The hostile environment in primary care: Qualitative analysis of a cross sectional survey of health care professionals in primary care.

Background: In 2014 the UK government rolled out the then called hostile environment as a series of punitive policies designed to disenfranchise undocumented migrants from living in Britain. As part of these measures upfront charging was introduced in 2017 which saw patients being denied treatment without prior full payment based on their immigration status.

Aim: Assess the knowledge of the charging regulations in a sample of primary care practitioners.

The impact of NHS charging regulations on healthcare access and utilisation among migrants in England: a systematic review.

Background: The NHS Charges to Overseas Visitors Regulations 2015 outline when healthcare costs should be recuperated from overseas visitors in England. National and global stakeholders have expressed concerns that charging may exacerbate health inequalities and undermine public health efforts especially among vulnerable migrant groups. This review aims to systematically describe the evidence regarding the impact of NHS charging regulations on healthcare access and utilisation and health outcomes for migrants in England.

Selective 5HT3 antagonists and sensory processing: a systematic review.

Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson's disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing.

G-protein αq gene expression plays a role in alcohol tolerance in .

Ethanol is a psychoactive substance causing both short- and long-term behavioural changes in humans and animal models. We have used the fruit fly to investigate the effect of ethanol exposure on the expression of the Gαq protein subunit. Repetitive exposure to ethanol causes a reduction in sensitivity (tolerance) to ethanol, which we have measured as the time for 50% of a set of flies to become sedated after exposure to ethanol (ST50).

Pharmacological targeting of the GABA receptor alters Drosophila's behavioural responses to alcohol.

When exposed to ethanol, Drosophila melanogaster display a variety of addiction-like behaviours similar to those observed in mammals. Sensitivity to ethanol can be quantified by measuring the time at which 50% of the flies are sedated by ethanol exposure (ST50); an increase of ST50 following multiple ethanol exposures is widely interpreted as development of tolerance to ethanol. Sensitivity and tolerance to ethanol were measured after administration of the gamma-aminobutyric acid receptor B (GABA ) agonist (SKF 97541) and antagonist (CGP 54626), when compared with flies treated with ethanol alone.

Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in .

Alcohol use disorder (AUD) is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE) in that measures the flies' preference for ethanol-containing food.

β3-integrin is required for differentiation in OC-2 cells derived from mammalian embryonic inner ear.

Background: The mammalian inner ear contains the organ of Corti which is responsible for the conversion of sound into neuronal signals. This specialised epithelial tissue is the product of a complex developmental process where a common precursor cell type differentiates into the sound transducing hair cells and the non-innervated supporting cells. We hypothesised that integrin proteins, which are involved in cell attachment to extracellular matrix proteins and cellular signalling, play a role in the differentiation process of the precursor inner ear epithelial cells.

Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats.

Background: Pseudoephedrine is a drug commonly prescribed as a nasal decongestant and bronchodilator and is also freely available in cold remedies and medications. The structural and pharmacological similarity of pseudoephedrine to amphetamine has led to evaluation of its psychomotor stimulant properties within the central nervous system. Previous investigations have shown that the acute responses to pseudoephedrine were similar to those of amphetamine and other psychostimulants.

Relationship of opioid receptors with GABAergic neurons in the rat inferior colliculus.

The inferior colliculus is a critical structure for processing auditory information and receives ascending and descending synaptic auditory projections. In addition to GABAergic and glutamatergic innervations, other neurotransmitter systems are also reported in the inferior colliculus, including opioid peptides. In the present study, the relative distribution of each type of opioid receptor, mu (MOR), delta (DOR) and kappa (KOR) within GABAergic neurons in the inferior colliculus was examined.

The existence of opioid receptors in the cochlea of guinea pigs.

Several independent investigations have demonstrated the presence of opioid peptides in the inner ear organ of Corti and in particular in the efferent nerve fibers innervating the cochlear hair cells. However, the precise innervation pattern of opioid fibers remains to be investigated. In the present study the expression of opioid receptors and their peptides is demonstrated in young adult guinea pig cochlea.

Opioid modulation of GABA release in the rat inferior colliculus.

Background: The inferior colliculus, which receives almost all ascending and descending auditory signals, plays a crucial role in the processing of auditory information. While the majority of the recorded activities in the inferior colliculus are attributed to GABAergic and glutamatergic signalling, other neurotransmitter systems are expressed in this brain area including opiate peptides and their receptors which may play a modulatory role in neuronal communication.

Results: Using a perfusion protocol we demonstrate that morphine can inhibit KCl-induced release of [3H]GABA from rat inferior colliculus slices.

The inner ear contains heteromeric channels composed of cx26 and cx30 and deafness-related mutations in cx26 have a dominant negative effect on cx30.

Cx26 and cx30 co-localize in tissues of the mammalian cochlea. Transfected HeLa cells were used to examine interactions between cx26 and cx30 and the effects on cx30 of four point mutations in cx26 that are associated with dominantly inherited hearing loss--W44S, G59A, D66H and R75W. When co-expressed, wtcx26 and wtcx30 trafficked to the same gap junction plaques.

Gap junctions in the inner ear: comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals.

The distribution and size of gap junctions (GJ) in the sensory epithelia of the inner ear have been examined in a reptile (gecko), birds (chicken and owl), and mammals (mouse, guinea pig, gerbil, and bat), and the connexin composition of GJs in the mammalian inner ear has been assessed. Freeze fracture revealed a common pattern of GJ distribution in auditory and vestibular sensory epithelia in the different vertebrate classes. In all these tissues, GJs are numerous, often occupying more than 25% of the plasma membrane area of supporting cells and sometimes composed of more than 100,000 channels.

The opioid receptors in inner ear of different stages of postnatal rats.

There is increasing evidence that the opioid system has a role in hearing. To provide further evidence for such a role, the expression of opioid receptor mRNAs and proteins in the inner ear of rats was studied during development from birth (P0) to postnatal day 16 (P16). A semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to detect changes in the expression of delta- (DOR) kappa- (KOR) and mu- (MOR) opioid receptor mRNAs in rat cochleae at P0, P4, P8 and P16.

Postnatal touch stimulation acutely alters corticosterone levels and glucocorticoid receptor gene expression in the neonatal rat.

Environmental manipulation early in life can alter the development of the hypothalamic-pituitary-adrenal (HPA) axis by mechanisms that are still unclear. The aim of the present work was to study the acute effects of postnatal touch stimulation, in an attempt to understand the mechanism by which touch stimulation early in life alters the HPA response to stress in adult animals. Rat pups were gently brushed for 15 min daily during the 1st postnatal week.

The presence of opioid receptors in rat inner ear.

Opioid peptides have been identified in the inner ear but relatively little information is available about the expression and distribution of their receptors. The aim of the present study was therefore to identify and localize the mu (MOR), delta (DOR) and kappa (KOR) opioid receptor subtypes within the rat cochlea. The expression of these opioid receptor subtypes was determined by reverse transcriptase-polymerase chain reaction followed by nested polymerase chain reaction analysis.

Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30.

Mutations in the gene (GJB2) encoding connexin 26 (cx26) have been linked to sensorineural hearing loss either alone or as part of a syndrome. Here we compare the properties of four cx26 mutants derived from point mutations associated with dominantly inherited hearing loss, either non-syndromic (W44S, R75W) or with various skin disorders (G59A, D66H, R75W). Since cx26 and cx30 are co-localized within the inner ear the effect of the dominant cx26 mutations on both of these wild-type proteins was determined.

Connexins and gap junctions in the inner ear.

Mutations in the genes for three different isotypes of the gap junction channel protein connexin are associated with deafness. This indicates an important role for gap junctions in auditory function and provides an opportunity to explore structure-function relationships in the connexin molecule. We have been examining the distribution of gap junctions and the pattern of connexin expression in the mature inner ear and during development, and the effect of specific mutations on the processing and functionality of the expressed connexin proteins in an in vitro system.

Morphine induces short-lived changes in G-protein gene expression in rat prefrontal cortex.

We have utilized a reverse transcriptase-polymerase chain reaction (RT-PCR) methodology followed by enzymatic restriction analysis to detect changes in G-protein mRNA levels in morphine-treated rats. The relative distribution of mRNA levels for Galpha(o) Galpha(i1), Galpha(i2), Gbeta(1) and Gbeta(2) in the nucleus accumbens, striatum, locus coeruleus and prefrontal cortex was found to be similar to that previously estimated with other techniques. Morphine-induced changes of G-protein mRNA levels were detected only in the prefrontal cortex.

Stress, anxiety and peripheral benzodiazepine receptor mRNA levels in human lymphocytes.

Peripheral benzodiazepine receptor (PBR) mRNA levels were measured in lymphocytes obtained from a cohort of university students and clinically diagnosed anxious patients. The average level of PBR mRNA was decreased in anxious patients compared to a control group. This data confirms previously published results, but it also indicates that PBR mRNA levels cannot be used as a sole diagnostic measure of anxiety because the range of the individual PBR mRNA levels of the anxious group overlapped the range of the PBR mRNA levels of the control group.

Properties of connexin26 gap junctional proteins derived from mutations associated with non-syndromal heriditary deafness.

Three point mutations of the connexin26 (GJB2) gene associated with hereditary deafness were studied using in vitro expression systems. Mutation M34T results in an amino acid substitution in the first transmembrane domain of the connexin protein, W77R is located in the second transmembrane domain and W44C is in the first extracellular loop. Wild-type and mutated connexin vectors were constructed and transfected into communication-deficient HeLa cells to obtain transient expression of the connexin proteins.

Gene expressions of opioid receptors and G-proteins in pineal glands.

In our previous studies, the opioid receptors located on pinealocytes have been identified and characterized, and these receptors have been found to play a stimulatory role in melatonin synthesis by activating the rate limiting enzyme, N-acetyltransferase (NAT). In the present study, by using reverse transcriptase polymerase chain reaction (RT-PCR) followed by nested-PCR, segments of delta and mu opioid receptors have been amplified from mRNA of rat pineal gland and cerebral cortex. In addition, segments of delta and mu opioid receptors have also been amplified from mRNA of human pineal gland.

Pseudoephedrine, a sympathomimetic agent, induces Fos-like immunoreactivity in rat nucleus accumbens and striatum.

The pharmacological properties of the ephedrine derivative pseudoephedrine were investigated at the nuclear level. Following intraperitoneal injection of Sprague Dawley rats with pseudoephedrine, Fos induction was measured in various brain areas by Western blots and immunocytochemistry. Pseudoephedrine induced Fos-like immunoreactivity in the nucleus accumbens and striatum in a time and concentration-dependent manner with maximal effect at 60 mg/kg 2 h after injection.

A sugar transporter as a candidate for the outer hair cell motor.

Forces developed by cochlear outer hair cells (OHCs) are responsible for the sharp tuning that underlies sensitivity and frequency selectivity in the ear. OHCs exhibit a voltage-dependent motility involving a 'motor' protein embedded in the basolateral membrane. The motor has so far resisted molecular identification.