Evaluation of acute and sub-chronic oral toxicities of Neoneaster in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Jaundice is a condition caused by the elevation of bilirubin level in the blood. Due to the neurological and neurodevelopmental sequalae of jaundice in newborns, the high cost of the treatment, and the side effects of the currently used therapies, novel therapeutically approaches are needed. Purgative manna (Shir-e-Khesht) has been used in Persian traditional medicine to reduce serum bilirubin levels of neonates. Neoneaster® is a natural health product formulated by a unique method from the manna of Cotoneaster nummularius Fisch. & C.A.Mey. for treating neonatal jaundice and managing constipation. The main component of Neoneaster®, mannitol, is an osmotic laxative which could increase intestinal transit and reduce the re-absorption of bilirubin in the enterohepatic cycle. AIM OF THE STUDY: We conducted this study to investigate acute and sub-chronic oral toxicities of Neoneaster in Wistar rats. MATERIALS AND METHODS: In the acute oral toxicity test, based on OECD 423 we administered Neoneaster to the Wistar rats at doses of 5, 50, 300, and 2000 mg/kg(OECD, 2002). Toxicological effects, including mortality and behavioral changes, were recorded for 14 days and compared to the control group. We also carried out histopathological assessments of the tissues of liver, heart, kidney, and spleen after this period. To evaluate sub-chronic toxicity, while administering 2000 mg/kg of Neoneaster daily to the Wistar rats, we recorded for changes in mortality and behavior for 45 days and compared these to the values of the control group. We also carried out biochemical, hematological, and histopathological assessments after this period. RESULTS: In both acute and sub-chronic oral toxicity tests, no mortalities, behavioral abnormalities, and histological signs of toxicity was observed in any of the administered doses in comparison to the control group. The percentage of weight gains in acute toxicity test and the weight gain in sub-chronic test were not significant (P>0/05). There were also no significant differences in hematological and biochemical markers (P>0/05). Based on our finding, Neoneaster can be classified as category 5 in the Globally Harmonized Chemical Classification and Labeling System (GHS) as its Lethal Dose 50 (LD50) is higher than 2000 mg/kg. CONCLUSIONS: This study suggests that Neoneaster is safe and can be classified as category 5 in the GHS system.

Efficacy and safety of date palm leaf-based ointment for treatment of cutaneous warts: A pilot clinical trial.

Despite the considerably high prevalence of cutaneous warts, no optimally effective and safe treatment is available. Leaves of date palm (Phoenix dactylifera L.; Arecaceae) have long been used in Iran's folk medicine as a remedy for warts. To assess the state-of-the-art evidence on using P. dactylifera L. for warts, we conducted a systematic review using CINAHL (via EBSCO), Embase, Medline (via PubMed), ProQuest, Scopus, and Web of Science. We conducted an open-label uncontrolled pilot clinical study to evaluate the efficacy and safety of a proprietary topical date palm leaf-based ointment for the treatment of various types of nongenital warts. This study consisted of an 8-week treatment phase and a 4-week follow-up phase. The assessed outcomes included complete clearance, patient satisfaction (on Likert scale), and the occurrence of any adverse effect. The systematic review demonstrated that the effects of date palm on warts have not been scientifically studied. Thirty patients entered the study with a mean age of 29.5 years (SD = 14.04); among which 17 were female and 13 were male. The patients presented diverse types of warts: verruca vulgaris 15 (50%), plantar 9 (30%), plane 2 (7%), periungual 2 (7%), and warts at multiple sites 2 (7%). In this trial, 19 patients (63.3%) experienced complete clearance and 5 patients (16.6%) experienced partial clearance. Eight patients (26.67%) dropped out during the study. 21 (70%) patients were very satisfied (score on Likert scale = 5) while 1 (3.3%) patient with partial clearance was somewhat satisfied (score on Likert scale = 4). No adverse effect was observed. The results of this pilot study indicate that the date palm leaf-based ointment is a promising treatment whose efficacy and safety should be further investigated in a randomized controlled clinical trial.

Tonic, Burst, and Burst-Cycle Spinal Cord Stimulation Lead to Differential Brain Activation Patterns as Detected by Functional Magnetic Resonance Imaging.

OBJECTIVE: The objective of this preclinical study was to examine the responses of the brain to noxious stimulation in the presence and absence of different modes of spinal cord stimulation (SCS) using blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI). MATERIALS AND METHODS: Sprague-Dawley rats were randomized to groups based on the mode of SCS delivered which included tonic stimulation (n = 27), burst stimulation (n = 30), and burst-cycle stimulation (n = 29). The control (sham) group (n = 28) received no SCS. The SCS electrode was inserted between T10 and T12 spinal levels prior to fMRI session. The experimental protocol for fMRI acquisition consisted of an initial noxious stimulation phase, a treatment phase wherein the SCS was turned on concurrently with noxious stimulation, and a residual effect phase wherein the noxious stimulation alone was turned on. The responses were statistically analyzed through paired t-test and the results were presented as z-scores for the quantitative analysis of the fMRI data. RESULTS: The treatment with different SCS modes attenuated the BOLD brain responses to noxious hindlimb stimulation. The tonic, burst, and burst-cycle SCS treatment attenuated BOLD responses in the caudate putamen (CPu), insula (In), and secondary somatosensory cortex (S2). There was little to no corresponding change in sham control in these three regions. The burst and burst-cycle SCS demonstrated greater attenuation of BOLD signals in CPu, In, and S2 compared to tonic stimulation. CONCLUSION: The high-resolution fMRI study using a rat model demonstrated the potential of different SCS modes to act on several pain-matrix-related regions of the brain in response to noxious stimulation. The burst and burst-cycle SCS exhibited greater brain activity reduction in response to noxious hindlimb stimulation in the caudate putamen, insula, and secondary somatosensory cortex compared to tonic stimulation.

Stress-Strength Parameter Estimation under Small Sample Size: A Testing Hypothesis Approach.

In this paper, uniformly most powerful unbiased test for testing the stress-strength model has been presented for the first time. The end of the paper is recommending a method which is appropriate for no large data where a normal asymptotic distribution is not applicable. The previous methods for inference on stress-strength models use almost all the asymptotic properties of maximum likelihood estimators. The distribution of components is considered exponential and generalized logistic. A corresponding unbiased confidence interval is constructed, too. We compare presented methodology with previous methods and show the method of this paper is logically better than other methods. Interesting result is that our recommended method not only uses from small sample size but also has better result than other ones.

Classical and Bayesian Inference of Conditional Stress-Strength Model under Kumaraswamy Distribution.

Stress-strength models have been frequently studied in recent years. An applicable extension of these models is conditional stress-strength models. The maximum likelihood estimator of conditional stress-strength models, asymptotic distribution of this estimator, and its confidence intervals are obtained for Kumaraswamy distribution. In addition, Bayesian estimation and bootstrap method are applied to the model.

Is urinary ß2-microglobulin a reliable marker for assessment of renal tubular dysfunction in chronic hepatitis B patients receiving tenofovir therapy?

BACKGROUND AND AIM: Urinary ß2-microglobulin (ß2-M) is a marker for renal tubular dysfunction. The current study aimed to assess urinary ß2-M as a reliable marker for early prediction of tenofovir disoproxil fumarate (TDF)-related nephrotoxicity among hepatitis B virus (HBV) patients. METHODS: Forty-two HBV patients who were a candidate for TDF therapy or have recently started it (for less than 6 months) were enrolled and subjected to demographic, clinical, laboratory assessment, abdominal ultrasound and transient elastography. The glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. Also, urinary ß2-M was measured by the ELISA method within 6 months after the introduction of TDF treatment and 6 months later. RESULTS: Mean age was 41.8 (9.55) years, 27 were males and 59.5% of patients have elevated urinary ß2-M after 6 months follow-up of TDF therapy. Urinary ß2-M was 0.07 ± 0.07 µg/ml at baseline and insignificantly increased up to 0.09 ± 0.08 µg/ml after 6 months follow-up. Despite the insignificant increase in serum creatinine from 0.85 ± 0.23 mg/dl at baseline to 0.9 ± 0.21 mg/dl after 6 months and the insignificant decrease in eGFR from 126.2 ± 39.72 ml/min at baseline and 117.64 ± 42.23 ml/min at 6 months follow-up. No correlation was found between the changes in urinary ß2-M and the changes in other renal function indices at baseline and 6 months follow-up. CONCLUSIONS: Short-term TDF therapy is associated with nonsignificant changes either in eGFR or urinary ß2-M; these changes are not clinically relevant that indicates disease progression. Therefore, the suitability of urinary ß2-M as a screening tool for tenofovir induced tubular dysfunction should be further.

Characterization and application of microalgae hydrochar as a low-cost adsorbent for Cu(II) ion removal from aqueous solutions.

Hydrochar prepared from the hydrothermal liquefaction of microalgae is characterized and investigated for copper removal from aqueous solution. Two hydrochars were prepared at 210 °C (HD210) and 250 °C (HD250). The effect of the initial solution pH, the initial Cu(II) concentration, the contact time, and the temperature will be investigated. According to the elemental analysis, the volatile matter in the hydrochars was lower and ash content was higher than those of microalgae. Also, pore characteristic analysis revealed that the surface area of the HD250 was higher than that of the HD210 suggesting a higher potential for the adsorption process. FTIR analysis and Boehm titration showed that both hydrochars contained oxygen-containing functional groups (OFG) on the surface which were effective for the copper removal. The adsorption experiments indicated that the amount of copper adsorbed reached a maximum value at the pH of 5 which was considered as the optimum solution pH. In addition, HD250 had a higher amount of copper adsorption than that of HD210 at all values of the solution pH. The adsorption data at the optimum solution pH was well fitted by the Langmuir's isotherm model and the adsorption process could be well described by the pseudo-2nd order kinetic model. Moreover, thermodynamic analysis revealed that copper adsorption onto the hydrochar was a physical endothermic process.

Effect of spiritual care education on postpartum stress disorder in women with preeclampsia.

INTRODUCTION: Posttraumatic stress disorder is an anxiety disorder that occurs after exposure to an event that causes injury or threat. The prevalence of preeclampsia was reported to be 28%. Considering the significant role of spiritual care in physical and psychological outcomes of patients, this study was conducted to determine "the effect of spiritual care education on postpartum stress disorder in women with preeclampsia". MATERIALS AND METHODS: In this randomized clinical trial, 72 pregnant women (36 in each group) were selected in a convenient way between the ages of 34 and 38 weeks who had preeclampsia and admitted to two public hospitals in Mashhad. The questionnaires such as Duke University Religion Index, DASS 21, the Posttraumatic Stress Disorder Checklist (PCL), and Prenatal Posttraumatic Stress Questionnaire (PPQ) were used at the beginning in two groups. In the intervention group, first, women were educated each day based on Richards and Bergin's pattern, in three sessions, which lasted 45-60 min. The control group also received routine cares. All units completed questionnaires such as Prenatal Posttraumatic Stress Questionnaire (PPQ) at the 4th-6th postpartum period. Results were analyzed by independent t-test, Mann-Whitney test, Chi-square test, and SPSS version 16. RESULTS: The mean change score of postpartum stress disorder in the intervention and control groups was different after intervention (P = 0.001). CONCLUSION: Providing spiritual care to pregnant mothers with preeclampsia reduces their risk of postpartum stress disorder. Therefore, this kind of care as an effective intervention is included in the routine care of this group with high-risk pregnancies.

Persian sturgeon insulin-like growth factor I: molecular cloning and expression during various nutritional conditions.

The effects of different periods of starvation (1, 2, 3, and 4 weeks) and subsequent re-feeding (over a 4 week) on the compensatory growth performance and insulin-like growth factor I (IGF-I) mRNA expression in liver and white muscle were investigated in juvenile Persian sturgeon (Acipenser persicus). First, a fragment of 617 nucleotides coding for IGF-I was cloned from liver, which included an open reading frame of 486 nucleotides, encoding a 162 amino acid preproIGF-I. This is composed of a 45 aa for signal peptide, a 117 aa for the mature peptide comprising the B, C, A, and D domains, and a 47 aa for E domain. The mature Persian sturgeon IGF-I exhibits high sequence identities with other sturgeon species and teleost, ranging between 68 and 95 %. The pattern of IGF-I mRNA expression in the liver and white muscle was measured in response to different periods of starvation and subsequent re-feeding. Nutritional status influenced IGF-I mRNA expression pattern in both liver and muscle. IGF-I mRNA expression in the liver increased during starvation, before decreasing after re-feeding. Furthermore, white muscle IGF-I mRNA expression showed better responses to nutritional status and decreased following starvation and increased by re-feeding. However, changes in the expression of IGF-I mRNA were not significantly different between any of the treatments in both tissues. These data suggest that muscle and liver IGF-I mRNA expression do not have a regulatory role for somatic growth induced by compensatory growth in Persain sturgeon.

Induction of meiotic gynogenesis in ship sturgeon Acipenser nudiventris using UV-irradiated heterologous sperm.

Diploid gynogenesis was induced in ship sturgeon Acipenser nudiventris using UV-irradiated sperm from Siberian sturgeon Acipenser baerii. The optimal condition for the retention of the second polar body in ship sturgeon was determined to be 10 min after activation/fertilization in experiments. The temperature of cold shock and its duration were 2.5 °C and 30 min, respectively. A total of 30 gynogens of known parentage from experimental treatments were screened using microsatellite DNA analysis, and uniparental transmission in meiogens was confirmed. The results show that heterologous Siberian sturgeon sperm is applicable as UV-irradiated sperm for the induction of gynogenesis in ship sturgeon. This technique may recover the critically endangered sturgeon species that are becoming extinct.

Oral administration of hyperimmune IgY: an immunoecological approach to curbing acute infectious bursal disease virus infection.

Infectious bursal disease (IBD) is one of the most important viral diseases of poultry. Hygienic management and proper vaccination are currently the only economic approach for control of this disease. Attempts have been made to control the disease after the onset of an outbreak using parenteral administration of hyperimmune IgY preparations. Such attempts are usually cumbersome and time consuming with an overall reduced economic return. We investigated the use of oral administration of hyperimmune chicken IgY to control IBDV outbreaks early after their discovery in poultry farms. Our approach attempted to change the environmental viral load around susceptible birds and, to modify the host's initial immune-contact with the virulent virus and the subsequent balance of the immune response to that virus. An experimental exposure/protection model that simulates a natural infection in susceptible populations was developed. IBDV hyperimmune yolk was orally administered to a group of IBDV-exposed susceptible layer chicks via drinking water. Disease patterns and mortality rates were monitored up to 10 days post exposure and compared to that in the exposed-untreated group of the same breed and age. Mortality rates dropped by 66.6% in the exposed-treated group compared to the control exposed-untreated group. Similarly, the morbidity shifted towards a milder syndrome in the exposed-treated group as compared to the control exposed-untreated group. To our knowledge, this is the first report of a successful control of an experimental IBDV infection in susceptible poultry populations using oral administration of hyperimmune yolk preparations.