First-in-Human Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of Single Doses of NTM-1633, a Novel Mixture of Monoclonal Antibodies against Botulinum Toxin E.

Botulism is a rare, life-threatening paralytic disease caused by botulinum neurotoxin (BoNT). Available treatments including an equine antitoxin and human immune globulin are given postexposure and challenging to produce and administer. NTM-1633 is an equimolar mixture of 3 human IgG monoclonal antibodies, E1, E2, and E3, targeting BoNT serotype E (BoNT/E). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1633. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy volunteers to receive a single intravenous dose of NTM-1633 (0.033, 0.165, or 0.330 mg/kg) or saline placebo. Safety monitoring included physical examinations, clinical laboratory studies, and vital signs. Blood sampling was performed at prespecified time points for PK and immunogenicity analyses. Twenty-four subjects received study product (18 NTM-1633; 6 placebo), and no deaths were reported. An unrelated serious adverse event was reported in a placebo subject. Adverse events in the NTM-1633 groups were generally mild and similar in frequency and severity to the placebo group, and no safety signal was identified. NTM-1633 has a favorable PK profile with a half-life >10 days for the 0.330 mg/kg dose and an approximately linear relationship with respect to maximum concentration and area under the concentration-time curve (AUC0→t). NTM-1633 also demonstrated low immunogenicity. NTM-1633 is well tolerated at the administered doses. The favorable safety, PK, and immunogenicity profile supports further development as a treatment for BoNT/E intoxication and postexposure prophylaxis.

Neurosífilis e infección por el virus de inmunodeficiencia humana. Una puesta al día / Neurosyphilis and infection by the virus human immunodeficiency. Update

Medical literature shows that the co-infection of syphilis and human immunodeficiency virus (HIV) is increasing dramatically worldwide. HIV infection and syphilis have a synergistic relationship. Syphilis increases the risk of HIV transmission and acquisition, while HIV affects the presentation, diagnosis, progression and response to syphilis treatment. The diagnosis of syphilis is made with a non-treponemal reactive test (VDRL or RPR) confirmed with a treponemal test (FTA-ABS or MHA-TP). The opportune diagnosis of neurosyphilis is essential, particularly in the asymptomatic stages, given the high risk of serious sequels and lethality. All patients co-infected with HIV and syphilis with neurological symptoms must be studied with PL and other complementary tests. There is controversy about when to perform a lumbar puncture in co-infected patients who do not have neurological symptoms. However, there is consensus that a CD4 count lower than 350/µl or RPR title greater than 1/32 has indication for the study of cerebrospinal fluid. Therapy with penicillin G in high doses is the treatment of choice, in addition to clinical and serological follow-up that must be done to these patients. (AU)

Isolation, Identification and Partial Characterization of a Lactobacillus casei Strain with Bile Salt Hydrolase Activity from Pulque.

The aim of this study was to isolate, from pulque, Lactobacillus spp. capable of survival in simulated gastrointestinal stress conditions. Nine Gram-positive rods were isolated; however, only one strain (J57) shared identity with Lactobacillus and was registered as Lactobacillus casei J57 (GenBank accession: JN182264). The other strains were identified as Bacillus spp. The most significant observation during the test of tolerance to simulated gastrointestinal conditions (acidity, gastric juice and bile salts) was that L. casei J57 showed a rapid decrease (p ≤ 0.05) in the viable population at 0 h. Bile salts were the stress condition that most affected its survival, from which deoxycholic acid and the mix of bile salts (oxgall) were the most toxic. L. casei J57 showed bile salt hydrolase activity over primary and secondary bile salts as follows: 44.91, 671.72, 45.27 and 61.57 U/mg to glycocholate, taurocholate, glycodeoxycholate and taurodeoxycholate. In contrast, the control strain (L. casei Shirota) only showed activity over tauroconjugates. These results suggest that L. casei J57 shows potential for probiotic applications.

Dynamics of carbon and nitrogen in a mixture of polycyclic aromatic hydrocarbons contaminated soil amended with organic residues.

Contamination of soil with polycyclic aromatic hydrocarbons (PAHs) through oil spills occurs frequently in Mexico. PAHs are highly resistant to degradation and restoration of these contaminated soils might be achieved by applying readily available organic material. A clayey soil was contaminated in the laboratory with different forms of PAHs, i.e. phenanthrene, anthracene and benzo(a)pyrene, and amended with maize or biosolids while production of carbon dioxide (CO2), dynamics of ammonia (NH4-), nitrate (NO3-) and PAHs were monitored. The largest CO2 production rate was found in soil added with maize and biosolids and the lowest in the unamended soil. The concentration of PAHs added to the sterilized soil did not change significantly over time and addition of organic material had no significant effect on it. The concentration of PAHs in unsterilized soil decreased sharply in the first weeks independent of addition of organic material and changes were small thereafter. After 100 days, 77% of benzo(a)pyrene was removed from soil, but 91% and 93% of phenanthrene and anthracene, respectively was removed. It was concluded that the autochthonous microbial population degraded phenanthrene, anthracene and benzo(a)pyrene, but neither biosolids nor maize accelerated the decomposition of PAHs or affected their residual concentration.

Población expuesta a ruido de tráfico vehicular en la comuna de Ñuñoa 1989, 2001 / Population exposed to road traffic noise in the commune of Ñuñoa 1989, 2001

En la Región Metropolitana (RM) se han realizado dos estudios sobre exposición a ruido, uno en el año 1989 y otro en el 2001, con la misma metodología. En ambos estudios se determinaron los niveles de ruido ambiental en 23 comunas de la RM, y se compararon con criterios internacionales sobre niveles de riesgo para la salud. Se reanalizaron los datos de ambos estudios para estimar la población de la comuna de Ñuñoa expuesta a niveles de ruido de riesgo para la salud, entre 1989 y 2001, y se estimó la proporción de la población expuesta a niveles de ruido con efectos en salud: perturbación del sueño, exposición a 45 decibeles (dB(A) o nivel de presión sonora continuo equivalente para el período nocturno (entre las 22:00 y 7:00 hrs.); Molestias e inferencia con el sueño: exposición a 55 dB(A) o nivel continuo equivalente para el período de 24 horas; y pérdida auditiva a largo plazo: exposición a 70 dB(A) o nivel continuo equivalente para el período completo de 24 horas. Dentro de los resultados el 15 por ciento de la población estuvo expuesta a perturbación del sueño y molestia e interferencia con actividades diarias, sin variaciones en los años estudiados. El distrito de Pucara muestra la proporción más baja de población expuesta a niveles asociados a perturbación del sueño y molestias e interferencia con actividades (2,6 por ciento), el distrito Plaza Zañartu presenta la mayor población expuesta (23,6 por ciento), sin variación en el período. La población expuesta a daño auditivo a largo plazo tiene tendencia al descenso. La población menos expuesta es la residente de calle Tobalaba (0,3 por ciento) y la más expuesta la de la calle Irarrázaval (3,4 por ciento), sin variación en el período. Los resultados obtenidos señalan la necesidad de revisar las normativas relacionadas con las fuentes emisoras de ruido en las ciudades, la calidad acústica ambientales y las condiciones acústicas de la edificación.

Dynamics of carbon, nitrogen and hydrocarbons in diesel-contaminated soil amended with biosolids and maize.

Contamination of soil with hydrocarbons occurs frequently when petroleum ducts are damaged. Restoration of those contaminated soils might be achieved by applying readily available organic material. An uncontaminated clayey soil sampled in the vicinity of a duct carrying diesel which ruptured recently, was contaminated in the laboratory and amended with or without maize or biosolids while production of carbon dioxide (CO(2)), dynamics of ammonia (NH(4)(+)), nitrates (NO(3)(-)), and total petroleum hydrocarbons (TPH) were monitored. The fastest mineralization of diesel, as witnessed by production of CO(2), was found when biosolids were added, but the amount mineralized after 100 days, approximately 88%, was similar in all treatments. Approximately 5 mg of the 48 mg TPH kg(-1) found in the sterilized soil at the beginning of the experiment could not be accounted for after 100 days. The concentration of TPH in the unsterilized soil decreased rapidly in all treatments, but the rate of decrease was different between the treatments. The fastest decrease was found in the soil amended with biosolids and approximately 30 mg TPH kg(-1) or 60% could not be accounted for within 7 days. The decrease in concentration of TPH at the onset of the incubation was similar in the other treatments. After 100 days, the concentration of TPH was similar in all soils and appear to stabilize at 19 mg TPH kg(-1) soil. It was concluded that biosolids accelerated the decomposition of diesel and TPH due to its large nutrient content, but after 100 days the amount of diesel mineralized and the residual concentration of TPH was not affected by the treatment applied.

Paragonimosis in the Cajabamba and Condebamba districts, Cajamarca, Peru.

Stool samples from 409 pre-school and school students, living in six villages of the Cajabamba and Condebamba districts, Cajamarca, Perú, were examined using wet preparations and Lumbreras' method, looking for Paragonimus eggs. Fecal and sputum samples from two children (0. 5%) of 6 and 8 year-old showed eggs of Paragonimus. One hundred and twenty freshwater crabs, Hypolobocera chilensis eigenmanni, were collected from the Condebamba valley and 21 (17.5%) of them were infected with P. mexicanus (syn. P. peruvianus) metacercariae. Our results show the persistence of Paragonimus in human beings and in the main source of infection, the crabs.