Cognitive Functioning and Assessment in Adults with Cerebral Palsy: A Scoping Review.

In this scoping review, we summarize the current knowledge of cognitive functioning in adults with cerebral palsy (CP), and identify the neuropsychological tests typically used in this population. 39 studies from the period January 1990 - August 2023 were included in the review, and they differ widely in their aims and approach to studying cognition. Very few studies have cognitive assessment as their core aim and use a neuropsychological test battery. The included studies show great variability in reported intelligence and cognitive functioning in adults with CP, and cognitive deficits have been reported in all cognitive domains. Most of the studies suffer from methodological limitations, and there is ample room for improvement within the field. We conclude by suggesting a number of recommendations that may contribute to increasing our understanding of cognitive impairments in adults with CP.

Colour perception deficits after posterior stroke: Not so rare after all?

Cerebral achromatopsia is an acquired colour perception impairment caused by brain injury, and is generally considered to be rare. Both hemispheres are thought to contribute to colour perception, but most published cases have had bilateral or right hemisphere lesions. In contrast to congenital colour blindness that affects the discrimination between specific hues, cerebral achromatopsia is often described as affecting perception across all colours. Most studies of cerebral achromatopsia have been single cases or case series of patients with colour perception deficits. Here, we explore colour perception deficits in an unbiased sample of patients with stroke affecting the posterior cerebral artery (N = 63) from the Back of the Brain project. Patients were selected based on lesion location only, and not on the presence of a given symptom. All patients were tested with the Farnsworth D-15 Dichotomous Colour Blindness Test and performance compared to matched controls (N = 45) using single case statistics. In patients with abnormal performance, the patterns of colour difficulties were qualitatively analysed. 22% of the patients showed significant problems with colour discrimination (44% of patients with bilateral lesions, 28% with left hemisphere lesions and 5% with right hemisphere lesions). Lesion analyses identified two regions in ventral occipital temporal areas in the left hemisphere as particularly strongly related to impaired performance in colour perception, but also indicated that bilateral lesions are more strongly associated with impaired performance that unilateral lesions. While some patients only had mild deficits, colour perception impairments were in many cases severe. Many patients had selective deficits only affecting the perception of some hues. The results suggest that colour perception difficulties following PCA stroke are common, and that they vary in severity and expression. In addition, the results point towards bilateral processing of colour perception with a left hemispheric domination, contradicting previous reports.

Fungal endophytes vary by species, tissue type, and life cycle stage in intertidal macroalgae.

Fungal symbionts of terrestrial plants are among the most widespread and well-studied symbioses, relatively little is known about fungi that are associated with macroalgae. To fill the gap in marine fungal taxonomy, we combined simple culture methods with amplicon sequencing to characterize the fungal communities associated with three brown (Sargassum muticum, Pelvetia canaliculata, and Himanthalia elongata) and two red (Mastocarpus stellatus and Chondrus crispus) macroalgae from one intertidal zone. In addition to characterizing novel fungal diversity, we tested three hypotheses: fungal diversity and community composition vary (i) among species distributed at different tidal heights, (ii) among tissue types (apices, mid-thallus, and stipe), and (iii) among "isomorphic" C. crispus life cycle stages. Almost 70% of our reads were classified as Ascomycota, 29% as Basidiomycota, and 1% that could not be classified to a phylum. Thirty fungal isolates were obtained, 18 of which were also detected with amplicon sequencing. Fungal communities differed by host and tissue type. Interestingly, P. canaliculata, a fucoid at the extreme high intertidal, did not show differences in fungal diversity across the thallus. As found in filamentous algal endophytes, fungal diversity varied among the three life cycle stages in C. crispus. Female gametophytes were also compositionally more dispersed as compared to the fewer variable tetrasporophytes and male gametophytes. We demonstrate the utility of combining relatively simple cultivation and sequencing approaches to characterize and study macroalgal-fungal associations and highlight the need to understand the role of fungi in near-shore marine ecosystems.

Category-selective deficits are the exception and not the rule: Evidence from a case-series of 64 patients with ventral occipito-temporal cortex damage.

The organisational principles of the visual ventral stream are still highly debated, particularly the relative association/dissociation between word and face recognition and the degree of lateralisation of the underlying processes. Reports of dissociations between word and face recognition stem from single case-studies of category selective impairments, and neuroimaging investigations of healthy participants. Despite the historical reliance on single case-studies, more recent group studies have highlighted a greater commonality between word and face recognition. Studying individual patients with rare selective deficits misses (a) important variability between patients, (b) systematic associations between task performance, and (c) patients with mild, severe and/or non-selective impairments; meaning that the full spectrum of deficits is unknown. The Back of the Brain project assessed the range and specificity of visual perceptual impairment in 64 patients with posterior cerebral artery stroke recruited based on lesion localization and not behavioural performance. Word, object, and face processing were measured with comparable tests across different levels of processing to investigate associations and dissociations across domains. We present two complementary analyses of the extensive behavioural battery: (1) a data-driven analysis of the whole patient group, and (2) a single-subject case-series analysis testing for deficits and dissociations in each individual patient. In both analyses, the general organisational principle was of associations between words, objects, and faces even following unilateral lesions. The majority of patients either showed deficits across all domains or in no domain, suggesting a spectrum of visuo-perceptual deficits post stroke. Dissociations were observed, but they were the exception and not the rule: Category-selective impairments were found in only a minority of patients, all of whom showed disproportionate deficits for words. Interestingly, such selective word impairments were found following both left and right hemisphere lesions. This large-scale investigation of posterior cerebral artery stroke patients highlights the bilateral representation of visual perceptual function.

Measurement of hydraulic pressure on the sinus membrane for safer control during transcrestal sinus lifting.

The aim of this study was to determine the hydraulic pressures necessary to separate and lift the sinus membrane from the sinus floor in order to ensure a more controlled and safer hydraulic transcrestal sinus lifting surgery and prevent sinus membrane perforation. A flow-regulating hydrodynamic device with a pressure sensor was used in nine patients. The hydraulic pressure was found to increase steadily up to a mean peak of 25.0±13.0kPa, which is comparable to the medium suction power of ordinary vacuum cleaners. Subsequently, there was a short plateau followed by a sharp decrease in the hydraulic pressure.

Neural Pathways of Craniofacial Muscle Pain: Implications for Novel Treatments.

Craniofacial muscle pain is highly prevalent in temporomandibular disorders but is difficult to treat. Enhanced understanding of neurobiology unique to craniofacial muscle pain should lead to the development of novel mechanism-based treatments. Herein, we review recent studies to summarize neural pathways of craniofacial muscle pain. Nociceptive afferents in craniofacial muscles are predominantly peptidergic afferents enriched with TRPV1. Signals from peripheral glutamate receptors converge onto TRPV1, leading to mechanical hyperalgesia. Further studies are needed to clarify whether hyperalgesic priming in nonpeptidergic afferents or repeated acid injections also affect craniofacial muscle pain. Within trigeminal ganglia, afferents innervating craniofacial muscles interact with surrounding satellite glia, which enhances the sensitivity of the inflamed neurons as well as nearby uninjured afferents, resulting in hyperalgesia and ectopic pain originating from adjacent orofacial tissues. Craniofacial muscle afferents project to a wide area within the trigeminal nucleus complex, and central sensitization of medullary dorsal horn neurons is a critical factor in muscle hyperalgesia related to ectopic pain and emotional stress. Second-order neurons project rostrally to pathways associated with affective pain, such as parabrachial nucleus and medial thalamic nucleus, as well as sensory-discriminative pain, such as ventral posteromedial thalamic nuclei. Abnormal endogenous pain modulation can also contribute to chronic muscle pain. Descending serotonergic circuits from the rostral ventromedial medulla facilitate activation of second-order neurons in the trigeminal nucleus complex, which leads to the maintenance of mechanical hyperalgesia of inflamed masseter muscle. Patients with temporomandibular disorders exhibit altered brain networks in widespread cortical and subcortical regions. Recent development of methods for neural circuit manipulation allows silencing of specific hyperactive neural circuits. Chemogenetic silencing of TRPV1-expressing afferents or rostral ventromedial medulla neurons attenuates hyperalgesia during masseter inflammation. It is likely, therefore, that further delineation of neural circuits mediating craniofacial muscle hyperalgesia potentially enhances treatment of chronic muscle pain conditions.

The Architect Who Lost the Ability to Imagine: The Cerebral Basis of Visual Imagery.

While the loss of mental imagery following brain lesions was first described more than a century ago, the key cerebral areas involved remain elusive. Here we report neuropsychological data from an architect (PL518) who lost his ability for visual imagery following a bilateral posterior cerebral artery (PCA) stroke. We compare his profile to three other patients with bilateral PCA stroke and another architect with a large PCA lesion confined to the right hemisphere. We also compare structural images of their lesions, aiming to delineate cerebral areas selectively lesioned in acquired aphantasia. When comparing the neuropsychological profile and structural magnetic resonance imaging (MRI) for the aphantasic architect PL518 to patients with either a comparable background (an architect) or bilateral PCA lesions, we find: (1) there is a large overlap of cognitive deficits between patients, with the very notable exception of aphantasia which only occurs in PL518, and (2) there is large overlap of the patients' lesions. The only areas of selective lesion in PL518 is a small patch in the left fusiform gyrus as well as part of the right lingual gyrus. We suggest that these areas, and perhaps in particular the region in the left fusiform gyrus, play an important role in the cerebral network involved in visual imagery.

Management of isolated recurrence after surgery for pancreatic adenocarcinoma.

BACKGROUND: Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well established. METHODS: Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large-volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities. RESULTS: Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non-surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection. CONCLUSION: Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.

Face and Word Recognition Can Be Selectively Affected by Brain Injury or Developmental Disorders.

Face and word recognition have traditionally been thought to rely on highly specialised and relatively independent cognitive processes. Some of the strongest evidence for this has come from patients with seemingly category-specific visual perceptual deficits such as pure prosopagnosia, a selective face recognition deficit, and pure alexia, a selective word recognition deficit. Together, the patterns of impaired reading with preserved face recognition and impaired face recognition with preserved reading constitute a double dissociation. The existence of these selective deficits has been questioned over the past decade. It has been suggested that studies describing patients with these pure deficits have failed to measure the supposedly preserved functions using sensitive enough measures, and that if tested using sensitive measurements, all patients with deficits in one visual category would also have deficits in the other. The implications of this would be immense, with most textbooks in cognitive neuropsychology requiring drastic revisions. In order to evaluate the evidence for dissociations, we review studies that specifically investigate whether face or word recognition can be selectively affected by acquired brain injury or developmental disorders. We only include studies published since 2004, as comprehensive reviews of earlier studies are available. Most of the studies assess the supposedly preserved functions using sensitive measurements. We found convincing evidence that reading can be preserved in acquired and developmental prosopagnosia and also evidence (though weaker) that face recognition can be preserved in acquired or developmental dyslexia, suggesting that face and word recognition are at least in part supported by independent processes.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.

Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial.

BACKGROUND: In the PALOMA-3 study, palbociclib plus fulvestrant demonstrated improved progression-free survival compared with fulvestrant plus placebo in hormone receptor-positive, HER2- endocrine-resistant metastatic breast cancer (MBC). This analysis compared patient-reported outcomes (PROs) between the two treatment groups. PATIENTS AND METHODS: Patients were randomized 2 : 1 to receive palbociclib 125 mg/day orally for 3 weeks followed by 1 week off (n = 347) plus fulvestrant (500 mg i.m. per standard of care) or placebo plus fulvestrant (n = 174). PROs were assessed on day 1 of cycles 1-4 and of every other subsequent cycle starting with cycle 6 using the EORTC QLQ-C30 and its breast cancer module, QLQ-BR23. High scores (range 0-100) could indicate better functioning/quality of life (QoL) or worse symptom severity. Repeated-measures mixed-effect analyses were carried out to compare on-treatment overall scores and changes from baseline between treatment groups while controlling for baseline. Between-group comparisons of time to deterioration in global QoL and pain were made using an unstratified log-rank test and Cox proportional hazards model. RESULTS: Questionnaire completion rates were high at baseline and during treatment (from baseline to cycle 14, ≥95.8% in each group completed ≥1 question on the EORTC QLQ-C30). On treatment, estimated overall global QoL scores significantly favored the palbociclib plus fulvestrant group [66.1, 95% confidence interval (CI) 64.5-67.7 versus 63.0, 95% CI 60.6-65.3; P = 0.0313]. Significantly greater improvement from baseline in pain was also observed in this group (-3.3, 95% CI -5.1 to -1.5 versus 2.0, 95% CI -0.6 to 4.6; P = 0.0011). No significant differences were observed for other QLQ-BR23 functioning domains, breast or arm symptoms. Treatment with palbociclib plus fulvestrant significantly delayed deterioration in global QoL (P < 0.025) and pain (P < 0.001) compared with fulvestrant alone. CONCLUSION: Palbociclib plus fulvestrant allowed patients to maintain good QoL in the endocrine resistance setting while experiencing substantially delayed disease progression. CLINICAL TRIAL REGISTRATION: NCT01942135.

The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and α,ß-methylene adenosine triphosphate (αßmeATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain and mechanical hyperalgesia. Mechanistic studies elucidating transcriptional or post-translational regulation of TRPA1 expression under pathological pain conditions should provide important basic information to further advance the treatment of craniofacial muscle pain conditions.

The role of TRPM2 in hydrogen peroxide-induced expression of inflammatory cytokine and chemokine in rat trigeminal ganglia.

Trigeminal ganglia (TG) contain neuronal cell bodies surrounded by satellite glial cells. Although peripheral injury is well known to induce changes in gene expression within sensory ganglia, detailed mechanisms whereby peripheral injury leads to gene expression within sensory ganglia are not completely understood. Reactive oxygen species (ROS) are an important modulator of hyperalgesia, but the role of ROS generated within sensory ganglia is unclear. Since ROS are known to affect transcription processes, ROS generated within sensory ganglia could directly influence gene expression and induce cellular changes at the soma level. In this study, we hypothesized that peripheral inflammation leads to cytokine and chemokine production and ROS generation within TG and that transient receptor potential melastatin (TRPM2), a well known oxidative sensor, contributes to ROS-induced gene regulation within TG. The masseter injection of complete Freund's adjuvant (CFA) resulted in a significantly elevated level of ROS within TG of the inflamed side with a concurrent increase in cytokine expression in TG. Treatment of TG cultures with H2O2 significantly up-regulated mRNA and protein levels of cytokine/chemokine such as interleukin 6 (IL-6) and chemokine (C-X-C motif) ligand 2 (CXCL2). TRPM2 was expressed in both neurons and non-neuronal cells in TG, and pretreatment of TG cultures with 2-aminoethoxydiphenyl borate (2-APB), an inhibitor of TRPM2, or siRNA against TRPM2 attenuated H2O2-induced up-regulation of IL-6 and CXCL2. These results suggested that activation of TRPM2 could play an important role in the modulation of cytokine/chemokine expression within TG under oxidative stress and that such changes may contribute to amplification of nociceptive signals leading to pathological pain conditions.

Ablation of galectin-3 induces p27(KIP1)-dependent premature senescence without oncogenic stress.

Premature senescence induced by oncogenic stimuli or tumor suppressor activation plays opposing roles in tumorigenesis. Here, we propose that galectin-3, a ß-galactoside-binding lectin, regulates premature senescence without oncogenic stress. We detected premature senescence, decreased Skp2, and increased p27(KIP1) expression in galectin-3 knockout MEFs and galectin-3-depleted gastric cancer cells. Interestingly, galectin-3 depletion did not affect other senescence inducers such as p14(ARF), p16(INK4A), and p21(WAF1/CIP1), suggesting that galectin-3-regulated senescence is p27(KIP1) dependent. We demonstrate that galectin-3 depletion decreases retinoblastoma protein (Rb) phosphorylation (Ser780, Ser807/811), cyclin D1 and CDK4 expression, and E2F1 transcriptional activation. Galectin-3 directly interacts with the cyclin D1/CDK4 complex and promotes hyperphosphorylation of Rb. It also blocks the inhibition of E2F1 transcription, thereby increasing the expression of Skp2 and reducing the stability of p27(KIP1) to promote the proliferation of gastric cancer cells. Xenograft mice with galectin-3-depleted gastric cancer cells display tumor growth retardation that is reversed by Skp2 overexpression. Increased expression of galectin-3 is also associated with the advanced TNM (tumor, lymph node, metastasis) system, clinicopathological stage, and lymph node metastases. The probability of survival was significantly decreased in gastric cancer patients with galectin-3(high) p27(KIP1-low)cells. Taken together, our results show that galectin-3 may accelerate gastric tumorigenesis by inhibiting premature senescence.

Sex differences in µ-opioid receptor expression in trigeminal ganglia under a myositis condition in rats.

BACKGROUND: Peripheral opioid receptor expression is up-regulated under inflammatory conditions, which leads to the increased efficacy of peripherally administered opioids. Sex differences in the effects of inflammation, cytokines and gonadal hormones on µ-opioid receptor (MOR) expression in trigeminal ganglia (TG) are not well understood. METHODS: MOR mRNA and protein levels in TG from male and female Sprague Dawley rats following complete Freund's adjuvant (CFA)-induced muscle inflammation were assessed. Cytokine-induced changes in MOR mRNA expression from TG cultures prepared from intact and gonadectomized male and female, and gonadectomized male rats with testosterone replacement were examined. Behavioural experiments were then performed to examine the efficacy of a peripherally administered MOR agonist in male, female and gonadectomized male rats under a myositis condition. RESULTS: CFA and cytokine treatments induced significant up-regulation of MOR expression in TG from male, but not from female, rats. The cytokine-induced up-regulation of MOR mRNA expression was prevented in TG from orchidectomized (GDX) male rats, which was restored with testosterone replacement. Peripherally administered DAMGO, a specific MOR agonist, significantly attenuated CFA-induced masseter mechanical hypersensitivity only in intact male rats. CONCLUSIONS: Collectively, these data indicate that testosterone plays a key role in the regulation of MOR in TG under inflammatory conditions, and that sex differences in the anti-hyperalgesic effects of peripherally administered opioids are, in part, mediated by peripheral opioid receptor expression levels.

Peripheral G protein-coupled inwardly rectifying potassium channels are involved in δ-opioid receptor-mediated anti-hyperalgesia in rat masseter muscle.

BACKGROUND: Although the efficacy of peripherally administered opioid has been demonstrated in preclinical and clinical studies, the underlying mechanisms of its anti-hyperalgesic effects are poorly understood. G protein-coupled inwardly rectifying potassium (GIRK) channels are linked to opioid receptors in the brain. However, the role of peripheral GIRK channels in analgesia induced by peripherally administered opioid, especially in trigeminal system, is not clear. METHODS: Expression of GIRK subunits in rat trigeminal ganglia (TG) was examined with reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry. Chemical profiles of GIRK-expressing neurons in TG were further characterized. Behavioural and Fos experiments were performed to examine the functional involvement of GIRK channels in δ-opioid receptor (DOR)-mediated anti-hyperalgesia under an acute myositis condition. RESULTS: TG expressed mRNA and proteins for GIRK1 and GIRK2 subunits. Majority of GIRK1- and GIRK2-expressing neurons were non-peptidergic afferents. Inhibition of peripheral GIRK using Tertiapin-Q (TPQ) attenuated antinociceptive effects of peripherally administered DOR agonist, [D-Pen(2), D-Pen(6) ]-enkephalin (DPDPE), on mechanical hypersensitivity in masseter muscle. Furthermore, TPQ attenuated the suppressive effects of peripheral DPDPE on neuronal activation in the subnucleus caudalis of the trigeminal nucleus (Vc) following masseteric injection of capsaicin. CONCLUSIONS: Our data indicate that peripheral DOR agonist-induced suppression of mechanical hypersensitivity in the masseter muscle involves the activity of peripheral GIRK channels. These results could provide a rationale for developing a novel therapeutic approach using peripheral GIRK channel openers to mimic or supplement the effects of peripheral opioid agonist.

Impact of pharmaceutical excipients on in vitro association of saquinavir to chylomicrons.

This study was performed to investigate the impact of pharmaceutical excipients commonly used for lymphatic transport on in vitro drug association with chylomicrons (CM). A CM association study was conducted using saquinavir solubilized in four different pharmaceutical excipients. We observed a linear relationship between saquinavir solubility and drug association, suggesting that the solubility of saquinavir in excipients is a key determinant for successful lymphatic delivery. Broadly, these results suggest that excipients with good solubilization properties may be advantageous for enhancing lymphatic drug delivery.