Search PubMedSearch

Biomedical subjects

M Riccio

Publications and source records attributed to M Riccio.

At least 19 recordsLinked to original sources

The type 2 ryanodine receptor of neurosecretory PC12 cells is activated by cyclic ADP-ribose. Role of the nitric oxide/cGMP pathway.

Of two neurosecretory PC12 cell clones that respond to NO donors and 8-bromo-cGMP with similar increases in cADP-ribose and that possess molecularly similar Ca2+ stores, only one (clone 16A) expresses the type 2 ryanodine receptor, whereas the other (clone 27) is devoid of ryanodine receptors. In PC12-16A cells, activation of the NO/cGMP pathway induced slow [Ca2+]i responses, sustained by release from Ca2+ stores. In contrast, PC12-27 cells were insensitive to NO donors. Likewise, in PC12-16A cells preincubated with NO donors, Ca2+ stores were partially depleted, as revealed by a test with thapsigargin, whereas those in clone 27 were unchanged. The NO-induced Ca2+ release was increased synergistically by caffeine, and the corresponding store depletion was magnified by ryanodine. The specificity for the NO/cGMP pathway was confirmed by the effects of two blockers of cGMP-dependent protein kinase I, while the role of cADP-ribose was demonstrated by the effects of its antagonist, 8-amino-cADP-ribose, administered to permeabilized cells. These results demonstrate in neurosecretory cells a ryanodine receptor activation pathway similar to that known in sea urchin oocytes. The signaling events described here could be of great physiological importance, especially in the nervous system.

Adenosine Diphosphate Ribose

A modified surgical technique for temporalis transfer.

A modification of the temporalis muscle transfer for facial animation in facial palsy is described. Seven cases are presented which demonstrate the advantages of the procedure, especially the avoidance of temporal hollowing and the greater power due to less dissection of the muscle belly, a more direct line of pull and the absence of a pulley. In addition, food pooling in the buccal sulcus is reduced, and the procedure is less extensive and thus better tolerated.

Adult

Orthotopic vascularized osteochondral allografts in an immunosuppressed rat model.

This study examined the survival of orthotopic, vascularized, osteochondral allografts, following 12 weeks of immunosuppression and transfer into a naive, allograft host up to 14 weeks later, and compared the results with those previously reported for similar grafts in a heterotopic position. Knee-joint allografts between DA (donor) and Lewis (recipient) rat strains were assessed by quantitative histology up to 6 months after transplantation, and graft microcirculation was examined by India-ink infusion. Graft repopulation was assessed by re-transferring the graft to a naive, non-suppressed allograft host 12 to 26 weeks after the initial transplantation. Isografts survived for as long as grafts were examined (6 months) and showed good healing of the graft/host bone junction, although long-term isografts showed some deterioration of the growth plate. Non-suppressed allografts rejected within 2 weeks. Allografts in hosts immunosuppressed for 12 weeks remained healthy and healed in a similar manner to the isografts. Following cessation of immunosuppression, allografts progressively deteriorated, with mononuclear cell infiltration apparent in graft bone marrow and muscle in the later stages examined. Transfer to second non-suppressed hosts resulted in rapid rejection of the allografts, indicating that, as shown previously in heterotopic, osteochondral allografts, little or no graft repopulation by host-derived cells had occurred during the protected period in the first host.

Animals

Nitric oxide action on growth factor-elicited signals. Phosphoinositide hydrolysis and [Ca2+]i responses are negatively modulated via a cGMP-dependent protein kinase I pathway.

The role of nitric oxide (NO) in the phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis and intracellular Ca2+ release responses induced by epidermal, platelet-derived, and fibroblast growth factors was investigated in three cell lines, a clone of NIH-3T3 fibroblasts overexpressing epidermal growth factor receptors and the tumoral epithelial cells A431 and KB. In all three cell types, pretreatment with NO donors decreased growth factor-induced PIP2 and Ca2+ responses, whereas pretreatment with NO synthase inhibitors increased them. The Ca2(+)-dependent PIP2 hydroysis induced by micromolar concentrations of the Ca2+ ionophore, ionomycin, was also modulated negatively and positively by NO donors and synthase inhibitors, respectively. In contrast, the Ca2+ content of the intracellular stores was unaffected by the various pretreatments employed. NO donors and synthase inhibitors induced an increase and decrease, respectively, of the intracellular cGMP formation in all three cell lines investigated. All of the effects of the NO donors were mimicked by 8-bromo-cGMP administration and abolished by pretreatment with the specific blocker of the cGMP-dependent protein kinase I, KT5823, which by itself mimicked the effects of the synthase inhibitors. Together with previous observations on G protein-coupled receptors, the present results demonstrate that PIP2 hydrolysis and Ca2+ release occur under the feedback control of NO, independently of the phospholipase C (beta, gamma, or delta type) involved and of the mechanism of activation. Such a control, which appears to be effected by the cGMP-dependent protein kinase I acting at the level of the phospholipases C themselves, might ultimately contribute to the inhibitory role of NO on growth previously observed with various cell types.

Alkaloids

Neurophysiological evaluation of zidovudine in asymptomatic HIV-1 infection: a longitudinal placebo-controlled study.

The effect of early antiretroviral medication with zidovudine on neurophysiological functions was evaluated in subjects with asymptomatic HIV-1 infection. Patients were recruited participants of a larger double-blind randomised placebo-controlled treatment trial with zidovudine (Concorde). The main outcome measures included: quantitative electroencephalography (QEEG), auditory event-related potentials (AEP) and pattern-reversal visual evoked potentials (PRVEP), as well as standard clinical, virological and immunological markers. No significant impairment and no difference between treatment groups was found in visual P100 latency and auditory long-latency P3 responses which is in agreement with the absence of neurological and neuropsychological impairment over the study period. Significant treatment effects were revealed by quantitative electroencephalography (QEEG). While the placebo group showed a significant increase in delta and theta slow frequency QEEG activity over the study period, slow wave amplitude remained unchanged in the zidovudine group after a mean follow-up period of 28 months. In summary, the data provide evidence for a low level neuropathological process in asymptomatic HIV-1 infection which can be effectively suppressed by antiretroviral medication.

Adult

Long-term zidovudine reduces neurocognitive deficits in HIV-1 infection.

OBJECTIVE: To determine the efficacy of zidovudine (ZDV) in preventing decline of neurocognitive functions in HIV-1 infection. DESIGN: Retrospective evaluation of subjects enrolled in a natural history study. Two analyses were made to evaluate the effect of (1) current ZDV, irrespective of length of treatment and (2) long-term ZDV treatment for at least 1 year. SETTING: Subjects were recruited from HIV out-patient clinics. PATIENTS: HIV-1-seropositive subjects were assigned to one of three groups according to the Centers for Disease Control and Prevention classification: asymptomatic infection (n = 60), symptomatic infection but without AIDS (n = 51), and AIDS (n = 32). MAIN OUTCOME MEASURES: Standardized neuropsychological and neurophysiological measures [electroencephalogram (EEG) and long-latency evoked potentials]. RESULTS: Long-term ZDV use was associated with improved cognitive performance in subjects with early symptomatic HIV-1 infection and AIDS, compared to subjects in the same clinical stage but without previous ZDV treatment. This was corroborated by neurophysiological evidence of reduced slow-wave EEG amplitude in the ZDV-treated subjects. The advantage of ZDV treatment was evident despite lower immune status in most treated subjects. CONCLUSIONS: The findings in this natural history study indicate that long-term ZDV treatment may be an effective prophylactic to reduce neurocognitive deficits in symptomatic HIV-1 infection, thereby lowering the risk for developing HIV-1-associated dementia.

Acquired Immunodeficiency Syndrome

Platelet-activating factor (PAF) receptor antagonism by WEB 2170 improves the survival of ischaemic skeletal muscle.

The platelet-activating factor (PAF) receptor antagonist, WEB 2170, significantly improved the survival of ischaemic rabbit skeletal muscle from 42% in saline-infused muscle to 65% in WEB 2170-infused muscle at 24 hours post reperfusion. Evidence is presented which suggests that WEB 2170 inhibits neutrophil infiltration during reperfusion. In addition, tissue lipid peroxide levels and the release into blood of the enzyme creatine kinase were inhibited by local infusion of WEB 2170. In contrast, the level of oedema in muscles receiving an infusion of WEB 2170 was not different from that in saline controls. It is concluded that infusion of a PAF antagonist into ischaemic skeletal muscle at the time of reperfusion inhibits neutrophil recruitment and activation. These results provide an impetus for PAF receptor antagonism as a means of reducing reperfusion injury in limb replantation surgery.

Animals

A longitudinal study of the neuropsychiatric consequences of HIV-1 infection in gay men. I. Neuropsychological performance and neurological status at baseline and at 12-month follow-up.

The aim of this study was to determine whether HIV infection is associated with neurological or neuropsychological impairment in the asymptomatic and early symptomatic stages of disease. Subjects included 61 gay men (41 HIV-, 20 HIV+) who were assessed at the time of requesting their first HIV test and again 12 months later. The assessments at baseline were conducted double-blind to HIV serostatus. Measures included a neuropsychological battery, neurological examination and full psychiatric assessment. There were no differences between the asymptomatic HIV+ and HIV- groups at baseline or at follow-up in terms of mean scores on neuropsychological tests. Mean scores were within the normal range for all neuropsychological tests for both groups. Multiple regression analysis was used to predict each individual's performance at follow-up on the basis of their baseline performance, psychiatric state, neurological history and drug use for each of the neuropsychological tests. HIV+ subjects were more likely than control subjects to perform at a significantly lower level at follow-up on one or more tests than predicted on the basis of their baseline performance.

AIDS Dementia Complex

A longitudinal study of the neuropsychiatric consequences of HIV-1 infection in gay men. II. Psychological and health status at baseline and at 12-month follow-up.

The aim of this study was to determine whether HIV infection is associated with increased psychosocial distress in the asymptomatic and early symptomatic stages of disease and to determine the factors associated with reporting health symptoms. Subjects included 61 gay men (41 HIV--, 20 HIV+) who were assessed at the time of requesting their first HIV test and again 12 months later. Measures included a detailed standardized psychiatric interview (Present State Examination, PSE), a range of psychosocial self-report measures and a physical symptom checklist. There were no differences between the HIV+ and HIV-- groups in terms of self-reported symptoms. Multiple regression analysis showed that the symptom reporting was not associated with clinical or immunological markers of disease progression but was associated with measures of psychosocial distress. Although both groups showed elevated levels of psychosocial distress at the time of HIV testing, there were no differences between serostatus groups at follow-up. Multiple regression analysis indicated that the best predictors of PSE scores at follow-up were baseline PSE score and a history of psychiatric illness. Early HIV disease is not associated with increased psychosocial distress and symptom reporting is more closely related to psychological measures than to clinical or immunological markers of disease.

AIDS Dementia Complex

The psychosocial impact of HIV infection in women.

The aim of the investigation was to study the prevalence of current and past psychiatric morbidity and psychosocial problems in HIV seropositive (HIV +ve) asymptomatic women. A cross-sectional controlled study including 57 HIV +ve women belonging to CDC group II and III (43 intravenous drug users and 14 non-IVDUs heterosexuals) and 23 HIV -ve women (15 intravenous drug users and 8 non-IVDUs heterosexuals) is reported. Outcome measures included, past psychiatric history, current psychological status (Zung Anxiety and Depression scales, Symptom Check List 90-Revised), Social Supports and Locus of Control Scales, and information on changes in work, social and sexual life after HIV testing. Results showed that HIV +ve women differed very little from HIV -ve controls regarding outcome measures and indeed for some variables HIV infected women had lower levels of psychological morbidity. Multiple regression analyses showed that alcohol misuse and a predominantly external locus of control accounted for the 29% of the variance of psychiatric distress (F = 9.23, p < 0.0006). The implications of the findings are discussed.

Adaptation, Psychological

Neuropsychiatric aspects of HIV-1 infection in gay men: controlled investigation of psychiatric, neuropsychological and neurological status.

The aim of this study was to determine whether HIV infection is associated with psychiatric morbidity or neuropsychological impairment in asymptomatic and early symptomatic stages of disease in gay men. The subjects were 100 gay men (68 HIV-ve, 32 HIV+ve, 6 being CDC IV). All subjects were recruited at the time of requesting their first HIV test and the assessment was double-blind to HIV serostatus. There were no differences in psychiatric status or neuropsychological performance between the HIV-ve and HIV+ve groups. Multiple regression analysis and logistic regression were used to identify factors associated with psychiatric morbidity, neuropsychological impairment and subjective reporting of memory problems and physical symptoms for all 100 subjects. Previous psychiatric history and current illegal (non-dependent) drug use were associated with psychiatric morbidity, poor education was associated with neuropsychological impairment and psychiatric status (score on HAD and PSE) was associated with subjective reporting of memory problems and physical symptoms.

AIDS Dementia Complex

Detection of subclinical motor dysfunctions in early symptomatic HIV infection with topographical EEG.

Motor dysfunctions are amongst the earliest and most common signs of brain impairment caused by human immunodeficiency virus (HIV) infection. Topographical EEG was recorded in patients both with asymptomatic and early symptomatic infection (without acquired immunodeficiency syndrome (AIDS) defining illness), as well as in seronegative controls under resting and motor activation conditions. While patients' motor performance did not differ from control values, the EEG showed a consistent increase in rhythmic activity in Theta, Alpha and Beta frequency bands in Symptomatics. This amplitude increase was evident in different topographical regions during resting states as compared with motor activation, findings which suggest concurrent involvement of several motor areas possibly due to a functional impairment in subcortical integratory mechanisms. Comparing motor task and baseline both patient groups showed less consistent patterns of task-related EEG amplitude reduction than found in the control group. Here topographical EEG in connection with motor activation procedures was found to be more sensitive than behavioral measures of motor performance and offers a technique to assess treatment effects before the development of motor abnormalities in patients with HIV infection.

Adult

The psychosocial impact of HIV infection in gay men, drug users and heterosexuals. Controlled investigation.

The aim of this study was to establish the prevalence of current and past psychiatric morbidity in HIV seropositive asymptomatic subjects belonging to three transmission categories (gay men, intravenous drug users, and heterosexuals) compared with that found in HIV seronegative controls from the same groups. A cross-sectional, controlled study including 279 seropositive subjects belonging to groups II and III defined by the Center for Disease Control (94 gay men, 157 intravenous drug users, and 28 heterosexuals) and 159 seronegative subjects (38 gay men, 91 intravenous drug users, and 30 heterosexuals) is reported. Outcome measures included standardised, self-report questionnaires and a semistructured interview to assess current psychopathological status and past psychiatric history. In addition, a psychiatric diagnosis according to DSM-III-R criteria Axis I and II was made in the seropositive subjects. Results showed that these subjects differed very little from the controls and that overall levels of psychiatric disturbances in both groups were low and similar to those found in other life-threatening illnesses. Furthermore, intravenous drug users, regardless of HIV serological status, had the highest levels of psychological morbidity. Psychosocial distress was associated with previous and current lifestyle, independently of HIV status.

Adult

Factors associated with psychological help-seeking in HIV disease.

The study was aimed at evaluating the psychosocial and psychopathological characteristics of individuals with Human Immunodeficiency Virus (HIV) infection seeking psychological help compared with a sample not seeking help. Two hundred and seventy-one HIV seropositive (HIV+ve) subjects belonging to three transmission categories (90 gay men, 154 intravenous drug users and 27 heterosexuals) who were assessed at their first clinic appointment and offered access to psychological help were studied. Subsequently, it was found that 45 (17%) took advantage of the offer of psychological help, and attended a specialist clinic, while 226 (83%) did not seek help. Stepwise logistic regression analysis was used to establish the characteristics of subjects who received psychological help. Results showed that five factors identified at the time of first clinic appointment were significantly associated with seeking psychological help subsequently: (1) having a current DSM-III-R Axis I psychiatric diagnosis; (2) being single; (3) belief of being affected by a serious physical illness (negative correlation); (4) higher level of education; and (5) no past or current history of substance misuse. The implications of the findings are discussed.

Adaptation, Psychological

Risk of deliberate self-harm and factors associated with suicidal behaviour among asymptomatic individuals with human immunodeficiency virus infection.

The study was aimed at evaluating the risk of deliberate self-harm (DSH) and factors associated with suicidal behaviour in 213 asymptomatic individuals with human immunodeficiency virus (HIV) infection in 3 transmission categories (68 gay men, 123 intravenous drug users and 22 heterosexuals). The results showed that 12 HIV-seropositive (HIV+) subjects were involved in DSH after the notification of a positive HIV test result, of which 8 occurred within 6 months and 4 between 6 months and 3 years. HIV+ subjects with a past psychiatric history showed a 7.7-fold increase in the relative risk of DSH, and HIV+ subjects with a history of DSH showed a 5-fold increase in the relative risk of DSH compared with HIV+ individuals without a past psychiatric history and a history of DSH. Professionals involved in the care of HIV+ individuals need to be aware of this risk, especially in the first few months after notification of HIV status and also at later stages of acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome