3D fibre architecture of fibre-reinforced sand.

The mechanical behaviour of fibre-reinforced sands is primarily governed by the three-dimensional fibre architecture within the sand matrix. In laboratory, the normal procedures for sample preparation of fibre-sand mixtures generally produce a distribution of fibre orientations with a preferential bedding orientation, generating strength anisotropy of the composite's response under loading. While demonstrating the potential application of X-ray tomography to the analysis of fibre-reinforced soils, this paper provides for the first time a direct experimental description of the three-dimensional architecture of the fibres induced by the laboratory sample fabrication method. Miniature fibre reinforced sand samples were produced using two widely used laboratory sample fabrication techniques: the moist tamping and the moist vibration. It is shown that both laboratory fabrication methods create anisotropic fibre orientation with preferential sub-horizontal directions. The fibre orientation distribution does not seem to be affected by the concentration of fibres, at least for the fibre concentrations considered in this study and, for both fabrication methods, the fibre orientation distribution appears to be axisymmetric with respect to the vertical axis of the sample. The X-ray analysis also demonstrates the presence of an increased porosity in the fibre vicinity, which confirms the assumption of the "stolen void ratio" effect adopted in previous constitutive modelling. A fibre orientation distribution function is tested and a combined experimental and analytical method for fibre orientation determination is further validated.

Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat.

OBJECTIVE: To assess epicardial fat volume (EFV), myocardial TG content (MTGC) and metabolic profile in severely obese patients, and to determine whether ectopic fat depots are linked to metabolic disorders or myocardial function. RESEARCH DESIGN AND METHODS: Sixty-three subjects with normal LV function and no coronary artery disease, including 33 lean (BMI: 21.4 ± 2.0 kg m(-2)) and 30 obese (BMI: 41.8 ± 6 kg m(-2)) patients, underwent 3-T cardiovascular MRI, and anthropometric, biological and visceral abdominal fat (VAT) assessments. EFV was measured by short-axis slice imaging and myocardial (intra-myocellular) TG content was measured by proton magnetic resonance spectroscopy. RESULTS: EFV and MTGC were positively correlated (r=0.52, P<0.0001), and were both strongly correlated with age, BMI, waist circumference and VAT, but not with severity of obesity. EFV and MTGC were significantly higher in obese patients than in lean controls (141 ± 18 versus 79 ± 7 ml, P=0.0001; 1.0 ± 0.1 versus 0.6 ± 0.1%, P=0.01, respectively), but some differences were found between the two cardiac depots: EFV was higher in diabetic obese subjects as compared with that in non-diabetic obese subjects (213 ± 34 versus 141 ± 18 ml, P=0.03), and was correlated with parameters of glucose tolerance (fasting plasma glucose, insulin and HOMA-IR), whereas MTGC was not. EFV and MTGC were both associated with parameters of lipid profile or inflammation (TGs, CRP). Remarkably, this was VAT-dependent, as only VAT remained independently associated with metabolic parameters (P<0.01). Concerning myocardial function, MTGC was the only parameter independently associated with stroke volume (ß=-0.38, P=0.01), suggesting an impact of cardiac steatosis in cardiac function. CONCLUSIONS: These data show that VAT dominates the relationship between EFV, MTGC and metabolic measures, and uncover specific partitioning of cardiac ectopic lipid deposition.

Participación de componentes inmunológicos en la etiopatogenia de la queratopatía climática esferoidea / Involvement of immune components in the etiopathogenia of climatic droplet keratopathy

Objetivo. Investigar si componentes de la inmunidad innata están involucrados en la iniciación/perpetuación de las anormalidades estructurales observadas en la capa de Bowman y el estroma superficial de la córnea de pacientes con queratopatía climática esferoidea (QCE). Materiales y métodos. En el estudio participaron 8 pacientes con QCE y 12 individuos sanos del Departamento El Cuy, Provincia de Río Negro, y 10 individuos sanos de la ciudad de Córdoba. Todos ellos, luego de firmar el consentimiento informado, recibieron un examen oftalmológico completo y se recolectaron muestras de lágrima para estudiar las concentraciones de diferentes citocinas, niveles y formas de metaloproteinasas de matriz (MMPs), y el inhibidor natural de MMPs (TIMP-1). Se realizó microscopía confocal in vivo (MCF) en algunos pacientes y controles. Biopsias de córneas provenientes de pacientes que fueron tratados con queratoplastia penetrante también fueron estudiadas mediante inmunohistoquímica (IHQ). Resultados. Los resultados de MCF indicaron claramente una progresión en la cantidad de depósitos a nivel subepitelial, a medida que la enfermedad avanza. El daño progresivo de las fibras nerviosas sub basales y estromales en los estadios 2 y 3 se correlaciona con pérdida de la sensibilidad corneal. Además de estas alteraciones, observamos que el número de células dendríticas (CD) en el limbo corneal aumentó significativamente a medida que la QCE progresa. En lágrimas de pacientes con QCE se detectaron concentraciones significativamente superiores de citocinas proinflamatorias (IL1ß e IL-8) que en individuos controles (p<0,005). No se halló IL-2, IL-17, IL-4, IL-13 ni IL-10 en pacientes y ni controles. Las actividades de gelatinasas (MMP-9 y -2) fueron significativamente mayores en QCE que en los controles (p<0,001), mientras que los niveles de TIMP-1 fueron significativamente menores en los pacientes (p<0,05). La concentración de MMP-8 fue mayor en controles pero los niveles de esta colagenasa-2 fueron 30 veces superiores, tanto en QCE como controles, con respecto a los valores de los individuos de un centro urbano. Mediante IHC observamos reactividad para MMP-9 en la mayoría de las células epiteliales, solamente en córneas con QCE. Conclusión. Demostramos un rol protagónico del eje citocinas proinflamatorias - gela-tinasas en el desarrollo de la QCE. Los altos niveles de IL-1ß e IL-8 en lágrimas de pacientes facilitan la producción de MMP-8 y gelatinasas, y los efectos de las mismas se exacerban, ya que los pacientes tienen bajos niveles de sus inhibidores naturales (TIMP-1). La MMP-9, además de degradar componentes de la matriz extracelular, cataliza la activación postranscripcional de IL-1ß, potenciando el proceso inflamatorio. Estos resultados son los primeros en explicar mecanismos inmunológicos involucrados en la etiopatogénesis de la QCE y aportan nuevas alternativas para el desarrollo de terapias preventivas utilizando inhibidores de IL-1ß y/o gelatinasas(AU)

Objective. To investigate whether components of innate immunity are involved in the initiation / perpetuation of the structural abnormalities observed in Bowman's layer and superficial stroma of the córnea of patients with Climatic droplet keratopathy (CDK). Materials and Methods. The study included 8 CDK patients and 12 healthy individuals from Department El Cuy, Province of Río Negro, and 10 healthy subjects from the city of Córdoba. All of them, after signing informed consent, received a thorough eye exam and tear samples were collected to study the concentrations of different cytokines, and levels and forms of matrix metalloproteinases (MMPs) and their natural inhibitor (TIMP-1). In vivo confocal microscopy (CFM) was performed in some patients and controls. Corneal biopsies from CDK patients treated with penetrating keratoplasty were also studied by immunohistochemistry (IHC). Results. CFM results clearly indicated a progression in the amount of deposits at corneal sub epithelial level as the disease progresses. The progressive damage in the nerve plexus in stages 2 and 3 correlated with a loss of corneal sensitivity. In addition to these alterations, we observed that the number of dendritic cells (DC) in the limbus increased significantly as the disease progresses.In tears of patients with CDK we detected significantly higher concentrations of pro-inflammatory cytokines (IL-1ß and IL-8) than in control subjects (p < 0.005). We found no IL-2, IL-17, IL-4, IL-13 and IL-10 in patients and controls. The activities of gelatinases (MMP-9 and -2) were significantly higher in CDK than in controls (p < 0.001), while TIMP-1 levels were significantly lower in patients (p < 0.05). The concentration of MMP-8 was higher in controls, but levels of this collagenase-2 were 30 times higher, both in CDK and controls, with respect to MMP-8 values of individuals inhabiting an urban area. By IHC we observed reactivity for MMP-9 in most epithelial cells only in CDK corneas. Conclussion. We demonstrated a key role of the axis pro-inflammatory cytokines ­ gelatinases in the development of CDK. High levels of IL-1ß and IL-8 in tears of patients facilitate the production of MMP-8 and gelatinases, and the effects of these molecules are exacerbated because patients have low levels of their natural inhibitors (TIMP-1). Since MMP-9 besides degrading extracellular matrix components, catalyzes the post translational activation of IL-1ß, the inflammatory process is fuelled. These results are the first to explain immunological mechanisms involved in the pathogenesis of the QCE and provide new alternatives for the development of preventive therapies using inhibitors of IL-1ß and / or gelatinases.(AU)

Anticholinergic syndrome due to 'Devil's herb': when risks come from the ancient time.

We describe a case of Mandragora autumnalis poisoning which occurred in a 72-year-old female patient who had eaten the venenous M. Autumnalis, picked near her home, mistaking it for the edible Borago Officinalis. M. Autumnalis is a solanaceous plant, common in the Sicilian countryside, which contains a variable concentration of solanum alkaloids, causing gastrointestinal irritation, and tropane alkaloids, with anticholinergic properties. Unluckily, M. Autumnalis is often mistaken for the edible B. Officinalis, likewise widespread in Sicilian countryside. The diagnosis of Mandragora poisoning was made on the basis of clinical symptoms and signs of anticholinergic syndrome associated with a history of vegetable meal of uncontrolled origin, moreover analysing the vegetable obtained from gastric lavage. Decontamination and symptomatic treatment were useful in our patient to control acute poisoning.

Echinococcosis: historical landmarks and progress in research and control.

Although hydatid cysts were recognised and described in ancient times, in both livestock and humans, it was not until the 17th Century that their biological nature began to be understood. The past 50 years have seen a veritable revolution in knowledge and technology applicable to the biology of the cestodes and the diseases they cause. The parasites that form hydatid cysts belong to the genus Echinococcus, which is now recognized as a complex of closely related cestode parasites adapted to a variety of host-assemblages linked by predator-prey relationships. Synanthropic transmission in dogs and domestic livestock greatly increases the possibilities of zoonotic transmission, and the highest prevalences of Echinococcus infection in humans therefore occur in populations engaged in livestock rearing in which domestic dogs have access to the viscera of the livestock that serve as intermediate hosts. The application of modern scientific technology over the last few decades has not only revealed the diversity of host-parasite relationships within the genus Echinococcus but also led to greatly improved technology for the diagnosis and treatment of the echinococcoses in humans and lower animals. Although control programmes have led to marked reductions in transmission in certain geographical and socio-political settings, transmission and the resultant diseases continue unabated throughout most of the parasites' world-wide distribution.

Taenia solium infection in a rural community in the Peruvian Andes.

An epidemiological study was conducted in a highland, rural community in Peru, to determine the seroprevalences of human and porcine infection with Taenia solium and the risk factors associated with human infection. The seroprevalences, determined using an assay based on enzyme-linked-immuno-electrotransfer blots (EITB), were 21% (66/316) in the humans and 65% (32/49) in the pigs. The human subjects aged <30 years were more likely to be positive for anti-T. solium antibodies than the older subjects (P < 0.001). The risk factors associated with human seropositivity were lack of education beyond the elementary level [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.09-6.65] and pig-raising (OR=1.68; CI=0.96-2.92). Curiously, sheep-raising was inversely associated with human T. solium infection (OR=0.50; CI=0.28-0.90). The study site appears to be a new endemic focus for T. solium in the central Peruvian Andes. Although, in earlier studies, the seroprevalence of T. solium infection has generally been found to increase with age, the opposite trend was observed in the present study. The results of follow-up studies should help determine if the relatively high seroprevalence in the young subjects of the present study is the result of a transient antibody response.

Gallstone disease in Peruvian coastal natives and highland migrants.

BACKGROUND: In a previous study, we found that gallstones were a common occurrence in the high altitude villages of the Peruvian Andes. AIMS: To determine if high altitude (> or = 1500 m) is a contributing risk factor for gallstone disease. METHODS: We conducted a cross sectional study in a periurban community in Lima, Peru, and compared the prevalence of gallstone disease between coastal natives, highland (Sierra) natives and Sierra natives who had migrated to the coast. We also compared the prevalence rates from this study with those from a previous study conducted at high altitude. We examined 1534 subjects >15 years of age for gallstone disease. Subjects were interviewed for the presence or absence of risk factors. RESULTS: Gallstone disease was more common in females (16.1 cases per 100, 95% CI 13.8-18.2) than in males (10.7 per 100, 95% CI 8.0-13.4). Females had a greater risk of gallstone disease, especially if they had used oral contraception and/or had four or more children. The age adjusted prevalence was not significantly different between coastal natives, Sierra migrants, and Andean villagers. The prevalence of gallstone disease was not associated with time since migration or with having native Sierra parents. After adjusting for other risk factors, Sierra natives who migrated to the coast had a lower prevalence of gallstone disease than coastal natives (odds ratio 0.74, 95% CI 0.58-0.94). CONCLUSIONS: This study indicates that high altitude is not a positive risk factor for gallstone disease and confirms that this disease is common in Peruvians, which may be attributable to Peruvian-Indian ethnicity.

Human hydatidosis in the central Andes of Peru: evolution of the disease over 3 years.

To document the natural history of Echinococcus granulosus infection and response to treatment of human hydatidosis, we reexamined 28 of 37 subjects with E. granulosus infection diagnosed in an epidemiological study conducted in 1994. Twenty-six (70%) of those 37 subjects underwent abdominal ultrasonography, chest radiography, and enzyme-linked immunoelectrotransfer blot assay in 1997. Medical records from two additional individuals were reviewed. Eight patients had their cysts surgically removed during the 3-year follow-up interval; no surgical complications or recurrences occurred. Among eight patients with cystic disease not treated by surgery, four had cyst-growth ranging from 0.4 to 1.4 cm during the 3-year interval. One patient developed a new cyst and another's simple cyst became septate; two developed new calcifications. Of 12 seropositive subjects with no cysts present in 1994, 10 reverted to seronegative, a finding that suggests a significant proportion of seropositive subjects in echinococcus-endemic regions may have only transient infection without disease. When cysts do develop, their growth rates and time courses are highly variable; over the 3-year period, we observed growth, septation, degeneration, and calcification of cysts.

Oxfendazole treatment of sheep with naturally acquired hydatid disease.

A blinded, randomized placebo-controlled trial assessed the efficacy and safety of oxfendazole for the treatment of ovine hydatid disease. Cyst fertility and parasite viability were measured following daily, weekly, and monthly treatment schedules with 30 mg of oxfendazole per kg of body weight. The 12-week trial was conducted in 215 adult sheep in the central Peruvian Andes and was masked for both treatment group and scheduling. In this trial oxfendazole significantly reduced protoscolex viability relative to controls in all treatment groups. In the daily, weekly, and monthly groups, 100, 97, and 78% of sheep, respectively, were either cured or improved following treatment, compared to 35% cured or improved animals in the control group. However, daily dosing at 30 mg of oxfendazole per kg proved highly toxic to sheep, resulting in a 24% death rate in the daily group as compared to a 4 to 6% mortality rate in all other groups. If found safe in humans, oxfendazole may prove to be a useful and inexpensive treatment for cestode infections in humans. This study suggests that a staggered dosing regimen of oxfendazole, and possibly other benzimidazoles, may be as efficacious as daily treatment regimens for hydatidosis while decreasing both the cost and adverse effects associated with daily dosing.

Gallstone disease in high-altitude Peruvian rural populations.

OBJECTIVE: Cholelithiasis is a common problem in hospitals of the Peruvian Andes; however, its prevalence in Andean communities is unknown. To estimate the prevalence of gallstone disease in this locale, we conducted a cross-sectional community study in three high-altitude Peruvian rural villages (i.e., > 3000 m above sea level). METHODS: We examined 911 volunteers > 15 yr of age from three villages for gallstone disease by history and ultrasonography. Risk factors for gallstone disease were examined in 382 volunteers from one village. RESULTS: The age-adjusted prevalence of gallstone disease ranged from 4-10% in men and from 18-20% in women. Women had significantly higher age-adjusted prevalence rates than did men. The prevalence of gallstone disease increased significantly with age and decreased significantly with alcohol consumption. Although not statistically significant, we found a positive association between gallstone disease and body mass index. CONCLUSION: The results of this study indicate that gallstone disease, commonly perceived as a disease of the developed world, is also a common problem in high-altitude Peruvian communities.

Field diagnosis of Echinococcus granulosus infection among intermediate and definitive hosts in an endemic focus of human cystic echinococcosis.

Human, canine and ovine echinococcosis prevalence was determined in a highland community located in the central Peruvian Andes during 1997 and 1998. Human echinococcosis was determined using portable ultrasonography, chest X-ray examination, and an enzyme-linked immunoelectrotransfer blot (EITB) assay. Canine echinococcosis was determined using microscopy stool examinations and a coproantigen detection enzyme-immunoassay (EIA) for Echinococcus granulosus. Ovine echinococcosis was determined by an EITB assay for sheep echinococcosis and necropsy examination of viscera from domestic slaughtered animals. An abdominal ultrasound, a chest X-ray examination and an EITB for echinococcosis were performed on 214 subjects (45% of the village population). The frequency of presumptive liver/abdominal, lung and liver-lung hydatid cysts was 5.1% (11/214), 3.7% (8/214) and 0.5% (1/214), respectively. The overall prevalence of human cystic echinococcosis was 9.3% (20/214). The frequency of canine echinococcosis was 46% (23/50) and 32% (16/50) by the coproantigen EIA test and arecoline purging, respectively. The frequency of sheep echinococcosis was 65% (22/34) by the EITB and 38% (13/34) by necropsy. We demonstrated a high prevalence of human and animal echinococcosis in this Peruvian village. In remote areas where echinococcosis is endemic, both the coproantigen EIA and arecoline purging may be used for the study of canine echinococcosis; the EITB is useful in establishing the diagnosis of echinococcosis in sheep prior to necropsy.

Intestinal parasites of the grey fox (Pseudalopex culpaeus) in the central Peruvian Andes.

The intestines of 20 grey Peruvian foxes (Pseudalopex culpaeus) were examined for the presence of Echinococcus granulosus and other intestinal parasites. Echinococcus granulosus was not found in foxes but Taenia hydatigena and T. multiceps were found in 7 and 4 animals respectively. The grey fox may not be a suitable definitive host for E. granulosus. However, it may act as a sylvatic reservoir of T. hydatigena and T. multiceps in the central Peruvian Andes.

Quinoxaline chemistry. Part 8. 2-[Anilino]-3-[carboxy]-6(7)-substituted quinoxalines as non classical antifolate agents. Synthesis and evaluation of in vitro anticancer, anti-HIV and antifungal activity.

Thirty quinoxalines bearing a substituted anilino group on position 2, a carboethoxy or carboxy group on position 3 and a trifluoromethyl group on position 6 or 7 of the heterocycle were prepared in order to evaluate in vitro anticancer activity. Preliminary screening performed at NCI showed that most derivatives exhibited a moderate to strong growth inhibition activity on various tumor panel cell lines between 10(-5) and 10(-4) molar concentrations. Interesting selectivities were also recorded between 10(-8) and 10(-6) M for a few compounds. One single compound exhibited good activity against Candida albicans.

Epidemiology of Echinococcus granulosus infection in the central Peruvian Andes.

The prevalence of human, canine, and ovine echinococcosis was determined in an endemic area of the Peruvian Andes where control programmes have not been operational since 1980. Prevalence of infection in humans was determined using portable ultrasound, chest X-rays, and an enzyme-linked immunoelectrotransfer blot (EITB) assay. Canine and ovine echinococcal prevalence was determined by microscopic stool examinations following arecoline purging for tapeworm detection and by examination of the viscera from slaughtered livestock animals, respectively. The prevalence among 407 humans surveyed was 9.1%. The frequency of disease in the liver, lung, and in both organs was 3.4%, 2.0%, and 0.2%, respectively. Portable ultrasound or portable chest X-ray has shown that, compared to adults, children under 11 years had significantly higher seropositive rates without evidence of hydatid disease (P < 0.05). Among the 104 dogs inspected for echinococcus after arecoline purging, 33 (32%) were positive for adult tapeworms. Among the 117 sheep slaughtered at the local abattoir, 102 (87%) had hydatid cysts. The prevalence of human hydatidosis in this endemic area of Peru is one of the highest in the world and nearly five times higher than previously reported in 1980. An increase in echinococcosis prevalence may result after premature cessation of control programmes.

Distribution of hydatidosis and cysticercosis in different Peruvian populations as demonstrated by an enzyme-linked immunoelectrotransfer blot (EITB) assay. The Cysticercosis Working Group in Peru (CWG).

A serosurvey for human hydatidosis and cysticercosis was performed in different regions of Peru. Those regions included a known endemic area for cystic hydatid disease, a cooperative in the central Peruvian Andes near the city of Tarma, Department of Junin; three areas endemic for cysticercosis in the Departments of Ancash, Cuzco, and San Martin, where the status of hydatid disease is not well defined; and an urban shantytown near Lima, where neither zoonosis is known to be present. A seroprevalence for hydatidosis 1.9% (6 of 309) was found with both the enzyme-linked immunoelectrotransfer blot (EITB) and double diffusion assays in the area endemic for hydatidosis. Seroprevalence in the other zones tested was zero using only the EITB assay. Cysticercosis seroprevalence was high in pig-raising zones but low in the high-altitude, sheep-raising areas and in the seaport of Callao. No cross-reactions between Echinococcus granulosus and cysticercosis were noted in any of the regions studied. Hydatid infection remains a major health problem in the central Peruvian Andes where sheep raising is widely practiced; however, in those regions where mainly swine are raised, human hydatid infection is not a problem.