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This study investigates the effectiveness of gender-mainstreamed aid in mitigating gender inequality. We develop a robust theoretical model that accounts for the potential positive and perceived negative effects of shifts toward gender parity, capturing diverse societal perspectives. Utilizing a comprehensive dataset on aid activities focused on gender (in)equality and women’s empowerment across 118 countries from 2009 to 2022, primarily low-income nations, we employ panel fixed-effects and mixed-effects random coefficient models to examine the impact of gender-related aid on gender inequality. Our findings reveal that significant gender-related aid (SGRA), which integrates gender considerations into broader development projects, reduces gender inequality in 115 out of 118 countries. In contrast, principal gender-related aid (PGRA), which explicitly targets gender equality, shows significant effects in only 85 countries. When analyzing the effects of both components of gender-related aid, we find that SGRA consistently impacts gender inequality. However, the effectiveness of PGRA becomes less clear-cut. This observation, coupled with the variation in the effectiveness of the components across countries, underscores the importance of developing strategies tailored to country-specific needs and conditions in promoting gender parity effectively.

Abstract Acetazolamide is an old drug used as an antiepileptic agent, amongst other indications. The drug is seldom used, primarily due to perceived poor efficacy and adverse events. Acetazolamide acts as a noncompetitive inhibitor of carbonic anhydrase, of which there are several subtypes in humans. Acetazolamide causes an acidification of the intracellular and extracellular environments activating acid‐sensing ion channels, and these may account for the anti‐seizure effects of acetazolamide. Other potential mechanisms are modulation of neuroinflammation and attenuation of high‐frequency oscillations. The overall effect increases the seizure threshold in critical structures such as the hippocampus. The evidence for its clinical efficacy was from 12 observational studies of 941 patients. The 50% responder rate was 49%, 20% of patients were rendered seizure‐free, and 30% were noted to have had at least one adverse event. We conclude that the evidence from several observational studies may overestimate efficacy because they lack a comparator; hence, this drug would need further randomized placebo‐controlled trials to assess effectiveness and harm.

This study investigates the effectiveness of gender-mainstreamed aid in mitigating gender inequality. We develop a robust theoretical model that accounts for the potential positive and perceived negative effects of shifts toward gender parity, capturing diverse societal perspectives. Utilizing a comprehensive dataset on aid activities focused on gender (in)equality and women's empowerment across 118 countries from 2009 to 2022, primarily low-income nations, we employ panel fixed-effects and mixed-effects random coefficient models to examine the impact of gender-related aid on gender inequality. Our findings reveal that significant gender-related aid (SGRA), which integrates gender considerations into broader development projects, reduces gender inequality in 115 out of 118 countries. In contrast, principal gender-related aid (PGRA), which explicitly targets gender equality, shows significant effects in only 85 countries. When analyzing the effects of both components of gender-related aid, we find that SGRA consistently impacts gender inequality. However, the effectiveness of PGRA becomes less clear-cut. This observation, coupled with the variation in the effectiveness of the components across countries, underscores the importance of developing strategies tailored to country-specific needs and conditions in promoting gender parity effectively. [ABSTRACT FROM AUTHOR]

Introduction: Dementia is now responsible for the greatest burden of disease of any chronic illness in older Australians. Rural and remote communities bear the impacts of this disproportionately. Additional training and education for healthcare staff to support people living with dementia is needed. Objective: The objective of this scoping review was to map and synthesise the evidence related to barriers and enablers of accessing dementia training for Australian healthcare workers located in rural and remote areas. Design: This scoping review systematically searched multiple databases in January 2023 for peer‐reviewed literature on the topic. Reviewers used Covidence to screen titles and abstracts of located sources, and to screen full‐text articles. Findings: From 187 articles screened, seven peer‐reviewed journal articles were included in the final data analysis; all were from Australia or Canada. The most common barrier described was low staffing, precluding release of staff for dementia training. Enablers to participation in dementia training were availability of online training programs, as well as training providers collaborating with end users to ensure the training met their learning needs. Discussion: This review provides evidence of barriers and enablers specific to rural and remote healthcare workers accessing dementia training. It also explores other approaches to training that have been trialled successfully in different settings. Conclusion: Addressing the identified barriers and enablers may assist in developing training approaches appropriate for existing staff, and in meeting training needs for the future workforce. [ABSTRACT FROM AUTHOR]

Ictal arrhythmias are disturbances of cardiac conduction that occur during clinical or electrographic seizures. Ictal asystole (IA) is rare, and its incidence can range from 0.3–0.4% in patients with epilepsy who were monitored by video-EEG (van der Lende et al., 2015).We report on ten patients (six males and four females) with an age ranging from 31 to 70 years old) who were monitored in our video-EEG (VEEG) unit over the last eight years. These patients were selected based on the history of documented ictal asystole during inpatient VEEG monitoring). In our series the mean latency from the seizure onset to the onset of ictal asystole was 22 seconds and the mean duration of the IA was 15.8 seconds. During the asystolic phase the seizures may clinically continue or syncopal signs may supervene.In our case series all the patients had either left or right temporal lobe epilepsy, six of which were lesional. We found two patterns of ictal semiology in our series. The first group of patients included five patients who experienced a rapid onset of IA in their seizure and the second group where the latency of ictal asystole was relatively late. All our cohort had a permanent pacemaker following the diagnosis, six of these patients have been event free since placement.

Acetazolamide is an old drug used as an antiepileptic agent, amongst other indications. The drug is seldom used, primarily due to perceived poor efficacy and adverse events. Acetazolamide acts as a noncompetitive inhibitor of carbonic anhydrase, of which there are several subtypes in humans. Acetazolamide causes an acidification of the intracellular and extracellular environments activating acid‐sensing ion channels, and these may account for the anti‐seizure effects of acetazolamide. Other potential mechanisms are modulation of neuroinflammation and attenuation of high‐frequency oscillations. The overall effect increases the seizure threshold in critical structures such as the hippocampus. The evidence for its clinical efficacy was from 12 observational studies of 941 patients. The 50% responder rate was 49%, 20% of patients were rendered seizure‐free, and 30% were noted to have had at least one adverse event. We conclude that the evidence from several observational studies may overestimate efficacy because they lack a comparator; hence, this drug would need further randomized placebo‐controlled trials to assess effectiveness and harm. [ABSTRACT FROM AUTHOR]

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.

To evaluate the quality of whole‐exome sequencing (WES) reporting in the epilepsy literature. We aimed to assess the quality of reporting of WES in epilepsy. We compared studies based on journal type and if outcome reporting biases exist. We used a self‐constructed benchmark to quantitatively analyze studies. We included 451 publications. Reporting was heterogeneous with poor reporting of (1) ACMG guideline application 13% and (2) Human Phenotype Ontology (HPO) numbers in 3% of studies, 3) VUS in 19%. Predictors of reporting included journal type and journal impact factor. Date of publication and publication type were not predictors of poor reporting. Pairwise comparisons of genetics versus neurology journals using relative risks yielded significant differences in reporting of ACMG guideline application (RR 1.88, 95% CI 1.04–3.38); HPO numbers (RR 8.62, 95% CI 1.08–63.37) and deposition of findings to ClinVar (RR 2.50, 95% CI 1.03–6.1). Reporting of WES literature is heterogeneous in quality, and poor reporting hinders collaboration and accession of data into large databases like OMIM and OrphaNet. This study highlights reporting bias in this area and, formal structural guidelines like the CONSORT guidelines used in the reporting of clinical trials are needed to address the issue. [ABSTRACT FROM AUTHOR]

Pregnant women affected by female genital mutilation/cutting are at risk of adverse maternal outcomes compared to unaffected women, and sometimes require procedures to facilitate giving birth that midwives and doctors do not routinely perform. These women require culturally sensitive care. Current health professional literature provides evidence that midwives and doctors need further knowledge and training in this area. This audit aimed to describe the demographic characteristics of pregnant women with female genital mutilation/cutting giving birth at two Perth maternity units, in addition to assessing health provider compliance with the local female genital mutilation/cutting Clinical Guideline. The clinical database used by public maternity units in Western Australia was used to identify affected women who gave birth during 2014 at King Edward Memorial Hospital or Osborne Park Hospital. Demographic characteristics and information about antenatal care and maternal outcomes were collected. 53 women fulfilled the audit criteria. Prevalence of pregnant women with female genital mutilation/cutting varied from 0.33% to 2.18% between the two units. Compliance with the Female Genital Mutilation/Cutting Clinical Guideline was generally suboptimal. While no woman was deinfibulated antenatally, 26% of women required intrapartum deinfibulation to give birth. Women with female genital mutilation/cutting make up more than 2% of the antenatal population in some Perth metropolitan maternity units. Health care provider knowledge of, and compliance with, the Female Genital Mutilation/Cutting Clinical Guideline was poor in the two units studied. It appears that healthcare professionals need more education and training to provide affected women with the best care. [ABSTRACT FROM AUTHOR]

Trade policy barriers and high transaction costs hinder developing countries from taking the full advantages of the global trading system. In order to help developing countries overcome the problem, the World Trade Organization (WTO) launched the Aid for Trade (AFT) initiatives in its Ministerial Conference held in Hong Kong in 2005. We examine the effects of AFT inflows on bilateral trade costs facing 133 developing countries while accounting for differences in their location on the contours of various measures of institutional quality. Our results from the estimation of a mixed effects (random-intercept and random-coefficient) model indicate that institutional quality significantly affects the extent to which AFT reduces bilateral trade costs. An important policy implication of our findings is that an economically robust and sustainable reduction in bilateral trade costs facing developing countries requires the presence of both promulgated and effectively functioning institutions such as regulatory power and the rule of law. [ABSTRACT FROM AUTHOR]

Using the first comprehensive estimates of ad valorem tariff equivalent bilateral trade costs spanning the time period 2002-10, we examine whether the aid-for-trade ( AFT) inflows reduce bilateral trade costs facing aid recipients. If so, we ask whether the trade costs reduction effects of AFT from bilateral and multilateral sources are complementary. By showing the extent to which the observed trade cost reduction effects of AFT from bilateral (multilateral) sources correlate with the magnitudes of AFT disbursements from multilateral (bilateral) sources, we present plausible explanation for the cross-country variations in the extent to which AFT promotes trade flows. Our findings have, thus, important policy implications for shaping future discourses on the coordination of disbursements for enhancing the effectiveness of AFT. [ABSTRACT FROM AUTHOR]

The search for novel drugs and alternative medicine has led to increased research in medicinal plants. Among such plants is the orange fruit. Its peels have been utilized for long as an active ingredient in most traditional medicines. This study aims at investigating the chemical properties of the hexane and dichloromethane (DCM) extracts of orange peel as well as their biological potentials. Blended peels were extracted with n-hexane and n-dichloromethane, respectively. The resulting extracts were subjected to gas chromatography mass spectrometry (GCMS) characterization. The extracts were also assayed for free radical scavenging ability against 1,1 –diphenyl –2 picrylhydrazyl (DPPH), antioxidative burst via measuring luminol –amplified chemiluminescence response in human blood, and phytotoxicity against lemna minor. GCMS analysis revealed a predominance of fatty acid methyl esters in the hexane extract, while the DCM extract had more ketone metabolites. The DCM extract had significant (p <.05) higher free radical scavenging and antioxidative burst activities compared to the hexane. Both extracts revealed a significantly (p <.05) high phytotoxicity activity. Results from this study indicated that solvent type played a vital a role in the extraction of secondary metabolites, which are responsible for the observed biological activities. The higher activities by the DCM extract can be attributed to its constituents as revealed by GCMS analysis. There is great need to explore the phytotoxicity potentials of both extracts as natural herbicides. [ABSTRACT FROM AUTHOR]

Objective Many different gene families are currently being investigated for their potential role in epilepsy and in the response to antiepileptic drugs. A common research challenge is identifying the members of a gene family that are most significantly dysregulated within the human epileptic focus, before taking them forward for resource-intensive functional studies. Published data about transcriptomic changes within the human epileptic focus remains incomplete. A need exists for an accurate in silico system for the prediction of dysregulated genes within the epileptic focus. We present such a bioinformatic system. We demonstrate the validity of our approach by applying it to the solute carrier ( SLC) gene family. There are >400 known SLCs. SLCs have never been systematically studied in epilepsy. Methods Using our in silico system, we predicted the SLCs likely to be dysregulated in the epileptic focus. We validated our in silico predictions by identifying ex vivo the SLCs dysregulated in epileptic foci, and determining the overlap between our in silico and ex vivo results. For the ex vivo analysis, we used a custom oligonucleotide microarray containing exon probes for all known SLCs to analyze 24 hippocampal samples obtained from surgery for pharmacoresistant mesial temporal lobe epilepsy and 24 hippocampal samples from normal postmortem controls. Results There was a highly significant (p < 9.99 × 10−7) overlap between the genes identified by our in silico and ex vivo strategies. The SLCs identified were either metal ion exchangers or neurotransmitter transporters, which are likely to play a part in epilepsy by influencing neuronal excitability. Significance The identified SLCs are most likely to mediate pharmacoresistance in epilepsy by enhancing the intrinsic severity of epilepsy, but further functional work will be needed to fully evaluate their role. Our successful in silico strategy can be adapted in order to prioritize genes relevant to epilepsy from other gene families. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM PUBLISHER]

In this article we re-examine the relationship between remittances and economic growth placing special attention on the nonlinearity of this relationship. Previous studies have ignored the non-linearity of the relationship between remittances and economic growth or have used a quadratic term to capture nonlinearity. We show that the relationship between remittances and growth is neither linear nor quadratic and propose the use of a semiparametric model to avoid the risk of misspecification bias from imposing an arbitrary functional form. We find evidence of a positive relationship between remittances and growth in parametric estimations; however, such a relationship disappears when nonlinearity is taken into account using non-parametric techniques. [ABSTRACT FROM AUTHOR]

So far, the alcohol dehydrogenase-catalysed conversion of longer chain aliphatic substrates has been challenging due to their low solubility in aqueous solution. However, by utilising the ketone directly as a second organic phase, the straightforward synthesis of long chain aliphatic chiral alcohols is enabled. [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]

Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objecctive of the present study was to evaluate effects of benzothiazole analogs (compounds 1–26 ) for their immunomodulatory activities. Eight compounds ( 2 , 4 , 5 , 8 – 10 , 12 , and 18 ) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC 50 ranging from 3.7 to 11.9 μM compared to that of the standard drug, prednisolone <1.5 μM. Some compounds ( 2, 4 , 8 , and 18 ) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC 50 values ranging between <4.0 and 12.8 μM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2 , 8 , 9 , and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC 50 values between <4.0 and 15.2 μM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4 , 8 , 9 , and 18 at a concentration of 25 μg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5 , 8 , 12 , and 18 showed significant ( P < 0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC 50 range of <4.0 to 40.3 μM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases. [ABSTRACT FROM AUTHOR]

The synthetic indole Mannich bases 1 – 13 have been investigated for their ability to modulate immune responses measured in vitro . These activities were based on monitoring their affects on T-lymphocyte proliferation, reactive oxygen species (ROS), IL (interleukin)-2, IL-4, and nitric oxide production. Compound 5 was found to be the most potent immunomodulator in this context. Four of the synthesized compounds, 5 , 11 , 12 , and 13 , have significant potent inhibitory effects on T-cell proliferation, IL-4, and nitric oxide production. However, none of the thirteen indole compounds exerted any activity against ROS production. [ABSTRACT FROM AUTHOR]