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Biomedical subjects

A Sanna

Publications and source records attributed to A Sanna.

At least 19 recordsLinked to original sources
PubMed2006

Superconductivity in lithium, potassium, and aluminum under extreme pressure: a first-principles study.

Extreme pressure strongly affects the superconducting properties of "simple" elemental metals, such as Li, K, and Al. Pressure induces superconductivity in Li (as high as 17 K) while suppressing it in Al. We report first-principles investigations of the superconducting properties of dense Li, K, and Al based on a recently proposed, parameter-free, method. Our results show an unprecedented agreement with experiments, assess the predictive power of the method over a wide range of densities and electron-phonon couplings, and provide predictions for K, where no experiments exist so far. More importantly, our results help uncover the physics of the different behaviors of Li and Al in terms of phonon softening and Fermi surface nesting in Li.

Journal Article↗
PubMed2006

Glatiramer acetate reduces lymphocyte proliferation and enhances IL-5 and IL-13 production through modulation of monocyte-derived dendritic cells in multiple sclerosis.

Dendritic cells (DC), as the most effective antigen presenting cells, are protagonists of the complex immune network involved in multiple sclerosis (MS) lesion formation. Glatiramer acetate (GA), a synthetic random copolymer, is thought to exert its therapeutical effect in MS by favouring both Th2 cell development and IL-10 production from peripheral lymphocytes as well as by systemically affecting the antigen presenting cells. In the present study we further analysed the mechanisms of action of GA by using an autologous DC-lymphocytes (Ly) coculture system from 11 MS patients and 12 matched healthy controls (HC). We found that, in MS patients, pretreatment with GA significantly decreases the in vitro proliferative effect of DC on lymphocytes as compared to HC and to unpulsed or myelin basic protein (MBP)-pulsed DC from MS patients (P < 0.05). In addition, GA-treated DC from both MS patients and HC significantly increase the lymphocyte production of IL-5 and IL-13 as compared to MBP-treated DC (P < 0.05). In conclusion our in vitro study may provide new therapeutical mechanisms of GA on lymphocytes, antiproliferative and Th2-favouring effects, which are mediated by monocyte-derived DC.

Adult↗
PubMed2006

Intrathecal chitotriosidase and the outcome of multiple sclerosis.

Activated macrophages are major effectors at all stages of lesion formation in multiple sclerosis (MS) brain. Here, we report that the macrophage enzyme chitotriosidase (Chit) is significantly elevated both in plasma and cerebrospinal fluid (CSF) of patients with MS as compared to healthy controls and other neurological patients (P<0.001). Furthermore, the Chit activity in blood significantly associates with the MS clinical course (higher in secondary progressive relative to relapsing-remitting, P=0.01) and the clinical severity as measured by Kurtkze's Expanded Disability Status Scale (P<0.001). Also, we found that Chit activity is compartmentalized in the central nervous system of early MS patients and that its CSF/plasma quotient, in the presence of a preserved albumin quotient, correlates with the extent of future clinical deterioration (r=0.91; P<0.001). These findings confirm that innate immunity, here represented by Chit, is clinically relevant in MS and allows, if confirmed, reconsidering novel MS therapeutic strategies specifically aimed at this branch of the immune response.

Adult↗
PubMed2005

Multiple sclerosis: interferon-beta induces CD123(+)BDCA2- dendritic cells that produce IL-6 and IL-10 and have no enhanced type I interferon production.

Interferon-beta (IFN-beta), an approved drug for multiple sclerosis (MS), acts on dendritic cells (DC) by suppressing IL-12p40 and increasing IL-10. This results in Th2-biased immune responses. The nature of IFN-beta-modulated DC remains elusive. Previously, we observed that IFN-beta dose dependently induces expression of CD123, i.e., a classical marker for plasmacytoid DC, on human blood monocyte-derived myeloid DC. Such IFN-beta-modulated DCs produce predominantly IL-10 but are IL-12 deficient, with potent Th2 promotion. In the present study, we further characterize IFN-beta-modulated DC by using recently identified blood DC antigens (BDCA), and investigate their ability to produce type I IFN in response to virus stimulation. We show that IFN-beta induces development of CD123+ DC from human blood monocytes, which coexpress BDCA4+ but are negative for BDCA2-, a specific marker for plasmacytoid DC. Such IFN-beta-modulated DC can produce IL-6 and IL-10 but not IL-12p40, and have no enhanced IFN-alpha and IFN-beta production. The findings indicate that IFN-beta-modulated DCs represent a myeloid DC subset with diminished CD11c, BDCA-1 and CD1a expression. They may promote Th2 and B cell differentiation through IL-6 and IL-10 production, and suppression of IL-12p40, but they have no enhanced antiviral capacity.

Adult↗
PubMed2004

Sexing of in vitro produced ovine embryos by duplex PCR.

The aim of this article was to develop a fast and easy duplex polymerase chain reaction (PCR) method, for sex determination of ovine in vitro produced embryos prior to implantation. We tested the approach with 107 samples of autosomal cells (oviductal sheep cells and male lamb fibroblasts), divided into three groups for each sex according to the number of cells employed (30, 5, 2, respectively). We then used the test on 21 embryos at blastocyst stage. On the same day the embryos were transferred in pairs into 11 recipient synchronized ewes. The PCR utilized two different sets of primers: the first pair recognized a bovine Y-chromosome-specific sequence (SRY), that showed 100% homology with the corresponding sequence of the ovine Y-chromosome and is amplified in males only. The second pair recognized the bovine 1.715 satellite DNA (SAT) which was amplified in all ovine samples but, when submitted to the GenBank database did not show homology with any of the reported ovine sequences. However, after sequencing, ovine amplification product showed 98% homology with the bovine specific satellite sequence. The autosomal samples were amplified with 85.0% efficiency and 91.2% accuracy, while amplification was successful with all 21 embryos (100% efficiency). Eight lambs were born and the sex as determined by PCR corresponded to the anatomical sex in seven (87.5% accuracy). These results confirm that this method can be applied in ovine breeding programs to manipulate sex ratio of offspring.

Animals↗
PubMed2003

Respiratory-related evoked potential and upper airway transmural pressure change by using the negative expiratory pressure (NEP) device.

OBJECTIVE: Several studies have previously shown respiratory related evoked potentials (RREP) in humans elicited by mechanical stimuli applied on upper airways (UA). According to us, heterogeneous findings, concerning latencies and amplitudes, have been reported because of the different timing of stimuli application during the respiratory cycle and/or features of pressure stimuli. Therefore we evaluated the cortical response evoked by transmural pressure changes at the mouth induced by a negative expiratory pressure (NEP) device. METHODS: RREP were recorded in 22 healthy non-obese, non-snoring volunteers. The subjects were studied awake in seated position during quiet breathing. Three different pressure levels were applied, in a random order, 200 ms after the beginning of expiration. Cortical electrical responses were recorded from scalp electrodes at Fz, Cz, and Pz scalp location (international 10-20 system) referenced to the linked earlobes. RESULTS: RREP responses consisted of two negative (N45, N120) and two positive (P22, P85) waves. There was no significant effect of pressure or electrode on component latencies. The P22 wave (PRESSURE: F(df 2,42)=6.66, P<0.01), the N45 wave (PRESSURE: F(df 2,42)=16.51, P<0.001), and the P85 wave (PRESSURE: F(df2,42)=15.15, P<0.001) increased significantly theyr amplitude with increasing from pressure stimuli 1 to 10 cmH2O. CONCLUSIONS: The present results suggest that the UA NEP application in humans is a reliable way of evoking cortical responses. The experimental features that we described allow us to minimize the confounding factors in evaluating RREPs. The NEP device appears to be a useful tool for investigation of the neurobiology of UA sensation in humans.

Adult↗
PubMed2003

Alpha B-crystallin is not a dominant peripheral T-cell autoantigen in multiple sclerosis amongst Sardinians.

The heat shock protein alpha B-crystallin appears to be the dominantly recognized autoantigen in the early demyelinative process of multiple sclerosis (MS) in brain of patients. In Sardinia, MS is linked to human leucocyte antigen (HLA)-DR alleles that might influence the production of cytokines from peripheral lymphocytes. We tested the nature of peripheral anti-alpha B-crystallin-specific T-cell response in the context of predisposing HLA haplotypes both in MS patients and healthy controls. The alpha B-crystallin specific T-cell lines were generated by using the 'split-well' technique. The results indicate that the presence of short-term T-cell lines towards alpha B-crystallin is numerically comparable between the two groups and not restricted to MS-predisposing HLA-DR alleles. As for the T-cell characterization, CD4+ anti-alpha B-crystallin T cells secreting high levels of interferon-gamma are similarly identified in MS and healthy donors. In conclusion, the peripheral response towards the myelin antigen alpha B-crystallin is neither quantitatively nor qualitatively peculiar to MS, in contrast to the theoretical paradigm suggesting peripheral activation of myelin-reactive T cells to be the prerequisite for MS induction.

Alleles↗
PubMed2003

The role of laparoscopy in patients with suspected peritonitis: experience of a single institution.

PURPOSE: In this report, we retrospectively evaluate the effect of a laparoscopic approach in the diagnosis and treatment of acute abdominal pain in patients with suspected peritonitis. PATIENTS AND METHODS: We evaluated the clinical records of patients admitted to our institution between January 1995 and July 2001 with a diagnosis of acute abdomen and suspected peritonitis. RESULTS: Ninety four of 229 patients underwent diagnostic laparoscopy. In this series, 83 (88.3%) of the cases were successfully treated by emergent laparoscopy for an acute abdomen. Eleven (11.7%) required conversion to an open laparotomy procedure. Overall, the preoperative diagnosis was confirmed by laparoscopy in 67 (71.27%) of the cases. It was not confirmed in 27 (28.73%). Postoperative mortality was 4.25%. Morbidity was 8.5%. DISCUSSION: Data reported in the literature establish that laparoscopy offers adequate visualization of the entire abdomen and pelvic cavity in the diagnosis of an abdomen acute secondary to peritonitis. In this series, laparoscopy confirmed the diagnosis in 97.8% of the patients, and minimally invasive treatment was achieved in 88.3% of the cases. Female patients with gynecologic disease particularly benefitted from a laparoscopic approach, which permitted the correct evaluation of this condition and may have prevented unnecessary laparotomy. We believe that laparoscopy is an accurate modality for the diagnosis and treatment of patients with an acute abdomen and suspected peritonitis when the diagnosis cannot be clearly made by physical examination and noninvasive methods.

Abdomen, Acute↗
PubMed2002

Serum uric acid and multiple sclerosis.

Several studies indicate that patients with multiple sclerosis (MS) have low serum levels of the endogenous antioxidant uric acid (UA), although it has not been established whether UA is primarily deficient or secondarily reduced due to its peroxynitrite scavenging activity. We measured serum urate levels in 124 MS patients and 124 age- and sex-matched controls with other neurological diseases. In addition, we compared UA levels when MS patients were stratified according to disease activity (by means of clinical examination and MRI), duration, disability and course. MS patients had significantly lower serum urate levels than controls (p= 0.001). However, UA levels did not significantly correlate with disease activity, duration, disability or course. Our study favors the view that reduced UA in MS is a primary, constitutive loss of protection against oxidative agents, which deserves further pathogenetic elucidation aimed at future therapeutic strategies.

Adolescent↗
PubMed2002

Radiation-induced angiosarcoma of the breast: case report and self-criticism of therapeutic approach.

Angiosarcoma (AS) of the breast is a rare and highly aggressive vascular cancer. It presents as a primitive or radioinduced form. The case of a 46-year-old woman who underwent quadrantectomy of the breast plus axillary lymph node dissection and radiotherapy postoperatively (QUART) for ductal infiltrant carcinoma is reported in the following. Ten years later, the patient underwent mastectomy with immediate reconstruction, for local recurrence that was diagnosed as an AS of the breast at final pathological examination. She did not receive any adjuvant treatment due to local post-operative complications related to breast reconstruction. We criticize our therapeutic approach and we recommend more attention about local recurrence suggesting that tru-cut needle biopsy of local recurrence of the breast after QUART, should be the correct diagnostic approach.

Biopsy↗
PubMed2002

Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy.

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high- and low-risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world-wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population.

Humans↗
PubMed2001

Glatiramer acetate and IFN-beta act on dendritic cells in multiple sclerosis.

Glatiramer acetate (GA; Copolymer 1; Copaxone) and interferon-beta (IFN-beta) modulate the course of multiple sclerosis (MS), but probably by different mechanisms. GA, a mixture of synthetic peptides, is believed to act as an altered peptide ligand with inhibitory effects on autoreactive T cells and promoting Th2 cells. It is unknown whether GA affects dendritic cells (DCs), which, besides strong antigen presenting capacity, orchestrate Th1 and Th2 responses. IFN-beta inhibits IL-12 production by DCs over unknown mechanisms. This study was designed to investigate in vitro effects of GA and IFN-beta on the development and function of DCs from MS patients and healthy controls, and to explore their possible synergistic effects on DCs. DCs were generated from adherent blood mononuclear cells (MNCs). GA or IFN-beta or both, when added at initiation of DC cultures, rapidly promoted the development of adherent MNCs into floating, activated DCs as reflected by up-regulation of HLA-DR and CD86 expression. IFN-beta, but not GA, induced IL-3R expression on DCs. Compared to DCs from healthy controls, MS patients' DCs expressed higher levels of the myeloid DC marker CD1a and produced lower amounts of IL-10. GA reduced IL-12 production by DCs. IFN-beta also reduced IL-12, but increased IL-10 production by DCs from both MS patients and healthy controls. GA and IFN-beta synergistically suppressed CD1a and enhanced CD86 expression on MS DCs. These findings document novel mechanisms of action of GA and IFN-beta at the DC level in MS.

Adjuvants, Immunologic↗
PubMed2001

Immunogenetic heterogeneity of multiple sclerosis in Sardinia.

Multiple sclerosis (MS) predisposition is thought to be influenced by a complex, yet unclear interaction of genetic and environmental factors. Studying ethnically selected populations may reduce genetic and environmental heterogeneities and help clarify the underlying mechanisms of MS susceptibility. Sardinians kept a homogeneous genetic structure and have among the highest MS frequency rates worldwide. Interestingly, MS in Sardinia is linked to otherwise rare HLA alleles. In this light, recent findings from epidemiological and immunogenetic studies of Sardinian MS are presented. Results confirm that, likely due to significant genetic differences at a microgeographic level, even in this homogeneous population MS is immunogenetically heterogeneous and tends to preferentially cluster in some more archaic areas of the island.

Female↗
PubMed2001

[A new conservative approach in the treatment of postoperative digestive-tract fistulas. Mechanical closure by a balloon-catheter].

BACKGROUND: Digestive fistulas represent troublesome complication in patients operated in modern surgical wards where the improved surgical procedures and better intensive care enhance the surgeon to perform more aggressive approaches with a high surgical risk index. The management of a patient presenting a digestive-tract fistula is never easy, being its approach either conservative (TPN) or surgical. We applied an alternative surgical procedure consisting in a mechanical closure of the fistula using a balloon-catheter so as to improve outcome in those patients in whom medical tratment did not show satisfactory RESULTS. METHODS: We treated 7 patients presenting a postoperative fistula following several surgical procedures for neoplasms of the digestive system. These fistulas were closed using a Foley or Fogarthy balloon catheter preceeded by radiological and/or endoscopy controls. Once the catheter was placed, oral nutrition was started and some patients were discharged. A progressive deflation of the balloon was performed until complete removal of the catheter upon approx 10 days. RESULTS: We obtained a complete healing of the fistula in 6 patients, within 10 days since catheter placement. Only one patient required another operation. CONCLUSIONS: Our case-series may seem statistically not significant, but varied concerning location and type of fistulas. We observed an excellent outcome using this procedure which allows very short healing period thanks to an early oral nutrition uptake and a decrease in costs mainly due to a short hospital stay and a minor use of expensive drugs (TPN).

Aged↗
PubMed2001

Heart metastases from gastric sarcoma. A case report.

Cardiac involvement by metastatic gastric sarcoma is a rare event. We describe an unusual case of gastric sarcoma involving the heart in a 29-year-old man who presented with heart failure. The diagnosis was made at two-dimensional echocardiography. Heart metastases prolapsing into and obstructing the mitral valve orifice were located in the left atrium. In an attempt to excise the left atrial mass, the patient underwent heart surgery twice. The resections were non-curative. The patient died of refractory heart failure 9 months after the onset of symptoms. This case report is an example of a secondary intracavitary tumor that causes obstruction of the mitral valve orifice. Two-dimensional echocardiography has been confirmed as the examination of choice for the early diagnosis of cardiac tumors.

Adult↗
PubMed2000

Pharmacokinetics and tissue penetration of vancomycin in patients undergoing prosthetic mammary surgery.

Vancomycin concentrations in periprosthetic breast tissues were evaluated in 24 women undergoing reconstructive surgery after mastectomy for breast cancer. Patients were given a single prophylactic dose of vancomycin (1 g iv) 1-8 h before surgery, and mean capsular and pericapsular tissue concentrations were measured by HPLC. Vancomycin was not detectable in the majority of patients belonging to the 1-3 h post-dose groups, whereas in the 4-8 h post-dose groups, mean capsular and pericapsular concentrations were as follows: at 4 h, 4.0 mg/kg and 5.9 mg/kg; at 6 h, 4.1 mg/kg and 4. 8 mg/kg; at 8 h, 5.9 mg/kg and 11.1 mg/kg, respectively. Vancomycin tissue concentrations thus were equal to or exceeded the breakpoint of 4 mg/L in most samples collected 4-8 h after dosing. In conclusion, our data suggest that appropriate timing of vancomycin prophylaxis should be considered to allow the maintenance of adequate tissue concentrations throughout the surgical procedure.

Aged↗