The Counter Effect of Exercise on Cisplatin-Induced Cognitive and Proliferation Impairments.

Background Cisplatin, a widely used chemotherapeutic agent, offers therapeutic benefits for cancer treatment but often leads to adverse effects on neurogenesis and oxidative stress, causing cognitive impairment. Concurrent physical activity has been proposed as a potential strategy to counteract these side effects. This study aimed to investigate the impact of physical exercise on cisplatin-induced cognitive impairment in a mouse model. Methods Adult male mice (n=45) were divided into three groups: control, cisplatin-treated (2.3 mg/kg), and exercise/cisplatin. Cisplatin was administered intraperitoneally over one month, while the exercise/cisplatin group underwent moderate-intensity exercise alongside cisplatin treatment. Spatial memory was evaluated using the novel object recognition (NOR) task, and hippocampal proliferation and oxidative stress were examined using Ki-67 and glutathione peroxidase (GPx) immunohistochemistry (IHC) staining, respectively. Statistical analyses were performed using the GraphPad Prism 4.0 software (GraphPad Software, San Diego, CA). Results The cisplatin-treated mice exhibited significantly lower preference index (PI) scores in the NOR task compared to the control (p<0.001) and exercise/cisplatin (p<0.001) groups. IHC staining revealed impaired hippocampal proliferation and increased oxidative stress in the cisplatin-treated group relative to the control and exercise/cisplatin groups. The introduction of a moderate-intensity exercise protocol appeared to mitigate the decline in hippocampal proliferation and oxidative damage induced by cisplatin. Additionally, cisplatin-treated mice experienced weight loss, while exercise attenuated this effect. Conclusion Cisplatin treatment resulted in decreased memory, hippocampal proliferation, and weight loss in mice. Concurrent moderate-intensity exercise seemed to alleviate these effects, suggesting a potential role for physical activity in ameliorating cisplatin-induced cognitive decline. This study underscores the importance of incorporating exercise as a complementary strategy to enhance cognitive outcomes in cancer patients undergoing cisplatin treatment.

Active gas aspiration in reducing pain after laparoscopic cholecystectomy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative pain is a common issue following laparoscopic cholecystectomy. This meta-analysis aimed to determine if active gas aspiration is more effective than passive gas aspiration in reducing postoperative pain and analgesic requirements. METHODOLOGY: The study conducted a systematic search of various databases, including Embase, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) via Ovid. It also searched trial registries and reference lists of included studies, with no date restrictions but limited to English language, up to December 21, 2022. The study included all randomized clinical trials that had documented elective laparoscopic cholecystectomy procedure and reported at least one relevant outcome. Articles that included subdiaphragmatic drain, intraperitoneal normal saline infusion, or pulmonary recruitment maneuver were excluded from the analysis. Two reviewers independently and in duplicate assessed the eligibility of studies and extracted data. The study reported findings according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The risk of bias of the included trials was assessed using the Revised Cochrane Risk of Bias Assessment Tool. The study used a random-effects model to pool data. RESULTS: This meta-analysis included 5 randomized clinical trials with 367 participants and found that active gas aspiration resulted in significantly lower residual gas volume and total analgesia requirements compared to passive gas aspiration. Active gas aspiration also led to significantly lower shoulder pain scores at 24 h postoperatively. However, no significant differences were observed in hospital stay duration or abdominal pain scores. CONCLUSION: The study found that active gas aspiration can be effective in reducing postoperative shoulder pain and analgesic requirements after laparoscopic cholecystectomy, which has important implications for patient care and healthcare costs. Importantly, this intervention does not impose any additional time or financial burden. However, further research is needed to evaluate its impact on other laparoscopic procedures.

Metformin use is associated with longer survival in glioblastoma patients with MGMT gene silencing.

PURPOSE: New treatments are needed to improve the overall survival of patients with glioblastoma Metformin is known for anti-tumorigenic effects in cancers, including breast and pancreas cancers. In this study, we assessed the association between metformin use and overall survival in glioblastoma patients. METHODS: We retrospectively studied 241 patients who underwent surgery at diagnosis of glioblastoma between 2014 and 2018. Metformin was used for pre-existing type 2 diabetes mellitus or in the prevention or management of glucocorticoid induced hyperglycemia. Kaplan-Meier curves and log-rank p test were used for univariate analysis. Cox-proportional hazards model was used to generate adjusted hazard ratios for multivariate analysis. RESULTS: Metformin use was associated with longer survival in patients with tumors that had a methylated O6-methylguanine DNA methyltransferase gene (MGMT) promoter (484 days 95% CI: 56-911 vs. 394 days 95% CI: 249-538, Log-Rank test: 6.5, p = 0.01). Cox regression analysis shows that metformin associates with lower risk of death at 2 years in patients with glioblastoma containing a methylated MGMT promoter (aHR = 0.497, 95% CI 0.26-0.93, p = 0.028). CONCLUSION: Our findings suggest a survival benefit with metformin use in patients with glioblastomas having methylation of the MGMT promoter.

Nutritional Rickets Among Children: A Retrospective Study from Saudi Arabia.

Background: Nutritional rickets remains a significant concern in certain countries, with increasing prevalence attributed to factors such as limited sunlight exposure and undernourishment. This study aimed to identify the factors associated with rickets due to nutritional deficiency in children from Jazan Province, southwestern Saudi Arabia. Methods: A retrospective cross-sectional study was conducted using descriptive data from medical records at a tertiary hospital in Jazan Province. Records of patients diagnosed with rickets between January 2010 and December 2020 were analyzed. Symptomatic rickets cases from pediatric clinics were included, and diagnoses were based on biochemical and clinical tests. Risk factors were assessed using patient medical records. Data were analyzed using percentages, mean, and standard deviation. Results: The study included 84 patients with rickets (53 females and 31 males), primarily between 11-18 years old. The mean body mass index (BMI) of the participants was 21.21. The most common risk factor was nutritional deficiencies, including vitamin D deficiency or calcium deficiency, with 75 patients reporting a family history of vitamin D deficiency. The children had limited sunlight exposure and low levels of calcium and vitamin D. Malnutrition was identified as the highest risk factor for rickets in the study population. Conclusion: Nutritional rickets appears to be prevalent in the Jazan Province, emphasizing the need for government organizations to address this preventable disease. Adequate sun exposure and recommended dietary vitamin D intake are crucial to prevent rickets, as this study detected inadequate levels of calcium and vitamin D in children. National studies are required to further identify risk factors and develop appropriate strategies.

Cleavage of the V-ATPase associated prorenin receptor is mediated by PACE4 and is essential for growth of prostate cancer cells.

Phosphatase and tensin homolog (PTEN) mutation is common in prostate cancer during progression to metastatic and castration resistant forms. We previously reported that loss of PTEN function in prostate cancer leads to increased expression and secretion of the Prorenin Receptor (PRR) and its soluble processed form, the soluble Prorenin Receptor (sPRR). PRR is an essential factor required for proper assembly and activity of the vacuolar-ATPase (V-ATPase). The V-ATPase is a rotary proton pump required for the acidification of intracellular vesicles including endosomes and lysosomes. Acidic vesicles are involved in a wide range of cancer related pathways such as receptor mediated endocytosis, autophagy, and cell signalling. Full-length PRR is cleaved at a conserved consensus motif (R-X-X-R↓) by a member of the proprotein convertase family to generate sPRR, and a smaller C-terminal fragment, designated M8.9. It is unclear which convertase processes PRR in prostate cancer cells and how processing affects V-ATPase activity. In the current study we show that PRR is predominantly cleaved by PACE4, a proprotein convertase that has been previously implicated in prostate cancer. We further demonstrate that PTEN controls PRR processing in mouse tissue and controls PACE4 expression in prostate cancer cells. Furthermore, we demonstrate that PACE4 cleavage of PRR is needed for efficient V-ATPase activity and prostate cancer cell growth. Overall, our data highlight the importance of PACE4-mediated PRR processing in normal physiology and prostate cancer tumorigenesis.

Characterization of perioperative glycemic status and dexamethasone use with associated postoperative complications in glioblastoma patients.

PURPOSE: Postoperative morbidity in glioblastoma (GBM) patients can be due to the disease course but can also come from postoperative complications. Our objective was to study the association of dexamethasone use and perioperative hyperglycemia with postoperative complications in GBM patients. METHODS: A single-center, retrospective cohort study was conducted in patients who underwent surgery for primary GBM from 2014-2018. Patients with perioperative fasting blood glucose (FBG) measurements and adequate follow-up to assess for complications were included. RESULTS: A total of 199 patients were included. More than half (53%) had poor perioperative glycemic control (FBG ≥ 7 mM for ≥ 20% perioperative days). Higher dexamethasone dose (≥ 8 mg) was associated with higher FBG on postoperative days 2-4 and 5 (p = 0.02,0.05,0.004,0.02, respectively). Poor glycemic control was associated with increased odds of 30-day any complication and 30-day infection on univariate analysis (UVA), and 30-day any complication and increased length of stay (LOS) on multivariate analysis (MVA). Higher average perioperative daily dexamethasone dose was associated with increased odds of 30-day any complication and 30-day infection on MVA. Elevated hemoglobin A1c (HgbA1c, ≥ 6.5%) was associated with increased odds of 30-day any complication, 30-day infection, and LOS on UVA. In a multivariate linear regression model, only the diagnosis of diabetes mellitus predicted perioperative hyperglycemia. CONCLUSIONS: Perioperative hyperglycemia, higher average dexamethasone use and elevated preoperative HgbA1c are associated with increased risk of postoperative complications in GBM patients. Avoiding hyperglycemia and limiting dexamethasone use in postoperative period may decrease the risk of complications. Select HgbA1c screening may allow the identification of a group of patients at higher risk of complications.

Electrocorticography-Guided Resection Enhances Postoperative Seizure Freedom in Low-Grade Tumor-Associated Epilepsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Low-grade cerebral neoplasms are commonly associated with medically intractable epilepsy. Despite increasing evidence that epileptogenic brain regions commonly extend beyond visible tumor margins, the utility of extended surgical resections leveraging intraoperative electrocorticography (ECoG) remains unclear. OBJECTIVE: To determine whether ECoG-guided surgery is associated with improved postoperative seizure control. METHODS: We performed a systematic review and meta-analysis encompassing both adult and pediatric populations. The primary outcome measure was postoperative seizure freedom as defined by Engel class I outcome. Class I/II outcome served as a secondary measure. Relevant clinical and operative data were recorded. A random-effects meta-analysis based on the pooled odds ratio (OR) of seizure freedom was performed on studies that reported comparative data between ECoG-guided surgery and lesionectomy. RESULTS: A total of 31 studies encompassing 1115 patients with medically refractory epilepsy met inclusion criteria. Seven studies reported comparative data between ECoG-guided surgery and lesionectomy for meta-analysis. Tumor resection guided by ECoG was associated with significantly greater postoperative seizure freedom (OR 3.95, 95% CI 2.32-6.72, P < .0001) and class I/II outcome (OR 5.10, 95% CI 1.97-13.18, P = .0008) compared with lesionectomy. Postoperative adverse events were rare in both groups. CONCLUSION: These findings provide support for the utilization of ECoG-guided surgery to improve postoperative seizure freedom in cases of refractory epilepsy associated with low-grade neoplasms. However, this effect may be attenuated in the presence of concomitant cortical dysplasia, highlighting a need for improved presurgical and intraoperative monitoring for these most challenging cases of localization-related epilepsy.

Deformation behavior of single-crystal magnesium during Nano-ECAP simulation.

Molecular dynamics was applied to simulate ECAP of single-crystal magnesium at room temperature. Four samples with different orientations were processed, and the grain structure, grain fragmentation, slip systems, strain, and twin formation were analyzed. The initial orientation played a substantial role in the strain and deformation experienced by the samples during both stages of deformation. Compressions initially occurred before extrusion, and simple shear occurred in the deformation zone during extrusion. The samples nucleated a { 10 1 ¯ 2 } tension twin during compression, and the tension twin grew to immediately cover the entire sample, effectively changing the orientation of the sample. Additionally, stacking faults acted as a precursor for the { 10 1 ¯ 2 } tension twin. The strain was strongly correlated with the shear factor, that is, a high shear factor resulted in low strain. Moreover, discrepancy occurred between theoretical and actual shear strain due to two factors. First, theoretical shear is considered to be simple shear occurring entirely in the deformation zone; it does not consider the shear strain due to the normal stress in the compression phase. Second, deformation is considered to be homogenous and isotropic, and it does not take into account the initial grain orientation and the anisotropic nature of magnesium.

Elevated V-ATPase Activity Following PTEN Loss Is Required for Enhanced Oncogenic Signaling in Breast Cancer.

PTEN loss-of-function contributes to hyperactivation of the PI3K pathway and to drug resistance in breast cancer. Unchecked PI3K pathway signaling increases activation of the mechanistic target of rapamycin complex 1 (mTORC1), which promotes tumorigenicity. Several studies have suggested that vacuolar (H+)-ATPase (V-ATPase) complex activity is regulated by PI3K signaling. In this study, we showed that loss of PTEN elevated V-ATPase activity. Enhanced V-ATPase activity was mediated by increased expression of the ATPase H+ transporting accessory protein 2 (ATP6AP2), also known as the prorenin receptor (PRR). PRR is cleaved into a secreted extracellular fragment (sPRR) and an intracellular fragment (M8.9) that remains associated with the V-ATPase complex. Reduced PTEN expression increased V-ATPase complex activity in a PRR-dependent manner. Breast cancer cell lines with reduced PTEN expression demonstrated increased PRR expression. Similarly, PRR expression became elevated upon PTEN deletion in a mouse model of breast cancer. Interestingly, concentration of sPRR was elevated in the plasma of patients with breast cancer and correlated with tumor burden in HER2-enriched cancers. Moreover, PRR was essential for proper HER2 receptor expression, localization, and signaling. PRR knockdown attenuated HER2 signaling and resulted in reduced Akt and ERK 1/2 phosphorylation, and in lower mTORC1 activity. Overall, our study demonstrates a mechanism by which PTEN loss in breast cancer can potentiate multiple signaling pathways through upregulation of the V-ATPase complex. IMPLICATIONS: Our study contributed to the understanding of the role of the V-ATPase complex in breast cancer cell tumorigenesis and provided a potential biomarker in breast cancer.

V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss.

Phosphatase and tensin homolog (PTEN) tumor suppressor protein loss is common in prostate cancer (PCa). PTEN loss increases PI3K/Akt signaling, which promotes cell growth and survival. To find secreted biomarkers of PTEN loss, a proteomic screen was used to compare secretomes of cells with and without PTEN expression. We showed that PTEN downregulates Prorenin Receptor (PRR) expression and secretion of soluble Prorenin Receptor (sPRR) in PCa cells and in mouse. PRR is an accessory protein required for assembly of the vacuolar ATPase (V-ATPase) complex. V-ATPase is required for lysosomal acidification, amino acid sensing, efficient mechanistic target of Rapamycin complex 1 (mTORC1) activation, and ß-Catenin signaling. On PCa tissue microarrays, PRR expression displayed a positive correlation with Akt phosphorylation. Moreover, PRR expression was required for proliferation of PCa cells by maintaining V-ATPase function. Further, we provided evidence for a potential clinical role for PRR expression and sPRR concentration in differentiating low from high Gleason grade PCa. Overall, the current study unveils a mechanism by which PTEN can inhibit tumor growth. Lower levels of PRR result in attenuated V-ATPase activity and reduced PCa cell proliferation.

An Uncharacterized Major Facilitator Superfamily Transporter From Planococcus maritimus Exhibits Dual Functions as a Na+(Li+, K+)/H+ Antiporter and a Multidrug Efflux Pump.

Within major facilitator superfamily (MFS), up to 27 unknown major facilitator families and many members of 60 well-characterized families have been functionally unknown as yet, due to their sharing no or significantly low sequence identity with characterized MFS members. Here we present the first report on the characterization of one functionally unknown MFS transporter designated MdrP with the accession version No. ANU18183.1 from the slight halophile Planococcus maritimus DS 17275T. During the screening of Na+/H+ antiporter genes, we found at first that MdrP exhibits Na+(Li+, K+)/H+ antiport activity, and propose that it should represent a novel class of Na+(Li+, K+)/H+ antiporters. However, we speculate that MdrP may possess an additional protein function. The existence of the signature Motif A of drug/H+antiporter (DHA) family members and phylogenetic analysis suggest that MdrP may also function as a drug efflux pump, which was established by minimum inhibitory concentration tests and drug efflux activity assays. Taken together, this novel MFS transporter exhibits dual functions as a Na+(Li+, K+)/H+ antiporter and a multidrug efflux pump, which will be very helpful to not only positively contribute to the function prediction of uncharacterized MFS members especially DHA1 family ones, but also broaden the knowledge of Na+/H+ antiporters.

Dentoskeletal Effects of the Modified Tandem Appliance vs the Facemask Appliance in the Treatment of Skeletal Class III Malocclusion: A Single-center, Randomized Controlled Trial.

AIMS: The aim of this randomized controlled trial was to compare the skeletal and dentoalveolar effects of the modified tandem appliance (MTA) vs the facemask (FM) with rapid maxillary expansion. MATERIALS AND METHODS: Thirty-two patients, aged 7 to 9 years were recruited. Eligibility criteria included skeletal class III malocclusion that resulted from the retrusion of the maxilla. Randomization was accomplished to divide the sample into two equal groups to be treated with either MTA or FM. Lateral cephalometric radiographs were obtained before treatment and after 2 mm positive overjet was achieved. Intragroup comparisons were performed using paired-sample t-test, and intergroup comparisons were performed using two-sample t-test at the p ≤ 0.05 level. RESULTS: Thirty-two patients (16 in each group) were available for statistical analysis. The pretreatment variables of both groups were similar. Both treatment therapies showed similar significant increase in the SNA and ANB angles, accompanied by slight decrease in the SNB angle. The increase in the SN:GoMe angle, Bjork's sum, and the overjet were significantly greater in the FM group. The forward movement of upper dentition was similar in both groups. Although the lower incisors retrusion was significantly greater in the FM group than in the MTA group, the uprighting of the lower molars was significantly greater in the MTA group. CONCLUSION: Both appliances showed similar effects apart from less clockwise rotation of the mandible, less retrusion of the lower incisors, and greater uprighting of the lower molars in the MTA group. CLINICAL SIGNIFICANCE: Both the MTA and the FM groups are effective in treating class III malocclusion. The MTA group is more efficient in controlling the clockwise rotation and gaining some space in the lower arch.

Deletion of the gene encoding G0/G 1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice.

AIMS/HYPOTHESIS: Obesity is a global epidemic resulting from increased energy intake, which alters energy homeostasis and results in an imbalance in fat storage and breakdown. G0/G1 switch gene 2 (G0s2) has been recently characterised in vitro as an inhibitor of adipose triglyceride lipase (ATGL), the rate-limiting step in fat catabolism. In the current study we aim to functionally characterise G0s2 within the physiological context of a mouse model. METHODS: We generated a mouse model in which G0s2 was deleted. The homozygous G0s2 knockout (G0s2 (-/-)) mice were studied over a period of 22 weeks. Metabolic variables were measured including body weight and body composition, food intake, glucose and insulin tolerance tests, energy metabolism and thermogenesis. RESULTS: We report that G0s2 inhibits ATGL and regulates lipolysis and energy metabolism in vivo. G0s2 (-/-) mice are lean, resistant to weight gain induced by a high-fat diet and are glucose tolerant and insulin sensitive. The white adipose tissue of G0s2 (-/-) mice has enhanced lipase activity and adipocytes showed enhanced stimulated lipolysis. Energy metabolism in the G0s2 (-/-) mice is shifted towards enhanced lipid metabolism and increased thermogenesis. G0s2 (-/-) mice showed enhanced cold tolerance and increased expression of thermoregulatory and oxidation genes within white adipose tissue, suggesting enhanced 'browning' of the white adipose tissue. CONCLUSIONS/INTERPRETATION: Our data show that G0s2 is a physiological regulator of adiposity and energy metabolism and is a potential target in the treatment of obesity and insulin resistance.

The prion protein ligand, stress-inducible phosphoprotein 1, regulates amyloid-ß oligomer toxicity.

In Alzheimer's disease (AD), soluble amyloid-ß oligomers (AßOs) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrP(C)). However, it is unknown whether other ligands of PrP(C) can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrP(C) in the vicinity of the AßO binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in AßO toxicity. We confirmed the specific binding of AßOs and STI1 to the PrP and showed that STI1 efficiently inhibited AßO binding to PrP in vitro (IC50 of ∼70 nm) and also decreased AßO binding to cultured mouse primary hippocampal neurons. Treatment with STI1 prevented AßO-induced synaptic loss and neuronal death in mouse cultured neurons and long-term potentiation inhibition in mouse hippocampal slices. Interestingly, STI1-haploinsufficient neurons were more sensitive to AßO-induced cell death and could be rescued by treatment with recombinant STI1. Noteworthy, both AßO binding to PrP(C) and PrP(C)-dependent AßO toxicity were inhibited by TPR2A, the PrP(C)-interacting domain of STI1. Additionally, PrP(C)-STI1 engagement activated α7 nicotinic acetylcholine receptors, which participated in neuroprotection against AßO-induced toxicity. We found an age-dependent upregulation of cortical STI1 in the APPswe/PS1dE9 mouse model of AD and in the brains of AD-affected individuals, suggesting a compensatory response. Our findings reveal a previously unrecognized role of the PrP(C) ligand STI1 in protecting neurons in AD and suggest a novel pathway that may help to offset AßO-induced toxicity.

Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein.

Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the STI1 gene, supported a unique role for STI1 during embryonic development. The response of STI1 haploinsufficient mice to cellular stress seemed compromised, and mutant mice showed increased vulnerability to ischemic insult. At the cellular level, ischemia increased the secretion of STI1 from wild-type astrocytes by 3-fold, whereas STI1 haploinsufficient mice secreted half as much STI1. Interesting, extracellular STI1 prevented ischemia-mediated neuronal death in a prion protein-dependent way. Our study reveals essential roles for intracellular and extracellular STI1 in cellular resilience.

Breakdown of K selection in 178Hf.

Coulomb activation of the four quasiparticle Kpi=16+ 178Hf isomer (t1/2=31 y) has led to the measurement of a set of Elamda matrix elements coupling the isomer band to the ground band. The present data combined with earlier 178 Hf Coulomb excitation data have probed the components in the wave functions and revealed the onset and saturation of K mixing in low-K bands, whereas the mixing is negligible in the high-K bands. The implications can be applied to other quadrupole-deformed nuclei.

Evidence for second-phonon nuclear wobbling.

The nucleus 163Lu has been populated through the reaction 139La(29Si,5n) with a beam energy of 157 MeV. Three triaxial, strongly deformed (TSD) bands have been observed with very similar rotational properties. The first excited TSD band has earlier been assigned as a one-phonon wobbling excitation built on the lowest-lying (yrast) TSD band. The large B(E2)(out)/B(E2)(in) value obtainable for one of four observed transitions between the second and first excited TSD bands is in good agreement with particle-rotor calculations for a two-phonon wobbling excitation.

Intraperitoneal infusion of homocysteine increases intimal hyperplasia in balloon-injured rat carotid arteries.

Hyperhomocysteinemia is a significant risk factor in atherosclerosis and thrombosis. However, its role in the development of intimal hyperplasia after arterial reconstructive procedures remains uncertain. We therefore studied the effect of homocysteine on intimal hyperplasia in a rat model of carotid artery balloon injury. Twenty-four Sprague-Dawley rats were divided into three groups: control (saline infusion), and low dose (0.14 mg/day) and high dose (0.71 mg/day) homocysteine delivered continuously via osmotic pumps implanted intraperitoneally. All animals underwent left common carotid artery balloon denudation with sacrifice after 14 days. Plasma homocysteine levels, intimal hyperplasia, and cell proliferation of rat carotid arteries were determined. In vitro rat smooth muscle cell (SMC) proliferation with homocysteine treatment was also performed. Plasma homocysteine levels at sacrifice were 1.80+/-0.35, 2.65+/-0.05 and 3.50+/-0.22 microM in three groups, respectively. Intimal hyperplasia developed in all balloon-injured arteries in both control and homocysteine-treated animals. The intimal area and intima/media area ratio were increased by 92% (P<0.05) and 105% (P<0.05), respectively, in the high dose-homocysteine-treated animals as compared to the control animals. Homocysteine (high dose) also significantly promoted the intimal cell proliferation (bromodeoxyuridine incorporation) by 2.2-fold as compared to controls. Furthermore, homocysteine treatment in the cell culture study showed a concentration-dependent increase of rat SMC proliferation. These data demonstrate that the continuous intraperitoneal administration of homocysteine significantly increases intimal hyperplasia and SMC proliferation after carotid artery balloon injury in the rat as well as in vitro SMC proliferation. This study suggests that, following arterial reconstructive procedures, elevated plasma homocysteine may increase the complications of clinical restenoses that are associated with intimal hyperplasia.

Identification of the I(pi) = 10(+) Yrast rotational state in 24Mg.

Spins and parities of high spin states above the particle-binding threshold in 24Mg were determined with a basis expansion technique using triple and quadruple angular correlations between alpha particles and gamma rays. The first unambiguous identification of a 10(+) state is reported. Located at 19.2(1) MeV, this state decays predominantly by alpha emission, although a candidate gamma-decay branch with a 5.927 MeV transition connecting this 10(+) level to the rotational 8(+) state at 13.2 MeV was identified as well. The corresponding gamma-alpha branching ratio is 7(3)x10(-4).