Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

Δ6-fatty acid desaturase and fatty acid elongase mRNA expression, phagocytic activity and weight-to-length relationships in channel catfish (Ictalurus punctatus) fed alternative diets with soy oil and a probiotic.

A time-course feeding trial was conducted for 120 days on juvenile channel catfish (Ictalurus punctatus) to study the effects of diets differing in oil source (fish oil or soy oil) and supplementation with a commercial probiotic. Relative levels of Δ6-fatty acid desaturase (Δ6-FAD) and fatty acid elongase (FAE) expression were assessed in brain and liver tissues. Both genes showed similar expression levels in all groups studied. Fish weight-to-length relationships were evaluated using polynomial regression analyses, which identified a burst in weight and length in the channel catfish on day 105 of treatment; this increase was related to an increase in gene expression. Mid-intestinal lactic acid bacterium (LAB) count was determined according to morphological and biochemical criteria using API strips. There was no indication that intestinal LAB count was affected by the modified diets. The Cunningham glass adherence method was applied to evaluate phagocytic cell activity in peripheral blood. Reactive oxygen species (ROS) generation was assessed through the respiratory burst activity of spleen macrophages by the NBT reduction test. Probiotic-supplemented diets provided a good substrate for innate immune system function; the phagocytic index was significantly enhanced in fish fed soy oil and the probiotic, and at the end of the experimental period, ROS production increased in fish fed soy oil. The substitution of fish oil by soy oil is recommended for food formulation and will contribute to promoting sustainable aquaculture. Probiotics are also recommended for channel catfish farming as they may act as immunonutrients.

Glycerol as substrate for the production of biosurfactant by Pseudomonas aeruginosa UCP0992.

In this work the influence of the carbon source concentration, of the type and concentration of the nitrogen source and of the cultivation conditions (temperature, aeration and agitation speed) in mineral medium formulated with glycerol was studied for biosurfactant production by Pseudomonas aeruginosa UCP0992. The kinetics of microorganism growth and biosurfactant production have been described for the medium supplemented with 3% glycerol and 0.6% NaNO(3), at 28 degrees C during 120 h under 200 rpm, showing a growth-associated production. The isolated biosurfactant corresponded to a concentration of 8.0 g/l after 96 h. The medium surface tension was reduced to 27.4 mN/m and the emulsification index of hexadecane reached 75-80% after 72 h. A CMC of 700 mg/l and an interfacial tension against hexadecane of 2 mN/m were obtained. The biosurfactant showed stability when submitted at 90 degrees C during 2 h, and thermal (4-120 degrees C) and pH (4-12) stability regarding the surface tension reduction and the emulsification capacity of vegetable oils and hydrocarbons, and tolerance under high salt concentrations (2-10%). The biosurfactant was characterized as a group of rhamnolipids with anionic nature. The crude biosurfactant did not show toxicity against the microcrustacean Artemia salina and the cabbage (Brassica oleracea), while the isolated biosurfactant showed toxicity against the microcrustacean at the CMC. The application of the biosurfactant in diesel recovery from sand was demonstrated by removal percentiles above 85%. The results obtained in this work are noteworthy for possible biosurfactant production from glycerol with potential of application in the environment.

Larvicidal activities against Aedes aegypti of some Brazilian medicinal plants.

Larvicidal activities against Aedes aegypti have been determined in the ethanolic extracts obtained from 51 Brazilian medicinal plants. Eleven of the 84 extracts studied showed significant (LC50 < 100 microg mL(-1)) activities against larvae, with extracts from Annona crassiflora (root bark, LC50 = 0.71 microg mL(-1); root wood, LC50 = 8.94 microg mL(-1)) and Annona glabra (seed, LC50 = 0.06 microg mL(-1)) showing the highest activities. The results obtained should be of value in the search for new natural larvicidal compounds.

A study of the larvicidal and molluscicidal activities of some medicinal plants from northeast Brazil.

In a search for natural products that could be used to control the vectors of tropical diseases, 23 extracts of medicinal plants from the northeast of Brazil have been tested for molluscicidal activity against egg masses and adults of the snail Biomphalaria glabrata, for larvicidal activity against the larvae of the mosquito Aedes aegypti, and for general toxicity against the larvae of the brine shrimp Artemia salina. Of these extracts, two were active against the adult snail, one against snail egg masses, eight against the larvae of the mosquito, and 16 showed toxicity towards the brine shrimp. Chemical tests indicated that a wide variety of natural product classes were present in those extracts that showed significant activities in the bioassays.

Silymarin induces recovery of pancreatic function after alloxan damage in rats.

Alloxan has been widely used to produce experimental diabetes mellitus syndrome. This compound causes necrosis of pancreatic beta-cells and, as is well known, induces oxidant free radicals which play a relevant role in the etiology and pathogenesis of both experimental and human diabetes mellitus. Previously we have reported hypoglycemic and antilipoperoxidative actions of silymarin in serum and pancreatic tissue respectively. The aim of this study was to test whether silymarin could reduce the hyperglycemia and revert the pancreatic damage in alloxan treated rats, tested with silymarin in two protocols: using both compounds simultaneously for four or eight doses, or using the compound 20 days after alloxan administration for 9 weeks. Serum glucose and insulin were determined, and pancreatic fragments were used for histology and insulin immunohistochemistry. Pancreatic islets were isolated to assess insulin and Pdx1 mRNA expression by RT-PCR. Our results showed that 72 hours after alloxan administration, serum glucose increased and serum insulin decreased significantly, whereas pancreatic tissue presented morphological abnormalities such as islet shrinkage, necrotic areas, loss of cell organization, widespread lipoid deposits throughout the exocrine tissue, and loss of beta cells, but insulin and glucagon immunoreactivity was scattered if any. In contrast the pancreatic tissue and both insulin and glucose serum levels of rats treated with silymarin were similar to those of control animals. In addition, insulin and glucagon immunoreactive cells patterns in Langerhans islets were also normal, and normal insulin and Pdx1 mRNA expression patterns were detected during pancreatic recovery in Langerhans islets. The overall results suggest that silymarin induces pancreatic function recovery demonstrated by insulin and glucagon expression protein and normoglycemia after alloxan pancreatic damage in rats.

Comentarios a la reciente normativa de tratamiento de la tuberculosis de la ATS/CDC/IDS / Comments on recent guidelines for the treatment of tuberculosis by the American Thoracic Society, the Centers for Disease Control and Prevention, and the Infectious Diseases Society of America

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Factores de riesgo en asma / Risk factors in asthma

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Experimental retinopathy of prematurity: angiostatic inhibition by nimodipine, ginkgo-biloba, and dipyridamole, and response to different growth factors.

PURPOSE: To investigate whether commonly used vasodilating drugs ameliorate angiogenesis in experimental retinopathy of prematurity (ROP), and to study the response of these drugs to different growth factors. METHODS: We used a rat and mouse model of oxygen-induced ischemic retinopathy. Animals were treated with nimodipine, gingko-biloba and dipyridamole intraperitoneally starting the day before exposure to room air (day 1). Controls were injected with vehicle solution only. Eyes were processed histopathologically with serial sections and neovascularization was measured by counting the nuclei within the retinal internal limiting membrane, by a masked observer. Retinal and vitreous tissues were assayed by ELISA for VEGF, PDGF and TGFbeta2. RESULTS: Nimodipine significantly inhibited the growth of new vessels in rats. The number of nuclei was 310 +/- 69 in the control group (n:14) and 121 +/- 53 in the treated ones (n:14), (p<0.0005). Similar results were found with ginkgo-biloba extracts: 344 +/- 53 (n:15) in controls, and 136 +/- 29 (n:11) in treated ones (p<0.0005), and with dipyridamole: 303 +/- 69 (n:13) in controls, and 131 +/- 48.5 in treated rats (p<0.0005). Results were similar in mice. 186 +/- 45 (n:7) nuclei counted in controls against 90 +/- 25 (n:6) for dipyridamole treated (p<0.0005); and 81 +/- 21 for ginkgo-biloba treated animals (p<0.0005). A gradual, very significant increase in VEGF values in response to relative hypoxia (room air) contrasted with the significant inhibition noted both with ginkgo-biloba extracts and dipyridamole. TGFbeta2 and PDGF both showed a gradual increase in relative hypoxia at days 2 and 4 of room air (p<0.0005). Treated animals showed marked inhibition of the three growth factors. CONCLUSIONS: All three drugs markedly inhibited angiogenesis in experimental ROP. Growth factors were elevated in hypoxic conditions. Treated animals showed significant decreases of PDGF, VEGF, and TGFbeta2 in retinal and vitreous tissues.

Effect of crude extracts of Erythrina americana Mill. on aggressive behavior in rats.

Three alkaloid fractions were obtained from seeds of Erythrina americana: free alkaloids in hexane, free alkaloids in methanol and liberated alkaloids. The pharmacological evaluation of these fractions on rats showed that, administered in a dose of 3 mg/kg, the three fractions diminished the aggressive behavior. This is comparable when diazepam is used as a control. An interaction between the cholinergic and GABAergic system could be suggested.

Consenso Latinoamericano sobre infecciones en bronquitis crónica / Latin American consensus on infections in chronic bronchitis

Dos tercios de las exacerbaciones agudas de la bronquitis crónica (EABC) se asocian con infección bacteriana y se caracterizan por recrudecimiento súbito de la tos, disnea y aumento en el volumen y el aspecto purulento del esputo. Las infecciones bacterianas crónicas o recurrentes, inician y perpetúan un círculo vicioso de daño a las vías aéreas, que se produce mediante la estimulación persistente de la cascada inflamatoria por los productos bacterianos. De los microorganismos causales, el más común es H. influenzae. Otros patógenos frecuentes incluyen M. catarrhalis, la mayoría resistentes a aminopenicilinas y S. Pneumoniae, el cual ha incrementado recientemente a su resistencia a penicilinas y macrólidos a nivel orbital. Si bien algunos estudios recientes han demostrado de manera clara el beneficio del tratamiento antibiótico de los EABC, existen ciertas dudas relacionadas con la manera de clasificar la enfermedad y con los criterios utilizados para la inclusión y exclusión de los pacientes, que permitan esclarecer de manera definitiva el beneficio del antimicrobiano en cada uno de los grupos en los que se ha clasificado su severidad. Con el fin de lograr un consenso sobre algunas de estas variables y establecer lineamientos racionales que permitan abordar el tratamiento de estos pacientes, se reunieron recientemente (noviembre del 96 y marzo del 97) un grupo de destacados expertos latinoamericanos en infectología y neumología. El consenso identificó una serie de factores de riesgo que permitieron diseñar una clasificación de EABC que establece cuatro grados de severidad; estos a su vez están relacionados con un grupo específico de microorganismos que varían con las circunstancias y desde luego en la sensibilidad a los antibióticos. Asimismo el grupo de expertos estableció que la resistencia de los gérmenes que comúnmente afectan a estos enfermos (H. influenzae, S. pneumoniae y M. catarrhalis) requieren de antimicrobianos que sean activos contra más del 90 por ciento de las cepas causantes. Como lineamientos prácticos terapéuticos, se sugirió que la traqueobronquitis aguda (clase I) no requiere en general de antibióticos; que la amoxicilina permanece como el tratamiento de elección para las exacerbaciones leves (clase II), mientras que para la bronquitis crónica complicada (clase III), algunas fluoroquinolonas (p.ej.: ciprofloxacina), los nuevos macrólidos, combinaciones con inhibidores de betalactamasa o cefalosporina orales de 3º generación...

Antiresorptive therapy in hyperthyroid patients: longitudinal changes in bone and mineral metabolism.

The effect of antiresorptive therapy with nasal calcitonin (CT) in recently diagnosed hyperthyroid patients on conventional medical therapy as well as the evolution of bone metabolism were assessed. Forty-five patients with recent-onset hyperthyroidism (<12 weeks) were sex and menopause stratified and randomly allocated to treatment with carbimazole (Neotomizol), carbimazole plus low dose CT (Calsynar; 100 IU/day, 2 days/week), or carbimazole plus high dose CT (Calsynar; 100 IU/day, 14 days/month). Bone mineral density was measured by dual x-ray absorptiometry in lumbar spine, femoral neck, and Ward's triangle at 0, 9, and 18 months of treatment. We also determined free T4, free T3, TSH, osteocalcin, total and bone alkaline phosphatases, tartrate-resistant acid phosphatase, type I collagen C telopeptide, and urinary hydroxyproline every 3 months of follow-up. No significant difference was observed among treatments. A euthyroid state was attained at 3 months. Bone mass increased significantly at the 9 month evaluation (P < 0.05), with a 5-10% net gain during follow-up. Nevertheless, final bone mass was 4-8% smaller than expected. Bone formation markers were increased at 0 and 3 months, with reductions at 6-9 months; resorption bone markers showed a significant reduction at the 3 month evaluation. These results indicate that the euthyroid state partially reduces hyperthyroidism-associated osteopenia, with a bone mass recovery period during the 6-9 early months of effective treatment. This recovery phase is characterized by raised bone formation markers and reduced bone resorption markers. The treatment with nasal CT at the doses assayed has no additional effect over that of attainment of the euthyroid state.

Pyroglutamyl peptidase I levels and their left-right distribution in the rat retina and hypothalamus are influenced by light-dark conditions.

To evaluate the effects of light and darkness on pyroglutamyl peptidase I activity (pGluPI) and its left-right distribution, pGluPI was measured bilaterally in the retina and hypothalamus under selected light-dark schedules. Rats under a 12 h light-dark cycle were divided into four experimental groups. After the end of the 12 h dark period, the animals were kept two additional hours in darkness (group 1), or light (group 2). After the end of the 12 h light period, the animals were kept two additional hours in darkness (group 3), or light (group 4). Experiments were done in light or darkness depending on the 2 h period. In the retina, a previous 12 h light period led to higher values of enzyme activity than dark periods. Left-right predominance, however, depended on the previous 2 h period: the light period led to left predominance, whereas right predominance was found after the 2 h dark period. In the hypothalamus, a left predominance was found only in group 3. These results demonstrate that environmental light conditions influence pGluPI activity in the rat retina and hypothalamus.

Interleukin-4 as a bone regulatory factor: effects on murine osteoblast-like cells.

Bone remodelling is regulated at the local level by an incompletely elucidated cytokine network. In the present study we have determined the effect of interleukin-4 (IL-4), a cytokine produced by T lymphocytes and other cells, on the activity of murine osteoblasts. IL-4 (0.1-10 ng/ml) did not influence the proliferation rate of the osteoblast-like cell line MC3T3, but inhibited the expression of alkaline phosphatase. In long-term cultures supplemented with ascorbic acid and glycerophosphate such an effect was accompanied by a retardation of matrix mineralization. IL-4 also stimulated M-CSF expression by MC3T3 cells, both at the RNA and bioactivity levels. However, no stimulation of IL-1, IL-6, GM-CSF or PGE2 production was observed. An IL-4-induced inhibition of alkaline phosphatase expression and retardation of mineralization was also found in cultures of primary osteoblast-like cells isolated from neonatal mice calvariae. These results suggest that IL-4, probably released by cells within the bone marrow, may locally influence the activity of bone-forming cells.