Welfare-maximizing transmission capacity expansion under uncertainty.

We apply the JuDGE optimization package to a multistage stochastic leader-follower model that determines a transmission capacity expansion plan to maximize expected social welfare of consumers and producers who act as Cournot oligopolists in each time period. The problem is formulated as a large-scale mixed integer programme and applied to a 5-bus instance over scenario trees of varying size. The computational effort required by JuDGE is compared with solving the deterministic equivalent mixed integer programme using a state-of-the-art integer programming package. This article is part of the theme issue 'The mathematics of energy systems'.

Afecciones cutáneas en trabajadores con empleos de subsistencia y su relación con factores socioambientales y laborales. Medellín, Colombia / Skin conditions in workers with subsistence jobs and related socio-environmental and labor factors. Medellin Colombia

Introducción: La información acerca de lesiones en piel y sus factores asociados, en trabajadores informales en América Latina y el Caribe aun es escasa. Objetivo: Determinar la relación existente entre las condiciones sociodemográficas, ambientales, laborales y la prevalencia de afecciones en la piel auto-reportada por trabajadores informales “venteros” del centro de Medellín. Material y Métodos: Estudio transversal con intención analítica y fuente primaria de información. Se incluyeron 686 trabajadores. Se aplicó encuesta asistida, previa realización de prueba piloto y estandarización de los encuestadores. Variable dependiente; prevalencia de afecciones en piel. Variables independientes; condiciones laborales, sociodemográficas y ambientales. Se realizó control de errores con análisis estadísticos y sesgos de selección e información. Se realizaron análisis univariado, bivariado y multivariado. Resultados: Trabajadores fundamentalmente hombres (57.6%), edades entre 45-59 años, 60,0% procedente de zona rural. Trabajaban > 8 horas/día (80,6%), toda la semana, con > 20 años (50,7%) en su labor. El 72,2% no utilizaba mecanismos de protección personal. 61,5% consideraba que la contaminación ambiental afectaba su labor y su salud. 19,83% presentó afectaciones cutáneas, como; alergias (12,0%), prurito y sarpullido. Menor prevalencia de alergias en hombres (24,0%) y ≥ 60 años. Mayores prevalencias en quienes laboraban >8 horas/día (94,0%), toda la semana (43,0%), con exposición a sustancias químicas (RP=1,88.IC=1,11;3,20), vendedores de mercancía y cacharro (RP =2,06.IC: 1,08;3,91). Conclusión: Explican mayor prevalencia de alergias proceder de la zona urbana, vender mercancía y cacharro, trabajar >8 horas/día, toda la semana, exponerse a sustancias químicas, considerar que la calidad del aire afecta su labor, y presentar comorbilidades (AU)

Introduction: The information on skin lesions and their associated factors in informal workers in Latin America is scarce. Objective: To determine the existing relationship between sociodemographic, environmental and labor conditions and the prevalence of skin conditions, self-reported by informal workers “venteros” from the Medellin downtown. Material and Methods: Cross-sectional study with analytical intention and primary source of information. 686 workers were included. An assisted survey was applied, after conducting a pilot test and standardization of the interviewers. The presence of skin conditions was considered as the dependent variable and the working, sociodemographic and environmental conditions as independent variables. Error control was performed with statistical analysis, selection and information biases were controlled. Univariate and bivariate analysis was performed. Results: Mainly male workers (57.6%), ages 45-59 years, 60.0% from rural areas. They worked> 8 hours / day (80.6%), all week, with> 20 years (50.7%) in their work. 72.2% did not use personal protection mechanisms. 61.5% considered that environmental pollution affected their work and their health. 19.83% presented skin affectations, such as allergies (12.0%), pruritus and rash. Lower prevalence of allergies in men (24.0%) and ≥60 years. Higher prevalences in those who worked> 8 hours / day (94.0%), all week (43.0%), with exposure to chemical substances (PR = 1.88, IC = 1.11, 3.20), sellers of merchandise and equipment (PR = 2.06.IC: 1.08; 3.91). Conclusion: They explain a higher prevalence of allergies coming from the urban area, selling merchandise and junk, working> 8 hours / day, all week, being exposed to chemical substances, considering that air quality affects their work, and presenting comorbidities (AU)

First-line tuberculosis treatment with double-dose rifampicin is well tolerated.

OBJECTIVE: To compare the occurrence of unfavourable treatment and safety outcomes of double-dose rifampicin (RMP; 20 mg/kg/d, intervention) with standard dose (10 mg/kg/d, control) in a first-line tuberculosis (TB) treatment regimen for smear-positive TB patients in Bangladesh.DESIGN: This was a randomised clinical trial. The primary efficacy and safety endpoints were the occurrence of an unfavourable treatment outcome (death, failure, relapse or loss to follow-up) and the occurrence of any serious drug-related adverse event (SAE).RESULTS: In primary efficacy analysis, among 343 control and 347 intervention patients, respectively 15.5% and 11.8% had an unfavourable outcome. In safety analysis, among 349 intervention and 352 control patients, respectively 4.3% and 2.6% experienced an SAE. These differences were not significant. There was a significantly lower occurrence of SAEs, explained by a lower occurrence of hepatic toxicity, in a RMP double-dosed but erroneously HZE (isoniazid+pyrazinamide+ethambutol) under-dosed subgroup.CONCLUSIONS: Our findings show that there is no statistically significant difference in terms of efficacy and safety between standard and double-dose RMP. An accidental finding (related to dosage levels of the standard regimen) suggests that high-dose RMP is potentially a lesser cause of hepatotoxicity. Larger trials with more power, or trials with at least a triple-dose might be needed to clearly see the effect of high-dose RMP on unfavourable outcomes.

Pullout strength of a novel hybrid fixation technique (Tape Locking Screw™) in soft-tissue ACL reconstruction: A biomechanical study in human and porcine bone.

INTRODUCTION: A novel hybrid anterior cruciate ligament (ACL) reconstruction technique known as Tape Locking Screw™ (TLS) is gaining popularity. Utilizing a suspension-type construct in conjunction with an interference screw, this technique has demonstrated successful initial clinical results with the use of quadruple hamstring graft. However, there is currently limited data available on the biomechanical strength of this fixation. This study investigates the pullout strength of the construct in human distal femora as well as in a porcine model. The construct is tested in isolation, without the use of any graft. We hypothesized that the pullout strength of this construct would be similar to or better than current fixation systems available. MATERIALS AND METHODS: The Tape Locking Screw hybrid fixation system was implanted into twenty-two fresh frozen human distal femora (50-89 years old) randomized to 10×20mm titanium or polyether ether ketone (PEEK) screws by a single sports fellowship trained orthopedic surgeon. Given that the graft is secured to polyethylene terephthalate tape within the construct, the construct was implanted without any graft in order to isolate the device for biomechanical testing. After implantation, a tensile force was applied directly to the loop of tape at a loading rate of 5mm/min using an electromechanical testing system. The failure load was calculated from the resultant load-displacement curve. Specimens were then visually examined for mode of failure. Similar biomechanical tests were performed on sixteen porcine femora. RESULTS: In the human model, the mean pullout strength was 523±269N with the PEEK screw and 578±245N with the titanium screw. In the porcine femur model, mean strength was 616±177N with PEEK, 584±245N with titanium. There was no statistically significant difference in failure loads between these four groups. Tape slippage at the screw bone interface was the primary mode of failure in all the groups tested. DISCUSSION: Our results demonstrate that the hybrid technique provides excellent pullout strength in comparison to other soft-tissue ACL fixation methods, with tape slippage being the mode of failure in all specimens tested. This data, in addition to the advantages of the TLS system, support its consideration in the armamentarium of constructs available for soft-tissue ACL reconstruction. LEVEL OF EVIDENCE: Laboratory controlled study level 2.

Ser viejo en Colombia tiene su costo laboral / Being old in Colombia has its labor costs / Ser velho na Colômbia tem seu custo trabalhista

Introducción: hacer una revisión sobre el tema del sistema social y económico;sistema en el cual se privilegia la belleza y la juventud por encima de la experiencia y los conocimientos.Métodos: se realizó una revisión bibliográfica de algunos autores que abordan la situación laboral del adulto mayor. Resultados: las sociedades actuales discriminan a los adultos mayores desconociendo su experiencia, sabiduría y el conocimiento acumulado a lo largo de los años. El crecimiento de la población adulta mayor y de la económicamente activa, posibilita el envejecimiento de la fuerza de trabajo que podría afectar el incremento económico y el funcionamiento del mercado laboral; por ello tradicionalmente se espera que las personas mayores dejen su sitio de trabajo a las poblaciones más jóvenes.Conclusiones: la edad tiene un alto costo en el sistema laboral y productivocolombiano, asumido por los adultos mayores e ignorado por el Estado.

Objective: to do a revision on the subject of the social and economic system; System in which youth and beauty are privileged and considered above all experience and knowledge. Materials and methods: a bibliographic revision of some authors that have addressed the subject of the work situation of an older adult was conducted. Results: today’s societies discriminate against older adults, failing to recognize their experience, knowledge and wisdom that have been gathered throughout the years. The growth of the older adult population and that of the economically active makes it possible for the work force to grow older, which could affect the economic growth and the correct functioning of the work force; for this reason, older people are expected to leave their work for the younger populations. Conclusions: age has a high cost in the productive work force in Colombia, assumed by the older adults and ignored by the State.

Objetivo: fazer uma revisão sobre o sistema social e econômico, sistema que privilegia a beleza e a juventude mais que a experiência e os conhecimentos. Materiais e métodos: fez-se uma revisão bibliográfica de autores que tratam da situação trabalhista de pessoas mais velhas. Resultados: a sociedade atual discrimina as pessoas mais velhas, ignorando sua experiência, sabedoria e o conhecimento acumulado ao longo dos anos. O crescimento da população adulta mais velha e da economicamente ativa possibilita o envelhecimento da força de trabalho, que poderia afetar o incremento econômico e o funcionamento do mercado trabalhista; por isso, tradicionalmente se espera que as pessoas mais velhas deixem seus locais de trabalho às populações mais jovens. Conclusões: a idade tem um alto custo no sistema trabalhista e produtivo colombiano, assumido pelos adultos mais velhos e ignorado pelo Estado.

Transforming pathways unleashed by a HDAC2 mutation in human cancer.

Although disruption of histone modification patterns is a common hallmark of human cancer, our knowledge of the mechanistic role of histone-modifying enzymes in its generation is very limited. We have recently identified an inactivating mutation in the histone deacetylase-2 (HDAC2) in sporadic carcinomas with microsatellite instability and in tumors arising in individuals with hereditary nonpolyposis colorectal cancer syndrome. Since HDAC2 seems to be a central player in epigenetic gene repression, we wondered whether HDAC2-truncating mutations conferred a particular expression signature on these cancer cells. Using unsupervised clustering analysis in microsatellite-unstable colorectal cancer cell lines, we have found that HDAC2 mutant cells (RKO and Co115) show a characteristically different expression microarray signature from HDAC2 wild-type cells (HCT-116, SW48, HCT-15 and LoVo). HDAC2 mutant cells exhibit upregulation of tumor-promoting genes, such as those of tyrosine kinases, mediators of cell cycle progression and angiogenic factors. The overexpression of these genes is associated with a loss of HDAC2 recruitment and a gain of histone H4 hyperacetylation in their particular 5'-end promoters, as observed by chromatin immunoprecipitation. Transfection of wild-type HDAC2 in mutant cells reverted this epigenetic pattern by repressing the transforming genes in association with HDAC2 promoter occupancy. These results suggest a role for HDAC2 mutations in human tumorigenesis through the derepression of key genes from multiple cellular transformation pathways.

High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability.

The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors. Regression analysis of these EPHB2 mutation data on the basis of our previously proposed statistical model identified EPHB2 as a selective target of frameshift mutations in MSI gastric cancers but not in MSI endometrial carcinomas. These results suggest a functional role for EPHB2 in gastric tumor progression, and emphasize the differences between the tumorigenic processes in MSI gastrointestinal and endometrial cancer.

Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis.

Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression profiling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 x 10(-7)), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by expression profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.

Gene expression signatures for colorectal cancer microsatellite status and HNPCC.

The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary non-polyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers (34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours (10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.

Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells.

The platinum compound oxaliplatin has been shown to be an effective chemotherapeutic agent for the treatment of colorectal cancer. In this study, we investigate the molecular mechanisms of action of oxaliplatin to identify means of predicting response to this agent. Exposure of colon cancer cells to oxaliplatin resulted in G2/M arrest and apoptosis. Immunofluorescent staining demonstrated that the apoptotic cascade initiated by oxaliplatin is characterised by translocation of Bax to the mitochondria and cytochrome c release into the cytosol. Oxaliplatin treatment resulted in caspase 3 activation and oxaliplatin-induced apoptosis was abrogated by inhibition of caspase activity with z-VAD-fmk, but was independent of Fas/FasL association. Targeted inactivation of Bax or p53 in HCT116 cells resulted in significantly increased resistance to oxaliplatin. However, the mutational status of p53 was unable to predict response to oxaliplatin in a panel of 30 different colorectal cancer cell lines. In contrast, the expression profile of these 30 cell lines, assessed using a 9216-sequence cDNA microarray, successfully predicted the apoptotic response to oxaliplatin. A leave-one-out cross-validation approach was used to demonstrate a significant correlation between experimentally observed and expression profile predicted apoptosis in response to clinically achievable doses of oxaliplatin (R=0.53; P=0.002). In addition, these microarray experiments identified several genes involved in control of apoptosis and DNA damage repair that were significantly correlated with response to oxaliplatin.

c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis.

The proto-oncogene c-Myc is overexpressed in 70% of colorectal tumours and can modulate proliferation and apoptosis after cytotoxic insult. Using an isogenic cell system, we demonstrate that c-Myc overexpression in colon carcinoma LoVo cells resulted in sensitisation to camptothecin-induced apoptosis, thus identifying c-Myc as a potential marker predicting response of colorectal tumour cells to camptothecin. Both camptothecin exposure and c-Myc overexpression in LoVo cells resulted in elevation of p53 protein levels, suggesting a role of p53 in the c-Myc-imposed sensitisation to the apoptotic effects of camptothecin. This was confirmed by the ability of PFT-alpha, a specific inhibitor of p53, to attenuate camptothecin-induced apoptosis. p53 can induce the expression of p21(Waf1/Cip1), an antiproliferative protein that can facilitate DNA repair and drug resistance. Importantly, although camptothecin treatment markedly increased p21(Waf1/Cip1) levels in parental LoVo cells, this effect was abrogated in c-Myc-overexpressing derivatives. Targeted inactivation of p21(Waf1/Cip1) in HCT116 colon cancer cells resulted in significantly increased levels of apoptosis following treatment with camptothecin, demonstrating the importance of p21(Waf1/Cip1) in the response to this agent. Finally, cDNA microarray analysis was used to identify genes that are modulated in expression by c-Myc upregulation that could serve as additional markers predicting response to camptothecin. Thirty-four sequences were altered in expression over four-fold in two isogenic c-Myc-overexpressing clones compared to parental LoVo cells. Moreover, the expression of 10 of these genes was confirmed to be significantly correlated with response to camptothecin in a panel of 30 colorectal cancer cell lines.

Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia.

Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer disease (EOAD, onset age at or before 65 years). In order to assess the genetic contribution of these genes in a series of Colombian AD cases, we performed a systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42 sporadic AD patients (34% with age of onset < or = 65 years). No APP missense mutations were identified. In three autosomal dominant cases (27.2%), two different PSEN1 missense mutations were identified. Both PSEN1 mutations are missense mutations that occurred in early-onset autosomal AD cases: an I143T mutation in one case (onset age 30 years) and an E280A mutation in two other cases (onset ages 35 and 42 years). In addition, a novel PSEN1 V94M mutation was present in one early-onset AD case without known family history (onset age 53 years) and absent in 53 controls. The E318G polymorphism was present in five AD cases and absent in controls. In PSEN2, two different silent mutations were detected, including one not reported elsewhere (P129). The majority of the Colombian AD cases, predominantly late-onset, were negative for PSEN and APP mutations.

c-myc/p53 interaction determines sensitivity of human colon carcinoma cells to 5-fluorouracil in vitro and in vivo.

Colon carcinoma cells overexpress c-myc due to defective Wnt signaling, but only patients whose tumors have an amplified c-myc gene show improved disease-free and overall survival in response to 5-fluoruracil (5FU). Here we show that in two colon carcinoma cell lines that do not have an amplified c-myc gene but differ in their p53 status, high c-myc levels can be further elevated by introducing a c-myc expression vector. Whereas sensitivity to low serum-induced apoptosis was imposed on the parental lines independent of p53 status and was unaffected by further elevation of c-myc, sensitivity to 5FU-induced apoptosis was dependent on both the higher c-myc levels due to the expression vector and wild-type p53 function. The elevated c-myc levels led to higher c-myc transactivation activity in the p53 wild-type cell line, but not in the mutant p53 cell line. The requirement for both elevated c-myc and p53 for 5FU sensitivity was confirmed using antisense c-myc and pifithrin-alpha, a specific inhibitor of p53. Finally, the in vitro data predicted that only patients with both amplified c-myc and wild-type p53 in their primary tumors would be responsive to 5FU-based therapy, which was borne out by analysis of tumors from 135 patients entered into a Phase III clinical trial of 5FU-based adjuvant therapy. The data provide significant insight into mechanisms that establish colon tumor cell sensitivity to 5FU, clearly demonstrate the necessity of exercising caution in considering combining novel strategies that target elevated c-myc with standard 5FU-based therapy, and suggest alternative therapeutic strategies that target c-myc and/or p53 mutations in the treatment of colon cancer.

APOE epsilon4 and Alzheimer's disease: positive association in a Colombian clinical series and review of the Latin-American studies.

OBJECTIVE: As the strength of the association between the APOE epsilon4 allele and Alzheimer's disease (AD) varies across ethnic groups, we studied if there was such an association in Colombian patients. METHOD: We performed apolipoprotein E (APOE) genotyping in a clinical sample of 83 unrelated AD patients, predominantly late-onset (>65 yrs) including familial ( n =30) and sporadic AD cases (n= 53) diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary team. Control subjects (n = 44) had no significant cognitive impairment by medical interview and neuro-psychological testing. RESULTS: We found a high association (OR= 5.1 95%CI 1.9 -13.6) between APOE epsilon4 and AD, in this series with predominantly late-onset cases with familial aggregation in 24 cases (28.9%). A significant negative association was found between epsilon2 and AD (OR= 0.2 95% CI 0.05-0.75). CONCLUSION: Further population-based surveys in Colombia are warranted to precise a possible dose effect of APOE epsilon4.

Diagnostic ultrasound induces change within numbers of cryptal mitotic and apoptotic cells in small intestine.

Recent work on gas filled organs, including the lung and small intestine, has concentrated on the hemorrhaging effects of ultrasound, with little attention paid to cell cycle perturbations and apoptosis--two very sensitive indicators of environmental insult. This study addresses this by exploring the effects of ultrasound on these two features. The anterior abdominal surface of anaesthetised male, adult CD1 mice was shaved and exposed to ultrasound. An 8 MHz linear array transducer was manually swept from the midline to the left mouse flank on a continuous basis. Each mouse was scanned for 15 minutes with B mode and color flow modes selected. The Thermal Index registered 1.0. Groups of mice were killed at various times after treatment, the small intestine was excised and histologically examined. Analysis of the data demonstrates a statistically significant 22% reduction in numbers of mitotic figures at 4.5 hours after the ultrasonic insult (p = 0.011). Numbers of apoptotic bodies increased by 153% (p=0.003), 166% (p=0.014) and 160% (0.001) at 1, 3 and 4.5 hours post-treatment respectively. These preliminary results suggest that bioeffects of ultrasound maybe more diverse than previously described. Further work will establish thresholds and explore mechanisms for these deterministic effects.

BB-10010, an analog of macrophage inflammatory protein-1alpha, protects murine small intestine against radiation.

Irradiation of the small intestine can result in depletion of the epithelial stem cell compartment and is often the dose-limiting factor for radiotherapeutic treatment of tumors in the abdominal and pelvic region. Since mitotic cells are most sensitive to radiation, significant radioprotection can be achieved by reducing the number of cells in mitosis at the time of irradiation. We have previously shown that administration of macrophage inflammatory protein (MIP) -1alpha induces a transient 50% reduction in the number of mitotic cells in small intestinal crypts, including the stem cell region, and therefore, MIP-1alpha pretreatment before radiation exposure could result in a substantial reduction of the side effects associated with radiotherapy. Groups of adult mice were exposed to different doses of radiation (6, 8, 10, or 12 Gy), with or without prior administration of 200 microg BB-10010/kg 3 hr before irradiation and radiation damage was assessed by means of the microcolony survival assay. MIP-1alpha pretreatment resulted in significantly increased numbers of surviving crypts (10%) when compared to untreated irradiated animals. The observed radioprotective effects of MIP-1alpha in the small intestine should translate into reduced side effects in a clinically relevant radiotherapy context and could allow larger doses of radiation to be delivered to patients with tumors in the abdominal or pelvic region.

Dose-effect relationship of BB-10010/MIP-1 alpha on proliferation in murine small intestinal epithelium: single and double administration protocols.

BB10010/MIP-1 alpha reduces the number of proliferating cells in the small intestine, strongly suggesting a radioprotective potential in this organ. This study was designed to optimize BB10010 administration for maximal radioprotection. In single administration protocols 1 or 4 mg/kg of BB10010 was injected into mice 2, 4 or 10 hr before death. In double administration protocols an initial dose of either 0.4 or 200 microg/kg, and a second dose (2.5 hr apart) of 200 microg/kg 4 hr before death were administered. The number of vincristine-arrested metaphases were counted on individually microdissected crypts from the midpoint of the small intestine. When compared to the smaller doses of BB 10010 used in our previous studies, the higher doses used in these experiments did not result in any further reduction in the number of proliferating cells under any of the protocols assessed. Furthermore, some values were found to be above not only those observed with the smaller doses, but also above untreated controls. It is concluded that a single dose of 200 microg/kg of BB10010 offers the most consistent reduction of mitotic cells, and is, therefore, considered optimal for assessment of radioprotection.

BB-10010, an analogue of macrophage inflammatory protein-1 alpha, reduces proliferation in murine small-intestinal crypts.

BACKGROUND: The small-intestinal epithelium, a rapidly proliferating tissue, is highly sensitive to cycle-specific agents such as radiation. Macrophage inflammatory protein (MIP)-1 alpha has been shown to reduce cell proliferation in bone marrow, seminiferous epithelium, and skin. The current work investigates the activity of an MIP-1 alpha variant, BB-10010, in the gut. METHODS: A single dose of either 0.4 microg/kg or 200 microg/kg was administered to mice 2, 4, 6, 8, 10, 12, or 14 h before animal death. Fifteen crypts from the midpoint of the small intestine were dissected from each animal and squashed, and the numbers of vincristine-arrested metaphases was counted for each fifth of the crypts. RESULTS: A 40%-50% reduction of accumulated metaphases throughout all crypt segments was observed in animals injected with 200 microg/kg of BB-10010 2 h and 4 h before death (P < 0.0001). The animals that received 0.4 microg/kg showed a similar effect at 4 h (P < 0.0001). CONCLUSIONS: The results provide evidence of a significant reduction in numbers of intestinal cryptal cells passing through mitosis at specific time periods after a single administration of BB-10010. By putting these cells temporarily out of the mitotic phase of the cell cycle this protein might reduce the side effects of radiation therapy to patients undergoing abdominal or pelvic treatments.

[Botanical studies in the illustrated plans of the Vice-Royalty of New Grenada]. / Los estudios de botánica en los planes ilustrados del virreinato de la nueva Granada.

During the kingdoms of the New Granada, the first plan of teaching which was presented by the botanical department was made during the Viceroy Caballero y Góngora (1787). Later, beginning in the 19th century, during the political and ideological repression in the universities, the plans of the Baron Carondelet (1800) were presented with the idea of the creation of the Botanical Department in the University of Quito, and the creole Eloy Valenzuela presented the teaching of botanical studies in the course of study of philosophy in the College-University of Mompox in 1806. He carried out a model of botanical expedition to realize in the villa of Mompox. This was included in the general laws in the College-University of Mompox. These plans were not approved by controversy and administrative procedures. Only, the Plan of Valenzuela had partial application.