Age-related functional and structural retinal modifications in the Igf1-/- null mouse.

BACKGROUND: Mutations in the gene encoding human insulin-like growth factor-I (IGF-I) cause syndromic neurosensorial deafness. To understand the precise role of IGF-I in retinal physiology, we have studied the morphology and electrophysiology of the retina of the Igf1(-/-) mice in comparison with that of the Igf1(+/-) and Igf1(+/+) animals during aging. METHODS: Serological concentrations of IGF-I, glycemia and body weight were determined in Igf1(+/+), Igf1(+/-) and Igf1(-/-) mice at different times up to 360days of age. We have analyzed hearing by recording the auditory brainstem responses (ABR), the retinal function by electroretinographic (ERG) responses and the retinal morphology by immunohistochemical labeling on retinal preparations at different ages. RESULTS: IGF-I levels are gradually reduced with aging in the mouse. Deaf Igf1(-/-) mice had an almost flat scotopic ERG response and a photopic ERG response of very small amplitude at postnatal age 360days (P360). At the same age, Igf1(+/-) mice still showed both scotopic and photopic ERG responses, but a significant decrease in the ERG wave amplitudes was observed when compared with those of Igf1(+/+) mice. Immunohistochemical analysis showed that P360 Igf1(-/-) mice suffered important structural modifications in the first synapse of the retinal pathway, that affected mainly the postsynaptic processes from horizontal and bipolar cells. A decrease in bassoon and synaptophysin staining in both rod and cone synaptic terminals suggested a reduced photoreceptor output to the inner retina. Retinal morphology of the P360 Igf1(+/-) mice showed only small alterations in the horizontal and bipolar cell processes, when compared with Igf1(+/+) mice of matched age. CONCLUSIONS: In the mouse, IGF-I deficit causes an age-related visual loss, besides a congenital deafness. The present results support the use of the Igf1(-/-) mouse as a new model for the study of human syndromic deaf-blindness.

Carbon paste electrodes modified with biosolids, soils and biocomposites utilized to study the interaction between organic matter and copper.

Carbon paste electrodes (CPEs) modified with a biosolid, two types of soils with different amounts of organic matter (OM), and two biocomposites (soils mixed with a biosolid) were used to assess and compare the Cu(II) ion retention properties of the organic matter contained in the samples. The accumulation of Cu(II) on the surface of the modified carbon paste electrodes (MCPEs) was performed under open-circuit conditions. When comparing the response of the MCPEs while assessing parameters such as pH, preconcentration time, and adsorption/desorption capacity, it was found that the reaction mechanism of the two soils is different between the soils and dissimilar from the biosolid; while the biocomposites show reaction mechanisms that are intermediate between those of the soils and the biosolid. This was proven with the use of infrared spectroscopy, since the FTIR spectra show similarities between the two soils and significant differences between the soils and the biosolid.

Standardized low-molecular-weight heparin bridging regimen in outpatients on oral anticoagulants undergoing invasive procedure or surgery: an inception cohort management study.

BACKGROUND: Bridging therapy with low-molecular-weight heparin is usually recommended in patients who must stop oral anticoagulants before surgical or invasive procedures. To date, there is no universally accepted bridging regimen tailored to the patient's thromboembolic risk. This prospective inception cohort management study was designed to assess the efficacy and safety of an individualized bridging protocol applied to outpatients. METHODS AND RESULTS: Oral anticoagulants were stopped 5 days before the procedure. Low-molecular-weight heparin was started 3 to 4 days before surgery and continued for 6 days after surgery at 70 anti-factor Xa U/kg twice daily in high-thromboembolic-risk patients and prophylactic once-daily doses in moderate- to low-risk patients. Oral anticoagulation was resumed the day after the procedure with a boost dose of 50% for 2 days and maintenance doses afterward. The patients were followed up for 30 days. Of the 1262 patients included in the study (only 15% had mechanical valves), 295 (23.4%) were high-thromboembolic-risk patients and 967 (76.6%) were moderate- to low-risk patients. In the intention-to-treat analysis, there were 5 thromboembolic events (0.4%; 95% confidence interval, 0.1 to 0.9), all in high-thromboembolic-risk patients. There were 15 major (1.2%; 95% confidence interval, 0.7 to 2.0) and 53 minor (4.2%; 95% confidence interval, 3.2 to 5.5) bleeding episodes. Major bleeding was associated with twice-daily low-molecular-weight heparin administration (high-risk patients) but not with the bleeding risk of the procedure. CONCLUSIONS: This management bridging protocol, tailored to patients' thromboembolic risk, appears to be feasible, effective, and safe for many patients, but safety in patients with mechanical prosthetic valves has not been conclusively established.

Antioxidant effect of phenolic compounds (PC) at different concentrations in IEC-6 cells: A spectroscopic analysis.

Phenolic compounds (PC) have been proposed as natural antioxidant agents that protect cells against oxidative stress-related diseases. Nonetheless, their low bioavailability forecasts controversy about mechanisms on their in vivo scavenging activity against reactive oxygen species (ROS). It has been proposed that PC reduce directly ROS concentration. An alternative or complementary action of PC could be the activation of the cell's antioxidant pathway, involving the regulation of gene expression, like that initiated by the Nrf2 transcription factor. To date there is not enough experimental data to support or discard this possibility. In the present study, we evaluated the use of several PC to prevent peroxidation of macromolecules and to elicit the activation of the Nrf2 transcription factor in H2O2-stresed IEC-6 enterocytic cell line. Synchrotron microspectroscopy demonstrated that PC compounds protected proteins, lipids and nucleic acids against oxidation induced by H2O2. Immunofluorescence results showed that treatment with quercetin (Qc), catechin (Cat) and capsaicin (Cap) induced the translocation of Nrf2 into the nucleus, at the same level as did H2O2 treatment, thus mimicking the action of the endogenous cell response to peroxidation. Even though the detailed mechanism still needs to be elucidated, we demonstrated the activation of Nrf2 by PCs in response to oxidative stress.

[Registry of mild craniocerebral trauma: multicentre study from the Spanish Association of Pediatric emergencies]. / Registro de traumatismos craneoencefálicos leves: estudio multicéntrico de la Sociedad Española de Urgencias Pediátricas.

OBJECTIVE: To determine management practices of minor head trauma in children evaluated at Spanish Hospital Emergency Departments and to determine patient variables associated with intracranial injury. METHODS: Multicenter and prospective study during 18 months in 9 hospitals in Spain. Patients up to the age of 18 years with minor head trauma (Glasgow Coma Scale score higher than or equal to 13 on admission), treated in Emergency Departments and with a maximum onset of 72h since the traumatism, were included in the study. RESULTS: A total of 1070 patients were studied with a median age of 2.4 years (p25-75 0.9-6.4 years); 61.2% were male. The median time between head trauma and medical consultation was 1 hour (p25-75 0.6-2.5h). Skull X-rays were performed on 64.5% of the children and a head CT scan on 9%; 91.4% of X-ray and 84.4% of CT were normal. The prevalence of intracranial injury was 1.4% (95% CI: 0.8-2.3). Twenty-five point three percent of the patients were admitted; 4 (3.7%) required neurosurgical intervention during admission. None of the patients died. Multiple logistic regression analysis identified loss of consciousness (OR 4.2, 95% CI: 1.1-17; P=0.045), neurological deterioration (OR 8.8, 95% CI: 2.1-37.6; P=0.003) and cephalhaematoma (OR 14.6, 95% CI: 4.9-44; P <0.001) as independent predictors of intracranial injury. CONCLUSIONS: The combination of clinical parameters allows selection of patients with minor head trauma who need complementary explorations. In consequence, the routine use of skull X-ray in their initial evaluation is unnecessary.

Inhibition of α-amylase by flavonoids: Structure activity relationship (SAR).

Flavonoids are recognized to regulate animals' food digestion processes trough interaction with digestive enzymes. The binding capacity of hesperetin (HES), luteolin (LUT), quercetin (QUE), catechin (CAT) and rutin (RUT) with pancreatic α-amylase were evaluated, using UV-Vis spectroscopy, fluorescence and molecular docking. Using p-nitrophenyl-α-d-maltopentoside (pNPG5) as substrate analog, LUT showed the best inhibitory capacity, even better than that of the positive control, acarbose (ACA). A mixed-type inhibition was observed for HES, LUT and QUE, a competitive-type for ACA, while no inhibition was observed with CAT and RUT. In agreement with kinetic results, α-amylase presented a higher affinity for LUT, when analyzed by fluorescence quenching. The binding of flavonoids to amylase followed a static mechanism, where the binding of one flavonoid per enzyme molecule was observed. Docking analysis showed that flavonoids bound near to enzyme active site, while ACA bound in another site behind the catalytic triad. Extrinsic fluorescence analysis, together with docking analysis pointed out that hydrophobic interactions regulated the flavonoid-α-amylase interactions. The present study provides evidence to understand the relationship of flavonoids structure with their inhibition mechanism.

[Hepatocyte oxidant stress and alcoholic liver disease]. / Estrés oxidativo hepatocitario y hepatopatía alcohólica.

Acute and chronic alcohol consumption increases the production of reactive oxygen species (ROS), and enhances lipid peroxidation of lipids, proteins, and DNA. The mechanism by which alcohol causes cell injury is still not clear but a major role for ROS and lipid peroxidation-end products is considered. Many pathways have been suggested to play a role on how ethanol induces a state of "oxidative stress", including redox-state changes, acetaldehyde production, damage to the mitochondria, membrane injury, apoptosis, ethanol-induced hypoxia, effects on the immune system and altered cytokine production, increased endotoxin levels and activation of Kupffer cells, mobilization of iron, changes in the antioxidant defense, particularly mitochondrial glutathione (GSH), one electron oxidation of ethanol to 1-hydroxy-ethyl radical, and induction of CYP2E1. These pathways are not exclusive of one another and it is likely that several, indeed many systems contribute to the ability of ethanol to induce a state of oxidative stress.

[Neurotrophic action of insulin-like growth factor-I in the inner ear]. / Acciones neurotróficas del factor de crecimiento similar a la insulina de tipo I en el oído interno.

INTRODUCTION: Loss of hearing constitutes one of the most frequent disabling sensory impairments in the developed world. Different therapeutic approaches are currently being studied, including treatment with stem cells, genetic manipulation and pharmacological protection. AIM: To evaluate the role played by insulin-like growth factor-I (IGF-I) in the development, maintenance and repair of auditory functioning. DEVELOPMENT: Proper development of the inner ear is dependent on a suitable coordination of the cell processes of proliferation, differentiation, neurogenesis and programmed cell death, which are regulated by different factors, one of which is IGF-I. During the embryogenesis of the inner ear, this factor is expressed in abundance and is essential for cell survival and maintaining neuronal precursors. Studies conducted in Igf-1-/- null mice have highlighted its importance in the development and continued functioning of the inner ear. Mice with a deficit in this gene display morphological disorders that correspond to severe functional deficiencies, which are confirmed by analysing brainstem auditory evoked potentials. A deficit of IGF-I in humans is also accompanied by profound sensory hypoacusis. CONCLUSIONS: In a scenario like this, IGF-I appears as a key factor in the development of auditory functioning and a candidate for regenerative therapy of the inner ear.

IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1 and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.

Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a crucial role in modulating neuronal function and synaptic plasticity in the adult brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple anomalies in the inner ear and spiral ganglion. An issue that remains unknown is whether, in addition to these peripheral abnormalities, IGF-1 deficiency also results in structural changes along the central auditory pathway that may contribute to an imbalance between excitation and inhibition, which might be reflected in abnormal auditory brainstem responses (ABR). To assess such a possibility, we evaluated the morphological and physiological alterations in the cochlear nucleus complex of the adult mouse. The expression and distribution of the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory transporter (VGAT), which were used as specific markers for labeling excitatory and inhibitory terminals, and the involvement of the activity-dependent myocyte enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in the cochlear nucleus area and cell size along with cell loss in the cochlear nuclei of the deficient mouse. Additionally, our results demonstrate that there is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of MEF2 transcription factors together with increased wave II amplitude in the ABR recording. Our observations provide evidence of an abnormal neuronal cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that the increased efficacy of glutamatergic synapses might be mediated by MEF2 transcription factors.

Maitotoxin-induced calcium entry in human lymphocytes: modulation by yessotoxin, Ca(2+) channel blockers and kinases.

We have studied the effect of the ciguatera-related toxin maitotoxin (MTX) on the cytosolic free calcium concentration ([Ca(2+)]i) of human peripheral blood lymphocytes loaded with the fluorescent probe Fura2 and the regulation of MTX action by different drugs known to interfere in cellular Ca(2+) signalling mechanisms and by the marine phycotoxin yessotoxin (YTX). MTX produced a concentration-dependent elevation of [Ca(2+)]i in a Ca(2+)-containing medium. This effect was stimulated by pretreatment with YTX 1 microM and NiCl(2) 15 microM. The voltage-independent Ca(2+) channel antagonist 1-[beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenyl]-1H-imidazole hydrochloride (SKF96365) blocked the MTX-induced [Ca(2+)]i elevation, while the L-type channel blocker nifedipine had no effect. Pretreatment with NiCl(2) or nifedipine did not modify YTX-induced potentiation of MTX effect, and SKF96365-induced inhibition was reduced in the presence of YTX, which suggest different pathways to act on [Ca(2+)]i. Preincubation with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide.2HCl (H-89) or genistein (10 microM) also had no effect on the MTX-induced [Ca(2+)]i increment. In contrast, the PKC inhibitor bisindolilmaleimide I (GF109203X 1 microM) potentiated the MTX effect, whereas phosphatidylinositol (PI) 3-kinase inhibition with wortmannin (10 nM) reduced the MTX-elicited Ca(2+) entry. In summary, MTX produced Ca(2+) influx into human lymphocytes through a SKF96365-sensitive, nifedipine-insensitive pathway. The MTX-induced [Ca(2+)]i elevation was stimulated by the marine toxin YTX through a mechanism insensitive to SKF96365, nifedipine or NiCl(2). It was also stimulated by the divalent cation Ni(2+) and PKC inhibition and was partially inhibited by PI 3-kinase inhibition.

HCO(3)(-) ions modify the role of PKC isoforms in the modulation of rat mast cell functions.

PKC and the intracellular calcium signal are two well-known intracellular signaling pathways implicated in the induction of mast cell exocytosis. Both signals are modified by the presence or absence of HCO(3)(-) ions in the external medium. In this work, we studied the regulation of the exocytotic process by PKC isozymes and its relationship with HCO(3)(-) ions and PKC modulation of the calcium entry. The calcium entry, induced by thapsigargin and further addition of calcium, was inhibited by PMA, a PKC activator, and enhanced by 500 nM GF109203X, which inhibits Ca(2+)-independent PKC isoforms. PMA inhibition of the Ca(2+) entry was reverted by 500 and 50 nM GF109203X, which inhibit Ca(2+)-independent and Ca(2+)-dependent isoforms, respectively, and Gö6976, a specific inhibitor of Ca(2+)-dependent PKCs. Thus, activation of Ca(2+)-dependent and Ca(2+)-independent PKC isoforms inhibit Ca(2+) entry in rat mast cells, either in a HCO(3)(-)-buffered or a HCO(3)(-)-free medium. PMA, GF109203X, Gö6976 and rottlerin, a specific inhibitor of PKC delta, were also used to study the role of PKC isoforms in the regulation of exocytosis induced by thapsigargin, ionophore A23187 and PMA. The results demonstrate that Ca(2+)-dependent PKC isoforms inhibit exocytosis in a HCO(3)(-)-dependent way. Moreover, Ca(2+)-independent PKC delta was the main isoform implicated in promotion of Ca(2+)-dependent mast cell exocytosis in the presence or absence of HCO(3)(-). The role of PKC isoforms in the regulation of mast cell exocytosis depends on the stimulus and on the presence or absence of HCO(3)(-) ions in the medium, but it is independent of PKC modulation of the Ca(2+) entry.

Modulation of thapsigargin-induced calcium mobilisation by cyclic AMP-elevating agents in human lymphocytes is insensitive to the action of the protein kinase A inhibitor H-89.

Ca2+ mobilisation from internal stores and from the extracellular medium is one of the primary events involved in lymphocyte activation and proliferation. Regulation of these processes by adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) was studied in Fura2-loaded human peripheral blood lymphocytes. Cytosolic Ca2+ concentration ([Ca2+]i) was measured in single cells by the use of a ratio imaging fluorescence microscope and Ca2+ mobilisation was achieved by the use of the endoplasmic reticulum (ER) Ca2+ ATPase inhibitor, thapsigargin (Thg). Our results show that both activation and inhibition of PKA, with forskolin (FSK) and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide.2HCl (H-89), respectively, inhibited the Thg-induced Ca2+ entry. Furthermore, FSK also reduced the ability of Thg to release Ca2+ from internal stores. This reduction was inhibited by the adenylyl cyclase (AC) inhibitor 9-(tetrahydro-2-furanyl)-9-H-purin-6-amine (SQ22,536), but not by the PKA inhibitor H89, indicating that cAMP but not PKA is responsible for this effect. FSK effect was mimicked by dibutyryl cAMP (dbcAMP) and by inhibition of phosphodiesterases (PDEs) with rolipram (ROL) and milrinone (MIL). We also showed that a very high concentration of H-89 (100 microM) releases Ca2+ from an intracellular pool, although this action is probably independent of PKA inhibition. Neither 10 microM H-89 nor other cAMP/PKA-modulating drugs had any effect on the basal [Ca2+]i of human lymphocytes. We conclude that PKA may act as a fine modulator of capacitative Ca2+ entry, while cAMP has a PKA-independent interaction with the Ca2+ stores of human lymphocytes.

Modulation of cytosolic calcium levels of human lymphocytes by yessotoxin, a novel marine phycotoxin.

Yessotoxin (YTX) is a polyether toxin of marine origin that has been classified among the diarrheic shellfish poisoning (DSP) toxins group due to its lipophilic nature. However, unlike other DSP toxins, YTX does not produce diarrhea and its mechanisms of action are unknown. We studied the effect of YTX on the cytosolic calcium levels of freshly isolated human lymphocytes by means of fluorescence imaging microscopy. We showed that YTX produced a calcium influx through nifedipine and SKF 96365 (1-[beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenyl]-1H-imidazole hydrochloride)-sensitive channels. This Ca2+ entry was not affected by the DSP toxin okadaic acid, which inhibits protein phosphatases. In addition, YTX also produced an inhibition of capacitative calcium entry activated by thapsigargin or by preincubation in a Ca2+-free medium. This capacitative calcium entry was not sensitive to nifedipine. Furthermore, the inhibitory effect of YTX was dependent on the time of addition of the toxin. We suggest that YTX may interact with calcium channels in a way similar to that described for other polyether marine compounds such as brevetoxins and maitotoxin, although an involvement of other second messengers is also likely.

Dimethylsphingosine increases cytosolic calcium and intracellular pH in human T lymphocytes.

N,N-Dimethyl-D-erythro-sphingosine (DMS) is the N-methyl derivative of sphingosine; both are activators of sphingosine-dependent protein kinases. The aim of this work was to study the effect of DMS on cytosolic calcium and intracellular pH (pHi) in human T lymphocytes. The variations of calcium and pH were determined by fluorescence digital imaging using Fura-2-AM and BCECF-AM, respectively. DMS increased both pHi and Ca(2+)-cytoslic in human T lymphocytes. These effects were dose-dependent. This drug induced a fast increase in pHi and a release of calcium from different intracellular calcium pools than thapsigargin. DMS also induced a Ca(2+)-influx different from the store-operated calcium channels, since drug effect was not modified by 30 microM SKF 96365. The influx of calcium induced by DMS was completely blocked by preincubation in the presence of nickel, or lanthanum, while the increase in pHi was no affected. However, the presence of cadmium reduced but does not block Ca(2+)-influx. The inhibition of G-protein by 100 ng/mL pertussis toxin, and the inhibition of tyrosine kinases by genistein significantly reduced the cytosolic calcium increase induced by DMS by an inhibition of both, release of calcium from intracellular pools and influx from extracellular medium. The inhibition of pools emptiness by these drugs was related with the inhibition that they induce in the DMS cytosolic alcalinization. In summary, DMS increases pHi and as consequence releases calcium from intracellular pools, and it increases calcium-influx through a channel different from store-operated channel (SOC). Both cytosolic calcium and pHi increase are modulated by G-proteins and tyrosine kinases.

Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a.

The occurrence of thyroid abnormalities and the appearance of organ- and non-organ-specific autoantibodies during long-term recombinant interferon alpha-2a (IFN-alpha) therapy were studied in 86 and 51 consecutive outpatients with hepatitis C and B virus-related chronic active hepatitis (CAH-HCV and CAH-HBV), respectively. Most patients had longstanding community-acquired hepatitis. At baseline, 9.3% of CAH-HCV and 3.9% of CAH-HBV patients showed clinical and/or biochemical signs of thyroid dysfunction. The remaining patients were euthyroid, although anti-thyroid autoantibodies were found in 33/78 (42.3%) of CAH-HCV and in 5/49 (10.2%) of CAH-HBV patients. During IFN-alpha treatment, increased anti-thyroid autoantibody levels were seen in 40% of CAH-HCV initially negative patients, while they became detectable in no more than 10% of CAH-HBV patients. Interferon-alpha-induced hypo- or hyperthyroidism was recorded in 12 of 35 CAH-HCV patients treated for 12 months (34.3%). Only one CAH-HBV patient developed hyperthyroidism. High titers of anti-nuclear autoantibodies (ANA) were recorded at enrollment in 5/36 (13.8%) of CAH-HCV and in 3/16 (18.7%) of CAH-HBV patients. Only one CAH-HCV patient displayed anti-parietal cell antibodies (PCA). After IFN-alpha treatment, ANA were found in 10/28 (35.7%) and PCA in 2/28 (7.1%) of CAH-HCV patients, while an additional CAH-HBV patient developed PCA, but not ANA. However, no signs of systemic autoimmune disease were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced percentage of Leu M3+DR+ and Leu M3+CD25+ cells in newly diagnosed IDDM patients.

The percentage of Leu M3+DR+ and of Leu M3+CD25+ cells was determined by means of immunofluorescence analysis in a group of patients with insulin dependent diabetes mellitus (IDDM). Our results show that an increased percentage of these cells may occur in the early stage of the disease. These data provide evidence for a "phenotypical" activation of Leu M3+ cells at the onset of the disease and warrant future studies to evaluate the potential role of these cells in the pathogenesis of IDDM.

What is the pathogenetic role of antiphospholipid antibodies?

The association between antiphospholipid antibodies (aPL) and arterial or venous thrombosis, fetal loss and thrombocytopenia defines the so-called "antiphospholipid syndrome" (APS). Despite serial studies in recent years, a clear pathogenetic mechanism(s) has not yet been demonstrated. Several authors have investigated the interaction between aPL and the membranes of blood cells (endothelial cells and platelets) involved in coagulation. aPL is also thought to affect the balance between the procoagulant and anticoagulant states by interacting with plasma or tissue cofactors. Finally, the strong association between aPL and experimental animal models of fetal loss supports a direct pathogenetic role for aPL in inducing a poor pregnancy outcome in APS women.

[Distribution of T-lymphocyte subpopulations in non-Hodgkin's lymphomas]. / Distribuzione delle sottopopolazioni linfocitarie T nei linfomi non Hodgkin.

Percentage OKT3, OKT11+, OKT4+ and OKT8+ lymphocytes were measured in the peripheral blood of 16 patients with untreated non-Hodgkin B lymphoma aged 37-63 (11 males and 5 females). Patients were classified according to the histological type and clinical stage of the disease. In all cases, T3+, T4+, T8+ and T11+ levels were higher then in the controls but the OKT4/OKT8 ratio remained normal in 14 out of 16 cases.

[The OKT4/OKT8 ratio in benign monoclonal gammopathies]. / Il rapporto OKT4/OKT8 nelle gammopatie monoclonali benigne.

The percentages of OKT 4 helper and OKT 8 suppressor lymphocytes were studied in 58 patients in whom a monoclonal protein was accidentally identified in the absence of any clinical signs of multiple myeloma, macroglobulinaemia, amyloidosis or lymphoma. The patients were aged 32-63 and were followed-up for 6 years. The F test used in this study revealed a statistically significant difference between the healthy controls and the patients with BMG in one of the parameters examined: OKT 8. This produced a statistically significant alteration in the OKT 4/OKT 8 ratio.

[Great vessel and temporal artery involvement in temporal arteritis]. / Arteritis de células gigantes con compromiso de grandes vasos y arteria temporal.

The importance of this case report resides in the unusual initiation of an arterial inflammatory disease. The patient presented ischemic symptoms and signs with bilateral upper limb claudication and Raynaud's phenomenon, with ulcerations on her left hand. We describe the patient's clinical history, diagnosis and therapy.