Urinary Malondialdehyde (MDA) Concentrations in the General Population-A Systematic Literature Review and Meta-Analysis.

Oxidative stress has been associated with various inflammation-related human diseases. It is defined as an imbalance between the production and elimination of reactive oxygen species (ROS). ROS can oxidize proteins, lipids, and DNA, and some of these oxidized products are excreted in urine, such as malondialdehyde (MDA), which is considered a biomarker for oxidative damage of lipids. To interpret changes of this biomarker as a measure of oxidative species overproduction in humans, a background range for urinary MDA concentration in the general population is needed. We sought to establish urinary MDA concentration ranges for healthy adult populations based on reported values in the available scientific literature. We conducted a systematic review and meta-analysis using the standardized protocol registered in PROSPERO (CRD42020146623). EMBASE, PubMed, Web of Science, and Cochrane library databases were searched from journal inception up to October 2020. We included 35 studies (divided into 47 subgroups for the quantitative analysis). Only studies that measured creatinine-corrected urinary MDA with high-performance liquid chromatography (HPLC) with mass spectrometry (MS), fluorescence detection, or UV photometry were included. The geometric mean (GM) of urinary MDA concentration was 0.10 mg/g creatinine and 95% percentile confidence interval (CI) 0.07-0.12. Age, geographical location but not sex, and smoking status had a significant effect on urinary MDA concentrations. There was a significant increasing trend of urinary MDA concentrations with age. These urinary MDA values should be considered preliminary, as they are based on mostly moderate to some low-quality evidence studies. Although urinary MDA can reliably reflect excessive oxidative stress in a population, the influence of physiological parameters that affect its meaning needs to be addressed as well as harmonizing the chemical analytical methods.

Reference Ranges of 8-Isoprostane Concentrations in Exhaled Breath Condensate (EBC): A Systematic Review and Meta-Analysis.

Isoprostanes are physiopathologic mediators of oxidative stress, resulting in lipid peroxidation. 8-isoprostane seems particularly useful for measuring oxidative stress damage. However, no reference range values are available for 8-isoprosante in exhaled breath condensate (EBC) of healthy adults, enabling its meaningful interpretation as a biomarker. We conducted this systematic review and meta-analysis according to the protocol following PROSPERO (CRD42020146623). After searching and analyzing the literature, we included 86 studies. After their qualitative synthesis and risk of bias assessment, 52 studies were included in meta-analysis. The latter focused on studies using immunological analytical methods and investigated how the concentrations of 8-isoprostane differ based on gender. We found that gender had no significant effect in 8-isoprostane concentration. Among other studied factors, such as individual characteristics and factors related to EBC collection, only the device used for EBC collection significantly affected measured 8-isoprostane concentrations. However, adjustment for the factors related to EBC collection, yielded uncertainty whether this effect is due to the device itself or to the other factors. Given this uncertainty, we estimated the reference range values of 8-isoprostane stratified by gender and EBC collection device. A better standardization of EBC collection seems necessary; as well more studies using chemical analytical methods to extend this investigation.

Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis.

Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant system, but when in excess concentration, they can oxidize proteins, lipids, and DNA. DNA damage is usually repaired, and the oxidized products are excreted in urine. 8-hydroxy-2-deoxyguanosine is considered a biomarker for oxidative damage of DNA. It is needed to define background ranges for 8-OHdG, to use it as a measure of oxidative stress overproduction. We established a standardized protocol for a systematic review and meta-analysis to assess background ranges for urinary 8-OHdG concentrations in healthy populations. We computed geometric mean (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis. We retrieved an initial 1246 articles, included 84 articles, and identified 128 study subgroups. We stratified the subgroups by body mass index, gender, and smoking status reported. The pooled GM value for urinary 8-OHdG concentrations in healthy adults with a mean body mass index (BMI) ≤ 25 measured using chemical methods was 3.9 ng/mg creatinine (interquartile range (IQR): 3 to 5.5 ng/mg creatinine). A significant positive association was observed between smoking and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was observed.

Focal uterine T-cell lymphoma in an ovariectomized cat.

CASE DESCRIPTION A 14-year-old ovariectomized domestic shorthair cat was evaluated because of periuria and perineal licking of 3 days' duration. CLINICAL FINDINGS On initial examination, an abdominal mass was palpable cranial to the urinary bladder. The perineal area was soiled with a blood-tinged mucous fluid. Abdominal ultrasonography revealed a vascularized, focal, and circumferential thickening of the right uterine horn, involving particularly the muscular layer. No evidence of dissemination was noted. TREATMENT AND OUTCOME Hysterectomy was performed, revealing a localized, 2.5 × 4-cm firm mass with a smooth surface within the right uterine horn. Results of histologic examination and immunohistochemical analysis of tissue samples from the mass suggested high-grade T-cell uterine lymphoma. Owners declined medical and chemotherapeutic treatments. One year later, the cat developed diabetes mellitus, which was medically treated. Nineteen months following the uterine lymphoma diagnosis, a central corneal ulcer associated with a right retrobulbar mass was diagnosed. The cat was euthanized, and the retrobulbar mass was removed. Immunohistochemical staining revealed evidence of high-grade B-cell retrobulbar lymphoma. CLINICAL RELEVANCE The clinical outcome of this cat with uterine lymphoma was favorable for 19 months after diagnosis, with no treatment other than hysterectomy. Whether the same outcome could be expected for other cats with this rarely reported neoplasm remains to be determined. Uterine lymphoma should be considered as a possible cause of dysuria in an ovariectomized cat.

Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.

BACKGROUND: Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo (control group), benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all groups received in addition 0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days. RESULTS: Benazepril, robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs and no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables. The primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma clearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of benazepril plus robenacoxib compared to the other three groups, and was also significantly higher in females receiving only benazepril compared to the control. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system, evidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group in cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by robenacoxib (males only). Benazepril, robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by furosemide. CONCLUSIONS: The combination of benazepril and robenacoxib was well tolerated and either increased or had a neutral effect on GFR in healthy cats without or with concomitant furosemide. The combination of benazepril and robenacoxib reduced plasma aldosterone concentrations increased by furosemide. It is recommended to test the efficacy and safety of the combined use of benazepril and robenacoxib in cats with clinical disease, notably proteinuric chronic kidney disease.

Unilateral persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous in a rabbit.

A 3-month wild rabbit was presented for examination of ocular opacities in the left eye. A complete bilateral ocular examination including slit-lamp examination, indirect ophthalmoscopy, tonometry, and ultrasound biomicroscopy was performed. Biomicroscopy of the lens of the left eye showed a retrolental fibrovascular membrane causing leukocoria. The opacity prevented biomicroscopy of the vitreous and funduscopy OS. No other disorder was present in either eye. Ultrasound examination did not show any difference between the right and left eye. Histopathological examination showed a 50-µm thick, preretinal, retrolental, nonpigmented, fibrovascular tissue. Posterior synechiae were present, but no other lesion of the posterior segment was found in this eye. These ocular abnormalities are consistent with a persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous (PHTVL/PHPV), similar to those described in other species.

Mastocytemia associated with a visceral mast cell tumor in a Sumatran tiger (Panthera tigris).

A 6-yr-old male Sumatran tiger (Panthera tigris) with no significant past clinical history was anesthetized for clinical examination after 5 days of lethargy. Clinically, the animal presented with anorexia, pale mucous membranes, and icterus. Hematologic results indicated moderate anemia and severe thrombocytopenia and showed a circulating population of atypical mast cells. The tiger died during anesthesia. On postmortem examination, abdominal hemorrhage associated with marked diffuse hepato-splenomegaly and mesenteric, hepatic, and splenic lymph node hypertrophy were observed. A visceral mast cell tumor was confirmed by histologic examination and toluidine blue staining, with splenic, hepatic, lymphoid, renal, and pulmonary infiltration. Hematologic, postmortem, and histologic findings were consistent with mastocytemia associated with the splenic form of mast cell tumor described in domestic cats.

Patent ductus arteriosus in an adult amur leopard (Panthera pardus orientalis).

A clinically healthy 16-yr-old female leopard (Panthera pardus orientalis) was diagnosed with a patent ductus arteriosus on echocardiography and later confirmed on necropsy A murmur was heard on auscultation during a routine examination, and the congenital defect was an incidental finding. The animal had been asymptomatic its entire life. This deformity is rarely observed in nondomestic felids and may be asymptomatic, as has been described in domestic cats.

Intestinal T-cell lymphoma in a fossa (Cryptoprocta ferox).

A 10-year-old male fossa (Crytoprocta ferox) exhibited clinical signs of diarrhea, anorexia and weight loss. Chemistry values and echographic results were suggestive of intestinal lymphoma. Postmortem examination revealed severe multifocal wall thickening of the small intestine with severe enlargement of the pancreatic lymph node. Microscopically, the small intestine was multifocally transmurally infiltrated by large neoplastic round cells also found in the pancreatic lymph node and the liver. On immunohistochemistry, the neoplastic cells stained intensely with CD3 and didn't stain with CD79a. Based on these findings, a diagnosis of intestinal T-cell lymphoma with pancreatic lymph node and liver involvement was made. To the authors' knowledge, this is the first report of a lymphoma with immunohistochemical phenotyping in a fossa.