A 1000-year-old mystery solved: Unlocking the molecular structure for the medieval blue from Chrozophora tinctoria, also known as folium.

The molecular structure of the medieval watercolor known as folium has finally been solved in the 21st century. The interdisciplinary approach taken was the key to producing extracts that had been prepared following medieval instructions, and shows the blue/purple chromophore as the major dye in Chrozophora tinctoria fruits (shell). A multi-analytical characterization of its structure was made using HPLC-DAD-MS, GC-MS, NMR (1H, 13C, COSY, HSQC, HMBC, INADEQUATE), and computational studies. The results demonstrate that the blue compound corresponds to 6'-hydroxy-4,4'-dimethoxy-1,1'-dimethyl-5'-{[3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-[3,3'-bipyridine]-2,2',5,6(1H,1'H)-tetraone, a hermidin derivative, which we named chrozophoridin. Experimental data and computational modeling studies show that this mono-glycosylated dimer is represented by two stable isomers (atropisomers). This is an indispensable piece of knowledge for the characterization of this medieval dye in works of art such as medieval manuscript illuminations and for testing its stability and contributes to the preservation of our cultural heritage.

Living-Donor Kidney Transplantation: Donor-Recipient Function Correlation.

BACKGROUND: With the rising prevalence of living-donor kidney transplantation, evaluation of factors correlated with renal function in the donor-recipient pair constitutes a main goal for kidney transplantation clinicians. Our objective was to analyze the more relevant donor characteristics that contribute to donor and recipient estimated glomerular filtration rates (eGFR) after 1 year. METHODS: We evaluated 48 consecutive donor-recipient pairs from our unit. RESULTS: Mean donor age was 46 ± 11 years, with 71% being women. Mean recipient age was 35 ± 12 years, with 54% being men. Mean duration of donor hospitalization was 7 ± 2 days. Donor eGFR was 104 ± 11 mL/min/1.73 m2 before donation and 70 ± 14 mL/min/1.73 m2 at discharge. After 1 year, donor eGFR was 71 ± 12 mL/min/1.73 m2 and recipient eGFR was 69 ± 10 mL/min/1.73 m2. Donor eGFR <100 mL/min/1.73 m2 before donation and age >50 years correlated with 17.7- and 8.9-fold increased risks, respectively, of recipient eGFR <60 mL/min/1.73 m2 after 1 year. Donor being female, although statistically associated with worse graft function, compared with a male donor (P = .020), did not represent a significantly increased risk of recipient eGFR <60 mL/min/1.73 m2. Higher donor body mass index (BMI) also associated with a lower kidney function for donors (P = .048). In multivariate linear regression to predict pairs' eGFRs after 1 year, only donor eGFR before donation and at discharge retained statistical significance (P ≤ .001 and P = .045, respectively). CONCLUSIONS: Excluding unpredictable complications in the post-transplantation period, donor eGFR before donation, eGFR at discharge, and age were the best parameters to predict recipient and donor eGFRs after 1 year and can be used as a tool for managing expectations regarding the post-transplantation period.

A little key to oxalate formation in oil paints: protective patina or chemical reactor?

By means of synchrotron based techniques, we propose an integrated mechanism for the degradation of 19th century chrome yellow oil paints based on pigment reconstructions from historical recipes. We show that for certain paint formulations the darkening of these colours is triggered by the binder photodegradation which leads to the formation of calcium oxalate at the expense of the filler CaCO3, and the reduction of the chrome yellow pigment (Cr6+/Cr3+). Considering that calcium oxalate is formed as a thin superficial layer, that may prevent light absorption by the paint bulk, we discuss its role as protective patina.

Living kidney donor transplantation: an alternative with limitations.

BACKGROUND: The major issues involved in the decision to donate are the perioperative risk and the risk of chronic kidney disease or even end-stage renal disease. The usual glomerular filtration rate (GFR) in kidney donors after transplantation is approximately 70% of the predonation rate; however, some have a GFR <60 mL/min/1.73 m(2). So after kidney donation, mild to moderate renal insufficiency may occur. Thus, it is important to identify predictor factors of postdonation kidney function. OBJECTIVES: To evaluate the influence of predictor factors in the evolution of the remaining kidney function and to quantify nonpredictable and unexpected developments in GFR at 1 year post donation. METHODS: We performed a study of the evolution of renal function pre- and postnephrectomy of 55 living donors without perioperative comorbidities and a mean follow-up of 6.03 ± 2.7 years. RESULTS: One year after nephrectomy donor function was 32% lower than the prenephrectomy value and 21% of donors had an eGFR <60 mL/min/1.73 m(2). In multivariate logistic regression a living donor with a predonation eGFR <100 but >80 mL/min/1.73 m(2) had 5.24 times a chance of having an eGFR <60 mL/min/1.73 m(2) at 1 year post donation than if he had an eGFR ≥100 mL/min/1.73 m(2). Among 15 donors with prenephrectomy eGFR ≥80 and <100 mL/min/1.73m(2), 8 (53%), RR = 3.26 (1.517-7.012) had eGFR <60 mL/min/ 1.73 m(2). CONCLUSIONS: The eGFR predonation and donor age influenced the first-year postnephrectomy eGFR. Some donors had a more accelerated eGFR fall, not always related to predonation eGFR and age.

Impact of conversion from Advagraf to twice-daily generic tacrolimus in kidney transplant recipients: a single-center study.

BACKGROUND: The conversion of twice-daily (Prograf) to once-daily tacrolimus (Advagraf) as well as from Prograf to a generic tacrolimus preparation was proved to be safe in kidney transplant patients. There are no published studies comparing the clinical outcomes of patients who were receiving Advagraf and were switched to generic preparations of tacrolimus. OBJECTIVES: To evaluate the impact, safety profile, side effects, and renal graft function after the conversion of Advagraf to a generic preparation of tacrolimus. POPULATION AND METHODS: This prospective study was conducted over a 9-month period. The conversion to twice-daily generic tacrolimus was performed on a 1 mg:1 mg basis, total daily dose. We included 123 kidney transplant recipients (55% male). The mean (± SD) age was 49.9 ± 12 years. There were 100 (81%) Caucasian patients; the mean (± SD) time from transplantation to conversion was 4.6 ± 4.4 years. RESULTS: A significant increase in blood levels (18%; P = .000) was reported. There was a necessary tacrolimus dose reduction of 17% (P = .000) and ≥ 3 blood trough levels to adjust the initial tacrolimus blood levels. The mean serum creatinine remained stable before conversion, at months 1 and 6 (1.40, 1.43, and 1.46 mg/dL, respectively). Significant adverse effects were reported in 9% of our patients. There were no episodes of acute rejection or graft loss during the study. CONCLUSIONS: The conversion proved to be safe. A drug reduction was necessary to ensure stable renal function and good tolerability.

Renal transplantation in type 1 diabetes mellitus: an unusual case report.

Diabetes mellitus (DM) may progress to diabetic nephropathy (DN) in approximately 40% of cases and it accounts for one of the most common causes of end-stage of renal disease (ESRD). The pathogenesis of DN involves complex interactions between metabolic and hemodynamic factors. DM type 1 has a dominant impact on morbidity and mortality after renal transplantation. We report a kidney transplantation patient with DM and DN as the etiology of end-stage renal disease and whose post-transplantation evolution over 19 years was remarkably atypical. DM was diagnosed at the age of 7 years and the patient suffered a rapid and aggressive progression of her disease with early development of DN and diabetic retinopathy. Nineteen years post-transplantation, the patient shows neither deterioration of graft function nor clinical reactivation of DN. There seems to be two quite distinct answers to the same injury supported by a group of factors that led to micro- and macrovascular lesions, all present before transplantation and potentially aggravated through some immunosuppressive therapy. This clinical evolution suggests the hypothesis that not only the graft but also the donor may have inherent characteristics that enabled him to display the resistance to DN despite the genetic susceptibility of the receptor. The answers to these questions would help to explain why some patients with diabetes progress to macro- and microvascular complications and others remain resistant to developing these vascular disorders. In this case, the resistance to DN is apparently a feature related to the donor.

Excited-state isomerization of leuco indigo.

The photoreaction of indigo and two other derivatives in its reduced (leuco) form was investigated by absorption and fluorescence (steady-state and time-resolved) techniques. The fluorescence quantum yield (φ(F)) dependence with the UV irradiation time was found to increase up to a value of φ(F) ≈ 0.2-0.3 (after 16 min) for indigo and φ(F) = 0.2 (at ~150 min) for its derivative 4,4'-dibutoxy-7,7'-dimethoxy-5,5'-dinitroindigo (DBMNI). With a model compound, where rotation around the central C-C bond is blocked, the φ(F) value was found constant with the UV irradiation time. Time-resolved fluorescence revealed that initially the decays are fitted with a biexponential law (with 0.12 and 2.17 ns), ending with an almost monoexponential decay (~2.17 ns). Quantum yields for the isomerization photoreaction (φ(R)) were also obtained for indigo and DBMNI with values of 0.9 and 0.007, respectively. The results are rationalized in terms of a photoisomerization (conversion) reaction occurring in the first excited singlet state of trans to cis forms of leuco indigo.

[Epidemiological study of lung cancer in Portugal (2000/2002)]. / Estudo epidemiológico do cancro do pulmão em Portugal nos anos de 2000/2002.

Lung cancer is the most common form of cancer death in the world. Five-year survival is about 15%, without any change to this picture envisaged. It is the 3rd most prevalent type of cancer in Portugal and the primary cause of cancer death. 85% of lung cancer cases are attributable to smoking. One study performed in Portugal for 3 years (2000/2002) by the Lung Oncology Work Committee of the Portuguese Society of Pulmonology in 22 Hospitals showed that of a total of 4396 patients with lung cancer, 81.8% were male and 18.2% were female, with a mean age of 64.49 +/- 11.28 years. About 70% of patients were smokers or former smokers, with 50.3% of patients presenting with performance status (Zubrod) 1. Histologically, 37.5% were adenocarcinoma, followed by squamous carcinoma in 30.5% of cases, and small cell lung cancer in 12.5%; neuroendocrine carcinoma presented in 1.4% of cases; non small cell lung cancer in 10.5%; mixed carcinoma in 0.7%; large cell carcinoma in 2.3%; and others/not specified in 4.6% of cases. Staging (known in 4097 patients), showed 113 patients in stage IA (2.8%)and 250 patients in stage IB (6.1%); only 0.8% in stage IIA and 4.5% in stage IIB; 9.1% in stage IIIA and 29.9% in stage IIIB; 46.9% were already in stage IV by the time of diagnosis. The first therapeutic option was known in 3855 patients. Surgery was performed in 8.2% and 21.8% of cases were treated with combined therapies (surgery and chemotherapy or radiotherapy, or combination of chemotherapy and radiotherapy); chemotherapy alone was first choice in 43.7% of patients and in 20.3% only best support therapy was chosen.

Revisiting Perkin's dye(s): the spectroscopy and photophysics of two new mauveine compounds (B2 and C).

Two new components have been identified in an early sample prepared according to the original recipe of Perkin, and perhaps even by Perkin himself around 1860--a new isomer of Perkin's mauveine B (designated as mauveine B2) together with a new mauveine compound (mauveine C)--and these compounds were synthesized again using starting materials chosen to reproduce Perkin's original synthesis and isolated by HPLC-DAD, identified by (1)H NMR, MS and their spectroscopic (UV/Vis and emission) and photophysical behaviour investigated.

Photophysics of an indigo derivative (keto and leuco structures) with singular properties.

Spectral and photophysical properties of the indigo derivative Cibalackrot in keto and reduced (leuco) forms were studied by absorption spectra, fluorescence and pulse radiolysis and compared with the structurally similar indigo. With the keto form of this dye, fluorescence (phiF = 0.76) and intersystem crossing (phiT = 0.11) are dominant, whereas with indigo, efficient internal conversion (phiIC = 0.99) is observed, probably involving proton transfer through intramolecular hydrogen bonds. With Cibalackrot, this pathway is blocked, supporting the above model for indigo. With the reduced form of Cibalackrot, more than 98% of the absorbed quanta are dissipated through S1 approximately --> S0 internal conversion, which contrasts with leuco-indigo, where fluorescence (phiF = 0.35), internal conversion (phiIC = 0.53) and intersystem crossing (phiT = 0.125) are found to be competitive. In addition, a synthetic precursor of Cibalackrot (preCiba) was also investigated. This has a rigid molecular structure (with a moiety identical to Cibalackrot and the other to indigo), but intra- or intermolecular proton transfer is allowed between adjacent carbonyl and N-H groups. With this precursor in its keto structure the photophysical parameters are generally very close to those of the keto form of indigo, and different from those of Cibalackrot. A more detailed investigation of the time-decay profiles of preCiba in dioxane (and with added water and D2O) has shown that these follow biexponential laws with a shorter component of 14-25 ps, which appears associated with a risetime at longer wavelength emissions (and to a positive preexponential at shorter emission wavelengths) and a longer lived (decay) component of 104-130 ps. In the steady-state spectra of preCiba, the variation with temperature reveals a blue shift of the emission maxima, which is interpreted as the presence (simultaneous emission) of two species (keto and enol) in the excited state. Indigo and deuterated indigo are also found to present a similar behavior. The overall data are interpreted as to be due to an excited-state process involving the proton transfer between keto and enol forms. Rate constants with values of 7 x 10(10) s-1 for preCiba and 1.6 x 10(11) s-1 for deuterated indigo were obtained. This inverse isotope effect is justified on the basis of the proposed model for proton-transfer excited-state deactivation.

Incontinencia pigmentaria / Incontinence of pigment

No disponible

Lenograstim as support for ACE chemotherapy of small-cell lung cancer: a phase III, multicenter, randomized study.

This phase III study was conducted to evaluate the usefulness of lenograstim as support for ACE (doxorubicin, cyclophosphamide, and etoposide) chemotherapy in previously untreated patients with small-cell lung cancer. Patients were randomized to receive up to six 3-week cycles of either ACE alone (n = 139) or ACE with lenograstim support (150 microg/m2/day subcutaneously, days 4-13, n = 141). Compared with the chemotherapy-alone group, the lenograstim support group was more likely to achieve neutrophil recovery (absolute neutrophil count, > or =1.5 x 10(9) cells/l) by day 14 (95.8-100% vs. 14.3-24.1% across the cycles) and less likely to experience at least one infectious episode (36.7 vs. 54.0%; p = 0.004), chemotherapy delay (51.8 vs. 56.2%; NS), or dose reduction (17.3 vs. 27.7%; p = 0.037). Objective response and event-free and overall survival rates were similar. Lenograstim was well tolerated. Lenograstim may allow the interval between cycles of ACE to be reduced to 2 weeks; such dose intensification may lead to more favorable objective response and survival rates.

[Cerebral ischemic infarction in newborn infants. Diagnosis using pulsed and color Doppler imaging]. / Infarctus ischémique cérébral du nouveau-né. Diagnostic par doppler pulsé et couleur.

In newborn infant, cerebral infarction is often difficult to distinguish from cerebral hemorrhage, both pathologies being moreover frequently associated. We report a left anterior stroke in a fullterm newborn who had seizures on the third day of life. Ultrasound scanning showed a hyperechogenic zone in the territory of the left anterior cerebral artery. Pulsed and color Doppler imaging showed a decreased blood flow velocity in comparison to the opposite side, thus enabling the diagnosis.

Neonatal cerebral Doppler: arterial and venous flow velocity measurements using color and pulsed Doppler system.

OBJECTIVE: To contribute to the establishment of reference values of blood flow velocity assessed by cerebral Doppler in healthy infants related to gestational age and birth weight during the first week of life. METHODS: Five arteries and three veins were evaluated respectively in 120 (74 premature) newborns and in 100 (70 preterm) infants. In a quarter of the latter three recordings at 5-minute intervals were made to assess reproducibility. The relation between flow measurements and gestational age was assessed by linear regression, means by analysis of variance (or Kruskall-Wallis test) and paired samples by Student's t test. RESULTS: There was a significant increase of arterial velocities with increasing gestational age and birth weight, but not for venous velocities. Significant higher values were found in the internal carotid artery followed by the medium cerebral artery. The venous velocities were highly reproducible and the main patterns observed were bandlike and sinusoid type. CONCLUSION: The knowledge of normal cerebrovascular physiology is essential to understand the pathogenesis of neonatal brain damage and can help pediatricians in an accurate interpretation of the flow profile in neurological pathology.

Glutathione S-transferase mu polymorphism and susceptibility to lung cancer in the Portuguese population.

Epidemiological studies have led to the suggestion that a genetic basis may exist in the individual variation in predisposition to cancer. Interindividual differences in human toxicological response to carcinogenic exposure have been attributed to heritable polymorphisms in metabolism, namely glutathione S-transferases (GSTs) coding for enzymes that are known to be detoxifiers of carcinogens. Within the human GST mu class, there is a specific isozyme that is frequently lacking. To check whether or not this association exists in the Portuguese population with lung cancer, we used polymerase chain reaction (PCR)-based genotyping to examine GSTM1 polymorphism (nulled and non-nulled) in 84 individuals as a control healthy population and a group of 98 lung cancer patients. In this study we were able to find a frequency of the GSTM1 phenotype among our healthy control subjects consistent with earlier genotyping studies in other Caucasoid populations. For the group of individuals with lung cancer as a whole, or in subsets of histological subtypes, our data for the Portuguese population did not show a positive correlation between the null allele and this neoplasm. In contrast, we found a slight increase in the frequency of the wild-type allele in our lung cancer group.