Mechanisms of decreased lipoprotein lipase activity in adipocytes of starved rats depend on duration of starvation

The aim of this study was to delineate the mechanisms by which varying periods of starvation decrease lipoprotein lipase (LPL) activity in rat adipose tissue. LPL mRNA levels and rates of LPL synthesis, degradation and secretion were compared in adipocytes from male rats that had been fed or starved for 1 or 3 d. The decreased LPL activity after 3 d of starvation (-76%) was explained mainly by a 50% decrease in the relative abundance of LPL mRNA levels (P < 0.05) and a parallel 50% decrease in relative rates of LPL biosynthesis (P < 0.05). In contrast, starvation for 1 d decreased total LPL activity by 47% (P < 0.05) but did not affect LPL mRNA levels or relative rates of LPL biosynthesis. Pulse-chase studies demonstrated that 1 d of starvation increased the rate of degradation of newly synthesized LPL (P < 0.05) and markedly decreased its secretion into the medium (P < 0.05). A decrease in overall protein synthesis also contributed to the decreased LPL activity after 1 and 3 d of starvation. We conclude that the relative importance of pre- and post-translational mechanisms in regulating adipose tissue LPL activity depends on the duration of starvation. During short-term starvation, degradation of newly synthesized LPL is an important determinant to its secretion from the adipocyte and hence its functional activity at the capillary endothelium.     

Placental protein 14 in endometrium during menstrual cycle and effect of early luteal phase mifepristone administration on its expression in implantation stage endometrium in the rhesus monkey

Placental protein 14 (PP14) is a glycoprotein which is secreted by secretory phase endometrium and decidua in women. Despite the suggestion that PP14 is involved in the process of endometrial maturation for blastocyst implantation, our understanding in this regard is poor. In the present study, the concentrations and distribution patterns of immunodetectable PP14 in the endometrium during proliferative and secretory phases of normal ovulatory menstrual cycles, as well as in implantation stage endometrium in naturally mated ovulatory cycles with or without early luteal phase mifepristone treatment, were investigated using the rhesus monkey as a primate model. Immunopositive PP14 was observed mainly in epithelial cells of glands and it was detected in one major immunopositive band at Mr 28 kDa in tissue homogenate and spent medium. The area of immunopositive precipitation of PP14 in glands was minimal in follicular phase endometrium, and was higher (P < 0.01) in early, mid- and late luteal phase endometrium compared with that in pre- and periovulatory phases of the cycle, but there was no change in its area profile in the glandular compartment throughout the luteal phase. Immunopositivity for PP14 in luminal contents of gland displayed an increasing profile from early to late secretory phases. Thus, the concentrations and the distribution of immunodetectable PP14 in luteal phase endometrium of the rhesus monkey showed marked similarity with those of human endometrium during the natural menstrual cycle. Although there was no marked change in the band characterstics for the protein in implantation stage endometrium following early luteal phase mifepristone treatment, it was markedly decreased (P < 0.01) in tissue homogenate and in vitro spent medium along with a lesser (P < 0.02) degree of immunoprecipitation in the glands in implantation stage samples of mifepristone treatment group compared with that in control group samples. Thus, the contragestional effect of early luteal phase mifepristone treatment appears to be associated with a decrease in the concentration of immunodetectable PP14 in implantation stage endometrial glands and its secretion in the rhesus monkey. It remains to be seen whether this decline is caused from direct antiprogesterone action on endometrial glands during progesterone dominance, or secondarily from associated retarded development of endometrium.     

Developing a brief measure of smoking in the home: description and preliminary evaluation

The insulin-like growth factors (IGF-I and IGF-II) play a key role in cellular proliferation and are involved in cellular transformation. The expression of the IGF-I receptor has been demonstrated in a variety of human tumor cell lines including ovarian cancer cells. Phosphorothioate antisense oligodeoxynucleotides (S-ODNs) were analyzed for their potential to suppress the IGF-I receptor in the NIH: OVCAR-3 ovarian cancer cell line. The application of the antisense S-ODN reduced potently the cell growth of unstimulated NIH:OVCAR-3 cells, whereas sense and mismatch S-ODNs were without any effect. This effect resembled that of the monoclonal antibody (MAb) alphaIR-3. In contrast to the antisense compound, this MAb only partially inhibited the IGF-I-induced proliferation of ovarian cancer cells. The concentration of the antisense S-ODN to exhibit an identical inhibition of cell proliferation was reduced to 50 nM when the oligonucleotides were delivered by the cationic lipid formulation lipofectin. The specificity of the antisense S-ODN action was confirmed by reduction of the receptor protein and of the receptor mRNA, as assayed by flow cytometry and by Northern blot hybridizations. Our data demonstrate the potency of antisense S-ODNs to target the IGF-I receptor message and show that antisense strategies against the IGF-I receptor may provide new strategies for the therapy of ovarian cancer.     

Female gonadal sex steroids potentiate the anti-convulsant activity of phenytoin sodium

Neither estrogen (E), progesterone (P), E + P nor phenytoin could protect the rats against maximal electroshock seizure. However phenytoin administration in the E, P, or E + P pre-treated animals provided significant protection in terms of absence of hind limb extension and a decrease in the extension/flexion ratio. The results suggest that there is an existing beneficial influence of the oral contraceptives both individually and in combination on the anti-convulsant activity of phenytoin, and this needs to be further probed.     

Effect of pregnancy and lactation on lipoprotein and cholesterol metabolism in the rat

Origins of hyperlipidemia and cholestasis that occur during pregnancy were investigated by examining expression of key elements related to plasma and hepatic cholesterol metabolism during pregnancy, lactation, and post-lactation in the rat model. Among major findings were: during pregnancy, the activities of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, acyl coenzyme A:cholesterol acyltransferase, acyl coenzyme A:diacylglycerol acyltransferase, cholesterol 7alpha-hydroxylase, cholesterol ester hydrolases, low density lipoprotein receptors, LRP, and mdr2 were significantly lower or similar to non-pregnant controls while SR-B1 was elevated. Once lactation began, reductase, cholesterol acyltransferase, 7alpha-hydroxylase activities, low density lipoprotein receptors, and mdr2 increased while SR-B1 decreased. In later stages of lactation most hepatic elements returned to near control levels. Plasma cholesterol levels were higher than control at birth and during lactation with increase in LDL-size particles. By 24 h post-lactation, plasma triglycerides were 3.7-fold higher while cholesterol remained unchanged. Very large lipoproteins were present while LDL-size particles were now absent. Hepatic cholesterol acyltransferase had decreased to 27% of control while diacylglycerol acyltransferase increased 3-fold and low density lipoprotein receptors doubled. Most elements were normalized 3 weeks after weaning except for LRP and low density lipoprotein receptors which were elevated. These studies provide an integrated picture of expression of key elements of hepatic and plasma cholesterol metabolism during pregnancy and lactation and advance understanding of hyperlipidemia and cholestasis during these states.     

Frontal sinus mucoceles causing proptosis--two case reports

BACKGROUND: Blood requirements for Head and Neck surgical procedures have not been studied carefully. In order to set up an autotransfusion program, the blood loss and transfusion requirements should be known precisely. METHODS: The blood bank database was used to determine which Head and Neck procedures required blood transfusion during the previous 5 years. A list of 10 transfusion-associated operations was established, the records of all patients who underwent these procedures during a 5-year period were reviewed, and average the blood loss and number of units transfused determined. RESULTS: All procedures were for cancer resection. The operations were classified in 3 groups according to their transfusion probability: high (> 80%), low (< 5%) and moderate. For the moderate transfusion group, age, preoperative hemoglobin, and past medical history of cardiac and pulmonary disease were associated with higher incidence of transfusion. An average delay of 3 weeks was found between the diagnosis and the actual surgery. CONCLUSION: The transfusion requirements of Head and Neck surgical procedures could be safely met by an autotransfusion protocol, given the average delay of 3 weeks between diagnosis and surgery.     

Immunostimulatory CpG oligodeoxynucleotides enhance the immune response to vaccine strategies involving granulocyte-macrophage colony-stimulating factor

Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can activate various immune cell subsets and induce production of a number of cytokines. Prior studies have demonstrated that both CpG ODN and granulocyte-macrophage colony-stimulating factor (GM-CSF) can serve as potent vaccine adjuvants. We used the 38C13 murine lymphoma system to evaluate the immune response to a combination of these two adjuvants. Immunization using antigen, CpG ODN, and soluble GM-CSF enhanced production of antigen-specific antibody and shifted production towards the IgG2a isotype, suggesting an enhanced TH1 response. This effect was most pronounced after repeat immunizations with CpG ODN and antigen/GM-CSF fusion protein. A single immunization with CpG ODN and antigen/GM-CSF fusion protein 3 days before tumor inoculation prevented tumor growth. CpG ODN enhanced the production of interleukin-12 by bone marrow-derived dendritic cells and increased expression of major histocompatibility complex class I and class II molecules, particularly when cells were pulsed with antigen/GM-CSF fusion protein. We conclude that the use of CpG ODN in combination with strategies involving GM-CSF enhances the immune response to antigen and shifts the response towards a TH1 response and that this approach deserves further evaluation in tumor immunization approaches and other conditions in which an antigen-specific TH1 response is desirable.     

Motor speech impairment in a case of childhood basilar artery stroke: treatment directions derived from physiological and perceptual assessment

The perceptual and physiological characteristics of the speech of a nine year old child who suffered a basilar artery stroke at the age of five years were investigated using a battery of perceptual and physiological instrumental measures. Perceptual tests administered included the Frenchay Dysarthria Assessment, a perceptual analysis of a speech sample based on a reading of the Grandfather Passage and a phonetic intelligibility test. Instrumental procedures included: spirometric and kinematic analysis of speech breathing; electroglottographic evaluation of laryngeal function, nasometric assessment of velopharyngeal function and evaluation of lip and tongue function using pressure transducers. Physiological assessment indicated the most severe deficits to be in the respiratory and velopharyngeal sub-systems with significant deficits in the articulatory sub-system, all of which resulted in severely reduced intelligibility. These results were compared and contrasted with the subject's performance on the perceptual assessment battery. In a number of instances the physiological assessments were able to identify deficits in the functioning of components of the speech production apparatus either not evidenced by the perceptual assessments or where the findings of the various perceptual assessments were contradictory. The resulting comprehensive profile of the child's dysarthria demonstrated the value of using an assessment battery comprised of both physiological and perceptual methods. In particular, the need to include instrumental analysis of the functioning of the various subcomponents of the speech production apparatus in the assessment battery when defining the treatment priorities for children with acquired dysarthria is highlighted. Treatment priorities determined on the basis of both the perceptual and physiological assessments for the present CVA case are discussed.