Marine Chitosan-Oligosaccharide Ameliorated Plasma Cholesterol in Hypercholesterolemic Hamsters by Modifying the Gut Microflora, Bile Acids, and Short-Chain Fatty Acids.

This study evaluated the cholesterol-alleviating effect and underlying mechanisms of chitosan-oligosaccharide (COS) in hypercholesterolemic hamsters. Male hamsters (n = 24) were divided into three groups in a random fashion, and each group was fed one particular diet, namely a non-cholesterol diet (NCD), a high-cholesterol diet (HCD), and an HCD diet substituting 5% of the COS diet for six weeks. Subsequently, alterations in fecal bile acids (BAs), short-chain fatty acids (SCFAs), and gut microflora (GM) were investigated. COS intervention significantly reduced and increased the plasma total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) levels in hypercholesteremic hamsters. Furthermore, Non-HDL-C and total triacylglycerols (TG) levels were also reduced by COS supplementation. Additionally, COS could reduce and increase food intake and fecal SCFAs (acetate), respectively. Moreover, COS had beneficial effects on levels of BAs and GM related to cholesterol metabolism. This study provides novel evidence for the cholesterol-lowering activity of COS.

Successful Management of a Young Patient Suffering From Pyoderma Gangrenosum Following Gastric Bypass Surgery: A Case Report.

Pyoderma gangrenosum (PG) is a pathogenetically ill-defined neutrophilic dermatosis frequently characterized by severely painful ulcerations with no identifiable infective pathogens. There are no diagnostic criteria for PG, nor specific gold standard management, which may complicate the process of dealing with patients suffering from this disease. Here, we report a case of a 27-year-old male patient, with a history of gastric bypass surgery three years ago, who presented with a left leg non-healing ulcer diagnosed as a PG by the clinical presentation and biopsy of the ulcer. He was managed by the administration of systemic immunomodulators, a surgical debridement procedure, and the application of a vacuum. The patient was discharged with vitamin B complex and vitamin D supplements as well as zinc sulfate and folic acid. Also, multiple doses of Infliximab intravenously and vitamin B 12 intramuscularly result in a satisfactory healing process of the ulcer. Since PG is a diagnosis of exclusion, clinicians must be aware of the need for highly specific history-taking, previous surgical history, laboratory investigations, and histopathological workup in order to reach the diagnosis.

Anti-Hyperlipidemia, Hypoglycemic, and Hepatoprotective Impacts of Pearl Millet (Pennisetum glaucum L.) Grains and Their Ethanol Extract on Rats Fed a High-Fat Diet.

This study tested the anti-hyperlipidemic, hypoglycemic, hepatoprotective, and anti-inflammatory effects of whole pearl millet grain powder (MPG) and its ethanol extract (MPGethaolE) in obese rats fed a high-fat diet. The rats were divided into eight groups based on the treatments they received: control, high fat diet (HFD), HFD + MGE (25 mg/Kg), HFD + MPGethaolE (50 mg/Kg), HFD + MPGethaolE (100 mg/Kg), HFD + MPG (10%), HFD + MPG (20%), and HFD + MPG (30%). The final body weight, visceral, epididymal fat pads, and the liver weight were significantly decreased, in a dose-dependent manner, in HFD fed rats that were co-administered either the MPG powder or MPGethaolE. In the same line, serum levels of triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein-cholesterol (LDL-c), as well as fasting glucose, insulin, HOMA-IR, and serum levels of lipopolysaccharides (LPS), interleukine-6 (IL-6), interleukine-10 (IL-10), C-reactive protein (CRP), tumor necrosis factor (TNF-α), and adiponectin were progressively decreased while serum levels of high-density lipoproteins (HDL-c) were significantly increased when increasing the doses of both treatments. In conclusion, both the raw powder and ethanolic extract of MP have a comparative dose-dependent anti-obesity, hypoglycemic, hypolipidemic, anti-inflammatory, and anti-steatotic in HFD-fed rats.

Crop growth, hydrology, and water quality dynamics in agricultural fields across the Western Lake Erie Basin: Multi-site verification of the Nutrient Tracking Tool (NTT).

Agricultural field- and watershed-scale water quality models are used to assess the potential impact of management practices to reduce nutrient and sediment exports. However, observed data are often not available to calibrate and verify these models. Three years of data from the U.S. Department of Agriculture-Agricultural Research Service's 12 paired edge-of-field sites in northwest Ohio were used to calibrate and validate the Nutrient Tracking Tool. The goal of this study was to identify a single optimal parameter set for the Nutrient Tracking Tool in simulating annual crop yields, water balance, and nutrient loads across the Western Lake Erie Basin. A multi-site and multi-objective auto-calibration subroutine was developed in R to perform model calibration across the edge-of-field sites. The statistical metrics and evaluation criteria used in comparing the simulated results with the observed data were: Cohen's D Effect Size (Cohen's D < 0.20) and Percent bias (PBIAS ± 10% for crop yields, subsurface (tile) discharge, and surface runoff and ± 25% for dissolved reactive phosphorus (DRP) and nitrate­nitrogen (nitrate-N) in tile discharge, and DRP, particulate phosphorus, and nitrate-N in surface runoff). In both calibration and validation, the Cohen's D and PBIAS for annual crop yields, tile discharge, surface runoff, DRP, particulate P, and nitrate-N showed that the average simulated results were similar to the average observed values for each variable. The calibrated model simulated well the annual averages of crop yields, flows, and nutrient losses across fields. The tile drainage and phosphorus transport subroutines in the Nutrient Tracking Tool should be further improved to better simulate the dynamics of discharge and phosphorus transport through subsurface drainage. Stakeholders can use the verified model to evaluate the effectiveness of conservation practices in improving the water quality across the Western Lake Erie Basin.

Prevalence and risk factors for low vitamin D status among breastfeeding mother-infant dyads in an environment with abundant sunshine.

PURPOSE: Evaluation of vitamin D (vD) status and risk factors for low vD among breastfeeding mother-infant dyads in a population at high risk for vD deficiency. SUBJECTS AND METHODS: We measured serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone at 1 month postpartum in 60 consecutive exclusively breastfeeding Arab mother-infant dyads enrolled in a high dose vD supplementation study to prevent vD deficiency in Doha, Qatar, (latitude 25°N) during summer months. Data were collected on demography, sun exposure, and vD supplementation. Comparison with a US cohort was evaluated. vD deficiency was defined as serum 25(OH)D <50 nmol/L and severe deficiency categorized as 25(OH)D <25 nmol/L in mothers and infants. RESULTS: Mean maternal age was 29 years and 77% had college or university education. Maternal median 25(OH)D was 32.5 nmol/L and 78% were vD-deficient and 20% had 25(OH)D <25 nmol/L. Only 42% of mothers had reportedly taken vD supplements postpartum and median dietary vD intake (119 IU/day) and calcium (490 mg/day) were low. Maternal median sun index score (sun exposure [hours/week] × body surface area exposed while outdoors) was 0. Maternal 25(OH)D correlated with percent body surface area exposure while outdoors (rs=0.37, P=0.004). Infant median 25(OH)D was 20 nmol/L and 83% were deficient, while 58% had 25(OH)D <25 nmol/L. Infant 25(OH)D correlated with maternal levels (rs=0.41, P=0.001). None of the infants received vD supplement at 1 month of age and median sun index score was 0. Infant's parathyroid hormone showed negative correlations with 25(OH)D (rs=-0.28, P=0.03). Sun exposure, vD supplementation rate, and vD status were lower in Doha than Cincinnati, US cohort. CONCLUSION: vD deficiency is common in breastfeeding mother-infant dyads in this sunny environment and is associated with sun avoidance and low vD intake. We suggest corrective vD supplement of breastfeeding mothers and their infants, which should preferably start during pregnancy.

Ciliary neurotrophic factor reverses aberrant mitochondrial bioenergetics through the JAK/STAT pathway in cultured sensory neurons derived from streptozotocin-induced diabetic rodents.

Mitochondrial dysfunction occurs in sensory neurons and contributes to diabetic neuropathy. Ciliary neurotrophic factor (CNTF) stimulates axon regeneration in type 1 diabetic rodents and prevents deficits in axonal caliber, nerve conduction, and thermal sensation. We tested the hypothesis that CNTF enhances sensory neuron function in diabetes through JAK/STAT (Janus kinase/signal transducers and activators of transcription) signaling to normalize impaired mitochondrial bioenergetics. The effect of CNTF on gene expression and neurite outgrowth of cultured adult dorsal root ganglia (DRG) sensory neurons derived from control and streptozotocin (STZ)-induced diabetic rodents was quantified. Polarization status and bioenergetics profile of mitochondria from cultured sensory neurons were determined. CNTF treatment prevented reduced STAT3 phosphorylation (Tyr 705) in DRG of STZ-diabetic mice and also enhanced STAT3 phosphorylation in rat DRG cultures. CNTF normalized polarization status of the mitochondrial inner membrane and corrected the aberrant oligomycin-induced mitochondrial hyperpolarization in axons of diabetic neurons. The mitochondrial bioenergetics profile demonstrated that spare respiratory capacity and respiratory control ratio were significantly depressed in sensory neurons cultured from STZ-diabetic rats and were corrected by acute CNTF treatment. The positive effects of CNTF on neuronal mitochondrial function were significantly inhibited by the specific JAK inhibitor, AG490. Neurite outgrowth of sensory neurons from age-matched control and STZ-induced diabetic rats was elevated by CNTF and blocked by AG490. We propose that CNTF's ability to enhance axon regeneration and protect from fiber degeneration in diabetes is associated with its targeting of mitochondrial function and improvement of cellular bioenergetics, in part, through JAK/STAT signaling.

Diabetes impairs an interleukin-1ß-dependent pathway that enhances neurite outgrowth through JAK/STAT3 modulation of mitochondrial bioenergetics in adult sensory neurons.

BACKGROUND: A luminex-based screen of cytokine expression in dorsal root ganglia (DRG) and nerve of type 1 diabetic rodents revealed interleukin-1 (IL-1α) and IL-1ß to be significantly depressed. We, therefore, tested the hypothesis that impaired IL-1α and IL-1ß expression in DRG may contribute to aberrant axon regeneration and plasticity seen in diabetic sensory neuropathy. In addition, we determined if these cytokines could optimize mitochondrial bioenergetics since mitochondrial dysfunction is a key etiological factor in diabetic neuropathy. RESULTS: Cytokines IL-1α and IL-1ß were reduced 2-fold (p<0.05) in DRG and/or nerve of 2 and 5 month streptozotocin (STZ)-diabetic rats. IL-2 and IL-10 were unchanged. IL-1α and IL-1ß induced similar 2 to 3-fold increases in neurite outgrowth in cultures derived from control or diabetic rats (p<0.05). STAT3 phosphorylation on Tyr705 or Ser727 was depressed in DRG from STZ-diabetic mice and treatment of cultures derived from STZ-diabetic rats with IL-1ß for 30 min raised phosphorylation of STAT3 on Tyr705 and Ser727 by 1.5 to 2-fold (p<0.05). shRNA-based or AG490 inhibition of STAT3 activity or shRNA blockade of endogenous IL-1ß expression completely blocked neurite outgrowth. Cultured neurons derived from STZ-diabetic mice were treated for 24 hr with IL-1ß and maximal oxygen consumption rate and spare respiratory capacity, both key measures of bioenergetic fidelity that were depressed in diabetic compared with control neurons, were enhanced 2-fold. This effect was blocked by AG490. CONCLUSIONS: Endogenous synthesis of IL-1ß is diminished in nerve tissue in type 1 diabetes and we propose this defect triggers reduced STAT3 signaling and mitochondrial function leading to sup-optimal axonal regeneration and plasticity.

Beneficial Effects of Rosmarinus Officinalis for Treatment of Opium Withdrawal Syndrome during Addiction Treatment Programs: A Clinical Trial.

BACKGROUND: Withdrawal syndrome may influence patient's motivation for participation in addiction treatment programs. Management of the symptoms can improve the success rate of addiction treatment programs. In the present study, we have evaluated the efficiency of an herbal product as adjunct therapy for alleviation of withdrawal syndrome in opium abuse. METHODS: In the present clinical trial, 81 patients were assigned into case and control groups. The control group was treated with methadone and placebo for 4 weeks. The case group was treated with methadone and powdered dried leaves of Rosmarinus officinalis for the same interval. Occurrence of withdrawal syndrome was compared between groups on days 3, 7, and 14 after beginning of the treatment, and the possible signs and symptoms of withdrawal syndrome were checked. The clinical opioid withdrawal scale (COWS) was used for evaluation of withdrawal syndrome in the patients. FINDINGS: Patients in the case group experienced less severe withdrawal syndrome compared to those in the control group; chiefly bone pain, perspiration, and insomnia. CONCLUSION: The present study showed that rosemary can be used as an optional extra drug for treatment of withdrawal syndrome during treatment programs for opium addiction and possibly addiction to other opioids.

Ciliary neurotrophic factor activates NF-κB to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents.

Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether the NF-κB signal transduction pathway was mobilized by CNTF. Neurite outgrowth of sensory neurons derived from streptozotocin (STZ)-induced diabetic rats was reduced compared to neurons from control rats and exposure to CNTF for 24 h enhanced neurite outgrowth. CNTF also activated NF-κB, as assessed by Western blotting for the NF-κB p50 subunit and reporter assays for NF-κB promoter activity. Conversely, blockade of NF-κB signaling using SN50 peptide inhibited CNTF-mediated neurite outgrowth. Studies in mice with STZ-induced diabetes demonstrated that systemic therapy with CNTF prevented functional indices of peripheral neuropathy along with deficiencies in dorsal root ganglion (DRG) NF-κB p50 expression and DNA binding activity. DRG neurons derived from STZ-diabetic mice also exhibited deficiencies in maximal oxygen consumption rate and associated spare respiratory capacity that were corrected by exposure to CNTF for 24 h in an NF-κB-dependent manner. We propose that the ability of CNTF to enhance axon regeneration and protect peripheral nerve from structural and functional indices of diabetic peripheral neuropathy is associated with targeting of mitochondrial function, in part via NF-κB activation, and improvement of cellular bioenergetics.