Stearoyl-CoA desaturase 1 inhibitor supplemented with gemcitabine treatment reduces the viability and fatty acid content of pancreatic cancer cells in vitro

Objective::Pancreatic cancer (PC) is an aggressive cancer with ineffective treatment. Inhibition of stearoyl-CoA desaturase 1 (SCD1) suppresses cancer prolifera...     

Diffusion-weighted MRI and the evaluation of spinal cord axonal integrity following injury and treatment

Diffusion-based magnetic resonance imaging (MRI) (DWI) has been shown experimentally to detect both injury and functionally significant neuroprotection of injured spinal cord white matter that would otherwise go undetected with conventional MRI techniques. The diffusion of water in the central nervous system (CNS) is thought to be affected by both its location (intracellular or extracellular), and by diffusion barriers formed by cell membranes and myelin sheaths. There is, however, controversy concerning how to obtain, interpret, and present DWI data. Computer simulations and MR microscopy have been helpful in resolving some of these issues, as well as determining exact histologic correlates to DWI findings.     

Chondrosarcoma of the jaws: clinical findings, histopathology, and treatment

Three cases of chondrosarcoma involving the jaws are presented, one in the maxilla and two in the mandible. The salient points of clinical presentation elucidated by this series of cases are that a widened periodontal ligament space is present in chondrosarcomas as well as in osteosarcomas, and that a slowly increasing diastema may be the earliest clinical sign. The most important lesson to be learned from the histopathology is that one should not accept a diagnosis of a benign cartilaginous tumor of the jaws. Treatment of these lesions should consist of wide surgical excision and consideration of adjunctive or palliative radiotherapy, especially in the maxilla. It should also be noted that recurrences may develop 10 to 20 years later, and follow-up should be lifelong.     

An atlas of glycine- and GABA-like immunoreactivity and colocalization in the cochlear nuclear complex of the guinea pig

Summary The distribution and colocalization of -aminobutyric acid (GABA)- and glycine-like immunoreactivity in the cochlear nuclear complex of the guinea pig have been studied to produce a light microscopic atlas. The method used was based on post-embedding immunocytochemistry in pairs of 0.5-m-thick plastic sections treated with polyclonal antibodies against conjugated GABA and glycine respectively. Immunoreactive cells, presumably short axon neurones, predominated in the dorsal cochlear nucleus, with mostly single-GABA-labelled cells in the superficial layer, double-labelled in the middle, and single-glycine-labelled in the deep layers. A few large single-glycine-labelled cells, interpreted as commissural neurons, occurred in the ventral nucleus. Scattered double-labelled cells, probably Golgi cells, were seen in the granule cell domain. Immunolabelled puncta of all three staining categories occurred in large numbers throughout the complex, apposed to somata and in the neuropil, showing a differential distribution onto different types of neuron. Three immunolabelled tracts were noted: the tuberculoventral tract, the commissural acoustic stria, and the trapezoidal descending fibres. Most of the fibres in these tracts were single-labelled for glycine, although in the last mentioned tract single-GABA- and double-labelled fibres were also found. Some of the immunolabelled cell types described here are proposed as the origins of the similarly labelled puncta and fibres on the basis of known intrinsic connections.Abbreviations 1-4 DCN layers 1 to 4 - as acoustic stria - AVCN anteroventral cochlear nucleus - C caudal - cap cap area - cas commissural acoustic stria - cnr cochlear nerve root - co commissural cell - CRVCN central region of the VCN - cw cartwheel cell - CZ confluence zone - d dendrite - D dorsal - das dorsal acoustic stria - DCN dorsal cochlear nucleus - df descending fibres - ep ependyma - flocc flocculus - g glial cell - GABA -aminobutyric acid - GLY glycine - gi giant cell - gl/gla globular cell/area - Go Golgi cell - gr granule cell - ias intermediate acoustic stria - icp inferior cerebellar peduncle - lam granule cell lamina - mp/mpa multipolar cell/area - oc/oca octopus cell/area - PVCN posteroventral cochlear nucleus - py pyramidal cell - R rostral - sgl superficial granule cell layer - spcg subpeduncular corner of granule cells - sph/spha spherical cell/area - st stellate cell - tb trapezoid body - tv tuberculoventral cell - TVT tuberculoventral tract - V ventral - VCN ventral cochlear nucleus - vn vestibular nerve     

Strain differences and laminar localization of structural neurochemical changes in aging rat

To obtain comparisons of age-related microchemical changes in cerebral cortex of two comonly employed rat strains (Fischer 344 and Sprague-Dawley), neurochemical assays of substances regarded as quantitative indices of structural entities in brain were performed. These included DNA as a marker for cells, lipid sialoganglioside as an index of neuronal membrane mass, and galactocerebroside as an index of myelin. Fischer 344 rats were studied at 3–4 months (young), 14–16 months (middle age) and 25–28 months (old). Sprague-Dawleys were examined at 3–6 months (young), 14–17 months (middle age) and 25–28 months (old). Significant differences in the time courses of changes occurred; Fischer rats increased their brain weight at each aging point, while Sprague-Dawley rats reached stable brain weights by 4 months of age. Neither strain had a significant change in cell packing density of somatosensory cortex as measured by DNA. However, total ganglioside sialic acid declined in both strains, occurring by middle age in the Fischer and not until senescence in the Sprague-Dawley cortex. Cerebroside galactose increased in the Fischer between young and middle age, and was not further elevated in the older group. The Sprague-Dawley had its major increase in this marker between the middle aged and senescent groups. Intralaminar assays of these same markers in young and old Fisher 344 rats again indicated that DNA did not change, and that sialoganglioside was lost from all layers of the cortex in equal amounts. However, the increase in galactocerebroside resulted entirely from increases in the lower lamina of somatosensory cortex (lamina IV and below), suggesting on-going myelination of afferent and efferent axons. The time course of lipid membrane alteration is strain-dependent and selective as to cortical laminar localization. The findings are discussed in reference to human aging change in the same neurochemical indices.     

Relationship between stress hormones and testosterone with prolonged endurance exercise

Previous pharmacological and pathological studies have reported negative relationships between circulating testosterone and certain stress hormones (i.e., cortisol and prolactin) in humans. These relationships have subsequently been used in hypotheses explaining the subclinical resting testosterone levels often found in some endurance-trained males, but as of yet no one has specifically examined these relationships as they relate to exercise. Thus, we examined the relationship between total and free testosterone levels and cortisol, and between total and free testosterone and prolactin following prolonged endurance exercise in trained males. Twenty-two endurance-trained males volunteered to run at 100% of their ventilatory threshold (VT) on a treadmill until volitional fatigue. Blood samples were taken at pre-exercise baseline (B0); volitional fatigue (F0); 30 min (F30), 60 min (F60), and 90 min (F90) into recovery; and at 24 h post-baseline (P24 h). At F0 [mean running time = 84.8 (3.8) min], exercise induced significant changes (P<0.05) from B0 in total testosterone, cortisol and prolactin. All three of these hormones were still significantly elevated at F30; but at F60 only cortisol and prolactin were greater than their respective B0 values. Free testosterone displayed no significant changes from B0 at F0, F30, or the F60 time point. At F90, neither cortisol nor prolactin was significantly different from their B0 values, but total and free testosterone were reduced significantly from B0. Cortisol, total testosterone and free testosterone at P24 h were significantly lower than their respective B0 levels. Negative relationships existed between peak cortisol response (at time F30) versus total testosterone (at F90, r=–0.53, P<0.05; and at P24 h, r=–0.60, P<0.01). There were no significant relationships between prolactin and total or free testosterone. In conclusion, the present findings give credence to the hypothesis suggesting a linkage between the low resting testosterone found in endurance-trained runners and stress hormones, with respect to cortisol.     

Determinants of the competing outcomes of intrauterine infection,abruption, or spontaneous preterm birth after preterm premature rupture of membranes*

Objective: Patients with PPROM are at risk for a variety of outcomes, including chorioamnionitis (CA), placental abruption (PA), or preterm labor (PTL). Competing risk regression can analyze a cohort’s risk of individual outcomes while accounting for ongoing deliveries secondary to competing events.

Methods: A secondary analysis of the subjects from MFMU BEAM study of neuroprotection after preterm birth (BEAM) with conservative PPROM management. Deliveries were categorized as: PA, CA, PTL, “elective” or “indicated”. The association between outcomes of PA, CA or PTL and clinical predictors of twins, ethnicity, parity, gestational age at rupture, bleeding, contractions, cervical dilation, preterm birth history, weight, and genitourinary infections were evaluated via competing risk regression.

Result: 1970 subjects were included. The significance and directionality of predictors varied according to specific outcomes. Patients with twins had an increased PTL hazard (1.85) though reductions in CA- (0.66) or PA-specific (0.56) hazards. Decreased latency in African-Americans was almost entirely due to an increased CA hazard (1.44) without a significant association with PTL. Increasing gestational age at membrane rupture was associated with a decreasing hazard of CA although increasing hazard of PTL.

Conclusions: For patients with PPROM, the hazards associated with different clinical predictors vary according to exact outcomes.