Inhibition of liver glutaminase activity by Diallyl disulfide in experimentally induced hepatoma in mice

Background: Cancer cells addiction to glutamine, an essential non-essential amino acid, has stirred up the interest in researchers across the globe. Increased glutamine metabolism (glutaminolysis) is a hallmark of cancer. Targeting glutaminolysis via glutaminase inhibition emerges as a promising strategy to disrupt cancer metabolism and tumor progression. Diallyl disulfide (DADS), a major organosulfur compound derived from garlic, is known for its anticancer properties. The mechanisms of action of DADS include activation of metabolic enzymes that detoxify carcinogens, suppression of the formation of DNA adducts, antioxidant effects, regulation of cell-cycle progression, induction of apoptosis, and inhibition of angiogenesis and metastasis. Aim: to assess the effect of diallyl disulfide on liver glutaminase activity in experimentally induced hepatoma in mice. Materials & Methods: Swiss albino male mice were divided into four groups - normal, control, preventive and curative groups. Hepatoma was induced by intraperitoneal injection of Ehrlich ascites carcinoma (EAC) cells. DADS (100 mg/kg body weight/mouse/day) was orally fed to protective and curative group mice for a stipulated time period. Mice of all the groups were sacrificed, and liver tissue glutaminase activity were measured. Results: The present study shows a significant decrease in glutaminase activity in protective (p >0.001) and curative groups (p >0.001) as compared to control group. Conclusion: DADS at the dosage employed shows inhibitory effects on liver glutaminase activity which may be attributed to anti-inflammatory properties of DADS, specifically in suppression of NF-kB signalling pathway.

Effect of diallyl disulfide on liver nucleotide metabolism in experimentally induced hepatoma in mice.

Background: The antitumorigenic effects of active ingredient of garlic, diallyl disulfide (DADS), has been extensively studied & found to retard the growth of neoplastic cells than any other allyl sulfur compounds of garlic. Earlier we have reported antitomorogenic properties of DADS, showing tumor regression by interfering with the liver glucose utilization, protein synthesis as well as lipid synthesis in tumor cells. Aim: To assess the effect of diallyl disulfide on liver nucleotide metabolism in experimentally induced hepatoma in mice. Materials & Methods: Swiss albino male mice were divided into four groups - normal, control, preventive and curative groups. Hepatoma was induced by intraperitoneal injection of Ehrlich ascites carcinoma (EAC) cells. DADS (100 mg/kg body weight/mouse/day) was orally fed to protective and curative group mice for a stipulated time period. Mice of all the groups were sacrificed, and liver tissue adenosine deaminase (ADA) activity and uric acid (UA) levels were measured. Results: The present study shows a significant decrease in ADA activity and UA levels in protective (p >0.001) and curative groups (p >0.01) as compared to control group. Conclusion: DADS has inhibitory effects on nucleotide metabolism by inhibiting the activities of ADA and xanthine oxidase enzymes, and by reducing the production of deoxy ribonucleotides, probably by involving in thiol-disulfide exchange reactions.

Prevalence, clinical profile, and stroke risk of atrial fibrillation in rural Andhra Pradesh, India (the AP-AF study)

The burden of atrial fibrillation (AF) is increasing worldwide. It is often asymptomatic, with stroke being the first manifestation in some. AF burden in the community and the practice of stroke prophylaxis has not been studied in India. The problem might be higher in rural regions due to poor health awareness and challenges to healthcare access. This study aimed to estimate the prevalence of AF, clinical profile and stroke risk in rural India. Methods: This is a community-based cross-sectional study done in rural Andhra Pradesh (AP). Adults from 40 villages formed the study population. We did a door-to door survey to collect information on demographics, and medical history. Electrocardiogram was recorded using a smart phone based Alivecor device. Participants diagnosed with AF underwent echocardiogram. Study cardiologists assessed the cardiovascular risk profile and collected detailed medical history. Results: Fourteen of the 4281 individuals screened had AF (0.3%). The mean age of the sampled population was 44 ± 16.5 years with 56% women. The mean age of participants with AF was 71 ±7.8 years; males were 71%. Except for one, all were non-valvular AF. Majority had a CHA2D2S2Vasc score of 2. Three had history of stroke. Two were on anticoagulant therapy but without INR monitoring. Conclusion: The prevalence of AF is lower in this study compared to studies from the developed countries. Non-rheumatic cardiovascular risk factors were primary causes for AF. Non-adherence to stroke prophylaxis is a major threat that needs to be addressed

Surgical 'safari' vs. educational program: experience with international cardiac surgery missions in nigeria

Abstract Introduction: In any country, the development and growth of open-heart surgery parallel stable political climate, economic growth, good leadership, and prudent fiscal management. These were lacking in Nigeria, which was under a military rule. The enthronement of democratic rule, in 1999, has caused desirable changes. The objective of this study is to report our experience with foreign cardiac teams that visited the National Cardiothoracic Center of Excellence, University of Nigeria Teaching Hospital, for seven years, in order to restart its open-heart surgery program. Methods: To achieve the desired open-heart surgery training, our center received regular and frequent visits from foreign cardiac teams who would perform open-heart surgery with the local team. Results: During the period of seven years, a total of 266 open-heart operations involving both adults and children were performed, with a mean of 38 cases per year; 150 (54.4%) males and 116 (43.6%) females were treated, with a ratio of 1.0:0.8. Six different teams visited the center at different periods. Conclusion: After these years of cardiac missions to our center, the experience of the local team, especially the surgeons, is far from desirable because each team visit usually lasted about a week or two and each team, with exception of the CardioStart International/William Novick Global Cardiac Alliance, adopted the surgical 'safari' method.

Evaluation of serum 25-hydroxyvitamin D levels in calcific rheumatic mitral stenosis— A cross sectional study

Background and aim of the study Rheumatic mitral stenosis (RMS) is an autoimmune, progressive destructive valve disease occurring as a sequele of streptococcal infection. Epidemiological studies support an association of vitamin D deficiency with initial susceptibility and severity of autoimmune diseases. The aim of the present study was to assess serum level of 25 hydroxyvitamin D in subjects of RMS and assess if any correlation exists with serum levels of vitamin D and severity of disease along with calcification assessed semi-quantitatively by echocardiography by applying Wilkins score. Method Fifty five patients of RMS without any calcification of the valves (Group A) assessed by echocardiography along with fifty five patients of RMS with mild to moderately calcified valves (Group B, Wilkins calcium score 1 or 2) and 55 patients with severely calcified valves (Group C, Wilkins calcium score 3 or 4) were enrolled for the study. All subjects underwent clinical, echocardiographic, and biochemical evaluation. The total Wilkins score, Wilkins calcium score along with serum level of 25 hydroxyvitamin D was evaluated in all the patients. Results The median serum level of 25 hydroxyvitamin D was significantly lower in Group B (20.4 ng/ml, p < 0.001) and group C (11.4 ng/ml, p < 0.001) compared to Group A patients (27.9 ng/ml). Similarly serum level of 25 hydroxyvitamin D in Group C patients were significantly less than Group B patients (p < 0.001). A significant inverse correlation was identified between serum level of 25 hydroxyvitamin D and total Wilkins score (r = −0.65, p < 0.001) as well as Wilkins calcium score (r = −0.69, p < 0.001). But no correlation was identified between 25 hydroxyvitamin D levels and other echocardiographic parameters of RMS. Conclusion Our study showed a significantly lower level of 25 hydroxyvitamin D in subjects of RMS with severely damaged and calcified valves as compared to those with less severely damaged non-calcified valves and it correlated with both Wilkins score and Wilkins calcification score. Thus a link may exist between vitamin D deficiency (an immunomodulator) and severity of autoimmune injury on the valves.