Adipose tissue and liver lipid metabolism in obese children: role of the body mass index and the presence of acanthosis nigricans.

AIMS: The aims of our study were to determine if insulin resistance is associated with increased plasma levels of non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate and triglycerides in obese children. We also studied whether the presence of acanthosis nigricans (AN) led to further alterations in the above parameters. METHODS: A total of 101 children were studied on their first visit to the paediatric endocrine clinic. Seventy-four were obese, 30 of them with AN. The remaining 27 were non-obese healthy children (control group). NEFAs, glycerol, triglycerides, 3-hydroxybutyrate, insulin, leptin, adiponectin and glucose were determined in blood samples obtained after overnight fasting. The insulin resistance index (IRI) was calculated following the homeostasis model assessment (HOMA). Data from the three groups were compared using appropriate statistical tests. RESULTS: No differences in age, sex ratio and pubertal stage were observed among the three groups. The group of children with the highest body mass index (BMI) showed higher plasma levels of insulin and leptin, higher IRI and lower plasma levels of adiponectin. As insulin and IRI increased, NEFA and 3-hydroxybutyrate decreased and triglycerides increased. When obese children were categorized by BMI, the presence of AN further exacerbated these differences. CONCLUSIONS: In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss.     

Hepatic encephalopathy secondary to porto-systemic shunt satisfactorily treated with interventionist radiology

Hepatic encephalopathy is a reversible state of altered cognition that may occur in patients with acute or chronic liver disease or porto-systemic shunt, and in which known neurological or psychiatric signs may develop. Nitrogenated substances from intestinal digestion reach the brain without being cleared by their passage through the liver due to the presence of porto-systemic shunt. We report two cases of patients with porto-systemic shunt diagnosed with recurrent chronic hepatic encephalopathy refractory to conventional medical treatment. They were satisfactorily treated with shunt embolization using interventionist radiology techniques.     

The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors.

Members of the R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11) are found in the mouse CNS. The expression of these proteins was effectively reduced in different neural structures by blocking their mRNA with antisense oligodeoxynucleotides (ODNs). This was achieved without noticeable changes in the binding characteristics of labeled beta-endorphin to opioid receptors. Knockdown of R7 proteins enhanced the potency of antinociception promoted by morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO)-both agonists at mu-opioid receptors. The duration of morphine analgesia was greatly increased in RGS9-2 and in RGS11 knockdown mice. The impairment of R7 proteins brought about different changes in the analgesic activity of selective delta agonists. Knockdown of RGS11 reduced [D-Ala(2)]deltorphin II analgesic effects. Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase. RGS9-2 impairment also promoted a similar pattern of change for [D-Pen(2,5)]-enkephalin (DPDPE). RGS7-deficient mice showed an increased response to both [D-Ala(2)]deltorphin II and DPDPE analgesic effects. A single intracerebroventricular (i.c.v.) ED(80) analgesic dose of morphine gave rise to acute tolerance in control mice, but did not promote tolerance in RGS6, RGS7, RGS9-2, or RGS11 knockdown animals. Thus, R7 proteins play a critical role in agonist tachyphylaxis and acute tolerance at mu-opioid receptors, and show differences in their modulation of delta-opioid receptors.     

Composite prostheses for the repair of abdominal wall defects: effect of the structure of the adhesion barrier component

The component of a composite prosthesis, which makes contact with the visceral peritoneum, can be reabsorbable or non-reabsorbable, and laminar or reticular. This study was designed to determine whether the composition of this second, barrier component could improve its behavior at this interface. Abdominal wall defects in rabbits were repaired using a polypropylene prosthesis (PP), or the composites Sepramesh (PP+h) or Vicryl (PP+v). Fourteen days after surgery, the implants were evaluated by light and scanning electron microscopy, and immunohistochemistry. Prosthetic areas occupied by adhesions (PP: 71.08±5.09, PP+h: 18.55±4.96, P+v: 69.69±16.81%), neoperitoneal thickness (PP: 256.17±21.68, PP+h: 83.11±19.63, PP+v:213.72±35.90 μm) and macrophage counts (PP: 8.73±1.16, PP+h: 27.33±4.13, PP+v: 31.24±3.08%) showed significant differences (P<0.05). The tested biomaterials induced an optimal recipient tissue infiltration. Least adhesion formation was observed on the PP+h implants. This suggests that the second component, although reabsorbable, should be smooth in structure.     

Effect of dithranol therapy on membrane, basement membrane and nuclear markers in psoriasis lesions

We investigated the effects of anti-psoriatic therapy with dithranol (1/20-1%) in salicylic acid (0.5%) in white petrolatum on lesional skin. FITC-labeled lectins and pemphigus vulgaris antibodies (PV) served as analytical means to study the glycocalyx. Antibodies of bullous pemphigoid (BP) were used as basal membrane markers. Nuclear antigens were recorded according to the binding of speckled, anti-nuclear antibodies (ANA) as well as antibodies to dsDNA. With some lectins, dithranol therapy resulted in pronounced fluorescence of the lower parts of the basal cells. ConA was fixed by the basal cell layer. To a lesser degree, ANA were fixed by nuclei of keratinocytes. PV antibodies were not fixed at all.     

Conventional and experimental drug therapy in myelofibrosis with myeloid metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (ie, BCR-ABL-negative) myeloproliferative disorder characterized by anemia, multiorgan extramedullary hematopoiesis, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Stem cell transplantation can be curative, but many patients either are not appropriate candidates or do not choose to accept the significant risks associated with transplantation. Current pharmacologic therapy has been beneficial mainly in terms of palliating disease-associated cytopenias, constitutional symptoms, splenomegaly, and other organ damage from excess myeloproliferation. Novel treatment strategies are under investigation, including targeted inhibition of JAK2^V617F, the activating tyrosine kinase point mutation present in about half of patients with MMM. In this article, we review both the old and new pharmacologic options for MMM.     

Congestive gastropathy

15 patients with congestive gastropathy were reported including clinical and pathological characteristics of the disease. Every patient had alcoholic liver cirrhosis and portal hypertension. 6 patient's stomach was resected while in 2 further cases the disease was found at autopsy. In additional 7 cases the characteristic microvascular changes were observed in endoscopic biopsy specimens from the gastric mucosa. The authors presume that this disease has an acute and a chronic stage. In the acute stage dilated capillaries are present under the surface, not related to the inflammation of gastric mucosa. This phenomenon was described in the literature. In the chronic stage there are dilated and tortuous vessels in the submucosal layer surrounded by collagenous connective tissue. The authors suppose that the thick and fibrotic submucosal layer causes microcirculatory disturbances in the gastric mucosa. The impaired microcirculation may cause extensive ulcers with profuse and sometimes lethal bleeding.