Kinetic modelling of ultrasound-triggered chemotherapeutic drug release from the surface of gold nanoparticles.

Therapeutic ultrasound can be used to trigger the on-demand release of chemotherapeutic drugs from gold nanoparticles (GNPs). In the previous work, our group achieved doxorubicin (DOX) release from the surface of GNPS under low-intensity pulsed ultrasound (LIPUS) exposure. However, the specific release kinetics of ultrasound-triggered DOX release from GNPs is not known. Here, we present a release kinetics study of DOX from GNPs under ultrasound exposure for the first time. A novel dialysis membrane setup was designed to quantify DOX release from LIPUS-activated GNPs at 37.0 °C and 43.4 °C (hyperthermia temperature range). Contributions of thermal and non-thermal mechanisms of LIPUS-triggered DOX release were also quantified. Non-thermal mechanisms accounted for 40 ± 7% and 34 ± 5% of DOX release for 37.0 °C and 43.4 °C trials, respectively. DOX release under LIPUS exposure was found to follow Korsmeyer-Peppas (K-P) kinetics, suggesting a shift from a Fickian (static) to a non-Fickian (dynamic) release profile with the addition of non-thermal interactions. DOX release was attributed to an anomalous diffusion release mechanism from the GNP surface. A finite element model was also developed to quantify the acoustic radiation force, believed to be the driving force of non-thermal DOX release inside the dialysis bag.

A community genomics approach to natural hybridization.

Hybridization is a complicated, oft-misunderstood process. Once deemed unnatural and uncommon, hybridization is now recognized as ubiquitous among species. But hybridization rates within and among communities are poorly understood despite the relevance to ecology, evolution and conservation. To clarify, we examined hybridization across 75 freshwater fish communities within the Ozarks of the North American Interior Highlands (USA) by single nucleotide polymorphism (SNP) genotyping 33 species (N = 2865 individuals; double-digest restriction site-associated DNA sequencing (ddRAD)). We found evidence of hybridization (70 putative hybrids; 2.4% of individuals) among 18 species-pairs involving 73% (24/33) of study species, with the majority being concentrated within one family (Leuciscidae/minnows; 15 species; 66 hybrids). Interspecific genetic exchange-or introgression-was evident from 24 backcrossed individuals (10/18 species-pairs). Hybrids occurred within 42 of 75 communities (56%). Four selected environmental variables (species richness, protected area extent, precipitation (May and annually)) exhibited 73-78% accuracy in predicting hybrid occurrence via random forest classification. Our community-level assessment identified hybridization as spatially widespread and environmentally dependent (albeit predominantly within one diverse, omnipresent family). Our approach provides a more holistic survey of natural hybridization by testing a wide range of species-pairs, thus contrasting with more conventional evaluations.

Clinical and Quality of Life Benefits for End-Stage Workers' Compensation Chronic Pain Claimants following H-Wave® Device Stimulation: A Retrospective Observational Study with Mean 2-Year Follow-Up.

Previously promising short-term H-Wave® device stimulation (HWDS) outcomes prompted this retrospective cohort study of the longer-term effects on legacy workers' compensation chronic pain claimants. A detailed chart-review of 157 consecutive claimants undergoing a 30-day HWDS trial (single pain management practice) from February 2018 to November 2019 compiled data on pain, restoration of function, quality of life (QoL), and polypharmacy reduction into a summary spreadsheet for an independent statistical analysis. Non-beneficial trials in 64 (40.8%) ended HWDS use, while 19 (12.1%) trial success charts lacked adequate data for assessing critical outcomes. Of the 74 final treatment study group charts, missing data points were removed for a statistical analysis. Pain chronicity was 7.8 years with 21.6 ± 12.2 months mean follow-up. Mean pain reduction was 35%, with 89% reporting functional improvement. Opioid consumption decreased in 48.8% of users and 41.5% completely stopped; polypharmacy decreased in 36.8% and 24.4% stopped. Zero adverse events were reported and those who still worked usually continued working. An overall positive experience occurred in 66.2% (p < 0.0001), while longer chronicity portended the risk of trial or treatment failure. Positive outcomes in reducing pain, opioid/polypharmacy, and anxiety/depression, while improving function/QoL, occurred in these challenging chronic pain injury claimants. Level of evidence: III.

Perioperative Nutritional Supplementation Decreases Wound Healing Complications Following Elective Lumbar Spine Surgery: A Randomized Controlled Trial.

BACKGROUND: The prevalence of malnutrition in patients undergoing lumbar spine surgery ranges from 5% to 50% and is associated with higher rates of surgical site infections, medical complications, longer lengths of stay, and mortality. PURPOSE: To determine if perioperative nutritional intervention decreases wound healing complications in patients undergoing lumbar spine surgery. STUDY DESIGN/SETTING: A prospective randomized controlled trial. MATERIALS AND METHODS: Patients aged 55+ undergoing elective primary lumbar surgery were included. Patients with a preoperative albumin<3.5 g/dL were defined as malnourished. Intervention group received nutritional supplementation (protein shake) twice daily from postoperative day 0 to two weeks postdischarge. Control group was instructed to continue regular daily diets. Primary outcomes included minor in-hospital complications (wound drainage, electrolyte abnormalities, hypotension, ileus, deep venous thrombus) and wound healing complications within 90 days. Secondary outcomes included 90-day emergency room visits, readmissions, and return to the operating room. Baseline data were compared between groups using means comparison tests. Multivariable analysis evaluated association of outcomes with nutritional supplementation. Subanalysis of malnourished patients assessed effects of nutritional supplementation on outcomes. RESULTS: One hundred three patients were included. Thirty-seven (35.9%) were considered malnourished preoperatively. Forty-six (44.7%) received nutritional intervention and 57 (55.3%) served as controls. Adjusted analysis found patients receiving supplementation had lower rates of in-hospital minor complications (2.1% vs. 23.2%, P <0.01), and perioperative wound healing complications (3.4% vs. 17.9%, P <0.05). Subgroup analysis of 37 malnourished patients demonstrated that malnourished patients who received perioperative nutritional supplementation had lower rates of minor complications during admission (0.0% vs. 34.4%, P =0.01) and return to the operating room within 90 days (0.0% vs. 12.4%, P =0.04). CONCLUSIONS: Over one third of patients undergoing lumbar surgery were malnourished. Nutritional supplementation during the two-week perioperative period decreased rates of minor complications during admission and wound complications within 90 days. Malnourished patients receiving supplementation less often returned to the operating room. To our knowledge, this is the first study to investigate the effects of perioperative nutritional intervention on wound healing complications for patients undergoing elective lumbar spine surgery. LEVEL OF EVIDENCE: I.

Job-Related Performance and Quality of Life Benefits in First Responders Given Access to H-Wave® Device Stimulation: A Retrospective Cohort Study.

Current chronic pain treatments primarily target symptoms and are often associated with harmful side-effects and complications, while safer non-invasive electrotherapies like H-Wave® device stimulation (HWDS) have been less explored. The goal of this study is to evaluate first responder-reported effects of HWDS on job-related and quality-of-life measures. This is a retrospective cohort study where first responders were surveyed following voluntary use of HWDS regarding participant experience, frequency of use, job-related performance, and quality-of-life. Responses were analyzed using means comparison tests, while bivariate analysis assessed responses associated with HWDS usage. Overall, 92.9% of first responder HWDS users (26/28) reported a positive experience (p < 0.0001), with 82.1% citing pain reduction (p = 0.0013), while 78.6% indicated it would be beneficial to have future device access (p = 0.0046). Participants using H-Wave® were at least six times more likely to report higher rates of benefit (100% vs. 0%, p = 0.022), including pain reduction (91.3% vs. 8.7%, p = 0.021) and improved range-of-motion (93.3% vs. 69.2%, p = 0.044). Spending more time with family was associated with better job performance following frequent HWDS use (50% vs. 8.3%, p = 0.032). Repetitive first responder H-Wave® use, with minimal side effects and easy utilization, resulted in significant pain reduction, improvements in job performance and range-of-motion, and increased time spent with family, resulting in overall positive experiences and health benefits. Level of Evidence: III.

Site-Specific Conjugation Quantitation of a Cysteine-Conjugated Antibody-Drug Conjugate Using Stable Isotope Labeling Peptide Mapping LC-MS/MS Analysis.

Drug-load (DL) characterization of antibody-drug conjugates (ADCs) is an important analytical task due to its designation as a critical quality attribute (CQA) affecting potency and stability. Intact and subunit liquid chromatography-mass spectrometry (LC-MS) analyses can determine global drug-to-antibody ratios (DARs) that correlate well with other orthogonal analytical methods; however, peptide mapping liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has struggled to provide complementary site-specific quantitation of drug conjugation sites. The peptide mapping method described herein utilizes stable isotope labeling to accurately quantitate the site-specific conjugation levels of a cysteine-conjugated ADC to provide "bottom-up" DAR characterization in parallel with protein sequence and post-translational modification (PTM) characterization in one multi-attribute analytical method (MAM).

H-Wave® Device Stimulation: A Critical Review.

Pain treatments have historically centered on drugs, but an "opioid crisis" has necessitated new standards of care, with a paradigm shift towards multi-modal pain management emphasizing early movement, non-narcotics, and various adjunctive therapies. Electrotherapies remain understudied and most lack high-quality clinical trials, despite a desperate need for effective adjunctive options. A systematic search of human clinical studies on H-Wave® device stimulation (HWDS) was conducted as well as a comprehensive review of articles articulating possible HWDS mechanisms of action. Studies unrelated to H-Wave were excluded. Data synthesis summarizes outcomes and study designs, categorized as pre-clinical or clinical. Pre-clinical studies demonstrated that HWDS utilizes a biphasic waveform to induce non-fatiguing muscle contractions which positively affect nerve function, blood and lymph flow. Multiple clinical studies have reported significant benefits for diabetic and non-specific neuropathic pain, where function also improved, and pain medication usage substantially dropped. In conclusion, low- to moderate-quality HWDS studies have reported reduced pain, restored functionality, and lower medication use in a variety of disorders, although higher-quality research is needed to verify condition-specific applicability. HWDS has enough reasonable evidence to be considered as an adjunctive component of non-opioid multi-modal pain management, given its excellent safety profile and relative low cost. Level of Evidence: III.

Hierarchical contributions of linguistic knowledge to talker identification: Phonological versus lexical familiarity.

Listeners identify talkers more accurately when listening to their native language compared to an unfamiliar, foreign language. This language-familiarity effect in talker identification has been shown to arise from familiarity with both the sound patterns (phonetics and phonology) and the linguistic content (words) of one's native language. However, it has been unknown whether these two sources of information contribute independently to talker identification abilities, particularly whether hearing familiar words can facilitate talker identification in the absence of familiar phonetics. To isolate the contribution of lexical familiarity, we conducted three experiments that tested listeners' ability to identify talkers saying familiar words, but with unfamiliar phonetics. In two experiments, listeners identified talkers from recordings of their native language (English), an unfamiliar foreign language (Mandarin Chinese), or "hybrid" speech stimuli (sentences spoken in Mandarin, but which can be convincingly coerced to sound like English when presented with subtitles that prime plausible English-language lexical interpretations based on the Mandarin phonetics). In a third experiment, we explored natural variation in lexical-phonetic congruence as listeners identified talkers with varying degrees of a Mandarin accent. Priming listeners to hear English speech did not improve their ability to identify talkers speaking Mandarin, even after additional training, and talker identification accuracy decreased as talkers' phonetics became increasingly dissimilar to American English. Together, these experiments indicate that unfamiliar sound patterns preclude talker identification benefits otherwise afforded by familiar words. These results suggest that linguistic representations contribute hierarchically to talker identification; the facilitatory effect of familiar words requires the availability of familiar phonological forms.

Talker identification: Effects of masking, hearing loss, and age.

The ability to identify who is talking is an important aspect of communication in social situations and, while empirical data are limited, it is possible that a disruption to this ability contributes to the difficulties experienced by listeners with hearing loss. In this study, talker identification was examined under both quiet and masked conditions. Subjects were grouped by hearing status (normal hearing/sensorineural hearing loss) and age (younger/older adults). Listeners first learned to identify the voices of four same-sex talkers in quiet, and then talker identification was assessed (1) in quiet, (2) in speech-shaped, steady-state noise, and (3) in the presence of a single, unfamiliar same-sex talker. Both younger and older adults with hearing loss, as well as older adults with normal hearing, generally performed more poorly than younger adults with normal hearing, although large individual differences were observed in all conditions. Regression analyses indicated that both age and hearing loss were predictors of performance in quiet, and there was some evidence for an additional contribution of hearing loss in the presence of masking. These findings suggest that both hearing loss and age may affect the ability to identify talkers in "cocktail party" situations.

Brain and behavior changes associated with an abbreviated 4-week mindfulness-based stress reduction course in back pain patients.

INTRODUCTION: Mindfulness-based stress reduction (MBSR) reduces depression, anxiety, and pain for people suffering from a variety of illnesses, and there is a growing need to understand the neurobiological networks implicated in self-reported psychological change as a result of training. Combining complementary and alternative treatments such as MBSR with other therapies is helpful; however, the time commitment of the traditional 8-week course may impede accessibility. This pilot study aimed to (1) determine if an abbreviated MBSR course improves symptoms in chronic back pain patients and (2) examine the neural and behavioral correlates of MBSR treatment. METHODS: Participants were assigned to 4 weeks of weekly MBSR training (n = 12) or a control group (stress reduction reading; n = 11). Self-report ratings and task-based functional MRI were obtained prior to, and after, MBSR training, or at a yoked time point in the control group. RESULTS: While both groups showed significant improvement in total depression symptoms, only the MBSR group significantly improved in back pain and somatic-affective depression symptoms. The MBSR group also uniquely showed significant increases in regional frontal lobe hemodynamic activity associated with gaining awareness to changes in one's emotional state. CONCLUSIONS: An abbreviated MBSR course may be an effective complementary intervention that specifically improves back pain symptoms and frontal lobe regulation of emotional awareness, while the traditional 8-week course may be necessary to detect unique improvements in total anxiety and cognitive aspects of depression.

Common Questions About Chronic Prostatitis.

Chronic prostatitis is relatively common, with a lifetime prevalence of 1.8% to 8.2%. Risk factors include conditions that facilitate introduction of bacteria into the urethra and prostate (which also predispose the patient to urinary tract infections) and conditions that can lead to chronic neuropathic pain. Chronic prostatitis must be differentiated from other causes of chronic pelvic pain, such as interstitial cystitis/bladder pain syndrome and pelvic floor dysfunction; prostate and bladder cancers; benign prostatic hyperplasia; urolithiasis; and other causes of dysuria, urinary frequency, and nocturia. The National Institutes of Health divides prostatitis into four syndromes: acute bacterial prostatitis, chronic bacterial prostatitis (CBP), chronic nonbacterial prostatitis (CNP)/chronic pelvic pain syndrome (CPPS), and asymptomatic inflammatory prostatitis. CBP and CNP/CPPS both lead to pelvic pain and lower urinary tract symptoms. CBP presents as recurrent urinary tract infections with the same organism identified on repeated cultures; it responds to a prolonged course of an antibiotic that adequately penetrates the prostate, if the urine culture suggests sensitivity. If four to six weeks of antibiotic therapy is effective but symptoms recur, another course may be prescribed, perhaps in combination with alpha blockers or nonopioid analgesics. CNP/CPPS, accounting for more than 90% of chronic prostatitis cases, presents as prostatic pain lasting at least three months without consistent culture results. Weak evidence supports the use of alpha blockers, pain medications, and a four- to six-week course of antibiotics for the treatment of CNP/CPPS. Patients may also be referred to a psychologist experienced in managing chronic pain. Experts on this condition recommend a combination of treatments tailored to the patient's phenotypic presentation. Urology referral should be considered when appropriate treatment is ineffective. Additional treatments include pelvic floor physical therapy, phytotherapy, and pain management techniques. The UPOINT (urinary, psychosocial, organ-specific, infection, neurologic/systemic, tenderness) approach summarizes the various factors that may contribute to presentation and can guide treatment.

Talker identification across source mechanisms: experiments with laryngeal and electrolarynx speech.

PURPOSE: The purpose of this study was to determine listeners' ability to learn talker identity from speech produced with an electrolarynx, explore source and filter differentiation in talker identification, and describe acoustic-phonetic changes associated with electrolarynx use. METHOD: Healthy adult control listeners learned to identify talkers from speech recordings produced using talkers' normal laryngeal vocal source or an electrolarynx. Listeners' abilities to identify talkers from the trained vocal source (Experiment 1) and generalize this knowledge to the untrained source (Experiment 2) were assessed. Acoustic-phonetic measurements of spectral differences between source mechanisms were performed. Additional listeners attempted to match recordings from different source mechanisms to a single talker (Experiment 3). RESULTS: Listeners successfully learned talker identity from electrolarynx speech but less accurately than from laryngeal speech. Listeners were unable to generalize talker identity to the untrained source mechanism. Electrolarynx use resulted in vowels with higher F1 frequencies compared with laryngeal speech. Listeners matched recordings from different sources to a single talker better than chance. CONCLUSIONS: Electrolarynx speech, although lacking individual differences in voice quality, nevertheless conveys sufficient indexical information related to the vocal filter and articulation for listeners to identify individual talkers. Psychologically, perception of talker identity arises from a "gestalt" of the vocal source and filter.

Evidence for shared cognitive processing of pitch in music and language.

Language and music epitomize the complex representational and computational capacities of the human mind. Strikingly similar in their structural and expressive features, a longstanding question is whether the perceptual and cognitive mechanisms underlying these abilities are shared or distinct--either from each other or from other mental processes. One prominent feature shared between language and music is signal encoding using pitch, conveying pragmatics and semantics in language and melody in music. We investigated how pitch processing is shared between language and music by measuring consistency in individual differences in pitch perception across language, music, and three control conditions intended to assess basic sensory and domain-general cognitive processes. Individuals' pitch perception abilities in language and music were most strongly related, even after accounting for performance in all control conditions. These results provide behavioral evidence, based on patterns of individual differences, that is consistent with the hypothesis that cognitive mechanisms for pitch processing may be shared between language and music.

Influence of short-term consumption of the caffeine-free, epigallocatechin-3-gallate supplement, Teavigo, on resting metabolism and the thermic effect of feeding.

Green tea is purported to promote weight loss. Resting metabolic rate (RMR) and the thermic effect of feeding (TEF) are significant components of total daily energy expenditure and are partially determined by the sympathetic nervous system via catecholamine-mediated stimulation of ß-adrenergic receptors. Epigallocatechin-3-gallate (EGCG: the most bioactive catechin in green tea) inhibits catechol-O-methyltransferase, an enzyme contributing to the degradation of catecholamines. Accordingly, we hypothesized that short-term consumption of a commercially available EGCG supplement (Teavigo) augments RMR and TEF. On two separate occasions, seven placebo or seven EGCG capsules (135 mg/capsule) were administered to 16 adults (9 males, 7 females, age 25 ± 2 years, BMI 24.6 ± 1.2 kg/m(2) (mean ± s.e.)). Capsules (three/day) were consumed over 48 h; the final capsule was consumed 2 h prior to visiting the laboratory. Energy expenditure (ventilated hood technique) was determined at rest and for 5 h following ingestion of a liquid meal (caloric content: 40% RMR). Contrary to our hypothesis, RMR was not greater (P = 0.10) following consumption of EGCG (6,740 ± 373 kJ/day) compared with placebo (6,971 ± 352). Similarly, the area under the TEF response curve (Δ energy expenditure) was also unaffected by EGCG (246,808 ± 23,748 vs. 243,270 ± 22,177 kJ; P = 0.88). EGCG had no effect on respiratory exchange ratio at rest (P = 0.29) or throughout the TEF measurement (P = 0.56). In summary, together RMR and TEF may account for up to 85% of total daily energy expenditure; we report that short-term consumption of a commercially available EGCG supplement did not increase RMR or TEF.

Neural characteristics of successful and less successful speech and word learning in adults.

A remarkable characteristic of the human nervous system is its ability to learn to integrate novel (foreign) complex sounds into words. However, the neural changes involved in how adults learn to integrate novel sounds into words and the associated individual differences are largely unknown. Unlike English, most languages of the world use pitch patterns to mark individual word meaning. We report a study assessing the neural correlates of learning to use these pitch patterns in words by English-speaking adults who had no previous exposure to such usage. Before and after training, subjects discriminated pitch patterns of the words they learned while blood oxygenation levels were measured using fMRI. Subjects who mastered the learning program showed increased activation in the left posterior superior temporal region after training, while subjects who plateaued at lower levels showed increased activation in the right superior temporal region and right inferior frontal gyrus, which are associated with nonlinguistic pitch processing, and prefrontal and medial frontal areas, which are associated with increased working memory and attentional efforts. Furthermore, we found brain activation differences even before training between the two subject groups, including the superior temporal region. These results demonstrate an association between range of neural changes and degrees of language learning, specifically implicating the physiologic contribution of the left dorsal auditory cortex in learning success.

Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of Down syndrome.

Ts65Dn, a mouse model of Down syndrome (DS), demonstrates abnormal hippocampal synaptic plasticity and behavioral abnormalities related to spatial learning and memory. The molecular mechanisms leading to these impairments have not been identified. In this study, we focused on the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) gene that is highly expressed in the hippocampus region. We studied the expression pattern of GIRK subunits in Ts65Dn and found that GIRK2 was overexpressed in all analyzed Ts65Dn brain regions. Interestingly, elevated levels of GIRK2 protein in the Ts65Dn hippocampus and frontal cortex correlated with elevated levels of GIRK1 protein. This suggests that heteromeric GIRK1-GIRK2 channels are overexpressed in Ts65Dn hippocampus and frontal cortex, which could impair excitatory input and modulate spike frequency and synaptic kinetics in the affected regions. All GIRK2 splicing isoforms examined were expressed at higher levels in the Ts65Dn in comparison to the diploid hippocampus. The pattern of GIRK2 expression in the Ts65Dn mouse brain revealed by in situ hybridization and immunohistochemistry was similar to that previously reported in the rodent brain. However, in the Ts65Dn mouse a strong immunofluorescent staining of GIRK2 was detected in the lacunosum molecular layer of the CA3 area of the hippocampus. In addition, tyrosine hydroxylase containing dopaminergic neurons that coexpress GIRK2 were more numerous in the substantia nigra compacta and ventral tegmental area in the Ts65Dn compared to diploid controls. In summary, the regional localization and the increased brain levels coupled with known function of the GIRK channel may suggest an important contribution of GIRK2 containing channels to Ts65Dn and thus to DS neurophysiological phenotypes.

Fecal incontinence in elderly patients: common, treatable, yet often undiagnosed.

It is important for primary care physicians to take fecal incontinence seriously and not dismiss it as a normal part of aging. Elderly patients may be reluctant to admit fecal incontinence, so clinicians need to ask about it. Two of the most common causes are fecal impaction (especially in nursing home patients) and rectosphincter dysfunction in people with diabetes.

Variability in position of the subthalamic nucleus targeted by magnetic resonance imaging and microelectrode recordings as compared to atlas co-ordinates.

BACKGROUND: Traditional methods for localisation of target nuclei for deep brain stimulation (DBS) have used brain atlas co-ordinates for initial targeting. It is now possible to visualise the subthalamic nucleus (STN) on magnetic resonance imaging (MRI) and determine the individual variability of its position. METHODS: The present study was performed in patients undergoing STN DBS for Parkinson's disease. The STN was directly targeted from axially obtained MRI and verified with microelectrode recordings. Postoperatively, the most effective contact was identified for each patient, and its position was calculated. RESULTS: Fifty electrodes were inserted in 25 patients. The target position varied considerably in relation to the mid-commissural point. The mean effective contact position lies just dorsal to the location of the STN in a standard brain atlas. CONCLUSION: The STN varies in position, and can be accurately targeted from MRI alone.

Comparison of effects on colonic motility and stool characteristics associated with feeding olestra and wheat bran to ambulatory mini-pigs.

The goal of this study was to compare the stool-softening effects of olestra and wheat bran and to determine if changes in patterns of propagating colonic motility were associated with the observed stool softening. Mini-pigs were fed chow (control) or chow supplemented with olestra (80 g/day) or wheat bran (80 g/day) for four days. Proximal colonic motility was monitored continuously, stool viscosity and fecal output measured daily, and cecal-to-anal transit time determined. Compared to controls, olestra and wheat bran significantly softened stool but had no effect on fecal wet weight or colonic transit time. Neither olestra nor wheat bran changed the number of propagating contractions per day, amplitude, motility index, propagation velocity, or the relative distribution of fast and slow propagating contractions. Our data suggest that the stool-softening effects of olestra and wheat bran are not due to direct stimulation of propagating contractions in the colon of the mini-pig.

Anti-diarrhoeal effects of seirogan in the rat small intestine and colon examined in vitro.

BACKGROUND: Seirogan is a beechwood extract composed of guaiacol, creosol and other related phenolic compounds which is widely used as an anti-diarrhoeal agent in Asia. Abnormalities in water and electrolyte transport are often the cause of diarrhoea, but the mechanism of action of seirogan on small intestinal and colonic mucosal ion transport is unknown. AIM: To examine the effect of seirogan on electrogenic ion transport in vitro. METHODS: Sheets of rat jejunum and colon were mounted in Ussing chambers, and transmural potential difference (PD) was used as an electrical marker of changes in mucosal ion transport. Hypersecretory conditions were induced by acetylcholine (ACh). RESULTS: Serosal or mucosal application of seirogan (0.1-100 microg/mL) decreased basal jejunal transmural PD. Pre-treatment of the tissue with the neurotoxin, tetrodotoxin, did not inhibit the seirogan-induced changes in basal electrical activity. Seirogan had no effect on basal transmural PD in the ileum and colon. Under ACh-induced hypersecretory conditions in the small intestine and colon, addition of serosal or mucosal seirogan produced antisecretory effects determined indirectly by measurement of transmural PD. CONCLUSION: The ability of seirogan to decrease basal transmural PD in the jejunum, and inhibit the ACh-induced electrical responses, may contribute to its anti-diarrhoeal action.