Prevalence of mitral valve regurgitation in 102 asymptomatic Chinese Crested dogs.

INTRODUCTION: Mitral regurgitation (MR) is one of the main features of myxomatous mitral valve disease (MMVD), which is the most common heart disease in dogs. Myxomatous mitral valve disease affects many small breed dogs, and some breeds such as Cavalier King Charles Spaniels, Dachshunds, Yorkshire terriers, and Miniature Schnauzers have been studied more in detail. Breed-specific information regarding MMVD is valuable for providing appropriate advice on management and breeding. Data, based on insurance statistics in Sweden, show that Chinese Crested dogs (CCD) are twice as likely to visit the veterinarian for a heart-related problem than other breeds. ANIMALS: One-hundred two privately owned, healthy CCD were recruited via the Swedish CCD club. MATERIALS AND METHODS: This was a prospective observational study, in which clinical examinations, blood pressure measurements, and echocardiographic and Doppler examinations were performed in all dogs. Pulsed wave tissue Doppler imaging was performed in 87 dogs. RESULTS: Mitral regurgitation was present in 39 (38%) dogs, whereas a systolic murmur was present in 35 (34%) dogs. Mitral valve prolapse was present in 32 (31%) dogs. Tricuspid regurgitation was found in 29 (28%) dogs. Dogs in the MR group were older (median 9.5 years), and males were overrepresented compared with the non-MR group. Differences were also found between groups regarding left atrial size and transmitral E wave velocity. CONCLUSIONS: The prevalence of MR in CCD is similar to reports in other small breeds. Whether the MR detected in these dogs is a sign of MMVD is unknown.

Increased placental trophoblast inclusions in placenta accreta.

INTRODUCTION: Trophoblast inclusions (TIs) are often found in placentas of genetically abnormal gestations. Although best documented in placentas from molar pregnancies and chromosomal aneuploidy, TIs are also associated with more subtle genetic abnormalities, and possibly autism. Less than 3% of non-aneuploid, non-accreta placentas have TIs. We hypothesize that placental genetics may play a role in the development of placenta accreta and aim to study TIs as a potential surrogate indicator of abnormal placental genetics. METHODS: Forty cases of placenta accreta in the third trimester were identified in a search of the medical records at one institution. Forty two third trimester control placentas were identified by a review of consecutively received single gestation placentas with no known genetic abnormalities and no diagnosis of placenta accreta. RESULTS: Forty percent of cases with placenta accreta demonstrated TIs compared to 2.4% of controls. More invasive placenta accretas (increta and percreta) were more likely to demonstrate TIs than accreta (47% versus 20%). Prior cesarean delivery was more likely in accreta patients than controls (67% versus 9.5%). DISCUSSION: Placenta accreta is thought to be the result of damage to the endometrium predisposing to abnormal decidualization and invasive trophoblast growth into the myometrium. However, the etiology of accreta is incompletely understood with accreta frequently occurring in women without predisposing factors and failing to occur in predisposed patients. CONCLUSION: This study has shown that TIs are present at increased rates in cases of PA. Further studies are needed to discern what underlying pathogenic mechanisms are in common between abnormal placentation and the formation of TIs.

Hypothalamic control of adipose tissue.

A detailed appreciation of the control of adipose tissue whether it be white, brown or brite/beige has never been more important to the development of a framework on which to build therapeutic strategies to combat obesity. This is because 1) the rate of fatty acid release into the circulation from lipolysis in white adipose tissue (WAT) is integrally important to the development of obesity, 2) brown adipose tissue (BAT) has now moved back to center stage with the realization that it is present in adult humans and, in its activated form, is inversely proportional to levels of obesity and 3) the identification and characterization of "brown-like" or brite/beige fat is likely to be one of the most exciting developments in adipose tissue biology in the last decade. Central to all of these developments is the role of the CNS in the control of different fat cell functions and central to CNS control is the integrative capacity of the hypothalamus. In this chapter we will attempt to detail key issues relevant to the structure and function of hypothalamic and downstream control of WAT and BAT and highlight the importance of developing an understanding of the neural input to brite/beige fat cells as a precursor to its recruitment as therapeutic target.

Protective effects of glycoursodeoxycholic acid in Barrett's esophagus cells.

Barrett's esophagus (BE) is a premalignant condition associated with the development of esophageal adenocarcinoma (EAC). Previous studies have implicated hydrophobic bile acids and gastric acid in BE and EAC pathogenesis. In this study, we tested the hypothesis that DNA damage, cytotoxicity and oxidative stress induced by bile acids and gastric acid can be attenuated by the cytoprotective, hydrophilic bile acid glycoursodeoxycholic acid (GUDCA). Non-dysplastic BE cells were exposed for 10 min to pH 4 and/or bile acid cocktail or to pH 4 and a modified cocktail consisting of a mixture of bile acids and GUDCA. DNA damage was evaluated by the comet assay; cell viability and proliferation were measured by trypan blue staining and the MTS assay; reactive oxygen species (ROS) were measured using hydroethidium staining; oxidative DNA/RNA damage was detected by immunostaining with antibody against 8-OH-dG; thiol levels were measured by 5-chloromethylfluorescein diacetate (CMFDA) staining; and the expression of antioxidant proteins was evaluated by western blotting. DNA damage and oxidative stress were significantly increased, while thiol levels were decreased in BE cells treated with pH 4 and bile acid cocktail compared with cells treated with pH 4 alone or untreated cells. Bile acids and low pH also significantly decreased cell proliferation. Expression of the antioxidant enzymes, MnSOD and CuZnSOD, was elevated in the cells treated with bile acids and low pH. When GUDCA was included in the medium, all these effects of pH 4 and bile acids were markedly reduced. In conclusion, treatment of BE cells with acidified medium and a bile acid cocktail at physiologically relevant concentrations induces DNA damage, cytotoxicity, and ROS. The cytoprotective bile acid, GUDCA, inhibits these deleterious effects by inhibiting oxidative stress.

Multimilliwatt ultrashort pulses continuously tunable in the visible from a compact fiber source.

We report on a single-pass device that efficiently converts the broadband near-infrared output from a femtosecond fiber laser into a narrow spectrum in the visible. With fan-out poled MgO:LiNbO3 we obtain sub-picosecond, continuously tunable pulses in the 520-700 nm range. Conversion efficiencies as high as 30% are observed at typical pump power levels of 30 mW, corresponding to average output powers up to 9.5 mW. The specifications of our device are ideal for applications in confocal microscopy and frequency metrology.

Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: a randomized multinational trial.

OBJECTIVES: To compare change from baseline in HIV RNA and fasting low-density lipoprotein (LDL) cholesterol levels in protease inhibitor (PI)-experienced patients receiving unboosted atazanavir 400 mg once daily versus lopinavir 400 mg boosted with ritonavir 100 mg twice daily, with two nucleoside reverse transcriptase inhibitors (NRTIs). Secondary objectives included virologic response, CD4 cell count changes, other lipid changes, safety, and tolerability. METHODS: Randomized, open-label, multinational, 48-week study in patients with one PI-regimen failure, HIV RNA > or = 1000 copies/mL, and CD4 count > or = 50 cells/mm3. RESULTS: Three hundred patients were randomized; 290 treated (144 atazanavir, 146 lopinavir/ritonavir). Lopinavir/ritonavir resulted in a significantly greater reduction in HIV RNA than unboosted atazanavir (-2.02 vs -1.59 log10 copies/mL, p < 0.001) at week 48. Secondary efficacy endpoints also favored lopinavir/ritonavir; the differences in efficacy between regimens were also observed in secondary analyses comparing those subjects who were susceptible and those subjects who were resistant to their respective PIs at baseline. However, both regimens were equally effective in subjects who had no baseline NRTI mutations. From baseline to week 48, atazanavir resulted in either no change or decreases in fasting LDL cholesterol, total cholesterol, and fasting triglycerides (-6%, -2%, and +1%), whereas lopinavir/ritonavir resulted in increases (+3%, +12%, and +53%) (p < 0.05, all between-treatment comparisons). Fewer patients were administered lipid-lowering therapy in the atazanavir arm (6% vs 20% for lopinavir/ritonavir). Both regimens were safe and well tolerated. CONCLUSIONS: While both treatments demonstrated good antiviral efficacy, relatively greater antiviral suppression was observed with lopinavir/ritonavir. In those patients with no NRTI mutations at baseline, both regimens demonstrated comparable virologic suppression. Atazanavir-treated patients demonstrated a superior lipid profile and required less frequent lipid-lowering treatment.

Bacillus subtilis locus encoding a killer protein and its antidote.

We have isolated mutations that block sporulation after formation of the polar septum in Bacillus subtilis. These mutations were mapped to the two genes of a new locus, spoIIS. Inactivation of the second gene, spoIISB, decreases sporulation efficiency by 4 orders of magnitude. Inactivation of the first gene, spoIISA, has no effect on sporulation but it fully restores sporulation of a spoIISB null mutant, indicating that SpoIISB is required only to counteract the negative effect of SpoIISA on sporulation. An internal promoter ensures the synthesis of an excess of SpoIISB over SpoIISA during exponential growth and sporulation. In the absence of SpoIISB, the sporulating cells show lethal damage of their envelope shortly after asymmetric septation, a defect that can be corrected by synthesizing SpoIISB only in the mother cell. However, forced synthesis of SpoIISA in exponentially growing cells or in the forespore leads to the same type of morphological damage and to cell death. In both cases protection against the killing effect of SpoIISA can be provided by simultaneous synthesis of SpoIISB. The spoIIS locus is unique to B. subtilis, and since it is completely dispensable for sporulation its physiological role remains elusive.

Radiographic comparison of grit-blasted hydroxyaptite and arc-deposited hydroxyapatite acetabular components. A four-year follow-up study.

High rates of aseptic loosening have been reported for microstructured hydroxyapatite-coated acetabular components. A macrostructured component surface (arc-deposition) not only improves resistance to shear forces experienced by the acetabular component and increases initial stability, but also provides channels for bone ingrowth. The purpose of this investigation was to radiographically compare a series of grit-blasted (microstructured) and arc-deposited (macrostructured) hydroxyapatite-coated acetabular components. A minimum 4-year retrospective radiographic analysis of acetabular components was performed on a total of 50 total hip arthroplasties. At 4 years, arc-deposited components were associated with fewer radiolucent lines in all Charnley zones, particularly Charnley zone III. While the 4-year results for arc-deposited hydroxyapatite acetabular components are superior to their microstructured predecessors, long-term results are still unknown.

[Quality of life assessment one year after total hip or knee arthroplasty]. / Evaluation à un an de la qualité de vie après arthroplastie totale de hanche et de genou.

PURPOSE OF THE STUDY: The development of quality of life (QOL) instruments has made it possible to obtain an objective assessment of the impact of surgical procedures taking into consideration the physical, psychological and social aspects of the patient's everyday activities. The aim of this work was to evaluate the short-term and long-term course of QOL after total hip arthroplasty (THA) and total knee arthroplasty (TKA). MATERIALS AND METHODS: This study included a prospective multicentric cohort of patients with a first intention indication for degenerative bone and joint disease. Clinical assessment was obtained preoperatively and 6 weeks, 6 months and 12 months postoperatively. The Merle d'Aubigné and Harris scores were determined for THA and the Hospital Special Surgery score for TKA. Clinical data (pain, walking distance), and QOL scores [French version of the Nottingham Health Profile (NHP) and the French version of the Arthritis Impact Measurement Scale 2 (AIMS2)] were also obtained. RESULTS: One hundred twenty-three patients had a THA (mean age 62 years) and 60 had a TKA (mean age 68 years). Preoperative clinical features were those commonly found in these populations. For THA, the 6-week, 6-month and 1-year assessments showed an improvement (2.7 and 2.8 points on the 0 to 10 NHP). For TKA, improvement came later and was less significant with 0.8, 1.8 and 1.5 point improvements. The AIMS 2 did not appear to be perfectly adapted to measure this dimension. Improvement in pain came earlier and was greater for THA than for TKA on all measurement scales. For THA, psychological capacity improved by 0.7, 1.4 and 1.5 points on the 0 to 10 AIMS 2 at 6 weeks, 6 months and 12 months respectively. For TKA, improvement was to the same order with 1.1 and 1.2 point improvements at 6 weeks and 6 months respectively. DISCUSSION: These findings confirm the clear improvement in QOL after THA and TKA, mainly due to physical and psychological dimensions. The QOL measurements allow comparisons with other surgical procedures in other fields. They provide supplementary information, notably concerning pain and are particularly useful in orthopedic surgery. The questionnaires are generally well accepted by the patients, particularly short self-administered questionnaires. They provide useful information on the efficacy of THA and TKA in terms of human and social costs and open new perspectives for analysis of prognostic factors for optimal QOL of operated patients.

Zinc elevates neuropeptide Y levels in rat pheochromocytoma cells by a mechanism independent of L-channel mediated inhibition of release.

Both zinc and neuropeptide Y (NPY) have been implicated as playing a role in seizures and feeding behavior. We investigated the hypothesis that zinc could regulate levels of NPY, and found that chronic exposure to 50-100 microM zinc increased levels of cellular NPY in cultured PC12 cells grown in the presence of nerve growth factor. Zinc's effect on NPY was specific, time- and concentration-dependent, and independent of inhibition of NPY release secondary to blockade of dihydropyridine-sensitive calcium channels. These results are consistent with a role for zinc in regulating hippocampal NPY following high-frequency neuronal activity.

A novel family of mammalian taste receptors.

In mammals, taste perception is a major mode of sensory input. We have identified a novel family of 40-80 human and rodent G protein-coupled receptors expressed in subsets of taste receptor cells of the tongue and palate epithelia. These candidate taste receptors (T2Rs) are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. Notably, a single taste receptor cell expresses a large repertoire of T2Rs, suggesting that each cell may be capable of recognizing multiple tastants. T2Rs are exclusively expressed in taste receptor cells that contain the G protein alpha subunit gustducin, implying that they function as gustducin-linked receptors. In the accompanying paper, we demonstrate that T2Rs couple to gustducin in vitro, and respond to bitter tastants in a functional expression assay.

T2Rs function as bitter taste receptors.

Bitter taste perception provides animals with critical protection against ingestion of poisonous compounds. In the accompanying paper, we report the characterization of a large family of putative mammalian taste receptors (T2Rs). Here we use a heterologous expression system to show that specific T2Rs function as bitter taste receptors. A mouse T2R (mT2R-5) responds to the bitter tastant cycloheximide, and a human and a mouse receptor (hT2R-4 and mT2R-8) responded to denatonium and 6-n-propyl-2-thiouracil. Mice strains deficient in their ability to detect cycloheximide have amino acid substitutions in the mT2R-5 gene; these changes render the receptor significantly less responsive to cycloheximide. We also expressed mT2R-5 in insect cells and demonstrate specific tastant-dependent activation of gustducin, a G protein implicated in bitter signaling. Since a single taste receptor cell expresses a large repertoire of T2Rs, these findings provide a plausible explanation for the uniform bitter taste that is evoked by many structurally unrelated toxic compounds.

Varied effects of 1-octanol on gap junctional communication between ovarian epithelial cells and oocytes of Oncopeltus fasciatus, Hyalophora cecropia, and Drosophila melanogaster.

In insect gap junctions, species-specific differences occur in response to the purported gap junction uncoupling agent, 1-octanol. Changes in gap junctional communication between oocytes and their epithelial cells following treatment with 1-octanol were assayed in Oncopeltus fasciatus (the milkweed bug), Hyalophora cecropia (the American silk moth), and Drosophila melanogaster. In all three species, microinjection of untreated control follicles with Lucifer yellow CH revealed extensive dye coupling among epithelial cells and between epithelial cells and their oocytes. Also for all three species, treatment with octanol appeared to completely block dye coupling and increase oocyte input resistance. The effect on electrical coupling varied. In Drosophila, octanol diminished the electrical coupling from 64% (0.64 coupling coefficient) in controls to 53% in treated follicles. In Hyalophora, the coupling ratio remained the same following treatment. In Oncopeltus, octanol actually increased the electrical coupling ratio from 84% in controls to 94% in treated follicles. While 0.5 mM octanol left some Oncopeltus epithelial cells dye coupled to the oocyte, the electrical coupling ratio was increased slightly more by this concentration than by 1 or 5 mM octanol solutions, although the differences were not significant. While input resistance (R(o )) increased in all three following treatment with octanol, there was considerable difference in the magnitude of the response. Average oocyte R(o ) for Oncopeltus increased the least of the three species, rising from 196-240 kOhm. Both Hyalophora, with a nearly fourfold increase from 230-900 kOhm or more, and Drosophila, with a twofold increase from 701 kOhm to over 1.2 MegOhm showed much larger changes. Results shown here indicate that insect gap junctions have more varied responses to this common gap junction antagonist than have been reported for their vertebrate counterparts. Arch.

Analysis of frozen sections of intraoperative specimens obtained at the time of reoperation after hip or knee resection arthroplasty for the treatment of infection.

BACKGROUND: Despite the effectiveness of a two-stage exchange protocol for the treatment of deep periprosthetic infection, infection can persist after resection arthroplasty and treatment with antibiotics, leading to a failed second-stage reconstruction. Intraoperative analysis of frozen sections has been shown to have a high sensitivity and specificity for the identification of infection at the time of revision arthroplasty; however, the usefulness of this test at the time of reoperation after resection arthroplasty and treatment with antibiotics is, to our knowledge, unknown. METHODS: The medical records of sixty-four consecutive patients who had had a resection arthroplasty of either the knee (thirty-three patients) or the hip (thirty-one patients) and had had intraoperative analysis of frozen sections of periprosthetic tissue obtained at the time of a second-stage operation were reviewed. The mean interval between the resection arthroplasty and the attempted reimplantation was nineteen weeks. The results of the intraoperative analysis of the frozen sections were compared with those of analysis of permanent histological sections of the same tissues and with those of intraoperative cultures of specimens obtained from within the joint. The findings of the analyses of the frozen sections and the permanent histological sections were considered to be consistent with acute inflammation and infection if a mean of ten polymorphonuclear leukocytes or more per high-power field (forty times magnification) were seen in the five most cellular areas. RESULTS: The intraoperative frozen sections of the specimens from two patients (one of whom was considered to have a persistent infection) met the criteria for acute inflammation. Four patients were considered to have a persistent infection on the basis of positive intraoperative cultures or permanent histological sections. Overall, intraoperative analysis of frozen sections at the time of reimplantation after resection arthroplasty had a sensitivity of 25 percent (detection of one of four persistent infections), a specificity of 98 percent, a positive predictive value of 50 percent (one of two), a negative predictive value of 95 percent, and an accuracy of 94 percent. CONCLUSIONS: A negative finding on intraoperative analysis of frozen sections has a high predictive value with regard to ruling out the presence of infection; however, the sensitivity of the test for the detection of persistent infection is poor.

Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity.

Taste represents a major form of sensory input in the animal kingdom. In mammals, taste perception begins with the recognition of tastant molecules by unknown membrane receptors localized on the apical surface of receptor cells of the tongue and palate epithelium. We report the cloning and characterization of two novel seven-transmembrane domain proteins expressed in topographically distinct subpopulations of taste receptor cells and taste buds. These proteins are specifically localized to the taste pore and are members of a new group of G protein-coupled receptors distantly related to putative mammalian pheromone receptors. We propose that these genes encode taste receptors.