Apoptotic effect of Bulbine Natalensis and Chlorophytum Comosum in myelogenous Leukemia K562 cell line / Efeito apoptótico da natalensia bulbina e do clorofito comoso na linhagem celular mielogênea da leucemia K562

Abstract Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 μg/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p < 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.

Resumo Bulbine natalensis Baker e Chorophytum comosum (Thunb.) Jacques são potenciais fontes medicinais para o tratamento de cânceres. A Leucemia Mieloide Crônica (LMC) é um distúrbio das células-tronco hematopoiéticas que é tratado com inibidores da tirosina quinase, mas frequentemente, causa recorrência da leucemia após a interrupção da terapia, portanto, requer um tratamento alternativo. Este estudo determinou o efeito anticancerígeno de extratos metanólicos e aquosos de folha, raiz e bulbo de B. natalensis e C. comosum na linhagem celular de leucemia mieloide humana crônica (K562) por ensaios de MTT, Hoechst bis-benzimida nuclear e anexina V. O extrato metanólico da raiz de B. natalensis e C. comosum apresentou alta citotoxidade de 8,6% e 16,7% respectivamente, na linhagem celular K562 com a concentração de 1,000 μg / ml. Perda morfológica da integridade da membrana celular causando degradação dos núcleos, citoplasma e encolhimento celular foi observada no extrato metanólico da raiz de ambas as plantas. Uma alta apoptose (p <0,0001) foi induzida nas células K562 por extratos de folhas e raízes de C. comosum em comparação com B. natalensis. Este estudo mostrou que ambas as plantas possuem efeito apoptótico contra leucemia mieloide in vitro que contribui para as propriedades anticâncer gerais de B. natalensis e C. comosum para justificar futuras aplicações terapêuticas contra câncer de sangue de LMC.

Apoptotic effect of Bulbine Natalensis and Chlorophytum Comosum in myelogenous Leukemia K562 cell line

Abstract Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 g/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.

Resumo Bulbine natalensis Baker e Chorophytum comosum (Thunb.) Jacques são potenciais fontes medicinais para o tratamento de cânceres. A Leucemia Mieloide Crônica (LMC) é um distúrbio das células-tronco hematopoiéticas que é tratado com inibidores da tirosina quinase, mas frequentemente, causa recorrência da leucemia após a interrupção da terapia, portanto, requer um tratamento alternativo. Este estudo determinou o efeito anticancerígeno de extratos metanólicos e aquosos de folha, raiz e bulbo de B. natalensis e C. comosum na linhagem celular de leucemia mieloide humana crônica (K562) por ensaios de MTT, Hoechst bis-benzimida nuclear e anexina V. O extrato metanólico da raiz de B. natalensis e C. comosum apresentou alta citotoxidade de 8,6% e 16,7% respectivamente, na linhagem celular K562 com a concentração de 1,000 g / ml. Perda morfológica da integridade da membrana celular causando degradação dos núcleos, citoplasma e encolhimento celular foi observada no extrato metanólico da raiz de ambas as plantas. Uma alta apoptose (p 0,0001) foi induzida nas células K562 por extratos de folhas e raízes de C. comosum em comparação com B. natalensis. Este estudo mostrou que ambas as plantas possuem efeito apoptótico contra leucemia mieloide in vitro que contribui para as propriedades anticâncer gerais de B. natalensis e C. comosum para justificar futuras aplicações terapêuticas contra câncer de sangue de LMC.

Comparative study of serum ferritin levels and hepatic transaminases between uncomplicated paediatric dengue inpatients and other febrile illnesses in Kanchipuram, India

Background: Fever is the most common complaint with bringing children for hospital consultation. Dengue is a cause of public health concern with case fatality rate of 1%. Ferritin is an acute-phase reactant which is produced in response to infection and inflammation. Liver enzymes are also considered as markers of febrile illness. Aim of this study was to assess serum ferritin levels, aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) levels in pediatric inpatients with febrile illness, to correlate it with patient’s Dengue profile and to analyse these parameters with sub-group analysis of dengue and OFI.Methods: Among 120 children admitted for fever of more than 3 days duration were included in the study. 58 were Dengue-NS1 positive and the remaining 62 were considered to be OFI. Serum ferritin levels, AST and ALT were the investigative parameters measured at the time of admission for the study and treated as per WHO Dengue Guidelines. Data was coded and entered in Microsoft Excel 2013. Data was analysed using SPSS v16. p value of <0.05 was considered statistically significant.Results: Ferritin levels were higher in Dengue-IgM positive subgroup than in OFI subgroup (U= 173, Z score -6.09, p<0.00001). AST levels are higher in Dengue-NS1 positive subgroup than in OFI subgroup (U= 103, Z score -8.08, p<0.00001). AST levels were also higher in Dengue-IgM positive subgroup than in OFI subgroup (U= 377.5, Z score -4.86, p<0.00001). ALT levels are higher in Dengue-NS1 positive subgroup than in OFI subgroup (U=76, Z score -8.95, p<0.00001) as well as in Dengue-IgM positive subgroup than in OFI subgroup (U= 417, Z score -4.4, p<0.00001).Conclusions: Hyperferritinemia and elevation of hepatic-transaminases is seen in dengue. Although elevated in other febrile illnesses, it is elevated more so in dengue. This can be a predictor of severity of dengue fever, but needs to be confirmed in larger studies.

India Diverges in Gender Proportion in COVID-19: A Health Management Study

The primary objective of this study was to investigate the male and female proportion for variouscountries and India. The secondary aim of the study was to identify the multiple influencing factorsthat are playing a role in the male to female ratio and how India differs from other countries. For thisstudy, we have used the available data and reports from various countries, health organisations andWHO from Dec 2019 to May 2020 for comparison and interpretation. There are multiple influencersfor women getting less infected by COVID-19. There are biological reasons such as chromosomesand oestrogen; lifestyle reasons such as smoking and drinking habits, and controlled food habits;social causes such as working hard in rural areas, less exposure to the crowd and minimalinternational travelling opportunities; cultural reasons such as less social gathering, default socialdistancing system and also there is an assumption that Indian women are culturally more disciplined.It is vital to understand gender-based differences in the human immune systems and how it affects thespread of the virus. Knowing the steps and precautionary measures can help us to prevent the spreadof coronavirus. Prevention is always better than cure. By following the advisories from WHO andother nation’s health organisation, making a collaborative effort, we all should be able to managebetter.

Clinical outcomes after percutaneous coronary intervention in patients with coronary artery disease: six months results from a single centre study

Background: The study aimed to evaluate clinical outcomes in patients with coronary artery diseases (CAD) who underwent percutaneous coronary intervention (PCI), to identify the factors associated with clinical outcomes and survival among such patients, to explore the procedure related complications, and to assess restenosis and stent thrombosis rates following PCI.Methods: This retrospective, single-center, observational study was conducted at a tertiary-care center in India, which included patients with CAD undergoing PCI from January 2016 to December 2016. Angiographic and clinical success and complications related to both procedural and vascular access were noted. Patient were followed-up for clinical outcomes up to 6-months. Primary outcome of the study was all-cause mortality. Secondary outcome measures were cardiovascular mortality, and event free survival, angina, cardiovascular events and restenosis and stent thrombosis.Results: A total of 831 patients were included of which majority were males (83.5%). Smoking was found in 33.7%, diabetes in 35.6%, and hypertension in 37.7%. At 6-months, follow-up was obtained for 711 patients. The clinical composite endpoint seen in 9.8% of patients. Angina (13.2%), acute coronary syndrome (3.1%), stent thrombosis (1.0%), in-stent restenosis (3.9%), cardiovascular and all-cause mortality (2.7%), heart failure (7.3%) and stroke (1.7%) were reported at 6-months follow-up.Conclusions: The PCI in a tertiary-care centre leads to low rates of periprocedural events and low rates of clinical outcomes at 6-months follow-up. Moreover, left ventricular ejection fraction was shown to be major predictor for cardiovascular mortality in post-PCI patients. Hypertension was significantly associated with stroke post-PCI.

Role of Sildenafil in ovulation induction A comparative study of outcomes with Sildenafil in ovulation induction cycles with Clomiphene Citrate

Background: Intraperitoneal instillations of local anaesthetic agents alone or in combination dexmedetomidine have been found to reduce post-operative pain following laparoscopic cholecystectomy. Aim: Comparing antinociceptive effects of intraperitoneal instillation of bupivacaine plain and bupivacaine with dexmedetomidine in patients undergoing laparoscopic cholecystectomy. Materials and methods: Study was conducted on 100 adult patients of ASA physical status 1 and 2 in the age group of 18 years to 60 years, posted for elective laparoscopic cholecystectomy under general anaesthesia. Patients were randomly divided on an alternate basis into two groups of 50 each. Group B: (n=50) patients received Intraperitoneal bupivacaine 50 ml 0.25% + 5 ml normal saline. Group DB: (n=50) Intraperitoneal bupivacaine 50 ml 0.25% + dexmedetomidine 1 μg/kg with normal saline 5 ml. Results: Mean pain scores were significantly lower in the group BD when compared to group B during the entire duration of the study. There was statistically significant difference in VAS pain score at 6, 8, 12, 18, 24 hours after surgery. Mean pain scores were significantly lower in the group BD Srinivas Rapolu, K Anil Kumar, Syed Ali Aasim. A comparative study on intraperitoneal bupivacaine alone or with dexmedetomidine for post-operative analgesia following laparoscopic cholecystectomy. IAIM, 2016; 3(12): 33-40. Page 34 when compared to group B during the entire duration of the study. There was statistically significant difference in VAS pain score at 6, 8, 12, 18, 24 hours after surgery. There was statistically significant difference between two groups of patients in terms of heart rate, systolic and diastolic blood pressure from 1 hour to 12 hours. 4 patients (8%) of group B and only 5 (10%) patients of groups B + D had postoperative nausea/vomiting, and 7 (14%) patients of group B and 2 (4%) patients of groups B+D had postoperative shoulder pain. Conclusion: Intraperitoneal instillation of dexmedetomidine with bupivacaine prolongs the duration of postoperative analgesia as compared to that with bupivacaine alone.

Tumor retention and biodistribution studies of etoposide loaded tripalmitin nanoparticles after intratumoral administration in Dalton's Iymphoma tumor bearing mice

The objective of the present work is to study the biodistribution and tumor retention properties of etoposide (anticancer agent) and etoposide loaded tripalmitin nanoparticles (ETPL) after intratumoral administration in Dalton's lymphoma tumor bearing mice. ETPL nanoparticles were prepared by melt-emulsification and high pressure homogenization followed by spray drying technique. The nanoparticles were uniform and possessed 387 nm mean diameter and negative charge with excellent redispersibility in aqueous media. Radiolabeling of etoposide and ETPL nanoparticles with Technetium-99m (99mTc) resulted in complexes with high labeling efficiency and low radiocolloid formation. The labeled complexes showed good in vitro stability as indicated by low transchelation in presence of DTPA and cysteine and stability in human serum. Biodistribution and tumor retention studies were performed for etoposide and ETPL nanoparticles after intratumoral injection in mice bearing Dalton's lymphoma tumor. Etoposide experienced rapid clearance from the tumor, while the disposition of ETPL nanoparticles was slower. The tissue concentrations of ETPL nanoparticles increased with time (i.e. at 6h and 24h post injection) indicating its retention in tumor site for a longer time. Tumor retention of both etoposide and ETPL nanoparticles was studied upto 48h post injection. The tumor concentration of both etoposide and ETPL nanoparticles was high initially (8.57 percent and 41.8 percent injected dose at 0.5h post injection) and decreased with time (0.12 percent and 1.68 percent injected dose at 48h post injection). The concentration of etoposide rapidly declined from the tumor site while the tumor retention of ETPL nanoparticles was significantly higher than free etoposide (P < 0.001) at all the time points studied. The over all many fold higher tumor retention of ETPL nanoparticles (14 folds even at 48h post injection) compared to etoposide, coupled with lower tissue distribution signifies...

Lymphatic transport of orally administered drugs.

Several therapeutic molecules such as lipophilic drugs and peptides suffer from the problems of low oral bioavailability. Improvement of their bioavailability and simultaneous prevention of the oral degradation of the prone molecules appears to be a challenge. Lymphatic system, which is responsible for the maintenance of fluid balance, immunity and metastatic spread of cancers, is also found to play a major role in the oral absorption of lipids and lipophilic drugs from intestine. The specialized structure of gut associated lymphoid tissue can be utilized as a gateway for the delivery of particulate systems containing drugs. Even though a large gap has existed in the field of lymphatic drug delivery, the introduction of a large number of lipophilic drugs and peptides has brought a renewed interest of research in this area. In this review, the mechanisms of intestinal lymphatic drug transport, approaches taken for the delivery of macromolecules, lipophilic and peptide drugs, biochemical barriers involved in intestinal drug absorption, and animal models used in the studies of intestinal lymphatic drug transport has been discussed.

Effect of physicochemical parameters on skin permeability of antihypertensive.

Studies were carried out to establish a correlation of skin permeability with physicochemical parameters using five antihypertensive drugs. In vitro skin permeation was carried out in vertical type diffusion cells. When steady-state fluxes of the drugs were correlated with physicochemical properties, good correlation was obtained with the reciprocal of melting point. Weak correlation was obtained with partition coefficient, molecular weight and solubility. However skin permeability versus solubility profiles revealed an interesting trend. The initial permeation rates of the poorly water soluble drugs, prazosin hydrochloride and reserpine were higher than their steady-state fluxes and moderately water soluble drug atenolol showed more or less similar permeation throughout the entire span of the study. This trend changed gradually and reversed completely in the highly water soluble drug diltiazem hydrochloride. The study suggests that drug derivatives of low melting point and good aqueous solubility could be favorable candidates for transdermal delivery.

Enhancer aided in vitro permeation of atenolol and prazosin hydrochloride through mice skin.

Effect of penetration enhancers were studied on the permeation of antihypertensive drugs prazosin hydrochloride and atenolol through full thickness skin of swiss albino mice. Atenolol was delivered to skin from saturated alcoholic solution containing 5% of 1-decanol and alcohol alone, while prazosin hydrochloride was saturated in dimethyl formamide(DMF, 5% v/v in water) and dimethyl sulfoxide(DMSO, 5% v/v in water). Atenolol permeation was augmented significantly in decanolic solution and also in pure alcohol. In case of prazosin hydrochloride, significant enhancement of permeation was shown by DMSO but not by DMF.

Comparison of skin permeability of drugs in mice and human cadaver skin.

In vitro percutaneous absorption of four antihypertensive drugs were carried out across the mice and human cavader skin in order to compare their skin permeability. An interesting trend was noticed in these experiments. Poorly water soluble drug prazosin hydrochloride showed 13 times enhanced flux in the mice skin whereas the steady-state flux of the water soluble drug propranolol hydrochloride was almost same in both human cadaver and mice skin. The permeation rate of prazosin hydrochloride and propranolol hydrochloride through the human cadaver skin fluctuated widely over time, but in mice skin, distinct trends were noticed. The study indicates that the overall permeation rate in mice skin is higher than that in the cadaver skin and the meeting of the target-flux in mice skin does not guarantee its good permeability in human skin.

Effect of inadequate frequency response of direct writing electrocardiograph on rat electrocardiogram.

Fairly good electrocardiograms of rats can be recorded by using a band width of 0.5 to 75 Hz. Change in low frequency did not alter the wave pattern or duration. Change in high frequency altered the durations and wave pattern grossly. 50 Hz filter is useful in avoiding AC interference but creates artificial notches in all the waves.

Effect of hippocampal lesion on acquisition of conditioned avoidance behaviour in albino rats.

Control, hippocampal and Sham control male albino rats weighing 150-200 gms were trained for acquisition of conditioned avoidance behavioural response using escape avoidance apparatus. Parameters like rate of performance, error scores, conditioned stimulus latency and unconditioned stimulus latency were studied. It was observed that there was a facilitation in the behavioural response with less error scores in hippocampal animals as compared to Sham control and control groups. Our observations are similar to those of Douglas and Pribram and Douglas and it is concluded that the hippocampus acts as a gate restricting the range of stimuli to which an intact animal attends.

Effect of change in limb position on mean electrical axis and amplitudes of QRS complex of rat electrocardiogram.

The effect of altered fore limb alignment to trunk on mean electrical axis (MEA) and on amplitude of the QRS complex of frontal plane leads was studied in both prone and supine postures in 32 albino rats. It was found that in both postures bilateral extension of fore limbs caused a significant change in MEA to right. Unilateral change in the fore limb alignment caused a shift in MEA to right only in supine position, but was ineffective in prone position. The amplitudes of QRS complexes also changed with change in MEA. The changes in MEA with change in limb alignment and subsequent alteration in amplitude of QRS complexes can be attributed to the alteration in anatomical orientation of the heart in the chest cavity.

Sensory nerve conduction in diabetes mellitus and diabetic neuropathy.

Electrophysiological evaluation of conduction in sensory fibres of right ulnar and median nerves were carried out in normal subjects and diabetics with and without neuropathy. The sensory conduction velocities of ulnar as well as median nerves are significantly depressed in both groups of diabetics, particularly in those with neuropathy. The diabetics with or without neuropathy require a higher strength of stimulus for conduction in both median and ulnar nerves as compared to the normal subjects. The amplitude of action potentials is also lowered in both ulnar and median nerves of the two groups of diabetics. Estimation of conduction velocities of sensory fibres can be considered as a more useful parameter than the measurement of amplitude of action potentials in the diagnosis and evaluation of neuropathy in diabetics. It is concluded that assessment of sensory nerve conduction in median nerve is a better indicator than that of ulnar nerve for this purpose.

Production of myocardial lesions in a graded fashion by noninvasive technique in albino rats.

Systematic study of producing graded lesions of myocardium with the use of Isoproterenol (IPT) reveals that mild to severe degree of infarction can be induced by administering the compound for one to four consecutive days in the dose of 85 mg/kg body weight in rats. These findings differ slightly from those of Rona et al. where they have not attempted to produce the lesions in a graded fashion. The experimental period can be reduced to two days by using high dose (170 mg/kg), but such procedure increases significantly the mortality in these animals and lesions are not produced in graded fashion.

Cardiovascular effects of acetaldehyde in guinea pigs.

The hemodynamic effects of intravenous administration of acetaldehyde were determined in anesthetized control (group I), propranolol pretreated (group II) and phentolamine pretreated (group III) guinea pigs. Acetaldehyde produced an immediate and significant increase in mean arterial pressure followed by its progressive decrease resulting in hypotension. Heart rate increased significantly. In propranolol treated animals, acetaldehyde-induced tachycardia was not produced whereas in phentolamine treated animals, the initial pressor response was converted into a depressor one. Hence the increase in mean arterial pressure and heart rate produced by acetaldehyde are likely to be due to catecholamine release from adrenergic nerve endings.