Zoledronic Acid,Bevacizumab and Dexamethasone-Induced Apoptosis,Mitochondrial Oxidative Stress,and Calcium Signaling Are Decreased in Human Osteoblast-Like Cell Line by Selenium Treatment

Increased intracellular free calcium ion (Ca²⁺) concentration induces excessive oxidative stress and apoptosis. Medical procedures such as zoledronic acid (Zol), bevacizumab (Bev), and dexamethasone (Dex) are usually used in the treatment of bone diseases (osteoporosis, Paget’s disease, etc.) and to prevent metastasis in the bone although the procedures induce osteonecrosis of the jaw through excessive production of reactive oxygen species (ROS). Recently, we observed regulator roles of selenium (Se) on apoptosis and Ca²⁺ entry through transient receptor potential vanilloid 1 (TRPV1) channels in the cancer cell lines. Therefore, Se may modulate Zol, Bev, and Dex-induced oxidative stress and apoptosis through regulation of TRPV1 channel. In the current study, we investigated the protective effects of Se on apoptosis and oxidative stress through TRPV1 in Zol, Bev, and Dex-induced osteoblast-like cell line. We used human osteoblast-like cell line (Saos-2), and the cells were divided into 12 groups as control, Zol, Bev, Dex, Se, Zol+Se, Bev+Se, Dex+Se, Zol+Dex, Zol+Dex+Se, Zol+Bev, and Zol+Bev+Se which were incubated with drugs (Zol, Bev, Dex, and Se) for 24 h. The cytosolic free Ca²⁺ concentration was increased by Zol, Bev, Dex, Zol+Bev, and Zol+Dex, although it was reduced by Se treatment. However, Zol, Bev, and Dex-induced increase in apoptosis, caspase 3, caspase 9, poly (ADP-ribose) polymerase 1 expression levels, and intracellular ROS production values in the cells were decreased by Se treatments. In conclusion, we observed that Zol, Bev, and Dex-induced apoptosis, mitochondrial oxidative stress, and calcium signaling are decreased in human osteoblast-like cell line by the Se treatment. Our findings may be relevant to the etiology and treatment of Zol, Bev, and Dex-induced osteonecrosis by Se.     

Efficacy of Boric Acid,Monopotassium Phosphate and Sodium Metabisulfite on the Control of Apple Scab

In vitro experiments indicated that boric acid, monopotassium phosphate, sodium metabisulfite and synthetic fungicide fluopyram + tebuconazole were effective in inhibiting conidia germination and germ‐tube elongation of Venturia inaequalis. Monopotassium phosphate even at the highest concentration used in the study reduced conidia germination and germ‐tube elongation of V. inaequalis by 22.1% and 28.8%, respectively; however, the difference between two compounds at lower concentrations except 0.05% (for conidia germination) and 0.1% (for germ‐tube elongation) of boric acid was statistically significant (P ≤ 0.05). Complete inhibition was achieved by 0.01% sodium metabisulfite, 0.035% fluopyram + tebuconazole and 0.2% boric acid. Two orchard trials were conducted on the highly susceptible cv. Mutsu to apple scab to ascertain the efficacy of 0.2% boric acid, 0.5% monopotassium phosphate, 0.5% sodium metabisulfite and 0.035% fluopyram + tebuconazole for the control of apple scab. In both 2013 and 2014, except for the applications of monopotassium phosphate and sodium metabisulfite, the applications of boric acid and fluopyram + tebuconazole to trees at 10‐day intervals significantly reduced disease incidence and severity on leaves and fruit compared to the water‐treated control. In both years, the efficacy of boric acid and fluopyram + tebuconazole treatments was similar in reducing both disease incidence and severity on leaves and fruit in all monthly assessments from July to September. All treatments were neither phytotoxic to leaves and fruit nor did they adversely affect quality parameters of harvested fruit. These results show that boric acid treatment may be applied as an alternative chemical for the control of apple scab.     

Sustainability in Supply Chain Management: Aggregate Planning from Sustainability Perspective

Supply chain management that considers the flow of raw materials, products and information has become a focal issue in modern manufacturing and service systems. Supply chain management requires effective use of assets and information that has far reaching implications beyond satisfaction of customer demand, flow of goods, services or capital. Aggregate planning, a fundamental decision model in supply chain management, refers to the determination of production, inventory, capacity and labor usage levels in the medium term. Traditionally standard mathematical programming formulation is used to devise the aggregate plan so as to minimize the total cost of operations. However, this formulation is purely an economic model that does not include sustainability considerations. In this study, we revise the standard aggregate planning formulation to account for additional environmental and social criteria to incorporate triple bottom line consideration of sustainability. We show how these additional criteria can be appended to traditional cost accounting in order to address sustainability in aggregate planning. We analyze the revised models and interpret the results on a case study from real life that would be insightful for decision makers.     

Changes in circulating levels of immunoreactive follicle stimulating hormone, luteinizing hormone, and testosterone during sexual development in the rhesus monkey, Macaca mulatta

Basal serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) and the responsiveness of these hormones to a challenge dose of luteinizing hormone releasing hormone (LHRH), were determined in juvenile, pubertal, and adult rhesus monkeys. The monkey gonadotrophins were analyzed using RIA reagents supplied by the World Health Organization (WHO) Special Programme of Human Reproduction. The FSH levels which were near the assay sensitivity in immature monkeys (2.4 +/- 0.8 ng/ml) showed a discernible increase in pubertal animals (6.4 +/- 1.8 ng/ml). Compared to other two age groups, the serum FSH concentration was markedly higher (16.1 +/- 1.8 ng/ml) in adults. Serum LH levels were below the detectable limits of the assay in juvenile monkeys but rose to 16.2 +/- 3.1 ng/ml in pubertal animals. When compared to pubertal animals, a two-fold increase in LH levels paralleled changes in serum LH during the three developmental stages. Response of serum gonadotrophins and T levels to a challenge dose of LHRH (2.5 micrograms; i.v.) was variable in the different age groups. The present data suggest: an asynchronous rise of FSH and LH during the pubertal period and a temporal correlation between the testicular size and FSH concentrations; the challenge dose of LHRH, which induces a significant rise in serum LH and T levels, fails to elicit an FSH response in all the three age groups; and the pubertal as compared to adult monkeys release significantly larger quantities of LH in response to exogenous LHRH.     

Seasonal changes in epididymis and the effects of FSH and testosterone in the spiny-tailed lizard,Uromastix hardwicki

Seasonal changes in epididymal weight and histology were studied in relation to testicular function in the adult spiny-tailed lizard, Uromastix hardwicki, over a period of 1 year. The eipdidymal weights, tubular diameter, and epithelial height increased in March, reaching a peak in April. This peak coincided with sperm maturation, elevated plasma testosterone levels, and release of sperm into the epididymis. The epididymal weights decreased in May following a sudden regression of the testis early in the month. The epididymal weights decreased further during June and remained low until February. The diameter of the duct and the height of the epithelial cells also decreased in May and the epididymal epithelium maintained a low histological profile from June to February. The fall testicular recrudescence was not accompanied by a change either in the weight or the histological structure of the epididymis. Administration of oFSH (0.1 mg) daily for 7 days during the sexually quiescent period induced a significant increase in the weight of the epididymis and epithelial height of the duct. Administration of testosterone alone, (2.0 mg) daily for the same period and under identical conditions, did not induce a change in the weight of epididymis or its histology. A possible permissive role of gonadotrophin in the hormonal regulation of the lizard epididymis has been suggested.     

Possible modulation of N-methyl-D,L-aspartic acid induced prolactin release by testicular steroids in the adult male rhesus monkey

N-methyl-D,L-aspartic acid (NMA), an agonist of the neurotransmitter glutamate has been shown to acutely stimulate the release of prolactin (PRL) in intact rats and monkeys. To further investigate the role of neuroexcitatory amino acids in PRL secretion, the effects of NMA administration were examined on PRL release in long term orchidectomized adult rhesus monkeys, in both the absence and presence of testosterone. Intact and long term castrated adult male monkeys weighing between 8-13 kg, were implanted with a catheter via the saphenous vein for blood withdrawal and drug infusion. Blood samples were collected at 10 min intervals for 50 min before and 70 min after administration of the drug or vehicle. Plasma PRL concentrations were estimated using radioimmunoassay. Whereas a single iv injection of NMA (15 mg/kg BW) induced a prompt discharge of PRL in intact monkeys, an identical dose had surprisingly no effect on PRL secretion in orchidectomized animals. On the other hand, plasma PRL increases in response to a challenge dose of thyrotropin releasing hormone (TRH; 6 micrograms/kg BW, iv) were similar in magnitude in the two groups of monkeys. Testosterone replacement in orchidectomized animals by parenteral administration of testosterone enanthate (200 mg/wk) reinitiated the PRL responsiveness to acute NMA stimulation. These results indicate that N-methyl-D-aspartic acid (NMDA) dependent drive to PRL release in the adult male rhesus monkey may be overtly influenced by the sex steroid milieu.     

Intracellular chromium reduction

Two steps are involved in the uptake of Cr(VI): (1) the diffusion of the anion CrO4(2-) through a facilitated transport system, presumably the non-specific anion carrier and (2) the intracellular reduction of Cr(VI) to Cr(III). The intracellular reduction of Cr(VI), keeping the cytoplasmic concentration of Cr(VI) low, facilitates accumulation of chromate from extracellular medium into the cell. In the present paper, a direct demonstration of intracellular chromium reduction is provided by means of electron paramagnetic (spin) resonance (EPR) spectroscopy. Incubation of metabolically active rat thymocytes with chromate originates a signal which can be attributed to a paramagnetic species of chromium, Cr(V) or Cr(III). The EPR signal is originated by intracellular reduction of chromium since: (1) it is observed only when cells are incubated with chromate, (2) it is present even after extensive washings of the cells in a chromium-free medium; (3) it is abolished when cells are incubated with drugs able to reduce the glutathione pool, i.e., diethylmaleate or phorone; and (4) it is abolished when cells are incubated in the presence of a specific inhibitor of the anion carrier, 4-acetamido-4'-isothiocyanatostilbene-2-2'-disulfonic acid.