Vaginal neutrophils eliminate sperm by trogocytosis.

STUDY QUESTION: What is the vaginal polymorphonuclear (PMN) spermicidal mechanism to reduce the excess of sperm? SUMMARY ANSWER: We show that PMNs are very efficient at killing sperm by a trogocytosis-dependent spermicidal activity independent of neutrophil extracellular traps (NETs). WHAT IS KNOWN ALREADY: Trogocytosis has been described as an active membrane exchange between immune cells with a regulatory purpose. Recently, trogocytosis has been reported as a mechanism which PMNs use to kill tumour cells or Trichomonas vaginalis. STUDY DESIGN, SIZE, DURATION: We used in vivo murine models and human ex vivo sperm and PMNs to investigate the early PMN-sperm response. PARTICIPANTS/MATERIALS, SETTING, METHODS: We set up a live/dead sperm detection system in the presence of PMNs to investigate in vivo and ex vivo PMN-spermicidal activity by confocal microscopy, flow cytometry and computer-assisted sperm analysis (SCA). MAIN RESULTS AND THE ROLE OF CHANCE: We revealed that PMNs are highly efficient at killing sperm by way of a NETs-independent, contact-dependent and serine proteases-dependent engulfment mechanism. PMNs 'bite' sperm and quickly reduce sperm motility (within 5 min) and viability (within 20 min) after contact. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was conducted using murine models and healthy human blood PMNs; whether it is relevant to human vaginal PMNs or to cases of infertility is unknown. WIDER IMPLICATIONS OF THE FINDINGS: Vaginal PMNs attack and immobilize excess sperm in the vagina by trogocytosis because sperm are exogenous and may carry pathogens. Furthermore, this mechanism of sperm regulation has low mucosal impact and avoids an exacerbated inflammatory response that could lead to mucosal damage or infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was partially supported by Ministry of Economy and Competitiveness ISCIII-FIS grants, PI16/00050, and PI19/00078, co-financed by ERDF (FEDER) Funds from the European Commission, 'A way of making Europe' and IiSGM intramural grant II-PI-MRC-2017. M.R. holds a Miguel Servet II contract (CPII14/00009). M.C.L. holds IiSGM intramural contract. There are no competing interests.

Needs and its relation to symptom dimensions in a sample of outpatients with schizophrenia.

OBJECTIVE: To analyse the association between symptom dimensions in schizophrenia and number and type of met and unmet needs. METHOD: A sample of 231 outpatients randomly selected from a register that included all patients treated in 5 mental health care centres (MHCC) was evaluated. Assessment instruments included the Camberwell Assessment of Needs (CAN) questionnaire and the PANSS. RESULTS: Number of needs are related to overall severity of psychopathology. Patients with more symptoms have more total needs (p < 0.001) and unmet needs (p < 0.001). A multiple lineal regression model showed that the disorganized and excited dimensions of the PANSS are the most important components for explaining the variance of number of needs. Type of needs is related to subtypes of schizophrenia, specially with disorganized and excited symptoms. CONCLUSION: Psychosocial needs are related to schizophrenia subtypes. Patients with more needs are those with more disorganized and excitatory symptoms.

Administration of transforming growth factor-alpha reduces infarct volume after transient focal cerebral ischemia in the rat.

Growth factors promote cell growth and survival and protect the brain from developing injury after ischemia. In this article, the authors examined whether transforming growth factor-alpha (TGF-alpha) was protective in transient focal ischemia and whether alteration of cerebral circulation was involved. Rats received intraventricular TGF-alpha (50 ng, either split into 2 doses given 30 minutes before and 30 minutes after middle cerebral artery occlusion (MCAO), or 1 dose given 30 minutes after MCAO) or vehicle. Rats were subjected to 1-hour intraluminal MCAO and cerebral blood flow was recorded continuously by laser-Doppler flowmetry. Infarct volume was measured 1 and 4 days later. The effects of TGF-alpha on arterial tone were assessed in isolated rabbit basilar and common carotid arteries. Transforming growth factor-alpha before and after ischemia reduced infarct volume by 70% at 1 day and 50% at 4 days. Transforming growth factor-alpha given only after ischemia also did reduce infarct volume by 70% at 1 day and 80% at 4 days. The protective effect was more marked in cortex than in striatum. Transforming growth factor-alpha did not change cortical microvascular perfusion and did not modify arterial passive tone nor agonist-induced active tone. It can be concluded that TGF-alpha reduces infarct volume, even when the factor is exclusively administered at reperfusion, and that this effect is not mediated by changes in microvascular perfusion or cerebral arteries. It is therefore suggested that TGF-alpha has a protective effect against neuronal cell death after transient focal ischemia.

Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca(2+) entry inhibition.

Estrogens account for gender differences in the incidence and outcome of stroke, but it remains unclear to what extent neuroprotective effects of estrogens are because of parenchymal or vascular actions. Because reproductive steroids have vasoactive properties, the authors assessed the effects and mechanisms of action of 17-beta-estradiol in rabbit isolated basilar artery. Cumulative doses of 17-beta-estradiol (0.3 micromol/L to 0.1 mmol/L) induced concentration-dependent relaxation that was larger in basilar than carotid artery, in male than female basilar artery, and in KCl-precontracted than UTP-precontracted male basilar artery. Endothelium removal did not modify relaxation induced by 17-beta-estradiol in basilar artery, whereas relaxation induced by acetylcholine (1 nmol/L to 0.1 mmol/L) was almost abolished. Neither the estrogen receptor antagonist ICI 182,780 (1 micromol/L), nor the protein synthesis inhibitor cycloheximide (1 micromol/L) affected 17-beta-estradiol-induced relaxations. Relaxations induced by the K(+) channel openers NS1619 and pinacidil in the same concentration range were greater and lower, respectively, when compared with relaxation to 17-beta-estradiol, which was not significantly modified by incubation with the K(+) channel blockers charybdotoxin (1 nmol/L and 0.1 micromol/L) or glibenclamide (10 nmol/L and 1 micromol/L). Preincubation with 17-beta-estradiol (3 to 100 micromol/L) produced concentration-dependent inhibition of CaCl(2)-induced contraction, with less potency than the Ca(2+) entry blocker nicardipine (0.01 to 10 nmol/L). The authors conclude that 17-beta-estradiol induces endothelium-independent relaxation of cerebral arteries with tissue and gender selectivity. The relaxant effect is because of inhibition of extracellular Ca(2+) influx to vascular smooth muscle, but activation of estrogen receptors, protein synthesis, or K(+) efflux are not involved. Relatively high pharmacologic concentrations of 17-beta-estradiol causing relaxation preclude acute vascular effects of physiologic circulating levels on the cerebral circulation.

[Warm air convection system and heat loss during vascular surgery]. / Sistema convectivo de aire caliente y pérdida de calor durante la cirugía vascular.

OBJECTIVES: To assess the efficacy of a warm air convection (WAC) system to supplement the usual physical means (electric blanket, warm i.v. fluids and covering of exposed surfaces) for preventing an correcting hypothermia during surgery in 2 patient groups scheduled for vascular surgery. PATIENTS AND METHODS: We studied 70 consecutive patients scheduled for vascular surgery. Group I: a WAC system, in addition to the usual methods, was used to attempt to maintain normal body temperatures in 35 consecutive patients. Fifteen were undergoing aortic surgery (group Ia) and 20 were undergoing revascularization of the lower extremities (group Ib). Group II: only the usual physical methods were used to maintain normal temperature in the remaining 35 patients, 15 of whom required aortic surgery (group IIa) and 20 of whom were undergoing revascularization of the lower extremities (group IIb). Type of anesthesia and monitoring were the same in all cases. Esophageal temperature (ET) and room temperatures were recorded at baseline and every 30 min until the end of surgery. ET was not allowed to fall below 35 degrees C in any patient and WAC was provided to patients in group II if they required it. RESULTS: All patients in group II experienced a gradual decrease in ET, which became significant 30 min after start of surgery in group IIa and 60 min after start of surgery in group IIb. Temperature was stable during surgery in all patients in group I. All patients with ET of 35 degrees C in group II experienced a rise in temperature, which was significant after 60 min. when WAC was used. CONCLUSIONS: In vascular surgery, whether aortic or peripheral, patient temperature fell in spite of use of the usual physical methods for warming. Adding WAC for upper body warming prevented loss of heat. The WAC system was also effective for patients who needed to be rewarmed.

Prevalence of hepatitis B infection in long-stay mentally handicapped adults.

The objective was to determine the prevalence of hepatitis B virus (HBV) infection in long-stay institutionalized mentally handicapped adults and to develop a vaccination programme for them. The study was carried out in 1994. The subjects were 171 mentally handicapped adults aged 37-76 (median age 56) with a median hospital stay of 30 years (range 6-47). Markers for infection were determined using ELISA. Seronegative patients were vaccinated using the standard schedule, and the titre of antiHBs reached was determined later. The prevalence of seropositive subjects was 81.3%. Seropositive subjects had a longer hospital stay (median stay of 32 years, range: 15-47) than seronegative ones (median stay of 15 years, range: 6-33). A total of 43.3% of the vaccinated subjects developed antiHBs antibodies (GMT: 135 IU/l). The high prevalence of HBV exposure is probably a legacy of a past era which is reflected in patients with prolonged institutionalisation in a closed regime. The need for immediate vaccination of mentally handicapped subjects is of the utmost importance, as it has been shown that the response to the vaccine worsens with age.

Chemotherapy of advanced gastric carcinoma (stage IV): a randomized study of FAM versus 5-FU plus BCNU.

Forty-six patients with advanced gastric carcinoma (Stage IV) were evaluated in a prospective randomized comparison of two chemotherapy regimens (FAM versus 5-FU plus BCNU) to identify therapeutic activity. Treatment groups were well balanced with respect to known prognostic factors. Thirty-three patients had measurable disease and thirteen had only microscopic residual disease in the resection margins. The overall median survival of the entire group was 13.2 months. Two (6%) patients with measurable disease reached complete response (CR), 1 (3%) partial response (PR), 12 (36%) had stable disease (SD) and 18 (56%) had progressive disease (PD). The responders had not reached the median survival yet, the patients with SD had a median survival of 14.7 months and the PD 9.5 months. In the FAM arm there were 3 (18%) responders (2 CR and 1 PR), 7 (41%) SD and 7 (41%) PD, versus O responders, 5 (31%) SD and 11 (69%) PD in the 5-FU plus BCNU arm. In the FAM arm the median survival was 15.7 months versus 9.9 months in the other therapeutic arm. The statistical analysis indicated that survival associated with FAM regimen was superior to that reached with the 5-FU plus BCNU regimen. Thirteen patients with unmeasurable disease had a median survival of 15.9 months.

Comparison of genotypic and phenotypic techniques for assessing the variability of the fungus Epicoccum nigrum.

AIMS: The diversity within a collection of worldwide isolates of Epicoccum nigrum has been studied using several phenotypic approaches. In addition, the abilities of phenotypic and genotypic techniques for the differentiation of a set of isolates are compared. METHODS AND RESULTS: The methodology used include the study of isozymes (acetyl esterase and alkaline phosphatase), HPLC profile of metabolites and antibiotic activities against a panel of bacteria, yeasts and filamentous fungi, and cytotoxicity against three mammalian cell lines. Two procedures for assessing the relationships within a collection of isolates, using a combination of the techniques, were evaluated, comparing the advantages and disadvantages of each method. CONCLUSIONS: The results showed that each individual technique allows differentiation of the isolates studied to some degree and that the information provided by each technique could be considered as complementary. Genotypic techniques were more powerful than the phenotypic ones to discriminate among the strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This work evaluates the predictive value of several phenotypic techniques on a collection of fungal isolates, and compares the results obtained with genotypic techniques performed on the same strains.

Screening of basidiomycetes for antimicrobial activities.

As a part of a screening programme developed to evaluate the antimicrobial activity of basidiomycetes, 317 isolates representing 204 species collected in Spain were screened against a range of human clinical pathogens and laboratory controls. Extracts from 45% of the isolates, representing 109 species, showed antimicrobial activity. Antibacterial activity was more pronounced than antifungal activity. The proportion of extracts from basidiomycetes showing antimicrobial activity was similar to or above that obtained for representative orders of Ascomycetes, such as Pezizales and Xylariales, but lower than that produced by members of the orders Diaporthales, Eurotiales, Hypocreales, Leotiales and Sordariales. Suprageneric taxa (orders and families) did not show pronounced differences in their antimicrobial activities though such differences were observed at the genus level, suggesting that the ability to produce these bioactive compounds is not homogenously distributed amongst the basidiomycetes. Isolates from some species showed large differences in their ability to produce metabolites with antimicrobial activity, possibly reflecting genetic differences at the infraspecific level.