Influence of the Anatomical Site on Adipose Tissue-Derived Stromal Cells' Biological Profile and Osteogenic Potential in Companion Animals.

Adipose tissue-derived stromal cells (ADSCs) have generated considerable interest in the field of veterinary medicine, particularly for their potential in therapeutic strategies focused on bone regeneration. These cells possess unique biological characteristics, including their regenerative capacity and their ability to produce bioactive molecules. However, it is crucial to recognize that the characteristics of ADSCs can vary depending on the animal species and the site from which they are derived, such as the subcutaneous and visceral regions (SCAT and VAT, respectively). Thus, the present work aimed to comprehensively review the different traits of ADSCs isolated from diverse anatomical sites in companion animals, i.e., dogs, cats, and horses, in terms of immunophenotype, morphology, proliferation, and osteogenic differentiation potential. The findings indicate that the immunophenotype, proliferation, and osteogenic potential of ADSCs differ according to tissue origin and species. Generally, the proliferation rate is higher in VAT-derived ADSCs in dogs and horses, whereas in cats, the proliferation rate appears to be similar in both cells isolated from SCAT and VAT regions. In terms of osteogenic differentiation potential, VAT-derived ADSCs demonstrate the highest capability in cats, whereas SCAT-derived ADSCs exhibit superior potential in horses. Interestingly, in dogs, VAT-derived cells appear to have greater potential than those isolated from SCAT. Within the VAT, ADSCs derived from the falciform ligament and omentum show increased osteogenic potential, compared to cells isolated from other anatomical locations. Consequently, considering these disparities, optimizing isolation protocols becomes pivotal, tailoring them to the specific target species and therapeutic aims, and judiciously selecting the anatomical site for ADSC isolation. This approach holds promise to enhance the efficacy of ADSCs-based bone regenerative therapies.

Retinoic acid induces the osteogenic differentiation of cat adipose tissue-derived stromal cells from distinct anatomical sites.

Mesenchymal stromal cells-based regenerative orthopedic therapies have been used in cats as a promising and innovative therapeutic approach to enhance the repair of bone defects. Adipose tissue-derived stromal cells (ADSCs) can be obtained from two main sites-subcutaneous and visceral-with established differences regarding structure, composition, cell content, and functionality. However, in cats, to the best of the authors' knowledge, no studies have been conducted to compare the functional activity of the ADSCs isolated from the two sites, and the impact of these differences on the induced osteogenic potential. Additionally, retinoic acid has been recently regarded as a new osteogenic inducer within cells of distinct species, with undisclosed functionality on cat-derived cell populations. Thus, the present study aimed to evaluate the functional activity of ADSCs isolated from the subcutaneous and visceral adipose sites (SCAT and VAT, respectively) of the cat, as well as the effects of two osteogenic-inducing conditions-the classic dexamethasone, ß-glycerophosphate and ascorbic acid-supplemented media (Dex + ß + AAM), and Retinoic Acid-supplemented media (RAM). The adipose tissue of subcutaneous and visceral origin was isolated, characterized, and ADSCs were isolated and grown in the presence of the two osteogenic-inducing conditions, and characterized in terms of proliferation, metabolic activity, morphology, and osteogenic activity. Our results demonstrated a distinct biological profile of the two adipose tissue sites regarding cell size, vascularization, and morphology. Further, osteogenic-induced ADSCs from both sites presented an increased expression of alkaline phosphatase activity (ALP) and cytochemical staining, as compared with control. Overall, RAM induced higher levels of ALP activity than Dex + ß + AAM, supporting an increased osteogenic activation. Additionally, VAT was the tissue with the best osteogenic potential, showing higher levels of ALP expression, particularly with RAM. In conclusion, different characteristics were found between the two adipose tissue sites-SCAT and VAT, which probably reflect the differences found in the functionality of isolated ADSCs from both tissues. Furthermore, for cat, VAT shows a greater osteogenic-inductive capacity than SCAT, particularly with RAM, which can be of therapeutic relevance for regenerative medicine applications.

An Orthodenticle Homeobox 2 (OTX2) Mutation in a Patient With Combined Pituitary Hormone Deficiency, Pituitary Malformation, and Retinitis Pigmentosa.

Heterozygous mutations of orthodenticle homeobox 2 (OTX2)can result in ocular malformations, pituitary abnormalities, or hypopituitarism spanning from isolated growth hormone (GH) deficiency to combined pituitary hormone deficiency. We present a patient exhibiting growth and pubertal disturbances, developmental delay, and pigmentary retinopathy. Further examination revealed deficiencies in GH following clonidine stimulation, hypogonadism, and, subsequently, central hypothyroidism. Brain magnetic resonance imaging uncovered hypoplasia of the pituitary and an ectopic pituitary tissue. Sequence analysis of OTX2 identified a novel heterozygous mutation c.555_556dup, p.(Ser186Ilefs*21), indicative of a frameshift mutation. Replacement therapy with recombinant human GH, testosterone enanthate, and levothyroxine was started. Notably, GH therapy resulted in significant catch-up growth. This case report contributes to our comprehension of the molecular and clinical findings, particularly highlighting endocrine manifestations and a rare ophthalmologic manifestation associated with mutations in the OTX2 gene.

The Osteogenic Potential of Falciform Ligament-Derived Stromal Cells-A Comparative Analysis between Two Osteogenic Induction Programs.

Mesenchymal stromal cells (MSCs) have gained special relevance in bone tissue regenerative applications. MSCs have been isolated from different depots, with adipose tissue being acknowledged as one of the most convenient sources, given the wide availability, high cellular yield, and obtainability. Recently, the falciform ligament (FL) has been regarded as a potential depot for adipose tissue-derived stromal cells (FL-ADSCs) isolation. Nonetheless, the osteogenic capability of FL-ADSCs has not been previously characterized. Thus, the present study aimed the detailed characterization of FL-ADSCs' functionality upon osteogenic induction through a classic (dexamethasone-based-DEX) or an innovative strategy with retinoic acid (RA) in a comparative approach with ADSCs from a control visceral region. Cultures were characterized for cell proliferation, metabolic activity, cellular morphology, fluorescent cytoskeletal and mitochondrial organization, and osteogenic activity-gene expression analysis and cytochemical staining. FL-derived populations expressed significantly higher levels of osteogenic genes and cytochemical markers, particularly with DEX induction, as compared to control ADSCs that were more responsive to RA. FL-ADSCs were identified as a potential source for bone regenerative applications, given the heightened osteogenic functionality. Furthermore, data highlighted the importance of the selection of the most adequate osteogenic-inducing program concerning the specificities of the basal cell population.

Trust-Based Decision-Making in the Health Context Discriminates Biological Risk Profiles in Type 1 Diabetes.

Theoretical accounts on social decision-making under uncertainty postulate that individual risk preferences are context dependent. Generalization of models of decision-making to dyadic interactions in the personal health context remain to be experimentally addressed. In economic utility-based models, interactive behavioral games provide a framework to investigate probabilistic learning of sequential reinforcement. Here, we model an economic trust game in the context of a chronic disease (Diabetes Type 1) which involves iterated daily decisions in complex social contexts. Ninety-one patients performed experimental trust games in both economic and health settings and were characterized by a multiple self-report set of questionnaires. We found that although our groups can correctly infer pay-off contingencies, they behave differently because patients with a biological profile of preserved glycemic control show adaptive choice behavior both in economic and health domains. On the other hand, patients with a biological profile of loss of glycemic control presented a contrasting behavior, showing non-adaptive choices on both contexts. These results provide a direct translation from neuroeconomics to decision-making in the health domain and biological risk profiles, in a behavioral setting that requires difficult and self-consequential decisions with health impact. Our findings also provide a contextual generalization of mechanisms underlying individual decision-making under uncertainty.

Hypoglycemia unawareness in type 1 diabetes patients using intermittent continuous glucose monitoring: Identification of risk factors and glycemic patterns.

BACKGROUND: Hypoglycemia unawareness designates failure to detect eminent hypoglycemia. Clarke's questionnaire is one of the most used systems to evaluate this problem. AIMS: To relate Clarke's questionnaire (QQ) results with continuous glucose monitoring data. METHODS: Application of the questionnaire in a sample of type 1 diabetes mellitus (T1DM) patients using intermittent continuous glucose monitoring (iCGM). RESULTS: 111 T1DM patients were evaluated, 56.8% female, mean age 35.0 ± 12.4 years and mean disease duration 18.8 ± 10.5 years. According to CQ, 13.5% had unawareness, 76.6% awareness and 9.9% indeterminate awareness to hypoglycemia. Those with unawareness had longer disease duration (25.1 ± 10.4 vs 18.2 ± 10.3 for awareness and 14.9 ± 9.9 for indeterminate awareness, p = 0.047), more time below range (10.3 ± 4.9% vs 6.3 ± 5.1 and 6.3 ± 4.8; p = 0.009) and higher mean duration of hypoglycemia (131.7 ± 38.6 vs 116.6 ± 49.6 and 131.7 ± 38.6; p = 0.008). In multivariate analysis, mean duration of hypoglycemia was an independent predictor of CQ results. In a receiver operating curve (AUC 0.746; p = 0.004) a mean duration of hypoglycemia ≥106.5 min showed 84.6% sensitivity/64.4% specificity for unawareness. CONCLUSIONS: Our sample had a significative prevalence of hypoglycemia unawareness which increased with longer diabetes duration. iCGM data can be indicative of this problem, with a mean hypoglycemia duration ≥106.5 min being suggestive, albeit unspecific.

Maturity-Onset Diabetes of the Young (MODY) in Portugal: Novel GCK, HNFA1 and HNFA4 Mutations.

Maturity-onset diabetes of the young (MODY) is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. The most frequent subtypes are due to mutations of the GCK (MODY 2), HNF1A (MODY 3), and HNF4A (MODY 1) genes. We undertook the first multicenter genetic study of MODY in the Portuguese population. The GCK, HNF1A, and HNF4A genes were sequenced in 46 unrelated patients that had at least two of the three classical clinical criteria for MODY (age at diagnosis, family history, and clinical presentation). The functional consequences of the mutations were predicted by bioinformatics analysis. Mutations were identified in 23 (50%) families. Twelve families had mutations in the GCK gene, eight in the HNF1A gene, and three in the HNF4A gene. These included seven novel mutations (GCK c.494T>C, GCK c.563C>G, HNF1A c.1623G>A, HNF1A c.1729C>G, HNF4A c.68delG, HNF4A c.422G>C, HNF4A c.602A>C). Mutation-positive patients were younger at the time of diagnosis when compared to mutation-negative patients (14.3 vs. 23.0 years, p = 0.011). This study further expands the spectrum of known mutations associated with MODY, and may contribute to a better understanding of this type of diabetes and a more personalized clinical management of affected individuals.

[The Impact of Prolonged Use of Continuous Subcutaneous Insulin Infusion in the Control of Type-1 Diabetes]. / Impacto do Uso Prolongado da Terapêutica Subcutânea Contínua com Insulina no Controlo da Diabetes Mellitus Tipo 1.

INTRODUCTION: The use of continuous subcutaneous insulin infusion therapy in type 1 diabetes mellitus has increased due to its benefits on glycemic control and on the lifestyle flexibility. The aim of this study was to assess the impact of continuous subcutaneous insulin infusion therapy on glycemic control, body mass index, total daily dose of insulin and complications associated with this therapy, during 20 years of experience in Centro Hospitalar e Universitário de Coimbra. MATERIAL AND METHODS: This retrospective study included patients with type 1 diabetes mellitus who started continuous subcutaneous insulin infusion therapy up until 2005, followed at Centro Hospitalar e Universitário de Coimbra. Glycated hemoglobin A1c, body mass index, total daily dose of insulin and acute complications associated with continuous subcutaneous insulin infusion therapy were evaluated immediately prior to initiation of continuous subcutaneous insulin infusion therapy with follow-up at six months, one year, five, 10, 15 and 20 years. The frequency of acute complications associated with this type of therapy was also evaluated. RESULTS: This study included 20 patients (seven males, 13 females) with mean disease duration up to the start of continuous subcutaneous insulin infusion therapy of 16.1 ± 7.9 years, mean age of onset of continuous subcutaneous insulin infusion therapy of 31.1 ± 8.4 years and follow-up during 13.2 ± 2.3 years. The reasons for initiating pump therapy were: inadequate metabolic control in 15 patients, history of asymptomatic or severe hypoglycemia in four patients, and pregnancy/pregnancy planning in one patient. The previous median of glycated hemoglobin A1c was 9.3% (6.5 - 16.0) and, at six months, decreased to the minimum value of 7.2% (5.3 - 9.8); p < 0.0125. The reduction of glycated hemoglobin A1c remained statistically significant in the first 10 years of follow-up. There was a statistically significant difference in the body mass index variation at 10 years with continuous subcutaneous insulin infusion therapy compared to previous body mass index; 24.7 kg/m2 (18.9 - 31.8) vs 25,5 kg/m2 (18.9 - 38.9), p <0.0125. Daily insulin requirements were reduced from 56.5 U (32.0 - 94.0) to 43.8 U (33.0 - 64.0) (p < 0.0125) at six months and no statistical differences were found in the remaining follow-up. There were two severe episodes of hypoglycemia (incidence 0.0095/patient/year), five episodes of diabetic ketoacidosis (0.0238/patient/year) and no infections at the site of catheter insertion. DISCUSSION: This study shows that continuous subcutaneous insulin infusion therapy improved glycemic control, especially during the first 10 years of follow-up and allowed a significant decrease in total daily dose of insulin in the first six months. The rate of acute complications was low. CONCLUSION: Treatment with continuous subcutaneous insulin infusion therapy seems effective in achieving metabolic control in selected patients with type 1 diabetes mellitus.

Introdução: O uso da terapêutica com perfusão subcutânea contínua de insulina na diabetes mellitus tipo 1 é cada vez mais frequente devido aos seus efeitos benéficos no controlo glicémico e na flexibilidade do estilo de vida. Constituiu objetivo deste estudo avaliar o impacto da terapêutica com perfusão subcutânea contínua de insulina no controlo glicémico, índice de massa corporal, dose diária total de insulina e complicações desta modalidade terapêutica durante vinte anos de experiência no Centro Hospitalar e Universitário de Coimbra. Material e Métodos: Estudo retrospetivo que inclui doentes com diabetes mellitus tipo 1 seguidos no Centro Hospitalar e Universitário de Coimbra, que iniciaram terapêutica com perfusão subcutânea contínua de insulina até 2005 e com pelo menos 10 anos de tratamento com terapêutica com perfusão subcutânea contínua de insulina. Avaliou-se a hemoglobina glicada A1c, o índice de massa corporal e a dose diária total de insulina imediatamente antes e seis meses, um ano, cinco, 10, 15 e 20 anos após terapêutica com perfusão subcutânea contínua de insulina a partir dos registos médicos. Avaliou-se ainda a frequência de complicações agudas associadas a este tipo de terapêutica. Resultados: Obtiveram-se dados de 20 doentes (sete homens; 13 mulheres) com duração média de doença até início da terapêutica com perfusão subcutânea contínua de insulina de 16,1 ± 7,9 anos, idade média de início de terapêutica com perfusão subcutânea contínua de insulina de 31,1 ± 8,4 anos e seguimento durante 13,2 ± 2,3 anos. As indicações para colocação de bomba foram: inadequado controlo metabólico em 15 doentes, história de hipoglicemias assintomáticas ou severas em quatro doentes, e gravidez/planeamento de gravidez em um doente. A mediana de hemoglobina glicada A1c prévia foi 9,3% (6,5 - 16,0) tendo diminuído aos seis meses para o valor mínimo de 7,2% (5,3 - 9,8); p < 0,0125. A redução da hemoglobina glicada A1c manteve-se estatisticamente significativa nos primeiros 10 anos de seguimento. Verificou-se uma diferença estatisticamente significativa na variação do índice de massa corporal após 10 anos de seguimento comparativamente com o valor prévio à terapêutica com perfusão subcutânea contínua de insulina; 24,7kg/m2 (18,9 - 31,8) vs 25,5 kg/m2 (18,9 - 38,9), p < 0,0125. As necessidades diárias de insulina foram reduzidas de 56,5 U (32,0 - 94,0) para 43,8 U (33,0 - 64,0) (p < 0,0125) nos primeiros seis meses e não se encontraram diferenças estatísticas no restante seguimento relativamente às necessidades prévias à terapêutica com perfusão subcutânea contínua de insulina. Verificaram-se duas hipoglicemias severas (incidência 0,0095/doente/ano), cinco cetoacidoses diabéticas (0,0238/doente/ano) e nenhuma infeção no local de inserção do cateter. Discussão: Este estudo demonstrou a eficácia da terapêutica com perfusão subcutânea contínua de insulina, que está associada a uma diminuição significativa da hemoglobina glicada A1c sustentada durante 10 anos e a uma redução da dose diária total de insulina, significativa nos primeiros seis meses. A taxa de complicações agudas foi baixa. Conclusão: A evidência sugere que a terapêutica com perfusão subcutânea contínua de insulina é efetivamente vantajosa no controlo metabólico em doentes com diabetes mellitus tipo 1 selecionados.

[Late onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency: revision of literature and preconception genetic study of five couples]. / Hiperplasia congénita da suprarenal de expressão tardia por deficiência de 21-hidroxilase: revisão da literatura e estudo genético preconcepção de cinco casais.

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.

Sources of hepatic glycogen synthesis during an oral glucose tolerance test: Effect of transaldolase exchange on flux estimates.

Sources of hepatic glycogen synthesis during an oral glucose tolerance test were evaluated in six healthy subjects by enrichment of a 75-g glucose load with 6.67% [U-(13)C]glucose and 3.33% [U-(2)H(7)]glucose and analysis of plasma glucose and hepatic uridine diphosphate-glucose enrichments (sampled as urinary menthol glucuronide) by (2)H and (13)C nuclear magnetic resonance. The direct pathway contribution, as estimated from the dilution of [U-(13)C]glucose between plasma glucose and glucuronide, was unexpectedly low (36 +/- 5%). With [U-(2)H(7)]glucose, direct pathway estimates based on the dilution of position 3 (2)H-enrichment between plasma glucose and glucuronide were significantly higher (51 +/- 6%, P = 0.05). These differences reflect the exchange of the carbon 4, 5, and 6 moiety of fructose-6-phosphate and glyceraldehyde-3-phosphate catalyzed by transaldolase. As further evidence of this exchange, (2)H-enrichments in glucuronide positions 4 and 5 were inferior to those of position 3. From the difference in glucuronide positions 5 and 3 enrichments, the fraction of direct pathway carbons that experienced transaldolase exchange was estimated at 21 +/- 4%. In conclusion, the direct pathway contributes only half of hepatic glycogen synthesis during an oral glucose tolerance test. Glucose tracers labeled in positions 4, 5, or 6 will give significant underestimates of direct pathway activity because of transaldolase exchange.

Análise e comparação de variáveis da gestão de higienização hospitalar entre o serviço próprio do Hospital de Clínicas de Porto Alegre e o serviço terceirizado do Hospital Nossa Senhora da Conceição

Este projeto pretende analisar e comparar algumas variáveis de determinados modelos de gestão de dois dos maiores hospitais de Porto Alegre: HCPA e HNSC, sendo a área escolhida para análise a Gestão de Higienização. A metodologia escolhida foi a fundamentação teórica através de pesquisa bibliográfica e de dados históricos das empresas analisadas. Tem como público alvo administradores hospitalares, profissionais e acadêmicos da área da saúde

[Diabetes in the elderly: our reality]. / A diabetes na quarta idade: a nossa realidade.

AIM: To evaluate the impact of the aging of our population in the growing of diabetes prevalence, among patients treated inward at our department. MATERIAL AND METHODS: The clinical files of 242 diabetics older than eighty years, treated between 1999 and 2002 were studied retrospectively. Demographic (sex, age, year of first contact), clinical (causes of admission, co-morbidities, duration of diabetes, previous hypoglycaemic treatment, duration of hospitalisation and evolution) and biochemical (glycaemia, HbA1c, lipaemia and C-peptide) data were recorded. RESULTS: A progressive rising in the number of aged patients was found during this period (seven in 1999 to 55 in 2002), with a large proportion of women (73%). The more frequent causes of in-hospital treatment were hyperglycaemia (20.6%) and feet ulcers (septic or necrotic) (16.5%). In nearly 42% of the cohort an acute infection was found. Diabetes was unknown in 13% of cases and less than ten years of duration in 38%. In this cohort most of the patients (77%) were treated with oral hypoglycaemic drugs, mostly sulfonylureas. HbA1c mean value was 10.4 +/- 2.2%; C -peptide was measured in a subset of cases (n=79), suggesting deficient insulin secretion in 18% of them. The global mean duration of hospitalisation was eleven days. Nineteen patients (8%) died during the hospitalization. CONCLUSIONS: In this study, we concluded that diabetes in people older than 75 years, is being progressively more often diagnosed. The general metabolic control was bad (HbA1c mean value--10.4 +/- 2.2%), with a significant number of patients presenting a deficient C-peptide secretion, worsened by frequent coexisting infections. So, a strengthened clinical care, directed to a careful diagnosis and treatment, may effectively contribute to a better prognosis and quality of life of aged diabetic patients.

Noninvasive analysis of hepatic glycogen kinetics before and after breakfast with deuterated water and acetaminophen.

The contributions of hepatic glycogenolysis to fasting glucose production and direct pathway to hepatic glycogen synthesis were quantified in eight type 1 diabetic patients and nine healthy control subjects by ingestion of (2)H(2)O and acetaminophen before breakfast followed by analysis of urinary water and acetaminophen glucuronide. After overnight fasting, enrichment of glucuronide position 5 relative to body water (G5/body water) was significantly higher in type 1 diabetic patients compared with control subjects, indicating a reduced contribution of glycogenolysis to glucose production (38 +/- 3 vs. 46 +/- 2%). Following breakfast, G5/body water was significantly higher in type 1 diabetic patients, indicating a smaller direct pathway contribution to glycogen synthesis (47 +/- 2 vs. 59 +/- 2%). Glucuronide hydrogen 2 enrichment (G2) was equivalent to body water during fasting (G2/body water 0.94 +/- 0.03 and 1.02 +/- 0.06 for control and type 1 diabetic subjects, respectively) but was significantly lower after breakfast (G2/body water 0.78 +/- 0.03 and 0.82 +/- 0.05 for control and type 1 diabetic subjects, respectively). The reduced postprandial G2 levels reflect incomplete glucose-6-phosphate-fructose-6-phosphate exchange or glycogen synthesis from dietary galactose. Unlike current measurements of human hepatic glycogen metabolism, the (2)H(2)O/acetaminophen assay does not require specialized on-site clinical equipment or personnel.

Simple measurement of gluconeogenesis by direct 2H NMR analysis of menthol glucuronide enrichment from 2H2O.

The contribution of gluconeogenesis to fasting glucose production was determined by a simple measurement of urinary menthol glucuronide (MG) 2H enrichment from 2H2O. Following ingestion of 2H2O (0.5% body water) during an overnight fast and a pharmacological dose (400 mg) of a commercial peppermint oil preparation the next morning, 364 micromol MG was quantitatively recovered from a 2-h urine collection by ether extraction and a 125 micromol portion was directly analyzed by 2H NMR. The glucuronide 2H-signals were fully resolved and their relative intensities matched those of the monoacetone glucose derivative. The pharmacokinetics and yields of urinary MG after ingestion of 400 mg peppermint oil as either gelatin or enteric-coated capsules 1 h before breakfast were quantified in five healthy subjects. Gelatin capsules yielded 197 +/- 81 micromol of MG from the initial 2-h urine collection while enteric-coated capsules gave 238 +/- 84 micromol MG from the 2- to 4-h urine collection.

[Pancreas transplantation]. / Transplantação pancreática.

A clinic case of simultaneous pancreas/kidney transplantation on a type 1 diabetic patient is described. A six years follow-up was made with both organs functionating and a good quality of live. Then the authors make a review of the available surgical techniques, indications and complications of this form of treatment. A comparison between the Portuguese and the International experience was discussed.

[ACTH-dependent Cushing's syndrome: a revision of 43 cases]. / Síndroma de cushing ACTH-dependente: estudo retrospectivo de 43 casos.

AIM: To evaluate the characteristics and outcomes of the patients diagnosed as ACTH-dependent Cushing syndrome, registered in the department. MATERIAL AND METHODS: We reviewed the files of forty-three patients followed from 1974 to 2002. RESULTS: A progressive rise in the number of patients diagnosed was found, being 80% females. Clinical suspicion was based mostly on the typical fat distribution; hirsutism and amenorrhoea were important in women. The more reliable diagnostic tests were: 11 pm cortisol, day curve of ACTH and cortisol, and dexamethasone suppression tests. The ACTH response to CRH during inferior petrosal sinus sampling permitted the diagnosis of ectopic source. In thirty-seven patients a pituitary adenoma was diagnosed. The three patients diagnosed before 1985 went for bilateral adrenalectomy (Nelson's syndrome in two); the others were submitted to transsphenoidal pituitary adenomectomy, obtaining remission in twenty six at the first operation and in two others at the second. Three patients had a recidive. Of the six patients with persistent disease (all treated with metyrapone or ketoconazole), three were submitted to radiotherapy, two to bilateral adrenalectomy, and one was waiting for surgery. Four patients had a bronchial carcinoid, successfully removed in three. One patient was lost to follow-up and another was still being evaluated. CONCLUSIONS: We found a positive evolution in the capacity to diagnose and treat these patients. Neurosurgical ability to achieve remission was 80% in the operated cases. More effective technical methods and drugs, as well as a multidisciplinary and dedicated medical team, lead to long lasting remissions in most of the patients.

[Radiotherapy of pituitary tumors]. / Radioterapia em tumores hipofisários.

The aim of this study is to evaluate the use of conventional external radiotherapy in patients with pituitary adenomas. Between October 1970 and May 1998, 27 patients with pituitary adenoma were followed at the Department of Endocrinology and Diabetes of the Hospitais da Universidade de Coimbra. They received radiation therapy at Instituto Português de Oncologia. Seven of those tumors were classified as nonfunctioning adenomas, 17 as growth-hormone-secreting adenomas, 2 as prolactinomas and 1 as adrenocorticotropic adenoma. Twenty-six patients received radiation as adjuvant therapy after incomplete resection and one patient as primary treatment. The majority of these cases were treated using the parallel opposed-field technique with a total dose between 45 and 52 Gy. The patients were submitted, before and after radiotherapy, to a protocol in order to assess the efficacy of this treatment. Some of the results were analyzed. Reduction of tumor mass was achieved in 66.6% of nonfunctioning tumors and in 25% of the secreting ones. Reduction or stabilization of hormonal levels was achieved in 55% of the cases and normalization in 30%. The average duration of follow-up was 126.3 months. Complications observed: hypopituitarism, stroke (3 patients), cerebral edema (1 patient), memory loss (2 patients) and hearing loss (2 patients). None of the patients developed brain tumors.

[Diabetic nephropathy. Study protocol for pre-kidney transplantation]. / Nefropatia diabética. Protocolo de estudo pré-transplantação renal.

Between May 1990 and October 1998, 67 diabetic patients with end-stage renal disease, on dialysis, were submitted to a standardized protocol in order to assess the coexistence and degree of other diabetic and nondiabetic complications that could affect transplantation. Some of the results were analysed. Type 2 diabetic patients had more abnormal results on the lower limbs doppler ultrasound and on the lower limbs arteriography than type 1 (p < 0.05). Type 2 diabetic patients had more cardiovascular complications so the decision to transplant should be taken on a case by case basis.

[Leptin]. / Leptina.

Leptin is a product of the ob gene. It is syntetized by the adipocytes. This review will summarize the current findings of the physiopathology and actions of leptin.