Targeted Brain Delivery of Dendrimer-4-Phenylbutyrate Ameliorates Neurological Deficits in a Long-Term ABCD1-Deficient Mouse Model of X-Linked Adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a genetic disorder that presents neurologically as either a rapid and fatal cerebral demyelinating disease in childhood (childhood cerebral adrenoleukodystrophy; ccALD) or slow degeneration of the spinal cord in adulthood (adrenomyeloneuropathy; AMN). All forms of ALD result from mutations in the ATP Binding Cassette Subfamily D Member (ABCD) 1 gene, encoding a peroxisomal transporter responsible for the import of very long chain fatty acids (VLCFA) and results mechanistically in a complex array of dysfunction, including endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction, and inflammation. Few therapeutic options exist for these patients; however, an additional peroxisomal transport protein (ABCD2) has been successfully targeted previously for compensation of dysfunctional ABCD1. 4-Phenylbutyrate (4PBA), a potent activator of the ABCD1 homolog ABCD2, is FDA approved, but use for ALD has been stymied by a short half-life and thus a need for unfeasibly high doses. We conjugated 4PBA to hydroxyl polyamidoamine (PAMAM) dendrimers (D-4PBA) to a create a long-lasting and intracellularly targeted approach which crosses the blood-brain barrier to upregulate Abcd2 and its downstream pathways. Across two studies, Abcd1 knockout mice administered D-4PBA long term showed neurobehavioral improvement and increased Abcd2 expression. Furthermore, when the conjugate was administered early, significant reduction of VLCFA and improved survival of spinal cord neurons was observed. Taken together, these data show improved efficacy of D-4PBA compared to previous studies of free 4PBA alone, and promise for D-4PBA in the treatment of complex and chronic neurodegenerative diseases using a dendrimer delivery platform that has shown successes in recent clinical trials. While recovery in our studies was partial, combined therapies on the dendrimer platform may offer a safe and complete strategy for treatment of ALD.

Neck Location on the Outer Convexity is a Predictor of Incomplete Occlusion in Treatment with the Pipeline Embolization Device: Clinical and Angiographic Outcomes.

BACKGROUND AND PURPOSE: With the increasing use of the Pipeline Embolization Device for the treatment of aneurysms, predictors of clinical and angiographic outcomes are needed. This study aimed to identify predictors of incomplete occlusion at last angiographic follow-up. MATERIALS AND METHODS: In our retrospective, single-center cohort study, 105 ICA aneurysms in 89 subjects were treated with Pipeline Embolization Devices. Patients were followed per standardized protocol. Clinical and angiographic outcomes were analyzed. We introduced a new morphologic classification based on the included angle of the parent artery against the neck location: outer convexity type (included angle, <160°), inner convexity type (included angle, >200°), and lateral wall type (160° ≤ included angle ≤200°). This classification reflects the metal coverage rate and flow dynamics. RESULTS: Imaging data were acquired in 95.3% of aneurysms persistent at 6 months. Complete occlusion was achieved in 70.5%, and incomplete occlusion, in 29.5% at last follow-up. Multivariable regression analysis revealed that 60 years of age or older (OR, 5.70; P = .001), aneurysms with the branching artery from the dome (OR, 10.56; P = .002), fusiform aneurysms (OR, 10.2; P = .009), and outer convexity-type saccular aneurysms (versus inner convexity type: OR, 30.3; P < .001; versus lateral wall type: OR, 9.71; P = .001) were independently associated with a higher rate of incomplete occlusion at the last follow-up. No permanent neurologic deficits or rupture were observed in the follow-up period. CONCLUSIONS: The aneurysm neck located on the outer convexity is a new, incomplete occlusion predictor, joining older age, fusiform aneurysms, and aneurysms with the branching artery from the dome. No permanent neurologic deficits or rupture was observed in the follow-up, even with incomplete occlusion.

Placental Gene Expression and Offspring Temperament Trajectories: Predicting Negative Affect in Early Childhood.

Exposure to prenatal stress increases offspring risk for long-term neurobehavioral impairments and psychopathology, such as Attention Deficit Hyperactivity Disorder (ADHD). Epigenetic regulation of glucocorticoid pathway genes may be a potential underlying mechanism by which maternal conditions 'program' the fetal brain for downstream vulnerabilities. The present study aims to investigate whether mRNA expression of glucocorticoid pathway genes in the placenta predict offspring negative affect during early childhood (between 6 and 24 months). Participants include 318 mother-child dyads participating in a longitudinal birth cohort study. Placental mRNA expression of glucocorticoid pathway genes (HSD11B1, HSD11B2, NR3C1, NCOR2) were profiled and negative affect traits of the offspring were measured at 6, 12, 18, and 24 months. HSD11B1 mRNA expression significantly predicted negative affect (ß = -.09, SE = .04; p = .036), and Distress to Limitations trajectories (ß = -.13, SE = .06; p = .016). NCOR2 mRNA expression significantly predicted Distress to Limitations (ß = .43, SE = .21; p = .047), and marginally predicted Sadness trajectories (ß = .39, SE = .21; p = .068). HSD11B2 and NR3C1 did not predict trajectories of Negative Affect or subscale scores. Infant negative affect traits were assessed via maternal self-report, and deviated from linearity across follow-up. mRNA expression of glucocorticoid pathway genes in the placenta may be a potentially novel tool for early identification of infants at greater risk for elevated negative affect. Further study is needed to validate the utility of mRNA expression of glucocorticoid pathway genes in the placenta.

Centrifugal lipodystrophy of the scalp manifesting as centrifugal lipodystrophic alopecia.

Centrifugal lipodystrophy (CLD), characterized by a depressed lesion in the abdominal skin, is a chronic disease occurring more often among younger patients of East Asian descent. We present an extremely unusual case of CLD of the scalp associated with reversible hair loss. The patient demonstrated alopecia in the frontal, temporal and occipital areas of the scalp, which connected to form a ring-shaped area of hair loss. Curiously, the area of hair loss gradually expanded outwards while the central region showed normal hair regrowth. Immunohistochemical analysis demonstrated reduced expression of leptin, an adipokine capable of inducing the anagen phase of the hair cycle, in the adipose tissue, associated with active inflammation. By contrast, recovery of leptin expression was observed at sites of healed inflammatory lesions, suggesting that reversible hair loss might be caused by a change in leptin expression in adipose tissue.

A randomized cross-over study comparing the performance of HD integra™ central concentrate system versus pre-produced concentrate in hemodialysis.

BACKGROUND: Pre-produced bicarbonate concentrates (PPC) are still widely used in developing countries despite its cost and risk but Central Concentrate System (CCS) is lacking in data to support its wider adoption. METHODS: We conducted an 8-week randomized crossover study on 16 Hemodialysis machines to compare CCS versus PPC. Performance is assessed by solute concentrations while safety is assessed by microbial count, endotoxin level and adverse event reporting. RESULTS: Microbial counts and endotoxin levels were monitored on 48 occasions during the 8-week study for the CCS arm of the study. The levels were all below the action limit during the study. No patient reported any adverse events. Dialysate Sodium, Chloride and Bicarbonate concentrations were measured on a total of 128 occasions for each arm of the study. The relative deviations of Sodium, Chloride and Bicarbonate concentration were within ±5% of their nominal values for both. The 95% Confidence Intervals for the ratio of the mean solute concentrations on the CCS to PPC lie within the tolerance limit of ±5%. CONCLUSION: Modern CCS is bacteriologically safe and its performance statistically equivalent to PPC.

Occult pneumothorax in blunt trauma: is there a need for tube thoracostomy?

INTRODUCTION/BACKGROUND: Occult pneumothorax (OPTX) is defined as air within the pleural cavity that is undetectable on normal chest X-rays, but identifiable on computed tomography. Currently, consensus is divided between tube thoracostomy and conservative management for OPTX. METHODS: The aim of this retrospective study is to determine whether OPTX can be managed conservatively and whether any adverse events occur under conservative management. Data on all trauma patients from 1 Jan 2010 to 31 December 2012 were obtained from our hospital's trauma registry. All patients with occult pneumothorax who had chest X-ray (CXR) and any CT scan visualizing the thorax were included. The exclusion criteria included those with penetrating wounds; CXR showing pneumothorax, hemothorax, or hemopneumothorax; those with prophylactic chest tube insertion before CT; and those with no CT diagnosis of OPTX. The complications of these patients were analyzed to determine if tube thoracostomy is necessary for OPTX and whether not inserting it would alter the outcome significantly. RESULTS: A total of 1564 cases were reviewed and 83 patients were included. Of these 83 patients, 35 (42.2 %) had tube thoracostomy after OPTX detection and 48 (57.8 %) were observed initially. Patients who had tube thoracostomy had similar ISS compared to those without (median ISS 17 vs. 18.5, p = 0.436). Out of the 48 patients who did not have tube thoracostomy on detection of an OPTX, 4 (8.3 %) had complications. In the group of 35 patients who had tube thoracostomy on detection of an OPTX, 7 (20 %) had complications. Of the 83 patients, a total of 12 patients had IPPV, of which 7 (58.3 %) had tube thoracostomy and 5 (41.7 %) did not. Patients who had tube thoracostomy under our care have a statistically significant likelihood of experiencing any complication compared to those without tube thoracostomy (odds ratio 9.92. The median length of stay was also longer (13 days) in those who had tube thoracostomy compared to those without (5 days) (p value = 0.008). CONCLUSIONS: Our study suggests that patients with OPTX can be managed conservatively with close monitoring, but only in areas with ready access to emergency facilities should any adverse events occur.

Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner.

Ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality after liver surgery. The role of Sirtuin 1 (SIRT1) in hepatic I/R injury remains elusive. Using human and mouse livers, we investigated the effects of I/R on hepatocellular SIRT1. SIRT1 expression was significantly decreased after I/R. Genetic overexpression or pharmacological activation of SIRT1 markedly suppressed defective autophagy, onset of the mitochondrial permeability transition, and hepatocyte death after I/R, whereas SIRT1-null hepatocytes exhibited increased sensitivity to I/R injury. Biochemical approaches revealed that SIRT1 interacts with mitofusin-2 (MFN2). Furthermore, MFN2, but not MFN1, was deacetylated by SIRT1. Moreover, SIRT1 overexpression substantially increased autophagy in wild-type cells, but not in MFN2-deficient cells. Thus, our results demonstrate that the loss of SIRT1 causes a sequential chain of defective autophagy, mitochondrial dysfunction, and hepatocyte death after I/R.

Emergency angio-embolisation in the operating theatre for trauma patients using the C-Arm digital subtraction angiography.

BACKGROUND AND AIMS: Angio-embolisation in trauma is a relatively new technique that is gaining popularity and recognition in identifying and arresting bleeding in trauma patients. We studied the possibility whether angio-embolisation using the Digital Subtraction Angiography (DSA), in the operating theatre (OT) could achieve successful haemostasis in trauma patients. We further studied the feasibility of using this technique as part of trauma resuscitation/damage control. METHODS: A retrospective study of trauma patients, with Injury Severity Score (ISS ≥ 9), admitted to Tan Tock Seng Hospital (TTSH) from January 2004 to December 2008 was done. Patients who had received angio-embolisation in the OT or angiography suite were evaluated in terms of age, gender, ISS, the site and type of angioembolisation used. The primary end point was to assess the success rate of angioembolisation using the C-Arm DSA in the OT, and whether there were any complications necessitating a repeat procedure or surgical intervention. The secondary end points of the study were aimed at studying the cost effectiveness of this technique, logistical feasibility and evaluating this technique as part of the initial trauma resuscitative efforts. RESULTS: A total of 43 trauma patients received angioembolisation. 32 patients had the angio-embolisation done using the C-Arm DSA in the OT (n = 32). None of the patients who received angioembolisation in the operating theatre (n = 32) had any re-bleeding. 15 out of 32 survived. There were no complications related to the angio-embolisation procedure. The majority of angio-embolisations done were for pelvic fractures. CONCLUSION: The success of angio-embolisation in the OT using the C-Arm DSA for a trauma patient and its complication rates are similar to that done in a dedicated angio-graphic suite. We conclude that angio-embolisation in the operating theatre using the C-Arm DSA is feasible, cost effective and can be a modality in the initial trauma resuscitation/damage control in any lead lined operating theatre. We believe that we are the first to describe this method of angio-embolisation using the C-Arm DSA in a conventional lead lined trauma operating theatre and its use as a feasible option in a trauma resuscitation/damage control algorithm.

A remote operating slit lamp microscope system. Development and its utility in ophthalmologic examinations.

OBJECTIVES: To develop a remote-operating slit lamp microscope system (the remote slit lamp) as the core for highly specialized ophthalmology diagnoses, and to compare the utility of this system with the conventional slit lamp microscope system (the conventional slit lamp) in making a diagnosis. METHODS: The remote slit lamp system was developed. Three factors were evaluated in comparison to the conventional slit lamp. The ability to acquire skills was investigated using a task loading system among specialists and residents in ophthalmology. Participants repeated a task up to ten times and the time required for each task was analyzed. The consistency of the two systems in making a diagnosis was investigated using eyes of patients with ocular diseases as well as healthy volunteers. RESULTS: The remote slit lamp is composed of a patient's unit and ophthalmologist's unit connected by high-speed internet. The two units share images acquired by the slit lamp in addition to the images and voices of patients and ophthalmologists. Both ophthalmology specialists and residents could minimize the completion times after several trials. The remote slit lamp took more time than the conventional slit lamp. Both systems showed a high consistency in evaluations among eyes with healthy eyes or those with ocular diseases. CONCLUSIONS: The remote slit lamp has a similar diagnostic ability, but required more examination time in comparison to the conventional slit lamp. The currently developed remote slit lamp has the potential to be employed for tele-medicine purposes in the field of ophthalmology.

Treatment and renal outcome of lupus nephritis: single center experience.

Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease with renal involvement being one of the most frequent and serious manifestations of the disease. The aim of the study is to analyze the treatment and renal outcome of patients with lupus nephritis (LN) WHO class III and IV on cyclophosphamide (CYC). We retrospectively identified 41 patients with biopsy proven LN who was given either oral or intravenous CYC. The male: female ratio was 4:37; with a mean age of 31.7 +/- 9.8 years at presentation. 36 patients (87.8%) had LN class IV and only five patients (12.2%) with LN class III. The mean serum creatinine at presentation was 87.4 +/- 37.2 micromol/L with mean follow-up of 84 +/- 78 months. A total of 30 patients (73.2%) completed 12 courses of IV CYC and one patient (2.4%) completed three months of oral CYC. 71.0% (n = 22) had complete response (CR), 25.8% (n = 8) had partial response and 3.2% (n = 1) had no response (NR). Of the remaining 11 patients, two patients (4.9%) died during the treatment, three patients (7.3%) defaulted treatment and five patients (12.2%) are still receiving ongoing treatment. Presence of hypertension (p < 0.003) and evidence of chronicity on renal biopsy (p < 0.016) were significantly correlated with the progressive deterioration of renal function in our population. In conclusion, hypertension and evidence of chronicity on renal biopsy, proved to be risk factors for progressive renal impairment in our study population. The achieved global outcome can be considered good.

Comparison of patient survival between various subgroups among renal transplant patients: a single center experience.

OBJECTIVES: To compare patient graft survival between various subgroups among renal transplant patients. PATIENTS AND METHODS: A retrospective analysis of all renal transplant patients from January 1, 1993, to June 1, 2003, was performed using follow-up records and data submitted to the National Renal Registry. RESULTS: A total of 91 renal transplant patients were followed, with a male-to-female ratio of 57:34 (62.6%:37.4%) and mean age at transplant 35.6 +/- 12.1 years (range 10.1-64.4 years) with 38 (41.8%) cases transplanted locally and 53 (58.2%) cases transplanted overseas, of which 36 (39.6%) were from live donors and the remaining 55 (60.4%) from cadavers. As of June 1, 2003, 50 transplant patients are on regular follow-up, with 41 patients lost due to 12 (29.3%) deaths, 16 (39.0%) graft failures, 11 (26.8%) transfers, and 2 (4.9%) lost to follow-up. Overall patient and graft survival rates at 2, 5, and 10 years were 93.1%, 77.4%, and 49.2%, respectively. Survival rates for male transplant patients were 91.4%, 71.9%, and 46.7% compared to 96.1%, 86.9%, and 53.6% for females. Survival rates for Malay race patients were 92.0%, 59.5%, and 28.6%; Chinese rates were 96.0%, 81.6%, and 54.8%, and Indian rates were 81.0%, 81.0%, and 46.3%, respectively. The survivals for transplants from living donors were 96.9%, 85.6%, and 62.3% compared to cadaveric kidney transplants namely 89.9%, 71.3%, and 35.0%. The local transplant survival rates were 96.9%, 82.3%, and 60.8% compared to overseas transplants, with survival rates of 89.9%, 73.5%, and 35.7%. Finally, living-related donor transplantation survival rates were 96.8%, 84.9%, and 62.2% compared to nonrelated donors-90.1%, 71.3%, and 35.0%-at 2 years, 5 years, and 10 years, respectively. CONCLUSION: Overall survival has been good. The survival rates were better among female gender, Chinese race, local transplantation, and kidneys from living-related donors.

Capsule endoscopy: a single-centre experience with the first 226 capsules.

BACKGROUND: Capsule endoscopy (CE) refers to a novel diagnostic method of imaging the gastrointestinal tract using a wireless capsule that transmits images to a data recorder while the device traverses the small intestine. OBJECTIVE: To review the authors' experience with CE to determine the indications, outcomes and management of positive findings. METHODS: Patients were prepared for CE with a single dose of magnesium citrate. Following an 8 h fast, a sensor array system was applied to the abdomen, the capsule was swallowed and the images were transmitted to a data recorder worn on the patient's side. Typically, the battery life of the capsule is 8 h, following which the data recorder is returned, downloaded to a computer workstation and reviewed. RESULTS: To date, 226 capsule studies have been performed in 209 patients. The indications included obscure bleeding (167 studies: 88 overt, 79 occult), anemia (14 studies), evaluation for inflammatory bowel disease (12 studies), screening for polyps (10 studies), pain (19 studies) and abnormal radiological imaging (4 studies). In the setting of obscure bleeding, a definitive source of bleeding was discovered in 85 studies. This included angiodysplasia (52 studies), mitotic lesions (10 studies) and ulcers (23 studies). A probable source of bleeding was found in another 10 capsule studies. In the setting of anemia without evidence of bleeding, the definitive findings included ulcers (three studies), angiodysplasia (two studies), mitotic lesions (one study) and celiac disease (one study). Of four patients with abnormal radiological imaging, CE demonstrated lesions in two. The results of 35 capsule studies led to laparotomy with curative surgical resection. In eight studies, the capsules became lodged within a stricture; none led to obstruction and three were managed endoscopically. CONCLUSION: The yield of CE in carefully selected patients with obscure bleeding approximates 51%. There appear to be few complications, and patient satisfaction appears high. Cost analysis and further studies of clinical outcomes are required to elucidate appropriate indications for this device.

Proliferation and apoptosis in long-term surviving low grade gliomas in relation to radiotherapy.

Identification of patients with a low grade glioma with a long-term recurrence-free survival is of clinical value as radiotherapy can be postponed until recurrence. The recurring glioma may increase in malignancy compared to the original tumor, which is possibly related to radiotherapy. We studied proliferation by counting mitotic figures and by MIB-1 labeling, apoptosis by TUNEL and expression of proteins related to cell cycle regulation by immunohistochemical analysis of p53, p21, bcl-2 and bax expression in 48 low grade gliomas. Astrocytomas (A, n = 14) and oligodendrogliomas (O, n = 4) with a recurrence-free survival of more than 9 years after surgery had a signficantly lower p53 index compared to A (n = 18) and O (n = 12) with a histopathologically documented recurrence. Additionally, the recurrence-free A had a higher p21 index. No significant differences were observed in MIB-LI, TUNEL-LI, bcl-2 and bax expression. Initially low grade gliomas and their corresponding recurrences were compared (n = 30). In the gliomas without radiotherapy (n = 15), no differences in mitotic rate, TUNEL-LI, p53, p21, bcl-2 and bax expression were found between primary tumors and their recurrences. Only MIB-LI was higher in the recurrent tumors. In the gliomas with radiotherapy (n = 15) no differences were detected in these parameters between the original tumor and the recurrent tumor except for a higher number of mitoses in the recurrent tumors. We conclude that low grade gliomas with a long-term recurrence-free survival were characterized by a low p53 protein expression and, in the case of A, a higher p21 index. We found no evidence that radiotherapy is involved in changes of proliferation, apoptosis or expression of proteins related to cell cycle regulation in recurring gliomas.

Cryopreservation of porcine fetal ventral mesencephalic tissue for intrastriatal transplantation in Parkinson's disease.

In this study we examined the efficacy of cryopreserving porcine fetal mesencephalic tissue. After microscopical dissection of the ventral mesencephalon (VM) from E28 pig fetuses, the collection of explants was randomly divided into two equal parts. One part was directly prepared as cell suspension. The other part was stored in hibernation medium for less than 2 days and then cryopreserved as tissue fragments and stored in liquid nitrogen. After 2 weeks up to 1 year, these tissue fragments were thawed and processed as cell suspensions. After cell counting and assessment of viability, these cell suspensions were used to examine survival, morphology, and neurite formation of the dopaminergic neurons in cell culture as well as after intrastriatal implantation in 6-OHDA-lesioned rats. Comparison of cryopreserved with fresh VM cell suspensions showed no significant difference with respect to cell viability and the average number of living cells per VM explant. The morphology of cultured dopaminergic neurons after cryopreservation was identical to that of fresh cells. After intrastriatal implantation, survival and outgrowth of cryopreserved dopaminergic neurons as well as functional effects did not differ from those of fresh cells. In conclusion, the cryopreservation technique we used proves to be a reliably effective method for storing porcine fetal VM tissue.

Hypothermia induces T-cell production of immunosuppressive cytokines.

BACKGROUND: Hypothermia is associated with increased postoperative infectious complications. We hypothesized that hypothermia suppresses the inflammatory response by altering T-cell cytokine production from a proinflammatory to an antiinflammatory profile, thus explaining the increased susceptibility to infectious complications associated with perioperative hypothermia. METHODS: Forty rats were randomized to either a Hypothermia (30 degrees C) or Control (38 degrees C) group. Blood samples taken at baseline and after 8 h of thermoregulation were stimulated with phorbol 12-myristate 13-acetate and ionomycin. Interleukin (IL)-2 receptor expression and intracellular IL-10 production were measured using monoclonal antibodies and flow cytometry in CD4 and CD8 T cells. Differences in IL-10 production and IL-2 receptor expression for stimulated samples in the Hypothermia and Control groups were compared. RESULTS: Stimulated CD4 cells demonstrated an antiinflammatory cytokine expression profile after hypothermia. Intracellular IL-10 production increased in the Hypothermia group but remained the same in the Control group (% change = 40 [3,87] and 2 [-36,26], respectively; P = 0.043). The increase in IL-2 receptor expression observed in the control group was suppressed after hypothermia (% change = 12[8,30] and 1 [-3,13], respectively; P = 0.026). We observed a greater increase in IL-10 production by CD8 cells from hypothermic animals than in those from control animals (% change = 41 [-8,90] and -4 [-40,5], respectively; P = 0.019). CD8 IL-2 receptor expression in hypothermic animals was similar to that of control animals (% change = 23 [-7,37] vs 25 [2,80], respectively; P = 0.32). CONCLUSIONS: Hypothermia induced an antiinflammatory T-cell cytokine profile.

Thermolysis of tert-butyl phenylperacetates: delicate control of the rates through contributions from translational and rotational entropy.

The first-order rate constants (k(Y)) at several temperatures in CDCl(3) were measured for thermal decompositions of YC(6)H(4)CH(2)CO(3)C(CH(3))(3) with Y being p-OCH(3), p-OPh, p-CH(3), p-Ph, p-H, p-Cl, m-Cl, and p-NO(2). The relative rates (k(Y)/k(H)) exhibit excellent rho(+)/sigma(+) Hammett correlations with rho(+) < 0, indicating a polar TS. Activation parameters (DeltaH()(Y) and DeltaS()(Y)) and their differential terms (DeltaDeltaH()(Y)(-)(H) and DeltaDeltaS()(Y)(-)(H)) were obtained from the Eyring plot. Differential activation terms (DeltaDeltaH()(Y)(-)(H) and DeltaDeltaS()(Y)(-)(H)) disclose an isokinetic relation with p-CH(3), p-Ph, p-H, p-Cl, and m-Cl (isokinetic temp, 230 K). However, p-OCH(3), and p-OPh show negative deviations, and a positive deviation occurs with p-NO(2). Plot of DeltaDeltaH()(Y)(-)(H) vs sigma(+) exhibits a good linear relation (r = 0.95) with a slope (alpha(1) = -3.34). A better linear correlation (r = 0.97) and steeper slope (alpha(2) = -5.22) were observed for TDeltaDeltaS()(Y)(-)(H) vs sigma(+). Negatively larger slope (alpha(2) = -5.22) may point to entropy control of rates. Differential activation parameters (DeltaDeltaH()(Y)(-)(H) and DeltaDeltaS()(Y)(-)(H)) reflect variations of activation process. Differential activation entropies (DeltaDeltaS()(Y)(-)(H)) are discussed in terms of contributions of translational and rotational entropies. Similar deviation behaviors of p-OCH(3), p-OPh, and p-NO(2) were again observed for the both plots. p-NO(2) can strongly destabilize the cationic site of the polar TS but serves an eminent spin delocalizer for the homolytic TS.

Decreased CRH mRNA expression in the fetal guinea pig hypothalamus following maternal nutrient restriction.

The regulation of corticotropin-releasing hormone (CRH) mRNA expression following maternal nutrient restriction was examined in the fetal hypothalamus. Pregnant guinea pigs were food restricted for 48 h or fed normally during late gestation. After nutrient restriction, CRH mRNA levels in the hypothalamic paraventricular nucleus of the fetus were determined using in situ hybridization and were found to be significantly decreased (P<0.0001) compared to controls. In conclusion, we have successfully sequenced the coding sequence of the guinea pig CRH gene, and have shown that a short period (48 h) of maternal nutrient restriction inhibits CRH mRNA expression in the fetal hypothalamus.

Wegener's granulomatosis with onset of acute pancreatitis and rapid progress. A case report.

Although Wegener's granulomatosis is a rare disorder, the clinical and histological characteristics are well known. However, Wegener's granulomatosis with the onset of acute pancreatitis has rarely been reported. We discuss the case of Wegener's granulomatosis in a 65-year-old man, presenting with acute pancreatitis and whose disease progressed rapidly.