On the ozonolysis of unsaturated tosylhydrazones as a direct approach to diazocarbonyl compounds.

The scope and limitations are described of reacting unsaturated tosylhydrazones with O3 followed by Et3N for the generation of 1,4- and 1,5-diazocarbonyl systems. Tosylhydrazones, from tosylhydrazide condensation with readily available δ- and ε-unsaturated α-ketoesters, led in the former case to a 2-pyrazoline whereas the latter cases led to α-diazo-ε-ketoesters, although a terminal alkene produced a tetrahydropyridazinol. Using the ozonolysis-Et3N strategy, tosylhydrazones from cyclic enones give 2,5- and 2,6-diazoketones with aldehyde or ester functionality at the 1-position; the α-diazoaldehydes prefer the s-trans conformation, with a rotation barrier of 74 kJ mol-1 at 25 °C determined by NMR. This one-pot ozonolysis/Bamford-Stevens chemistry demonstrates both the tolerance of tosylhydrazones to ozone, and the subsequently added amine playing a dual role to directly transform the intermediate tosylhydrazone ozonides into products containing reactive diazo and ketone functionalities; such adducts are of particular value as precursors to cyclic carbonyl ylides for 1,3-dipolar cycloadditions.

Pulmonary vascular resistance and proper timing of percutaneous balloon mitral valvotomy.

It is frequent to see pulmonary hypertension (PH) in patients with mitral stenosis (MS) secondary to increased pulmonary vascular resistance (PVR), data about the effect of PVR on the results of percutaneous balloon mitral valvotomy (PBMV) are insufficient. To detect the role of PVR in predicting residual PH immediately after PBMV. This prospective study comprised 49 consecutive patients with moderate to severe MS who were investigated pre and within 48 h post a successful PBMV for the first time. Echocardiography was used to assess the mitral valve area (MVA), mean transmitral pressure gradient (MPG), mitral valve resistance (MVR), right ventricular systolic pressure (RVSP) and PVR. Patients were classified into two groups according to the pre PVR (≥ 1.6 WU as group I and < 1.6 as group II). At baseline compared to group II (32 patients), Group I (17 patients) had higher MPG (13.6 ± 5.2 vs. 11.7 ± 3.7 mmHg, P < 0.05), RVSP (45.6 vs. 37.9 mmHg, P < 0.001) and PVR (2.2 ± 0.1 vs. 1.2 ± 0.1WU, P < 0.001) with no significant difference regarding age, gender, MVS, MVA and MVR. Patients of group I had comparatively lower improvement immediate post procedural of RVSP and PVR with no significant difference in immediate post procedural improvement in NYHA classification, MVA, MPG and MVR. Basal PVR > 1.8WU was proved to be a highly specific (91%), a good predictor (AUC 0.78) of persistent elevation of RVSP > 50 mmHg post PMV. Pathological rise of PVR that associates MS had provided a strong and an independent predictor of persistent pulmonary hypertension post PBMV and by this aspect it could be used as a valuable tool as MVA and MPG to send patients earlier for PBMV even with less severe MS. PVR > 1.81 WU could be used as a noninvasive parameter for predicting regression of PH immediately after PBMV.

Solution NMR studies reveal the location of the second transmembrane domain of the human sigma-1 receptor.

The sigma-1 receptor (S1R) is a ligand-regulated membrane chaperone protein associated with endoplasmic reticulum stress response, and modulation of ion channel activities at the plasma membrane. We report here a solution NMR study of a S1R construct (S1R(Δ35)) in which only the first transmembrane domain and the eight-residue N-terminus have been removed. The second transmembrane helix is found to be composed of residues 91-107, which corresponds to the first steroid binding domain-like region. The cytosolic domain is found to contain three helices, and the secondary structure and backbone dynamics of the chaperone domain are consistent with that determined previously for the chaperone domain alone. The position of TM2 provides a framework for ongoing studies of S1R ligand binding and oligomerisation.

High-resolution NMR studies of structure and dynamics of human ERp27 indicate extensive interdomain flexibility.

ERp27 (endoplasmic reticulum protein 27.7 kDa) is a homologue of PDI (protein disulfide-isomerase) localized to the endoplasmic reticulum. ERp27 is predicted to consist of two thioredoxin-fold domains homologous with the non-catalytic b and b' domains of PDI. The structure in solution of the N-terminal b-like domain of ERp27 was solved using high-resolution NMR data. The structure confirms that it has the thioredoxin fold and that ERp27 is a member of the PDI family. (15)N-NMR relaxation data were obtained and ModelFree analysis highlighted limited exchange contributions and slow internal motions, and indicated that the domain has an average order parameter S(2) of 0.79. Comparison of the single-domain structure determined in the present study with the equivalent domain within full-length ERp27, determined independently by X-ray diffraction, indicated very close agreement. The domain interface inferred from NMR data in solution was much more extensive than that observed in the X-ray structure, suggesting that the domains flex independently and that crystallization selects one specific interdomain orientation. This led us to apply a new rapid method to simulate the flexibility of the full-length protein, establishing that the domains show considerable freedom to flex (tilt and twist) about the interdomain linker, consistent with the NMR data.

Tratamento homeopático de epilepsia canina: relato de caso / Homeopathic treatment of canine epilepsy: a case report

A epilepsia é a doença neurológica crônica mais comum em cães caracterizada pela manifestação de crises convulsivas recorrentes e involuntárias, com ou sem perda de consciência; a epilepsia de etiologia idiopática é a mais frequente nessa espécie. No caso relatado a cadela Mel, que recebeu o diagnóstico de epilepsia idiopática, foi submetida ao tratamento homeopático, sem associação com medicamentos alopáticos, cuja prescrição inclui os medicamentos homeopáticos Pulsatilla nigricans e Cicuta virosa, em diferentes potências e frequências ao longo da evolução clínica do paciente. A resposta terapêutica foi muito satisfatória, promovendo controle eficaz das convulsões com qualidade de vida do animal e seu proprietário, atingindo com sucesso os objetivos do tratamento sem expor o paciente a qualquer tipo de risco. Portanto, a homeopatia demonstrou ser uma opção terapêutica segura e eficiente para a epilepsia canina.

Avaliação in vitro da eficácia de extratos de plantas medicinais do Cerrado frente Staphylococcus aureus isolado de diferentes fontes de propriedades leiteiras / In-vitro evaluation of extract of medicinal plants from Cerrado against the Staphylococcus aureus isolated from different origins on dairy farms

O presente estudo teve como objetivo avaliar o potencial de atividade antimicrobiana in vitro dos extratos de algumas plantas endêmicas do Cerrado tais como Baccharis dracunculifolia. Cochlospermum regium. Croton antisyphiliticus. Eugenia dysenterica e Lippia sidoides, frente ao agente Staphylococcus aureus isolado de leite mastítico, ósteo do teto da vaca, equipamento de ordenhadeira, fossas nasais e garganta do ordenhador. Os extratos foram preparados a partir das partes aéreas e sistema radicular das plantas utilizando os solventes metanol, hexano e clorofórmio na concentração de 10%. Para avaliação da atividade antimicrobiana foi aplicada a técnica de microdiluição em caldo para determinação da Concentração Inibitória Mínima (CIM) seguida da determinação da Concentração Bactericida Mínima (MBC). Os extratos de Baccharis dracunculifolia. Croton antisyphiliticus, seguido do extrato de Lippia sidoides, apresentaram, respectivamente, melhor atividade inibitória sobre a multiplicação da bactéria Staphylococcus aureus. Os resultados obtidos demonstraram, ainda, que as estirpes isoladas do leite e das fossas nasais do ordenhador foram resistentes a gentamicina, princípio ativo muito utilizado no combate à mastite bovina, porém sensíveis aos extratos das plantas referidas, reforçando a importância das plantas medicinais como recurso terapêutico e sua aplicabilidade.

The objective of this study is to evaluate the potencial microbial activity in-vitro from the extract of some endemic plants from Cerrado such as Baccharis dracunculifolia. Cochlospermum regium. Croton antisyphiliticus. Eugenia dysenterica and Lippia sidoides, against the agent Staphylococcus aureus isolated from bovine mastitic milk, osteo from cow's teat, milker equipament, nasal cavitites and milker's gullet. The extracts were prepared from aerial parts as well as the reticular systems of plants using the solvents methanol, hexane and chloroform at a concentration of 10%. To evaluate the antimicrobial activity, the technique of microdilution in broth was used for determining the Minimal Inibitory Concentration (MIC) followed by the determination of Minimal Bactericidal Concentration (MBC). The extracts from Baccharis dracunculifolia and Croton antisyphiliticus, followed by extracts from Lippia sidoides, reported respectively, presented better inhibitory activity against the multiplication of the bacteria Staphylococcus aureus. Furthermore, the results demonstrate that the isolated strains from the milk and nasal cavities of the milker showed strong resistance against gentamicin, active agent commonly applied to combat mastitis bovine. However, there was sensitivity against extracts from the reported plants, reinforcing the importance of the medicinal plants as a therapeutic resource and its aplicability.

The effect of attribute order on judgment in Chinese and English.

The authors found that the order of attribute presentation had a stronger effect on judgment in English than in Chinese. In Experiment 1, with a sample of 102 female and 63 male bilingual Singaporeans, the authors found that participants' memory-based judgments showed a stronger primacy effect in English than in Chinese that was mediated by recall from long-term memory. In contrast, participants' online (immediate) judgments showed a primacy effect in both languages that was unmediated by recall from short-term memory. In Experiment 2, with a sample of 67 female and 53 male bilingual Singaporeans, the authors found that participants' online judgments were more influenced by the attribute order of a previously seen competitive advertisement in English than in Chinese. A cross-cultural field study in Mainland China and the United Kingdom provided external validity for the experimental results.

Selective attention determines emotional responses to novel visual stimuli.

Distinct complex brain systems support selective attention and emotion, but connections between them suggest that human behavior should reflect reciprocal interactions of these systems. Although there is ample evidence that emotional stimuli modulate attentional processes, it is not known whether attention influences emotional behavior. Here we show that evaluation of the emotional tone (cheery/dreary) of complex but meaningless visual patterns can be modulated by the prior attentional state (attending vs. ignoring) used to process each pattern in a visual selection task. Previously ignored patterns were evaluated more negatively than either previously attended or novel patterns. Furthermore, this emotional devaluation of distracting stimuli was robust across different emotional contexts and response scales. Finding that negative affective responses are specifically generated for ignored stimuli points to a new functional role for attention and elaborates the link between attention and emotion. This finding also casts doubt on the conventional marketing wisdom that any exposure is good exposure.

Mark-recapture of Culex erythrothorax in Santa Cruz County, California.

The dispersal of the tule mosquito, Culex erythrothorax, was studied in the proximity of Lake Tynan in the city of Watsonville, CA. From July 18 to 20, 2000, approximately 43,000 female Cx. erythrothorax were marked with luminous powder and released, using a distinct color each day. Recaptures were sampled by using 21 carbon dioxide-baited traps ranging in distance from zero to 2.8 km from the release site. During the 5 days of postrelease sampling, 319 marked mosquitoes were recaptured. The percentage of the marked mosquitoes that were recaptured was 0.46, 0.50, and 0.55% based on the 3 releases, respectively. Overall, the mosquitoes dispersed 0.57 km/day; the mean distance traveled increased during the 5-day sampling period from 0.42 km/day to 0.89 km/day from day 1 to day 5, respectively. Based on the Lincoln index, the estimated total population size for Cx. erythrothorax in the study area ranged from 3.8 to 94 million mosquitoes. This species was found to constitute a nuisance to local residents because of the abundance of this species and its capability to disperse into proximal communities.

A double blind randomized controlled trial of Maharishi Vedic vibration technology in subjects with arthritis.

To explore ancient Vedic medical techniques, one hundred and seventy-six subjects with arthritis participated in a controlled study through the non-pharmacologic approach known as the Maharishi Vedic Vibration Technology (MVVT). Using a double-blinded and randomized experimental design, the findings showed significant reductions of pain and stiffness, and improvement in range of motion in the study sample. One hundred percent relief of symptoms was the most commonly reported category of improvement due to treatment. For the group as a whole, differences in mean response of treatment and control conditions with respect to relief of pain, limitation of motion, and reduction in stiffness were highly significant: t values ranged from a low of 5.609 in stiffness to a high of 20.950 in pain, p = 0.000009 to <10-49 respectively. Analysis by sub-categories of peripheral arthritis, painful conditions of the spine, and rheumatoid arthritis likewise produced significant results. Mechanisms of action were proposed, drawing on Maharishi Vedic Science, developments in quantum field theory, and specifically the theories of chaos and self-organizing systems as they relate to physiological functioning. The instantaneous relief of pain and improvement in function in such a high proportion of subjects with chronic arthritis is unparalleled in modern medical science

Maharishi Vedic vibration technology on chronic disorders and associated quality of life.

There is a growing interest for more effective, innovative programs to address the chronic illness suffered by approximately 40 percent of the U.S. population. The purpose of this study was to evaluate the effects of a new Maharishi Vedic Medicine program-the Maharishi Vedic Vibration Technology-on the quality of life of individuals with chronic disorders. A total of 213 individuals took part in the study (mean age=48.55 years; average length of time of chronic illness=18.42 years). Results showed that over three sessions, the average self-reported improvement in chronic illness was 40.97 percent. Conditions related to neck pain improved the most (51.25%), followed by respiratory ailments (48.00%), digestive problems (46.90%), mental health, including anxiety and depression (46.34%), arthritis (41.57%), insomnia (37.38%), back pain (36.32%), headaches (35.83%), cardiovascular conditions (22.31%), and eye problems (21.19%). Findings also showed significant reductions in frequency of discomfort or pain (p<.000001), intensity of discomfort (p<.000001), and disabling effects of the discomfort in daily activity (p<.000001), in addition to overall improvement in mental health (p<.000001) and vitality (p<.000125). Possible mechanisms of action are presented.

Improvements in chronic diseases with a comprehensive natural medicine approach: a review and case series.

Approximately 40% of the US population report using complementary and alternative medicine, including Maharishi Vedic Medicine (MVM), a traditional, comprehensive system of natural medicine, for relief from chronic and other disorders. Although many reports suggest health benefits from individual MVM techniques, reports on integrated holistic approaches are rare. This case series, designed to investigate the effectiveness of an integrated, multimodality MVM program in an ideal clinical setting, describes the outcomes in four patients: one with sarcoidosis; one with Parkinson's disease; a third with renal hypertension; and a fourth with diabetes/essential hypertension/anxiety disorder. Standard symptom reports and objective markers of disease were evaluated before, during, and after the treatment period. Results suggested substantial improvements as indicated by reductions in major signs, symptoms, and use of conventional medications in the four patients during the 3-week in-residence treatment phase and continuing through the home follow-up program.

Sustained attention and related perceptuomotor functions.

The present study examined the relationship between two measures of sustained attention on the Continuous Performance Test (reaction time and omission errors) and several performance measures on neuropsychological tests. Analysis suggests that sustained attention as measured by processing speed predicts performance on neuropsychological measures of relatively greater complexity and that the Stroop test, which requires maintaining steady focus on a changing stimulus field, may be more sensitive to lapses in attention than other neuropsychological tests.

Sustained attention on a continuous performance test.

The present study compared means of 54 nonpatients on two Continuous Performance Test measures in five administration conditions. Both response measures differentiated performance among the conditions, certain of which may have an alerting function that facilitates deployment of attention. Appreciable attentional demand or effort, however, may limit this facilitative effect.

L-threonine in the treatment of spasticity.

Preclinical data indicate that the administration of the amino acid L-threonine increases glycine levels in rat spinal cord. In order to investigate glycinergic mechanisms in spasticity, and other signs of the upper motor syndrome, we gave 4.5 and 6.0 g/day of L-threonine to 18 patients with familial spastic paraparesis (FSP) according to a double-blind, crossover protocol. The response to treatment at the end of each 2-week period was based upon three measures: the physician's global impressions; the patients' global impressions; and semiquantitative ratings of strength, muscle tone, DTRs, walking, hopping, and running. Blood and CSF were collected during each treatment period for amino acid analyses. Based upon the severity rating scales, there was a statistically significant (p less than 0.02) decrease in motor impairment and spasticity during L-threonine administration compared to placebo treatment; significant treatment effects were not found on the physician's and patients' global impressions. Plasma and CSF levels of threonine increased significantly during L-threonine treatment but glycine levels did not change. These data indicate that L-threonine significantly suppressed the signs of spasticity even though the benefits were not clinically valuable.

d-Fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression.

The ability of d-fenfluramine, a drug that releases brain serotonin and blocks its reuptake, to relieve premenstrual depression and excessive calorie and carbohydrate intakes was examined in 17 women with premenstrual syndrome. Subjects received d-fenfluramine (15 mg twice daily) or placebo, in random order, during the luteal phases of six menstrual cycles; ie, for three control and three treatment cycles each. Behavior was assessed with the Hamilton Rating Scale for Depression and its Addendum, and intakes of calories and nutrients were measured by allowing subjects unlimited access to isocaloric meal and snack foods rich in carbohydrates or protein. Pre-treatment follicular scores using the Hamilton Rating Scale for Depression and its Addendum were 2.0 +/- 0.5 and 0.5 +/- 0.5 (mean +/- SEM), respectively; corresponding luteal scores were 21.2 +/- 0.8 and 10.2 +/- 0.6 (P less than .0001). Luteal phase intakes of kilocalories, carbohydrates, and fats were also increased above follicular levels (P less than .01). d-Fenfluramine decreased premenstrual Hamilton Rating Scale for Depression and Addendum scores by 62% (P less than .001) and 60% (P less than .001), respectively; placebo reduced them by only 28% (P less than .02) and 30% (P less than .02). d-Fenfluramine also fully suppressed the premenstrual rise in kilocalorie, carbohydrate, and fat intakes (P less than .01).

Calorie and nutrient intakes of elderly and young subjects measured under identical conditions.

The calorie and nutrient intakes of elderly and young healthy males and females were monitored for four days at the MIT Clinical Research Center. Subjects were free to select foods for meals and snacks from among a variety of high protein and high carbohydrate foods; when necessary, fat was added to make the foods isocaloric. The elderly subjects consumed significantly fewer calories, carbohydrates, and fat than the young subjects, both absolutely and when adjusted for differences in body weight (p less than .001). Mealtime protein intake when adjusted for body weight was similar among males of both age groups and significantly greater than the intakes of both young and elderly females (p less than .001). However, young males consumed more protein from snacks than young females or older adults and thus exhibited the highest daily protein intakes. The two age groups differed significantly in their pattern of food intake from meals and snacks. Elderly adults consumed almost 85% of their total calories from meals, whereas the younger adults consumed about 72% (p less than .001) from meals. Both groups snacked mainly on carbohydrate-rich foods. The elderly subjects consumed significantly fewer snacks than the young; their daily average consumption was 2.2 and that of the young, 4.5 (p less than .001). The persistence of different patterns of food intake between young and elderly individuals when measured under identical clinical conditions suggests that age per se, in addition to age-associated lifestyle changes, may affect eating behavior.

The circadian rhythm of plasma melatonin during the normal menstrual cycle and in amenorrheic women.

Plasma melatonin, PRL, and LH levels were measured in samples collected every 2 h for 24 h from 14 normally cycling women during the early follicular, periovulatory, and luteal phases of their menstrual cycles. Plasma melatonin levels also were measured in samples collected at the same interval from 7 patients with hypothalamic amenorrhea. A distinct daily rhythm in plasma melatonin was evident in all subjects, with peaks occurring around 0300 h. Each woman's rhythm was remarkably consistent throughout the menstrual cycle (in terms of the phase, amplitude, and total melatonin secreted). Plasma PRL levels also exhibited daily rhythms which did not change during the menstrual cycle; the nocturnal peak plasma PRL level tended to occur 1-2 h after that for melatonin. Among the amenorrheic women, both daytime and nighttime melatonin levels were significantly higher (P less than 0.005) than in the normal women. Their plasma PRL levels were similar to those in the normal women. We conclude that, as for PRL, the circadian rhythm of melatonin secretion does not change significantly during the normal menstrual cycle. The elevated plasma melatonin levels in women with hypothalamic amenorrhea suggest that the hormone may be involved in the neuroendocrine pathology underlying this disorder.