Crisis in the Chest: Acute Chest Syndrome as a Sequela of Tricuspid Valve Endocarditis.

The management of acute chest syndrome (ACS) in sickle cell disease occurring concurrently with pulmonary embolism resulting from tricuspid valve endocarditis poses an atypical challenge. We present a case in which this complex interaction occurs and the prompt interventions that were utilized to give the best possible outcome.

Pregnancies in Elderly Mothers over 40 years: What to Expect from the Rising New Age High-Risk Cohort?

Introduction: Elderly women are believed to experience many risks associated with pregnancy. Literature fails to provide a clear consensus on the age group in which there is a rise in risk and pathophysiology contributing. 'Pregnancies over forty' are increasing in society, owing to changing lifestyles and sensibilities of youth and the advent of assisted reproductive techniques. In India, studies on elderly pregnant women above 40 years of age are lacking. The aim of this study is to assess these pregnancies, their course, obstetric and perinatal outcomes in women delivering above 40 years. Methods: The study group (Group A) comprised of pregnancies in 50 women at age ≥ 40 years on the date of delivery. The control group (Group B) had 50 women who delivered subsequent to the study group and age < 40. Various parameters and outcomes including parity, gestational age, number of gestations, co-existing medical illnesses, the incidence of hypertensive diseases of pregnancy (HDP), gestational diabetes mellitus (GDM), pre-term labor, mode of delivery, birth weight and obstetric and neonatal outcomes were compared. Chi-square test and independent T test were used for statistical analysis. Results: While a good number of patients conceived spontaneously and with basic infertility management, i.e., 84% in the elderly gravid group (Group A) and 96% in the control group (Group B), the number of patients who required ART in Group A were statistically significant (Group A 16% and Group B 4%). Incidence of pre-existing medical diseases like hypertension, diabetes mellitus, thyroid dysfunction, other auto-immune diseases and chronic diseases were noted to be high (26%) in Group A (statistically significant difference). Incidence of HDP, GDM and fetal growth restriction were high in Group A. Tendency to have the presence of fibroid uterus was high in patients in Group A, i.e., 24%, compared to only 8% in the control group; difference was statistically significant. Proportion of pre-term deliveries were high in Group A. Cesarean section rate was high in Group A, though it was not statistically significant. Other perinatal observations and neonatal outcomes were comparable in both groups; differences were not statistically significant. Conclusion: The study reveals an association of a high-risk course of pregnancies in women above the age of 40 years. Proportions of IVF pregnancies are higher in elderly women. Interestingly, the proportion of women in elderly group who conceived spontaneously and with basic infertility management including IUI was 84% in the present study. Medical comorbidities and incidence of fibroids were high in elderly women. Obstetric and neonatal outcomes of these pregnancies when managed efficiently are favorable.

The Impact of Glucagon-Like Peptide-1 Receptor Agonist on the Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis and Systematic Review.

Background: Since 2005, the cardioprotective effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have garnered attention. The cardioprotective effect could be an added benefit to the use of GLP-1 RA. This systematic review and meta-analysis aimed at summarizing observational studies that recruited type 2 diabetes individuals with fewer cardiovascular (CV) events before enrolling in the research. Methods: Systematically, the databases were searched for observational studies reporting compound CV events and deaths in type 2 diabetics without having the risk of cardiovascular diseases (CVDs) compared to other glucose-lowering agents. A meta-analysis was carried out using random effects model to estimate the overall hazard ratio (HR) with a 95% confidence interval (CI). Five studies were found eligible for the systematic review including a total of 64,452 patients receiving either liraglutide (three studies) or exenatide (two studies). Results: The pooled HR for major adverse cardiac event (MACE) and extended MACE was 0.72 (95% CI: 0.65 - 0.93, I2 = 68%) and 0.93 (95% CI: 0.89 - 0.98, I2 = 29%), respectively. The pooled HR for hospitalization due to heart failure (HHF) and occurrence of HF was 0.84 (95% CI: 0.77 - 0.91, I2 = 79%) and 0.83 (95% CI: 0.75 - 0.94, I2 = 95%), respectively. For stroke, GLP-1 RA was associated with a significant risk reduction of 0.86 (95% CI: 0.75 - 0.98, I2 = 81%). There was no significant myocardial infarction (MI) risk reduction with GLP-1 RA. As for all-cause mortality, the pooled HR for the occurrence of all-cause mortality was 0.82 (95% CI: 0.76 - 0.88, I2 = 0%). The pooled HR for the occurrence of CV death was 0.75 (95% CI: 0.65 - 0.85, I2 = 38%). GLP-1 RA therapy was associated with a significantly low risk of MACE, extended MACE, all-cause mortality, and CV mortality. Except for MACE, the heterogenicity among the studies was low. Conclusion: We conclude that GLP-1 RA is associated with a low risk of CV events composites and mortality. The findings support the cardioprotective effect of GLP-1 RA.

Prevalence and significance of extracardiac uptake on pyrophosphate imaging in the SCAN-MP study: the first 379 cases.

INTRODUCTION: Technetium-labeled bone-avid radiotracers can be used to diagnose transthyretin cardiac amyloidosis (ATTR-CA). Extracardiac uptake of technetium pyrophosphate (Tc-99m PYP) in this context has not been extensively explored and its significance is not well characterized. We assessed extracardiac Tc-99m PYP uptake in individuals undergoing nuclear scintigraphy and the extent of clinically actionable findings. METHODS: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study utilizes Tc-99m PYP imaging to identify ATTR-CA in self-identified Black and Caribbean Hispanic participants ≥ 60 years old with heart failure. We characterized the distribution of extracardiac uptake, including stratification of findings by timing of scan (1 hour vs 3 hours after Tc-99m PYP administration) and noted any additional testing in these subjects. RESULTS: Of 379 participants, 195 (51%) were male, 306 (81%) Black race, and 120 (32%) Hispanic ethnicity; mean age was 73 years. Extracardiac Tc-99m PYP uptake was found in 42 subjects (11.1%): 21 with renal uptake only, 14 with bone uptake only, 4 with both renal and bone uptake, 2 with breast uptake, and 1 with thyroid uptake. Extracardiac uptake was more common in subjects with Tc-99m PYP scans at 1 hour (23.8%) than at 3 hours (6.2%). Overall, four individuals (1.1%) had clinically actionable findings. CONCLUSION: Extracardiac Tc-99m PYP uptake manifested in about 1 in 9 SCAN-MP subjects but was clinically actionable in only 1.1% of cases.

Prognosis of Transthyretin Cardiac Amyloidosis Without Heart Failure Symptoms.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure (HF). Advances in diagnosis and therapy have increased the number of patients diagnosed at early stages, but prognostic data on patients without HF symptoms are lacking. Moreover, it is unknown whether asymptomatic patients benefit from early initiation of transthyretin (TTR) stabilizers. Objectives: The aim of this study was to describe the natural history and prognosis of ATTR-CM in patients without HF symptoms. Methods: Clinical characteristics and outcomes of patients with ATTR-CM without HF symptoms were retrospectively collected at 6 international amyloidosis centers. Results: A total of 118 patients (78.8% men, median age 66 years [IQR: 53.8-75 years], 68 [57.6%] with variant transthyretin amyloidosis, mean left ventricular ejection fraction 60.5% ± 9.9%, mean left ventricular wall thickness 15.4 ± 3.1 mm, and 53 [45%] treated with TTR stabilizers at baseline or during follow-up) were included. During a median follow-up period of 3.7 years (IQR: 1-6 years), 38 patients developed HF symptoms (23 New York Heart Association functional class II and 14 functional class III or IV), 32 died, and 2 required cardiac transplantation. Additionally, 20 patients received pacemakers, 13 developed AF, and 1 had a stroke. Overall survival was 96.5% (95% CI: 91%-99%), 90.4% (95% CI: 82%-95%), and 82% (95% CI: 71%-89%) at 1, 3, and 5 years, respectively. Treatment with TTR stabilizers was associated with improved survival (HR: 0.31; 95% CI: 0.12-0.82; P = 0.019) and remained significant after adjusting for sex, age, ATTR-CM type, and estimated glomerular filtration rate (HR: 0.18; 95% CI: 0.06-0.55; P = 0.002). Conclusions: After a median follow-up period of 3.7 years, 1 in 3 patients with asymptomatic ATTR-CM developed HF symptoms, and nearly as many died or required cardiac transplantation. Treatment with TTR stabilizers was associated with improved prognosis.

PRE-084 ameliorates adenine-induced renal fibrosis in rats.

2-(4-morpholinoethyl)- 1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084) is a selective sigma 1 receptor agonist. It has been shown that PRE-084 protected various tissues from experimental injury. However, no reports are available on its effect on renal fibrosis. Rat model of adenine-induced chronic kidney disease was chosen to study this. Adenine feeding in rats caused renal dysfunction as shown by increased serum creatinine and reduced creatinine clearance along with increased high molecular weight (HMW) urine protein excretion. Further, adenine feeding induced profibrotic changes in the kidney as reflected by increased expression of alpha-smooth muscle actin (α-SMA), fibroblast specific protein-1 (FSP-1) and matrix metalloproteinase-2 (MMP-2) activity; reduced cytokeratin expression. Further, there was excess deposition of extracellular matrix in the kidney, a striking character of fibrosis. However, administration of PRE-084 to adenine fed rats led to reduction in creatinine and proteinuria parameters partly. This was accompanied by reduced expression of α-SMA, FSP-1 and MMP-2 activity and slight restoration of cytokeratin levels leading to reduced extracellular matrix deposition in the kidney. These data demonstrate that PRE-084 partly ameliorated renal dysfunction and exhibited anti-fibrotic potential in the kidney of adenine fed rats.

Racial Differences in Val122Ile-Associated Transthyretin Cardiac Amyloidosis.

BACKGROUND: The valine-to-isoleucine substitution (Val122Ile) is the most common variant of transthyretin (TTR) amyloidosis in the United States, affecting primarily individuals of African descent. This variant has been identified recently in a cluster of white individuals in Italy. METHODS AND RESULTS: Clinical phenotype and chamber performance of Black and white individuals with Val122Ile TTR cardiac amyloidosis (ATTR-CA) were compared. Compared to white patients (n = 17), Black individuals (n = 53) had lower systolic blood pressures (110 vs 131 mmHg, <0.001), reduced pulse pressures (41 vs 58 mmHg; P < 0.001), and impaired renal function (eGFR 46 vs 67 mL/min/1.73m2; P < 0.001) at presentation. Systolic properties and arterial elastance were similar. Black patients had end-diastolic pressure-volume relationships that were shifted upward and leftward relative to those of white patients, indicating reduced left ventricular chamber capacitance. Pressure-volume area at a left ventricular end-diastolic pressure of 30 mmHg was lower in Black than in white individuals (8055 mmHg/mL vs 11,538 mmHg/mL; P = 0.008). CONCLUSION: Despite presenting at ages similar to those of white patients, Black individuals with Val122Ile-associated ATTR-CA had a greater degree of cardiac chamber dysfunction at the time of diagnosis due to impaired ventricular capacitance. Whether these differences are attributable to amyloidosis or other cardiovascular disease requires further study.

Fermentability of select polyphenol-rich substrates in the canine faecal inoculum and their interaction with a canine-origin probiotic: an in vitro appraisal.

BACKGROUND: This in vitro study aimed to compare the hindgut fermentability and digestibility of four different sources of polyphenols, namely orange (Citrus sinensis) peel (ORP), pomegranate (Punica granatum) peel (PMP), Indian blackberry (Syzygium cumini) pulp (IBP), and Jerusalem artichoke (Helianthus tuberosus) tuber (JAT), and their influence on the viability of a canine-origin probiotic, Lactobacillus johnsonii CPN23. RESULTS: An in vitro gas production test carried out using the four substrates for a period of 72 h with dog faecal inoculum indicated that the total gas production, dry matter, and organic matter digestibility were significantly (P < 0.001) higher with JAT, whereas they were lowest for PMP. Short-chain fatty acids production was significantly higher (P < 0.001) with ORP and JAT, with the least values recorded for PMP. The ammonia-nitrogen production was significantly (P < 0.001) higher with JAT than with ORP, IBP, and PMP, and a lower (P < 0.001) pH was evident with ORP, JAT, and IBP than with PMP. Viability of L. johnsonii CPN23 was tested in the presence of the polyphenol-rich extract from each of the four sources at varying doses (50, 500, 1000, 2500, and 5000 µg mL-1 ). PMP extract showed the highest inhibitory effect on the probiotic bacteria's growth in a dose- and time-dependent manner (P < 0.001). ORP and IBP extracts were stimulatory at the optimum dosage, whereas JAT reduced probiotic activity significantly at all doses tested. CONCLUSION: Overall, the results indicate a higher hindgut fermentability of JAT, ORP, and IBP, suggesting their potential beneficial effects for gut health application. An interaction study between polyphenol extract and L. johnsonii CPN23 showed a stimulatory effect of polyphenolic extracts from ORP and IBP on probiotic growth at optimal dosage. Consistent with the fermentation study findings, PMP extract reduced the growth of L. johnsonii CPN23 irrespective of the doses tested. © 2021 Society of Chemical Industry.

COVID-19 outcomes in hospitalized patients with active cancer: Experiences from a major New York City health care system.

BACKGROUND: The authors sought to study the risk factors associated with severe outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients with cancer. METHODS: The authors queried the New York University Langone Medical Center's records for hospitalized patients who were polymerase chain reaction-positive for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and performed chart reviews on patients with cancer diagnoses to identify patients with active cancer and patients with a history of cancer. Descriptive statistics were calculated and multivariable logistic regression was used to determine associations between clinical, demographic, and laboratory characteristics with outcomes, including death and admission to the intensive care unit. RESULTS: A total of 4184 hospitalized SARS CoV-2+ patients, including 233 with active cancer, were identified. Patients with active cancer were more likely to die than those with a history of cancer and those without any cancer history (34.3% vs 27.6% vs 20%, respectively; P < .01). In multivariable regression among all patients, active cancer (odds ratio [OR], 1.89; CI, 1.34-2.67; P < .01), older age (OR, 1.06; CI, 1.05-1.06; P < .01), male sex (OR for female vs male, 0.70; CI, 0.58-0.84; P < .01), diabetes (OR, 1.26; CI, 1.04-1.53; P = .02), morbidly obese body mass index (OR, 1.87; CI, 1.24-2.81; P < .01), and elevated D-dimer (OR, 6.41 for value >2300; CI, 4.75-8.66; P < .01) were associated with increased mortality. Recent cancer-directed medical therapy was not associated with death in multivariable analysis. Among patients with active cancer, those with a hematologic malignancy had the highest mortality rate in comparison with other cancer types (47.83% vs 28.66%; P < .01). CONCLUSIONS: The authors found that patients with an active cancer diagnosis were more likely to die from COVID-19. Those with hematologic malignancies were at the highest risk of death. Patients receiving cancer-directed therapy within 3 months before hospitalization had no overall increased risk of death. LAY SUMMARY: Our investigators found that hospitalized patients with active cancer were more likely to die from coronavirus disease 2019 (COVID-19) than those with a history of cancer and those without any cancer history. Patients with hematologic cancers were the most likely among patients with cancer to die from COVID-19. Patients who received cancer therapy within 3 months before hospitalization did not have an increased risk of death.

Cardiopulmonary exercise testing in patients with Cardiac Amyloidosis.

BACKGROUND: Cardiac involvement and dysfunction are common in patients presenting with AL and ATTR Amyloidosis. Cardiopulmonary exercise testing (CPET) performance is the gold standard to quantify functional capacity. PATIENTS AND METHODS: In this study, we evaluated CPET measurements in 41 patients with cardiac Amyloidosis and their correlation with current amyloid specific staging criteria. RESULTS: In both AL and ATTR cardiac Amyloidosis, percent predicted peak VO2 is significantly reduced and correlates with biomarker abnormalities. The association of cardiac biomarkers with peak VO2 is stronger for AL Amyloidosis (NT-proBNP (r = -0.57, P=0.006), Troponin (r = -0.70, p < 0.001) than ATTR (NT-proBNP (r = -0.4, P = 0.04) and Troponin (r = -0.57, P = 0.002) despite lower left ventricular mass in the former, suggesting that this may be further evidence for light chain toxicity in AL amyloidosis. CONCLUSION: Our findings suggest further evidence for AL toxicity.

Sex Differences in the Phenotype of Transthyretin Cardiac Amyloidosis Due to Val122Ile Mutation: Insights from Noninvasive Pressure-Volume Analysis.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is an under-recognized cause of heart failure with preserved ejection fraction. In the United States, the valine-to-isoleucine substitution (Val122Ile) is the most common inherited variant. Data on sex differences in presentation and outcomes of Val122Ile associated ATTR-CA are lacking. METHODS AND RESULTS: In a retrospective, single-center study of 73 patients diagnosed with Val122Ile associated ATTR-CA between 2001 and 2018, sex differences in clinical and echocardiographic data at the time of diagnosis were evaluated. Pressure-volume analysis using noninvasive single beat techniques was used to compare chamber performance. Compared with men (n = 46), women (n = 27) were significantly older at diagnosis, 76 years vs 69 years; P < .001. The end-systolic pressure-volume relationship, 5.1 mm Hg*m2/mL vs 4.3 mm Hg*m2/mL; P = .27, arterial elastance, 5.5 mm Hg*m2/mL vs 5.7 mm Hg*m2/mL; P = .62, and left ventricular capacitance were similar between sexes as was pressure-volume areas indexed to a left ventricular end-diastolic pressure of 30 mm Hg, a measure of overall pump function. The 3-year mortality rates were also similar, 34% vs 43%; P = .64. CONCLUSIONS: Despite being significantly older at time of diagnosis with Val122Ile associated ATTR-CA, women have similar overall cardiac chamber function and rates of mortality to men, suggesting a less aggressive disease trajectory. These findings should be confirmed with longitudinal studies.

Diagnosing Transthyretin Cardiac Amyloidosis by Technetium Tc 99m Pyrophosphate: A Test in Evolution.

OBJECTIVES: This study aimed to characterize trends in technetium Tc 99m pyrophosphate (99mTc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA. BACKGROUND: 99mTc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of 99mTc-PYP can facilitate identification of ATTR-CA, but appropriate use is critical for accurate diagnosis in an era of high-cost targeted therapeutics. METHODS: Patients undergoing 99mTc-PYP scanning 1 h after injection at a quaternary care center from 2010 to 2019 were analyzed; clinical information was abstracted; and SPECT results were analyzed. RESULTS: Over the decade, endomyocardial biopsy rates remained stable with scanning rates peaking at 132 in 2019 (p < 0.001). Among 753 patients (516 men, mean age 77 years), 307 (41%) had a visual score of 0, 177 (23%) of 1, and 269 (36%) of 2 or 3. Of 751 patients with analyzable heart to contralateral chest ratios, 249 (33%) had a ratio ≥1.5. Monoclonal protein testing status was assessed in 550 patients, of these, 174 (32%) did not undergo both serum immunofixation and serum free light chain analysis tests, and 331 (60%) did not undergo all 3 tests-serum immunofixation, serum free light chain analysis, and urine protein electrophoresis. Of 196 patients with confirmed ATTR-CA, 143 (73%) had genetic testing for transthyretin mutations. In 103 patients undergoing cardiac biopsy, grades 2 and 3 99mTc-PYP had sensitivity of 94% and specificity of 89% for ATTR-CA with 100% specificity for grade 3 scans. With respect to SPECT as a reference standard, planar imaging had false positive results in 16 of 25 (64%) grade 2 scans. CONCLUSIONS: Use of noninvasive testing with 99mTc-PYP scanning for evaluation of ATTR-CA is increasing, and the inclusion of monoclonal protein testing and SPECT imaging is crucial to rule out amyloid light chain amyloidosis and distinguish myocardial retention from blood pooling.

An appraisal of the gut health modulatory effects of a calf faecal-origin probiotic Lactobacillus salivarius CPN60 using Wistar rats with dextran sulfate sodium-induced colitis.

BACKGROUND: Probiotics of varied origins are being developed for augmenting the gut health of human and animals. The present study aimed to evaluate the effect of a calf-origin probiotic supplement on the gut health of Wistar rats for both healthy and colitis conditions. RESULTS: Forty-eight rats were randomly distributed into four equal groups. The 42-day study involved feeding basal diet alone (CON) or diet supplemented with the calf-origin Lactobacillus salivarius strain CPN60 (PRO). The third (CONc) and fourth (PROc) groups of rats also received the same dietary treatments (CON and PRO, respectively) but were subjected to dextran sulfate sodium (DSS)-induced colitis after 32 days of feeding. The results of a digestion trial conducted after 5 days of DSS administration revealed no influence of probiotic on the digestibility of nutrients. However, the reduced digestibility of protein and fat seen in the CONc rats was improved in the PROc group. The concentrations of lactate and acetate, propionate and butyrate, as well as total short-chain fatty acids (SCFA), were increased (P < 0.05) in the caecal and colonic digesta upon probiotic supplementation, together with significantly reduced colonic ammonia levels. Furthermore, there were reductions (P < 0.05) in acetate, butyrate and total SCFA levels in the caecal contents as a result of colitis. Probiotic supplementation increased (P < 0.05) lactobacilli and bifidobacteria counts in the colon, whereas clostridia and coliform counts were reduced (P < 0.05). These were reversed by the probiotic supplementation. CONCLUSION: Dietary supplementation of L. salivarius CPN60 had a positive effect with respect to improving the overall gut health of healthy rats, as well as that of rats exposed to experimental colitis. © 2020 Society of Chemical Industry.

Systemic Amyloidosis due to Monoclonal Immunoglobulins: Cardiac Involvement.

Amyloid light chain amyloidosis (AL) is the most commonly diagnosed systemic form of amyloidosis, resulting from deposition of amyloid fibrils into various organs, such as the heart. Over the past several decades, significant advances in diagnosis and treatment have reduced overall mortality. Short-term survival, however, has not improved, in large part due to cardiovascular mortality from advanced AL cardiac amyloidosis. Early clinical suspicion of cardiac involvement is critical in order to initiate appropriate treatment and referrals for successful management. This review discusses the current challenges in diagnosis as well as available treatment options for different stages of cardiac involvement.

Adding α-tocopherol-selenium and ascorbic acid to periparturient sow diets influences hemogram, lipid profile, leptin, oxidant/antioxidant imbalance, performance and neonatal piglet mortality.

Alpha-tocopherol-selenium (ATS) and ascorbic acid (AA) are the potent antioxidants. The present study investigated whether supplementation of ATS and AA in periparturient sows has positive effects on amelioration of oxidative stress, serum immunoglobulin G (IgG), lipid profile and sows performance. For this, twenty-four pregnant multiparous sows (landrace×indigenous) were randomly distributed into four groups (6 sows per group) 20 days before expected date of farrowing as Control (basal diet); ATS (basal diet + ATS); AA (basal diet + AA) and ATS-AA (basal diet + ATS plus AA). The results of the study revealed that the concentrations of triglyceride and cholesterol significantly reduced from day -7 to day 7 of farrowing irrespective of supplementations to sows, but the leptin concentration significantly reduced on day 7 of farrowing in ATS-AA supplemented sows (p<0.05). Moreover, sows of supplemented groups experienced decreased oxidative stress and cortisol level than control sows. The serum IgG concentration was significantly increased on day 7 post-farrowing in ATS group but it was much earlier on day 2 of farrowing in ATS-AA group (p<0.001). Supplementing sows with ATS and/or AA did not influence significantly the birth weight, weaning weight and litter size at weaning (p>0.05). Although piglet survival rate was not affected significantly by supplementation, however, piglet mortality rate was lowest in ATS-AA than any other groups. It was concluded that supplementation of ATS and/or AA to sows during late gestating and early lactating period ameliorated oxidative stress, improved lipid profile and serum IgG level without influencing reproductive performance.

Nutrient digestibility, hindgut metabolites and antioxidant status of dogs supplemented with pomegranate peel extract.

The present study assessed the effect of dietary supplementation of pomegranate peel (methanolic) extract (PPE) on the nutrient digestibility, faecal fermentative metabolites and antioxidant status of dogs. Six medium-sized dogs of mixed breeds were allocated to two groups in a replicated cross-over design and fed a basal diet with and without supplementation of PPE at 50 mg/kg body weight. Each of the experimental periods consisted of 30 d, with a 21 d washout period in between. Results indicated that PPE supplementation led to no significant changes in nutrient digestibility except a trend of improvement (P = 0·070) in crude fibre digestibility. PPE supplementation significantly (P < 0·001) influenced faecal pH, ammonia and lactate production, indicative of positive effects of PPE polyphenols. PPE supplementation further increased faecal SCFA concentration accompanied by a reduction (P < 0·01) in branched-chain fatty acids. PPE supplementation also improved (P < 0·05) indices of erythrocytic antioxidants, namely reduced glutathione, catalase, glutathione peroxidase and glutathione S-transferase together with an improvement in lipid peroxidation. Overall, it can be concluded that dietary supplementation with PPE at 50 mg/kg body weight had a positive impact on hindgut fermentation and antioxidant status in dogs, thereby demonstrating its potential as a gut health-promoting nutraceutical.

Comparative assessment of canine-origin Lactobacillus johnsonii CPN23 and dairy-origin Lactobacillus acidophillus NCDC 15 for nutrient digestibility, faecal fermentative metabolites and selected gut health indices in dogs.

The present experiment was undertaken to validate a probiotic of canine origin for its potential use in dogs. A total of fifteen adult female Labrador dogs were allocated to three equal groups and fed a basal diet without probiotic (control) or with probiotic of either canine (Lactobacillus johnsonii CPN23; cPRO) or dairy (L. acidophilus NCDC 15; dPRO) origin for 9 weeks. The digestibility of most macronutrients remained similar among the groups; however, fibre digestibility was improved (P = 0·034) in dogs receiving cPRO. The faecal fermentative metabolites ammonia (P < 0·05) and lactate (P = 0·094) were altered favourably, indicating a positive influence of both probiotics. Faecal concentrations of acetate, propionate and butyrate were increased (P < 0·01) in both probiotic groups. However, improvements were higher in cPRO v. dPRO. The delayed-type hypersensitivity reaction to intradermal inoculation of phytohaemagglutinin-P was higher (P = 0·053) in cPRO as compared with control. The antibody response to sheep erythrocytes was, however, similar across the three groups. Overall, in dogs, the canine-origin probiotic was superior when compared with the dairy-origin probiotic.

Vitamin B12 levels are not affected by radioiodine ablation of the thyroid.

OBJECTIVE: Radioiodine administered for the treatment of hyperthyroidism and thyroid cancer can be taken up by many non-thyroid tissues which express sodium iodide symporter. Though gastric mucosa takes up radioiodine, its impact on parietal cell has not been evaluated. The aim of the present study was to compare vitamin B12 and homocysteine concentrations in patients with thyroid disorders treated by radioiodine ablation with those in control population without radioiodine exposure. METHODS: Patients with Graves' disease, toxic multinodular goiter (TMNG), toxic adenoma (TA) or differentiated thyroid cancer (DTC) who had received 131I were included as "patients". Healthy persons and patients having Graves' disease but without exposure to radioiodine were recruited as "controls". A total of 35 patients and 35 controls were included. Patients were divided into Graves' disease and non-Graves' disease (TMNG, TA, DTC) groups. Graves' disease patients were compared with Graves' disease controls while non-Graves' disease patients were compared with healthy controls. RESULTS: In the Graves' disease group, median vitamin B12 concentration was 240 pg/ml (IQR: 148 - 371) in patients (n=23) and 195 pg/ml (IQR: 140 - 291 pg/ml) (p=0.13, ns) in controls (n=24). In the non-Graves' disease group, median serum vitamin B12 concentration was 147 pg/ml (IQR: 124 - 325pg/ml) in patients (n=12) and 190 pg/ml (IQR: 157 - 373 pg/ml) (p=0.34, ns) in healthy controls (n=11). Homocysteine concentrations were also similar in compared groups of patients and controls. CONCLUSIONS: Radioiodine ablation does not cause vitamin B12 deficiency. However, a prospective study with a larger number of patients is required to confirm this finding.

Time course pathogenesis of sulphur mustard-induced skin lesions in mouse model.

Sulphur mustard (SM) is a bifunctional alkylating agent that causes cutaneous blistering in humans and animals. In this study, we have presented closer views on pathogenesis of SM-induced skin injury in a mouse model. SM diluted in acetone was applied once dermally at a dose of 5 or 10 mg/kg to Swiss albino mice. Skin was dissected out at 0, 1, 3, 6, 12, 24, 48, 72 and 168 hours, post-SM exposure for studying histopathological changes and immunohistochemistry of inflammatory-reparative biomarkers, namely, transforming growth factor alpha (TGF-α), fibroblast growth factor (FGF), endothelial nitric oxide synthase (eNOS) and interlukin 6 (IL-6). Histopathological changes were similar to other mammalian species and basal cell damage resembled the histopathological signs observed with vesication in human skin. Inflammatory cell recruitment at the site of injury was supported by differential expressions of IL-6 at various stages. Time-dependent expressions of eNOS played pivotal roles in all the events of wound healing of SM-induced skin lesions. TGF-α and FGF were strongly associated with keratinocyte migration, re-epithelialisation, angiogenesis, fibroblast proliferation and cell differentiation. Furthermore, quantification of the tissue leukocytosis and DNA damage along with semiquantitative estimation of re-epithelialisation, fibroplasia and neovascularisation on histomorphologic scale could be efficiently used for screening the efficacy of orphan drugs against SM-induced skin injury.