Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity.

Poly(ADP-ribose)glycohydrolase (PARG) is the major enzyme capable of rapidly hydrolyzing poly(ADP-ribose) (PAR) formed by the diverse members of the PARP enzyme family. This study presents an alternative splice mechanism by which two novel PARG protein isoforms of 60 kDa and 55 kDa are expressed from the human PARG gene, termed hPARG60 and hPARG55, respectively. Homologous forms were found in the mouse (mPARG63 and mPARG58) supporting the hypothesis that expression of small PARG isoforms is conserved among mammals.

Experimental transmission and induction of ranaviral disease in Western Ornate box turtles (Terrapene ornata ornata) and red-eared sliders (Trachemys scripta elegans).

An experimental transmission study was designed to determine whether a causal relationship exists between a Ranavirus (BSTRV) isolated from a Burmese star tortoise that died and the lesions observed in that tortoise. A pilot study was performed with 3 box turtles (Terrapene ornata ornata) and 3 red-eared sliders (RESs; Trachemys scripta elegans) to assess their suitability in a larger study. Based on the outcome of this study, RESs were selected, and 2 groups of 4 RESs received either an oral (PO) or intramuscular (IM) inoculum containing10(5) 50% Tissue Culture Infecting Dose (TCID(50)) of a BSTRV-infected cell lysate.

The regulatory T cell gene FOXP3 and genetic susceptibility to thyroid autoimmunity: an association analysis in Caucasian and Japanese cohorts.

FOXP3 is a key gene in the development of regulatory T cells (Treg). FOXP3 expression commits naïve T cells to become Treg cells. Indeed, mutations in the FOXP3 gene cause severe systemic autoimmune diseases in humans and in mice.

Water maze performance in young male Long-Evans rats is inversely affected by dietary intakes of niacin and may be linked to levels of the NAD+ metabolite cADPR.

Niacin is converted in tissues to NAD(+), which is required for synthesis of the intracellular calcium signaling molecule cyclic ADP-ribose (cADPR). cADPR is involved in many aspects of cognitive function, including long-term depression, in the hippocampus, a brain region that regulates spatial learning ability. The objective of this study was to determine whether niacin deficiency and pharmacological nicotinamide supplementation have an effect on spatial learning ability in young male Long-Evans rats as assessed by the Morris Water Maze, and whether brain NAD(+) and cADPR are modified by dietary niacin intake.

The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future.

Autoimmune thyroid diseases (AITD) are common autoimmune diseases, affecting up to 5% of the general population. Thyroid-directed autoimmunity is manifested in two classical autoimmune conditions, Hashimoto's thyroiditis, resulting in hypothyroidism and Graves' disease resulting in hyperthyroidism. Autoimmune thyroid diseases arise due to an interplay between environmental and genetic factors.

A CD40 Kozak sequence polymorphism and susceptibility to antibody-mediated autoimmune conditions: the role of CD40 tissue-specific expression.

Previously, we and others have demonstrated the association of a C/T single nucleotide polymorphism (SNP), in the Kozak sequence of CD40, with Graves' disease (GD). Here, using an expanded data set of patients, we confirm the association of the CD40 SNP with GD (n=210, P=0.002, odds ratio (OR)=1.

Respiratory bronchoscopy of subadult American alligators (Alligator mississippiensis) and tracheal wash evaluation.

Twelve healthy approximately 3-yr-old captive-born 4.5-9 kg American alligators (Alligator mississipiensis) each had bronchoscopy and tracheal washes performed four times during a 10-mo period to evaluate seasonal respiratory microbiology and cytology. Cytologic evaluation of most samples showed a small amount of mucus and low numbers of ciliated columnar epithelium, cubodial epithelium, and keratinized squamous cells.

Plasma concentrations of enrofloxacin after single-dose oral administration in loggerhead sea turtles (Caretta caretta).

Plasma concentrations and pharmacokinetics of enrofloxacin were determined in 12 loggerhead sea turtles (Caretta caretta) after oral administration. Six turtles in group 1 and group 2 received enrofloxacin at 10 mg/kg and 20 mg/kg of body weight, respectively. Blood was collected from the cervical sinus before administration and at timed intervals up to 168 hr following administration.

Altered poly(ADP-ribose) metabolism impairs cellular responses to genotoxic stress in a hypomorphic mutant of poly(ADP-ribose) glycohydrolase.

Genotoxic stress activates nuclear poly(ADP-ribose) (PAR) metabolism leading to PAR synthesis catalyzed by DNA damage activated poly(ADP-ribose) polymerases (PARPs) and rapid PAR turnover by action of nuclear poly(ADP-ribose) glycohydrolase (PARG). The involvement of PARP-1 and PARP-2 in responses to DNA damage has been well studied but the involvement of nuclear PARG is less well understood. To gain insights into the function of nuclear PARG in DNA damage responses, we have quantitatively studied PAR metabolism in cells derived from a hypomorphic mutant mouse model in which exons 2 and 3 of the PARG gene have been deleted (PARG-Delta2,3 cells), resulting in a nuclear PARG containing a catalytic domain but lacking the N-terminal region (A domain) of the protein.

A pilot study evaluating the efficacy of topically applied niacin derivatives for treatment of female pattern alopecia.

Background: Female pattern alopecia is a common dermatologic condition that manifests after puberty. The only approved drug treatment for this condition is 2% minoxidil for topical application.

Aims: This pilot study examined the effect of topical application of two niacin derivatives, octyl nicotinate and tetradecyl nicotinate, on hair fullness in female alopecia.

Analysis and stability study of myristyl nicotinate in dermatological preparations by high-performance liquid chromatography.

Myristyl nicotinate is an ester prodrug under development for delivery of nicotinic acid to skin for treatment and prevention of conditions that involve skin barrier impairment such as chronic photodamage and atopic dermatitis or for mitigating skin barrier impairment that results from therapy such as retinoids or steroids. The formulation stability of myristyl nicotinate is crucial because even small amounts of free nicotinic acid cause skin flushing, an effect that is not harmful but would severely limit tolerability. We report here reversed-phase HPLC methods for the rapid analysis of myristyl nicotinate and nicotinic acid in dermatological preparations.

A rapid HPLC method for simultaneous determination of tretinoin and isotretinoin in dermatological formulations.

A rapid method using an isocratic high-pressure liquid chromatography and UV detection for determination of both all-trans retinoic acid (tretinoin) and 13-cis retinoic acid (isotretinoin) in dermatological preparations is presented. Tretinoin and isotretinoin samples were extracted with acetonitrile by a procedure that can be completed in less than 10 min. Subsequent separation and quantification of amounts as low as 10 pmol was accomplished in less than 15 min using reversed-phase HPLC with isocratic elution with 0.

Future directions in reptile medical education.

Reptile medicine has emerged as a specialty area within the broader field of zoological medicine. It encompasses the medical needs of approximately 7,500 vertebrate species. This vertebrate class is highly diversified, having biological and medical peculiarities that differ both between and within major groups.

Neurological disease in wild loggerhead sea turtles Caretta caretta.

Beginning in October 2000, subadult loggerhead sea turtles Caretta caretta showing clinical signs of a neurological disorder were found in waters off south Florida, USA. Histopathology indicated generalized and neurologic spirorchiidiasis. In loggerhead sea turtles (LST) with neurospirorchiidiasis, adult trematodes were found in the meninges of the brain and spinal cord of 7 and 3 affected turtles respectively, and multiple encephalic intravascular or perivascular eggs were associated with granulomatous or mixed leukocytic inflammation, vasculitis, edema, axonal degeneration and occasional necrosis.

A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease.

Background: Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease.

Materials And Methods: We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive).

Pain after elective arthroscopy of the knee: a prospective, randomised, study comparing conventional NSAID to coxib.

Although outpatient knee arthroscopy is probably by far the most frequently performed orthopaedic procedure, there are limited guidelines or consensus concerning the peroral postoperative pain management. A diversity of analgesics both in potency and action is prescribed. The purpose of the present investigation was to grade the pain and need for rescue medication during the first 4 days after the knee arthroscopy, comparing a conventional nonsteroidal anti-inflammatory drug (NSAID) with a selective cox-II-inhibitor (coxib) as postoperative pain medication.

Seroepidemiology of parapoxvirus infections in captive and free-ranging California sea lions Zalophus californianus.

Cutaneous nodular lesions caused by parapoxvirus infections are commonly observed in stranded pinnipeds following their arrival at rehabilitation facilities. An indirect enzyme-linked immunosorbent assay (ELISA) was developed and validated to determine exposure to parapoxviruses in California sea lions Zalophus californianus in captivity and in the wild. The diagnostic performance of this assay was evaluated using receiver-operating characteristic analysis.

Pathology and preliminary characterization of a parapoxvirus isolated from a California sea lion (Zalophus californianus).

Cutaneous pox-like lesions are a common complication in the rehabilitation of pinnipeds. However, the exact identity, taxonomy, and host range of pinniped parapoxviruses remain unknown. During a poxvirus outbreak in May 2003 in California sea lions (Zalophus californianus) at a marine mammal rehabilitation facility, multiple raised, firm, 1-3-cm skin nodules from the head, neck, and thorax of one sea lion weanling pup that spontaneously died were collected.

Intranuclear coccidiosis in tortoises: nine cases.

Chelonian intranuclear coccidiosis has been reported once, in two radiated tortoises (Geochelone radiata), and is apparently rare. We describe intranuclear coccidiosis diagnosed histologically in two radiated tortoises, three Travancore tortoises (Indotestudo forstenii), two leopard tortoises (Geochelone pardalis), one bowsprit tortoise (Chersina angulata), and one impressed tortoise (Manouria impressa). Infection was systemic and involved alimentary, urogenital, respiratory, lymphoid, endocrine, and integumentary systems.

Parapoxviruses of seals and sea lions make up a distinct subclade within the genus Parapoxvirus.

Poxviruses of seals and sea lions have been tentatively identified as both orthopoxviruses and parapoxviruses, but their exact identity remained unconfirmed. Here, poxviral DNA sequences were generated from 39 clinical cases and compared to sequences from earlier poxvirus isolates from seals (Phocidae) and sea lions (Otariidae). Six genetically distinct poxvirus strains were detected, of which three were previously unrecognized.

Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection.

Endogenous chromophores in human skin serve as photosensitizers involved in skin photocarcinogenesis and photoaging. Absorption of solar photons, particularly in the UVA region, induces the formation of photoexcited states of skin photosensitizers with subsequent generation of reactive oxygen species (ROS), organic free radicals and other toxic photoproducts that mediate skin photooxidative stress. The complexity of endogenous skin photosensitizers with regard to molecular structure, pathways of formation, mechanisms of action, and the diversity of relevant skin targets has hampered progress in this area of photobiology and most likely contributed to an underestimation of the importance of endogenous sensitizers in skin photodamage.

Reversible Epstein-Barr virus-negative lymphadenopathy and bone marrow involved by Hodgkin's lymphoma in a rheumatoid arthritis patient undergoing long-term treatment with low-dose methotrexate: a case report and review of the literature.

We report a case of spontaneous regression of Epstein-Barr virus (EBV)-negative methotrexate-associated lymphadenopathy occurring with Hodgkin's lymphoma in the bone marrow of a 48-year-old woman with rheumatoid arthritis. Following 10 years of treatment with low-dose methotrexate, the patient developed pancytopenia, hypercalcemia, and elevated levels of liver enzymes over the course of 2 months. A computed tomography scan of the abdomen revealed splenomegaly and enlarged abdominal lymph nodes.

Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites.

Several lines of evidence suggest that rutin, flavonoid in fruits and vegetables, or one of its metabolites may effectively modulate advanced glycation end product (AGE) formation. Following ingestion, rutin forms metabolites that include 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3,4-dihydroxytoluene (3,4-DHT), m-hydroxyphenylacetic acid (m-HPAA), 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA) and 3,5,7,3',5'-pentahydroxyflavonol (quercetin). We studied the effects of rutin and its metabolites on the formation of AGE biomarkers such as pentosidine, collagen-linked fluorescence, N(epsilon)-carboxymethyllysine (CML) adducts, glucose autoxidation and collagen glycation, using an in vitro model where collagen I was incubated with glucose.