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Introduction: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real‐world clinical practice. Methods: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. Results: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/μL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non‐nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV‐RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1–92.6) by intention‐to‐treat (ITT) and 94.2% (95% CI 91.3–96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low‐density lipoprotein‐cholesterol, glutamic–pyruvic transaminase (GPT), gamma‐glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. Conclusions: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real‐world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one‐third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function. [ABSTRACT FROM AUTHOR]

Objectives: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. Methods: Primary RAHC infection was diagnosed when anti‐HCV antibody seroconversion was documented. In anti‐HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. Results: All 350 patients tested negative for anti‐HCV at baseline and had at least one follow‐up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person‐years were 3.77 (0.5–12.9) in 2016, 1.85 (0.6–4.3) in 2017, 1.49 (0.4–3.8) in 2018 and 1.98 (0.6–4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93–172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38–54.15; P = 0.026) and sharing chem‐sex drugs (IRR: 4.93, 95% CI: 1.17–20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. Conclusions: The incidence of RAHC among HIV‐infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem‐sex drugs among MSM. [ABSTRACT FROM AUTHOR]

Oestrid flies (Diptera: Oestridae) do not feed during the adult stage, so they depend on an efficient assimilation and storage of nutrients during their parasitic larval stage. We describe the general morphology and provide volumetric data for the digestive and excretory organs of the three larval instars of the nasal bot fly Oestrus ovis L., using micro‐computed tomography. The size of the digestive and excretory organs greatly increased across larval instars. In all instars, the two salivary glands were remarkably large and formed a 'glandular band' by coming together, but without lumina uniting, at their posterior ends. The distal region of the anterior Malpighian tubules was greatly enlarged and full of highly radio‐opaque concretions. Moreover, the anatomy of O. ovis third‐instar larva was compared to that of two species of, respectively, similar and different feeding habits: Cephenemyia stimulator (Clark) and Hypoderma actaeon Brauer. Whereas the general morphology and arrangement of the digestive and excretory systems of C. stimulator was similar to that of O. ovis, some differences were observed in H. actaeon: a swollen anterior region of the midgut, salivary glands shorter and not forming a 'band' and anterior Malpighian tubules narrowly uniform throughout their entire length. [ABSTRACT FROM AUTHOR]

Summary: A methodology for the calculation of gradients with respect to design parameters in general fluid‐structure interaction problems is presented. It is based on fixed‐point iterations on the adjoint variables of the coupled system using algorithmic differentiation. This removes the need for the construction of the analytic Jacobian for the coupled physical problem, which is the usual limitation for the computation of adjoints in most realistic applications. The formulation is shown to be amenable to partitioned solution methods for the adjoint equations. It also poses no restrictions to the nonlinear physics in either the fluid or structural field, other than the existence of a converged solution to the primal problem from which to compute the adjoints. We demonstrate the applicability of this procedure and the accuracy of the computed gradients on coupled problems involving viscous flows with geometrical and material nonlinearities in the structural domain. [ABSTRACT FROM AUTHOR]

Background and Purpose: Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension.Experimental Approach: Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg · kg(-1) · day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg · kg(-1) · day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg · kg(-1) · day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used.Key Results: Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-α expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment.Conclusions and Implications: COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage. [ABSTRACT FROM AUTHOR]

Background and Purpose Toll-like receptor 4 ( TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II ( AngII)-induced hypertension and the associated vascular structural, mechanical and functional alterations. Experimental Approach AngII was infused (1.44 mg·kg−1·day−1, s.c.) for 2 weeks in C57BL6 mice, treated with a neutralizing anti- TLR4 antibody or IgG (1 μg·day−1); systolic BP (SBP) and aortic cytokine levels were measured. Structural, mechanical and contractile properties of aortic and mesenteric arterial segments were measured with myography and histology. RT-PCR and Western blotting were used to analyse these tissues and cultured vascular smooth muscle cells ( VSMC) from hypertensive rats (SHR). Key Results Aortic TLR4 mRNA levels were raised by AngII infusion. Anti- TLR4 antibody treatment of AngII-treated mice normalised: (i) increased SBP and TNF-α, IL-6 and CCL2 levels; (ii) vascular structural and mechanical changes; (iii) altered aortic phenylephrine- and ACh-induced responses; (iv) increased NOX-1 m RNA levels, superoxide anion production and NAD(P)H oxidase activity and effects of catalase, apocynin, ML-171 and Mito- TEMPO on vascular responses; and (v) reduced NO release and effects of L- NAME on phenylephrine-induced contraction. In VSMC, the MyD88 inhibitor ST-2825 reduced AngII-induced NAD(P)H oxidase activity. The TLR4 inhibitor CLI-095 reduced AngII-induced increased phospho- JNK1/2 and p65 NF- κB subunit nuclear protein expression. Conclusions and Implications TLR4 up-regulation by AngII contributed to the inflammation, endothelial dysfunction, vascular remodelling and stiffness associated with hypertension by mechanisms involving oxidative stress. MyD88-dependent activation and JNK/NF- κB signalling pathways participated in these alterations. [ABSTRACT FROM AUTHOR]

Oestrus ovis L. (Diptera: Oestridae) is a cosmopolitan agent of myiasis in sheep and goats. The parasitic phase begins after adult females deposit first-stage larvae (L1) into the nostrils of hosts; these larvae develop into L2 and L3 in the nasal and sinus horn cavities. Sneezing and nasal discharges are the major clinical signs in infected animals. The pathogenesis of O. ovis infection is caused by: (a) the trauma resulting from the mechanical action of spines and hooks during larval movement on mucosal membranes, and, more importantly, (b) an allergenic reaction provoked by molecules excreted/secreted by larvae, of which salivary antigens are those mainly recognized by the host's immune system. The recruitment of immune reactive cells increases gradually from the nasal to sinus cavities in infected hosts. Mast cells, eosinophils, macrophages and lymphocytes are always more numerous in infected than non-infected animals. Humoral (antibody) systemic response of immunoglobulin G (IgG) usually reaches seroconversion 2-4 weeks post-first infection and the highest levels are observed during the development of L2 and L3 larvae. Local antibody responses include specific IgG, which has been found to negatively correlate with larval survival and development. Hypersensitivity reaction, immunomodulation, immunization trials and mixed infections of O. ovis and helminths are discussed. [ABSTRACT FROM AUTHOR]

Objectives: To chart saliva crystallisation patterns throughout pro-oestrus and oestrus in bitches, and to assess their reliability as a tool for optimising the timing of breeding. Methods: Six beagle bitches with normal reproductive activity were used. Saliva ferning patterns were established during pro-oestrus and oestrus. Vaginal cytology, progesterone (P4) levels and behavioural signs were used to determine the optimum mating time. Receiver operating characteristic (ROC) analysis was performed. Results: Different ferning patterns were scored from 0 to 2. Although variations in saliva crystallisation were noted during the follicular phase of the oestrous cycle in bitches, the test did not prove accurate; test sensitivity was 40·6%, i.e. too low to reliably discriminate the fertile period, while specificity was 86·1%. Clinical Significance: This test could be used to complement other methods of determining the fertile period in bitches, but its potential capacity remains to be demonstrated. [ABSTRACT FROM AUTHOR]

Background Short-term antiretroviral therapy (START) to prevent mother-to-child transmission (MTCT) is currently recommended for all HIV-1-infected pregnant women. The objective of this study was to assess the effect on CD4 cell counts and viral load dynamics the withdrawal of START after birth could generate. Methods This was a 5-year cohort study involving HIV-1-infected pregnant women who presented with CD4 counts >300 cells/μL and had received START to prevent MTCT. Results Seventy-five pregnancies were assessed. In 24 cases, there was a history of antiretroviral therapy prior to prophylaxis. The median baseline CD4 count was 573 cells/μL. In 75% of cases, prophylaxis was started after 26.6 weeks of gestation. The median CD4 cell count increase over baseline during prophylaxis was 24.5%. In only five cases did HIV-1 viral load remain detectable during prophylaxis. After START, CD4 cell counts did not drop significantly, and the HIV-1 viral load plateau was near the baseline level. The estimated mean time for CD4 count to fall below 300 cells/μL was 3.5 years and was directly associated with high baseline CD4 cell count, as well as with CD4 increase after prophylaxis, whereas it was negatively correlated with previous use of antiretroviral (ARV) drugs and persistence of detectable HIV-1 viral load during prophylaxis. Conclusions A potent, well-tolerated prophylactic ARV regimen can improve CD4 cell counts during and after START. In women receiving such prophylaxis, there is a remarkable time interval for CD4 cell counts to drop to levels that indicate treatment. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to analyse the prevalence of cervical lipomatosis (CL) in HIV-infected patients on highly active antiretroviral therapy (HAART) and the factors associated with its development. Methods This was a multicentre, observational, 1:1 case-control study. HIV-infected patients with CL (cases) and HIV-infected patients from the same cohort, controlled for age (±5 years), sex and body mass index (±2.5 kg/m2) (controls), were included in the study, and a multiple conditional logistic regression was performed to identify factors related to CL. Results CL was reported in 80 patients (1.8%) from a cohort of 4214 patients on HAART followed up in 10 Spanish hospitals. CL was associated with time of exposure to stavudine [for each 6-month increase, odds ratio (OR) 5.82, 95% confidence interval (CI) 5.70-5.94, P=0.0073] and lipoatrophy (OR 8.04, 95% CI 2.93-22.02, P=0.00001). Conclusions Although lipodystrophy is very frequent among HIV-infected patients on HAART, CL is an uncommon type of fat redistribution in this population, and in our cohort it was related to time of exposure to stavudine and lipoatrophy. [ABSTRACT FROM AUTHOR]

Objectives To analyse the characteristics of HIV-infected patients admitted to an Intensive Care Unit (ICU) and to compare them in the pre-highly active antiretroviral therapy (HAART) and HAART eras. Methods All HIV-infected patients who were admitted to the ICU of our hospital between January 1990 and December 2003 were reviewed. Patients were divided into two groups based on whether they were admitted before or after the advent of HAART, the cut-off date being 31 December 1996. Results Data were collected on 66 patients, 17 in the pre-HAART and 49 in the HAART era. The proportion of HIV-infected patients admitted to the ICU in our HIV-infected population increased after the introduction of HAART (3.8 vs 0.5%; P=0.001), and the largest diagnostic group was respiratory pathology in both periods. More than a third of patients were diagnosed with HIV infection during the ICU income, and only 31.2% were on antiretroviral therapy. The in-hospital mortality was 53.0%, and later survival was high. There were no significant differences between the pre-HAART and HAART eras. Conclusions Our results suggest that the characteristics of HIV-infected patients admitted to ICU have not changed: respiratory diseases are still the most frequent cause of admission, in-hospital mortality is high, and later survival rates are good. [ABSTRACT FROM AUTHOR]

Objectives To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment. Methods A prospective, observational study of 95 HIV-positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow-up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg] was defined according to international criteria. Results Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4-cell count on SBP increase. Conclusions Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV-infected patients on HAART. [ABSTRACT FROM AUTHOR]

Meat allergy is rarely reported. Most of the described cases are sensitizations to bovine serum albumin. The aim of the study was to describe a case of allergy to a new meat allergen and, after its characterization. A 35-year-old nonatopic female with allergic episodes after ingestion of several types of meat was studied. Skin tests (prick and prick-to-prick); total and specific immunoglobulin E (IgE) determination; sodium dodecyl sulphate-polyacrylamide gel electrophoresis and specific IgE determination by immunoblotting under different conditions were performed. A 17-kDa allergen was semipurified by ethanol fractionation and its amino-terminal sequence was determined. The existence of specific IgE directed to this protein was studied by immunoblot in 80 atopic patients. The patient showed specific IgE antibodies to a 17-kDa protein. During the isolation of this allergen it was found that a 70–90% (vol/vol) ethanol concentration was able to purify the protein. The characterization revealed that it was a heat-resistant protein without disulfide bonds. N-terminal amino acid sequence (16 residues) showed identity with myoglobin. The study of specific IgE to this allergen among atopic patients showed that it was recognized by about 1% of the subjects. We describe a case of meat allergy caused by myoglobin. This is the first described case of monosensitization to this protein. [ABSTRACT FROM AUTHOR]

Abstract. The process of testicular maturation in relation to intrapuparial development was studied in the sheep nasal bot fly, Oestrus ovis L. (Diptera: Oestridae). After formation of the puparium during larval–pupal apolysis and the cryptocephalic pupal stage (≈ 24–72 h), spermatogonia had undergone mitotic divisions and sperm cysts had been formed. Five days after pupariation, spermatogonia transformed into primary spermatocytes during the phanerocephalic pupal stage, and secondary spermatocytes first appeared during the pupal–adult apolysis. Secondary spermatocytes began undergoing the second meiotic division by day 8 (transparent-eye pharate adult stage). By days 9 and 10, round spermatids were present and began to elongate by day 11. By day 12, the first bundles of tailed spermatozoa had appeared. By day 15 (the yellow-orange eye pharate adult stage), round, elongated, tailed and bundled spermatids were predominant and by day 17 differentiating spermatids occupied nearly 35% of the testicular cavity, and 60% was occupied by free sperm. By day 21 (the red-brown eye pharate adult stage), spermatozoa colonized the seminal vesicle. At emergence (≈ day 22), a complement of free sperm occupied the testis and the seminal vesicle, but groups of developing cells frequently remained in certain zones. Spermatogenesis was carried out after pupariation and spermiogenesis occurred during the pharate adult stage. After emergence, males possessed fully formed spermatozoa ready for ejaculation. [ABSTRACT FROM AUTHOR]

Human autologous-rosette-forming T cells (Tar cells) have many of the characteristics of post- thymic precursor cells. Thus, they bind to sheep erythrocytes but have neither receptors for the Fc portion of IgG nor for that of IgM. They include a subpopulation that binds peanut agglutinin which suggests that they are immature and, as opposed to T cells with either receptors for the FC portion of IgM (Tμ) or of IgG (Tγ), Tar cells adhere to nylon wool, another possible indicator of immaturity, as is their extreme sensitivity to hydrocortisone both in vitro and in vivo. There are more Tar cells in cord blood than in the peripheral blood of young adults and there are more Tar cells in the peripheral blood of young adults than in the peripheral blood of elderly subjects. By co-culturing Tμ and B cells, or Tμ, or Tar and B cells in the presence of pokeweed mitogen (PWM) we were able to determine that these cells cause feedback inhibition, a function considered characteristic of post-thymic precursors. In co-cultures in which we placed mononuclear cells (MNC) or MNC plus Tar cells, or MNC depleted of Tar cells or MNC depleted of Tar cells plus Tar cells stimulated with PWM, we determined that Tar cells play a role in the generation of suppression thereby confirming that human Tar cells are precursor cells. We also found that Tar cells proliferated and generated Tγ and Tμ cells both spontaneously and in greater numbers, under the effect of serum thymic factor. [ABSTRACT FROM AUTHOR]

Sensitization to the flower of saffron, a plant commonly grown in Spain for commercial purposes, and its clinical significance as an occupational allergen were studied. The prick test and RAST, with saffron pollen, stamen. and pistil extracts, were used to evaluate the cutaneous and specific antibody responses in the studied population. Provocation tests in patients with clinical findings were used to verify the implication of saffron components in these symptoms. Fifty saffron workers were evaluated. Three of them were sensitized to saffron pollen and stamen proteins, giving prick and RAST positive values. One patient presented asthma, showing a positive bronchial provocation test, and two patients rhinoconjunctivitis, showing positive conjunctival provocation tests. Of a general allergic population of 237, 10 patients also presented cutaneous test and IgE positive to saffron. Saffron allergens (from pollen and stamens) were characterized by SDS-PAGE immunoblotting. A relevant allergen of 15.5 kDa with profilinic nature was detected and further purified by high-resolution gel filtration chromatography. No allergenic components were demonstrated in pistils. cross-reactivity of saffron extracts was evaluated by RAST inhibition with respect to other pollen species commonly causing sensitization in the same area of study. A significant degree of cross-reactivity was demonstrated between saffron and Lolium, Salsola, or Olea. The identification of the protein components involved in the cross-reactions was investigated by blot inhibition. [ABSTRACT FROM AUTHOR]

A method based on ion-exchange column chromatography to enhance the protein content of fruit allergenic extracts was found to help make the subsequent SDS-PAGE immunoblotting assays possible; otherwise, they were difficult to achieve due to the high carbohydrate content. Fractionated extracts of apple, pear, and peach (peel and pulp) were obtained by anion-exchange chromatography (Q-Sepharose™ column), providing clear electrophoretic patterns which allowed IgE detection by enzymatic assays of the transferred membranes. This chromatographic method produced in one single step an enriched extract directly from the standard crude aqueous one, with an increment in the protein content of more than sixfold, on average; thus, it proved to be more suitable than the usual chemical fractionation procedures. [ABSTRACT FROM AUTHOR]

Four different commercially available raw materials of dog epithelia (dander, hair and skin scraping, skin scraping, and whole skin) were compared by means of biochemical methods such as SDS-PAGE and chromatography with the SMART™ System, immunochemical methods such as RAST and SDS-PAGE immunoblotting, and cutaneous tests. Dander extract clearly exhibited the highest IgE binding and in vivo allergenic activity. The dog major allergens Can fI and the 19-kDa protein were adequately detected only in dander extract. Thus, it is concluded that dander is the most suitable epithelial source for preparing dog allergenic-extracts. [ABSTRACT FROM AUTHOR]

We have compared previous studies of the immune response to dextran (Dx) B512 in thymus-deficient nu/nu and thymectomized, lethally irradiated, and bone marrow-reconstituted mice with those obtained with cyclosporin A (CyA) as a T-cell-inhibiting drug. Our data show that only immune responses to TD forms of Dx B512 are susceptible to suppression by CyA, whereas anti-alpha 1-6 and anti-DNP antibodies induced by high molecular weight dextran and DNP-native Dx, respectively, were not inhibited. Similar results were obtained when polyclonal responses were studied. The polyclonal response induced by another dextran preparation, the polyanion dextran sulphate (DxS), was inhibited by CyA to the same extent as polyclonal T-cell activation by T-cell mitogens. [ABSTRACT FROM AUTHOR]

The autologous rosette-forming T cells (Tar cells) isolated by means of their ability to form rosettes with autologous erythrocytes were characterized by the use of OKT monoclonal anti-human T-cell subset antibodies and a monoclonal anti-HLA-DR antibody. We found that the phenotype of Tar cells was OKT 3+4+8+Dr- as determined by both indirect immunofluorescence microscopy and complement-mediated killing of 51Cr-labelled Tar cells. In addition, we found that Tar lymphocytes were able to develop cytotoxicity against allogeneic and trinitrophenol (TNP)-conjugated autologous target cells in the presence of interleukin-2 (IL-2) or serum thymic factor. However, these cells showed little or no cytotoxicity in the absence of interleukin-2 or serum thymic factor. Tar lymphocytes generated helper function for B lymphocytes in the presence of interleukin-2 in both pokeweed mitogen (PWM)- and purified protein derivative (PPD)-stimulated cultures. Nevertheless, non-IL-2-treated Tar cells did not exhibit any helper activity on B cells. Finally, pretreatment of Tar cells with 1000-1500 rad of X ray made these cells unable to develop helper function for B lymphocytes. It is concluded that: (1) OKT 3+4+8+Dr- Tar cells are able to generate cytotoxicity against alloantigens and TNP-labelled self structures provided they are stimulated by IL-2 or serum thymic factor; (2) these cells need both to proliferate and to receive help from IL-2 to develop helper cells capable of assisting B-lymphocyte differentiation into plasma cells in both PWM- and PPD-stimulated cultures. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) infection of stimulator cells significantly increased the proliferative response of T cells in the autologous mixed lymphocyte reaction (AMLR). The addition of a monoclonal anti-HLA-DR antibody to AMLR cultures in which either EBV-infected or non-infected non-T cells were used as stimulator cells strongly inhibited the proliferative response irrespective of the presence of EBV. It is concluded that EBV does not by itself activate the responding cells and that HLA-DR antigens are necessary to trigger T cells. Increased generation of suppressor T cells, determined in both alloantigen-induced DNA synthesis and pokeweed-mitogen-stimulated immunoglobulin production, was found after an EBV infection of stimulator cells. Similarly, EBV-infected non-T cells significantly increased the generation of killer T cells, determined in three different types of target cells: phytohaemagglutinin-stimulated mononuclear cells, EBV-transformed cells, and concanavalin- A-activated murine spleen cells. The increased T-cell responses after an EBV infection may reflect the attempts in vivo to control and hold in check the viral infection. [ABSTRACT FROM AUTHOR]

Monoclonal anti-HLA-DR antibodies inhibited the production of interleukin-2 (IL-2) when added from the initiation of autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reactions, but not 60 h later. The inhibitory activity of the anti-DR sera became apparent 8 h after initiation of the cultures and was maintained throughout the culture period. Interleukin-1 (IL-1) added to cultures carried out in the absence of the anti-DR antibodies significantly enhanced the production of IL-2, whereas addition of IL-1 to anti-DR-treated AMLR and MLR cultures did not restore or increase the synthesis of IL-2. However, when the anti-DR antibodies were added to IL-1-supplemented AMLR and MLR cultures 60 h or more after initiation of the reactions, the antiserum no longer inhibited the capacity of I L-I to promote the synthesis of IL-2 or the production of IL-2. Finally, resting T cells were unresponsive to IL-1 and did not produce IL-2. It thus seemed that the anti-DR antibodies inhibited production of IL-2 in AMLR and MLR by rendering the IL-2 producer T cells unresponsive to IL-1. Cyclosporin-A, a drug that abrogates activation of T cells by blocking their receptors for HLA-DR antigens, also rendered IL-2-producer T cells unresponsive to IL-1 and abrogated the production of IL-2 in AMLR and MLR. Since resting T cells do not respond to IL-1 or produce IL-2, it is concluded that HLA-DR antigens of the stimulator cells participate in the production of IL-2 in AMLR and MLR by enabling the IL-2 producer T lymphocytes to respond to IL-1. Interleukin-1 promotes the production of IL-2 by IL-1-sensitive T cells. Once the IL-2-producer T cells become sensitive to IL-1, there is no further requirement for HLA-DR antigens. [ABSTRACT FROM AUTHOR]

Adult peripheral blood T lymphocytes activated in autologous mixed lymphocyte reactions (A M LR) exerted cytotoxicity on both phytohaemagglutinin-stimulated cells and Epstein-Barr virus-transformed cells. When autologous rosette-forming T cells were removed from total T lymphocytes, there was no generation of cytotoxicity. Re-addition of autologous rosette-forming T cells (Tar cells) to a population of T cells depleted of Tar cells restored the cytotoxic activity. Treatment of Tar cells with niitomycin C before their activation in AMLR caused loss of their capacity to give rise to killer cells. Furthermore, resting Tar cells did not show any cytotoxic activity as determined in the two different types of target cells used. Since Tar cells are able to differentiate into T gamma cells and since T gamma cells possess spontaneous cytotoxic activity, it is likely that Tar cells participate in the generation of spontaneous killer cells in AMLR as precursors of cytotoxic effector cells. [ABSTRACT FROM AUTHOR]

Reports on a case of clinical sensitization to lettuce (Lactuca sativa) on a patient who presented mucocutaneous manifestations after its ingestion, with positive skin tests, histamine release test and serum specific immunoglobulin E (IgE) to lettuce. Indication of antigenic community between lettuce and mugwort; IgE-binding properties in four protein bands from the lettuce extracts.

Examines the case of a patient who experienced an anaphylactic reaction to Quercus ilex acorn nut. Assessment of the hypersensivity reaction to acorn; Signs and symptoms; Characterization of allergenic proteins involved in the reaction.

Background Profilin, an actin-binding protein, was previously described as a panallergen which is involved in about 20% of the crossreactivity found among pollen and food allergic patients. This allergen is usually under-represented in natural extracts used for allergy diagnosis. Objectives To obtain an immunologically active and soluble recombinant profilin from Cynodon dactylon pollen which could be used for diagnostic and therapy. Methods Isolation of cDNA clones was performed by polymerase chain reaction amplification using degenerate primers. Expression in Escherehia coli BL21 (DE3) was carried out using vector pKN172, and the expressed product was isolated by affinity chromatography on poly L-proline-Sepharose. Results Four cDNA inserts coding for Cynodon dactylon (Bermuda grass) pollen profilin (Cyn d 12) were cloned and sequenced. Full-length C dactylon profilin gene was expressed in Escherichia coli as non fusion protein. Induced cells could produce high amounts of recombinant Cyn d 12, and after a single purification step on poly (L-proline)-Sepharose, up to 45 mg of pure allergen per litre culture could be obtained. The reactivity of recombinant Cyn d 12 with IgE antibodies present in sera from Bermuda grass-allergic patients is comparable to that of the natural Bermuda grass allergen. Recombinant Bermuda grass pollen profilin was shown to share B-epitopes with sunflower profilin. Conclusions Our results showed that this heterologous expression system and purification procedure are suitable for the production of large amounts of pure allergen which can be used for the characterization of allergenic epitopes recognized by T and B cells and finally for diagnostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Background: Tetranychus urticae (TU) is a macroscopic mite which is found infesting a large number of plants of economic interest. It has rarely been described as a cause of occupational allergic disease in agricultural workers. Objective: To describe U sensitization in greenhouse workers attending the outpatient allergy unit and its clinical associations, and to characterize the allergens involved. Materials and methods: Twenty-four consecutive carnation greenhouse workers with allergy-related symptoms, referred to our outpatient clinic during a 6-month period, were included. We made the diagnostic extract from carnation leaves heavily infested with TU. Skin-prick test, specific IgE measurement and bronchial provocation test with TU extract were carried out in all subjects. Allergen characterization as achieved by SDS-PAGE (sodium dodecylsulfate-polyacrylamide gel electrophoresis) and immunoblotting. Results Sixteen patients (66% presented positive skin-prick test and specific IgE and were diagnosed allergic to TU. Fifteen patients suffered from bronchial asthma, 14 rhinitis and five urticaria. Twelve exhibited positive bronchial provocation test to the TU extract. On RAST-inhibition studies, there was no evidence of crossreactivity between TU extract and D. pteronyssinus. An allergen at 19kDa was determined in the TU extract by SDS-PAGE immunoblotting studies. Conclusion: TU could be an important occupational allergen in greenhouse workers showing allergic symptomatology. There is no crossreactivity between this mite and the house dust mite D. pteronyssinus. [ABSTRACT FROM AUTHOR]

The article presents a study on the diagnosis of a 20-year-old patient with food allergy and who suffered from anaphylaxis associated with olives' ingestion. The study used skin prick test (SPT), immunoblotting of lipoproteins extracted from olives, hazelnut, and sesame seed, and basophil activation test (BAT). Results showed that the patient's allergy and anaphylactic reactions resulted from his sensitization to lipoproteins of olives.

Reports on a case involving a patient suffering from honey allergy. Main allergens involved in allergy to honey; Symptoms exhibited by the patient; Method of treatment administered on the patient.

Presents the case of patients with immunoglubin E-mediated contact urticaria caused by canned asparagus. Possible cross-reactivity among garlic, onion and asparagus; Subfamilies under the Liliaceae family; Allergic disorders related to asparagus; Clinical presentation of the condition; Diagnosis; Treatment administered.

Examines the occurrence of adverse reactions to pomegranate. Symptoms of the allergy; Employment of skin prick tests; Sensitivity of patients to pollens.

Examines the incidence of occupational immunoglobulin E-mediated hypersensitivity due to lettuce and chicory. Cytologic analysis of nasal secretion and sputum specimens; Application of skin prick test with inhalant allergens; Calculation of the peak expiratory flow.

Purpose Iron overload (IO) has been associated with increased cardiovascular risk (CVR) and metabolic syndrome (MS) in the general population; both elevated CVR and MS are frequent in HIV-patients. Our aim was to analyze the prevalence of IO in a cohort of asymptomatic patients with HIV infection, and related factors. Methods Cross-sectional study of a cohort of HIV outpatients in regular follow-up. Demographic, epidemiological, clinical, analytical and therapeutic data were collected. Patients completed a questionnaire about CVR factors and 10-year CV disease risk estimation (Framingham score), underwent a physical exam, and a fasting blood analysis. IO was defined as a plasma ferritin level higher than 200 μ/L in women and 300 μ/L in men. Results 571 patients (446 men, 125 women), with a mean age of 43.2 years, sexual transmission of HIV in 68.5%, median CD4 count 474 cell/μL (IQR: 308-666), and 36.3% Aids cases. 86.2% were on antiretroviral therapy (ART), and 74.8% of them had undetectable HIV viral load. 14.6% met MS criteria, and mean CVR at 10 years was 6.67%. IO was detected in 11% of cases. Patients with IO were more immunosuppressed (CD4 count 369 vs 483/μL, p<0.0001), presented a higher prevalence of detectable HIV viral load (17.6% vs 8.9%; p<0.005), and of Aids cases (14.9% vs 8.7%; p<0.023), and lower plasma levels of cholesterol, HDLc and LDLc (154 vs 183, 34 vs 43, 93 vs 110 mg/dL, respectively; p<0.0001. In the multivariate analysis, the only related factor was CD4 count <350 cell/μL (OR 2.86, 95% CI 1.6-4.9; p<0.0001). IO was not associated with CVR nor with MS. Conclusions IO is not uncommon in HIV patients, and it is only related with immunosuppression defined as CD4 count <350 cell/μL, and in contrast to general population, it is not related with increased CVR nor with MS. [ABSTRACT FROM AUTHOR]

Purpose Several studies have shown that HIV patients are at higher risk of lung cancer. Our aim is to analyse the prevalence and features of lung cancer in HIV-infected patients. Methods The clinical charts of 4,721 HIV-infected patients seen in three hospitals of southeast Spain (study period 1992-2012) were reviewed, and all patients with a lung cancer were analysed. Results There were 61 lung cancers, giving a prevalence of 1.2%. There was a predominance of men (82.0%), and smokers (96.6%; mean pack-years 35.2), with a median age of 48.0 (41.7-52.9) years, and their distribution according to risk group for HIV was: intravenous drug use 58.3%, homosexual 20.0%, and heterosexual 16.7%. Thirty-four (56.7%) patients were Aids cases, and 29 (47.5%) had prior pulmonar events: tuberculosis 16, bacterial pneumonia 9, and P. jiroveci pneumonia 4. The median nadir CD4 count was 149/mm3 (42-232), the median CD4 count at the time of diagnosis of the lung cancer was 237/mm3 (85-397), and 66.1%<350/mm3. 66.7% were on ART, and 70% of them had undetectable HIV viral load. The most common histological types of lung cancer were adenocarcinoma and epidermoid, with 24 (40.0%) and 23 (38.3%) cases, respectively. There were 49 (80.3%) cases with advanced stages (III and IV) at diagnosis. The distribution of treatments was: only palliative 23 (39.7%), chemotherapy 14 (24.1%), surgery and chemotherapy 8 (13.8%), radiotherapy 7 (12.1%), surgery 4 (6.9%), and other combined treatments 2 (3.4%). Forty-six (76.7%) patients died, with a median survival time of 3 months. The Kaplan-Meier survival rate at 6 months was 42.7% (at 12 months 28.5%). Conclusions The prevalence of lung cancer in this cohort of HIV-patients is high. People affected are mainly men, smokers, with transmission of HIV by intravenous drug use, and around half of them with prior opportunistic pulmonary events. Most patients had low nadir CD4 count, and were immunosuppressed at the time of diagnosis. Adenocarcinoma is the most frequent histological type. The diagnosis is usually made at advanced stages of the neoplasm, and mortality is high. [ABSTRACT FROM AUTHOR]

Purpose HIV-infected patients treated for syphilis may be at increased risk for serological failure and serofast state. Our aim was to analyse serological response to treatment in HIV-infected patients diagnosed with syphilis, and factors associated with serological cure and serofast state. Methods Open-label, no controlled study of a series of HIV-patients diagnosed with syphilis during 2004-2011. Patients were categorized by rapid plasma reagin titer (RPR) into success (4-fold decrease in RPR by 12 or 24 months after treatment of early or late syphilis), serofast (success with persistently stable reactive RPR), and failure/re-infection (failure to decrease 4-fold in RPR by 12 or 24 months after treatment or sustained 4-fold increase in RPR after treatment response). Results 141 HIV-patients were diagnosed with syphilis during the study period (104 early syphilis, 36 late or indeterminate latent syphilis). The mean age was 36.3 years, 98.5% were male, and 87.2% homosexual men. In 46 (32.6%) cases, HIV and syphilis infection diagnosis were coincident (mean CD4 457/mm3 and HIV-VL 4.72 log10). Among patients with prior known HIV infection, 65 were on antiretroviral therapy (ART) at syphilis diagnosis (mean CD4 469/mm3, 76.9% undetectable HIV-VL). 116 patients satisfied criteria for serological response analysis (89 early, 24 late/indeterminate). At 12 months of early syphilis treatment (89.2% penicillin) there were 16 (18%) failures, and at 24 months of late/indeterminate syphilis (91.7% penicillin) there were 5 (18.5%) failures. Overall, 36 (31.0%) patients presented serofast state. Treatment failure was related with lower CD4 count (295 vs 510/mL; p=0.045) only in patients with coincident diagnosis. Serofast state was related with older age (41 vs 36 years; p=0.024), and lower CD4 count (391 vs 513/mm3; p=0.026). Conclusions In this series of HIV-infected patients, with many patients on ART and with good immunological and virological parameters, serological failure and serofast state were frequent. Immunological status, and age could influence on serological response to syphilis treatment in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Purpose Bone turnover markers (BTM) - aminoterminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide of type 1 collagen (β-CTX) - are related to bone density and fracture risk. A high prevalence of osteopenia/osteoporosis and hypovitaminosis D has been reported in HIV patients, however there are few data about BTM in this population. Our aim was to analyse the prevalence of elevated serum levels of BTM in HIV patients before starting antiretroviral therapy (ART), and related factors. Methods Cross-sectional study of a series of HIV-patients who started ART during June/11-June/12 in our hospital. Patients with presence of diseases or treatments known to affect bone metabolism were excluded. Epidemiological, clinical, and immunovirological data in addition to serum fasting levels of glucose, lipid profile, calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D3 (25OHD), parathyroid hormone (PTH), P1NP, and β-CTX were collected. Definitions: hypovitaminosis D if 25OHD<30 ng/ml, vitamin D deficiency if 25OHD<20 ng/ml; elevated levels of BTM if β-CTX (ng/ml) >0.64 (men<70 years),>0.85 (men >70 years),>0.58 (pre-menopause women), >0.99 (post-menopause women), or P1NP (ng/mL)>69.4 (men <60 years), >71.1 (men>60 years), >55.7 (pre-menopause women), >61.2 (post-menopause women). Results 47 patients were included, 91.5% men, median age 37.1 years (30.0-44.3), and 93.6% sexual transmission of HIV (34 HMX, 10 HTX). Median time since the diagnosis of HIV was 3.4 months (1.4-31.7); there were 7 (14.9%) Aids cases, median CD4 count was 277/mm3 (155-433), and HIV-VL 4.8 log10 (4.1-5.2). Median serum 25OHD was 29 µg/L (21.9-41.1), with a prevalence of hypovitaminosis of 52.2%, and deficiency of 17.4%. PTH was in range in all cases. Median serum P1NP was 33.3 ng/mL (24.5-52.5) and β-CTX 0.25 ng/mL (0.20-0.45); five (11.4%) patients presented high levels of BTM: 4 men, median age 37.1 years, median CD4 count 247/mm3, median HIV-VL 5.18 log10, and one with hypovitaminosis D. Elevated BTM were related with no clinical, analytical, immunovirological parameters nor with serum levels of 25OHD nor PTH. Conclusions The prevalence of elevated BTM was high in this series of HIV-patients, mostly young men, with short time of HIV infection and with no immunovirologic control. BTM were related with no clinical nor analytical data. [ABSTRACT FROM AUTHOR]

Background The interaction between lipid disturbances and inflammatory markers is not well known in patients on antiretroviral therapy (ART). As nevirapine (NVP) is associated with a better lipid profile than efavirenz (EFV), we investigated the relationships between lipid profiles, lipoprotein subclasses and inflammatory biomarkers in patients with prolonged viral suppression with either NVP or EFV and no obvious clinical inflammation. Methods 122 clinically stable HIV-infected patients with HIV-1 RNA <20 copies longer than 6 months on NNRTI therapy were studied. 72 (59%) were on EFV and 50 (41%) on NVP. Any potentially inflammatory co-morbid diseases (concurrent viral hepatitis, diabetes, hypertension, chronic liver or renal diseases), or statin treatment, were exclusion criteria. Inflammatory biomarkers included hsCRP, LpPLA2, sCD40L, IL-6, IL-8, t-PA, MCP-1, p-selectin and VCAM-1. Lipoprotein subclass measures (VLDL, LDL, IDL and HDL particle number and size) were obtained by the use of proton nuclear magnetic resonance spectroscopy. Results 82% were male; median age 45 years. Median CD4 count 550/μL (IQR 324). Median time since HIV diagnosis 96 months (IQR 102) and accumulated time on ART 50 months (IQR 101). Patients on NVP had higher time since HIV diagnosis (126.9 [66.7] vs. 91.3 [6.6] months, p=0.008) a prolonged time on ART (89.6 [54.6] vs. 62.3 [52.2] months, p=0.01) and were older (47.7 vs. 40.7 years, p=0.001) than those on EFV. NVP-treated patients presented increased HDL-c (55.8 [16] vs. 48.8 [10.7] mg/dL, p=0.007) and apoA1 levels (153.4 [31.9] vs. 141.5 [20.5] mg/dL, p=0.02), and reduced apoB/apoA1 ratio (0.68 [0.1] vs 0.61 [0.1], p=0.003) than EFV-treated patients. No differences in inflammatory markers or lipoprotein subclasses were found between NVP and EFV. In patients with extreme lipid values (less favorable: 75th percentiles of LDL, small/dense LDLp and small HDLp, or more favorable: HDL p75 and apoB/apoA1 ratio p25), no consistent differences in inflammatory biomarkers were found. Conclusions Patients with prolonged viral suppression on NVP present significantly higher HDL and apoA1 levels and reduced apoB/apoA1 ratios than those on EFV, but no differences were found in lipoprotein particles nor inflammatory biomarkers. Relationships between lipid parameters and inflammatory biomarkers in NNRTI-treated patients are complex and do not show a linear relationship in this study. [ABSTRACT FROM AUTHOR]

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]

Background: Ole e 1 has been considered the major allergen of olive (Olea europaea) pollen. Some other relevant allergens (Ole e 2, 3, 4, and 6) have been recently described. This work aimed to study the IgE-binding frequency of a 36-kDa protein from O. europaea pollen in a large population of olive-allergic patients, its allergenic reactivity in vivo, and its presence in olive pollens of different origin, as well as in other relevant allergenic pollens. Methods: Identification of IgE-binding components from O. europaea pollen extracts was elucidated by inhibition of SDS–PAGE immunoblotting using recombinant profilin (Ole e 2) and Ole e 1 molecules. The IgE-binding frequency of the 36-kDa protein was estimated by Western blot in a sample of 120 sera from olive-allergic patients. The cutaneous test with the 36-kDa protein was performed by intradermoreaction in allergic patients and control subjects. Results: Exactly 83% of the sera from O. europaea-allergic patients recognized a protein with an apparent molecular weight of 36 kDa, under reducing conditions. It was detected by sera from monosensitized and polysensitized patients, showing a higher IgE frequency than the major allergen Ole e 1 (59%) and the minor profilin (Ole e 2) allergen (27%). Similar reactivity rates (79%) was found by intradermal test. Extracts from olive pollens collected in California presented a much higher amount (around 16-fold on average) of the 36-kDa protein than those from pollens of Spanish origin. The presence of similar allergens was detected only in closely related species (Syringa, Fraxinus, Ligustrum), and not in other common allergenic pollens. Conclusions: The 36-kDa protein constitutes a major allergen for olive-sensitized patients, but it is not equally represented in O. europaea pollens of different origins. Abbreviations: BSA: bovine serum albumin; PVDF: polyvinylidene difluoride; SDS–PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TBS:... [ABSTRACT FROM AUTHOR]

In controlled human infection studies (CHIs), participants are deliberately exposed to infectious agents in order to better understand the mechanism of infection or disease and test therapies or vaccines. While most CHIs have been conducted in high-income countries, CHIs have recently been expanding into low- and middle-income countries (LMICs). One potential ethical concern about this expansion is the challenge of obtaining the voluntary informed consent of participants, especially those who may not be literate or have limited education. In some CHIs in LMICs, researchers have attempted to address this potential concern by limiting access to literate or educated populations. In this paper, we argue that this practice is unjustified, as it does not increase the chances of obtaining valid informed consent and therefore unfairly excludes illiterate populations and populations with lower education. Instead, we recommend that investigators improve the informed consent process by drawing on existing data on obtaining informed consent in these populations and interventions aimed at improving their understanding. Based on a literature review, we provide concrete suggestions for how to follow this recommendation and ensure that populations with lower literacy or education are given a fair opportunity to protect their rights and interests in the informed consent process., (© 2020 John Wiley & Sons Ltd.)

Background: NADPH Oxidase 5 (Nox5) is a calcium-sensitive superoxide-generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro-contractile signaling and vascular function., Methods and Results: Transgenic mice expressing human Nox5 in a vascular smooth muscle cell-specific manner (Nox5 mice) and Rhodnius prolixus , an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5-expressing mice, agonist-induced vasoconstriction was exaggerated and endothelium-dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by N -acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by GKT137831 (Nox1/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca 2+ ] i , increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro-contractile signaling molecules MLC20 (myosin light chain 20) and MYPT1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild-type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In R. prolixus , gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by VAS2870 (Nox1/2/4 inhibitor)., Conclusions: Nox5 is a pro-contractile Nox isoform important in redox-sensitive contraction. This involves calcium-calmodulin and endoplasmic reticulum-regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro-contractile molecular machinery in vascular smooth muscle cells., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Unlabelled: The modern removable partial denture (RPD), in response to the increased esthetic demands of our patients, is no longer acceptable if it requires visible buccal and facial clasp arms for retention. By eliminating the bracing arm and having its functions taken by paralleled guide planes and precise, positive rests, the retentive element, a lingual circumferential wire clasp arm, will provide the same amount of retentive force as if it were placed on the buccal surface and will not be visible. Designs for the major connector either plate the lingual surface of the abutment or, as in a lingual bar, leave that surface open. Both of these situations are adaptable to the lingual retentive clasp and are illustrated in this article., Clinical Significance: Design features such as metal clasps needed for the retention of RPDs can be very unsightly, creating an esthetic problem. This article reviews the concepts for creating lingual clasp arms that enhance the esthetic quality of prostheses.

Background: Meat allergy is rarely reported. Most of the described cases are sensitizations to bovine serum albumin., Objective: The aim of the study was to describe a case of allergy to a new meat allergen and, after its characterization., Methods: A 35-year-old nonatopic female with allergic episodes after ingestion of several types of meat was studied. Skin tests (prick and prick-to-prick); total and specific immunoglobulin E (IgE) determination; sodium dodecyl sulphate-polyacrylamide gel electrophoresis and specific IgE determination by immunoblotting under different conditions were performed. A 17-kDa allergen was semipurified by ethanol fractionation and its amino-terminal sequence was determined. The existence of specific IgE directed to this protein was studied by immunoblot in 80 atopic patients., Results: The patient showed specific IgE antibodies to a 17-kDa protein. During the isolation of this allergen it was found that a 70-90% (vol/vol) ethanol concentration was able to purify the protein. The characterization revealed that it was a heat-resistant protein without disulfide bonds. N-terminal amino acid sequence (16 residues) showed identity with myoglobin. The study of specific IgE to this allergen among atopic patients showed that it was recognized by about 1% of the subjects., Conclusions: We describe a case of meat allergy caused by myoglobin. This is the first described case of monosensitization to this protein.