Human-Derived Amniotic Membrane Is Associated With Decreased Postoperative Intraperitoneal Adhesions in a Rat Model.

BACKGROUND: Complications from adhesions after intra-abdominal surgery accounts for ~6% of hospital admissions. Currently, hyaluronate/carboxymethylcellulose represents the main option to prevent postoperative adhesion formation. Human amniotic membrane contains inherent anti-inflammatory properties that mitigate adhesion formation. OBJECTIVE: This study aimed to evaluate adhesion generation after surgical trauma with amniotic membranes compared with standard intraperitoneal adhesion barriers. DESIGN: This study is a double-blinded, prospective evaluation. SETTING: This study was conducted at an animal research facility. ANIMALS: Forty male rats were studied. INTERVENTION: Laparotomy was performed with peritoneal disruption to the cecum. Animals were randomly assigned to 1 of 5 groups: sham, control, saline, hyaluronic acid membrane, or amniotic membrane. Animals were euthanized at 14 days. MAIN OUTCOME MEASURES: Independent gross and histological assessments of adhesions were analyzed between groups by using adhesion scoring and microscopy. Scoring was based on the percentage of the cecum involved (0-4), vascularity of adhesions (0-3), strength (0-3), inflammation (0-3), and fibrosis (0-3). Adhered tissue was harvested for polymerase chain reaction analysis for gene regulation activity. RESULTS: All rats survived 14 days. Adhesions were observed in all animals. There were significantly fewer adhesions in the amniotic membrane group (2) versus hyaluronic acid (3) group (p = 0.01). The percentage of adhesion to the cecum was lower in the amniotic membrane group (29%) than in the hyaluronic acid group (47%, p = 0.04). Histological examination showed no significant difference between or within the 3 groups for inflammation or fibrosis. Genetic analysis of adhered tissues supported high rates of epithelialization and inhibition of fibrosis in the amniotic membrane group. LIMITATIONS: We are limited by the small sample size and the preclinical nature of the study. CONCLUSION: Human-derived amniotic membrane is effective at reducing intraperitoneal adhesion after surgical trauma and is superior to the current antiadhesion barriers. Amniotic membranes are well absorbed and demonstrate short-term safety. See Video Abstract at http://links.lww.com/DCR/A554.

Astrocytic dynamin-like protein 1 regulates neuronal protection against excitotoxicity in Parkinson disease.

Mitochondrial dynamics has recently become an area of piqued interest in neurodegenerative disorders, including Parkinson disease (PD); however, the contribution of astrocytes to these disorders remains unclear. Here, we show that the level of dynamin-like protein 1 (Dlp1; official name DNM1L), which promotes mitochondrial fission, is lower in astrocytes from the brains of PD patients, and that decreased astrocytic Dlp1 likely represents a relatively early event in PD pathogenesis. In support of this conclusion, we show that Dlp1 knockdown dramatically affects mitochondrial morphological characteristics and localization in astrocytes, impairs the ability of astrocytes to adequately protect neurons from the excitotoxic effects of glutamate, and increases intracellular Ca(2+) in response to extracellular glutamate, resulting from compromised intracellular Ca(2+) buffering. Taken together, our results suggest that astrocytic mitochondrial Dlp1 is a key protein in mitochondrial dynamics and decreased Dlp1 may interfere with neuron survival in PD by disrupting Ca(2+)-coupled glutamate uptake.

Microarray and functional cluster analysis implicates transforming growth factor beta1 in endothelial cell dysfunction in a swine hemorrhagic shock model.

BACKGROUND: Trauma leading to massive hemorrhage results in widespread tissue hypoxia, anaerobic metabolism, and production of inflammatory cytokines and oxidative molecules injurious to the vascular endothelium. Although trauma-related endothelial cell pathophysiology has been extensively studied, very little is known regarding gene transcriptional changes that occur during the event, particularly in endothelia. Thus, we employed fluorescent microarray analysis of gene transcription to elucidate critical pathways and gene products involved in endothelial dysfunction. MATERIALS AND METHODS: A trauma-hemorrhage/shock (T-H/S) model mimicking the physiologic changes seen in human trauma was performed on 10 Yorkshire swine, consisting of 35% blood volume hemorrhage followed by 6 h of full resuscitation. Aortic endothelium was analyzed by microarray and functional clusters were identified through the use of Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. RESULTS: Injured swine developed profound acidosis, coagulopathy, massive resuscitative fluid requirements, and microscopic changes of ischemia/reperfusion injury. While 1007 transcripts were down-regulated, 529 transcripts were up-regulated. DAVID functional clustering analysis revealed 21 significantly altered biological processes that were grouped into 12 distinct functional categories. The transforming growth factor beta (TGFß) family of genes was the most interrelated. In addition, vascular endothelial growth factor (VEGF) signaling members and leukocyte chemoattractants were also altered. CONCLUSIONS: Our model identified two major signaling pathways, TGFß and VEGF, which undergo early transcriptional changes in injured endothelial cells. Our results suggest that TGFß and VEGF may play a crucial role in the development of endothelial cell injury leading to increased vascular permeability during shock-trauma.

Transcriptional analysis of novel hormone receptors PGRMC1 and PGRMC2 as potential biomarkers of breast adenocarcinoma staging.

BACKGROUND: The expression of progesterone receptor membrane component 1 (PGRMC1) in breast cancer has generated interest in this recently discovered protein because of its role in tumorigenesis. However, correlations between patient age, PGRMC1 gene expression, breast cancer morphology, and breast cancer stage have not been adequately studied. Furthermore, very little is known about possible roles for other PGRMC isoforms in breast cancer, like PGRMC2. Thus, we examined the expression of PGRMC1 and PGRMC2 mRNA by relative quantitative PCR (RelqPCR) and determined whether transcript levels correlate with age, breast cancer staging, estrogen receptor alpha (ERα) status, and other morphometric features routinely used during the pathological examination of breast ductal adenocarcinomas. METHODS: Twenty-eight frozen or paraffin embedded breast cancer samples (ductal carcinoma in situ and stages I thru IV invasive ductal adenocarcinoma) and 10 control benign breast tissue samples were randomly selected and interrogated by RelqPCR to determine PGRMC1, 2, and ERα mRNA transcript levels. To control for slight variations in sample preparation, receptor transcript was normalized to the housekeeping gene phosphoglycerate kinase 1 (PGK1). Descriptive statistics and ANOVA of multiparametric datasets were used to correlate transcript levels with pathological staging parameters. RESULTS: PGRMC1 mRNA levels decreased significantly with patient age (Pearson's correlation -0.369; P=0.035), whereas PGRMC2 levels did not. Although the mean relative expression of PGRMC1 significantly decreased in stage II breast cancer compared with controls (P=0.050), it was no longer significant when age was considered a covariance (P=0.371). On the other hand, PGRMC2 mRNA transcript was significantly decreased in stage II breast cancer when compared to stage III cancer (P=0.028) in a manner independent of age (corrected model Bonferroni pair wise comparison, P=0.036). Furthermore, PGRMC2 levels positively correlated with ERα mRNA transcripts in patients with ER positive tumors (Pearson's correlation 0.503, P=0.096). CONCLUSIONS: Decreases in PGRMC1 mRNA are partially explained by increasing patient age. On the other hand, compared to stage III, PCRMC2 mRNA was significantly decreased in stage II adenocarcinoma of the breast in an age-independent manner. Additionally, PGRMC2 mRNA levels displayed a positive correlation with ERα transcripts. Thus, in addition to morphometric pathologic staging criteria, measurements of PGRMC2 mRNA may be useful for distinguishing low stage tumors from higher stages that require more aggressive clinical management, and may be a useful test when tumor ER IHC results are equivocal.

Extracutaneous Manifestations of Calciphylaxis: Ogilvie's Syndrome With Perforation.

Calciphylaxis or calcific uremic arteriolopathy is a rare entity associated with the end-stage renal disease that presents with necrotic cutaneous lesions that may require surgical management. Extracutaneous manifestations of calciphylaxis including visceral ischemia have been reported; however, surgical intervention for colonic ischemia has only been reported twice. We report a 49-year-old male with calciphylaxis who subsequently developed Ogilvie's syndrome complicated by perforation requiring total abdominal colectomy with end ileostomy. Surgeons treating this disease should have a heightened awareness of the extracutaneous sequelae of calciphylaxis.

Evidence for the partial dopamine-receptor agonist aripiprazole as a first-line treatment of psychosis in patients with iatrogenic or tumorogenic hyperprolactinemia.

BACKGROUND: Antipsychotic drugs have many side effects, including elevation of prolactin levels through tuberoinfundibular dopamine-receptor blockade. Although a number of studies claim that aripiprazole is a prolactin-sparing antipsychotic drug that may even lower prolactin levels, there has not been an exhaustive evaluation of this claim. OBJECTIVE: The authors analyzed the burgeoning literature suggesting that aripiprazole is efficacious in treating iatrogenic and tumorogenic hyperprolactinemia. METHOD: The authors conducted a literature search for case studies, reports, and placebo-controlled trials that measured prolactin levels in adult patients taking aripiprazole. RESULTS: The search identified 17 studies, in which 3,489 psychotic patients were given aripiprazole alone, as an adjuvant to haloperidol or risperidone, or to treat psychosis with a concomitant prolactinoma. Across all studies, aripiprazole lowered prolactin levels an average of 74.3%, even in psychotic patients with prolactinoma, whereas haloperidol and risperidone increased prolactin levels by as much as 272%. CONCLUSION: These findings suggest that aripiprazole may play an important niche role in treating psychotic patients sensitive to elevated prolactin and patients with prolactin-secreting pituitary tumors.

"Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model" - Experimental research.

BACKGROUND: Optimizing nerve regeneration and mitigating muscle atrophy are the keys to successful outcomes in peripheral nerve damage. We investigated whether mesenchymal stem cell (MSC) therapy can improve limb function recovery in peripheral nerve damage. MATERIALS AND METHODS: We used sciatic nerve transection/repair (SNR) and individual nerve transection/repair (INR; branches of sciatic nerve - tibial, peroneal, sural) models to study the effect of MSCs on proximal and distal peripheral nerve damages, respectively, in male Lewis rats. Syngeneic MSCs (5 × 106; passage≤6) or saline were administered locally and intravenously. Sensory/motor functions (SF/MF) of the limb were assessed. RESULTS: Rat MSCs (>90%) were CD29+, CD90+, CD34-, CD31- and multipotent. Total SF at two weeks post-SNR & INR with or without MSC therapy was ∼1.2 on a 0-3 grading scale (0 = No function; 3 = Normal); by 12 weeks it was 2.6-2.8 in all groups (n ≥ 9/group). MSCs accelerated SF onset. At eight weeks post-INR, sciatic function index (SFI), a measure of MF (0 = Normal; -100 = Nonfunctional) was -34 and -77 in MSC and vehicle groups, respectively (n ≥ 9); post-SNR it was -72 and -92 in MSC and vehicle groups, respectively. Long-term MF (24 weeks) was apparent in MSC treated INR (SFI -63) but not in SNR (SFI -100). Gastrocnemius muscle atrophy was significantly reduced (P < 0.05) in INR. Nerve histomorphometry revealed reduced axonal area (P < 0.01) but no difference in myelination (P > 0.05) in MSC treated INR compared to the naive contralateral nerve. CONCLUSION: MSC therapy in peripheral nerve damage appears to improve nerve regeneration, mitigate flexion-contractures, and promote limb functional recovery.

Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. OBJECTIVE: The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. METHODS: A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. RESULTS: Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. CONCLUSIONS: Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

Inducing metabolic suppression in severe hemorrhagic shock: Pilot study results from the Biochronicity Project.

BACKGROUND: Suspended animation-like states have been achieved in small animal models, but not in larger species. Inducing metabolic suppression and temporary oxygen independence could enhance survivability of massive injury. Based on prior analyses of key pathways, we hypothesized that phosphoinositol-3-kinase inhibition would produce metabolic suppression without worsening organ injury or systemic physiology. METHODS: Twenty swine were studied using LY294002 (LY), a nonselective phosphoinositol-3-kinase inhibitor. Animals were assigned to trauma only (TO, n = 3); dimethyl sulfoxide only (DMSO, n = 4), LY drug only (LYO, n = 3), and drug + trauma (LY + T, n = 10) groups. Both trauma groups underwent laparotomy, 35% hemorrhage, severe ischemia/reperfusion injury, and protocolized resuscitation. Laboratory, physiologic, cytokine, and metabolic cart data were obtained. Histology of key end organs was also compared. RESULTS: Baseline values were similar among the groups. Compared with the TO group, the LYO group had reversible decreases in heart rate, mean arterial pressure, cardiac output, oxygen consumption, and carbon dioxide production. Compared with TO, LY + T showed sustained decreases in heart rate (113 vs. 76, p = 0.03), mean arterial pressure (40 vs. 31 mm Hg, p = 0.02), and cardiac output (3.8 vs. 1.9 L/min, p = 0.05) at 6 hours. Metabolic parameters showed profound suppression in the LY + T group. Oxygen consumption in LY + T was lower than both TO (119 vs. 229 mL/min, p = 0.012) and LYO (119 vs. 225 mL/min, p = 0.014) at 6 hours. Similarly, carbon dioxide production was decreased at 6 hours in LY + T when compared with TO (114 vs. 191 mL/min, p = 0.043) and LYO (114 vs. 195 mL/min, p = 0.034) groups. There was no worsening of acidosis (lactate 6.4 vs. 8.3 mmol/L, p = 0.4) or other endpoints. Interleukin 6 (IL-6) showed a significant increase in LY + T when compared with TO at 6 hours (60.5 vs. 2.47, p = 0.043). Tumor necrosis factor α and IL-1ß were decreased, and IL-10 increased in TO and LY + T at 6 hours. Markers of liver and kidney injury were no different between TO and LY + T groups at 6 hours. CONCLUSIONS: Phosphoinositol-3-kinase inhibition produced metabolic suppression in healthy and injured swine without increasing end-organ injury or systemic physiologic markers and demonstrated prolonged efficacy in injured animals. Further study may lead to targeted therapies to prolong tolerance to hemorrhage and extend the "golden hour" for injured patients.

Functional circuits mediating sensorimotor integration: quantitative comparisons of projections from rodent barrel cortex to primary motor cortex, neostriatum, superior colliculus, and the pons.

Motor performance depends on somatosensory feedback, and consistent with this finding, primary somatosensory (SI) cortex projects to several regions involved in motor control. Although the pathways mediating sensorimotor integration are known, few studies have compared their projection patterns. Therefore, in each animal, we injected two anterograde tracers into SI barrel cortex and compared the relative density and spatial extent of the labeled projections to the primary motor (MI) cortex, neostriatum, superior colliculus, and basal pons. Quantitative analysis revealed that these projections terminated most extensively in the neostriatum, to a lesser extent in MI cortex, and innervated the least amount of neuropil in the superior colliculus and pontine nuclei. Tracer overlap in the pontine nuclei was significantly higher than in the other three brains regions, and was strongly correlated with overlap in the superior colliculus, presumably because some projections to these two brain regions represent collaterals of the same neurons. The density of labeled varicosities was highest in the pons and lowest in MI. As a proportion of total labeling, densely packed clusters of labeled terminals were most prevalent in the pons, less prevalent in neostriatum and superior colliculus, and least prevalent in MI cortex. These results are consistent with physiological evidence indicating strong coherence between SI barrel cortex and the cerebellum during whisking behavior.

Retained viable plant material in the calcaneus: a case report of a 22-year-old soldier with atypical heel pain.

Foreign bodies can be difficult to diagnose and should be considered in the differential diagnosis of unexplained pain, even in the absence of recalled trauma. We present the case of a 22-year-old male with a painful left heel. The patient did not recall a specific traumatic incident, and there were no clinical signs of trauma or infection. Plain films of the foot were nonrevealing, but magnetic resonance imaging revealed a sinus tract and left calcaneal defect. A biopsy of the calcaneal defect revealed viable woody material embedded and partially integrated with the surrounding bone. Postoperatively the patient's pain completely resolved. This case illustrates the importance of radiopathologic pursuit of an etiology of unexplained foot pain in an otherwise healthy person.

Sugar or salt? The relative roles of the glucocorticoid and mineralocorticoid axes in traumatic shock.

BACKGROUND: Glucocorticoid deficiency (GD) has been proposed as a key contributor to shock states, but the presence and role of acute mineralocorticoid deficiency may be of equal or greater significance. We sought to analyze the incidence and degree of acute mineralocorticoid deficiency and GD in an animal model of severe hemorrhage and shock. METHODS: Fifty-seven swine underwent 35% volume-controlled hemorrhage followed by aortic cross-clamping for 50 minutes to induce truncal ischemia-reperfusion. Protocol-guided resuscitation was performed. Laboratory analysis included cortisol, aldosterone, and plasma renin activity. The aldosterone-to-renin ratio (ARR) was calculated at each time point, and changes were correlated to markers of perfusion. RESULTS: Mean baseline cortisol levels were 5.8 µg/dL. Following hemorrhage, there was a significant increase in mean cortisol to 9.2 µg/dL (p < 0.001). After 1 hour of reperfusion, there was no change in mean cortisol levels (9.8 µg/dL, p = 0.12). Mean baseline aldosterone was 13.3 pg/mL. Aldosterone levels before cross-clamp removal increased significantly to 115.1 pg/mL (p < 0.001) and then rapidly declined to 49.2 pg/mL (p < 0.001) after 1 hour of reperfusion. Conversely, baseline plasma renin activity was 0.75 ng/mL per hour and increased significantly before cross-clamp removal (1.8) and at 1 hour (8.9, both p < 0.001). The ARR at baseline was 96.1 and increased to 113.5 (p = 0.68) before cross-clamp removal but significantly declined following 1 hour of reperfusion to 7.6 (p < 0.001). Overall, this represented a 93% reduction in mean ARR following reperfusion. The degree of aldosterone deficiency correlated with degree of systemic shock as measured by arterial base deficit (r = 0.47, p = 0.04), while cortisol showed no correlation. CONCLUSION: Hemorrhagic shock with ischemia-reperfusion injury resulted in only modest impact on the glucocorticoid axis, but major dysfunction of the mineralocorticoid axis and severe hyperreninemic hypoaldosteronism. The degree of aldosterone deficiency may provide prognostic information or offer potential targets for pharmacologic intervention. LEVEL OF EVIDENCE: Diagnostic study, level III.

Sensorimotor corticocortical projections from rat barrel cortex have an anisotropic organization that facilitates integration of inputs from whiskers in the same row.

We used a dual anterograde-tracing paradigm to characterize the organization of corticocortical projections from primary somatosensory (SI) barrel cortex. In one group of rats, biotinylated dextran amine (BDA) and Fluoro-Ruby (FR) were injected into separate barrel columns that occupied the same row of barrel cortex; in the other group, the tracers were deposited into barrel columns residing in different rows. The labeled corticocortical terminals in the primary motor (MI) and secondary somatosensory (SII) cortices were plotted, and digital reconstructions of these plots were quantitatively analyzed. In all cases, labeled projections from focal tracer deposits in SI barrel cortex terminated in elongated, row-like strips of cortex that corresponded to the whisker representations of the MI or SII cortical areas. When both tracers were injected into separate parts of the same SI barrel row, FR- and BDA-labeled terminals tended to merge into a single strip of labeled MI or SII cortex. By comparison, when the tracers were placed in different SI barrel rows, both MI and SII contained at least two row-like FR- and BDA-labeled strips that formed mirror image representations of the SI injection sites. Quantitative analysis of these labeling patterns revealed three major findings. First, labeled overlap in SII was significantly greater for projections from the same barrel row than for projections from different barrel rows. Second, in the infragranular layers of MI but not in the supragranular layers, labeled overlap was significantly higher for projections from the same SI barrel row. Finally, in all layers of SII and in the infragranular layers of MI, the amount of labeled overlap was proportional to the proximity of the tracer injection sites. These results indicate that SI projections to MI and SII have an anisotropic organization that facilitates the integration of sensory information received from neighboring barrels that represent whiskers in the same row.

Three-dimensional topography of corticopontine projections from rat sensorimotor cortex: comparisons with corticostriatal projections reveal diverse integrative organization.

The major cortical-subcortical re-entrant pathways through the basal ganglia and cerebellum are considered to represent anatomically segregated channels for information originating in different cortical areas. A capacity for integrating unique combinations of cortical inputs has been well documented in the basal ganglia circuits but is largely undefined in the precerebellar circuits. To compare and quantify the amount of overlap that occurs in the first link of the cortico-ponto-cerebellar pathway, a dual tracing approach was used to map the spatial relationship between projections originating from the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), and the primary motor cortex (MI). The anterograde tracers biotinylated dextran amine and Fluoro-Ruby were injected into homologous whisker representations of either SI and SII, or SI and MI. The ensuing pontine labeling patterns were analyzed using a computerized three-dimensional reconstruction approach. The results demonstrate that whisker-related projections from SI and MI are largely segregated. At some locations, the two projections are adjoining and partly overlapping. Furthermore, SI contributes significantly more corticopontine projections than MI. By comparison, projections from corresponding representations in SI and SII terminate in similar parts of the pontine nuclei and display considerable amounts of spatial overlap. Finally, comparison of corticopontine and corticostriatal projections in the same experimental animals reveals that SI-SII overlap is significantly larger in the pontine nuclei than in the neostriatum. These structural differences indicate a larger capacity for integration of information within the same sensory modality in the pontocerebellar system compared to the basal ganglia.

Quantitative comparisons of corticothalamic topography within the ventrobasal complex and the posterior nucleus of the rodent thalamus.

To compare the topographic precision of corticothalamic projections to the ventrobasal (VB) complex and the medial part of the posterior (POm) complex, different anterograde tracers were placed in neighboring parts of the primary (SI) and secondary (SII) somatosensory cortical areas. The location of labeled corticothalamic terminals and their beaded varicosities were plotted, and the digital reconstructions were analyzed quantitatively to determine the extent of overlapping projections from the cortical injection sites. Among animals that received all tracer injections in SI cortex, tracer overlap in the thalamus varied according to the proximity of the cortical injection sites. Regardless of which combination of somatic representations were injected in SI, within each animal the amount of tracer overlap in POm was similar to that observed in VB, and a matched-sample statistical analysis failed to reveal significant differences in the proportion of the labeled regions that contained overlapping projections from the injected cortical sites. Among those animals in which the tracers were injected into the whisker representations of SI and SII, the amount of tracer overlap in the thalamus was not affected by the proximity of the cortical injection sites. Instead, tracer overlap appeared to be related to the degree of somatotopic correspondence. Furthermore, within each of these animals, the amount of tracer overlap in POm was similar to that found in the VB complex. These results indicate that POm has a well-defined topographic organization that is comparable to the degree of topography observed in the VB complex.

Expression patterns of progesterone receptor membrane components 1 and 2 in endometria from women with and without endometriosis.

Endometriosis is a hormone-dependent inflammatory condition associated with pain and infertility. A growing body of evidence supports attenuated secretory-phase progesterone responsiveness in women with this disease. Herein, we compare the expression of progesterone receptor membrane components (PGRMC) 1 and 2 in eutopic endometrium from 11 women with laparoscopically and/or histologically proven stage III/IV endometriosis and 23 disease-free women. Menstrual cycle phase was determined using a combination of reported cycle day, serum hormone profile, and endometrial histologic dating. The PGRMC-1 (fold change -3.3; P < .05) and PGRMC-2 (fold-change -8.8; P < .05) gene expression were significantly downregulated in secretory phase, eutopic endometrium from women with endometriosis. Immunohistochemistry demonstrated decreased PGRMC-1 and PGRMC-2 protein expression in the secretory phase endometrial stroma cells of women with endometriosis. Consistent with the preclinical work of others, our results reflect downregulation of endometrial PGRMC-1 and PGRMC-2 expression in secretory phase endometrium from women with advanced stage endometriosis. Understanding the molecular mechanisms of attenuated progesterone action in endometriosis has important diagnostic and therapeutic implications.

Projections from primary somatosensory cortex to the neostriatum: the role of somatotopic continuity in corticostriatal convergence.

We characterized the organization of corticostriatal projections from rodent primary somatosensory cortex (SI), testing the hypothesis that projections from SI areas representing subcomponents of the forelimb exhibit greater neostriatal overlap than projections from areas representing separate body parts. The anterograde tracers Fluoro-Ruby (FR), Alexa Fluor (AF), and biotinylated dextran amine (BDA) were injected into physiologically identified regions of rat SI. Injection locations were confirmed by examining the SI barrel fields and limb representations in tangential sections processed for cytochrome oxidase (CO). Experimental animals were divided into two groups: one group received multiple tracer injections in neighboring SI regions that represent separate body parts (whiskers, forepaw, and hindpaw); the other group received injections in SI areas that represent different components of the forelimb (forepaw, antebrachium, and brachium). The distribution of labeled terminals and their varicosities in the neostriatum and in the thalamus were plotted and quantitatively analyzed. For most animals, tracer overlap in the thalamus was either minimal or completely absent. In the neostriatum, projections from the whisker, forelimb, and hindlimb representations terminated in regions that rarely overlap with each other, while those originating from different parts of the forelimb representation were more likely to terminate in overlapping parts of the neostriatum. To the extent that neostriatal activation depends on corticostriatal convergence, the corticostriatal projections in the sensorimotor channel appeared to be organized so that neostriatal neurons may signal when multiple components of the same body part are activated simultaneously.