Bridging pro-inflammatory signals, synaptic transmission and protection in spinal explants in vitro.

Multiple sclerosis is characterized by tissue atrophy involving the brain and the spinal cord, where reactive inflammation contributes to the neurodegenerative processes. Recently, the presence of synapse alterations induced by the inflammatory responses was suggested by experimental and clinical observations, in experimental autoimmune encephalomyelitis mouse model and in patients, respectively. Further knowledge on the interplay between pro-inflammatory agents, neuroglia and synaptic dysfunction is crucial to the design of unconventional protective molecules. Here we report the effects, on spinal cord circuits, of a cytokine cocktail that partly mimics the signature of T lymphocytes sub population Th1. In embryonic mouse spinal organ-cultures, containing neuronal cells and neuroglia, cytokines induced inflammatory responses accompanied by a significant increase in spontaneous synaptic activity. We suggest that cytokines specifically altered signal integration in spinal networks by speeding the decay of GABAA responses. This hypothesis is supported by the finding that synapse protection by a non-peptidic NGF mimetic molecule prevented both the changes in the time course of GABA events and in network activity that were left unchanged by the cytokine production from astrocytes and microglia present in the cultured tissue. In conclusion, we developed an important tool for the study of synaptic alterations induced by inflammation, that takes into account the role of neuronal and not neuronal resident cells.

Psychological distress is associated with altered cognitive functioning in family caregivers of patients with disorders of consciousness.

OBJECTIVES: To analyse the possible presence of reduced cognitive efficiency in family caregivers of patients with prolonged disorders of consciousness (DOC). SUBJECTS: The participants were 27 caregivers of 25 patients with DOC admitted to the severe brain injury units of the ICS Maugeri, Institutes of Telese Terme and Sciacca, Italy. METHODS: We examined cognitive functions such as short- and long-term memory, executive functions and attention by means of standardized tests. We also assessed features of psychological distress such as anxiety, depression, psychophysiological symptoms, prolonged grief disorder, psychological burden and quality of life. All scores on neuropsychological tests were compared with those of the 15 matched control subjects. RESULTS: Enrolled family caregivers showed high frequency of clinically relevant depressive symptoms and anxiety; half of them met the criteria for prolonged grief disorder. Caregivers achieved scores lower than the matched controls on tests for selective attention, verbal fluency and long-term spatial memory. CONCLUSIONS: Family caregivers' burden is associated with a reduced efficiency of selected executive measures and visuospatial learning. These results emphasize the need for appropriate psychological and cognitive supporting therapies for family caregivers of patients with DOC, also considering their delicate involvement in clinical decision-making and in providing care.

Effects of near-infrared laser radiation on the survival and inflammatory potential of Candida spp. involved in the pathogenesis of chemotherapy-induced oral mucositis.

Candida spp. usually colonize ulcerative lesions of atrophic mucosa in patients with chemotherapy-induced oral mucositis inducing severe inflammation. The spread of antifungal-resistant strains strongly encouraged the search of complementary or alternative therapeutic strategies to cure inflamed mucosa. In this paper, we studied the effects of a near-infrared (NIR) laser system with dual-wavelength emission (808 nm + 904 nm) on the survival and inflammatory potential of C. albicans, C. glabrata, and C. parapsilosis. Laser treatment was performed with a Multiwave Locked System laser. Survival and apoptosis of fungal strains were evaluated by colony-forming units (CFU) counting and annexin V staining. Cytokine production was evaluated by ImmunoPlex array. Laser treatment significantly affected the survival of Candida spp. by inducing apoptosis and induced a lower production of inflammatory cytokines by dendritic cells compared to untreated fungi. No differences in the survival and inflammatory potential were recorded in treated or untreated Saccharomyces cerevisiae cells, used as the control non-pathogenic microorganism. Laser treatment altered the survival and inflammatory potential of pathogenic Candida spp. These data provide experimental support to the use of NIR laser radiation as a co-adjuvant of antifungal therapy in patients with oral mucositis (OM) complicated by Candida infections.

Low molecular weight, non-peptidic agonists of TrkA receptor with NGF-mimetic activity.

Exploitation of the biologic activity of neurotrophins is desirable for medical purposes, but their protein nature intrinsically bears adverse pharmacokinetic properties. Here, we report synthesis and biologic characterization of a novel class of low molecular weight, non-peptidic compounds with NGF (nerve growth factor)-mimetic properties. MT2, a representative compound, bound to Trk (tropomyosin kinase receptor)A chain on NGF-sensitive cells, as well as in cell-free assays, at nanomolar concentrations and induced TrkA autophosphorylation and receptor-mediated internalization. MT2 binding involved at least two amino-acid residues within TrkA molecule. Like NGF, MT2 increased phosphorylation of extracellular signal-regulated kinase 1/2 and Akt proteins and production of MKP-1 phosphatase (dual specificity phosphatase 1), modulated p38 mitogen-activated protein kinase activation,sustained survival of serum-starved PC12 or RDG cells, and promoted their differentiation. However, the intensity of such responses was heterogenous, as the ability of maintaining survival was equally possessed by NGF and MT2, whereas the induction of differentiation was expressed at definitely lower levels by the mimetic. Analysis of TrkA autophosphorylation patterns induced by MT2 revealed a strong tyrosine (Tyr)490 and a limited Tyr785 and Tyr674/675 activation, findings coherent with the observed functional divarication. Consistently, in an NGF-deprived rat hippocampal neuronal model of Alzheimer Disease, MT2 could correct the biochemical abnormalities and sustain cell survival. Thus, NGF mimetics may reveal interesting investigational tools in neurobiology, as well as promising drug candidates.

Low molecular weight, non-peptidic agonists of TrkA receptor with NGF-mimetic activity.

Exploitation of the biologic activity of neurotrophins is desirable for medical purposes, but their protein nature intrinsically bears adverse pharmacokinetic properties. Here, we report synthesis and biologic characterization of a novel class of low molecular weight, non-peptidic compounds with NGF (nerve growth factor)-mimetic properties. MT2, a representative compound, bound to Trk (tropomyosin kinase receptor)A chain on NGF-sensitive cells, as well as in cell-free assays, at nanomolar concentrations and induced TrkA autophosphorylation and receptor-mediated internalization. MT2 binding involved at least two amino-acid residues within TrkA molecule. Like NGF, MT2 increased phosphorylation of extracellular signal-regulated kinase1/2 and Akt proteins and production of MKP-1 phosphatase (dual specificity phosphatase 1), modulated p38 mitogen-activated protein kinase activation, sustained survival of serum-starved PC12 or RDG cells, and promoted their differentiation. However, the intensity of such responses was heterogenous, as the ability of maintaining survival was equally possessed by NGF and MT2, whereas the induction of differentiation was expressed at definitely lower levels by the mimetic. Analysis of TrkA autophosphorylation patterns induced by MT2 revealed a strong tyrosine (Tyr)490 and a limited Tyr785 and Tyr674/675 activation, findings coherent with the observed functional divarication. Consistently, in an NGF-deprived rat hippocampal neuronal model of Alzheimer Disease, MT2 could correct the biochemical abnormalities and sustain cell survival. Thus, NGF mimetics may reveal interesting investigational tools in neurobiology, as well as promising drug candidates.

Role of MDR1 gene polymorphisms in gingival overgrowth induced by cyclosporine in transplant patients.

BACKGROUND AND OBJECTIVE: The aim of the present study was to determine the association between genotypes of the MDR1 gene, encoding P-glycoprotein, and gingival overgrowth in transplant patients treated with cyclosporine, and to evaluate the effect of periodontal treatment in these patients. MATERIAL AND METHODS: Fifty transplant patients receiving therapy with cyclosporine and suffering from gingival overgrowth were subjected to nonsurgical periodontal treatment and received oral hygiene instructions. Hyperplastic index, periodontal probing depths, bleeding and plaque scores were recorded at baseline and after 3 and 6 mo. Patients were dichotomized into two groups: those with a hyperplastic index of < 30% (minimal gingival overgrowth) and those with a hyperplastic index of > or = 30% (clinically significant gingival overgrowth). MDR1 C3435T and G2677T polymorphisms were evaluated in all patients and in 100 controls. RESULTS: At baseline, 32 patients (64%) had minimal gingival overgrowth and 18 patients (36%) had clinically significant gingival overgrowth. The mutated C3435T genotype was significantly more frequent in the second group (p < 0.019). The significant association between gingival overgrowth and the 3435TT genotype was confirmed by logistic regression analysis (p < 0.031). The differences in hyperplastic index, observed at baseline between patients with the TT genotype and those with the CC/CT genotype disappeared in the second and third evaluation. The mean monthly change of the square root of the gingival overgrowth scores for all patients, assessed using linear models, was significantly different from baseline (-0.17 points per month, p < 0.00001); and this was particularly evident in subjects with renal transplant (-1.62, p < 0.01). CONCLUSION: Aetiological periodontal and self-performed maintenance therapy is effective in reducing gingival overgrowth, particularly in subjects with the 3435TT genotype and in patients with renal transplant.

[Thyroid maltoma: report of a case without coexistent Hashimoto's thyroiditis]. / Maltoma della tiroide: presentazione di un caso non associato a tiroidite di Hashimoto.

Maltomas of the thyroid are rare neoplasms that originate from parafollicular B lymphocytes and are often associated with autoimmune thyroiditis (Hashimoto's disease). The authors describe a case of a primary thyroid lymphoma in which no evidence for a previous thyroiditis could be found during clinical evaluation (clinical progression of the tumor, diagnostic studies, preoperative cytology, histology of the surgical specimen). Noteworthy was the development of a severe form of pure red cell aplasia (PRCA) about 6 months after the operation without detectable autoantibodies or signs of previous viral infection. The aplasia resolved completely with corticosteroid therapy.

[The tension-free hernioplasty for primary inguinal hernias: personal experience]. / Il trattamento dell'ernia inguinale con tecnica "tension free". Esperienza personale.

The Authors report their experience in the treatment of primary inguinal hernias using Trabucco's tension-free technique. Since April 1998 to June 2002 four hundred and fifteen patients (399 men and 16 women) were treated in our Department for primary inguinal hernia. The results demonstrate the efficacy of this technique in reducing post-operative complications and in preventing relapses. The reduction of costs is related to a shorter hospitalization and an earlier return to work.

Abrikossoff's tumour: report of a rare case in anal perianal region.

The authors report a rare case of a 47-year old man suffered from Crohn's disease and depression with multiple prominent lesions in the anal and perianal region. The biopsy of these lesions showed the presence of Abrikossoff's tumour. This tumour is very rare in the anal region and usually the lesions are small (0.5-3 cm) and solitary. The authors report this case because they considered it an interesting case for the localization and the appearance of the lesions.

[Risk factors conditioning the incidence and severity of cyclosporine A-induced gingival overgrowth and methods of prevention]. / Fattori condizionanti l'incidenza e la severità dell'ipertrofia gengivale indotta da ciclosporina A e possibilità di prevenzione.

Cyclosporin A (CsA) induced gingival overgrowth is one of the major side-effects conditioning the quality of life of the patient under immunosuppressive therapy. This adverse effect has been first reported in 1983 and affects almost 30% of treated patients. Several papers have been published concerning the cellular/molecular mechanisms by which CsA may induce, at the same time, an immunosuppressive and proliferative action. In this review various factors concerning the patient and his milieu that account for the different prevalence of the severity of gingival overgrowth in clinical studies are analyzed and briefly discussed. In particular, age, sex, pharmacokinetic properties, pharmaceutical preparation, genetic predisposition, association with other drugs and the parodontal conditions before transplantation are considered. In addition, a unique approach to the patients with gingival overgrowth as well as effective methods of prevention and therapy are suggested.

[Gastrointestinal stromal tumors: clinical considerations]. / Considerazioni cliniche sui tumori gastrointestinali stromali.

Gastrointestinal stromal tumors (61ST) are an heterogeneous group of non epithelial tumors of the gastrointestinal tract. They are peculiar to extreme cellular variability and uncertain malignancy. Gist are rare tumors that arise from primitive mesenchymal cells located in all gastrointestinal tract. Till now they are object of discussion about their origin, diagnostic standards, prognostic factors, histopathological classification. They are more frequently in over 40 years old people without difference in two sex, but they can appear in the child too and in the young man suffering from HIV. The authors relate two cases of recent observation, and discuss on the biological behaviour of these rare tumors.

[Pilonidal sinus: an retrospective analysis of 205 cases]. / Sinus Pilonidale. Analisi retrospettiva di 205 casi. Metodo chiuso versus metodo aperto.

Sinus pilonidalis or the sacrococcigea cyst, normally is considered a "small surgical pathology" and actually it is controversial disease regarding its pathogenesis and treatment. Today the congenital hypothesis of this pathology is not considered. The etiopathogenesis exclude vestigia embryonic origin and consider it an inflammatory disease. Traumatism of the sacral region, hirsutism, hormonal secretion stimulating, and furrow sacral furrow cutaneous, explain the prevalence of this pathology in the male sex and in the puberale age. It usually appears after the pubertà and extension one various frequency of presentation in males sex (1.3%) regarding females (0.11%). The symptomatology can be rare or introduce itself in violent and intense way with on abscess of the region, or with only or multiple fistulas orifices from which exit materialclarly purulent. Normally cystic cavity is one, situated in the subcutaneous tissue with annexed inflammatory phenomena. This cavity to times communicates with the skyn fistulating. The treatment of election is surgical and must weighted and be regulated in relation to the entity of the lesion and its inflammatory picture. Sometimes the medical therapy with anti-inflammatory and antibiotic is not control the symptomatology and it need the surgical treatment.

Correction of the unfavourable effects of vasopressin by nitroglycerin infusion.

Nitroglycerin was administered with vasopressin to prevent adverse effects. Vasopressin 0.25U . 70 kg-1 min-1 was infused intravenously in four dogs for 40 minutes, when a venous infusion of nitroglycerin 1.2 micrograms . kg-1 . min-1 was added for 20 minutes. Nitroglycerin 1.2 micrograms . kg-1 . min-1 alone was infused intravenously in another four dogs for 40 minutes. The venous blood pressures (mesenteric and central) and arterial pressures (mesenteric and femoral), the electrocardiogram and arterio-venous difference were recorded. Nitroglycerin was shown to annul the unfavourable effects of vasopressin without altering its efficacy upon portal pressure.