Coupling biological detection to liquid chromatography: a new tool in drug discovery.

Procedures to characterize drugs that can be obtained from plant extracts or combinatorial chemistry are tedious, and they consume considerable resources (e.g., animals) and time. Thus, we have looked for a way to streamline this process. We describe here a novel system for the pre-characterization of drugs based on liquid chromatography coupled to biological detection using perifused or perfused organs. This novel system allows the on-line detection of pharmacologically active substances in hydrosoluble mixtures from vegetal extracts or combinatorial chemistry libraries. Depending on the volume of drug solution and concentration of the samples, the procedure can work through either medium pressure liquid chromatography or HPLC, and it enables the fingerprints of drugs to be assessed based on their contractile activity on combinations of different isolated tissues. As an example, we show how the system can identify active fractions from an extract of Stevia rebaudiana Bertoni, an activity that was later associated with rebaudioside N. Coupling liquid chromatography to biological detection offers a rapid way to focus attention on active products in complex samples, mostly from hydrosoluble species, helping to considerably reduce the time and cost of the pre-characterization of drugs.

Algae biomass cultivation in nitrogen rich biogas digestate.

Because microalgae are known for quick biomass growth and nutrient uptake, there has been much interest in their use in research on wastewater treatment methods. While many studies have concentrated on the algal treatment of wastewaters with low to medium ammonium concentrations, there are several liquid waste streams with high ammonium concentrations that microalgae could potentially treat. The aim of this paper was to test ammonium tolerance of the indigenous algae community of Lake Mälaren and to use this mixed consortia of algae to remove nutrients from biogas digestate. Algae from Lake Mälaren were cultivated in Jaworski's Medium containing a range of ammonium concentrations and the resulting algal growth was determined. The algae were able to grow at NH4-N concentrations of up to 200 mg L(-1) after which there was significant inhibition. To test the effectiveness of the lake water algae on the treatment of biogas digestate, different pre-cultivation set-ups and biogas digestate concentrations were tested. It was determined that mixing pre-cultivated suspension algae with 25% of biogas digestate by volume, resulting in an ammonium concentration of around 300 mg L(-1), produced the highest algal growth. The algae were effective in removing 72.8±2.2% of NH4-N and 41.4±41.4% of PO4-P.

Theoretical characterization of triangular CdS nanocrystals: a tight-binding approach.

We provide theoretical modeling of the optical spectrum of recently synthesized triangular CdS nanocrystals by means of atomistic tight-binding theory. Both zinc blende and wurtzite structures are considered. Optical properties predicted for triangular prisms are very different from the ones obtained for tetrahedral quantum dots when z-polarized light is employed. In particular, the ground transition is dim for triangular prisms, whereas it is bright and highly intense for tetrahedra. The high sensitivity of the fine optical properties on the quantum dot shape allows us to discriminate between truncated tetrahedra and triangular prisms and also to estimate the thickness of the nanocrystals.

Advantages of the piggy back technique on intraoperative transfusion, fluid compsumption, and vasoactive drugs requirements in liver transplantation: a comparative study.

INTRODUCTION: The piggyback technique was first described in adult liver transplantation in 1989, although it has been used in conjunction with venous bypass, with cross-clamping the vena cava, or both. In this study, the inferior vena cava was not occluded at any time during the liver transplant. OBJECTIVE: We compared the use of intraoperative blood products, fluid requirements, and vasoactive drugs among patients managed with bypass, without bypass, and with the piggyback technique. MATERIAL AND METHODS: Between May 1986 and October 2002, 875 liver transplants included 50 patients divided into three groups (cases considered to be the preliminary series on each group): group A/piggyback (17 patients:34%), group B/ bypass (16 patients: 32%), and group C/no bypass (17 patients:34%). There were no differences in mean age, gender, UNOS or Child-Pugh score, and indications for liver transplantation. RESULTS: Mean follow up was 134.63+/-32.19 months. At the end of the study, 91.3% of the patients are alive with no operative mortality. There were no differences in postoperative complications, postreperfusion syndrome rate, and postoperative renal failure. However, the number of packed red blood cell units consumed intraoperatively (12+/-7.43 vs 18.03+/-11.46 vs 17.59 +/- 23.8; P =.043), the need for intraoperative crystaloids (3.1 L+/-1.6 vs 6.8+/-4.8 vs 9.1 L+/-3.6; P=.001) and the requirement for vasoactive drugs (18% vs 38% vs 24%; P=.043) was notably lower in group A vs group B vs group C. Operative time was longer in group A (121.54+/-37.77 vs 78.73+/-11.89 vs 87.07+/-14.33 minutes). CONCLUSIONS: The piggyback technique requires a longer operative time but offers the advantages of reducing the red blood cell requirements and preventing severe hemodynamic instability by virtue of reducing the need for vasoactive drugs and for a larger volume of intraoperative fluids.

Alkaloids from Delphinium staphisagria.

Three new diterpenoid alkaloids, isoazitine (1), 19-oxodihydroatisine (2), and 22-O-acetyl-19-oxodihydroatisine (3), and eight known alkaloids-azitine (4), dihydroatisine (5), delphinine, neoline, bullatine C (14-acetylneoline), chasmanine, 14-acetylchasmanine, and the quaternary base atisinium chloride (7)-were isolated from the aerial parts of Delphinium staphisagria. Structures of the new alkaloids were established mainly by 1D and 2D NMR spectroscopy, including (1)H COSY, HMQC, HMBC, and ROESY. The (1)H and (13)C NMR data for alkaloids 4 and 5 are also reported.

Sesquiterpene lactones and other constituents of Centaurea napifolia.

Aerial parts of Centaurea napifolia furnished the sesquiterpene lactones cnicin, 4'-acetoxycnicin, melitensin, dehydromelitensin, two known esters of dehydromelitensin, lappaol and a lappaol isomer, and a 1,2-diacylated glucose.

Antinociceptive, anti-inflammatory and antipyretic effects of lapidin, a bicyclic sesquiterpene.

Lapidin, a bicyclic sesquiterpene from Ferula linkii Webb, has been evaluated for antinociceptive, anti-inflammatory, and antipyretic activities in mice and rats. Lapidin, vehicle, or the appropriate reference analgesic and anti-inflammatory compounds (acetylsalicylic acid [ASA] and indomethacin) were injected i.p. The more conspicuous effects of lapidin were: 1) a significant protective effect (17-62%; 2.5-20 mg/kg) towards writhings and stretchings induced by acetic acid in mice; 2) a significant antinociceptive effect on jumping responses in the hot-plate test (120 seconds at 15 mg/kg vs. 40 and 85 seconds in vehicle and ASA-treated mice, respectively); 3) a significant dose-dependent (5-15 mg/kg) antinociceptive effect against mechanical noxious stimuli; 4) a dose-dependent anti-inflammatory effect in the carrageenan-induced edema which, at the higher dose (20 mg/kg), was comparable (65% inhibition of paw swelling at 3 hours) to that obtained after indomethacin (10 mg/kg); and 5) a moderate antipyretic effect against yeast-induced hyperthermia. Present results demonstrate that lapidin possesses antinociceptive, anti-inflammatory, and less pronounced antipyretic effects comparable to those of classical non-steroid anti-inflammatory drugs, which make it worthy of further investigations as an antinociceptive and anti-inflammatory drug.

Cellular differences in ring glands of flesh fly pupae as a consequence of diapause programming.

The ultrastructure of the ring gland (corpus cardiacum (CC), prothoracic gland (PG) and corpus allatum (CA)) was examined in diapausing and nondiapausing flesh fly pupae. The diapause developmental state, which is environmentally regulated and coordinated by the brain-ring gland complex, is associated with differences in the ultrastructure of PG and CA cells but not in the CC. During diapause the PG and CA cells have extensive arrays of rough endoplasmic reticulum and spherical mitochondria. The PG cells also contain lipid droplets surrounded by an electron dense amorphous coat not seen in PG cells from nondiapausing pupae. In nondiapausing pupae, the PG and CA cells contain large amounts of ribosomes throughout the cytoplasm but very little rough endoplasmic reticulum and elongated mitochondria. The fact that ring glands from diapausing pupae readily incorporate (35)S-methioninc indicates that the gland is actively synthesizing proteins, thus the contrasts in ring gland ultrastructure are not due to cellular quiescence during diapause but reflect fundamental cellular and physiological differences between the diapause and nondiapause developmental program.

Analysis of actin and tropomyosin in hearts of cardiac mutant axolotls by two-dimensional gel electrophoresis, western blots, and immunofluorescent microscopy.

When homozygous, recessive mutant gene c in Ambystoma mexicanum results in a failure of embryonic heart function. This failure is apparently due to abnormal inductive influences from the anterior endoderm resulting in an absence of normal sarcomeric myofibril formation. Biochemical and immunofluorescent studies were undertaken to evaluate the contractile proteins actin and tropomyosin in normal and mutant hearts. For the immunofluorescent studies, cardiac tissues were fixed in periodate-lysine-paraformaldehyde, frozen sectioned, and immunostained by an indirect method with monospecific polyclonal antibodies produced against highly purified chicken heart actin and tropomyosin. In normal hearts, both antiactin and antitropomyosin stained the myofibrillar I-bands intensely. In mutant hearts, intensity of staining with antiactin antibody was similar to normal, although sarcomeric patterns were not observed. Staining intensity for tropomyosin with antitropomyosin antibody was significantly reduced in mutant hearts when compared to normal. Biochemical studies were used to evaluate antibody specificity, antigenic variability, and relative protein concentrations of actin and tropomyosin in normal and mutant cardiac tissues. Tissue homogenates were electrophoresed in two dimensions, and second-dimension slab gels were either Coomassie Blue silver-stained or transblotted onto nitrocellulose and the proteins stained with antibodies. Stained gels and immunoblots of cardiac proteins reveal that the amounts of actin isoforms are identical in normal and mutant hearts. However, these methods demonstrate a significantly reduced amount of tropomyosin in mutant tissue. This confirms earlier studies suggesting reduced amounts of tropomyosin in mutant hearts based upon immunological assays. Thus, failure of normal myofibrillogenesis in gene c mutant hearts does not appear to result from a change in actin isoform composition but may be related to a deficiency in tropomyosin.

[Etiology and clinical forms of hoof diseases in bulls]. / Etiologiia i klinichni formi na kopitnite zaboliavaniia pri bitsi.

Investigations were carried out to establish the diseases of hooves in breeder bulls raised under the conditions of modern technologies with restricted movements. It was found that hoof diseases were highest in percent (28%) of all non-infectious diseases. Highest was the percent of the typical traumatic ulcer (62 per cent) and of the local and diffuse aseptic and suppurative pododermatitis (34 per cent), whereas the diseases of the hind hooves prevailed--55 per cent as against 45 per cent for the forelimb ones. Higher was the percent of diseases observed in the hooves of the right limbs--63 per cent as against 36 per cent for the cases of diseases observed in the hooves of the left limbs. The higher liveweight of bulls correlated with the frequency at which hoof diseases were recorded. The pigmented hoof horn tissue was found to be more resistant to the effect of external factors and the hoof diseases associated with them. In the months of May, June, and July the cases of diseased hooves were more numerous than in the remaining months of the year due to the lower resistance of the hoof horn over the rainy period.

Estudio de un brote de intoxicacion alimentaria / Study of an outbreak of food poisoning

Se estudia un brote epidemico por probable intoxicacion por alimentos en 41 personas, pertenecientes a la Escuela Secundaria Tecnica No. 21 de Mexico, D.F. Al analizar los datos se encontro correlacion estadistica entre la ingestion de un pastel de nuez con crema chantilly y enfermedad, por incidencia en expuestos de 0.70, en no expuestos de 0.50 y riesgos relativos de 1.4 y desigualdad relativa de 2.37. En los demas alimentos consumidos las cifras no fueron estadisticamente significativas. El Laboratorio Central de la S.S.A. no encontro contaminacion de los alimentos analizados, ni por compuestos organicos fosforados ni por metales pesados. Se aislo estafilococo dorado en los cultivos de los restos de alimentos (crema chantilly) y en los corpocultivos. En sindrome diarreico con secrecion aumentada que presentaron los sujetos que enfermaron constituyo un modelo natural que permitio la valoracion de la lidamidina, un medicamento antisecretorio intestinal. Existe la posibilidad de que el alimento causante haya sido el pastel de nuez con crema chantilly. Esta sebasa la correlacion estadistica y en los hallazgos de laboratorio

Valoracion doble ciega sobre la efectividad del clorhidrato de lidamidina (WHR - 1142A) VS. loperamida VS.placebo en el tratamiento de la diarrea aguda / Double blind clinical of trial of the effectiveness of lidamidine hydrochloride (WHR -1142A) vs.loperamide vs placebo in the treatment of acute diarrhea

RESUMEN Durante 1980 en el Distrito Sanitario V de México. D. F., se registraron 11.228 casos de diarrea aguda. La etiología fue bacteriana y viral en 69.2% de los casos y los restantes fueron casos de disentería amebiana aguda. Del total de los casos 84.5% correspondieron a pacientes menores de 14 años. Con el propósito de valorar la seguridad y eficacia antidiarreica del clorhidrato de lidumidina (WHR·1142A). versus la lcperamida y un placebo. se llevó al cabo un estudio doble ciego al azar. Del total de la población registrada en el periodo de un año solamente 105 pacientes satisfacieron los requisitos del protocolo (mayores de 12 años, con un mínimo de tres o más evacuaciones Iiquidas o con fragmentos semisólidos, en un periodo previo de 24 horas, sin signas ni síntomas de infección y sin medicación previa). Los pacientes se distribuyeron al azar en tres grupos iguales que recibieron cápsulas idénticas conteniendo 2 mg de lidamidina o 2 mg de loperamida o un placebo. La dosis inicial (2 cápsulas) fue administrada bajo la supervisión del investigador principal y las dosis subsecuentes (1 cápsula) fueron administradas después de cada evacuación líquida. hasta un máximo de 8 cápsulas diarias, durante 72 horas. Al término del estudio y al identificar las cápsulas utilizadas se realizó el análisis estadística. que reveló disminución del número y frecuencia de las evacuaciones con mayor signifícacíón en el grupo tratado con lidamidina, tanto en cada uno de los intervalos de 24 horas como en el periodo total de duración del estudio (72 horas). En comparación con el placebo, tanto la lidamidina como la loperamida fueron efectivas para reducir los pesos promedio de las heces y para modificar favorablemente su consistencia, pero a partir del segundo día de tratamiento los resultados obtenidos fueron más favorables. para la lidamidina. En algunos casos tratados con loperamidina o placebo se presentaron dolor abdominal y timpanismo. Durante el desarrollo del estudio los signos vitales y los valores de las pruebas de laboratorio se mantuvieron dentro de límites normales, sin haberse presentado ningún abandono al tratamiento debido a reacciones secundarias

[Evaluation of the safety and effectiveness of WHR-1142A in the treatment of non-specific acute diarrhea]. / Valoración de la seguridad y eficacia del WHR-1142A en el tratamiento de la diarrea aguda inespecífica.

A randomized double-blind placebo controlled trial of the safety and efficacy of lidamidine hydrochloride (WHR-1142A) in thirty patients with acute nonspecific diarrhea was conducted. During their 29-hour hospital treatment period, the average number of bowel movements for each ten patient treatment group was: placebo, 5.1: lidamidine hydrochloride (10 mg), 2.4; lidamidine hydrochloride (18 mg), 2.5. The average weight of the feces of the patients in each treatment group was: placebo, 576 grams; lidamidine hydrochloride (10 mg), 364 grams; lidamidine hydrochloride (18 mg), 435 grams. Time intervals between each of the first two doses were greater for those patients in the active treatment groups (lidamidine hydrochloride) when compared to the placebo group. Overall evaluation of therapy was rated by physician and patient at end of study: placebo, 10 of 10, not effective; lidamidine hydrochloride (10 mg), 10 of 10 (100%) effective; lidamidine hydrochloride (18 mg), 10 of 10 (100%) effective. Vital signs and laboratory values remained within normal ranges throughout the duration of study, and no clinically significant adverse effects were reported.

[Participation of health centers in the training of technical and auxiliary personnel]. / Participación de los centros de salud en la enseñanza de personal técnico y auxiliar.

The authors propose that the training of technicians and auxiliaries for health institutions must be geared to the historic, economic, and cultural setting of the health problems in a given region. To this end, training and health establishments must set for themselves coordinated, specific objectives designed to meet the community's real health needs. They suggest that a training service be set up in health centers, with programs based on the participation of teachers and trainees and designed to bring the latter into direct contact with the health problems they will encounter in their future employment.