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Biomedical subjects

L Martins

Publications and source records attributed to L Martins.

At least 19 recordsLinked to original sources

Cyclosporine versus tacrolimus in kidney transplantation: are there differences in nephrotoxicity?

Cyclosporine and tacrolimus, two calcineurin inhibitors, show different side effects and toxicities. The data concerning their nephrotoxicity are few and conflicting. A retrospective study was performed in 2 groups of renal transplant recipients treated with cyclosporine or tacrolimus to evaluate graft function and side effects. All patients had completed at least 6 months of follow-up before inclusion in the study. Group I included 10 patients who were converted from cyclosporine to tacrolimus, due to cosmetic problems or due to chronic graft dysfunction with creatinine values <3 mg/dL. After conversion, there was a significant reduction in creatinine values (from 2.43 +/- 1.21 to 1.86 +/- 0.72 mg/dL; P =.023) and an improvement in creatinine clearance (from 47.5 +/- 19.2 to 56.1 +/- 18.9 mL/min; P =.047). The lipid profile did not change, but there was a trend to better blood pressure control with less antihypertensive drugs. Group II compared 2 subgroups of patients receiving kidneys from the same donor, one treated with cyclosporine and the other with tacrolimus. Tacrolimus patients showed better renal function; namely, creatinine was 1.15 +/- 0.27 versus 1.44 +/- 0.33 mg/dL (P =.029) and creatinine clearance was 87.7 +/- 27.1 versus 60.3 +/- 25.9 mL/min (P =.043). Lipid and blood pressure values were not different between the 2 subgroups, but tacrolimus patients tended to need a lower number of antihypertensive medications. The incidence of de novo diabetes mellitus was approximately 20% among patients using tacrolimus. We concluded that tacrolimus may be less nephrotoxic than cyclosporine. Tacrolimus patients showed better graft function and easier blood pressure control, but a high incidence of posttransplantation diabetes mellitus.

Blood Pressure↗

Chromosome aberrations and cell inactivation induced in mammalian cells by ultrasoft X-rays: correlation with the core ionizations in DNA.

PURPOSE: To study the frequency of chromosome aberrations induced by soft X-rays. To see if the core ionization of DNA atoms is involved in this end-point as much as it appears to be in cell killing. MATERIALS AND METHODS: V79 hamster cells were irradiated by synchrotron radiation photons iso-attenuated in the cell (250, 350, 810eV). The morphological chromosome aberrations detected in the first post-irradiation cell division (dicentrics and centric rings) were studied by Giemsa staining. RESULTS: The chromosome aberrations at 350eV were, respectively, 2.6 +/- 0.8 and 2.1 +/- 0.8 times more numerous than at 250 and 810eV for the same average dose absorbed by the nucleus. These relative effectivenesses are comparable with the ones already measured for cell killing. Moreover, they roughly vary such as the relative numbers of core ionizations (including in the phosphorus L-shell) produced in DNA and its bound water (water being involved only at 810eV through the oxygen atoms). In particular, they reproduce the characteristic twofold enhancement at 350eV, above the carbon K threshold. CONCLUSIONS: Correlations suggest that the core ionization process is likely a common and essential mechanism initiating both chromosome aberration and cell killing end-points at these photon energies.

Animals↗

Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines.

Smad proteins have been shown tomediate the signal transduction pathway downstream of the transforming growth factor beta (TGFbeta). TGFbeta induces the phosphorylation of Smad2 and Smad3 which associate with Smad4 and translocate to the nucleus where they regulate gene transcription; besides these stimulatory Smads, the inhibitory Smads, Smad6 and Smad7, oppose signaling by blocking receptors and interrupting the phosphorylation of Smads2/3. The loss of TGFbeta-sensitivity, caused by inactivation of components of TGFbeta signaling, as Smad4, underlies a wide variety of human disorders, including cancer. In addition, the overexpression of the inhibitory Smad7, which prevents the phosphorylation of Smad2/3 and consequently inhibits TGFbeta signaling pathways, was observed in some diseases. In the present study we investigated the expression of Smad4 and Smad7 in thyroid cell lines (NPA papillary carcinoma, WRO follicular carcinoma and ARO anaplastic carcinoma) by RT-PCR and immunocytochemistry. Our results show that Smad4 was expressed in all thyroid cell lines and controls analyzed, differently from other classes of tumors where Smad4 expression was deleted. On the other hand, Smad7 was overexpressed in ARO anaplastic cell line, the most malignant follicular thyroid carcinoma. Our data suggest that the abrogation of the TGFbeta response by Smad7 overexpression may be a mechanism for the tumor aggressiveness observed in undifferentiated thyroid tumors.

Adenocarcinoma, Follicular↗

Biological effects induced by K photo-ionisation in and near constituent atoms of DNA.

In order to assess the lethal efficiency and other biological effects of inner shell ionisations of constituent atoms of DNA ('K' events), experiments were developed at the LURE synchrotron facility using ultrasoft X rays as a probe of K events. The lethal efficiency of ultrasoft X rays above the carbon K threshold was especially investigated using V79 cells and compared with their efficiency to induce double strand breaks in dry plasmid-DNA. A correlation between the K event efficiencies for these processes is shown. Beams at 340 eV were found to be twice as efficient at killing cells than were beams at 250 eV. In addition, a rough two-fold increase of the relative biological effectiveness for dicentric + ring induction has also been observed between 250 and 340 eV radiations.

Animals↗

Lupus nephritis: a retrospective review of 78 cases from a single center.

UNLABELLED: Lupus nephritis (LN) is a frequent and serious manifestation of systemic lupus erythematosus. However, the outcome has progressively improved in the last 3 decades and this was due to more efficient and early treatment of LN and comorbid situations. The aim of our study was to analyze our experience and outcome in LN, to evaluate clinicopathologic and clinicolaboratory correlations and to search for risk factors for renal and patient survival. PATIENTS AND METHODS: We conducted a retrospective study of 78 patients with biopsy-proven LN. RESULTS: Acute renal failure and subnephrotic proteinuria with microhematuria occurred each one in 39.7% of the patients, nephrotic syndrome in 16.7% and nephritic syndrome in 3.8%. The mean serum creatinine at presentation was 1.45 +/- 1.03 mg/dl and the creatinine clearance was 68.2 +/- 40.3 ml/min. Class IV LN existed in 71.8%, Class III in 20.5%, Class V in 6.4% and Class VI in 1.3%. The treatment included steroids and cytotoxic agents in 87.5% of the patients with proliferative LN. Hypertension, serum creatinine and acute renal failure at presentation, as well as significant chronicity on renal biopsy, were significantly correlated with the progression to chronic renal failure in our population. Males were more prone to develop renal flares. 3.8% of the patients died, 9% lost their renal function, 26.9% are in remission, 33.3% still have subnephrotic proteinuria and microhematuria, 7.7% have nephrotic syndrome and 19.2% have chronic renal failure. The mean global follow-up was 102 +/- 74 months and 96.2% of the patients survived. The actuarial renal survival was 96.1% in the first year; 89.9% at 5 years; and 83.7% at 10 and 20 years. CONCLUSION: We can say that hypertension, serum creatinine and acute renal failure at the onset and significant chronicity on renal biopsy, proved to be risk factors for chronic renal failure in our study population. Male gender was a risk factor for renal flares. The achieved global outcome can be considered a good result.

Acute Kidney Injury↗

Heart failure, aging, and renal synthesis of dopamine.

The present study evaluates renal dopaminergic activity in 23 patients with heart failure (HF), 10 age-matched controls, and 10 young subjects during normal-salt (NS) intake and after 8 days of low-salt (LS) intake (patients with HF and age-matched controls only). LS intake produced a marked reduction in urine volume in patients with HF but failed to affect urine volume in age-matched controls. Urinary sodium and fractional excretion of sodium were markedly reduced by LS intake in patients with HF and age-matched controls. Daily urinary excretion of L-3,4-dihydroxyphenylalanine (L-dopa) and dopamine was lower in patients with HF than in age-matched controls. LS intake failed to alter L-dopa and dopamine urinary excretion in control subjects. In patients with HF, LS intake produced a significant decrease in urinary L-dopa excretion, but failed to alter the urinary excretion of dopamine. No significant differences were observed in urinary L-dopa, dopamine, and dopamine metabolite levels between aged controls and young healthy subjects. Urinary dopamine-L-dopa ratios in patients with HF on LS intake (24.5 +/- 7.1) were significantly greater than those with NS intake (11.6 +/- 1.3). Urinary dopamine-L-dopa ratios in old control subjects (LS, 9.7 +/- 1.3; NS, 9.3 +/- 1.1) did not differ from those in young healthy subjects (9.2 +/- 0.8). LS intake produced a marked increase in plasma aldosterone levels in both patients with HF (84.6 +/- 14.4 to 148.2 +/- 20.4 pg/mL; P = 0.0008) and controls (102.1 +/- 13.4 to 151.6 +/- 15.7 pg/mL; P < 0.04). Plasma norepinephrine levels were not significantly affected by LS intake in controls (5.1 +/- 1.62 to 6.3 +/- 1.6 pmol/mL; P = 0.22), but were significantly increased in patients with HF (5.8 +/- 0.8 to 7.1 +/- 0.9 pmol/mL; P = 0.04). In conclusion, patients with HF are endowed with an enhanced ability to take up (or decarboxylate) filtered L-dopa, which might counterbalance the reduced renal delivery of L-dopa, contributing to a relative preservation of dopamine synthesis. This may result as a compensatory mechanism, activated by stimuli leading to sodium reabsorption. Age seems to have no influence on renal dopamine production.

3,4-Dihydroxyphenylacetic Acid↗

Predictors of prognosis in patients with stable mild to moderate heart failure.

BACKGROUND: A number of prognostic indexes have been developed to predict the outcome of patients with severe heart failure (HF). In patients with mild to moderate HF, however, there is no consensus regarding the usefulness of such indexes. The goal of this study is to determine the prognostic value of selected clinical variables in the latter group of patients. METHODS AND RESULTS: We prospectively evaluated the prognostic value of the functional capacity evaluation, the ventricular function, biochemical metabolic indicators, and brain natriuretic peptide (BNP) levels in 139 consecutive patients with mild to moderate HF. A clinical and echocardiographic examination (M-mode, 2D and pulsed Doppler of the mitral inflow); a 6-minute walk test; and a determination of serum sodium, uric acid, and BNP levels were performed. Death by any cause was predefined as the study end-point. Variables found to be related with survival in a univariate Cox regression analysis were NYHA class; ischemic origin for HF; left ventricular ejection fraction; deceleration time of the E wave; and 6-minute walk distance, serum sodium, uric acid, and BNP levels. In a multivariate analysis, ischemic origin of HF, 6-minute walk distance, deceleration time of the E wave, and BNP levels were found to be independent prognostic factors. The clustering of the independent prognostic factors was associated with the worse prognosis. CONCLUSIONS: These results suggest that the noninvasive evaluation used in this study and in our population of patients with mild to moderate HF allows the identification of individuals with the worst prognosis. The selected variables might prove to be very helpful in stratifying HF patients and identifying those that might benefit the most from a HF management program.

Activities of Daily Living↗

Arterial distensibility in subjects with white-coat hypertension with and without diabetes or dyslipidaemia: comparison with normotensives and sustained hypertensives.

BACKGROUND: Arterial distensibility can be assessed by measuring pulse-wave velocity (PWV). OBJECTIVE: To determine whether diabetes, smoking and dyslipidaemia were associated with greater than normal stiffness of aortic walls in subjects with white-coat hypertension. METHODS: Arterial distensibility was assessed by automatic measurement of carotid-femoral PWV in 35 healthy normotensives, 46 white-coat hypertensives (WCH, clinic blood pressures >140/90 mm Hg, daytime blood pressures <130/85 mm Hg) and 81 ambulatory hypertensives (clinic blood pressures >140/90 mmHg, daytime blood pressures > or =130 mm Hg systolic or > or =85 mm Hg diastolic, or both) all matched for age, sex and body mass index. Nineteen normotensives (subgroup A), 28 WCH (subgroup A) and 37 ambulatory hypertensives (subgroup A) had only one or no other major cardiovascular risk factor whereas 16 normotensives (subgroup B), 18 WCH (subgroup B) and 44 ambulatory hypertensives (subgroup B) had also some combination of non-insulin-dependent diabetes, a smoking habit and dyslipidaemia. RESULTS: Both for the WCH and for ambulatory hypertensives diabetes and dyslipidaemia (subgroups B) were associated with higher (P<0.04) PWV (11.6+/-0.3 and 12.8+/-0.3m/s, respectively) than for subgroups A (9.3+/-0.5 and 10.9+/-0.6 m/s, respectively). In contrast, PWV for WCH in subgroup A (9.3+/-0.5m/s) did not differ (P>0.35) from those for the normotensive subgroups A (9.2+/-0.3m/s) and B (9.6+/-0.4m/s). PWV was not correlated to levels of glycaemia, glycosylated haemoglobin and cholesterolaemia. CONCLUSIONS: These results suggest that, both for ambulatory hypertensives and for WCH, diabetes and dyslipidaemia are associated with an impairment of arterial distensibility that can entail a greater than normal cardiovascular risk, which might dictate a more than usually stringent treatment of concomitant risk factors and possibly of high blood pressure. In contrast, PWV in WCH of the subgroup A did not differ from those in normotensives, reinforcing the hypothesis that WCH is associated with a benign cardiovascular outcome in the absence of other cardiovascular risk factors.

Adult↗