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Due to their perceived role in making content visible, engagement metrics are core concerns for people and businesses that generate revenue on social media platforms. While scholars have focused on...

LGBTQ+ people face unique organizational communication dilemmas at work. In the United States, LGBTQ+ workers communicate their gender, sexuality, and other intersecting identities and experiences through complex interactions with coworkers, supervisors, customers, publics, organizations, and institutions. They also utilize specific communication strategies to navigate exclusionary policies and practices and organize for intersectional justice. Five central research themes for LGBTQ+ workers in the current literature include (a) workplace discrimination, (b) disclosure at work, (c) navigating interpersonal relationships at work, (d) inclusive and exclusive policies, and (e) intersectional work experiences and organizing. First, the lived experiences of discrimination, exclusion, and violence in organizations, including from coworkers, managers, and customers, present a plethora of challenges from organizational entry to exit. LGBTQ+ workers face high levels of unemployment and underemployment and experience frequent microaggressions. Queer, trans, and intersex workers also experience prevalent workplace discrimination, uncertainty, and systemic barriers when attempting to use fluctuating national and state laws for workplace protections. Second, such discrimination creates unique risks that LGBTQ+ workers must navigate when it comes to disclosing their identities at work. The complexities of workplace disclosure of LGBTQ+ identities and experiences become apparent through closeting, passing, and outing communication. These three communication strategies for queer, trans, and intersex survival are often read as secretive or deceptive by heterosexual or cisgender coworkers and managers. Closeting communication may also involve concealing information about personal and family relationships at work and other identity intersections. Third, LGBTQ+ people must navigate workplace relationships, particularly with heterosexual and/or cisgender coworkers and managers and in organizations that assume cisheteronormativity. Fourth, policies structure LGBTQ+ workers’ lives, including both the positive impacts of inclusive policies and discrimination and violence via exclusionary policies. Fifth and finally, intersectionality is crucial to theorize when examining LGBTQ+ workers’ communication. It is not enough to just investigate sexuality or gender identity, as they are interwoven with race, class, disability, religion, nationality, age, and more. Important exemplars also showcase how intersectional organizing can create transformative and empowering experiences for LGBTQ+ people. By centering LGBTQ+ workers, this article examines their unique and complex organizational communication needs and proposes future research.

In this article, I theorize how communication creates participants’ organizational identification with nonprofit organizations (NPOs) and their co-construction of organizational identities. Findings from my 3-year organizational ethnography of an NPO serving transgender people, the Transgender Resource Center of New Mexico (TGRC), showcase how Directors, staff, and “guests” (those being served by the NPO) co-constructed a “family” organizational identity and their subsequent organizational identification through communication. My analysis reveals how TGRC’s shared cultural values, physical space, language, and artifacts both supported and shaped their family organizational identity. Ethnographic findings illustrate how TGRC participants constructed family through cultural elements including TGRC as a home space while simultaneously going beyond an organizational container to embrace discourses and texts to construct their identity. I end with calls for future research on organizational culture, identity, and identification co-construction to include the people organizations serve and for more ethnographic and arts-based research to enrich such pursuits.

Service industry workers experience challenging labor conditions in the United States, including pay below the minimum wage, expected emotional labor, and harassment. Additionally, in part because they work long shifts in high stress environments in restaurants and bars, many build and form personal workplace relationships (PWRs). In 2021, we interviewed 38 service industry workers and managers during the COVID-19 pandemic where we examined occupational challenges they faced in the state of Texas, USA. Through our interpretive research, this essay showcases our inductive findings on how service industry workers and managers utilize communication to create and sustain PWRs. We identified how some PWRs are sustained through a unique form of occupational identification that cultivates a “service industry family”, which we term familial personal workplace relationships (familial PWRs). This extends past organizational communication scholarship on family to consider occupational identification. Furthermore, our research reveals that while PWRs may build communities through care and support, they also perpetuate organizational violence, like sexual harassment and bullying.

Recently it has been postulated that there is an atypical facioscapulohumeral muscular dystrophy (FSHD) phenotype with isolated axial myopathy. Involvement of paraspinal and limb muscles was evaluated in six patients with molecularly proven FSHD and a predominant bent spine phenotype. Consistent with the camptocormia phenotype, the most severely affected muscles in all six patients were the thoracic and lumbar spinal tract together with hamstrings. MRI disclosed severe axial muscle degeneration but mostly subclinical involvement of limb muscles. The involvement of hip extensor muscles in FSHD might considerably contribute to the clinical phenotype of camptocormia due to axial muscle involvement.

Neuromuscular diseases accompanying thymoma include myasthenia gravis, polymyositis, dermatomyositis, and neuromyotonia. Usually 50% of patients with thymoma develop myasthenia gravis. However, only 5% show polymyositis as an accompanying paraneoplastic phenomenon. We report the case of a patient with thymoma showing myasthenia gravis as well as polymyositis. Due to the simultaneous occurrence of these paraneoplastic diseases, the criteria for exact diagnosis (serum creatine kinase, EMG, ocular involvement) overlap. This diagnostic dilemma can appreciably complicate the therapeutic approach.

In patients with late-onset glycogen storage disease type II, one mutation, c.−32−13T>G, in the α-glucosidase (GAA) gene is identified frequently in European populations from different regions along with many rarer mutations. We have performed molecular genetic investigations in 18 German index patients with late-onset disease. The c.−32−13T>G, c.525delT (p.Glu176fsX45), and c.2481+102_2646+31del mutations were detected by PCR/restriction enzyme digest. Other mutations were detected by sequencing. All patients were compound heterozygous and 17 patients harboured the c.−32−13T>G mutation. Seven other previously described mutations (including the c.−32−13T>G) were identified, of which the p.C103G (c.307T>G) and the c.2481+102_2646+31del mutations were present each in three unrelated patients. Sequencing revealed five novel mutations. Conclusions: Genetic testing was able to identify the genetic defects in all patients and screening of the c.−32−13T>G mutation identified 94% of the cases. This is important for quick and reliable diagnosis, especially in view of enzyme replacement. Among the rarer mutations, c.2481+102_2646+31del and p.C103G are rather frequent in Germany.

Neuromyelitis optica (NMO; Devic's Syndrome) is an idiopathic, often relapsing, severe inflammatory disorder preferentially affecting optic nerves and spinal cord. The distinction of NMO from multiple sclerosis (MS) as a separate disease entity has been controversally discussed for a long time. Though both diseases show demyelinisation, they differ in typical clinical, imaging and immunopathological findings. The recent identification of serum aquaporin (AQP)-4 antibody clearly separates NMO from MS. In addition, the identification of AQP-4 antibodies supports peripheral humoral autoimmune pathogenesis in NMO and permits early initiation of effective therapy for prevention of attack-related disability.

ZusammenfassungUnter den immunologisch bedingten neurologischen Erkrankungen haben die Erkrankungen der neuromuskulären Übertragung große klinische Bedeutung. Klassisches Beispiel dafür ist die Myasthenia gravis. Diese erworbene Autoimmunerkrankung ist meist durch Antikörper gegen Azetylcholinrezeptoren bedingt. Eine Untergruppe der Myasthenie, bei der Azetylcholinrezeptor-Antikörper nicht nachweisbar sind, ist durch Antikörper gegen die muskelspezifische Rezeptor-Thyrosinkinase (MuSK-Antikörper) charakterisiert. Beim Lambert-Eaton-Syndrom bedingen Antikörper gegen spannungsabhängige Kalziumkanäle eine verminderte Ausschüttung von Azetylcholin in den synaptischen Spalt. Die Neuromyotonie ist eine Erkrankung, bei der häufig Antikörper gegen spannungsabhängige Kaliumkanäle nachweisbar sind. Diese neuromuskulären Übertragungsstörungen werden im Folgenden zusammenfassend vorgestellt.

The nonischemic forearm exercise test (NIFET) has been shown to be as effective as the classic ischemic forearm exercise test (IFET) in the diagnosis of patients with McArdle disease. Recently, the lactate increase normalized to the mechanical energy production in NIFET was suggested to have a intermediate sensitivity and satisfactory specifity for the screening of mitochondrial disorders.NIFET at 80% maximal contraction force (MCF) was performed in normal controls (n = 41), patients with mitochondrial disorders (n = 15) and other myopathies (diseased controls, n = 20). 26 healthy volunteers also underwent IFET at 80% MCF. The ratio of lactate increase and workload was defined as specific lactate production (mmol x s/N x l).In normal controls there was no significant different lactate increase during NIFET and IFET. The workload performed showed only a weak significant positive correlation with the lactate increase in the NIFET in normal controls (r(2) = 0.20) but not in IFET and NIFET with patients. A moderate negative correlation of specific lactate production and the absolute workload was found in all groups and in both protocols (r(2) = 0.22-0.34). The specific lactate production was highest in patients with other myopathies, intermediate in patients with mitochondrial disorders and lowest in normal controls. NIFET showed a sensitivity of only 20 % and a specifity of 95% for normal controls, but only 75 % for diseased controls.The specific lactate production during NIFET is neither sufficiently specific nor sensitive for the diagnosis of mitochondrial disorders. Increased specific lactate production during rest-to-work transition period might be caused by increased acetyl group deficits.

Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. Methods. 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP’s were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an “intent-to-treat” (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. Results. Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. Conclusion. Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.

Although the gene for facioscapulohumeral muscular dystrophy (FSHD) has not been identified so far, 4q35 deletion represents a diagnostic marker of the disease. In the present study, 46 consecutive symptomatic patients with 4q35 FSHD deletions or typical FSHD clinical features were evaluated. The patients were divided into three groups: 33 patients (72%) with typical FSHD phenotype and 4q35 FSHD deletion, eight (17%) with atypical (non-Landouzy-Dejerine) FSHD phenotype but with 4q35 FSHD deletion, and five patients (11%) with the typical FSHD phenotype but without FSHD 4q35 deletion. Apparently, the 4q35 deletion is associated not only with Landouzy-Dejerine FSHD but also with a variety of "atypical" FSHD forms. On the other hand, the Landouzy-Dejerine FSHD phenotype is possibly a polyetiological syndrome caused in some patients by other genetic effects than 4q35 deletion.

Beevor's sign, an upward deflection of the umbilicus on flexion of the neck, is the result of paralysis of the inferior portion of the rectus abdominis muscle, so that the upper fibers predominate, pulling the umbilicus upwards. The condition may be caused by spinal cord injury at or below the level of Th10. It has also been observed in patients with facioscapulohumeral muscular dystrophy (FSHD). Positive Beevor's sign has been described as a sign of more than 90% sensitivity and specificity with regard to diagnosis of FSHD. We investigated 28 patients with FSHD, proven by genetic analysis, and 65 non-FSHD patients with other neuromuscular diseases. In 13 patients classical FSHD phenotype was observed, in 15 patients phenotype was atypical. Beevor's sign was positive in 15 out of 28 FSHD patients as well as in two of the 65 non-FSHD patients. In patients with typical FSHD phenotype, Beevor's sign was positive in 11/13. Only 4/15 patients with atypical FSHD phenotype showed Beevor's sign. Beevor's sign is less frequent in patients with atypical phenotype. Although Beevor's sign is significantly more frequent in FSHD patients than in patients with other neuromuscular diseases, Beevor's sign is not as sensitive as previously reported. However, especially in atypical cases, Beevor's sign might help in the diagnosis of FSHD.

In this letter resource pricing is applied to peer-to-peer (P2P) networks to ensure a fair allocation of resources. The differences to congestion pricing in IP networks are described and a distributed algorithm based on locally available information is proposed. Asymptotic stability for the global optimum of the proposed system is proven based on a Lyapunov function

The effect of several series of compounds on the biosynthesis of leukotriene B4 in human polymorphonuclear granulocytes (PMNL) was measured after stimulation of the cells by the Ca(2+) ionophore A23187. Phenylhydrazone derivatives and some pyrrole derivatives strongly inhibited 5-lipoxygenase activity at 10 µM. In contrast, 4-aminopyrrolopyrimidines and 4-oxopyrrolopyrimidmes did not exhibit any effect. The compounds examined for inhibition of 5-lipoxygenase were also tested in a chemiluminescence assay for potential effects on the emission of photons as a measure of activated oxygen species generated by the stimulated granulocytes. There was a good correlation between lipoxygenase inhibition and suppression of chemiluminescence; however, some derivatives with no inhibitory activity against lipoxygenase still reduced chemiluminescence, which suggests that an alternative inhibitory mechanism of chemiluminescence must be present. Cyclooxygenase inhibitors such as aspirin did not suppress chemiluminescence of granulocytes. It is, therefore, unlikely that cyclooxygenase is required in the chemiluminescence reaction. In contrast, LTB4 seems to play an important role in the zymosan-induced chemiluminescence of PMNL.

An acylation reaction of biological polyamines by thalidomide has been postulated to explain the teratogenic activity of this drug (Fabro et al. 1965). In a further study, thalidomide has been reported to acylate polyamines at physiological pH; the teratogenic activity of this drug appears to be linked to its high acylating power towards polyamines (Audit 1994). In the present study, the action of the thalidomide molecule and its two chemical moieties (phthalimide and glutarimide rings) on Pleurodeles embryonic development has been investigated. The phthalimide moiety, which displays acylating activity, appears to generate Pleurodeles teratogenesis. The occurrence of a correlation between acylating activity and teratogenicity was confirmed using homothalidomide and partially hydrolyzed thalidomide. The glutarimide moiety has been found to act as an enhancer of phthalimide activity and to cause moderate alterations of newt development. As the acylation of polyamines by thalidomide would deprive the embryo of these essential compounds, the effects of polyamine biosynthesis inhibitors have been compared to those of thalidomide. Both thalidomide and polyamine antimetabolites altered the early cleavage process of the Pleurodeles egg and arrested early development.

Nuclear magnetic resonance (NMR) is a useful tool for 3D-structure eludication. For example, the Nuclear Overhauser Effect (NOE) has been widely used. In this study, we are trying to develop a new complementary modelling method, using the classical [1H]-NMR theory of anisotropic effect. The phenomenon consists of a conformation-dependent chemical shift of an observed hydrogen atom, caused by neighbouring substituents. The ModAnE software includes all mathematical descriptions about the subject. It can be directly addressed as a new module in the SYBYL molecular modelling package. A Monte-Carlo program has been integrated into the ModAnE software in order to allow for conformational refinement. Different classes of molecules have been tested using this Monte-Carlo simulation.

The phosphorylation of 2,3,4-tri- O -acetyl-α-D-fucopyranose with o -phenylene phosphochloridate yielded α-D-fucopyranosyl phosphate which was used for condensation with uridine 5′-monophosphomorpholidate to give uridine 5′-(α-D-fucopyranosyl diphosphate) (UDP-α-D-fucose). A crude enzyme preparation from young leaves of Digitalis lanata EHRH has been shown to catalyze the transfer of D-fucose from synthetic UDP-α-D-fucose to cardenolide aglycones, such as digitoxigenin. The reaction product was identified and characterized by chemical synthesis, HPLC , and spectral methods as the 3 β- O -β-D-fucopyranoside of digitoxigenin (digiproside).

The structure of (5H)-2-Amino-3-hydroxy-5-phenyl-furan-4-one (lb) was determined by NMR-spectroscopy in solution and in the solid state. The structure of its oxidation product, 3,4-Dihydro-3,3,4,4-tetrahydroxy-5-phenyl-furan-2(5H)-one (7), given in the literature as 5-Phenyl-2,3,4-(5H)-furan-trione, was determined by NMR spectroscopy and crystal structure analysis. The solid state NMR spectrum of 7 was compared to the spectrum of dehydroascorbic acid

Boyd's Creek, situated in Barren County, is recognized as the birthplace of the oil industry in the Commonwealth of Kentucky. Naturally occurring oil seeps were identified as early as the 1820s. Commercial crude-oil drilling production began in the early 1860s.3 From the early days to present, countless unrecorded exploration wells were drilled and many of these wells have been found to be improperly abandoned. The Corniferous limestone is the first oil producing interval and is situated at an average subsurface depth of 135 feet. The potential for impacting natural resources is high because of the shallow depth(s) of the Corniferous limestone and the presence of overlying artesian sulfur-water zones which routinely mix with brine and oil in uncased boreholes. The occurrence of limestone related (karstic) features, such as fractures and dissolution cavities, and the close proximity of the Boyd's Creek oil field to nearby surface streams are also of concern. Initially, two abandoned wells were identified as flowing into nearby streams. Pursuant to federal removal authority provided by Subsection (c) of Section 311 of the Federal Water Pollution Control Act in accordance with Subtitle ? of the Oil Pollution Act of 1990 and the National Contingency Plan, the Environmental Protection Agency has initiated cleanup operations within properties nearest to Boyd's Creek. Most wells are difficult to identify because they lack any casing strings and/or they have been buried with soil to hide uncontrolled flows at the surface. Field operations have included the utilization of multiple geophysical techniques to identify anomaly areas thought to represent buried unplugged wells. These include the excavation of surface soils down to the underlying limestone bedrock to search for cable tool and rotary boreholes, the drilling out of old wells using conventional industry technology and standards to plug them permanently with cement, the construction of temporary underflow dams downgradient from identified oil spills to minimize impacts on Boyd's Creek and its adjoining tributaries, and the burning of spilled product in temporary holding pits to minimize associated cleanup cost. In undertaking these actions, the agency is eliminating potential sources of petroleum related contamination.

Proximal myotonic myopathy is an autosomal dominantly inherited multisystem disorder, clinically similar to but genetically distinct from myotonic dystrophy (DM). A recently mapped second locus for myotonic dystrophy was thought to be an attractive candidate locus for PROMM, and this hypothesis was supported by reports of linkage to this locus in some PROMM families. We present a large German pedigree with PROMM in which linkage to this locus could be excluded, showing that PROMM is genetically heterogeneous.

Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid alpha-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers' maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers' test, the CK levels and the 6-min walk test (341 +/- 149.49 m, median 342.25 m at baseline; 393 +/- 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.

Neuromuscular diseases accompanying thymoma include myasthenia gravis, polymyositis, dermatomyositis, and neuromyotonia. Usually 50% of patients with thymoma develop myasthenia gravis. However, only 5% show polymyositis as an accompanying paraneoplastic phenomenon. We report the case of a patient with thymoma showing myasthenia gravis as well as polymyositis. Due to the simultaneous occurrence of these paraneoplastic diseases, the criteria for exact diagnosis (serum creatine kinase, EMG, ocular involvement) overlap. This diagnostic dilemma can appreciably complicate the therapeutic approach.

Objective: To compare muscle imaging findings in different subtypes of myofibrillar myopathies (MFM) in order to identify characteristic patterns of muscle alterations that may be helpful to separate these genetic heterogeneous muscular disorders. Methods: Muscle imaging and clinical findings of 46 patients with MFM were evaluated (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 αB-crystallinopathy, and 3 ZASPopathy). The data were collected retrospectively in 43 patients and prospectively in 3 patients. Results: In patients with desminopathy, the semitendinosus was at least equally affected as the biceps femoris, and the peroneal muscles were never less involved than the tibialis anterior (sensitivity of these imaging criteria to detect desminopathy in our cohort 100%, specificity 95%). In most of the patients with myotilinopathy, the adductor magnus showed more alterations than the gracilis muscle, and the sartorius was at least equally affected as the semitendinosus (sensitivity 90%, specificity 93%). In filaminopathy, the biceps femoris and semitendinosus were at least equally affected as the sartorius muscle, and the medial gastrocnemius was more affected than the lateral gastrocnemius. The semimembranosus mostly showed more alterations than the adductor magnus (sensitivity 88%, specificity 96%). Early adult onset and cardiac involvement was most often associated with desminopathy. In patients with filaminopathy, muscle weakness typically beginning in the 5th decade of life was mostly pronounced proximally, while late adult onset (>50 years) with distal weakness was more often present in myotilinopathy. Conclusions: Muscle imaging in combination with clinical data may be helpful for separation of distinct myofibrillar myopathy subtypes and in scheduling of genetic analysis.

Peer-to-peer technology has the potential to achieve scalability, fault-tolerance and robustness in a cost-efficient way. These properties are not only of interest for Internet applications, but benefits can also be realized in industrial applications. In this short article we discuss the use of P2P networks for the control of microgrids, small islanded parts in electrical power systems. Although deployment of P2P seems far from now, the importance of open networks for the control and supervision of critical infrastructure will increase.

Neuromyelitis optica (NMO; Devic's Syndrome) is an idiopathic, often relapsing, severe inflammatory disorder preferentially affecting optic nerves and spinal cord. The distinction of NMO from multiple sclerosis (MS) as a separate disease entity has been controversally discussed for a long time. Though both diseases show demyelinisation, they differ in typical clinical, imaging and immunopathological findings. The recent identification of serum aquaporin (AQP)-4 antibody clearly separates NMO from MS. In addition, the identification of AQP-4 antibodies supports peripheral humoral autoimmune pathogenesis in NMO and permits early initiation of effective therapy for prevention of attack-related disability.

A series of derivatives of 7-deazapurines with varying substituents in the 2-, 6-, and 9-position was synthesized in an attempt to improve the adenosine receptor affinity and A1 or A2 selectivity. The adenosine receptor affinities were assessed by measuring the inhibition of [3H]-(R)-N6-(phenylisopropyl) adenosine (R-PIA) binding to rat brain A1 and inhibition of [3H]-5'-(N-ethylcarboxamido)adenosine (NECA) binding to rat striatum A2 adenosine receptors. A selected set of compounds representing the main structural variations was further examined in adenosine receptor coupled adenylate cyclase assays. All tested compounds antagonized the inhibition of adenylate cyclase elicited by interaction of R-PIA with A1 receptors in rat fat cell membranes and the activation of adenylate cyclase elicited by interaction of NECA with A2 receptors of pheochromocytoma PC12 cell membranes. The results indicate that 7-deazahypoxanthines have a potential for A2 selectivity, while all 7-deazaadenines are A1 selective. Introduction of a phenyl residue in the 2-position of 7-deazaadenines increases A1 activity tremendously. 2-(p-Chlorophenyl)-7,8-dimethyl-9-phenyl-7-deazaadenine (29) is potent and specific for the A1 receptors of rat brain (Ki = 122 nM), having no affinity for the A2 receptors of rat striatum. The compound has low activity at the A2 receptors of rat PC12 cell membranes where it appears to act as a noncompetitive inhibitor. A 1-phenylethyl substituent at the 9-position was found to be superior to a phenyl residue in terms of A1 affinity. The most potent A1 antagonist in the present series is the highly A1 selective (790-fold) (R)-7,8-dimethyl-2-phenyl-9-(1-phenylethyl)-7-deazaadenine (31, Ki = 4.7 nM), which is 30-35 times more potent at A1 receptors than its S enantiomer. The solubility of six of the potent 7-deaza-2-phenyladenines was determined by means of an A1 binding assay. Chloro substitution of the 2-phenyl ring appeared to improve the solubility as well as the solubility over A1 affinity ratio of 9-phenyl- and 9-(1-phenylethyl)-substituted 7-deazadenines.

During the revision of the dimenhydrinate monograph of the European Pharmacopoeia a HPLC-UV method was developed. The procedure described allows a qualitative and quantitative determination of both dimenhydrinate compounds and of thirteen related substances. Furthermore a hitherto unknown impurity was identified and integrated into the purity check. Also 18 samples of dimenhydrinate have been tested. Thereby the relevant impurities of dimenhydrinate could be nominated and quantified.