Helena Maria Calil

Clinical diagnostic criteria for premenstrual syndrome and guidelines for their quantification for research studies

Premenstrual syndrome (PMS) encompasses a variety of symptoms appearing during the luteal phase of the menstrual cycle. Although PMS is widely recognized, the etiology remains unclear and it lacks definitive, universally accepted diagnostic criteria. To address these issues an international multidisciplinary group of experts evaluated the current definitions and diagnostic criteria of PMS and premenstrual dysphoric disorder (PMDD). Following extensive correspondence, a consensus meeting was held with the aim of producing updated diagnostic criteria for PMS and guidelines for clinical and research applications. This report presents the conclusions and recommendations of the group. It is hoped that the criteria proposed by the group will become widely accepted and eventually be incorporated into the next edition of the World Health Organizations International Classification of Diseases (ICD-11). It is also hoped that the proposed guidelines for quantification of criteria will be used by clinicians and investigators to facilitate diagnostic uniformity in the field as well as adequate treatment modalities when warranted.

Pharmacology of lemongrass (Cymbopogon citratus Stapf). III. Assessment of eventual toxic, hypnotic and anxiolytic effects on humans☆

A herbal tea (called an abafado in Brazil) prepared from the dried leaves of lemongrass was administered to healthy volunteers. Following a single dose or 2 weeks of daily oral administration, the abafado produced no changes in serum glucose, urea, creatinine, cholesterol, triglycerides, lipids, total bilirubin, indirect bilirubin, GOT, GPT, alkaline phosphatase, total protein, albumin, LDH and CPK. Urine analysis (proteins, glucose, ketones, bilirubins, occult blood and urobilinogen) as well as EEG and EKG showed no abnormalities. There were slight elevations of direct bilirubin and of amylase in some of the volunteers, but without any clinical manifestation. These results taken together indicate that lemongrass as used in Brazilian folk medicine is not toxic for humans. The eventual hypnotic effect of lemongrass was investigated in 50 volunteers who ingested samples of lemongrass and a placebo under double-blind conditions. The parameters (i.e. sleep induction, sleep quality, dream recall and rewakening) did not show any effect of lemongrass as compared to the placebo. Eighteen subjects with high scores of trait-anxiety were submitted to an anxiety-inducing test following taking lemongrass or placebo under double-blind conditions. Their anxiety levels were similar, indicating that the abafado of the plant does not have anxiolytic properties. It is concluded that lemongrass, one of the most popular Brazilian herbal medicines, used for its alleged CNS-depressant effects, is atoxic but lacks hypnotic or anxiolytic properties.

Depressão: o mesmo acometimento para homens e mulheres?

The authors perform a narrative review of literature. They describe epidemiological, biological, social, and psychological aspects linked to gender differences in depressions. There are several differences between sexes regarding depressive manifestations such as the prevalence proportion of two women to one man, thoroughly described in the literature and result of well conducted trials. However, a number of uncertainties remain in basic aspects of this subject.The authors perform a narrative review of literature. They describe epidemiological, biological, social, and psychological aspects linked to gender differences in depressions. There are several differences between sexes regarding depressive manifestations such as the prevalence proportion of two women to one man, thoroughly described in the literature and result of well conducted trials. However, a number of uncertainties remain in basic aspects of this subject.

Serum levels of neuroleptics measured by dopamine radioreceptor assay and some clinical observations

A new dopamine radioreceptor assay was used to measure serum concentrations of neuroleptics during treatment of 58 patients. Results of this assay are expressed as chlorpromazine equivalents. Serum concentrations varied with different drugs, with extremely high levels in patients receiving thioridazine or mesoridazine. No detectable serum levels were found in 11 patients, probably either due to low drug doses or noncompliance in taking medication. Best results with the assay were obtained in the 22 patients treated with haloperidol. Serum concentrations of haloperidol were correlated with dose and were related to the Brief Psychiatric Rating Scale (BPRS) total pathology score, as well as to BPRS factor scores for thinking disturbance and paranoid disturbance. Serum concentrations of haloperidol were not different among patients with or without the presence of extrapyramidal symptoms or among patients receiving or not receiving concurrent antiparkinson medication.

Inflammatory aspects of depression.

A bidirectional relation between depression and natural immunity has been identified: depressive episodes are associated to a relative immunodeficiency, conversely inflammatory activity has been implicated in the development of depressive symptoms and in the pathophysiology of depression. Depression has been associated with a decrease in the number and activity of NK lymphocytes and hence patients with depression may show immunodeficiency towards intracellular microorganisms and tumors. Paradoxically, depression is sometimes accompanied by an inflammatory state, developed from the peripheral stimuli (atopy) or central stimuli (chronic stress) and mediated by proinflammatory cytokines (IL-6, TNF and IL-1). These cytokines can play a role in the pathophysiology of depression and of various diseases, supporting the hypothesis that many chronic diseases are individual manifestations of a common proinflammatory denominator.

Involvement of the opioid system in the development and expression of sensitization to the locomotor-activating effect of ethanol

Previous studies have shown that pretreatment with naloxone (Nlx), an opiate antagonist, attenuates the stimulating effect of ethanol. The purpose of the present study was to determine the influence of Nlx on the development and expression of the sensitization to ethanol. Initially, effects of different doses of Nlx on the response to a low dose of ethanol (2.0 g/kg) were assessed. Nlx (1.0 and 3.0 mg/kg i.p.) decreased the stimulating effect of ethanol. Groups of mice were treated with saline or Nlx (1.0 mg/kg i.p.) plus saline or ethanol (2.0 g/kg i.p.) during 21 d. On day 25 of treatment all animals received an ethanol challenge (2.0 g/kg i.p.). It significantly increased the locomotor activity of mice that had received chronic ethanol (2.0 g/kg) once daily as compared to those that had received saline. Chronic administration of Nlx (1.0 mg/kg i.p.), during the same period of time, did not change the locomotor activity of the mice. However, the group concomitantly treated with Nlx+ethanol did not develop sensitization to the locomotor-activating effect of ethanol. Another experiment was carried out to determine the effects of Nlx on the expression of sensitization to ethanol. Acute pretreatment with Nlx did not change the response of the mice that had developed sensitization to ethanol. These data show Nlxs prevention of the development of ethanol-induced sensitization but not of its expression, suggesting an important role of the opioid neurotransmitter systems modulating the development of sensitization to the locomotor-activating effect of ethanol.

Acute effects of low doses of melatonin on the sleep of young healthy subjects

This study was undertaken to evaluate the acute effects of single low doses of melatonin given to healthy volunteers in the evening. Six healthy male volunteers (age range 22–24 years) participated in this study, after signing an informed consent form. They received in a double‐blind fashion placebo or 0.3 or 1.0 mg melatonin at three fixed times: 18:00, 20:00, and 21:00 hr. Polysomnographic recordings began immediately thereafter, with their being allowed to sleep. Prior to each experimental session and in the following morning, subjects completed a sleep quality questionnaire, the Profile of Mood States, the Stanford Sleepiness Scale, and underwent a visual reaction test. Significant decrease on sleep latencies was found following melatonin treatment at 18:00 and 20:00 hr. In addition, melatonin tended to improve sleep efficiency and to reduce intermittent wakefulness. However, at 21:00 hr, 0.3 mg melatonin increased latency to sleep onset and 1.0 mg melatonin had no effect on sleep variables. Furthermore, melatonin given at different times did not alter subjective sleepiness, mood, and reaction time in the following morning. The results from the present study support the notion that administration of low doses of melatonin, mimicking the nocturnal physiological concentration of this hormone may exert immediate sleep‐inducing effects.

Seasonal variation of suicide in Brazil

Most of what is known about the seasonal variation in suicide rate originates from studies conducted in the northern hemisphere; very few studies have been done in the southern hemisphere. The purpose of the present study was to explore the possibility that in Brazil, the seasonal variation of suicides is a function of photoperiod. This was accomplished by analyzing monthly suicide data for a 12 yr period (1979 to 1990), within latitudes ranging from 2°N to 33°S. Single cosinor analyses with periods of 12 or 6 months were applied to time series of monthly total and suicidal deaths, separated by gender and state. Significant spring or early summer peaks of suicide were found only in the south of Brazil for both men and women, except for the latter in one state. These peaks did not coincide with those found for total deaths, which occurred in the autumn or winter in all areas. No significant six‐month period was found. In the present study, the chance of a suicide was typically 10–17% higher during the peak period than during the other months of the year. Although this moderate seasonal effect might not be sufficient to justify planning large scale prophylactic interventions, those dealing with patients who have suicide ideation should be aware of this high risk time.

Hormonal responses to zimelidine and desipramine in depressed patients

Plasma prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and cortisol were repeatedly measured during the morning over a 4-hour period in patients who received single or chronic doses of desipramine (DMI) or zimelidine (ZIM). Preclinical studies had suggested that DMI, an uptake inhibitor specific for norepinephrine, would have different effects than ZIM, a selective serotinin uptake inhibitor. The GH response to DMI was blunted in the depressed patients. Neither DMI nor ZIM produced changes in LH or cortisol. DMI acutely increased plasma PRL, whereas ZIM had an effect only after chronic pretreatment. Chronic DMI but not ZIM increased baseline PRL. The patterns and magnitude of responses raise questions concerning the role of serotonin and norepinephrine in PRL release in man and the applicability of current preclinical models.

Ethanol-induced sensitization depends preferentially on D1 rather than D2 dopamine receptors

Behavioral sensitization, defined as a progressive increase in the locomotor stimulant effects elicited by repeated exposure to drugs of abuse, has been used as an animal model for drug craving in humans. The mesoaccumbens dopaminergic system has been proposed to be critically involved in this phenomenon; however, few studies have been designed to systematically investigate the effects of dopaminergic antagonists on development and expression of behavioral sensitization to ethanol in Swiss mice. We first tested the effects of D(1) antagonist SCH-23390 (0-0.03 mg/kg) or D(2) antagonist Sulpiride (0-30 mg/kg) on the locomotor responses to an acute injection of ethanol (2.0 g/kg). Results showed that all tested doses of the antagonists were effective in blocking ethanols stimulant effects. In another set of experiments, mice were pretreated intraperitoneally with SCH-23390 (0.01 mg/kg) or Sulpiride (10 mg/kg) 30 min before saline or ethanol injection, for 21 days. Locomotor activity was measured weekly for 20 min. Four days following this pretreatment, all mice were challenged with ethanol. Both antagonists attenuated the development of ethanol sensitization, but only SCH-23390 blocked the expression of ethanol sensitization according to this protocol. When we tested a single dose (30 min before tests) of either antagonist in mice treated chronically with ethanol, both antagonists attenuated ethanol-induced effects. The present findings demonstrate that the concomitant administration of ethanol with D(1) but not D(2) antagonist prevented the expression of ethanol sensitization, suggesting that the neuroadaptations underlying ethanol behavioral sensitization depend preferentially on D(1) receptor actions.