Electrocardiographic and biochemical analysis of anthracycline induced cardiotoxicity in breast cancer patients from Southern Sri Lanka.

BACKGROUND: The clinical application of anthracycline chemotherapy is hindered due to the cumulative dose-dependent cardiotoxicity followed by the oxidative stress initiated during the mechanism of action of anthracyclines. Due to a lack of prevalence data regarding anthracycline-induced cardiotoxicity in Sri Lanka, this study was conducted to determine the prevalence of cardiotoxicity among breast cancer patients in Southern Sri Lanka in terms of electrocardiographic and cardiac biomarker investigations. METHODS: A cross-sectional study with longitudinal follow-up was conducted among 196 cancer patients at the Teaching Hospital, Karapitiya, Sri Lanka to determine the incidence of acute and early-onset chronic cardiotoxicity. Data on electrocardiography and cardiac biomarkers were collected from each patient, one day before anthracycline (doxorubicin and epirubicin) chemotherapy, one day after the first dose, one day and six months after the last dose of anthracycline chemotherapy. RESULTS: Prevalence of sub-clinical anthracycline-induced cardiotoxicity six months after the completion of anthracycline chemotherapy was significantly higher (p < 0.05) and there were strong, significant (p < 0.05) associations among echocardiography, electrocardiography measurements and cardiac biomarkers including troponin I and N-terminal pro-brain natriuretic peptides. The cumulative anthracycline dose, > 350 mg/m2 was the most significant risk factor associated with the sub-clinical cardiotoxicity in breast cancer patients under study. CONCLUSION: Since these results confirmed the unavoidable cardiotoxic changes following anthracycline chemotherapy, it is recommended to carry out long-term follow-ups in all patients who were treated with anthracycline therapy to increase their quality of life as cancer survivors.

Association of dietary intake with body mass index and glycemic profile among newly diagnosed patients with type 2 diabetes mellitus.

INTRODUCTION: Dietary intake plays an important role in determining body mass index (BMI) and glycemic profile in patients with type 2 diabetes mellitus (T2DM). Our aim was to describe habitual dietary intake and its associations with BMI and glycemic profile in a cohort of patients with newly diagnosed T2DM in Sri Lanka. METHODS: A cross-sectional study was carried out among 158 patients with newly diagnosed T2DM in Galle, Sri Lanka. Data on demographic, lifestyle, and family history of diabetes mellitus, and clinical measures were collected. The dietary information was collected using a 24-h dietary recall. RESULTS: Among the total number of study subjects, only 12.0%, 5.7% and 1.3% met the recommended daily consumption value of protein, fat, and fiber, respectively, whereas 99.4% of subjects had taken carbohydrates that exceeded the recommended consumption. There was a positive association between carbohydrate intake and BMI (0.004, [0.002], p = .048) and carbohydrate intake and glycated hemoglobin (HbA1C ) (0.001, [0.000], p = .049). Fat intake showed positive associations with BMI (0.029, [0.011], p = .006) and HbA1C (0.005, [0.002], p = .050). Protein intake showed a positive association with HbA1C (0.006, [0.003], p = .023). The aforementioned associations were observed after adjusting for demographic, lifestyle, and history of diabetes among the first-degree family members. The carbohydrate intake was positively associated with BMI (0.010, [0.003], p = .003) and HbA1C (0.001, [0.000], p = .050) with further adjustment in nutrient intake (except when used as an independent variable). Furthermore, the fat intake was associated with BMI (0.031, [0.011], p = .004) and HbA1C (0.005 [0.002], p = .050) with additional adjustments. CONCLUSIONS: The diet of the majority of newly diagnosed T2DM patients in this cohort consisted of a higher carbohydrate intake than the recommended level. However, they did not meet the recommended daily intake of protein, fat, and fiber. Both carbohydrate and fat intake were significantly and positively associated with BMI and HbA1C in patients with newly diagnosed T2DM.

Cinnamomum zeylanicum Blume (Ceylon cinnamon) bark extract attenuates doxorubicin induced cardiotoxicity in Wistar rats.

Anti-tumour efficacy of doxorubicin is hindered by the cumulative dose-dependent cardiotoxicity induced by reactive oxygen species during its metabolism. As Cinnamomum zeylanicum has proven antioxidant potential, objective of this study was to investigate the cardioprotective activity of Cinnamomum bark extract against doxorubicin induced cardiotoxicity in Wistar rats. Physicochemical and phytochemical analysis was carried out and dose response effect and the cardioprotective activity of Cinnamomum were determined in vivo. 180 mg/kg dexrazoxane was used as the positive control. Plant extracts were free of heavy metals and toxic phytoconstituents. In vivo study carried out in Wistar rats revealed a significant increase (p < 0.05) in cardiac troponin I, NT-pro brain natriuretic peptide, AST and LDH concentrations in the doxorubicin control group (18 mg/kg) compared to the normal control. Rats pre-treated with the optimum dosage of Cinnmamomum (2.0 g/kg) showed a significant reduction (p < 0.05) in all above parameters compared to the doxorubicin control. A significant reduction was observed in the total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activity while the lipid peroxidation and myeloperoxidase activity were significantly increased in the doxorubicin control group compared to the normal control (p < 0.05). Pre-treatment with Cinnamomum bark showed a significant decrease in lipid peroxidation, myeloperoxidase activity and significant increase in rest of the parameters compared to the doxorubicin control (p < 0.05). Histopathological analysis revealed a preserved appearance of the myocardium and lesser degree of cellular changes of necrosis in rats pre-treated with Cinnamomum extract. In conclusion, Cinnamomum bark extract has the potential to significantly reduce doxorubicin induced oxidative stress and inflammation in Wistar rats.

Value of simple clinical parameters to predict insulin resistance among newly diagnosed patients with type 2 diabetes in limited resource settings.

BACKGROUND: Insulin resistance (IR) has been considered as a therapeutic target in the management of type 2 diabetes mellitus (T2DM). Readily available, simple and low cost measures to identify individuals with IR is of utmost importance for clinicians to plan optimal management strategies. Research on the associations between surrogate markers of IR and routine clinical and lipid parameters have not been carried out in Sri Lanka, a developing country with rising burden of T2DM with inadequate resources. Therefore, we aimed to study the utility of readily available clinical parameters such as age, body mass index (BMI), waist circumference (WC) and triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-C) in the fasting lipid profile in predicting IR in a cohort of patients with newly diagnosed T2DM in Sri Lanka. METHODS AND FINDINGS: We conducted a community based cross sectional study involving of 147 patients (age 30-60 years) with newly diagnosed T2DM in a suburban locality in Galle district, Sri Lanka. Data on age, BMI, WC, fasting plasma glucose (FPG) concentration, fasting insulin concentration and serum lipid profile were collected from each subject. The indirect IR indices namely homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI) and McAuley index (MCA) were estimated. Both clinical and biochemical parameters across the lowest and the highest fasting insulin quartiles were compared using independent sample t-test. Linear correlation analysis was performed to assess the correlation between selected clinical parameters and indirect IR indices. The area under the receiver operating characteristic (ROC) curve was obtained to calculate optimal cut-off values for the clinical markers to differentiate IR. BMI (p<0.001) and WC (p = 0.01) were significantly increased whereas age (p = 0.06) was decreased and TG/HDL-C (p = 0.28) was increased across the insulin quartiles. BMI and WC were significantly correlated (p<0.05) with HOMA, QUICKI and MCA. Out of the clinical parameters, age showed a borderline significant correlation with QUICKI and TG/HDL-C showed a significant correlation only with MCA. The area under ROC of BMI was 0.728 (95% CI 0.648-0.809; p<0.001) and for WC, it was 0.646 (95% CI 0.559-0.734; p = 0.003). The optimized cut-off value for BMI and WC were 24.91 kg/m2 and 81.5 cm respectively to differentiate the patients with IR or ID. Study limitations include small sample size due to recruitment of patients only from a limited geographical locality of the country and not totally excluding of the possibility of inclusion of some patients with slowly progressive type 1 DM or Latent onset diabetes of adulthood from the study population. CONCLUSIONS: The results revealed that there was a significant positive correlation between BMI, WC and HOMA while a significant negative correlation with QUICKI and MCA among the cohort of patients with newly diagnosed T2DM. The cut-off values of BMI and WC as 24.91 kg/m2 and 81.5 cm respectively could be used as simple clinical parameters to identify IR in newly diagnosed patients with T2DM. Our results could be beneficial in rational decision making in the management of newly diagnosed patients with T2DM in limited resource settings.

Antidiabetic Activity of Widely Used Medicinal Plants in the Sri Lankan Traditional Healthcare System: New Insight to Medicinal Flora in Sri Lanka.

The use of medicinal plant extracts and their isolated bioactive compounds for the management of diabetes mellitus has been tremendously increased in recent decades. The present study aimed at providing in-depth information on medicinal flora that has been widely used in the Sri Lankan traditional healthcare system for the management of diabetes mellitus. The data of this review article were obtained from published articles from January 2000 to September 2020 in scientific databases of PubMed, Web of Science, and Google Scholar. In this review, a total number of 18 medicinal plants with the antidiabetic activity were expressed, and their isolated antidiabetic active compounds were highlighted as new drug leads. Results of the reported studies revealed that medicinal plants exert a potent antidiabetic activity via both in vitro and in vivo study settings. However, bioactive compounds and antidiabetic mechanism (s) of action of many of the reported medicinal plants have not been isolated/elucidated the structure in detail, to date. Reported antidiabetic medicinal plants with other properties such as antioxidant and antihyperlipidemic activities deliver new entities for the development of antidiabetic agents with multiple therapeutic targets. This is a comprehensive review on potential antidiabetic activities of the Sri Lankan medicinal plants that have been widely used in the traditional healthcare system. The information presented here would fill the gap between the use of them by traditional healers in the traditional medicine healthcare system in Sri Lanka and their potency for development of new drug entities in future.

Efficacy and safety of a herbal drug of Coccinia grandis (Linn.) Voigt in patients with type 2 diabetes mellitus: A double blind randomized placebo controlled clinical trial.

BACKGROUND: Several lines of preclinical studies have shown promising antidiabetic effects of the aqueous leaves extract of Coccinia grandis (Linn.) Voigt (Cucurbitaceae) in vivo and in vitro. PURPOSE: The present study was conducted to evaluate the efficacy and safety of a newly developed herbal formulation of C. grandis in newly diagnosed patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: A three months long, randomized, double blind, placebo controlled clinical trial in patients with newly diagnosed T2DM. METHOD: Based on fasting plasma glucose (FPG) concentration, a total number of 158 newly diagnosed patients with T2DM (45 ± 15 years age) were recruited for the present trial from the University Medical Clinic, Teaching Hospital, Karapitiya, Galle, Sri Lanka. They were randomly assigned to the test or placebo group to receive 500 mg of herbal drug (n = 79) or placebo drug (n = 79) once daily for three months. Patients and investigators were blinded for the treatment. Percentage of glycated hemoglobin (HbA1C %), insulin and lipid profile parameters were estimated at the base line and at the end of the intervention. Serum concentration of fructosamine was assessed at every other visit of the trial. The homeostatic model assessment for insulin resistance (HOMA-IR), atherogenic index (AI), cardio-protective index (CPI) and coronary risk index (CRI) were calculated. Furthermore, fasting plasma glucose concentration, renal and liver toxicity parameters, hematological parameters, blood pressure (BP) were assessed throughout the study in two weekly intervals till the end of three months. RESULTS: Out of 158, a total number of 145 patients completed the entire clinical trial period successfully. Mean (SD) changes of variables from the baseline to the end of the intervention in test and placebo groups were 0.65 (0.54) and 0.08 (0.66) for HbA1C % (p < 0.001), 1.91 (3.07) and -1.28 (9.77) for insulin (p < 0.001), 0.02 (0.03) and -0.01 (0.04) for frucosamine (p < 0.001), 1.51 (0.49) and 0.05 (0.50) for FPG (p < 0.001), 1.73 (1.36) and -0.37 (3.38) for HOMA-IR (p < 0.001), 0.16 (0.18) and -0.04 (0.42) for TG (p < 0.001), 0.07 (0.08) and -0.02 (0.19) for VLDL-C (p < 0.001), respectively. However, the herbal drug of C. grandis was unable to change other outcome variables significantly when compared to the placebo (p > 0.05). All the renal, liver and toxicity parameters, hematological parameters and BP were within the normal physiological reference ranges at each visit. CONCLUSION: Treatment with herbal drug of C. grandis (500 mg per day) for three months for patients with newly diagnosed T2DM significantly improved their glycemic and selected lipid profile parameters with well tolerated safety.

Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients from Southern Sri Lanka: An Echocardiographic Analysis.

Anthracycline-induced cardiotoxicity has never been investigated in Sri Lanka. Therefore, this study was conducted to determine the prevalence of anthracycline-induced cardiotoxicity in breast cancer patients using echocardiographic findings. A prospective cohort study was performed. All newly diagnosed breast cancer patients who were administered with anthracycline and cyclophosphamide (AC schedule) for the first time were enrolled in the study. In the hospital setting, anthracycline is administered only as a combination therapy, and only this combination was selected to limit the effect of other cardiotoxic chemotherapy agents. Records of echocardiography were obtained: one day before anthracycline chemotherapy (baseline), one day after the first chemotherapy dose, one day after the last chemotherapy dose, and six months after the completion of anthracycline chemotherapy. Following parameters were recorded from the echocardiography results: ejection fraction (EF, %), fractioning shortening (FS, %), posterior wall thickness, left ventricle (PWT, mm), the thickness of interventricular septum (IVS, mm), left ventricular end-diastolic diameter (LVEDD, mm), and left ventricular end-systolic diameter (LVESD, mm). Statistical analysis of the echocardiography results was performed using ANOVA at four stages. A p value <0.05 was considered significant. Subclinical cardiac dysfunction was defined as a fall of EF >10% during the follow-up echocardiography. There was no significant change (p > 0.05) between the baseline echocardiographic parameters and one day after the 1st anthracycline dose. However, significant differences (p < 0.05) were observed between the baseline echocardiographic parameters and one day after the last anthracycline dose and six months after the completion of anthracycline therapy with a gradual and progressive deterioration in functional parameters including EF, FS, PWT, and IVS over time. There were 65 patients out of 196 (33.16%) who developed subclinical cardiac dysfunction six months after the completion of anthracycline chemotherapy. The prevalence of subclinical anthracycline-induced cardiotoxicity was relatively higher in these patients. An equation was also developed based on left ventricular ejection fraction (LVEF) to predict the anthracycline-induced cardiotoxicity of a patient six months after the completion of anthracycline chemotherapy. We believe that this will help in the monitoring of patients who undergo anthracycline therapy for cardiotoxicity. It is recommended to carry out a long-term follow-up to detect early-onset chronic progressive cardiotoxicity in all patients who were treated with anthracycline therapy.

ß-cell Regenerative Potential of Selected Herbal Extracts in Alloxan Induced Diabetic Rats.

BACKGROUND: Effective ß-cell regeneration is a recognized therapeutic strategy in the treatment of type 1 diabetes mellitus. Regeneration of ß-cells could be achieved via exogenous natural sources as medicinal plant extracts. Medicinal plants selected for the investigation were Spondias pinnata (Linn. f.) Kurz, Coccinia grandis (L.) Voigt and Gmelina arborea Roxb. The objective was to determine the ß-cell regenerative potential of these plant extracts in alloxan-induced diabetic rats. Alloxan monohydrate was used to induce diabetes (150 mg/kg, ip). METHODS: Wistar albino rats were divided into six groups (n=6); healthy untreated rats (healthy control), alloxan-induced diabetic untreated rats (diabetic control), diabetic rats received the extracts (treatment groups) of S. pinnata (1.0 g/kg), C. grandis (0.75 g/kg), G. arobrea (1.00 g/kg) and diabetic rats received glibenclamide (0.5 mg/kg; positive control). The above treatment was continued for 30 days. On the 30th day, the rats were sacrificed and biochemical parameters were determined. In addition, histopathology and immunohistochemistry on the pancreatic tissue were done on the 30th day. RESULTS: According to the results obtained for biochemical parameters, there was a significant increase in the concentrations of serum insulin and C-peptide in plant extracts treated diabetic rats (p < 0.05). The extract of C. grandis produced the highest degree of ß-cell regeneration demonstrated through an increase in the number of islets and percentage of the insulin-secreting ß-cells (75%) in the pancreas of diabetic rats (p < 0.05) based on the histopathology and immunohistochemistry findings. CONCLUSION: The results revealed that the selected extracts of C. grandis (0.75 g/kg), G. arborea (1.00 g/kg) and S. pinnata (1.00 g/kg) exerted ß-cell regenerative potential in diabetic rats. The three plant extracts would be valued as natural agents of prompting the ß-cell regeneration in vivo.

Corrigendum to "Gmelina arborea Roxb. (Family: Verbenaceae) Extract Upregulates the ß-Cell Regeneration in STZ Induced Diabetic Rats".

[This corrects the article DOI: 10.1155/2016/4513871.].

Gmelina arborea Roxb. (Family: Verbenaceae) Extract Upregulates the ß-Cell Regeneration in STZ Induced Diabetic Rats.

Gmelina arborea Roxb. (common name: Et-demata, Family: Verbenaceae) has been used traditionally in Sri Lanka as a remedy against diabetes mellitus. The objective of the present study was to evaluate antidiabetic mechanisms of the aqueous bark extract of G. arborea in streptozotocin induced (STZ) diabetic male Wistar rats. Aqueous bark extract of G. arborea (1.00 g/kg) and glibenclamide as the standard drug (0.50 mg/kg) were administered orally using a gavage to STZ diabetic rats (65 mg/kg, ip) for 30 days. The antidiabetic mechanisms of aqueous extract of G. arborea (1.00 g/kg) were determined at the end of the experiment. The fasting blood glucose concentration was significantly lowered and the serum insulin and C-peptide concentrations were increased by 57% and 39% in plant extract treated rats on day 30, respectively (p < 0.05). The histopathology and immunohistochemistry results of the plant extract treated group showed a regenerative effect on ß-cells of the pancreas in diabetic rats. In addition, serum lipid parameters were improved in G. arborea extract treated diabetic rats. The results revealed that the aqueous stem bark extract of G. arborea (1.00 g/kg) showed beneficial effects against diabetes mellitus through upregulating the ß-cell regeneration and biosynthesis of insulin in diabetic rats.