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Aerial parts of Salvia Mirzayanii was extracted with methanol. Methanol extract was suspended in water and defatted with petroleum ether. The defatted part was then partitioned between ethyl acetate and water. The ethyl acetate partition was chromatographed on a silica gel column to afford several fractions. Lymphocyte proliferation inhibitory assay of the resulted fractions was compared in-vitro and the fraction with more immunosuppressive activity was subjected to more purification to yield three methoxylated flavones: 5,7-dihydroxy,6,4'- dimethoxyflavone(1), 5-hydroxy,6,7,3',4'-tetramethoxyflavone(2) and 5,3'-dihydroxy,6,7,4'- trimethoxyflavone (3). Compounds 2 and 3 potently suppressed the proliferation of human blood lymphocytes with IC50 values of 1.3 ± 0.04 µg/mL and 1.3 ± 0.21 µg/mL in comparison with prednisolone as one of the lymphocyte suppressor drugs (IC50=1.45 ± 0.6 µg/mL). In phagocyte chemiluminescence assay, compounds 1 and 3 in peripheral mononuclear cells (PMNCs) exerted suppressive moderate activity against ROS with IC50 of 55.3 ± 0.4 and 36.2 ± 0.7 µg/mL, respectively, while compound 2 showed weak activity with IC50 values more than 100 µg/mL. In conclusion, compounds 2 and 3 have a similar suppressive effect more than compound 1 on PHA-activated lymphocyte proliferation, which might be because of their C-3' oxidation pattern of ring B. It is indicated that the presence of 3'-OH or 3'-OMe in flavone ring B, caused more antiproliferation activity than 3'-H. Oxidative burst assay showed more activity for compound 1 which is less methoxylated than others. It also showed more activity for compounds 3 than 2, which differ only in 3'-OH instead of 3'-OMe. [ABSTRACT FROM AUTHOR]

Background: Patients diagnosed with New Daily Persistent Headache and Persistent Post-Traumatic Headache belong to a heterogeneous group of primary and secondary headache disorders, with the common clinical feature that these conditions start abruptly, continue unabated, and are refractory to conventional migraine preventive treatments. Objective: This is a real-world, medium-term audit to explore whether erenumab improves quality of life in a pooled group of 82 abrupt-onset, unremitting and treatment refractory patients, where the diagnosis is new daily persistent headache and persistent post-traumatic headache in the majority of cases. Methods: Eighty-two patients were treated with erenumab every 28 days over a two to three-year period, beginning in December 2018. These patients were "longstanding chronic" and refractory with a median of eight (IQR 4–12) prior failed migraine preventive treatments and median duration of disease of seven (IQR 3–11) years. The starting dose of erenumab was 70 mg in 79% of cases and 140 mg in the remaining patients (individuals with a BMI of more than 30). All patients were asked to complete three migraine specific Quality of Life questionnaires or Patient Reported Outcome Measures before starting treatment and typically at 3–12 intervals until the end of June 2021 or cessation of treatment. The Patient Reported Outcome Measures included: Headache Impact Test-6, Migraine Associated Disability Assessment test and Migraine-Specific Quality-of-Life Questionnaire. Patients generally only stayed on treatment after 6–12 months if there was deemed to be an improvement of at least 30% and there were no significant side effects. The longest treated cases have quality of life data for 30 months after starting erenumab. Results: Of the 82 patients, 29 (35%) had improvement in Quality of Life scores, with no significant side effects, and wished to stay on treatment. Fifty-three patients (65%) stopped treatment during the first 6–25 months due to lack of efficacy and/or patient reported side effects (n = 33 and n = 17, respectively) or a combination of both, pregnancy planning (n = 2), and lost to follow up (n = 1). Conclusion: Significant improvements in Quality of Life scores were recorded by one-third of patients over a period of 11–30 months, with a 35% persistence after a median of 26 months of treatment. This contrasts with our recently published, treatment resistant, chronic migraine cohort where the persistence with erenumab treatment was almost 55% after a median time of 25 months. [ABSTRACT FROM AUTHOR]

Using data on stocks of Foreign Direct Investment (FDI) from 131 countries spanning the years 1984 to 2004 and the number of products exported by each country, we examine the effect of FDI on horizontal export diversification. To quantify the effects, we utilize parametric (quantile) and semi-parametric econometric methods. Results from both approaches indicate that, in general, an increase in the stock of FDI enhances the horizontal diversification of exports. The actual magnitude of the effect however, varies greatly across countries depending on the existing stock of FDI and stage of diversification, giving rise to an almost inverted U-shaped relationship. A further look at our results provides useful insights on the circumstances under which FDI may aid or inhibit the horizontal expansion of exports. [ABSTRACT FROM AUTHOR]

The Grewia asiatica (commonly known as Phalsa or Fasla) is a shrub or small tree found in southern Asia. It produces purple to black color fruit when ripe. In folk medicine the edible Grewia asiatica fruit is used in a number of pathological conditions. The current study described the effects of Grewia asiatica fruit on glycemic index (GI) and phagocytosis in healthy non-diabetic human subjects. The results showed that Grewia asiatica fruit has low GI value of 5.34 with modest hypoglycemic activity. Luminol-enhanced chemiluminescence assay was carried out to determine the production of reactive oxygen species (ROS) in the oxidative burst activity of whole blood. ROS production was found to be significantly affected, having the 78.3, 58.6 and 30.8% when the subjects were fed with D-glucose, mixture of D-glucose and Grewia asiatica fruit and Grewia asiatica fruit alone respectively as compared to the control. The aqueous, methanolic and butanolic extracts of Grewia asiatica fruits were found to produce a stimulatory effect on ROS production however; the chloroform, hexane and ethanol-acetate extracted exerted significant inhibitory effect. These results demonstrated that Grewia asiatica fruit has desirable effects on blood glucose metabolism manifested as low glycemic response and modulation of ROS production. [ABSTRACT FROM AUTHOR]

Background: Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures. Results: Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxylmethyl)- 5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)- 17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2-5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1-7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 μg/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay. Conclusion: Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs. [ABSTRACT FROM AUTHOR]

In 2018, the Therapeutic Goods Administration asked its Advisory Committee on Vaccines to provide independent expert advice on the available safety data on influenza vaccination in pregnancy with regards to the pregnancy category of influenza vaccines. Following the publication of the Advisory Committee on Vaccines statement, two of the four adult influenza vaccines and one of the two acellular pertussis vaccines used to vaccinate pregnant women in Australia have changed their pregnancy category to Category A. These changes show that the Australian regulator is receptive to feedback from the medical community on how to improve immunisation rates. Effect of package insert language on health-care providers' perceptions of influenza vaccination safety during pregnancy. [Extracted from the article]

Background: Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy., Objectives: To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy., Search Methods: We searched the Cochrane Epilepsy Group's Specialized Register (28 March 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field., Selection Criteria: Randomized, placebo-controlled, double-blinded, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary odds ratios were estimated for each outcome., Main Results: Two trials were included representing 961 randomized patients.Overall Odds Ratio (OR) (95% Confidence Interval (CIs)) for 50% or greater reduction in seizure frequency compared to placebo 2.96 (2.20, 4.00).Treatment withdrawal OR (95% CIs) compared to placebo 2.17 (1.59, 2.97).Side effects: OR (99% CIs) compared to placebo, ataxia 2.93 (1.72, 4.99); dizziness 3.05 (1.99, 4.67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine., Authors' Conclusions: Oxcarbazepine has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy, both in adults and children. However, trials reviewed were of relatively short duration, and provide no evidence about the long-term effects of oxcarbazepine. Results cannot be extrapolated to monotherapy or to patients with other epilepsy types.

The great majority of randomised controlled trials (RCTs) that compare antiepileptic drugs are industry sponsored and have the objective of obtaining a monotherapy license for a drug. Such trials do not inform everyday clinical practice as they tend to be too short and to depart from clinical practice by restricting clinicians in their choice of actions. The data that exists provides evidence that drugs with actions on voltage-gated sodium channels provide best seizure control for localised onset seizures and epilepsy syndromes, while valproate provides best seizure control for generalised epilepsy and unclassified syndromes. Drugs do, however, vary in their tolerability over the short term and in their risk for rare serious idiosyncratic adverse events, chronic toxicity and teratogenicity; issues that cannot be examined within the scope of RCTs.