Antioxidative and anti-inflammatory effects of repaglinide in plasma of diabetic animals.

Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense, is considered to be an important pathogenic factor in diabetes mellitus and its complications. In diabetic state, ROS might also be implicated in promoting a state of systemic inflammation. Recently, it was demonstrated that antioxidant therapy could be used to stop the initiation and propagation of this inflammatory response. Repaglinide is a new oral antidiabetic agent with a possible antioxidant activity. Therefore, in the present study, a possible therapeutic value of repaglinide in ameliorating the oxidative and inflammatory processes was tested in diabetic animals. In the study, the levels of total antioxidant status (TAS), ascorbic acid (AA), protein carbonyl groups (PCG) and interleukin-6 (IL-6) were determined in plasma of diabetic rabbits after 4 and 8 weeks of repaglinide treatment (1mg daily). Ex vivo analysis revealed that there were significant differences in these markers between hyperglycemic and control animals (P<0.05). Some of these parameters were ameliorated by repaglinide treatment. In diabetic rabbits treated with repaglinide, protein oxidation was diminished by 17.8% after 8 weeks of experiment. The level of AA in plasma of diabetic treated animals was higher than in non-treated diabetic groups (by 9.4 and 22.6% after 4 and 8 weeks, respectively). In diabetic treated animals, the TAS level was also significantly increased (by 23.6 and 16.7%). However, in diabetic rabbits, repaglinide did not affect the concentration of IL-6.     

Successful pregnancy in primary glomerular disease

The course of 66 pregnancies was studied in 48 women with primary glomerular diseases. In all cases diagnoses were established by biopsy before pregnancy. They were: membranoproliferative glomerulonephritis in 16 patients, focal glomeruloesclerosis in 13, IgA nephropathy in 10, membranous nephropathy in seven and focal glomerulonephritis in two women. The clinical status of the nephropathy before conception was that 43 had only mild renal dysfunction, five had moderate renal insufficiency, serum creatinine (1.3 to 1.9 mg%), eight women had hypertension (150/100 mm Hg) and eight had nephrotic range proteinuria. Their clinical course was compared with a control group of 36 women with primary glomerular disease who did not become pregnant, and were matched for similar age, histological type, and status of nephropathy (renal function, blood pressure and proteinuria). After one year and at the end of the five year follow-up period, the incidence of hypertension, proteinuria, and renal failure was similar in the two groups. The fetal survival rate was 92%; 51 pregnancies ended in full-term delivery, with a mean birthweight of 3,242 +/- 320 g. There were seven pre-term deliveries (2,170 +/- 135 g), three small for gestational-age (2,340 +/- 135 g), two stillbirths and three spontaneous abortions. These patients had more pre-term deliveries (10.6%) and perinatal mortality (31%) than a normal population (5.5% and 9.6%, respectively). Blood pressure increased during pregnancy in 13 women; in 10 it was reversible, and in four it persisted after delivery. Ten gravidas developed increased proteinuria (reversible in six of them) and two others developed permanent impairment of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective study of antigenemia,plasma viremia and lymphocytic viremia in HIV-infected hemophiliacs

A total of 186 blood samples from 24 HIV-1 seropositive hemophiliac patients, monitored every four months for 29 months, were investigated for the presence of viral antigen in plasma. In addition, peripheral blood mononuclear cells (PBMC) were cultured for HIV-1, using normal PBMC as a target for replication. Antigenemia was detected in 51 % of the patients and from PBMC in 87.5 % of the patients. The incidence of HIV isolation in asymptomatic patients (42.8 %) was similar to that found in symptomatic patients (51.4 %). Patients with opportunistic infections had a higher incidence of lymphocytic viremia (p<0.05). Plasma viremia was closely associated (p<0.05) with low CD4+ counts and infection progression. The persistence of antigenemia was also a marker of a poor clinical course. In treated patients, plasma viremia was the marker that better correlated with the clinical course, and it did not appear during the first nine months of therapy. Zidovudine doses of >500 mg/day significantly lowered the appearance of antigenemia and lymphocytic viremia (p<0.05).     

Congenital healed cleft lip

Congenital “healed” cleft lip (CHCL) is an unusual anomaly including a paramedian “scar” of the upper lip, which appears as if a typical cleft lip has been corrected in utero. The CHCL is frequently associated with an ipsilateral notch in the vermilion, and “collapsed” nostril. Twenty-five CHCL cases are presented, eighteen of which were an isolated malformation found among the 3,950,715 births examined in two similar birth defect registries: ECEMC in Spain and ECLAMC in Latin America. Like open cleft lip, of which it seems to be a variant, CHCL is most frequently seen among males (14/18 isolated cases), it preferentially affects the left side (10/18 cases), and it segregated together with cleft lip in one family. The five CHCL cases with other congenital anomalies included: two cases with hydrocephalus, two VACTERL associations, and one atypical oblique facial cleft infant with single umbilical artery. CHCL may result from a defective fusion of the frontonasal and maxillary processes (before week 7 of embryonic life), or from a spontaneously repaired open cleft lip, later on. In either way, these cases heal with a visible scar, and the pre-occurrence of CHCL in two families suggests a familial predisposition to this phenomenon. © 1995 Wiley-Liss, Inc.     

Early organization of the pituitary gland in Sparus aurata L. (Teleostei) An ultrastructural study

The cell organization of the pituitary gland and the relationship between neurohypophysis and adenohypophysis in the early developmental stages of the gilthead sea bream, Sparus aurata, were studied by electron microscopy. In newly hatched larvae, the pituitary gland was embedded in the ventral floor of the diencephalon and separated from the hypothalamus by a continuous basal lamina. Elongated mesenchymal cells next to the ventral surface were observed. At this stage, there was no neurohypophysis and the adenohypophysis consisted of undifferentiated endocrine cells with small scarce secretory granules and a few stellate cells, with no distinctive zonation. An incipient neurohypophysis was present in 1-day-old larvae. The first evagination of the neurohypophysis into the adenohypophysis were observed in 2-day-old larvae and developed progressively with age, being deeper in the caudal zone. Two regions in the adenohypophysis, one anterior — the presumptive pars distalis — and one posterior — the presumptive pars intermedia — were found in 2-day-old larvae. Three regions (rostral and proximal pars distalis and pars intermedia) were clearly distinguishable in 4-day-old larvae. The ultrastructural features of the pituitary endocrine cells varied during gland differentiation, with the secretory granules gradually increasing in number and size, accompanying organelle development. Nevertheless, even in the oldest larvae studied (65 days), undifferentiated cells similar to those in the earliest stages were observed. The first blood vessels appeared in the neurohypophysis around 16 days after hatching. During early development, the pituitary gland progressively emerged from the ventral floor of the brain. By 16 days, the principal pattern of the pituitary gland architecture appeared to be established.     

Variations in peroxisomal catalase of neonatal rat hepatocyte subpopulations

Alcohol consumption during pregnancy is teratogenic and induces severe alterations in hepatocytes. In the hepatocyte peroxisomal system, ethanol is converted in the presence of H₂O₂ to acetaldehyde and water. Therefore, peroxisomal catalase also acts as an antioxidant defence mechanism by removing H₂O₂ and preventing the formation of hydroxyl radicals in the cell. Alterations in peroxisomal catalase after pre- and pre+postnatal alcohol exposure were investigated in the rat. The effect of pre- and postnatal exposure to ethanol on hepatocyte subpopulations was analysed in isolated hepatocytes originating from periportal, intermediate and perivenous zones. Analysis of catalase revealed that the total activity and content of this enzyme were higher in 12-day-old cells than in cells from newborns and that this increment was more pronounced in treated cells. In controls, the amount of peroxisomal catalase increased mainly in periportal cells, whereas alcohol exposure induced a significant increase in the catalase of perivenous hepatocytes. We conclude that pre- and postnatal alcohol exposure mainly affects the perivenous hepatocyte peroxisomes and that the increase in peroxisomal catalase could constitute a defence mechanism against free radical generation induced by alcohol exposure during the perinatal period.