A Comparison of Mesenchymal Stem Cell-derived Hepatocyte-like Cells and HepG2 Cells for Use in Drug-Induced Liver Injury Studies.

Liver cell lines obtained from hepatomas, for example, HepG2 cells, are commonly used in drug toxicity studies. However, functional hepatocyte-like cells derived from mesenchymal stem cells (MSCs) could be a better option for use in the study of drug metabolism and toxicity. Overdose of acetaminophen (APAP) and excess alcohol consumption are common causes of liver damage. The objective of the present study was to investigate the use of MSC-derived hepatocyte-like cells (MSCdH) in the assessment of drug-induced liver injury (by using APAP and ethanol), and to compare the toxic effects observed in the MSCdH with those exhibited by HepG2 cells. MSCs were isolated from umbilical cord and their functionality confirmed by their ability to differentiate into adipocytes, osteocytes and hepatocyte-like cells. It was shown that the MSCs successfully differentiated into hepatocyte-like cells, and these cells were further characterised by using various enzyme assays and by assessing albumin secretion and urea synthesis. Cytotoxicity was evaluated in the HepG2 and MSCdH after exposure to ethanol and APAP, with cell viability being determined by using the MTT assay. After exposure to ethanol and to APAP, cell viability decreased in a concentration-dependent manner for both types of hepatocytes. The respective EC50 values of ethanol-induced toxicity for HepG2 and MSCdH cells were 2.5% and 1.3% v/v (p < 0.001); for APAP-induced toxicity they were 19.1 mM and 12.6 mM (p < 0.001). These findings show that there is a distinct difference between the two types of hepatocytes in terms of APAP-induced and ethanol-induced liver injury.

Therapeutic uses of post-partum tissue-derived mesenchymal stromal cell secretome.

Human post-partum tissue mesenchymal stromal cells (hPPT-MSCs) are widely used in research to investigate their differentiation capabilities and therapeutic effects as potential agents in cell-based therapy. This is ascribed to the advantages offered by the use of MSCs isolated from hPPT over other MSC sources. A paradigm shift in related research is evident that focuses on the secretome of the human MSCs (hMSCs), as therapeutic effects of hMSCs are attributed more so to their secreted growth factors, cytokines and chemokines and to the extracellular vesicles (EVs), all of which are components of the hMSC secretome. Positive therapeutic effects of the hPPT-MSC secretome have been demonstrated in diseases related to skin, kidney, heart, nervous system, cartilage and bones, that have aided fast recovery by replacing damaged, non-functional tissues, via differentiating and regenerating cells. Although certain limitations such as short half -life of the secretome components and irregular secreting patterns exist in secretome therapy, these issues are successfully addressed with the use of cutting-edge technologies such as genome editing and recombinant cytokine treatment. If the current limitations can be successfully overcome, the hPPT-MSC secretome including its EVs may be developed into a cost-effective therapeutic agent amenable to be used against a wide range of diseases/disorders.

Recurrent empty follicle syndrome with different stimulation protocols - A case report.

We report a case of recurrent empty follicle syndrome (EFS) where no oocytes were aspirated in two separate IVF cycles using two different protocols. In the second cycle, oocyte aspiration in one ovary was delayed for 24 hours after administering a second dose of human chorionic gonadotropin injection (hCG) and still no oocytes were recovered. In view of the presence of severe male factor infertility and failure to retrieve oocytes in 2 stimulated cycles, the couple was offered donor embryo transfer which resulted in a singleton pregnancy. A baby girl weighing 2800 g was delivered by an elective caesarean section at term. This case highlights that the change of protocol or repeat hCG administration is unlikely to change the outcome of genuine empty follicle syndrome.

Inequalities in the prevalence of diabetes mellitus and its risk factors in Sri Lanka: a lower middle income country.

BACKGROUND: Explorations into quantifying the inequalities for diabetes mellitus (DM) and its risk factors are scarce in low and lower middle income countries (LICs/LMICs). The aims of this study were to assess the inequalities of DM and its risk factors in a suburban district of Sri Lanka. METHODS: A sample of 1300 participants, (aged 35-64 years) randomly selected using a stratified multi-stage cluster sampling method, were studied employing a cross sectional descriptive design. The socioeconomic indicators (SEIs) of the individual were education level and occupational category, and at the household level, the household income, social status level and area deprivation level. DM was diagnosed if the fasting plasma glucose was ≥126 and a body mass index (BMI) of > 27.5 kg/m2 was considered high. Asian cut-off values were used for high waist circumference (WC). Validated tools were used to assess the diet and level of physical activity. The slope index of inequality (SII), relative index of inequality (RII) and concentration index (CI) were used to assess inequalities. RESULTS: The prevalence of DM and its risk factors (at individual or household level) showed no consistent relationship with the three measures of inequality (SII, RII and CI) of the different indices of socio economic status (education, occupation, household income, social status index or area unsatisfactory basic needs index). The prevalence of diabetes showed a more consistent pro-rich distribution in females compared to males. Of the risk factors in males and females, the most consistent and significant pro-rich relationship was for high BMI and WC. In males, the significant positive relationship with high BMI for SII ranged from 0.18 to 0.35, and RII from 1.56 to 2.25. For high WC, the values were: SII from 0.13 to 0.27 and RII from 1.9 to 3.97. In females the significant positive relationship with high BMI in SII ranged from 0.13 to 0.29, and RII from 2.3 to 4.98. For high WC the values were: SII from 028 to 0.4 and RII 1.99 to 2.39. Of the other risk factors, inadequate fruit intake showed a consistent significant pro-poor distribution only in males using SII (- 0.25 to - 0.36) and in both sexes using CI. Smoking also showed a pro-poor distribution in males especially using individual measures of socio-economic status (i.e. education and occupation). CONCLUSIONS: The results show a variable relationship between socioeconomic status and prevalence of diabetes and its risk factors. The inequalities in the prevalence of diabetes and risk factors vary depending on gender and the measures used. The study suggests that measures to prevent diabetes should focus on targeting specific factors based on sex and socioeconomic status. The priority target areas for interventions should include prevention of obesity (BMI and central obesity) specifically in more affluent females. Males who have a low level of education and in non-skilled occupations should be especially targeted to reduce smoking and increase fruit intake.

Polyphenols contribute to the antioxidant and antiproliferative activity of Phyllanthus debilis plant in-vitro.

BACKGROUND: Phyllanthus debilis (Elapitawakka) is a medicinal plant used in traditional systems of medicine in Sri Lanka. Present study was carried out to evaluate in-vitro anti-oxidant and anti-proliferative activity of the water extracts of aerial parts (AP) and roots (RP) of P.debilis plant and the role of polyphenolic compounds in view of its medicinal use. METHOD: Total polyphenols, flavonoids and proanthocyanidin content of the extracts were quantified. DPPH, hydroxyl radical, nitric oxide and hydrogen peroxide scavenging potentials and the total antioxidant capacity, ferric ion reducing power were determined to evaluate antioxidant capacity. Anti-proliferative activity was assessed with MTT assay for Human Rhabdomyosarcoma (RD) and normal rat liver cells (CC1) after 24 h exposure to the plant extracts. DPPH and MTT assays were carried out for AP and RP extracts after removal of polyphenols to assess the contribution of polyphenols on antioxidant and anti-proliferative activity of Phyllanthus debilis. RESULTS: Flavonoid content of the AP extract was significantly lower than that of RP (P < 0.001) while no significant difference was observed in polyphenolic as well as in proanthocyanidin contents. All the assays except for phosphomolybdate assay demonstrated that the RP extract had higher antioxidant capacity (p < 0.001) compared to AP. Further, antioxidant capacity and anti-proliferative activity were lower (p < 0.001) in AP and RP in the absence of polyphenols compared to the crude extract. CONCLUSION: Root contains higher levels of flavonoids than the aerial part. Moreover, the presence of polyphenols is required for antioxidant and anti-proliferative activities of both AP and RP.

A survey on socioeconomic determinants of diabetes mellitus management in a lower middle income setting.

BACKGROUND: Information on socioeconomic determinants in the management of diabetes mellitus is scarce in lower middle income countries. The aim of this study is to describe the socioeconomic determinants of management and complications of diabetes mellitus in a lower middle income setting. METHODS: Cross sectional descriptive study on a stratified random sample of 1300 individuals was conducted by an interviewer administered questionnaire, clinical examinations and blood investigations. A single fasting venous blood sugar of ≥126 mg/dl was considered diagnostic of new diabetics and poor control of diabetes mellitus as HbA1C > 6.5 %. RESULTS: There were 202 (14.7 %) with diabetes mellitus. Poor control was seen in 130 (90.7 %) while 71 (49.6 %) were not on regular treatment. Highest proportions of poor control and not on regular medication were observed in estate sector, poorest social status category and poorest geographical area. The annual HbA1C, microalbuminuria, retinal and neuropathy examination were performed in less than 6.0 %. Social gradient not observed in the management lapses. Most (76.6 %) had accessed private sector while those in estate (58.1 %) accessed the state system. The microvascular complications of retinopathy, neuropathy and microalbuminuria observed in 11.1 %, 79.3 % and 54.5 % respectively. Among the macrovascular diseases, angina, ischaemic heart disease and peripheral arterial disease seen in 15.5 %, 15.7 % and 5.5 % respectively. These complications do not show a social gradient. CONCLUSIONS: Diabetes mellitus patients, irrespective of their socioeconomic status, are poorly managed and have high rates of complications. Most depend on the private healthcare system with overall poor access to care in the estate sector.

A cross sectional survey on social, cultural and economic determinants of obesity in a low middle income setting.

INTRODUCTION: Obesity is an increasing problem in South Asian countries and Sri Lanka is no exception. The socioeconomic determinants of obesity in Sri Lanka, and in neighbouring countries are inadequately described. Aim was to describe social, cultural and economic determinants of obesity in a representative sample from Kalutara District in Sri Lanka. METHODS: This was a cross sectional descriptive study conducted among adults aged 35-64 years. A representative sample was selected using stratified random cluster sampling method from urban, rural and plantation sectors of Kalutara District. Data were collected using a pre-tested questionnaire. A body mass index of 23.01 kg/m(2)-27.50 kg/m(2) was considered as overweight and ≥27.51 kg/m(2) as obese. Waist circumference (WC) of ≥ 90 cm and ≥80 cm was regarded as high for men and women respectively. Significance of prevalence of obesity categories across different socio-economic strata was determined by chi square test for trend. RESULTS: Of 1234 adults who were screened, age and sex adjusted prevalence of overweight, obesity and abdominal obesity (high WC) were 33.2% (male 27.3%/female 38.7%), 14.3% (male 9.2%/female 19.2%) and 33.6% (male 17.7%/female 49.0%) respectively. The Muslims had the highest prevalence of all three obesity categories. Sector, education, social status quintiles and area level deprivation categories show a non linear social gradient while income shows a linear social gradient in all obesity categories, mean BMI and mean WC. The differences observed for mean BMI and mean WC between the lowest and highest socioeconomic groups were statistically significant. CONCLUSION: There is a social gradient in all three obesity categories with higher prevalence observed in the more educated, urban, high income and high social status segments of society. The higher socioeconomic groups are still at a higher risk of all types of obesity despite other public health indicators such as maternal and infant mortality displaying an established social gradient.

Social, cultural and economical determinants of diabetes mellitus in Kalutara district, Sri Lanka: a cross sectional descriptive study.

INTRODUCTION: Sri Lanka is a country that is expected to face a high burden of diabetes mellitus (DM). There is a paucity of data on social and demographic determinants of DM, especially in the plantation sector. AIMS: To describe social and economic correlates and inequalities of DM in Kalutara District. METHODS: A cross sectional descriptive study was carried out among adults over the age of 35 years. A sample of 1300 individuals was selected using stratified random cluster sampling method from 65 Grama Niladari Divisions (GND), which were representative of urban, rural and plantation sectors. Twenty households were randomly selected from each division and one adult was randomly selected from each household. Data were collected using a pre-tested questionnaire. Fasting plasma blood sugar of ≥126mg/dl was used to define DM. Significance of prevalence of diseases and risk factors across different socio-economic strata were determined by chi square test for trend. RESULTS: Of 1234 adults who were screened (628 males), 202 (14.7%) had DM. Higher DM proportions (16.1%) were seen in the highest income quintile and in those educated up to Advanced Levels (AL) and above (17.3%). Prevalence in the urban, rural and plantation sectors were 23.6%, 15.5% and 8.5% respectively. Prevalence among Sinhalese, Tamils and Muslims were 14.4%, 29.0% and 20.0% respectively. There was a gradient in prevalence according to the unsatisfactory basic needs index of the GND with the highest proportion (20.7%) observed in the richest GND. The highest social status quintile demonstrated the highest proportion (17.4%) with diabetes mellitus. CONCLUSION: There is a higher prevalence of diabetes mellitus in the more affluent and educated segments of society. There is also a higher prevalence among urban compared to rural and estates. Sri Lanka is in an early stage of the epidemic where the wealthy people are at a higher risk of DM.