Biomedical subjects

M Rossi

Publications and source records attributed to M Rossi.

At least 37 records · Page 2Linked to original sources

PubMed2006

Long-term outcomes in liver transplant patients with hepatic C infection receiving tacrolimus or cyclosporine.

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.

Adult↗

PubMed2006

The intensity level of physical exercise and the bone metabolism response.

This study investigated the short-term effects of the intensity level of physical exercise on bone metabolism and related hormones. The responses of calciotropic hormones and bone biochemical markers were evaluated in seven male cyclists (mean age 24.4 years, range 20-39) during two 50-min cycling tests performed 15% below (-VT) and 15% above (+VT) the ventilatory threshold. In each test, venous blood samples were drawn at rest, at the 30th and 50th min of exercise, and after 15 min of recovery. For both intensity levels, no significant variation in calcium, 25-hydroxyvitamin D, 1.25-dihydroxyvitamin D, or cortisol level was observed. Intact parathyroid hormone (iPTH) level increased significantly after the last minute of the test (41%, p < 0.05) and peaked during the recovery (80%, p < 0.05) only in response to exercise performed at +VT. Serum phosphorus concentration rose during both tests, while albumin levels increased only at +VT. Concerning bone cell activity, osteocalcin, and type I-C telopeptide breakdown products transiently increased only in response to exercise performed at +VT (11% and 16.8%, respectively; p < 0.05). Bone alkaline phosphatase increased similarly for both intensity levels after 30 min (12%, p < 0.05) and 50 min (12% for -VT vs. 14% for +VT, p < 0.05). All markers of bone turnover returned to initial values during the recovery. In conclusion, a no-impact but intense and sustained exercise performed at +VT transiently stimulated bone turnover and iPTH secretion, suggesting the existence of a bone stimulation threshold. In addition to the well known effect of mechanical constraints, both the duration and intensity of exercise may induce changes in bone turnover.

Adult↗

PubMed2006

Spectral analysis of skin blood flowmotion before and after exercise in healthy trained and in sedentary subjects.

Cutaneous blood flowmotion (CBF) can contribute to a reduction in the resistance in skin microvascular networks. The increase of CBF during exercise can improve the capacity of skin microvascular networks to transport and eliminate heat. In order to verify if the physical training could increase the skin blood flowmotion during exercise, we performed spectral analysis of cutaneous forearm laser Doppler signal, before and after acute maximal exercise in 15 healthy trained subjects (TS) and in 15 control sedentary subjects (SS). Within the total spectrum of 0.009 - 2.3 Hz, five frequency intervals of CBF were analysed: 0.009 - 0.02 Hz (endothelial activity), 0.02 - 0.06 Hz (sympathetic activity), 0.06 - 0.2 Hz (vascular myogenic activity), 0.2 - 0.6 Hz (respiratory activity), and 0.6 - 2.3 Hz (heart activity). In basal conditions, no difference between TS and SS was observed in the cutaneous blood perfusion (CBP), expressed in conventional perfusion units (PU), and in the mean value of CBF total spectrum power density (PD), measured in PU/Hz, while the absolute PD of the endothelial and myogenic CBF components was significantly higher (p < 0.05) in TS (0.69 +/- 0.62 PU/Hz and 0.47 +/- 0.43 PU/Hz, respectively) than in SS (0.29 +/- 0.16 PU/Hz and 0.23 +/- 0.16 PU/Hz, respectively). In both TS and SS, acute exercise induced a significant increase of CBP mean value (30.91 +/- 20.28 PU, p < 0.0005 and 16.45 +/- 7.02 PU, p < 0.0005; respectively) and of CBF total spectrum PD (6.65 +/- 4.13 Hz/PU, p < 0.001 and 4.17 +/- 1.86 Hz/PU, p < 0.05; respectively), with a significant difference of these two parameters between the two groups (p < 0.05). After exercise, CBF components regarding endothelial and myogenic activities maintained a higher PD mean value in TS in respect to SS (1.69 +/- 1.34 PU/Hz and 1.59 +/- 0.93 versus 0.91 +/- 0.44 and 0.98 +/- 0.48 PU/Hz respectively, p < 0.05). These findings suggest that physical training is associated with the increase of CBF and particularly on its endothelial and myogenic components in response to exercise. This can favour a greater reduction of resistance in skin microvascular networks during exercise and consequently an increase of its capacity to transport and eliminate heat.

Adult↗

PubMed2006

Comparison of diagnostic methods in the diagnosis of dermatomycoses and onychomycoses.

Direct microscopic examination of potassium hydroxide (KOH)-prepared specimens is the simplest, cheapest method used for the diagnosis of mycotic infections of the skin. However, KOH preparations have been reported to have 5-15% of false-negative results, possibly because of the low visibility of scant, scattered fungal material of the nail scrapings and because the detection of fungal elements depends on the skill of the observer [Arch Dermatol133 (1997) 1317; Clin Microbiol Rev8 (1995) 240]. We compared two different KOH-based staining methods in order to obtain reliable results in shorter time than expected for cultures. A total of 124 patients with suspect diagnosis of dermatomycosis or onychomycosis were enrolled. Two scrapings from the same lesion of each patient were stained with KOH-Chlorazole and KOH-Acridine Orange (AO), respectively; cultural examination of the same specimen was considered as diagnostic gold standard. The two methods showed neither significantly different sensitivity nor specificity; however, for onychomycoses, we observed a slightly higher sensitivity for KOH-Chlorazole and a higher specificity for KOH-AO. We suggest the use of both techniques in order to improve detection of fungal infection, especially for onychomycoses.

Acridine Orange↗

PubMed2006

Clinical evaluation of fibrin glue in the prevention of anastomotic leak and internal hernia after laparoscopic gastric bypass: preliminary results of a prospective, randomized multicenter trial.

BACKGROUND: Gastro-jejunal anastomotic leak and internal hernia can be life-threatening complications of laparoscopic Roux-en-Y gastric bypass (LRYGBP), ranging from 0.1-4.3% and from 0.8-4.5% respectively. The safety and efficacy of a fibrin glue (Tissucol) was assessed when placed around the anastomoses and over the mesenteric openings for prevention of anastomotic leaks and internal hernias after LRYGBP. METHODS: A prospective, randomized, multicenter, clinical trial commenced in January 2004. Patients with BMI 40-59 kg/m2, aged 21-60 years, undergoing LRYGBP, were randomized into: 1) study group (fibrin glue applied on the gastro-jejunal and jejuno-jejunal anastomoses and the mesenteric openings); 2) control group (no fibrin glue, but suture of the mesenteric openings). 322 patients, 161 for each arm, will be enrolled for an estimated period of 24 months. Sex, age, operative time, time to postoperative oral diet and hospital stay, early and late complications rates are evaluated. An interim evaluation was conducted after 15 months. RESULTS: To April 2005, 204 patients were randomized: 111 in the control group (mean age 39.0+/-11.6 years, BMI 46.4 +/- 8.2) and 93 in the fibrin glue group (mean age 42.9+/-11.7 years, BMI 46.9+/-6.4). There was no mortality or conversion in both groups; no differences in operative time and postoperative hospital stay were recorded. Time to postoperative oral diet was shorter for the fibrin glue group (P = 0.0044). Neither leaks nor internal hernias have occurred in the fibrin glue group. The incidence of leaks (2 cases, 1.8%) and the overall reoperation rate were higher in the control group (P=0.0165). CONCLUSION: The preliminary results suggest that Tissucol application has no adverse effects, is not time-consuming, and may be effective in preventing leaks and internal hernias in morbidly obese patients undergoing LRYGBP.

Adult↗

PubMed2006

A novel metronomic chemotherapy regimen of weekly platinum and daily oral etoposide in high-risk non-small cell lung cancer patients.

The aim of this pilot phase II trial was to investigate the toxicity and anti-tumour activity of a novel metronomic regimen of weekly cisplatin (CDDP) and oral etoposide (VP16) in high-risk patients with advanced NSCLC. The study enrolled 31 high-risk patients (27 men and 4 women aged 16-82 years; mean, 64.3) with NSCLC (18 stage IIIB and 13 stage IV) and an ECOG performance status of < or = 3, all of whom received weekly CDDP 30 mg/m2 iv on days 1, 8, 14 and 28 of each cycle and oral daily etoposide 50 mg/m2 on 21 of the 28 days. The most frequent adverse events were grade III leukopenia and anemia; nevertheless, three patients died of pulmonary embolism after 2, 3 and 6 weeks of treatment. The objective response (OR) rate was 45.2% (2 complete and 12 partial), and the disease control rate was 58.1% (14 ORs and 4 disease stabilisations). The mean time to progression and survival were respectively nine months (95% CI, 6.3-15.8 months) and thirteen months (95% CI, 9.1-20.5 months). Pharmacological analysis showed that this metronomic regimen allows a much greater median monthly area under the curve of CDDP and VP16 than conventional treatment schedules. Our findings also suggest that this treatment schedule may affect tumour growth and neoangiogenesis by changing peripheral blood vascular-endothelial growth factor levels. These preliminary results indicate that our metronomic regimen is well tolerated and active, even in patients with a very poor prognosis.

Administration, Oral↗

PubMed2005

Conversion of a CHO cell culture process from perfusion to fed-batch technology without altering product quality.

During the development of a new drug product, it is a common strategy to develop a first-generation process with the aim to rapidly produce material for pre-clinical and early stage clinical trials. At a later stage of the development, a second-generation process is then introduced with the aim to supply late-stage clinical trials as well as market needs. This work was aimed at comparing the performance of two different CHO cell culture processes (perfusion and fed-batch) used for the production of a therapeutically active recombinant glycoprotein at industrial pilot-scale. The first-generation process was based on the Fibra-Cel packed-bed perfusion technology. It appeared during the development of the candidate drug that high therapeutic doses were required (>100mg per dose), and that future market demand would exceed 100 kg per year. This exceeded by far the production capacity of the first-generation process, and triggered a change of technology from a packed-bed perfusion process with limited scale-up capabilities to a fed-batch process with scale-up potential to typical bioreactor sizes of 15m(3) or more. The productivity per bioreactor unit volume (in product m(-3)year(-1)) of the fed-batch process was about 70% of the level reached with the first-generation perfusion process. However, since the packed-bed perfusion system was limited in scale (0.6m(3) maximum) compared to the volumes reached in suspension cultures (15m(3)), the fed-batch was selected as second-generation process. In fact, the overall process performance (in product year(-1)) was about 18-fold higher for the fed-batch compared to the perfusion mode. Data from perfusion and fed-batch harvests samples indicated that comparable product quality (relative abundance of monomers dimers and aggregates; N-glycan sialylation level; isoforms distribution) was obtained in both processes. To further confirm this observation, purification to homogeneity of the harvest material from both processes, followed by a complementary set of studies (e.g. full physico-chemical characterization, assessment of in vitro and in vivo bioactivity, comparative pharmacokinetics and pharmacodynamics studies in relevant species, etc.) would be required. Finally, this illustrates the need to fix the production process early during the development of a new drug product in order to minimize process conversion efforts and to shorten product development time lines.

Animals↗

PubMed2005

Skin blood flowmotion response to insulin iontophoresis in normal subjects.

In order to explore the mechanisms directly involved in the insulin vasodilatory activity, we studied skin blood flowmotion by means of spectral analysis of the skin forearm laser Doppler (LD) signal registered before and after iontophoresis of insulin in saline (I.S.) (0.1 ml Humulin R 100 IU/ml diluted 1/10 in 0.9% saline) or pure saline (P.S.) (0.1 ml of 0.9% saline) in twenty normal subjects. Skin LD blood perfusion was also measured in conventional perfusion unit (PU; 1 PU=10 mV). Using a Fast Fourier transform algorithm, power density (PD) of the total flowmotion spectrum, from 0.009 to 1.6 Hz, was measured in PU/Hz. Power density of five skin flowmotion frequency intervals (F.I.) within 0.009-0.02 Hz, 0.02-0.06 Hz, 0.06-0.2 Hz, 0.2-0.6 Hz and 0.6-1.6 Hz (referred to endothelial, sympathetic, myogenic, respiratory and heart activity, respectively) was also measured in PU/Hz. The mean skin LD perfusion increment (expressed as percent change from baseline) was significantly higher after I.S. than after P.S. (P<0.001, ANOVA for repeated measures). Skin flowmotion total spectrum mean PD value significantly increased following iontophoresis of both P.S. (from 1.06+/-0.62 to 1.86+/-0.94 PU/Hz, P<0.005) and I.S. (from 1.07+/-0.92 to 2.39+/-1.73 PU/Hz P<0.00005), however, the mean PD increment was significantly higher after I.S. than after P.S. (1.27+/-0.98 PU/Hz versus 0.69+/-0.67 PU/Hz, P<0.05). Only the flowmotion component referred to myogenic activity showed a percent PD increase from baseline significantly higher in response to I.S. than to P.S. iontophoresis (114.5+/-21.8% versus 58.8+/-17.9%, respectively, P<0.05). These findings show that insulin has a vasodilatory activity on skin microvascular district. The higher increase of total blood flowmotion PD and particularly of the component related to the myogenic activity in response to insulin iontophoresis suggests that the cutaneous vasodilatory activity of insulin is, in part, related to an important action of this hormone on skin microvascular smooth muscle.

Adult↗

PubMed2005

Age, menopausal status and homocysteine levels in women around menopause.

OBJECTIVE: To obtain data on the relation between age, menopause and homocysteine levels in women around menopause, we collected data for a sample of about 500 women attending a menopause clinic in Milan, Italy. STUDY DESIGN: Eligible for the study were all women aged 45-75 years, never HRT users consecutively observed for the first time at the Menopause Center of the 1st Obstetric Gynecological Clinic of the University of Milan. Fasting blood samples for total homocysteine plasma levels were collected during the visit. Of the 490 study subjects, 107 were pre-menopausal and 383 post-menopausal. RESULTS: In the total series, the mean homocysteine level was 8.3 micromol/L (S.D. 3.7, range 3.2-48.8). The values increased from 7.8 micromol/L in women aged <47 years to 9.0 micromol/L in those aged >59. Among pre-menopausal women the mean homocysteine level was 7.7 micromol/L compared to 8.3 micromol/L in post-menopausal women: this difference disappeared on the adjusted values. In post-menopausal women only, no clear relationship emerged between years since menopause and homocysteine levels. CONCLUSION: In our population, age, and not menopausal status, was the main determinant of homocysteine levels in women around menopause.

Adult↗

PubMed2005

Small intestinal enteropathy in non-obese diabetic mice fed a diet containing wheat.

AIMS/HYPOTHESIS: A deranged mucosal immune response and dietary factors may play an important role in the pathogenesis of type 1 diabetes. The aims of our work were to look for the presence of small intestinal enteropathy in non-obese diabetic (NOD) mice in relation to the presence of wheat proteins in the diet, and to assess their role in the risk of developing diabetes. METHODS: Female NOD mice were fed a standard or gluten-free diet or a gluten-free diet with the addition of wheat proteins (MGFD). Small intestine architecture, intraepithelial CD3(+) infiltration, epithelial expression of H2-IA, mRNA for IFN-gamma and IL-4 were assessed. RESULTS: NOD mice fed a standard diet showed reduced villous height, increased intraepithelial infiltration by CD3(+) cells and enhanced expression of H2-IA and IFN-gamma mRNA when compared with mice on the gluten-free diet. The cumulative diabetes incidence at 43 weeks of age was 65% in the latter and 97% in the former (p<0.01). Mice on MGFD also showed increased epithelial infiltration and a higher incidence of diabetes. CONCLUSIONS/INTERPRETATION: Mice fed a wheat-containing diet showed a higher incidence of diabetes, signs of small intestinal enteropathy and higher mucosal levels of proinflammatory cytokines.

Animal Feed↗

PubMed2005

Changes in osteoprotegerin/RANKL system, bone mineral density, and bone biochemicals markers in patients with recent spinal cord injury.

This study analyzed the temporal and regional variations in bone loss and explored bone cell activities via biochemical markers during an extended follow-up in patients with spinal cord injury (SCI). In parallel, the possible role of the osteoprotegerin (OPG)/RANKL system in disuse osteoporosis was investigated. Seven male patients with acute and complete SCI (31.3 +/- 9.5 years) and 12 able-bodied (AB) men (26.9 +/- 4.2 years) participated in the study. Measurements were performed 16, 24, 36, 48, and 71 weeks after injury. At week 16, marked calcium homeostasis disturbance and a concomitant increase in bone resorption markers were observed, reflecting an intense bone degradation process. Resorption activity decreased continuously with time. Contrasting with the great rise in the resorption markers, the bone formation markers showed little variation. During the period of investigation, a loss in bone mineral density (BMD) was demonstrated for the total body (-4.3%), pelvis (-15.7%) and lower limbs (-15.2%), whereas BMD did not change at the lumbar spine, upper limbs, or skull. At all stages, SCI patients had lower serum RANKL levels and higher serum OPG levels than did AB controls, but no significant variation with time was observed for either cytokine. These findings suggest that bone resorption persisted long after SCI and specifically affected BMD at sublesional sites. The marked modification of serum OPG/RANKL levels in SCI patients suggests that this system is affected, in disuse osteoporosis. However, the precise biologic role of the OPG/RANKL system in the bone tissue of SCI patients has yet to be determined.

Absorptiometry, Photon↗

PubMed2005

Identification of 14 novel mutations in DHCR7 causing the Smith-Lemli-Opitz syndrome and delineation of the DHCR7 mutational spectra in Spain and Italy.

The Smith-Lemli-Opitz syndrome (SLOS) is a phenotypically variable metabolic malformation and mental retardation syndrome for which more than 80 mutations in the DHCR7 disease-causing gene have been described. The DHCR7 mutational spectra differ significantly in different areas of Europe, and several common putative founder mutations account for a substantial fraction of all mutations in some ethnic groups. Here we have analysed 47 SLOS patients and describe 14 newly identified mutations in 18 SLOS patients of Ashkenazi Jewish, Austrian, British, German, Italian, Irish, Polish, Portuguese, and Spanish origins. Half of the new mutations are in the transmembrane domains of the protein. In addition, there were two null mutations, one mutation in the 4th cytoplasmic loop, two mutations in the first and last codons, and three mutations in other regions such as the second cytoplasmic loop and the first endoplasmic loop. The analysis included 20 Spanish and 12 Italian SLOS patients and revealed very different mutation spectra in these patients compared to previously described patients from Czechoslovakia, Germany, Poland, and the UK and implicated p.Thr93Met on the J haplotype as the most frequent Mediterranean founder mutation.

Adolescent↗

PubMed2005

[The Ahmed glaucoma valve. Medium term results].

BACKGROUND: In complicated glaucoma, when classical filtrating surgery would be ineffective, aqueous shunts may be used. Complications due to hypotonia are reduced by valved systems, such as the Ahmed glaucoma valve (AGV). METHOD: In a retrospective case control study, 28 patients with complicated glaucoma were included. In addition to the clinical examination, we examined the size and function of the filtering area using ultrasound. RESULTS: The medium term follow-up was 25+/-16 months, the preoperative intraocular pressure (IOP) 35.5 mmHg+/-10.3 while 17 eyes were pseudophakic and nine aphakic. In the first weeks after AGV implantation, the mean IOP was 6.3+/-2.5 mmHg. In nine eyes, the pressure was less than 5 mmHg and five developed a temporary choroidal detachment. At the last visit, IOP was regulated in 22 eyes (82.1%). There was no correlation between IOP regulation and the size of the filtering bleb or the increase in the latter by digital pressure. CONCLUSION: In the management of complicated glaucoma, if there is a high risk of failure due to conjunctival scarring, AGV implantation can be used as a save procedure with a success rate comparable to other glaucoma implants.

Adolescent↗

PubMed2005

Vitamin D status in patients affected by Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol biosynthesis characterized by developmental delay and multiple malformations. Some of the patients have skin photosensitivity and therefore tend to avoid direct exposure to sunlight.SLOS patients typically have low concentrations of cholesterol and abnormally high concentrations of its precursor 7-dehydrocholesterol (7-DHC) in biological fluids and tissues. 7-DHC is also a precursor in the cutaneous synthesis of vitamin D. Sunlight exposure plays a major role in this pathway and reactions transforming 7-DHC into vitamin D and then into 25-hydroxyvitamin D are known not to be specifically regulated. The aim of this study was to evaluate vitamin D status in SLOS patients. We measured 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations and markers of calcium metabolism in five SLOS patients. Despite abnormally high concentrations of 7-DHC, circulating concentrations of vitamin D metabolites were not significantly different from appropriate controls matched for sex, age and season of blood collection. The analysis of historical serum samples stored in our laboratory from the same cases plus 10 other SLOS patients further supported these findings. Our data suggest that SLOS patients have a peculiar vitamin D metabolism that protects them from vitamin D intoxication. This appears to be due in most cases to decreased transformation of 7-DHC into 25-hydroxyvitamin D, perhaps depending on reduced sunlight exposure as a consequence of photosensitivity. Possible alternative mechanisms are discussed.

Adolescent↗

PubMed2005

Generalised wavelet analysis of cutaneous flowmotion during post-occlusive reactive hyperaemia in patients with peripheral arterial obstructive disease.

The purpose of the present study was to assess whether the generalised wavelet analysis (GWA) of the leg cutaneous laser Doppler (LD) flowmotion waves recorded during baseline (Bsl) and after skin post-occlusive hyperaemia (POH) can provide information on the leg cutaneous microcirculatory adaptation to stage II peripheral arterial obstructive disease (PAOD). With this aim the flowmotion was characterised in 20 healthy subjects (HS) and 20 stage II PAOD patients by GWA of LDF tracings during Bsl and POH test. The vascular endothelial and smooth muscle function was also evaluated exploring the arm skin vasodilatory response to iontophoretically delivered acetylcholine (Ach) and sodium nitroprusside (SNP) using LD. During Bsl there was no significant difference in leg skin perfusion between HS and PAOD patients (7.3+/-5.6 vs. 5.8+/-2.9 AU, respectively). PAOD patients revealed higher peak powers in the frequency interval of 0.007-0.02 Hz (120+/-82 vs. 85+/-62 AU(2)/Hz; P < 0.05), 0.02-0.06 Hz (116+/-128 vs. 63+/-48 AU(2)/Hz, respectively; P < 0.05) and 0.06-0.2 Hz (39+/-49 vs. 14+/-10 AU(2)/Hz; P < 0.05). These flowmotion frequencies are related to vascular endothelium activity, sympathetic activity and vessel wall myogenic activity, respectively. During POH the mean peak power of the flowmotion waves increased significantly (P < 0.05) in HS respect to Bsl with the only exception of the 0.02-0.06 Hz band. In the PAOD patients, compared to Bsl the amplitude of the flowmotion waves did not significantly change during POH. In addition, the PAOD patients presented an increased time from release to peak-flux (18.25+/-15.5 vs. 2.16+/-1.28 s, respectively; P < 0.05), an increased time from release to recovery of the basal perfusion (90.26+/-39.14 vs. 26.55+/-14.05 s, respectively; P < 0.05) and a lower slope of the POH curve (10+/-15 vs. 54+/-17 degrees , respectively; P < 0.05), compared with HS. The cutaneous arm vasodilatory response to Ach and to SNP was reduced in PAOD patients in comparison with HS (P < 0.001). In conclusion, our findings showed an increased amplitude of the frequency interval 0.007-0.02, 0.02-0.06 and 0.06-0.2 Hz during Bsl in PAOD patients which did not change during the POH test. All data suggest that in stage II PAOD patients the leg skin perfusion is not impaired during Bsl because of a compensatory mechanism related to increased endothelial, myogenic and sympathetic activities. However during reactive hyperaemia these mechanisms appear to be exhausted in accordance with the reduced vasoreactivity to Ach and SNP.

Acetylcholine↗

PubMed2005

Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation.

BACKGROUND: The alpha isotype of actin expressed by hepatic stellate cells reflects their activation to myofibroblast-like cell and has been directly related to experimental liver fibrogenesis, and indirectly to human fibrosis in chronic liver disease. AIMS: To evaluate the changes in distribution and percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the correlation with the degree of the fibrosis in cirrhotic livers, as well as in patients with recurrent HCV chronic hepatitis after liver transplantation. METHODS: Human liver biopsies were divided in four groups: (1) normal livers obtained from cadaveric liver donors (n=35), (2) cirrhosis post-HBV hepatitis (n=11), (3) cirrhosis post-HCV hepatitis (n=10), and (4) post-transplant recurrent HCV chronic hepatitis (n=13). Samples were stained with anti-alpha-smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively evaluated. Liver fibrosis was assessed from specimens stained with Masson's trichrome and quantified by computer image analysis. RESULTS: The percentage of alpha-smooth muscle actin-positive hepatic stellate cells was significantly higher in the HBV cirrhosis, HCV cirrhosis and post-transplant HCV recurrent hepatitis groups (36.1+/-15.2, 23.8+/-19.7 and 27.8+/-16.4%, respectively) compared to the liver donor group (2.9+/-4.0%). The alpha-smooth muscle actin-positive hepatic stellate cells to fibrous tissue ratio were significantly higher in the post-transplant recurrent HCV hepatitis group (2.36+/-1.12) compared to both the donor livers and the HCV cirrhosis groups (0.74+/-1.09 and 1.03+/-0.91, respectively). The alpha-smooth muscle actin-positive hepatic stellate cell percentage and fibrosis correlated positively in the post-transplant recurrent HCV hepatitis group and negatively in the HCV cirrhosis group. No difference in the immunohistochemical and morphometrical variables was found between the HCV cirrhosis and HBV cirrhosis groups. CONCLUSIONS: These results indirectly confirm that, in vivo, alpha-smooth muscle actin expression is a reliable marker of hepatic stellate cells activation which precedes fibrous tissue deposition even in the setting of recurrent HCV chronic hepatitis after liver transplantation, and it could be useful to identify the earliest stages of hepatic fibrosis and monitoring the efficacy of the therapy. In the presence of advanced cirrhosis other factors, rather than alpha-smooth muscle actin-positive hepatic stellate cells, may sustain fibrosis deposition.

Actins↗

PubMed2005

[Late manifestations of Lyme borreliosis].

Month to years after an early local or an early disseminated infection some patients develop late manifestations of lyme borreliosis. Most frequently involved organs are the skin (acrodermatitis chronica atrophicans), joints (Lyme arthritis) and the nervous system. A history of exposure and the clinical picture may suggest Lyme borreliosis, however, confirmation by serological and other tests is needed. Antibiotic treatment during early stages normally prevents development of late manifestations. Late stages persist if not treated. By adequate antimicrobial therapy they are treatable and usually show a good prognosis. Recovery may be delayed, some patients suffer from residual difficulties. Currently there is no accepted case definition for a "post lyme syndrome". The term "chronic Lyme disease" suggests (a never proven) persistent infection by viable bacteria. Repeated and prolonged antibiotic treatments are not indicated.

Acrodermatitis↗

PubMed2005

Effect of chronic aerobic exercise on cutaneous microcirculatory flow response to insulin iontophoresis and to ischemia in elderly males.

The aim of this study was to assess whether chronic aerobic exercise can favourably influence the vascular activity of insulin in elderly subjects. We measured in arbitrary units (A. U.) the cutaneous blood flow basally and in response to iontophoresis of insulin, by the means of a Laser Doppler flowmeter, on the right arm of 10 elderly athletes (10 males, aged 65 +/- 6 years) and of 10 sex- and age-matched sedentary subjects. The cutaneous blood flow response to ischemia was also explored in the right leg of the same subjects by means of the same instrument. No significant differences in cutaneous arm and leg blood flow were observed basally between athletes and sedentary subjects (7.25 +/- 2.65 A. U. versus 6.35 +/- 4.04 A. U. and 9.74 +/- 5.11 A. U. versus 9.41 +/- 6.40 A. U., respectively). Cathodal iontophoresis (six poulses of 0.1 mA each for 20 s, with 40-s interval between stimulations) of regular insulin (0.1 ml Humulin R 100 IU/ml diluted 1/10 with 0.9 % saline) induced a significant increase of cutaneous blood flow in both groups (p < 0.01 in athletes, p < 0.01 in sedentary subjects). However the maximal cutaneous blood flow response to insulin was higher in athletes than in sedentary subjects (24.69 +/- 13.34 A. U. versus 14.33 +/- 7.73 A. U., respectively, p < 0.05) as well as the curve of the net blood flux response to insulin iontophoresis (% change from baseline in response to insulin minus % change from baseline in response to saline iontophoresis) (p < 0.001 ANOVA for repeated measures). After ischemia there was a significant increase of leg cutaneous blood flow in both groups (p < 0.001 in athletes and in sedentary subjects) with higher blood flow response in athletes than in sedentary subjects (38.18 +/- 17.08 A. U. versus 26.01 +/- 6.39 A. U., respectively, p < 0.05). The time reached from the release of ischemia to peak-flow was significantly longer in sedentary subjects than in athletes (43.5 +/- 28.5 s versus 20.0 +/- 9.3 s, p < 0.05, respectively). These results suggest that chronic aerobic exercise increases insulin vasodilatory activity and improves endothelial function in elderly subjects.

Aged↗