The source and action of histamine in the isolated guinea-pig gallbladder

We have investigated the effects of histamine on motility of the gallbladder and characterized the receptor types involved. Histamine and the histamine H₁-receptor agonist, 2-thiazolylethylamine (2-TEA) contracted the isolated guinea-pig gallbladder strip in a dose dependent manner. The contractile response to histamine was shifted to the right by the H₁-receptor antagonist, mepyramine. In pre-contracted gallbladder strips, the H₂-receptor agonist dimaprit reduced the tension generated in a dose dependent fashion. The histamine H₂-receptor antagonist, ranitidine shifted the histamine concentration effect curve to the left and attenuated the dose dependent relaxations elicited at high concentrations. The histamine H₃-receptor agonist, (R)--methylhistamine (RMHA) elicited dose dependent contraction of the tissue which was significantly inhibited in the presence of mepyramine. The effects of electrical field stimulation (EFS) on the strips were not significantly altered by the presence of RMHA (10^–10–10^–7 M) indicating little pre-synaptic H₃ activity in this tissue. Histamine immunoreactivity (IR) was detected in gallbladder whole mount preparations of the mucosa and the muscularis/serosa. The histamine IR appeared cell bound in cells of varying morphological characteristics but no IR was detected in nerve fibres or cell bodies (ganglia). Alcian blue staining was consistent with the distribution of histamine IR cells as mast cells. The results indicate that histamine is distributed in the guinea-pig gallbladder and it can regulate contractile activity via activation of H₁ and H₂ but not H₃ receptors.     

Development of a diagnostic test for Entamoeba histolytica using idiotype expression in human

The protozoan parasite Entamoeba histolytica is the etiological agent of human amebiasis. The pathology of the disease starts with the cytolysis of the host target cells by amoebae. It is initiated by the adhesion of trophozoites to the host cells, through surface lectin via specific receptors. These adherence lectins have been demonstrated to be highly conserved, and can be recognised by serum antibodies from patients with invasive amebiasis.Some of these molecules have been used as antigens in serologic studies, which has been very helpful in the diagnosis of invasive intestinal amebiasis. However, false-positive serologic reactivity can occur using E. histolytica extracts and purified antigens. Additional problems are because the extracts display a great enzymatic activity. Several diagnostic methods, using different molecules and techniques, have been described. However, the problem still remains since these tests are not capable of differentiating between amoebic liver abscess (ALA) and intestinal amebiasis.Here, the research has been addressed to the 66-kDa antigen, which is a part of the outer membrane proteins from the E. histolytica strain HM1-IMSS trophozoites. First of all, we characterized the 66-kDa antigen in order to prove the relevance. We found that the 66-kDa antigen is a part of the plasma membranes and is distributed rather homogeneously on the cell surface of trophozoites. Apparently, the 66-kDa antigen is a glycoprotein. Using a monoclonal antibody (MAb), we found 25% of inhibition in the erythrophagocytosis by the trophozoites.Starting form one monoclonal antibody, we prepared an anti-idiotype (anti-Id) antibody reagent, with the purpose of searching for the different expressions of the idiotype between the sera from ALA and the intestinal amebiasis patients. Moreover, we produced the antibody Ab3 that is capable of recognising the 66-kDa antigen; it means that the Ab2 displays the internal image of the antigen. We found that 91.6% of the serum from ALA patients displayed the expression of the Id. In contrast, 15.7% of the E. histolytica asymtomatic cyst carriers displayed the Id expression, 6.6% of the patients with another parasite infection, and 11% of the negative controls (serum from umbilical cords of newborn babies). Our results showed that the expression of the Id could be differentiated among the AHA patients from the other groups with a 91.6% sensibility and 88.3% specificity.     

The Effect of Telephone-Administered Psychotherapy on Symptoms of Depression and Attrition: A Meta-Analysis

Increasingly, the telephone is being used to deliver psychotherapy for depression, in part as a means to reduce barriers to treatment. Twelve trials of telephone-administered psychotherapies, in which depressive symptoms were assessed, were included. There was a significant reduction in depressive symptoms for patients enrolled in telephone-administered psychotherapy as compared to control conditions ( d  = 0.26, 95% confidence interval [CI] = 0.14–0.39, p  < .0001). There was also a significant reduction in depressive symptoms in analyses of pretreatment to posttreatment change ( d  = 0.81, 95% CI = 0.50–1.13, p  < .0001). The mean attrition rate was 7.56% (95% CI = 4.23–10.90). These findings suggest that telephone-administered psychotherapy can produce significant reductions in depressive symptoms. Attrition rates were considerably lower than rates reported in face-to-face psychotherapy.     

The partition of sodium fluxes in isolated toad oocytes

1. The rate constant for Na efflux from the oocyte calculated from (d/dt) (ln [Na^*]_i]) is only approximately 52% of that calculated from (d/dt)[(ln(d[Na^*]_i)dt)]. The difference may be interpreted by supposing that 48% of the internal Na of the oocyte is either bound to proteins or sequestered in cell organelles.2. The mean rate constant for Na efflux was 6·4 × 10^-3 min^-1 corresponding to an apparent Na efflux rate of 13·3 p-mole/cm².sec. When this is corrected for the increase in surface area produced by microvilli the true efflux rate is 1·1-1·3 p-mole/cm².sec.3. The action of ouabain (1-5 μM) appears to involve two different effects: (a) there is 48-65% inhibition of the membrane Na pump, and (b) there is a release of some of the sequestered Na in the cell.4. Removal of external K causes a 40% reduction in Na efflux although this value may be an underestimation owing to the presence of K which has leaked from the cell and may be retained near the cell surface.5. Raising the external K concentration to 15 mM reduces the inhibitory effect of ouabain by approximately a half.6. It was concluded that the Na pump in the toad oocyte may have a slightly lower level of activity than that in frog muscle, but that its general properties are similar to those in frog muscle and some other animal cells.     

Investigation of Gamma-aminobutyric acid (GABA) A receptors genes and migraine susceptibility

Background  

Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ε (GABRE) and type θ (GABRQ) genes and their involvement in migraine.     

Locomotor-like rhythms in a genetically distinct cluster of interneurons in the mammalian spinal cord

Electrophysiological and morphological properties of genetically identified spinal interneurons were examined to elucidate their possible contribution to locomotor-like rhythmic activity in 1- to 4-day-old mice. In the transgenic mice used in our study, the HB9 promotor controlled the expression of the reporter gene enhanced green fluorescent protein (eGFP), giving rise to GFP+ motoneurons and ventral interneurons. However, only motoneurons and a small group of bipolar, GFP+ interneurons expressed the HB9 protein. The HB9(+)/GFP+ interneurons were clustered close to the medial surface in lamina VIII along segments L1-L3. The correlation between activity pattern in these visually identified interneurons and motoneuron output was examined using simultaneous whole cell and ventral root recordings. Neurochemically induced rhythmic membrane depolarizations in HB9/GFP interneurons were synchronous with ventral root rhythms, indicating that the interneurons received synaptic inputs from rhythm-generating networks. The frequency of excitatory postsynaptic currents significantly increased during ventral root bursts, but there was no change in the frequency of inhibitory postsynaptic currents during the cycle period. These data implied that HB9/GFP interneurons received primarily excitatory inputs from rhythmogenic interneurons. Neurobiotin-filled axon terminals were in close apposition to other neurons in the cluster and to motoneuron dendrites, raising the possibility that HB9/GFP interneurons formed synaptic connections with each other and with motoneurons. The expression of the vesicular glutamate transporter 2 in axon terminals of HB9/GFP interneurons indicated that these were glutamatergic interneurons. Our findings suggest that the visually identified HB9/GFP interneurons are premotor excitatory interneurons and putative constituents of networks generating locomotor rhythms in the mammalian spinal cord.     

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning. We integrate physiological and behavioral neuroscience studies conducted in both rodents and human to illustrate translational findings of interest for the treatment of obesity or metabolic impairments. Collectively, the literature discussed herein highlights a model where ghrelin and GLP-1 regulate food reward-motivated behaviors via both competing and independent neurobiological and behavioral mechanisms.     

Machine Learning Algorithms to Predict Mortality and Allocate Palliative Care for Older Patients With Hip Fracture

ObjectivesTo evaluate a machine learning model designed to predict mortality for Medicare beneficiaries aged >65 years treated for hip fracture in Inpatient Rehabilitation Facilities (IRFs).DesignRetrospective design/cohort analysis of Centers for Medicare & Medicaid Services Inpatient Rehabilitation Facility–Patient Assessment Instrument data.Setting and ParticipantsA total of 17,140 persons admitted to Medicare-certified IRFs in 2015 following hospitalization for hip fracture.MeasuresPatient characteristics include sociodemographic (age, gender, race, and social support) and clinical factors (functional status at admission, chronic conditions) and IRF length of stay. Outcomes were 30-day and 1-year all-cause mortality. We trained and evaluated 2 classification models, logistic regression and a multilayer perceptron (MLP), to predict the probability of 30-day and 1-year mortality and evaluated the calibration, discrimination, and precision of the models.ResultsFor 30-day mortality, MLP performed well [acc = 0.74, area under the receiver operating characteristic curve (AUROC) = 0.76, avg prec = 0.10, slope = 1.14] as did logistic regression (acc = 0.78, AUROC = 0.76, avg prec = 0.09, slope = 1.20). For 1-year mortality, the performances were similar for both MLP (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.96) and logistic regression (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.95).Conclusion and ImplicationsA scoring system based on logistic regression may be more feasible to run in current electronic medical records. But MLP models may reduce cognitive burden and increase ability to calibrate to local data, yielding clinical specificity in mortality prediction so that palliative care resources may be allocated more effectively.     

Impact of COVID-19 Among Immigrant and Communities of Color Living with HIV in Oregon, 2020: Two Pandemics Rooted in Racism

Journal of Immigrant and Minority Health - Over 8100 people living with HIV (PLWH) in Oregon are at risk of acquiring COVID-19, and communities of color are disproportionately impacted by both...