Abnormalities in subsets of B and T cells in Mexican patients with inborn errors of propionate metabolism: observations from a single-center case series.

BACKGROUND: Propionate inborn errors of metabolism (PIEM), including propionic (PA) and methylmalonic (MMA) acidemias, are inherited metabolic diseases characterized by toxic accumulation of propionic, 3-hydroxypropionic, methylcitric, and methylmalonic organic acids in biological fluids, causing recurrent acute metabolic acidosis events and encephalopathy, which can lead to fatal outcomes if managed inadequately. PIEM patients can develop hematological abnormalities and immunodeficiency, either as part of the initial clinical presentation or as chronic complications. The origin and characteristics of these abnormalities have been studied poorly. Thus, the aim of the present work was to evaluate and describe lymphoid, myeloid, and erythroid cell population profiles in a group of clinically stable PIEM patients. METHODS: This was a retrospective study of 11 nonrelated Mexican PIEM patients. Clinical, biochemical, nutritional, hematological, and lymphocyte subsets were analyzed. RESULTS: Despite being considered clinically stable, 91% of patients had hematological or immunological abnormalities. The absolute lymphocyte subset counts were low in all patients but one, with CD4+ T-cell lymphopenia, being the most common one. Furthermore, of the 11 studied subjects, nine presented with a low CD4/CD8 ratio. Among the observed hematological alterations, bicytopenia was the most common (82%) one, followed by anemia (27%). CONCLUSION: Our results contribute to the landscape of immunological abnormalities observed previously in PIEM patients; these abnormalities can become a life-threatening chronic complications because of the increased risk of opportunistic diseases. These findings allow us to propose the inclusion of monitoring immune biomarkers, such as subsets of lymphocytes in the follow up of PIEM patients.

Microdeletion 22q11.2 syndrome: Does thymus incidental surgical resection affect its immunological profile?

BACKGROUND: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. METHODS: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. RESULTS: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/µL vs 16.1µL in the non-thymus group (p=0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. CONCLUSION: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure.

Efficacy of naproxen with or without esomeprazole for pain and inflammation in patients after bilateral third molar extractions: A double blinded crossover study.

BACKGROUND: Using a double-blinded randomized crossover design, this study aimed to evaluate acute postoperative pain management, swelling and trismus in 46 volunteers undergoing extractions of the two lower third molars, in similar positions, at two different appointments who consumed a tablet of either NE (naproxen 500 mg + esomepraz ole 20 mg) or only naproxen (500 mg) every 12 hours for 4 days. MATERIAL AND METHODS: Parameters were analyzed: self-reported pain intensity using a visual analog scale (VAS) pre- and postoperative mouth opening; incidence, type and severity of adverse reactions; total quantity consumed of rescue medication; and pre- and postoperative swelling. RESULTS: Female volunteers reported significantly more postoperative pain at 1, 1.5, 2, 3 and 4hrs after surgery while also taking their first rescue medication at a time significantly earlier when consuming NE when compared to naproxen (3.7hrs and 6.7hrs). Conversely, no differences were found between each drug group in males. CONCLUSIONS: In conclusion, throughout the entire study, pain was mild after using either drug in both men and women with pain scores on average well below 40mm (VAS), although in women naproxen improved acute postoperative pain management when compared to NE.

Development of high-temperature strain instrumentation for in situ SEM evaluation of ductility dip cracking.

Nowadays, the implementation of sophisticated in situ electron microscopy tests is providing new insights in several areas. In this work, an in situ high-temperature strain test into a scanning electron microscope was developed. This setup was used to study the grain boundary sliding mechanism and its effect on the ductility dip cracking. This methodology was applied to study the mechanical behaviour of Ni-base filler metal alloys ERNiCrFe-7 and ERNiCr-3, which were evaluated between 700°C and 1000°C. The ductility dip cracking susceptibility (threshold strain; εmin) for both alloys was quantified. The εmin of ERNiCrFe-7 and ERNiCr-3 alloys were 7.5% and 16.5%, respectively, confirming a better resistance of ERNiCr-3 to ductility dip cracking. Furthermore, two separate components of grain boundary sliding, pure sliding (Sp) and deformation sliding (Sd), were identified and quantified. A direct and quantitative link between grain boundary tortuosity, grain boundary sliding and ductility dip cracking resistance has been established for the ERNiCrFe-7 and ERNiCr-3 alloys.

Airborne ultrasonic application on hot air-drying of pork liver. Intensification of moisture transport and impact on protein solubility.

Nowadays, there is increasing interest in developing strategies for the efficient and sustainable use of animal by-products, such as pork liver. In order to stabilize the product, a prior dehydration stage may be required due to its high perishability. The water removal process of pork liver is energy costly and time consuming, which justifies its intensification using novel technologies. In this sense, the aim of this study was to assess the effect of the airborne application of power ultrasound on the hot air-drying of pork liver. For that purpose, drying experiments were carried out at 30, 40, 50, 60 and 70 °C on pork liver cylinders at 2 m·s-1 with (US) and without ultrasonic application (AIR). The drying process was modeled from the diffusion theory and, in the dried pork liver, the protein solubility was analyzed in order to determine the effect of drying on the protein quality. The ultrasound application increased the drying rate, shortening the drying time by up to 40% at 30 °C. The effect of power ultrasound at high temperatures (60 and 70 °C) was of lesser magnitude. Drying at 70 °C involved a noticeable reduction in the protein solubility for dried liver, while the impact of ultrasound application on the solubility was not significant (p > 0.05).

Update of the PANCCO clinical practice guidelines for the treatment of ulcerative colitis in the adult population.

Ulcerative colitis (US) is a chronic disease of unknown etiology. It is incurable and its clinical course is intermittent, characterized by periods of remission and relapse. The prevalence and incidence of the disease has been increasing worldwide. The update presented herein includes the participation of healthcare professionals, decision-makers, and a representative of the patients, all of whom declared their conflicts of interest. Answerable clinical questions were formulated, and the outcomes were graded. The information search was conducted on the Medline/PubMed, Embase, Epistemonikos, and LILACS databases, and covered grey literature sources, as well. The search was updated on November 30, 2020, with no restrictions regarding date or language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system was implemented to establish the strength of the recommendation and quality of evidence. A formal consensus was developed, based on the RAND/UCLA methodology and the document was peer reviewed. The short version of the Clinical Practice Guidelines for the Treatment of Ulcerative Colitis in the Adult Population is presented herein, together with the supporting evidence and respective recommendations. In mild-to-moderate UC, budesonide MMX is an option when treatment with 5-ASA fails, and before using systemic steroids. In moderate-to-severe UC, infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib can be used as first-line therapy. If there is anti-TNF therapy failure, ustekinumab and tofacitinib provide the best results. In patients with antibiotic-refractory pouchitis, anti-TNFs are the treatment of choice.

Ultrasound intensification of Ferrochelatase extraction from pork liver as a strategy to improve ZINC-protoporphyrin formation.

The enzyme Ferrochelatase (FeCH), which is naturally present in pork liver, catalyses the formation of Zinc-protoporphyrin (ZnPP), a natural pigment responsible for the typical color of dry-cured Italian Parma ham. The aim of this study was to evaluate the feasibility of using high power ultrasound in continuous and pulsed modes to intensify the extraction of the enzyme FeCH from pork liver. US application during FeCH extraction led to an improved enzymatic activity and further increase in the formation of ZnPP. The optimal condition tested was that of 1 min in continuous US application, in which time the enzymatic activity increased by 33.3 % compared to conventional extraction (30 min). Pulsed US application required 5 min treatments to observe a significant intensification effect. Therefore, ultrasound is a potentially feasible technique as it increases the catalytic activity of FeCH and saves time compared to the conventional extraction method.

Polyphenols from guaraná after in vitro digestion: Evaluation of bioacessibility and inhibition of activity of carbohydrate-hydrolyzing enzymes.

Guaraná (Paullinia cupana) is a typical product from Amazon biota that exerts antioxidant capacity due to the presence of phenolic compounds, such as catechin, epicatechin and proanthocyanidins. The objective of this study was to evaluate the potential inhibitory activity of guaraná extracts, after digestion in vitro, on carbohydrates-metabolism enzymes and to assess the bioacessibility of guaraná polyphenols. The guaraná samples before and after enzymatic digestion, were compared for total phenolic content and phenolic profile. Furthermore, we investigated the uptake of polyphenols from guarana, using Caco-2 cells, and the effect of digested guaraná on carbohydrate metabolism enzymes. The amount of total phenolic compounds extracted from guaraná decreased after digestion in vitro, and native phenolics were not identified after cell permeation. On the other hand, polyphenols from guaraná were able to inhibit α-glucosidase and α-amylase activities. In conclusion, guaraná can be considered as a dietary source with anti-hyperglycemic potential.

Efficacy of oral diclofenac with or without codeine for pain control after invasive bilateral third molar extractions.

Postoperative pain and inflammation after oral surgery is mostly managed using non-steroidal anti-inflammatory drugs (NSAIDs). However, opioids combined with NSAIDs may improve pain management in patients, especially after traumatic oral surgery. Few studies have compared NSAIDs with and without opioid use after oral and maxillofacial surgery. This randomized, double-blind, cross-over study compared the clinical efficacy of either diclofenac (50mg) and codeine (50mg) or diclofenac alone (50mg) for the management of postoperative pain after invasive third molar surgery. Volunteers (n=46) who were scheduled to undergo the removal of symmetrically positioned lower third molars in two separate appointments were included. They reported significantly less postoperative pain at various time points within 24h after surgery and also consumed significantly less rescue medication (paracetamol (acetaminophen)) throughout the study when they took diclofenac combined with codeine than when they took only diclofenac. In conclusion, oral diclofenac with codeine was more effective for managing postoperative pain than diclofenac without codeine. It was expected that patients taking two pain medications after surgery would generally have less pain than when taking only one of the two medications. The prospective cross-over design of the present work makes this study distinct from many others.

Biochemical pharmacology of functional foods and prevention of chronic diseases of aging.

The major mechanisms and consequences of free radicals in foods and biological systems that result in the occurrence of chronic diseases of aging (atherosclerosis, cataract, cancers, diabetes, neurological diseases, immune-inflammatory disorders) are described. The main antioxidant defense mechanisms from foods and cells and tissues are also reported. Many nutraceutical substances, with their respective beneficial actions (antioxidant, detoxifying, apoptotic actions) and effects, and most common food sources are also described. There are many options of foods to prevent cancer and chronic diseases, to improve life's quality in maturity.

Parameters determining the quality of charqui, an intermediate moisture meat product.

Charqui is a typical Brazilian meat product obtained by salting and sun-drying beef samples. The chemical, physical and microbiological characteristics of the charqui were evaluated throughout processing and storage. The results confirm charqui is an intermediate moisture meat product (A(w) = 0·70-0·75). A close relationship between moisture, pretein and ash vaiues was found, suggesting the possibility of using the resulting charqui A(w) value as a parameter to define the product instead of the official moisture and mineral residue contents. The TBA determination, which expresses the state of lipid oxidation, rapidly reached the maximum value, corroborating the previous observations on the salt pro-oxidant role, and then decreased gradually. A gradual decrease in microorganism count during processing and storage of charqui was also observed. These results indicate the feasibility of obtaining a final product with a low level of microbial count when raw materials of good quality, and adequate handling conditions, are used for charqui production.

Immunological disturbance in West and Lennox-Gastaut syndromes.

Cell-mediated and humoral immunity were investigated in 18 patients with West syndrome, 12 with Lennox-Gastaut syndrome and 19 healthy controls. The study included determination of T and B peripheral blood lymphocytes, serum levels of IgG, IgA and IgM, skin sensibilization with DNCB, intracutaneous PHA, leucocyte migration inhibition test and lymphocyte blastic transformation in the presence of PHA. Cell-mediated deficiency was detected in 28 children whereas low levels of immunoglobulins were observed only in 6 children. Immunological disturbances were more prominent in children with West syndrome.

Steroid therapy in fulminant hepatic failure secondary to autoimmune hepatitis.

Autoimmune hepatitis is a chronic inflammatory liver disorder of unknown etiology associated with serum autoantibodies and hypergammaglobulinemia. This disease has a broad spectrum of presentations ranging from asymptomatic to fulminant hepatic failure. A 36 year old female with past history of hypothyroidism developed jaundice 2 months prior to admission. Outpatient evaluation revealed ANA and anti-SMA antibodies in high titers, negative viral markers for hepatitis, and hypergammaglobulinemia. A presumptive diagnosis of autoimmune hepatitis was made; steroids were recommended but the patient did not take them. She was admitted to the University Hospital due to increased jaundice, general malaise and ascites 5 weeks later. She deteriorated developing coagulopathy, encephalopathy and increasing hyperbilirubinemia. Intravenous corticosteroids were started. The patient improved and was discharged 3 weeks after admission. Fulminant hepatic failure has a high mortality and may require liver transplant. Our patient survived fulminant hepatic failure that resolved after corticosteroid therapy. It is important to identify and distinguish autoimmune hepatitis from other forms of liver disease because of the high percentage of response to immuno-suppressive therapy. Early diagnosis and treatment of this condition could improve survival, quality of life, and defer liver transplantation.

Esophageal motility patterns in a Puerto Rican population.

One hundred consecutive patients underwent esophageal motility testing at the Gastroenterology Section of the University Hospital for symptoms of esophageal dysfunction. These were dysphagia (55), non cardiac chest pain (11), gastroesophageal reflux (32), and other (2). Fifty five studies were abnormal. The most frequent findings were achalasia in fourteen patients and nonspecific esophageal motility disorder in fourteen. When the clinical presentation was correlated with the results of the study, 35 of the 55 patients with dysphagia had an abnormal study, as compared with 5 of 11 with chest pain and only 12 of 32 with reflux symptoms. These findings compare with those reported elsewhere and suggest that esophageal motility studies are most useful in the diagnosis of patients presenting with dysphagia or non cardiac chest pain.

Cerebral thrombosis associated with active Crohn's disease.

An increased incidence of cerebral thromboembolic events has been reported in young patients with inflammatory bowel disease (IBD). It has been suggested that a hypercoagulable state is associated with clinical activity of the disease, with elevation of factors V, VIII, fibrinogen and platelets and a lowering of anti-thrombin III. We present the case of a 35 y/o male with refractory Crohn's disease who complained of headaches, blurred vision and tonic-clonic seizures. The studies demonstrated an ischemic stroke of the left cerebral hemisphere, without vascular abnormalities. Elevation of factor VIII, platelets, and antithrombin III were found. The symptoms were relieved with medical treatment and the patient has continued in good health after resection of the diseased terminal ileum.

Idiopathic hemochromatosis: a study in a large Puerto Rican family.

We studied 13 first-degree relatives in a large family with an index case of idiopathic hemochromatosis to detect the relatives with evidence of iron overloading. Serum iron, total iron binding capacity (TIBC), and serum ferritin levels were measured in all family members. We also performed HLA typing to identify the relatives who are homozygous with the proband and genetically predisposed to develop the disease. The family was composed of the parents and 12 siblings including the index case. The mean age of the siblings was 25 years. None presented with evidence of iron overload by the iron biochemical tests. HLA typing demonstrated six homozygous siblings with the proband. In separate analysis these siblings did not present abnormalities in any of the iron biochemical tests. These homozygous relatives were followed for one year after initial evaluation and none presented abnormalities in the iron studies during this period. These results are contradictory to other previous studies done in families with idiopathic hemochromatosis. The most feasible explanations for these findings are the young age of these siblings and the predominance of females among them. We consider that these homozygous relatives must be followed for their life-times with iron studies to detect a possible increase in iron stores as expected in later ages.

Osteopenia in Puerto Ricans with Crohn's disease.

BACKGROUND: Osteopenia has been reported in association to Inflammatory Bowel Disease, and in particular Crohn's disease. The use of corticosteroids, resection of the ileum, malabsorption, poor calcium intake, and the effect of inflammatory cytokines have all been considered as contributing factors. As Crohn's disease is more prevalent in young people, when peak bone mass is achieved, the presence of osteopenia is especially significant. OBJECTIVES: The aim of this study was to evaluate the bone density of patients with Crohn's disease in the University of Puerto Rico IBD Clinic; to determine the prevalence of osteopenia in these patients and to correlate bone mineral density with risk factors for osteopenia. METHODS: Sixty-six patients, 30 males and 36 females were included. After informed consent, demographic, clinical and metabolic data was obtained. Serum albumin, calcium, inorganic phosphorus and alkaline phosphatase were measured. Body mass index (BMI) was calculated. Bone density was determined by DEXA of the lumbar spine and femur and expressed as the Z score (standard deviations from normal correlated with sex and age). Severe osteopenia was a Z score > or = -2 and osteopenia was Z < or = -1.99 or > or = 1.01. Results were expressed in means. Pearson correlation coefficient was used for quantitative variables and Pearson chi-square for categorical values. RESULTS: Osteopenia was present in the hip in 69% and in the lumbar spine in 68%. Most patients had received steroids; the difference between treated and not treated patients was not significant. Osteopenia did not correlate with ileal resection, gender, BMI, disease characteristics or biochemical parameters. CONCLUSIONS: Low bone density was frequent in patients with Crohn's disease, but no specific risk factors could be identified. Bone density should be determined in patients with Crohn's disease in order to institute appropriate therapeutic measures.

Seroprevalence of Schistosoma mansoni in Puerto Ricans with inflammatory bowel disease.

BACKGROUND: The etiology of Inflammatory Bowel Diseases, Crohn's disease (CD) and ulcerative colitis (UC), is unknown. These diseases have a higher incidence in industrialized countries and their pathogenesis involves an over-reaction of the immune system. A genetic factor is believed to predispose to the development of chronic inflammation in response to an unidentified stimulus. Exposure to infections in childhood may modulate future immune responses. Parasitosis, particularly Schistosomiasis, stimulate Th2 immune responses. It has been hypothesized that the absence of these parasitic infections, as seen in economically developed countries, favors a Th1 response that may result in the clinical appearance of Crohn's disease later in life. OBJECTIVE: To determine the prevalence of Schistosoma mansoni antibodies in Puerto Ricans with Inflammatory Bowel Disease and controls. METHODS: Serum from 92 Puerto Ricans with IBD and 106 controls was screened for S. mansoni adult microsomal antigens (MAMA) using the FAST:ELISA assay. Those positive were confirmed with an enzyme-linked immunoelectrotransfer blot test. RESULTS: Seven serum samples (3 UC and 4 controls) were positive for S. mansoni antibodies. There was no significant difference between groups in gender, municipality of origin or seroprevalence of Schistosomiasis. The control group was slightly older than the IBD group. CONCLUSIONS: Our study did not demonstrate an inverse relation between Schistosomiasis and IBD. However, the decreasing prevalence of Schistosomiasis in the general population of Puerto Rico may account for this result.

Profile of the inflammatory bowel disease patient with depressive disorders.

OBJECTIVE: To describe the demographic and clinical characteristics of patients attending the Inflammatory Bowel Disease Clinic of the University of Puerto Rico School of Medicine and determine whether these characteristics are risk factors for the development of a depressive disorder. METHOD: Sixty-seven patients attending the Inflammatory Bowel Disease Clinic of the University of Puerto Rico School of Medicine were assessed for the presence of depressive symptoms using a simple questionnaire (CES-D) and a detailed diagnostic evaluation (CIDI-DSM IV Module E). Age, gender, education, time of IBD diagnosis, duration of treatment, psychiatric history, treatment with corticosteroids, and activity of IBD were determined and correlated with the presence of depressive symptoms and depressive diagnosis. Study data was tabulated on Epi-Info 6.0 and it was analyzed using SPSS version 10. Univariate (includes means and frequencies), bivariate (t-student, Kruskal Wallis and Chi-square) and multivariate analyses (logistic regression) were performed. RESULTS: Patients older than 34 years old had three times higher probability of developing a depressive disorder (p = 0.043, OR = 3.22). Patients with a psychiatric history had seven times higher probability of developing depressive disorder (p = 0.004, OR = 7). CONCLUSION: The risk factors identified with an increased probability of developing a depressive disorder were age older than 34 years and psychiatric history.

Fine-needle aspiration diagnosis of hydatid cyst.

The diagnosis of hydatid disease outside endemic areas is usually not suspected. Hydatid cysts in imaging studies can be confused with hepatic tumors, abscesses, cystadenomas, liver cysts or other lesions. Serology is the usual confirmatory test, but cytologic diagnosis has been described. Aspiration of the cysts has not been employed as a routine diagnostic method for fear of spillage and anaphylactic reactions. We report a case of unsuspected hepatic echinococcosis that was confirmed by fine-needle aspiration of the lesion and cytologic confirmation without complications.