A complex evaluation of the asymmetry of dermatoglyphs.

Altogether 20 traits of the fingers, 22 traits of the palm and 8 traits of the sole were taken into consideration, on both sides of the bodies of 1652 males and 1628 females. Numbers of asymmetrical variants of the traits within the whole complex of 25 pairs of traits were determined individually. In the case of descriptive traits, asymmetry was deemed to be the occurrence on either side of the body of non-identical variants of the traits, and for quantitative traits, the absolute difference of at least two ridges was accepted. These differences were marked with the value 1 (additionally 0.5 on the fingers when the difference concerned only the direction of the pattern). The sum of these values constituted the total number of asymmetric traits, which was expressed by the index: IA=number of asymmetric traits×100/25. For individual traits, the frequency of asymmetric variants was determined, and here the measure of asymmetry was expressed as the relations of their sum to the total numbers. In both sexes, the lowest level of asymmetry concerns patterns of the II inter-digital area, the thenar, the IV, III and I areas of the sole, and fingers 5 and 3, while the highest level concerns patterns of finger 2, asymmetry of C-line and A-line exits, the ridge count on the fingers and in the inter-digital areas of the palm. The greatest dimorphism is demonstrated by the asymmetry of the patterns of the II inter-digital area of the palm, finger 4, the IV area of the sole, the thenar, finger 1, line B and the ridge count on finger 2. As a consequence, the mean of the asymmetry index (IA) in males (46.24) is higher than in females (44.43). The proposed index of dermatoglyphic asymmetry (IA) may be used for comparative purposes in population, clinical, auxological and genetic research.

Involvement of the different extracts from roots of Salvia miltiorrhiza Bunge on acute hypobaric hypoxia-induced cardiovascular effects in rats--preliminary report.

The present study was carried out to investigate the protective effects of roots of Salvia miltiorrhiza Bunge on hypobaric hypoxia. Two extracts of S. miltiorrhiza (extract 1: ethanol : water - 50 : 50; extract 2: 96% ethanol) were used. The experiments were performed after 7 consecutive days of administration of the extracts (200 mg/kg b.w., intragastrically) to male Wistar rats. Next, after placing animals for 60 min in the controlled acute hypobaric hypoxia (500 mm Hg) the systolic arterial blood pressure (SAP) in conscious rats, bioelectric heart activity in unconscious rats and analysis of oxidative stress parameters in the blood of rats: malonyldialdehyde (MDA) and lipid peroxidase (LPO) concentration, activity of superoxide dismutase (SOD) or glutathione peroxidase (GPX) were assayed. It was found out that the extract 1 augmented the lowering of SAP shown in hypoxia affected control rats. On the contrary the extract 2 reversed SAP to values obtained in control animals. Moreover, both extracts led to the normalization of hypoxia-induced tachycardia and levels of MDA, LPO and SOD. It seems that the above-mentioned effects are coupled with different active compounds content in the extracts, however more studies are needed to confirm this hypothesis.

Dose-dependent in vivo effect of Rhodiola and Echinacea on the mitogen-induced lymphocyte proliferation in mice.

Echinacea purpurea (EP) and Echinacea angustifolia (EA) are ones of the most important world's herbs with immunotropic activity. They were traditional medicinal plants used by North American Indians for the treatment of various illnesses. Now they are cultivated in many countries and are used mainly to treat respiratory tract infections. Rhodiola rosea (RR) and Rhodiola quadrifida (RQ) are medicinal plants originated from Asia and used traditionally as adaptogens, antidepressants, and anti-inflammatory remedies. We previously reported, that extracts of underground parts of RR and RQ exhibited immunotropic activity. We have demonstrated in pigs that in vitro RR or RQ supplementation of blood lymphocyte cultures stimulated T cell proliferative response to Con A in lower, and inhibited it in higher Rhodiola extract concentrations. The aim of this work was to evaluate the in vivo effect of these herbal remedies on the in vitro proliferative response of mouse splenic lymphocytes to another T-cell mitogen- Phaseolus vulgaris haemagglutinin (PHA). We have found significant stimulation of proliferative response, in comparison to the controls, in mice fed lower doses of tested remedies, and inhibition, no effect or lower stimulation, in mice fed higher doses of these drugs.

The right of patients in mental hospitals to refuse drug treatment.

The use of antipsychotic drugs has caused conflicts between the medical decision concerning what is in a patient's best interests and the legal decision as to what treatment constitutes a violation of the mental patient's right to due process. The medical profession has a duty to treat patients; patients have a right to refuse medical treatment. With legislation leading to the release of mental patients into the community, the focus has turned away from treatment of a disease and toward prevention through changes in social policy. The law has recognized that the state has an interest in compelling treatment and that the patient has a right to refuse medical treatment. The rights of the state and the patient are not absolute and must be balanced by the judiciary. The result is that a mental patient's right to refuse antipsychotic drugs mut be determined on a case by case basis. The authors propose that states pass legislation covering the rights of mental patients. A model bill is proposed at the end of the article. It establishes a procedural system which addresses the issues of informed consent, competency, emergencies, medical review, and judicial review.

The metabolism and excretion of buprenorphine in humans.

Buprenorphine, a powerful mixed agonist-antagonist analgesic which shows promise of providing maintenance pharmacotherapy for heroin addicts, is metabolized in male human subjects to norbuprenorphine and to conjugated buprenorphine and norbuprenorphine. Following subcutaneous, sublingual, and oral buprenorphine administration to a single subject, total metabolite excretion in urine was 2, 13.4, and 12.1%, respectively. No free parent drug was detected in urine. The amount of norbuprenorphine metabolite excreted in urine generally exceeded that of conjugated buprenorphine. In contrast, free and conjugated buprenorphine equaled or greatly exceeded total norbuprenorphine content in fecal samples following oral or sublingual administration. The greatest amount of drug and metabolite eliminated in feces occurred at 4 to 6 days following buprenorphine administration at times when there was very little urinary excretion of conjugated buprenorphine. This latter evidence indicates an enterohepatic circulation of buprenorphine in humans.

Stability of the 6,14-endo-ethanotetrahydrooripavine analgesics: acid-catalyzed rearrangement of buprenorphine.

Buprenorphine (I), a member of the 6,14-endo-ethanotetrahydrooripavine series of analgesics, undergoes an acid-catalyzed rearrangement reaction when exposed to acid and heat. The product was shown by 1H-NMR and GC-MS to have undergone overall elimination of a molecule of methanol with concurrent formation of a tetrahydrofuran ring at C(6)-C(7) of I. Short-term stability studies across a wide range of pH and temperature conditions indicate that I is stable in aqueous solution at pH greater than 3 for 24 h at 36-38 degrees C. Under the more extreme conditions of the autoclave, significant loss of I occurred. Long-term stability studies (10 weeks) of I in aqueous solution (pH 1 and pH 5) at 0-4 degrees C and 26-28 degrees C indicate only minor conversion (4%) to the rearrangement product. Eight other 6,14-endo-ethanotetrahydrooripavine derivatives were subjected to extremes of acid (pH 0) and temperature (autoclave) to determine if similar rearrangement reactions occur. GC-MS indicated that hydrolysis products were produced whose spectra were consistent with the proposed rearrangement structures.

Oxymorphone metabolism and urinary excretion in human, rat, guinea pig, rabbit, and dog.

Oxymorphone was extensively metabolized by human, rat, dog, and guinea pig and to a lesser extent by rabbit. The most abundant metabolite in urine for all species was conjugated oxymorphone (12.7-81.7% administered dose) followed by 6 beta- and 6 alpha-carbinols produced by 6-keto reduction of oxymorphone. 6 beta-Oxymorphol (0.2-3.1%) was found in the urine of all species, whereas 6 alpha-oxymorphol (0.1-2.8%) was found only in human, rabbit, and guinea pig. Small amounts of free oxymorphone (less than or equal to 10%) were excreted by all species except rabbit, which excreted 31.7%. Overall recoveries of oxymorphone and metabolites from urine ranged from 15-96%, of which greater than 80% was excreted in the first 24 hr by all species except dog. Only 35% was excreted by dog during the first day. Stereoselectivity of 6-keto- reduction was observed for all species with the 6 beta-carbinol metabolite being most abundant in the urine of all but guinea pig. Considerable individual variability occurred in the excretion of free and conjugated oxymorphone by six human subjects following oral dosing. Species trends in the metabolism of 6-keto-opioids are discussed.

Assay for codeine, morphine and ten potential urinary metabolites by gas chromatography--mass fragmentography.

A mass fragmentography (MF) assay is described for ten potential, minor urinary metabolites of codeine (C) and morphine (M). Samples were hydrolyzed, extracted, derivatized with Tri-Sil Z and analyzed by methane chemical ionization (CI)-MF. The method is sensitive to ca. 0.01 microgram/ml for all compounds with the exception of normorphine (NM) which was difficult to extract with chloroform. The sensitivity of the MF assay for NM was only ca. 0.10 microgram/ml. Various solvent systems were investigated for optimization of extraction efficiency of all metabolites. A separate method for the extraction of NM is reported which utilizes a solid buffer--solvent combination, i.e., potassium carbonate--isopropanol. This latter method provided the best overall recovery of NM (39.0 +/- 3.4%). Gas chromatographic (GC) retention times of C, M and metabolites are reported for three liquid phases (3%) on Gas-Chrom Q (100-120 mesh). Resolution of metabolites (as trisilyl derivatives) was best on Silar-5CP and this phase was used in metabolic studies of C and M. GC resolution was not complete for all compounds; however, selection of specific ions for monitoring by MF provided the required specificity for all compounds except the 6 alpha- and 6 beta-hydroxy isomers. CI spectra for all metabolites are reported. The MF assay was used for urinary analysis of samples from guinea pigs that received single doses of C (15 mg/kg) or M (8 mg/kg). Following C administration 6 alpha- and 6 beta-hydrocodol, 6 alpha, beta-hydromorphol (undifferentiated), HM and M were measured. Following M administration only 6 alpha, beta-hydromorphol was found. The amount of total metabolite as percent dose for each component was calculated as less than 1%.

Analytical controls in drug metabolic studies. II. Artifact formation during chloroform extraction of drugs and metabolites with amine substituents.

Chemical artifacts are readily produced during chloroform extractions of drugs and metabolites with amine substituents by the reaction of chloroform contaminants, phosgene and ethyl chloroformate, to form carbamoyl chlorides and carbamates. Chloroform obtained from three different suppliers was examined with regard to the effects of preservatives and exposure to air on the quantity and nature of these contaminants. Extractions with chloroform obtained from a supplier's sealed bottle and containing ethanol preservative produced the least amount of artifact. With previously opened bottles (prior exposure to air, open), the amount of artifact formation rose substantially. Chloroform without preservative or with a nonpolar hydrocarbon preservative likewise produced large amounts of artifacts during extraction. Attempts to purify chloroform showed that distillation was ineffective for the removal of phosgene or ethyl chloroformate, whereas their effective removal was accomplished by solvent elution through a column of activated alumina or upon standing over calcium hydroxide powder. Possible artifact formation must be considered in drug-metabolism studies and appropriate controls included for the detection and elimination of chemical artifacts.

Detection and measurement of opium alkaloids and metabolites in urine of opium eaters by methane chemical ionization mass fragmentography.

A gas chromatographic-mass spectrometric assay for eight opium alkaloids in human urine following opium ingestion is described. The compounds were extracted from urine with methylene chloride-isopropanol (7:3, v/v) at pH 9.5, evaporated, derivatized with Tri-Sil Z and analyzed by methane chemical ionization mass fragmentography. The method in sensitive to ca. 0.01 microgram/ml for morphine and codeine and ca. 0.05 microgram/ml for the other compounds. Adsorption problems on the gas chromatography column prevented obtaining reproducible results for the measurement of noscapine. Extraction efficiencies over the pH range of 8-11 for the eight compounds are reported. Retention times of the opium alkaloids were determined using five different liquid phases (3%) on Gas-Chrom Q (100-120 mesh) and two column lengths (36 cm and 183 cm). The 36-cm column packed with OV-210 was selected for use in the assay. Ions were selected for monitoring for each component from their methane chemical ionization spectrum to provide the needed sensitivity and specificity for analysis of a multi-component mixture. The assay was used for the analysis of an "opium eater's" urine. Morphine, codeine, nomorphine, norcodeine and noscapine were detected; however, no evidence was obtained for thebaine, papaverine or oripavine. Unconjugated morphine (0.64 microgram/ml) was present at nearly twice the concentration of codeine (0.37 microgram/ml) and normorphine and norcodeine were present in equal amounts (ca. 0.15 microgram/ml).

Phencyclidine metabolism: resolution, structure, and biological activity of the isomers of the hydroxy metabolite, 4-phenyl-4-(1-piperidinyl)cyclohexanol.

One of the major biotransformation pathways in the metabolism of phencyclidine is hydroxylation at C-4 of the cyclohexane ring to give 4-phenyl-4-(1-piperidinyl)cyclohexanol (1). Since the latter compound can exist as cis and trans isomers and the synthetic mixture has been reported to be biologically active, it was of interest to separate the isomers, test them for biological activity, and determine their ratio as metabolic products of phencyclidine. The synthetic mixture of 1 was separated by TLC and the individual isomers were characterized by 13C and 1H NMR and MS analyses. Preliminary testing of the isomers in the mouse rotarod assay indicates that the trans isomer (1b) is only slightly more active then the cis isomer (1a). Both isomers produced seizure activity and lethality at doses required to produce maximal ataxia.

Simultaneous determination of phencyclidine and monohydroxylated metabolites in urine of man by gas chromatography-mass fragmentography with methane chemical ionization.

Phencyclidine and monohydroxy metabolites were measured in human urine using gas chromatography-mass fragmentography with methane chemical ionization. Samples were extracted either untreated or following acid hydrolysis, derivatized with heptafluorobutyric anhydride, separated on a 3% SE-30 column and analyzed by mass fragmentography. The assay was sensitive to ca. 0.01 microgram/ml for phencyclidine and ca. 0.05 microgram/ml for the metabolites. Urine samples from five human subjects enrolled in a methadone maintenance program who had ingested phencyclidine were analyzed. The phencyclidine concentration ranged from 0.3 to 23.7 microgram/ml. The concentrations of metabolites ranged from 0 to 1.8 microgram/ml. A new monohydroxy metabolite was detected in the samples, but its structure was not fully elucidated. The specificity of the assay was examined.

The effect of L-tryptophan on spinal cord C-fiber reflexes.

C-fiber reflex were recorded from an ipsilateral S1 ventral root in the acute decerebrate spinal (T10) cat after stimulation of the superficial peroneal nerve. L-Tryptophan, infused in a dose of 150 mg/kg, increased the C-fiber reflex to 210% (S.E.M. +/- 30.1%) of control. This effect was antagonized by cyproheptadine, 0.5 mg/kg. L-Tryptophan increased the C-fiber reflex to 176% (S.E.M. +/- 13.0%) of control after p-chlorophenylalanine pretreatment. Pretreatment of the cats with the decarboxylase inhibitor alpha-methyldopa, 100 mg/kg, 30 minutes before infusion, antagonized the facilitatory effects of L-Tryptophan. L-Tryptophan, 150 mg/kg, had no effect on the monosynaptic or short latency polysynaptic reflexes. 5-Hydroxytryptophan, 20 mg/kg, had erratic effects on the C-fiber reflex producing both facilitation and depression which were not statistically significant. The recovery of tryptamine from brain perfusates, after perfusion of the anterior cerebellum and pons, with a modified Gaddum push-pull cannula, decreased across time. L-Tryptophan caused a slight increase in tryptamine release which was not statistically significant, whereas in cats pretreated with p-chlorophenyl alanine, a significant increase in tryptamine release was seen.

Neurochemical evidence for tryptaminergic ascending and descending pathways in the spinal cord of the dog.

The brain and spinal cord of the chronic spinal dog contained higher levels of tryptamine than comparable regions of the intact dog. The most significant brain elevations were found in the cerebellum and mesencephalon. Further, tryptamine in the white matter of the spinal cord above the level of transection was higher than below. These findings have been interpreted as indicating that there are tryptaminergic pathways descending in the white matter of the spinal cord from the mesencephalon, cerebellum and rostral spinal cord. The level of tryptamine below the transection was not different from that found in the intact dog, suggesting that there are not only descending but ascending tryptaminergic pathways and that when the axons are transected. tryptamine accumulates proximal to the level of transection.