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J Torrado

Publications and source records attributed to J Torrado.

At least 19 recordsLinked to original sources

Therapeutic actions of insulin-like growth factor I on APP/PS2 mice with severe brain amyloidosis.

Transgenic mice expressing mutant forms of both amyloid-beta (Abeta) precursor protein (APP) and presenilin (PS) 2 develop severe brain amyloidosis and cognitive deficits, two pathological hallmarks of Alzheimer's disease (AD). One-year-old APP/PS2 mice with high brain levels of Abeta and abundant Abeta plaques show disturbances in spatial learning and memory. Treatment of these deteriorated mice with a systemic slow-release formulation of insulin-like growth factor I (IGF-I) significantly ameliorated AD-like disturbances. Thus, IGF-I enhanced cognitive performance, decreased brain Abeta load, increased the levels of synaptic proteins, and reduced astrogliosis associated to Abeta plaques. The beneficial effects of IGF-I were associated to a significant increase in brain Abeta complexed to protein carriers such as albumin, apolipoprotein J or transthyretin. Since levels of APP were not modified after IGF-I therapy, and in vitro data showed that IGF-I increases the transport of Abeta/carrier protein complexes through the choroid plexus barrier, it seems that IGF-I favors elimination of Abeta from the brain, supporting a therapeutic use of this growth factor in AD.

Amyloid beta-Peptides↗

[Type III glycogen storage disease associated with hepatocellular carcinoma].

Type III glycogen storage disease is a hereditary disorder with autosomal recessive transmission. It is characterized by accumulation of abnormal glycogen in the liver and, in 80% of patients, in muscle. The liver can also show fibrosis and sometimes cirrhosis. Until 2000, 9 cases of cirrhosis had been published, 3 of which showed associated hepatocarcinoma. We present the case of a 31-year-old woman, diagnosed in childhood with type III glycogen storage disease, who 30 years after onset developed a hepatocellular carcinoma with portal thrombosis in the context of advanced cirrhosis. This is the first case to be reported in the Spanish literature of type III glycogen storage disease associated with hepatocellular carcinoma.

Adult↗

[Liver alterations due to alpha-1-antitrypsin deficiency in adults. Study of 5 patients and analysis of the cases reported in the Spanish literature].

BACKGROUND: To determine the epidemiological characteristics of liver disease secondary to alpha-1-antitrypsin deficiency and associated processes in the Spanish population. PATIENTS AND METHOD: We reviewed the medical records of adults with liver abnormalities due to alpha-1-antitrypsin deficiency diagnosed between 1981 and 2001 in the Hospital Donosti in San Sebastian (Spain) as well as the cases published in the literature before 1999. Diagnosis was based on clinical and biochemical data, imaging tests and/or liver biopsy and/or necroscopy together with serum values of alpha-1-antitrypsin and phenotyping. RESULTS: Fifty cases of liver disease secondary to alpha-1-antitrypsin deficiency (45 from the literature and 5 from our hospital) were included. There were 34 men and 16 women aged between 18 and 77 years. Fifteen (30%) had relatives with alpha-1-antitrypsin deficiency. Hepatitis and/or neonatal cholestasis were confirmed in 4 and alcoholism was confirmed in 17. Of the series, 8 (16%) had portal fibrosis and 29 (58%) had cirrhosis. Cirrhosis was mainly macro-micronodular and was decompensated in 48% of the cases. Of the patients with cirrhosis, 12 were ZZ homozygotes and 12 were heterozygotes, mainly MZ and SZ. The most frequent associated process was respiratory disease (emphysema and/or chronic bronchitis) in 25 of the 50 cases (50%). CONCLUSIONS: The presence of cirrhosis in alpha-1-antitrypsin deficiency is low, approximately 2.2/100,000 for ZZ homozygotes. Age at diagnosis of cirrhosis or fibrosis was more than 50 years. The male-to-female ratio was 2 to 1. In one-third of the patients alcohol could have been a coadjuvant or aggravating factor in the liver disease. No differences were found between homo- and heterozygote phenotypes in patients with cirrhosis. The most frequently associated processes were respiratory diseases due to alpha-1-antitrypsin deficiency.

Adolescent↗

Effect of two formulations of benzimidazole carbamates on the viability of cysts of Echinococcus granulosus in vivo.

Two different preparations, solution and suspension, of three benzimidazole carbamate drugs, mebendazole, albendazole and ricobendazole, were compared by analyzing their in vivo activity against Echinococcus granulosus cysts in a mouse model. Polyvinylpyrrolidone was used for the elaboration of drug solutions and these formulations manifested better results in terms of reduction of number of viable hydatid cysts in mice than the reference drug suspensions. The effect was more prominent on mebendazole-treated mice, at doses of 25-50 mg/kg. There was a correlation between ED50 and pharmacokinetical parameters of AUC0-infinity and Cmax, showing that a significant improvement on solubility affects the in vivo activity of these drugs.

Albendazole↗

Pharmacological characteristics of parenteral IGF-I administration.

Insulin-like growth factor-I (IGF-I) is a naturally occurring single chain polypeptide of 7649 Da that is produced primarily in the liver. The metabolic activities of IGF-I are similar to those of insulin and its effects on growth, development, regeneration and metabolism have been widely studied. Indeed, IGF-I is currently being used clinically for the treatment of growth related disorders and its therapeutic value is also being evaluated in diabetes, IGF-I-induced neuroprotection, and in promoting bone healing. However, like many other peptides, IGF-I has a short biological half-life and is rapidly removed from circulation following systemic administration. In the vascular system, this is normally compensated for by the association of IGF-I with IGF-binding proteins (IGFBPs), that also appear to regulate the activities of IGF-I. Here, we describe the biopharmaceutical properties of different parenteral formulations of IGF-I. The pharmaceutical characteristics of conventional formulations such as aqueous IGF-I solutions are compare with new controlled release formulations such as multivesicular liposomes, osmotic minipumps, and poly (DL-lactic-co-glycolic) acid (PLGA) microspheres.

Animals↗

[Fasciola hepatica. study of a series of 37 patients].

BACKGROUND: To analyze the clinical, bacteriologic, diagnostic and therapeutic features of patients with Fasciola hepatica (FH) in our hospital. PATIENTS AND METHOD: We reviewed all the patients with a diagnosis of fascioliasis from 1975 to 1999 in the Aranzazu Hospital in San Sebastián (Guipúzcoa, Spain). Diagnosis was made by direct vision of adult parasites during surgery and/or the presence of ova in stool examinations and/or positive serologic tests in patients with symptoms consistent with parasitosis. RESULTS: Thirty-seven patients were included (23 men and 14 women), aged 19 to 71 years. Ingestion of watercress was confirmed in 27. Seven cases occurred as part of familiar outbreaks. Thirty-two were in the liver invasive stage and in 5 the biliary tree was invaded. The most common features were eosinophilia (91.8%), malaise and weight loss (75.6%), elevated alkaline phosphatase (74.2%), and abdominal pain (72.9%). Adult worms in the biliary ducts were observed in 3 patients and ova in feces were observed in 6. In 13 of 27 patients indirect hemagglutination test was ( 1/1,280. Data significant to confirmation of liver involvement were provided by laparoscopy in 12 of 13 patients and by imaging techniques in 13 of 31 patients. Four patients had cholelithiasis and of these, 2 also showed adult parasites in the common bile duct. Three patients underwent surgery. Therapy with dehydroemetine and/or bithionol was followed by complete remission in 30 patients, although 6 required repeat treatment cycles. The remaining 4 patients were cured by praziquantel. CONCLUSIONS: Most of the patients in these series reported consumption of watercress and all patients showed the symptoms typical of parasite disease. Imaging techniques proved to be of great utility in confirming the diagnosis of hepato-biliary disease. In most of the patients therapy with dehydroemetine and/or bithionol (in one or several cycles) was followed by complete remission.

Adult↗

[Krukenberg tumor secondary to gastric carcinoma in a woman in her eighth month of pregnancy].

The association of gastric cancer and pregnancy is rare. The cases reported by non-Japanese authors are unusual. Tumors tend to be in advanced stage when diagnosed since the symptoms of gastric cancer are easily presumed to be secondary to those of normal pregnancy. We report the case of a 43-year-old female with gastric carcinoma presenting as a Krukenberg's tumor in the eighth month of gestation. A healthy child was born and after delivery, partial gastrectomy was performed and adjuvant chemotherapy was administered. The patient died 12 months after diagnosis.

Adult↗

Improving bioavailability and anthelmintic activity of albendazole by preparing albendazole-cyclodextrin complexes.

The bioavailability and anthelmintic activity of albendazole-cyclodextrin complexes (ABZ-CDC) compared to albendazole suspensions in carboxymethylcellulose (ABZ-CMC) was assessed in a mouse model for Trichinella infections. Swiss CD-1 mice experimentally infected with T. spiralis were treated with both formulations against enteral (adult worms) and parenteral (migrating and encysted larvae). Oral bioavailability was assessed in age matched mice treated with 50 mg/kg of both formulations. The anthelmintic effects and plasma concentration of the active metabolite albendazole-sulphoxide (ABZSO) enantiomer (-) were significantly increased following administration of ABZ-CDC in relation to ABZ-CMC.

2-Hydroxypropyl-beta-cyclodextrin↗

Role of fucosyltransferases in the association between apomucin and Lewis antigen expression in normal and malignant gastric epithelium.

BACKGROUND: In normal gastric epithelium, MUC5AC is detected in superficial epithelium associated with Lewis type 1 antigens and MUC6 is detected in antral glands with Lewis type 2. Therefore, the stomach constitutes an excellent model to examine the role of glycosyltransferases in determining the specificity of apomucin glycosylation. AIMS: To determine the molecular basis of this association and to examine changes in expression of gastric and intestinal apomucins and their association with Lewis antigens during the gastric carcinogenesis process. METHODS: Fucosyltransferase (FUT1, FUT2, FUT3) and mucin (MUC5AC, MUC6) transcripts were detected using reverse transcription-polymerase chain reaction. Apomucin (MUC2, MUC4, MUC5AC, MUC6) and Lewis antigen (types 1 and 2) expression were analysed using single and double immunohistochemistry and in situ hybridisation. RESULTS: In the normal stomach, FUT1 is exclusively detected associated with MUC6; FUT2 is only detected when MUC5AC is present. This co-regulation is lost in gastric tumours, as is differential expression of MUC5AC and MUC6 in normal gastric epithelial cells. In gastric tumours, especially those with the intestinal phenotype, MUC2 and MUC4 genes are upregulated, and gastric-type and intestinal-type mucins are coexpressed. These changes are early events in the gastric carcinogenesis process, as they are detected in intestinal metaplasia. CONCLUSIONS: The glycosylation pattern found in normal gastric epithelium is dictated by the specific set of fucosyltranferases expressed by the cells rather than by the apomucin sequence. The development of intestinal metaplasia and gastric cancer is associated with the appearance of cellular phenotypes that are absent from normal epithelium.

Antigens, Tumor-Associated, Carbohydrate↗

Lewis antigen alterations in a population at high risk of stomach cancer.

Anomalous Lewis(a) antigen and sulfomucin expression are considered as markers of progression in precursor lesions of gastric cancer. Additionally, Lewis antigen and secretor phenotype have been related to Helicobacter pylori infection and gastric epithelial damage. The two objectives of this study were to correlate Lewis antigen alterations with histochemical changes and to explore the relationship between Lewis and secretor phenotypes and gastric epithelial damage related to H. pylori infection. The study subjects were selected from a chemoprevention trial in Tachira State, Venezuela, an area with a high risk of gastric cancer. Anomalous Lewis(a) antigen expression in Lewis (a-b+) phenotype individuals was closely related to the severity of the histological lesions, especially to dysplasia and type III intestinal metaplasia lesions. A weak relationship was observed between nonsecretor individuals and more advanced lesions of IM, but this association was not statistically significant. There was no relationship between secretor phenotype and H. pylori status, atrophy, regenerative activity, erosion, or ulcer.

Adult↗

Blood-group phenotypes, sulfomucins, and Helicobacter pylori in Barrett's esophagus.

Barrett's esophagus, morphologically analogous to gastric intestinal metaplasia, often precedes the development of esophageal adenocarcinoma. In the stomach, expression of sulfomucins and aberrant Lewis(a) (Le[a]) antigen is an excellent predictor of premalignant progression, and Helicobacter pylori infection is a crucial determinant for the development of atrophy, metaplasia, and adenocarcinoma. In the esophagus, the significance of sulfomucin expression is controversial, the aberrant expression of Le(a) has not been explored, and the role of H pylori in the evolution of preneoplastic conditions is unknown. We investigated in 155 patients referred for endoscopy the association of Barrett's esophagus with expression of sulfomucins, Lewis, secretor, and ABO phenotypes, and H pylori infection. We report a subtype of intestinal metaplasia, present in all patients with esophageal adenocarcinoma, similar to gastric intestinal metaplasia of colonic type (type III or incomplete), that expresses sulfomucins and aberrant Le(a) in goblet and columnar cells. Lewis(a+b-), nonsecretor and blood group A phenotypes, were all positively associated with esophageal adenocarcinoma, suggesting a genetic susceptibility. H pylori infection was detected in 75% of patients with esophageal adenocarcinoma.

ABO Blood-Group System↗

Lewis, secretor, and ABO phenotypes, and sulfomucin expression in gastric intestinal metaplasia.

The closely interrelated Lewis, secretor, and ABO phenotypes have long been linked to the risk of peptic ulcers and gastric cancer and may modulate the interaction between Helicobacter pylori and the gastric surface epithelium. We explored the association between the expression of sulfomucins in gastric intestinal metaplasia, a known marker of preneoplastic progression, and the expression of Lewis, secretor, and ABO phenotypes, in 523 subjects from Nariño, Colombia, and 856 subjects from northern Spain. In both study populations, Lewis (a+/b-) and nonsecretor phenotypes showed a significant positive association with the expression of sulfomucins (odds ratios, 2.4 and 2.6, respectively).

ABO Blood-Group System↗

[Intestinal autograft: creation of an isolated intestinal segment by entero-enteropexy].

An isolated bowell segment (IBS) was created in rats by a two-stage procedure. Initial lateral entero-enteropexy between small and colonic bowell was performed. Six weeks later, the small bowell mesentery was divided. After four weeks, the survival animals were killed, the viability of the segment is maintained by developing vascular collateral across the coaptation between both intestinal segments, under light microscopy the willi were atrophied on 50% of animals.

Animals↗