Presynaptic α₂-adrenoceptors control the inhibitory action of presynaptic CB₁ cannabinoid receptors on prefrontocortical norepinephrine release in the rat

Endocannabinoids play a crucial neuromodulator role in both physiological and pathological states in various brain regions including the prefrontal cortex (PFC). We examined, whether presynaptic cannabinoid receptors are involved in the modulation of basal and electrical field stimulation-evoked [³H]norepinephrine ([³H]NE) release from rat PFC slices. WIN55,212-2, a nonselective CB₁ receptor (CB₁R) agonist, inhibited the electrical stimulation-evoked efflux of [³H]NE in a concentration-dependent fashion, which was antagonized by the CB₁R antagonist/inverse agonist, AM251 (1 μM). Idazoxan, a selective α₂-adrenoceptor antagonist, augmented the evoked [³H]NE release. In the presence of idazoxan, the effect of WIN55,212-2 was exacerbated or attenuated, depending on the applied concentration and stimulation frequency. Moreover their combined, but not individual application elicited a depressive-like phenomenon in the forced-swim test. These data were bolstered with fluorescent and confocal microscopy analysis, which revealed that CB₁R immunoreactivity co-localized with dopamine-β-hydroxylase positive (i.e. noradrenergic) fibers and the inhibitory α_2A adrenergic autoreceptors (α_2AR) in the PFC. Furthermore, idazoxan triggered a decrease in CB₁R density in the PFC, suggesting that high extracellular level of norepinephrine downregulates CB₁Rs.     

Risk of Low Energy Availability among Female and Male Elite Runners Competing at the 26th European Cross-Country Championships

Low energy availability (LEA) causes impaired physiological functioning. Cross-country running is a weight-sensitive sport, making athletes more prone to LEA. We aimed to estimate the prevalence of elite European cross-country athletes at risk of LEA using the LEA in Females Questionnaire (LEAF-Q) and to analyze demographic and physical characteristics that are associated with LEA. Athletes ≥ 18 years competing at the 26th European Cross-Country Championships (n = 602) were invited to complete a questionnaire (sociodemographic, training, anthropometric characteristics, and LEAF-Q). A total of 207 valid surveys were collected (83 females, 22.1 (4.0) years, and 124 males, 22.3 (4.1) years), and 16 surveys were excluded. A high prevalence of athletes at risk of LEA (64.3%) was observed, being higher in females than in males (79.5 and 54.0% respectively, p < 0.001). More than half of athletes (54.1%, n = 112) reported bowel movements once a week or more rarely, while 33 female athletes (41.3%) did not report normal menstruation. Overall, cross-country athletes are at high risk of LEA. Moreover, a high prevalence of gastrointestinal and menstrual impairments was reported. Hence, athletes should be followed by multidisciplinary teams to inform, prevent, and treat LEA and its effects.     

Bioequivalence study of two different film-coated tablet formulations of losartan-hydrochlorothiazide in healthy volunteers

The study was conducted in order to assess the bioequivalence of two film-coated formulations containing 100 mg of losartan (CAS 124750-99-8) and 12.5 mg of hydrochlorothiazide (CAS 58-93-5). Seventy-three healthy subjects were enrolled in a randomised, single-dose, open-label, two-way crossover study, with a minimum washout period of 7 days. A total of 21 blood samples were collected up to 36 h post-dosing. Losartan, losartan carboxy acid and hydrochlorothiazide levels were determined by liquid chromatography with tandem mass detection (lower limit of quantification: 1.01 ng/mL for hydrochlorothiazide, 2.02 ng/mL for losartan and 2.51 ng/mL for losartan carboxy acid). Pharmacokinetic parameters used for bioequivalence assessment (AUC(0-t) and Cmax as primary and AUC(0-inf) as secondary pharmacokinetic parameters) were determined from the losartan and hydrochlorothiazide concentration data using non-compartmental analysis. Data from losartan carboxy acid was reported and presented as supportive data. The 90% confidence intervals (obtained by ANOVA) for losartan were 97.05-118.48% for Cmax 100.76-106.10% for AUC(0-t) and 100.80-106.10% for AUC(0-inf) whereas for hydrochlorothiazide the 90% confidence intervals obtained were 103.94-115.33% for Cmax, 101.97-109.61% for AUC(0-t) and 101.77-109.02% for AUC(0-inf), and for losartan carboxy acid the intervals obtained were 98.31-107.82% for Cmax, 97.89-104.30% for AUC(0-t) and 98.06-104.30% for AUC(0-inf). All the 90% confidence intervals obtained for all the parameters assessed were within the predefined ranges (80-125%). Based on these results, it can be concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption.     

Comparative bioavailability/ bioequivalence of two different sertraline formulations: a randomised, 2-period x 2-sequence, crossover clinical trial in healthy volunteers

An open-label, randomised, crossover single dose study, using 2 periods x 2 sequences, with a minimum washout period of 4 weeks, was conducted in order to assess the comparative bioavailability of two formulations of sertraline hydrochloride (CAS 79617-96-2) 100 mg tablets. Plasma samples were obtained at intake (baseline) and at +1 h, +2 h, +3 h, +4 h, +5 h, +6 h, +7 h, +8 h, +9 h, +12 h, +24 h, +48 h, +72 h and +96 h post administration. Sertraline plasma concentrations were determined by high pressure liquid chromatography with tandem mass detection (HPLC-MS/MS) and the lower limit of quantification was set at 100.15 pg/mL. Pharmacokinetic parameters used for bioequivalence assessment (AUClast, AUCinf and Cmax) were determined by non-compartmental analysis. Classical 90 % confidence intervals (90CI) were calculated for the overall sample, and for males and females separately, and gender effects were investigated using an appropriate model. The results showed that overall classical 90CI were 84.55-100.32 % for Cmax 86.96-98.68 % for AUClast, and 86.79-98.93 for AUCinf, that is, they were all within the predefined ranges for bioequivalence acceptance. Separate gender analysis showed very similar results for males and females when analysed independently, and no gender effects were detected in bioequivalence analysis (p > 0.05). It may be therefore concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption.     

Rickettsiae and rickettsioses in Portugal

The only rickettsiae recorded in Portugal till now were Rickettsia conorii and Coxiella burnetii. Boutonneuse fever is one of the most important transmissible diseases in Portugal. Though the annual number of cases is not exactly known, it is estimated to be not far from 20,000 in some years. Q fever is the other rickettsiosis widely disseminated throughout the country. The serological prevalence and the incidence of those rickettsioses in Portugal are presented in this communication. In recent research in southern Portugal, about 4,000 adult ticks of nine species were screened by the haemocyte test for rickettsiae and rickettsia-like organisms (RLO). In addition to R. conorii three microscopically different RLO were observed. Two of them, i.e. ovoid and bacillary-like, were positive in the immunofluorescence test with spotted fever (R. conorii) antiserum. The first occurred mainly in Rhipicephalus sanguineus ticks, the second one also in other tick species. The latter agent was cultivated in half-engorged R. sanguineus females and in Vero cells. The third organism was found in R. sanguineus, where it exhibited a massive infestation in haemocytes resembling that seen in experimentally infected ticks with C. burnetii, but not being this agent. The investigation of the isolates and their identification and characterization are being continued.Presented at the 4th International Symposium on Rickettsiae and Rickettsial Diseases, Pietany, C.S.F.R., 1–6 October, 1990.     

Prevalence of anti BK virus antibody in Portugal and Norway

Specific IgG antibodies against BK virus measured by ELISA were used as a marker of previous infection. Results with sera from healthy people of different counties in Portugal were compared with previous findings in Norwegian sera. No significant difference between the prevalence and level of BKV IgG could be found between Portugal and Norway, and when comparing the different counties of Portugal. Thus, the way of transmission seemed to follow the same routes both in rural and urban counties in Portugal, and in Norway.     

Dhori virus induced lesions in mice

Dhori and Thogoto viruses are till now the only recognized tick-borne orthomyxoviruses. Like Thogoto virus, also Dhori is highly hepatotropic for laboratory mice; the lesions in several organs resemble those described for influenza virus.     

c-erbB-2 proto-oncogene expression and its relationship to survival in gastric carcinoma: an immunohistochemical study on archival material.

The c-erbB-2 proto-oncogene encodes a growth factor receptor which is over-expressed in a variety of human adenocarcinomas. Recent reports suggest that it may be of value in arriving at prognosis in breast and ovarian cancer. In this study, c-erbB-2 expression was investigated in 93 routinely processed cases of gastric carcinoma, using an immunohistochemical technique. c-erbB-2 membrane immunoreactivity was observed in 11% (10/93) of tumours, all of which were of the well differentiated intestinal type (p less than 0.01). Overall, patients with tumours expressing this proto-oncogene had a significantly improved prognosis (p less than 0.05). Within the group of intestinal-type tumours, those that were c-erbB-2-positive formed a distinct sub-population which had a better prognosis (p less than 0.02), suggesting possible differences in aetiology.