Acute effectors of GLUT1 glucose transporter subcellular targeting in CIT3 mouse mammary epithelial cells

Lactogenic hormones cause intracellular targeting of glucose transporter 1 (GLUT1) for transport of glucose to the site of lactose synthesis in mammary glands. Our aim was to study the intracellular trafficking mechanisms involved in GLUT1 targeting and recycling in CIT3 mouse mammary epithelial cells. Fusion proteins of GLUT1 and enhanced green fluorescent protein (EGFP) were expressed in CIT3 cells maintained in growth medium (GM), or exposed to secretion medium (SM), containing prolactin. Agents acting on Golgi and related subcellular compartments and on GLUT1 and GLUT4 targeting in muscle and fat cells were studied. Wortmannin and staurosporine effects on internalization of GLUT1 were not specific, supporting a basal constitutive GLUT1 membrane-recycling pathway between an intracellular pool and the cell surface in CIT3 cells, which targets most GLUT1 to the plasma membrane in GM. Upon exposure to prolactin in SM, GLUT1 was specifically targeted intracellularly to a brefeldin A-sensitive compartment. Arrest of endosomal acidification by bafilomycin A1 disrupted this prolactin-induced GLUT1 intracellular trafficking with central coalescence of GLUT1-EGFP signal, suggesting that it is via endosomal pathways. This machinery offers another level of regulation of lactose synthesis by altering GLUT1 targeting within minutes to hours.     

Oral administration of a non-absorbable plant cellexpressed recombinant anti-TNF fusion protein induces immunomodulatory effects and alleviates nonalcoholic steatohepatitis

AIM To evaluate the immunomodulatory effect of oral administration of PRX-106 in the high-fat diet model.METHODS For 22 wk, C57BL/6 HFD-fed mice received daily oral treatments with BY-2 cells expressing recombinant antitumor necrosis factor alpha fusion protein(PRX-106). Mice were followed for serum liver enzyme and triglyceride levels, liver histology and intrahepatic and systemic FACS.RESULTS The orally administered non-absorbable PRX-106 w a s b i o l o g i c a l l y a c t i v e. A l t e r e d d i s t r i b u t i o n o f CD4+CD25+Fox P3+ between the liver and spleen and an increase in the intrasplenic-to-intrahepatic CD4+CD25+Fox P3+ ratio and a decrease in the intrasplenic-to-intrahepatic CD8+CD25+Fox P3+ ratio were observed. An increase in intrahepatic NKT cells and a decrease in the intrasplenic-to-intrahepatic NKT ratio were noted. Assessment of the CD4-to-CD8 ratios showed sequestration of CD8+ lymphocytes in the liver. These effects were associated with a decrease in serum triglyceride levels, decrease in the aspartate aminotransferase levels, serum glucose levels, and HOMA-IR score. A decrease in hepatic triglycerides content was observed in the high dose-treated mice.CONCLUSION Orally administered PRX-106 shows biological activity and exerts an immunomodulatory effect, alleviating liver damage. The data suggest that PRX-106 may provide an oral immunotherapy for nonalcoholic steatohepatitis.     

Pathological gambling: a review of phenomenological models and treatment modalities for an underrecognized psychiatric disorder

Pathological gambling (PG) is a prevalent and highly disabling impulse-control disorder. Two dominant phenomenological models for PG have been presented in the literature. According to one model, PG is included as an obsessive-compulsive spectrum disorder, while according to the second model, PG represents a form of nonpharmacologic addiction. In this article, we present an expanded conceptualization of the phenomenology of PG. On the basis of our clinical research experience and a review of data in the field, we propose 3 subtypes of pathological gamblers: the "impulsive" subtype, the "obsessive-compulsive" subtype, and the "addictive" subtype. We also review the current pharmacologic and nonpharmacologic treatment strategies for PG. A further aim of this article is to encourage awareness of the importance of improved screening procedures for the early detection of PG.     

Nonprogressive familial leukoencephalopathy with porencephalic cyst and focal seizures

Two siblings with a similar white-matter disease but different clinical symptoms are described. The first sibling suffers from nonprogressive spastic hemiparesis secondary to a congenital periventricular porencephalic cyst. Her brother has focal epilepsy. On magnetic resonance imaging, both patients show diffuse white-matter involvement predominantly of the posterior periventricular area. We suggest that this is a familial white-matter disorder with minimal symptoms and no progression in early childhood.     

The impact of previous strokes on the rehabilitation of elderly patients sustaining a hip fracture

OBJECTIVE: To evaluate whether a previous stroke may affect the functional outcome gain of elderly patients undergoing rehabilitation for a hip fracture. DESIGN: A retrospective cohort study. SETTING: The division of geriatric medicine with rehabilitation wards at a university-affiliated referral hospital. PARTICIPANTS: Patients with hip fractures (N=460) undergoing a standard rehabilitation course. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The functional outcome of previous stroke- and nonprevious stroke (NPS)-affected patients assessed by the FIM instrument at admission and discharge from the rehabilitation facility. Data were analyzed by t tests, Pearson correlation, chi-square tests, and linear regression analysis. RESULTS: Both admission and discharge total FIM scores were significantly higher in NPS compared with previous stroke patients (63.53+/-19.89 vs 52.19+/-19.37, P<.001) and (84.23+/-24.93 vs 71.37+/-25.03, P=.001), respectively. However, changes in total FIM (20.70+/-11.68 vs 19.17+/-13.32, P=.38) and in motor FIM (19.84+/-10.63 vs 17.96+/-11.21, P=.23) at discharge were not statistically significant between the 2 groups. A linear regression analysis showed that a previous stroke was not predictive of a worse total FIM gain at discharge (P=.58). CONCLUSIONS: NPS hip fracture elderly patients show higher admission and discharge FIM scores compared with previous stroke patients. Nevertheless, both groups achieve similar FIM gains during rehabilitation period. A previous stroke should not be considered as adversely affecting the rehabilitation of such patients.     

Functional outcome of ischemic stroke: a comparative study of diabetic and non-diabetic patients

BACKGROUND AND PURPOSE: Diabetes is associated with more ischemic strokes and diabetic patients have up to a three-fold increased risk for suffering a stroke, compared with non-diabetics. The aim of this study is to evaluate whether diabetes mellitus may also affect the functional outcome of patients with acute ischemic stroke, undergoing post-acute care rehabilitation. METHODS: A retrospective charts analysis of consecutive older patients with acute ischemic stroke admitted for rehabilitation at a tertiary hospital with post-acute care geriatric rehabilitation wards. Functional outcome of diabetics and non-diabetics was assessed by the Functional Independence Measurement scale (FIM) at admission and discharge. Data were analysed by t-tests, Pearson correlation, and Chi-square test, as well as by linear regression analysis. RESULTS: A total number of 527 patients were admitted, of whom 39% were diabetics. Compared with non-diabetics, diabetic stroke patients were slightly younger (p = 0.0001) but had similar admission FIM scores. FIM gain parameters (total FIM gain, motor FIM gain, daily total and motor FIM gains) upon discharge were similar in both groups. A linear regression analysis showed that higher MMSE scores (beta = 0.08; p = 0.01) and higher admission total FIM scores (beta = 0.87; p < 0.001) predicted higher total FIM scores upon discharge. Diabetes mellitus was not interrelated, whatsoever, with better total FIM scores upon discharge (beta = -0.03; p = 0.27). CONCLUSIONS: The findings suggest that there is no difference in the functional outcome of diabetic and non-diabetic patients, presenting for rehabilitation after acute ischemic stroke. Diabetes should not be considered as adversely affecting rehabilitation of such patients.     

The influence of propranolol on the concentration of heme and on the activity of δ-aminolevulinate synthase in monolayers of chick embryo liver cells

The addition of propranolol to monolayers of chick embryo liver cells caused a rapid increase in cellular heme, followed by an equally rapid decrease. Subsequently the concentration of heme rose at a relatively slower rate. About 10 hr after addition of propranolol to the medium a plateau level was reached at ± 35% above control values. Changes in the activity of δ-aminolevulinate synthase (ALAS) were negatively correlated with those of cellular heme. Cycloheximide prevented the above phenomenon. ALAS activity was not clearly correlated with the rapid, partial inhibition of protein synthesis, caused by propranolol.These observations are related to the beneficial influence of administration of hemin or of propranolol to patients with acute attacks of hepatic porphyria.     

The influence of seat adjustment and a thoraco-lumbar-sacral orthosis on the distribution of body-seat pressure in children with scoliosis and pelvic obliquity

PURPOSE: To determine the effect of a thoraco-lumbar-sacral orthosis (TLSO) on the distribution of body-seat interface pressure in children with concomitant scoliosis and pelvic obliquity and to determine the effects of two methods commonly used in customized seating--elevation (push up) of the lower side of the pelvis or a wedge insertion beneath the raised pelvis--on the distribution of body-seat interface pressure. METHODS: The study population comprised 15 children with an underlying neuromuscular disorder. All had scoliosis and pelvic obliquity when seated, and used a TLSO during sitting. Body-seat interface pressure was measured using the QA Pad. Maximum pressure, mean pressure and contact area were recorded at baseline and at 10 degrees 'push up' and 10 degrees wedge insertion, with and without the TLSO. X-rays were performed with and without the orthosis at baseline position. RESULTS: The TLSO reduced the scoliosis deformity by a mean of 5.3 degrees and significantly (p < 0.05) reduced the mean pressure and contact area in the sub-group of patients whose pelvic obliquity was contralateral to the side of the curve. Seat adjustment did not have any significant effect on pressure readings. CONCLUSION: Application of a TLSO in a child with scoliosis and contralateral pelvic obliquity significantly reduced the spinal curvature and interface sitting pressure. Manipulation of sitting by use of wedges under the pelvis had no significant effect on pressure distribution.     

The significance of plasma progesterone levels during early pregnancies achieved after in vitro fertilization (IVF) treatment

Objective Corpus luteum steroidogenesis is lower for in vivo ectopic pregnancy than for intrauterine pregnancy. There is a progesterone hallmark level distinguishing between viable intrauterine pregnancy and nonviable or ectopic pregnancy. This study attempts to answer whether this is also true for in vitro fertilization-treated patients. Study Design Using information retrieved from a computerized database, we compared the plasma 17Β-estradiol (E ₂) and progesterone during the luteal phase and for every 2 to 3 days for several weeks during early pregnancy between those patients with proven ectopic pregnancies and those with singleton and multiple intrauterine pregnancies. Vaginal ultrasonography to detect an intrauterine gestational sac was performed from day 19. A total of 73 pregnancies resulted from the replacement of fresh embryos in our in vitro fertilization-embryo transfer program. Results Only at day 10 post embryo transfer did those patients with ectopic pregnancy show statistically lower mean (SD) serum levels of E ₂ [2257 (SD, 2351) pmol/L] and plasma progesterone [PP; 221 (SD, 283) nmol/L] compared with patients with intrauterine pregnancy, whose mean E₂ was 8846 (SD, 5871) pmol/Land mean PP was 805 (SD, 582) nmol/L (P=0.008). For the rest of the follow-up until surgery was performed in ectopic pregnancy, there were no differences of statistical significance between extrauterine pregnancy and the intrauterine pregnancy groups. Furthermore, only on day 10 post embryo transfer, did we find a discriminatory zone (confidence interval, 95%) for E ₂ levels (903 to 3502 pmol/L for EP vs 6116 to 9493 pmol/L for a singleton and 4875 to 9493 pmol/L for multiple pregnancies). PP levels were 26 to 283 nmol/L for ectopic pregnancy versus 496 to 1096 nmol/L for both singleton and multiple pregnancies. An intrauterine gestational sac was visualized at a mean of 23.2 (SD, 4) days after embryo transfer. On this day, the mean P levels were 982.6 (SD, 286.2) nmol/L for intrauterine and 804.5 (SD, 502.4) nmol/L for ectopic pregnancies (P=NS. Conclusions Except for day 10 post embryo transfer, the steroidogenesis in ectopic pregnancy after in vitro fertilization treatment does not differ from successful intrauterine pregnancy. This observation negates an impaired steroidogenesis for ectopic pregnancy after in vitro fertilization and makes the PP level irrelevant in the diagnosis of pregnancy implantation.