Resolving the Extragalactic γ-Ray Background above 50 GeV with the Fermi Large Area Telescope.

The Fermi Large Area Telescope (LAT) Collaboration has recently released a catalog of 360 sources detected above 50 GeV (2FHL). This catalog was obtained using 80 months of data re-processed with Pass 8, the newest event-level analysis, which significantly improves the acceptance and angular resolution of the instrument. Most of the 2FHL sources at high Galactic latitude are blazars. Using detailed Monte Carlo simulations, we measure, for the first time, the source count distribution, dN/dS, of extragalactic γ-ray sources at E>50 GeV and find that it is compatible with a Euclidean distribution down to the lowest measured source flux in the 2FHL (∼8×10^{-12} ph cm^{-2} s^{-1}). We employ a one-point photon fluctuation analysis to constrain the behavior of dN/dS below the source detection threshold. Overall, the source count distribution is constrained over three decades in flux and found compatible with a broken power law with a break flux, S_{b}, in the range [8×10^{-12},1.5×10^{-11}] ph cm^{-2} s^{-1} and power-law indices below and above the break of α_{2}∈[1.60,1.75] and α_{1}=2.49±0.12, respectively. Integration of dN/dS shows that point sources account for at least 86_{-14}^{+16}% of the total extragalactic γ-ray background. The simple form of the derived source count distribution is consistent with a single population (i.e., blazars) dominating the source counts to the minimum flux explored by this analysis. We estimate the density of sources detectable in blind surveys that will be performed in the coming years by the Cherenkov Telescope Array.

Searching for Dark Matter Annihilation from Milky Way Dwarf Spheroidal Galaxies with Six Years of Fermi Large Area Telescope Data.

The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on γ-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in γ rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass ≲100 GeV annihilating via quark and τ-lepton channels.

Inferred cosmic-ray spectrum from Fermi large area telescope γ-ray observations of Earth's limb.

Recent accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. We use the Fermi Large Area Telescope observations of the γ-ray emission from Earth's limb for an indirect measurement of the local spectrum of CR protons in the energy range ∼90 GeV-6 TeV (derived from a photon energy range 15 GeV-1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68±0.04 and 2.61±0.08 above ∼200 GeV, respectively.

Traumatic abdominal wall hernia as a component of the seatbelt syndrome: A case report of complete abdominal wall muscle transection.

INTRODUCTION AND IMPORTANCE: Seat belt syndrome (SBS) is a rare condition described as injuries sustained due to thoracic, abdominal, and pelvic compression in the context of traffic accidents. These injuries can range from minor skin abrasions to large lesions of internal organs and spinal cord involvement. Traumatic abdominal wall hernias (TAWH) are one of the injuries that can be associated. CASE PRESENTATION: A 21-year-old male suffered a severe injury, resulting in complete transection of all abdominal wall musculature due to SBS, with associated visceral injury. Emergency surgery included intestinal and sigmoid colon resection, along with cava vein repair. After a prolonged recovery, a second-stage surgery for abdominal wall reconstruction was planned. Prehabilitation involved botulinum toxin and pneumoperitoneum, with surgical planning utilizing CT scan and 3D reconstruction. The second-stage surgery included transversus abdominis release and placement of double mesh. CLINICAL DISCUSSION: Managing traumatic abdominal wall hernias in polytrauma patients necessitates emergent surgery for vital injuries, while reconstructive surgery timing is crucial, with patient preparation being essential. Surgical planning, including 3D reconstructions, enhances accuracy, and safety, with repair technique selection depending on anatomical features. Given our patient's athletic background and preoperative vascular CT findings, flapless reconstructive surgery was chosen to mitigate vascular risks. CONCLUSION: The therapeutic approach to traumatic abdominal wall injuries should be individualized to each patient, with a focus on addressing vital injuries first and considering abdominal wall reconstruction surgery at a subsequent stage. Utilizing CT scan with 3D reconstruction can be a valuable tool for preoperative planning in cases involving significant abdominal wall defects.

A retrospective analysis of early and late outcome of biodegradable stent placement in the management of refractory anastomotic colorectal strictures.

BACKGROUND: Benign colorectal strictures are treated conventionally by endoscopic dilation. Experience using SEMS for benign colonic strictures is limited, and outcomes to date have been disappointing. Refractory colorectal strictures remain challenging to be treated with surgery. Polydioxanone-based stent are biodegradable (BD) stent CE approved for esophageal strictures. This study was designed to investigate retrospectively the safety and the efficacy of these stents for the management of strictures refractory to multiple sessions of dilation. METHODS: Patients with postsurgical benign strictures located within 20 cm from anal verge, refractory to mechanical or pneumatic dilation (at least 3 sessions) were included in this analysis. Clinical success was defined as the absence of occlusive symptoms and the ability to pass through the stricture with a regular size colonoscope. All patients were predilated before stent placement. Stents were released under fluoroscopic control. All patients were under stool softeners for 3 months. Follow-up was scheduled with endoscopic and fluoroscopic controls within 90 days from stent deployment and afterwards by telephone interview and/or ambulatory consultation. RESULTS: Eleven patients (7 males, mean age 62.3 ± 8.5 years) were included. Technical success was achieved in all the patients. Stent migration was observed in four patients within the first 2 weeks after stent placement. Stent migration was followed by recurrence of stricture and obstructive symptoms in all the cases. Among the seven patients who completed the process of stent biodegradation, five of them had complete resolution of the stricture and relief of symptoms. Two of 11 patients required surgical treatment during the follow-up period (mean 19.8 (range 42-15) months). The overall success rate of the BD stent was 45 %. CONCLUSIONS: This retrospective analysis of a limited number of patients demonstrated that nondedicated esophageal BD stents are associated with high risk of migration and clinical success in less than 50 % of patients. Dedicated stents with large diameter and antimigration findings could potentially improve the outcome of patients with refractory benign colorectal strictures.

A pilot risk assessment study of strontium chromate among painters in the aeronautical industry.

OBJECTIVE: A method for risk assessment of occupational exposure to strontium chromate (SrCrO4) in painters employed in the aeronautical industry is described. METHODS: Assessment was made of 21 male workers of the painting division, potentially exposed to SrCrO4 (exposed), and 20 male workers of the tests and warehouse divisions (controls). All participants completed a questionnaire about work tasks, lifestyle habits, hobbies and diet. Personal active sampling for the determination of Cr and Sr was performed both during paint-spraying and during other operations in the painting division area. On the same day as environmental sampling, urine samples were collected at the beginning and end of the work shift in exposed workers to determine urinary chromium (CrU), and only at the end of the shift in controls. In the second half of the shift, a blood sample was taken in 10 exposed workers and 10 controls, to determine Cr in plasma (CrP) and in red blood cells (CrRBC). RESULTS: During paint-spraying, Cr concentrations ranged between 1.38 and 17.10 microg/m3, versus 0.02 to 0.07 microg/mi in the painting division area, while the Sr concentration was 22.90 microg/m3 in the paint-spray booth versus 0.07 microg/m3 in the painting division area. CrU at the end of the work shift, CrP and CrRBC, did not show significant differences between exposed workers and controls. Moreover, in exposed workers there were no differences between CrU measured at the beginning and at the end of the work shift. CONCLUSIONS: This approach, consisting of simultaneous environmental and biological monitoring, suggested no absorption of chromium in the painters thanks to the efficacy of the technical, organizational and personal protection measures adopted. However, the evident exposure to high levels of SrCrO4 during paint-spraying highlights how absolutely essential it is to ensure strict compliance with all the preventive measures foreseen by the EU and national regulations for occupational exposure to carcinogens.

Measurement of separate cosmic-ray electron and positron spectra with the fermi large area telescope.

We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting Earth's shadow, which is offset in opposite directions for opposite charges due to Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 and 200 GeV. We confirm that the fraction rises with energy in the 20-100 GeV range. The three new spectral points between 100 and 200 GeV are consistent with a fraction that is continuing to rise with energy.

Safety of cold polypectomy for <10mm polyps at colonoscopy: a prospective multicenter study.

BACKGROUND: Cold polypectomy techniques (without electrocautery) by means of biopsy forceps or snare are widely adopted for the removal of subcentimetric polyps. However, few data are available on the safety of this approach. The aim of this study was to assess the safety of cold polypectomy for subcentimetric polyps, as well as the rate of advanced neoplasia in these lesions. PATIENTS AND METHODS: In a prospective multicenter trial, consecutive patients with at least one < 10-mm polyp at colonoscopy were prospectively included. All of the < 10-mm polyps detected within the study period were removed by cold polypectomy. The rates of immediate or delayed bleeding and other complications were assessed at 7 and 30 days after cold polypectomy by telephone calls. The rate of advanced histology was also assessed. Predictive variables of postpolypectomy bleeding or advanced neoplasia were identified by multivariate analysis. RESULTS: A total of 1015 < 10-mm polyps in 823 patients (15.5 % on antiplatelet agents) were removed. Of these, 822 (81 %) were ≤ 5 mm and 193 (19 %) were 6 - 9 mm. Immediate postpolypectomy bleeding occurred in 18 patients, corresponding to a per-patient and per-polyp bleeding rate of 2.2 % (95 % confidence interval [CI] 1.2 % - 3.2 %) and 1.8 % (95 %CI 1 % - 2.6 %), respectively. Therapy with antiplatelet agents (odds ratio [OR] 4; 95 %CI 1.5 - 10.6) and larger polyp size (OR 2; 95 %CI 1.1 - 6.9) were independent predictors of bleeding. Bleeding was successfully treated by endoscopic hemostasis in all cases and required no further medical intervention. Advanced neoplasia prevalence in polyps ≤ 5 mm was as high as 8.7 %. CONCLUSIONS: The results from this study showed the high safety of a cold polypectomy approach for subcentimetric polyps. This was due to the low rate of postpolypectomy bleeding and to the high efficacy of endoscopic hemostasis in its treatment. The high rate of advanced neoplasia in polyps ≤ 5 mm should prompt some caution on the management of these lesions following detection at computed tomography colonography or colon capsule endoscopy.

Constraining dark matter models from a combined analysis of Milky Way satellites with the Fermi Large Area Telescope.

Satellite galaxies of the Milky Way are among the most promising targets for dark matter searches in gamma rays. We present a search for dark matter consisting of weakly interacting massive particles, applying a joint likelihood analysis to 10 satellite galaxies with 24 months of data of the Fermi Large Area Telescope. No dark matter signal is detected. Including the uncertainty in the dark matter distribution, robust upper limits are placed on dark matter annihilation cross sections. The 95% confidence level upper limits range from about 10(-26) cm3 s(-1) at 5 GeV to about 5×10(-23) cm3 s(-1) at 1 TeV, depending on the dark matter annihilation final state. For the first time, using gamma rays, we are able to rule out models with the most generic cross section (∼3×10(-26) cm3 s(-1) for a purely s-wave cross section), without assuming additional boost factors.

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial.

OBJECTIVES: Little evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity. METHODS: Twenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2. RESULTS: At T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016). At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group. CONCLUSIONS: tDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections. SIGNIFICANCE: This study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.

Particle-image velocimetry study of a pediatric ventricular assist device.

Particle-image velocimetry (PIV) was used to visualize the flow within an optically transparent pediatric ventricular assist device (PVAD) under development in our laboratory. The device studied is a diaphragm type pulsatile pump with an ejection volume of 30 ml per beating cycle intended for temporary cardiac assistance as a bridge to transplantation or recovery in children. Of particular interest was the identification of flow patterns, including regions of stagnation and/or strong turbulence that often promote thrombus formation and hemolysis, which can degrade the usefulness of such devices. For this purpose, phase-locked PIV measurements were performed in planes parallel to the diaphragm that drives the flow in the device. The test fluid was seeded with 10 microm polystyrene spheres, and the motion of these particles was used to determine the instantaneous flow velocity distribution in the illumination plane. These measurements revealed that flow velocities up to 1.0 m/s can occur within the PVAD. Phase-averaged velocity fields revealed the fixed vortices that drive the bulk flow within the device, though significant cycle-to-cycle variability was also quite apparent in the instantaneous velocity distributions, most notably during the filling phase. This cycle-to-cycle variability can generate strong turbulence that may contribute to greater hemolysis. Stagnation regions have also been observed between the input and output branches of the prototype, which can increase the likelihood of thrombus formation.

Down regulation of CD11b and CD18 expression in children with hypercholesterolemia: a preliminary report.

BACKGROUND AND AIM: Cell adhesion molecules play an important role in the development of atherosclerosis mediating the attachment of monocytes to the endothelium. The aim of our study was to assess the cell surface expression of CD11b/CD18 integrin on the phagocytes of children affected by hypercholesterolemia. METHODS AND RESULTS: Twenty-six children with hypercholesterolemia (15 males, mean age 8.3, range 2-18) with a family history of early cardiovascular disease, as well as 26 children with normocholesterolemia matched for gender and age (15 males, mean age 8.3) were studied. Cell surface expression of CD11b/CD18 on peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry. The geometric mean percentages of CD11b and CD18 expression were significantly lower in the hypercholesterolemic group [52 (95% confidence intervals, 40-68) and 88 (84-93)] than in the control group [87 (83-91), P<0.0001 and 93 (89-96), P<0.05], respectively. After correction for age, gender, and pubertal status, CD11b cell surface expression on PBMC was inversely and independently correlated with total cholesterol concentrations (r=-0.395; P<0.01) and LDL (r=-0.307; P<0.05), as well as with triglycerides (r=-0.406; P<0.01). CONCLUSIONS: In children with hypercholesterolemia, cell surface expression of CD11b and CD18 on PBMC was significantly decreased. Follow-up studies are necessary to determine the clinical implications of these findings in the context of the natural course and progression of atherosclerosis in high risk children.

Review article: the management of steroid dependency in ulcerative colitis.

BACKGROUND: Approximately 20% of patients with ulcerative colitis have a chronic active disease often requiring several courses of systemic steroids in order to achieve remission, but followed by relapse of symptoms during steroid tapering or soon after their discontinuation. Although short term control of symptoms can be achieved with steroid treatment, this pattern of drug response, known as steroid-dependency, leads to important complications of the treatment, while a significant proportion of patients requires colectomy. AIM: To review the studies currently available specifically evaluating the management of steroid-dependent ulcerative colitis. RESULTS: The clinical and biological mechanisms of steroid-dependency are not well understood compared with those determining steroid-refractoriness. Very few evidence-based data are available concerning the management of patients with steroid-dependent ulcerative colitis. The therapeutic role of aminosalicylates, thiopurines, methotrexate, infliximab, leukocyte apheresis and other drugs in the treatment of steroid-dependent ulcerative colitis are evaluated. CONCLUSIONS: Outcomes of studies in steroid-refractory patients may not be applicable to steroid-dependency. Trials are needed to define the correct approaches and new strategies to ameliorate the therapy of steroid-dependent ulcerative colitis.

Early bacterial infection of the pancreas and course of disease in cerulein-induced acute pancreatitis in rats.

BACKGROUND: Bacterial infection of the pancreas aggravates the course of acute pancreatitis. Since bacterial translocation from the gut is likely to be an early event, in an animal model of pancreatitis, we investigated the effect of early bacterial supra-infection of the pancreas on the course of the disease. METHODS: Six hours after the induction of acute pancreatitis in male Wistar rats (n = 180) by supramaximal stimulation with cerulein (or placebo in a control group), the animals were operated and a suspension of Helicobacter pylori, Escherichia coli or saline were introduced either in the pancreatic duct or interstitium (12 groups of 15 rats each); after 24 h, animals were killed and the following parameters analysed: macroscopic and histologic appearance of the pancreas (score), wet-to-dry weight ratio, pancreas trypsinogen activation peptide level, serum amylase, interleukin-6 and phospholipase A2 activity. RESULTS: All parameters were increased in rats with cerulein-induced pancreatitis in comparison to placebo. Interstitial and intraductal application of bacteria increased the pancreatic damage. This effect was more evident with the application of E. coli in both cerulein and placebo groups. Application of E. coli but not of H. pylori determined pancreatic activation of trypsinogen, increased mortality and induced the production of interleukin-6. CONCLUSIONS: Bacterial invasion of the pancreas worsens the histologic and clinical picture of disease and induces a systemic inflammatory response.

Merkel cell carcinoma: experience of 14 cases and literature review.

Merkel cell carcinoma is an aggressive skin cancer, with a significant incidence of locoregional lymphnode involvement, which requires timely diagnosis, adequate staging and aggressive therapy based essentially on surgical procedures. The aim of this study is to report our experience and to compare our results with literature findings, in order to discuss the role of the procedures adopted and their influence on prognosis. From July 1995 to April 2005, 14 patients were treated and followed-up for MCC in the National Cancer Institute of Naples. Tumor location was: buttocks (43%), extremities (36%) head (7%), unknown (14%). There were 7 Stage I, 5 Stage II and 2 Stage III patients. Surgical treatment consisted in wide excision (WE) in Stage I cases, WE and regional lymphadenectomy followed by radio- or chemo-therapy in Stage II and combined surgical and pre- and post-operative medical treatments in Stage III. Overall disease specific survival rate was 64% (median follow up 44 months). Recurrence occurred in 86% of Stage I and 20% of Stage II patients and involved, in 83.3% of Stage I patients, the lymph nodal draining basin. The treatment of recurrence implied surgery and radio or radiochemotherapy. Overall survival rate of recurrent patients was 57% (median follow-up 37.2 months). Due to the particular lymphotrophism of MCC, major care should be set on investigation and treatment of tumor lymph nodal draining basin. As long as the disease remains surgically manageable the prognosis for patients with MCC is favourable. The role of radio and chemotherapy is not yet assessed.

Quality of life in patients treated by adjuvant radiotherapy for endometrial and cervical cancers: correlation with dose-volume parameters.

INTRODUCTION: Modern multidisciplinary cancer treatments aim at obtaining minimal influence on patients' quality of life (QoL). The purpose of this study was to assess QoL and correlate it with dose-volume parameters of organ at risks (OARs) in patients who received adjuvant radiotherapy for endometrial and cervical cancers. MATERIALS AND METHODS: We administered the EORTC QLQ-C30 and EN24 or CX24 questionnaires to 124 patients, 100 with endometrial cancer and 24 with cervical cancer treated with postoperative radiotherapy ± chemotherapy in regular follow-up. Bladder function, fecal incontinence or urgency and sexual functioning were investigated and correlated with dose-volume parameters of OAR by multiple linear regression analysis. This correlation was assessed by R (2) value. RESULTS: QoL was very high in the majority of patients (82.3 % of patients). Few patients referred urinary incontinence (3.2 %) or abdominal discomfort of high grade (4.0 %). We found a significant correlation between bladder V40, i.e., absolute percentage of bladder volume that received a dose of 40 Gy, and global health status (p < 0.05, R (2) = 0.17), urinary urgency (p < 0.05, R (2) = 0.24), urinary incontinence (p < 0.05, R (2) = 0.23) and dyspareunia (p < 0.05, R (2) = 0.04). We found also a correlation between global health status and mean dose to vagina (p < 0.05, R (2) = 0.17) and between maximum dose to lumbo-sacral plexus and abdominal pain (p < 0.05, R (2) = 0.07). CONCLUSIONS: Women treated with surgery and adjuvant radiotherapy for endometrial and cervical cancers have good QoL with minimal limitations of daily activities. QoL was correlated with dose-volume parameters such as bladder V40, mean dose to vagina, maximum dose to trigone and LSP.

The neuroactive steroid allopregnanolone suppresses hypothalamic gonadotropin-releasing hormone release through a mechanism mediated by the gamma-aminobutyric acidA receptor.

The central nervous system (CNS) is able to synthesize and/or metabolize steroid hormones. These neuroactive steroids are capable of modulating several brain functions and, among these, they seem to regulate the hypothalamic-pituitary-gonadal (HPG) axis. Indeed, recent observations have shown that 5 alpha-pregnane-3 alpha-ol-20-one (allopregnanolone), one of the most abundant naturally occurring neuroactive steroids, suppresses ovulation and sexual behaviour when administered within the CNS. The present study was undertaken to evaluate the effects of allopregnanolone and its inactive stereoisomer, 5 alpha-pregnane-3 beta-ol-20-one, upon the release of gonadotropin-releasing hormone (GnRH) from individually-incubated hemihypothalami. Allopregnanolone suppressed GnRH release in a concentration-dependent manner with maximal activity in the nanomolar range, a range at which this neurosteroid is capable of playing a biological action. The specificity of allopregnanolone suppression of GnRH release was provided by the lack of effect of its known inactive stereoisomer. To evaluate the involvement of gamma-aminobutyric acidA (GABAA) receptor, we examined the effects of two neurosteroids with GABA-antagonistic properties, pregnanolone sulfate (PREG-S) and dehydroepiandrosterone sulfate (DHEAS), and of bicuculline, a selective antagonist of the GABA binding site on the GABAA receptor, on allopregnanolone (10 nM)-suppressed GnRH release. Both PREG-S and bicuculline overcame the inhibitory effects of allopregnanolone on GnRH release, whereas DHEAS did not. To substantiate the involvement of the GABAA receptor further, we tested the effects of muscimol, a selective agonist for this receptor, which suppressed GnRH release. In conclusion, allopregnanolone suppressed hypothalamic GnRH release in vitro and this effect appeared to be mediated by an interaction with the GABAA receptor. We speculate that the inhibitory effect of allopregnanolone on the HPG axis may also be caused by its ability to suppress hypothalamic GnRH release.

Sexual health innovations in undergraduate medical education.

Recent national and global initiatives have drawn attention to the importance of sexual health to individuals' well-being. These initiatives advocate enhancement of efforts to address this under-represented topic in health professions curricula. University of Massachusetts Medical School (UMMS) has undertaken a comprehensive effort to develop an integrated curriculum in sexual health. The UMMS project draws upon the expertise of a multidisciplinary faculty of clinicians, basic scientists, a medical ethicist, and educators. This article describes the project's genesis and development at UMMS, and reports on three innovations in sexual health education implemented as part of this endeavor.

Gamma-aminobutyric acid (GABA) A and B receptors mediate the stimulatory effects of GABA on the human sperm acrosome reaction: interaction with progesterone.

OBJECTIVE: To evaluate which gamma-aminobutyric acid (GABA) receptor mediates the stimulatory effects of this neurotransmitter on the human sperm acrosome reaction, and to examine the interaction of progesterone, a physiologic inducer of the acrosome reaction, with the GABA(A) receptor. DESIGN: Prospective study. SETTING: A university clinic of andrology. PATIENT(S): Men with normal sperm analysis parameters. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The acrosome reaction of motile spermatozoa. RESULT(S): The acrosome reaction was stimulated by GABA in a dose-dependent manner. This effect was inhibited completely by bicuculline, a GABA(A) receptor antagonist, and only partially by saclofen, a GABA(B) receptor antagonist. Accordingly, muscimol, a GABA(A) receptor agonist, stimulated the acrosome reaction to the same extent as GABA, whereas baclofen, a GABA(B) receptor agonist, was less effective. Preincubation with progesterone followed by the addition of GABA resulted in a significant increase in the percentage of acrosome-reacted spermatozoa compared with progesterone alone. However, this increase was less than a simple addition of effects, suggesting that GABA and progesterone act through the same receptor and/or use the same mechanism of action. To test this hypothesis, the ability of progesterone to induce acrosome reaction was tested in the presence of bicuculline, which suppressed the stimulatory effects of progesterone. Given that the GABA(A) receptor is linked to the chloride channel, we tested whether picrotoxin, a blocker of this channel, could modulate the effects of progesterone or GABA. Picrotoxin completely suppressed the acrosome reaction induced by progesterone and only partially suppressed that caused by GABA. CONCLUSION(S): gamma-Aminobutyric acid stimulated the acrosome reaction in human spermatozoa, acting mainly through the GABA(A) receptor and to a lesser extent through the GABA(B) receptor. Progesterone interacted with the GABA(A) receptor to induce the acrosome reaction, and the functional integrity of the chloride channel was vital for this effect.