Cortical-subcortical interactions in goal-directed behavior.

Flexibly selecting appropriate actions in response to complex, ever-changing environments requires both cortical and subcortical regions, which are typically described as participating in a strict hierarchy. In this traditional view, highly specialized subcortical circuits allow for efficient responses to salient stimuli, at the cost of adaptability and context specificity, which are attributed to the neocortex. Their interactions are often described as the cortex providing top-down command signals for subcortical structures to implement; however, as available technologies develop, studies increasingly demonstrate that behavior is represented by brainwide activity and that even subcortical structures contain early signals of choice, suggesting that behavioral functions emerge as a result of different regions interacting as truly collaborative networks. In this review, we discuss the field's evolving understanding of how cortical and subcortical regions in placental mammals interact cooperatively, not only via top-down cortical-subcortical inputs but through bottom-up interactions, especially via the thalamus. We describe our current understanding of the circuitry of both the cortex and two exemplar subcortical structures, the superior colliculus and striatum, to identify which information is prioritized by which regions. We then describe the functional circuits these regions form with one another, and the thalamus, to create parallel loops and complex networks for brainwide information flow. Finally, we challenge the classic view that functional modules are contained within specific brain regions; instead, we propose that certain regions prioritize specific types of information over others, but the subnetworks they form, defined by their anatomical connections and functional dynamics, are the basis of true specialization.

Histidine Self-assembly and Stability on Mineral Surfaces as a Model of Prebiotic Chemical Evolution: An Experimental and Computational Approach.

The abiotic synthesis of histidine under experimental prebiotic conditions has proven to be chemically promising and plausible. Within this context, the present results suggest that histidine amino acid may function as a simple prebiotic catalyst able to enhance amino acid polymerization. This work describes an experimental and computational approach to the self-assembly and stabilization of DL-histidine on mineral surfaces using antigorite ((Mg, Fe)3Si2O5(OH)4), pyrite (FeS2), and aragonite (CaCO3) as representative minerals of prebiotic scenarios, such as meteorites, and subaerial and submarine hydrothermal systems. Experimental results were obtained through polarized-light microscopy, IR spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC). Molecular dynamics was performed through computational simulations with the MM + method in HyperChem software. IR spectra suggest the presence of peptide bonds in the antigorite-histidine and aragonite-histidine assemblages with the presence of amide I and amide II vibration bands. The FTIR second derivative inspection supports this observation. Moreover, DSC data shows histidine stabilization in the presence of antigorite and aragonite by changes in histidine thermodynamic properties, particularly an increase in histidine decomposition temperature (272ºC in antigorite and 275ºC in aragonite). Results from molecular dynamics are consistent with DSC data, suggesting an antigorite-histidine closer interaction with decreased molecular distances (cca. 5.5 Å) between the amino acid and the crystal surface. On the whole, the experimental and computational outcomes support the role of mineral surfaces in prebiotic chemical evolution as enhancers of organic stability.

First molecular detection of Mycobacterium bovis in environmental samples from a French region with endemic bovine tuberculosis.

AIMS: The aim of the study was to determine the prevalence of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) in environmental matrices within a French region (Côte d'Or) affected by this zoonotic disease. METHODS AND RESULTS: We report here the development and the use of molecular detection assays based on qPCR (double fluorescent dye-labelled probe) to monitor the occurrence of Mycobacterium tuberculosis complex (MTBC) or Myco. bovis in environmental samples collected in pastures where infected cattle and wildlife had been reported. Three qPCR assays targeting members of the MTBC (IS1561' and Rv3866 loci) or Myco. bovis (RD4 locus) were developed or refined from existing assays. These tools were validated using Myco. bovis spiked soil, water and faeces samples. Environmental samples were detected positive for the presence of MTBC strains and Myco. bovis in the environment of bTB-infected farms in the Côte d'Or region. CONCLUSIONS: The development of molecular assays permitted testing of several types of environmental samples including spring water, sediment samples and soils from badger setts entrance located in the vicinity of these farms, which were repeatedly contaminated with Myco. bovis (up to 8·7 × 10(3) gene copies per gram of badger sett soil). For the first time, direct spoligotyping of soil DNA enabled identification of Myco. bovis genotypes from environmental matrices. SIGNIFICANCE AND IMPACT OF THE STUDY: All together, these results suggest that Myco. bovis occurs at low levels in environmental matrices in Côte d'Or within the bTB-infected area. Drinking contaminated water or inhaling contaminated bioaerosols might explain cattle infection in some cases.

Esophageal motor disorders in subjects with incidentally discovered Chagas disease: a study using high-resolution manometry and the Chicago classification.

In patients with chronic indeterminate Chagas disease, conventional manometry has shown that 25-48% had esophageal motor disorders. Recently, esophageal high-resolution manometry (HRM) has revolutionized the assessment of esophageal motor function. In this study, we performed esophageal HRM in a group of subjects with incidentally positive serological findings for Trypanosoma cruzi. In this prospective observational study, we evaluated subjects who had positive serological tests for Chagas disease detected during a screening evaluation for blood donation. All subjects underwent symptomatic evaluation and esophageal HRM with a 36 solid-state catheter. Esophageal abnormalities were classified using the Chicago classification. Forty-two healthy subjects (38 males) aged 18-61 years (mean age, 40.7 years) were included. When specific symptoms questionnaire was applied, 14 (33%) subjects had esophageal symptoms. Esophageal high-resolution manometry revealed that 28 (66%) of the subjects had an esophageal motility disorder according to the Chicago classification. Most common findings were hypocontractile disorders in 18 subjects (43%) and esophagogastric junction (EGJ) outflow obstruction in 6 (15%). Esophageal high-resolution manometry reveals that up to two thirds of the subjects with an incidental diagnosis of Chagas disease have esophageal abnormalities. This technology increases the detection and allows a more complete assessment of esophageal motor function in subjects infected with T. cruzi even in the early stages of the disease.

Ammonium depletion associated with the COVID-19 pandemic in the Mexican Caribbean.

The Mexican Caribbean contributes significantly to Mexico's gross national product. The number of tourists declined from 16.7 million in 2019 to 8.8 million in 2020 due to the COVID-19 pandemic, with a rapid recovery of 13.5 million in 2021. Wastewater discharge is the primary contamination source associated with the tourism sector's demand for goods and services. Water quality could improve due to fewer tourists arriving during the COVID-19 sanitary emergency. This study aimed to quantify ammonium concentrations at eleven locations to evaluate water quality during the sanitary restriction due to the pandemic in the Mexican Caribbean. The ammonium concentrations were 85 % (Nov-2019), 89 % (Feb-2020), and 86 % (Feb-2021) higher than in Nov-2020, where six of the eleven sampled stations were below the detection limit (0.15 µM). Lower ammonium concentrations coincide with the sanitary restriction period and a decrease in affluent tourists.

Potential of ceragenin CSA-13 and its mixture with pluronic F-127 as treatment of topical bacterial infections.

AIMS: Ceragenin CSA-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA-13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127. METHODS AND RESULTS: CSA-13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F-127, CSA-13 antibacterial activity was only slightly decreased, but CSA-13 haemolytic activity was significantly inhibited. CSA-13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (-) bacteria. CSA-13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA-13, determined by the use of a standard checkerboard assay, reveals an increase in CSA-13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL-37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA). CONCLUSION: These results suggest that CSA-13 may be useful to prevent and treat topical infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.

Three-dimensional microscale hanging drop arrays with geometric control for drug screening and live tissue imaging.

Existing three-dimensional (3D) culture techniques are limited by trade-offs between throughput, capacity for high-resolution imaging in living state, and geometric control. Here, we introduce a modular microscale hanging drop culture where simple design elements allow high replicates for drug screening, direct on-chip real-time or high-resolution confocal microscopy, and geometric control in 3D. Thousands of spheroids can be formed on our microchip in a single step and without any selective pressure from specific matrices. Microchip cultures from human LN229 glioblastoma and patient-derived mouse xenograft cells retained genomic alterations of originating tumors based on mate pair sequencing. We measured response to drugs over time with real-time microscopy on-chip. Last, by engineering droplets to form predetermined geometric shapes, we were able to manipulate the geometry of cultured cell masses. These outcomes can enable broad applications in advancing personalized medicine for cancer and drug discovery, tissue engineering, and stem cell research.

Distinct prefrontal top-down circuits differentially modulate sensorimotor behavior.

Sensorimotor behaviors require processing of behaviorally relevant sensory cues and the ability to select appropriate responses from a vast behavioral repertoire. Modulation by the prefrontal cortex (PFC) is thought to be key for both processes, but the precise role of specific circuits remains unclear. We examined the sensorimotor function of anatomically distinct outputs from a subdivision of the mouse PFC, the anterior cingulate cortex (ACC). Using a visually guided two-choice behavioral paradigm with multiple cue-response mappings, we dissociated the sensory and motor response components of sensorimotor control. Projection-specific two-photon calcium imaging and optogenetic manipulations show that ACC outputs to the superior colliculus, a key midbrain structure for response selection, principally coordinate specific motor responses. Importantly, ACC outputs exert control by reducing the innate response bias of the superior colliculus. In contrast, ACC outputs to the visual cortex facilitate sensory processing of visual cues. Our results ascribe motor and sensory roles to ACC projections to the superior colliculus and the visual cortex and demonstrate for the first time a circuit motif for PFC function wherein anatomically non-overlapping output pathways coordinate complementary but distinct aspects of visual sensorimotor behavior.

Compression stiffening in biological tissues: On the possibility of classic elasticity origins.

Compression stiffening, or an increase in shear modulus with increasing compressive strain, has been observed in recent rheometry experiments on brain, liver, and fat tissues. Here we extend the known types of biomaterials exhibiting this phenomenon to include agarose gel and fruit flesh. The data reveal a linear relationship between shear storage modulus and uniaxial prestress, even up to 40% strain in some cases. We focus on this less-familiar linear relationship to show that two different results from classic elasticity theory can account for the phenomenon of linear compression stiffening. One result is due to Barron and Klein, extended here to the relevant geometry and prestresses; the other is due to Birch. For incompressible materials, there are no adjustable parameters in either theory. Which one applies to a given situation is a matter of reference state, suggesting that the reference state is determined by the tendency of the material to develop, or not develop, axial stress (in excess of the applied prestress) when subjected to torsion at constant axial strain. Our experiments and analysis also strengthen the notion that seemingly distinct animal and plant tissues can have mechanically similar behavior at the quantitative level under certain conditions.

Behavioral effects of Bj-PRO-7a, a proline-rich oligopeptide from Bothrops jararaca venom.

The heptapeptide Bj-PRO-7a, isolated and identified from Bothrops jararaca (Bj) venom, produces antihypertensive and other cardiovascular effects that are independent on angiotensin converting enzyme inhibition, possibly relying on cholinergic muscarinic receptors subtype 1 (M1R). However, whether Bj-PRO-7a acts upon the central nervous system and modifies behavior is yet to be determined. Therefore, the aims of this study were: i) to assess the effects of acute administration of Bj-PRO-7a upon behavior; ii) to reveal mechanisms involved in the effects of Bj-PRO-7a upon locomotion/exploration, anxiety, and depression-like behaviors. For this purpose, adult male Wistar (WT, wild type) and spontaneous hypertensive rats (SHR) received intraperitoneal injections of vehicle (0.9% NaCl), diazepam (2 mg/kg), imipramine (15 mg/kg), Bj-PRO-7a (71, 213 or 426 nmol/kg), pirenzepine (852 nmol/kg), α-methyl-DL-tyrosine (200 mg/kg), or chlorpromazine (2 mg/kg), and underwent elevated plus maze, open field, and forced swimming tests. The heptapeptide promoted anxiolytic and antidepressant-like effects and increased locomotion/exploration. These effects of Bj-PRO-7a seem to be dependent on M1R activation and dopaminergic receptors and rely on catecholaminergic pathways.

Toward the improvement of total nitrogen deposition budgets in the United States.

Frameworks for limiting ecosystem exposure to excess nutrients and acidity require accurate and complete deposition budgets of reactive nitrogen (Nr). While much progress has been made in developing total Nr deposition budgets for the U.S., current budgets remain limited by key data and knowledge gaps. Analysis of National Atmospheric Deposition Program Total Deposition (NADP/TDep) data illustrates several aspects of current Nr deposition that motivate additional research. Averaged across the continental U.S., dry deposition contributes slightly more (55%) to total deposition than wet deposition and is the dominant process (>90%) over broad areas of the Southwest and other arid regions of the West. Lack of dry deposition measurements imposes a reliance on models, resulting in a much higher degree of uncertainty relative to wet deposition which is routinely measured. As nitrogen oxide (NOx) emissions continue to decline, reduced forms of inorganic nitrogen (NHx = NH3 + NH4+) now contribute >50% of total Nr deposition over large areas of the U.S. Expanded monitoring and additional process-level research are needed to better understand NHx deposition, its contribution to total Nr deposition budgets, and the processes by which reduced N deposits to ecosystems. Urban and suburban areas are hotspots where routine monitoring of oxidized and reduced Nr deposition is needed. Finally, deposition budgets have incomplete information about the speciation of atmospheric nitrogen; monitoring networks do not capture important forms of Nr such as organic nitrogen. Building on these themes, we detail the state of the science of Nr deposition budgets in the U.S. and highlight research priorities to improve deposition budgets in terms of monitoring and flux measurements, leaf- to regional-scale modeling, source apportionment, and characterization of deposition trends and patterns.

The influence of glutathione modulators on the course of Leishmania major infection in susceptible and resistant mice.

Glutathione (GSH) has an important dual role in parasite-host relationship in Leishmania major infection. Our previous studies showed that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in the protection of Leishmania against the toxic effect of nitrogen-derived reactive species. On the other hand, GSH also is very important to the modulation of the effective immune response, inducting NO production and leishmanicidal activity of macrophages. In the present study, we investigated the role of host GSH during the course of L. major infection, analysing the size of footpad lesions and parasite load from mice treated with two GSH modulators, N-acethyl-l-cysteine (NAC) and buthionine sulphoximine (BSO). Resistant mice treated with BSO, which depletes GSH develop exacerbated lesions, but only harbour higher parasite load in their lesions 2 weeks post-infection. Although the NAC treatment does not affect the footpad lesions development in susceptible BALB/c mice, it significantly reduced the tissue parasitism in the lesions throughout the course of infection. Interestingly, the treatment with BSO did not change the course of L. major infection on susceptible mice when compared with nontreated mice. These results suggest that GSH is an important antioxidant modulator during anti-Leishmania immune response in vivo.

[Postoperative functional angular anatomy in patients with anterior cruciate ligament with autologous graft]. / Anatomía angular funcional postquirúrgica en pacientes con sustitución del ligamento cruzado anterior con injerto autólogo.

BACKGROUND: Reconstruction of the anterior cruciate ligament (ACL) aims to restore the original anatomy. The clinical outcome could be imperfect when graft placement is not in an anatomical position; moreover, the conventional transtibial reconstruction of the ACL often locates the graft away from the anatomical site, leading to abnormal biomechanical behavior and kinematics of the knee. The objective of this work was to assess the importance of the angular reconstruction of the anterior cruciate ligament during arthroscopic replacement and to compare the postoperative functional results. MATERIAL AND METHODS: We studied 21 patients to whom the IKDC 2000 form of objective and subjective evaluation was applied; radiographic evaluation in anteroposterior and lateral bending at 30o. We made an statistical analysis with Pearson P, correlating the anteroposterior and lateral angulation of the graft direction and the subjective projection of the operated knee function, as well as age and time of evolution with the operated knee. RESULTS: We included 21 patients of 18 to 56 years of age; follow-up: one to three years. Objective evaluation: 95.24% normal and 4.76% almost normal. Subjective assessment: average 84.31% (range 70.93 to 97.99%), CI 95%. AP angle: 68.8o, range: 62o to 77o. Average sagittal angle: 64.9o, range: 58o to 75o. Correlations: AP angle and subjective function -0.19, angle in sagittal and subjective function -0.54, age and subjective function -0.77, duration and subjective function -0.74. Function average: 84.31%. DISCUSSION: The anatomical angular reconstruction of the ACL graft is key to the stability of the knee; the evaluated patients got a more similar direction to that of the native ACL, better stability and knee function.

ANTECEDENTES: La reconstrucción del ligamento cruzado anterior (LCA) tiene como objetivo la restauración de la anatomía original. El resultado clínico puede ser imperfecto cuando la colocación del injerto no se encuentra en una posición anatómica; además, la reconstrucción del LCA transtibial convencional que a menudo localiza el injerto lejos de la ubicación anatómica conduce a un comportamiento biomecánico y cinemática anormal de la rodilla. El objetivo de este trabajo fue comprobar la importancia de la reconstrucción angular del ligamento cruzado anterior durante la sustitución artroscópica y compararla con los resultados funcionales postquirúrgicos. MATERIAL Y MÉTODOS: Se estudiaron 21 pacientes; se aplicó formulario IKDC 2000 de valoración objetiva y subjetiva; evaluación radiográfica en proyección anteroposterior y lateral a 30o de flexión. Se realizó análisis estadístico con P de Pearson, correlacionando la angulación en proyección anteroposterior y lateral de la dirección del injerto y la función subjetiva de la rodilla intervenida, así como la edad y el tiempo de evolución con la función subjetiva de la rodilla intervenida. RESULTADOS: Fueron 21 pacientes de 18 a 56 años, tiempo de seguimiento: de uno a tres años. Evaluación objetiva: 95.24% normales y 4.76% casi normales. Valoración subjetiva promedio: 84.31% (rango: de 70.93 a 97.99%), IC 95%. Ángulo AP: 68.8o, rango: de 62o a 77o. Ángulo sagital promedio: 64.9o, rango: de 58o a 75o. CORRELACIONES: ángulo en AP y función subjetiva -0.19, ángulo en sagital y función subjetiva -0.54, edad y función subjetiva -0.77, tiempo de evolución y función subjetiva -0.74. DISCUSIÓN: La reconstrucción angular anatómica del injerto LCA es punto clave para la estabilidad de la rodilla, los pacientes estudiados obtuvieron una dirección más parecida a la del LCA nativo, mejores resultados de estabilidad y función de la rodilla.

Endocarditis bacteriana a propósito de un caso / Bacterial endocarditis case report

OBJETIVO: informar acerca de un caso de endocarditis bacteriana. Paciente varón de 34 años de edad, con único antecedente de rinitis alérgica con tratamiento irregular. Él es procedente de Valparaiso Chile, se encuentra en sus vacaciones en la ciudad de La Paz, acude al servicio de medicina interna ­ emergencias, con clínica compatible con edema agudo de pulmón de la altura y edema cerebral de la altura, asociado a sepsis de foco pulmonar, que progresa a choque séptico, durante su internación intercurre con alzas térmicas continuas, asociado a hallazgo ecocardiográfico de vegetación en ventrículo derecho con hemocultivo positivo, por lo que se llega al diagnóstico de endocarditis bacteriana, se realizó el tratamiento correspondiente, y resolución del cuadro.

OBJECTIVE: to report a case of bacterial endocarditis A 34-year-old male patient with a unique history of allergic rhinitis with irregular treatment. He comes from Valparaiso Chile, is on vacation in the city of La Paz, goes to the service of internal medicine - emergencies with compatible clinical with acute pulmonary edema of height and cerebral edema of height, associated with sepsis of focus pulmonary disease, which progresses to septic shock, during internment with continuous hyperthermia, associated vegetation in right ventricle for echocardiography, also positive blood culture, so that a diagnosis of bacterial endocarditis is reached, Corresponding treatment was carried out, and resolution of pathology..

Associating high intensity and modulated frequency of TENS delays analgesic tolerance in rats.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive analgesic resource extensively used in painful conditions. However, preclinical studies suggest that the prolonged use of TENS results in the development of tolerance to its analgesic effect. The present study investigated the analgesic effect and development of tolerance to TENS with four different stimulation protocols. METHODS: Male Wistar rats induced with joint inflammation were divided into four groups: sensory intensity, low motor intensity, high motor intensity and sham groups. TENS was applied daily for 20 min with alternating frequency between 4 and 100 Hz until tolerance development was evidenced. Mechanical hyperalgesia was measured before and after each TENS daily application. RESULTS: After TENS, tolerance was evidenced There was a significant reduction in the mechanical withdrawal threshold in all groups 24 h after induction of inflammation (p < 0.01). We observed a loss of analgesic efficacy of TENS around the 12th, 19th and 19th days in the groups treated with sensory intensity, low motor intensity and high motor intensity, respectively (p < 0.02) when analysed using paired measurements and compared with the control. CONCLUSIONS: The association between frequency variation and intensity at motor level promotes a delay in the development of analgesic tolerance to TENS, optimizing and extending its therapeutic effectiveness.

Effect of active and passive immunization with luteinizing hormone-releasing hormone on serum luteinizing hormone and follicle-stimulating hormone levels and the ultrastructure of the pituitary gonadotrophs in castrated male rats.

The effect of active and passive immunization with luteinizing hormone-releasing hormone (LHRH) on serum LH and follicle-stimulating hormone (FSH) levels and the ultrastructure of the pituitary gonadotrophs was investigated in castrated male rats. Two weeks after castration, the animals were immunized with Glu1-LHRH conjugated with human serum albumin (hSA), immunized with hSA only, or left uninjected. Immunogens were administered every 2 weeks. Four weeks after the initiation of immunization with hSA-Glu1-LHRH, 2 out of 4 rats showed parallel decreases in serum LH and FSH levels associated with a rise of serum antibody titer to LHRH. Serum LH and FSH levels remained suppressed throughout the experiment in these rats. On the other hand, both LH and FSH levels in hSA-immunized rats or non-immunized rats remained elevated, and typical castration cells containing large vacuoles were found in the pituitary. Although castration cells existed in the pituitary of rats which produced antibody to LHRH by active immunization, these cells were markedly degranulated, and secretory granules were scarce in the cytoplasm. In another experiment, rats were injected iv with one ml sheep anti-LHRH gamma-globulin (anti-LHRH) or normal sheep gamma-globulin (NSG) every 2 days for 3 weeks, starting one day after castration, when serum LH and FSH levels were already elevated. All the animals which received anti-LHRH showed a decrease in both serum LH and FSH levels, which remained low throughout the study, in a range comparable to those in intact normal male rats. On the other hand, in the animals which received NSG, both LH and FSH levels remained high or increased further throughout the experiment, and the pituitary contained numerous castration cells. Castration cells were completely absent from the pituitaries of rats treated with anti-LHRH, suggesting that castration cells are formed as a result of increased secretion of LHRH. Some FSH gonadotrophs in these castrated rats were atrophic. It was difficult to distinguish the LH gonadotrophs in rats which were either actively or passively immunized with LHRH; however, they seem not to have contributed significantly to the development of castration cells. In any case, antibody to the LHRH decapeptide drastically affected both LH and FSH cells, providing additional evidence for the concept that LHRH represents the physiological LHRH and FSHRH.

Effect of administration of anti-serum to luteinizing hormone-releasing hormone on gonadal function during the estrous cycle in the hamster.

One-half ml of sheep-anti-LHRH-serum (No. 772) completely blocked ovulation when administered iv or sc at any stage of the estrous cycle in cycling hamsters. This anti-ovulatory activity lasted 12-13 days. The minimal effective iv dose (MED) of the anti-LHRH serum for completely blocking the preovulatory LH surge and ovulation when administered at 1200 h on proestrus was 0.2 ml. Injection of LHRH on the afternoon of P (proestrus) induced ovulation in the antiserum-treated hamsters when the antiserum was injected on P, but not when injected on D1 (diestrus 1) or D2 (diestrus 2). This suggests that the anti-LHRH serum acts differently in blocking ovulation during D and P, by suppressing follicular development and inhibiting preovulatory surge of gonadotropins, respectively. Serum estradiol levels, measured by radioimmunoassay, were significantly reduced but not completely suppressed after injection of 0.5 ml of anti-LHRH-serum. Histological examinations of the ovaries revealed that an arrest of follicular maturation resulted 3 days after antiserum injection. 17-beta-Estradiol administered 22 h before the presumptive preovulatory LH surge improved significantly (P less than 0.05) the LH response to LHRH in the antiserum-blocked hamsters. This suggests a direct modulation of pituitary LH responsiveness by estradiol in the absence of endogenous LHRH activity. When the integrated levels of serum LH following an injection of a minimum effective dose of exogenous LHRH to induce full ovulation in anti-serum-blocked hamsters were compared with those during the physiological preovulatory LH surge, it was found that only 11% of the amount of LH released on the afternoon of proestrus was sufficient for inducing full ovulation.

Termination of pregnancy by sheep anti-LHRH gamma globulin in rats.

The effect of the administration of sheep anti-LHRH gamma-globulin (anti-LHRHG) on the maintenance of pregnancy was investigated in rats. Nidation was confirmed by laparotomy on day 7 or 8 of pregnancy. In one experiment, rats were then injected iv with 1 ml anti-LHRHG or normal sheep gamma-globulin (NSG) daily from days 7 to 11. The uteri were inspected again on day 14 of pregnancy, when it was found that complete resorption of the fetuses had occurred in the anti-LHRHG-treated rats, but that the fetuses were normal in the NSG-treated control rats. The effect of a single injection of 1 ml of anti-LHRHG on day 7, 8, 9, 10, 11, or 12 of pregnancy was also investigated. Administration on day 9 or 10 resulted in complete resorption of the fetuses by the time of the 2nd inspection on day 14, and treatment on day 8 or 11 was partially effective. However, treatment on day 7 or 12 exerted little effect on viability of the fetuses. None of the rats showed vaginal bleeding following treatment with anti-LHRHG. Termination of pregnancy by anti-LHRHG could be prevented by SC injection of 1 mug LHRH twice daily, or by 4 progesterone SC once daily, from days 9 through 12 of pregnancy. The ovaries of the rats treated with anti-LHRHG from days 7 to 11 were smaller than those of the NSG-treated control rats, and some of the corpora lutea underwent cystic degenerative changes. Lutein cells of the former were also smaller than those of the latter. Serum progesterone levels were reduced after a single injection of anti-LHRHG on day 9 or 10, but not on day 7 or 12 of pregnancy. There was excellent agreement between the reduction of serum progesterone and fetal resorption. Serum LH levels were low on days 7 through 12 in the anti-LHRHG-treated as well as the NSG-treated rats, and the possible suppressive effect of anti-LHRHG on LH could not be revealed because of insufficient sensitivity of the radioimmunoassay method. No significant difference was observed in serum prolactin levels between the groups of rats. The results clearly indicate that LHRH, by maintaining progesterone secretion, is indispensable on days 9 and 10 of pregnancy for the maintenance of pregnancy.

NAD(P)H:quinone oxidoreductase activity is increased in hippocampal pyramidal neurons of patients with Aalzheimer's disease.

NAD(P)H:quinone oxidoreductase (QR) catalyzes the two-electron reduction of quinones, preventing their participation in redox cycling and subsequent generation of reactive oxygen species. Pretreatment of neuroblastoma cells with compounds, such as tert-butylhydroquinone and dimethyl fumarate, that increase QR expression protect cells from oxidative stress-induced cell death by glutamate, H(2)O(2,) and dopamine. The potential neuroprotective role of QR as well as the evidence for oxidative stress-induced neuronal cell death in Alzheimer's disease (AD) led us to examine the expression pattern of QR from AD and control patients. Histochemical staining of hippocampal sections from AD patients revealed QR activity in pyramidal neurons. The presence of QR protein in these neurons also was confirmed by immunoreactivity. In control patients, hippocampal pyramidal neurons were negative for both QR enzymatic activity and QR immunoreactivity. In addition, the QR positive neurons of AD patients were selectively located in areas where neuronal populations exhibited tau immunostaining. Our data demonstrate that QR is up-regulated in hippocampal pyramidal neurons of AD patients. We hypothesize that this is part of a neuroprotective system up-regulated in response to the AD process. Understanding this system may lead to further insights into the pathogenesis and potential new avenues of treatment for AD.

Measles outbreaks in Micronesia, 1991 to 1994.

BACKGROUND: Several islands in Micronesia experienced large measles outbreaks, during 1991 through 1994. Except for Guam, none of the islands had reported measles outbreaks during the previous 20 years. METHODS: To characterize the outbreaks, measles surveillance data, hospital records and death certificates were reviewed. Preoutbreak vaccination coverage rates were assessed by reviewing public health vaccination records. Viral isolates were genetically sequenced to determine the source of transmission. Linear regression analysis was performed to assess the effectiveness of outbreak control measures. RESULTS: Between 1991 and 1994 more than 1300 measles cases and 16 measles-related deaths were reported in Micronesia. Preoutbreak vaccination coverage rates among 2-year-old children were 55 to 94%. Genetic sequencing of the viral isolates and epidemiologic investigations suggested transmission between islands and new importations from outside of Micronesia. The highest attack rates were among children ages < 5 years (20/1000) and 10 to 19 years (38/1000). Compared with attack rates among children ages < 1 and 10 to 19 years, attack rates were lower among those ages 5 to 9 years, in whom 2-dose vaccination coverage rates were highest (P < 0.001). Early and rapid implementation of mass vaccination campaigns was significantly associated with shorter duration of outbreaks (P = 0.049). CONCLUSION: The measles outbreaks in Micronesia show that island populations may be highly susceptible to measles. High two-dose vaccination coverage levels must be maintained to prevent such outbreaks. Early and rapidly implemented mass measles vaccination campaigns were effective in control of island outbreaks. Strengthening public health infrastructure and surveillance is necessary for early identification of outbreaks and rapid implementation of mass campaigns.