Characterization of the prostaglandin E2 pathway in a rat model of esophageal adenocarcinoma.

UNLABELLED: Accumulating evidence indicates that the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays a key role in esophageal carcinogenesis. A better understanding of the pathway downstream of COX-2 may reveal novel targets for the prevention of esophageal adenocarcinoma (EAC). The objective of this study was to characterize the profile of genes involved in PGE2 metabolism and signaling in an experimental model of EAC. Esophagojejunostomy with gastric preservation was performed in wistar rats to induce gastroduodenal reflux. Rats were sacrificed 2 or 4 months after surgery. Nine non-operated rats were used to obtain normal (control) esophageal tissues. RESULTS: All rats that underwent esophagojejunostomy developed inflammation. In addition, 90% of the animals showed intestinal metaplasia; of those, 40% progressed to AC. This process was accompanied by a significant increase in esophageal PGE2 levels and the induction of both mRNA and protein levels of COX-2, COX-1, prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, and PGE2 receptors EP3, EP4 and especially EP2, which rose to particularly high levels in experimental rats. In addition, exposure to a selective COX-2 inhibitor (SC58125) or an EP1/EP2 antagonist (AH6809), but not an EP4 antagonist (AH23848B), significantly reduced cell proliferation of esophageal explants in 24 hour-organ culture experiments. Our data suggest that, in addition to COX-2, other components of the PGE2 pathway, including COX-1, may play important roles in the development of EAC induced by gastroduodenal reflux in the rat. Although it must be confirmed in vivo, the EP2 receptor may represent a promising selective target in the prevention of Barrett's associated AC.

Computational calculations in microwave-assisted organic synthesis (MAOS). Application to cycloaddition reactions.

Computational calculations represent a very useful tool to study separately the occurrence of thermal and non-thermal effects of microwave irradiation through the determination of the thermodynamic and kinetic parameters of the reaction. In this paper, we approach the computational study of two previously reported cycloaddition reactions. All of the outcomes indicate the presence of a thermal effect alone for the microwave irradiation that produces changes in the regioselectivity or in the reaction mechanism.

Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: Accumulating evidence suggests that cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) is involved in oesophageal adenocarcinogenesis. PGE2 exerts its biological action by binding to specific receptors (EP1, EP2, EP3 and EP4). AIM: To investigate which PGE2 receptor subtypes regulate PGE2 signals in the oesophageal adenocarcinoma sequence. METHODS: Expression was determined in oesophageal biopsies from 85 patients with oesophagitis, Barrett's metaplasia, intraepithelial neoplasia, oesophageal adenocarcinoma and normal oesophagus. Levels of mRNA and protein expression were determined by quantitative PCR, immunohistochemistry and western-blot. Expression of EP receptors was also determined in response to acid and bile exposure in the Barrett's adenocarcinoma cell line OE33. RESULTS: All four EP receptors subtypes were expressed in human oesophageal tissues. COX-2 and, especially, EP2 were increased in the Barrett's metaplasia-intraepithelial neoplasia-adenocarcinoma sequence. Expression of the EP4 receptor protein was increased in oesophageal adenocarcinoma. In contrast, expression levels of COX-1 and EP3 receptor were decreased along the sequence. No differences in EP1 expression were found. Treatment with the bile acid deoxycholate increased COX-2, EP1, EP2 and EP4 expression in OE33 cells. CONCLUSIONS: Our data suggest that in addition to COX-2, EP2 and EP4 receptors could be a selective target in the prevention and/or treatment of the Barrett's-associated adenocarcinoma.

The nigrostriatal pathway: axonal collateralization and compartmental specificity.

This paper reviews two of the major features of the nigrostriatal pathway, its axonal collateralization, and compartmental specificity, as revealed by single-axon labeling experiments in rodents and immunocytological analysis of human postmortem tissue. The dorsal and ventral tiers of the substantia nigra pars compacta harbor various types of neurons the axons of which branch not only within the striatum but also in other major components of the basal ganglia. Furthermore, some nigrostriatal axons send collaterals both to thalamus and to brainstem pedunculopontine tegmental nucleus. In humans, the compartmental specificity of the nigrostriatal pathway is revealed by the fact that the matrix compartment is densely innervated by dopaminergic fibers, whereas the striosomes display different densities of dopaminergic terminals depending on their location within the striatum. The nigral neurons most severely affected in Parkinson's disease are the ventral tier cells that project to the matrix and form deep clusters in the substantia nigra pars reticulata.

[Transitional carcinoma and malignant priapism]. / Carcinoma transicional y priapismo metastático.

Malignant priapism is rare and usually secondary to genitourinary tumors. The prognosis is poor since it generally indicates the presence of multiorgan metastasis. A case of malignant priapism or priapism secondary to penile metastasis from transitional carcinoma is presented and the literature is reviewed.

Amphioxus Evx genes: implications for the evolution of the Midbrain-Hindbrain Boundary and the chordate tailbud.

Evx genes are widely used in animal development. In vertebrates they are crucial in gastrulation, neurogenesis, appendage development and tailbud formation, whilst in protostomes they are involved in gastrulation and neurogenesis, as well as segmentation at least in Drosophila. We have cloned the Evx genes of amphioxus (Branchiostoma floridae), and analysed their expression to understand how the functions of Evx have evolved between invertebrates and vertebrates, and in particular at the origin of chordates and during their subsequent evolution. Amphioxus has two Evx genes (AmphiEvxA and AmphiEvxB) which are genomically linked. AmphiEvxA is prototypical to the vertebrate Evx1 and Evx2 genes with respect to its sequence and expression, whilst AmphiEvxB is very divergent. Mapping the expression of AmphiEvxA onto a phylogeny shows that a role in gastrulation, dorsal-ventral patterning and neurogenesis is probably retained throughout bilaterian animals. AmphiEvxA expression during tailbud development implies a role for Evx throughout the chordates in this process, whilst lack of expression at the homologous region to the vertebrate Midbrain-Hindbrain Boundary (MHB) is consistent with the elaboration of the full organiser properties of this region being a vertebrate innovation.

Kidney androgen-regulated protein interacts with cyclophilin B and reduces cyclosporine A-mediated toxicity in proximal tubule cells.

The gene for kidney androgen-regulated protein (KAP) is the most abundant and specific gene expressed in mouse kidney proximal tubule cells, where it is tightly regulated by steroid and thyroid hormones in different tubule segments. Despite the cell-specific expression, strict regulatory mechanisms, and relative abundance, nothing is known of the function of its encoded protein, which does not exhibit known structural or functional domains, or homologies with other sequences in the data bases. We raised monoclonal antibodies against KAP, which specifically recognize a protein with an apparent molecular mass of 20 kDa in crude kidney homogenates, the distribution and regulation of which parallel that of its mRNA. To gain insight into its function, we performed a yeast two hybrid screen and determined that KAP specifically interacts with cyclophilin B. Furthermore, cyclosporine A (CsA)-treated mice exhibited a significant decrease in KAP levels, and tetracycline-controlled overexpression of KAP in stably transfected proximal tubule cells significantly decreased the toxic effects of CsA. Taken together, these results indicate a functional relationship among KAP-, cyclophilin B-, and CsA-mediated nephrotoxicity and suggest an important role of KAP in renal physiology, providing new data on the molecular mechanisms implied in the toxic effects of CsA.

[Cardiovascular risk factors in schoolchildren of the city of Cuenca]. / Factores de riesgo cardiovascular en escolares de la ciudad de Cuenca.

OBJECTIVE: To calculate the levels of different cardiovascular risk factors among 9 and 10 year old schoolchildren in the city of Cuenca. DESIGN: An observational crossover study (cross-sectional). SETTING: The community: three state schools in the city of Cuenca. PARTICIPANTS: 156 boys and 151 girls doing 4th and 5th year EGB (basic). MEASUREMENTS AND MAIN RESULTS: As well as socio-demographic variables, the following anthropometric variables were determined: weight, height, body mass index (Khosla-Lowe index), systolic and diastolic blood pressure. After collecting samples of venous blood after 12 to 14 hours fasting, overall cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were determined. The average levels of the lipidic parameters measured in mgrs/dl for men and women respectively were 182.4 and 187.2 for overall cholesterol, 110.9 and 117.0 for LDL-cholesterol, 60.9 and 58.1 for HDL-cholesterol and 53.4 and 61.3 for triglycerides. These differences were statistically significant in all the parameters except overall cholesterol. Neither the pressure levels nor the anthropometric variables showed significant differences between genders. CONCLUSIONS: The lipid levels found in our study for both for male and female schoolchildren display the highest cardiovascular risk levels yet observed in Spain. The blood pressure levels are also among the highest published in our country.

[A system of efficient appointments for interviewing persons over 65]. / Un sistema de citación eficaz para realizar entrevistas a las personas mayores de 65 años.

OBJECTIVE: To validate an appointment system which leads to a high compliance of people over 65 invited to attend an interview. DESIGN: A descriptive observational study of a crossover type, between February and June 1990. SETTING: Primary Care; community activity. PATIENTS OR OTHER PARTICIPANTS: A representative sample of the population over 65 registered at the Cuenca 1 Health Centre, selected by means of systematic sampling. MEASUREMENTS AND MAIN RESULTS: Personal letters, signed by the patients' own doctor, to make the appointment. If they did not attend, a second appointment was made by 'phone when possible or by letter if not. The overall reply was 73.79% (221 after the first appointment call and 55 after the second). 8.29% did not wish to carry out the interview; 12.30% were not located; 3.48% were incapacitated and 2.14% had died or were no longer registered at the centre. CONCLUSIONS: The following all favour the level of response: the personalized invitation, signed by the patient's doctor, stating the day and time; carrying out the interview at their Health Centre or home; and making a second appointment where necessary. At the same time these measures contribute to bringing our records up-to-date.

[Non-radical treatment and bladder conservation in infiltrating tumor of the bladder]. / Tratamiento no radical y conservación vesical para el tumor infiltrante de vejiga.

The fate of some infiltrant tumours of the bladder locally advanced (pT2-3NxM0) which were radically resected, with or without association to other treatments, has been similar to those in which initial radical treated was used. To carry out simultaneously a radical RTU as a local action plus systemic chemotherapy (M-VAC), for microscopic metastasis, clinically undetected, seems to us the most effective combination. In our Urology Unit, the evolution (September 88-January 91) of 9 patients presenting this tumour and preservation of the bladder is being followed-up. The primary tumour was treated with radical RTU in 7 cases and partial cystectomy in 2. There are 5 tP2, 1 pT2 + "in situ" carcinoma (Ca) and 3 pT3, 4 G1, 4 G2 and 1 G3. All tumours were single, small (2-4 cm), with varied location and nearly all with medium to low differentiation. Later all patients underwent systemic chemotherapy with M-VAC (3 cycles). Following RTU and QMT every three months, the likely local and systemic progression of the disease has been evaluated through cystoscopy and multiple biopsies including from the prostatic urethra, RTU of anterior scar, two-hand palpation, urinary cytology, blood testing, CAT, abdominal ECO, chest X-ray and laparoscopic lymphadenectomy (coinciding with its development within the Unit) in the last case. Average follow-up (at the time of the review) has been 15.77 months (6-28 months).(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnostic and therapeutic management of testicular tumors. Review of 15 years]. / Manejo diagnóstico y terapéutico de los tumores testiculares. Revisión de quince años.

We reviewed our data on the diagnosis and treatment of testicular tumors during the period spanning January, 1975 to December, 1989 and compared them with the data reported in the literature. The records of 26 cases of germ cell tumors were analyzed. These had a follow-up ranging from 6 to 162 months (mean 36 months). We highlight the usefulness of CT and tumor markers in the diagnosis, staging and follow-up. We consider radical inguinal orchiectomy to be the initial treatment. The therapeutic approach thereafter depends on the histological findings and tumor stage. Currently, patients are followed very carefully after orchiectomy of stage I tumors. Multiple chemotherapy of tumors in the advanced stages has increased the incidence of survival and complete remission. Furthermore, this chemotherapeutic approach has occasionally converted surgery into and adjuvant treatment modality.

[Obstruction of the upper urinary tract caused by a malignant retrovesicular schwannoma. Therapeutic strategy]. / Obstrucción del tracto urinario superior causada por un Schwannoma maligno retrovesical. Estrategia terapéutica.

We present a case of malignant Schwannoma (MS) of uncommon, retroperitoneal and retrovesical localization in a 42-year-old male, which provoked bilateral ureteral obstruction as a urological manifestation. We show our therapeutic strategy by means of a schedule of systemic neoadjuvant chemotherapy with vincristine, adriamycin, cyclophosphamide, decarbacine combined with exeresis and urinary continuity reconstruction surgery. We point out that it is a low incidence but highly aggressive tumour and that treatment continues to be local radical excision, whilst chemotherapy probably continues to have little value.

[Camey II type substitution ileocystoplasty. Our experience]. / Ileocistoplastia de sustitución tipo Camey II. Nuestra experiencia.

We present our experience in the performance of Camey II type substitution ileocystoplasty. The operation was performed between January 1988 and February 1989 on 11 patients who had been diagnosed as having vesical tumour by means of transurethral resection. All of them had received preoperative systemic chemotherapy. Technically, we single out the performance of ileo-obturating lymphadenectomy prior to the cystoprostatovesiculectomy in the same operation, creation of the neobladder with detubulized terminal ileum, uretero-ileal reimplantation according to Le Duc-Camey technique and use of mechanical sutures to reestablish intestinal continuity. Operative and postoperative mortality has been null. As complications, we may mention a urthro-ileal fistula as a result of the suture tension at this level, due to shortness of the mesointestine, and which yielded with conservative measures. Amongst tardive complications we may single out a urethro-ileal stenosis, which required performance of an internal urethrotomy. Daytime continence in all patients, except one. Night continence in six cases. Absence of ureteral reflux and upper urinary tract with correct function and morphology in all cases. The follow-up time ranges from 3 to 16 months. We conclude that this type of vesical substitution offers all patients a good quality of living and adequate mictional comfort.