PubMed Health⌕ Search

Biomedical subjects

G Grassi

Publications and source records attributed to G Grassi.

At least 19 recordsLinked to original sources
PubMed2006

Rovibrational photoionization dynamics of methyl and its isotopomers studied by high-resolution photoionization and photoelectron spectroscopy.

High-resolution photoionization and pulsed-field-ionization zero-kinetic-energy photoelectron spectra of CH(3), CH(2)D, CHD(2), and CD(3) have been recorded in the vicinity of the first adiabatic ionization threshold following single-photon excitation from the ground neutral state using a narrow-bandwidth vacuum-ultraviolet laser. The radicals were produced from the precursor molecules methyl-bromide, methyl-iodide, dimethyl-thioether, acetone, and nitromethane by 193 nm excimer photolysis in a quartz capillary and were subsequently cooled to a rotational temperature T(rot) approximately equal to 30 K in a supersonic expansion. Nitromethane was identified as a particularly suitable photolytic precursor of methyl for studies by photoionization and threshold photoelectron spectroscopy. Thanks to the cold rotational temperature reached in the supersonic expansion, the rotational structure of the threshold ionization spectra could be resolved, and the photoionization dynamics investigated. Rydberg series converging on excited rotational levels of CH(3) (+) could be observed in the range of principal quantum number n=30-50, and both rotational autoionization and predissociation were identified as decay processes in the threshold region. The observed photoionization transitions can be understood in the realm of an orbital model for direct ionization but the intensity distributions can only be fully accounted for if the rotational channel interactions mediated by the quadrupole of the cation are considered. Improved values of the adiabatic ionization thresholds were derived for all isotopomers [CH(3): 79 356.2(15) cm(-1), CH(2)D: 79 338.8(15) cm(-1), CHD(2): 79 319.1(15) cm(-1), and CD(3): 79 296.4(15) cm(-1)].

Journal Article↗
PubMed2006

Rheological properties of aqueous Pluronic-alginate systems containing liposomes.

Rheological and erosion studies regarding a liposome-containing polymeric blend that is propaedeutic to its use in paving techniques in tubular organs, such as blood vessels, are reported. Attention is focused on an aqueous polymeric blend composed of Pluronic (PF127) and alginate (Protanal LF 10/60) because both polymers, when dissolved in water at a sufficiently high concentration, are subjected to different structural mechanisms, which are driven by temperature increase and addition of bivalent cations, respectively, and both result in marked viscoelastic and plastic properties. After proving the compatibility between PF127 and alginate, we show that the structural transition temperature of the blend, T(ST), can be properly modulated. In particular, we found that T(ST) for an aqueous solution of pure Pluronic 20% w/w is about 21 degrees C and that even slight reductions in polymer concentration result in considerable T(ST) decrease. The addition of salts or alginate (provided as Na-alginate) provokes a substantial decrease of T(ST) and thus the alginate concentration in the blend should not exceed 1% w/w. In addition, liposomes slow down the structural transition but do not substantially affect the rheological properties of the system in the final state at higher temperatures, thus showing that they can be added to the polymeric blend without significant effects. Finally, erosion tests show that after contact with a source of bivalent cations, the polymeric blend containing PF127 and alginate shows an erosion resistance neatly improved with respect to the simple structured Pluronic system having the same polymer concentration. As a whole, all these results constitute the basis for future potential applications of the considered polymeric blend in tubular organs such as blood vessels.

Alginates↗
PubMed2005

Comparison between recombinant baculo- and adenoviral-vectors as transfer system in cardiovascular cells.

The development of effective gene-therapeutic applications for cardiovascular disorders is in part limited by the lack of appropriate delivery systems. In an attempt to overcome this deficiency, we investigated the ability of baculoviral vectors to transduce human cardiovascular cells, for which data are missing in literature. Additionally, baculovirus ability to transduce target cells was compared to that of an adenoviral vector, a well characterized and widely used viral vector. Transduction experiments, performed using baculo/adenoviral vectors expressing the enhanced green fluorescence protein, revealed that, under the experimental condition considered, baculoviruses but not adenoviruses efficiently transduce human coronary smooth muscle cells (hCSMC); an opposite behavior was noticed for human coronary endothelial cells (hCEC). Thus, baculoviral vectors are potentially indicated as transfer system in the treatment of coronary restenosis, where growth inhibitory genes should reach hCSMC but not hCEC. When used to transduce human cardiomyocytes and fibroblasts, both vectors behaved similarly. Finally, studies on cellular DNA replication revealed a more prolonged and pronounced negative effect on cells transduced by adenoviral compared to baculoviral vectors. Our data indicate that baculoviruses represent an attractive alternative to adenoviruses as transfer vectors in cardiovascular cells and that baculovirus have the potential to be used as gene transfer system in cardiovascular diseases such as restenosis.

Adenoviridae↗
PubMed2005

Mortality within the first 10 years of the disease in type 2 diabetic patients.

BACKGROUND AND AIMS: An excess of long-term mortality in type 2 diabetes is mainly due to cardiac diseases, predicted by diabetes-related conditions; less is known about early death from clinical diagnosis. The aim of this study was to evaluate pattern and predictors of mortality after a 4.5 year follow-up in a cohort of type 2 diabetic patients, according to diabetes duration. METHODS AND RESULTS: A mortality follow-up was carried out in 1200 patients with < or = 5 years diabetes duration and 2692 patients with >5 (median 2 and 15) years diabetes duration in 1995. Four-year survival was 92.0% and 83.7%, respectively; most deaths are due to cardiovascular diseases (36% and 41%, respectively). The duration of diabetes is no longer a significant predictor of death after adjustments for age, HbA1c and chronic complications (which are all significantly higher in patients who have had diabetes for longer time). In a Cox proportional hazard model, best predictors of death are nephropathy, insulin therapy and pre-existent co-morbidity in both groups. Nephropathy is significantly associated with cardiovascular deaths in the younger cohort. CONCLUSION: Clinical nephropathy is a significant predictor of early and late mortality from clinical diagnosis, above all cardiovascular deaths, indicating that an aggressive approach should be adopted for prevention or treatment of renal impairment right from the clinical onset of diabetes.

Age Factors↗
PubMed2005

Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome.

AIMS/HYPOTHESIS: Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction. METHODS: In 43 healthy control subjects (age 48.2+/-1.0 years, mean+/-SEM) and in 48 untreated age-matched subjects with metabolic syndrome (National Cholesterol Education Program's Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure (Finapres), heart rate (ECG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation (vasoactive drug infusion technique). RESULTS: Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment (HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects (61.1+/-2.6 vs 43.8+/-2.8 bursts/100 heartbeats, p<0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference (r=0.46, p<0.001) and HOMA index (r=0.49, p<0.001) and was inversely related to baroreflex sensitivity (r=-0.44, p<0.001), which was impaired in the metabolic syndrome. CONCLUSIONS/INTERPRETATION: These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality (1) is also detectable when blood pressure is normal and (2) depends on insulin resistance as well as on reflex alterations.

Adult↗
PubMed2005

Hammerhead ribozymes targeted against cyclin E and E2F1 cooperate to down-regulate coronary smooth muscle cell proliferation.

BACKGROUND: Anti-proliferative drugs released from endo-vascular stents have substantially contributed to reduce in-stent restenosis rates in coronary arteries bearing single primary lesions by down-regulating coronary smooth muscle cell (CSMC) growth. However, the considerably lower drug efficacy shown in treatment of more complex coronary lesions suggests that alternative anti-proliferative approaches can be beneficial. Thus, we explored the use of hammerhead ribozymes as tools to knock down cyclin E and E2F1, two potent activators of cell proliferation which cooperate to promote the G1 to S phase transition. METHODS: Two ribozymes, one directed against cyclin E and the other against E2F1 mRNAs, were delivered by liposomes to cultured human CSMCs. The influences on cell proliferation were measured evaluating BrdU incorporation into newly synthesised DNA. The effects on cell cycle phase distribution were determined by BrdU and 7-aminoactinomycin D incorporation into DNA. RESULTS: Both ribozymes exhibited a sequence-specific and dose-dependent reduction in BrdU incorporation, which, at a concentration of 280 nM, persisted up to 4 days after transfection of CSMCs. A combined administration of the two ribozymes (210+210 nM) resulted in a more pronounced decrease in BrdU incorporation compared to the administration of an equimolar amount (420 nM) of each of them. Finally, both ribozymes induced a significant (P<0.05) reduction in S phase cells with a concomitant increase of G1/G0 and G2-M phase cells, compared to controls. CONCLUSIONS: The ribozymes selected represent potent tools to prevent CSMC proliferation, especially when administered together, and thus are ideal candidates for in vivo application.

Cell Cycle↗
PubMed2005

Hypertension, antihypertensive treatment and stroke prevention.

Despite intensive research efforts, few effective treatments are available once stroke has occurred. Thus, stroke prevention should be a primary focus for all health care provides. The purpose of this article is to review the pathophysiological relevance of hypertension as a leading cause of stroke. This will be followed by an analysis of the evidence that blood pressure lowering with different antihypertensive drugs reduces the risk. Finally recent data suggest that the angiotensin II (ATII)-receptor antagonist losartan may offer advantages beyond blood pressure lowering, including attenuation of the central aortic reflected pressure wave, molecule-specific properties and neural protective influences on brain ATII type 2 receptors.

Angiotensin II Type 2 Receptor Blockers↗
PubMed2005

Off pump treatment of aortic arch rupture: extraanatomic hybrid reconstruction.

We present a possible alternative technique to treat the rupture of aortic arch aneurysms on beating heart without necessity of cardiopulmonary bypass (CPB), hypothermic circulatory arrest and cerebral protection, using a bifurcated vascular prosthesis to revascularize the subclavian and carotid arteries and an endovascular prosthesis to repair the aortic arch. We report the case of a 78-year-old woman successfully treated with this technique. Since in our institution endovascular prostheses are placed by the interventional cardiologists, the operation was done in cooperation between cardiac surgeons and interventional cardiologists.

Aged↗
PubMed2005

Renal damage in patients with Type 2 diabetes: a strong predictor of mortality.

AIMS: (i) To compare mortality rates in a cohort of Type 2 diabetic patients with those of the general population; (ii) to assess the prognostic role of pre-existing chronic conditions; (iii) to evaluate the impact of different severity of renal damage on mortality. METHODS: All 3892 patients with Type 2 diabetes attending our Diabetic Clinic during 1995 and alive on 1 January 1996 were identified and followed for 4.5 years. Information on vital status (100% complete) and causes of death (98.5% complete) for 599 deceased subjects was derived from death certificates. RESULTS: In comparison with the general population, standardized mortality ratios (x 100) were: 125 (95% confidence interval 104-148) in patients aged < 75 and 85 (75-95) in patients > or = 75 years. Cardiovascular diseases and diabetes were responsible for most of the excess deaths. In a Cox-proportional hazard model, renal damage was a powerful predictor of death (hazard ratio = 2.39; 95% confidence intervals = 2.00-2.85). The severity of renal damage was associated with increasing hazard ratios for death from all-cause mortality and from specific causes (especially coronary artery disease, other cardiovascular causes and diabetes) after multiple adjustments. Other significant predictors of death were: greater age, glycated haemoglobin, smoking, lower body mass index, pre-existing coronary and peripheral artery disease and known co-morbidity (cirrhosis and cancer). CONCLUSIONS: Renal damage of any severity is significantly associated with subsequent mortality from all causes and from cardiovascular diseases. These associations are not confounded by pre-existing co-morbidity or coronary diseases.

Age Factors↗
PubMed2005

Body movements on the men's competition mushroom: a three dimensional analysis of circular swings.

OBJECTIVES: To develop a method for the three dimensional analysis of body movements and body positions during the performance of circular swings on the competition mushroom, an apparatus used by young gymnasts for pommel horse training. METHODS: Five experienced male gymnasts, all of national level, performed three series of 10 circular swings on the competition mushroom. An optoelectronic instrument was used for the detection of the three dimensional movement of 13 body landmarks. From landmark trajectories, several technical measurements were obtained: diameters of ideal circles of ankles, hips, shoulders; deviation of the ankle diameters from circularity and from the horizontal plane; angle between the shoulder, hip, and ankle. The values were used for a quantitative assessment of performance of the five gymnasts. RESULTS: During the exercise, each ankle should follow a nearly horizontal circular path (deviation from circularity ranged from 3.6% to 6%, deviation from horizontality was 9.4-19.7%), there should be an angle of about 180 degrees at the hips (actual values 146-153 degrees ), and the shoulders should move as little as possible, and only in the lateral plane, without major anteroposterior movements (shoulder movement was 27-31% of ankle movement, hip movement was 16-20%). CONCLUSIONS: The method could help coaches and gymnasts to determine which parts of the body are not repeating a selected movement with sufficient accuracy and to quantify improvements made after a specific training programme.

Adolescent↗
PubMed2004

Preemptive pancreas-kidney transplantation: multidisciplinary follow-up starts too late.

BACKGROUND: Preemptive pancreas-kidney transplantation is increasingly considered at early stages of nephropathy in type 1 diabetics. A multidisciplinary approach is required, but referral to the nephrologist is often delayed. OBJECTIVE: To analyze the referral pattern of type 1 diabetics to a dedicated nephrology unit and to test the prevalence of indications for pancreas-kidney transplantation in this population, according to early preemptive criteria (creatinine >/= 2 mg/dL and/or nephrotic syndrome). PATIENTS AND METHODS: The setting of study was the first Italian Nephrology Outpatient Unit dedicated to diabetics during 1991 to 2002. The main biochemical and clinical parameters were analyzed at referral. RESULTS: Ninety type 1 diabetics underwent at least one nephrological visit during the period; 85 had data at referral. The referral pattern was stable: 1991 to June 1996 [22 men, 24 women of median age 36 (18 to 65) years; diabetological follow-up 18.0 (3 to 37) years] and July 1996 to March 2002 [26 men, 18 women median age 40 (18 to 65); diabetological follow-up 21.5 (11 to 36) years]. The main biochemical data at referral were superimposable: serum creatinine: 1.2 (0.6 to 3.2) versus 1.3 (0.6 to 7) mg/dL; proteinuria: 0.9 (0 to 11) versus 1.01 (0.05 to 12.3) g/24 hours. Diabetes follow-up was greater in July 1996 to March 2002 [18 (3 to 37) versus 21.5 (11 to 36) years] suggesting an effect of improvements in diabetic care. At referral 76.6% were macroproteinuric 85.6% had signs of end-organ damage other than nephropathy; and 30.6% had indications for pancreas-kidney grafting (creatinine >/= 2 mg/dL: n = 6 cases; nephrotic syndrome: n = 10; or both n = 10). CONCLUSIONS: One new frontier of transplantation is the need for early multidisciplinary evaluation of type 1 diabetic patients.

Adolescent↗
PubMed2004

Complete reversal of the nephrotic syndrome after preemptive pancreas-kidney transplantation: a case report.

BACKGROUND: Nephrotic syndrome due to diabetic nephropathy is presently considered an indication for pancreas-kidney transplantation even in the absence of severe renal failure. Reversal of the nephrotic syndrome has been reported, but the mechanisms of this effect are unclear. AIM: To describe the renal morphofunctional pattern and the pattern of proteinuria before and after preemptive pancreas-kidney transplantation. METHODS: Methods included quantitative and qualitative assessment of proteinuria as well as renal ultrasound and scintiscan. CASE REPORT: A 42-year-old woman with type 1 diabetes since age 24 had widespread end-organ damage. Renal biopsy (2001) showed a mainly nodular pattern of diabetic nephropathy. Following referral (1999), her serum creatinine ranged from 1.6 to 2.2 mg/dL, with nephrotic range proteinuria (glomerular nonselective, tubular complete). Renal scintiscan revealed bilateral, symmetric, well-perfused kidneys. The functional data before pancreas-kidney graft (February 2003) were: serum creatinine 1.6 mg/dL, creatinine clearance 58 mL/min, serum albumin 2.6 g/dL, proteinuria 9.1 g/d. At hospital discharge (March 2003), the creatinine was 1.2 mg/dL, the creatinine clearance 97 mL/min, the proteinuria 0.676 g/d. Two months later, the creatinine was 1.2 mg/dL and proteinuria 0.421 g/d. A renal scintiscan demonstrated the functional prevalence of the grafted kidney (77% of total function), with vital, almost completely excluded native kidneys (functional contribution, 11.5% each). Proteinuria, ranging from 0.3 to 0.6 g/d, showed a physiological pattern. CONCLUSIONS: Functional exclusion of the native kidneys by renal scintiscan gives morphological support to reversal of the nephrotic syndrome.

Adult↗
PubMed2004

Isolated systolic hypertension in a cohort of type 2 diabetic patients.

BACKGROUND AND AIMS: Previous studies of the adverse effects of isolated and borderline isolated systolic hypertension excluded or under-represented type 2 diabetic patients. The aim of this study was to evaluate the prevalence and role of isolated and borderline isolated systolic hypertension in a cohort of 3892 type 2 diabetic patients. METHODS AND RESULTS: The hypertensive patients were classified as treated (n= 1806; 46.4%), untreated diastolic hypertension (n=407; 10.4%), untreated isolated systolic hypertension (n=166; 4.3%) and untreated borderline isolated systolic hypertension (n=625; 16%). A Cox proportional hazard model including several confounders showed that the patients with untreated isolated systolic hypertension were at significantly higher risk of hospital admissions due to cerebrovascular diseases than the normotensive and untreated diastolic hypertensive patients (HR=2.05; 95% CI: 1.2-3.4 and HR=1.97; 95%CI: 1.1-3.5, respectively). In the same model, borderline isolated systolic hypertension significantly correlated with admissions for cerebrovascular diseases in comparison with normotensive patients (HR=1.73; 95% CI: 1.2-2.6). CONCLUSIONS: This is the first report concerning the prevalence of isolated and borderline isolated systolic hypertension in a large cohort of type 2 diabetic patients. The results are in line with population-based estimates. Our data show that isolated systolic hypertension is an independent predictor of hospital admissions due to cerebrovascular diseases.

Age Distribution↗
PubMed2004

Pre-pubertal onset of type 1 diabetes and appearance of retinopathy.

OBJECTIVES: It was suggested that the years of diabetes preceding puberty may not contribute to the development of retinopathy but evidence for this is conflicting. To verify the influence of pre-pubertal diabetes, we compared the correlations between prevalence of retinopathy and diabetes duration in patients who developed type 1 diabetes before and after puberty. METHODS: Six hundred and twenty-eight patients with diabetes onset at age< or =29, on insulin treatment and aged< or =60 at the time of screening for retinopathy were considered retrospectively. Pre-pubertal age was defined as 0-12 in males and 0-11 in females. Two hundred patients had developed diabetes before puberty and 428 after puberty. Screening was by ophthalmoscopy + 35 mm photography or digital photography. RESULTS: Prevalence of retinopathy was lower among patients with pre-pubertal onset and diabetes durations 10-14 and 15-19 years (p=0.006 and p=0.003, respectively) but prevalence rates became similar after 20 yrs duration. CONCLUSION: That retinopathy is infrequent and mild during childhood, is probably due to the short duration of diabetes rather than a specific protective effect of pre-puberty. After 20 years' duration, however, the prevalence of retinopathy is no longer influenced by age at onset, suggesting that, in the longer term, pre-pubertal years do contribute to the onset of retinopathy.

Adolescent↗
PubMed2004

A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic-based cohort of patients with diabetes onset over 50 years.

AIMS: To assess if a clinically orientated approach improves screening for latent autoimmune diabetes in adults (LADA) in patients developing diabetes over age 50. METHODS: From a clinic-based cohort of 3327 patients with Type 2 DM diagnosed over age 50 we recruited those with at least one feature suggestive of insulin deficiency: (i) fasting blood glucose > or = 15 mmol/l and/or HbA(1c) > or = 10% in spite of adequate compliance to diet and treatment; (ii) decreasing body weight > or = 10% in the previous 3 months in spite of constant diet; (iii) BMI < 25 mg/kg(2). A control group of 240 patients not presenting any of the previous criteria was randomly selected from the out-patient clinic. RESULTS: We identified 220 (6.6%) patients, of whom 70 were positive for glutamic acid decarboxylase antibodies (GADA) and/or islet cell antibodies (ICA), giving a prevalence of LADA of 31.8% (95% CI 25.7-38.4). In contrast, no patient randomly selected from the remaining cohort had marker positivities. With respect to patients negative for both ICA and GADA, those who were positive had lower C-peptide values (0.53 +/- 0.51 vs. 0.88 +/- 0.42 nmol/l, P < 0.001); the lowest levels were found in patients in whom both antibodies were positive. In linear regression analysis, variables independently associated with fasting C-peptide were GADA (beta = -0.25, P < 0.001), ICA (beta = -0.15, P = 0.04), BMI (beta = 0.03, P < 0.001) and duration of diabetes (beta = -0.02, P < 0.001). CONCLUSION: This study shows that: (i) a clinically orientated approach increases the efficiency of a screening programme for LADA, so that one in three screened patients are classified correctly; (ii) ICA and GADA positivity were negatively associated with residual beta-cell function, independent of BMI and duration of the disease; (iii) positivity for both ICA and GADA identifies patients with the lowest residual beta-cell function.

Age of Onset↗
PubMed2004

Therapeutic potential of hammerhead ribozymes in the treatment of hyper-proliferative diseases.

The limited efficacy of current therapeutic approaches for a number of socially relevant human diseases such as cancer and cardiovascular pathologies, has required the exploration of alternative and more effective therapeutic strategies. In the last two decades, nucleic acid based drugs have emerged as an attractive and novel alternative with great therapeutic potential. Among these molecules, hammerhead ribozymes were the first to be extensively studied and predicted to be of potential practical utility. Hammerhead ribozymes are catalytic RNA molecules capable of inducing the site-specific cleavage of a phosphodiester bond within an RNA molecule. Thus, they can be used to reduce the intracellular level of a specific mRNA coding for a protein which affects cellular metabolism or environment, causing disease. As hammerhead ribozymes can be engineered to reduce the level of virtually any mRNA, they have a very broad applicability. Among the several pathological conditions amenable for a hammerhead ribozyme based therapeutic approach, we focused our attention on pathologies sustained by a dis-regulated and excessive cellular proliferation, being sure to properly demonstrate their usefulness. Trying to be as objective as possible in regard to the feasibility of hammerhead ribozyme employment as therapeutics, a technical section, describing some of the unresolved problems in this field, has been also included. Although some aspects of hammerhead ribozymes as therapeutics can and should be optimized, the encouraging results displayed so far fully justifies further efforts, economic and scientific, to bring them closer to the clinical practice.

Animals↗
PubMed2003

Inhibitors of DNA methylation and histone deacetylation activate cytomegalovirus promoter-controlled reporter gene expression in human glioblastoma cell line U87.

The expression of many cellular genes is modulated by DNA methylation and histone acetylation. These processes can influence malignant cell transformation and are also responsible for the silencing of DNA constructs introduced into mammalian cells for therapeutic or research purposes. As a better understanding of these biological processes may contribute to the development of novel cancer treatments and to study the complex mechanisms regulating gene silencing, we established a cellular system suitable to dissect the mechanisms regulating DNA methylation and histone acetylation. For this purpose, we stably transfected the neuroblastoma cell line U87 with a cytomegalovirus promoter-driven reporter gene construct whose expression was analyzed following treatment with the DNA methylation inhibitor 5'-aza-2'-deoxycytidine or histone deacetylation inhibitor trichostatin A. Both substances reactivated the silenced cytomegalovirus promoter, but with different reaction kinetics. Furthermore, whereas the kinetics of reactivation by trichostatin A did not substantially change over the time range considered (5 days), reactivation induced by 5'-aza-2'-deoxycytidine showed profound differences between day 1 and longer time points. We showed that this effect is related to the down-regulation of DNA replication by 5'-aza-2'-deoxycytidine. Finally, we have shown that the simultaneous administration of trichostatin A and 5'-aza-2'-deoxycytidine results in reactivation of the CMV promoter according to a cooperative, not synergistic or additive, mechanism. In conclusion, our cellular system should represent a powerful tool to investigate the complex mechanisms regulating gene silencing and to identify new anticancer drugs.

Animals↗
PubMed2003

Diabetic retinopathy.

UNLABELLED: Blindness is one of the most feared complications of diabetes but also one of the most preventable. Diabetic retinopathy (DR) in the way of proliferative retinopathy (PDR) and macular oedema (ME) is the commonest cause of new cases of legal blindness in Europe as in North America in the age group 30 to 70-74 years. DR is due to microangiopathy affecting the retinal precapillary arterioles, capillaries, and venules. Detection of the earliest signs of DR is an essential requirement of diabetics care leading to early preventive and treatment strategies which can arrest progression of this serious consequence of diabetes. Glycemic control and stricter control of hypertension have a clear effect on the development of the microvascular complications of diabetes like DR, while treatment options of severe non proliferative and proliferative forms of DR are limited to laser photocoagulation and vitrectomy. Photocoagulation has proven efficacy in slowing down the progression of DR and vitrectomy can prevent vision loss in case of advanced DR. Older and newer pathogenesis-based approaches to medical treatment are currently under evaluation by randomized controlled clinical studies still with inconclusive RESULTS: A review of these studies is proposed.

Angiotensin-Converting Enzyme Inhibitors↗