Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

Ventricular septal defects: a surgical viewpoint

Seventy-six cardiac autopsy specimens with ventricular septal defects were studied from a surgical viewpoint. The defects were classified as being conoventricular (n = 25), in the right ventricular outlet (n = 21), in the inlet septum (n = 11) or in the trabecular septum (n = 19) with each category having several subcategories. The left ventricular outflow tract relations of the defects are emphasized. The borders of the ventricular septal defects are described in detail, with use of the prefix "juxta" to indicate the immediate adjacency of the defect to a structure such as the tricuspid valve.     

Synthetic peptides corresponding to the sequence of noxiustoxin indicate that the active site of this K+ channel blocker is located on its amino-terminal portion

Summary A nonapeptide Thr-Ile-Ile-Asn-Val-Lys-Cys-Thr-Ser (NTX_1–9) and a decapeptide Met-Asn-Gly-Lys-Cys-Lys-Cys-Tyr-Asn-Asn (NTX_30–39) corresponding to the N-terminal and C-terminal sequences respectively of Noxiustoxin (NTX) were synthesized by the solid phase method of Merrifield (1963). The first synthetic peptide (NTX_1–9) was shown to be toxic to mice independently of the route of administration: intraperitoneally, subcutaneously or intraventricularly (100–200 g/20 g mouse weight). The second (NTX_30–39) was not toxic even at higher dose (400 g/20 g mouse). When the effects of the peptide NTX_1–9 and of the authentic toxin (Noxiustoxin) were studied on the liberation of [³H] 4-aminobutyric acid (³H-GABA) from mouse synaptosomes, both gave essentially the same results, except that peptide NTX_1–9 was needed at higher concentration. Synthetic peptide NTX_30–39 had no effect in the same preparation at even higher doses. The GABA release produced by toxic peptide NTX_1–9 was not affected by tetrodotoxin but was completely abolished by the presence of the K⁺ ionophore valinomycin, mimicking the effect of native NTX in the same system (Sitges et al., 1986). These results indicate that the toxic active site of Noxiustoxin is possibly located in or near the N-terminal amino acid portion of the molecule.Abbreviations used BOC amino acids ter-butyloxycarbonyl-amino acids - BOC amino acid-PAM-resin ter-butyloxycarbonyl-aminoacyl-4-(oxymethyl)-phenacetamidomethyl-resin - GABA 4 aminobutyric acid - HPLC high performance liquid chromatography - MSA mouse serum albumin - NTX Noxiustoxin - NTX _(numbers) synthetic peptides with amino acid sequences of NTX at position start (first number) to position end (second number) of the sequence according to Fig. 1 - TTX tetrodotoxin Supported in part by the Mexican Council of Science and Technology (CONACyT), grants PVT/QF/NAL/84/2182, PVT/AI/NAL/85/3029 to L.D.P.; PCSACNA 022640 to A.B. A patent request claiming rights on the use of synthetic NTX and related peptides was presented in Washington, DC (U.S.A.), Serial number 07/132,169, filing date December 14, 1987.     

Increased [Met]enkephalin and decreased substance P in spinal cord following thermal injury to one limb.

Thermal injury to one hind limb of rats was induced by immersion into water at 62 degrees C. Both a mild (15 s) or severe (30 s) lesion caused inflammation of the limb when observed 24 h later; but at this time the animals used the injured limb when they walked. Animals with a severe lesion of the injured limb subsequently withdrew it from use when walking. Limb withdrawal did not occur following a mild lesion. At 24 h following the lesion, lumbar spinal cord levels of [Met]enkephalin, as measured by radioimmunoassay, were elevated (70%) bilaterally in both hemisegments, ipsi- and contralateral to the lesion. At seven days following either mild or severe hind limb lesion [Met]enkephalin levels were elevated only in the ipsilateral lumbar hemisegment. At that time no changes in thoracic [Met]enkephalin levels were observed. Substance P levels were decreased (20-25%) bilaterally in the lumbar cord 24 h following a severe limb lesion, but no change was observed at seven days in any cord segment following a mild or severe lesion. Changes in spinal cord [Met]enkephalin content occur in response to thermal injury to one hind limb. However, the changes do not appear to be related to the withdrawal of the damaged limb from use following a severe lesion. Peptide changes in the spinal cord may reflect pain or injury to the damaged limb following a thermal lesion. In contrast, limb withdrawal may be a physiological rest mechanism related to altered basal ganglia peptide function.     

Use of HeLa cell guanine nucleotides by Chlamydia psittaci.

Exogenous guanine was found to be incorporated into the nucleic acids of Chlamydia psittaci when the parasite was grown in HeLa cells containing hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) activity but not when the parasite was grown in transferase-deficient HeLa cells. No evidence for a chlamydia-specific transferase activity was found in either transferase-containing or transferase-deficient infected HeLa cells. It is concluded that C. psittaci is incapable of metabolizing guanine, but that the parasite can use host-generated guanine nucleotides as precursors for nucleic acid synthesis.     

Waardenburg syndrome: clinical differentiation between types I and II

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the I variant of WS.     

Long-term social isolation in the rat induces opposite changes in binding to alpha 1- and alpha 2-adrenoceptors in the brain and vas deferens

Rats isolated at the time of calcification of the incisors show, after 14-18 months of social deprivation, an increased number of alpha 1-adrenoceptors labeled with [3H]WB 4101, both in the striatum and in the vas deferens, as well as a decreased number of alpha 2-adrenoceptors labeled with [3H]-clonidine in the vas deferens. Social isolation does not, however, modify the density of [3H]clonidine binding sites in the cerebral cortex. The functional state of alpha-adrenoreceptors in the vas deferens from isolated rats appears to correlate with the binding studies since the isolated tissue is hypersensitive to the contractile effect of exogenous noradrenaline and subsensitive to the inhibitory effect of clonidine on the electrically stimulated preparation.