Narcolepsia secundaria a enfermedad rara y fatal / Narcolepsy secondary to a rare fatal disease

Introducción: La ROHHAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation) es una enfermedad rara, con escasamente dos centenas de casos documentados hasta la fecha, que se inicia en niños previamente sanos y en la que el primer signo suele ser la obesidad, seguido de una disfunción hipotalámica y trastornos respiratorios del sueño, que progresan rápidamente hasta el fallecimiento del paciente. La ROHHAD con narcolepsia es aún más infrecuente, con sólo dos casos descritos hasta el momento. Caso clínico: Niño que, desde los 5 años, presenta señales de obesidad y somnolencia. A los 7 años sufre dos crisis tonicoclónicas y, durante los cuatro años siguientes, muestra síntomas y signos propios de una disfunción hipotalámica importante, por lo que, tras múltiples pruebas, se le diagnosticó ROHHAD. A pesar de los múltiples tratamientos recibidos, el paciente falleció a los 11 años de edad. Conclusión: Es necesario aclarar la fisiopatología de esta enfermedad para poder investigar futuros tratamientos que resulten eficaces.(AU)

Introduction: ROHHAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation) is a rare disease, with only about two hundred cases reported to date, that starts in previously healthy children. The first sign is usually obesity, followed by hypothalamic dysfunction and sleep-disordered breathing, which rapidly progresses until the death of the patient. ROHHAD with narcolepsy is even rarer, with only two cases described so far. Case report: We report the case of a boy who showed signs of obesity and sleepiness since he was 5 years old. At the age of 7, he suffered two tonic-clonic seizures and, over the next four years, displayed signs and symptoms of significant hypothalamic dysfunction; after multiple tests, he was then diagnosed with ROHHAD. Despite receiving a large number of treatments, the patient died at the age of 11. Conclusion: The pathophysiology of this disease needs to be clarified in order to investigate effective treatments in the future.(AU)

Narcolepsia multirresistente / Multidrug resistant narcolepsy

Introducción: La narcolepsia de tipo 1 es una enfermedad degenerativa focal del hipotálamo que afecta selectivamente a las neuronas productoras de orexina (hipocretina). Presenta múltiples manifestaciones clínicas, tanto en vigilia como en sueño. Con frecuencia, los síntomas son tan disruptivos que ocasionan enorme sufrimiento y deterioro de la calidad de vida de los pacientes. Aunque en ocasiones es suficiente con un abordaje no farmacológico, la gran mayoría de los enfermos necesita medicación para un adecuado control clínico. Caso clínico: Varón que a los 43 años comenzó a presentar de forma aguda excesiva somnolencia diurna y episodios de cataplejía. Tras un exhaustivo estudio se le diagnosticó narcolepsia de tipo 1. A lo largo de la evolución de la enfermedad se le prescribieron antidepresivos, neuroestimulantes y oxibato sódico, en monoterapia o en combinación. La respuesta al tratamiento farmacológico fue insuficiente y se acompañó de numerosos efectos secundarios. Tras la introducción de pitolisant se objetivó una franca mejoría de los síntomas, y se consiguió reducir la dosis de los otros fármacos y de sus efectos adversos. Conclusión: Son numerosas las medidas disponibles en la actualidad para abordar los síntomas cardinales de la enfermedad, aunque siguen existiendo casos resistentes al tratamiento antinarcoléptico. Los fármacos con mecanismos de acción sobre receptores del sistema histaminérgico pueden resultar de gran utilidad en estos casos.(AU)

Introduction: Narcolepsy type 1 is a focal degenerative disease of the hypothalamus that selectively affects orexin (hypocretin)-producing neurons. It presents multiple clinical manifestations, both in wakefulness and in sleep. The symptoms are often so disruptive that they cause enormous suffering and impair patients’ quality of life. Although a non-pharmacological approach is sometimes sufficient, the vast majority of patients need medication for adequate clinical management. Case report: A male who, at 43 years of age, began to present acutely with excessive daytime sleepiness and episodes of cataplexy. After a thorough examination, he was diagnosed with narcolepsy type 1. Throughout the course of the disease, he was prescribed antidepressants, neurostimulants and sodium oxybate, in monotherapy or in combination. The response to pharmacological treatment was insufficient and accompanied by numerous side effects. Following the introduction of pitolisant, there was a marked improvement in his symptoms and a reduction in the dose of the other drugs and their adverse effects was achieved. Conclusion: A number of measures are now available to address the cardinal symptoms of the disease, although there are still cases that are resistant to anti-narcoleptic treatment. Drugs with mechanisms of action that act upon receptors in the histaminergic system can be very useful in these cases.(AU)

Farm level bio-economic modelling of aquatic animal disease and health interventions.

A farm level bio-economic model, for aquatic animal production, of the relationships between inputs (e.g. purchased animals), outputs (e.g. harvested animals) and gross margin (GM) was developed to assess ex-ante the economics of disease and animal health interventions. Feed costs were calculated from estimates of food conversion ratio (FCR), animals harvested and mortality. The model was applied to a typical grow-out rainbow trout (Oncorhynchus mykiss) farm on Lake Titicaca, Peru and a typical shrimp (Paenus vannamei) farm in the Mekong Delta, Vietnam. The model was used in two analyses. Firstly, an approach to assess the burden of disease developed by the Global Burden of Animal Diseases (GBADs) project was adopted. Output under conditions of 'ideal health' was estimated by reducing mortality to zero and removing health costs. GM in both systems increased by approximately 25% when production was kept constant (and stocking rates reduced) and more than doubled if production was allowed to rise (and initial stocking increased). The increase in GM under conditions of ideal compared with current production provided an estimate of the maximum possible benefit from improved health management. Secondly, break-even analysis was used to assess the economics of vaccination against infectious pancreatic necrosis (IPN) vaccine (rainbow trout - RBT) and probiotics (shrimp). If initial stocking was kept constant, and production allowed to rise, break-even points for the intervention (when GM was the same with and without the intervention) were achieved when mortality was reduced by 16% in RBT fry and juvenile and 28% in shrimp. If production was kept constant and benefit realised by reduced initial stocking, the break-even point was achieved for i) vaccination of RBT when mortality in fry and juveniles was reduced by 39%, and ii) probiotics in shrimp production when there was a 15% reduction in mortality (nursery and grow-out), 10% increase in shrimp weight at harvest and 10% improvement in FCR. The results demonstrate how relatively simple models, parameterised with basic farm production data, can assess the burden of disease and quantify ex-ante the potential benefit of interventions. In the absence of trial data, these analyses support decision-making by farmers. The models can be adapted for many aquaculture systems. Farm level results can be extrapolated to estimate disease burden, and benefits of interventions, at regional or national level and thus support informed decision-making and allocation of resources to health management.

[Narcolepsy secondary to a rare fatal disease]. / Narcolepsia secundaria a enfermedad rara y fatal.

INTRODUCTION: ROHHAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation) is a rare disease, with only about two hundred cases reported to date, that starts in previously healthy children. The first sign is usually obesity, followed by hypothalamic dysfunction and sleep-disordered breathing, which rapidly progresses until the death of the patient. ROHHAD with narcolepsy is even rarer, with only two cases described so far. CASE REPORT: We report the case of a boy who showed signs of obesity and sleepiness since he was 5 years old. At the age of 7, he suffered two tonic-clonic seizures and, over the next four years, displayed signs and symptoms of significant hypothalamic dysfunction; after multiple tests, he was then diagnosed with ROHHAD. Despite receiving a large number of treatments, the patient died at the age of 11. CONCLUSION: The pathophysiology of this disease needs to be clarified in order to investigate effective treatments in the future.

TITLE: Narcolepsia secundaria a enfermedad rara y fatal.Introducción. La ROHHAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation) es una enfermedad rara, con escasamente dos centenas de casos documentados hasta la fecha, que se inicia en niños previamente sanos y en la que el primer signo suele ser la obesidad, seguido de una disfunción hipotalámica y trastornos respiratorios del sueño, que progresan rápidamente hasta el fallecimiento del paciente. La ROHHAD con narcolepsia es aún más infrecuente, con sólo dos casos descritos hasta el momento. Caso clínico. Niño que, desde los 5 años, presenta señales de obesidad y somnolencia. A los 7 años sufre dos crisis tonicoclónicas y, durante los cuatro años siguientes, muestra síntomas y signos propios de una disfunción hipotalámica importante, por lo que, tras múltiples pruebas, se le diagnosticó ROHHAD. A pesar de los múltiples tratamientos recibidos, el paciente falleció a los 11 años de edad. Conclusión. Es necesario aclarar la fisiopatología de esta enfermedad para poder investigar futuros tratamientos que resulten eficaces.

Regulation of Tau protein phosphorylation by glucosamine-induced O-GlcNAcylation as a neuroprotective mechanism in a brain ischemia-reperfusion model.

Purpose:Tau hyperphosphorylation is a modification frequently observed after brain ischemia which has been related to the aggregation of this protein, with subsequent cytoskeletal damage, and cellular toxicity. The present study tests the hypothesis of using glucosamine, an agent that increases protein O-GlcNAcylation, to decrease the levels of phosphorylation in Tau during ischemia-reperfusion.Material and methods: Transient focal ischemia was artificially induced in male Wistar rats by occlusion of the middle cerebral artery (MCAO) with an intraluminal monofilament. A single dose of intraperitoneal glucosamine of 200 mg/kg diluted in normal saline (SSN) was administered 60 min before ischemia. Histological brain sections were processed using indirect immunofluorescence with primary antibodies (anti-O-GlcNAc and anti pTau-ser 396). The Image J software was used to calculate the immunofluorescence signal intensity.Results: The phosphorylation of Tau at the serine residue 396 had a significant decrease with the administration of glucosamine during ischemia-reperfusion compared with the administration of placebo.Conclusions: These results show that glucosamine can reduce the phosphorylation levels of Tau in rodents subjected to ischemia and cerebral reperfusion, which implies a neuroprotective role of glucosamine.

PHARMACOLOGICAL AND MECHANISTIC STUDIES OF UREQUINONA, A MOLECULE FROM ROOTS OF PENTALINON ANDRIEUXII MUELL-ARG THAT HEALS MURINE LEISHMANIA MEXICANA INFECTION.

In this work we tested both the in vitro and in vivo anti-Leishmania mexicana activity of a molecule we originally identified in the root of Pentalinon andrieuxii Muell-Arg, a plant that is widely used in Mayan traditional medicine. The chemical name of this molecule is 24-methylcholesta-4-24(28)-dien-3-one, but for simplicity's sake, we assigned the short and trivial name of urequinona that will be used throughout this work. It induces necrosis and apoptosis of promastigotes cultured in vitro and extensive ultrastructural damage of amastigotes. It also induces production of Interleukin (IL)-2 and interferon (IFN)-γ by splenic cells from infected and urequinona treated mice stimulated in vitro with parasite antigen (Ag) but inhibits the production of IL-6 and IL-12p70 by bone-marrow-derived macrophages (BMM) infected in vitro and then treated with urequinona. It also induces activation of transcription factors such as NFkB and AP-1 (NFkB/AP-1) in RAW reporter cells. We also developed a novel pharmaceutical preparation of urequinona encapsulated in hydroxyethyl cellulose for dermal application that significantly reduced (P < 0.05) experimentally induced ear lesions of C57BL/6 mice. We conclude the preparation containing this molecule is a good candidate for a novel anti-leishmanial drug's preparation.

PET/CT with 18F-Fluordesoxyglucose in patients with suspected endovascular prosthesis infection. / PET/TC con 18F-Fluordesoxiglucosa en pacientes con sospecha de infección de prótesis endovasculares.

OBJECTIVE: Infection of large vessel prostheses is a rare but critical complication. The aim of this work is to assess the impact of PET/CT with 18F-Fluordesoxyglucose (PET-FDG) on the diagnosis of infection in our environment. MATERIAL AND METHODS: Thirty-five patients (38 scans) were evaluated for suspected prosthetic infection. A qualitative analysis was performed taking into account the distribution of the radiopharmaceutical, categorizing the studies as positive or negative for infection. Those with focal or multifocal deposits along the vascular prosthesis were considered positive, and negative if a homogeneous and diffuse distribution over the whole prosthesis was observed, or a total absence of uptake. A semi-quantitative analysis was performed using SUVmax and average SUV values, and a metabolic index was calculated (SUVmax of the graft / average SUV of the normal vascular pool). RESULTS: The PET-FDG study was positive in 20 patients, with a diagnostic accuracy of 84%. The 38 PET-FDG scans performed showed positive capture patterns (focal in 6, multifocal in 15, diffuse in 4) and negative pattern in the remaining 13. The sensitivity, specificity, positive and negative predictive values obtained for the PET-FDG were 95%, 89%, 90% and 94%, and for the AngioTC study 50%, 73%, 73% and 50%, respectively. The area values under the ROC curve were as follows: for the AngioTC 0.642 (not significant), and for the SUVmax values of 0.925 (p<0.005), average SUV of 0.922 (p<0.005) and for the metabolic index of 0.917 (p<0.005). CONCLUSIONS: The PET-FDG proves to be a tool with high diagnostic accuracy in the infection of vascular prosthesis, both visual analysis according to patterns and semi-quantitative.

Metabarcoding by capture using a single COI probe (MCSP) to identify and quantify fish species in ichthyoplankton swarms.

The ability to determine the composition and relative frequencies of fish species in large ichthyoplankton swarms could have extremely important ecological applications However, this task is currently hampered by methodological limitations. We proposed a new method for Amazonian species based on hybridization capture of the COI gene DNA from a distant species (Danio rerio), absent from our study area (the Amazon basin). The COI sequence of this species is approximately equidistant from all COI of Amazonian species available. By using this sequence as probe we successfully facilitated the simultaneous identification of fish larvae belonging to the order Siluriformes and to the Characiformes represented in our ichthyoplankton samples. Species relative frequencies, estimated by the number of reads, showed almost perfect correlations with true frequencies estimated by a Sanger approach, allowing the development of a quantitative approach. We also proposed a further improvement to a previous protocol, which enables lowering the sequencing effort by 40 times. This new Metabarcoding by Capture using a Single Probe (MCSP) methodology could have important implications for ecology, fisheries management and conservation in fish biodiversity hotspots worldwide. Our approach could easily be extended to other plant and animal taxa.

Decanethiol functionalized silver nanoparticles are new powerful leishmanicidals in vitro.

We evaluated, for the first time, the leishmanicidal potential of decanethiol functionalized silver nanoparticles (AgNps-SCH) on promastigotes and amastigotes of different strains and species of Leishmania: L. mexicana and L. major isolated from different patients suffering from localized cutaneous leishmaniasis (CL) and L. mexicana isolated from a patient suffering from diffuse cutaneous leishmaniasis (DCL). We recorded the kinetics of promastigote growth by daily parasite counting for 5 days, promastigote mobility, parasite reproduction by CFSE staining's protocol and promastigote killing using the propidium iodide assay. We also recorded IC50's of promastigotes and amastigotes, therapeutic index, and cytotoxicity by co-culturing macrophages with AgNps-SCH or sodium stibogluconate (Sb) used as reference drug. We used Sb as a reference drug since it is used as the first line treatment for all different types of leishmaniasis. At concentrations 10,000 times lower than those used with Sb, AgNps-SCH had a remarkable leishmanicidal effect in all tested strains of parasites and there was no toxicity to J774A.1 macrophages since > 85% were viable at the concentrations used. Therapeutic index was about 20,000 fold greater than the corresponding one for Sb treated cells. AgNps-SCH inhibited > 80% promastigote proliferation in all tested parasites. These results demonstrate there is a high leishmanicidal potential of AgNps-SCH at concentrations of 0.04 µM. Although more studies are needed, including in vivo testing of AgNps-SCH against different types of leishmaniasis, they can be considered a potential new treatment alternative.

Treating murine Kala-azar with a Mayan plant induces immunochemical changes.

Pentalinon andrieuxii Muell Arg is a Mexican-Central American plant anciently used by local people to treat cutaneous leishmaniasis. We evaluated a hexane extract of the root we called PAE for its chemical content and for its immunochemical and in vitro activity against Leishmania donovani and healing of experimental Kala-azar. Chemical analysis using gas chromatography coupled to mass spectrometry (GC-MS) identified hexadecanoic acid, hexadecanoic acid ethyl ester, 9, 12-octadecadienoic acid ethyl ester, octadecanoic acid ethyl ester, 9-octadecenoic acid ethyl ester and diethyl phthalate as the main compounds present in PAE. We also demonstrated PAE kills promastigotes and amastigotes in vitro and significantly reduces parasite loads in liver and spleen of infected Balb/c mice. PAE induces expression of NFkB/AP-1 transcription factors and production of IL-2 and IFN-γ by spleen cells of PAE treated but not in the untreated control mice. Furthermore, there were not IL-6, IL-10 nor TNF production in macrophages treated in vitro with PAE. We developed an affordable extract of P. andrieuxii effective to treat experimental Kala-azar in Balb/c mice.

"It Ruined My Life": The effects of the War on Drugs on people who inject drugs (PWID) in rural Puerto Rico.

BACKGROUND: The War on Drugs has raised the incarceration rates of racial minorities for non-violent drug-related crimes, profoundly stigmatized drug users, and redirected resources from drug prevention and treatment to militarizing federal and local law enforcement. Yet, while some states consider shifting their punitive approach to drug use, to one based on drug treatment and rehabilitation, nothing suggests that these policy shifts are being replicated in Puerto Rico. METHODS: This paper utilizes data from 360 PWID residing in four rural towns in the mountainous area of central Puerto Rico. We initially recruited 315 PWID using respondent-driven sampling (RDS) and collected data about risk practices and conducted HIV and HCV testing. During a second phase, we conducted 34 micro-ethnographic assays, in which we randomly recruited 34 participants from the first phase and included their ego networks in this phase. Our ethnographic inquiry produced significant data regarding the effects of the war on drugs on the local drug trade, drug availability, and injectors' social networks. RESULTS: Findings suggest that repressive policing has been ineffective in preventing drug distribution and use among those in our study. This type of law enforcement approach has resulted in the disproportionate incarceration of poor drug users in rural Puerto Rico, and mainly for nonviolent drug-related crimes. In addition, incarceration exposes PWID to a form of a cruel and unusual punishment: having to quit heroin "cold turkey" while the prison environment also represents a HIV/HCV risk. In turn, the war on drugs not only diverts resources from treatment but also shapes treatment ideologies, punishing non-compliant patients. CONCLUSION: Shifting the emphasis from repression to treatment and rehabilitation is likely to have a positive impact on the health and overall quality of life of PWID and their communities.

DNA Metabarcoding of Amazonian Ichthyoplankton Swarms.

Tropical rainforests harbor extraordinary biodiversity. The Amazon basin is thought to hold 30% of all river fish species in the world. Information about the ecology, reproduction, and recruitment of most species is still lacking, thus hampering fisheries management and successful conservation strategies. One of the key understudied issues in the study of population dynamics is recruitment. Fish larval ecology in tropical biomes is still in its infancy owing to identification difficulties. Molecular techniques are very promising tools for the identification of larvae at the species level. However, one of their limits is obtaining individual sequences with large samples of larvae. To facilitate this task, we developed a new method based on the massive parallel sequencing capability of next generation sequencing (NGS) coupled with hybridization capture. We focused on the mitochondrial marker cytochrome oxidase I (COI). The results obtained using the new method were compared with individual larval sequencing. We validated the ability of the method to identify Amazonian catfish larvae at the species level and to estimate the relative abundance of species in batches of larvae. Finally, we applied the method and provided evidence for strong temporal variation in reproductive activity of catfish species in the Ucayalí River in the Peruvian Amazon. This new time and cost effective method enables the acquisition of large datasets, paving the way for a finer understanding of reproductive dynamics and recruitment patterns of tropical fish species, with major implications for fisheries management and conservation.

A New Antileishmanial Preparation of Combined Solamargine and Solasonine Heals Cutaneous Leishmaniasis through Different Immunochemical Pathways.

Little has been done during the past 100 years to develop new antileishmanial drugs. Most infected individuals live in poor countries and have a low cash income to be attractive targets to pharmaceutical corporations. Two heterosidic steroids, solamargine and solasonine, initially identified as major components of the Brazilian plant Solanum lycocarpum, were tested for leishmanicidal activity. Both alkaloids killed intracellular and extracellular Leishmania mexicana parasites more efficiently than the reference drug sodium stibogluconate. A total of 10 µM each individual alkaloid significantly reduced parasite counts in infected macrophages and dendritic cells. In vivo treatment of C57BL/6 mice with a standardized topical preparation containing solamargine (45.1%) and solasonine (44.4%) gave significant reductions in lesion sizes and parasite counts recovered from lesions. Alkaloids present different immunochemical pathways in macrophages and dendritic cells. We conclude that this topical preparation is effective and a potential new and inexpensive treatment for cutaneous leishmaniasis.

Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats.

Tumor Necrosis Factor-alpha (TNF-α) is an immunomodulatory and proinflammatory cytokine implicated in neuro-inflammation and neuronal damage in response to cerebral ischemia. The present study tested the hypothesis that anti-TNF-α agents may be protective against cerebral infarction. Transient focal ischemia was artificially induced in anesthetized adult male Wistar rats (300-350 g) by middle cerebral artery occlusion (MCAO) with an intraluminal suture. TNF-α function was interfered with either a chimeric monoclonal antibody against TNF-α (infliximab-7 mg/kg) aiming to TNF-α soluble and membrane-attached form; or a chimeric fusion protein of TNF-α receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-α soluble form. Both agents were administered intraperitoneally 0 or 6 h after inducing ischemia. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral infarct volume was significantly reduced in either etanercept or infliximab-treated group compared with non-treated MCAO rats 24 h after reperfusion. These results suggest that anti-TNF-α agents may reduce focal ischemic injury in rats.

Histological development of the digestive system of the Amazonian pimelodid catfish Pseudoplatystoma punctifer.

The organogenesis of the digestive system was described in the Amazonian pimelodid catfish species Pseudoplatystoma punctifer from hatching (3.5 mm total length, TL) to 41 days post-fertilization (dpf) (58.1 mm TL) reared at 28°C. Newly hatched larvae showed a simple digestive tract, which appeared as a straight undifferentiated and unfolded tube lined by a single layer of columnar epithelial cells (future enterocytes). During the endogenous feeding period, comprised between 20 and 96 h post-fertilization (3.5 to 6.1 mm TL), the larval digestive system experienced a fast transformation with the almost complete development and differentiation of most of digestive organs (buccopahrynx, oesophagus, intestine, liver and exocrine pancreas). Yolk reserves were not completely depleted at the onset of exogenous feeding (4 dpf, 6.1 mm TL), and a period of mixed nutrition was observed up to 6 to 7 dpf (6.8 to 7.3 mm TL) when yolk was definitively exhausted. The stomach was the organ that latest achieved its complete differentiation, characterized by the development of abundant gastric glands in the fundic stomach between 10 and 15 dpf (10.9 to 15.8 mm TL) and the formation of the pyloric sphincter at the junction of the pyloric stomach and the anterior intestine at 15 dpf (15.8 mm TL). The above-mentioned morphological and histological features observed suggested the achievement of a digestive system characteristic of P. punctifer juveniles and adults. The ontogeny of the digestive system in P. punctifer followed the same general pattern as in most Siluriform species so far, although some species-specific differences in the timing of differentiation of several digestive structures were noted, which might be related to different reproductive guilds, egg and larval size or even different larval rearing practices. According to present findings on the histological development of the digestive system in P. punctifer, some recommendations regarding the rearing practices of this species are also provided in order to improve the actual larval rearing techniques of this fast-growing Neotropical catfish species.

The validity of incremental exercise testing in discriminating of physiological profiles in elite runners.

The goal of this study was to determine whether traditional ergoespirometric incremental exercise testing carried out to the point of exhaustion could be useful in distinguishing the physiological profiles of elite runners that compete in races that lasted about 8 minutes versus those that lasted about 2 hours. Ten male marathon runners (performance time: 2:12:04, coefficient of variation (CV) = 2.33%) and 8 male 3000 m steeplechase runners (performance time: 8:37.83, CV = 2.12%) performed an incremental test on the treadmill (starting speed 10 km·h-1; increments, 2 km·h-1; increment duration, 3 min to exhaustion). Heart rate (HR), VO2, and lactate concentrations were measured at the end of each exercise level. At maximal effort, there were no differences between the groups regarding VO2max and maximal HR; however, the workload time, vVO2max and peak treadmill velocity were significantly higher in the 3000 m steeplechase group (p<0.05). At submaximal effort, there were no significant differences between groups for VO2 (ml·kg-1·min-1), HR, or lactate. Our results show that this type of testing was not sufficient for discriminating the physiological profiles of elite runners who competed in middle-distance versus long-distance events (e.g. in the marathon and the 3000 m steeplechase).

Efficacy of short-duration (twice weekly) intralesional sodium stibogluconate in treatment of cutaneous Leishmaniasis in India.

BACKGROUND: Cutaneous leishmaniasis (CL) is caused by Leishmania major and L. tropica in the old world. Bikaner, the 'Thar Desert', situated in the north-western corner of India, is an endemic pocket for CL caused by L. tropica. Skin lesions of CL heal slowly, causing disfiguring scars if remaining untreated. Current recommended treatment for CL comprises systemic administration of sodium stibogluconate (SSG) for 2-3 weeks. Five to seven injections of SSG intralesionally have also been found to be effective. OBJECTIVES: To determine the efficacy of a short-duration, twice-weekly intralesional SSG treatment for CL. METHODS: Two hundred and twenty patients with CL having 298 lesions were included in the present study. They were divided into groups A and B (110 patients each). Patients were treated with five to seven intralesional injections of SSG in doses of 50 mg cm(-2) of lesion either once (group A) or twice (group B) weekly. Improvement was recorded at 6, 8, 10, 12, 16, 20 and 24 weeks and the rate of complete cure was compared. RESULTS: Complete cure rate at 6, 8 and 10 weeks was higher (20%, 57% and 73%, respectively) in group B as compared with group A (12%, 36% and 62%, respectively). The differences in cure rates at these time points were statistically significant (P < 0.05). The complete cure rate at 24 weeks was similar in both groups (96% in group B and 92% in group A). The remaining 4% and 8% of patients in groups B and A were 'nonresponders', respectively. No major side-effects were observed in either group. In all cured cases, there were no relapses reported up to 2 years after treatment. CONCLUSIONS: A short-duration, twice-weekly intralesional SSG treatment for CL accelerates cure and is highly effective and well tolerated.

La familia Zamiaceae en Guatemala / The family Zamiaceae in Guatemala

La actualización del conocimiento de las Coniferas de Guatemala comprende 57 especies de plantas, de las cuales 28 especies son nativas y 29 son exóticas, agrupadas en diferentes familias, una de ellas, la familia Zamiaceae, que es un grupo de plantas parecidas a las palmas y que se estudiaron a través del Proyecto Universitario de Investigación en Ciencias Básicas PUICB.057 Actualización de la flora de Guatemala, capítulo I Pinophyta. Se colectaron y georeferenciaron ejemplares de las distintas especies que conforman las Zamiáceas, ello permitió preparar mapas de distribución de las especies nativas, incluidas en los géneros Ceratozamia (1 especie) y Zamia (4 especies) además se documentaron especies exóticas como Dioon mejiae y Zamia furfuraceae, empleadas como ornamentales...

17Beta-estradiol increases Leishmania mexicana killing in macrophages from DBA/2 mice by enhancing production of nitric oxide but not pro-inflammatory cytokines.

We have previously shown that female DBA/2 mice are significantly more resistant to Leishmania mexicana compared with males. Here, we have analyzed the effect of 17beta-estradiol (E(2)) on function and cytokine production in male and female DBA/2 macrophages in vitro. We show that E(2) increases NO production and parasite killing in L. mexicana-infected male and female DBA/2 macrophages without increasing production of pro-inflammatory cytokines. These data indicate that E(2) may enhance leishmanicidal activity in macrophages by directly regulating production of NO.