Reversal of arterial oxygen desaturation with the use of an oxygen concentrator during injectable anaesthesia in feral cats positioned in the Trendelenburg, dorsal or lateral surgical position.

INTRODUCTION: This study observed the effects of oxygen supplementation, via an oxygen concentrator, on peripheral arterial blood oxygenation (SpO2) measured by pulse oximetry in anaesthetised cats undergoing spay in three different surgical positions. A total of 192 female feral cats were investigated for a large-scale trap-neuter-release program. Cats were anaesthetised with an intramuscular combination of butorphanol (0,4 mg / kg), ketamine (7-10 mg / kg) and medetomidine (0,03-0,05 mg / kg). Cats were randomly allocated to undergo spay in either Trendelenburg (TR) (70° downward head tilt), lateral (LR) or dorsal (DR) recumbency. Cats were breathing spontaneously either room air or 2 L/minute oxygen via a tight-fitting face mask. Pulse rate (in beats per minute), respiratory rate (in breaths per minute) and SpO2 (in percentage) were measured at baseline in left lateral recumbency and afterwards continuously after being positioned in allocated surgical position. At the end of surgery, cats were placed again in left recumbency, and all parameters were re-evaluated after five minutes. Overall, 33 % of cats showed severe arterial oxygen desaturation (SpO2 < 90 %) at baseline when breathing room air. When oxygen was supplemented during the procedure, arterial oxygen desaturation resolved in all cats. At the end of the procedure, 29 % of cats were hypoxaemic when oxygen was not supplemented, with an overall higher percentage of hypoxaemic cats in TR as compared to DR and LR recumbencies. All cats recovered well from surgery and were released within 24 hours post-anaesthesia. Arterial oxygen desaturation is frequent in cats anaesthetised with injectable anaesthesia for spay under field conditions. Oxygen supplementation administered via a tight-fitting mask resolved arterial oxygen desaturation in this feral cat population regardless of the surgical position and therefore oxygen supplementation is recommended in any case.

INTRODUCTION: Cette étude a observé les effets d'une supplémentation en oxygène, via un concentrateur d'oxygène, sur l'oxygénation du sang artériel périphérique (SpO2) mesurée par oxymétrie de pouls chez des chats anesthésiés subissant une stérilisation dans trois positions chirurgicales différentes. Au total, 192 chats sauvages femelles ont été examinés dans le cadre d'un programme de piégeage, de stérilisation et de remise en liberté à grande échelle. Les chats ont été anesthésiés avec une combinaison de butorphanol (0,4 mg / kg), de kétamine (7­10 mg / kg) et de médétomidine (0,03­0,05 mg / kg) appliquée par voie intramusculaire. Les chats ont été répartis au hasard pour subir une stérilisation en position de Trendelenburg (TR) (inclinaison de la tête de 70° vers le bas), en décubitus latéral (LR) ou en décubitus dorsal (DR). Les chats respiraient spontanément soit de l'air ambiant, soit de l'oxygène à raison de 2 L/minute par l'intermédiaire d'un masque facial bien ajusté. Le pouls (en battements par minute), la fréquence respiratoire (en respirations par minute) et la SpO2 (en pourcentage) ont été mesurés au départ en décubitus latéral gauche, puis en continu après avoir été placés dans la position chirurgicale attribuée. À la fin de l'opération, les chats ont été replacés en décubitus latéral gauche et tous les paramètres ont été réévalués au bout de cinq minutes. Dans l'ensemble, 33 % des chats présentaient une désaturation sévère en oxygène artériel (SpO2 < 90 %) au départ lorsqu'ils respiraient de l'air ambiant. Lorsque de l'oxygène a été ajouté pendant la procédure, la désaturation en oxygène artériel s'est résorbée chez tous les chats. À la fin de l'intervention, 29 % des chats étaient hypoxémiques lorsque l'oxygène n'était pas administré, avec un pourcentage global plus élevé de chats hypoxémiques en décubitus dorsal qu'en décubitus latéral. Tous les chats se sont bien remis de l'opération et ont été libérés dans les 24 heures suivant l'anesthésie. La désaturation en oxygène artériel est fréquente chez les chats anesthésiés par injection pour la stérilisation dans des conditions de terrain. La supplémentation en oxygène administrée via un masque étanche a résolu la désaturation en oxygène artériel dans cette population de chats sauvages, quelle que soit la position chirurgicale et la supplémentation en oxygène est donc recommandée dans tous les cas.

Butorphanol induces anxiety-like -behaviour and distress in piglets.

INTRODUCTION: In a previous study that used butorphanol in pigs before castration performed under isoflurane anaesthesia, severe adverse effects were recorded. As in pigs, this has not been reported before, we aimed to investigate the effects of butorphanol in piglets. In this study ten 27 days old piglets were randomly allocated to receive either 0,2 mg/kg butorphanol (group B) or saline 0,9% (control group C) intramuscularly. Their behaviour was assessed for 60 minutes by two independent observers from videotapes. Two to 15 minutes after application, piglets in group B showed restlessness, distress and excessive vocalisation. Locomotor activity was increased, the piglets laid down considerably less frequently (p = 0,034) and for shorter time periods (p = 0,0014) during the first 40 minutes compared to group C. Group C animals slept most time of the experiment (45,1 ± 2,9 minutes in group C vs 12,7 ± 2,9 minutes in group B, p .

INTRODUCTION: Le butorphanol induit des comportements anxieux et de la détresse chez les porcelets Dans une précédente étude utilisant le butorphanol chez les porcs avant la castration réalisée sous anesthésie à l'isoflurane, des effets indésirables sévères ont été rapportés. Cela n'étant pas décrit auparavant chez les porcs, nous avons cherché à étudier les effets du butorphanol chez les porcelets. Dix porcelets âgés de 27 jours ont été répartis aléatoirement (en double aveugle) pour recevoir 0,2 mg/kg de butorphanol (groupe B) ou du sérum physiologique à 0,9% (groupe de contrôle C) par voie intramusculaire. Leur comportement a été évalué pendant 60 minutes par deux observateurs indépendants à partir d'enregistrements vidéo. Deux à 15 minutes après l'injection, les porcelets du groupe B ont présenté de l'agitation, de la détresse et des vocalisations excessives. L'activité locomotrice a augmenté : lors des 40 premières minutes, les porcelets se sont couchés significativement moins fréquemment (p = 0,034) et pour des périodes plus courtes (p = 0,0014) par rapport au groupe C. Les animaux du groupe C ont dormi la majorité du temps de l'expérience (45,1 ± 2,9 minutes dans le groupe C vs 12,7 ± 2,9 minutes dans le groupe B, p .

Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs.

In the past two decades, average litter size (ALS) in Entlebucher Mountain dogs decreased by approximately 0.8 puppies. We conducted a GWAS for ALS using the single-step methodology to take advantage of 1632 pedigree records, 892 phenotypes and 372 genotypes (173 662 markers) for which only 12% of the dogs had both phenotypes and genotypes available. Our analysis revealed associations towards the growth differentiation factor 9 gene (GDF9), which is known to regulate oocyte maturation. The trait heritability was estimated at 43.1%, from which approximately 15% was accountable by the GDF9 locus alone. Therefore, markers flanking GDF9 explained approximately 6.5% of the variance in ALS. Analysis of WGSs revealed two missense substitutions in GDF9, one of which (g.11:21147009G>A) affected a highly conserved nucleotide in vertebrates. The derived allele A was validated in 111 dogs and shown to be associated with decreased ALS (-0.75 ± 0.22 puppies per litter). The variant was further predicted to cause a proline to serine substitution. The affected residue was immediately followed by a six-residue deletion that is fixed in the canine species but absent in non-canids. We further confirmed that the deletion is prevalent in the Canidae family by sequencing three species of wild canids. Since canids uniquely ovulate oocytes at the prophase stage of the first meiotic division, requiring maturation in the oviduct, we conjecture that the amino acid substitution and the six-residue deletion of GDF9 may serve as a model for insights into the dynamics of oocyte maturation in canids.

A novel KIT deletion variant in a German Riding Pony with white-spotting coat colour phenotype.

White spotting phenotypes in horses may be caused by developmental alterations impairing melanoblast differentiation, survival, migration and/or proliferation. Candidate genes for white-spotting phenotypes in horses include EDNRB, KIT, MITF, PAX3 and TRPM1. We investigated a German Riding Pony with a sabino-like phenotype involving extensive white spots on the body together with large white markings on the head and almost completely white legs. We obtained whole genome sequence data from this horse. The analysis revealed a heterozygous 1273-bp deletion spanning parts of intron 2 and exon 3 of the equine KIT gene (Chr3: 79 579 925-79 581 197). We confirmed the breakpoints of the deletion by PCR and Sanger sequencing. Knowledge of the functional impact of similar KIT variants in horses and other species suggests that this deletion represents a plausible candidate causative variant for the white-spotting phenotype. We propose the designation W28 for the mutant allele.

Optimization of analgesia for piglet castration under isoflurane anaesthesia with parenteral butorphanol, meloxicam or intratesticular lidocaine.

INTRODUCTION: This blinded prospective study investigated analgesic effects of intramuscular (IM) butorphanol, meloxicam or intratesticular (IT) lidocaine for castration of 7-14 days old piglets under isoflurane anaesthesia. 66 piglets were randomly injected with: meloxicam IM (0.4 mg/kg; group M), butorphanol IM (0.2 mg/kg; group B), or both (group BM) 20 minutes prior to castration, or lidocaine IT (4 mg/kg (group ML4) or 8 mg/kg (group ML8)) together with meloxicam IM (0.4 mg/kg) under anaesthesia with 1.8% end-tidal isoflurane. Heart rate, respiratory rate, mean arterial blood pressure and end-tidal carbon dioxide were recorded. Anaesthesia quality was scored and postoperative behaviour assessed. As butorphanol caused unacceptable side effects, its use was stopped. Group M showed worse anaesthesia quality than ML4 and ML8 (higher incidence of movements: 11/17, 3/18 and 4/17, respectively). There were no significant differences between groups regarding parameters measured during castration. Postoperative behaviour did not differ between groups. For castration of 7-14 days old piglets under isoflurane anaesthesia, IT lidocaine provides an additional side effect free analgesia.

INTRODUCTION: Cette étude prospective en aveugle étudie l'effet analgésique de l'injection intramusculaire (IM) de butorphanol et de méloxicam ou de l'injection intra-testiculaire (IT) de lidocaïne pour la castration, sous anesthésie à l'isoflurane, de porcelets âgés de 7 à 14 jours. Soixante-six porcelets ont reçu de manière aléatoire soit du méloxicam IM (0.4 mg/kg; groupe M), soit du butorphanol IM (0.2 mg/kg; groupe B), soit les deux substances (groupe MB) 20 minutes avant la castration, soit de la lidocaïne IT (4 mg/kg (groupe ML4) ou 8 mg/kg (groupe ML8)) ainsi que du méloxicam IM (0.4 mg/kg), avec une anesthésie à l'isoflurane à 1.8% en fin d'expiration. Les fréquences cardiaques et respiratoires, la pression artérielle moyenne et le CO2 en fin d'expiration ont été documentés. La qualité de l'anesthésie a été estimée et le comportement post-opératoire observé. Le butorphanol a causé des effets secondaires inacceptables et son usage a été stoppé. Le groupe M montrait une plus mauvaise qualité d'anesthésie que les groupes ML4 et ML8 (plus grande incidence de mouvements : 11/17, 3/18 et 4/17). Les autres paramètres intra opératoires ne présentaient pas de différences significatives et on a pas constaté de différences entre les groupes dans la phase postopératoire. Pour la castrations de porcelets âgés de 7 à 14 jours sous anesthésie à l'isoflurane, l'utilisation intra testiculaire de lidocaïne représente une analgésie supplémentaire dépourvue d'effets secondaires.

Evaluation of different dose rate combinations of ketamine, romifidine and azaperone for castration of 3-4 and 5-6 weeks old piglets.

INTRODUCTION: In this study dose rate combinations of ketamine, azaperone and romifidine were tested in 3-4 (G3-4) and 5-6 weeks (G5-6) old piglets according to a dose rate decision tree (DRT) to provide calm anaesthesia induction, reaction-free anaesthesia for castration and smooth recovery within 2 hours. When a combination failed to meet those criteria in 2 piglets, the next dosage of the DRT was tested. In G3-4 four combinations were tested in 14 piglets with dose rates of 10-20 mg/kg ketamine, 3 mg/kg azaperone and 0.15-0.20 mg/kg romifidine IM. Induction was smooth in all piglets, but depth of anaesthesia or recovery (11 and 6 piglets) were insufficient. In G5-6 five combinations were tested in 37 piglets with dose rates of 10-20 mg/kg ketamine, 3-4 mg/kg azaperone and 0.15-0.20 mg/kg romifidine IM. Induction was smooth in all piglets but 2. Depth of anaesthesia or recovery (17 and 7 piglets, respectively) were insufficient. In the present study with 3-4 and 5-6 weeks old piglets, acceptable quality of anaesthesia could not be achieved despite using high drug dose rates.

INTRODUCTION: Des combinaisons de doses de kétamine, azapérone et romifidine ont été testées sur la base d'un arbre de décision de dose afin de définir la dose qui assurait, chez des porcelets de 3-4 (G3-4) et de 5-6 (G5-6) semaines une induction tranquille, une anesthésie sans réaction lors de la castration et une phase de réveil calme, terminée en deux heures. Lorsqu'une combinaison de ces critères n'était pas obtenue chez 2 porcelets, on passait à la dose suivante proposée par l'arbre de décision. Dans le G3-4, 4 combinaisons avec des doses de 10-20 mg/kg de kétamine, 3 mg/kg d'azapérone et 0.15-0.20 mg/kg de romifidine IM ont été testées chez 14 porcelets. L'induction était calme chez tous les porcelets mais la profondeur de l'anesthésie ou la phase de réveil étaient insuffisantes chez 11 respectivement 6 porcelets. Dans le G5-6, 5 combinaisons avec des doses de 10-20 mg/kg de kétamine, 3-4 mg/kg d'azapérone et 0.15-0.20 mg/kg de romifidine IM ont été testées chez 37 porcelets. L'induction était calme à deux exceptions près mais la profondeur de l'anesthésie ou la phase de réveil étaient insuffisantes chez 17 respectivement 7 porcelets. Lors de la présente étude, il n'a pas été possible, malgré l'utilisation de doses élevées, d'obtenir chez des porcelets de 3-4 respectivement de 5-6 semaines une qualité d'anesthésie acceptable.

Hydrogen-deuterium exchange experiments to probe the decomposition reaction of sodium alanate.

NaAlH(4) is the archetypical complex hydride for hydrogen storage. The extraordinary effect of dopants on the sorption kinetics triggered the investigation of this empirical finding. In this paper, a short review of the state of the art is given. To gain further understanding of the mechanisms involved we label the interacting species during the sorption process. This was experimentally realized by hydrogen-deuterium exchange measurements during the decomposition of NaAlH(4) followed by thermogravimetry, Raman spectroscopy and mass spectrometry. By these experiments we are able to obtain specific information on the diffusing species and formation of intermediates. The activation energy of tracer diffusion in NaAlH(4) is found to be 0.28 eV. The results are evidence for a vacancy-mediated desorption process of NaAlH(4).

Hydrogen-deuterium exchange in bulk LiBH4.

Because of its apparent simplicity, diffusion of hydrogen in solids can be regarded as a general model system for diffusion. However, only rudimentary knowledge exists for the dynamics of hydrogen in complex hydrides. Insight into the specific diffusion process is given by hydrogen-deuterium exchange experiments. Thermogravimetry and Raman spectroscopy are used to measure the hydrogen-deuterium exchange during the decomposition of LiBH4. At a temperature of 523 K the self-diffusion constant of deuterium in LiBH4 is estimated to be D approximately 7 x 10(-14) m(2) s(-1). A careful analysis of the Raman spectra shows that hydrogen is statistically exchanged by deuterium in LiBH4; i.e., the diffusing species is assumed to be the single hydrogen atom.

Glycosphingolipids promote entry of a broad range of human immunodeficiency virus type 1 isolates into cell lines expressing CD4, CXCR4, and/or CCR5.

Treatment of human osteosarcoma cells, expressing CD4 and various chemokine receptors, with the glucosylceramide synthase inhibitor 1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP), blocked target membrane glycosphingolipid (GSL) biosynthesis and reduced the susceptibility of cells to infection and fusion mediated by envelope glycoproteins from a variety of human immunodeficiency virus type 1 (HIV-1) isolates that utilize CXCR4 and/or CCR5. PPMP treatment of the cell lines did not significantly change the cell surface expression of CD4, CXCR4, and/or CCR5, nor did it alter the chemokine receptor association with CD4. PPMP-treated cells exhibited no changes in chemokine-induced Ca(2+) mobilization and chemotaxis. However, massive envelope glycoprotein conformational changes triggered by CD4 and the appropriate chemokine receptor on the target membrane were inhibited when the target cells were treated with PPMP. Addition of various purified GSLs to PPMP-treated target cells showed that for all isolates tested, globotriaosylceramide (Gb3) was the most potent GSL in restoring the fusion susceptibility of target cells with cells expressing HIV-1 envelope glycoproteins; addition of the monosialoganglioside GM3 yielded a slight enhancement of fusion susceptibility. Our data are consistent with the notion that a limited number of specific GSL species serve as crucial elements in organizing gp120-gp41, CD4, and an appropriate chemokine receptor into a membrane fusion complex.

Influenza virus upregulates CXCR4 expression in CD4+ cells.

We examined the effect of prior influenza virus infection on the susceptibility of CD4+ cells to HIV-1 infection. Influenza virus infection of HeLa-CD4 cells resulted in a marked increase in susceptibility to infection by CXCR4-dependent but not CCR5-dependent HIV isolates. Influenza virus infection resulted in an increase in the steady state level of CXCR4 transcripts and an increase in cell surface CXCR4 expression. Our observations suggest that infectious agents such as influenza may contribute to HIV disease progression by modulating coreceptor availability.

Role of glycosphingolipids in HIV-1 entry: requirement of globotriosylceramide (Gb3) in CD4/CXCR4-dependent fusion.

We have recently shown that addition of human erythrocyte glycosphingolipids (GSL) to non-human CD4+ or GSL-depleted human CD4+ cells rendered those cells susceptible to gp120-gp41-mediated cell fusion (Puri et al., BBRC, 1998). One GSL fraction (Fraction 3) isolated from human erythrocyte GSL mixture exhibited the highest recovery of fusion following incorporation into CD4+ non-human and GSL-depleted HeLa-CD4 cells (HeLa-CD4/GSL-). Structural analysis of Fraction 3 showed that this GSL had identical head group as the known GSL, Gal(alpha1-->4)Gal(beta1-->4)Glc-Ceramide (Gb3) (Puri et al., PNAS, 1998). Here we report that presence of Gb3 in CD4+/CXCR4+ cells but not CD4+/CXCR4 cells allows fusion with HIV-1Lai-envelope glycoprotein expressing cells (TF228). Therefore, Gb3 functions in conjunction with HIV-1 co-receptor, CXCR4 to promote fusion. We propose that Gb3 functions by recruiting CD4 and/or CXCR4 at the fusion site through structurally specific interactions.

The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein.

Previously, we showed that the addition of human erythrocyte glycosphingolipids (GSLs) to nonhuman CD4(+) or GSL-depleted human CD4(+) cells rendered those cells susceptible to HIV-1 envelope glycoprotein-mediated cell fusion. Individual components in the GSL mixture were isolated by fractionation on a silica-gel column and incorporated into the membranes of CD4(+) cells. GSL-supplemented target cells were then examined for their ability to fuse with TF228 cells expressing HIV-1LAI envelope glycoprotein. We found that one GSL fraction, fraction 3, exhibited the highest recovery of fusion after incorporation into CD4(+) nonhuman and GSL-depleted HeLa-CD4 cells and that fraction 3 contained a single GSL fraction. Fraction 3 was characterized by MS, NMR spectroscopy, enzymatic analysis, and immunostaining with an antiglobotriaosylceramide (Gb3) antibody and was found to be Gal(alpha1-->4)Gal(beta1-->4)Glc-Cer (Gb3). The addition of fraction 3 or Gb3 to GSL-depleted HeLa-CD4 cells recovered fusion, but the addition of galactosylceramide, glucosylceramide, the monosialoganglioside, GM3, lactosylceramide, globoside, the disialoganglioside, GD3, or alpha-galactosidase A-digested fraction 3 had no effect. Our findings show that the neutral GSL, Gb3, is required for CD4/CXCR4-dependent HIV-1 fusion.

Human erythrocyte glycolipids promote HIV-1 envelope glycoprotein-mediated fusion of CD4+ cells.

We examined the role of target membrane glycolipids in CD4-mediated HIV-1 fusion by altering the glycolipid levels in CD4+ cells. CD4+ human cells exhibited 50% reduction in extent of fusion with gp120-gp41 expressing cells (TF228) when grown in the presence of a glycolipid synthesis inhibitor PPMP. We added erythrocyte glycolipids (GL) to fusion-incompetent CD4+ non-human cells by influenza-hemagglutinin-mediated fusion between GL-containing liposomes and target cells. Human erythrocyte GL (HuGL)-modified CD4+ non-human cells became susceptible to fusion with TF228 cells. Transfer of bovine erythrocyte glycolipids (BoGL) to CD4+ non-human cells under similar conditions did not complement HIV-1 fusion. Furthermore, addition of HuGL, but not BoGL, to PPMP-inhibited cells rescued fusion to the original levels. Our observations demonstrate that human erythrocyte glycolipids promote CD4-mediated HIV-1 fusion and certain glycolipid(s) from human erythrocytes may serve as alternative and/or additional cofactors in HIV-1 entry.

Semicochliodinol A and B: inhibitors of HIV-1 protease and EGF-R protein tyrosine kinase related to asterriquinones produced by the fungus Chrysosporium merdarium.

The known bisalkylated 2,5-dihydroxybenzoquinones didemethylasterriquinone D and isocochliodinol as well as the new metabolites semicochliodinol A and B have been isolated as inhibitors of HIV-1 protease from the culture broth of the fungus Chrysosporium merdarium P-5656. The structures were elucidated by spectroscopic methods. The NMR spectra of two compounds were completely assigned. The metabolites inhibit HIV-1 protease with an IC50 value as low as 0.17 microM and epidermal growth factor receptor protein tyrosine kinase at 15 to 60 microM and are therefore valuable lead compounds for these targets. Molecular modelling of the HIV-1-protease-inhibitor complexes showed hydrogen bonding between the dihydroxybenzoquinone moiety of didemethylasterriquinone D and isocochliodinol to both active-site aspartic acids (Asp25/Asp25') of the protease and the indole parts of the inhibitors filling the P2 and P2' pockets of the protease.

Further minor metabolites of staurosporine produced by a Streptomyces longisporoflavus strain.

From the staurosporine producing strain R-19 Streptomyces longisporoflavus various minor metabolites were isolated: They include new compounds with a keto function at carbon 4' of staurosporine and several metabolites related to TAN-1030A. The new structures were elucidated by spectroscopic methods, mainly 1H NMR and 13C NMR and by comparison with TAN-1030A. The new compounds inhibited protein kinase C with IC50 values in the micromolar range with the exception of those compounds that are alkylated at the lactam nitrogen.

Balmoralmycin, a new angucyclinone, and two related biosynthetic shunt products containing a novel ring system.

A new angucyclinone, named balmoralmycin (1), was isolated as an inhibitor of protein kinase C-alpha (PKC-alpha) from the Streptomyces strain P6417. Chemical screening of extracts of the same strain resulted in the detection of two decaketides with unusual structural features (2 and 3). Both compounds belong to a recently described structural class of secondary metabolites which arises from engineered biosynthesis of a recombinant Streptomyces strain. The isolation of compounds of this class from a wild-type strain has never been reported before.

Paeciloquinones A, B, C, D, E and F: new potent inhibitors of protein tyrosine kinase produced by Paecilomyces carneus. II. Characterization and structure determination.

Paeciloquinones A to F and versiconol have been isolated as inhibitors of protein tyrosine kinases from the culture broth of the fungus Paecilomyces carneus P-177. The structures of the new anthraquinones were determined by spectroscopic methods, mainly 1H NMR and 13C NMR. The substitution pattern was established by investigation of the respective methylated derivatives.

A nitro analogue of staurosporine and other minor metabolites produced by a Streptomyces longisporoflavus strain.

From the staurosporine-producing strain Streptomyces longisporoflavus R-19 various minor metabolites were isolated: They include a new compound with a nitro function in C-4' and other metabolites related to staurosporine. The new structures were elucidated by spectroscopic methods, mainly 1H NMR and 13C NMR and by comparison with TAN-1030A. The new compounds inhibited protein kinase C with IC50 values in the nanomolar range.