[A European clinical trial register in the pediatric field: DEC-net].
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Child↗
Biomedical subjects
I Fuentes
Publications and source records attributed to I Fuentes.
Phosphatase-1 and -2A inhibition modulates apoptosis in human osteoarthritis chondrocytes independently of nitric oxide production.
OBJECTIVE: To characterise the role of phosphatase-1 and -2A (PP1/2A) in the modulation of apoptosis in human osteoarthritis (OA) chondrocytes. METHODS: Human OA chondrocytes were isolated from cartilage obtained from the femoral heads of patients undergoing joint replacement surgery. Cell viability was evaluated by MTT assay. Apoptosis was quantified by ELISA, which measures DNA fragmentation. Nitric oxide (NO) production was evaluated by the Greiss method, and inducible nitric oxide synthase (iNOS) protein synthesis was studied by western blotting. RESULTS: Inhibition of PP1/2A by the specific inhibitor okadaic acid (OKA) dose and time dependently caused a reduction of cell viability (OKA at 50 nmol/l: a reduction to 60% and 43% at 48 and 72 hours, respectively). Genomic DNA from chondrocytes treated with OKA at 50 and 100 nmol/l for 48 hours displayed increased internucleosomal DNA fragmentation by 11 and 13 fields, respectively. Light microscopy and DAPI studies showed that OKA induced DNA condensation and fragmentation, typical of death by apoptosis. The caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK increased cell viability, reduced by OKA at 50 nmol/l to 87% and 73%, respectively. OKA did not increase iNOS protein synthesis or NO production. CONCLUSION: PP1/2A modulate apoptosis in human OA chondrocytes; this is independent of NO production but dependent on caspases.
Amino Acid Chloromethyl Ketones↗
Solubilization of p-nitrophenol in aggregates formed by hydrophobically modified polyelectrolytes.
The solubilization of p-nitrophenol into the hydrophobic microdomains provided by polyelectrolytes carrying alkyl side chains of different length has been investigated in aqueous solutions of pH 5.0 and 8.0. Under these pH conditions p-nitrophenol is predominantly present in its neutral and ionic forms, respectively. Potassium salts of poly(maleic acid-co-1-olefins), PA-nK2 with n = 12, 14, 16, 18, were synthesized, and the pseudo-phase model was used to determine the distribution coefficient KS, and the standard free energy of transfer Deltamut0 of p-nitrophenol between water and polymer aggregates. The results indicate that at both pH's the solubilization of p-nitrophenol increases with increasing size of the side alkyl chain; i.e., the values of KS follow the order PA-18K2 > PA-16K2 > PA-14K2 > PA-12K2. The free energies, Deltamut0, were plotted as a function of the number of carbon atoms in the side alkyl chain and a linear relation was found. From these plots contributions of -0.324 and -0.676 kJ mol(-1) per methylene group were determined at pH 5.0 and 8.0, respectively. The effect of aggregate size on the solubility of phenol is attributed to the hydrophobic contribution per CH2 group to the free energy of transfer. The hydrophobic nature of the CH2 group is suggested to derive largely from the enthalpic contribution.
Journal Article↗
[Progressive deterioration in an elderly patient].
Vasculitis is diagnosed with increasing frequency in the elderly. We hereby present the case of an 84-year-old male, who had weight loss, low-degree fever, anemia and epigastric pain. After 14 days of study with the tentative diagnosis of digestive neoplasia, a progressive renal insufficiency was detected. This clinical picture was secondary to ANCA-positive vasculitis. The case poses the differential diagnosis of non-oliguric acute renal failure (FRA) in elder people and the systematics of the study of renal insufficiency in individuals with previously unknown renal function. Also, this patient's history emphasizes the importance of acute deterioration of renal function as a guiding symptom for orienting the interpretation of clinical data. In the present case, a diagnostic hypothesis based only in the pursue of an occult digestive tumor misguided the attention from the main cause of the disease.
Abdominal Pain↗
Muscle fibre types in the suprahyoid muscles of the rat.
Five muscle fibre types (I, IIc, IIa, IIx and IIb) were found in the suprahyoid muscles (mylohyoid, geniohyoid, and the anterior and posterior bellies of the digastric) of the rat using immuno and enzyme histochemical techniques. More than 90% of fibres in the muscles examined were fast contracting fibres (types IIa, IIx and IIb). The geniohyoid and the anterior belly of the digastric had the greatest number of IIb fibres, whilst the mylohyoid was almost exclusively formed by aerobic fibres. The posterior belly of the digastric contained a greater percentage of aerobic fibres (83.4%) than the anterior belly (67.8%). With the exception of the geniohyoid, the percentage of type I and IIc fibres, which have slow myosin heavy chain (MHCbeta), was relatively high and greater than has been previously reported in the jaw-closing muscles of the rat, such as the superficial masseter. The geniohyoid and mylohyoid exhibited a mosaic fibre type distribution, without any apparent regionalisation, although in the later MHCbeta-containing fibres (types I and IIc) were primarily located in the rostral 2/3 region. In contrast, the anterior and posterior bellies of the digastric revealed a clear regionalisation. In the anterior belly of the digastric 2 regions were observed: both a central region, which was almost exclusively formed by aerobic fibres and where all of the type I and IIc fibres were located, and a peripheral region, where type IIb fibres predominated. The posterior belly of the digastric showed a deep aerobic region which was greater in size and where type I and IIc fibres were confined, and a superficial region, where primarily type IIx and IIb fibres were observed.
Animals↗
Genotypic characterization of Toxoplasma gondii strains associated with human toxoplasmosis in Spain: direct analysis from clinical samples.
Genetic analysis of the SAG2 locus was performed to determine the prevalence of the different genotypes of Toxoplasma gondii (strain types I, II, and III) associated with human toxoplasmosis in Spain. This determination was made directly from primary clinical samples, obviating the previous process of isolation in mice or cell culture. A total of 34 isolates of T. gondii, collected from immunocompromised patients and congenital infection cases, were analyzed. Restriction fragment length polymorphism in PCR-amplified SAG2 products was used to group strains into one of the three genotypes of T. gondii. Complete characterization of the SAG2 gene was successful in 76.5% of the cases, demonstrating the feasibility of direct genotype analysis from clinical samples of different origins. Strains of T. gondii type II were the most prevalent in immunocompromised patients, with 52% of cases, while strains of type I were present in 75% of the congenital infection cases. These data differ from previous reports that show type II strains to be mostly associated with all kinds of human toxoplasmosis. These differences might be an effect of selection in the process of culture and isolation of the samples performed by other researchers prior to strain characterization.
Animals↗
[Validation of the Spanish version of the Epworth Sleepiness Scale in patients with a sleep apnea syndrome].
A Spanish version of the Epworth Sleepiness Scale (ESS-Sp) was developed by translation, back-translation, formal discussion, and a meeting of researchers with a group of patients with sleep apnea syndrome (SAS). The translated questionnaire was then tested in 345 patients, 275 with SAS at various levels of severity and 70 without SAS. Significant differences existed between the two groups as to age (53 +/- 11 years versus 47 +/- 13, p < 0.001) and BMI (32 +/- 5 versus 29.5 +/- 5, p < 0.001). Patients with SAS had significantly higher scores (14 +/- 5) than did those without SAS (10 +/- 5) (p < 0.001). Reproducibility was tested in 146 patients (113 SAS and 33 non-SAS), with no significant differences found among patients with SAS (14.9 +/- 5 versus 14.2 +/- 5, p = n.s.); significant differences in BMI were found, however, among the 33 non-SAS patients (12 +/- 5 versus 10 +/- 5, p < 0.01). Total scores and individual item scores were related in both groups. Likewise, each item was related to total score in patients with SAS. Sensitivity to post-treatment changes was assessed in 77 SAS patients, with initial scores of 16 +/- 4 seen to decrease to 4 +/- 3 after continuous positive airway pressure. ESS-Sp scores over 10 were recorded for 85% of patients with SAS: 78% of those with mild SAS, 85% of those with moderate disease and 92% of those whose SAS was severe. Significant inter-group differences were found upon applying a test of variance (p < 0.001). Differences continued to be detected when multiple correlations were looked for, with differences increasing with severity. SAS patients with ESS-Sp level one scores (< 10) had lower apnea-hypopnea indices (AHI) (35 +/- 18 versus 42 +/- 20, p < 0.05), lower desaturation levels (21 +/- 21 versus 34 +/- 28, p < 0.01) and higher minimum saturation (80 +/- 10 versus 75 +/- 12, p < 0.05), with no differences in age or BMI. A significant correlation was found between ESS-Sp score and respiratory variables recorded during polysomnography: AHI, r = 0.23 (p < 0.001); percent time in apnea-hypopnea, r = 0.18 (p < 0.01); desaturation index, r = 0.27 (p < 0.01) and minimum saturation (r = -0.14, p < 0.05). We conclude that the Spanish version of the ESS is equivalent to the original, is reproducible in patients with SAS, sensitive to post-treatment changes and seems to discriminate level of severity, showing correlation with polysomnograph variables.
Adult↗
Nocturnal oximetry for the diagnosis of the sleep apnoea hypopnoea syndrome: a method to reduce the number of polysomnographies?
BACKGROUND: Polysomnography (PSG) is currently the "gold standard" for the diagnosis of the sleep apnoea hypopnoea syndrome (SAHS). Nocturnal oximetry (NO) has been used with contradictory results. A prospective study was performed to determine the accuracy of NO as a diagnostic tool and to evaluate the reduction in the number of PSGs if the diagnosis of SAHS had been established by this method. METHODS: Two hundred and seventy five patients with a clinical suspicion of SAHS were admitted to undergo, in the same night, full PSG and NO. Desaturation was defined as a fall in the haemoglobin saturation level (SaO(2)) to lower than 4% from the baseline level and an oxygen desaturation index per hour (ODI) was obtained in each patient with three cut off points: >/= 5 (ODI-5), >/= 10 (ODI-10), and >/= 15 (ODI-15). RESULTS: SAHS was diagnosed in 216 patients (194 men). After withdrawing patients with abnormal lung function (forced expiratory volume in one second (FEV(1)) lower than 80% predicted), sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of NO were: ODI-5 (80%, 89%, 97%, 48%); ODI-10 (71%, 93%, 97%, 42%); ODI-15 (63%, 96%, 99%, 38%). The accuracy for each ODI was 0.81, 0.75, and 0.70, respectively. If NO had been considered as a diagnostic tool and PSG had been performed only in patients with a negative NO (false negative and true negative) and those with a positive NO and abnormal pulmonary function tests, 135/275 (ODI-5), 156/275 (ODI-10), and 170/275 (ODI-15) PSGs would have been performed, a reduction of 140, 119, and 105, respectively. CONCLUSION: Nocturnal oximetry in patients with suspected SAHS and normal spirometric values permits the institution of therapeutic measures in most patients.
Female↗
[Myopathy secondary to the treatment with inhibitors of HMG-CoA reductase].
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Creatine Kinase↗
Muscle fibre types and their distribution in the biceps and triceps brachii of the rat and rabbit.
Muscle fibre type composition and distribution in the biceps brachii (long head) and triceps brachii (long head) of the rat and rabbit were investigated using the following histochemical techniques: myosin ATPase, with preincubation at pH 10.4 and 4.35; succinate dehydrogenase (SDH) and glycogen phosphorylase. The muscle fibres were classified into slow-twitch (SO), fast-twitch glycolytic (FG), fast-twitch oxidative glycolytic (FOG and FOg) and fast-twitch oxidative fibres (FO). Significant differences in the regional distribution of muscle fibre types have been observed between the rat and the rabbit. In the rat, SO fibres were restricted to the deep regions of both biceps and triceps brachii, whereas FG fibres were located in the intermediate and superficial regions (the superficial regions contained the highest percentages of FG fibres). In the rabbit, SO and FG fibres were spread over the entire muscle, although SO and FG fibres were most abundant in the deep and superficial regions respectively. These findings indicate that the biceps and triceps brachii are more regionalised in the rat than in the rabbit.
Adenosine Triphosphatases↗
Absorption studies of albendazole and some physicochemical properties of the drug and its metabolite albendazole sulphoxide.
In several studies of patients with neurocysticercosis under treatment with albendazole the pharmacokinetic data were difficult to interpret, probably because of slow and erratic drug dissolution response and absorption problems in-vivo. Because there is no information available about the physicochemical properties of the drug, the aim of this work was to explain this erratic behaviour by fully characterizing the solution behaviour of the drug and its metabolite. To accomplish this, the physicochemical properties, pKa and solubility, and in-vitro plasma binding of albendazole and its main metabolite, albendazole sulphoxide, were studied by conventional methods. The intestinal and gastric absorption and dissolution behaviour of albendazole were also studied. The solubility of both compounds is very low. Both are amphoteric molecules with two ionization steps, with pKa values of 10.26 and 2.80 for albendazole and 9.79 and 0.20 for albendazole sulphoxide; low pKa values were obtained by performing linear free energy relationship calculations. On the other hand, protein binding studies showed that albendazole is 89-92% bound to plasma proteins whereas for albendazole sulphoxide the figure is 62-67%. This metabolite is bound by albumin and to alpha1-glycoprotein. Absorption of albendazole occurs along the gastrointestinal tract and is limited by its solubility. Good dissolution profiles were observed when 0.1 M HCl was used as dissolution medium. The results show that 0.1 M HCl enables discrimination between the drug-release characteristics of different products.
Albendazole↗
The distribution of 10-hydroxy carbazepine in blood compartments.
The distribution of 10-hydroxy carbazepine (MHD), the main metabolite of oxcarbazepine (OXC), was investigated in plasma and red cells. After the oral administration of 600mg of OXC to nine healthy volunteers, blood samples were withdrawn for the next 56h and packed red cells were separated from plasma by centrifugation. Also, in vitro studies of plasma binding of MHD were carried out by a dialysis technique. Results showed that the in vitro protein binding was low. The mean bound concentration ranged from 37 to 40%; however, an affinity of MHD to red corpuscles was found. These observations indicate that MHD red blood cell concentrations together with plasma measurements could be useful in cases of inefficacy or toxicity in order to make the appropriate drug adjustments.
Administration, Oral↗
Urine sample used for congenital toxoplasmosis diagnosis by PCR.
The diagnosis of toxoplasmosis in congenitally infected infants can be difficult; serology is unreliable, and diagnosis must be based on the combination of symptomatology and direct demonstration of the parasite. Four infants suspected of having Toxoplasma gondii infection were studied by serological analysis, tissue culture, and PCR determination. T. gondii was isolated from the urine of one patient. The parasite was detected by PCR in the blood and cerebrospinal fluid of three infants and in the urine in all patients. Because nested PCR proved to be a sensitive, relatively rapid, and specific method and because it can be applied to a variety of different clinical samples, PCR can be a valuable technique for the identification of T. gondii infections in children. The present study indicates that PCR examination of urine, a fluid never before used for diagnosis in this age group, may be valuable in diagnosing cases of congenital toxoplasmosis.
Animals↗
[Cerebral toxoplasmosis in patients with human immunodeficiency virus (HIV) infection. Clinico-radiological and therapeutic aspects in 63 patients].
We have retrospectively reviewed 63 cases of encephalic toxoplasmosis (ET) in HIV-infected patients in order to determine clinical and radiological characteristics, the diagnostic value of serologic determinations, and the response to antioxoplasmic therapy. ET was the AIDS-defining condition in 44% of the patients. Eighty of the patients had a CD4 cell count < 100/microliters when ET was diagnosed. Only 4.8% of the patients had been taking anti-Pneumocytis carinii prophylaxis with cotrimoxazol. The most frequent clinical presentation was focal neurologic signs in 80.9% of the patients, with headache and fever in 53.3% and 42.4%, respectively. The most frequent cerebral CT finding was hipodense lesions (92%) with ring enhancement (68.9%). They were most frequently had a hemisferic location. Seroconversion was detected in two patients (6%), whereas 55 patients had serologic evidence of latent infection by Toxoplasma gondii (87.3%). Ninety eight percent of the patients were treated with sulphadiazine plus pyrimethamine. However, such therapy should be discontinued in 22% of them and switched to clindamycin plus pyrimethamine. The overall mortality rate during the acute phase of the disease was 7.9%, but 41.4% of the survivors exhibited neurologic sequelae. Relapsing ET was detected in 33.3% of the patients, and it was usually due to discontinuation of treatment. The mean survival time after the diagnosis of ET was 11.5 months. ET is the most common opportunistic infection of the central nervous system among our AIDS patients. Primary prophylaxis for toxoplasmic infection seems advisable in our epidemiologic environment, when CD4 cell count is less than 200/microliters and there is serologic evidence of latent infection. Acute ET usually has a good response to therapy, and the acute mortality rate is low. However, most of the survivors will remain with neurologic sequelae. The high frequency of adverse effects to sulphamide therapy with clindamycin make the need of alternative treatment strategies urgent.
Acquired Immunodeficiency Syndrome↗
[Evaluation of chromogenic medium CPS ID2 (bioMérieux) in urine cultures].
BACKGROUND: The aim of the study was to evaluate the chromogenic agar plate CPS ID2 (bioMérieux) and determine its cost-benefit ratio. METHODS: A total of 2,193 urinary sediments were processed. The urine culture was carried out in CPS ID2 agar and in cystine-lactose electrolyte deficient (CLED) agar, when needed. Identification of the microorganisms was performed following standard microbiologic procedures through biochemical tests prepared in our laboratory. The identification, from CPS ID2 agar, by direct detection in medium of four metabolic activities: beta-glucuronidase, beta-glucosidase, deaminase, and indol production, was performed following to manufacturer's instructions. RESULTS: A total of 289 urine cultures were positive, 18 were negative and 34 were contaminated samples. The identification, directly performed from the colonies detected in CPS ID2 agar, was correct in 96% of 166 Escherichia coli, in 92% of 24 Proteus mirabilis and in 97% of 38 enterococci. CPS ID2 agar exhibited 94% and 100% sensitivity and specificity, respectively in E. coli identification, 92% and 100% in P. mirabilis and 97% and 99% in Enterococcus. The use of this new media, CPS ID2, in our laboratory, implies a budgetary increment. However, if commercial galleries are used for routine identification, the cost will be reduced using this new media. CONCLUSIONS: The CPS ID2 agar allows the isolation and direct identification of the most frequent urinary tract pathogens: E. coli, P. mirabilis and Enterococcus in primary isolation medium. Using this medium, bacteriologists will be able to save time and reagents when identifying the most common uropathogens. Furthermore, the use of this medium would reduce costs in some laboratories.
Agar↗
[IgA antibodies in the diagnosis of toxoplasmosis].
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Animals↗
Human subcutaneous dirofilariasis caused by Dirofilaria repens in Ibiza, Spain.
A case of human subcutaneous dirofilariasis contracted in Ibiza, Spain is reported. An incomplete nematode extracted from the eyelid of a woman patient was identified on the basis of its anatomic and histologic characteristics as a nongravid adult female of the species Dirofilaria repens. The subcutaneous location of the worm, together with the epidemiologic data, support this finding.
Adult↗
Campylobacter species: identification and resistance to quinolones.
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Anti-Infective Agents↗