Aglicons flavònics de les Labiades

A review is made of the flavonoid aglycones identified up to date in the Labiatae, commenting their essential features from the phytochemical and chemotaxonomic standpoints (main kinds of flavonoids present, substitution patterns, and so on)

Estudi de la variabilitat biològica en el posttrasplantament renal : optimització del protocol analític assistencial /

Consultable des del TDXTítol obtingut de la portada digitalitzadaEl motiu d'aquesta tesi ha estat trobar indicadors analítics capaços de senyalar canvis significatius en l'estat de salut dels pacients transplantats renals, abans de qualsevol manifestació clínica. En el seguiment de pacients es sol·liciten repetidament proves analítiques al llarg del temps, essent molt important determinar la diferència mínima entre resultats consecutius, d'una mateixa magnitud biològica, que expressen un canvi significatiu. Aquest és el anomenat «valor de referència d'un canvi». L'aplicació clínica que d'aquest valor es deriva és clau per a prendre decisions correctes, per la qual cosa s'ha de tenir en compte l'opinió del metge a l'hora d'establir el valor de referència d'un canvi per a cada situació clínica concreta. Està demostrat que el valor de referència d'un canvi depèn de la variabilitat biològica intraindividual, el valor de la qual està publicat per un gran nombre de magnituds biològiques en persones sanes. Els pacients transplantats es troben en «un cert estat de salut «, en el qual és important optimitzar el seguiment , perquè la detecció precoç de possibles alteracions funcionals és decisiva per a decidir el tractament més adient. En aquesta tesi s'han utilitzat les dades obtingudes al aplicar el protocol assistencial de seguiment dels pacients posttrasplantats renals, per establir l'equilibri homeostàtic (període de màxima estabilitat) en aquests pacients. Comença entre les 2 i 8 setmanes després del trasplant, depenent del pacient, comprèn un interval de 8 determinacions i es manté durant una mitjana de 3 mesos. Durant aquest període s'han estimat els components de variabilitat biològica intra e interindividual, havent-se comprovat que la obtenció de mostres en intervals de temps irregulars no influeix els valors de variabilitat biològica intraindividual obtinguts. Així s'ha constatat que el protocol assistencial és apropiat per estimar la variabilitat biològica, la qual cosa fa que aquest model d'estudi pugui ser extrapolat a altres patologies. Els valors de variabilitat biològica intra e interindividual en el posttrasplantament renal són diferents dels obtinguts en persones sanes. Les magnituds amb més gran individualitat, idònies per a detectar canvis significatius, són creatinina i urats en sang. S'ha calculat el valor de referència d'un canvi (VRC) per aquestes dues magnituds. Per augmentar el valor predictiu d'un canvi en l'estat de salut, s'han utilitzat valors VRC combinant les dues magnituds, un cop demostrada la independència entre ambdues durant el període de màxima estabilitat. La validesa diagnòstica dels VRC combinats de creatinina i urats s'ha estimat en un grup de 75 pacients trasplantats renals (57 clínicament estables i 18 amb rebuig agut desprès d'un curt període d'estabilitat clínica), calculant els VRC a diferents intervals de probabilitat. Amb la finalitat d'optimitzar la utilitat clínica dels VRC calculats, s'ha tingut en compte el criteri mèdic. Per això, s'ha desenvolupat una enquesta dirigida als nefròlegs responsables del seguiment del pacient trasplantat renal. Dels resultats obtinguts es dedueix que els VRC de creatinina de 18.1% i d'urats de 19.8% (interval de probabilitat del 85%) presenten la millor combinació en quant a sensibilitat, especificitat i valor predictiu per a detectar rebuig o complicacions renals. S'ha verificat la utilitat clínica del model definit (VRC combinat de creatinina i urats) en un altre grup de pacients, constatant la detecció de potencials crisis subclíniques en aquest nou grup. Com a conseqüència pràctica d'aquesta tesi s'ha previst incorporar, en el sistema informàtic del laboratori, un algoritme de càlcul dels VRC als resultats de creatinina i urats de tots els pacients posttrasplantats renals . Qualsevol resultat que superi els VRC definits, serà específicament assenyalat com a indicatiu de canvi significatiu.The aim of this thesis was to encounter analytic markers that indicate significant changes in the health status of kidney transplant recipients before clinical manifestations are evident. During patient follow-up for many pathologies, repeated analytic tests are requested over time. In specific biological constituents, it is useful to determine the minimum difference in consecutive results that expresses a significant change in health status. This difference is termed reference change value. Clinical application of this concept affects decisions regarding treatment; therefore, the opinion of clinicians must be considered when establishing the reference change value for specific clinical situations. It has been demonstrated that the reference change value depends on intraindividual biological variation. Published values for intraindividual variation of many constituents in healthy subjects are now available. The situation of renal transplanted patients can be considered a certain state of health, in which it is important to optimize follow-up, since early detection of potential functional alterations is decisive for determining appropriate treatment. This thesis used data obtained from application of a hospital follow up protocol for renal transplant patients in order to establish the time of homeostatic balance (period of maximum stability) in this clinical situation. It was found that the stable period begins 2 to 8 weeks after transplantation, depending on the patient, includes an interval of 8 determinations, and is maintained for a mean of 3 months. Intra- and interindividual biological variation were estimated during this period, after confirming that analysis of samples collected over irregular intervals of time does not affect the intraindividual biological variability results obtained. This point is important because it means that values found with an established hospital protocol can be used for estimating biological variation, making it easier to use the model for the study of other pathologies. The intra- and interindividual biological variation values in renal post-transplantation are different from those in healthy subjects. The constituents with highest individuality, ideal for detecting significant changes, were found to be serum creatinine and urates. The reference change value (RCV) was calculated for these two constituents and it was determined that their values during the maximum stability period were independent of each other. Thus, the RCV of the two in combination could be used to increase the predictive value of a change in health status. The diagnostic validity of the combined RCVs of serum creatinine and urates was then estimated in 75 renal transplant recipients (57 clinically stable and 18 with acute rejection after a short period of clinical stability), calculating the RCV at different levels of probability. With the aim of optimizing the clinical usefulness of the RCVs calculated, medical criteria were taken into account. A structured questionnaire was designed to know the opinion of nephrologists responsible for the follow up of renal transplant patients. From the results obtained it was deduced that an RCV of 18.1% for creatinine and 19.8% for urates (interval of probability of 85%) presented the best combination in terms of sensitivity, specificity and predictive value to detect rejection or renal complications. The clinical utility of the model defined (combined RCV of creatinine and urates) was verified by using it in another group of transplant patients. Potential subclinical crises were also detected in this new group. As a practical consequence of this thesis, the hospital laboratory will incorporate an algorithm in its data processing system to calculate the RCVs for creatinine and urates during serial testing of all renal transplanted patients. Results surpassing the defined RCVs will be highlighted by a marking system to advise clinicians that a significant change has occurred in patient status

Valorization of artichoke wastewaters by integrated membrane process

In this work an integrated membrane system was developed on laboratory scale to fractionate artichoke wastewaters. In particular, a preliminary ultrafiltration (UF) step, based on the use of hollow fibre membranes, was investigated to remove suspended solids from an artichoke extract. The clarified solution was then submitted to a nanofiltration (NF) step. Two different 2.5 × 21 in. spiral-wound membranes (Desal DL and NP030) with different properties were investigated. Both membranes showed a high rejection towards the phenolic compounds analysed (chlorogenic acid, cynarin and apigenin-7-O-glucoside) and, consequently, towards the total antioxidant activity (TAA). On the other hand, the Desal DL membrane was characterized by a high rejection towards sugar compounds (glucose, fructose and sucrose) (100%) when compared with the NP030 membrane (4.02%). The performance of selected membranes in terms of permeate flux, fouling index and water permeability recovery was also evaluated. On the base of experimental results, an integrated membrane process for the fractionation of artichoke wastewaters was proposed. This conceptual process design permitted to obtain different valuable products: a retentate fraction (from the NP030 membrane) enriched in phenolic compounds suitable for nutraceutical, cosmeceutical or food application; a retentate fraction (from the Desal DL membrane), enriched in sugar compounds, of interest for food applications; a clear permeate (from the Desal DL membrane) which can be reused as process water or for membrane cleaning.Conidi, C.; Cassano, A.; García Castelló, EM. (2014). Valorization of artichoke wastewaters by integrated membrane process. Water Research. 48:363-374. doi:10.1016/j.watres.2013.09.047S3633744

Avaliação do efeito do eucaliptol nas convulsões induzidas por pentilenotetrazol em camundongos

The developmental process of epilepsies involves diverse mechanisms that culminate in the hyperactivity of a population of neurons, resulting in a pattern of repeated and rhythmic depolarizations. Antiepileptic drugs act by increasing GABAergic neurotransmission, reducing the effects of glutamate, or blocking ion channels, and are endowed with serious adverse effects that make it difficult for patients to adhere to treatment. This fact has encouraged the search for compounds of natural origin with potential anticonvulsant effect. Thus, the present study aimed to evaluate the effect of eucalyptol in seizures induced by pentylenetetrazole (PTZ). For this, male Swiss mice, orally treated with monotrepene, were used. The first protocol evaluated the toxicity and the estimated LD50 of the compound. Based on the value of LD50, the doses of terpene used in the behavioral and neurochemical tests were selected. For the behavioral tests, groups of mice were pretreated with saline (10 mL/kg, vol), diazepam (2 mg/kg, ip) and eucalyptol (100, 200 and 400 mg/kg, vol) and then with pentylenetetrazole 80 mg/kg, ip) and evaluated for the following parameters: seizure intensity, latency for first seizure and time of death. For neurochemical tests, groups of mice were pretreated with saline (10 mL/kg, v.o.) and eucalyptol (400 mg/kg, i.p.) and subsequently with pentylenetetrazole (80 mg/kg, i.p.); The determination of the concentration of neurotransmitters (monoamines - dopamine, noradrenaline and serotonin) and oxidative stress markers (nitrite and thiobarbituric acid reactive substances - TBARs) were the parameters evaluated. The results were analyzed by ANOVA or Kruskal-Wallis, followed by Student-Newman-Keuls, and Dunns, respectively. Values of p <0.05 were considered significant. The results showed that oral administration of eucalyptol had low toxicity and the estimated LD50 was greater than 2000 mg / kg. In the PTZ-induced seizure test, only the higher dose of monoterpene (400 mg/kg) significantly reduced seizure intensity by 60%, increased latency for onset of the first seizure by 85% and time of death of the animals in 75% in relation to the control. Similarly, treatment with eucalyptol (400 mg/kg) significantly reduced the concentration of noradrenaline, dopamine and serotonin by 50%, 33% and 70%, respectively, in relation to the PTZ-treated group (80 mg/kg). In addition, treatment with eucalyptol (400 mg/kg) significantly reduced the concentration of TBARs by 33%, but not nitrite, relative to the PTZ treated group (80 mg/kg). Taken together, the results show that the monoterpene studied has low oral toxicity and an important anticonvulsant effect, since its administration is capable of attenuating the convulsions chemically induced by pentylenetetrazol with consequent reduction of the concentration of monoamines and the reactive substances of thiobarbituric acid, elements whose increase is associated with the epileptogenesis phenomenon.O processo de desenvolvimento das epilepsias envolve mecanismos diversos que culminam na hiperatividade de uma população de neurônios, resultando em um padrão de despolarizações repetidas e rítmicas. Os fármacos antiepilépticos agem através do aumento da neurotransmissão GABAérgica, da redução dos efeitos do glutamato, ou do bloqueio de canais iônicos, sendo dotados de efeitos adversos sérios que dificultam a adesão do paciente ao tratamento. Este fato tem incentivado a busca por compostos de origem natural com potencial efeito anticonvulsivante. Desta forma, o presente trabalho teve como objetivo avaliar o efeito do eucaliptol nas convulsões induzidas por pentilenotetrazol (PTZ). Para tanto, foram utilizados camundongos Swiss machos, tratados oralmente com o monotrepeno. O primeiro protocolo realizado avaliou a toxicidade e a DL50 estimada do composto. Com base no valor da DL50, foram selecionadas as doses do terpeno utilizadas nos testes comportamentais e neuroqímicos. Para os testes comportamentais, grupos de camundongos foram previamente tratados com salina (10 mL/kg, v.o.), diazepam (2 mg/kg, i.p.) e eucaliptol (100, 200 e 400 mg/kg, v.o.) e posteriormente com pentilenotetrazol (80 mg/kg, i.p.) e avaliados quanto aos seguintes parâmetros: intensidade das convulsões, latência para primeira convulsão e tempo de morte. Para os testes neuroquímicos, grupos de camundongos foram previamente tratados com salina (10 mL/kg, v.o.) e eucaliptol (400 mg/kg, i.p.) e posteriormente com pentilenotetrazol (80 mg/kg, i.p.); a determinação da concentração de neurotransmissores (monoaminas – dopamina, noradrenalina e serotonina) e dos marcadores de estresse oxidativo (nitrito e substâncias reativas do ácido tiobarbitúrico – TBARs) foram os parâmetros avaliados. Os resultados foram analisados por ANOVA ou Kruskal-Wallis, seguido dos testes de Student-Newman-Keuls, e Dunns, respectivamente. Foram considerados significativos os valores de p < 0,05. Os resultados mostraram que a administração oral do eucaliptol apresentou baixa toxicidade e a DL50 estimada foi superior a 2000 mg/kg. No teste das convulsões induzidas por PTZ apenas a dose maior do monoterpeno (400 mg/kg) reduziu de forma significativa a intensidade das convulsões em 60%, aumentou a latência para aparecimento da primeira convulsão em 85% e o tempo de morte dos animais em 75% em relação ao controle. De forma semelhante, o tratamento com eucaliptol (400 mg/kg) reduziu de forma significativa a concentração de noradrenalina, dopamina e serotonina, em 50%, 33% e 70%, respectivamente, em relação ao grupo tratado com PTZ (80 mg/kg). Além disso, o tratamento com eucaliptol (400 mg/kg) reduziu de forma significativa a concentração de TBARs em 33%, mas não de nitrito, em relação ao grupo tratado com PTZ (80 mg/kg). Tomados em conjunto, os resultados mostram que o monoterpeno estudado apresenta baixa toxicidade oral e importante efeito anticonvulsivante, visto que sua administração é capaz de atenuar as convulsões quimicamente induzidas por pentilenotetrazol com consequente redução da concentração de monoaminas e das substâncias reativas do ácido tiobarbitúrico, elementos cujo aumento está associado ao fenômeno da epileptogênese