Marked enantioselective protein binding in humans of ketorolac in vitro: Elucidation of enantiomer unbound fractions following facile synthesis and direct chiral hplc resolution of tritium-labelled ketorolac

The protein binding of the enantiomers of the nonopiate analgesic, ketorolac, was investigated in vitro using human plasma and solutions of human serum albumin (HSA) at physiological pH and temperature. In order to detect the very low levels of unbound enantiomers in protein solutions, tritium-labelled rac-ketorolac was synthesised by regiospecific isotopic exchange of the parent drug with tritiated water as the isotope donor. Radio-chemical purification of this compound by reversed-phase HPLC followed by direct resolution using a chiral α₁-acid glycoprotein (Chiral-AGP) HPLC column afforded labelled enantiomers of high specific activity. The in vitro use of (R)- and (S)-[³H₄]ketorolac enabled reproducible radiometric detection of enantiomers in protein solution ultrafiltrate. The unbound fractions of (R)- and (S)-ketorolac [fu(R) and fu(S), respectively] were determined when drug was added to various plasma or albumin solutions as either the separate enantiomers or as the racemate. Over an enantiomeric plasma concentration range of 2.0—15.0 μg/ml, fu(S) (mean range: 1.572—1.795%) was more than 2-fold greater (P < 0.001) than fu(R) (mean range: 0.565—0.674%). Both fu(R) and fu(S) were constant over this concentration range, and each was unaffected by the presence of the corresponding antipode (P > 0.05). At a concentration of 2.0 μg/ml in 40.0 g/liter fatty acid-free HSA, fu(R) and fu(S) were approximately 0.5 and 1.1%, respectively, and both values declined with increasing concentrations of the long chain fatty acid, oleic acid. We have previously shown that the pharmacokinetics of ketorolac in humans are markedly enantioselective and suggest in this report that these differences are largely the result of substantial differences in the protein binding of ketorolac enantiomers. These findings stress the importance of monitoring the unbound concentrations of the enantiomers of chiral drugs if correct interpretations are to be made of enantioselective pharmacokinetic data. © 1994 Wiley-Liss, Inc.     

Self-reported symptoms associated with exposure to electromagnetic fields: a questionnaire study

In the last years, it has been discussed frequently whether there are any harmful effects of electromagnetic fields on human health. Electromagnetic fields are generated by several natural and man-made sources. Part of the electromagnetic spectrum called Radiofrequency is used in communication systems such as mobile (cellular) phone and computer. The aim of our study was to explore different self-reported symptoms that may be associated with exposure to electromagnetic fields. This survey study was conducted, using a questionnaire, on 350 people aged +9 years in Turkey. The chi-square test was used for data analysis. Self-reported symptoms were headache, vertigo/dizziness, fatigue, forgetfulness, sleep disturbance-insomnia, tension-anxiety, joint and bone pain, lacrimation of the eyes, hearing loss and tinnitus. As a result of the survey, the study has shown that users of mobile phone and computer more often complained of headache, joint and bone pain, hearing loss, vertigo/dizziness, tension-anxiety symptoms according to time of daily usage (p?p?相似文献   

Comparative Phenomenology of Ataques de Nervios,Panic Attacks,and Panic Disorder

This article examines a clinicalsample of 66 Dominican and Puerto Ricansubjects who reported ataques de nerviosand also psychiatric disorder, and disentanglesthe phenomenological experiences of ataquede nervios, panic attacks, and panic disorder. In-depth cultural interviews assessed thesymptomatic phenomenology of ataqueepisodes from the local perspective as well asin terms of key panic features, such asrecurrence, rapid peaking of symptoms, and lackof provocation. Independent diagnosticassessments of panic attacks and disorder werealso used to establish the phenomenologicaloverlap between ataque and panic. Ourfindings indicate that 36 percent ofataques de nervios fulfill criteria for panicattacks and between 17 percent and 33 percentfor panic disorder, depending on the overlapmethod used. The main features distinguishingataques that fulfill panic criteria fromataques that do not include whether theepisodes were provoked by an upsetting event inthe person's life and the rapidity of crescendoof the actual attack. A key finding is thatataques often share individualphenomenological features with panic episodes,but that these features usually do not ``runtogether' during the ataque experience.This confirms previous findings thatataque is a more inclusive construct thanpanic disorder. The importance of thesefindings for the clinical diagnosis andtreatment of persons with ataques isdiscussed.     

Seasonality of dizziness and vertigo in a tropical region

Vertigo and dizziness are among the most common medical complaints in the emergency room, and are associated with a considerable personal and health care burden. Scarce and conflicting reports indicate those symptoms may present a seasonal distribution. This study aimed at investigating the existence of a seasonal distribution of vertigo/dizziness in a tropical region, and the correlations of these findings with climatic variables. The charts of all patients consecutively admitted between 2009 and 2012 in the emergency room of a Brazilian general hospital were reviewed. A total of 4920 cases containing these terms were sorted from a sample of 276?076 emergency records. Seasonality was assessed using Cosinor Analysis. Pearson's correlations were performed between the incidence of consultations, considering separately dizziness and vertigo and each of the predictor climatic variables of that index month. Significant seasonal patterns were observed for dizziness and vertigo in the emergency room. Vertigo was more frequent in late winter–spring, negatively correlating to humidity (r?=??0.374; p?=?0.013) and rainfall (r?=??0.334; p?=?0.020). Dizziness peaked on summer months, and positively correlated to average temperatures (r?=?0.520; p?<?0.001) and rainfall (r?=?0.297; p?=?0.040), but negatively to atmospheric pressure (r?=??0.424; p?=?0.003). The different seasonal patterns evidenced for dizziness and vertigo indicate possible distinct underlying mechanisms of how seasons may influence the occurrence of those symptoms.     

Expression of the human FUSED protein in <Emphasis Type="Italic">Drosophila</Emphasis>

The Drosophila segment polarity gene fused, which encodes a serine threonine kinase, is required to transmit the Hedgehog (Hh) signal in imaginal discs. To explore the functional homology between the human protein FUSED (hFU) and the Drosophila protein fused (dFu), we have subjected hFU to a precise and well-defined Hh signalling assay of Drosophila wing development. In the wildtype, hFU affects the expression of Hh target genes leading thus to defects in adult wings. In fu mutants, overexpression of hFU cannot rescue the fu phenotype. These results suggest that hFU in Drosophila interferes with endogenous Hh signalling probably by competing with endogenous dFu when binding its partners but cannot perform the normal Fu function.Edited by C. Desplan     

Psychiatric and Medical Symptoms in Binge Eating in the Absence of Compensatory Behaviors

Objective: To explore the extent to which binge eating in the absence of compensatory behaviors (BE) is associated with psychiatric and medical symptoms in men and women and to control for the independent effects of BMI. Research Methods and Procedures: A series of regression models was applied to questionnaire data on 8045 twins, 18 to 31 years old, from a population‐based Norwegian registry. Results: BE was significantly associated with elevated obesity, overweight, symptoms of eating disorders, symptoms of anxiety and depression, panic attacks, depressive episodes, and reduced life satisfaction in both men and women. In women, BE was independently associated with insomnia and early menarche. In men, BE was independently associated with specific phobia, daily smoking, alcohol use, use of pain medication, impairment due to mental health, neck‐shoulder, lower back, and chronic muscular pain, and impairment due to physical health. Both men and women with BE reported higher rates of psychiatric treatment. Discussion: Our results indicate that there is substantial comorbidity between BE and psychiatric symptoms independently of BMI for both men and women. Medical symptoms co‐occur less frequently than previously reported from treatment‐seeking populations in women. Across all domains, the array of symptoms exhibited by men with BE was broader than that observed in women with BE. This observation suggests the importance of considering gender differences in future studies of psychiatric and medical morbidity, binge eating, and obesity.     

Ataques de nervios in the Puerto Rican diagnostic interview schedule: The impact of cultural categories on psychiatric epidemiology

This paper examines the effect of the cultural category ataques de nervios on responses to the Puerto Rican Diagnostic Interview Schedule (DIS), a Spanish version of structured psychiatric diagnostic interview developed for the NIHM Epidemiologic Catchment Area study. An ataque de nervios scale was created from the Somatization items of the DIS to explore the effect of this culturally meaningful category of distress on responses to a standard psychiatric interview. Analysis of 1,513 cases from a representative sample of the island of Puerto Rico indicated that people reporting ataque symptoms fit the social characteristics described for ataques sufferers in the ethnographic literature. Qualitative data indicated that Puerto Ricans were reporting ataques de nervios in the panic section of the DIS. Questions are raised about the validity of the somatization and panic sections of the DIS in cross-cultural research with Hispanics.     

Pena in the Ecuadorian Sierra: A psychoanthropological analysis of sadness

In highland Ecuador, pena refers to a state of mind characterized by a mixture of sadness and anxiety as well as to an illness state resembling depression. This paper attempts to illustrate, through an analysis of the discourse on pena, how the ideology in which it is embedded serves to interpret a bodily problem at the same time as it reflects a more global attitude toward life. In essence, the folk theory states that the physical complaints caused by suffering are the result of a disturbance of the heart, the central organ of man, and of the emotional life which it controls. Because this suffering is often attributed to the immediate family group of the victim, the community at large often formulates accusations against one of its members. Though the therapy is limited to a cure of the symptoms through herbal remedies, a formal request can be made to a perceived wrongdoer to amend his behavior. The pena is also a state which can lead to colerin, a dangerous and sometimes lethal illness which is characterized by a sudden explosion of anger or madness and which will follow an unattended state of pena.     

Linkage disequilibrium detected between myotonic dystrophy and the anonymous marker D19S63 in the Spanish population

Summary We used the following polymorphic markers: APOC2 (BanI, BglI, TaqI), CKMM (NcoI, TaqI), and D19S63 (PstI) to haplotype 33 Spanish myotonic dystrophy (DM) families. We analysed the allele and haplotype frequencies of our sample, and the possible association of alleles or haplotypes with the disease. We found a slight linkage disequilibrium between APOC2 (BanI) and DM, but no disequilibrium when using all other APOC2 and CKMM RFLPs; this agrees with data previously reported. In addition, we found a very strong linkage disequilibrium when using D19S63 (PstI), the + allele being associated with the DM locus. This disequilibrium in the Spanish population indicates that D19S63 is very close to the DM locus.     

Association between somatosensory,motor and psychological variables by levels of disability in patients with cervicogenic dizziness

Abstract

Cervicogenic dizziness is a musculoskeletal disorder mainly characterized by dizziness associated with neck pain. The aim of this study was to assess the association between somatosensory, motor and psychological variables by levels of disability due to dizziness in patients with cervicogenic dizziness. A total of 64 patients were classified into two groups according to the presence of higher and lower levels of disability due to dizziness. The degree of disability due to dizziness, the magnitude of chronic pain, catastrophizing and kinesiophobia were evaluated by self-reports. The cervical active range of motion and the pressure pain thresholds were also assessed. The psychosocial variables showed significant differences. Higher values were found in the group with the highest level of disability due to dizziness (d?=?0.80). Regarding motor variables, some differences were found in extension (d?=?0.52) and in right rotation cervical movement (d?=?0.90), with lower values in the group with greater disability due to dizziness. No differences were observed in the somatosensory variables (p?>?.05). In the group with lower levels of disability due to dizziness, negative associations were found with the range of cervical motion and positive associations were found with kinesiophobia. Our results suggest that levels of disability due to dizziness could be an important factor to consider in patients with cervicogenic dizziness. The influence of psychological factors and some ranges of cervical movement should be considered clinically.     

Pattern formation in the wing veins of the fused mutant (Drosophila melanogaster).

In order to analyze the effects of the mutation fused (fu) on vein pattern formation, wings mosaic for fused and non-fused tissue were obtained. Analysis of these wings (1) confirmed that fused does not involve the production of a freely diffusible substance; (2) showed that a genotypically fu fourth longitudinal vein (LV 4) develops a normal phenotype nonautonomously if the third longitudinal vein (LV 3) and most of the first posterior cell are non-fused; (3) showed that in the reciprocal situation, a non-fused fourth longitudinal vein often exhibited autonomous differentiation; (4) demonstrated that small groups of cells (either fu or non-fu) could be incorporated into structures characteristic of the opposite genotype; and (5) offered evidence that the dorsal wing surface may play an important role in the control of vein formation. Additionally, the fused phenotype itself was examined in some detail, and the anterior-posterior compartment border was defined. This examination suggests that in the more extreme cases LV 4 does not fuse with LV 3, but simply fails to form.     

<Emphasis Type="Italic">Ataques De Nervios</Emphasis> In Relation to Anxiety Sensitivity Among Island Puerto Ricans

This study investigated the symptom profile of ataques de nervios (ADN) among Puerto Rican volunteers from the community who self-identified as having experienced at least one ataque. As expected, the most commonly reported ataques-specific symptoms were crying, anger, nervousness, and becoming hysterical. Comparing the responses of those with ADN to those with no history of ADN but who reported elevated anxiety sensitivity (AS) indicated that both groups were comparable on measures of depression, state and trait anxiety, and associated panic symptoms. As expected, both groups scored significantly higher on all measures than did participants with no history of ADN and low AS with the exception of the measure of state anxiety. It is unclear, however, whether the overlap in symptom severity between those with ADN and those with elevated anxiety sensitivity indicates that ADN and AS are the same or distinct conditions.     

Dizziness in peri- and postmenopausal women is associated with anxiety: a cross-sectional study

Background

Although dizziness is one of the most common symptoms of menopause, the underlying mechanism is not precisely known. Therefore, this study aimed to investigate the prevalence of, and the factors associated with, dizziness in peri- and postmenopausal women.

Methods

We conducted a cross-sectional study in which we analyzed the first-visit records of 471 Japanese women aged 40 to 65?years who enrolled in a health and nutrition education program at a menopause clinic. The prevalence of dizziness was estimated according to the participants’ responses to the Menopausal Health-Related Quality of Life Questionnaire. The background characteristics of age, menopause status, body composition, cardiovascular parameters, basal metabolism, and physical fitness; other menopausal symptoms, including vasomotor, insomnia, depression, and anxiety symptoms; and lifestyle characteristics were assessed for their associations with dizziness.

Results

The percentage of women who suffered from dizziness once a week or more frequently was 35.7%. Compared to the women without dizziness, those with the symptom were younger; had a higher body weight, body mass index, body fat percentage, muscle mass, and waist-to-hip ratio; had higher systolic pressure; were slower in reaction time; had higher physical and psychological symptom scores of menopause; exercised less regularly; and consumed less alcohol. A multivariate logistic regression analysis revealed that the anxiety symptom, which was evaluated by the Hospital Anxiety and Depression Scale, was the sole factor that was independently associated with dizziness (adjusted odds ratio 1.14; 95% confidence interval 1.08–1.20).

Conclusions

Dizziness is highly prevalent in Japanese peri- and postmenopausal women and it is associated with anxiety. The treatment of anxiety in this population might improve the symptom.

     

The first report of luminescent liver tissue in fishes: Evolution and structure of bioluminescent organs in the deep‐sea naked barracudinas (Aulopiformes: Lestidiidae)

Bioluminescent organs that provide ventral camouflage are common among fishes in the meso‐bathypelagic zones of the deep sea. However, the anatomical structures that have been modified to produce light vary substantially among different groups of fishes. Although the anatomical structure and evolutionary derivation of some of these organs have been well studied, the light organs of the naked barracudinas have received little scientific attention. This study describes the anatomy and evolution of bioluminescent organs in the Lestidiidae (naked barracudinas) in the context of a new phylogeny of barracudinas and closely related alepisauroid fishes. Gross and histological examination of bioluminescent organs or homologous structures from preserved museum specimens indicate that the ventral light organ is derived from hepatopancreatic tissue and that the antorbital spot in Lestrolepis is, in fact, a second dermal light organ. In the context of the phylogeny generated from DNA‐sequence data from eight gene fragments (7 nuclear and 1 mitochondrial), a complex liver with a narrow ventral strand running along the ventral midline evolves first in the Lestidiidae. The ventral hepatopancreatic tissue later evolves into a ventral bioluminescent organ in the ancestor of Lestidium and Lestrolepis with the lineage leading to the genus Lestrolepis evolving a dermal antorbital bioluminescent organ, likely for light‐intensity matching. This is the first described hepatopancreatic bioluminescent organ in fishes. J. Morphol. 276:310–318, 2015. © 2014 Wiley Periodicals, Inc.     

Period Prevalence of Dizziness and Vertigo in Adolescents

Objectives

To assess the period prevalence and severity of dizziness and vertigo in adolescents.

Methods

In 1661 students in 8^th-10^th grade in twelve grammar schools in Munich, Germany information on vertigo/dizziness was assessed by a questionnaire in the class room setting. Three month prevalence of dizziness/vertigo was estimated; symptoms were categorized as orthostatic dizziness, spinning vertigo, swaying vertigo or unspecified dizziness. Duration of symptoms and impact on daily life activities were assessed.

Results

72.0% (95%-CI = [69.8–74.2]; N = 1196) of the students (mean age 14.5±1.1) reported to suffer from at least one episode of dizziness or vertigo in the last three months. Most adolescents ticked to have symptoms of orthostatic dizziness (52.0%, 95%-CI = [49.5–54.4], N = 863). The period prevalence for the other types of vertigo were spinning vertigo: 11.6%, 95%-CI = [10.1–13.3], N = 193; swaying vertigo: 12.2%, 95%-CI = [10.6–13.8], N = 202; and unspecified dizziness: 15.2%, 95%-CI = [13.5–17.1], N = 253. About 50% of students with spinning vertigo and swaying vertigo also report to have orthostatic dizziness. Most vertigo/dizziness types were confined to less than one minute on average. The proportion of students with any dizziness/vertigo accounting for failure attending school, leisure activities or obliging them to stay in bed were more pronounced for spinning or swaying vertigo.

Conclusion

Dizziness and vertigo in grammar school students appear to be as common as in adults. In face of the high period prevalence and clinical relevance of dizziness/vertigo in adolescents there is a need for prevention strategies. Risk factors for dizziness/vertigo need to be assessed to allow for conception of an intervention programme.     

Genetic analysis of viable and lethalfused mutants ofDrosophila melanogaster

Summary Fused is a segmentation gene belonging to the segment-polarity class. Mutations at thefused locus are known to display pleiotropic effects, causing zygotically determined anomalies of ovaries and of some adult cuticular structures, and maternally determined embryonic segmentation defects. In order to determine the amorphic phenotype offused and to study the genetical basis of its pleiotropy, newfused alleles (18 viable and 11 lethal) were isolated. The phenotype of these mutants and of others already known are described, taking into account zygotic and maternal effects. The main results provided by this analysis are as follows. Firstly, allfused alleles show the whole complex fused phenotype, and a good correlation is observed between the strength of the wing and segmentation defects, suggesting that a single function is involved in both processes. Secondly, all embryonic and larval lethals carry deficiencies which allow us to localizefused between the 17C4 and 17D2 bands of the X-chromosome. Thirdly, the 24 viable and 2 pupal lethals examined behave as point mutants, as shown cytologically or by Southern blot analysis. However, only one of them, the pupal lethalfu ^mH63 was proven to carry a nullfused allele, since it displays in germ-line clones a strong maternal phenotype and a very low zygotic rescue, similar to those of the small deficiencyDf(1)fu ^z4. The phenotype of the amorphic mutant indicates that zygotic ezpression offused is required for normal metamorphosis, while maternal expression is necessary for a normal segmentation pattern, since a complete loss offused expression during oogenesis cannot be compensated zygotically.     

Panic attacks and supraventricular tachycardias: the chicken or the egg?

Panic attacks occur in about 2 % of the population. Symptoms include a racing or pounding heart beat, chest pain, dizziness, light-headedness, nausea, difficulty in breathing, tingling or numbness in the hands, flushes or chills, dreamlike sensations or perceptual distortions. The symptoms of paroxysmal supraventricular tachycardia (PSVT) may be similar. A PSVT is often difficult to document on the ECG since it has often ceased before the patient comes to medical attention. Besides, a tachycardia may still be present and even be documented but interpreted as a phenomenon secondary to the panic attack. In addition, ECG abnormalities between episodes can often not be identified. The evidence that in some patients paroxysmal SVT is the cause, but not the consequence of a panic attack, is based on observations that catheter ablation was able to cure patients presenting with panic disorders. To better establish the prevalence of SVT as the underlying mechanism of a panic attack, there is a need for prospective studies and/or registries. Whereas gastric ulcer has in some patients changed from a psychosomatic disorder to an infectious disease, we may hypothesise that a certain proportion of panic disorders may mutate into an underlying arrhythmia rather than a primary psychiatric disorder.     

Distyly and heteromorphic incompatibility in oceanic island species ofErythroxylum (Erythroxylaceae)

Surveys of oceanic island floras have shown that heterostyly is usually absent in such regions, probably because this floral polymorphism is often associated with a self-incompatibility system. In this context we describe the floral biology of three species ofErythroxylum on La Réunion island and examine the compatibility relationships of one of these species,E. laurifolium. All three species are distylous but differ in relative stigma-anther separation in the different morphs. In general, short-styled flowers have greater stigma-anther separation than long-styled flowers, which are often homostylous in appearance. This lack of stigma-anther separation in long-styled flowers is due to style twisting which improves reciprocity at the high organ level. The reduced stigma-anther separation does not appear to be associated with the evolution of selfing asErythroxylum laurifolium shows heteromorphic self-incompatibility. The presence of heteromorphic incompatibility in a group of species that have colonized an oceanic island is discussed.     

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

 The present study is an analysis of the frequencies of HFE mutations in patients with different forms of iron overload compared with the frequencies found in healthy subjects from the same region. The frequencies of HLA-A and -B antigens and HLA haplotypes were also analyzed in the same subjects. The study population included: 71 healthy individuals; 39 genetically and clinically well-characterized patients with genetic hemochromatosis (HH); and 25 patients with non-classical forms of iron overload (NCH), excluding secondary hemochromatosis. All subjects were HLA-typed and HFE-genotyped by the oligonucleotide ligation assay (OLA). The gene frequencies found for the C282Y and H63D mutations of HFE were respectively: 0.03 and 0.23 in healthy individuals, 0.86 and 0.04 in HH patients, and 0.08 and 0.48 in NCH patients. An expected significant association between HH and HLA-A3 was observed, which was found to be in linkage disequilibrium with the C282Y mutation. A new association was seen, however, between HLA-A29 and NCH, in linkage disequilibrium with the H63D mutation. Again as expected, the HLA-B antigen B7 was associated with HH in linkage disequilibrium with HLA-A3. In addition, the HLA-B antigen B44 was found to be associated with NCH but not in linkage disequilibrium with either A29 or the H63D mutation. In conclusion, a new association of the HFE H63D mutation with forms of hemochromatosis other than HH and a new association between the HLA phenotype A29 and the HFE H63D mutation were found in the same patients. These findings reinforce evidence for the involvement of the major histocompatibility class I in iron metabolism, supporting the notion of a physiological role for the immunological system in the regulation of iron load. Received: 11 June 1997 / Revised: 29 October 1997