CT-guided core needle biopsy of small (≤20 mm) subpleural pulmonary lesions: value of the long transpulmonary needle path.

AIM: To evaluate the accuracy and complications of computed tomography (CT)-guided core needle biopsy (CNB) of small (≤20 mm) subpleural pulmonary lesions with the use of the long transpulmonary needle path. MATERIALS AND METHODS: A retrospective study was undertaken comprising 235 patients who underwent CT-guided CNB of small (≤20 mm) subpleural pulmonary lesions. One of two needle paths was used: a long (≥10 mm) transpulmonary needle path (n=164, group A) or a short (<10 mm) transpulmonary needle path (n=71, group B). Diagnostic accuracy, pneumothorax, and bleeding rates were compared between the two groups. RESULTS: The diagnostic accuracy in group A was significantly higher than that in group B (93.9% versus 81.7%, p=0.004), particularly in patients with 5-10 mm lesions (89.2% versus 53.3%, p=0.013). The mean length of the transpulmonary needle path was 23.9 mm in group A and 5.9 mm in group B (p<0.001). The mean number of pleural punctures in group A was 1.01 and 1.11 in group B (p=0.016), but for patients with more than one puncture, the short transpulmonary path was not associated with a higher accuracy rate. The incidence of bleeding was 22% in group A and 9.9% in group B (p=0.028). CONCLUSION: Diagnostic accuracy for small subpleural pulmonary lesions with the use of the long transpulmonary needle path was higher than that with the use of the short transpulmonary needle path, especially for 5-10 mm lesions; however, the long transpulmonary needle path was associated with a higher rate of bleeding.

[Cross-sectional study on clinic behavior and therapeutic status of patients with psoriatic arthritis in multi-center].

OBJECTIVE: To investigate and analyse the features of treatment behavior and standardized therapeutic status of patients with psoriatic arthritis (PsA). METHODS: Out patients diagnosed with PsA in People's Hospital of Peking University, Haidian Hospital, People's Hospital of Jianyang City, Central Hospital of Xinxiang City, Integrated Traditional Chinese and Western Medicine Hospital of Cangzhou City, The Third Hospital of Hebei Medical University from February to June 2018 were enrolled in this investigation. The data including gender, age of onset, course of disease, site of first consulting department, time of the first visit and definite diagnosis, follow-up interval, and use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and biological DMARDs (BioDMARDs) were collected and analyzed. RESULTS: In the cross-sectional study, 133 PsA patients were investigated. The mean age of onset was (47±11) years, the male to female ratio was 1.3:1, and mean disease duration was (16±8) years. Rheumatology department was the most common site of first hospital visit (37.6%, 50/133). Orthopedics department and dermatological department were visited by 24.1% (32/133) and 23.3% (31/133), respectively. Ratio of definite diagnosis was the highest in rheumatology department which was 78% (39/50). The ratio of definite diagnosis of dermatological department was the second highest, which was 19.4% (6/31). The mean definite diagnosed time was 7.6 months since the first visit of PsA patients, and diagnosed time was the shortest in rheumatology department, which had statistical significance. 37% PsA patients were treated appropriately in 3 months, 17.3% PsA patients were treated in 3-6 months and 40.2% patients with PsA visited their doctor more than once a year. 48.8% patients hadn't received standardized treatment before visit, and one third patients never received the therapy of DMARDs. Methotrexate was the most commonly used cDMARDs (58.3%), followed by leflunomide (20.5%) and BioDMARDs (19.7%), and biologicals were tumor necrosis factor antagonists. CONCLUSION: In this multi-center study, the first visit department of PsA patients was widely distributed, and most patients were definitely diagnosed in Rheumatology Department. The time of their first visit and definite diagnosis were delayed due to multi factors. Nearly half of the patients did not receive standardized treatment.

[Clinicopathological features and prognosis of 488 patients with neuroendocrine tumors].

Objective: To investigate the clinicopathological features and prognosis of patients with neuroendocrine tumors (NETs). Methods: The clinicopathologic data of enrolled patients with NETs between October 2012 and October 2017 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results: Among the 488 NETs patients, the average age was (51.0±15.8) years, and the sex ratio (male/female) was 1∶1.1. Of the NETs, 370 were located in the digestive system (75.8%), 63 were pulmonary (12.9%), 14 were mediastinal (2.9%), 7 were of unknown primary origin (1.4%), and 34 were located in other sites (7.0%). Among the NETs, the pancreas, rectum and stomach were the most common sites. In the digestive system NETs, the most common tumor grade was G1 (190 cases, 51.4%), followed by G2 (143 cases, 38.6%) and NET-G3 (37 cases, 10.0%). In pulmonary NETs, typical and atypical carcinoid tumors was 47.6% and 52.4%, respectively. There were 310 patients at stage Ⅰ/Ⅱ, 53 at stage Ⅲ, 69 at stage Ⅳ and 56 at stage undiagnosed, respectively. The relationships among age, stage, grade, metastasis, treatment and prognosis were analyzed. All these factors could influence the survival rate of NET patients. Multivariate Cox analysis showed that age (>50 years old) (HR=2.831, 95%CI:1.414-7.029, P=0.025) and distant metastasis (HR=10.208, 95%CI:4.110-25.355, P<0.001) were independent risk factors. Conclusions: The most common primary sites of NETs are the pancreas, rectum, and stomach. Age and distant metastasis are independent risk factors for the prognosis of NETs.

Direct Observation of "Pac-Man" Coarsening.

We report direct observation of a "Pac-Man" like coarsening mechanism of a self-supporting thin film of nickel oxide. The ultrathin film has an intrinsic morphological instability due to surface stress leading to the development of local thicker regions at step edges. Density functional theory calculations and continuum modeling of the elastic instability support the model for the process.

Influence of glucose metabolism on cognitive function of patients with acute small-artery occlusion.

The aim of this study was to evaluate the influence of abnormal glucose metabolism on cognitive function of patients with acute small-arterial occlusion (SAO). The present study included 1,211 patients, with small-artery occlusion according to the Trial of Org 10172 in acute stroke treatment (TOAST) classification, admitted between March 2014 and December 2016 to The Second Hospital of Jiaxing. According to cognitive function, the patients were divided into a group of normal cognitive function, a mild cognitive impairment group (MCI group) and a dementia group. The patients were also divided into normal a blood sugar group, an impaired glucose regulation group (IGR group) and a diabetes mellitus (DM) group based on glucose metabolism. Cognitive functions of patients in the different glucose metabolism groups were compared based on Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). General data, medical history, neuropsychological assessment and haematological index of the patients in each group were analyzed. Logistic regression analysis was used to study independent risk factors influencing cognitive impairment. When comparing the group of normal cognitive function with the MCI group, there were no statistical significant differences between the MMSEs scores of patients among the three groups, but the difference in MoCAs scores had statistical significance. Hypertension history, hyperhomocysteinemia (Hhcy) and sedentariness were independent risk factors for SAO patients with MCI. When comparing the group of normal cognitive function with the dementia group, there were statistically significant differences (P<0.05) between the MMSE and MoCA scores of patients among the three groups. Abnormal glucose metabolism, old age, female, high blood pressure, Hhcy, family stroke history and sedentariness were independent risk factors for SAO patients with dementia. In conclusion, abnormal glucose metabolism impairing cognitive function is not an independent risk factor for SAO patients with MCI, but is an independent risk factor for SAO patients with dementia.

[The impact of donor human leukocyte antigen-Bw4 allele on natural killer cell reconstitution and transplant-related mortality in haploidentical transplantation].

Objective: To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion. Methods: This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning. Results: Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM. Conclusion: In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

[Analysis of etiology and complications in children with stage 5 chronic kidney disease].

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ2=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ2=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ2=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ2=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ2=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.

Knockdown of the gene encoding Drosophila tribbles homologue 3 (Trib3) improves insulin sensitivity through peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in a rat model of insulin resistance.

AIMS/HYPOTHESIS: Insulin action is purportedly modulated by Drosophila tribbles homologue 3 (TRIB3), which in vitro prevents thymoma viral proto-oncogene (AKT) and peroxisome proliferator-activated receptor-γ (PPAR-γ) activation. However, the physiological impact of TRIB3 action in vivo remains controversial. METHODS: We investigated the role of TRIB3 in rats treated with either a control or Trib3 antisense oligonucleotide (ASO). Tissue-specific insulin sensitivity was assessed in vivo using a euglycaemic-hyperinsulinaemic clamp. A separate group was treated with the PPAR-γ antagonist bisphenol-A-diglycidyl ether (BADGE) to assess the role of PPAR-γ in mediating the response to Trib3 ASO. RESULTS: Trib3 ASO treatment specifically reduced Trib3 expression by 70% to 80% in liver and white adipose tissue. Fasting plasma glucose, insulin concentrations and basal rate of endogenous glucose production were unchanged. However, Trib3 ASO increased insulin-stimulated whole-body glucose uptake by ~50% during the euglycaemic-hyperinsulinaemic clamp. This was attributable to improved skeletal muscle glucose uptake. Despite the reduction of Trib3 expression, AKT2 activity was not increased. Trib3 ASO increased white adipose tissue mass by 70% and expression of Ppar-γ and its key target genes, raising the possibility that Trib3 ASO improves insulin sensitivity primarily in a PPAR-γ-dependent manner. Co-treatment with BADGE blunted the expansion of white adipose tissue and abrogated the insulin-sensitising effects of Trib3 ASO. Finally, Trib3 ASO also increased plasma HDL-cholesterol, a change that persisted with BADGE co-treatment. CONCLUSIONS/INTERPRETATION: These data suggest that TRIB3 inhibition improves insulin sensitivity in vivo primarily in a PPAR-γ-dependent manner and without any change in AKT2 activity.

[The efficacy and safety of salvage surgery for local recurrent nasopharyngeal carcinoma: a systematic review and Meta-analysis].

Objective: To assess the current evidence regarding the efficacy, safety, and potential advantages of endoscopic compared with open salvage surgery for patients with local recurrent nasopharyngeal carcinoma. Methods: A systematic search of Pubmed/Medline, Embase, and Cochrane databases ranged between 2000 and 2017 was conducted. Included studies reported specific residual or local recurrent nasopharyngeal cancer survival data. Proportional Meta-analysis was performed on both outcomes with a random-effects model and the 95% confidential intervals were calculated by Stata 12.0 software. Results: A total of 24 case series studies were included in the Meta-analysis.The pooled 2-year overall survival rates of endoscopic and open group were 84% (95%CI:72%-93%), 68%(95%CI:59%-77%),respectively.The pooled 2-year disease-free survival rates of endoscopic and open group were 68%(95%CI:53%-81%), 65%(95%CI:54%-75%),respectively. The pooled 5-year overall survival rates of endoscopic and open group were 72%(95%CI:37%-97%), 48% (95%CI:40%-56%),respectively.The pooled 5-year disease-free survival rates of endoscopic and open group were 65%(95%CI:29%-93%), 50%(95%CI:43%-57%),respectively.The combined outcome of endoscopic was higher than open procedure. In addition, less severe complications, lower local recurrence rates(27%vs32%).The 2-year overall survival rates of endoscopic was higher than open procedure in the staging of rT1, rT2, and rT3 (93%vs87%; 77%vs63%; 67%vs53%) , but was equal to open in the staging for rT4 (35%vs35%) .Meta-regression showed that the heterogeneity was correlated with advanced tumor ratio. Conclusions: The present Meta-analysis reveals that endoscopic approach offers a safe and efficient alternative to open approach with better short-term outcome and fewer postoperative complications in selecting patients strictly.

In vitro study on the influence of strontium-doped calcium polyphosphate on the angiogenesis-related behaviors of HUVECs.

Angiogenesis is of great importance in bone tissue engineering, and has gained large attention in the past decade. Strontium-doped calcium polyphosphate (SCPP) is a novel biodegradable material which has been proved to be able to promote in vivo angiogenesis during bone regeneration. An in vitro culture system was developed in the present work to examine its influence on angiogenesis-related behaviors of human umbilical vein endothelial cells (HUVECs), including cell adhesion, spreading, proliferation and migration. The effects of microtopography, chemical property and the ingredients in the degradation fluid (DF) on cell behaviors were discussed. The results showed that cells attached and spread better on SCPP scaffold than on calcium polyphosphate (CPP), which might partially result from the less rough surface of SCPP scaffold and the less hydrogel formed on the surface. In addition, cell proliferation was significantly improved when treated with SCPP DF compared with the treatment with CPP DF. Statistical analysis indicated that Sr(2+) in SCPP DF might be the main reason for the improved cell proliferation. Moreover, cell migration, another important step during angiogenesis, was evidently stimulated by SCPP DF. The improved in vivo angiogenesis by SCPP might be assigned to its better surface properties and strontium in the DF. This work also provides a new method for in vitro evaluation of biodegradable materials' potential effects on angiogenesis.

Methylation of the protein phosphatase 2A catalytic subunit is essential for association of Balpha regulatory subunit but not SG2NA, striatin, or polyomavirus middle tumor antigen.

Binding of different regulatory subunits and methylation of the catalytic (C) subunit carboxy-terminal leucine 309 are two important mechanisms by which protein phosphatase 2A (PP2A) can be regulated. In this study, both genetic and biochemical approaches were used to investigate regulation of regulatory subunit binding by C subunit methylation. Monoclonal antibodies selectively recognizing unmethylated C subunit were used to quantitate the methylation status of wild-type and mutant C subunits. Analysis of 13 C subunit mutants showed that both carboxy-terminal and active site residues are important for maintaining methylation in vivo. Severe impairment of methylation invariably led to a dramatic decrease in Balpha subunit binding but not of striatin, SG2NA, or polyomavirus middle tumor antigen (MT) binding. In fact, most unmethylated C subunit mutants showed enhanced binding to striatin and SG2NA. Certain carboxy-terminal mutations decreased Balpha subunit binding without greatly affecting methylation, indicating that Balpha subunit binding is not required for a high steady-state level of C subunit methylation. Demethylation of PP2A in cell lysates with recombinant PP2A methylesterase greatly decreased the amount of C subunit that could be coimmunoprecipitated via the Balpha subunit but not the amount that could be coimmunoprecipitated with Aalpha subunit or MT. When C subunit methylation levels were greatly reduced in vivo, Balpha subunits were found complexed exclusively to methylated C subunits, whereas striatin and SG2NA in the same cells bound both methylated and unmethylated C subunits. Thus, C subunit methylation is critical for assembly of PP2A heterotrimers containing Balpha subunit but not for formation of heterotrimers containing MT, striatin, or SG2NA. These findings suggest that methylation may be able to selectively regulate the association of certain regulatory subunits with the A/C heterodimer.

UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells.

Uncoupling proteins (UCPs) are a family of mitochondrial transporter proteins that have been implicated in thermoregulatory heat production and maintenance of the basal metabolic rate. We have identified and partially characterized a novel member of the human uncoupling protein family, termed uncoupling protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins. Unlike other known UCPs, UCP4 transcripts are exclusively expressed in both fetal and adult brain tissues. UCP4 maps to human chromosome 6p11.2-q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain.

Effects of acute exercise on hepatic lipogenic enzymes in fasted and refed rats.

The effects of an acute bout of prolonged exhaustive exercise on the activities of hepatic lipogenic enzymes have been investigated. Male Sprague-Dawley rats were randomly divided into three groups: fasted for 48 h without refeeding (FA) and fasted for 48 h and refed a diet high in fructose (RF) or in cornstarch (RC). One-half of each group of rats exercised on a treadmill at 20 m/min, 5% grade, until exhaustion and the other half rested for the same amount of time without food. Dietary intakes during refeeding were kept equal between the exercised and rested control animals. Activities of all hepatic lipogenic enzymes measured, i.e., fatty acid synthase (FAS), L-type pyruvate kinase (L-PK), ATP citrate lyase, malic enzyme, and glucose-6-phosphate dehydrogenase, were induced dramatically by fasting-refeeding and were significantly higher in the RF than in the RC rats (P < 0.05). FAS activity was increased 19- and 39-fold, respectively, in the RC and RF rats compared with the FA rats. Exercise decreased FAS activity to approximately one-third of the resting control value in both RC and RF rats (P < 0.05) but not in FA rats. L-PK activity was elevated by 55% in RC and 100% in RF rats compared with FA rats (P < 0.05). FA and RF rats also showed a reduction of L-PK activity with exercise. No significant alteration of other lipogenic enzymes was observed after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Rates of mitochondrial and peroxisomal beta-oxidation of palmitate change during postnatal development and food deprivation in liver, kidney and heart of pigs.

We measured total, mitochondrial and peroxisomal capacities for beta-oxidation of [1-14C]palmitate in homogenates of liver, kidney and heart from pigs within 0.5 h after birth (0 h, unfed) and at 24 h (suckled or unfed), 10 d (suckled or 24-h food-deprived), 21 d (suckled or 24-h food-deprived) and 5 mo (overnight food-deprived) of age. Assays were conducted in the absence (total beta-oxidation) or presence (peroxisomal beta-oxidation) of antimycin A and rotenone. Mitochondrial beta-oxidation was calculated as total minus peroxisomal beta-oxidation. Acid-soluble products (ASP) from incubation of tissue homogenates from 24-h-old unfed pigs with [1-14C]palmitate were analyzed by radio-HPLC. Total and mitochondrial beta-oxidation capacities were greater (P < 0.05) at 24 h after birth in liver, and at 10 d in kidney and heart, than at 0 or 24 h. Peroxisomal beta-oxidation capacity was increased (P < 0. 05) at 24 h after birth in liver and at 10 and 21 d in heart; in kidney, the capacity was higher during the preweaning period than in adults. Across ages, peroxisomal beta-oxidation capacity represented 37 to 51%, 28 to 41%, and 26 to 31% of total beta-oxidation capacity in liver, kidney, and heart, respectively. Food deprivation increased hepatic total beta-oxidation at 10 d and decreased peroxisomal beta-oxidation at 24 h but had no effect in kidney and heart. Regardless of the presence of respiratory inhibitors, 32%, 31 to 40%, and 45 to 50% of palmitate carboxyl carbon in acid-soluble products was accumulated in acetate in liver, kidney, and heart, respectively. We suggest that a high percentage contribution of peroxisomal beta-oxidation may act as a compensatory mechanism for piglets to oxidize milk fatty acids during postnatal development. Furthermore, acetogenesis may be an important fate of acetyl-CoA from beta-oxidation of fatty acids in various piglet tissues.

Differential induction of peroxisomal beta-oxidation enzymes by clofibric acid and aspirin in piglet tissues.

Peroxisomal beta-oxidation (POX) of fatty acids is important in lipid catabolism and thermogenesis. To investigate the effects of peroxisome proliferators on peroxisomal and mitochondrial beta-oxidation in piglet tissues, newborn pigs (1-2 days old) were allowed ad libitum access to milk replacer supplemented with 0.5% clofibric acid (CA) or 1% aspirin for 14 days. CA increased ratios of liver weight to body weight (P < 0.07), kidney weight to body weight (P < 0.05), and heart weight to body weight (P < 0.001). Aspirin decreased daily food intake and final body weight but increased the ratio of heart weight to body weight (P < 0.01). In liver, activities of POX, fatty acyl-CoA oxidase (FAO), total carnitine palmitoyltransferase (CPT), and catalase were 2.7-, 2.2-, 1.5-fold, and 33% greater, respectively, for pigs given CA than for control pigs. In heart, these variables were 2.2-, 4.1-, 1.9-, and 1.8-fold greater, respectively, for pigs given CA than for control pigs. CA did not change these variables in either kidney or muscle, except that CPT activity was increased approximately 110% (P < 0.01) in kidney. Aspirin increased only hepatic FAO and CPT activities. Northern blot analysis revealed that CA increased the abundance of catalase mRNA in heart by approximately 2.2-fold. We conclude that 1) POX and CPT in newborn pigs can be induced by peroxisomal proliferators with tissue specificity and 2) the relatively smaller induction of POX in piglets (compared with that in young or adult rodents) may be related to either age or species differences.

Perspectives on the biology of uncoupling protein (UCP) homologues.

In mammals, it is believed that a portion of tissue metabolic rate is driven by counteraction of uncoupling, in which the energetically inefficient process of proton leak acts to diminish the mitochondrial electrochemical membrane potential. It is proposed that specific proteins associated with the mitochondrion catalyse uncoupling, and the biology of such putative uncoupling proteins (UCPs) is the subject of active research efforts. UCP4 and UCP5 are interesting in light of their abundant expression in the brain, which may signal an important metabolic function in thermogenesis or regulation of reactive oxygen species in that tissue. While each is expressed to various degrees outside of the brain, their impact on whole-animal metabolism remains to be clarified further. Transgenic mice expressing murine UCP5(L), the long isoform of UCP5, using an inducible metallothionine promoter (to drive expression of the transgene in liver, testis, heart, lung, spleen, intestine, kidney and brain) did not display any overt metabolic phenotype, despite liver UCP5(L) mRNA expression equivalent to that of normal mouse brain. This highlights the need for further studies to examine the nature of UCP5 physiology. Evidence for uncoupling behaviour has recently emerged from studies of the human 2-oxoglutarate carrier (OGC), indicating that the possibility of physiological proton leak elicited by the OGC and other mitochondrial carriers warrants further experimental evaluation.

Food deprivation changes peroxisomal beta-oxidation activity but not catalase activity during postnatal development in pig tissues.

Peroxisomal beta-oxidation and catalase activity were investigated in liver, kidney and heart from pigs at the following timepoints: within 0.5 h after birth (0 h, unfed) and at 24 h (suckled or unsuckled), 10 d (suckled or 24-h food-deprived), 21 d (suckled or 24-h food-deprived) and 5 mo (overnight food-deprived). In liver, peroxisomal beta-oxidation increased about twofold at 24 h for suckled pigs (P < 0.001) but did not change for unsuckled pigs. The rate was further increased in 21-d-old pigs compared with 0- (P < 0. 001) or 24-h-old (P < 0.05) pigs, but was lower at 5 mo than at 10 or 21 d (P < 0.01). The rate was higher for food-deprived pigs than suckled pigs at 10 d (P < 0.001) of age. In kidney, peroxisomal beta-oxidation was unchanged during the first 24 h but was higher (P < 0.05) at 10 d for suckled pigs and at 21 d than at 0 h. Nutritional state did not influence renal peroxisomal beta-oxidation. In heart, peroxisomal beta-oxidation did not change with age or nutritional state. The developmental pattern of fatty acyl-CoA oxidase activity was similar to that of peroxisomal beta-oxidation in each tissue. Developmental increases of peroxisomal beta-oxidation were greater than those for first-cycle peroxisomal beta-oxidation reported earlier, suggesting that peroxisomal beta-oxidation became more complete in older pigs. Catalase activity did not change during the first 24 h after birth but then increased 10.5-, 2.9-fold and 33% at 10 d in liver, kidney and heart, respectively. The concentration of catalase mRNA was only 1.1- and 1. 3-fold higher at 10 d than at 24 h in liver and kidney, respectively. Catalase activity was not affected by food deprivation. We concluded the following: 1) peroxisomal beta-oxidation develops rapidly after birth and may be important for piglets to oxidize milk fatty acids; 2) food is required for the initial induction after birth; and 3) rapidly increased catalase activity during the first 10 d of life resulted from both pretranslational and post-translational regulation.