Test Dose Research Articles

Comparison of glucagon stimulation test and low dose ACTH test in assessing hypothalamic-pituitary-adrenal (HPA) axis in children.

Children with a pituitary hormone deficiency are at risk for secondary adrenal insufficiency (AI). A stimulation test is usually performed for diagnosing AI, evaluating both the hypothalamic-pituitary-adrenaland growth hormone (GH)-IGF-1 axes. This single test is preferred by clinicians and is considerably more tolerable by patients. The objective of this study was to evaluate the glucagon stimulation test (GST), which is commonly used to assess both axes. Its diagnostic capability for GHdeficiencyis high and well accepted, however its utility for determining secondary AI has not been well established. This retrospective study involved 120 patients under 18 years of age with short stature who had undergone both a GST and low dose ACTH stimulation test (LDACTH test). Twenty-six children who had more than 6months elapsed between the two tests were excluded from the study. The study was conducted on patients of the Pediatric Endocrinology Department at Soroka University Hospital, a tertiary medical centre in Beer Sheva, Israel. Statistical analyses were carried out via IBM SPSS (v. 22), with a significance level determined at p < .05. Different cortisol cut-off values were assessed for GST and it was determined that the highest combined sensitivity and specificity yielded a cut-off point of 320 nmol/L (56% sensitivity and 83% specificity) while the currently accepted cut-off value (500 nmol/L) yielded 100% sensitivity and 6% specificity. The results of this study show that GST is not an optimal tool for diagnosing secondary AI. Therefore, clinicians using this test should interpret its results with caution.

Evaluation of Deoxyribonucleic Acid Damage Using Neutral Comet Assay for High Radiation Doses: A Feasibility Study.

This study aims to investigate the use of the neutral comet assay to assess deoxyribonucleic acid (DNA) damage in lymphocytes exposed to high doses of radiation. The research was conducted by obtaining informed consent, after which blood samples were taken from seven healthy individuals and this study was approved by the institutional ethics committee. At first, for the determination of dose-effect curves, samples obtained from the first five individuals were irradiated for doses ranging from 0 to 35 Gy after which they were processed under neutral comet assay. In order to verify the determined dose-effect curves, a test dose of 15 Gy was delivered to the samples obtained from the sixth and seventh individuals. The amount of DNA damage from the obtained comet assay images was analyzed using four comet assay parameters namely % tail DNA, tail length, tail moment (TM), and Olive TM (OTM). The most suitable comet assay parameter was evaluated based on the obtained dose-effect curves. Furthermore, the distribution of individual cells for each dose point was evaluated for all the four comet assay parameters to find the optimal parameter. From our results, it was found that from 0 to 25 Gy all the four comet assay parameters fit well into a linear quadratic curve and above 25 Gy saturation was observed. Based on the individual cell distribution data, it was found that % tail DNA could be an optimal choice to evaluate DNA damage while using neutral comet assay for high-dose ionizing radiation. The neutral comet assay could be a potential tool to assess DNA damage from high doses of ionizing radiation greater than 5 Gy.

TOXIC SYMPTOMS IN WISTAR STRAIN RATS ON SINGLE AND REPEATED DOSAGE FROM THE EXTRACT OF RED BETEL LEAF (Piper crocatum) AS A TOXICITY TEST OF PERIODONTAL POCKET THERAPY

Red betel leaf (Piper crocatum) is one of the potential medicinal plants known to have properties to cure various diseases. The main components of betel leaf exhibit antiseptic, bactericidal, and antioxidant effects. The betel leaf was concentrated into an essential oil containing the antiseptic chemical. The antibacterial power of betel leaf essential oil is due to the content of phenolic compounds and their derivatives that can denature bacterial cell proteins, so it was considered to have potential as a material that could develop for periodontal therapy. After going through the stages of toxicity testing and repeated dose in terms of mortality, changes in body weight, and relative organ index of Wistar strain rats, the study continued to observe the effects that occurred after using single and repeated doses of 100, 400, and 1000 mg/kg BW in vivo using red betel leaf extract with the parameters of observing the behavior of rats studied for 14 days. Observation of the behavior of the test animals on toxic symptoms at each visit consisted of motor activity, straub phenomenon, piloerection, ptosis, corneal reflex, pineal reflex, lacrimation, vasodilation, catalepsy, dangling, reestablishment, walking backwards, circular walking, flexion, haffner, writhing, grooming, tremor, body shaking, vocalizations, urination, defecation, heart rate, salivation, mortality, posture, and breath changes before and after dosing for 14 days. From the observations, the analysis of the data obtained is primary data. Primary data in the form of qualitative data was obtained from data on effects that occurred after the rats were given a dose. After processing the data, the data is presented in tabular and narrative form based on the observations by showing the test dose used, the number of animals showing a toxic effect, the time of onset of a toxic effect and the percentage of animals in a group showing a toxic result. Based on the results of the study, red betel leaf extract with doses of 100, 400, and 1,000 mg/kg BW which was observed on the first and 14th days, did not cause toxic symptoms in all groups of rats, both on single administration and repeated administration for 14 days.

Documented Penicillin Allergies Should Not Preclude Use of Preoperative Cefazolin in Hip and Knee Arthroplasty

Perioperative cefazolin administration for total joint arthroplasty is a first-line antibiotic recommended by the American Academy of Orthopaedic Surgeons (AAOS) guidelines for the prevention of periprosthetic joint infections (PJIs). We aim to analyze the clinical viability of giving patients with a documented penicillin allergy (PA) a perioperative full-strength cefazolin "test dose" under anesthesia. This is a retrospective chart review of 2,451 total joint arthroplasties from a high-volume arthroplasty orthopaedic surgeon over a 5-year period from January 2013 through December 2017. This surgeon routinely gave patients with a documented PA a full-strength cefazolin test dose while under anesthesia instead of administrating a second-line antibiotic. The primary outcomes examined were allergic reaction and postoperative infection. Cefazolin was given to 87.1% of all patients (1,990) and 46.0% of patients with a PA (143). The total rate of allergic reactions among all patients was 0.5% (11). Only one patient with a documented PA who received cefazolin had an allergic reaction. The reaction was not severe and did not require any additional treatment. In patients who had no reported allergies and received cefazolin, 0.3% (6) had an allergic reaction. There was no statistically significant difference in the rate of allergic reaction when comparing patients with and without a PA (P = 0.95). Patients receiving cefazolin had an overall PJI rate of 2.9% (57) versus those patients receiving antibiotics other than cefazolin who sustained a 5.5% PJI rate (16), which was statistically significant (P = 0.02). This study found that utilization of a full-strength test dose of cefazolin in patients with a documented PA is a feasible, safe, and effective way of increasing the rate of cefazolin administration and thus mitigating the risk of PJIs.

Testing Doses and Treatment Timelines of Anti-Angiogenic Drug Bevacizumab Numerically as a Single-Agent for the Treatment of Ovarian Cancer

An anti-angiogenic drug in cancer treatment prevents the growth of new blood vessels in tumors by binding to VEGF molecules, which otherwise induce endothelial cells inside blood vessels to sprout the blood supply toward the tumor. This would prevent the growth of new blood cells which will deprive the tumor of nutrients, thus decreasing its carrying capacity, and ultimately shrinking its volume. With new vascularization absent, the tumor will be isolated, making it easier to treat. Although there is an availability of various anti-angiogenic drugs, their effectiveness is low compared to other cancer treatments. We are specifically pinpointing the various combination of doses and the treatment timelines as reasonable factors to increase the effectiveness of the anti-angiogenic drug Bevacizumab, which can possibly prolong the patient’s survival rate and offer lower toxicity compared to other treatment modalities such as radiotherapy and chemotherapy. We have numerically analyzed different doses of Bevacizumab, including 15 mg/kg, an FDA-approved dose if offered in conjunction with chemotherapy drugs, carboplatin and paclitaxel, as a single-agent treatment option. Based on the results, the tumor volume was observed to be stabilizing for the duration of the treatment, which was chosen to be 400 days. The toxicity levels of these doses with Bevacizumab as a single-agent treatment option have not been tested in a clinical setting. However, these mathematically promising results can provide a gateway for the successful treatment of ovarian cancer in the future.

Pharmacokinetic and bioequivalence study of two capecitabine tablets in Chinese patients with breast, colorectal or gastric cancer under fed condition: A multicentric, randomized, open-label, single-dose, two-period, two-way crossover clinical trial

ObjectiveThe aim of this study was to examine the pharmacokinetics, bioequivalence, and safety of two tablet formulations of capecitabine 500 mg in Chinese patients with breast, colorectal or gastric cancer under fed condition. MethodsA multicentric, randomized, open-label, single-dose, two-period, two-way crossover trial was conducted by randomizing a single oral dose of test (T) or reference (R, Xeloda®) capecitabine (500 mg) to patients of either sex with colon, colorectal or breast cancer under fed condition (high-fat and high-calorie diet). Pharmacokinetic parameters were calculated using non-compartmental methods. Patients were monitored for safety and tolerability throughout the study. Results74 subjects were randomly enrolled. The T/R geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for Cmax, AUC0-t and AUC0-∞ of capecitabine were 96.60% (85.87–108.67%), 99.07% (95.40–102.89%), 99.17% (95.29–103.21%), respectively. All 90% CIs fell within the bioequivalence acceptance range of 80.00–125.00%. The common adverse events (AEs) included clinically significant laboratory abnormalities and gastrointestinal diseases. There were no serious adverse events (SAEs) or deaths during the study. No subject withdrew from the study due to AEs. ConclusionSingle oral intake of test and the reference capecitabine tablets were bioequivalent under fed condition and had similar favourable safety profiles in Chinese patients with breast, colorectal or gastric cancer. Trial registrationchinadrugtrials.org.cn (CTR20182110).

The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice

AimsTo investigate the influence of the dose in the FITC-Dextran 4kDa (FD-4) permeability test in an obese mouse model, we tested the bodyweight dose regimen and a lean body mass-based dose regimen in high fat diet (HFD) mice and low fat diet (LFD) mice. We hypothesized that the FD-4 permeation result would be dose-dependent.MethodsThe two dose regimens were compared in HFD and LFD mice. Furthermore, we conducted a dose-response study to test the effect of a low or high dose of FD-4 in weight-stratified lean mice. Gene analysis of tight junctions was also carried out.ResultsThe FD-4 intestinal permeability test was dose-dependent as we found a significant increase in plasma levels of FD-4 in obese mice with the bodyweight dose regimen. However, this difference was not detectable with the lean body mass dose regimen, even with variability-adjusted group sizes. However, the qPCR analysis revealed a decrease in tight junction gene expression in obese mice. Furthermore, we found a dose-dependent significant increase in FD-4 measured in plasma samples in lean mice. No significant difference in intestinal weight was observed between lean and obese mice.ConclusionEvaluation of the intestinal permeability by FD-4 with the typical bodyweight dose regimen in obese mice will be confounded by the significant difference in dose given when compared to a lean control group. If the test dose is based on lean body mass, no significant difference in intestinal permeability is observed, even with large group sizes. Furthermore, we showed a dose-dependent difference in plasma FD-4 levels in lean mice. Therefore, we conclude that the dose should be based on lean body mass for the FD-4 permeability test if mice with considerable obesity differences are to be compared or to use another test with fixed doses.

Recommendations for advancing test protocols examining the photo-induced toxicity of petroleum and polycyclic aromatic compounds

Photo-induced toxicity of petroleum products and polycyclic aromatic compounds (PACs) is the enhanced toxicity caused by their interaction with ultraviolet radiation and occurs by two distinct mechanisms: photosensitization and photomodification. Laboratory approaches for designing, conducting, and reporting of photo-induced toxicity studies are reviewed and recommended to enhance the original Chemical Response to Oil Spills: Ecological Research Forum (CROSERF) protocols which did not address photo-induced toxicity. Guidance is provided on conducting photo-induced toxicity tests, including test species, endpoints, experimental design and dosing, light sources, irradiance measurement, chemical characterization, and data reporting. Because of distinct mechanisms, aspects of photosensitization (change in compound energy state) and photomodification (change in compound structure) are addressed separately, and practical applications in laboratory and field studies and advances in predictive modeling are discussed. One goal for developing standardized testing protocols is to support lab-to-field extrapolations, which in the case of petroleum substances often requires a modeling framework to account for differential physicochemical properties of the constituents. Recommendations are provided to promote greater standardization of laboratory studies on photo-induced toxicity, thus facilitating comparisons across studies and generating data needed to improve models used in oil spill science.

Bioequivalence Study Comparing a Generic and Innovator Drug of Rosuvastatin 20 mg

The bioequivalence study was conducted to compare the bioavailability of two rosuvastatin 20 mg film-coated tablet formulations (test and reference formulation). This study was an open-label, randomized, single-dose, two-periods, twotreatments, and crossover study which included 32 healthy adult male and female subjects under fasting conditions. Each of the two study periods was separated by a 7 days washout period. A single oral dose of test or reference drug was administered to the subject in each period based on the randomization scheme. Plasma concentrations of the drug were determined by LC-MS/MS method. The pharmacokinetic parameters assessed in this study were the area under the plasma concentration-time curve from time zero to 72 h (AUC0-72h), area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), the peak plasma concentration of the drug (Cmax), time needed to achieve the peak plasma concentration (Tmax), and the elimination half-life (T1/2). The geometric mean ratio (GMR) and 90% Confidence Interval (90% CI) for AUC0-72h and Cmax of test/reference drug for rosuvastatin were 97.05 % (89.07%– 105.74%) and 101.15% (89.53%– 114.26%). Since the 90% CI with α 0.05% for AUC0-72h and Cmax of rosuvastatin were within the standard bioequivalence range (80.00– 125.00%), it was concluded that the two rosuvastatin film-coated tablets (test and reference drug) were bioequivalence in terms of the rate and extent of absorption.

Reduced specificity for the local lymph node assay for lipophilic chemicals: Implications for the validation of new approach methods for skin sensitization

Meaningful and accurate reference data are crucial for the validation of New Approach Methodologies (NAMs) in toxicology. For skin sensitization, multiple reference datasets are available including human patch test data, guinea pig data and data from the mouse local lymph node assay (LLNA). When assessed against the LLNA, a reduced sensitivity has been reported for in vitro and in chemico assays for lipophilic chemicals with a LogP ≥3.5, resulting in reliability restrictions within the h-CLAT OECD test guideline.Here we address the question of whether LLNA data are an appropriate reference for chemicals in this physicochemical range. Analysis of LLNA vs human reference data indicates that the false-discovery rate of the LLNA is significantly higher for chemicals with LogP ≥3.5. We present a mechanistic hypothesis whereby irritation caused by testing lipophilic chemicals at high test doses leads to unspecific cell proliferation. The accompanying analysis indicates that for lipophilic chemicals with negative calls in in vitro and in chemico assays, resorting to the LLNA is not necessarily a better option. These results indicate that the validation of NAMs in this particular LogP range should be based on a more holistic evaluation of the reference data and not solely upon LLNA data.

ДОКЛИНИЧЕСКАЯ ОЦЕНКА СУБСТАНЦИИ «ГАЛF127КELМУ1М2П» НА ОСНОВЕ ПОЛИМЕРНЫХ МАТРИЦ

The design of the preparative hygienic substance "GALF127KELMU1m2p" and the study of its bio-pharmaco-toxicological properties based on aloe juice and methyluracil on a metellar site was carried out. In appearance, the substance is a homogeneous transparent liquid of light yellow color. The stability of the obtained during storage was studied at room temperature, in a place protected from light for 24 months. During the period of studying the substance, the original color and appearance are preserved and correspond to the original properties. After drying, a transparent film is formed. The concentration of hydrogen ions pH was in the range of 5.8...6.0 throughout the entire study period, the harmlessness in the test dose was in the range of 0.5...0.55 ml per mouse. For 30 days, the substance was subjected to "accelerated aging" in a thermostat at a temperature of +37oC. The expiration date was set at 1167 days or 3 years 2.4 months. When frozen, thawed and stored at room temperature, it does not delaminate and does not lose these properties. Intragastric administration of the substance to rats and mice in the maximum possible dose does not lead to violations of physiological functions and death of animals. The skin application of the substance "GALF127KELMU1m2p" to the trimmed area of the skin 1 time a day for 14 days to rabbits in doses from 6000 to 10000 mg / kg does not adversely affect the life support indicators of experimental animals. The sensitivity of rats and mice to the general toxic effect of the drug has no significant differences and according to the degree of exposure to the body according to GOST 12.1.007 belongs to hazard class 4 – low-hazard substances. It has been established that the hygiene product does not have an irritating effect on the mucous membranes of the eyes and skin. So after 15 minutes of application to the conjunctiva of the eye, there are no corneal opacities, the iris is without visible changes, there is no chymotosis. Hygienic means after application to the udder nipple after milking, a transparent blue film is created, which is retained in the period between milking.

Anaesthetic management of parturient posted for elective caesarean section with cerebral arteriovenous malformation

Sir, Cerebral arteriovenous malformation (AVM) has a prevalence of 0.01–0.05%.[1] We present a case of a 25-year-old primigravida at 37 weeks gestation, a known case of left frontoparietal AVM and epilepsy posted for elective cesarean section. Five years ago, she presented with weakness of the right upper and lower limbs. She was diagnosed with left frontoparietal AVM [Figures 1 and 2]. She had multiple seizure episodes and was started on T. levetiracetam 500 mg BD, T. lacosamide 200 mg BD, T. clobazam 10 mg BD, and T. phenytoin 100 mg OD.Figure 1: MR venogram showing large draining veins joining superior sagittal sinusFigure 2: MRI of the brain showing numerous flow voids along the left frontoparietal lobe and atrophy of neuroparenchyma in the left cerebral hemisphereA pre-anesthetic evaluation was done. She gave a history of seizure attacks 4 days back. She was premedicated with oral pantoprazole 40 mg and metoclopramide 10 mg 1 h before surgery and kept nil per oral for 6 h. All antiepileptic drugs were continued. In the operating room, the wedge was placed under her right hip. Standard pre-induction monitors were attached and intravenous (IV) access was secured. The cesarean section was done under general anesthesia. Rapid sequence induction was performed with IV thiopentone 5 mg/kg and rocuronium 1.2 mg/kg. The patient was intubated with a 7 mm internal diameter endotracheal tube after 1 min. Anesthesia was maintained with oxygen, air, and isoflurane. After delivery of a live female baby of 2.2 kg, IV fentanyl 2 mg/kg, midazolam 2 mg, ondansetron 4 mg, and oxytocin infusion were given. The patient was hemodynamically stable and the postoperative pain was managed with an ultrasound-guided bilateral transverses abdominis plane block. The parturient was extubated and shifted to the intensive care unit (ICU). She had an uneventful postoperative period. Cerebral AVM usually presents with intracranial hemorrhage, seizures, focal neurologic deficits, and headaches.[2] The symptoms of AVM may be mistaken with pregnancy-associated disorders such as eclampsia. computed tomography (CT) and magnetic resonance imaging (MRI) (with abdomen shielding) help to confirm the diagnosis. It is mandatory to document the neurological deficits, optimize antiepileptics, counsel regarding the potential complications, and the need for neurosurgery. The neurosurgeon and intervention radiologist were alerted regarding the patient’s delivery plan and the neurologist’s opinion was taken to optimize the antiepileptics. There are no conclusive data regarding the risk of AVM hemorrhage during pregnancy.[3,4] AVM hemorrhage during pregnancy is associated with 28% maternal and 14% neonatal mortality. Most centers prefer elective cesarean sections even though normal vaginal deliveries do not increase the risk of AVM hemorrhage. Uterine contractions during normal labor may increase the stress on the abnormal veins. Hence, if vaginal delivery is planned, epidural labor analgesia and assisted instrumental vaginal delivery are recommended. For cesarean section, general anesthesia is preferred over regional anesthesia to avoid neurological complications. cerebrospinal fluid (CSF) release with subarachnoid block causes a sudden change in the transmural pressure across the AVM predisposing it to rupture. An accidental intravascular injection of local anesthetic containing epinephrine test dose during the initiation of the test dose following epidural anesthesia could predispose to the rupture of AVM. The main aim of anesthetic management is to maintain the mean arterial and intracranial pressure within the normal range to reduce the risk of hemorrhage and cerebral hypoperfusion. Hypertensive responses to laryngoscopy and extubation should be obtunded. Thiopentone is the preferred induction agent.[5] Ketamine is avoided as it can increase blood pressure and intracranial pressure. Suxamethonium has to be avoided and a high dose of rocuronium 1.2 mg/kg is used for rapid sequence induction.[6] General anesthesia with controlled ventilation is used to keep PaCO2 at a low normal range to minimize cerebral vasodilatation and rise in intracranial pressure. Hypotension during surgery is avoided by optimal fluid resuscitation and vasopressors. Supine hypotension is avoided by the use of a wedge under the hip. Thus, multi-disciplinary care involving an obstetrician, intervention radiologist, neurologist, neurosurgeon, and obstetric anesthesiologist is required to ensure good pregnancy outcomes in these high-risk parturients. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Toxicity test of gelatin capsule materials from pangasius skin (Pangasius sp.) on mice (Mus musculus)

Gelatin is produced from animal skin and bones, which can be used as an ingredient in medicine capsules. There are issues regarding the mad cow disease and certain religious rules that do not allow the consumption of gelatin from pigs and cows, opening up opportunities for developing gelatin derived from fish. This study aims to determine the level of toxicity of pangasius skin gelatin capsules (Pangasius sp.) using the fixed-dose procedure method in mice based on the LD50 value. The 2,000 mg/kg BW dose is determined as the initial dose of the main test after the preliminary test. The test animals were divided into 2 groups, each containing 5 female mice of the DDY strain. The first group was the control group, and the second group was the test animal group which was treated with a dose of 2,000 mg/kg BW. The results showed that the LD50 value of pangasius skin gelatin was > 2,000 mg/kg BW. Pangasius skin gelatin is not toxic, as evidenced by the absence of death and changes in the average body weight of mice. Based on the significant difference in relative weight, only the lungs were affected by pangasius skin gelatin.

An Old Technique for Epidural Intravascular Test Dose in Parturients: Fentanyl Injection

An Old Technique for Epidural Intravascular Test Dose in Parturients: Fentanyl Injection

Sodium Arsenite in Drinking Water is a Continuous Threat to Maturing Reproductive System: a Study in Prepubertal Male Mice

Human exposure to arsenic in countries known for heavy arsenic load, where ground water arsenic level exceeds the WHO limit, can be detrimental for developing gonads. Developmental and reproductive toxicity of arsenic in rodents after in utero exposure is although known but information on the toxic effects of arsenic on postnatal gonadal development is scant. This aspect was the focus of the present investigation. Postnatal day 25 prepubertal male mice were challenged with sub-chronic and chronic (up to PND 53 & PND 114 respectively) oral exposure (drinking water) to low and high doses (0.01, 5, and 10 mg.L-1) of sodium arsenite. Data were compared statistically at P<0.05. Sub-chronic exposure to high arsenic doses led to significant increase in the production of reactive oxygen species and lipid peroxidation, while simultaneous significant reduction occurred in the activity of antioxidant enzymes catalase, superoxide dismutase and peroxidase, hormone concentrations (folliclestimulating hormone, luteinizing hormone, testosterone) and sperm parameters. Testicular cell damage and sperm DNA damage, as revealed by comet assay, were evident at 10 mg.L-1arsenic dose. Chronic exposure further aggravated the adverse effects. Severe testicular oxidative stress, reduction in hormones and pronounced histological alterations in testis and epididymis, and sperm parameters together with excessive sperm DNA damage were noticeable even at the lowest test dose of 0.01 mg.L-1. The study concludes that arsenic exposure considerably affects the prepubertal gonad, may cause irreversible damage to the developing reproductive system of males and that minute quantity of arsenic in drinking water can be a serious health hazard.

Determination of withdrawal time, efficacy, and safety test of enrofloxacin in carp (Cyprinus carpio)

The use of antibiotic such as enrofloxacin for the treatment of fish diseases needs to be appropriately controlled so that the medicine function effectively and does not cause antibiotic residues above the maximum residues limit (MRL). The study aims to determine the duration of administration, efficacy, and safety of enrofloxacin in carp. The size of the carp used was 10-40 g, with a length of 8-12 cm. The methods used in this study were (a) withdrawal time test, (b) efficacy and safety test, and (c) histopathology analysis. The results of determining enrofloxacin withdrawal time for 0.5 MRL and 1 MRL were two days and eight days, respectively. The survival rates of carp in post-challenge with Aeromonas hydrophila for the positive control and efficacy groups were 86.7% and 88.9%, respectively, and were not significantly different. The results of histopathological observations on the liver, spleen, kidney, and muscle of the carp showed no significant pathological changes between the safety test dose treatment and the control treatment.

Preclinical evaluation of analgesic activities of Barringtonia Racemosa

Background: Pain is the major devastating health problems. Barringtonia racemosa Roxb. (Lecythidaceae) is the one which is frequently used to treat pain by traditional healers in Ethiopian folk medicine. However, the plant has not been scientifically evaluated for its traditionally claimed use. The present study aimed at the investigation of analgesic activities of ethanol root extract of Barringtonia racemosa Roxb in Albino rats (Wistar) model. Methods: Successive maceration was used as a method of extraction using solvents ethanol. After extraction of the roots, the crude extract was evaluated for its analgesic activities using tail flick and hot plate method. The extract was evaluated at 100, 200 and 400 mg/kg doses. The positive control groups were treated with Aspirin 20 mg/ kg i.p, distilled water (10 mL/kg) treated rat were assigned as negative controls. Results: Barringtonia racemosa Roxb root extract at all test doses showed statistically significant antinociceptive activity in both model in a dose dependent manner (p &lt; 0.01 and p &lt; 0.001). The greater analgesic activity was observed by the maximum dose of the extract (400 mg/kg) in both tail flick and hot plate method method. Conclusion: In general, the data obtained from the present study elucidated that the extract possessed a significant analgesic activities and recommended for further studies.

Comparative study on intravenous iron sucrose versus intravenous ferric carboxymaltose in the management of iron deficiency anaemia in pregnancy in a tertiary care hospital, Bengaluru

Background: Iron deficiency is the most common nutritional deficiency worldwide; it affects 1.6 billion people Iron deficiency (ID) and iron deficiency anemia (IDA) are often encountered in the general population, particularly among children and women with abnormal uterine bleeding (AUB) and during pregnancy as well as postpartum period Intravenous (IV) iron replacement can deliver the total amount of required iron over a short period. Currently, the most commonly used IV iron formulations are iron sucrose (IS) and ferric carboxymaltose (FCM) [4-6]. Iron sucrose does not require test dose and is safe. Ferric carboxymaltose (FCM) is the latest I.V. iron formulation which can be used at high doses and allows rapid administration (up to 1000 mg in a single dose infused in 15 minutes) The present study was a comparative study of parenteral iron therapy (intravenous iron sucrose versus intravenous ferric carboxymaltose in the management of iron deficiency anaemia in pregnancy.Methods: In the present study, 50 pregnant women with IDA were randomly distributed into two groups of 25 each. Group - A: 25 receiving intravenous iron sucrose therapy; Group - B: 25 receiving intravenous ferric carboxymaltose therapy.Results: Majority of the study participants in Group A had gestational age between 20–25 weeks (48%). The mean age of the study participants in Group A was found to be 22.86+4.42 weeks. Majority of the study participants in Group B had gestational age between 20-25 weeks (36%). The mean age of the study participants was found to be 23.01+3.01 weeks. Majority of the study participants in Group A had nil parity (40%). 36% of the study participants in Group B had nil parity. 60% of the study participants in group A had Mild degree of anaemia with 52% in group B having mild degree of anaemia. 40% and 44% of the study participants in group A and group B had Moderate degree of anaemia respectively. The association was found to be statistically significant between the mean Hb and Ferritin values pre-treatment, 3rd and 6th week follow-up post treatment and the 2 groups of study participants. The adverse effects were comparatively lower among Group B (IV ferric carboxymaltose) than Group A (IV iron sucrose) of the study participants.Conclusions: IV ferric carboxymaltose administration increases the hemoglobin level more rapidly as compared to iron sucrose in women with iron deficiency anemia in the pregnancy. It also stores iron more rapidly. No serious adverse effects were recorded. Ferric carboxymaltose is well tolerated, safe and effective alternative to iron sucrose in iron deficiency anemia of pregnancy. FCM has the advantage of a large dose administration per sitting and early rise in hemoglobin level.

A Prospective Randomized Trial of Ropivacaine 5 mg with Sufentanil 2.5 μg as a Test Dose for Detecting Epidural and Intrathecal Injection in Obstetric Patients.

Objectives: Traditional epidural test dose is somewhat unsuited in obstetrics because of potential risk of severe adverse effects when it is accidentally injected into the subarachnoid space. Some hospitals use a proportion of the total dose of epidural labor analgesia as a test dose. The aim of our study was to assess the effectiveness and safety of ropivacaine 5 mg with sufentanil 2.5 μg to detect intrathecal injection. Methods: This prospective randomized study enrolled parturients who had the demand for epidural labor analgesia and randomly divided them into two groups. Then, 5 mL of 0.1% ropivacaine with sufentanil 2.5 μg was injected into the epidural space or the subarachnoid space in the epidural (EP) group and the intrathecal (IT) group, respectively. The ability to detect intrathecal injection and side effects were assessed to work out the effectiveness and safety. Results: For spinal injection, the sensitivity and the specificity of the symptoms of either warmth or numbness or both assessed at 3 min were both 100%, and the observed negative predictive value (NPV) and positive predictive value (PPV) were 100%. All parturients in the IT group and 2.33% of parturients in the EP group had sensory blockade to cold or pinprick (p < 0.0001). A total of 77.55% (38 of 49) of parturients in the IT group were found to have a motor block. A 10 min assessment showed the median cephalad cold and pin levels were T8 and T10, respectively, and the median Bromage score was 4 in the IT group. Incidences of adverse effects in both groups were low. Conclusions: Ropivacaine 5 mg with sufentanil 2.5 μg is effective and safe to detect intrathecal injection as an epidural test dose in obstetric patients.

Prediction of Busulfan Clearance by Predose Plasma Metabolomic Profiling.

Intravenous busulfan doses are often personalized to a target plasma exposure (targeted busulfan) using an individual's busulfan clearance (BuCL). We evaluated whether BuCL could be predicted by a predose plasma panel of 841 endogenous metabolomic compounds (EMCs). In this prospective cohort of 132 hematopoietic cell transplantation (HCT) patients, all had samples collected immediately before busulfan administration (preBU) and 96 had samples collected 2 weeks before busulfan (2-week-preBU). BuCL was significantly associated with 37 EMCs after univariate linear regression analysis and controlling for false discovery (< 0.05) in the 132 preBU samples. In parallel, with preBU samples, we included all 841 EMCs in a least absolute shrinkage and selection operator-penalized regression which selected 13 EMCs as predominantly associated with BuCL. Then, we constructed a prediction model by estimating coefficients for these 13 EMCs, along with sex, using ordinary least-squares. When the resulting linear prediction model was applied to the 2-week-preBU samples, it explained 40% of the variation in BuCL (adjusted R2 =0.40). Pathway enrichment analysis revealed 18 pathways associated with BuCL. Lysine degradation followed by steroid biosynthesis, which aligned with the univariate analysis, were the top two pathways. BuCL can be predicted before busulfan administration with a linear regression model of 13 EMCs. This pharmacometabolomics method should be prioritized over use of a busulfan test dose or pharmacogenomics to guide busulfan dosing. These results highlight the potential of pharmacometabolomics as a precision medicine tool to improve or replace pharmacokinetics to personalize busulfan doses.