OBJECTIVE

To explore the underlying mechanism of scalp-acupuncture therapy in the treatment of acute cerebral ischemia (ACI) in the rat.

METHODS

A total of 140 SD female rats were randomly assigned to sham-operation (n=20), model (n=60), scalp-acupuncture (SA, n=60) groups, and the later two groups were further divided into 24 h, 48 h and 72 h subgroups separately, with 20 cases in each. Among them, 70 rats were used for cerebral tissue section, and the other 70 cases for homogenating cerebral tissue. ACI model was established by occlusion of the middle cerebral artery (MCAO) for 1 h and reperfusion. EA (2/100 Hz, 2 mA) was applied to bilateral "Dingnie Houxiexian" (MS 7) and "Dingnie Qianxiexian" (MS 6) for 20 min, once daily for 1 d, 2 d and 3 d respectively. The rat's neurological severity score (NSS) was assessed before and after EA. Blood and brain tissue were sampled for detecting TNF-alpha and IL-1beta contents respectively with enzyme-linked immunosorbent assay. Haematoxylin-eosine (H&E) staining method was used for displaying the inflammatory cells in the ischemic brain tissue.

RESULTS

(1) After ACI, NSS at each time-point increased significantly, while compared with model group, NSS of SA group decreased apparently 72 h after ACI (P<0.01). Compared with the corresponding time-points of sham-operation group, the number of inflammatory cells, plasma and cerebral TNF-alpha and IL-1beta contents at 24 h, 48 h and 72 h in model group increased considerably (P<0.01, 0.05). In comparison with the corresponding time-points of model group, the number of inflammatory cells at 48 h and 72 h, plasma and cerebral TNF-alpha and IL-1beta contents at 72 h in SA group declined significantly (P<0.01).

CONCLUSIONS

Scalp-acupuncture can relieve inflammatory cell infiltration, and reduce plasma and cerebral TNF-alpha and IL-1beta contents in ACI rats, which may contribute to its effect in promoting neurofunctional recovery.

OBJECTIVE

The GM2 gangliosidoses are a group of genetic disorders caused by the accumulation of ganglioside GM2 in neuronal cells. We examined the alpha- and beta-subunits of beta-hexosaminidases by a non-radioisotopes detecting system to evaluate whether it was a useful method for understanding of the pathophysiologies of GM2 gangliosidoses.

METHODS

We investigated the alpha- and beta-subunits of beta-hexosaminidases in cultured fibroblasts from cases of various forms of GM2 gangliosidosis by means of Western blotting and a chemiluminescence detection system.

RESULTS

In a patient with infantile Tay-Sachs disease [HEXA genotype, Int5-SA(g-1->>t)/Int5-SA(g-1->>t)], the mature alpha-subunit was undetectable. In a patient with infantile Sandhoff disease (HEXB genotype, C534Y/C534Y), the mature beta-subunit was deficient. However, a small amount of the mature beta-subunit was detected in a patient with adult Sandhoff disease (HEXB genotype, R505Q(+I207V)/R505Q(+I207V)), which may have resulted in the residual enzyme activity and mild clinical course. Normal amounts of alpha- and beta-subunits were detected in a patient with GM2 activator deficiency.

CONCLUSIONS

This method is easy and sensitive for detecting target proteins, and is useful for clarification of the pathophysiologies of GM2 gangliosidoses.

The efficacy of the Stereotactic Aqua-Stream and Aspirator (SAS&A) was experimentally investigated by using hematoma models in the test tube and in gelatin. Even a solid hematoma can be crushed by the water jet and aspirated easily. The greater the positive pressure of the water jet and the negative pressure of suction, the stronger the ability to remove clots. A water jet pressure of 10-20 kg/cm2 and a suction pressure of 100-200 mm Hg were sufficient to remove experimental clots from the test vessels. When the SAS&A was operated in the brain of dogs with a water jet pressure of 20 kg/cm2 and a suction pressure of 200 mm Hg, aspirated brain tissue was less than 15 mg/min in weight, and histological brain injuries were observed only in the area less than 2 mm from the window of the probe, indicating that the procedure with the SAS&A would be relatively atraumatic. We conclude that these observations indicate that the SAS&A can be safe and extremely useful for removal of hypertensive intracerebral hematomas, even in the acute stage.

Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus that can lead to visual impairment and blindness. There is no approved pharmacological treatment for DR; however, laser therapy, steroids and anti-VEGF agents appear to provide some benefit. Hyperglycemia, advanced glycation end products, growth factors, and elevated levels of circulating and vitreous cytokines and chemokines can all trigger an inflammatory response of the retinal vasculature. Features of DR can include diabetic macular edema, microhemorrhage, loss of capillaries, development of avascular areas and the vitreo-retinal proliferation of neovessels. The kallikrein-kinin system (KKS) has long been recognized as a key player of inflammatory processes in various organs. Intravitreally administered recombinant plasma kallikrein has been demonstrated to produce retinal vascular leakage and hemorrhage, while both kinin B1 and B2 receptor agonists have induced retinal edema. Furthermore, kallikrein inhibitors and peptide-based B1 receptor antagonists could reduce or block retinal vascular permeability in diabetic rats. In a diabetic rat model, FOV-2304 (Fovea Pharmaceuticals SA), a non-peptide selective B1 receptor antagonist, consistently blocked retinal vascular permeability, inhibited leukocyte adhesion and abolished the retinal mRNA expression of several inflammatory mediators. Although additional studies are required to investigate the role of the KKS in early capillary loss and late-stage neovascularization processes, the blockade of the KKS is a promising therapeutic strategy for DR.

Arterial segments (less than 250 micron o.d.) excised from canine ileum were mounted in a chamber that permitted arterial transmural pressure (TMP) to be altered and measured. Subsequently, the periarterial nerves were field stimulated with single pulses (0.1 msec, 70 V), and the resting membrane potential (Em) as well as the nerve-mediated alterations in smooth muscle Em were measured using intracellular microelectrodes at TMPs between 0 and 160 mm Hg. The resting Em was greatest at TMPs of 40 mm Hg (-54.7 +/- 2.6 mV) and depolarized as the TMP was increased, reaching a value of -44.8 +/- 3.1 mV at 160 mm Hg. At TMP greater than or equal to 60 mm Hg, a proportion of the preparations exhibited spontaneous electrical activity (SA) consisting of constant rhythmic oscillations in Em or action potentials (APs) or of trains of rhythmic APs that progressively decreased in amplitude, interrupted by periods of hyperpolarization. SA stopped when the TMP was lowered to 40 mm Hg and was reestablished when the TMP was reelevated to TMPs above 60 mm Hg. Nerve stimulation evoked excitatory junction potentials (ejps) or APs. At constant stimulus parameters, ejps of maximum amplitude having the greatest rate of potential rise and fall were produced at TMP of 100 mm Hg. At TMPs greater than 100 mm Hg or less than 100 mm Hg, the amplitude and the rate of rise and fall of the ejps decreased. Ejps formed in response to a constant single pulse stimulus (0.1 msec, 70 V) elicited APs only at TMPs greater than or equal to 60 mm Hg. Neither ejps nor APs were inhibited by alpha-receptor-blocking agents. These studies indicate that the TMP at which an artery is maintained plays an important role in determining the resting Em, the occurrence of spontaneous action potentials, and the alterations in Em associated with nerve stimulation.

BACKGROUND

The aim of the study was to evaluate the effects of micro-electric current on sodium hypochlorite's (NaOCl's) tissue-dissolution abilities, compared with other activation methods, including sonic, ultrasonic, pipetting, and temperature.

METHODS

Bovine muscle tissues (n = 154) with standard sizes and weights were prepared and divided into two temperature groups: room temperature and 45 °C. Each temperature group was divided into seven sub-groups by activation methods: D = distilled water (-control); NaOCl = 5.25 % passive NaOCl (+ control); P = 5.25 % NaOCl with pipetting; SA = 5.25 % NaOCl with sonic activation; UA = 5.25 % NaOCl with ultrasonic activation; E-NaOCl = 5.25 % NaOCl with micro-electric current; and E-NaOCl + P = 5.25 % NaOCl with micro-electric current and pipetting. Specimens were weighed before and after treatment. Average, standard deviation, minimum, maximum, and median were calculated for each group. Resulting data were analyzed statistically using multi-way ANOVA and Tukey HSD tests. The level of the alpha-type error was set at < 0.05.

RESULTS

At room temperature, the E-NaOCl + P group dissolved the highest amount of tissue (p < 0.05), and the UA, SA, and P groups dissolved significantly higher amounts of tissue than did the positive control or E-NaOCl groups (p < 0.05). At 45 °C, there was no significant difference between the SA and E-NaOCl groups (p>> 0.05), and the E-NaOCl + P group dissolved a higher amount of tissue than any other group (p < 0.05).

CONCLUSIONS

Using NaOCl with micro-electric current can improve the tissue-dissolving ability of the solution. In addition, this method can be combined with additional techniques, such as heating and/or pipetting, to achieve a synergistic effect of NaOCl on tissue dissolution.

The nucleotide sequence of bluetongue virus (BTV) serotype 17 segment 8 from North America (NA) coding for the nonstructural phosphoprotein, NS2, was determined. This segment contains 1125 base pairs and codes for a protein of 40,581 daltons containing 354 amino acids with a net charge of -8.5 at pH 7.0. The carboxyl terminal portion of the protein is very hydrophilic and has a high degree of potential alpha-helix. Serine is the major, if not the exclusive, phosphorylated amino acid residue and ten of the twenty serine residues present in NS2 are found in consensus phosphorylation sites. Comparison of the nucleotide sequence of BTV-17NA segment 8 with the sequence of BTV-10NA and BTV-10 South Africa (SA) revealed a greater degree of homology between different serotypes within the same geographical area, i.e., 17NA and 10NA, than between isolates of the same serotype located in different areas, i.e., 10NA and 10SA. The same homology relationship as above was found at the amino acid level.

OBJECTIVE

Validate the KIDSCREEN-27 for parents in the metropolitan area of Medellín, Colombia, including the Social Acceptance (SA) subscale of KIDSCREEN-52, as it evaluates the effect of bullying in Life Quality of children.

METHODS

The study population was made up by parents of children between 8 and 18, from Medellín and its metropolitan area. A sample of 1,150 parents was estimated according to the different psychometric properties to be measured. Construct validation was made by comparing the mean scores between groups of high and low socioeconomic conditions. The content validity and the measurement of reliability were verified by internal consistency and test-retest stability. The parent-child agreement was also measured.

RESULTS

The internal consistency was adequate (Cronbach alpha 0,76-0,83). Parents of children with better socio-economic status had higher scores in all dimensions (p<0,05). Scores were higher among healthy children. Women had lower scores than men, while children registered higher scores than adolescents. The intraclass correlation coefficient for the reliability assessment was above 0.7 in all dimensions, except in School Environment-SE- (ICC 0,6-0,92). The parent-child agreement reached moderate and good levels (ICC 0,49-0,69). The exploratory factorial analysis, including social acceptance subscale, registered eight dimensions, four of which in agreement with the original questionnaire: Physical activity, SE, Social Support, and SA subscale.

CONCLUSIONS

KIDSCREEN-27 for parents is a valid and reliable instrument to be used in the Colombian context.

High-amylose corn starch, that contains 70% of amylose chains and 30% of amylopectin, has been used to obtain substituted amylose (SA) polymers. Tablets have been prepared by direct compression, i.e. dry mixing of drug and SA, followed by compression, which is the easiest way to manufacture an oral dosage form. Until now, their controlled-release properties have been assessed only by an in vitro dissolution test. Amylose-based polymers are normally subject to biodegradation by alpha-amylase enzymes present in the gastrointestinal tract, but matrix systems show no significant degradation of tablets by alpha-amylase in vitro. High-amylose sodium carboxymethyl starch (HASCA) is an interesting excipient for sustained drug-release in solid oral dosage forms. In addition to the easy manufacture of tablets by direct compression, the results show that in vitro drug-release from an optimized HASCA formulation is not affected by either acidic pH value or acidic medium residence time. In addition, a compressed blend of HASCA with an optimized quantity of sodium chloride provides a pharmaceutical sustained-release tablet with improved integrity for oral administration. In vivo studies demonstrate extended drug absorption, showing that the matrix tablets do not disintegrate immediately. Nevertheless, acetaminophen does not seem to be the most appropriate drug for this type of formulation.

A rapid and convenient method for determining the backbone conformation of cyclic peptides results from the combination of 1D 1H NMR information and molecular modeling. phi Angle torsional constraints calculated from 3JHN.H alpha coupling constants are used to determine the position of multiple-welled potential energy penalty functions that are imposed on the force field used in the structure refinement (Amber* with GB/SA solvation model). Monte Carlo searches and minimizations lead to a collection of structures that are clustered by backbone similarity and then filtered according to hydrogen-bonding constraints determined by the chemical shift temperature dependencies of the amide protons. This approach was applied to five cyclic peptides whose structures had been determined previously using more extensive 2D NMR techniques, and the importance of the torsional, H-bonding, and solvation restraints were assessed. For the four peptides that adopt a predominant conformation, this method reproduced the reported structures closely; lack of convergence for the fifth structure reflected the multiple backbone conformations that this macrocycle adopts.

Avian influenza A (H5N1) virus infections have resulted in more than 100 human deaths; yet, human-to-human transmission is rare. We demonstrated that the epithelial cells in the upper respiratory tract of humans mainly possess sialic acid linked to galactose by alpha 2,6 linkages (SA alpha 2,6Gal), a molecule preferentially recognized by human viruses. However, many cells in the respiratory bronchioles and alveoli possess SA alpha 2,3Gal, which is preferentially recognized by avian viruses. These facts are consistent with the observation that H5N1 viruses can be directly transmitted from birds to humans and cause serious lower respiratory tract damage in humans. Furthermore, this anatomical difference in receptor prevalence may explain why the spread of H5N1 viruses among humans is limited. However, since some H5N1 viruses isolated from humans recognize human virus receptors, additional changes must be required for these viruses to acquire the ability for efficient human-to-human transmission.

Submandibular gland autotransplantation is effective for treating severe dry eye syndrome. However, more than 40% of patients show epiphora within 3-6 months after treatment. The mechanism underlying the hypersecretion in epiphora remains to be elucidated for developing novel interventions. Since salivary gland secretion is dependent on a variety of proteins, we analyzed the changes in protein expression in transplanted glands of epiphora patients with 2-D gel electrophoresis and electrospray ionization quadrupole/time-of-flight mass spectrometry and evaluated their possible roles in epiphora. There were 23 proteins that showed altered expression in the glands of epiphora patients, 15 being up-expressed and 8 being down-expressed. The expression of secretory proteins was decreased in these glands, including alpha-amylase, cystatin S, SA, and SN. In contrast, cytoskeletal proteins were all up-regulated, including actin and vimentin. Immunofluorescence revealed that the intensity ratio of F-actin in apical and lateral cytoplasm to total F-actin in acini was decreased in the glands of epiphora patients. Carbachol stimulation induced a similar redistribution of F-actin in the control glands. Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) was increased in both carbachol-stimulated and epiphora glands. Preincubation of submandibular glands with ERK1/2 inhibitors PD98059 or U0126 inhibited carbachol-induced F-actin redistribution. These results indicated that differentially expressed proteins participated in the hypersecretion of transplanted submandibular glands and the redistribution of F-actin might be involved in this hypersecretion in an ERK1/2-dependent manner.

1. The effects of ouabain on the action potentials and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined using the two-microelectrode technique. 2. Cumulative administrations of ouabain (10(-8) to 10(-6) M) caused a negative chronotropic effect in a concentration-dependent manner. The effect was not modified by atropine (10(-7) M). At 10(-6) M, ouabain prolonged the duration of action potentials, but other parameters were unaffected to any significant extent. Ouabain elicited an arrhythmia, and increasing concentrations increased the incidence of arrhythmia (75% at 3 x 10(-7) M). 3. Pretreatment with clonidine (10(-6) M), a selective agonist of presynaptic alpha 2-adrenoceptors, completely blocked the development of arrhythmia induced by ouabain (3 x 10(-7) M). Prazosin (10(-6) M), an alpha 1 antagonist, had similar effects, and yohimbine (10(-6) to 10(-5) M), an alpha 2 antagonist, did not affect the arrhythmias. 4. Ouabain (10(-8) to 10(-6) M) inhibited the slow inward and the time-dependent outward currents, but enhanced the hyperpolarization-activated inward current, in a concentration-dependent manner. The time course of inactivation phase for Isi was composed of two (fast and slow) components. Ouabain decreased the fast component and increased the slow component. The voltage of half-maximum activation for the outward current was not affected. Ouabain elicited a transient inward current on the repolarizing step, and also on the depolarizing step.(ABSTRACT TRUNCATED AT 250 WORDS)

Symptoms and complications of the obstructive sleep apnea (SAS) lead to a significant impairment of the health-related quality of life (HRQOL) of the affected individuals. Most HRQOL questionnaires have been published in English. Formal process of evaluation has to precede the introduction of a new language version of a HRQOL questionnaire. We conducted a comparative evaluation of the Polish versions of two HRQOL questionnaires: The Calgary Sleep Apnea Quality of Life Questionnaire (SAQLI) and The Functional Outcomes of Sleep Questionnaire (FOSQ). We examined the reliability, validity, stability and responsiveness of both questionnaires. Cronbach's alpha coefficient amounted to 0.94 for both questionnaires, which confirmed their reliability. Scores of both questionnaires highly correlated with measures of daily sleepiness, general health and SF-36 questionnaire scores. Both SAQLI and FOSQ gave stable results, but SAQLI was found to be more sensitive than FOSQ. The Polish version of FOSQ was proved to be a useful tool in cross-sectional assessment of HRQOL in patients with SAS. Stability and responsiveness of the Polish version of SAQLI and normal distribution of its scores make this questionnaire a preferable instrument in repeated assessments of HRQOL in the same group of patients.

Chapman and colleagues have developed symptom-oriented scales based on Meehl's manual of schizotypy, such as the Social Anhedonia (SA) and Physical Anhedonia (PhA) Scales, the Magical Ideation Scale (MIS), and the Perceptual Aberration Scale (PAS). Whereas Chapman's scales of psychosis proneness are the most internationally used instruments for the assessment of schizotypy, some of them, such as MIS and PAS, were still not available in French. We reported here the validation study of the MIS and the PAS French versions that we had published previously. This study was conducted in a sample of 233 students (males: n = 108; females: n = 125; mean age: 21.17 +/- 1.47; mean educational level: 13.36 +/- 1.06). The French versions of the MIS and the PAS have high internal reliability (MIS: Cronbach's alpha = 0.85; PAS: Cronbach's alpha = 0.88). French norms are given for each of these scales. They are respectively 19/30 for the MIS and 17/35 for the PAS high cutoff scores without any difference when gender was considered. These results are very closed to those found by Chapman and colleagues for University of Wisconsin undergraduate students.

Proinflammatory cytokines and their receptors are increased in the peripheral blood of patients with heart failure. We measured cytokines and their receptors in systemic artery (SA), coronary sinus (CS) and infra-renal inferior vena cava (IVC), in order to investigate their origin and influential factors. Thirty patients with idiopathic dilated cardiomyopathy were performed echocardiography at admission, and right heart catheterization after stabilization. Blood was drawn from 3 sites for measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and soluble tumor necrosis factor-alpha receptor (sTNFR) I, II. TNF-alpha at CS (3.25 +/- 0.34 pg/mL) was higher than those of SA (1.81 +/- 0.39 pg/mL) and IVC (1.88 +/- 0.38 pg/mL, p<0.05). IL-6 at CS (18.3 +/- 3.8 pg/mL) was higher than that of SA (5.8 +/- 1.2 pg/mL, p<0.01). The levels of sTNFR I, II showed increasing tendency in sequence of SA, IVC and CS. TNF-alpha and sTNFR I, II from all sites were proportional to worsening of functional classes at admission (p<0.05). E/Ea by Doppler study at admission, which reflects left ventricular end-diastolic pressure (LVEDP) was positively correlated with TNF-alpha from SA (R=0.71, p<0.01), CS (R=0.52, p<0.05) and IVC (R=0.46, p<0.05). Thus, elevated LVEDP during decompensation might cause cytokine release from myocardium in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE

To explore the mechanism of scalp acupuncture (SA) in treating cerebral ischemia.

METHODS

Sixty SD rats with middle cerebral artery occlusion (MCAO) were randomized into untreated group and SA-treated group, with another group of 10 SD rats without artery occlusion as sham-operated control. Neurological severity score (NSS), hemetoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay were applied to observing the changes of neurofunctional defect, inflammatory infiltration in cerebral tissue and content of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-10 at 24, 48 and 72 h after ischemia-reperfusion.

RESULTS

There existed significant difference in NSS between SA-treated group and untreated group (P<0.01), especially at 72 h after ischemia-reperfusion. The HE staining results of ischemic cerebral tissue showed an apparent reduction of inflamed lesions in SA-treated group as compared with the untreated group (P<0.01), especially at 72 h after ischemia-reperfusion. The content of TNF-alpha and IL-1beta at each phase point after ischemia-reperfusion in SA-treated was decreased as compared with that in the untreated group, and there were differences between SA-treated group and untreated group at 72 h after ischemia-reperfusion (P<0.01). An apparent increase was observed in IL-10 between SA-treated group and untreated group at each phase point after ischemia-reperfusion, and there were significant differences between SA-treated group and untreated group at 48 and 72 h after ischemia-reperfusion (P<0.05, P<0.01).

CONCLUSIONS

Scalp acupuncture can improve neurofunctional rehabilitation, suppress leukocyte infiltration, decrease the content of TNF-alpha and IL-1beta within a certain range and enhance IL-10 expression so as to suppress cytokines-mediated inflammatory reaction and attenuate cerebral ischemia-reperfusion injury.

BACKGROUND

The aim of this study was to determine whether sex and biochemical markers of inflammation have a role in left ventricular (LV) remodelling after aortic valve replacement in elderly patients with aortic valve stenosis.

METHODS

We studied 52 elderly patients with aortic valve stenosis (32 men, mean age 65 +/- 11 years and 20 women, mean age 68 +/- 9 years). Body surface area did not differ between men and women (1.81 +/- 0.15 versus 1.84 +/- 0.20, respectively). All patients underwent a complete echocardiographic examination for the determination of ejection fraction (EF), LV mass and mass index, peak and mean systolic pressure gradient, aortic valve area, early (E) and late (A) transmitral flow wave velocities and their ratio (E/A), tissue Doppler indexes of the mitral annulus (Sa, Ea, Aa), and the E/Ea ratio. In addition, levels of high sensitivity C-reactive protein (hsCRP), tumour necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) were measured from venous blood samples taken before, and 10 days, 3 months and 6 months after aortic valve replacement.

RESULTS

LV mass decreased from 297 +/- 99.7 g before aortic valve replacement to 210 +/- 67 g 3 months after surgery and to 210 +/- 74 g 6 months after surgery (p<0.001). LV EF did not change significantly (p=0.836). Peak and mean systolic pressure gradients decreased, whereas aortic valve area increased after valve replacement (p<0.001). These changes were similar in men and women. In women Sa was greater (p=0.017) and the E/Ea ratio lower (p=0.025) than in men. The long-term changes in peak and mean pressure gradients, aortic valve area and LV mass after aortic valve replacement were well correlated with the long-term changes in hsCRP, TNF-alpha and MCP-1 in both men and women.

CONCLUSIONS

LV remodelling is similar in elderly men and women with aortic valve disease who have similar body surface area. Although inflammatory markers are not correlated with echocardiographic parameters before aortic valve replacement, a strong correlation exists after operation. This correlation is similar in men and women.

BACKGROUND

Alpha-methylacyl-CoA racemase (AMACR), also known as P504S, is a protein that plays an important role in mitochondrial and peroxisomal beta-oxidation of branched-chain fatty acid and bile acid intermediates. AMACR has been established as a valuable diagnostic marker for prostate cancer and has recently been shown to be useful in the diagnosis of colorectal carcinoma. Despite the importance of lipid metabolism in sebum production by sebaceous glands of the skin, there are no studies evaluating the expression of AMACR in sebaceous neoplasms.

METHODS

Five samples of normal sebaceous glands as well as five cases each of sebaceous hyperplasia (SH), sebaceous adenoma (SA), basal cell carcinoma (BCC) with sebaceous differentiation and extraocular sebaceous carcinoma (SC) were evaluated for immunohistochemical (IHC) expression of AMACR. Each case was reviewed by a single dermatopathologist and graded using a semi-objective grading schema.

RESULTS

Normal sebaceous glands showed strong (4+) expression of AMACR. Among sebaceous neoplasms, SH showed the highest expression (4+), SA and BCC with sebaceous differentiation showed varied expression (2+ and 1+, respectively), and extraocular SC showed no expression of AMACR.

CONCLUSIONS

The expression of AMACR is increased in benign sebaceous glands and SH; with decreasing AMACR expression in tumors with less sebaceous differentiation (i.e. SA and SC). These findings provide insight into the potential pathogenesis of sebaceous neoplasms while assisting in the microscopic distinction of SA from SC.

OBJECTIVE

Serrated adenomas (SAs) of the colorectum can be broadly divided into two subtypes: type I more closely mimicking hyperplastic polyps, and type II unequivocal traditional adenomas. The aim of this study was to clarify their differential clinicopathologic and colonoscopic features.

METHODS

A total of 127 SAs (53 type I, 52 type II and 22 admixed type I+II) were investigated and colonoscopic surface patterns were divided into three categories: speckled, granular and cerebriform.

RESULTS

The cerebriform pattern was most frequently observed in all SA types. Types I+II (median size, 7.5 mm) or type II SAs (median size, 10 mm) were generally sessile or pedunculated polyps in the rectosigmoid colon whereas some type I lesions (median size, 5 mm) demonstrated a flat-elevated morphology and were found in the ascending colon and cecum. Co-existing (2/127: 1.6%) invasive carcinomas were only detected with type II SAs. In contrast, synchronous invasive carcinomas distant from SAs were more frequently observed with type I (31%) than types I+II (5%) or II (12%).

CONCLUSIONS

Clinicopathologic differences are apparent among the types of SAs. A type II SA-invasive carcinoma sequence might exist. We stress recognition of type I SA as a neoplastic, rather than a hyperplastic lesion, often accompanying invasive carcinomas at a distance from the SA.

The two-stage clonal expansion model is a popular model for carcinogenesis data. One common form of this model is based on the approximate hazard function. In certain situations, this formulation is not appropriate, and the exact hazard should be applied. However, the difficulty of implementing the model based on the exact hazard has deterred many from using it. This paper presents a program implementing the exact hazard model for piecewise constant dosing using SAS, a package that is readily available to most that are interested in this type of analysis. Also, an analysis of the ED01 data is presented using this program, and comparisons are made to an earlier analysis based on the approximate hazard. By allowing for an independent background tumor mechanism, an excellent fit to the bladder tumor incidence data was obtained.

Since primary infection with Cryptococcus neoformans usually occurs in the lungs, and since pulmonary cryptococcosis involves interactions between yeasts and alveolar epithelial cells, we have begun to study the effects of C. neoformans and its secreted antigens (SA) on epithelial reactions potentially associated with localized inflammation. We report here that SAs from encapsulated and acapsular strains of C. neoformans caused significant reductions in tumor necrosis factor-alpha (TNF-alpha)-induced intercellular adhesion molecule-1 (ICAM-1) expression on A549 lung epithelial cells in culture. We also present evidence that the reduction in ICAM-1 expression was not associated with SA-induced shedding of this adhesion molecule.

OBJECTIVE

Tumor necrosis factor (TNF)-alpha is a multifunctional cytokine that influences the clinical outcome in a number of diseases. This study was undertaken to evaluate its role in the differential diagnosis of malignant and benign tumors and in the follow-up of patients. We also studied the correlation of TNF-alpha levels with the stage and differentiation of the diseases.

METHODS

In this study, serum levels of TNF-alpha are determined by the immunoradiometric assay method in 26 patients with head and neck cancer, and results are compared with 8 control patients with benign diseases. In both groups, serum samples were taken before and after the therapy. After centrifugation, the sera was stored at -70 degrees C until analyzed. TNF-alpha levels were measured by TNF-alpha immunoradiometric assay (IRMA) kit (Medgenix, Diagnostics SA, Belgium).

RESULTS

The pretreatment mean value of TNF-alpha in the study group (814.1 pg/mL) was almost 100 times higher than in the control group (8.6 pg/mL) (P = .001). It was also noted that posttreatment mean value (94 pg/mL) was significantly lower than pretreatment mean value in the study group (P = .001). No statistically significant difference was found between serum TNF-alpha levels and the stage and differentiation of the tumor.

CONCLUSIONS

The serum levels of TNF-alpha may be an efficient tumor marker in the diagnosis of patients with head and neck cancer.

Synthetic cathinones are chemical derivatives of cathinone that are pharmacologically similar to cocaine and methamphetamine. Recently, abuse of synthetic cathinones among young people has increased.

The present study aimed to characterize the behavioral effects of alpha-pyrrolidinopentiothiophenone (PVT), an analog of alpha-pyrrolidinovalerophenone and second-generation synthetic cathinone, as well as to evaluate its abuse potential, using conditioned place preference, intravenous self-administration (SA), and drug discrimination paradigms in rodent models.

Alpha-PVT produced a significant place preference in mice at doses of 10, 30, and 50 mg/kg. In the SA experiment, alpha-PVT (0.1, 0.3, and 1.0 mg/kg/infusion) produced an inverted U-shaped dose-effect curve in rats. Under a progressive ratio schedule of reinforcement, there appeared to be a positive relationship between alpha-PVT dose and the breakpoints for alpha-PVT reinforcement. Additionally, alpha-PVT fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine in rats.

Our results indicate that alpha-PVT has rewarding and reinforcing effects and shares the interoceptive effects of cocaine and methamphetamine. To the best of our knowledge, the present study is the first to show that alpha-PVT has reinforcing properties when delivered on its own, which suggests possible abuse liability in humans.