7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments.

A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments

ABSTRACT A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

Synthesis, antibacterial and cytotoxic activities of new biflorin-based hydrazones and oximes.

Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution method for determining the minimum inhibitory concentration (MIC) against six bacterial strains. Tests have shown that these derivatives have potential against all bacterial strains. The cytotoxic activity was also evaluated against three strains of cancer cells, but none of the derivatives showed activity.

Chemical composition of the essential oil and fixed oil Bauhinia pentandra (Bong.) D. Dietr.

BACKGROUND: Bauhinia pentandrais popularly known as "mororó" and inhabits the Caatinga and Savannah biomes. OBJECTIVE: This paper reports the chemical composition of the essential and fatty oils of the leaves from B. pentandra. MATERIALS AND METHODS: The essential oil was obtained by hydrodistillation and the fixed oil by extraction with hexane, followed by saponification with KOH/MeOH, and methylation using MeOH/HCl. The constituents were analyzed by gas chromatography-mass spectrometry. RESULTS: The major constituent of the essential oil was the phytol (58.78% ±8.51%), and of the fatty oil were palmitic (29.03%), stearic (28.58%) and linolenic (10.53%) acids. CONCLUSION: Of the compounds identified in the essential oil, three are first reported in this species, and this is the first record of the chemical composition of the fixed oil.

Lithocholic acid and derivatives: Antibacterial activity.

In order to develop bioactive lithocholic acid derivatives, we prepared fifteen semi-synthetic compounds through modification at C-3 and/or C-24. The reactions showed yields ranging from 37% to 100%. The structures of all compounds obtained were identified on the basis of their spectral data (IR, MS, 1D- and 2D-NMR). The activity of lithocholic acid and derivatives was evaluated against the growth of Escherichia coli, Staphylococcus aureus, Bacillus cereus and Pseudomonas aeruginosa. The derivative 3α-formyloxy-5ß-cholan-24-oic acid (LA-06) showed the best activity, with MIC values of 0.0790 mM against E. coli (Ec 27) and B. cereus in both cases, and 0.0395 mM against S. aureus (ATCC 12692). Lithocholic acid and the derivatives with MIC⩽1.2 mM were evaluated on the susceptibility of some bacterial pathogens to the aminoglycoside antibiotics neomycin, amikacin and gentamicin was evaluated. There are no previously reported studies about these compounds as modifiers of the action of antibiotics or any other drugs.

[Analysis of neutrophil gelatinase-associated lipocalin in the critical patient]. / Análisis de la lipocalina asociada a la gelatinasa de neutrófilos en el paciente crítico.

OBJECTIVE: To determine if NGAL value exceeding 150 ng/mL is a good diagnostic test for acute renal failure in critically ill patients. DESIGN: Prospective, observational cohort. SETTING: Intensive Care Unit and Cardiac Surgery Intensive Care Service at Hospital Germans Trias I Pujol. PARTICIPANTS: Patients admitted to the Intensive Care department the Designated days in the studio. INTERVENTIONS: Analysis of serum creatinine blood given from 7 days prior to the start of the study, and daily during 4 weeks and by determination of NGAL urine test in frozen sample, analyzer ARCHITECT (Abbott Diagnostics) determined by immunoassay the day baseline and 2 times a week for 4 weeks, analysis of the stay and mortality. RESULTS: A total of 529 NGAL samples were obtained from 46 patients. 37% of patients had a value of NGAL>150 ng/mL. The Sensivity of the test to diagnose acute renal failure was 69%, Specifity was 75,7%. However, the Positive Predictive Test Value was 53%, which means that 47% of patients with high NGAL did not develop AKI. A NGAL >150 mg/dL was associated with a significantly higher SOFA and a longer stay in the ICU. The mortality of patients with elevated NGAL was 58.8%. CONCLUSIONS: A NGAL>150 ng/mL does not seem to be an excellent test for AKI in critically ill patients but is associated with a worse prognosis.

Rhegmatogenous retinal detachment treatment guidelines.

This paper outlines general guidelines following the initial diagnosis of rhegmatogenous retinal detachment. These include preoperative evaluation, treatment, possible intra- and post-operative complications, retinal re-detachment, and all therapeutic options available for each case. Treatment of the traumatic retinal detachment is also described, due to its importance and peculiarities. Treatment or prophylactic guidelines are suggested for the different types of retinal detachment described. These are based on both the experience of the ophthalmologists that have participated in preparing the guidelines, and also on evidence-based grading linked to bibliographical sources. However, these guidelines should not be interpreted as being mandatory. Given that there is a wide spectrum of options for treatment of retinal detachment, the surgeons' experience with one or other surgical technique will be of utmost importance in obtaining the best surgical result. As guidelines, they are intended as an additional aid to the surgeon during the decision-making process, with the expectation that the final choice will still be left to the surgeon's judgment and past experience.

Prognostic factors for acute toxicity in prostate cancer patients treated with high-dose hypofractionated radiotherapy.

PURPOSE: To prospectively study acute genitourinary (GU) and gastrointestinal (GI) toxicity during hypofractionated radiotherapy. PATIENTS AND MATERIALS: One-hundred and seventy-one consecutive men with cT1-T3cN0cM0 prostate cancer were treated at 2.6 Gy/fraction to a total dose of 67.6 for low risk (EQD2 = 79 Gy) and 70.2 Gy for intermediate-high risk (EQD2 = 82 Gy) over 5.2-5.4 weeks (α/ß 1.5). Acute toxicity was scored according to RTOG/EORTC toxicity extended criteria after completing a 22-item questionnaire (basal, weekly, at 6 months). RESULTS: Minimum and median follow-up were 36 and 54.2 months, respectively. GU toxicity grades 0, 1, 2 and 3 were found in 30.4, 37, 32 and 0.6 % of patients, respectively. The figures for grades 0, 1, 2 and 3 GI toxicity were 66, 24, 10 and 0 %. The highest degree of acute reactions was reached at 4-5 weeks. At 6 months, 15 % of patients had GU toxicity (11 % grade 1, 4 % grade 2) and 5.8 % GI toxicity (5.3 % grade 1, 0.5 % grade 2). Multivariate analysis shows that bladder volume receiving ≥65 Gy (V 65) is associated with an increased risk of GU complications (p = 0.017, HR = 1.143, 95 % CI = 1.025-1.276), while history of TURP is linked to lower risk (p = 0.002, HR = 0.310, 95 % CI 0.004-0.370). Mean rectal dose (p = 0.013, HR = 1.089, 95 % CI 1.018-1.116) and total dose (p = 0.019, HR = 0.734, 95 % CI 0.567-0.950) are significantly related to GI toxicity. CONCLUSIONS: This 5-week dose-escalation hypofractionated radiotherapy schedule that uses 3D-conformal radiotherapy without IGRT has resulted in <1 % grade 3 acute complications. Our study suggests that reducing the mean rectal dose and the bladder V 65 helps prevent acute toxicity. TURP before radiotherapy was associated with lower acute GU toxicity.

Vitreous levels of somatostatin in patients with chronic uveitic macular oedema.

PURPOSE: Intravitreal somatostatin (SST) levels are decreased in patients with diabetic macular oedema. This deficit may be involved in the pathogenesis of this condition. The aim of the present study was to determine SST concentration in the vitreous fluid of patients with chronic uveitic macular oedema (CUMO) and quiescent intraocular inflammation. METHODS: Plasma and vitreous fluid samples were obtained during vitrectomy from 11 eyes of patients with CUMO and from 42 eyes of control subjects (idiopathic epiretinal membrane, macular hole). SST concentration was measured by radioimmunoassay. STATISTICS: χ(2)-square test, Mann-Whitney U-test, Wilcoxon test, Spearman's rank correlation coefficient, and multivariant linear regression models. RESULTS: Plasma SST concentrations were similar in uveitic patients and controls (28.25 pg/ml (21.3-31) vs 28.7 pg/ml (22-29.5); P=0.869). A higher vitreous concentration of proteins was found in uveitic patients (1.59±0.38 mg/ml vs 0.73±0.32 mg/ml, P<0.0001). Vitreous SST was markedly lower in uveitic patients, both in absolute terms and after adjusting for total intravitreous protein concentration (39.37 pg/ml (6.16-172) vs 486.73 pg/ml (4.7-1833), P<0.0001; 33.1 pg/mg (3.9-215.74) vs 629.75 pg/mg (6.91-2024), P<0.0001). No correlations were found between plasma and vitreous concentration of SST in either group (ρ=0.191, P=0.57 and ρ=0.49, P=0.66). There were no correlations between vitreous SST concentration and visual acuity or macular thickness in uveitic patients (ρ=0.302, P=0.31 and ρ=0.45, P=0.13). CONCLUSIONS: Intravitreous SST is decreased in patients with CUMO and quiescent intraocular inflammation. The deficit of SST may have a role in the pathogenesis of this condition.

Vitreous levels of interleukine-8 and monocyte chemoattractant protein-1 in macular oedema with branch retinal vein occlusion.

PURPOSE: To investigate whether interleukine-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are related with macular oedema in patients with branch retinal vein occlusions (BRVOs). DESIGN: Retrospective case-control study. PARTICIPANTS: Nineteen patients who had macular oedema due to BRVO and nine patients with non-ischaemic ocular diseases (control group). METHODS: Macular oedema was examined by optical coherence tomography. Both venous blood and vitreous samples were obtained at the time of vitreoretinal surgery. IL-8 and MCP-1 levels in vitreous fluid and plasma were determined with enzyme-linked immunosorbent assay kits. Variables were compared with the Mann-Whitney U-test, Wilcoxon's signed-ranked test, and the chi2-test, when appropriate. To examine correlations, Spearman's rank-order correlation coefficients were calculated. Statistical significance was set at P<0.05. RESULTS: The vitreous fluid levels of IL-8 (median: 63.5 pg/ml) and MCP-1 (median: 1522.4 pg/ml) were significantly higher in the patients with BRVO than in the control group (median: 5.1 and 746.5 pg/ml respectively; P<0.001 and <0.001 respectively). Vitreous IL-8 and MCP-1 were significantly correlated in patients with BRVO (P=0.009). CONCLUSIONS: Both IL-8 and MCP-1 were elevated in the vitreous fluid of patients with BRVO and macular oedema. Both chemokines may contribute to the pathogenesis of macular oedema in patients with BRVO.

Vitreous levels of erythropoietin in patients with macular oedema secondary to retinal vein occlusions: a comparative study with diabetic macular oedema.

OBJECTIVE: In a recent study, we found high levels of erythropoietin (EPO) in patients with diabetic macular oedema (DME), suggesting a role of EPO in the pathogenesis of this condition. To investigate a possible relationship between EPO and other diseases causing macular oedema, we determined vitreous levels of this peptide in patients with macular oedema secondary to retinal vein occlusion (RVO) and compared them with levels in patients with DME and control patients. METHODS: Vitreous and serum samples were obtained from patients with macular oedema secondary to RVO, DME, epiretinal membrane, and macular hole (controls). EPO was measured by radioimmunoassay. RESULTS: No differences were found in median vitreous EPO levels between patients with RVO and controls: RVO, 76 mU/ml (30-806) vs controls, 25 mU/ml (10-75) (P=0.105). Median EPO concentration was higher in DME patients than in patients with RVO or controls: DME, 430 mU/ml (41-3000) vs RVO, 76 mU/ml (30-806) (P<0.0001) vs controls, 25 mU/ml (10-75) (P<0.0001). CONCLUSIONS: EPO levels are not elevated in patients with macular oedema secondary to RVO. Patients with DME have high levels of EPO. These results suggest that EPO could be involved in the pathogenesis of diabetic retinopathy, but not in macular oedema secondary to RVO.

Genomic organization and characterization of splice variants of the human histamine H3 receptor.

In the present paper we report the genomic organization of the human histamine H3-receptor gene, which consists of four exons spanning 5.5 kb on chromosome 20. Using PCR, six alternative splice variants of the H3 receptor were cloned from human thalamus. These variants were found to be coexpressed in human brain, but their relative distribution varied in a region-specific manner. These isoforms displayed either a deletion in the putative second transmembrane domain (TM), H3(DeltaTM2, 431aa) or a variable deletion in the third intracellular loop (i3), H3(Deltai3, 415aa), H3(Deltai3, 365aa), H3(Deltai3, 329aa) and H3(DeltaTM5+Deltai3, 326aa). In order to determine the biological role of the H3 receptor variants compared with the 'original' H3(445aa) receptor, three isoforms, namely H3(445aa), H3(DeltaTM2, 431aa) and H3(Deltai3, 365aa), were expressed in CHO cells and their pharmacological properties were investigated. Binding studies showed that H3(DeltaTM2, 431aa) transiently expressed in CHO cells was unable to bind [125I]iodoproxyfan, whereas both the H3(445aa) and H3(Deltai3, 365aa) receptors displayed a high affinity for [125I]iodoproxyfan [K(d)=28+/-5 pM (n=4) and 8+/-1 pM (n=5) respectively]. In addition, H3(Deltai3, 365aa) possessed the same pharmacological profile as the H3(445aa) receptor. However, in CHO cells expressing H3(Deltai3, 365aa), H3 agonists did not inhibit forskolin-induced cAMP production, stimulate [35S]guanosine 5'-[gamma-thio]triphosphate ([35S]GTP[S]) binding or stimulate intracellular Ca(2+) mobilization. Therefore the 80-amino-acid sequence located at the C-terminal portion of i3 plays an essential role in H3 agonist-mediated signal transduction. The existence of multiple H3 isoforms with different signal transduction capabilities suggests that H3-mediated biological functions might be tightly regulated through alternative splicing mechanisms.

NPY receptor subtypes involved in the contraction of the proximal colon of the rat.

Experiments were designed to determine the receptor subtype(s) involved in the contraction of the rat proximal colon to NPY. In this tissue, mRNA of Y2 and Y4 NPY receptor subtypes were highly expressed, whereas Y5 mRNA levels were very low and Y1 mRNA levels were intermediate. NPY analogues induced contractions with the following order of potency: rPP > hPP = PYY = NPY = [Leu31,Pro34]NPY > NPY(2-36) = [D-Trp32]NPY > NPY(33-36). Responses to NPY, PYY and NPY(13-36) were not or partially affected by tetrodotoxin, in contrast to the responses to [Leu31,Pro34]NPY, rPP, hPP and [D-Trp32]NPY which were fully blocked. Atropine did not inhibit the contractions to NPY, PYY and [Leu31,Pro34]NPY but significantly affected those to NPY(13-36), [D-Trp32]NPY, rPP and hPP. The specific Y1 receptor antagonist BIBP 3226 was ineffective but JCF 104 and JCF 105 (two compounds with preferential affinity toward the hY5 receptor versus the hY1 or hY2 receptor) abolished the contractions provoked by the NPY analogues. These results suggest that NPY activates three receptor subtypes, a Y2 subtype possibly by a direct action on the smooth muscle cells, as well as a Y4 and a Y5 (or 'Y5-like') subtype which, respectively, release acetylcholine and an unknown neurotransmitter.

[Prevalence of migraine in the medical student population as determined by means of the 'Alcoi 1992' questionnaire]. / Prevalencia de migraña en una población de estudiantes de medicina mediante el cuestionario 'Alcoi-1992'.

A group of medical students were interviewed using the 'Alcoi 1992' questionnaire based on the diagnostic criteria of the International Headache Society (IHS) in order to assess the prevalence and various characteristics of migraine. This questionnaire for headache diagnosis was approved in 1993, showing both high sensitivity and exactness in diagnosing migraine. Sensitivity, exactness, predictive value and agreement index of the questionnaire in migraine diagnosis were 100%, 94%, 90% (positive) or 100% (negative) and 0.71% respectively. The group was made up of 96 students of both sexes, with an average age of 23.3 years (standard deviation 1.87). A total of 92 students, 35 male and 57 female, reported headaches. The total prevalence rate for headache was 95.8%, the reliability interval (RI) being 76.7-114.9. In the case of female students, the prevalence rate for headache was 96.6% (RI 71.7-121.5) and in the case of male students it was 94.6% (RI 63-125.7). A total of 20 students, six male and 14 female, fulfilled the criteria for migraine. The overall prevalence rate for migraine was 20.8% (RI 11.9-29.7), the prevalence for females being 23.7% (RI 11.6-35.8) and that for males 16.2% (RI 3.7-28.7). The questionnaire would appear to be a useful, rapid and simple method in the assessment of migraine diagnostic.

Effects of hypothalamic peptides on electrical activity and membrane currents of 'patch perforated' clamped GH3 anterior pituitary cells.

'Perforated-patch' recordings of rat anterior pituitary GH3 cells allow long and stable monitoring of electrical activity and membrane currents. Under current clamp conditions, the biphasic effect of thryotropin releasing hormone (TRH) consisting of a transient hyperpolarization followed by a longer phase of increased action potential frequency is fully preserved. Somatostatin suppresses action potential activity and antagonizes the second phase of enhanced spiking caused by TRH. Voltage clamp records of isolated currents indicate that TRH affects calcium-dependent potassium currents, but does not alter either voltage-dependent potassium or calcium currents at times and concentrations at which the electrical activity is increased.