Prebiotic triose glycolysis promoted by co-catalytic proline and phosphate in neutral water.

Proline and phosphate promote a near-quantitative aldol reaction between glycolaldehyde phosphate and formaldehyde at neutral pH in water. Our results demonstrate the important role of general acid-base catalysis in water and underscore the essential role that amino acid catalysis may have played in early evolution of life's core metabolic pathways.

How can we improve embryo production and pregnancy outcomes of Holstein embryos produced in vitro? (12 years of practical results at a California dairy farm).

Genomic evaluations have revolutionized dairy cattle breeding, and the demand for embryos produced from very young heifers with high genetic merit has increased over time. The combination of low oocyte recovery, young age of donors, and milk production status can make the in vitro embryo production (IVP) of Holstein cattle incredibly challenging. Several factors need to be coordinated to obtain a live calf from an IVP embryo, but the quality of the oocyte at the start of the process is one of the key factors. Aspects related to oocyte quality, laboratory quality control, embryo quality and recipient selection are addressed here, based on the measures that the RuAnn Genetics Laboratory (Riverdale, California, USA) adopted in the last 12 years, with the goal of improving production of live, healthy calves from Holstein embryos. Follicular wave synchronization and stimulation with follicular stimulating hormone (FSH) is necessary to improve oocyte quality and consequently embryo production. Laboratory quality control and the use of high-quality supplies are essential to reduce variability in production and facilitate identification of other factors that might interfere with embryo production. High pregnancy rates can be achieved with good quality embryos selected at optimal time and stage of development, transferred by an experienced embryo transfer (ET) technician, to well managed recipients 7 or 8 days after estrus. Attention to detail at every step of the process is crucial to success.

Yicathins B and C and Analogues: Total Synthesis, Lipophilicity and Biological Activities.

Natural products have always been an important source of new hits and leads in drug discovery, with the marine environment being regarded as a significant source of novel and exquisite bioactive compounds. Yicathins B and C are two marine-derived xanthones that have shown antibacterial and antifungal activity. Herein, the total synthesis of these yicathins and six novel analogues is reported for the first time. As marine natural products tend to have very lipophilic scaffolds, the lipophilicity of yicathins and their analogues was evaluated in the classical octanol/water system and a biomimetic model-based system. As the xanthonic nucleus is a "privileged structure", other biological activities were evaluated, namely antitumor and anti-inflammatory activities. An interesting anti-inflammatory activity was identified for yicathin analogues that paves the way for the design of dual activity (anti-infective and anti-inflammatory) marine-inspired xanthone derivatives.

Structures, Activities and Drug-Likeness of Anti-Infective Xanthone Derivatives Isolated from the Marine Environment: A Review.

Marine organisms represent almost half of total biodiversity and are a very important source of new bioactive substances. Within the varied biological activities found in marine products, their antimicrobial activity is one of the most relevant. Infectious diseases are responsible for high levels of morbidity and mortality and many antimicrobials lose their effectiveness with time due to the development of resistance. These facts justify the high importance of finding new, effective and safe anti-infective agents. Among the variety of biological activities of marine xanthone derivatives, one that must be highlighted is their anti-infective properties. In this work, a literature review of marine xanthones with anti-infective activity, namely antibacterial, antifungal, antiparasitic and antiviral, is presented. Their structures, biological activity, sources and the methods used for bioactivity evaluation are described. The xanthone derivatives are grouped in three sets: xanthones, hydroxanthones and glycosylated derivatives. Moreover, molecular descriptors, biophysico-chemical properties, and pharmacokinetic parameters were calculated, and the chemical space occupied by marine xanthone derivatives is recognized. The chemical space was compared with marketed drugs and framed accordingly to the drug-likeness concept in order to profile the pharmacokinetic of anti-infective marine xanthone derivatives.

Synthesis, photochemical and in vitro cytotoxic evaluation of benzoselenazole-based aminosquaraines.

Squaraine dyes have recently attracted interest as potential second generation photosensitizers for photodynamic therapy. Several cationic aminosquaraine dyes bearing benzoselenazole terminal nuclei were synthezised and their cytotoxic activity was tested against four different human tumor cell lines - breast (MCF-7), non-small cell lung (NCI-H460), cervical (HeLa) and hepatocellular (HepG2) carcinomas - and against a non-tumor porcine liver primary cell line (PLP2), both in the absence of light and under irradiation. All dyes, which displayed strong absorption within the phototherapeutic window, were found to exhibit photodynamic activity and were shown to be, in most cases, more cytotoxic, both in the dark and upon irradiation, than their benzothiazole analogues.

Aminosquaraines as potential photodynamic agents: Synthesis and evaluation of in vitro cytotoxicity.

The synthesis of several aminosquaraine cationic dyes displaying strong absorption within the so-called phototherapeutic window (650-850nm) is described. Their cytotoxicity, under dark and illuminated conditions, was tested against several human tumor cell lines (breast, lung, cervical and hepatocellular carcinomas) and non-tumor porcine liver primary cells. All compounds showed to inhibit the growth of the tumor cells upon irradiation more than in the absence of light, in more or less extension, clearly exhibiting photodynamic activity. The photosensitizing ability against some cell lines, together with the low toxicity for the non-tumor primary PLP2 cells displayed by some of the compounds synthetized, turns them into potential candidates as photosensitizers for PDT.

Extraparenchymal neurocysticercosis in Albuquerque, New Mexico.

BACKGROUND: neurocysticercosis (NCC) prevalence is increasing throughout the United States mainly because of immigration from Latin America. Clinicians may fail to recognize the extraparenchymal disease because they do not consider the diagnosis. METHODS: to analyze neuroimaging and clinical characteristics of extraparenchymal NCC, we retrospectively reviewed all such cases presenting to a major general medical school hospital in the State of New Mexico. RESULTS: eleven (30%) of our 37 cases of NCC diagnosed using standard criteria from 1998 through 2004 had extraparenchymal disease. On neuroimaging, 36% of the patients lacked parenchymal cysts, 64% had intraventricular cysticerci, 64% had subarachnoid cysticerci, and 64% had hydrocephalus due to either basal arachnoiditis or direct obstruction of intraventricular pathways. Lumbar puncture was performed in 6 patients. All had a cerebrospinal fluid (CSF) pleocytosis, none had CSF or blood eosinophilia, and CSF antibody to NCC could be absent while present in serum. Response to treatment was frequently suboptimal. CONCLUSIONS: extraparenchymal NCC is more frequent than previously thought. Because clinicians outside the Southwest United States are often unfamiliar with NCC as a cause of chronic meningitis, chronic ventriculitis, or hydrocephalus without obvious cysts, the diagnosis of extraparenchymal NCC often depends on the correct interpretation of neuroimaging.

Ipsilesional trajectory control is related to contralesional arm paralysis after left hemisphere damage.

We have recently shown ipsilateral dynamic deficits in trajectory control are present in left hemisphere damaged (LHD) patients with paresis, as evidenced by impaired modulation of torque amplitude as response amplitude increases. The purpose of the current study is to determine if these ipsilateral deficits are more common with contralateral hemiparesis and greater damage to the motor system, as evidenced by structural imaging. Three groups of right-handed subjects (healthy controls, LHD stroke patients with and without upper extremity paresis) performed single-joint elbow movements of varying amplitudes with their left arm in the left hemispace. Only the paretic group demonstrated dynamic deficits characterized by decreased modulation of peak torque (reflected by peak acceleration changes) as response amplitude increased. These results could not be attributed to lesion volume or peak velocity as neither variable differed across the groups. However, the paretic group had damage to a larger number of areas within the motor system than the non-paretic group suggesting that such damage increases the probability of ipsilesional deficits in dynamic control for modulating torque amplitude after left hemisphere damage.

Functional magnetic resonance and spectroscopy in drug and substance abuse.

OBJECTIVES: Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) were utilized to evaluate functional and metabolic brain changes in drug abusers. METHODS: Functional neuroimaging studies in alcohol, cocaine, cigarette, and cannabis abusers were reviewed in the medical literature from 2000 to 2005. RESULTS: Brain activation with functional magnetic resonance imaging is different in drug abusers and may show more or less activation according to the task and gender. Lower concentrations of N-acetylaspartate and higher creatine are usually seen with 1H-MRS in the brains of cigarette smokers, people who are cocaine dependent, and alcohol abusers. CONCLUSIONS: Neural substrates of drug addition, craving, drug interaction, individual abstinence, and drug withdrawal can be studied with functional magnetic resonance imaging and proton magnetic resonance spectroscopy.

Neural correlates of telling lies: a functional magnetic resonance imaging study at 4 Tesla.

RATIONALE AND OBJECTIVE: Intentional deception (ie, lying) is a complex cognitive act, with important legal, moral, political, and economic implications. Prior studies have identified activation of discrete anterior frontal regions, such as the ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), dorsal medial prefrontal cortex (DMPFC), and anterior cingulate cortex (ACC) during deception. To extend these findings, we used novel real-time functional magnetic resonance imaging (fMRI) technology to simulate a polygraph experience in order to evoke performance anxiety about generating lies, and sought to ascertain the neural correlates of deception. MATERIALS AND METHODS: In this investigational fMRI study done with a 4-T scanner, we examined the neural correlates of lying in 14 healthy adult volunteers while they performed a modified card version of the Guilty Knowledge Test (GKT), with the understanding that their brain activity was being monitored in real time by the investigators conducting the study. The volunteers were instructed to attempt to generate Lies that would not evoke changes in their brain activity, and were told that their performance and brain responses were being closely monitored. RESULTS: Subjects reported performance anxiety during the task. Deceptive responses were specifically associated with activation of the VLPFC, DLPFC, DMPFC, and superior temporal sulcus. DISCUSSION: These findings suggest the involvement of discrete regions of the frontal cortex during lying, and that the neural substrates responsible for cognitive control of behavior may also be engaged during deception.

Proton magnetic resonance spectroscopy of brain tumors correlated with pathology.

RATIONALE AND OBJECTIVES: Evaluate proton magnetic resonance spectroscopy ((1)H-MRS) for assessing and grading brain tumors. MATERIALS AND METHODS: The research was done at Detroit Medical Center in a 1.5-T Siemens MR magnet using single-voxel or multivoxel MRS. This study consisted of 27 patients: 10 females and 17 males ages 22-83 years (average age 43.8). The data were recorded for three peaks-N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)-which were used to calculate the ratios Cho/NAA and Cho/Cr. RESULTS: Abnormal spectra were seen in 25 patients and normal spectra in 2. In 16 patients with brain astrocytoma of various grades, the pathology grading was correlated with Cho/NAA and Cho/Cr. These values were 6.53 and 3.35 for nine patients with Grade 4 astrocytoma; 1.85 and 1.62 for three patients with Grade 3 astrocytoma; 2.21 and 1.50 for three patients with Grade 2 astrocytoma; and 1.45 and 1.49 for one patient with Grade 1 astrocytoma. The remaining nine patients with abnormal spectra were also correlated with pathology. CONCLUSION: MRS ratios can be used to differentiate malignant and nonmalignant lesions from normal brain tissue. In general, high-grade astrocytoma have higher Cho/NAA and Cho/Cr ratios compared with low-grade astrocytoma.

Angiografia pela ressonância magnética nos aneurismas intracranianos: estudo comparativo com a angiografia cerebral / Magnetic resonance angiography of intracranial aneurysms: comparative study with cerebral angiography

Avaliamos por angiografia pela ressonância magnética e por angiografia cerebral 41 pacientes com 55 aneurismas intracranianos confirmados pela cirurgia. A angiorressonância detectou 52 aneurismas com sensibilidade de 94,5 por cento e a angiografia cerebral detectou 53 aneurismas com sensibilidade de 96,3 por cento. Pela näo invasibilidade, rapidez e baixo custo a angiorressonância poderá substituir a angiografia cerebral no diagnóstico de aneurismas intracranianos e no prognóstico da hemorragia subaracnóide

Neuroimagem estrutural na depressao de inicio tardio / Structural neuroimaging in the late onset depression

Serao discutidos os principais trabalhos que utilizaram a ressonancia magnetica estrutural na avaliacao de pacientes idosos deprimidos. As principais alteracoes relatadas foram no nivel dos ventriculos, ganglios basais, lobo frontal, lobo temporal e cerebelo...

Macroadenomas hipofisários: análise da ressonância magnética pré e pós-operatória em 20 casos / Pituitary adenomas: pre and postoperative MRI findings of 20 cases

Foram realizadas ressonâncias magnéticas (RM) pré e pós-operatórias em 20 pacientes com macro adenomas hipofisários (diâmetro variando entre 1,1 cm e 4,5 cm), que foram avaliados quanto aos achados normais (fisiológicos) e anormais, após a cirurgia transesfenoidal. As imagens foram obtidas a partir de aparelhos de 1,5 tesla, com cortes sagitais e coronais, antes e após a injeção de contraste paramagnético (gadopentato de dimeglumina). As alteraçöes fisiológicas encontradas após a cirurgia incluíram o material hemostático implantado ainda não reabsorvido, opacificaçöes do seio esfenoidal, reexpansão da glândula hipofisária e rebaixamento do quiasma óptico. O gelfoam implantado apareceu como imagem entra-selar, circular, com realce de contraste na periferia que, em estudos posteriores, diminuiu de tamanho. Os implantes de músculo e gordura apareceram como áreas de hipersinal, sendo o sinal do músculo menos intenso que o da gordura. Os tumores residuais foram diferenciados dos materiais implanados pela sua localização, características da intensidade dom sinal e padrão de realce.

Reavaliaçäo da secreçäo do hormônio do crescimento (GH) em pacientes com diagnóstico prévio de deficiência clássica de GH / Reavaluation of the growth hormone secretion in patients with diagnosis of classic GH deficiency

Reavaliamos a secreçäo de GH durante o teste da hipoglicemia induzida por insulina (ITT) em 32 pacientes (25 masculinos; IC de 4 a 20,6 anos) com diagnóstico de deficiência de GH "clássica"(DGH) baseado em dados auxológicos e laboratoriais. Todos eram pré-púberes e apresentaram pico de GH menor que 7,0 ng/ml em pelo menos dois testes de estímulo por ocasiäo do diagnóstico. A terapêutica com GH recombinante foi interrompida pelo menos 15 dias antes da reavaliaçäo. Pacientes com Tanner I de puberdade foram re-testados após a administraçäo de etinilestradiol (EE), 40mg/m2/dia por 2 dias. Pacientes com Tanner II e III foram reavaliados antes e após a administraçäo de EE. Pacientes com Tanner IV e V foram re-testados sem administraçao prévia de EE. Treze dos 32 pacientes (40,6 por cento) apresentaram normalizaçäo da resposta de GH na reavaliaçäo (pico de GH: 22,9+4,2 ng/ml; X+EP; variando de 7 a 52), sendo considerados como portadores de DGHt (DGH transitória). Os 19 pacientes restantes apresentaram diminuiçäo da secreçäo de GH na reavaliaçao (pico de GH: 1,3+0,2 ng/ml) em relaçao à época do diagnóstico (5,3 anos antes) e foram considerados como portadores de DGH permanente. Atrasos de idade óssea e velocidade de crescimento pré-tratamento näo foram diferentes entre ambos os grupos. Entretanto, o pico de GH durante o ITT realizado por ocasiäo do diagnóstico foi estatisticamente maior nos pacientes com DGHt comparado com aqueles com DGH permanente (3,8+0,4 ng/ml vs. 2,1+0,2 ng/ml, respectivamente). A ressonância magnéstica (RM) estava alterada em 14 de 15 pacientes com DGH permanente (13 com secçäo de haste hipofisária e um com ausência de sépto pelúcido), enquanto era normal em todos os sete com DGHt que realizaram este exame. Concluímos que a DGHt é freqüente em pacientes cujo diagnóstico de DGH "clássica"é feito durante o período pré-pubertário. Normalizaçäo da secreçäo de GH pode ocorrer durante a puberdade ou após a administraçäo de EE. Lesöes estruturais da regiäo hipotálamo-pituitária säo freqüentemente associadas com a DGH permanente.

Magnetic Resonance Imaging in Chronic Chagas' Disease: Correlation with Endomyocardial Biopsy Findings and Gallium-67 Cardiac Uptake.

BACKGROUND: We studied the correlation among cardiac magnetic resonance imaging (MRI), gallium-67 myocardial uptake, and right ventricular endomyocardial biopsy results in chronic Chagas' disease. To our knowledge, this represents the first attempt to correlate the histological findings with cardiac MRI and gallium-67 myocardial uptake for noninvasive diagnosis of inflammatory activity associated with Chagas' disease. METHODS: Ten male patients with cardiomyopathy secondary to Chagas' disease were studied (mean age, 47.7 +/- 7 years; congestive heart failure New York Heart Association [NYHA] functional class II [two patients], III [six patients], and IV [two patients]; and mean echocardiographic left ventricular [LV] ejection fraction [EF], 36 +/- 6%). The patients underwent right ventricular endomyocardial biopsy, cardiac MRI, and gallium-67 myocardial uptake testing. The results of this group were compared with those of a control group of patients with idiopathic dilated cardiomyopathy who were matched in age (mean age, 46 +/- 10 years), LV function (mean echocardiographic EF, 30 +/- 4%), and NYHA classification (one patient in class II, five patients in class III, and one patient in class IV). RESULTS: All patients with Chagas' disease showed higher signal intensity on MRI after the administration of gadolinium. The intensity of the septal signal changed from 0.90 +/- 0.11 to 1.56 +/- 0.19 (P < 0.001). In the control group, there was no difference in signal intensity with gadolinium (mean septal intensity, 0.94 +/- 0.12 before and 0.99 +/- 0.15 after; NS). On biopsy, eight chagasic patients had evident signs of myocarditis, and two patients had borderline evidence myocarditis. However, only one patient in the control group had a histological diagnosis of borderline myocarditis. Gallium-67 cardiac uptake was positive for myocardial inflammatory process in seven chagasic patients and borderline in one. On the other hand, only one patient in the control group had an uptake that was positive for inflammation, and one had a borderline result. CONCLUSIONS: In conclusion, the data from this study strongly suggest that myocarditis is frequently found in Chagas' disease. Cardiac MRI appears to be an accurate and alternative method for the diagnosis of inflammatory process associated with Chagas' disease.