Multiple phases of human occupation in Southeast Arabia between 210,000 and 120,000 years ago.

Changing climatic conditions are thought to be a major control of human presence in Arabia during the Paleolithic. Whilst the Pleistocene archaeological record shows that periods of increased monsoon rainfall attracted human occupation and led to increased population densities, the impact of arid conditions on human populations in Arabia remains largely speculative. Here, we present data from Jebel Faya in Southeast (SE) Arabia, which document four periods of human occupation between c. 210,000 and 120,000 years ago. The Jebel Faya record indicates that human occupation of SE Arabia was more regular and not exclusively linked to major humid periods. Our data show that brief phases of increased rainfall additionally enabled human settlement in the Faya region. These results imply that the mosaic environments in SE Arabia have likely formed a population refugia at the end of the Middle and the beginning of the Late Pleistocene.

Canine status epilepticus due to acute intoxication.

OBJECTIVES: The purpose of this study was to describe the type of toxin ingested, clinical presentation and outcome of dogs with status epilepticus (SE) due to acute poisoning presented to a large referral veterinary hospital. MATERIALS AND METHODS: Retrospective case series. Medical records of all dogs suffering from SE were reviewed (Jan 1, 2002 to April 30, 2009). RESULTS: Fourteen dogs with SE due to acute intoxication were identified. Toxicological analyses (qualitative analysis with gas chromatography/mass spectrometry; n=11) detected poisonings with carbofuran, crimidine, paraoxone, metaldehyde, strychnine and diazinon. In the other three cases the uptake of a known poison was observed (zink phosphide, metaldehyde). None of the dogs showed evidence of neurological disease up to the day of presentation. The dogs were hospitalised for 2-10 days (median 5 days). The survival rate was 85.7%. None of the dogs experienced any more seizures after discharge (median observation period 2.6 years). CONCLUSION AND CLINICAL RELEVANCE: Ancillary to the acute clinical presentation, preliminary reports (possible uptake of poisonous material) and an inconspicuous medical history may suggest a tentative diagnosis. Managed adequately, these patients can have a high survival rate. Clinicians should also keep uncommon intoxications in mind.

Drugs used in the treatment of opioid tolerance and physical dependence: a review.

Opioid drugs used in the treatment of severe pain are known to produce tolerance that requires a dose increase to maintain a sufficient analgesic effect. As this is connected with side effects such as respiratory depression, it is highly desirable to avoid or at least attenuate the development of tolerance. Closely related, but in some respect dissociable, is the phenomenon of physical dependence, which becomes apparent particularly in heroin withdrawal. Our knowledge about the mechanisms underlying tolerance has increased dramatically in recent years, but a final picture of the importance of each particular mechanism under in vivo conditions has not yet emerged. Recent studies suggest that the so-called receptor down-regulation is not the main mechanism in vivo. A desensitization on the basis of receptor decoupling, receptor internalization and increased alternative coupling to stimulatory G-proteins have been demonstrated. However, a functional antagonism of the opioid effects seems to be clinically most important, mediated by the activation of NMDA receptors, up-regulation of adenylyl cyclase and nitric oxide synthase. Drugs blocking these mechanisms are the most promising option in the treatment of tolerance. Namely, alpha2-adrenoreceptor agonists such as clonidine and NMDA antagonists such as ketamine or dextromethorphan have been used to minimize tolerance development during opioid treatment. Moreover, clinical strategies such as opioid rotation and multimodal analgesia, i.e. the simultaneous application of several analgetics of different type, have proven to be successful approaches.

Homo-phytochelatins are synthesized in response to cadmium in azuki beans.

In a recent report, it was claimed that azuki beans (Vigna angularis) do not synthesize phytochelatins (PCs) upon exposure to cadmium, although glutathione (GSH), the substrate for PC synthesis, is present in this plant. This legume species thus would be the first exception in the plant kingdom that would fail to complex heavy metals by PCs. Here, we report that not GSH, but only homoglutathione can be detected in this plant and that homo-phytochelatins are formed when azuki beans are challenged with heavy metals such as cadmium. We also show that the 5,5'-dithiobis(2-nitrobenzoic acid)-oxidized GSH reductase recycling assay, used for GSH quantification in the recent study of heavy metal tolerance in azuki beans, reacts both with GSH and homoglutathione and therefore cannot be used when biological samples should be analyzed exclusively for GSH.

Ceramide analysis utilizing gas chromatography-mass spectrometry.

Suitable analytical methods are a prerequisite of a detailed investigation of ceramides. Therefore, a new gas chromatograph-mass spectrometry method with electron impact ionization was developed. Samples have been prepared for gas chromatography by the formation of volatile trimethylsilyl derivatives. The method provides high separation efficiency, sensitivity and specificity. Mass spectra facilitate the structural characterization of each species, because certain fragments indicate the fatty acid as well as the sphingoid base moiety. In a 30-mm run even very similar ceramides are baseline separated. The method is compared to a recently published assay for liquid chromatography-mass spectrometry.

Affinity capillary electrophoresis in pharmaceutics.

The technique of Affinity capillary electrophoresis (ACE) is a useful tool to characterize complexation and partition equilibria. A wide range of applications in pharmaceutics has been presented: the determination of pKA values, of association constants between drugs and cyclodextrins or amphiphilic compounds as well as the characterization of drug affinities to several vehicle systems, such as micelles, microemulsions and liposomes. Due to the widespread use of capillary electrophoresis in drug analysis, the technical equipment is quite common. ACE is advantageous as a rapid and simple screening method which provides quantitative results about various interactions with a minimum of substance consumption and time spent.

Two examples of rapid and simple drug analysis in pharmaceutical formulations using capillary electrophoresis: naphazoline, dexamethasone and benzalkonium in nose drops and nystatin in an oily suspension.

Capillary electrophoresis is a versatile tool in pharmaceutical analysis. In the course of a revision of the "Standardrezepturen", a German formula of standard dispensings for preparation in pharmacies, this technique has been applied to drug analysis in pharmaceutical formulations. The present paper deals with two different examples. First, naphazoline, dexamethasone and the preservative benzalkonium are quantified in nose drops without any sample preparation. Second, the antifungal antibiotic nystatin is quantified using nonaqueous capillary electrophoresis in methanol after sample preparation from an oily suspension.

Characterization of micelles by capillary electrophoresis.

A practical approach for the characterization of pure micelles, and binary or ternary mixed micelles by capillary electrophoretic methods is presented. Interest is focused on the determination of mobility and composition of the micelles. The investigations are performed with bile salts, phosphatidylcholines and fatty acids. Pure bile salt micelles are characterized with the help of marking and displacement methods. Binary bile salt/phospholipid and ternary bile salt/phospholipid/fatty acid micelles are analyzed using capillary electrophoresis (CE) techniques with standard and improved UV detection, laser-induced fluorescence and electrospray ionization-mass spectrometry (ESI-MS). For both the binary and the ternary systems, only one stable mixed micellar phase is found with a high negative mobility.

Effect on the partition equilibrium of various drugs by the formation of mixed bile salt/phosphatidylcholine/fatty acid micelles. A characterization by micellar affinity capillary electrophoresis. Part IV.

Mixed micelles, which mimic the bile containing fatty acids in the gastrointestinal tract, were used as a pseudostationary phase in capillary electrophoresis. The mixed micellar system studied contained the dihydroxy bile salts sodium glycodeoxycholate or sodium taurodeoxycholate or the trihydroxy bile salt sodium taurocholate, in association with different sodium salts of fatty acids including lauric, myristic, palmitic, oleic, stearic and linoleic acid and lecithin or dipalmitoylphosphatidylcholine as phospholipid. The determination of the changing mobilities of ionic analytes in the presence of mixed micelles reflected interactions between the used drugs and the mixed micelles. These were determined as dependence on the fatty acid concentration in the bile salt/fatty acid micelles and the mixed bile salt/phosphatidylcholine/fatty acid micelles. The capacity factor kappa MMC, for the partition between mixed micellar and aqueous phase was calculated. The partition equilibrium of basic and acidic drugs depends considerably on shape and charge of the mixed micelles (dependent on the fatty acid concentration) as well as on the acid-base properties of the drug. The mobility of the micelle aggregates was determined as an important reference value to the calculations of kappa MMC. This paper also describes the use of laser-induced fluorescence detection and electrospray mass spectrometry and tandem mass spectrometry for the characterization of the mixed micelle composition.

Separation and quantitation of glycolipids as penetration modifiers in human skin using high-performance liquid chromatography-mass spectrometry with electrospray ionization.

An high-performance liquid chromatography-mass spectrometry method is presented for the measurement of glycolipids used as modulators of the penetration of drugs into human skin. In methanol extracts from different skin layers a detection limit of 100-400 pg/ml could be achieved. A routine analytical procedure could be set up with good quantitation reliability (relative standard deviation 6.6%).

Capillary zone electrophoresis in skin fatty acid analysis.

The development of a method for analyzing C12-C18 fatty acid alkali salts by capillary zone electrophoresis is described. Organic solvents were added to the aqueous separation buffer to achieve solubility of the fatty acids together with higher temperatures. Detection of these poorly UV absorbing species could be achieved by indirect photometric detection adding a highly UV absorbing co-ion to the separation buffer. Thus detection limits of 6 microM were recorded. The dynamic range of quantitation was limited to 10(1) due to association and micelle formation at higher concentrations. The relative standard deviation of the method was in the range of 4 to 10%. The described method could be successfully applied to the analysis of free fatty acids in human stratum corneum after solid phase extraction of the lipid fraction.