María Cristina Faingold

PPAR activation as a regulator of lipid metabolism, nitric oxide production and lipid peroxidation in the placenta from type 2 diabetic patients

Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors with crucial functions in lipid homeostasis, anti-inflammatory processes and placental development. Maternal diabetes induces a pro-inflammatory environment and alters placental development. We investigated whether PPARs regulate lipid metabolism and nitric oxide (NO) production in placental explants from healthy and type 2 diabetic (DM2) patients. We found decreased PPARα and PPARγ concentrations, no changes in PPARδ concentrations, and increased lipids, lipoperoxides and NO production in placentas from DM2 patients. PPARα agonists reduced placental concentrations of triglycerides and both PPARα and PPARδ agonists reduced concentrations of phospholipids, cholesteryl esters and cholesterol. PPARγ agonists increased lipid concentrations in placentas from DM2 patients and more markedly in placentas from healthy patients. Endogenous ligands for the three PPAR isotypes reduced NO production and lipoperoxidation in placentas from DM2 patients. We conclude that PPARs play a role in placental NO and lipid homeostasis and can regulate NO production, lipid concentrations and lipoperoxidation in placentas from DM2 patients.

Regulation of Matrix Metalloproteinases 2 and 9 Activities by Peroxynitrites in Term Placentas From Type 2 Diabetic Patients

Matrix metalloproteinases (MMPs) are proteolytic enzymes related to a proinflammatory environment in several diseases, including diabetes, which can be activated by reactive nitrogen species. This work aimed to determine MMP-2 and MMP-9 activities and nitration in term placentas from type 2 diabetic patients and verify the hypothesis that peroxynitrites are positive regulators of placental MMP-2 and MMP-9 activities. For this purpose, term placentas from healthy and type 2 diabetic patients were analyzed for MMP-2 and MMP-9 levels and activities, protein nitration, and nitration of MMP-2 and MMP-9. Villous explants were cultured in the presence of peroxynitrites for further evaluation of MMP-2 and MMP-9 activities. We found that MMP-2 and MMP-9 activities were increased in term placentas from diabetic patients. These changes were found even when MMP-2 protein concentrations were diminished and MMP-9 protein concentrations were not changed in the diabetic group. Increased protein nitration and specific nitration of MMP-2 and MMP-9 were found in term placentas from diabetic patients. Peroxynitrites were able to increase the activity of placental MMP-2 and MMP-9. Taken together, this study has shown for first time that peroxynitrites can nitrate and activate MMP-2 and MMP-9 in the placenta, a nitrative pathway possibly related to MMPs overactivity in the placentas from type 2 diabetic patients.

Differential Profile of Ultrasound Findings Associated with Malignancy in Mixed and Solid Thyroid Nodules in an Elderly Female Population

Objective. Ultrasonographic characteristics are associated with thyroid malignancy. Our aim was to compare the diagnostic value of ultrasound features in the detection of thyroid malignancy in both solid and mixed nodules. Methods. We prospectively studied female patients (≥50 years) referred to ultrasound-guided fine needle aspiration biopsy. Ultrasound features considered suspicious were hypoechogenicity, microcalcifications, irregular margins, high anteroposterior (AP)/axial-ratio, and absent halo. Associations were separately assessed in mixed and solid nodules. Results. In a group of 504 elderly female patients (age = 69 ± 8 years), the frequency of malignant cytology was 6%. Thirty-one percent of nodules were mixed and 60% were solid. The rate of malignant cytology was similar for mixed and solid nodules (7.4 versus 5.8%, P: 0.56). While in mixed nodules none of the ultrasound characteristics were associated with malignant cytology, in solid nodules irregular margins and microcalcifications were significant (all P < 0.05). The combination of irregular margins and/or microcalcifications significantly increased the association with malignant cytology only in solid nodules (OR: 2.76 (95% CI: 1.25–6.10), P: 0.012). Conclusions. Ultrasound features were of poor diagnostic value in mixed nodules, which harbored malignant lesions as often as solid nodules. Our findings challenge the recommended minimal size for ultrasound-guided fine needle aspiration biopsy in mixed nodules.

Myxedema madness complicating postoperative follow-up of thyroid cancer

Although hypothyroidism is associated with an increased prevalence of psychiatric manifestations, myxedema madness is rarely observed. We report the case of a 62-year-old woman with no prior history of psychiatric disorders, who presented to the emergency department with psychomotor agitation 6 weeks after total thyroidectomy for papillary thyroid cancer. Serum thyroid stimulating hormone (TSH) on admission was 62.9 mIU/L and free T4 was < 0.35 ng/dL, indicating severe hypothyroidism. After ruling out other possible causes, the diagnosis of myxedema madness was considered; hence, antipsychotic drug treatment and intravenous levothyroxine were prescribed. Behavioral symptoms returned to normal within 4 days of presentation, while levels of thyroid hormones attained normal values 1 week after admission. Recombinant TSH (Thyrogen®) was used successfully to prevent new episodes of mania due to thyroid hormone withdrawal in further controls for her thyroid cancer. This case illustrates that myxedema madness can occur in the setting of acute hypothyroidism, completely reverting with levothyroxine and antipsychotic treatment. Recombinant TSH may be a useful tool to prevent myxedema madness or any severe manifestation of levothyroxine withdrawal for the follow-up of thyroid cancer.

Diet only or diet and sulfonylureas in mild type II diabetes (niddm)? Pathophysiologic and therapeutic implications

SummaryPlasma glucose, insulin and C-peptide responses to a test meal were studied in 7 nonobese patients with type II diabetes mellitus (NIDDM) treated with diet alone and after 6 months of gliclazide therapy, as well as in 6 matched controls. The glycemic levels were significantly higher (p<0.05) in patients under diet alone than in controls and after gliclazide treatment (peak: 12.8±1.0; 7.9±0.4 and 10.0±0.5 mmol/l, respectively;

Diabetes y embarazo

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Guías para el tratamiento de la diabetes mellitus tipo 2. Sociedad Argentina de Diabetes

±SEM). Diet and gliclazide treated patients showed a reduced B-cell response during the first hour after the meal as indicated by insulin and C-peptide values and areas (insulin areas 0–60 min: controls 57.9 ± 10.9; p<0.01vs diet alone 14.2 ± 2.7 andvs gliclazide 22.1 ± 2.8 µU/ml/min). The hypoinsulinemic phase lasted from 20 to 60 min before gliclazide, and from 20 to 45 min after gliclazide. The first significant C-peptide increase, detected at 10 min in controls and at 30 min under diet alone, was advanced to 15 min after gliclazide treatment. In conclusion: patients with mild, diet-treated NIDDM show a sluggish and attenuated B-cell response to a physiologic challenge (test meal); this secretory impairment is present even after a complete post-prandial glycemic normalization, supporting the idea of a persistent defect. Nevertheless, the slight improvement observed in insulin secretion after gliclazide treatment may be promoting, at least partially, the normalization of prandial hyperglycemia. The benefits of this normalization in diabetic patients previously controlled by diet only await further investigation.