Autoimmune hypophysitis or lymphocytic hypophysitis

This entity, due to the pituitary lymphoplasmacytic infiltrate, was described for the first time in 1962. The clinical suspicion relies on a rapidly progressing hypopituitarism, particularly with adrenal involvement, affecting women in the peripartum period or patients with previously recognized autoimmune disease. Diabetes insipidus is also often reported. A sellar mass is found in 80% of cases. The diagnosis is confirmed by histology, due to the absence of a specific serological test. The endocrine deficiencies are frequently definitive. Corticotherapy is usually effective in reducing neurological symptoms due to pituitary enlargement, and frequently allows to avoid surgery. The disease-related deaths were due to acute adrenal insufficiency or ineffectively treated hypopituitarism. We are reporting a clinical case of probable lymphocytic hypophysitis in the early post partum of a woman with depression and Graves disease. She has hyperprolactinemia and ACTH deficiency, without pituitary changes in the magnetic resonance imaging. She was treated and her depression and hyperthyroidism were relieved. Hyperprolactinemia recovered spontaneously but she still needs glucocorticoid substitution

Effective fractionation of microalgae biomass as an initial step for its utilization as a bioenergy feedstock

Scenedesmus obliquus, a biotechnologically relevant microalgae, was grown in 70 L vertical photobioreactors using non-supplemented secondary brewery wastewater as a culture medium. Upon collection, by mechanical means, the cells were subjected to hydrothermal (autohydrolysis) and dilute acid hydrolysis (0.5 % sulfuric acid) pre-treatments carried out using pressure micro-reactors under isothermal conditions up to 300 min. Both processes enabled a high recovery of soluble sugars (~50 %) that were, in a great majority, present in the added-value oligomeric form (92 % and 90.5 % for autohydrolysis and dilute acid hydrolysis, respectively). Protein solubilization also presented relevant yields (35 % removal), with dilute acid hydrolysis allowing both higher oligosaccharides and protein productivities at a milder temperature. As compared to the current whole microalgae biomass-based upgrade strategies, the use of these mild processes is extremely promising, as they will enable the future co-production of added-value oligosaccharides, and protein, which can be relevant co-products of a biofuels-based biorefineryinfo:eu-repo/semantics/publishedVersio

CYP2D6 genetic polymorphisms are associated with susceptibility to pituitary tumors

Several polymorphisms of drug-metabolizing enzymes have been implicated in the susceptibility to tumor development. The role of the CYP2D6, GSTM1 and GSTT1 genes has been extensively studied, with alleles conferring different metabolic efficiencies and tumor risk. We studied the relationship between the main polymorphisms of these genes and the susceptibility to develop pituitary tumors, by performing a case-control study comprising 235 patients and 256 controls which were genotyped by means of PCR-RFLP based assays. Frequencies of the CYP2D6*1 and of the poor metabolizer allele CYP2D6*4, were determined along with the frequencies of the GSTM1 and GSTT1 null genotypes. CYP2D6 genotype frequencies were similar in patients and controls (p=0.087). CYP2D6*1 and CYP2D6*4 allele frequencies were 83.8%, 16.2% in cases and 78.3%, 21.7% in controls, showing a significant difference between the two groups (p=0.012). There were no significant differences between the frequencies of the GSTM1 and GSTT1 null genotypes in both groups. No association was found between histological type and any of the studied polymorphisms. Our data suggest an association of the CYP2D6*1 allele and the susceptibility to pituitary adenomas, which could be due to an increased metabolism of unidentified procarcinogens or to linkage disequilibrium with another gene involved in pituitary tumorigenesis

Genetic polymorphism of CYP2D6 influences susceptibility to papillary thyroid cancer

OBJECTIVE: Xenobiotic-metabolizing enzymes are widely polymorphic and confer interindividual variation in the ability to detoxify carcinogens or to activate pro-carcinogens. A common polymorphism of cytochrome P450 2D6 (CYP2D6) results in lack of enzyme activity and has been associated with an altered susceptibility to several cancers. The aim of this study was to investigate the association between the CYP2D6 poor metaboliser genotype and the risk of papillary thyroid cancer (PTC). DESIGN: Retrospective case-control study. PATIENTS: One hundred and eighty-seven patients with PTC and 256 controls. MEASUREMENTS: Genotyping was performed by PCR and restriction enzyme analysis to detect the presence of the common CYP2D6*4 poor metaboliser allele. RESULTS: The frequency of individuals with the homozygous poor metaboliser genotype was lower in the patient group [1.6 vs. 5.5%, P = 0.037, OR = 0.28 (95% CI 0.09-0.93)]. The CYP2D6*4 allele frequency was also lower in the patient group [13.4 vs. 21.7%, P = 0.002, OR = 0.56 (95% CI 0.39-0.80)]. CONCLUSIONS: The results suggest that the poor metaboliser genotype is associated with a protective effect against PTC. This could be explained by a possible role of CYP2D6 on the metabolic activation of putative environmental chemical thyroid carcinogens or by linkage to another cancer-causing gene. Further research may allow the identification of metabolic risk factors and contribute towards understanding the molecular mechanisms involved in thyroid carcinogenesis

Development of an innovative macroalgae biorefinery: Oligosaccharides as pivotal compounds

ABSTRACT: Macroalgae have significant advantages over land-living biomass resources and are promising pivotal feedstocks for the onset of the blue bioeconomy. Among these, Ulva lactuca has demonstrated a high potential due to its wide distribution and high productivity. In this work, a detailed chemical characterization of U. lactuca enabled the identification of polysaccharides as the main macromolecular component of the organic fraction. They present a high diversity of sugar constituents and hence can be a relevant source of added-value oligosaccharides for the food/feed industries. Four processes, with increasing operational temperatures, were compared for the selective production of oligosaccharides: Conventional Soxhlet Extraction, Accelerated Solvent Extraction, Hydrothermal treatment (HT) and Dilute Acid Hydrolysis (DAH). All processes presented high oligosaccharide/monosaccharide ratios, with HT and DAH exhibiting the highest oligosaccharides yields (10.6 and 16.6 g/100 g initial biomass, respectively). These oligosaccharides were obtained under milder, more economic conditions than the reported for lignocellulosic (land) plants and can represent an important added-value income of the algae biorefineries and thus contribute to their economic sustainability.info:eu-repo/semantics/publishedVersio

Late onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency: revision of literature and preconception genetic study of five couples

The deficiency of the enzyme 21-hydroxylase (21-HO) is responsible for about 90% to 95% of all cases of congenital adrenal hyperplasia (HCSR). This disorder is one of the most frequent hereditary illnesses of autosomal recessive trait. The illness can be presented in two clinical forms: 1 - classic, subdivided in saltwasting form and simple virilizing form; 2 - nonclassic or late-onset. The severity of the illness is correlated with the degree of enzymatic activity of 21-HO, which depends on the type of mutation that occurs in gene CYP21A2. The late onset congenital adrenal hyperplasia is that one where the enzymatic blockade is less intense. The clinical is variable: precocious pubarche, polycystic ovaries, hirsutism, oligoamenorrhea, acne and infertility. Gold standard for the diagnosis of late onset congenital adrenal hyperplasia consists on the test of the tetracosactide, considering itself diagnostic positive when 17-hidroxiprogesterona (17-OHP) is higher of 10-15 ng per mL. Many patients don't need treatment; however, if necessary, such a treatment essentially consists on the Administration of glucocorticoids and antiandrogens. Considering that affected individuals and the carriers may have a severe mutation in CYP21A2, they can have descendents with the classic form (if their partner is also a carrier of a severe mutation), it is mandatory the genetic study of the couple. The authors illustrate the importance of this genetic study through five clinical cases, whose common link is the desire to have children, as well as the presence on the feminine element of late onset congenital adrenal hyperplasia. The genetic study of the couple allows adequate pre-conception counseling and also prevents the use of corticoids throughout the pregnancy (if there's no risk of descendents being affected with the classic form). This aspect must be had in account in programming the pregnancy, in order to prevent therapeutics and unnecessary distrusts

The CTLA4 +49 A/G polymorphism is not associated with susceptibility to type 1 diabetes mellitus in the Portuguese population

CTLA4 genetic polymorphisms have been associated with type 1 diabetes. We genotyped 207 patients and 249 controls for the most frequently investigated polymorphism of the CTLA4 gene (+49A/G (rs231775)). No significant differences were observed, suggesting that this polymorphism is not strongly associated with type 1 diabetes in the Portuguese population

Recurrent hypercortisolism after removal of an ACTH secretor pituitary adenoma associated with an adrenal macronodule

A 29 years old patient was sent to our Outpatient Clinic of Endocrinology presenting clinic of hypercortisolism. Laboratorial study: High urinary free cortisol (UFC); serum cortisol - 25 microg/dl (8 am) (5-25) and 20 microg/dL (11pm); ACTH - 20 pg/mL (9-52) (8 am) and 14 pg/mL (11 pm); serum cortisol after dexamethasone suppression test: 14,9 mg/dL; CRH test: elevation of ACTH; Pituitary MRI: microadenoma; abdominal CT: nodule on the left adrenal. During inferior petrosal sinus sampling with CRH stimulation, ACTH reached 368 pg/mL on the right and 136 pg/mL on the left side. The patient was submitted to transsphenoidal surgery. After surgery, hypertension and physical stigmata improved. In 2006, a relapse of Cushing syndrome was suspected due to worsening of hypertension and increase of weight. A slight increase of UFC, undetectable ACTH and serum cortisol after dexamethasone suppression test equal to 16 microg/dL were found. On abdominal CT, the adrenal nodule kept the same characteristics. In December 2006, the patient was submitted to left adrenalectomy. After surgery, blood pressure normalized, UFC and serum cortisol were reduced, needing substitutive therapy. Progressive tapering of hydrocortisone doses lead to discontinuation in March 2007. He is clinically well, without any treatment. This is an unusual case, in which after surgical cure of Cushing disease, secretory autonomy of a coexisting adrenal nodule occurred. This clinical case is relevant, pointing out the complexity of hypercortisolism cases and the need of long follow-up

Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions

Several clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor γ (PPARγ) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34(+) cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34(+) cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34(+) cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction.info:eu-repo/semantics/publishedVersio