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Biomedical subjects

M Porat

Publications and source records attributed to M Porat.

7 recordsLinked to original sources

The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes.

HIV protease inhibitors (HPIs) are potent antiretroviral agents clinically used in the management of HIV infection. Recently, HPI therapy has been linked to the development of a metabolic syndrome in which adipocyte insulin resistance appears to play a major role. In this study, we assessed the effect of nelfinavir on glucose uptake and lipolysis in differentiated 3T3-L1 adipocytes. An 18-h exposure to nelfinavir resulted in an impaired insulin-stimulated glucose uptake and activation of basal lipolysis. Impaired insulin stimulation of glucose up take occurred at nelfinavir concentrations >10 micromol/l (EC(50) = 20 micromol/l) and could be attributed to impaired GLUT4 translocation. Basal glycerol and free fatty acid (FFA) release were significantly enhanced with as low as 5 micromol/l nelfinavir, displaying fivefold stimulation of FFA release at 10 micromol/l. Yet, the antilipolytic action of insulin was preserved at this concentration. Potential underlying mechanisms for these metabolic effects included both impaired insulin stimulation of protein kinase B Ser 473 phosphorylation with preserved insulin receptor substrate tyrosine phosphorylation and decreased expression of the lipolysis regulator perilipin. Troglitazone pre- and cotreatment with nelfinavir partly protected the cells from the increase in basal lipolysis, but it had no effect on the impairment in insulin-stimulated glucose uptake induced by this HPI. This study demonstrates that nelfinavir induces insulin resistance and activates basal lipolysis in differentiated 3T3-L1 adipocytes, providing potential cellular mechanisms that may contribute to altered adipocyte metabolism in treated HIV patients.

3T3 Cells↗

Effect of inhibition of glutathione synthesis on insulin action: in vivo and in vitro studies using buthionine sulfoximine.

Decreased cellular GSH content is a common finding in experimental and human diabetes, in which increased oxidative stress appears to occur. Oxidative stress has been suggested to play a causative role in the development of impaired insulin action on adipose tissue and skeletal muscle. In this study we undertook to investigate the potential of GSH depletion to induce insulin resistance, by utilizing the GSH synthesis inhibitor, L-buthionine-[S,R]-sulfoximine (BSO). GSH depletion (20-80% in various tissues), was achieved in vivo by treating rats for 20 days with BSO, and in vitro (80%) by treating 3T3-L1 adipocytes with BSO for 18 h. No demonstrable change in the GSH/GSSG ratio was observed following BSO treatment. GSH depletion was progressively associated with abnormal glucose tolerance test, which could not be attributed to impaired insulin secretion. Skeletal muscle insulin responsiveness was unaffected by GSH depletion, based on normal glucose response to exogenous insulin, 2-deoxyglucose uptake measurements in isolated soleus muscle, and on normal skeletal muscle expression of GLUT4 protein. Adipocyte insulin responsiveness in vitro was assessed in 3T3-L1 adipocytes, which displayed decreased insulin-stimulated tyrosine phosphorylation of insulin-receptor-substrate proteins and of the insulin receptor, but exaggerated protein kinase B phosphorylation. However, insulin-stimulated glucose uptake was unaffected by GSH depletion. In accordance, normal adipose tissue insulin sensitivity was observed in BSO-treated rats in vivo, as demonstrated by normal inhibition of circulating non-esterified fatty acid levels by endogenous insulin secretion. In conclusion, GSH depletion by BSO results in impaired glucose tolerance, but preserved adipocyte and skeletal muscle insulin responsiveness. This suggests that alternative oxidation-borne factors mediate the induction of peripheral insulin resistance by oxidative stress.

3T3 Cells↗

Prenatal sonographic diagnosis of upper airway obstruction: a challenge that can be achieved.

Congenital upper airway obstruction presents a life-threatening situation when encountered in the delivery room. We present a case in which in utero diagnosis of this malformation was suspected, but unfortunately the neonate did not survive due to the inability to provide adequate ventilation. The prenatal sonographic features of this rare malformation are outlined, and the literature reviewed.

Adult↗

[Thyroglossal duct cyst].

Thyroglossal duct cysts are embryologic anomalies arising from epithelial remnants of the duct left after the descent of the developing thyroid. Clinical, operative and pathological findings in 124 patients operated on in the past 14 years were analyzed. There were 60 males and 64 females. 69 (56%) were under 10 years of age and the youngest was 6 months old. 26 (21%) were over the age of 30, and the oldest was 72 years old. All excisions were performed in accordance with the Sistrunk procedure, which includes removal of the body of the hyoid bone. Overall recurrence was 6.4%, but in infected cysts or cysts with a fistula to the skin, it was 3.5 times greater. In 20% the cyst was located off the midline. The lining of the cysts was cuboidal, columnar, pseudostratified or stratified squamous epithelium, and varied according to the location of the cyst. There were no malignant changes.

Adolescent↗

Localized texture processing in vision: analysis and synthesis in the Gaborian space.

Recent studies of cortical simple cell function suggest that the primitives of image representation in vision have a wavelet form similar to Gabor elementary functions (EF's). It is shown that textures and fully-textured images can be practically decomposed into, and synthesized from, a finite set of EF's. Textured-images can be synthesized from a set of EF's using image coefficient library. Alternatively, texturing of contoured (cartoon-like) images is analogous to adding chromaticity information to contoured images. A method for texture discrimination and image segmentation using local features based on the Gabor approach is introduced. Features related to the EF's parameters provide efficient means for texture discrimination and classification. This method is invariant under rotation and translation. The performance of the classification appears to be robust with respect to noisy conditions. The results show an insensitivity of the discrimination to relatively high noise levels, comparable to the performances of the human observer.

Artificial Intelligence↗

Peritonsillar abscess. A prospective evaluation of outpatient management by needle aspiration.

Outpatient management of peritonsillar abscess by needle aspiration and oral antibiotic therapy was evaluated for its effectiveness in providing rapid symptom relief and cure and in preventing recurrence. Between 1984 and 1987, 124 patients with peritonsillar infection were treated in our department, and 115 were included in this prospective study. Needle aspiration was not carried out in 11 patients because of young age, noncooperation, or severe trismus. The other 104 patients underwent permucosal aspiration and were followed up for periods of four months to three years. Of these, findings of aspiration were positive in 75 (72%). Only nine (12%) of the 75 patients with positive aspirates had to be hospitalized. In 64 (85%) of the 75 patients, the abscess resolved without further therapy. Aspiration of pus, along with oral administration of antibiotics, thus appears to be a reasonable alternative to incision and drainage or "hot" tonsillectomy in patients with peritonsillar abscess. This conservative approach obviates the need for hospital admission in most patients, thus enabling a significant cost reduction.

Adolescent↗

Myringoplasty in the pediatric population.

The long-term results of myringoplasty in children, including closure of perforation and hearing improvement, were reviewed in relation to age, condition of the operated-on ear, and condition of the untreated ear. The overall success rate in 155 operations evaluated one year postoperatively was 79%. Children in the 5- to 8-year-old age group had a success rate comparable to that of older (9- to 12-year-old) children (77.7% vs 80.4%). Where graft failure occurred, it was usually within one year of surgery. The outcome of surgery could not be related to the presence or absence of chronic otitis media in the untreated ear, the status of the operated-on ear (whether dry or discharging), or the performance of adenoidectomy before myringoplasty. Results of postoperative hearing, analyzed by calculating the postoperative air-bone gap and by speech audiometry, were similar in the two age groups. It is concluded that myringoplasty has a good chance of success in children, regardless of age.

Audiometry, Pure-Tone↗