Binge drinking and insomnia in students from health sciences at one university in Rio de Janeiro, Brazil.

In spite of the many studies examining alcohol consumption, recent reviews have indicated that binge drinking has not been extensively studied. Furthermore, it is becoming increasingly clear that sleep is associated with many physiological functions and to drug addictions. The present study aimed to evaluate the relationship between alcohol binge drinking and insomnia in college students of health sciences. All first-year health sciences students (n=286) were evaluated in a cross-sectional study. Envelopes containing the Insomnia Severity Index (ISI), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and questions capturing sociodemographic data were distributed and collected in classes. It was found that most non-drinkers were female (70.6%), although there were no sex-related differences in the number of binge drinkers (more than 5 drinks on each occasion at least once a week), allowing statistical comparison. The Mann-Whitney U test indicated that the ISI scores were significantly greater in female than male binge drinkers (P=0.014). Moderate or severe insomnia was reported by 23% of the sample, with alcohol being the most frequently associated substance. A specialized intervention was suggested by ASSIST: brief for marijuana (19.2%) and tobacco (23.3%) use, and moderate (31.5%) or intensive (1.4%) for alcohol consumers. The data highlighted the need to pay attention to the habits of college students beyond obtaining scientific information. New data suggesting the influence of genetics on insomnia may be of importance when performing additional studies on the sex differences in alcohol binge drinking.

Binge drinking and insomnia in students from health sciences at one university in Rio de Janeiro, Brazil

In spite of the many studies examining alcohol consumption, recent reviews have indicated that binge drinking has not been extensively studied. Furthermore, it is becoming increasingly clear that sleep is associated with many physiological functions and to drug addictions. The present study aimed to evaluate the relationship between alcohol binge drinking and insomnia in college students of health sciences. All first-year health sciences students (n=286) were evaluated in a cross-sectional study. Envelopes containing the Insomnia Severity Index (ISI), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and questions capturing sociodemographic data were distributed and collected in classes. It was found that most non-drinkers were female (70.6%), although there were no sex-related differences in the number of binge drinkers (more than 5 drinks on each occasion at least once a week), allowing statistical comparison. The Mann-Whitney U test indicated that the ISI scores were significantly greater in female than male binge drinkers (P=0.014). Moderate or severe insomnia was reported by 23% of the sample, with alcohol being the most frequently associated substance. A specialized intervention was suggested by ASSIST: brief for marijuana (19.2%) and tobacco (23.3%) use, and moderate (31.5%) or intensive (1.4%) for alcohol consumers. The data highlighted the need to pay attention to the habits of college students beyond obtaining scientific information. New data suggesting the influence of genetics on insomnia may be of importance when performing additional studies on the sex differences in alcohol binge drinking.

Fibroblast Biomarkers of Sporadic Parkinson's Disease and LRRK2 Kinase Inhibition.

It has been uncertain whether specific disease-relevant biomarker phenotypes can be found using sporadic Parkinson's disease (PD) patient-derived samples, as it has been proposed that there may be a plethora of underlying causes and pathological mechanisms. Fibroblasts derived from familial PD patients harboring leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), and Parkin mutations show clear disease-relevant mitochondrial phenotypes, which are exacerbated under conditions of pharmacological stress. We utilized fibroblasts derived from non-familial sporadic PD patients (without LRRK2 mutations) or LRRK2 mutation carriers to directly compare the cellular phenotypes during and after mitochondrial stress. We then determined the effects of pharmacological LRRK2 kinase inhibition using LRRK2-in-1. We found that there were two distinct populations of sporadic PD patient-derived fibroblast lines. One group of sporadic PD lines was highly susceptible to valinomycin-induced mitochondrial depolarization, emulating the mutant LRRK2 phenotype. These lines showed elevated mitochondrial superoxide/ nitric oxide levels, displayed increased mitochondrial and lysosome co-localization, and an increased rate of mitochondrial collapse, which corresponded with changes in mitochondrial fission and fusion proteins. The application of LRRK2-in-1 reversed decreased levels of mitochondrial and lysosome co-localization and partially restored mitochondrial network associated proteins and the mitochondrial membrane potential in the fibroblasts. This study identifies novel mitochondrial biomarkers in sporadic PD patient-derived fibroblast lines, which could be used as preclinical tools in which to test novel and known neuroprotective compounds.

Nonfunctional overreaching leads to inflammation and myostatin upregulation in swiss mice.

The aims of the this study were a) to verify whether the performance decrease induced by nonfunctional overreaching (NFOR) is linked to high concentrations of cytokines in serum, skeletal muscles and liver; b) to verify muscle myostatin adaptation to NFOR; c) to verify the effects of chronic glucose supplementation on the parameters mentioned above. Mice were divided into control (C), trained (TR), overtrained (OTR) and supplemented overtrained (OTR + S). The incremental load test (ILT) and exhaustive test (ET) were used to measure performances before and after exercise protocols. 24 h after ET, muscles and liver were removed and stored at -80°C for subsequent measurements. Total blood was collected from decapitation for subsequent determination of cytokine concentrations. Generally, OTR and OTR + S presented higher contents of IL-6, TNF-alpha, GLUT-4 and myostatin in muscle samples compared to C and TR. Glucose supplementation attenuated the high contents of IL-6, TNF-alpha and IL-15 in liver, and of IL-6 in serum. In summary, NFOR led to low-grade chronic inflammation and myostatin upregulation.

Effect of chronic ethanol consumption in female rats subjected to experimental sepsis.

The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

Effects of chronic ethanol consumption in experimental sepsis.

AIMS: To evaluate the effects of chronic ethanol consumption on the development and the pathophysiology of sepsis, using an experimental model of polymicrobial peritonitis by feces i.p. injection. METHODS: Forty-day-old male Wistar rats were divided into groups for two experiments: A and B. Experiment A was performed for determination of mortality rates, while experiment B was designed for biochemical analysis and measurement of cytokines before and after sepsis. In both the experiments, treated animals were exposed to a 10% ethanol solution as the single drinking source for 4 weeks, while untreated animals were exposed to tap water over the same period. Food was provided ad libitum. After this period, the animals underwent i.p. fecal injection for induction of sepsis. RESULTS: Experiment A showed that higher doses of ethanol resulted in early mortality from sepsis that was correlated with the alcohol consumption (high dose = 85.7%, low dose = 14.3%, P = 0.027). In experiment B, cytokine analysis demonstrated important changes resulting from sepsis, which were further affected by ethanol exposure. In addition, glucose and creatinine levels decreased and increased, respectively, after sepsis, but a significant change occurred only in the ethanol group (P < 0.003 glucose, P < 0.01 creatinine). The levels of pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, increased after sepsis, but were less evident after ethanol exposure. CONCLUSION: These differences may be the result of either early mortality or an increase in the severity of the septic process. Taking into account the high mortality rate and the extreme severity of sepsis after alcohol consumption, often encouraged by advertising, a caution should be given to patients with severe infections and a history of alcohol abuse.

A Phe389Leu substitution in ergA confers terbinafine resistance in Aspergillus fumigatus.

Replacement of phenylalanine with leucine at position 391 in squalene epoxidase was identified as being responsible for terbinafine resistance in mutants of Aspergillus nidulans. The equivalent mutation was engineered into the ergA gene of Aspergillus fumigatus, resulting in an F389L substitution that also conferred resistance to this pathogenic mold.

Risk factors and characteristics of ocular complications, and efficacy of autologous serum tears after haematopoietic progenitor cell transplantation.

The objective of the study was to evaluate the frequency and clinical characteristics of ocular complications and their risk factors, as well as autologous serum tears (AST) for the treatment of dry eye in these patients. Data from the files of 124 patients who had undergone allogeneic haematopoietic progenitor cell transplantation (HPCT) were evaluated. In addition, 33 HPCT patients were examined and their data were compared with controls. Analysis of tears and AST was performed. Dry eye manifestation occurred in 32% of patients and was positively correlated with age over 27 years (P = 0.05), peripheral blood progenitor cell transplant (P = 0.002), chronic graft-versus-host disease (P = 0.0027), and chronic or acute myeloid leukaemia (P = 0.001). Dry mouth and Schirmer test < 5 mm were predictive factors for dry eye in HPCT patients (P = 0.002 and odds ratio 3.9 and P = 0.007, odds ratio = 5.9, respectively). Microbiological analysis revealed that six of 11 AST samples were contaminated after 30 days of use. The present study supports the role of potential risk factors for ocular complications and key elements to detect alterations in the tear film from HPCT patients. In addition, AST contamination must be considered after longer periods of use.

Increased expression of advanced glycation end-products and their receptor, and activation of nuclear factor kappa-B in lacrimal glands of diabetic rats.

AIMS/HYPOTHESIS: To assess the involvement of the AGE-specific receptor (AGER, also known as RAGE) axis and nuclear factor kappa-B (NFKB, also known as NF-kappaB) activation in the development of lacrimal gland and tear film dysfunction in diabetes, the present study evaluated: (1) lacrimal gland and tear film alterations in diabetic rats; and (2) the expression of AGE, AGER and NFKB in ocular tissues of normoglycaemic and diabetic rats. MATERIALS AND METHODS: Diabetes was induced in male Wistar rats with intravenous streptozotocin. Tear secretion parameters were measured and NFKB expression was evaluated in lacrimal glands of control and diabetic rats by western blot. Immunohistochemistry with confocal microscopy was used to assess AGE, AGER and NFKB expression in lacrimal glands of both groups. RESULTS: Lacrimal gland weight and tear film volume were lower in diabetic than in control rats (p=0.01 and 0.02, respectively). IL1B and TNF concentrations in tears were higher in diabetic than in control rats (p=0.007 and 0.02, respectively). NFKB protein was identified in rat cornea, conjunctiva and lacrimal glands. AGE, AGER and NFKB expression were greater in lacrimal glands of diabetic than in those of control rats. CONCLUSIONS/INTERPRETATION: Diabetes induces significant alterations in rat lacrimal gland structure and secretion. The higher expression of AGE, AGER and NFKB in lacrimal glands of diabetic rats suggests that these factors are involved in signalling and in subsequent inflammatory alterations related to dry eye in diabetes mellitus.

Young gymnasts' understanding of sport-related pain: a contribution to prevention of injury.

INTRODUCTION: Pain may signal impending or actual injury, or the achievement of optimum workload to produce a physical conditioning effect. These different functions of pain present a challenge for athletes wanting to improve their skill and conditioning level in the most efficient manner without injury. As children may be particularly vulnerable to exacerbating pain and injury owing to limited knowledge, it is important to learn more about the development of their understanding of pain concepts (e.g. pain as a signal of impending injury vs. soreness from exertion). METHODS: A structured interview and scoring criteria were developed to measure children's understanding of the functions of pain in sport and the consequences of pain and injury. Competitive gymnasts (6-13 years; n = 68; 63% girls) were interviewed and their responses were scored for indices of understanding of different types of pain. RESULTS: Age differences were found in: number of different types of pain identified; understanding of pain causality; understanding the value of pain; distinguishing pain from exertion; and use of pain descriptors. Analyses revealed that gymnasts responded differently to different types of pain and were aware of the need to stop their sport in some cases and to continue in others. Most did not describe social pressure to continue gymnastics while in pain. Gymnasts demonstrated an understanding that there was little they could do about chronic pain, yet appreciated that pain or damage could worsen with continued practice. DISCUSSION: This study was a first step in elucidating young gymnasts' understanding of sport-related pain. Further research is needed with athletes from other sports, and comparisons should be made with non-athletic children and those with pain from other sources. Within various sports, it will be important to determine the relative effects of age, sex, and number of hours spent training. Appreciation of individual differences in children's understanding of pain may contribute to prevention of injury in sport. For example, children who understand the difference between soreness from exertion and acute pain owing to injury may be able to make better decisions about pain management and continued practice.

Identification of genes involved in terbinafine resistance in Aspergillus nidulans.

AIMS: To determine the pattern and the genetic basis of resistance to terbinafine, a drug extensively used for the treatment of fungal infections in humans. METHODS AND RESULTS: Four resistant mutants from Aspergillus nidulans isolated after irradiation with ultraviolet light were crossed with the master strain F (MSF). Genetic analysis revealed that a single gene, located on chromosome IV, is responsible for resistance to terbinafine and that the alleles responsible for this resistance in these mutants are of a codominant or dominant nature at high terbinafine concentrations. Furthermore, the interaction of this mutation with another one identified on chromosome II causes the double mutant to be highly resistant. CONCLUSIONS: Periodic surveillance of antimycotic susceptibility would be an important measure in detecting the emergence and spread of resistance. Mutation in a single gene could be responsible for resistance to terbinafine and a genic interaction may be responsible for a higher level of antimycotic resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: The understanding of the mechanisms that lead to changes in the sensitivity of a fungus to a given antifungal agent is important both in order to define strategies for the use of such agent and to guide the development of new antifungal agents.

Regulation of insulin-stimulated tyrosine phosphorylation of Shc and Shc/Grb2 association in liver, muscle, and adipose tissue of epinephrine- and streptozotocin-treated rats.

Shc protein phosphorylation has been extensively characterized as the initial step that activates a complex mitogenic pathway through its association with Grb2. In the present study, we investigated the adrenergic control of insulin-induced Shc phosphorylation and Shc-Grb2 association, and the modulating effect of streptozotocin-induced diabetes mellitus on Shc phosphorylation and Shc/Grb2 association. Acute treatment with epinephrine, which leads to a normoglycemic insulin-resistant state, does not affect insulin-induced Shc tyrosine phosphorylation or Shc-Grb2 association in liver, muscle, or fat. By contrast, a significant increase in insulin-induced Shc phosphorylation is observed in liver and muscle of rats treated with streptozotocin. The association of Shc/Grb2 is also increased in both tissues following insulin treatment. These data suggest that while epinephrine preserves the insulin-induced phosphorylation of Shc and the mitogenic pathway stimulated by Shc-Grb2 association, treatment with streptozotocin leads to a tissue-specific increase in the activity of the initial step that ultimately results in the activation of the Shc/Grb2 mitogenic pathway.

[Prevalence of canine filariasis by Dirofilaria immitis and Dipetalonema reconditum in Maceió, Alagoas State, Brazil]. / Prevalência da filariose canina causada por Dirofilaria immitis e Dipetalonema reconditum em Maceió, Alagoas, Brasil.

A survey on the prevalence of Dirofilaria immitis and Dipetalonema reconditum was conducted in 1,519 dogs from Maceió and two coastal areas in the State of Alagoas, Northeast Brazil, from 1995 to 1999, by testing for microfilariae in blood. All blood samples were from exclusively domiciled dogs with a known history, showing that the infections were autochthonous, confirming transmission of canine filariasis in these areas. In Greater Metropolitan Maceió, 15 (1.3%) microfilaremic dogs were detected with D. immitis and 15 (1,3%) with D. reconditum. In the southern coastal area there was an estimated prevalence of 12.7% for D. immitis. D. immitis and D. reconditum microfilaria were 298.1 micrometer and 249.2 micrometer long and 7.3 micrometer and 4.4 micrometer wide, respectively. A Witness immunotest that detects D. immitis antigen was used to confirm parasitological results and reveal occult dirofilariasis cases. Of the total 6,579 females examined, 8 (0.1%) Culex quinquefasciatus were observed to be naturally infected with D. immitis larvae. These results proved dirofilariasis transmission in Maceió and demonstrated D. reconditum in the same geographic area.

Androgen influence on the meibomian gland.

PURPOSE: The hypothesis in the study was that androgens control meibomian gland function, regulate the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer. To test this hypothesis, a study was conducted to determine whether androgen receptor protein exists in the epithelial cell nuclei of rat meibomian glands and, in addition, whether androgen deficiency and/or treatment influences the gross morphology, neutral lipid content, and fatty acid profile of the rabbit meibomian gland, as well as the appearance of the tear film lipid layer. METHODS: Rat lids were obtained and processed for immunohistochemistry. Meibomian glands from intact, androgen- and/or placebo-treated rabbits were analyzed by histology, and glandular lipids were evaluated by gas chromatography, high-performance liquid chromatography (HPLC), and mass spectrometry. The rabbit tear film lipid layer was assessed by interferometry. RESULTS: In the current study androgen receptor protein existed within acinar epithelial cell nuclei of rat meibomian glands; androgen deficiency was associated with alterations in the lipid content of the rabbit meibomian gland; 19-nortestosterone treatment modulated the fatty acid profile in the total and neutral lipid fractions of the rabbit meibomian gland; and androgens did not appear to influence the gross morphology of meibomian tissue or to exert a demonstrable effect on the rabbit tear film lipid layer. CONCLUSIONS: The findings show that the meibomian gland is an androgen target organ and that androgens influence the lipid profile within this tissue. However, the extent to which androgens regulate the production of these lipids and whether this action may impact tear film stability remain to be determined.

The microfilarial periodicity of Wuchereria bancrofti in north-eastern Brazil.

The periodicity of Wuchereria bancrofti microfilariae (mff) in peripheral blood was analysed in 42 microfilaraemics living in Maceió, in Alagoas state, north-eastern Brazil. Nine blood samples were collected from each subject, over a 24-h period, and two quantitative (60-microliter) thick smears were prepared from each sample. Although all the subjects had detectable microfilaraemias from 23.00 hours to 06.00 hours, no mff could be detected in most (71.4%) of the smears prepared from samples collected at 15.00 hours. Samples collected during the day, at 15.00 hours, contained 170 times fewer mff/microliter than those collected at 01.00 hours, when microfilaraemias were generally most intense. For diagnosis of bancroftian filariasis in Maceió, blood samples should be collected between 22.00 and 03.00 hours, when microfilarial counts will be at least 90% of the peak counts. The circadian variation observed was independent of the subject's gender and microfilarial density. Mathematical analysis, using a simple harmonic-wave model, indicated a periodicity index of 127.6 and that maximum microfilarial densities occurred at 00.51 hours, confirming the nocturnal pattern of microfilaraemia in the study area.

Everyday pain responses in children with and without developmental delays.

OBJECTIVE: To examine whether children with developmental delays respond to painful events differently than nondelayed children. METHODS: Sixty families participated. Children between the ages of 2 and 6 years were observed at daycare centers while engaged in usual daily activities, such as free play. Spontaneous painful incidents and the child's responses were recorded using an observational measure (Dalhousie Everyday Pain Scale) designed to capture pain behavior. RESULTS: Children with developmental delays (n = 24) displayed a less intense distress response to an equivocal pain event than nondelayed children (n = 36). Children with developmental delays were more likely to display no reaction following a pain event, whereas children without delays cried more often. Further, children with developmental delays engaged in fewer help-seeking behaviors and were less likely to display a social response following a pain event than nondelayed children. CONCLUSIONS: Children with developmental delays appear to react in a different manner to pain events than nondelayed children do; we discuss a possible socio-communicative deficit.

GVHD dry eyes treated with autologous serum tears.

Two cases of GVHD with severe dry eyes are reported where conventional therapy failed to control ocular signs and symptoms. Autologous serum tears, however, resulted in a beneficial clinical effect with marked attenuation of the symptoms. This therapy proved to be safe during 10 months of treatment. Bone Marrow Transplantation (2000).

Infecçäo por Dirofilaria immitis em cäes de Maceió / Dirofilaria immitis infection in dogs from Maceió, Alagoas, Northeast region of Brazil

De 2.007 amostras de sangue examinadas de cäes da cidade de Maceió-AL, foram detectados 62 (3,1 por cento) animais positivos para a presença de microfilária (mf). Em 11 cäes, escolhidos aleatoriamente, foi colhido sangue venoso para a identificaçäo específica de Dirofilaria immitis. Para tal, foram utilizadas a motilidade, o tamanho, a morfologia das mf e a presença de antígenos solúveis do parasito, sendo encontrados cinco animais portadores de D. immitis. Mosquitos da espécies Culex quinquefasciatus foram alimentados com sangue de um cäo portador de D. immitis. O desenvolvimento de formas larvárias foi obsevado nos títulos de Malpighi, confirmando a ocorrência da dirofilariose canina por D. immitis na cidade de Maceió-AL

Identification of androgen, estrogen and progesterone receptor mRNAs in the eye.

PURPOSE: Previous research has demonstrated that sex steroids exert a significant influence on the structure and function of numerous ocular tissues. To begin to explore the underlying basis of this hormone action, we examined whether various anterior and posterior tissues of the eye contain androgen, estrogen and progesterone receptor mRNAs. METHODS: Tissue samples were obtained from adult male and female rats, rabbits and humans, processed for the isolation of total RNA and analyzed by RT-PCR, agarose gel electrophoresis and Southern blot hybridization. All PCR amplifications included positive and negative controls. RESULTS: Our findings showed that androgen, estrogen and/or progesterone receptor mRNAs are present in the lacrimal gland, lacrimal gland acinar epithelial cells, meibomian gland, lid, palpebral and bulbar conjunctivae, cornea, iris/ciliary body, lens, retina/uvea, retina/choroid and retinal pigment epithelial cells of rats, rabbits or humans. CONCLUSIONS: Our findings demonstrate that sex steroid receptor mRNAs exist in a variety of ocular tissues and suggest that these sites may represent target organs for androgens, estrogens and/or progestins.