Effectiveness of historical smallpox vaccination against mpox clade II in men in Denmark, France, the Netherlands and Spain, 2022.

BackgroundIn 2022, a global monkeypox virus (MPXV) clade II epidemic occurred mainly among men who have sex with men. Until early 1980s, European smallpox vaccination programmes were part of worldwide smallpox eradication efforts. Having received smallpox vaccine > 20 years ago may provide some cross-protection against MPXV.AimTo assess the effectiveness of historical smallpox vaccination against laboratory-confirmed mpox in 2022 in Europe.MethodsEuropean countries with sufficient data on case vaccination status and historical smallpox vaccination coverage were included. We selected mpox cases born in these countries during the height of the national smallpox vaccination campaigns (latest 1971), male, with date of onset before 1 August 2022. We estimated vaccine effectiveness (VE) and corresponding 95% CI for each country using logistic regression as per the Farrington screening method. We calculated a pooled estimate using a random effects model.ResultsIn Denmark, France, the Netherlands and Spain, historical smallpox vaccination coverage was high (80-90%) until the end of the 1960s. VE estimates varied widely (40-80%, I2 = 82%), possibly reflecting different booster strategies. The pooled VE estimate was 70% (95% CI: 23-89%).ConclusionOur findings suggest residual cross-protection by historical smallpox vaccination against mpox caused by MPXV clade II in men with high uncertainty and heterogeneity. Individuals at high-risk of exposure should be offered mpox vaccination, following national recommendations, regardless of prior smallpox vaccine history, until further evidence becomes available. There is an urgent need to conduct similar studies in sub-Saharan countries currently affected by the MPXV clade I outbreak.

Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC).

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Determinants of Sporadic Shiga Toxin-Producing Escherichia coli (STEC) Infection in Denmark, 2018-2020: A Matched Case-Control Study.

Infections with Shiga toxin-producing Escherichia coli (STEC) are increasing in Denmark and elsewhere. STEC is also the most frequent cause of haemolytic uraemic syndrome (HUS) in Danish children. Most cases are considered sporadic, while approximately one-third can be attributed to a known source of infection. Hence, we examined sources of sporadic STEC infection in Denmark. From January 2018 to December 2020, we conducted a prospective nationwide case-control study among Danish adults and children. Cases with confirmed positive STEC infection were notified infections within the national laboratory surveillance system. Control persons were randomly selected from the Danish Civil Registration System, individually matched in age in 5-year bands and sex. Participants were invited by an electronic letter to complete either an adult or child questionnaire online. Univariate and adjusted matched odds ratios were computed for adults and children using conditional logistic regression. The study recruited 1583 STEC cases and 6228 controls. A total of 658 cases (42%) and 2155 controls (35%) were included in the analysis. Depending on age, univariate analysis adjusted for socio-demographic determinants showed that the consumption of boiled beef (mOR = 2.2, 95% confidence interval (CI): 1.6-3.1) and fried minced beef (mOR = 1.6, CI: 1.2-2.1), drinking raw (unpasteurized) milk (mOR = 11, CI 1.1-110), eating grilled food (mOR = 9.8, CI: 5.6-17) and having a household member using diapers (mOR = 2.1, CI: 1.4-3.2) were determinants of sporadic STEC infection. Further multivariate adjusted analysis resulted in the same determinants. This study confirms that beef is an overall important risk factor for STEC infection in Denmark. We also present evidence that a proportion of sporadic STEC infections in Denmark are determined by age-specific eating habits, environmental exposures and household structure, rather than being exclusively food-related. These findings are relevant for targeted public health actions and guidelines.

Molecular epidemiology of SARS-CoV-2 variants in circulation in the state of Maranhão, Brazil.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus belonging to the beta CoV genus, responsible for SARS in humans, which became known as COVID-19. The emergence of variants of this virus is related to the presence of cases of reinfection, reduced vaccine effectiveness and greater transmission of the virus. Objective: In this study, we evaluated the molecular epidemiology of SARS-CoV-2 lineages circulating in the state of Maranhão. This is a cross-sectional and retrospective epidemiological study of genomic surveillance of SARS-CoV-2. The study comprised of 338 genomes sequenced by the Next Generation Sequencing technique on Illumina's Miseq equipment, submitted to Global Initiative on Sharing Avian Influenza Data, 190 (56.2%) are from samples of female and 148 (43.8%) from male patients. Sequencing performed covered samples of patients aged between 1 and 108 years, with emphasis on the age groups from 30 to 39 years with 15.0% of sequenced genomes and 20 to 29 years with 12.4%. As for the distribution of sequenced genomes by health macro-regions, 285 (84.3%) are from cities in the northern macro-region. We evidenced the circulation of 29 lineages and sub-lineages, four of which belonging to the Delta variant (AY.43, AY.99.1, AY.99.2 and AY.101 responsible for 4.5% of the genomes) and the others belonging to the Omicron variant, with emphasis on: BA.1 and sub-lineages (42.8%); BA.4, BA.5 and sub-lineages (5.3% and 41.1%); the sub-lineages DL.1 and BQ.1 (5% and 2%). A strong genomic surveillance system allows the study of the natural history of the disease, when there is a resurgence of SARS-CoV-2 cases.

Mpox in Children and Adolescents during Multicountry Outbreak, 2022-2023.

The 2022-2023 mpox outbreak predominantly affected adult men; 1.3% of reported cases were in children and adolescents <18 years of age. Analysis of global surveillance data showed 1 hospital intensive care unit admission and 0 deaths in that age group. Transmission routes and clinical manifestations varied across age subgroups.

Description of the first global outbreak of mpox: an analysis of global surveillance data.

BACKGROUND: In May 2022, several countries with no history of sustained community transmission of mpox (formerly known as monkeypox) notified WHO of new mpox cases. These cases were soon followed by a large-scale outbreak, which unfolded across the world, driven by local, in-country transmission within previously unaffected countries. On July 23, 2022, WHO declared the outbreak a Public Health Emergency of International Concern. Here, we aim to describe the main epidemiological features of this outbreak, the largest reported to date. METHODS: In this analysis of global surveillance data we analysed data for all confirmed mpox cases reported by WHO Member States through the global surveillance system from Jan 1, 2022, to Jan 29, 2023. Data included daily aggregated numbers of mpox cases by country and a case reporting form (CRF) containing information on demographics, clinical presentation, epidemiological exposure factors, and laboratory testing. We used the data to (1) describe the key epidemiological and clinical features of cases; (2) analyse risk factors for hospitalisation (by multivariable mixed-effects binary logistic regression); and (3) retrospectively analyse transmission trends. Sequencing data from GISAID and GenBank were used to analyse monkeypox virus (MPXV) genetic diversity. FINDINGS: Data from 82 807 cases with submitted CRFs were included in the analysis. Cases were primarily due to clade IIb MPXV (mainly lineage B.1, followed by lineage A.2). The outbreak was driven by transmission among males (73 560 [96·4%] of 76 293 cases) who self-identify as men who have sex with men (25 938 [86·9%] of 29 854 cases). The most common reported route of transmission was sexual contact (14 941 [68·7%] of 21 749). 3927 (7·3%) of 54 117 cases were hospitalised, with increased odds for those aged younger than 5 years (adjusted odds ratio 2·12 [95% CI 1·32-3·40], p=0·0020), aged 65 years and older (1·54 [1·05-2·25], p=0·026), female cases (1·61 [1·35-1·91], p<0·0001), and for cases who are immunosuppressed either due to being HIV positive and immunosuppressed (2·00 [1·68-2·37], p<0·0001), or other immunocompromising conditions (3·47 [1·84-6·54], p=0·0001). INTERPRETATION: Continued global surveillance allowed WHO to monitor the epidemic, identify risk factors, and inform the public health response. The outbreak can be attributed to clade IIb MPXV spread by newly described modes of transmission. FUNDING: WHO Contingency Fund for Emergencies. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Portuguese public procurement data for construction (2015-2022).

The Architecture, Engineering and Construction (AEC) sector currently exhibits a significant scarcity of systematised information in databases (DB). This characteristic is a relevant obstacle to implementing new methodologies in the sector, which have proven highly successful in other industries. In addition, this scarcity also contrasts with the intrinsic workflow of the AEC sector, which generates a high volume of documentation throughout the construction process. To help solve this issue, the present work focuses on the systematisation of the data related to the contracting and public tendering procedure in Portugal, summarising the steps to obtain and process this information through the use of scraping algorithms, as well as the subsequential translation of the gathered data into English. The contracting and public tendering procedure is one of the most well-documented procedures at the national level, having all its data available as open-access. The resulting DB comprises 5214 unique contracts, characterised by 37 distinct properties. This paper identifies future development opportunities that can be supported by this DB, such as the application of descriptive statistical analysis techniques and/or Artificial Intelligence (AI) algorithms, namely, Machine Learning (ML) and Natural Language Processing (NLP), to improve construction tendering.

Dent's disease: An unusual cause of kidney failure.

Dent's disease is an X-linked recessive disease characterized by proximal tubulopathy with low-molecular weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and kidney failure. It is mainly caused by mutations in the CLCN5 or OCRL1 genes, and only ~ 250 families have been identified with these mutations. We present a 31-year-old male referred to a nephrology consultation due to elevated serum creatinine and a history of nephrolithiasis. Complementary evaluation revealed protein/creatinine ratio of 1.9 g/g and albumin/creatinine ratio of 0.5 g/g, hypercalciuria and medullary nephrocalcinosis. These findings raised the suspicion of Dent's disease, which was confirmed by genetic testing. A missense mutation in the CLCN5 gene (c.810C>G, p.(Ser270Arg)), not previously reported in populational databases, was identified. During the evaluation of the patient, it came to our attention that a first-degree male cousin was being followed in our kidney transplantation unit. Given the unknown etiology of his chronic kidney disease, genetic testing was performed, identifying the same mutation. This case highlights the importance of considering the diagnosis of Dent's disease in the setting of a male patient with chronic kidney disease of unknown etiology, low-molecular-weight proteinuria, hypercalciuria, and nephrocalcinosis. Despite progression to end-stage kidney failure in a significant portion of male patients, there are no reports of recurrence after kidney transplantation.

Effects of Combined Inorganic Nitrate and Nitrite Supplementation on Cardiorespiratory Fitness and Skeletal Muscle Oxidative Capacity in Type 2 Diabetes: A Pilot Randomized Controlled Trial.

Nitric oxide (NO) stimulates mitochondrial biogenesis in skeletal muscle. However, NO metabolism is disrupted in individuals with type 2 diabetes mellitus (T2DM) potentially contributing to their decreased cardiorespiratory fitness (i.e., VO2max) and skeletal muscle oxidative capacity. We used a randomized, double-blind, placebo-controlled, 8-week trial with beetroot juice containing nitrate (NO3−) and nitrite (NO2−) (250 mg and 20 mg/day) to test potential benefits on VO2max and skeletal muscle oxidative capacity in T2DM. T2DM (N = 36, Age = 59 ± 9 years; BMI = 31.9 ± 5.0 kg/m2) and age- and BMI-matched non-diabetic controls (N = 15, Age = 60 ± 9 years; BMI = 29.5 ± 4.6 kg/m2) were studied. Mitochondrial respiratory capacity was assessed in muscle biopsies from a subgroup of T2DM and controls (N = 19 and N = 10, respectively). At baseline, T2DM had higher plasma NO3− (100%; p < 0.001) and lower plasma NO2− levels (−46.8%; p < 0.0001) than controls. VO2max was lower in T2DM (−26.4%; p < 0.001), as was maximal carbohydrate- and fatty acid-supported oxygen consumption in permeabilized muscle fibers (−26.1% and −25.5%, respectively; p < 0.05). NO3−/NO2− supplementation increased VO2max (5.3%; p < 0.01). Further, circulating NO2−, but not NO3−, positively correlated with VO2max after supplementation (R2= 0.40; p < 0.05). Within the NO3−/NO2− group, 42% of subjects presented improvements in both carbohydrate- and fatty acid-supported oxygen consumption in skeletal muscle (vs. 0% in placebo; p < 0.05). VO2max improvements in these individuals tended to be larger than in the rest of the NO3−/NO2− group (1.21 ± 0.51 mL/(kg*min) vs. 0.31 ± 0.10 mL/(kg*min); p = 0.09). NO3−/NO2− supplementation increases VO2max in T2DM individuals and improvements in skeletal muscle oxidative capacity appear to occur in those with more pronounced increases in VO2max.

Effects of Capacitive-Resistive Electric Transfer on Sports Performance in Paralympic Swimmers: A Stopped Randomized Clinical Trial.

Throughout history a variety of therapeutic tools have been studied as possible enhancers of sports activities. This study proposes the use of Capacitive-Resistive Electric Transfer (CRET) as a performance booster to paralympic athletes, specifically those belonging to the Spanish Paralympic swimming committee. The study was a randomized, single-blind, and observer-blind, crossover clinical trial. Six athletes were randomly assigned to three groups: one treated with CRET (A); a placebo group (B) and a control group (C). The CRET group attended a twenty-minute session before being subjected to pool trials at distances of 50 and 100 m at maximum performance. Measurements were in two dimensions: time in seconds and the Borg scale for perceived exertion. Comparisons between groups were made with respect to distance and the main variables. In the case of perceived exertion, no significant changes were observed in any of the distances; however, in the case of the time variable, a significant difference was observed between Group A vs. Personal Record at 100 m distance (76.3 ± 6.8 vs. 68.4 ± 3.3). The proposed protocol and level of hyperthermia applied suggest refusal of CRET use for the 100-m distance a few minutes before sports practice. Our analysis suggests the need to modify the presented protocol. ClinicalTrials.gov identifier under NCT number: NCT04336007.

A large multi-country outbreak of monkeypox across 41 countries in the WHO European Region, 7 March to 23 August 2022.

Following the report of a non-travel-associated cluster of monkeypox cases by the United Kingdom in May 2022, 41 countries across the WHO European Region have reported 21,098 cases and two deaths by 23 August 2022. Nowcasting suggests a plateauing in case notifications. Most cases (97%) are MSM, with atypical rash-illness presentation. Spread is mainly through close contact during sexual activities. Few cases are reported among women and children. Targeted interventions of at-risk groups are needed to stop further transmission.

Effects of Baru Almond Oil (Dipteryx alata Vog.) Treatment on Thrombotic Processes, Platelet Aggregation, and Vascular Function in Aorta Arteries.

Background: This study assessed the effects of Baru (Dipteryx alata Vog.) almond oil supplementation on vascular function, platelet aggregation, and thrombus formation in aorta arteries of Wistar rats. Methods: Male Wistar rats were allocated into three groups. The control group (n = 6), a Baru group receiving Baru almond oil at 7.2 mL/kg/day (BG 7.2 mL/kg, n = 6), and (iii) a Baru group receiving Baru almond oil at 14.4 mL/kg/day (BG 14.4 mL/kg, n = 6). Baru oil was administered for ten days. Platelet aggregation, thrombus formation, vascular function, and reactive oxygen species production were evaluated at the end of treatment. Results: Baru oil supplementation reduced platelet aggregation (p < 0.05) and the production of the superoxide anion radical in platelets (p < 0.05). Additionally, Baru oil supplementation exerted an antithrombotic effect (p < 0.05) and improved the vascular function of aorta arteries (p < 0.05). Conclusion: The findings showed that Baru oil reduced platelet aggregation, reactive oxygen species production, and improved vascular function, suggesting it to be a functional oil with great potential to act as a novel product for preventing and treating cardiovascular disease.

Incubation Period, Spore Shedding Duration, and Symptoms of Enterocytozoon bieneusi Genotype C Infection in a Foodborne Outbreak in Denmark, 2020.

BACKGROUND: Microsporidia are rarely reported to cause outbreaks of diarrhea. We describe a foodborne outbreak of microsporidiosis from a workplace canteen in November 2020 in Denmark. METHODS: A probable case was defined as any person using the canteen between 4 November and 13 December 2020, reporting at least one gastrointestinal symptom, whereas a confirmed case also had an Enterocytozoon bieneusi positive stool sample. A web-based questionnaire was used to collect clinical, epidemiological, and food exposure data. We performed a retrospective cohort study and tested stool samples from affected individuals for bacterial, viral, and parasitic pathogens, including E. bieneusi. RESULTS: Altogether, 195 individuals completed the questionnaire. We identified 52 cases (65% male; median age 45 years [range 25-65]). Diarrhea (90%), fatigue (83%), and abdominal pain (79%) were the most commonly reported symptoms. Eight cases were laboratory-confirmed and had E. bieneusi genotype C. The incubation period was between 5 and 12 days, and polymerase chain reaction (PCR)-detectable spore shedding occurred up to 43 days after symptom onset. Disease was associated with consuming food from the workplace canteen on 4 November 2020 (relative risk [RR[, 2.8 [95% confidence interval [CI]: 1.4 - 5.4]) and lunchboxes containing open sandwiches (RR, 3.2 [95% CI: 1.4 - 7.2]) served that day. CONCLUSIONS: This is the second documented foodborne outbreak of E. bieneusi genotype C-associated diarrhea worldwide. Epidemiological findings advocated an open sandwiches lunchbox from 4 November 2020, as a likely source. E. bieneusi may be an under-reported cause of outbreaks of diarrhea, and testing for it might be useful in foodborne outbreak investigations.

Application of Capacitive-Resistive Electric Transfer in Physiotherapeutic Clinical Practice and Sports.

Diathermy techniques embody an oscillating electrical current passaging through the body tissues generating therapeutic heat; use of this technique in the physiotherapy field has been introduced recently, and because there is scarce information, the following review is proposed, aiming to explore the available evidence on applying CRET in physiotherapy clinical practice and sports. A systematic search was led through a keyword search on PubMed, MedLine, DialNet, Scopus, PEDro, Web of Science and Clinicaltrials databases. Including randomised controlled trials and quasi-experimental studies, which applied radiofrequency diathermy in sports and physiotherapy fields, without any restrictions on dates, published in Spanish, English, Portuguese or Italian. Data extraction was conducted through the Cochrane data extraction form and presented in tabular format; 30 articles were included for analysis, and assessment of methodological quality was made through the PEDro scale with a "Good/Fair" general quality score. The nature of existing articles does not allow a quantitative analysis. Conclusion: identified fields of applications were musculoskeletal physiotherapy, treatment of pelvic floor and sexual dysfunctions, as well as dermato-functional physiotherapy and sports, evidencing an increase of skin temperature, enhanced skin and muscle blood perfusion, as well as reporting an increase in oxyhaemoglobin. Further research is needed. Prospero registration number: CRD42020215592.

Sexuality Attitudes and Beliefs Survey (SABS): Validation of the Instrument for the Spanish Nursing Students.

Patient sexuality is a fundamental subject in nursing student's education. However, beliefs about patient sexuality can influence the care offered. The aim of this psychometric study was to describe the validation process and the psychometrics properties of the Sexuality Attitudes and Beliefs Survey (SABS) for Spanish nursing students. The convenience sample was 283 nursing students from a state university in Spain. Participants ranged from 18 to 30 years (M = 19.66; SD = 1.85). Data collection happened in 2019-2020. The translation, back translation and adaptation to Spanish was discussed and refined, ensuring the semantic, idiomatic and conceptual meaning of the items. The psychometric properties were assessed through analysis of validity and reliability. The Cronbach's alpha for the final version of 12 items was 0.65. Although it has low reliability, the Spanish version of the SABS seems to be a valid and useful tool to measure nursing students' beliefs about patient sexuality. In addition, it can be a resource for the assessment of the ability of Spanish nursing faculty in engaging topics involving the student's vision of patient sexuality.

Novel SLC12A3 mutation in Gitelman syndrome.

Gitelman syndrome (GS) is an autosomal recessive disease characterised by the presence of hypokalaemic metabolic alkalosis with hypomagnesaemia and hypocalciuria. The prevalence of this disease is 1-10/40 000. GS is usually associated with mild and non-specific symptoms and many patients are only diagnosed in adulthood. The disease is caused by mutations in the SLC12A3 gene. We present the case of a 49-year-old man referred to a nephrology appointment due to persistent hypokalaemia and hypomagnesaemia. Complementary evaluation revealed hypokalaemia, hypomagnesaemia, metabolic alkalosis, hyperreninaemia, increased chloride and sodium urinary excretion, and reduced urinary calcium excretion. Renal function, remainder serum and urinary ionogram, and renal ultrasound were normal. A diagnosis of GS was established and confirmed with genetic testing which revealed a novel mutation in SLC12A3 (c.1072del, p.(Ala358Profs*12)). This novel mutation extends the spectrum of known SLC12A3 gene mutations and further supports the allelic heterogeneity of GS.

Virtual Screening of Natural Products Database.

Constant research on natural products has generated, over time, a large number of compounds with the potential to be evaluated in several biological tests and subsequently have been cataloged in databases that allow other researchers to perform virtual screenings of activity in various biological systems. This considerably reduces the time for the development of new drugs. This review describes the main databases of natural products available for searching bioactive compounds. It also describes the main features of virtual screening strategies for the identification of molecules with the potential to be used as new drugs. In addition, a search was made in the Web of Science database, using the search term "Virtual screening of natural products databases" from 2003 to 2018. The search criterion resulted in 230 articles, which had their abstracts evaluated with pertinence to the criteria required for this work, which are: a) be a research article; b) performing a virtual screening on databases of natural products or containing natural products; and c) works that identified drug candidate molecules. Based on these criteria, the bibliographic review on the topic was excluded. After this analysis, 104 works were selected for this review. We selected relevant papers describing the potential drug candidates that were distributed in 15 classes, of which the anticancer, antibacterial and anti-inflammatory hits were the most abundant. The works showing efforts to search for new molecules against various other diseases in distinct biological systems were also described. In this way, this work shows an overview of several methodologies and we hope they can help and inspire the development of new research to improve people's quality of life.

Virtual screening and assessment of anticancer potential of selenium-based compounds against HL-60 and MCF7 cells.

Aim: Selenium-based compounds have antitumor potential. We used a ligand-based virtual screening analysis to identify selenoglycolicamides with potential antitumor activity. Results & Conclusion: Compounds 3, 6, 7 and 8 were selected for in vitro cytotoxicity tests against various cell lines, according to spectrophotometry results. Compound 3 presented the best cytotoxicity results against a promyelocytic leukemia line (HL-60) and was able to induce cell death at a frequency similar to that observed for doxorubicin. The docking study showed that compound 3 has good interaction energies with the targets caspase-3, 7 and 8, which are components of the apoptotic pathway. These results suggested that selenium has significant pharmacological potential for the selective targeting of tumor cells, inducing molecular and cellular events that culminate in tumor cell death.

Effect of indole alkaloids from roots of Rauvolfia ligustrina in the noradrenergic neurotransmission.

The new glucosyl sarpagan alkaloid designated as 21(R*)-(O-ß-glucosyl)-hydroxy-sarpagan-17-oic acid, along with eleven known alkaloids were isolated from a soluble alkaloidal fraction from the ethanol extract of Rauvolfia ligustrina. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiment, GIAO 13C NMR calculations, and comparison with literature data. All the isolated alkaloids were screened by their neuroinhibitory effects using the electrically stimulated mice vas deferens bioassay. Compounds 1, 2 and 9 presented a potent inhibitory effect in the neurotransmission while 3 and 11 showed an acute neuroexcitatory effect. Compound 10 exhibited a very effective post-synaptic inhibitory activity.