Copper and zinc deficiency in an alcoholic patient: a case report of a therapeutic dilemma.

Copper deficiency often manifests with anemia and ataxia. The risk factors associated with the deficiency include gastrointestinal surgery, excessive zinc supplementation, and malabsorptive conditions. Little is known about the relationship between copper deficiency and alcohol consumption. Here we report a case of copper deficiency in a patient with alcohol use disorder who also had zinc deficiency, thereby posing a therapeutic dilemma because copper and zinc are competitively absorbed into the small intestine. Early recognition of copper deficiency is essential when treating zinc deficiency in such patients.

Novel protocol combining physical and nutrition therapies, Intensive Goal-directed REhabilitation with Electrical muscle stimulation and Nutrition (IGREEN) care bundle.

BACKGROUND: Although the combination of rehabilitation and nutrition may be important for the prevention of intensive care unit (ICU)-acquired weakness, a protocolized intervention of this combination has not yet been reported. We herein developed an original combined protocol and evaluated its efficacy. METHODS: In this single-center historical control study, we enrolled adult patients admitted to the ICU. Patients in the control group received standard care, while those in the intervention group received the protocol-based intervention. The ICU mobility scale was used to set goals for early mobilization and a neuromuscular electrical stimulation was employed when patients were unable to stand. The nutritional status was assessed for nutritional therapy, and target calorie delivery was set at 20 or 30 kcal/kg/day and target protein delivery at 1.8 g/kg/day in the intervention group. The primary endpoint was a decrease in femoral muscle volume in 10 days assessed by computed tomography. RESULTS: Forty-five patients in the control group and 56 in the intervention group were included in the analysis. Femoral muscle volume loss was significantly lower in the intervention group (11.6 vs 14.5%, p = 0.03). The absolute risk difference was 2.9% (95% CI 0.1-5.6%). Early mobilization to a sitting position by day 10 was achieved earlier (p = 0.03), and mean calorie delivery (20.1 vs. 16.8 kcal/kg/day, p = 0.01) and mean protein delivery (1.4 vs. 0.8 g/kg/day, p < 0.01) were higher in the intervention group. CONCLUSION: The protocolized intervention, combining early mobilization and high-protein nutrition, contributed to the achievement of treatment goals and prevention of femoral muscle volume loss. TRIAL REGISTRATION NUMBER: The present study is registered at the University Hospital Medical Information Network-clinical trials registry (UMIN000040290, Registration date: May 7, 2020).

Urinary Titin N-Fragment Evaluation in a Randomized Controlled Trial of Beta-Hydroxy-Beta-Methylbutyrate for Acute Mild Trauma in Older Adults.

The effects of beta-hydroxy-beta-methylbutyrate (HMB) complex administration and the significance of titin, a biomarker of muscle injury, in elderly minor trauma patients in acute phase has not been established. In this single-center, randomized controlled study, trauma patients aged ≥ 70 years with an injury severity score < 16 were included. Titin values on days 1 and 3 were measured and the intervention group received HMB complex (2.4 g of HMB + 14 g of glutamine + 14 g of arginine) and the control group received glutamine complex (7.2 g of protein including 6 g of glutamine). The cross-sectional area of the rectus femoris (RFCSA) on ultrasound, grip strength, and the Barthel Index were assessed on the first day of rehabilitation and after 2 weeks. We analyzed 24 HMB and 25 control participants. Titin values on day 3 correlated with grip strength (r = -0.34, p = 0.03) and the Barthel Index (r = -0.39, p = 0.01) at follow-up. HMB complex supplementation had no effect on the RFCSA (2.41 vs. 2.45 cm2, p = 0.887), grip strength (13.3 vs. 13.1 kg, p = 0.946), or the Barthel Index (20.0 vs. 50.0, p = 0.404) at follow-up. Titin values might associate with subsequent physical function. Short-term HMB complex supplementation from acute phase did not ameliorate muscle injury.

Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models.

Narcolepsy-cataplexy is a debilitating disorder of sleep/wakefulness caused by a loss of orexin-producing neurons in the lateroposterior hypothalamus. Genetic or pharmacologic orexin replacement ameliorates symptoms in mouse models of narcolepsy-cataplexy. We have recently discovered a potent, nonpeptide OX2R-selective agonist, YNT-185. This study validates the pharmacological activity of this compound in OX2R-transfected cells and in OX2R-expressing neurons in brain slice preparations. Intraperitoneal, and intracerebroventricular, administration of YNT-185 suppressed cataplexy-like episodes in orexin knockout and orexin neuron-ablated mice, but not in orexin receptor-deficient mice. Peripherally administered YNT-185 also promotes wakefulness without affecting body temperature in wild-type mice. Further, there was no immediate rebound sleep after YNT-185 administration in active phase in wild-type and orexin-deficient mice. No desensitization was observed after repeated administration of YNT-185 with respect to the suppression of cataplexy-like episodes. These results provide a proof-of-concept for a mechanistic therapy of narcolepsy-cataplexy by OX2R agonists.

The benefit of the supplementation of perioperative branched-chain amino acids in patients with surgical management for hepatocellular carcinoma: a preliminary study.

The aim of this work was to study the benefit of supplementation with a branched chain amino acids enriched nutrient mixture on the physical and mental condition following hepatic surgery in patients with hepatocellular carcinoma (HCC). A total of 41 patients with HCC who underwent hepatic surgery (36 hepatic resection and five radiofrequency ablation therapy) were enrolled in this comparative study. These patients were divided into two groups: 13 patients received perioperative supplementation of a branched chain amino acids enriched nutrient mixture (AEN group) and 28 patients did not (control group). Between these two groups, laboratory data, postoperative complications and the length of hospital stay were analyzed comparatively. Restoration of peripheral lymphocyte count and serum total cholesterol level at 3 months after the operation was significantly faster in the AEN group than in the control group (P < 0.05). The length of hospitalization in the AEN group was significantly shorter than in the control group (P < 0.05). This preliminary case control study suggested that the perioperative supplementation of a branched chain amino acids enriched nutrient mixture is of clinical benefit for nutritional support of patients surgically managed for HCC in chronic liver disease.

Relationship between hormonal receptors, HER-2, p53 protein, Bcl-2, and MIB-1 status and the antitumor effects of neoadjuvant anthracycline-based chemotherapy in invasive breast cancer patients.

PURPOSE: The purpose of this study was to evaluate the predictive value of six different biological factors for neoadjuvant chemotherapy (NAC) in breast conservation treatment (BCT) for invasive breast cancer. MATERIALS AND METHODS: Thirty invasive breast cancer patients (31 breasts) who received NAC as BCT and needle biopsy before chemotherapy were included in this study. Breast cancer tissue was obtained with an 18G core needle with ultrasound guidance. Patients received two to five courses of CAF (cyclophosphamide 600 mg/m(2), pirarubicin 20-40 mg, 5-fluorouracil 600 mg/m(2)). Tissue sections from formalin-fixed paraffin-embedded blocks were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER (human epidermal growth factor receptor)-2, p53 protein, Bcl-2, and MIB-1 (Ki-67). Tumor reduction rate was assessed by MRI before and after chemotherapy. RESULTS: The tumor reduction rate did not differ according to the number of courses of chemotherapy administered. In both the univariate and multivariate analyses, HER-2-negative status was the only significant predictive factor of response (P<0.05). There was no correlation between response and hormone receptors, MIB-1, p53 protein, or Bcl-2 expression. CONCLUSION: This study suggests that breast cancer cells that overexpress HER-2 may be resistant to low-doses of anthracycline-based chemotherapy.

Immunocytochemical characteristics of human osteosarcoma cell line HS-Os-1: possible implication in apoptotic resistance against irradiation.

In our previous study, we examined reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy irradiation. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of the hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation. In the succeeding study, we examined radiation-induced ROS formation, oxidative DNA damage, early apoptotic changes, and mitochondrial membrane dysfunction in the human osteosarcoma cell line HS-Os-1. We found that ROS formation and oxidative DNA damage were actually scarcely seen after irradiation of up to 30 Gy in these cells, that mitochondrial membrane potential was preserved, and that apoptotic changes were not demonstrated despite the relatively high-dose irradiation of 30 Gy. In the present study, we examined the immunocytochemical characteristics of the apoptotic-resistance of the HS-Os-1 cell line against irradiation in order to clarify its possible implications regarding radiosensitivity. The results showed that these cells lack P53 and Bax protein expression, and strong peroxidase activity was confirmed in the nuclei of the cells. Moreover, SODII (manganese superoxide dismutase II) protein expression was gradually increased in spite of irradiation of up to 30 Gy. Therefore, it is concluded that HS-Os-1 cells are originally apoptotic-resistant and that the cells possess a strong ability to scavenge for free radicals. To convert these cells to a state of apoptotic-susceptibility, a powerful oxidant such as hydrogen peroxide might exert such an effect in terms of the production of hydroxyl radicals in lysosomes in the cells as shown in our previous studies. The origin of the radioresistance of the human osteosarcoma cell line HS-Os-1 is considered to to be low degree of ROS formation following irradiation, reflecting the strong scavenging ability of these cells for free radicals including hydroxyl radicals.

Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic chondrocytes.

Both hyaluronic acid (HA) and cyclooxygenase-2 (COX-2) inhibitors are used in clinical practice in the treatment of osteoarthritis. There have been no reports regarding cross-talk between HA and COX-2 inhibitors in articular human chondrocytes. The purpose of this study was to investigate whether HA, COX-2 inhibitors or a combination of COX-2 inhibitors and HA have different effects in human articular between lower and highly degenerated chondrocytes. Isolated lower and highly degenerated chondrocytes were divided into 5 groups: ethanol (used as a control for the solvents), HA, COX-2 inhibitors, COX-2 inhibitors plus HA, or no additive. After incubating for 48 h, mitochondrial membrane potential analysis and western blotting of p38 and p44/42 mitogen-activated protein kinase (MAPK) were performed. Glycosaminoglycan, nitric oxide (NO) production and prostaglandin E2 (PGE2) concentrations were assessed. A combination of COX-2 inhibitors and HA resulted in dendritic, proliferating chondrocytes with strong red fluorescence enriched in the mitochondrial membrane, and indicated reduction of apoptosis in chondrocytes. COX-2 inhibitors alone, and a combination of COX-2 inhibitor and HA inhibited the activation of p38 in highly degenerated chondrocytes. A combination of COX-2 inhibitors and HA decreased NO production in highly degenerated chondrocytes. COX-2 inhibitors decreased PGE2 production, however, HA alone had no effect on PGE2 production. The present study demonstrated that COX-2 inhibitors and HA interacted synergistically the MAPK pathway and inhibition of NO production in highly degenerated chondrocytes. Administration of COX-2 inhibitors plus HA could be used as a new alternative way of treating osteoarthritis.