Tratamiento ambulatorio con insulina intravenosa a través de un catéter central en una paciente con síndrome de resistencia a la insulina subcutánea / Ambulatory intravenous insulin therapy by a venous central catheter access in a patient with subcutaneous insulin resistance syndrome

El síndrome de resistencia a la insulina subcutánea es una causa poco frecuente de diabetes inestable, caracterizada por un mal control glucémico pese al empleo de altas dosis de insulina subcutánea y que mejora, junto con la disminución de los requerimientos de insulina, cuando ésta se administra por vía intravenosa. Su etiología es desconocida y su manejo clínico resulta muy difícil, dada la necesidad de emplear una vía alternativa a la subcutánea para el tratamiento ambulatorio. Presentamos el caso de una paciente con este síndrome en la que se decidió colocar un acceso venoso central con bomba de infusión adaptada como solución provisional hasta contar con un dispositivo de administración de insulina intraperitoneal, que es el tratamiento más comúnmente aceptado en la actualidad (AU)

The subcutaneous insulin resistance syndrome is a rare cause of brittle diabetes, defined as diabetes mellitus poorly controlled with high doses of subcutaneous insulin, which ameliorates, together with a reduction of insulin requirements, when insulin is intravenously infused. Its cause is unknown and its clinical management very difficult, because of the need to use an alternative to the subcutaneous route for ambulatory therapy. We report the case of a patient with this syndrome, in which a venous central access connected to anadapted insulin pump was placed as a temporary solution until having an intraperitoneal insulin infusion device, the currently most accepted treatment for this condition (AU)

Influence of hepatocyte-rich liver cell mixture and liver fibroblasts on prolonging graft islet survival in rats without immunosuppressive drugs.

BACKGROUND: We noted that a liver cell suspension, made up of a mixture of several kinds of hepatic cells, affected allogenic islet survival when it was transplanted into the liver, mixed with the islets or separately. AIM: To study if this effect was related to a liver cell mixture rich in hepatocytes (hp) or to liver fibroblasts (fb). METHODS: We studied 14 groups of rats: (A) a sham group with saline; (B) a group receiving transplantation with hepatic cells alone; (C) a control group, with islets alone via the portal vein, without hepatic cells (hp or fb). For the other groups, we used a different ratio of cells/islets (100 : 1, 150 : 1 and 200 : 1) and different co-transplantation techniques with both types of cells. For the D, E, J groups, a mixture of hepatocytes (hepatocyte-rich liver cell mixture) or fibroblasts with islets was injected into the portal vein. For the other groups, we used a sequential procedure with a 15 minute interval between a first injection of hp or fb into the portal vein or into the vena cava, and a second injection of islets always into the portal vein; thus, it was a sequential portal/portal procedure with hepatocyte-rich liver cell mixture (hp) (F, G) or fibroblasts (K, L) and a sequential cava/portal with hp (H, I) or fibroblasts (M, N). RESULTS: Most of the co-transplantation groups showed functional islets (blood glucose < 250 mg/dl) on the first or second day of transplantation; after several days they once again had high glucose levels, though not as high as pre-transplantation. There was statistical significance (p < 0.001) between the presence or not of hepatic cells to obtain prolongation of graft survival (blood glucose < 250 mg/dl). Statistical significance (p < 0.001) was found for several sequential groups with hp (F, I) and fb (K, L). It was also remarkable that 3 rats (37.5 %) from the I group (sequential cava/portal with hp/islets 200 : 1) were euglycemic (blood glucose < 150 mg/dl) for more than 3 months. ANOVA showed a large interaction between the type of transplant performed and the cellular ratio used, with a significance of p < 0.001. Histological studies in rats with prolonged euglycemia, showed insulin-producing cell aggregates in the liver, while there was a remarkable decrease in insulin-producing cells in the remaining islets of pancreatic tissue. CONCLUSION: The results showed a marginal prolongation of islet graft survival when they are co-transplanted with a hepatocyte-rich liver cell mixture or with liver fibroblasts. The mechanism does not seem to be a cellular interaction between different hepatic cells and islets, but some kind of cellular interaction or released factor from either two cell types on the immune system, blocking or modulating it, at least temporarily.

Influencia del cocultivo de islotes pancreáticos con células hepáticas sobre la liberación de insulina y sobre la implantación de los islotes en hígado sin inmunosupresión / Influence of co-culture of pancreatic islets with hepatic cells on insulin release and on implantation of islets in liver without immunosuppression

El objetivo de este trabajo es estudiar la influencia de las células hepáticas sobre la liberación de insulina cuando se co-cultivan con islotes, así como la influencia que puedan tener sobre la implantación de los islotes en el hígado en ratas Wistar, sin el empleo de drogas inmunosupresoras. In vitro tenemos 2 grupos: A) Cultivo de islotes solos y B) Co-cultivo de islotes y células hepáticas, ambos durante 7 días. Se realiza un estudio morfológico, numérico y de liberación de insulina. In vivo tenemos 7 grupos de Tx: A) Tx ficticio con suero fisiológico (4), B) Tx-ch solas (4), C) Tx-1 solos (6), D) Tx-I solos tras cultivo 7 días (5), E) Tx-1 co-cultivados con ch 24 h (5), F) Tx-I co-cultivados con ch 7 días (7) y G) Tx-I co-cultivados con ch 48 h, en placas transwell (5). La proporción de ch/I ha sido de 150:1. ENI ha sido de 1678 ñ 343 con pureza del 90 por ciento. Análisis de datos mediante el test de ANOVA del SPSS 8.0.In vitro: observamos una gran diversidad celular hepática, un descenso en el ENI durante el co-cultivo, sin embargo la insulino-liberación es mayor en los islotes co-cultivados con ch (p < 0.005). In vivo: Los días de euglucemia tras el Tx han sido: grupo A (0 ñ 0), B (0 ñ 0), C( 2.0 ñ 3.098), D 1.8 ñ 2.17), E (8.6 ñ 12.33), F (9.14 ñ 11.02) y G (0 ñ 0). Los resultados de E y F, confirman un efecto favorable de las ch sobre la implantación de los islotes alogénicos en hígado, consiguiéndose un 20 por ciento y un 14.3 por ciento de reversión de la diabetes. El resultado de G parece indicar la posibilidad de que más que una interacción celular entre las ch e islotes, se trate más bien de la secreción constante de algún producto, y este sea el responsable de la supervivencia de los islotes implantados en hígado. (AU)

Nefropatía diabética / Diabetic nephropathy

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Co-trasplante alogénico de células hepáticas e islotes en ratas diabéticas / Allogen co-transplant of liver cells and islets in diabetic rats

Buscando una mayor tolerancia de los islotes sin necesidad de inmunosupresión, hemos realizado el co-trasplante (co-Tx) de islotes cultivados 3-5 días, mezclados una hora antes del trasplante con hepatocitos (y otras células hepáticas) recién aisladas, en una proporción aproximadamente de 100 y 200 hepatocitos por islote. La diabetes se ha inducido con estreptozotocina 60 mg/kg vía ip en ratas Wistar. Se han estudiado tres grupos de coTx: C) co-Tx islotes y células hepáticas frescas en proporción 1:100; D) co-Tx islotes y células hepáticas frescas en proporción 1:200, y E) co-Tx de islotes co-cultivados con células hepáticas 24 horas en proporción 1:100. Estos tres grupos se han comparado con dos grupos control: A) Tx con sólo células hepáticas y B) Tx con sólo islotes. El número de islotes trasplantados fue respectivamente de: B) 1.808 ñ 413; C) 1.515 ñ 198; D) 1.830 ñ 435, y E) 1.600 ñ 134.En los grupos A y B hubo una falta total de reversión de la diabetes. El grupo C (co-Tx con 1:100) mostró los mejores resultados con euglucemia global durante cuatro días, que en una de las ratas persistió un mes con valores menores de 200 mgldl. La reversión de la diabetes también se observó menos días en el grupo D sin que persistiera más de ocho días en ninguna rata. En el grupo E, co-Tx después del co-cultivo, los resultados fueron intermedios entre los grupos E y D. Estos resultados sugieren un efecto beneficioso de los hepatocitos (o de otras células hepáticas) sobre los islotes pancreáticos, facilitando su tolerancia o aumentando su viabilidad, sin necesidad de inmunosupresión medicamentosa. Considerando la novedad de estos resultados se hace necesario ampliar los estudios para aumentar la eficacia de la tolerancia y explicar el mecanismo de acción (AU)

Nefropatía diabética / Diabetic neprhropathy

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Influence of hepatic cells on allogeneic islet transplantation in rats without immunosuppressive drugs.

With the hypothesis of a possible helpful effect of the liver on islets transplanted into it, we have performed experiments that suggest some effect of hepatic cells for islet tolerance. We have studied 6 groups of Wistar rats made diabetic with streptozotocin and transplanted in sham conditions and with a mixture of islets and hepatic cells (allo-co-transplantation) in several conditions, all of them via the portal vein, and observed them over 30 days. Groups were as follows: Group A had a sham transplantation with saline. Group B was transplanted with hepatic cells alone. Group C was transplanted with islets alone without hepatic cells. Group D was co-transplanted with cultured islets and fresh hepatic cells (ratio 1:100). Group E was as group D with a ratio of 1:200. Group F also had co-transplantation, but after co-culture of islets and hepatic cells for 24 hours. Results show reversion of diabetes in group D for 4-5 days, and thereafter, a fall of blood glucose during the period observed. The effect was less marked in group F after co-culture of islets and hepatic cells. Paradoxically, when the ratio of islets and hepatic cell were 1:200, the results were not so good. These results suggest that hepatic cells have some helpful effect on islets when co-transplanted in the liver via the portal vein. More studies are needed to clarify if this effect can be related to some hepatic cell subpopulation; also if the effect is a membrane one, cell-to-cell contact, or through some secreted product.

El pie diabético / Diabetic foot

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Acerca del mal denominado 'hirsutismo idiopático' / On the misnamed 'idiopathic hirsutism'

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[Xeroderma pigmentosum and polycystic ovaries. An association not previously described. A case report]. / Xeroderma pigmentoso y ovarios poliquísticos. Una asociación no descrita. A proposito de un caso.

The case is presented of an 18 year old female patient who was diagnosed at the age of 2 of Xeroderma pigmentosum (XP), and that at the age of 17 presented amenorrhea and hirsutism with 18 months evolution, and diagnosed of polycystic ovaries (PCO). The possible causes of this rare association which has not been previously described are discussed.

[Relations between Sheehan's syndrome and empty sella turcica. A functional study apropos of 6 cases]. / Relación entre síndrome de Sheehan y silla turca vacía. Estudio funcional a propósito de 6 casos.

We evaluated six patients in whom a diagnosis of Sheehan's syndrome had been made. The plasma levels of the following hormones were measured: basal thyroxine (T4), estradiol and cortisol; and also follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), thyrotropin (TSH), prolactin (PRL) and adrenocorticotropic hormone (ACTH), basally and after acute challenge with LH releasing hormone (LHRH), GRF (1-29)NH2 or insulin hypoglycemia, TSH releasing hormone (TRH) and lysine-8-vasopressin, respectively. Two patients underwent chronic LHRH stimulation by pulsatile subcutaneous administration with infusion pump. In 4 cases, computed tomography (CT) was performed although cranial X-ray study was normal. A severe and generalized pituitary involvement was found in all patients, 3 of whom had diabetes mellitus. Probably, more insidious cases go unnoticed. The presence of asymptomatic partial empty sella (ES) in all the CTs that were carried out raises the possibility that it is another evolutive feature of SS.