Clinical importance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in dogs with leishmaniasis.

Leishmaniasis is a zoonotic disease caused by Leishmania spp., impacts multiple systems and organs. While hematological and biochemical profiles aren't definitive for diagnosis, recent studies have identified the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) as predictors of morbidity and mortality in critically ill human and dog patients. This study examined 100 dogs diagnosed with leishmaniasis, categorized by the International Renal Interest Society (IRIS) stages 1-4. Additionally, the dogs were divided based on whether they survived less or more than one year (L1Y and G1Y). Control group consisted of 43 dogs. The NLR increased as the disease progressed (IRIS 1-4), presenting statistically significant differences (P<0.05) when compared to the control group (2,37±2,08) IRIS 3 and 4 (4,59±13,39 and 6,99±12,86, respectively), and G1Y and L1Y (3,60±4,02 and 4,87±5,82, respectively). Significant changes in SII were only evident in short-term survivors (L1Y 951,93±1402) and advanced renal disease cases (IRIS 4 stage 1073,68±1901,09). Conversely, PLR remained largely unchanged. In conclusion, these results suggest that the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) may serve as potential markers for assessing disease progression and prognosis in dogs diagnosed with leishmaniasis.

Determination of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in dogs with leptospirosis.

Leptospirosis is a globally distributed zoonosis with multisystemic involvement in canine species, capable of causing a pulmonary hemorrhagic syndrome (LPHS) in the most severe cases. In humans, the neutrophil to lymphocyte ratio (NLR), platelets to lymphocytes (PLR) and systemic immune-inflammation index (SII) have been described as predictors of morbidity and mortality in various pathologies, but no such studies have been developed for canine leptospirosis. Hence, we aimed to assess the usefulness of NLR, PLR and SII in dogs affected with leptospirosis, focusing on those that died or survived after hospitalization, whether or not they developed LPHS. The leptospirosis group was composed by 36 dogs while the control group consisted of 32 healthy dogs. The NLR, associated with inflammation, demonstrated a threefold or greater increase in all leptospirosis groups compared to the control group (median 2.44 ± 1.66) (developing or not LPHS). Dogs that died (median 67.78 ± 158.67), developed LHPS (median 85.17 ± 143.77), or both developed LHPS and died (median 67.78 ± 155,14) had a lower PLR in comparison to the control group (median 101,82 ± 53,75) and the rest of groups, but no statistically significant differences were observed (p > 0.05). The SII was higher in leptospirosis-affected dogs that survived (median 1356,92 ± 2726,29) and statistically significant differences were observed in those who did not develop LPHS (median 1770,41 ± 2630,77; p < 0.05) compared to the control group (median 555,21 ± 313,26). Our data shows that NLR may be used as inflammation indicator, while more studies are needed for PLR and SII in canine leptospirosis.

Incidence and prevalence of juvenile idiopathic arthritis in Catalonia (Spain).

OBJECTIVE: To ascertain the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Catalonia (autonomous region in northeast Spain), examined according to the currently established disease subtypes. METHODS: Before initiating the study, we conducted an educational programme on paediatric rheumatology, addressed to all general paediatricians in Catalonia. A 2-year (2004-2006), prospective, population-based study was then carried out to determine the incidence of JIA. Prospective and retrospective data retrieval was performed to calculate prevalence. The International League of Associations for Rheumatology (ILAR, Edmonton revision) classification criteria were applied. RESULTS: Over the study period, 145 new cases of JIA were diagnosed. The mean annual incidence was 6.9/105 children aged less than 16 years (range 5.8-8.1 years; 9.0 years for girls and 4.8 years for boys). On separate analysis of patients ≤ 6 and > 6 years, the distribution in younger children was found to be similar for both girls and boys, whereas in older children, most girls belonged to the oligoarthritis and polyarthritis subgroups, and boys to the enthesitis-related arthritis and undifferentiated subgroups. The calculated prevalence of JIA (31 October 2006) was 39.7 (36.1-43.7)/105 children younger than 16. The relative risk of girls having JIA was 2.1 [95% confidence interval (CI) 1.7-2.7, p < 0.001]. In 70% of patients, the diagnosis was established before the age of 7. Subgroup distribution of prevalent cases mirrored that of incident cases. CONCLUSION: This is the first population-based study on the epidemiology of JIA in Catalonia. Incidence and prevalence rates are lower than those reported for several areas in Nordic countries of Europe. Oligoarthritis was the most common subtype.

Transformation of wheat with high molecular weight subunit genes results in improved functional properties.

The high molecular weight (HMW) subunits of wheat glutenin are major determinants of the elastic properties of gluten that allow the use of wheat doughs to make bread, pasta, and a range of other foods. There are both quantitative and qualitative effects of HMW subunits on the quality of the grain, the former being related to differences in the number of expressed HMW subunit genes. We have transformed bread wheat in order to increase the proportions of the HMW subunits and improve the functional properties of the flour. A range of transgene expression levels was obtained with some of the novel subunits present at considerably higher levels than the endogenous subunits. Analysis of T2 seeds expressing transgenes for one or two additional HMW subunits showed stepwise increases in dough elasticity, demonstrating the improvement of the functional properties of wheat by genetic engineering.

[New therapy strategies in secondary hyperparathyroidism on dialysis (I): new concepts, new treatments]. / Nuevas estrategias terapéuticas para el hiperparatiroicismo secundario en diálisis (I): nuevos conceptos, nuevos tratamientos.

Secondary hyperparathyroidism (SHP) is still an early and frequent complication of chronic renal disease (CRD). Currently, CRD is an independent cardiovascular risk factor, and calcium-phosphorus metabolism is one of the modifiable related factors. In this first article, we summarize the recent SHP treatment paradigm shift in dialysis patients, derived from the better knowledge and understanding of vascular calcification. We analyze the most recent guidelines (K/DOQI), and describe the general implications of hyperphosphatemia, as well as our therapeutic approach with phosphorus-binders. Since sevelamer additionally presents some pleiotropic effects and it attenuates the progression of vascular calcification, we consider it in the first-line of treatment despite it is not yet demonstrated a survival benefit. We also minimize the use of elemental calcium to a maximum of 1000 to 1500 mg/day. Lanthanum carbonate may well be an important therapeutic agent in the near future, especially if security concerns related to metal accumulation are overcome. Ferric citrate, colestilan and nicotinamide may soon play a role. All these drugs, isolated or in combination, are important in the treatment of SHP since a great deal of its success and the avoidance of some dialysis-related complications depend on an efficient phosphorus control.

[New therapeutic strategies in secondary hyperparathyroidism on dialysis (II): vitamin D analogues and calcium-mimetics]. / Nuevas estrategias terapéuticas para el hiperparatiroidismo secundario en diálisis (11): análogos de la vitamina D y calcimiméticos.

Secondary hyperparathyroidism (SHP) is a frequent complication of dialysis patients. In this second article we will analyze the new vitamin D analogs, capable of decreasing parathyroid hormone (PTH) levels with a lower effect on intestinal calcium and phosphorus absorption. Among other advantages described in the experimental setting, paricalcitol shows a survival benefit in dialysis patients as compared to calcitriol, at least in retrospective studies, and thus it became our first-line vitamin D derivative. Calcimimetics are unique since they decrease PTH levels without increasing serum calcium and phosphorus. Actually, calcium and phosphorus decrease in a significant number of patients. These drugs will soon be authorized in Spain, and we describe the better achievement of K/DOQI guidelines as well as other beneficial effects observed in the experimental animal with them. Finally, we mention the potential benefit of mild metabolic acidosis, the use of bisphosphonates, the role of bone morphogenetic protein BMP-7, and the use of teriparatide. The future treatment of SHP will probably require the independent management of calcium, phosphorus, vitamin D and PTH. Thus, low-dose combined treatments with selective drugs may prove more effective than sequential therapies.

Plasma and urinary heparin cofactor II levels in patients with nephrotic syndrome.

Heparin cofactor II (HC II) levels were measured by electroimmunoassay in plasmas and urines from 68 patients with nephrotic syndrome. In addition, antithrombin III (AT III) and protein C (PC) activities and antigens were measured also in the same group of patients. Seven of these patients had histories of thrombosis. Plasma HC II levels (mean +/- SD 105 +/- 43) were not different from levels in healthy subjects (94 +/- 17). Only 5 patients had low plasma levels of HC II. None of the patients with thrombosis had low HC II levels. Even though measurable amounts of HC II were found in 25 urines from 50 patients. There was a relationship in the urinary excretion between HC II and AT III and their urinary clearances were quite similar. However, no correlation was found between plasma HC II and AT III levels, and levels of AT III activity and antigen were significantly lower than in healthy subjects. Three patients with histories of thrombosis had low AT III levels. Most patients (including those with thrombosis histories) had high plasma PC levels and increased urinary loss. It is suggested that HC II does not play an important role in the pathogenesis of thrombosis in nephrotic syndrome.

Field evaluation and agronomic performance of transgenic wheat.

Seven transgenic lines of wheat have been evaluated under field conditions during 2 agonomic years. Four lines contained the transgenes for beta-glucuronidase ( uidA), herbicide resistance ( bar) and for one high-molecular-weight (HMW) subunit, and three lines contained only one transgene for one HMW glutenin subunit and no marker genes. Agronomic traits and yield components were studied in transgenic lines and compared with the non-transgenic parent and null segregant lines. Although phenotypic differences for many traits have been found, only heading date and the number of spikelets per spike showed clear genotypic differences for both field trials. All transgenic lines had a longer heading date than parent lines whereas the number of spikelets per spike in transgenic lines was around that for L88-31 and higher for L88-6 than the corresponding parent lines. No differences were found between lines constitutively expressing the uidA and bar genes from those which only expressed the HMW genes. We conclude that differences between transgenic lines and their parents are small, and could be eliminated by backcrossing transgenic lines with their parents and selecting for the wanted genotype.

Insertional tagging of regulatory sequences in tritordeum; a hexaploid cereal species.

As an approach to isolate novel cereal promoters, promoterless uidA constructs and particle bombardment were used to transform tritordeum. Five of eight transgenic lines containing uidA sequences showed evidence of promoter tagging. Expression of uidA was detected in four lines as: constitutive expression, expression in short cells of the epidermis of the spikelets, expression in pollen grains and in cells of the epidermis of the spikelet, and expression in anther primordia and pollen grains. In the fifth line, the uidA was shown by RT-PCR to be transcribed, but no GUS activity was detected. The different patterns of uidA expression indicate that different regulatory sequences were tagged in each of these lines. Analysis of the progeny resulting from self-fertilisation of the primary tagged plants, indicate that the transgenes integrated at one or two loci and the patterns of expression were stably inherited. To our knowledge, this is the first report of promoter tagging in cereals by direct gene transfer.

Analysis of particle bombardment parameters to optimise DNA delivery into wheat tissues.

The objective of this study was to identify the major parameters controlling DNA delivery by particle bombardment to wheat (Triticum aestivum L.) scutellum and inflorescence tissue. The main factors studied were the DNA/gold precipitation process, bombardment parameters and tissue culture variables. Efficiency of DNA (uidA gene) delivery was assessed by scoring transient GUS expression in bombarded tissues. Of the parameters analysed, amount of plasmid DNA, spermidine concentration, presence of Ca++ ions, calcium chloride concentration, amount of gold particles, gold particle size, acceleration pressure, chamber vacuum pressure, bombardment distance, osmotic conditioning of tissues and type of auxin had a clear influence on transient gene expression. A bombardment procedure suitable for elite wheat varieties was developed which allowed high-efficiency DNA delivery combined with reduced damage to target tissues.

[Study of the clinically useful interval in ambulatory monitoring of blood pressure]. / Estudio del intervalo clínicamente útil para monitorizar la presión arterial ambulatoria.

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) throughout 24 hours has been introduced for clinical practice, improving the diagnosis and treatment of hypertension. However, there is not an agreement concerning how often the blood pressure have to be measured. SUBJECTS AND METHODS: An ABPM was performed in 29 normotensive and hypertensive subjects (16-73 years) throughout 24 hours recording the blood pressure every 15 minutes. The average of systolic and diastolic blood pressure of the diurnal and nocturnal periods of the interval of 15 minutes, were compared with the two intervals of 30 minutes and the four of 60 minutes, according to Bland and Altman method. RESULTS: Between 90% and 100% of the differences of the interval 15 minutes versus 30 minutes, and 15 minutes versus 60 minutes, were within +2 and -2 standard deviation of the mean. However, only between 95% and 100% of the difference of the intervals 15 minutes versus 30 minutes were within the limits of agreement for systolic and diastolic blood pressure in the nocturnal period. CONCLUSIONS: A clinical satisfactory information using ABPM can be obtained monitoring the blood pressure every 15 minutes during the day and 30 minutes at night.

[Effect of antioxidative therapy on regeneration of ischemic liver]. / Efecto de terapéuticas antioxidantes en la regeneración del hígado isquémico.

Ischemia is a common situation, not always desirable, in liver surgery. In any case, it implies cellular damage that would be worth avoiding. In the present study, different antioxidant drugs (superoxide-dismutase, allopurinol and folinic acid) are administered prior to liver reperfusion in order to reduce ischemic damage. Liver regeneration, following a 70% hepatectomy and 15 minutes of normothermic hepatic ischemia, serves as an indirect functional test of the reperfused liver. SOD (6 mg/kg) and allopurinol (50 mg/kg) have accelerated hepatocytic DNA synthesis without increasing the number or percentage of activated hepatocytes. However, the folinic acid has proved to be very effective, counteracting the deleterious effect of liver ischemia on hepatocytic regeneration.

[Prevention of ischemic injury in hepatocellular transplant in the rat]. / Prevención del daño isquémico en el trasplante hepatocelular en la rata.

The aim of this study was to evaluate the efficacy of certain antioxidant and/or hepatotrophic drugs on the sensitivity to ischemia of hepatocytes implanted into the spleen. Twenty four hours after hepatocellular transplantation, animals were submitted to 15 minutes of normotermic ischemia followed by 70% hepatectomy. Hepatocytic function was assessed 24 h later by measuring the intensity of the regenerative response, both in the liver and in the spleen. All drugs increased the percentage of regenerating hepatocytes, but only allopurinol and cyclosporine achieved significance. However none of the drugs were useful for hepatocytes implanted in the spleen, allopurinol having a deleterious effect.

[Therapeutic usefulness of antioxidant drugs in experimental intestinal reperfusion syndrome]. / Utilidad terapéutica de fármacos antioxidantes en el síndrome de reperfusión intestinal experimental.

The intestinal reperfusion injury has been studied in Sprague-Dawley rats weighing 200 g. Intestinal ischemia has been induced by clamping the Superior Mesenteric Artery (SMA) for 120 minutes. In order to parallel clinical situations, free radical scavengers (allopurinol [ALLO]) and superoxide-dismutase [SOD] were inoculated at a low perfusion rate through the femoral vein during the last 20 minutes of the ischemic period. Both drugs have decreased the mortality rate (from 70% in control group, to 40%) and the mean percentage of damaged intestine (30.89% vs. 23.84% and 24.70%). Histologically, ALLO was less effective than SOD (12.54 control; 8.40 SOD; 11.54 ALLO). The modification of glucose, SGOT, SGPT and LDH found in all the ischemic animals shows the hepatocellular injury induced by intestinal reperfusion.

[Regenerative response of hepatocytes implanted in the spleen]. / Estudio de la respuesta regenerativa de hepatocitos implantados en el bazo.

Regenerative activity of syngenic hepatocytes inoculated into the spleen has been assessed. Partial hepatectomy and cyclosporine were used as regenerative stimuli. Nuclear DNA has been quantified by means of a cytophotometric method, and the intensity of the response has been defined as the Mean Percentage of Regenerating Hepatocytes (MPRH). Both hepatectomy and cyclosporine (alone or associated) have significantly increased splenic MPRH.

[The hepatotrophic action of cyclosporin A in a model of hepatic ischemia in the rat]. / Estudio de la acción hepatotrófica de la ciclosporina A en un modelo de isquemia hepática en la rata.

Liver ischemia is a common surgical situation. In this study the effect of 15 minutes of warm ischemia on liver regeneration in the rat is assessed. From hepatocytic DNA content (cytophotometrically measured), the percentage of regenerating hepatocytes (PRH) and the regenerative gradient (RG) are calculated in normal livers and following different regenerative stimuli: partial hepatectomy (70%) and cyclosporine (20 mg/kg i.p.). In resting livers (both controls and CsA-treated) the PRH and the RG were not modified by ischemia. However, liver regeneration following partial hepatectomy was significantly decreased by ischemia. In the other hand, CsA has increased the PRH and the RG in the four situations analyzed: resting and regenerating liver, both normoperfused or following 15 minutes liver ischemia. It is concluded that the hepatotrophic effect of CsA is not nullified by warm liver ischemia.

[Critical study of the Kennedy-LAD procedure]. / Etude critique de la plastie de Kennedy-Lad.

The authors report their experience with ligament repair, using the Kennedy-LAD technique in 19 cases of chronic anteromedial and anterolateral instability. The postoperative follow-up was 3 to 4 years. They conclude that this repair provides excellent stability, but that the results are jeopardized by serious problems of biocompatibility; in 63% there was recurrent synovitis. According to the "Arpège" criteria, there was a mean of 58% poor results and 42% good or excellent results. Twenty-one percent of the patients were satisfied with the operation, and 25% were seriously dissatisfied. Stability, as evaluated by the postoperative radiological active Lachman test, was normal in 84% of the patients (0-6 mm anterior tibial deplacement).

[Advancements in the genetics of cystinuria]. / Progrès dans la génétique de la cystinurie.

Cystinuria is an amino acid disease due to a defect of intestinal and renal tubular transport of cystine and various basic amino acids (lysine, arginine and ornithine). The disease is transmitted horizontally according to an autosomal recessive pattern. The overall prevalence is one per 7,000 live births. It is the commonest hereditary disease affecting amino acid transport (MIM 220100). This disease is characterized by excessive urinary excretion of cystine and basic amino acids. From a clinical point of view, almost 50% of homozygotes will develop cystine renal stones with urinary tract infection, renal colic, partial or total obstruction of the urinary tract and possibly loss of renal function.

[2,8 dihydroxyadenine(2,8 DHA) lithiasis. Report of 3 cases]. / Litiasis de 2,8 dihidroxiadenina (2,8 DHA). A próposito de tres casos.

Presentation of three cases of 2,8 dihydroxyadenine calculi. This is an infrequent but potentially serious form of lithiasis, of purinic origin, caused by a genetic abnormality (deficit of adenine phosphoribosyltransferase, APRT) affecting both sexes. Frequent confusion of this form with uric lithiasis forces to try the use of IR spectrum or X-ray diffraction. Long-term follow-up of these patients and treatment with allopurinol, avoiding alkalinizating agents, is essential.

Biotechnology of breadmaking: unraveling and manipulating the multi-protein gluten complex.

Breadmaking is one of humankind's oldest technologies, being established some 4,000 years ago. The ability to make leavened bread depends largely on the visco-elastic properties conferred to wheat doughs by the gluten proteins. These allow the entrapment of carbon dioxide released by the yeast, giving rise to a light porous structure. One group of gluten proteins, the high molecular weight (HMW) subunits, are largely responsible for gluten elasticity, and variation in their amount and composition is associated with differences in elasticity (and hence quality) between various types of wheat. These proteins form elastomeric polymers stabilized by inter-chain disulphide bonds, and detailed studies of their structures have led to models for the mechanism of elasticity. This work has also provided a basis for direct improvement of wheat quality by transformation with additional HMW subunit genes.