Differential effects of sulindac on renal hemodynamics and function in the rat

Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n=6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n=12). In the 5 mg/kg b.w. sulindac group (n=7), renal blood flow progressively and significantly increased from 7.88±0.36 to 8.98±0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n=7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n=5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P<0.025). Also, Na⁺ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n=15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n=21), it was decreased from 11.5±1.2 to 7.4±0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P<0.05; n=6). In conclusion, differential effects of sulindac on renal hemodynamics, Na⁺ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.     

Opticochiasmatic apoplexy

A 26-year-old patient presented with acute chiasmal syndrome. Computerized Tomography and Magnetic Resonance Imaging demonstrated an intrachiasmal hematoma which was evacuated via a right subfrontal approach. Histological examination revealed an arteriovenous malformation. In 21 similar cases in the literature, surgery generally resulted in the improvement of ophthalmological signs. In 3/4 of the cases, histology identified a subjacent lesion (arteriovenous malformation, cavernoma, venous angioma, glioma).     

Transplantation of embryonic noradrenergic neurons in two models of adult rat spinal cord injury: ultrastructural immunocytochemical study

The synaptic connections established by grafted noradrenergic (NA) neurons into the lesioned adult rat spinal cord were analysed using immunocytochemistry at the electron microscopic level. An embryonic cell suspension of the locus coeruleus region from E-13 rat embryos was transplanted into the spinal cord following either: (1) spinal cord transection or (2), partial selective denervation by 6-hydroxy dopamine (6-OH DA). One month after grafting, the NA-neurons established, in the two models, an innervation pattern similar to that found in the intact spinal cord. In both models, the transplanted NA-immunoreactive neurons formed extensive synaptic contacts with dendrites, spines and perikarya. The proportion of axodendritic and axospinous contacts was inverse in the two models. The first model thus reproduced more closely the normal synaptic pattern prefering dendritic targets, which could correspond to a better integration of the graft. In the second model, a partially NA-denervated spinal cord, there existed a competition between residual intrinsic and grafted neuron-derived fibres, which presumably affects synaptogenesis. In conclusion, the present study illustrate the complexity of cell interations conducting to the formation of a specific circuitry. Recognition phenomenon are likely modulated by space constraints, which ultimately shape-up the geometry of synaptic contacts.     

Hormone formation in the isolated fragment 1-171 of human thyroglobulin involves the couple tyrosine 5 and tyrosine 130.

The 22 kDa fragment (Asn1-Met171) purified from iodine-poor human thyroglobulin (hTg) is capable by itself to synthesize thyroxine at Tyr5, the preferential hormonogenic acceptor site of the protein, after iodination in vitro. To identify the corresponding donor site in this model we studied the fate of the six Tyr residues present in the 22 kDa peptide after in vitro hormone synthesis. Structural studies of the tyrosyl peptides showed that Tyr5 was the only thyroxine-forming site, the other tyrosines (29, 89, 97 and 107) were noniodinated and Tyr130 was recovered in alanine form after CNBH4 treatment of the Tyr130-containing peptide. Taking into account that alanine could arise from aminoreduced pyruvate species, these results showed that in the 22 kDa fragment (1) hormone formation involves the couple Tyr5 (acceptor)-Tyr130 (donor), and (2) dehydroalanine, the resultant product of donor tyrosine after hormone synthesis, has evolved in pyruvoyl form. To test whether Tyr130 could also act as donor in hTg hormone synthesis, the 22 kDa peptide was isolated from hTg iodinated under conditions leading to iodotyrosine formation followed or not by hormone formation and the tyrosyl peptides were analyzed. After hTg iodination and before coupling (i.e. hormone synthesis) only Tyr5 and Tyr130 were recovered in iodotyrosine form; after coupling thyroxine was found at Tyr5 whereas Tyr130 disappeared. Taken together these results, correlated with the previously reported cleavage of hTg chain at Tyr130 occurring during in vivo hormone synthesis, support the theory that the couple Tyr5 (acceptor)-Tyr130 (donor) would be the preferential hormonogenic site in human Tg.     

Mitochondrial DNA variability detected in a single wheat regenerant involves a rare recombination event across a short repeat

The mitochondrial genome of the selfed progeny of a plant regenerated from long-term somatic tissue culture displays specific structural rearrangements characterized by the appearance of novel restriction fragments. A mitochondrial DNA library was constructed from this selfed progeny in the SalI site of cosmid pHC79 and the novel fragments were subsequently studied. They were shown to arise from reciprocal recombination events involving DNA sequences present in the parental plant. The regions of recombination were sequenced and the nucleotide sequences were aligned with those of the presumptive parental fragments. We characterized an imperfect short repeated DNA sequence, 242 bp long, within which a 7-bb DNA repeat could act as a region of recombination. The use of PCR technology allowed us to show that these fragments were present in both parental plants and tissue cultures as low-abundance sequence arrangements.     

Upper and lower limb disarticulation in soft tissue and bone sarcomas

The authors have reviewed 23 patients with proximal disarticulations with the aim of assessing the therapeutic value in sarcoma, taking into account previous radio- and chemotherapy. The following criteria were especially examined: recurrences, survival, and quality of life. There were 14 soft tissue sarcomas, and 9 bone sarcomas. In 11 cases, the tumor was primary and treated for the first time while, in 12 cases, it was recurrent. Eighteen patients had been previously treated by nonradical surgery, 11 by radiotherapy, and 10 by chemotherapy. For upper limb tumors, 6 patients underwent an interscapulothoracic disarticulation, and 3 an interscapulothoracic resection according to Tikhoff-Linberg. For lower limb tumors, 8 patients were submitted to interilioabdominal disarticulation, 3 to coxofemoral disarticulation, and 1 to internal hemipelvectomy according to Eilber. The mean disease-free interval has been 34 months, and the mean survival, 38.5 months. Three (15%) of 20 evaluable patients recurred locally, although most of them benefited from second surgery. Quality of life has been excellent, in general, despite the fact that only 8 patients accepted to wear a prosthesis. The Karnofsky index ranged from 60 to 100%. No significant difference was seen, whether or not previous radio- and/or chemotherapy had been administered.

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Resumen Los autores han revisado 23 pacientes con desarticulaciónes proximales con el propósito de determinar el valor terapéutico en el sarcoma, habida consideración a radioterapia y quimioterapia previas. Los siguientes criterios fueron específicamente analizados: recurrencia, supervivencia, y calidad de la vida. La serie incluyó 14 sarcomas de tejidos blandos, y 9 sarcomas óseos. En 11 casos el tumor era primario y aparecía tratado por primera vez, y en 12 casos el tumor era recurrente. Diez y ocho pacientes habían sido previamente tratados con cirugía no radical, 11 con radioterapia, y 10 con quimioterapia. En cuanto a los tumores del miembro superior, 6 pacientes fueron sometidos a desarticulación interescápulotorácica, y 3 a resección interescapulotorácica según Tikhoff-Linberg. En cuanto a los tumores del miembro inferior, 8 pacientes fueron sometidos a desarticulación interilioabdominal, 3 a desarticulación coxofemoral, y 1 a hemipelvectomía interna según Eilber. El promedio de estado libre de enfermedad ha sido 34 meses, y el promedio de supervivencia, 38.5 meses. Tres (15%) de 20 pacientes valorables presentaron recurrencia aunque la mayoría de ellos se benefició con una segunda operación. En general, la calidad de la vida ha sido excelente a pesar de que solamente 8 pacientes aceptaron usar prótesis. El índice de Karnofsky osciló entre 60 y 100%. No se observó diferencia entre los pacientes que habían recibido radioterapia y/o quimioterapia y los que no la recibieron.

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Résumé Les auteurs ont étudié 23 cas de désarticulations proximales pour sarcome en ayant pour but d'apprécier la valeur de l'intervention, la désarticulation étant précédée de radiothérapie et de chimiothérapie. Les critères retenus furent: l'existence de récidives, la survie et la qualité de la vie. La série a concerné 14 sarcomes des parties molles, 9 sarcomes des os. Dans 11 cas il s'agissait d'une tumeur primitive, dans 13 cas de récidives tumorales. Sur ce groupe de malades, 18 avaient été traités par une intervention limitée, 11 par radiothérapie, et 10 par chimiothérapie. En ce qui concerne le membre supérieur, 6 ont été traités par désarticulations inter-scapulo-thoraciques, et 3 par une résection inter-scapulo-thoracique selon la technique de Tikhoff-Linberg. En ce qui concerne le membre inférieur, 8 malades ont été soumis à une désarticulation interilio-abdominale, 3 à une désarticulation ilio-coxo-fémorale, et 1 à une hémipelvectomie interne selon la technique de Eilber. La moyenne de durée de vie normale a été de 34 mois et la moyenne de la durée de la survie de 38.5 mois. Trois (15%) des 20 malades qui ont été revus ont présenté une récidive locale mais la majorité d'entre eux ont pu bénéficier d'une réintervention. La qualité de la vie a été excellente en général bien que 8 opérés seulement aient accepté le port d'une prothèse. L'index de Karnofsky a varié de 60 à 100%. Aucune différence significative n'a été observée que le malade ait été soumis ou non à la radiothérapie et/ou à la chimiothérapie.