Hydrolyzable tannins from Poincianella (Caesalpinia) microphylla fruits: Metabolite profiling and anti-Trichomonas vaginalis activity.

Poincianella (Caesalpinia) microphylla fractions were analyzed by LC-DAD-MS and by statistical tools to determine the possible bioactive compounds against T. vaginalis. Tannins enriched-fractions toxicity (M5 and M10) were analyzed in in vitro against human red cells and in in vivo model of Galleria mellonella. Twenty-six compounds were detected from the P. microphylla fractions. The main compounds identified were hydrolyzable tannins (gallotanins and ellagitannis), such as O-digalloyl hexoside, O-digalloyl HHDP -hexoside, tri-O-galloyl HHDP-hexoside, O-galloyl HHDP-DHHDP-hexoside and their isomers. In addition, procyanidin dimer, epicatechin, ellagic acid and O-(digalloyl) quinic acid were also identified. Based on univariate statistical analyses, stronger correlations with the anti-T. vaginalis properties were observed for the compounds 7 (O-galloyl HHDP-DHHDP-hexoside - Geraniin isomer), 3 (O-digalloyl HHDP -hexoside - mallotinic acid), 2 (O-digalloyl) quinic acid), 1 (O-digalloyl hexoside) and 9 (unknown). Tannins enriched-fractions (M5 and M10) presented anti-Trichomonas activity (IC50 70.41 µg/mL and 142.1 µg/mL, respectively) and no toxicity in the in vivo model of G. mellonella. This innovative approach allowed us to identify likely bioactive compounds in the extracts, although the mechanism(s) underlying anti-trichomonal activity encompass a complex trait.

Efficacy of application of Equisetum pyramidale Goldm. hydrogel for tissue restoration of induced skin lesions in Wistar rats / Eficácia da aplicação de Equisetum pyramidale Goldm. hidrogel na restauração tecidual em lesões cutâneas induzidas em ratos Wistar

Abstract Medicinal plants, such as E. pyramidale, are alternatives against infections and assist in the healing process of wounds. We evaluated the effects of Hydrogel of E. pyramidale on the healing of cutaneous wounds in animal models by morphological, morphometric and histological analyses, and elucidated major components. The ethanolic extract of E. pyramidale shoots was submitted to phytochemical analysis. For cicatrizing activity assay, Wistar rats were used, and the groups evaluated were hydrogel containing ethanolic extract of E. pyramidale at 2% compared to control groups. The treatment periods were 3, 7 and 21 days, and macroscopic and microscopic analyses were performed. Data were submitted to Analysis of Variance (p <0.05). Phytochemistry and quantification evidenced that flavonoids are main constituents and that they were evidenced by thin layer chromatography (TLC), high efficiency (HPLC) and infrared (IR) methods. In TLC, using flavonoid patterns, we observed pinocembrin. The hydrogel containing ethanolic extract of E. pyramidale at 2% was effective in wound regression. E. pyramidale can be used for the treatment of second intention wounds, and the effective healing may be due to a high flavonoid content.

Resumo As plantas medicinais, como E. pyramidale, são uma alternativa para combater infecções e ajudar o processo de cicatrização de feridas. Avaliar os efeitos do hidrogel de E. pyramidale na cicatrização de feridas cutâneas em modelos animais através de análises morfológicas, morfométricas e histológicas, bem como para elucidar os principais componentes. O extrato etanólico das partes aéreas de E. pyramidale foi submetido a análise fitoquímica. Para o ensaio de atividade cicatrizante, foram utilizados ratos Wistar e os grupos avaliados foram o hidrogel com extrato etanólico de E. pyramidale 2% em comparação com os grupos controle. Os períodos de tratamento foram 3, 7 e 21 dias e as análises macroscópicas e microscópicas foram realizadas e os dados submetidos à Análise de Variância (p <0,05). A fitoquímica e a quantificação indicaram que os flavonóides são os constituintes principais e que mesmos foram evidenciados na cromatografia de camada delgada (CCD), de alta eficiência (HPLC) e por infravermelho (IV). Em CCD, empregando padrões de flavonoides, foi observado a pinocembrina. O hidrogel com extrato etanólico de E. pyramidale 2% foi eficaz na regressão da ferida. E. pyramidale pode ser usado no tratamento de feridas de segunda intenção e a cura efetiva pode ser devido ao alto teor de flavonoides.

Efficacy of application of Equisetum pyramidale Goldm. hydrogel for tissue restoration of induced skin lesions in Wistar rats.

Medicinal plants, such as E. pyramidale, are alternatives against infections and assist in the healing process of wounds. We evaluated the effects of Hydrogel of E. pyramidale on the healing of cutaneous wounds in animal models by morphological, morphometric and histological analyses, and elucidated major components. The ethanolic extract of E. pyramidale shoots was submitted to phytochemical analysis. For cicatrizing activity assay, Wistar rats were used, and the groups evaluated were hydrogel containing ethanolic extract of E. pyramidale at 2% compared to control groups. The treatment periods were 3, 7 and 21 days, and macroscopic and microscopic analyses were performed. Data were submitted to Analysis of Variance (p <0.05). Phytochemistry and quantification evidenced that flavonoids are main constituents and that they were evidenced by thin layer chromatography (TLC), high efficiency (HPLC) and infrared (IR) methods. In TLC, using flavonoid patterns, we observed pinocembrin. The hydrogel containing ethanolic extract of E. pyramidale at 2% was effective in wound regression. E. pyramidale can be used for the treatment of second intention wounds, and the effective healing may be due to a high flavonoid content.

Strongly baryon-dominated disk galaxies at the peak of galaxy formation ten billion years ago.

In the cold dark matter cosmology, the baryonic components of galaxies-stars and gas-are thought to be mixed with and embedded in non-baryonic and non-relativistic dark matter, which dominates the total mass of the galaxy and its dark-matter halo. In the local (low-redshift) Universe, the mass of dark matter within a galactic disk increases with disk radius, becoming appreciable and then dominant in the outer, baryonic regions of the disks of star-forming galaxies. This results in rotation velocities of the visible matter within the disk that are constant or increasing with disk radius-a hallmark of the dark-matter model. Comparisons between the dynamical mass, inferred from these velocities in rotational equilibrium, and the sum of the stellar and cold-gas mass at the peak epoch of galaxy formation ten billion years ago, inferred from ancillary data, suggest high baryon fractions in the inner, star-forming regions of the disks. Although this implied baryon fraction may be larger than in the local Universe, the systematic uncertainties (owing to the chosen stellar initial-mass function and the calibration of gas masses) render such comparisons inconclusive in terms of the mass of dark matter. Here we report rotation curves (showing rotation velocity as a function of disk radius) for the outer disks of six massive star-forming galaxies, and find that the rotation velocities are not constant, but decrease with radius. We propose that this trend arises because of a combination of two main factors: first, a large fraction of the massive high-redshift galaxy population was strongly baryon-dominated, with dark matter playing a smaller part than in the local Universe; and second, the large velocity dispersion in high-redshift disks introduces a substantial pressure term that leads to a decrease in rotation velocity with increasing radius. The effect of both factors appears to increase with redshift. Qualitatively, the observations suggest that baryons in the early (high-redshift) Universe efficiently condensed at the centres of dark-matter haloes when gas fractions were high and dark matter was less concentrated.

Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ETA R) and the angiotensin II receptor type 1 (AT1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ETA R and anti-AT1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient.

Peripheral and central antinociceptive effects of the butanolic fraction of Byrsonima verbascifolia leaves on nociception-induced models in mice.

Byrsonima verbascifolia (Malpighiaceae), commonly known as 'murici', is used in folk medicine, for example, in the treatment of inflammation. The anti-inflammatory activity of the butanolic fraction of B. verbascifolia leaves (BvBF) was previously reported by our group, and the present study was designed to evaluate their antinociceptive effects. BvBF (25, 50, and 100 mg/kg) administered intraperitoneally (i.p.) inhibited acetic acid induced abdominal writhing. In the formalin test, BvBF (10, 30 and 100 mg/kg, i.p.) caused a reduction in licking time in both the neurogenic and inflammatory phases. Moreover, we demonstrated that BvBF (30 and 100 mg/kg, i.p.) caused an increase in the latency to response in the hot-plate test. These results demonstrate that BvBF possesses marked peripheral and central antinociceptive activities. Pre-treatment with the non-selective receptor antagonist naloxone (5 mg/kg, i.p.) abolished the antinociceptive effects of BvBF (100 mg/kg, i.p.) in the neurogenic phase of the formalin and hot-plate tests. The anti-inflammatory activity of BvBF (previously reported) as well as the participation of the opioidergic system seems to be responsible, at least in part, for these antinociceptive effects. Finally, BvBF at the doses investigated (25, 50 and 100 mg/Kg) did not cause any toxicity signals, showing that the antinociceptive activity is devoid of sedative and hypomotility effects.

Efficacy of application of Equisetum pyramidale Goldm. hydrogel for tissue restoration of induced skin lesions in Wistar rats

Abstract Medicinal plants, such as E. pyramidale, are alternatives against infections and assist in the healing process of wounds. We evaluated the effects of Hydrogel of E. pyramidale on the healing of cutaneous wounds in animal models by morphological, morphometric and histological analyses, and elucidated major components. The ethanolic extract of E. pyramidale shoots was submitted to phytochemical analysis. For cicatrizing activity assay, Wistar rats were used, and the groups evaluated were hydrogel containing ethanolic extract of E. pyramidale at 2% compared to control groups. The treatment periods were 3, 7 and 21 days, and macroscopic and microscopic analyses were performed. Data were submitted to Analysis of Variance (p 0.05). Phytochemistry and quantification evidenced that flavonoids are main constituents and that they were evidenced by thin layer chromatography (TLC), high efficiency (HPLC) and infrared (IR) methods. In TLC, using flavonoid patterns, we observed pinocembrin. The hydrogel containing ethanolic extract of E. pyramidale at 2% was effective in wound regression. E. pyramidale can be used for the treatment of second intention wounds, and the effective healing may be due to a high flavonoid content.

Resumo As plantas medicinais, como E. pyramidale, são uma alternativa para combater infecções e ajudar o processo de cicatrização de feridas. Avaliar os efeitos do hidrogel de E. pyramidale na cicatrização de feridas cutâneas em modelos animais através de análises morfológicas, morfométricas e histológicas, bem como para elucidar os principais componentes. O extrato etanólico das partes aéreas de E. pyramidale foi submetido a análise fitoquímica. Para o ensaio de atividade cicatrizante, foram utilizados ratos Wistar e os grupos avaliados foram o hidrogel com extrato etanólico de E. pyramidale 2% em comparação com os grupos controle. Os períodos de tratamento foram 3, 7 e 21 dias e as análises macroscópicas e microscópicas foram realizadas e os dados submetidos à Análise de Variância (p 0,05). A fitoquímica e a quantificação indicaram que os flavonóides são os constituintes principais e que mesmos foram evidenciados na cromatografia de camada delgada (CCD), de alta eficiência (HPLC) e por infravermelho (IV). Em CCD, empregando padrões de flavonoides, foi observado a pinocembrina. O hidrogel com extrato etanólico de E. pyramidale 2% foi eficaz na regressão da ferida. E. pyramidale pode ser usado no tratamento de feridas de segunda intenção e a cura efetiva pode ser devido ao alto teor de flavonoides.

Galaxies at redshifts 5 to 6 with systematically low dust content and high [C II] emission.

The rest-frame ultraviolet properties of galaxies during the first three billion years of cosmic time (redshift z > 4) indicate a rapid evolution in the dust obscuration of such galaxies. This evolution implies a change in the average properties of the interstellar medium, but the measurements are systematically uncertain owing to untested assumptions and the inability to detect heavily obscured regions of the galaxies. Previous attempts to measure the interstellar medium directly in normal galaxies at these redshifts have failed for a number of reasons, with two notable exceptions. Here we report measurements of the forbidden C ii emission (that is, [C II]) from gas, and the far-infrared emission from dust, in nine typical star-forming galaxies about one billion years after the Big Bang (z ≈ 5-6). We find that these galaxies have thermal emission that is less than 1/12 that of similar systems about two billion years later, and enhanced [C II] emission relative to the far-infrared continuum, confirming a strong evolution in the properties of the interstellar medium in the early Universe. The gas is distributed over scales of one to eight kiloparsecs, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z < 3 and being comparable in dust content to local low-metallicity systems.

Galaxy evolution. Evidence for mature bulges and an inside-out quenching phase 3 billion years after the Big Bang.

Most present-day galaxies with stellar masses ≥10(11) solar masses show no ongoing star formation and are dense spheroids. Ten billion years ago, similarly massive galaxies were typically forming stars at rates of hundreds solar masses per year. It is debated how star formation ceased, on which time scales, and how this "quenching" relates to the emergence of dense spheroids. We measured stellar mass and star-formation rate surface density distributions in star-forming galaxies at redshift 2.2 with ~1-kiloparsec resolution. We find that, in the most massive galaxies, star formation is quenched from the inside out, on time scales less than 1 billion years in the inner regions, up to a few billion years in the outer disks. These galaxies sustain high star-formation activity at large radii, while hosting fully grown and already quenched bulges in their cores.

Spontaneous involution of diffuse fibrous dysplasia of paranasal sinuses.

We report the case of a 25-year-old patient, diagnosed at age 10, with diffuse fibrous dysplasia of the paranasal sinuses, an extremely rare idiopathic condition. This diagnosis is possible only by cerebral computed tomography (CT), cerebral and anterior skull base magnetic resonance imaging (MRI), and histopathology. Surgical treatment is common. This boy had mild symptoms: moderate headache in the morning that did not affect his daily activity, and rhinitis, partially responsive to medication. The neurologic examination was abnormal. Radiographs, CT, and MRI showed a diffuse mass in the paranasal sinuses which had a histopathological diagnosis of fibrous dysplasias. The family refused to refer the patient to surgery. The boy has been monitored annually for 15 years. He has remained asymptomatic without headache since age 11, with normal, general and neurologic examinations. Serial MRIs showed a spontaneous partial involution of the mass.

Pain control after liver transplantation surgery.

BACKGROUND: Although post-liver transplantation pain is not as severe as expected from the size of the surgical incision, optimal pain control becomes crucial to aid compliance with the ventilator, improve respiratory function, and facilitate an early weaning from mechanical ventilation. METHODS: Because the majority of analgesics are primarily metabolized and excreted by the hepatobiliary system, a poor recovery of graft function will result in a decrease in clearance and reduced elimination of the drug. On the other hand, if the liver is working well, the metabolism of analgesics improves significantly with minimal accumulation. Morphine-based analgesia has been associated with a higher risk of sedation and respiratory depression compared with major abdominal surgical procedures. Fentanyl and sufentanil in continuous intravenous infusion may be preferred in the presence of hemodynamic instability or bronchospasm. Sufentanil produces shorter-lasting respiratory depression and long-lasting analgesia than does fentanyl. RESULTS: The provision of potent continuous analgesia, independent of the duration of infusion, and the unique pharmacokinetics, not significantly affected by the functional status of the graft, make remifentanil appropriate for the majority of liver-transplanted patients. Unlike for patients with very severe pain after major abdominal surgery, liver transplant recipients usually benefit from tramadol, either in repeated intravenous boluses or continuous intravenous infusion. Paracetamol has been included as adjuvant (or sole agent, rarely) in the analgesic treatment of mild to moderate postoperative pain. The combination treatment (paracetamol plus tramadol) is a reasonable, safe option with improved analgesia and concurrent reduction in the incidence of some opioid-related side effects. CONCLUSIONS: Frequent review of the patient's response is mandatory when potent opioids are used because dose-dependent respiratory depression is a serious and potentially life-threatening adverse effect. The benefits provided by epidural analgesia in this particular setting should be weighed against the risks because in the presence of markedly deranged perioperative blood clotting, the development of epidural hematoma represents a disastrous complication.

Nitric oxide metabolites (nitrite and nitrate) in several clinical condition.

We determined the concentration of nitric oxide metabolites (NO2-+NO3-), expressed as NOx, in several clinical conditions. Regarding this, we have examined 25 subjects with arterial hypertension, 41 subjects with chronic kidney disease in conservative treatment, 106 subjects with metabolic syndrome subdivided according to the presence (n = 43) or not (n = 63) of diabetes mellitus, 48 subjects with obstructive sleep apnea syndrome (OSAS), 14 women with systemic sclerosis complicated with Raynaud's phenomenon, 42 dialyzed subjects and 105 young subjects with acute myocardial infarction (AMI). In subjects with arterial hypertension, chronic kidney disease, metabolic syndrome, systemic sclerosis, as well as, in dialyzed and AMI subjects, we found at baseline a NOx increase. In dyalized subjects after a standard dialysis session, we observed a decrease in NOx. The increase in NOx in juvenile AMI was significantly influenced by cigarette smoking and less by cardiovascular risk factors and the extent of coronary lesions; at 3 and 12 months later than the initial event, we observed a decrease of NOx that remains significantly higher than the control group. In subjects with OSAS no difference in NOx was noted in comparison with normal controls, although their subdivision according to the apnea/hypopnea index operates a clear distinction regarding NOx concentration.

Liver transplantation in children with congenital cardiac defects: a case report and a short literature review.

Advances in surgical techniques and follow-up of patients with complex congenital heart disease who were corrected in childhood increasingly survive to adolescence or adulthood. Increasingly anesthesiologists encounter these cases for major noncardiac surgery, including orthotopic liver transplantation (OLT) wherein there is an augmented risk of significant perioperative hemodynamic instability. We performed a successful OLT in a 12-year-old boy with end-stage cryptogenetic liver fibrosis and hepatopulmonary syndrome who was born with a double outflow right ventricle, pulmonary atresia, and pulmonary artery hypoplasia corrected at the age of 1 month. By the time he was considered for OLT his altered pulmonary valve apparatus resulted in severe pulmonary regurgitation, dilated right atrium and ventricle, and elevated right heart pressures. After a temporarily successful angioplasty he was at first placed on the waiting list, then removed, and finally relisted following implantation of a prosthetic pulmonary valve that resulted in significant reduction of right heart pressures.

Leukocyte activation markers and oxidative status in chronic kidney disease.

AIM: In chronic kidney disease (CKD) cardiovascular risk is increased. Oxidative stress is strictly involved in the pathophysiology of this enhanced risk as well as leukocytes' activation. To better elucidate these phaenomena we evaluated some parameters of leukocyte activation and oxidative state on fasting blood samples obtained from CKD patients on conservative or hemodialysis (HD) treatment, compared to those obtained from control subjects. METHODS: We enrolled 41 patients (25 men and 16 women, mean age 64.7 ± 11.1 years) with CKD and 42 patients (21 men and 21 women, mean age 66.83 ± 14.8 years) with CKD on hemodialysis (HD) treatment. Hemodialyzed patients were evaluated before and after a standard HD session. Leukocyte activation was evaluated by determining plasma elastase and myeloperoxidase level employing ELISA methods. Lipid peroxidation was evaluated as thiobarbituric acid-reactive substances (TBARS), total antioxidant status using spectrophotometry. RESULTS: Elastase was higher in CKD on conservative and on HD treatment and its value increased after the HD session. Myeloperoxidase did not show any variation in CKD on conservative and HD treatment while after HD its value was increased. Lipid peroxidation was increased in CKD on conservative and on HD therapy and its value after dialysis showed no significant variation. Total antioxidant status was increased in CKD on HD treatment and significantly decreased after the HD session; no variation between normal controls and CKD subjects on conservative therapy was observed. CONCLUSION: Several aspects derive from these data considering the role of oxidative stress in the cardiovascular events that accompany CKD.

Noninvasive high-frequency percussive ventilation in the prone position after lung transplantation.

Noninvasive positive-pressure ventilation (NIV), which represents a consolidated treatment of both acute and chronic respiratory failure, is increasingly being used to maintain spontaneous ventilation in lung transplant patients with impending pulmonary complications. Adding a noninvasive inspiratory support plus positive end-expiratory pressure (PEEP) has proven to be useful in preventing endotracheal mechanical ventilation, airway injury, and infections. Lung recipients with closure of the small airways in the dependent regions may also benefit from the prone position, which is helpful to promote recruitment of nonaerated alveoli and faster healing of consolidated atelectatic areas. In patients with localized or diffuse lung infiltrates, high-frequency percussive ventilation (HFPV), by either an invasive airway or a facial mask, has been adopted as an alternative ventilatory mode to enhance airway opening, limit potential respirator-associated lung injury, and improve mucus clearance. In nonintubated lung recipients at risk for volubarotrauma with conventional mechanical ventilation, it allows oxygen diffusion into the distal airways at lower mean airway pressures while avoiding repetitive cyclical opening and closing of the terminal airways. We summarize the clinical course of 3 patients with post-lung transplantation respiratory complications who were noninvasively ventilated with HFPV in the prone position. Major advantages of this treatment included gradual improvement of spontaneous clearance of bronchial secretions, significant attenuation of graft infiltrates and consolidations, a reduction in the number of bronchoscopies required, a decrease in spontaneous respiratory rate and work of breathing, and a significant improvement in gas exchange. The patients found HFPV with either standard facial mask or total mask interface to be comfortable or only mildly uncomfortable, and after the sessions they felt more restored. HFPV by facial mask in the prone position may be an interesting and attractive alternative to standard NIV, one that is more useful when implemented before full-blown respiratory failure is established.

Early tracheostomy following lung transplantation.

BACKGROUND: Despite the common use of tracheostomy in lung transplant (LT) patients, little data exist regarding the indications, timing, periprocedural complications, and impact on outcomes of the procedure. METHODS: We retrospectively analyzed some characteristics and timing of all tracheostomies performed in our lung transplant recipients during a 5-year period. RESULTS: Between January 2004 and November 2009, 31 of 126 lung transplant patients (24.6%) underwent a tracheostomy. They included 14 men with a mean age of 42 years (range, 10 to 61 years) and 17 women with a mean age of 45 years (range, 10 to 64 years). Twenty eight patients undergoing a tracheostomy had a prior bilateral sequential LT and 4 had accepted a single lung. Tracheostomy was surgically performed (ST) in 6 of 31 patients (19.3%); percutaneous tracheostomy (PT) techniques were applied for the other 25 (80.6%) cases. The decision to perform a tracheostomy was made within 4 days from LT in 21 of 31 patients (67.7%), within 8 days in 6 (19.3%) and after 10 days for the other 4 (12.9%) cases. There were no major complications during the PT procedures; no conversion to ST, no loss of airway, no paratracheal insertion, and no accidental tracheal extubation. No pneumothorax, pneumomediastinum, hypotension, hypoxemia, or arrythmyas were recorded in the early post-procedural period. The mean post-LT duration of cannulation was 17 days (range, 5 to 72 days). DISCUSSION: An early tracheostomy may be of considerable benefit for the debilitated patient who will likely require prolonged mechanical ventilation because of a complicated intraoperative course and poor recovery of graft function. PT was performed more quickly and was associated with fewer postoperative complications than ST. We recommend an aggressive strategy in the immediate posttransplant period when extubation fails or is delayed for various reasons.

A candidate redshift z ≈ 10 galaxy and rapid changes in that population at an age of 500 Myr.

Searches for very-high-redshift galaxies over the past decade have yielded a large sample of more than 6,000 galaxies existing just 900-2,000 million years (Myr) after the Big Bang (redshifts 6 > z > 3; ref. 1). The Hubble Ultra Deep Field (HUDF09) data have yielded the first reliable detections of z ≈ 8 galaxies that, together with reports of a γ-ray burst at z ≈ 8.2 (refs 10, 11), constitute the earliest objects reliably reported to date. Observations of z ≈ 7-8 galaxies suggest substantial star formation at z > 9-10 (refs 12, 13). Here we use the full two-year HUDF09 data to conduct an ultra-deep search for z ≈ 10 galaxies in the heart of the reionization epoch, only 500 Myr after the Big Bang. Not only do we find one possible z ≈ 10 galaxy candidate, but we show that, regardless of source detections, the star formation rate density is much smaller (∼10%) at this time than it is just ∼200 Myr later at z ≈ 8. This demonstrates how rapid galaxy build-up was at z ≈ 10, as galaxies increased in both luminosity density and volume density from z ≈ 10 to z ≈ 8. The 100-200 Myr before z ≈ 10 is clearly a crucial phase in the assembly of the earliest galaxies.