Relations between basal ganglia and hippocampus: action of substantia nigra and pallidum

Several interrelationships exist between basal ganglia and hippocampus. The ventral striatum appears to be involved in the control of the dopaminergic nigro-striatal pathway. The caudate, in turn, seems to influence the hippocampal theta rhythm and to inhibit hippocampal spikes. In the present work the role played by globus pallidus pars interna and substantia nigra pars compacta on hippocampal bioelectrical activity is studied. Injection of sodium penicillin i.v. produces steady interictal spikes in the hippocampus. Substantia nigra stimulation induces regular theta rhythm and inhibits the spikes. Pallidal stimulation, on the contrary, appears to strongly enhance epileptiform activity, proceeding to generalised seizure activity. The results are discussed in the light of a putative feedback loop from basal ganglia to hippocampus, probably underlying co-participation of the two subcortical structures in the control of motor behaviour.     

gamma-ray spectrometry of soil samples from the Provincia dell'Aquila (Central Italy).

In the Abruzzo Region (Central Italy) there is a lack of measurements of gamma-ray activity in soils and waters. For this reason, we have planned to carry out a systematic measurement of soils in the area of the Provincia dell'Aquila, which covers about one-half of the entire region. In this paper we report the results obtained from 56 soil samples, collected in the northern part of the area of interest (about one-fourth of the total area under study). The results, in terms of content of uranium, thorium and potassium and the activity of caesium are reported, as well as the details on the experimental procedure. The results show a limited content of K and U, with no large variations from site to site, in agreement with the expectations based on the knowledge of the geo-lithological nature of the soil. The amount of Th is also quite limited, with a few exceptions where the Th content is up to five times the average value. Caesium, originated from the fall-out following the Chernobyl accident, is very irregularly distributed owing to the complicated orography of the land. Future plans are also shortly discussed.     

Simultaneous Pulmonary Leiomyosarcoma and Leiomyoma in Pediatric HIV Infection

The case of a 7-year-old girl with acquired immunodeficiency syndrome treated for 5 years with AZT and intravenous gamma globulin is reported. Shortly before her demise she developed a pulmonary leiomyosarcoma and leiomyoma. Does prolonged survival in pediatric acquired immune deficiency syndrome increase the incidence of secondary malignancies?     

Role of vasopressin on excitatory amino acids mediated pressor responses in the periaqueductal gray area

In order to evaluate the role played by vasopressin on pressor responses elicited by stimulation of the periaqueductal gray (PAG) area by excitatory amino acids we carried out in vivo studies in genetically vasopressin deficient rats (Brattleboro). Microinjections of l-glutamic acid (glutamate, 0.6 to 60 nmol/rat) or N-methyl-d-aspartic acid (NMDA, 0.07 to 7 nmol/rat) into the PAG area of freely moving Brattleboro rats induced increases of arterial blood pressure values significantly lower than those obtained in Long Evans rats (control) (glutamate in Brattleboro rats: from +2±1 mmHg to 16±3 mmHg; glutamate in Long Evans rats: from +16±2 mmHg to +36±4 mmHg; NMDA in Brattleboro rats: from +5±2 mmHg to +34 ±8 mmHg; NMDA in Long Evans rats: from +18±7 mmHg to 80±9 mmHg; n=5). Similarly, in anaesthetized Brattleboro rats (urethane 1.2 g/kg i.p.) pressor responses to NMDA microinjections (0.7 nmol/rat) into the PAG area were significantly lower than in Long Evans rats (controls) (+15±3 mmHg vs +24±4 mmHg). In Long Evans rats NMDA injection also reversed blood pressure decrease induced by ganglionic blocker, hexamethonium and/or losartan (3 mg/kg i.v.), an AT1 receptor antagonist. In Brattleboro rats, NMDA injection did not reverse blood pressure decreases induced by hexamethonium (5 mg/kg i.v.). Moreover, hexamethonium induced blood pressure decrease was not reversed by acetylcholine injection (137 nmol/rat) into the PAG area of anaesthetized Long Evans rats, but if injected before hexamethonium, acetylcholine was able to increase blood pressure (+25±3 mmHg). Our results document: i) the importance of the PAG area in the control of cardiovascular system; ii) the involvement of excitatory amino acids in the neural control of vasopressin release; iii) the close relationship between glutamate and vasopressin in the central blood pressure regulation. Received: 1 April 1997 / Accepted: 2 February 1998     

Periaqueductal grey CB1 cannabinoid and metabotropic glutamate subtype 5 receptors modulate changes in rostral ventromedial medulla neuronal activities induced by subcutaneous formalin in the rat

This study was undertaken to analyze the involvement of periaqueductal gray (PAG) cannabinoid or group I metabotropic glutamate receptors in the formalin-induced changes on the rostral ventromedial medulla (RVM) ON- and OFF-cells activities. S.c. injection of formalin into the hind paw produced a transient decrease (4-6 min) followed by a longer increase (25-35 min) in tail flick latencies. Formalin also increased basal activity in RVM ON-cells (42+/-7%) and decreased it in OFF-cells (35+/-4%). Intra-PAG microinjection of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) (2 nmol/rat), a cannabinoid receptor agonist, prevented the formalin-induced changes in RVM cell activities. Higher dosages of WIN 55,212-2 (4-8 nmol/rat) increased the tail flick latencies, delayed the tail flick-related onset to ON-cell burst, and decreased the duration of OFF-cell pause. Furthermore, WIN 55,212-2 at a dosage of 8 nmol/rat decreased RVM ON-cell (57+/-7%) and increased OFF-cell ongoing activities (26+/-4%). These effects were prevented by N-piperidino-5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-3-pyrazolecarboxamide SR141716A, (1 pmol/rat), a CB1 cannabinoid receptor antagonist, or by 2-methyl-6-(phenylethynyl)pyridine (MPEP 20 nmol/rat), a selective mGlu5 glutamate receptor antagonist. T7-(hydroxyimino) cyclopropa[b]chromen-1alpha-carboxylate ethyl ester (CPCOOE/50 nmol/rat) and (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385, 20 nmol/rat), selective mGlu1 glutamate receptor antagonists, were ineffective in preventing the WIN-induced effects. This study suggests that s.c. injection of formalin modifies RVM neuronal activities and this effect is prevented by PAG cannabinoid receptor stimulation. Moreover, the physiological stimulation of PAG mGlu5, but not mGlu1 glutamate receptors, seems to be required for the cannabinoid-mediated effect.     

Telepathology for routine light microscopic and frozen section diagnosis

Telepathology (TP) uses telecommunication linkages to electronically capture, store, retrieve, and transmit images to distant sites. We assessed the feasibility of a dynamic real-time TP system for light microscopic (LM) diagnosis of anatomic pathology specimens, including frozen sections. Six pathologists, in 2 separate periods, read a set of 160 retrospectively retrieved slides (80 of which were frozen sections) by TP and LM. Reading times were recorded. Diagnoses were compared with the reference diagnosis (established by a group of 5 independent pathologists) and graded on a scale of 0 to 2 (2, correct; 1, incorrect but no clinical impact; 0, incorrect with clinical impact). Overall, LM was more accurate than TP compared with the reference diagnosis (score, 1.68 vs 1.54). There was no difference in accuracy between frozen section and paraffin-embedded tissue. Intraobserver agreement ranged from 82.5% to 88.2%. The average reading time was 6.0 minutes for TP and 1.4 minutes for LM. During the study, reading time decreased for TP but not for LM. These results show that despite marginally lower accuracy and longer reading times, TP isfeasible for routine light microscopic diagnosis, including frozen sections.     

Striatonigral suppression of focal hippocampal epilepsy

Both caudate nucleus (CN) and substantia nigra (SN) appear to be involved in the control of epileptogenic events. Previous investigations had demonstrated that both CN and SN stimulations are able to induce hippocampal theta (theta) rhythm and an inhibition of epileptiform spikes. Since the two structures are reciprocally linked by fibre pathways, experiments were carried out to test the possibility that CN influences the hippocampus via SN or vice versa. To this end, changes in penicillin-induced hippocampal spikes by CN or SN stimulation were studied before and after destruction of SN and CN respectively. Steady interictal activity was induced in the hippocampus of encéphale isolé cats by local injection of penicillin. Stimulations of both CN and SN induced statistically significant reduction of hippocampal spike frequency, and in some cases a clear and regular theta-rhythm. These effects were unchanged by the destruction of either CN or SN. The results add further information to the role played by the basal ganglia and SN in the control of epilepsy, and underline the possibility that caudate and nigral influences on the hippocampus are mediated by different pathways.     

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.     

Vertical transmission of hepatitis C Virus: An epidemiological study on 2,980 pregnant women in Italy

The risk of mother-to-infant transmission of hepatitis C virus (HCV) varies according to the population studied and the tests used. Aim of the current study was to investigate HCV vertical transmission rate in children born to 30 HCV positive/HIV negative pregnant women in Italy. We investigated the potential vertical transmission of HCV by identifying HCV antibody seropositive pregnant women, by analyzing HCV-RNA in the peripheral blood using PCR and by prospectively following their offspring until 24 months of age. During the third trimester, 2,980 consecutive pregnant women were examined for anti-HCV antibodies by a second generation Enzyme-Linked Immunosorbent Assay (EIA2) and re-assayed by a second generation Recombinant Immunoblot Assay (RIBA2). A total of 32 mothers (1.07%) were positive for EIA2 test; 30 out of 32 had a reactive confirmatory RIBA2 test for HCV All anti-HCV positive mothers were negative for HIV. These 30 mothers and their 30 babies formed the study cohort. Of the 30 anti-HCV positive mothers, 10 were also positive for serum HCV-RNA by PCR. All the babies born to the 30 anti-HCV positive mothers were initially negative for HCV-RNA (cord blood specimens), but three babies became positive at three months of age and remained positive thereafter. These babies had been born to 3 of the 10 mothers with viremia during the third trimester of pregnancy. These results suggest that HCV vertical transmission is possible in 10% of anti-HCV positives and in about 33% of the HCV-RNA seropositive mothers.     

Enhancement of in vivo antitumor activity of classical anticancer agents by combination with the new, glutathione-interacting DNA minor groove-binder, brostallicin.

PURPOSE: Brostallicin (PNU-166196) is a alpha-bromoacrylic DNA minor groove binder, currently in clinical evaluation. This drug has the peculiarity of showing enhanced antitumor activity in cells with high glutathione S-transferase (GST)/glutathione content. The purpose of the study was to study multiple combinations of brostallicin with classical anticancer agents. EXPERIMENTAL DESIGN: The cis-dichloro-diammine-platinum (cDDP)/brostallicin combination was tested in the human colon carcinoma (HCT-116) model transplanted in nude mice. Two treatment schedules were tested: cDDP followed by brostallicin 48 h after or brostallicin followed by cDDP. These two schemes were selected from the observation that tumor cells in vitro show an increased activity of GST 48 h after cDDP treatment. The HCT-116 model was used also to test the irinotecan (cPT-11)/brostallicin combination. The effect of brostallicin in combination with doxorubicin (DX) was studied in the i.v. injected murine L1210 leukemia. Three administration schedules were tested. The antitumor activity of brostallicin and Taxotere was tested on the A549 lung cancer xenografts. RESULTS: In line with the increased GST activity observed after treatment with cDDP, the cDDP/brostallicin interaction was sequence-dependent, leading to a more than additive antitumor effect, without additional toxicity, only when cDDP was given before brostallicin. The antitumor effect of CPT-11 was enhanced significantly by brostallicin cotreatment. A more than additive antitumor effect, without additional toxicity, was observed when DX/brostallicin were sequentially administered in L1210-bearing mice. Finally, additivity was observed when brostallicin/Taxotere simultaneous combination was tested. CONCLUSIONS: Although the precise molecular mechanism of interaction between brostallicin and the other tested cytotoxics has not yet been identified, a clear therapeutic gain is observed in preclinical models when brostallicin is combined with anticancer agents such as cDDP, DX, CPT-11, and Taxotere. These results indicate the potential therapeutic value of brostallicin in cancer combination treatment therapy.