivatives N-(2-(dimethylamino)ethyl)-5-[18F]fluoropicolinamide ([18F]DMPY2) and N-(2-(dimethylamino)ethyl)-6-[18F]fluoronicotinamide ([18F]DMPY3) to detect primary and metastatic melanoma at an early stage and evaluated their performance in this task. [18F]DMPY2 and [18F]DMPY3 were synthesized by direct radiofluorination of the bromo precursor, and radiochemical yields were ∼15-20%. Cell uptakes of [18F]DMPY2 and [18F]DMPY3 were >103-fold and 18-fold higher, respectively, in B16F10 (mouse melanoma) cells than in negative control cells. Biodistribution studies revealed strong tumor uptake and retention of [18F]DMPY2 (24.8% injected dose per gram of tissue [ID/g] at 60 min) and [18F]DMPY3 (11.7%ID/g at 60 min) in B16F10 xenografts. MicroPET imaging of both agents demonstrated strong tumoral uptake/retention and rapid washout, resulting in excellent tumor-to-background contrast in B16F10 xenografts. In particular, [18F]DMPY2 clearly visualized almost all metastatic lesions in lung and lymph nodes, with excellent image quality. [18F]DMPY2 demonstrated a significantly higher tumor-to-liver ratio than [18F]fluorodeoxyglucose ([18F]FDG) and the previously reported benzamide tracers N-[2-(diethylamino)-ethyl]-5-[18F]fluoropicolinamide ([18F]P3BZA) and N-[2-(diethylamino)-ethyl]-4-[18F]fluorobenzamide ([18F]FBZA) in B16F10-bearing or SK-MEL-3 (human melanoma)-bearing mice. In conclusion, [18F]DMPY2 might have strong potential for the diagnosis of early stage primary and metastatic melanoma using positron emission tomography (PET).

Chromium picolinate attenuates cognitive deficit in ICV-STZ rat paradigm of sporadic Alzheimer's-like dementia via targeting neuroinflammatory and IRS-1/PI3K/AKT/GSK-3ß pathway.

Alzheimer's disease (AD) is prevalent in old age people and is one of the most common brain diseases. Brain insulin resistance, neuroinflammation, oxidative stress, and mitochondrial and cholinergic dysfunction are key features of the disease. In our study, streptozotocin (STZ) in a dose of 3 mg/kg was injected in male Wistar rats bilaterally through the intracerebroventricular (ICV) route on stereotaxic apparatus. Chromium picolinate (CrPic) was tested at doses of 1 mg/kg, 2 mg/kg, and 4 mg/kg, while rivastigmine (2 mg/kg) was used as reference standard drug. Cognitive dysfunction induced by STZ was assessed by behavioral tests like Morris water maze and novel object recognition test. Treatment with CrPic revealed attenuation of cognitive deficit. This was confirmed by behavioral tests, biochemical estimations of antioxidant enzymes, oxidative stress, nitrosative stress, and cholinergic and mitochondrial activity. CrPic did not change AchE activity significantly. STZ-induced neuroinflammation evident by increased TNF-α, IL-6, and CRP levels was also significantly decreased by CrPic. Dysfunctional insulin signaling after ICV-STZ was demonstrated by reduced IRS-1, PI3K, AKT, BDNF gene expression, and increased GSK-3ß, NF-κB gene expression with the help of qRT-PCR. CrPic treatment produced an improvement in insulin signaling revealed by increased gene expression of IRS-1, PI3-K, AKT, BDNF, and decreased gene expression of GSK-3ß and NF-κB. It was concluded that CrPic reversed AD pathology revealed by improved memory, reduced oxidative stress, neuroinflammation, mitochondrial dysfunction, and upregulated insulin signaling.

Inflammation-responsive functional Ru nanoparticles combining a tumor-associated macrophage repolarization strategy with phototherapy for colorectal cancer therapy.

Due to the complexity and heterogeneity of solid tumors, traditional clinical treatments often only achieve limited therapeutic effects. Tumor-associated macrophages (TAMs) play a key role in the development of solid tumors, and the elimination of solid tumors based on the tumor microenvironment has proven to be an effective therapeutic strategy. Here, we successfully developed Ru-based nanoparticles, Ru@ICG-BLZ NPs, with inflammation-responsive release ability, which could repolarize TAMs into M1 macrophages (with an antitumor role) and further produce hyperthermia and ROS to eliminate cancer cells. In vitro experiments showed that Ru@ICG-BLZ NPs had superior drug (ICG and BLZ-945) loading capacity and sensitive inflammation-responsive drug release behavior, which enhanced CT26 cell uptake and penetration ability. Furthermore, in vivo experiments showed that Ru@ICG-BLZ NPs could effectively up-regulate the expression of M1 markers (iNOS, and IL-12) and exert phototherapy to ablate solid tumor, without causing obvious damage to the surrounding tissues of the tumor. The lower toxicity and excellent antitumor ability of Ru@ICG-BLZ NPs could provide new ideas for the clinical transformation of nanomedicine.

Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.

Background: Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease. Methods: In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW). The primary endpoint was mean hemoglobin (Hb) change from pre-baseline average to midtrial (Weeks 7-8) and end-of-trial (Weeks 15-16) and was analyzed using available data (no imputation). Results: Overall, 80, 73 and 68% of subjects in the 300 mg QD, 450 mg QD, and 450 mg TIW dose cohorts respectively, completed the study. For all dose cohorts no statistically significant mean change in Hb from pre-baseline average was observed, and mean Hb concentrations-analyzed using available data-remained stable at mid- and end-of-trial. There was one subject with an Hb excursion >13 g/dL. Overall, 83% of subjects experienced an adverse event (AE); the proportion of subjects who experienced at least one AE was similar among the three dose cohorts. The most frequently reported AEs were nausea (11.7%), diarrhea (10.6%) and vomiting (9.6%). No deaths occurred during the study. No serious AEs were attributed to vadadustat. Conclusions: Vadadustat maintained mean Hb concentrations in subjects on hemodialysis previously receiving epoetin. These data support further investigation of vadadustat to assess its long-term safety and efficacy in subjects on hemodialysis.

Targeted radiotherapy of pigmented melanoma with 131I-5-IPN.

PURPOSE: There has been no satisfactory treatment for advanced melanoma until now. Targeted radionuclide therapy (TRNT) may be a promising option for this heretofore lethal disease. Our goal in this study was to synthesize 131I-N-(2-(diethylamino)ethyl)-5-(iodo-131I)picolinamide (131I-5-IPN) and evaluate its therapeutic ability and toxicity as a radioiodinated melanin-targeting therapeutic agent. METHODS: The trimethylstannyl precursor was synthesized and labeled with 131I to obtain 131I-5-IPN. The pharmacokinetics of 131I-5-IPN was evaluated through SPECT imaging, and its biodistribution was assessed in B16F10 tumor models and in A375 human-to-mouse xenografts. For TRNT, B16F10 melanoma-bearing mice were randomly allocated to receive one of five treatments (n = 10 per group): group A (the control group) received 0.1 mL saline; group B was treated with an equimolar dose of unlabeled precursor; group C received 18.5 MBq of [131I]NaI; group D and E received one or two dose of 18.5 MBq 131I-5-IPN, respectively. TRNT efficacy was evaluated through tumor volume measurement and biology study. The toxic effects of 131I-5-IPN on vital organs were assessed with laboratory tests and histopathological examination. The radiation absorbed dose to vital organs was estimated based on biodistribution data. RESULTS: 131I-5-IPN was successfully prepared with a good radiochemistry yield (55% ± 5%, n = 5), and it exhibited a high uptake ratio in melanin-positive B16F10 cells which indicating high specificity. SPECT imaging and biodistribution of 131I-5-IPN showed lasting high tumor uptake in pigmented B16F10 models for 72 h. TRNT with 131I-5-IPN led to a significant anti-tumor effect and Groups D and E displayed an extended median survival compared to groups A, B, and C. The highest absorbed dose to a vital organ was 0.25 mSv/MBq to the liver; no obvious injury to the liver or kidneys was observed during treatment. 131I-5-IPN treatment was associated with reduction of expression of proliferating cell nuclear antigen (PCNA) and Ki67 and cell cycle blockage in G2/M phase in tumor tissues. Decreased vascular endothelial growth factor and CD31 expression, implying reduced tumor growth, was noted after TRNT. CONCLUSION: We successfully synthesized 131I-5-IPN, which presents long-time retention in melanotic melanoma. TRNT with 131I-5-IPN has the potential to be a safe and effective strategy for management of pigmented melanoma.

Effects of chromium picolinate supplementation on growth performance, small intestine morphology and antioxidant status in ducks under heat stress conditions / Efectos de la suplementación con picolinato de cromo en el rendimiento de crecimiento, morfología del intestino delgado y estado antioxidante en patos bajo condiciones de estrés calórico

SUMMARY: The experiment was conducted to evaluate the effects of dietary supplemental chromium (Cr) on growth performance, meat quality, intestinal morphology, mucosa Hsp70 mRNA expression and antioxidant status of ducks reared under heat stress conditions. All ducks were randomly divided into three treatment groups, respectively, control group (Control, 23 ± 2 °C), heat stress group (HS, 32 ±2 °C), Cr picolinate group (CrPic, 32 ± 2 °C, 0.2 mg Cr/kg). Feed and distilled-deionized water were available ad libitum for an experimental phase of 35 days. Samples were collected on the day 14, 21 and 35 to determine biological and hematological values. Results showed that heat stress or dietary supplemental Cr both didn't have distinct influence on growth performance (P>0.05), compared to controls. Ducks fed 0.2 mg Cr/kg diet had greater ultimate pH (pHu)(P<0.05) than HS group. At day 14, the ratio of villus height to crypt depth (V/C) in CrPic group significantly increased (P<0.05) than that of HS group in jejunum. Heat stress remarkably increased Hsp70 mRNA expression in jejunum compared with controls (P<0.05). While the expression of Hsp70 mRNA in CrPic group was significantly decreased compared with HS (P<0.05). At day 21, the V/C of ileum in CrPic group significantly increased compared with HS group (P<0.05). Serum SOD levels in CrPic group were significantly higher than those in HS group (P<0.05). At day 35, Hsp70 mRNA expression and serum T-SOD levels in CrPic group significantly increased compared with controls (P<0.05). T-AOC in HS group significantly decreased compared with controls (P<0.05). Results indicate that dietary Cr supplementation doesn't influence ducks' growth performance, but has a positive effect on meat quality, small intestine morphology, also regulates Hsp70 mRNA expression under heat stress conditions, and enhances the antioxidant status.

RESUMEN: Se evaluó los efectos del cromo (Cr) dietético suplementario sobre el rendimiento del crecimiento, la calidad de la carne, la morfología intestinal, la expresión del ARNm Hsp70 en la mucosa y el estado antioxidante de los patos criados bajo condiciones de estrés por calor. Todos los patos se dividieron aleatoriamente en tres grupos: grupo control (control, 23 ± 2 °C), grupo de estrés térmico (HS, 32 ± 2 °C) y grupo de picolinato de Cr (CrPic, 32 ± 2 °C, 0,2 mg Cr / kg). El alimento y el agua desionizada destilada estuvieron disponibles ad libitum durante la fase experimental de 35 días. Las muestras se recogieron los días 14, 21 y 35 para determinar los valores biológicos y hematológicos. Los resultados mostraron que el estrés térmico o la suplementación dietética de Cr no tuvieron una influencia distinta en el rendimiento del crecimiento (P> 0,05), en comparación con los controles. Los patos alimentados con 0,2 mg de Cr / kg de dieta tuvieron un mayor pH final (pHu) (P <0,05) que el grupo HS. En el día 14, la relación de la altura de las vellosidades a la profundidad de la cripta (V / C) en el grupo CrPic aumentó significativamente (P <0,05) en relación a la del grupo de HS en el yeyuno. El estrés por calor incrementó notablemente la expresión del ARNm de Hsp70 en el yeyuno en comparación con los controles (P <0,05). Mientras que la expresión del ARNm de Hsp70 en el grupo CrPic se redujo significativamente en comparación con HS (P <0,05). En el día 21, la relación V / C del íleon en el grupo CrPic aumentó significativamente en comparación con el grupo HS (p <0,05). Los niveles séricos de SOD en el grupo CrPic fueron significativamente más altos que los del grupo HS (P <0,05). En el día 35, la expresión de ARNm de Hsp70 y los niveles séricos de T-SOD en el grupo CrPic aumentaron significativamente en comparación con los controles (P <0,05). T-AOC en el grupo HS disminuyó significativamente en comparación con los controles (P <0,05). Los resultados indican que la suplementación dietética de Cr no influye en el rendimiento de crecimiento de los patos, pero tiene un efecto positivo en la calidad de la carne, en la morfología del intestino delgado, y también regula la expresión de ARNm de Hsp70 en condiciones de estrés calórico y mejora el estado antioxidante.

Spatial Targeting of Tumor-Associated Macrophages and Tumor Cells with a pH-Sensitive Cluster Nanocarrier for Cancer Chemoimmunotherapy.

Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating agents, represents an appealing approach for improving cancer therapy. To optimize its therapeutic efficacy, differentially delivering multiple therapeutic drugs to target cells is desirable. Here we developed an immunostimulatory nanocarrier (denoted as BLZ-945SCNs/Pt) that could spatially target tumor-associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. BLZ-945SCNs/Pt undergo supersensitive structure collapse in the prevascular regions of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug conjugated small particles and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of TAMs. The released BLZ-945 can be preferentially taken up by TAMs to cause TAMs depletion from tumor tissues, while the small particles carrying Pt-prodrug enable deep tumor penetration as well as intracellularly specific drug release to kill more cancer cells. Our studies demonstrate that BLZ-945SCNs/Pt outperform their monotherapy counterparts in multiple tumor models. The underlying mechanism studies suggest that the designer pH-sensitive codelivery nanocarrier not only induces apoptosis of tumor cells but also modulates the tumor immune environment to eventually augment the antitumor effect of CD8+ cytotoxic T cells through TAMs depletion.

Liposomes Containing Lipid-Soluble Zn(II)-Bis-dipicolylamine Derivatives Show Potential To Be Targeted to Phosphatidylserine on the Surface of Cancer Cells.

Here we used a lipid-soluble Zn(II)-bis-dipicolylamine derivative as a membrane component to develop liposomal carriers that have potential to be targeted to phosphatidylserine (PS) rich surfaces on cancer cells and to preferentially kill cancer cells without using anticancer drugs. This DPA derivative (abbreviated as DPA-Cy3[22,22]) contains the fluorophore cyanine 3 (Cy3) and two 22-carbon chains that can be anchored into liposomal membrane bilayers. DPA-Cy3[22,22]/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) unilamellar vesicles (∼150 nm) showed selective binding to PS-containing liposomes as demonstrated by anion exchange chromatography. This binding does not result in vesicle fusion or aggregation. Flow cytometry showed that DPA-Cy3[22,22]/POPC liposomes have preferential binding to MCF-7 breast cancer cells over MCF-12A noncancer cells due to 3-7 times more PS exposures on MCF-7. The extent of liposome binding with MCF-7 cells was increased by two times after cells were pretreated with the apoptotic inducer camptothecin, which increased PS exposure to the cell surface. Moreover, our flow cytometry data also suggest that local cell membrane perturbations may occur upon liposome binding and internalization. This implies that DPA-Cy3[22,22]/POPC liposomes alone may have a PS-dependent cytotoxic effect. This assertion was supported by the cell proliferation assay, which showed that 9.1 mol % DPA-Cy3[22,22]/POPC liposomes exert cytotoxicity on MCF-7 cells 3.5 times higher than that on MCF-12A cells. These results indicate that DPA-Cy3[22,22]-containing liposomes hold great promise as efficient nano drug carriers.

Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trial.

AIM: To investigate the effect of chromium picolinate (CrP) on insulin resistance (IR) in polycystic ovary syndrome (PCOS). METHODS: This double blinded randomized controlled trial was conducted in the Gynecology outpatient clinics at Ain Shams University Women's Hospital. Using closed and randomly mixed envelopes, 100 women were selected out of 400 PCOS patients. Eighty-five patients finished the study and were analyzed, 44 in group I and 41 in group II. They were randomly allocated to 6 months of either 1000 µg CrP (50 patients), or placebo capsules (50 patients). Patients were seen monthly to encourage similar diet control and physical exercise plans. The primary outcome was fasting glucose insulin ratio (FGIR), secondary outcomes included ovulation, regularity of the cycle, body mass index (BMI), fasting blood sugar (FBS), fasting serum insulin (FSI), and serum testosterone level. RESULTS: There were no significant differences between women of both groups regarding pretreatment levels of FBS, FSI, FGIR, and serum testosterone. Use of CrP for 6 months was associated with significant reduction of BMI (P < 0.001) and FSI (P = 0.007), and significant rise in FGIR (P = 0.045). CrP significantly increased the chances of ovulation (P = 0.011) and regular menstruation (P = 0.002) by almost twofold after the fifth month of treatment. CONCLUSION: Chromium picolinate is useful in PCOS to reduce IR and stimulate ovulation.

Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats.

Chromium picolinate is advocated as an anti-diabetic agent for impaired glycemic control. It is a transition metal that exists in various oxidation states and may thereby act as a pro-oxidant. The present study has been designed to examine the effect of chromium picolinate supplementation on hyperglycemia-induced oxidative stress. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (50mg/kg body weight) and chromium was administered orally as chromium picolinate (1mg/kg body weight) daily for a period of four weeks after the induction of diabetes. As is characteristic of diabetic condition, hyperglycemia was associated with an increase in oxidative stress in liver in terms of increased lipid peroxidation and decreased glutathione levels. The activity of antioxidant enzymes like superoxide dismutase, catalase and glutathione reductase were significantly reduced in liver of diabetic animals. Levels of α-tocopherol and ascorbic acid were found to be considerably lower in plasma of diabetic rats. Chromium picolinate administration on the other hand was found to have beneficial effect in normalizing glucose levels, lipid peroxidation and antioxidant status. The results from the present study demonstrate potential of chromium picolinate to attenuate hyperglycemia-induced oxidative stress in experimental diabetes.

Chromium-picolinate therapy in diabetes care: individual outcomes require new guidelines and navigation by predictive diagnostics.

AIMS: Nephropathy is the leading secondary complication of metabolic syndrome. Nutritional supplement by chromium-picolinate is assumed to have renoprotective effects. However, potential toxic effects reported increase the concerns about the safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm individual oucomes through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. METHODS: The study was performed in a double-blind manner. Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium- picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using "Comet Assay"-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to get insights into central detoxification and cell-cycle regulating pathways under the treatment conditions. RESULTS: Experimental data revealed highly individual reaction towards the treatment conditions. The highest variability of DNA-damage was monitored under the prolonged treatment with high dosage of CrPic. Expression patterns demonstrated a correlation with the subcellular imaging and dosage-dependent suppression under the chromium-picolinate treatment. INTERPRETATION AND RECOMMENDATIONS: Population at-risk for diabetes is huge and increasing in pandemic scale. One of the reasons might be the failed attempt to prevent the disease by application of artificial supplements and drugs with hardly recognised individual risks. Consequently, a multimodal approach of integrative medicine by predictive diagnostics, targeted prevention and individually created treatment algorithms is highly desirable.

In patients with HIV-infection, chromium supplementation improves insulin resistance and other metabolic abnormalities: a randomized, double-blind, placebo controlled trial.

Chromium is an essential micronutrient; chromium deficiency has been reported to cause insulin resistance, hyperglycemia and hyperlipidemia. The aim was to investigate the effect of chromium supplementation on insulin-resistance, other metabolic abnormalities, and body composition in people living with HIV. This was a randomized, double-blind, placebo-controlled trial. Fifty-two HIV-positive subjects with elevated glucose, lipids, or evidence of body fat redistribution, and who had insulin-resistance based on the calculation of homeostasis model of assessment (HOMA-IR > or = 2.5) were assessed. Subjects who were on insulin or hypoglycemic medications were excluded. Subjects were randomized to receive either 400 microg/day chromium-nicotinate or placebo for 16 weeks. Forty-six subjects, 23 in each group, completed the study. Fasting blood insulin, glucose, lipid profile and body composition were measured before and after intervention. Chromium was tolerated without side effects and resulted in a significant decrease in HOMA-IR (median (IQR) (pre:4.09 (3.02-8.79); post: 3.66 (2.40-5.46), p=0.004), insulin (pre: 102 (85-226); post: 99 (59-131) pmol/L, p=0.003), triglycerides, total body fat mass (mean+/-SEM) (pre: 17.3+/-1.7; post: 16.3+/-1.7 kg; p=0.002) and trunk fat mass (pre: 23.8+/-1.9; post: 22.7+/-2.0 %; p=0.008). Blood glucose, C-peptide, total, HDL and LDL cholesterol, and hemoglobin A1c remained unchanged. Biochemical parameters did not change in the placebo group except for LDL cholesterol which increased significantly. Body weight and medication profile remained stable throughout the study for both groups. In summary, chromium improved insulin resistance, metabolic abnormalities, and body composition in HIV+ patients. This suggests that chromium supplements alleviate some of the antiretroviral-associated metabolic abnormalities.

Zinc picolinate in the prevention of leiomyoma in Japanese quail.

Epidemiologic studies suggest that zinc deficiency may be associated with increased risk of cancer. We investigated the effects of zinc picolinate supplementation on the development of leiomyomas, malondialdehyde (MDA), 8-isoprostane, 4-hydroxyalkenal (HAE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, and heat shock protein 70 (Hsp70) expression in Japanese quails. One hundred fifty quails (6 months old) were assigned to three treatment groups consisting of 50 birds in each group. Birds were fed either a basal diet or the basal diet supplemented with 30 mg or 60 mg of zinc/kg of diet. The animals were sacrificed after 350 days, and the tumors were identified. Zinc picolinate supplementation did not affect the number of leiomyomas compared to control birds (P > .05). However, the tumors in zinc-fed birds were smaller than those found in control birds (P = .01) Serum MDA, 8-isoprostane, and HAE levels were lower in the treatment groups than in the control group: MDA, 1.95 versus 0.93 micromol/L; 8-isoprostane, 108 versus 85 pg/mL; HAE, 1.55 versus 0.96 micromol/L (P = .01 for all three parameters). The concentrations of serum 8-OHdG, which is a marker of oxidative damage, in the groups were 28.5, 23.6, and 20.1 ng/mL, respectively (P = .01). Hsp70 expression was significantly decreased in zinc-treated birds (P < .01). The results indicate that dietary zinc picolinate supplementation reduces the growth of spontaneously occurring leiomyomas of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of zinc supplementation in the prevention and treatment of uterine leiomyoma in humans.

Monitoring blood glucose levels in female mink during the reproductive cycle: 2. Effects of short-term fish oil, chromium picolinate, and acetylsalicylic acid supplementation during late lactation.

Mink nursing sickness is a metabolic disorder characterized by hyperglycemia that is similar to the metabolic syndrome associated with type 2, or non-insulin-dependent, diabetes mellitus. This research studied the effects of short-term administration of antidiabetic supplements on the blood glucose concentration in female mink during late lactation. Female mink that had blood glucose levels < 5.5 mmol/L (normoglycemic [NG]) or > or = 5.5 mmol/L (hyperglycemic [HG]) early in lactation were given daily supplements of various combinations of herring oil (HerO, 3% in diet), chromium picolinate (CrPic, 200 microg), and acetylsalicylic acid (ASA, 100 mg) for 1 wk starting at day 21 post partum. In the NG mink, most of the treatments did not significantly change the blood glucose concentration from day 28 to 42 post partum. However, treatment with ASA alone and treatment with the combination HerO-CrPic-ASA elevated the blood glucose levels when compared with those of the control group, which had received just the basal diet. In the HG mink, all treatment combinations except CrPic alone and ASA alone, reduced the blood glucose concentration. Thus, in lactating mink with hyperglycemia, the blood glucose concentration may be effectively lowered by dietary antidiabetic supplementation; however, because hyperglycemia also occurs before nursing, preventive measures are recommended throughout the year.

Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome.

Trivalent chromium (1000 microg), as chromium picolinate, given without change in diet or activity level, caused a 38% mean improvement in glucose disposal rate in five obese subjects with polycystic ovary syndrome who were tested with a euglycemic hyperinsulinemic clamp technique. This suggests that chromium picolinate, an over-the-counter dietary product, may be useful as an insulin sensitizer in the treatment of polycystic ovary syndrome.

Effect of chromium supplementation on insulin resistance and ovarian and menstrual cyclicity in women with polycystic ovary syndrome.

In women with polycystic ovary syndrome, chromium picolinate (200 microg/d) improves glucose tolerance compared with placebo but does not improve ovulatory frequency or hormonal parameters. This pilot study indicates that future studies in the polycystic ovary syndrome population should examine higher dosages or longer durations of treatment.

Supplementation of zinc from organic or inorganic source improves performance and antioxidant status of heat-distressed quail.

Two sources of zinc [ZnSO4.H2O or ZnPicolinate (ZnPic)] supplementation were evaluated for their effects on performance, carcass weight, levels of malondialdehyde, and vitamins C, E, A in Japanese quail (Coturnix coturnix Japonica) exposed to high ambient temperature of 34 degrees C. The birds (n = 360; 10-d-old) were randomly assigned to 12 treatment groups consisting of 3 replicates of 10 birds each in a 2 x 2 x 3 factorial arrangement of treatments (temperatures, zinc sources, zinc levels). Birds were kept in wire cages in a temperature-controlled room at either 22 degrees C (thermoneutral) or 34 degrees C (heat stress) for 8 h/d (0900 to 1700 h) until the end of study, and fed a basal (control) diet or the basal diet supplemented with either 30 or 60 mg of Zn as ZnSO4 H2O or ZnPic/kg of diet. Heat exposure decreased (P = 0.001) live weight gain, feed intake, feed efficiency, and carcass weight when the basal diet was fed. A linear increase in feed intake (P = 0.01) and BW (P = 0.01), and improvement in feed efficiency (P = 0.01) and carcass weight (P < or = 0.05) were found in zinc-supplemented quail reared under heat-stress conditions. Serum vitamin C (P = 0.04), E (P = 0.05), and cholesterol (P = 0.01) concentrations increased linearly, whereas malondialdehyde concentrations decreased linearly (P = 0.02) as dietary zinc sulfate and ZnPic supplementation increased. An interaction between dietary zinc sources, temperature, and levels of supplementation (P < or = 0.05) for these parameters was detected. Serum vitamins C, E, and A concentrations were not different in supplemented birds reared at thermoneutral temperature. Supplementation with zinc improved carcass weight and antioxidant status of birds, and the effects of ZnPic were relatively greater than those of ZnSO4.H2O in heat-stressed quail. Results of the present study suggest that supplementation with ZnPic could be considered to be more protective than ZnSO4.H2O by reducing the negative effects of oxidative stress induced by heat stress in quail.

Antioxidant properties of chromium and zinc: in vivo effects on digestibility, lipid peroxidation, antioxidant vitamins, and some minerals under a low ambient temperature.

The effects of chromium (chromium picolinate, CrPic) and zinc (ZnSO(4)H(2)O) supplementation on serum concentrations of malondialdehyde (MDA) (an indicator of lipid peroxidation) and serum status of some antioxidant vitamins and minerals of laying hens (Hy-Line) reared at a low ambient temperature (6.8 degrees C) were evaluated. One hundred twenty laying hens (Hy-Line; 32 wk old) were divided into 4 groups, 30 hens per group. The hens were fed either a basal diet or the basal diet supplemented with either 0.4 mg Cr/kg of diet, 30 mg Zn/kg of diet, or 0.4 mg Cr plus 30 mg Zn/kg of diet. Digestibility of nutrients (dry matter [DM], organic matter [OM], crude protein [CP], and ether extract [EE]) increased by supplementation of chromium and zinc (p < 0.05). Supplemental chromium and zinc increased serum vitamins C and E but decreased MDA concentrations (p < 0.05). Additionally, supplemental chromium and zinc caused an increase in the serum concentrations of Fe, Zn, Mn, and Cr (p < 0.05). The present study showed that low ambient temperature causes detrimental effects on the digestibility of nutrients and antioxidant status and that such detrimental effects caused by low ambient temperature can be alleviated by chromium and zinc supplementation, particularly when Cr and Zn were simultaneously included into the diet. Data obtained in the present study suggest that such supplementation can be considered as a protective management practice in a diet of laying hens for alleviating negative effects of cold stress.

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.

The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation.