Solvent-free synthesis of hydrophobic and amphiphilic esters using a chemically modified lipase from Thermomyces lanuginosus: a comparative study with native and immobilized forms.

Using lipases to catalyze the synthesis of the most differentiated type of compounds remains one of the major challenges among scientists. Seeking more economic and advantageous catalysts is a current goal of green chemistry. In this work, we demonstrate the potential of a chemically modified form of lipase from Thermomyces lanuginosus (cmLTL) for the synthesis of both hydrophobic (heptyl heptanoate, heptyl octanoate, heptyl decanoate, decyl heptanoate, decyl octanoate and decyl decanoate) and amphiphilic (2-(2-ethoxyethoxy)ethyl oleate and 2-(2-ethoxyethoxy)ethyl linoleate) esters, in bulk. The results were compared with its native (LTL) and immobilized (imLTL) forms. The data revealed that LTL showed poor activity for all reactions performed with n-heptane (η<20 %). ImLTL was able to synthesize all hydrophobic esters (η>60 %), with exception of the short ester, heptyl heptanoate. cmLTL was the only form of LTL capable of producing hydrophobic and amphiphilic esters, without compromising the yield when the reactions were performed under solvent-free conditions (>50 %). Molecular modeling showed that the active pocket of cmLTL is able to deeply internalize transcutol, with stronger interactions, justifying the outstanding results obtained. Furthermore, owing to the possibility of cmLTL filtration, the reusability of the catalyst is ensured for at least 6 cycles, without compromising the reaction yields.

Deep Eutectic Solvents as Suitable Solvents for Lipase-Catalyzed Transesterification Reactions.

In this work, three deep eutectic mixtures (DES 1: choline chloride/urea; DES 2: choline chloride/glycerol; and DES 3: tetrabutylammonium bromide/imidazole) were investigated as mediums for the synthesis of glucose laurate and glucose acetate. Aiming to achieve a greener and more sustainable approach, the synthesis reactions were catalyzed by lipases from Aspergillus oryzae (LAO), Candida rugosa (LCR), and porcine pancreas (LPP). The hydrolytic activity of lipases against p-nitrophenyl hexanoate revealed no evidence of enzyme inactivation when DES were used as medium. Regarding the transesterification reactions, combining LAO or LCR with DES 3 resulted in the efficient production of glucose laurate (from glucose and vinyl laurate) (conversion >60 %). The best result for LPP was observed in DES 2, with 98 % of product production after 24 hours of reaction. When replacing vinyl laurate by a smaller hydrophilic substrate, vinyl acetate, a distinct behavior was observed. LCR and LPP performed better in DES 1, yielding more than 80 % of glucose acetate after 48 hours of reaction. The catalytic activity of LAO was less pronounced, reaching only nearly 40 % of product in DES 3. The results highlight the potential of combining biocatalysis with greener and environmentally-safer solvents, for the synthesis of differentiated chain-length sugar fatty acid esters (SFAE).

Long-term Effects of Radioiodine in Toxic Multinodular Goiter: Thyroid Volume, Function, and Autoimmunity.

CONTEXT: Long-term studies evaluating the treatment of toxic multinodular goiter (TMNG) with fixed activities of radioiodine (RAI) are lacking. OBJECTIVE: The objective of this work is to describe the effects of 15 mCi on thyroid volume, function, and autoimmunity in the long term. DESIGN AND SETTING: A population-based, retrospective analysis with up to 12 years of follow-up was conducted in Siena, Italy. PARTICIPANTS: Adult patients (n = 153) with TMNG, naive to RAI, were included. METHODS: Evaluation was performed of thyroid function, antithyroid antibodies, and ultrasound scans before and yearly after RAI. MAIN OUTCOME MEASURES: Evaluations included hyperthyroidism cure, hypothyroidism, volume reduction, nadir and regain, and antibody titer change. RESULTS: The study revealed mean volume reductions greater than or equal to 50% at 3 years after RAI; the greatest annual reduction was observed during the first year (30 ± 17.8%; P < .001). Most patients (60%) achieved their volume nadir 3 to 6 years after RAI. Although 22% patients showed volume regain, the net reduction was statistically significant as late as 9 years after RAI (P = .005). The mean time to hypothyroidism was 2.7 ± 2.4 years, and it was associated with greater reductions in volume (P = .01). During the first 3 years after treatment, hyperthyroid patients decreased approximately by 50% per year without additional RAI. There was no statistically significant association of antibody titers with thyroid function except for antithyrotropin receptor antibodies and hyperthyroidism (P = .004). At the end of follow-up there were 61.6% euthyroid patients, 11% hyperthyroid (4.8% overt), and 27.4% hypothyroid patients (2.7% overt). Hyperthyroidism was cured in 89%. CONCLUSIONS: The treatment of TMNG with 15 mCi of RAI induced low hypothyroidism rates while providing high cure rates and significant volume reduction, which was maintained in the long term.

The Effect of Changing Regular Care Provider in Type 2 Diabetes Mellitus: A Retrospective Study.

INTRODUCTION: Several studies have demonstrated the benefits of having a regular care provider on the control of chronic diseases. Our study intends to clarify the effects of the transition to a new diabetologist on metabolic control in type 2 diabetes patients followed-upin a tertiary care setting. MATERIAL AND METHODS: Retrospective study performed in an endocrinology outpatient clinic. We randomly selected 50 type 2 diabetespatients for a control group and 50 for a study group. In the study group, we registered the last evaluation before the physician change (year 0) and at the end of each year (year 1, 2 and 3) with the new doctor. Evaluated variables - body mass index, blood pressure, HbA1c and lipid profile - were compared yearly between groups. RESULTS: There was a decrease in mean HbA1c levels (0.4% - 0.5%, p < 0.05) in year 1 and 2 when compared to year 0 in the study group, but not in the control group. This reduction was superior (0.5% - 1.4%, p < 0.05) in patients whose baseline HbA1c was greater than 7%. The other studied variables did not vary significantly throughout follow-up in either group. DISCUSSION: In our study the transition to a different type 2 diabetes physician was associated with a decrease in mean HbA1c and this difference was greater in less well controlled patients. CONCLUSION: Switching to a new physician may not be harmful and may actually have benefits for the glycemic control of some type 2 diabetes patients.

Introdução: Vários estudos já demonstraram ser benéfico para o controlo de várias doenças crónicas manter seguimento com um mesmo médico assistente de forma prolongada. O nosso estudo pretende esclarecer os efeitos no controlo da doença associados à transição para um novo médico diabetologista em doentes diabéticos tipo 2 seguidos em cuidados de saúde terciários. Material e Métodos: Estudo retrospetivo realizado num serviço de consultas externas de Endocrinologia. Seleccionámos aleatoriamente 50 doentes diabéticos tipo 2 para um grupo controlo e 50 para um grupo estudo. No grupo estudo, registámos a última avaliação antes da mudança de médico (ano 0) e no fim de cada ano (ano 1, 2 e 3) com o novo médico. As variáveis avaliadas ­ índice de massa corporal, tensão arterial, HbA1c e perfil lipídico ­ foram comparadas anualmente entre os grupos. Resultados: Verificou-se uma diminuição na média da HbA1c (0,4% ­ 0,5%, p< 0,05) no ano 1 e 2 por comparação com o ano 0 no grupo estudo, mas não no grupo controlo. Esta redução foi maior (0,5% ­ 1,4%, p < 0,05) em doentes cuja HbA1c basal era superior a 7%. As outras variáveis estudadas não variaram significativamente em qualquer um dos grupos. Discussão: Neste estudo, a transição de doentes diabéticos tipo 2 para um novo médico diabetologista assistente associou-se a uma diminuição na média de HbA1c, de forma mais marcada em doentes com menor controlo metabólico. Conclusão: A mudança para um novo médico diabetologista assistente pode não ser prejudicial e inclusivamente associar-se a benefícios para o controlo glicémico de alguns doentes diabéticos tipo 2.

Thyrotoxicosis leading to adrenal crises reveals primary bilateral adrenal lymphoma.

Primary adrenal lymphoma is a rare malignancy. It frequently presents bilaterally and with symptoms of adrenal insufficiency. Amiodarone may induce secondary organ dysfunction, and thyrotoxicosis develops in 15% of cases. The symptomatology of both conditions is nonspecific, especially in the elderly, and a high suspicion index is necessary for appropriate diagnosis. A 78-year-old female presented to the emergency department with confusion, nausea and vomiting. She had recently been to the emergency department with urinary tract infection, vomiting and acute hypochloremic hyponatremia. Upon re-evaluation, the leukocyturia persisted and because of TSH 0.01 µU/mL and free-T4 68 (10-18) pmol/L, she was admitted to the Endocrinology ward. Further evaluation supported amiodarone-induced thyroiditis type 2. Sepsis ensued, in the setting of nosocomial pneumonia. Hemodynamic instability, hyponatremia, hypoglycemia and vomiting raised the suspicion of adrenocortical insufficiency. Fluid resuscitation and hydrocortisone led to clinical improvement, and adrenal insufficiency was admitted. The thoracoabdominal tomography suggested an endobronchic primary lesion with hepatic and adrenal secondary deposits (6.6 and 7 cm), but this was confirmed neither on pleural effusion nor on bronchofibroscopic fluid analyses. The adrenals were not accessible for biopsy. Despite high-dose hydrocortisone maintenance, the patient died before definite diagnosis. The autopsy confirmed primary non-Hodgkin lymphoma. LEARNING POINTS: Primary adrenal lymphoma is a rare cause of adrenal insufficiency, but progression can be fast and fatal.Hyperpigmentation is frequently absent.The presenting symptoms are nonspecific and might mimic infection. Disproportion of the general state with signs of specific organ symptomatology is a diagnostic clue.Infection may precipitate adrenal crisis and worsen thyroid function with further adrenal insufficiency exacerbation.In the context of thyrotoxicosis, there may be little clinical response to a therapeutic trial with standard dose glucocorticoids.High-dose glucocorticoid substitution may be required to achieve clinical stability in thyrotoxic patients.