Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is associated with increased leptin levels in women with type-2 diabetes mellitus.

OBJECTIVE: To analyze the relationship between the peroxisome proliferator-activated receptor-gamma (PPARgamma2) Pro12Ala variant and type-2 diabetes mellitus and its correlation with some cytokine determinants of insulin resistance such as tumor necrosis factor (TNF)-alpha and leptin. METHODS: The PPARgamma2 Pro12Ala genetic polymorphism was studied in 167 type-2 diabetic patients and 63 healthy controls. Serum leptin and plasma-soluble TNF-R2 were measured. RESULTS: Women carriers of the Pro12Ala mutation exhibited higher leptin levels than women non-carriers (median 31.4 vs. 17.5 ng/ml; p < 0.005). sTNF-R2 levels did not show differences between the two genotypes. Analysis by the multiple linear regression model of leptin-body mass index controlled by the PPARgamma2 genotype showed that leptin levels were determined by the Pro12Ala mutation in type-2 diabetic women but not in men. CONCLUSIONS: PPARgamma2 seems to be implicated in leptin homeostasis in type-2 diabetic women.

Bone mineral mass is associated with interleukin 1 receptor autoantigen and TNF-alpha gene polymorphisms in post-menopausal Mediterranean women.

Bone mass is known to be under genetic control. Interleukin-1 (IL-1), interleukin-6 (IL-6) and TNF-alpha are strong inductors of bone resorption. The estrogenic deficiency that occurs during menopause leads to an increase in the production of these cytokines. We analyzed the genetic susceptibility of several polymorphisms of the interleukin-1 receptor antagonist (IL-1ra), IL-6 and TNF-alpha genes in lumbar spine and hip bone mass in a sample of post-menopausal Caucasian Mediterranean women with osteoporosis. 104 post-menopausal osteoporotic women (58.6+/-4.8 yr) and 51 post-menopausal women without osteoporosis as the control group (57.2+/-4.5 yr) were studied. The osteoporotic group was in turn sub-classified into severe and non-severe osteoporosis. The variable number of tandem repeats IL1-ra, IL-6 SfaNI and TNF-alpha NcoI genetic polymorphisms were studied. Biochemical markers of bone turnover were measured in blood and urine. Women carrying the A2 allele (A2+) of the IL-1ra gene showed greater BMD in the lumbar spine (p=0.02) and hip (p=0.006), compared to those not carrying the allele (A2-). The IL-6 polymorphism studied in its 5' flanking region did not show any association with BMD values. The TNF-alpha gene G allele was associated with a greater bone mass in the non-severe osteoporotic subgroup, both in the lumbar spine (p=0.0007) and in the hip (p=0.02). Likewise, genotype combination A2+GG was associated to a greater hip BMD at the femoral neck and Ward triangle levels (p=0.02). We conclude that both IL-1ra and TNF-alpha can be candidate loci to be studied in the susceptibility to develop post-menopausal osteoporosis.

Lumbalgia de causa inflamatoria y metabólica. Actualización del diagnóstico y tratamiento / No disponible

El dolor lumbar de origen inflamatorio presenta unas características clínicas y exploratorias claramente diferentes del de origen mecánico. Descartadas situaciones clínicas que requieren un diagnóstico y tratamiento inmediatos, como infecciones y neoplasias, buscaremos como causa de dolor lumbar inflamatorio las espondiloartropatías. La anamnesis dirigida, una minuciosa exploración clínica, las pruebas de laboratorio y los estudios por la imagen, junto a criterios de diagnóstico individualizados (cuando existan), serán las claves para el diagnóstico de cada una de las entidades que forman este grupo de enfermedades reumatológicas que tienen especial predilección por el esqueleto axial. El tratamiento va dirigido fundamentalmente a controlar las manifestaciones inflamatorias articulares y extraarticulares que presenten los pacientes, ya que no existe en la actualidad un tratamiento curativo. En cuanto al dolor lumbar de origen metabólico, se revisa el diagnóstico, las indicaciones de tratamiento y los tratamientos actuales de la osteoporosis y la enfermedad ósea de Paget (AU)

Low back pain associated to inflammatory causes has clinical and exploratory features clearly different from those of pain associated to mechanical causes. After ruling out other clinical conditions which may re quire immediate diagnosis and treatment, such as infections and neoplasias, we will focus on spondylopathies as the cause of inflammatory low back pain. Directed anamnesis, a thorough clinical exam, laboratory tests and image studies, as well as individualized diagnostic criteria (when appropriate), will be the keys for the diagnosis of each of the entities included in this group of rheumatic diseases mainly involving the axial skeleton. Treatment is aimed mainly to the management of joint and extrajoint inflammatory signs developed by the patients, since there is currently no curative therapy. As regards low back pain associated to metabolic causes, the diagnosis is reviewed, as well as the therapeutic indications and current treatments for osteoporosis and Paget´s bone disease (AU)

[Vasculitis associated with proliferation of large granular lymphocytes]. / Vasculitis asociada con proliferación de linfocitos grandes granulares.

We report a patient with the syndrome of large granular lymphocytes in whom the initial clinical features were polyarthritis, hepatosplenomegaly and neutropenia. Relative lymphocytosis was also demonstrated at the expense of a subpopulation with morphology and surface markers characteristic of large granular lymphocytes (CD2+, CD8+, CD16+ and HNK-1+). After 6 months of asymptomatic course, without changes in clinical or laboratory data, the patient died from an acute abdomen with mesenteric ischemia of different likely causes as suggested by necropsy data (multivisceral diffuse infiltrate by large granular lymphocytes, systemic vasculitis and Clostridium sepsis). The association between this syndrome and systemic vasculitis is discussed.