Interspeaker variation in habitual speaking rate: additional evidence.

PURPOSE: The purpose of the present study was to test the hypothesis that talkers previously classified by Y.-C. Tsao and G. Weismer (1997) as habitually fast versus habitually slow would show differences in the way they manipulated articulation rate across the rate continuum. METHOD: Thirty talkers previously classified by Tsao and Weismer (1997) as having habitually slow (n = 15; 7 males, 8 females) and habitually fast (n = 15; 8 males, 7 females) articulation rates produced a single sentence at 7 different rates, using a magnitude production paradigm. Hence, the participants were not randomly assigned to conditions. RESULTS: Quadratic regression functions relating measured to intended articulation rates were all statistically significant, and most important, there were significant differences between the slow and fast groups in the y intercepts of the functions, for both males and females. CONCLUSIONS: This study provides a constructive replication of Tsao and Weismer (1997), showing a difference between slow and fast talkers with a new set of speech materials and in a new task. The findings appear to be consistent with a biological basis for intertalker rate differences.     

Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box–Behnken Experimental Design

Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT^®) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40–45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box–Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF’s was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0–t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.     

Novel flavonoid-based biodegradable nanoparticles for effective oral delivery of etoposide by P-glycoprotein modulation: an in vitro,ex vivo and in vivo investigations

Abstract

A receptor level interaction of etoposide with P-glycoprotein (P-gp) and subsequent intestinal efflux has an adverse effect on its oral absorption. The present work is aimed to enhance the bioavailability of etoposide by co-administering it with quercetin (a P-gp inhibitor) in dual-loaded polymeric nanoparticle formulation. Poly-lactic-co-glycolic acid (PLGA) nanoparticles were optimized for various parameters like o/w phase volume ratio, poly-vinyl alcohol concentration, PLGA concentration and sonication time. The cytotoxicity studies (MTT assay) revealed a 9- and 11-fold decrease in the IC 50 values for etoposide-loaded nanoparticles (ENP) and etoposide?+?quercetin dual-loaded nanoparticles (EQNP) when compared to that of free etoposide, respectively, and the results were further supported by florescent-activated cell sorter studies. The confocal imaging of the intestinal sections treated with ENP and EQNP containing fluorescent probe (rhodamine) showed the superiority of the EQNP to permeate deeper. Furthermore, pharmacokinetic studies on rats revealed that EQNP exhibited a 2.4-fold increase in bioavailability of etoposide than ENP with no quercetin. The developed loaded nanoparticles have the high potential to enhance the bioavailability of the etoposide and sensitize the resistant cells.     

Metabolic and pharmacological profiling of Penicillium claviforme by a combination of experimental and bioinformatic approaches

BackgroundPenicillium produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of Penicillium claviforme (P. claviforme) (FBP-DNA-1205) was studied alongside pharmacological research in this study.MethodsThe metabolic profile of P. claviforme fermented on Potato Dextrose Broth (PDB) was investigated in this work. The complete metabolomics studies of fungus were performed using GC-MS and LC-MS-QTOF techniques. An in vitro model was utilised to study the cytotoxic and antioxidant activities, while an in vivo model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis.ResultsGC-MS study showed the presence of alkanes, fatty acids, esters, azo and alcoholic compounds. Maculosin, obtain, phalluside, quinoline, 4,4’-diaminostilbene, funaltrexamine, amobarbital, and fraxetin were among the secondary metabolites identified using the LC-MS-QTOF technique. The n-hexane fraction of P. claviforme displayed significant cytotoxic activity in vitro, with an LD50 value of 92.22 µgml⁻¹. The antinociceptive effects in vivo were dose-dependent significantly (p < .001). Interestingly, during the 72 h of investigation, no acute toxicity was demonstrated. In addition, a docking study of tentatively identified metabolites against the inflammatory enzyme (COX-2) supported the antinociceptive effect in an in silico model.ConclusionMetabolic profile of P. claviforme shows the presence of biologically relevant compounds in ethyl acetate extract. In addition, P. claviforme exhibits substantial antioxidant and cytotoxic activities in an in vitro model as well as antinociceptive activity in an in vivo model. The antinociceptive action is also supported by a molecular docking study. This research has opened up new possibilities in the disciplines of mycology, agriculture, and pharmaceutics.

Key messages

• The first time explored complete metabolome through GC-MS and LC-MS-QTOF.
• Both in vivo & in vitro pharmacological investigation of P. claviforme.
• In silico molecular docking of LC-MS-QTOF metabolites.

     

Pandora's box: ethics of PGD for inherited risk of late-onset disorders

Until recently, the primary use of preimplantation genetic diagnosis (PGD) has been the selection of embryos to avoid lethal or debilitating gene mutations or abnormal chromosome complement. PGD can be used to reduce the risk of transferring to the uterus an embryo with Down syndrome, and parents who are carriers of severe genetic diseases may choose to avoid having children with these debilitating genetic conditions. The use of PGD is now being extended to include gene mutations that increase the risk of late-onset disorders such as breast and ovarian cancer. This paper argues for caution in advocating reproductive methods that are costly, have a limited chance of success, and for which the long-term outcome is unknown. Counselling should allow women a true choice of declining the option of PGD without recrimination, feelings of guilt or social pressure. There is concern that the Human Fertilisation and Embryology Authority has approved extension of PGD to late-onset multifactorial diseases without clear guidelines for its use. Guidelines for embryo selection should be revised to deal with potential conflict between reproductive success and genetic screening for disorders that do not profoundly affect the embryo or the children.     

Efficacy of crude neem seed kernel extracts against natural infestation of Sarcoptes scabiei var. ovis

This study was aimed to evaluate the efficacy of crude aqueous-methanol and aqueous extracts of neem (Azadirachta indica) seed kernel against sarcoptic mange of sheep. Crude aqueous-methanol (AME) and aqueous extracts (AE) of neem seed kernel (NSK) were prepared and formulated as 10% and 20% ointments (w/w), using Vaseline as vehicle. Forty-two lambs of Pak Karakul breed, having natural infection of sarcoptic mange were divided into seven experimental groups. Skin scrapings and clinical examination were carried out at scheduled intervals after treatment. Ivermectin (positive control) completely cleared infesting mites from animals after 10 days and 20% AME after 16 days. While, clinical mange was completely cured after 16 and 20 days with ivermectin and 20% AME, respectively, under field conditions. Only the higher concentration (20% AME) of NSK extracts completely cured the clinical mange, suggesting a dose-dependent response. Our results consolidate the belief that use of folk remedies can provide an effective and economic way of combating sarcoptic mange in sheep.     

An account of the botanical anthelmintics used in traditional veterinary practices in Sahiwal district of Punjab, Pakistan

AIM OF THE STUDY: The present study was aimed at documentation of botanical anthelmintics used in the traditional veterinary practices in Sahiwal district of Punjab, Pakistan. MATERIALS AND METHODS: In rapid rural appraisal, 331 traditional veterinary healers (TVH) were identified as key respondents in the study area followed by participatory rural appraisal for data collection using a well-structured questionnaire. Information was collected through interviews, focused group discussions and field visits over a period of 2 years. RESULTS: A total of 49 traditional recipes, with 41 plant species representing 39 genera and 27 families, were recorded for the treatment of helminthosis in animals. Most frequently used plants (>/=5 times) were Brassica campestris L. and Mallotus philippinensis (Lam.) Muell.-Arg. and most frequently used families (>/=5 times) were Brassicaceae, Euphorbiaceae and Solanaceae. Most frequently used part of the plant was leaves (n=10) followed in order by seeds (n=9), whole fruit (n=5), aerial parts and whole plant (n=4), fruit (n=3), bulb (n=2) and bark, rhizome, stem, stem plus root and twigs (n=1). Five recipes out of 49 (10.2%) contained more than one plant species and rest 44 (89.8%) contained single plant species. CONCLUSIONS: Twenty out of 41 plants (48.78%) are reported for the first time for their traditional use as anthelmintics in Pakistan. Further studies on pharmacokinetics using scientific procedures may prove these plants as promising candidates for their future use as anthelmintics.