Effects of Inorganic and Organic Selenium Supplementation on Blood and Milk Selenium Concentration in Dairy Cows

Selenium is an important trace element in the nutrition of dairy cows because it prevents oxidative damages of tissue and in that way protects the animals from the incidence of various disorders. Addition of various levels of selenium in food leads to its increase in the milk what is important for postnatal calves development in which in the first weeks of life the milk is the only source of selenium. Into the food for dairy cows the inorganic selenium is added in the forms of – sodium selenite or sodium selenate (SS) or organic selenium – seleniium-enriched yeast (SY). Numerous studies have shown that organic selenium (SY) added into food for dairy cows provides better bioavailability than inorganic selenium (SS), hence the content of selenium in blood and milk of cows fed organic form of selenium is higher than in the inorganic selenium. The opinions about the effect of organic selenium on the activity of seleno-enzyme glutathione peroxidase (GPx) have not been reconciled yet. Adding selenium into food for dairy cows has no effect on the quantity of produced milk nor on the milk composition (proteins, fats and lactose). Selenium reduces the number of somatic cells in milk and in that way prevents the occurrence of the disease of mammary gland

The Effect of Supplementation on Selenium and Zinc Content in Blood and Milk of Dairy Cows

Milk is an important source of microelements for calves during the suckling period as well as in human nutrition. Concentration of trace elements in blood and their secretion via milk can significantly change depending on food intake and composition. Proper control of selenium and zinc content in blood and in milk can improve the status of these microelements, so that the occurrence of deficiency or excessive quantity due to their increased intake can be prevented. This paper presents the results of the study on the concentration of selenium and zinc in the blood and milk of diary cows whose rations have been supplemented by organic forms of selenium (0.2 mg/kg DM) and zinc (40 mg/kg DM) during the last ten days of dry period and early lactation. Supplemented cows in trial groups A and B achieved significatly higher concentrations of these microelements in blood (Se 186.70±8.50 µg/L vs. 118.80±7.05 µg/L), blood serum (Zn 1204.70±109.5 µg/L vs. 1095.40±130.2 µg/L) and milk (Se 57.30±8.05 vs. 21.30±4.60 µg/L; Zn 2893.90±120.15 µg/L vs. 1952.10±130.50 µg/L) on 60th day postpartum compared to non-supplemented control

Preemptive analgesic effect of intrathecal applications of neuroactive steroids in a rodent model of post-surgical pain: Evidence for the role of T-type calcium channels

Preemptive management of post-incisional pain remains challenging. Here, we examined the role of preemptive use of neuroactive steroids with activity on low-voltage activated T-type C

Differential effects of the novel neurosteroid hypnotic (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile on electroencephalogram activity in male and female rats

BACKGROUND: We recently showed that a neurosteroid analogue, (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH), induced hypnosis in rats. The aim of the present study was to evaluate the hypnotic and anaesthetic potential of 3β-OH further using electroencephalography. METHODS: We used behavioural assessment and cortical electroencephalogram (EEG) spectral power analysis to examine hypnotic and anaesthetic effects of 3β-OH (30 and 60 mg kg RESULTS: We found dose-dependent sex differences in 3β-OH-induced hypnosis and EEG changes. Both male and female rats responded similarly to i.p. 3β-OH 30 mg kg CONCLUSIONS: Based on its behavioural effects and EEG signature, 3β-OH is a potent hypnotic in rats, with female rats being more sensitive than male rats

Neurosteroids in Pain Management: A New Perspective on an Old Player

Since the discovery of the nervous system’s ability to produce steroid hormones, numerous studies have demonstrated their importance in modulating neuronal excitability. These central effects are mostly mediated through different ligand-gated receptor systems such as GABAA and NMDA, as well as voltage-dependent Ca2+ or K+ channels. Because these targets are also implicated in transmission of sensory information, it is not surprising that numerous studies have shown the analgesic properties of neurosteroids in various pain models. Physiological (nociceptive) pain has protective value for an organism by promoting survival in life-threatening conditions. However, more prolonged pain that results from dysfunction of nerves (neuropathic pain), and persists even after tissue injury has resolved, is one of the main reasons that patients seek medical attention. This review will focus mostly on the analgesic perspective of neurosteroids and their synthetic 5α and 5β analogs in nociceptive and neuropathic pain conditions

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

The Role of Free Oxygen Radicals in Lasting Hyperexcitability of Rat Subicular Neurons After Exposure to General Anesthesia During Brain Development

A large number of preclinical studies have established that general anesthetics (GAs) may cause neurodevelopmental toxicity in rodents and nonhuman primates, which is followed by long-term cognitive deficits. The subiculum, the main output structure of hippocampal formation, is one of the brain regions most sensitive to exposure to GAs at the peak of synaptogenesis (i.e., postnatal day (PND) 7). We have previously shown that subicular neurons exposed to GAs produce excessive amounts of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), which is a known modulator of neuronal excitability. To further explore the association between GA-mediated increase in ROS levels and long-term functional changes within subicular neurons, we sought to investigate the effects of ROS on excitability of these neurons using patch-clamp electrophysiology in acute rat brain slices. We hypothesized that both acute application of H2O2 and an early exposure (at PND 7) to GA consisting of midazolam (9 mg/kg), 70% nitrous oxide, and 0.75% isoflurane can affect excitability of subicular neurons and that superoxide dismutase and catalase mimetic, EUK-134, may reverse GA-mediated hyperexcitability in the subiculum. Our results using whole-cell recordings demonstrate that acute application of H2O2 has bidirectional effects on neuronal excitability: lower concentrations (0.001%, 0.3 mM) cause an excitatory effect, whereas higher concentrations (0.01%, 3 mM) inhibited neuronal firing. Furthermore, 0.3 mM H2O2 increased the average action potential frequency of subicular neurons by almost twofold, as assessed using cell-attach configuration. Finally, we found that preemptive in vivo administration of EUK-134 reduced GA-induced long-lasting hyperexcitability of subicular neurons ex vivo when studied in neonatal and juvenile rats. This finding suggests that the increase in ROS after GA exposure may play an important role in regulating neuronal excitability, thus making it an attractive therapeutic target for GA-induced neurotoxicity in neonates