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PubMed2006

Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine.

We previously reported that brief (1 h), but not extended (6 h), daily access to cocaine results in a sensitized locomotor response to cocaine and in elevated c-Fos immunoreactivity and DAT binding in the nucleus accumbens (N.Acc) core. In order to better our understanding of the neural adaptations mediating the transition from controlled drug use to addiction, the current experiments were set to further explore the neural adaptations resulting from these two access conditions. Rats received either brief daily access to saline or cocaine, or brief daily access followed by extended daily access to cocaine. Subjects were then sacrificed either 20 min, or 14 or 60 days, after the last self-administration session. Samples of the ventral tegmental area (VTA), N.Acc core and shell, dorsal striatum, and medial prefrontal cortex (mPFC) were taken for analysis of D1 ([3H]SCH-23390), D2 ([3H]Spiperone), and NMDA ([3H]MK-801) receptor binding (using the method of receptor autoradiography). At 20 min into withdrawal, D2 receptors were elevated and NMDA receptors were reduced in the mPFC of the brief access animals while D1 receptors were elevated in the N.Acc shell of the extended access animals, compared to saline controls. D2 receptors were reduced in the N.Acc shell of the brief access animals compared to saline controls after 14 days, and compared to extended access animals after 60 days of withdrawal. In summary, extended access to cocaine resulted in only transient changes in D1 receptors binding. These results suggest that the development of compulsive drug use is largely unrelated to changes in total binding of D2 or NMDA receptors.

Adaptation, Physiological↗

PubMed2006

Extended breast cancer treatment with an aromatase inhibitor (Letrozole) after tamoxifen: why, who and how long?

Breast cancer remains a leading cause of cancer death in women worldwide, and the risk for disease recurrence continues despite improvements in screening and treatment and the use of prophylactic estrogen-inhibiting therapies such as tamoxifen. A number of long-term studies now indicate a significant risk for breast cancer recurrence among patients who have undergone the currently recommended five years of tamoxifen adjuvant therapy following successful treatment of their initial disease. This ongoing recurrence risk extends even to patients commonly considered at low risk for relapse, that is, those with low-grade, small tumors, and/or node-negative disease. Treatment with tamoxifen for more than five years appears detrimental rather than beneficial and, therefore, tamoxifen is not indicated for use beyond the initial five years. Endometrial cancer and thromboembolism are among the serious adverse events that have been observed with long-term tamoxifen treatment. The aromatase inhibitors are able to reduce overall estrogen levels and appear to be better tolerated over a long term. Letrozole is the most potent aromatase inhibitor and has been available in Europe since 1996 and in the United States since 1997. Letrozole has been approved for first-line treatment of postmenopausal women with hormone-receptor-positive or hormone-receptor-unknown, advanced or metastatic breast cancer in the United States and Europe, as well as for neoadjuvant treatment (primary systemic therapy) of early breast cancer prior to surgery in many countries. The results of the pivotal MA-17 trial demonstrate that letrozole is unique in its ability to improve disease-free survival in breast cancer patients who have undergone tamoxifen therapy for five years. The MA-17 results indicate that extended adjuvant therapy with letrozole reduces risk of recurrence in this setting by 42%, reduces risk of distant recurrence (metastasis), and may improve patient survival in the node-positive patient population. The results also show letrozole to be well tolerated and safe over the length of follow-up. The trial outcomes have led to the approval of letrozole for the extended adjuvant indication in more than 40 countries worldwide. Re-randomization of letrozole-treated patients from this pivotal trial is underway to investigate if ten years of extended adjuvant endocrine therapy leads to further improvement, and the results of this extension study should aid in resolving several open questions regarding extended adjuvant therapy, including who should be treated and for how long.

Aromatase Inhibitors↗

PubMed2007

The effect of excessive tibial torsion on the capacity of muscles to extend the hip and knee during single-limb stance.

Excessive tibial torsion, a rotational deformity about the long axis of the tibia, is common in patients with cerebral palsy who walk with a crouch gait. Previous research suggests that this deformity may contribute to crouch gait by reducing the capacity of soleus to extend the knee; however, the effects of excess external torsion on the capacity of other muscles to extend the stance limb during walking are unknown. A computer model of the musculoskeletal system was developed to simulate a range of tibial torsion deformities. A dynamic analysis was then performed to determine the effect of these deformities on the capacity of lower limb muscles to extend the hip and knee at body positions corresponding to the single-limb stance phase of a normal gait cycle. Analysis of the model confirmed that excessive external torsion reduces the extension capacity of soleus. In addition, our analysis revealed that several important muscles crossing the hip and knee are also adversely affected by excessive tibial torsion. With a tibial torsion deformity of 30 degrees , the capacities of soleus, posterior gluteus medius, and gluteus maximus to extend both the hip and knee were all reduced by over 10%. Since a tibial torsion deformity reduces the capacity of muscles to extend the hip and knee, it may be a significant contributor to crouch gait, especially when greater than 30 degrees from normal, and thus should be considered by clinicians when making treatment decisions.

Biomechanical Phenomena↗

PubMed2003

Is extended resection for adenocarcinoma of the body or tail of the pancreas justified?

Patients with body or tail tumors of the pancreas often have contiguous organ involvement or portal-splenic confluence adherence requiring extensive resection in order to obtain grossly negative margins. The aim of this study was to determine whether long-term survival is possible after contiguous organ or portal vein resection in patients with adenocarcinoma of the body or tail of the pancreas. Between 1983 and 2000, a total of 513 patients with adenocarcinoma of the body or tail of the pancreas were identified from a prospective database. Distal pancreatectomy with or without splenectomy was performed in 57 patients (11%). Extended resection was necessary in 22 patients (39%): 14 (64%) for contiguous organ involvement and eight (36%) for portal vein resection Estimated blood loss, blood transfused, and length of hospital stay were significantly greater in patients requiring extended resection compared to standard resection (P=0.02, P=0.01, and P=0.02, respectively). Median follow-up for patients still alive was 84 months (range 40 to 189 months). Median survival following resection was 15.9 months compared to 5.8 months in patients who were not resected (P<0.0001). Actual 5- and 10-year survival rates were 22% and 18%, respectively, following extended resection, 8% and 8% following standard resection, and 0% and 0% if no resection was attempted because of locally unresectable disease. Patients undergoing extended resection for adenocarcinoma of the pancreatic body or tail have long-term survival rates similar to those for patients undergoing standard resection; they also have markedly improved long-term survival compared to those who are not considered resectable because of locally advanced disease. Extended distal pancreatectomy is justified in this group of patients.

Adenocarcinoma↗

PubMed2004

Extended-release ciprofloxacin (Cipro XR) for treatment of urinary tract infections.

Symptomatic urinary tract infections (UTIs) constitute a major health problem throughout the Western world. In the USA, UTIs are responsible for 7-8 million outpatient visits each year and for over one-third of all hospital-acquired infections. Empiric antimicrobial therapy for UTIs, which are primarily caused by Escherichia coli, is increasingly being complicated by the emergence of resistance to the most widely used agents. Recent studies indicate that the prevalence of E. coli resistance to trimethoprim/sulphamethoxazole (TMP/SMX), the current first-line therapy for UTIs, exceeds 20% in many North American regions. Importantly, antibiotic resistance often translates into clinical failure. The use of antibiotics with favourable pharmacokinetic/pharmacodynamic profiles and convenient dosing schedules, which effectively increase bacterial eradication and patient compliance, can help to curb the current epidemic of resistance and reduce the rate of clinical failure associated with resistance. Fluoroquinolones have well-established efficacy in the treatment of multiple bacterial infections and, over the years, the rates of resistance to these antibiotics have remained very low. Fluoroquinolones are currently recommended for therapy of uncomplicated UTIs when the local incidence of TMP/SMX resistance is >or=10-20%, as well as for the treatment of complicated UTIs and acute pyelonephritis. Ciprofloxacin, one of the most widely used fluoroquinolones, has a potent bactericidal effect across the full spectrum of uropathogens, as well as a long and excellent efficacy and safety record in the management of UTI and other infections. A recently developed extended (modified)-release formulation of ciprofloxacin (Cipro XR or Cipro XL) provides higher maximum plasma concentrations with lower inter-patient variability than the conventional, immediate-release, twice-daily formulation. Additionally, therapeutic drug levels with extended-release ciprofloxacin are achieved rapidly and maintained over the course of 24 h, allowing once-daily dosing. Clinical trials in patients with cystitis and those with complicated UTIs or acute uncomplicated pyelonephritis indicate that extended-release ciprofloxacin is at least as effective as the immediate-release formulation. These studies have also confirmed good tolerability and safety of extended-release ciprofloxacin, similar to the immediate-release formulation. Therefore, extended-release ciprofloxacin is a convenient, well-tolerated and effective therapy for UTIs that may improve patients' compliance with treatment and thus decrease the risk of treatment failure and the spread of antibiotic resistance.

Bacterial Infections↗

PubMed2004

Extended prostate biopsy scheme improves reliability of Gleason grading: implications for radiotherapy patients.

BACKGROUND: With sextant prostate biopsies, there is up to a 1-in-3 chance that the underlying pathologic Gleason grade is higher. Knowledge of the underlying grade might have significantly altered the therapeutic recommendations and management for patients electing radiotherapy for localized prostate cancer (e.g., eligibility for brachytherapy, androgen suppression with external beam radiotherapy, elective pelvic radiotherapy). This study examines the concordance patterns between biopsy and matched radical prostatectomy Gleason grade among patients undergoing an extended 10-core biopsy scheme to assess its reliability compared to sextant biopsies. METHODS AND MATERIALS: Seventy-eight consecutive patients underwent an extended 10-core peripheral zone biopsy scheme (sextant plus two lateral mid and two lateral base biopsies) and subsequent radical prostatectomy at this institution between mid-2000 and mid-2003. No patient received androgen suppression. All histologic grading were made by a single pathologist (J.E.M.). Needle biopsies were characterized for location, linear involvement of cancer within positive cores, and total number of positive cores. Radical prostatectomy specimens were step-sectioned at 3-mm intervals and were characterized for total cancer volume and percentage of each Gleason grade present. Clinical parameters available included digital rectal exam, preoperative PSA, and ultrasound prostate volume. A "clinically significant" upgrading of the biopsy was defined as any of the following: (1) a biopsy Gleason score (bGS) of 6 to a pathologic GS (pGS) of 7 or higher, (2) a bGS 3 + 4 to a pGS of 4 + 3 or higher, and (3) a bGS of 7 to a pGS of 8 or higher. Statistical analyses were performed on the patterns Gleason score concordance between biopsies and matched radical prostatectomies. RESULTS: An exact Gleason score match between biopsy and prostatectomy was observed in 62% of patients using the sextant biopsy scheme (SB), an upgrading of 1 or more grade points was seen in 25% and a downgrading of 1 or more points in 13% for SB. These rates of grade discordance are comparable to those of published sextant series. An exact match using the extended biopsy scheme (EB) was 63% (p = 0.61 compared with SB), whereas upgrading was 13% (p = 0.045 compared with SB) and downgrading was 24% (p = 0.06 compared with SB). A "clinically significant" upgrading as defined here was present in 38.1% of the SB group compared with 23.1% of the EB group (p = 0.039). For patients with bGS of 6, a clinically significant upgrading occurred in 66.7% with SB and in 36.8% with EB (p = 0.068). Upgrading of the primary Gleason grade from 3 to 4/5 was seen in 41.8% for the SB and in 25.5% for the EB group (p = 0.078). No clinical factors (T-stage, PSA, prostate volume, % positive cores, linear extent of cancer) were found to predict for a clinically significant upgrading of biopsies on logistic regression analysis. CONCLUSIONS: The extended 10-core biopsy scheme significantly improves on sextant biopsies in predicting the underlying pathologic Gleason score for prostate cancer. In particular, it is superior to sextant biopsies in revealing the presence of an underlying high-grade component. The potential clinical impact this improvement has for patients ultimately selecting radiotherapy suggests that an extended biopsy scheme should become the standard of care. Nevertheless, even with this improvement, there still remains up to a 1-in-5 chance that the underlying grade will be higher.

Biopsy, Needle↗

PubMed2006

Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies.

PURPOSE: The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. METHODS AND MATERIALS: Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aortic lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. RESULTS: The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. CONCLUSIONS: Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising.

Aged↗

PubMed2007

Fossa navicularis reconstruction: impact of stricture length on outcomes and assessment of extended meatotomy (first stage Johanson) maneuver.

PURPOSE: We evaluated the significance of stricture length and severity on the outcome of fossa navicularis reconstruction. We also determined the efficacy and usefulness of an extended meatotomy (first stage Johanson) salvage maneuver in refractory cases. MATERIALS AND METHODS: Our 7-year experience with the surgical management of distal urethral strictures involving the fossa navicularis was reviewed. Stricture length, reconstructive method and outcomes were assessed in 40 consecutive cases performed at our institution from 1997 to 2003. Men undergoing flap or graft onlay reconstruction were divided into group 1-short, isolated fossa navicularis strictures (2.5 cm or less) and group 2-long pendulous urethral strictures (greater than 2.5 cm) extending into the fossa navicularis. Men treated with extended meatotomy for complex and/or reoperative distal strictures comprised group 3. RESULTS: Average followup was 52 months (range 28 to 81). The majority of men with short isolated fossa navicularis strictures (group 1 average length 2.2 cm, range 1.5 to 2.5) had successful onlay reconstruction (10 of 11, 91%). Those with longer strictures (group 2 average length 7.4 cm, range 4 to 16) had significantly poorer outcomes with onlay reconstruction (7 of 13, 54%, p <0.05). Failures presented in a delayed manner with recurrent stenosis of the distal segment. Extended meatotomy (group 3) proved to be successful in 14 of 16 men (87%) with complex or reoperative strictures. CONCLUSIONS: Stricture length influences the outcome of distal urethroplasty. Onlay repair via a penile fasciocutaneous flap technique is reliable for short perimeatal strictures, but is less well suited for longer distal strictures. Extended meatotomy appears to be a highly effective salvage maneuver for complicated strictures of the fossa navicularis.

Adolescent↗

PubMed2004

Effects of the supplementation of trehalose extender containing egg yolk with sodium dodecyl sulfate on the freezability of goat spermatozoa.

Two experiments were conducted to determine the effect of sodium dodecyl sulfate (SDS) added to a trehalose-egg yolk extender on the cryopreservation of goat spermatozoa. In Experiment 1, semen from four goats was frozen in trehalose extender (osmolality = 370, pH = 7) containing 4 and 20% (v/v) glycerol and egg yolk, respectively, and 0.035-0.2% SDS. After thawing, sperm motility and acrosome integrity were assessed using a computer-assisted sperm analysis (CASA) system and fluorescein isothiocyanate-conjugated peanut agglutinin (FITC-PNA). Both motility and progressive motility were improved (P < 0.05) by increasing the concentration of SDS in the trehalose-egg yolk extender, with the best results obtained with SDS at 0.1% (80.0 +/- 1.5% and 65.0 +/- 1.7%, respectively). There were no significant differences in path velocity when spermatozoa were frozen in a diluent containing 0.035, 0.05, 0.075, or 0.1% SDS, but path velocity decreased significantly with 0.2% SDS. The percentage of acrosome-intact sperm were highest (P < 0.05) when 0.05% (74.0 +/- 1.1) and 0.075% (70.0 +/- 1.2) SDS were used. In Experiment 2, the effect of diluent storage time (6, 24, or 48 h) before freezing on the cryoprotective effect of SDS was investigated. Prolonged storage of the diluent had slight cryoprotective effects when 0.2% SDS is used, while motility and the acrosome integrity of the cryopreserved spermatozoa improved slightly when the extender was stored for 48 h at 5 degrees C before use. In conclusion, goat sperm freezability was significantly improved when sperm were frozen in a trehalose-egg yolk extender containing an adequate concentration of SDS.

Acrosome↗

PubMed2005

Bacteriospermia in extended porcine semen.

Bacteriospermia is a frequent finding in freshly extended porcine semen and can result in detrimental effects on semen quality and longevity if left uncontrolled. The primary source of bacterial contamination is the boar. Other sources that have been identified include environment, personnel, and the water used for extender preparation. A 1-year retrospective study was performed on submissions of extended porcine semen for routine quality control bacteriological screening at the University of Pennsylvania. Out of 250 sample submissions, 78 (31.2%) tested positive for bacterial contamination. The most popular contaminants included Enterococcus spp. (20.5%), Stenotrophomonas maltophilia (15.4%), Alcaligenes xylosoxidans (10.3%), Serratia marcescens (10.3%), Acinetobacter lwoffi (7.7%), Escherichia coli (6.4%), Pseudomonas spp. (6.4%), and others (23.0%). Prudent individual hygiene, good overall sanitation, and regular monitoring can contribute greatly in controlling bacterial load. Strategies that incorporate temperature-dependent bacterial growth and hyperthermic augmentation of antimicrobial activity are valuable for effective control of susceptible bacterial loads. Aminoglycosides remain the most popular antimicrobial class used in porcine semen extenders, with beta-lactam and lincosamide use increasing. With the advent of more novel antimicrobial selection and semen extender compositions in swine, prudent application and understanding of in vitro pharmacodynamics are becoming paramount to industry success in the use of this breeding modality.

Animals↗

PubMed2005

Influence of extender, freezing rate, and thawing rate on post-thaw motility, viability and morphology of coyote (Canis latrans) spermatozoa.

The objective of this study was to examine the post-thaw effects of three cryoprotective extenders (Tris-fructose-citric acid extender, Tris-glucose-citric acid extender, and lactose extender), three linear freezing rates (-1, -6, and -20 degrees C/min), and three thawing rates (37 degrees C water bath for 120s, 60 degrees C water bath for 30s, and 70 degrees C water bath for 8s) on coyote spermatozoa. After thawing, the findings supported that cryopreservation of coyote (Canis latrans) spermatozoa frozen at a moderate freezing rate (-6 degrees C/min), in either a Tris-fructose or Tris-glucose extender, and thawed at a slow rate (37 degrees C water bath for 120s) or moderate rate (60 degrees C water bath for 30s), resulted in a more vigorous post-thaw motility (range, 57.5-44.0%) and viability (range, 64-49.6%) with the least amount of morphological and acrosomal abnormalities.

Acrosome↗

PubMed2006

Comparing ethylene glycol with glycerol for cryopreservation of canine semen in egg-yolk TRIS extenders.

The objective of this work was to evaluate the possibility of substituting glycerol (G) for ethylene glycol (EG) when cryopreserving dog semen. A total of 15 ejaculates from 13 dogs was pooled into five samples and frozen in egg-yolk Tris extenders with variable ethylene glycol and glycerol concentrations, with or without Equex STM Paste. Two widely used glycerol extenders (Uppsala Equex II and Norwegian) were utilized as controls. Semen quality parameters assessed after thawing were total subjective motility (TSM), computer assisted sperm analysis (CASA), eosin-nigrosin staining, and flow cytometry (FC) after staining with the PI/Fitc-PSA (fluorescein isotiocianate conjugated with the agglutinin of Pisum sativum, PSA) fluorochromes. No advantages were seen in using EG to replace G when freezing dog semen or combining EG and G in the freezing medium. The Uppsala Equex II provided the best overall post-thaw parameters, followed by the egg-yolk Tris experimental extender with 5% EG and Equex STM Paste. The extender with 4% EG produced similar results to the Norwegian extender. High correlations (r>0.98) were obtained between eosin-nigrosin staining and FC, as well as between subjective and computerized motility assessment (r>0.90).

Acrosome↗

PubMed2000

Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia.

This multicenter trial evaluated the safety and efficacy of escalating doses of Niaspan (niacin extended-release tablets) and placebo (administered once-a-day at bedtime) in patients with primary hyperlipidemia on the percent change from baseline in levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Extended-release niacin was initiated at a dose of 375 mg/day, raised to 500 mg/day, and further increased in 500-mg increments at 4-week intervals to a maximum of 3,000 mg/day. A total of 131 patients (n = 87, extended-release niacin; n = 44, placebo) were treated for 25 weeks with study medication after a 6-week diet lead-in/drug washout phase and 2-week baseline LDL cholesterol stability phase. Significant decreases from baseline in levels of LDL cholesterol and apolipoprotein B became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or =0. 05), reaching 21% and 20%, respectively, at the 3,000-mg/day dose. Significant increases from baseline in levels of high-density lipoprotein cholesterol became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or = 0.05), reaching 30% at the 3,000-mg dose. Significant decreases from baseline in triglycerides and lipoprotein(a) occurred at the 1,000-mg dose and were apparent at all subsequent doses (p < or =0.05), reaching 44% and 26%, respectively, at the 3,000-mg dose. The most common adverse events were flushing and gastrointestinal disturbance. Transaminase increases were relatively small, and the proportion of patients who developed liver function abnormalities on extended-release niacin was not significantly different from placebo. Thus, extended-release niacin was generally well tolerated and demonstrated a dose-related ability to alter favorably most elements of the lipid profile.

Adult↗

PubMed1999

Laterally extended endopelvic resection: surgical treatment of infrailiac pelvic wall recurrences of gynecologic malignancies.

OBJECTIVE: My purpose was to treat infrailiac pelvic wall recurrences of gynecologic malignancies with extended radical surgery. STUDY DESIGN: On the basis of cadaver dissection studies, I developed the laterally extended endopelvic resection techniques. The new operations were offered to patients with infrailiac sidewall disease during a 3-year feasibility study. RESULTS: Laterally extended endopelvic resections extending the lateral resection plane of pelvic exenteration to the medial aspects of the acetabulum, obturator membrane, sacrospinous ligament, and sacral plexus/piriformis muscle were performed in 18 consecutive patients. After this procedure, all patients had tumor-free intraoperative biopsy specimens taken from the remaining pelvic wall structures within the tumor bed area. The final histopathologic report confirmed clean margins in 6 patients and margins with microscopic tumor extensions only in 12 patients. Severe complications occurred in 4 patients (22%), without treatment-related deaths. CONCLUSION: Laterally extended endopelvic resection allows the complete surgical removal of infrailiac pelvic-side-wall tumors, the most frequent local recurrence of lower genital tract cancer, either with free margins or with potential microscopic residual tumor as a prerequisite for combined operative and radiation treatment.

Combined Modality Therapy↗

PubMed2002

The caudal sublenticular region/anterior amygdaloid area is the only part of the rat forebrain and mesopontine tegmentum occupied by magnocellular cholinergic neurons that receives outputs from the central division of extended amygdala.

Ascending cholinergic projections and the central nucleus of the amygdala (CeA) have both been implicated in attentional and orienting mechanisms leading to adaptive behavioral responses. In view of this, the present study was carried out to identify relevant neuroanatomical relationships in the form of projections from the CeA and a related structure, the dorsolateral divison of the bed nucleus of the stria terminalis (dlBST), to parts of the basal forebrain and mesopontine tegmentum that contain magnocellular cholinergic neurons. The CeA and dlBST are components of the 'central division of extended amygdala'. Following injections of the anterogradely transported compounds, Phaseolus vulgaris-leucoagglutinin or biotinylated dextran amine, into the CeA or dlBST, sections were processed with immunohistochemical reagents to localize the anterograde tracer and choline acetyltransferase (ChAT). The trajectories of efferent projections from CeA and dlBST were qualitatively similar. Few ChAT-immunoreactive (ir) neurons were present within the extended amygdala or regions containing the dense terminations of its efferent projections, with the striking exception of the caudal sublenticular/anterior amygdaloid region. The ChAT-ir neurons there, however, were significantly smaller and weakly ChAT-ir as compared to those located outside of the dense extended amygdaloid terminations. In the mesopontine tegmentum, the robust downstream projection from the extended amygdala was centered medial to ChAT-ir neurons of the pedunculopontine tegmental nucleus. The differentiated character of the relationships between extended amygdala and forebrain and mesopontine districts containing ChAT-ir neurons that give rise to ascending projections may have significant implications for the control of cortical and diencephalic acetylcholine release and accompanying effects on attention, vigilance and locomotor activation.

Acetylcholine↗

PubMed2003

Discrimination of striatopallidum and extended amygdala in the rat: a role for parvalbumin immunoreactive neurons?

Synaptic effects of parvalbumin-immunoreactive (-ir) interneurons (PVs) upon medium spiny neurons may be essential to neural processing in the striatum and, in effect, may serve as an additional feature distinguishing striatum from extended amygdala. The present immunohistochemical study in the rat was done to evaluate the distributions of PVs in the striatum and extended amygdala. Numerous PVs occupy all structures currently regarded as having a striatal composition, including the caudate-putamen, nucleus accumbens, and olfactory tubercle, as well as structures that receive outputs from these, including the globus pallidus, ventral pallidum, entopeduncular nucleus and substantia nigra reticulata. The morphologies of striatal PVs and their distribution were similar to what has been previously reported. In addition, we found that the density of larger neostriatal PVs with extensive and densely immunoreactive dendritic and local axonal arbors is greatest laterally, particularly in striatal districts with slight calbindin-ir, including the striatal patch compartment. In contrast to the situation in striatum, few PVs were observed in the central and medial divisions of the extended amygdala, including the bed nucleus of stria terminalis, interstitial nucleus of the posterior limb of the anterior commissure and central and medial nuclei of the amygdala, or in mesopontine, peribrachial and medullary structures that receive extended amygdala output. The paucity of PVs may be a characteristic feature distinguishing extended amygdala and its projection areas from striatopallidum, as well as the general character of neural processing that occurs in each.

Amygdala↗

PubMed1996

Effects of regular and extended-release gemfibrozil on plasma lipoproteins and apolipoproteins in hypercholesterolemic patients with decreased HDL cholesterol levels.

We have studied, in a prospective blinded fashion, the effects of regular and extended-release gemfibrozil on plasma lipoprotein and apolipoprotein (apo) levels in hypercholesterolemic subjects with decreased high density lipoprotein (HDL) cholesterol (C) levels. Study participants were men and women 19 to 80 years of age with baseline plasma low density lipoprotein (LDL) C levels > or = 4.5 mmol/l (175 mg/dl), HDL-C levels < or = 1.2 mmol/l (45 mg/dl), and triglyceride levels < or = 3.4 mmol/L (300 mg/dl). All subjects were stabilized on a diet for eight weeks prior to entry into two different protocols. In the first protocol 229 subjects were randomized to placebo or extended-release gemfibrozil (1200 mg/day) for 3 months (placebo trial). In the second protocol 655 subjects were randomized to regular or extended-release gemfibrozil (1200 mg/day) for 6 months (equivalency trial). Changes in lipids and apos were stratified by baseline HDL-C levels (< 0.9 mmol/l, and 0.9-12.2 mmol/l). In both studies, treatment with gemfibrozil, either regular or extended-release, was associated with significant (P < 0.05) decreases in plasma very low density lipoprotein (VLDL) C and triglyceride levels of 42-45% and 33-37%, respectively, in subjects with HDL-C level < 0.9 mmol/l, and of 38-47% and 32-39%, respectively, in patients with HDL-C levels of 0.9-1.2 mmol/l. Modest reductions from baseline in directly measured LDL-C levels were observed in both groups (3-6% and 8-9%, respectively). These reductions were less than those observed for calculated LDL-C (7-10% and 11%, respectively). For apo B, reductions were 11-14% and 16-17% in the two groups. HDL-C, apo A-I, and apo A-II levels increased by 15-16%, 5-6%, and 21-25%, respectively, in patients with HDL-C < 0.9 mmol/l, and by 6-7%, 2-3%, and 19-22%, respectively, in patients with HDL-C of 0.9-1.2 mmol/l. These differences in HDL-C levels reached statistical significance in the equivalency trial (P < 0.0001) and were independent of baseline triglyceride levels. Our data indicate that gemfibrozil, either regular or extended-release, is highly effective in lowering plasma triglyceride levels and increases HDL-C levels by approximately 15% in hypercholesterolemic patients with low HDL-C levels (< 0.9 mmol/l). Moreover, this agent lowers VLDL-C somewhat more than triglyceride, resulting in an underestimation of calculated VLDL-C reductions and in an overestimation of calculated LDL-C reductions. This agent also raises apo A-II levels much more than apo A-I levels.

Administration, Oral↗

PubMed2000

Influence of sugar supplementation of the extender on motility, viability and acrosomal integrity of dog spermatozoa during freezing.

Influence of different sugars supplemented to the extender on the motility, viability and intact acrosome rates of dog spermatozoa during dilution, equilibration and freezing was studied. The ejaculate was divided into 10 aliquots, which were diluted 1:3 with TRIS-citric acid extender containing 240 mMTRIS, 63 mM citric acid, 8% (v/v) glycerol, 20% (v/v) egg yolk and 70 mM sugar, which was either fructose, galactose, glucose, xylose (monosaccharide), lactose, trehalose, maltose, sucrose (disaccharide) or raffinose (trisaccharide). No sugar was added to the extender in the control group. Extended semen samples were cooled to 5 degrees C over 45 min, packaged in 0.25-mL straws, equilibrated for 2 h at 5 degrees C and frozen in liquid nitrogen vapor. Samples were thawed by placing straws into 37 degrees C water for 30 sec. Motility, viable sperm and intact acrosome rates decreased gradually in all groups after equilibration and consecutively freezing (P<0.001). The type of sugar significantly effected motility, viability and acrosomal integrity during equilibration and freezing (P<0.05). Galactose, lactose, trehalose, maltose and sucrose reduced damaged acrosome percentages in equilibrated samples (P<0.05). Sugar supplementation did not enhance motility and viability during equilibration. The disaccharides, except lactose, reduced post-thaw dead sperm and/or damaged acrosome percentages without promoting post-thaw motility (P<0.01), whereas monosaccharides, especially fructose and xylose, improved motility (P<0.05) along with viability and intact acrosome rates (P<0.05). Trehalose, xylose and fructose significantly increased total active sperm rates (motility x live sperm rate x normal acrosome rate) compared to other sugars (P<0.01) and control (P<0.0001) in frozen thawed samples. Therefore, sugar supplementation of the extender influenced post-equilibration and post-thaw sperm quality, and the type or locality of protective impact of the sugar on dog spermatozoa vary according to type of the sugar.

Acrosome↗