Activation of the manganese(I) tricarbonyl core by selective variation of bidentate ligands (L,L'-Bid = N,N' and N,O donor atom sets) in fac-[Mn(CO)3(L,L'-Bid)(CH3OH)](n) complexes.

A range of fac-[Mn(CO)3(L,L'-Bid)(H2O)](n) (L,L'-Bid = neutral or monoanionic bidentate ligands with varied L,L' donor atoms, N,N' and N,O, 1,10-phenanthroline, 2,2'-bipyridine, 2-picolinate, 2,4-quinolinate; n = 0, +1) has been synthesized and the methanol substitution has been investigated for the first time. The complexes were characterized by UV/vis, IR and NMR spectroscopy and X-ray crystallographic studies of the compounds fac-[Mn(CO)3(Bipy)(H2O)][CF3SO3] () and fac-[Mn(CO)3(Phen)(H2O)][CF3SO3] () are reported. A two order-of-magnitude of activation for the methanol substitution is induced as manifested by the second order rate constants with (N,N'-Bid) < (N,O-Bid). Forward and reverse rate and stability constants from slow and stopped-flow UV/vis measurements (k1, M(-1) s(-1); k-1, s(-1); K1, M(-1)) for pyridine as entering nucleophile are as follows: fac-[Mn(CO)3(Phen)(CH3OH)](+) (2.39 ± 5) × 10(-3), (1.5 ± 0.3) × 10(-5), 159 ± 32; fac-[Mn(CO)3(2,4-QuinH)(CH3OH)] (4.5 ± 0.2), (4 ± 1) × 10(-2), 113 ± 29. Activation parameters (ΔH, kJ mol(-1); ΔS, J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as indicated are as follows: fac-[Mn(CO)3(Phen)(CH3OH)](+) (bromide ions) 66.7 ± 0.6, -27 ± 2; (pyridine) 80 ± 3, -25 ± 11; fac-[Mn(CO)3(Pico)(CH3OH)] (bromide ions) 68 ± 2, -24 ± 5. A dissociative interchange mechanism is proposed.

Protein content of antivenoms and relationship with their immunochemical reactivity and neutralization assays.

CONTEXT: Therapy for snakebites relies on the application of antivenoms, which may be produced with different immunogenic mixtures of venom and possess different pharmaceutical characteristics. For these reasons, immunological cross-reactivity and heterologous neutralization were analyzed relative to the protein content of three antivenoms used in the Americas. METHODS: The antivenoms studied were composed of equine F(ab')2 fragments from animals immunized with Crotalinae venoms. The antivenoms were tested against venoms of seven pit viper species from Argentina, seven from Mexico, one from Costa Rica, and one from Colombia. RESULTS: Immunoblotting showed high cross-reactivity of all major protein bands with all the antivenoms tested. ELISA results also showed high cross-reactivity among the different venoms and antivenoms, and a high heterologous neutralization was observed. The results can be interpreted in different ways depending on whether the reactivity is considered in terms of the volume of antivenom used or by the amount of protein contained in this volume of antivenom. The antivenoms with high immunochemical reactivity and neutralizing capacity were those with higher protein content per vial; but when doses were adjusted by protein content, antivenoms of apparently lower neutralizing capacity and immunochemical reactivity showed at least similar potency and reactivity although volumetrically at higher doses. CONCLUSION: Protein content relative to neutralization potency of different products must be taken into account when antivenoms are compared, in addition to the volume required for therapeutic effect. These results show the importance of obtaining high-affinity and high-avidity antibodies to achieve good neutralization using low protein concentration and low-volume antivenoms.

Tetra-µ(3)-hydroxido-tetra-kis-[tricarbonyl-rhenium(I)] pyridine tetra-solvate.

The title compound, [Re(4)(µ(3)-OH)(4)(CO)(12)]·4C(5)H(5)N, crystallizes with one tetranuclear rhenium(I) cubane-like molecule and four pyridine mol-ecules in the asymmetric unit. The coordination environment of each Re(I) atom is distorted octahedral. Four intra-molecular O-H⋯N and four inter-molecular C-H⋯O hydrogen-bond inter-actions are observed. Relatively strong hydrogen bonds are found between the hydrogen-bond donor (µ(3)-OH) and acceptor (basic N atom of pyridine), with N⋯O distances between 2.586 (10) and 2.628 (10) Å. Inter-cube distances of 9.873 (2) and 12.376 (3) Šare observed.

N-Benzyl-isatin.

In the title compound, C(15)H(11)NO(2), two C-H⋯O hydrogen bonds are observed in the crystal structure, as well as π-π stacking with a centroid-centroid distance of 3.623 (2) Å. The planarity of the two ring systems is illustrated by very small deviations of all the atoms from these planes [largest deviations = 0.003 (3) and 0.010 (3) Šfor the phenyl and fused-benzene rings, respectively]. The dihedral angle between these two planes is 77.65 (9)°.

2-(Ammonio-meth-yl)pyridinium sulfate monohydrate.

In the crystal of the title hydrated molecular salt, C(6)H(10)N(2) (2+)·SO(4) (2-)·H(2)O, N-H⋯O and O-H⋯O hydrogen bonds link the mol-ecules into layers parallel to the ab plane. C-H⋯O hydrogen bonds are observed both within these layers and between mol-ecules and ions in adjacent layers.

5-(Trifluoro-meth-oxy)isatin.

THE TITLE COMPOUND [SYSTEMATIC NAME: 5-(trifluoro-meth-oxy)-1H-indole-2,3-dione], C9H4F3NO3, crystallized with two mol-ecules in the asymmetric unit. Inter-molecular N-H⋯O hydrogen bonds link the mol-ecules to form layers parallel to the ab plane. In addition, π-π stacking inter-actions are observed with a centroid-centroid distance of 3.721 (1) Å. The near planarity of the two isatin ring systems is illustrated by by the maximum deviations of 0.023 (1) and 0.025 (1) Šfor the N atom in each case.

(µ(1)-Methano-lato-κ(1)O)-µ(1)-methoxo-κ(1)O-(µ(2)-2-amino-1-methyl-5H-imidazol-4-one-κ(2)N:N')-hexa-carbonyl-dirhenium(I).

In the title compound, [Re(2)(CH(3)O)(2)(CO)(6)(C(4)H(6)N(3)O)], the two Re(I) atoms are linked by a methoxo and methanolato bridge, as well as by a creatinine ligand that coordinates in a bidentate fashion. Three fac-carbonyl ligands occupy the rest of the slightly distorted octa-hedral geometry around each Re(I) atom. The bridging methanolato and methoxo ligands are bent out of the Re(2)O(2) plane by 49.2 (4) and 47.8 (3)° respectively. This is normally associated with a methanolato-bridging-type coordination rather that the more planar methoxo-type bridging. Furthermore, the creatinine bridging molecule is very slightly distorted from the Re(2)N(2)C plane, indicating that the pyrazolo N atom bonded to the Rh(I) atom is not protonated. Charge balance can thus only be attained if one assumes a positional disorder for the methanolato/methoxo H atom. All attempts to locate disordered protons around these O atoms were unsuccessful. Four hydrogen bonds, one N-H⋯O and three C-H⋯O, are observed in the structure. The mol-ecules pack in a head-to-head and tail-to-tail fashion when viewed along the c axis, in alternating columns.

Lymphatic route of transport and pharmacokinetics of Micrurus fulvius (coral snake) venom in sheep.

The contribution of the lymphatic system to the absorption and systemic bioavailability of Micrurus fulvius venom after subcutaneous (SC) administration was assessed using a central lymph-cannulated sheep model. Micrurus fulvius venom was administered either by intravenous bolus (IV) or subcutaneous injection (SC) in 12 sheep with and without thoracic duct cannulation and drainage. Venom concentration in serum and lymph was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) in samples collected over a 6-hour period and in tissues harvested at the end of the experiment. Pharmacokinetic parameters were determined by a non-compartmental analysis. In the lymphatic cannulated group, over the 6 hours after the venom was administered, 69% of administered dose was accounted for in blood (45%) and lymph (25%). Negligible levels of venom were detected in organs and urine implying that the steady state observed after SC administration is maintained by a slow absorption process. Comparison of kinetics of the thoracic duct cannulated and non-cannulated groups showed that lymphatic absorption contributed in an important way to maintenance of this steady state. These results show that the limiting process in the pharmacokinetics of Micrurus fulvius venom following SC administration is absorption, and that the lymphatic system plays a key role in this process.

[Study on the venoms of the principal venomous snakes from French Guiana and the neutralization]. / Etude des venins des principaux serpents venimeux de Guyane française et de leur neutralisation.

We studied some biochemical, toxic and immunological characteristics of the venoms of Bothrops atrox, Bothrops brazili and Lachesis muta, Viperidae responsible for most of the bites of venomous snakes in French Guiana. Chromatographic (HPLC) and electrophoretical profiles (SDS-PAGE), lethal, hemorrhagic, defibrinogenating, coagulant, thrombin like, proteolytic, fibrino(geno)lytic and phospholipase activities were studied. In addition, the neutralization of some toxic activities conferred by four antivenins was compared. The chromatographic and electrophoretic profiles were different for the three venoms, showing differences between Bothrops and L. muta venoms. In general, bothropic venoms showed the highest toxic and enzymatic activities, while the venom of L. muta showed the lowest lethal, hemorrhagic and coagulant activities. The enzymes of bothropic venoms responsible for gelatinolytic activity were around 50-90 kDa. All the venoms were able to hydrolyze a and beta chains of the fibrinogen, showing different patterns of degradation. Although all the antivenoms tested were effective to various degrees in neutralizing the venom of B. brazili and B. atrox, neutralization of L. muta venom was significantly better achieved using the antivenom including this venom in its immunogenic mixture. For the neutralization of L. muta venom, homologous or polyvalent antivenoms that include the "bushmaster" venom in their immunogenic mixture should be preferred.

A two-year, single-group experience with rotational atherectomy.

Rotational atherectomy was introduced with a view to approaching percutaneously, cases that were suboptimal or unsuitable for conventional percutaneous transluminal coronary angioplasty (PTCA). In this article we present our findings for a period of two years starting in April 2001, when 60 procedures were performed on 54 patients. We found the procedure to be successful in B2 and C type lesions. It is our opinion that the lower burr-to-artery ratio used in our cases was significantly beneficial in decreasing immediate complications related to the procedure. Complimentary PTCA and stenting improved the angiographic end result. Using this strategy, we have achieved very acceptable clinical results.

Calcium supplementation to prevent pre-eclampsia--a systematic review.

BACKGROUND: Calcium supplementation during pregnancy may prevent high blood pressure and preterm labour. OBJECTIVE: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse outcomes. DESIGN: A systematic review of randomised trials that compared supplementation with at least 1 g calcium daily during pregnancy with placebo. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (October 2001) and the Cochrane Controlled Trials Register (Issue 3, 2001) were searched and study authors were contacted. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. Data were extracted and analysed. MAIN RESULTS: There was a modest reduction in the risk of pre-eclampsia with calcium supplementation (relative risk (RR) 0.68, 95% confidence interval (CI): 0.57-0.81). The effect was greatest for women at high risk of hypertension (RR 0.21, 95% CI: 0.11-0.39) and those with low baseline calcium intake (RR 0.32, 95% CI: 0.21-0.49). There was no overall effect on the risk of preterm delivery, although there was a reduction in risk among women at high risk of hypertension (RR 0.42, 95% CI: 0.23-0.78). There was no evidence of any effect of calcium supplementation on stillbirth or death before discharge from hospital. There were fewer babies with birthweight < 2,500 g (RR 0.83, 95% CI: 0.71-0.98). In one study, childhood systolic blood pressure > 95th percentile was reduced (RR 0.59, 95% CI: 0.39-0.91). CONCLUSIONS: Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. These benefits were confined to several rather small trials, and were not found in the largest trial to date, conducted in a low-risk population. Further research is required.

[Scorpions: spontaneous report in 2 reference centers in the city of Buenos Aires, 1997-2000]. / Escorpiones: denuncia espontánea en dos centros de referencia en la ciudad de Buenos Aires, 1997-2000.

From September 1997 to June 2000 148 scorpions (118 findings) from the province and city of Buenos Aires were sent to the INPB and the CeNDIE. The species involved were Tityus trivittatus (32/33 found in the city) and Bothriurus bonariensis (81/85 found in the province around the city). The population spontaneous report of both species increased from January 1999 to May 2000. The climatic, spatial and social variables that could be involved in these phenomena were analyzed. The influence of the media was essential for the 'peak' generation. However, the amount of findings or accident by scorpions, as well as the area of the city colonized by T. trivittatus, have shown a progressive increase during the last decades.

A study on the experimental envenomation in mice with the venom of Tityus trivitattus Kraepelin 1898 (Scorpiones, Buthidae) captured in Argentina.

Although Tityus trivitattus is the only scorpion species reported to cause severe human envenomation in Argentina, no previous studies on its venom have been done. Telson homogenates from T. trivitattus specimens collected in Santiago del Estero, Cordoba, and Buenos Aires were employed to study their protein composition and toxicity to mice. Regardless of the site of collection, electrophoretic analysis showed bands at 205, 150, 100, 40, 32, and 13 kDa or smaller. FPLC gel filtration showed three major peaks and 6-8 minor peaks with similar elution volumes. One of the minor peaks from FPLC containing a component of approximately 8 kDa was lethal to mice. Mice injected intravenously with different doses of homogenates presented severe autonomic signs like tachypnea, tachycardia, sialorrhea, lacrimation, profuse sweating, diarrhea, dyspnea, and death. Pathology studies of lungs showed severe congestion of alveolar capillaries, pulmonary edema, and hemorrhagic areas. The kidneys showed glomerular as well as tubular lesions and exocrine glands showed areas of necrosis. The calculated LD50 was 0.38 +/- 0.08 telsons per 20 g mouse, which suggests a lethal potency similar to that of T. serrulatus venom. The lethal potency of 5.0 LD50 of T. trivitattus telson homogenate was neutralized by both an anti-T. trivitattus and a heterologous anti Tityus with ED50 values of 41 +/- 19 and 170 +/- 42 microl, respectively.

trans-Diiodobis(1,3,5-triaza-7-phosphaadamantane)platinum(II).

The crystal structure of the title compound, trans-[PtI(2)(C(6)H(12)N(3)P)(2)], describes one of the few platinum(II) complexes containing two of the water-soluble 1,3,5-triaza-7-phosphaadamantane ligands reported to date. The complex crystallizes on an inversion centre with the most important bond lengths and angles being Pt-P 2.3128 (12) A, Pt-I 2.6022 (6) A, P-Pt-I 90.94 (3) degrees and P'-Pt-I 89.06 (3) degrees.

Escorpiones: denuncia espontánea en dos centros de referencia en la ciudad de Buenos Aires, 1997-2000. / [Scorpions: spontaneous report in 2 reference centers in the city of Buenos Aires, 1997-2000]

From September 1997 to June 2000 148 scorpions (118 findings) from the province and city of Buenos Aires were sent to the INPB and the CeNDIE. The species involved were Tityus trivittatus (32/33 found in the city) and Bothriurus bonariensis (81/85 found in the province around the city). The population spontaneous report of both species increased from January 1999 to May 2000. The climatic, spatial and social variables that could be involved in these phenomena were analyzed. The influence of the media was essential for the peak generation. However, the amount of findings or accident by scorpions, as well as the area of the city colonized by T. trivittatus, have shown a progressive increase during the last decades.

Packing effects on the geometry of neutral platinum(II) complexes due to solvate molecules: the structures of trans-dichlorobis(triphenylarsine)-platinum(II)

A series of structures of trans-dichlorobis(triphenylarsine)platinum(II), recrystallized from four different solvents, have been characterized by X-ray crystallography and were shown to crystallize as different solvates (same metal complex, different crystallization solvents). Their geometric differences induced by packing and solvent molecules were analysed with half-normal probability plots and root-mean-square deviations. The recrystallization solvents used in the investigation were 1,1,1-trichloroethane, dichloromethane, 1,2-dichloroethane and benzene, and the following crystallization modes were obtained. From 1,1,1-trichloroethane the metal complex crystallizes without solvent as trans-[PtCl2(AsPh3)2] in P2(1)/n with Z = 2, a = 9.271 (2), b = 19.726 (4), c = 9.830 (2) A, beta = 111.83 (3)degrees, V = 1668.8 (6) A3, R = 0.0262, and from dichloromethane with two solvent molecules as trans-[PtC12(AsPh3)2].2CH2C12 in Pbca with Z= 4, a = 20.582 (4), b = 8.146 (2), c = 23.491 (5) A, V = 3938.5 (14) A3 and R = 0.0316. From dichloroethane it crystallizes with one solvent molecule as trans-[PtC12(AsPh3)2].C2H4C12 in P1 with Z = 1, a = 9.390 (2), b= 9.548 (2), c = 11.931 (2) A, alpha = 109.70 (3), beta = 108.26 (3), gamma = 98.77 (3) , V= 915.6 (3) A3, R = 0.0390, and from benzene with half a solvent molecule as trans- [PtC12(AsPh3)2].0.5C6H6 in P2(1)/n with Z = 4, a = 11.778 (2), b = 18.712 (4), c = 16.647 (3) A, beta = 104.78 (3) , V= 3547.3 (12) A3 and R = 0.0303. In all four compounds platinum(II) coordinates to triphenylarsine and chloride in a pseudo-square-planar trans configuration. The Pt-As distances are in the range 2.4104 (4)-2.3923 (4) A and the Pt-C distances are in the range 2.309 (2)-2.2839 (9) A. The solvents have a large influence on the packing, resulting in different space groups or different occupancies in the same space group. Half-normal probability plots show that the largest geometric differences, within the metal complex, are in the bond and torsion angles around the As-C bonds. Very similar torsion angles were observed around the Pt-As bond for all the structures, except for one AsPh3 ligand in the benzene solvate, which differs by about 10 from the others. The metal-donor bond distance varies by as much as 0.019 and 0.025 A (95% confidence interval) for Pt-As and Pt-C1, respectively. The variations are essentially caused by intermolecular interactions. Packing efficiency is expressed as the volume filled by each metal complex in the unit cell and is calculated by subtracting the sum of the solvent molecule volumes from the total volume of the unit cell and then dividing by Z. The efficiency is largest in the dichloroethane solvate and smallest in the non-solvated compound, with a difference of approximately 22 A3 per metal complex.

A comparison of different methods to assess the hemorrhagic activity of Bothrops venoms.

The hemorrhagic activity of Bothrops (B.) alternatus, B. ammodytoides, B. jararaca, B. jararacussu, B. moojeni and B. neuwiedii venoms from specimens captured in Argentina was assayed after i.d. injection to mice. The hemorrhagic haloes produced by each venom had different color intensities, although no significant differences were observed by measurement of the average diameters or the weight of the excised hemorrhagic haloes. Conversely, important differences were found by measuring the amount of hemoglobin extracted from excised hemorrhagic haloes of similar size produced by different venoms. The relationship between the amount of hemoglobin extracted and the weight of the excised hemorrhagic haloes was linear, with a slope (hemoglobin released per gram of hemorrhagic halo) characteristic for each venom, and proportional to the potency. On this basis, the activity of B. alternatus, B. ammodytoides and B. jararaca is similar, about 1.5 times higher than that of B. jararacussu and B. moojeni venoms and threefold higher than that of B. neuwiedii venom. Thus, measurement of the of hemoglobin released provides additional information in comparative studies, and may be used to assess the antihemorrhagic potency of antivenoms.

Some toxic and enzymatic activities of Bothrops ammodytoides (yarará ñata) venom.

Bothrops ammodytoides, the smallest representative of this genus, is found only in Argentina. Venom was extracted from thirty adult specimens (35-70 cm in length, 90-300 g in weight) captured in the Province of Buenos Aires and kept in captivity. Venom yield was 3-30 mg. SDS-PAGE showed strong bands at 14.0; 23-25; 45; 54 and 63 kDa and weak bands at 17.0; 30.0; 40.0 and 85.0 kDa. Toxic activities were: LD50 (intravenous, mice) 0.5+/-0.2 microg/g; minimal procoagulant dose on human plasma (MPD-P) 35+/-2 mg/l; and minimal defibrinogenating dose (MDD, mice) 6-12 microg. Hemorrhagic and/or necrotic activities appear to play a major role in lethality; minimal hemorrhagic dose (MHD, mice) is 10+/-2 microg/g and minimal necrotizing dose (MND, mice) is 38+/-5 microg. The LD50, MPD-P and MND are among the lowest in venoms from Bothrops species found in Argentina. B. ammodytoides venom exhibited high proteolytic and phospholipase A2 activities. Most of the B. ammodytoides venom components cross-react with Bivalent Bothropic antivenom (Instituto Nacional de Producción de Biológicos ANLIS Dr. G. Malbrin, against B. alternatus and B. neuwiedii venoms). One ml of antivenom neutralizes 1.2 mg of B. ammodytoides venom.