Search PubMed⌕ Search

Biomedical subjects

M Cossu

Publications and source records attributed to M Cossu.

At least 19 recordsLinked to original sources
PubMed1999

Native human neocortex release-regulating dopamine D2 type autoreceptors are dopamine D2 subtype.

Dopamine (DA) autoreceptors expressed at DA nerve terminals regulate DA release. Considerable evidence has indicated that, in rodents, these autoreceptors belong to the D2 type of the DA receptor family, which, in turn, comprises the D2, D3 and D4 subtypes. We investigated here, for the first time, the subclassification of native human DA autoreceptors by studying the release of [3H]DA evoked by electrical stimulation in fresh human neocortical slices. The results have been compared with those obtained in three animal systems: rat neocortical and striatal slices and rat mesencephalic neuronal cultures. In human neocortical slices, the D2/D3 receptor agonist quinpirole (1 nM-10 microM) inhibited tritium release with a calculated EC50 of 17 nM and a maximal inhibition of approximately 75% reached at 1 microM. In the presence of the D2/D3 receptor antagonist (-)-sulpiride (0.1 and 1 microM), the concentration-response curve of quinpirole was shifted to the right, and the apparent pA2 mean value was 8.5 (8.14-8.77); on the other hand, the inhibitory effects of quinpirole were not affected by the D3 receptor-selective antagonist [7-N,N-dipropylamino-5,6,7, 8-tetrahydro-naphtho(2,3b) dihydro,2,3-furane] (S 14297) and the D4 receptor-selective antagonist 3-(4-[4-chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo [2,3-b]pyridine (L-745,870) (0.01-1 microM in each case). Superimposable results have been obtained when the release was elicited from rat striatal slices or dopamine mesencephalic neurons in culture, whereas quantitative differences emerged in the case of rat cortical slices. It is concluded that in human brain, as well as in rat brain, the release of DA in the terminal region of midbrain dopaminergic neurons is regulated through autoreceptors of the D2 subtype.

Adult↗
PubMed1998

Removal of tumours of the orbital apex via a postero-lateral orbitotomy.

BACKGROUND: The surgical management of pure apical tumours of the orbit may be problematic with traditional approaches. A postero-lateral approach, specifically designed for apical growths, provides a more favourable angle of vision through a relatively small bone opening. METHODS: A series of 103 consecutive cases of intraorbital tumours, operated on in a community-based institution, was retrospectively reviewed. Out of this series, 8 patients, harbouring lesions located in the posterior intraconal space, underwent a postero-lateral orbitotomy. This approach, through a small opening on the orbital and temporal portions of the greater wing of the sphenoid, with the lesser sphenoidal wing, the orbital plate of the frontal bone, the lateral rim of the orbit being maintained intact, allowed adequate exposure of the orbital apex and successful extirpation of the tumours. In four patients the histological examination disclosed a cavernoma; the other patients had, respectively, a dermoid cyst, a lymphoma, a hemangiopericytoma and a metastatic melanoma. RESULTS: No recurrences were observed in a follow-up period ranging from 1 to 7 years postoperatively (the patient with melanoma died 16 months after operation for systemic complications of her illness). One patient showed transient weakness of lateral rectus muscle due to surgical manipulation, which subsided in few months. CONCLUSIONS: The postero-lateral orbitotomy represents a reliable alternative to other traditional surgical approaches when dealing with tumours of the orbital apex, providing excellent exposure of this region with a low rate of operative morbidity.

Adult↗
PubMed1998

Immunocytochemical investigation of the subcellular distribution of some secretory products in human salivary glands.

The subcellular distribution of epidermal growth factor (EGF) and of Lewis antigens was demonstrated by means of a post-embedding immunogold cytochemical method in human parotid and submandibular gland. Acinar secretory granules were reactive for EGF and difucosylated Lewis antigens, cell surfaces of acini and striated ducts reacted only for difucosylated antigens; a great number of cytoplasmic vesicles in acinar and ductal cells were reactive for all Lewis antigens and EGF. These results suggest that substances which enter saliva are released not only through granule exocytosis by acinar cells, but also via other routes: the vesicular system revealed in both acinar and ductal cells could play a fundamental role in driving some products both towards the lumen and towards basolateral cell surfaces and intercellular spaces.

Epidermal Growth Factor↗
PubMed1997

Prolactin decrease and shift to a normal-like isoform profile during treatment with quinagolide in a patient affected by an invasive prolactinoma.

Prolactin (PRL) circulates as multiple molecular weight variants: glycosylated phosphorylated, deamidated and sulphated forms. The profiles of the forms, as determined by isoelectrofocusing (IEF), differ in physiological and pathological conditions. The case of a 72-year-old woman affected by an invasive prolactinoma is described. The patient had undergone surgical treatment followed by radiotherapy at the age of 71 years. Bromocriptine therapy followed (up to 10 mg/die), but the PRL levels were still extremely high (over 13,000 micrograms/l as determined by IRMA, after dilution). We therefore treated the patient with quinagolide, at increasing dosages, from 150 micrograms/die on day 0 to 600 micrograms/die on day 220. This treatment progressively lowered PRL to 23.2 micrograms/l. In addition to a decrease in PRL levels, a progressive change in the IEF profile was also noted. Indeed, on day 0, the PRL isoforms were very acidic and during treatment they progressively shifted toward a more basic range. For purpose of comparison PRL profiles were also determined in 8 women with pathological hyperprolactinaemia (group A, aged 16-50 years, PRL levels: 25.1-170.4 micrograms/l), in 6 normal women (group B, aged 25-29 years, PRL levels: 3.4-7.9 micrograms/l) and in 5 normal women during a TRH test (group C, aged 17-52 years, PRL levels: 2.7-10.3 micrograms/l). The profiles observed in group A had a single major peak at isoelectric point (pI) 6.5, while the group B and C profiles were more heterogeneous displaying multiple minor peaks, the majority of the molecules being in a more basic range (pI 6.9 for group B and pI 7.5 for group C). During treatment, the profiles of our subject at first resembled those of group A; subsequently, when the PRL levels had normalised, the profile resembled those noted in group B. Altered (immature?, more glycosilated?, less bioactive?) PRL molecules could be secreted by the tumour. These data show that quinagolide successfully reduced PRL levels, while inducing secretion of forms more similar to those found in women affected by pathological hyperprolactinaemia or in normal women.

Adolescent↗
PubMed1997

Activation of brain nitric oxide synthase in depolarized human temporal cortex slices: differential role of voltage-sensitive calcium channels.

1. Nitric oxide (NO) synthase activity was studied in slices of human temporal cortex samples obtained in neurosurgery by measuring the conversion of L-[3H]-arginine to L-[3H]-citrulline. 2. Elevation of extracellular K+ to 20, 35 or 60 mM concentration-dependently augmented L-[3H]-citrulline production. The response to 35 mM KCl was abolished by N(G)-nitro-L-arginine (100 microM) demonstrating NO synthase specific conversion of L-arginine to L-citrulline. Increasing extracellular MgCl2 concentration up to 10 mM also prevented the K+ (35 mM)-induced NO synthase activation, suggesting the absolute requirement of external calcium ions for enzyme activity. 3. However, the effect of high K+ (35 mM) on citrulline synthesis was insensitive to the antagonists of ionotropic and metabotropic glutamate receptors dizocilpine (MK-801), 6-nitro-7-sulphamoylbenzo(f)-quinoxaline-2-3-dione (NBQX) or L-2-amino-3-phosphonopropionic acid (L-AP3) as well as to the nicotinic receptor antagonist, mecamylamine. 4. The 35 mM K+ response was insensitive to omega-conotoxin GVIA (1 microM) and nifedipine (100 microM), but could be prevented in part by omega-agatoxin IVA (0.1 and 1 microM). The inhibition caused by 0.1 microM omega-agatoxin IVA (approximately 30%) was enhanced by adding omega-conotoxin GVIA (1 microM) or nifedipine (100 microM). Further inhibition (up to above 70%) could be observed when the three Ca2+ channel blockers were added together. Similarly, synthetic FTX 3.3 arginine polyamine (sFTX) prevented (50% at 100 microM) the K+-evoked NO synthase activation. This effect of sFTX was further enhanced (up to 70%) by adding 1 microM omega-conotoxin GVIA plus 100 microM nifedipine. No further inhibition could be observed upon addition of MK-801 or/and NBQX. 5. It was concluded that elevation of extracellular [K+] causes NO synthase activation by external Ca2+ entering cells mainly through channels of the P/Q-type. Other Ca2+ channels (L- and N-type) appear to contribute when P/Q-channels are blocked.

Alanine↗
PubMed1997

On-line predilution hemofiltration versus ultrapure high-flux hemodialysis: a multicenter prospective study in 23 patients. Sardinian Collaborative Study Group of On-Line Hemofiltration.

The aims of the present prospective multicenter study were to assess the clinical tolerance and well being, the correlation between nPCr and Kt/V and the pretreatment beta 2-microglobulin level in patients sequentially treated with high-flux dialysis with ultrapure bicarbonate hemodialysis (HD; phase 1) and predilution hemofiltration (HF) with on-line prepared bicarbonate substitution fluid (phase II). The same monitor (Gambro AK 100 ULTRA) and membrane (polyamide) were used. Twenty-three patients, all in a stable clinical condition, entered the study. The treatment was targeted to an equilibrated Kt/V (eqKt/V) of 1.4 for HD and 1.0 for HF. No mortality or relevant morbidity were observed. The number of hypotensive episodes was 1.78 +/- 2.8 per patient and month during HD vs. 1.17 +/- 3.1 during HF (p = 0.003) and the number of the hypertensive episodes 1.28 +/- 2.8 during HD vs. 0.42 +/- 0.8 during HF (p = 0.04). Incidences of arrhythmia, muscular cramps and headache were significantly less frequent during HF. Interdialytic cramps, arthralgia and fatigue were also significantly less frequent during the HF period. The average beta 2-microglobulin level was 27.1 +/- 14.7 mg/dl at the start of the study, 22.9 +/- 4.9 mg/dl at the beginning of phase II and 22.4 +/- 4 mg/dl at the end of phase II (p = 0.01 compared to the start). A significant linear correlation between the normalized protein catabolic rate and eqKt/V was obtained faster during HD than during HF (45 vs. 120 days) indicating that HF affects the nutritional status with mechanisms different from HD. The present study is in agreement with the hypothesis that HF gives and adequate nutritional status with improved clinical stability and well being at a lower Kt/V compared to HD. Both therapies were efficient in controlling the pretreatment beta 2-microglobulin level.

Aged↗
PubMed1997

A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. Italian Multicentre Study Group for Renal Transplantation (SIMTRe).

Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97% in monotherapy, 91% in double therapy, and 96% in triple therapy; the graft survival including death was 84%, 77%, and 88%, respectively; and the pure graft survival was 87%, 85% and 91%, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P < 0.01). Of the patients on monotherapy, 52% were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68%, and the pure graft survival was 72%, in comparison with 93% and 94%, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, wherease those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomization had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P < 0.0001), osteomuscular (P < 0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P < 0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early post-transplant period.

Adolescent↗
PubMed1997

Ultrastructural localization of blood group antigens in human exocrine pancreas by immunogold labelling.

The cytochemical distribution of ABH and Lewis antigens was investigated in human pancreas by means of a post-embedding immunogold staining method which permitted antigens associated with secretory materials to be distinguished from those bound to cell surfaces. H and Le-b antigens were found in secretory granules of acinar and interlobular duct cells. In the form of surface-associated antigens, H and Le-b were found in acini and interlobular ducts, Le-a in intralobular ducts. In ductal cells, the same antigens detected in cell surfaces were also found in small cytoplasmic vesicles. It is suggested that by the emptying of these vesicles blood group antigens may be released both into the lumen and into the interstitial spaces.

ABO Blood-Group System↗
PubMed1996

Ultrastructural localization of blood group antigens in human salivary glands.

The subcellular distribution of several blood group antigens was studied in human major and minor salivary glands by means of a postembedding immunogold staining method. In each gland, antigens were detected as secretory products and as cell surface components. A, B, H and Lewis (a,b,x,y) antigens were found in mucous cells depending on the ABO and secretor status; reactivities were confined to the secretory granules. In serous and ductal cells, both the secretory granules and cell membranes were reactive, but only for H, Le-b and Le-y irrespective of the ABO and secretor status.

ABO Blood-Group System↗
PubMed1996

Low-dosage ibopamine treatment in progressive renal failure: a long-term multicentre trial.

A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. The patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.

Adolescent↗
PubMed1995

Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome.

Mutations in the COL4A5 gene, which encodes the a5 chain of type IV collagen, are found in a large fraction of patients with X-linked Alport syndrome. The recently discovered COL4A6, tightly linked and highly homologous to COL4A5, represents a second candidate gene for Alport syndrome. We analyzed 177 Italian Alport syndrome families by Southern blotting using cDNA probes from both COL4A5 and COL4A6. Nine unrelated families, accounting for 5% of the cases, were found to have a rearrangement in COL4A5. No rearrangements were found in COL4A6, with the exception of a deletion encompassing the 5' ends of both COL4A5 and COL4A6 genes in a patient with Alport syndrome and leiomyomatosis. COL4A5 rearrangements were all intragenic and included 1 duplication and 7 deletions. Polymerase chain reaction (PCR) analysis was carried out to characterize deletion and duplication boundaries and to predict the resulting protein abnormality. The two smallest deletions involved a single exon (exons 17 and 40, respectively), while the largest ones spanned exons 1 to 36. The clinical phenotype of patients in whom a rearrangement in COL4A5 was detected was severe, with progression to end-stage renal failure in juvenile age and hypoacusis occurring in most cases. These data have some important implications in the diagnosis of patients with Alport syndrome.

Adolescent↗
PubMed1995

Postero-lateral microsurgical approach to orbital tumors.

A modification of the lateral orbitotomy is reported for the microsurgical approach to tumors located in the posterior intraconal space. The orbital apex is entered through a small bone opening on the orbital and temporal portions of the greater wing of the sphenoid, with the lesser sphenoidal wing, the orbital plate of the frontal bone, and the lateral orbital rim being left intact. This surgical technique was employed in 8 cases of pure apical tumors, out of a consecutive series of 103 orbital growths. It proved to be reliable with regard to either adequate exposure and radical excision of the lesions or low rate of operative morbility.

Adult↗
PubMed1995

The "VGF" protein in rat adenohypophysis: sex differences and changes during the estrous cycle and after gonadectomy.

Gene expression and cell localization of the neuroendocrine protein VGF were studied in the rat anterior pituitary. In females, four antisera against nonoverlapping regions of VGF immunostained a small number of lactotropes and many gonadotropes. In the latter cells, VGF immunoreactivity was localized to a subpopulation of secretory granules. Distinct changes were seen after estrus, with a significant increase in VGF messenger RNA (whole pituitary), whereas VGF immunostaining was strikingly reduced in gonadotropes and somewhat more abundant in lactotropes. In male rats, gene expression was low, and immunoreactivity was restricted to a few lactotropes. After castration or ovariectomy, VGF messenger RNA was high, and VGF immunoreactivity was abundant in gonadotropes. Selective localization and cyclic modulation suggest involvement of the VGF gene product(s) in pituitary gonadotrope and/or lactotrope function.

Animals↗
PubMed1994

Cortical blood flow recorded during early or delayed surgery for ruptured intracranial aneurysms.

Forty-three patients were operated on for ruptured intracranial aneurysms during a 12-month-period. Intraoperative evaluation of cortical blood flow by means of a thermal diffusion probe was performed in 23 out of the 41 patients who were operated on for aneurysms of the anterior circulation. The autoregulation index was determined at the time of raising the systemic blood pressure after clipping of the aneurysm(s). No statistically significant difference was found between the averages of the autoregulation indexes calculated in the subgroups of patients submitted respectively to early or delayed surgery. There was no correlation of both cortical blood flow and autoregulation with either age of the patients, or preoperative neurological grade. On the contrary, the autoregulation index showed a statistically significant correlation with outcome.

Adult↗