RESUMEN
Recent observations have revealed massive galactic molecular outflows that may have the physical conditions (high gas densities) required to form stars. Indeed, several recent models predict that such massive outflows may ignite star formation within the outflow itself. This star-formation mode, in which stars form with high radial velocities, could contribute to the morphological evolution of galaxies, to the evolution in size and velocity dispersion of the spheroidal component of galaxies, and would contribute to the population of high-velocity stars, which could even escape the galaxy. Such star formation could provide in situ chemical enrichment of the circumgalactic and intergalactic medium (through supernova explosions of young stars on large orbits), and some models also predict it to contribute substantially to the star-formation rate observed in distant galaxies. Although there exists observational evidence for star formation triggered by outflows or jets into their host galaxy, as a consequence of gas compression, evidence for star formation occurring within galactic outflows is still missing. Here we report spectroscopic observations that unambiguously reveal star formation occurring in a galactic outflow at a redshift of 0.0448. The inferred star-formation rate in the outflow is larger than 15 solar masses per year. Star formation may also be occurring in other galactic outflows, but may have been missed by previous observations owing to the lack of adequate diagnostics.
RESUMEN
The association of HLA-B27 with ankylosing spondylitis (AS) is the strongest among all inflammatory diseases. However, the exact role of these molecules in disease pathogenesis is still unknown. The existence of HLA-B27 variants rarely found in patients introduces a further level of complexity. It is now accepted that other genes of minor impact contribute to modify disease susceptibility and these genes might be diverse in different populations depending on the genetic background. We report here a study performed in Sardinia, an outlier population in which two major HLA-B27 subtypes are present, B (*)2705 strongly associated with AS and B (*)2709 which is not, and show the co-occurrence of the B (*)2705 allele with a single nucleotide polymorphism (SNP) mapping at 3'-UTR of the receptor 1 (VIPR1) for the vasoactive intestinal peptide (VIP), a neuropeptide with anti-inflammatory properties. This same SNP is associated with a different kinetics of down-modulation of the VIPR1 mRNA in monocytes after exposure to lipopolysaccharide (P=0.004). This particular setting, HLA-B (*)2705 and a functional polymorphism in VIPR1 gene, might be due to a founder effect or might be the result of a selective pressure. Irrespectively, the consequent downregulation of this receptor in the presence of a 'danger' signal might influence susceptibility to AS.
Asunto(s)
Efecto Fundador , Antígeno HLA-B27/genética , Espondilitis Anquilosante/genética , Péptido Intestinal Vasoactivo/genética , Alelos , Regulación hacia Abajo , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Italia , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
The sodium(Na)- and potassium(K)-activated adenosine-triphosphatase (Na,K-ATPase) is a membrane enzyme that energizes the Na-pump by hydrolysing adenosine triphosphate and wasting energy as heat, so playing a role in thermogenesis and energy balance. Na,K-ATPase regulation by insulin is controversial; in tissue of hyperglycemic-hyperinsulinemic ob/ob mice, we reported a reduction, whereas in streptozotocin-treated hypoinsulinemic-diabetic Swiss and ob/ob mice we found an increased activity, which is against a genetic defect and suggests a regulation by hyperinsulinemia. In human adipose tissue from obese patients, Na,K-ATPase activity was reduced and negatively correlated with body mass index, oral glucose tolerance test-insulinemic area and blood pressure. We hypothesized that obesity is associated with tissue Na,K-ATPase reduction, apparently linked to hyperinsulinemia, which may repress or inactivate the enzyme, thus opposing thyroid hormones and influencing thermogenesis and obesity development. Insulin action on Na,K-ATPase, in vivo, might be mediated by the high level of non-esterified fatty acids, which are circulating enzyme inhibitors and increase in obesity, diabetes and hypertension. In this paper, we analyse animal and human tissue Na,K-ATPase, its level, and its regulation and behaviour in some hyperinsulinemic and insulin-resistant states; moreover, we discuss the link of the enzyme with non-esterified fatty acids and attempt to interpret and organize in a coherent view the whole body of the exhaustive literature on this complicated topic.
Asunto(s)
Diabetes Mellitus Tipo 2/enzimología , Ácidos Grasos no Esterificados/metabolismo , Resistencia a la Insulina , Insulina/metabolismo , Obesidad/enzimología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Tejido Adiposo/enzimología , Animales , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Grasos no Esterificados/sangre , Humanos , Hiperglucemia/enzimología , Hiperglucemia/metabolismo , Hiperinsulinismo/enzimología , Hiperinsulinismo/metabolismo , Obesidad/metabolismoRESUMEN
Enzyme activities operative in glucose degradation and citrate cleavage pathway were studied in the adipose tissue of twenty-four patients with adult-onset diabetes and normal body weight, aged 59+/-9 years, and twenty-four matched controls. In normal tissue, type II (heat-inactivated) hexokinase moderately predominated over type I (heat-resistant). 6-Phosphofructokinase had an extremely low activity, which was by far the lowest among the ten glycolytic enzyme activities investigated, and which therefore might greatly limit the glycolytic rate. The level of glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) was elevated above that occurring in other tissues. This, especially if considered together with the low 6-phosphofructokinase activity, would suggest a major role of pentose cycle in glucose degradation. Of the citrate cleavage pathway enzymes, ATP citrate-lyase, although having a lower activity than malate dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), was readily measurable, which contrasts with previous data by others. This finding is consistent with the occurrence of lipogenetic capacity in human adipose tissue. In diabetic tissue, there was a decreased activity, both on a protein and on a wet-weight basis, of enzymes concerned with the glucose entry into metabolic pathways, namely hexokinase (both type I and, especially, type II) and pentose cycle dehydrogenases, as well as of pyruvate kinase. This could be connected with the defective glucose utilization by adipose tissue in diabetes. Beside the above-mentioned dehydrogenases, malate dehydrogenase (decarboxylating) (NADP) was also diminished. The reduction of these NADPH-forming enzymes, which supply reducing equivalents for fatty acid synthesis, would suggest a depressed lipogenesis.
Asunto(s)
Tejido Adiposo/enzimología , Citratos/metabolismo , Diabetes Mellitus/enzimología , Glucosa/metabolismo , ATP Citrato (pro-S)-Liasa/metabolismo , Anciano , Femenino , Glucosa-6-Fosfato Isomerasa/metabolismo , Glucosafosfato Deshidrogenasa/metabolismo , Glucólisis , Hexoquinasa/metabolismo , Humanos , Lípidos/biosíntesis , Malato Deshidrogenasa/metabolismo , Masculino , Persona de Mediana Edad , Pentosas/metabolismo , Fosfogluconato Deshidrogenasa/metabolismoRESUMEN
Bardet-Biedl syndrome (BBS) is a genetic autosomal-recessive disease (formerly grouped with Laurence-Moon-Biedl syndrome but considered today as a separate entity) characterized by abdominal obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism or hypogenitalism (limited to male patients) and kidney structural abnormalities or functional impairment. The expression and severity of the various clinical BBS features show inter- and intrafamilial variability. This study focuses on three cases of familial BBS--two sisters and one brother (66, 64 and 51 years of age, respectively)--with the main cardinal findings of the disease plus a classic 'metabolic syndrome' (characterized by abdominal obesity, atherogenic dyslipidaemia, raised blood pressure, insulin resistance with or without glucose intolerance, and prothrombotic risk and proinflammatory states). One female patient (not affected by reproductive dysfunction) had three healthy offspring, while the other two patients were unmarried. Another severely affected brother died at 70 years of age; two other brothers are lean but affected by nephropathy, retinopathy, slight mental retardation, polydactyly, hypertension and thrombotic diseases, and had healthy offspring. BBS is a rather rare but severe syndrome that is often mis- or undiagnosed. Ophthalmologists, endocrinologists and nephrologists should be aware of BBS because of its adverse prognosis--early onset of blindness, associated findings of metabolic syndrome and increased vascular risk, and severe renal impairment (the most frequent cause of reduced survival and death early in life).
Asunto(s)
Síndrome de Bardet-Biedl/diagnóstico , Síndrome de Bardet-Biedl/genética , Anomalías Múltiples/genética , Anciano , Síndrome de Bardet-Biedl/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Discapacidad Intelectual/etiología , Discapacidad Intelectual/genética , Masculino , Síndrome Metabólico , Persona de Mediana Edad , Obesidad/etiología , Obesidad/genética , PronósticoRESUMEN
The activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) of adipose tissue was markedly decreased, both on a protein and on a fat cell number basis, in nonobese diabetics compared to control subjects, but was unchanged in obese diabetics. Average value in the obese diabetics was about fourfold higher than in nonobese diabetics. On the other hand, the activity of malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was reduced by about 50% in both groups of diabetics. These findings suggest that in obese diabetics NADPH-generation in the adipose tissue, necessary for several biosynthetic processes, might be less severely depressed than in lean diabetics.
Asunto(s)
Tejido Adiposo/enzimología , Diabetes Mellitus/enzimología , Glucosafosfato Deshidrogenasa/análisis , Malato Deshidrogenasa/análisis , Obesidad/enzimología , Anciano , Peso Corporal , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We calculated insulin sensitivity indices (ISI) concerning the insulin effect on both glycemia and blood free fatty acids (FFA), named ISI(gly) and ISI(ffa), respectively, in 34 normal, 27 obese, and 11 obese-diabetic subjects by using the following formulas: ISI(gly)= 2/[(INSp x GLYp) +1], and ISI(ffa)= 2/[(INSp x FFAp)+1], in which INSp, GLYp, and FFAp = insulinemic, glycemic, and FFA areas during oral glucose tolerance test (OGTT) (75 g glucose, suggested sampling time: 0, 1, and 2 hours) of the person studied. A slight modification of these formulas allows the calculation of insulin resistance indices (IRI), ie, IRI(gly) and IRI(ffa). ISI and IRI are complementary, as their sum is always equal to 2, so that IRI can be deduced from ISI and vice versa. By using basal levels instead of areas, insulin sensitivity (or resistance) in the basal state can also be measured. Basal levels and areas are expressed by taking the mean normal value as 1, so that in normal subjects ISI(gly) and ISI(ffa), as well as IRI(gly) and IRI(ffa), are always around 1, with maximal variations comprised between 0 and 2. ISI(ffa) was markedly reduced in both the obese (mean, 0.47 +/- 0.04) and the obese-diabetic (mean, 0.41 +/- 0.06) subjects, whereas ISI(gly) was less reduced in the obese (mean, 0.57 +/- 0.04) than in the obese-diabetic (mean, 0.40 +/- 0.03) subjects. ISI(gly)-basal was less affected than ISI(ffa)-basal in both groups. Multiple regression showed that ISI(gly) and ISI(ffa) were significantly inversely correlated with age, body mass index (BMI), and diastolic (but not systolic) blood pressure. Meta-analysis of data from the literature showed that ISI(gly) was significantly correlated with the hyperinsulinemic-euglycemic clamp data. However, the "clamp" is performed under artificial, persistent hyperinsulinemia (which entails FFA suppression) as never occurs in the life of patients, whereas our indices are performed under physiologic conditions, and represent simple tools suitable for clinical or epidemiologic studies, allowing assessment of whole-body insulin sensitivity with regard to both glycemia and blood FFA.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus/sangre , Ácidos Grasos no Esterificados/sangre , Insulina/farmacología , Obesidad/sangre , Adulto , Índice de Masa Corporal , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Resistencia a la Insulina , Cinética , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
In a group of ten adult obese subjects, maintained for 15 days on a normal caloric intake and balanced diet, the activity of hexokinase (EC 2.7.1.1),6-phosphofructokinase (EC 2.7.1.11), and ATP citratelyase (EC 4.1.3.8) in the adipose tissue was significantly increased, both on a protein and on a fat cell number basis, compared to matched normal subjects. The activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), malate dehydrogenase (EC 1.1.1.37), and malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40), on the other hand, was unchanged. Since both hexokinase and 6-phosphofructokinase are rate-limiting in glycolysis, their enhanced activity would indicate the occurrence of an increased capacity to metabolize glucose and therefore to generate alpha-glycerophosphate. The elevation of ATP citrate-lyase would suggest increased lipogenesis, owing to the regulatory role that this enzyme plays in fatty acid synthesis. The normal activity of glucose-6-phosphate dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), which supply NADPH for the reduction of acetyl-CoA to fatty acids, would suggest that the change in lipogenesis is of moderate degree, thereb) affecting only the most rate-limiting enzyme, ATP citrate-lyase. These data, on the whole, are consistent with the occurrence of enhanced triglyceride formation. Whether the enzyme changes observed are adaptive or genetic in nature remains to be clarified.
Asunto(s)
Tejido Adiposo/enzimología , Lípidos/biosíntesis , Obesidad/enzimología , ATP Citrato (pro-S)-Liasa/metabolismo , Adulto , Anciano , Ensayos Clínicos como Asunto , Femenino , Glucosafosfato Deshidrogenasa/metabolismo , Hexoquinasa/metabolismo , Humanos , Malato Deshidrogenasa/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/genética , Fosfofructoquinasa-1/metabolismoRESUMEN
In obese hyperglycemic (ob/ob) mice, as compared to controls, hepatic pyruvate kinase (PK) activity was enhanced by 35.63% (214.75 +/- 13.60 nmol/min/mg protein v 158.33 +/- 10.47, P less than 0.01) when measured at saturating (6.6 mmol/L) concentration of the substrate phosphoenolpyruvate (total activity), but the activity recorded at subsaturating (1.3 mmol/L) substrate concentration (active fraction) was unchanged (86.37 +/- 6.42 v 85.66 +/- 13.59) or even decreased if expressed as percent of the total activity (40.21 +/- 2.56% v 54.10 +/- 5.07, P less than 0.05). Since insulin induces the synthesis of hepatic PK and favors the conversion of the inactive (phosphorylated) to the active (dephosphorylated) form, these findings suggest that in ob/ob mice the striking hyperinsulinemia, although it is able to increase the hepatic content of PK, fails to activate this enzyme. This may favor gluconeogenesis in these animals. The hepatic concentration of PK effectors (fructose-1,6-P2 and phosphoenolpyruvate) was unchanged in ob/ob mice, and the in vitro effect of the activator fructose-1,6-P2 (15 mumol/L), which would favor the activation (dephosphorylation) of PK, was preserved. It is suggested that hepatic PK in ob/ob mice is resistant to activation by insulin.
Asunto(s)
Hiperinsulinismo/enzimología , Resistencia a la Insulina , Hígado/enzimología , Ratones Obesos/metabolismo , Piruvato Quinasa/metabolismo , Animales , Activación Enzimática , Fructosadifosfatos/farmacología , Hígado/efectos de los fármacos , RatonesRESUMEN
After having previously shown that some noninsulin-sensitive tissues (capillaries and optic nerve) phosphorylate glucose in a concentration-dependent manner through a glucokinase-like enzyme, here, we report data on glucose phosphorylation in rabbit lens and retina at various glucose concentrations (1, 5, 10, 25, 50, and 100 mmol/L). In the 3000 g supernatant of lens and retina homogenates from two separate groups of female albino rabbits ten animals in each group; 1.8-2.0 kg body weight; mean +/- SEM morning glycemia: 8.19 +/- 0.28 and 8.12 +/- 0.24 mmol/L, respectively) was assayed glucose phosphorylating activity (NADP reduction measured as change in optical density at 366 nm at pH 7.5). The enzyme activity did not reach the maximum at low glucose concentration (1 mmol/L), as it occurs in several tissues, but increased progressively in both tissues with the increase in glucose concentration. Values (mean +/- SEM) for lens were 0.197 +/- 0.031 nmol/min/mg protein at 1 mmol/L and 0.327 +/- 0.051 (the highest value) at 50 mmol/L glucose (+65.99%, p < 0.01; r = 0.31, p < 0.05). Values for retina were 36.02 +/- 2.12 at 1 mmol/L glucose and 42.48 +/- 2.79 (the highest value) at 25 mmol/L glucose (+17.93%, p < 0.001; r = 0.32, p < 0.05). These kinetic characteristics, somewhat reminiscent of those shown by hepatic glucokinase, are still more pronounced when we calculated the "glucokinase component," obtained by subtracting the activity at 1 mmol/L glucose (hexokinase component) from that at the highest glucose concentration (total glucose phosphorylating activity). In five rabbits of similar age and weight, with spontaneous hyperglycemia (mean +/- SEM morning glycemia: 11.71 +/- 0.60) glucose phosphorylation in the retina was lower than normal, value at pH 7.5 and 1 mmol/L glucose being 24.52 +/- 2.20 versus 36.02 +/- 2.12 of normal animals (-31.93%, p < 0.01). This, if occurs also in other tissues, could contribute to the hyperglycemia by reducing glucose utilization. In these animals, however, the glucose phosphorylating activity retained the responsivity to increasing glucose concentrations, with value at 100 mmol/L of 28.65 +/- 2.10, corresponding to + 16.84% over the value at 1 mmol/L (p < 0.01). Therefore, the actual glucose phosphorylation in the retina of these animals would depend both upon the enzyme level (which is reduced) and glucose concentration (which is increased). Due to the in vivo inhibition of the hexokinase component by glucose 6-phosphate, the glucokinase component in retina and lens may be predominant in vivo, making the stimulating effect of hyperglycemia much more important than it would appear from our in vitro data. This might play a role in the chronic diabetic complications.
Asunto(s)
Glucoquinasa/metabolismo , Glucosa/metabolismo , Hiperglucemia/metabolismo , Cristalino/metabolismo , Retina/metabolismo , Animales , Femenino , Cristalino/enzimología , Fosforilación , Conejos , Valores de Referencia , Retina/enzimologíaRESUMEN
We have previously demonstrated that in some non-insulin-sensitive tissues (capillaries of eel swimbladder Rete mirabile, and rabbit eye choroidocapillary lamina, optic nerve, retina, and lens) glucose phosphorylation increases with the increase in the concentration of glucose, a characteristic relevant to the hyperglycemia of diabetes. In the present research we demonstrate an effect of the aldose reductase inhibitor, Tolrestat, on the glucose-phosphorylating activity of rabbit lens and optic nerve, by assaying the enzyme activity of tissue homogenates (in the presence of 10 mmol/L glucose) without or with 10 min preincubation with increasing concentrations of Tolrestat (2, 4, and 8 micromol/L). In the lens, a 18% inhibition (p < 0.01) was observed in the presence of 8 micromol/L Tolrestat. In the optic nerve, a 12% (p < 0.05) and a 21% (p < 0.01) reduction was recorded at 4 and 8 micromol/L Tolrestat, respectively. Significant inverse correlations existed between the concentration of Tolrestat and the phosphorylation rate of glucose of rabbit lens and optic nerve. The dose-dependent inhibition of glucose phosphorylation observed by us suggests that the inhibitory action of Tolrestat on glucose metabolism extends beyond the well-known effects of this compound on the polyol pathway, and might contribute to the refraining action of Tolrestat on the development and progression of late diabetic complications in non-insulin-sensitive tissues.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Glucosa/metabolismo , Cristalino/metabolismo , Naftalenos/farmacología , Nervio Óptico/metabolismo , Animales , Interpretación Estadística de Datos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Neuropatías Diabéticas/metabolismo , Inhibidores Enzimáticos/administración & dosificación , Femenino , Técnicas In Vitro , Naftalenos/administración & dosificación , Fosforilación , ConejosRESUMEN
The aim of this paper is to discuss, on the basis of an extensive literature review, the role of magnesium (Mg) in health and disease. Mg is an essential cation playing a crucial role in many enzyme systems. Quantitative Mg body stores are regulated by metabolic and hormonal effects on gastrointestinal absorption and renal excretion. Mg is a smooth muscle relaxant, dilates coronary arteries and peripheral vessels, exerts antiarrhythmic effects, may have a permissive effect on catecholamine actions and can play a role in various thrombogenic conditions. Today, hypomagnesemia has become a recognized medical occurrence which may be associated with many different diseases, either genetic or acquired. Mg deficiency is one of the most frequent electrolyte abnormalities in clinical practice, but it is probably the most underdiagnosed one. Clinical manifestations of hypomagnesemia may begin insidiously or dramatically sudden. A large part of the population (especially aged subjects) may have an inadequate Mg intake and a chronic latent Mg deficiency. Routine inclusion of serum Mg analysis in the electrolyte panel represents a continued need to recognize hypomagnesemia and to treat Mg-depleted patients. New clinical studies on Mg deficiency are necessary to ascertain the usefulness and cost-effectiveness of Mg replacement therapy.
Asunto(s)
Deficiencia de Magnesio/etiología , Magnesio/sangre , Electrólitos/metabolismo , Humanos , Magnesio/fisiología , Deficiencia de Magnesio/diagnóstico , Deficiencia de Magnesio/terapiaRESUMEN
FVII deficiency is a rather rare inherited hemocoagulation disorder that predisposes to hemorrhagic events, especially from mucous membranes, that are not predictable and severe as in hemophilia A. This defect produces prolonged prothrombin time (PT), reduced activity of FVII and normal activated partial thromboplastin time (aPTT). We report the case of a 43-year-old obese woman with severe deficiency of factor VII (FVII), probably genetic in nature, and meno-metrorrhagia associated with multiple fibromas of uterus. Our patient had no history of bleeding in infancy and young age, and in the past, before the disease was diagnosed, underwent major surgery operations (thyroidectomy and caesarian section) without hemorrhage. Patient's relatives with mild heterozygous deficiency of FVII (the father, a brother, a sister, a sister's daughter and the patient's son) did not show any bleeding tendency. This case report is discussed in the light of literature data ((source: Medline from 1964 to 1996). The different forms of congenital (isolated or combined with other clotting disorders) and acquired FVII deficiency, with the appropriate therapies, are reviewed. The clinician must consider FVII deficiency in cases of recurrent bleeding, and this disease, even if rather rare, should not be underestimated in clinical practice because it is potentially fatal.
Asunto(s)
Deficiencia del Factor VII/genética , Trastornos Hemorrágicos/genética , Adulto , Femenino , Humanos , Lactante , MasculinoRESUMEN
An automatic glycemic control system (Beta-like, Esaote) was used to calculate the insulin area (IA) required to keep glycemia within the normal range during OGTT (using NDDG criteria). IA was calculated by adding total endogenous insulin to insulin infused by the Betalike system (Actrapid HM, Novo). During the test, glycemia was obliged to follow a mean normal curve using an insulin infusion according to a special algorithm which automatically adapted to individual parameter variations during the different stages of OGTT. Fourteen blood samples were collected to assay metabolites (glucose, NEFA, lactate and alanine) and hormones (insulin, C peptide, glucagon). Data on insulinemia and glycemia were used to calculate the respective areas under the total and incremental curve (IA expressed in UL-1 min-1 and GA expressed in mM.L-1.min-1); an insulin resistance index was then calculated (total and incremental) using the following formula: IA/(normal GA/patient GA). This test allows us: a) to evaluate the insulin secretory response to a standard glycemic stimulus represented by a glycemic curve within the normal range; b) to calculate the quantity of insulin necessary to maintain the glycemic curve within the normal range; c) to evaluate the body's total insulin resistance according to an index calculated on the basis of the insulin area required; d) to compare the calculated insulin resistance index with NEFA and glucagon data obtained during the test; e) to identify the exact evolution of these events over time during OGTT.
Asunto(s)
Glucemia/análisis , Prueba de Tolerancia a la Glucosa/instrumentación , Resistencia a la Insulina , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Retroalimentación , Femenino , Humanos , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Persona de Mediana Edad , Obesidad/sangre , Obesidad/etiología , Obesidad/fisiopatologíaRESUMEN
The polyglandular autoimmune syndromes (PGA) are well known and are distinguished into type I, type II and type III. PGAI, also called APECED (autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy), is an autosomal recessive disorder, appearing in childhood and typically characterized by hypoparathyroidism (unusual in PGAII and PGAIII) and adrenal insufficiency. In APECED, autoimmune destruction of the pancreatic beta cells with development of insulin-dependent type 1 diabetes is possible, but less frequent than in the other PGAs, especially PGAII. The pathogenesis of this unique autoimmune disease is unknown. No HLA association seems to exist and genetic studies have assigned the autosomal APECED locus to chromosome 21. The case of a 28-years-old female suggesting the diagnosis of APECED, is presented, characterized by psycho-somatic abnormal development, teeth alterations, post-puberal gonadal failure with dystrophic hypoplasia of external genitalia, previous vaginal candidiasis, a slowly developing juvenile brittle diabetes. Intestinal malabsorption induced by Giardia lamblia occurred (probably resulting, like candidiasis, from immunological anergy). A strong familiarity linked to female sex was noticed (the mother, a sister, the little nice and some maternal female cousins being affected) while the father and a brother were healthy. Diabetes seems to be characterized by early onset and severe complications. In this patient no organo-specific antibodies were detected and the only immunologic disorder was a small decrease of CD3 and CD4/CD8 ratio, both CD4 and CD8 being at the lower normal range. This patient (and her female maternal relatives) needs a long-term follow-up in order to evaluate the function of endocrine glands and to initiate early treatment for hormonal deficits, as well as to detect the non-endocrine components of disease.
Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Poliendocrinopatías Autoinmunes/genética , Cromosoma X , Adulto , Femenino , Humanos , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/inmunología , Poliendocrinopatías Autoinmunes/psicología , Radiografía Panorámica , Anomalías Dentarias/diagnóstico por imagenRESUMEN
A case of familial Bardet-Biedl syndrome (BBS) in a 64-year-old woman is presented; it is characterized by abdominal obesity (BMI: 38.28; WHR: 0.98), slight mental retardation, polydactyly, pigmentary retinopathy and moderate renal failure, with insulin-resistant diabetes mellitus and severe inflammation of the left limb with necrosis of the last toe (the sixth) of the left foot. Four brothers and sisters of the patient presented the same syndrome. The patient had had healthy offsprings. The review of current literature indicates that BBS is a genetic autosomal recessive disease, formerly grouped with Laurence-Moon-Biedl syndrome but today considered as a separate entity. It is characterized by obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism in males, and renal structural abnormalities or functional impairment. Extra- and intrafamilial variability of expressivity and severity of the various clinical manifestations was reported, among affected families and also in the same family. BBS is a rare but important syndrome, that should be known by the endocrinologist and the specialist in internal medicine, because it has an adverse prognosis, with early onset of blindness, insulin-resistant diabetes mellitus and severe renal impairment. Renal failure is a frequent cause of death early in life, even in the infant-juvenile years.
Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Deformidades Congénitas del Pie/fisiopatología , Discapacidad Intelectual/fisiopatología , Fallo Renal Crónico/fisiopatología , Obesidad/fisiopatología , Retinitis Pigmentosa/fisiopatología , Femenino , Deformidades Congénitas del Pie/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Radiografía , SíndromeRESUMEN
Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler-Rose reaction, increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid syndrome with lung interstitial disorder, associated with silica exposure from dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51-B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune disease susceptibility. A 6-month follow-up, with adequate protection and without treatment, showed disappearance of the symptomatology and negative tests for Waaler-Rose reaction and rheumatoid factor. Exposure to silica should, therefore, be sought in the history of any patient with autoimmune or lupus-like syndrome and pulmonary changes. Symptoms associated with silica dust exposure from dental ceramic products should be recognised as being due potentially to an occupational disease, and dental technicians should be protected as workers at risk.
Asunto(s)
Artritis Reumatoide/inducido químicamente , Cerámica/efectos adversos , Técnicos Dentales , Polvo/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Dióxido de Silicio/efectos adversos , Adulto , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Exposición Profesional , Radiografía Torácica , Tomografía Computarizada por Rayos XRESUMEN
In order to combine several factors entailing protection or risk towards disease and to calculate a Protection Multiple Factor Index (PMFI) or, conversely, a Risk Multiple Factor Index (RMFI), we propose the following formulae: (1) PMFI = 2/[(mF)2 + 1] and (2) RMFI = 2/[(imF)2 + 1], where mF is the mean value of the factors considered and imF is the inverse (or reciprocal) of mF. In calculating mF, the value of each 'risk factor' observed in the patient under study (Vp) is expressed by taking the mean normal value (Vmn) as the unit, i.e. by calculating the ratio Vp/Vmn, whereas each 'protection factor' is expressed as the reciprocal of this ratio, i.e. as Vmn/Vp. The 'weight' of the various factors can be changed through multiplication by a number > 1 or < 1. Values of both PMFI and RMFI are always close to 1 in normal subjects, with extreme variations among patients between 0 and 2. The sum of the values of PMFI and RMFI is always equal to 2, so that one index can be deduced from the other. When factors are only two (F1 and F2), the formulae may be simplified as follows: PMFI = 2/[F1 x F2) + 1] and RMFI = 2/[(iF1 x iF2) + 1], where iF = 1/F, with only minimal changes in results.
Asunto(s)
Medicina Preventiva , Humanos , Modelos Teóricos , Factores de RiesgoRESUMEN
Today the number of women receiving breast implants of silicone gel, for augmentation or reconstruction of the breast, is increasing. Silicon implants may cause local complications (such as capsular contracture, rupture, closed capsulotomy, gel "bleed", nodular foreign body granulomas in the capsular tissue and lymph nodes) or general symptoms. An adverse immune reaction with signs and symptoms of rheumatoid disorders is also possible, although an increased frequency of true autoimmune systemic connective tissue diseases is controversial. The US Food and Drug Administration advised that these silicone implants should be used only in reconstructive surgery and as part of clinical trials. Silicone is not an inert substance and silicone compounds were found in the blood and liver of women with silicone breast implants. The development of disease related to silicone implants would depend on genetic factors, so that only a very few women are potentially at risk. HLA-DR53 may be a marker of predisposed subjects. Breast-feeding by women with silicone implants should not be recommended for possible autoimmune disorders in the children. We report the case of an adult female patient with silicone breast implantation for bilateral mastectomy (performed 12 months before) and a unique syndrome characterized by low-grade fever, chronic fatigue, arthralgias of the hands, dysphagia, dry eye, increased level of rheumatoid factor and decreased value of complement C3 and C4. No increased erythrocyte sedimentation rate occurred, and no ANA, nDNA, ENA and AAT autoantibodies were evidence. A critical review of literature (source: MEDLINE 1980-1997) was performed and our case seems to be the first one reported in Italy. The internist should become familiar with the immunological disorders related to silicone breast implants, often so marked to require the explantation of the prostheses to improve symptomatology. However, perhaps due to the leak and spreading of silicone, the progression to a severe systemic involvement may remain despite the implant removal.
Asunto(s)
Artritis Reumatoide/inducido químicamente , Implantes de Mama/efectos adversos , Siliconas/efectos adversos , Adulto , Anciano , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Aim of this paper is to discuss, on the basis of an extensive critical review of the recent literature, the case of a 56-yr-old male patient who suffered from cutaneous psoriasis and psoriatic arthritis mutilans (PA) (polyarticular, symmetric, destruent and erosive) with involvement of the hands, feet and spine, associated with android obesity and mild type 2 diabetes mellitus. HLA typing of the patient showed the HLA-A3-Ax, B14-B63 and Cw4-Cw6 haplotypes, some of which are associated or correlated with susceptibility to PA. Cutaneous psoriasis is a chronic inflammatory dermatitis, with onset at any age and affecting approximately 2% of the western populations. In 5-7% of patients, it is associated with articular manifestations or true arthritis. PA is a chronic, inflammatory, seronegative arthropathy which may develop in some psoriasis patients, may involve peripheral and axial (spondarthritis) joints and may lead to severe joint destruction. Genetic, immunologic and environmental (i.e., infectious agents or trauma) factors seem to play an important role in the onset and clinical appearance of PA. Although PA is a clinically monomorphic disease, it may show different heterogenous subgroups with differences in their etiopathogenesis. When PA is suspected, it is mandatory to analyze carefully the patient's familiar history, search attentively for the specific skin features, exclude a septic arthritis (especially if the involvement is monoarticular) and, in the cases of fulminant disease, consider always the possible coexistence of an acquired immunodeficiency syndrome. PA can occasionally be an aggressive, disfigurating and disabling disease and the treatment (incisive and precocious) should be similar to that for rheumatoid arthritis. At present, a definitive therapy does not yet exist, but the majority of PA patients can lead a fairly normal life and they do not show increased mortality rates (excluding the severe cases of erythrodermic or pustulosis psoriasis). However, as a result of the various problems of occupation and morbidity it causes, PA is a disease with great social involvement.