Methimazole Slows Hepatocyte Streaming in Rats

Hepatocytes are hypothesized to continuallystream from the portal tract to the terminal hepaticvein. By this model, when a cell divides, one of itsprogeny replaces the dividing ancestor and the other is displaced into a more remote location. Thepresent experiment aims to demonstrate thathypothyroidism affects liver cell turnover. Thirty maleadult rats were divided into two groups. One receivedmethimazole for two weeks and the other served as control.Each rat was injected intraperitoneally with 18.5 KBq[³H]thymidine/g body weight. Rats were killedafter 1 hr and two and four weeks. Autoradiography was done. The distance of the labeled cells fromthe portal tract was measured. The mean TSH levels ofthe methimazole-treated group and controls were 1.45 and0.25 mM/liter, respectively (P < 0.01). Hepatocyte streaming was lower in hypothyroid (1.8m/day) than in untreated rats (2.5 m/day) (P< 0.01). The respective labeling indices 1 hr afterlabeling were 0.9% and 1.24% (P < 0.05). We concludethat hypothyroidism diminishes hepatocyte and littoral cellturnover and slows down their streaming.     

The effects of nasal continuous positive airway pressure on platelet activation in obstructive sleep apnea syndrome

OBJECTIVE: A case-controlled study to assess the effects of nasal continuous positive airway pressure (CPAP) on platelet activation in patients with obstructive sleep apnea (OSAS) syndrome. METHODS: We recruited 65 patients with suspected OSAS for this study. Blood samples were taken with the patient in the supine position in the morning immediately after polysomnography, and 1 night and 3 months after the start of nasal CPAP therapy to measure an index of platelet activation (IPA+), which reflected both the quantity and quality of platelet activation. Significant OSAS was defined as an apnea-hypopnea index (AHI) of > or = 10 events per hour. RESULTS: There were 42 patients with significant OSAS and 23 control subjects with AHI < 10 events per hour. The mean (+/- SD) age for the OSAS patients was 48 +/- 9 years, the mean body mass index was 30.7 +/- 4.8, the mean AHI was 47 +/- 25 events per hour, the mean arousal index (AI) was 37 +/- 23 events per hour, and the mean minimum arterial oxygen saturation was 74 +/- 11%. Following multiple linear regression analyses of the clinical and polysomnography parameters, AI was the independent factor that correlated best with the baseline IPA+ (beta-coefficient, 0.386; p = 0.006). Following nasal CPAP treatment with a mean objective CPAP compliance of 3.9 +/- 1.9 h per night, there was a significant decrease in IPA+ from 15.1 +/- 12.2 U (at baseline) to 12.2 +/- 5.2 U (p < 0.001) and 9.8 +/- 4.3 U (p = 0.005), respectively, after 1 night and 3 months, whereas no significant change was noted among the control subjects. Using univariate analysis of variance to compare the changes in IPA+ between the two groups at 3 months with adjustment for the baseline value, nasal CPAP reduced IPA+ by 5.63 (SE, 1.85), whereas IPA+ increased in control subjects by 1.33 (SE, 1.27) [least-squared mean difference between groups, 3.34; 95% confidence interval, 0.42 to 6.26; p = 0.026]. CONCLUSIONS: OSAS, through repeated episodes of arousals, may lead to platelet activation, which can be reduced by nasal CPAP therapy.     

Usefulness of ultrasonography in predicting pleural effusions > 500 mL in patients receiving mechanical ventilation

STUDY OBJECTIVE: To assess the accuracy of chest ultrasonography in predicting pleural effusions > 500 mL in patients receiving mechanical ventilation. DESIGN: Prospective study. SETTING: Surgical and medical ICU in a teaching hospital. PATIENTS: Forty-four patients receiving mechanical ventilation with indications of chest drainage of a nonloculated pleural effusion. INTERVENTIONS: Diagnosis of pleural effusion was based on clinical examination and chest radiography. Chest drainage was indicated when considered as potentially useful for the patient (hypoxemia and/or weaning failure). Sonograms were performed before drainage at the bedside, in the supine position, and measurements were performed at the end of expiration. Effusions were classified as > 500 mL or < or = 500 mL according to the drained volume. MEASUREMENTS AND RESULTS: The drained volume ranged from 100 to 1,800 mL (mean, 730 +/- 440 mL [+/- SD]). The distance between the lung and posterior chest wall at the lung base (PLDbase) and the distance between the lung and posterior chest wall at the fifth intercostal space (PLD5) were significantly correlated with the drained volume (PLDbase, r = 0.68, p < 0.001; PLD5, r = 0.56, p < 0.001). A PLDbase > 5 cm predicted a drained volume > 500 mL with a sensitivity of 83%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 82%. Interobserver and intraobserver percentages of error were, respectively, 7 +/- 6% and 9 +/- 6% for PLDbase, and 6 +/- 5% and 8 +/- 5% for PLD5. The PaO2/fraction of inspired oxygen ratio significantly increased after chest drainage in patients with collected volumes > 500 mL (p < 0.01). CONCLUSIONS: Bedside pleural ultrasonography accurately predicted a nonloculated pleural effusion > 500 mL in patients receiving mechanical ventilation using simple and reproducible measurements.     

Duodenal tumor risk in Lynch syndrome

Background and aims

Lynch syndrome (LS) is associated with an increased risk of small bowel tumors but routine screening is not recommended in international guidelines. The aim of our study was to determinate the prevalence of duodenal tumors in a French cohort of LS patients.

Mutations of the Imprinted CDKN1C Gene as a Cause of the Overgrowth Beckwith–Wiedemann Syndrome: Clinical Spectrum and Functional Characterization

Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder associating macroglossia, abdominal wall defects, visceromegaly, and a high risk of childhood tumor. Molecular anomalies are mostly epigenetic; however, mutations of CDKN1C are implicated in 8% of cases, including both sporadic and familial forms. We aimed to describe the phenotype of BWS patients with CDKN1C mutations and develop a functional test for CDKN1C mutations. For each propositus, we sequenced the three exons and intron–exon boundaries of CDKN1C in patients presenting a BWS phenotype, including abdominal wall defects, without 11p15 methylation defects. We developed a functional test based on flow cytometry. We identified 37 mutations in 38 pedigrees (50 patients and seven fetuses). Analysis of parental samples when available showed that all mutations tested but one was inherited from the mother. The four missense mutations led to a less severe phenotype (lower frequency of exomphalos) than the other 33 mutations. The following four tumors occurred: one neuroblastoma, one ganglioneuroblastoma, one melanoma, and one acute lymphoid leukemia. Cases of BWS caused by CDKN1C mutations are not rare. CDKN1C sequencing should be performed for BWS patients presenting with abdominal wall defects or cleft palate without 11p15 methylation defects or body asymmetry, or in familial cases of BWS.     

Chronic zinc deficiency induces an antioxidant adaptive response in rat lung

Few studies are available about the role of dietary zinc (Zn) in respiratory diseases. Adult male rats were divided into 2 groups and fed respectively a moderate Zn-deficient diet and a Zn-adequate control diet. In lung tissue at 2 months, thiobarbituric acid-reactive species (TBARS), total glutathione, glutathione disulfide, protein carbonyls, metallothionein, and the activities of glutathione peroxidase (GPx), catalase, CuZn-superoxide dismutase (CuZnSOD) and glucose-6-phosphate dehydrogenase (G-6-PDH) were increased, but protein thiols decreased. In lung tissue at 4 months, TBARS, metallothionein, and the activities of CuZnSOD, Mn-superoxide dismutase (MnSOD) increased. The activities GPx, catalase, G-6-PDH were lower than control group. The changes were accompanied by histological alterations in Zn-deficient lung. The results provide evidence of the pro-oxidative effects of Zn-deficiency in lung, and suggest that the time of treatment play a key role in determining lung susceptibility to oxidative stress.     

Melanocortin 4 receptor signals at the neuronal primary cilium to control food intake and body weight

The melanocortin 4 receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis, and mutations in the MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R-expressing neurons are unknown. We recently reported that the MC4R localizes to the primary cilium, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether the MC4R functions in this organelle. Here, using mouse genetic approaches, we found that cilia were required specifically on MC4R-expressing neurons for the control of energy homeostasis. Moreover, these cilia were critical for pharmacological activators of the MC4R to exert an anorexigenic effect. The MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus of the hypothalamus (PVN) were essential to restrict food intake. MC4R activation increased adenylyl cyclase (AC) activity. As with the removal of cilia, inhibition of AC activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, the MC4R signaled via PVN neuron cilia to control food intake and body weight. We propose that defects in ciliary localization of the MC4R cause obesity in human inherited obesity syndromes and ciliopathies.