Impact of COVID-19 pandemic on ophthalmic presentations to an Australian outer metropolitan and rural emergency department: a retrospective comparative study.

BACKGROUND: To analyse ophthalmic presentations to an outer metropolitan and a rural emergency department (ED) during the first wave of the COVID-19 pandemic in New South Wales (NSW), Australia. METHODS: A retrospective comparative study of ophthalmic emergency presentations to Campbelltown Hospital (fifth busiest NSW metropolitan ED; population 310,000) and Bowral and District Hospital (rural ED; population 48,000) before and during COVID-19 was conducted. Patient demographics, triage category, referral source, diagnosis, length of stay, departure status, and follow-up location were assessed from coding data between March 1st to May 31st in 2019 and 2020, corresponding to the peak case numbers and restrictions during the first wave of the COVID-19 pandemic in NSW. Differences before and during COVID-19 were analysed using chi-squared tests or independent sample t-tests. RESULTS: There was no change in ophthalmic presentations at Campbelltown (n = 228 in 2019 vs. n = 232 in 2020; + 1.75%, p = 0.12) and an increase at Bowral (n = 100 in 2019 vs. n = 111 in 2020; + 11%, p < 0.01) during COVID-19. Urgent ophthalmic presentations (Triage Category 3) decreased at Bowral (p = 0.0075), while non-urgent ophthalmic presentations (Triage Category 5) increased at both hospitals (Campbelltown p < 0.05, Bowral p < 0.01). CONCLUSIONS: There was no change in the total number of ophthalmic presentations to an outer metropolitan and an increase to a rural ED during the first wave of the COVID-19 pandemic in New South Wales, Australia. A change in the type of ophthalmic presentations at these peripheral EDs suggest that a high demand for ophthalmic services remained despite the pandemic and its associated gathering and movement restrictions. A flexible healthcare delivery strategy, such as tele-ophthalmology, may optimise patient care during and after COVID-19.

CD44 targeting hyaluronic acid coated lapatinib nanocrystals foster the efficacy against triple-negative breast cancer.

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than the counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs treatment caused significant retardation of tumor growth and overall increase in animal survival probability because of their higher tumor localization, increased residence time. Our findings clearly suggest that HA coated LPT-NCs formulation enhances the activity of LPT against triple negative breast cancer. It exhibited magnificent therapeutic outcome at low dose thus presenting a strategy to reduce dose administrations and minimize dose related toxicity.

Centchroman induces redox-dependent apoptosis and cell-cycle arrest in human endometrial cancer cells.

Centchroman (CC) or Ormeloxifene has been shown to induce apoptosis and cell cycle arrest in various types of cancer cells. This has, however, not been addressed for endometrial cancer cells where its (CC) mechanism of action remains unclear. This study focuses on the basis of antineoplasticity of CC by blocking the targets involved in the cell cycle, survival and apoptosis in endometrial cancer cells. Ishikawa Human Endometrial Cancer Cells were cultured under estrogen deprived medium, exposed to CC and analyzed for proliferation and apoptosis. Additionally, we also analyzed oxidative stress induced by CC. Cell viability studies confirmed the IC50 of CC in Ishikawa cells to be 20 µM after 48 h treatment. CC arrests the cells in G0/G1 phase through cyclin D1 and cyclin E mediated pathways. Phosphatidylserine externalization, nuclear morphology changes, DNA fragmentation, PARP cleavage, and alteration of Bcl-2 family protein expression clearly suggest ongoing apoptosis in the CC treated cells. Activation of caspase 3 & 9, up-regulation of AIF and inhibition of apoptosis by z-VAD-fmk clearly explains the participation of the intrinsic pathway of programmed cell death. Further, the increase of ROS, loss of MMP, inhibition of antioxidant (MnSOD, Cu/Zn-SOD and GST) and inhibition of apoptosis with L-NAC suggests CC induced oxidative stress leading to apoptosis via mitochondria mediated pathway. Therefore, CC could be a potential therapeutic agent for the treatment of Endometrial Cancer adjunct to its utility as a contraceptive and an anti-breast cancer agent.

Genetic thromobophilia in pregnancy: a case-control study among North Indian women.

In the present study, an attempt is made to understand the role of genetic thrombophilias i.e. MTHFR C677T and FVL in the causation of various pregnancy complications like pregnancy induced hypertension (PIH), recurrent abortions, intra-uterine growth retardation (IUGR) and intra-uterine death on the whole and also individually along with the comparative assessment of pathophysiological basis of various pregnancy complications via the genetic proximities. One thousand and eleven (1,011) women of reproductive age group were recruited in the present study comprising various complications and controls. Recruitment criteria for all the pregnancy complications and controls was made and followed strictly. MTHFR C677T and FVL mutation detection was done in all the subjects. Vegetarianism was found to be significant risk factors for all the pregnancy complications and also when assessed individually. With respect to MTHFR C677T polymorphism, higher frequency of 677T allele was found among controls as compared to cases. 677T allele was found to pose decreased risk for various pregnancy complications on the whole and also individually. On adjusting the diet, regression analysis revealed no risk of mutant allele (T) for various pregnancy complications. FVL homozygous mutants were found to be absent among controls. In conclusion, the present study depicts dietary pattern as one of the most important factors in demonstrating the role of MTHFR C677T in various pregnancy complications and is indicative of a relatively deleterious effect of double dose of FVL in the presently studied population. Additionally, these polymorphisms play an important role in the orchestration of PIH to IUGR and vice versa.

Risk of age-related macular degeneration 3 years after cataract surgery: paired eye comparisons.

OBJECTIVE: To clarify possible associations between cataract surgery and progression of age-related macular degeneration (AMD). DESIGN: Clinic-based cohort. PARTICIPANTS: We followed cataract surgical patients aged 65+ years in the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study. Patients who remained unilaterally phakic for at least 24 months after recruitment were included. METHODS: We performed annual examinations with retinal photography. We assessed AMD using side-by-side grading of images from all visits. Paired comparisons between operated and nonoperated fellow eyes (defined as nonoperated or operated <12 months previously) were made using generalized estimating equation models. MAIN OUTCOME MEASURES: Incident early AMD was defined as the new appearance of soft indistinct/reticular drusen or coexisting retinal pigmentary abnormality and soft distinct drusen in eyes at risk of early AMD. Incident late AMD was defined as the new appearance of neovascular AMD or geographic atrophy (GA) in eyes at risk of late AMD. RESULTS: Among 2029 recruited, eligible participants, 1851 had cataract surgery performed at Westmead Hospital, Sydney, and 1244 (70.7%) had 36-month postoperative visits. Of these participants, 1178 had gradable photographs at baseline and at least 1 follow-up visit. Of 308 unilaterally operated participants at risk of late AMD, this developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.23-2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilaterally operated participants at risk of early AMD, this developed in 23 (10.6%) operated and 21 (9.7%) nonoperated fellow eyes (OR, 1.07; 95% CI, 0.74-1.65). Incident retinal pigment abnormalities were more frequent in operated than nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07-2.52). There was no difference in the 3-year incidence of large soft indistinct or reticular drusen between the 2 eyes (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79-1.60). CONCLUSIONS: Prospective follow-up data and paired eye comparisons of this older surgical cohort showed no increased risk of developing late AMD, early AMD, or soft/reticular drusen over 3 years. There was a 60% increased detection of retinal pigmentary changes in surgical eyes.

Standardising the cataract referral process for public hospitals: perspectives of optometrists in New South Wales, Australia.

BACKGROUND: Previous research has shown that cataract surgery referral letters to major metropolitan public hospitals in New South Wales have insufficient detail to inform patient triage or apply prioritisation tools. This study aimed to canvass the views of optometrists working in New South Wales and the Australian Capital Territory (NSW/ACT) on standardising the referral process for public hospital cataract surgery. METHODS: An online survey was sent to all NSW/ACT members of Optometry Australia in October 2017. Respondents were asked to select clinical and personal information to be included on a referral template using a list of 25 items. Data were also gathered on preferences for the cataract referral process and sources of cataract referral guidelines. RESULTS: Two hundred and thirteen (response rate 13 per cent) optometrists completed the survey. There was close to universal support for inclusion of items like visual acuity (99 per cent), whereas other items had low support, including the date and details of previous refraction (26 per cent), history of falls (29 per cent) and health insurance status (29 per cent). Three-quarters of optometrists stated they would be willing to administer and report data from a patient survey about the functional impact of their cataract and level of visual disability. The preferred format of a standardised cataract referral template varied, although time efficiency and ease of completion were commonly cited reasons for preferences. Confirmation of receipt of referral from the public hospital, and a copy of the referral letter for the optometrist's records were also desirable. For the 61 per cent of respondents who reported accessing guidelines for cataract referral, 69 per cent stated the main source was Optometry NSW/ACT with fewer accessing guidelines directly from a public hospital or the NSW Health website. CONCLUSION: Optometrists' preferences will be useful to inform the design and implementation of a standardised cataract referral template.

Glycemic index, retinal vascular caliber, and stroke mortality.

BACKGROUND AND PURPOSE: It is unclear whether diets with high glycemic index (GI) and low cereal fiber (CF) are associated with greater risk of stroke. We aimed to assess the relationship between dietary GI and CF content, retinal microvasculature changes, and stroke-related mortality. METHODS: The study consisted of a population-based cohort, 49+ years, examined at baseline (1992 to 1994). At baseline, participants completed validated food frequency questionnaires. Mean GI was calculated using an Australian database. Retinal arteriolar and venular diameters were measured from photographs. Mortality data were derived using the Australian National Death Index. RESULTS: Over 13 years, 95 of 2897 participants (3.5%) died from stroke. Increasing GI (hazard ratio, 1.91; 95% CI, 1.01 to 3.47, highest versus lowest tertile) and decreasing CF (hazard ratio, 2.13; 95% CI, 1.19 to 3.80, lowest versus highest tertile) predicted greater risk of stroke death adjusting for multiple stroke risk factors. Persons consuming food in the highest GI tertile and lowest CF tertile had a 5-fold increased risk of stroke death (hazard ratio, 5.06; 95% CI, 1.67 to 15.22). Increasing GI and decreasing CF were also associated with retinal venular caliber widening (P(trend)<0.01). Adjustment for retinal venular caliber attenuated stroke death risk associated with high GI by 50% but did not affect the risk associated with low CF consumption. CONCLUSIONS: High-GI and low-CF diets predict greater stroke mortality and wider retinal venular caliber. The association between a high-GI diet and stroke death was partly explained by GI effects on retinal venular caliber, suggesting that a high-GI diet may produce deleterious anatomic changes in the microvasculature.

Genistein potentiates Centchroman induced antineoplasticity in breast cancer via PI3K/Akt deactivation and ROS dependent induction of apoptosis.

AIMS: Recently, strategies of cancer treatment using combination of agents with distinct molecular mechanism(s) of action are considered more promising due to its high efficacy and reduced systemic toxicity. The study is aimed to improve the efficacy of selective estrogen receptor modulator, Centchroman (CC) by combination with the phytoestrogen Genistein (GN). METHODS: Cytotoxicity was evaluated by Sulforhodamine B assay. Cell cycle analysis was done through flow cytometry. Further, Apoptosis was analyzed using Annexin V/PI staining, tunel assay and electron microscopic examination and verified using western blot analysis. In order to validate the in vitro results, in vivo analysis was performed using 4T1-syngeneic mouse model. KEY FINDINGS: In this study, we report that the dietary isoflavone genistein (GN) synergistically improved antineoplasticity of CC in breast cancer by arresting cells at G2/M phase culminating in ROS dependent apoptosis. The combination of CC plus GN caused dysregulation of Bax and Bcl-2 ratio inducing mitochondrial dysfunction, activation of Caspase-3/7, -9 and PARP cleavage. Further, combination significantly suppresses phosphorylation of PI3K/Akt/NF-κB, enhancing apoptosis. Additionally, combination markedly reduced tumor growth compared to CC and GN alone in mouse 4T1 breast tumor model. SIGNIFICANCE: Together, these studies suggest that GN represents a potential adjunct molecule whose role in CC induced apoptosis deserves attention.

Dietary isoflavone daidzein synergizes centchroman action via induction of apoptosis and inhibition of PI3K/Akt pathway in MCF-7/MDA MB-231 human breast cancer cells.

BACKGROUND: Despite advancements in the prognosis and management of breast cancer, it remains a major cause of mortality in women worldwide. Centchroman (CC), an oral contraceptive has been found to exhibit anti-cancer potential against a wide range of cancer including breast cancer. PURPOSE: The present study is intended to evaluate the ability of soy isoflavone Daidzein (DZ) in enhancing the efficacy of CC in Human Breast Cancer Cells (HBCCs). METHODS/STUDY DESIGN: Sulforhodamine B assay was employed to determine the cytotoxicity induced by 10 µM CC & 50 µM DZ separately and together in MCF-7/MDA MB-231 HBCCs and non-tumorigenic Human Mammary Epithelial Cells (HMECs) MCF-10A as a control. Combination Index (CI) analysis was executed using CompuSyn software. Further, apoptosis was assessed using Annexin V/PI, AO/PI staining and tunel assay. Cell cycle, reactive oxygen species generation and mitochondrial membrane potential alteration was determined using flow cytometry. Western blot analysis was performed to check the expression of respective proteins. RESULTS: The results suggest that the combination exerts elevated toxicity as compared to control and each drug per se without affecting HMECs MCF-10A. This therefore implies cancer cell specific action of CC plus DZ administered together. Additionally, combination index analysis suggests synergistic action of CC and DZ combination in HBCCs. Cell cycle analysis, Annexin V/PI staining, tunel assay and western blot analysis confirms the induction of apoptosis by combination in HBCCs. Interestingly, western blot analysis also revealed that the combination down-regulated the expression of proteins involved in cell survival i.e. PI3K, Akt and mTOR, suggesting inhibition of cell survival pathway. CONCLUSION: The results overall demonstrate that CC plus DZ has higher anticancer efficacy as compared to either drug alone. Hence, the combination of CC plus DZ may offer a novel strategy for the management of breast cancer.

Centchroman regulates breast cancer angiogenesis via inhibition of HIF-1α/VEGFR2 signalling axis.

AIMS: Angiogenesis is a recognized hallmark of cancer which promotes cancer cell progression and metastasis. Inhibition of angiogenesis to attenuate cancer growth is becoming desirable strategy for breast cancer management. The present study is aimed to investigate the antiangiogenic efficacy of a novel selective estrogen receptor modulator Centchroman (CC) on human breast cancer cells. MAIN METHODS: Effect of CC on cell viability was evaluated using Sulforhodamine B assay. Endothelial cell proliferation, wound healing, Boyden chamber cell invasion, tube formation and chorioallantoic membrane (CAM) assays were performed to assess the effect of CC on migration, invasion and angiogenesis. Apoptosis, reactive oxygen species generation, caspase-3/7 and intracellular calcium ion level were measured through flow cytometry. Expression levels of HIF-1α, VEGF, VEGFR2, AKT and ERK were assessed by western blot analysis. KEY FINDINGS: CC selectively induces apoptosis in human breast cancer cells without affecting non-tumorigenic breast epithelial cells MCF-10A. Moreover, it inhibits migratory, invasive and mammosphere forming potential of breast cancer. Furthermore, CC also inhibited VEGF-induced migration, invasion and tube formation of HUVECs in vitro. CC effectively inhibited neovasculature formation in chicken CAM. Western blot analysis demonstrated that CC inhibited expression of HIF-1α and its downstream target VEGF. Interestingly, CC also suppressed VEGFR2 phosphorylation and consequently attenuated AKT and ERK phosphorylation. SIGNIFICANCE: Our findings suggest that CC downregulates VEGF-induced angiogenesis by modulating HIF-1α/VEGFR2 pathway and recommend it (CC) as a potential therapeutic drug for breast cancer treatment.

Long-term effects of smoking on retinal microvascular caliber.

Although cigarette smoking is a major cardiovascular risk factor, its microcirculatory effects are not well understood. The authors investigated cross-sectional and longitudinal relations between smoking and retinal microvascular caliber in an older Australian population. Retinal vessel calibers were measured from digitized retinal photographs at baseline (1992-1994; n = 3,006) and at 5-year follow-up examinations (1997-1999; n = 1,850) in the population-based Blue Mountains Eye Study. Smoking status and quantity and pack-years of smoking were defined from standardized questionnaires administered at both examinations. After adjustment for other factors, current and past smoking were associated with wider retinal venular caliber at baseline (p < 0.01). These cross-sectional findings were virtually identical at the 5-year follow-up examination (p < 0.001). Heavy smokers were more likely to have relatively large changes in venular caliber in either direction over the 5-year period (widening or narrowing more than 1 standard deviation greater than the mean change) than were nonsmokers (for continuous trend by pack-years or current amount smoked, p < 0.05). Weaker and less consistent associations between smoking and arteriolar caliber were observed. These results suggest long-term effects of smoking on venular caliber that may contribute to associations between smoking and cardiovascular disease.

Carbohydrate nutrition, glycemic index, and the 10-y incidence of cataract.

BACKGROUND: Although dietary carbohydrates are thought to play a role in cataractogenesis, few epidemiologic studies have examined links between carbohydrate nutrition and cataract. OBJECTIVES: We investigated the associations between dietary glycemic index (GI), glycemic load (GL), total carbohydrate intake, and 10-y incident nuclear, cortical, and posterior subcapsular cataract. DESIGN: Of 3654 baseline participants in an Australian population aged >/=49 y (1992-1994), 933 were seen after 5 and/or 10 y, had completed a detailed semiquantitative food-frequency questionnaire, had no previous cataract surgery or baseline cataract, and had photographs taken to assess incident cataract with the Wisconsin Cataract Grading System. Dietary information was collected with a validated food questionnaire. GI was calculated from a customized database of Australian foods. GI, GL, and all other nutrients were energy adjusted. Hazard ratios (HRs) and 95% CIs were calculated with the use of discrete logistic models. RESULTS: After age, sex, diabetes, and other factors were controlled for, each SD increase in GI significantly predicted incident cortical cataract (HR: 1.19; 95% CI: 1.01, 1.39). Participants within the highest compared with the lowest quartile of GI were more likely to develop incident cortical cataract (HR: 1.77; 95% CI: 1.13, 2.78; P for trend = 0.035). These findings were similar after excluding participants with diabetes, although they were slightly attenuated and marginally nonsignificant (HR: 1.16; 95% CI: 0.98, 1.37, per SD increase in GI). No association was found between GI and nuclear or posterior subcapsular cataract and between GL or carbohydrate quantity and any cataract subtype. CONCLUSION: In an Australian cohort, poorer dietary carbohydrate quality, reflected by high GI, predicted incident cortical cataract.

Age, blood pressure, and retinal vessel diameter: separate effects and interaction of blood pressure and age.

PURPOSE: The association of age and blood pressure (BP) with retinal vessel change is widely reported, with inverse relationships between retinal arteriolar and venular diameter and increasing age and elevated BP. No previous studies have dissected the separate effects of age and BP on the diameter of retinal vessels. METHODS: This was a population-based, cross-sectional study comprising 3654 participants (82.4% response) aged 49+ years from the Blue Mountains region of Australia. Retinal arteriolar and venular diameters were measured from digital retinal images, using a standardized method, and were summarized as central retinal arteriolar (CRAE) and central retinal venular (CRVE) equivalents. RESULTS: After adjustment for venular diameter, regression plots, and regression coefficients from linear models demonstrated an inverse relationship between arteriolar diameters and mean arterial BP (MABP) in all age groups-greatest in the <60 age group and progressively diminishing thereafter. Increasing age was associated with greater arteriolar narrowing (of lesser magnitude), in each MABP category (<100, 100-109, 109-129, and >120 mm Hg) with the greatest effect in persons with MABP <100. There was evidence of interaction between age and blood pressure in their effects on arteriolar diameter (P = 0.003). After adjustment for arteriolar diameter, age was inversely associated with venular diameter (the effect was progressively greater for persons with progressively higher MABP), and MABP was positively associated with venular diameter in subjects aged <80 years (interaction P = 0.05). CONCLUSIONS: These findings demonstrate the importance of elevated blood pressure in arteriolar narrowing, especially in those younger than 60 years and show that venules tend to widen rather than narrow with increasing blood pressure levels.

Prevalence and associations of enhanced retinal arteriolar light reflex: a new look at an old sign.

PURPOSE: To assess the prevalence, associated risk factors and prognosis (mortality) of the enhanced retinal arteriolar light reflex sign in an older Australian population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Three thousand six hundred fifty-four participants (82.4% response) ages >/=49 years from Australia's Blue Mountains region. METHODS: Retinal photographs of participants were graded for presence and severity of the enhanced arteriolar light reflex sign by comparison with standard photographs. Associations with systemic factors (subject-specific) and ocular variables (eye-specific) were assessed by logistic regression. Mortality data were obtained using the Australian National Death Index. Hazard ratios were calculated using Cox regression. MAIN OUTCOME MEASURES: Prevalence of enhanced arteriolar light reflex and associations with demographic variables (age, gender), blood pressure, blood parameters, health risk behaviors, cataract, retinal vessel wall signs, retinopathy, and 10-year incident mortality. RESULTS: The enhanced arteriolar light reflex sign was found in 1053 participants (31.7%, including 28.8% graded as mild and 2.9% as marked). Prevalence decreased with age (36.0%, 37.7%, 28.0%, and 18.8% for age groups < 60, 60-69, 70-79 and > or = 80 years, respectively, P(trend)<0.0001); odds ratio (OR) 0.78; and 95% confidence interval (CI) 0.72 to 0.85 per decade. Persons with cataract were less likely to have mildly enhanced light reflex (OR, 0.74; CI 0.64-0.87). After multivariate adjustment, mildly enhanced light reflex was significantly associated with serum glucose (OR 1.11 per SD increase), total cholesterol (OR 1.11), low-density lipoprotein (OR 1.55), triglycerides (OR 1.11), platelets (OR 0.89), and body mass index (OR 1.12). Markedly enhanced light reflex was significantly associated with mean arterial blood pressure (OR 1.24), heavy alcohol consumption (OR 2.66, > or = 40 grams alcohol per day), and serum glucose (OR 1.16). Strong associations were demonstrated between presence of mildly enhanced light reflex and either arteriovenous nicking (OR 3.12) or retinopathy (OR 1.96). There was no association between mildly or markedly enhanced light reflex and either all-cause or vascular mortality. CONCLUSIONS: In this older population, the enhanced retinal arteriolar light reflex sign was a relatively common finding. Although some associations of this sign with vascular risk factors were found, only a marked level of enhanced light reflex was correlated with elevated blood pressure, but not with poor survival.

Antiretroviral treatment in resource-poor settings: a view from India.

CONTEXT: The introduction of highly effective generic antiretroviral drugs at reduced cost has transformed the face of HIV/AIDS epidemic in developing countries like India. However, there is an urgent emphasis on developing and implementing guidelines for antiretroviral treatment monitoring by laboratory methods utilizing the available technologies in resource-limited settings. AIM: We studied the efficacy of antiretroviral treatment, adherence to therapy and motivation of patients for regular treatment monitoring by CD4 counts. SETTINGS AND DESIGN: A longitudinal cohort study on an established cohort of 166 HIV-1-infected Indian individuals. MATERIALS AND METHODS: Study subjects were followed up for the period from January 2002 to November 2006. Their clinical status and treatment regimen were recorded and CD4 counts were performed at each visit. STATISTICAL ANALYSIS: Repeated-measures ANOVA was used to compute changes in median CD4 counts at each visit in the different treatment groups. RESULTS: We observed a growing awareness and motivation for regular HIV disease monitoring among patients, accompanied by a trend of increasing median CD4 counts at all subsequent follow-up visits after initiation of antiretroviral treatment. CONCLUSIONS: The study gives an insight into the institutional efforts for the establishment of cohorts for longitudinal studies, which will help in designing effective treatment guidelines, thus providing impetus to the free public sector antiretroviral therapy program in India. Such formative research aims to fill the lacunae in the limited available data for the formulation of treatment-monitoring guidelines in resource-poor settings of developing countries like India.

Neem Seed Oil Induces Apoptosis in MCF-7 and MDA MB-231 Human Breast Cancer Cells

Background: In traditional Indian medicine, azadirachta indica (neem) is known for its wide range of medicinal properties. Various parts of neem tree including its fruit, seed, bark, leaves, and root have been shown to possess antiseptic, antiviral, antipyretic, anti-inflammatory, antiulcer, antimalarial, antifungal and anticancer activity. Materials and Methods: MCF-7 and MDA MB-231 cells were exposed to various concentrations of 2% ethanolic solution of NSO (1-30 µl/ml) and further processed for cell viability, cell cycle and apoptosis analysis. In addition, cells were analyzed for alteration in Mitochondrial Membrane Potential (MMP) and generation of Reactive Oxygen Species (ROS) using JC-1 and DCFDA staining respectively. Results: NSO give 50% inhibition at 10 µl/ml and 20 µl/ml concentration in MCF-7 and MDA MB-231 cells respectively and, arrests cells at G0/G1 phase in both the cell types. There was a significant alteration in mitochondrial membrane potential that leads to the generation of ROS and induction of apoptosis in NSO treated MCF-7 and MDA MB-231 cells. Conclusion: The results showed that NSO inhibits the growth of human breast cancer cells via induction of apoptosis and G1 phase arrest. Collectively these results suggest that NSO could potentially be used in the management of breast cancer.

Anticancer Potential of Steviol in MCF-7 Human Breast Cancer Cells.

OBJECTIVE: This study aimed to investigate the cytotoxicity, apoptosis induction, and mechanism of action of steviol on human breast cancer cells (Michigan Cancer Foundation-7 [MCF-7]). MATERIALS AND METHODS: Sulforhodamine-B assay was performed to analyze cytotoxic potential of Steviol whereas flow cytometer was used to analyze cell cycle, apoptosis, and reactive oxygen species generation. RESULTS: Studying the viability of cells confirms the IC50 of Steviol in MCF-7 cells which was 185 µM. The data obtained from fluorescence-activated cell sorter analysis reveal Steviol-mediated G2/M-phase arrest (P < 0.05) in addition to the presence of evident sub-G0/G1 peak (P < 0.05) in the MCF-7 cells, signifying the ongoing apoptosis. CONCLUSION: Thus, results suggest that induction of apoptosis in MCF-7 cells was due to dose-dependent effect of Steviol. Our first in vitro findings indicate Steviol as a promising candidate for the treatment of breast cancer. SUMMARY: Steviol remarkably inhibited the growth MCF-7 HBCCs in a dose dependent mannerIt abolishes cell cycle progression by arresting cells at G2/M phaseSteviol induces the cells to undergo apoptosisSteviol induces the cells to generate reactive oxygen species (ROS). Abbreviations used: MCF-7: Michigan Cancer Foundation-7; SRB: Sulforhodamine-B assay; FACS: Fluorescence-activated cell sorter; ROS: Reactive oxygen species; DNA: Deoxyribonucleic acid.

Retinal vessel signs and 10-year incident age-related maculopathy: the Blue Mountains Eye Study.

OBJECTIVE: To examine whether retinal vessel signs are independent predictors of the long-term development of age-related maculopathy (ARM). DESIGN: Prospective population-based cohort study. PARTICIPANTS: Blue Mountains Eye Study participants aged > or =49 years (n = 3654) were examined during 1992 through 1994; 2335 (75% of survivors) were reexamined after 5 years and 1952 (76% of survivors) were reexamined after 10 years. METHODS: Baseline focal arteriolar narrowing and arteriovenous (AV) nicking were assessed and vessel calibers were measured from retinal photographs. A side-by-side grading method was used to assess ARM incidence. Eye-specific data were analyzed using generalized estimating equation models, adjusting for age, gender, smoking, and blood pressure. MAIN OUTCOME MEASURES: Incident early ARM (soft indistinct or reticular drusen or combined soft distinct drusen and retinal pigment abnormality) was defined in eyes free of both early and late ARM at baseline. Incident late ARM (either geographic atrophy or neovascular macular degeneration) was defined in eyes free of these 2 lesions at baseline. RESULTS: Over a 10-year period, incident late ARM developed in 106/4745 eyes at risk of late ARM (2.2%). Eyes with mild (2.7%) or severe (4.6 %) AV nicking were more likely to develop late ARM than eyes without this sign (1.5%). The adjusted odds ratio (OR) was 1.4, 95% confidence interval (CI) 0.8 to 2.4 for mild and OR 2.6, 95% CI 1.2 to 5.5 for severe AV nicking. Eyes with focal narrowing were also more likely to develop late ARM (7.6% vs. 1.8%), adjusted OR 2.2, 95% CI 1.1 to 4.1. Incident early ARM developed in 398/4490 eyes at risk of early ARM (8.9%). Severe AV nicking, but not focal arteriolar narrowing, was associated with an increased long-term risk of early ARM (13.6% vs. 8.2%; OR 1.5; 95% CI 1.0-2.3). Neither arteriolar nor venular caliber was significantly associated with the incidence of either early or late ARM. CONCLUSIONS: These 10-year incidence data confirm our previous observation that structural retinal arteriolar changes may either contribute to ARM progression or share common pathologic pathways with ARM, independent of traditional vascular risk factors.