Antidyslipidemic Effect of Ocimum sanctum Leaf Extract in Streptozotocin Induced Diabetic Rats.

The antidyslipidemic activity of Ocimum sanctum leaf extract was studied in streptozotocin induced diabetic rats. In this model, there was significant increase in plasma markers of diabetic-dyslipidemia following diminution of lipid metabolizing enzymes. Oral administration of leaf extract (500 mg/kg b.w.p.o.) for 15 days resulted in significant decrease in diabetogenic and dyslipidemia parameters; namely blood glucose, glycosylated hemoglobin, lipid peroxide, free fatty acids, small dense low density lipoprotein, lipid and protein components of plasma lipoproteins, adipose and liver. The regulation of lipids was accompanied by stimulation of postheparin lipolytic activity, reactivation of lecithin cholesterol acyl transferase and hepatic lipoprotein lipase enzymes. The results of the present study demonstrated antidyslipidemic and antioxidant activities in leaf extract of O. sanctum which could be used in prevention of diabetic-dyslipidemia and related complications.

Hypolipidemic Activity of Cassia tora Seeds in Hyperlipidemic Rats.

The hypolipidemic activity of Cassia tora (Chakvat, Chakunda) (Family: Caesalpiniaceae) seeds extract have been studied in two models of hyperlipidemia in rats. In an acute model, hyperlipidemia was induced by injecting a single dose of Triton WR-1339 (400 mg/kg, b.w.) intraperitonially in rats. Feeding with C. tora seed extract at the dose of 500 mg/kg, b.w. exerted significant lipid lowering effect as assessed by the reversal of plasma levels of total cholesterol, phospholipids, triglyceride and reactivation of post heparin lipolytic activity. In the chronic model, hyperlipidemia was induced by feeding with cholesterol rich-HFD in rats. The treatment with seeds extract of C. tora (500 mg/kg, b.w.) simultaneously for 15 days also caused lowering of lipid levels in plasma and liver following reactivation of plasma post heparin lipolytic activity and hepatic lipoprotein lipase activity in animals. The hypolipidemic activity of C. tora seeds was compared with a standard drug guggulipid (200 mg/kg, b.w.) in both models.

Antidyslipidemic and Antioxidant Activities of Hibiscus rosa sinensis Root Extract in Alloxan Induced Diabetic Rats.

The antidyslipidemic activity of Hibiscus rosa sinensis (Malvaceae) root extract has been studied in alloxan induced diabetic rats. In this model, oral administration of root extract (500 mg/kg bw. p.o.) for 15 days resulted in significant decreased in the levels of blood glucose, plasma lipids and reactivated post heparin lipoprotein lipase activity in alloxan induced diabetic rats. Furthermore, the root extract (50-500 µg) when tested for its antioxidant activity, inhibited the generation of super oxide anions and hydroxyl radicals, in both enzymic and non enzymic systems in vitro. The results of the present study demonstrated antidyslipidemic and antioxidant activities in root extract of H. rosa sinensis which could be used in prevention of diabetic-dyslipidemia and related complications.

Combined Radiological and Endoscopic Evaluation of Sino Nasal Anatomical Variations in Patients of Chronic Rhinosinusitis: A North Indian Study.

To determine the prevalence of anatomical variations of nasal cavity and paranasal sinuses of patients with chronic rhinosinusitis (CRS) on CT scan imaging. To correlate the Anatomical variations with the extent of CRS. 100 patients attending the ENT outpatient department with clinically diagnosed CRS were selected for study based on inclusion and exclusion criteria. Patients were subjected to CT scan and diagnostic nasal endoscopy. The correlation of anatomical variation with severity of CRS based on radiological score and endoscopic score was observed. Deviated nasal septum was the most common anatomical variation observed in 71% cases. Followed by Agger nasi (68%), concha bullosa (55%), Onodi cell (25%), Haller cell (14%), frontal sinus hypoplasia (2%) and uncinate bulla (1%) respectively. Statistically significant relationship of radiological score with left side Bullous Concha Bullosa and highly statistically significant relationship with Haller Cell was observed. While statistically significant relationship between Deviated Nasal Septum on left side with endoscopic score was also observed. Correlation of anatomical variation with CRS concludes on the note that some variations cause impaired sinus drainage and ventilation leading to recurrent sinusitis. Also, incidence of these variations was comparable to other studies done in asymptomatic population therefore, simply detection of a solitary anatomical variant itself does not determine predisposition to disease or the pathogenesis of the CRS and that we should have a critical look out for these anatomical variations from point of view of surgical management.

Improving quality of care for pregnancy, perinatal and newborn care at district and sub-district public health facilities in three districts of Haryana, India: An Implementation study.

INTRODUCTION: Improving quality of care (QoC) for childbirth and sick newborns is critical for maternal and neonatal mortality reduction. Information on the process and impact of quality improvement at district and sub-district hospitals in India is limited. This implementation research was prioritized by the Haryana State (India) to improve the QoC for maternal and newborn care at the busy hospitals in districts. METHODS: This study at nine district and sub-district referral hospitals in three districts (Faridabad, Rewari and Jhajjar) during April 2017-March 2019 adopted pre-post, quasi-experimental study design and plan-do-study-act quality improvement method. During the six quarterly plan-do-study-act cycles, the facility and district quality improvement teams led the gap identification, solution planning and implementation with external facilitation. The external facilitators monitored and collected data on indicators related to maternal and newborn service availability, patient satisfaction, case record quality, provider's knowledge and skills during the cycles. These indicators were compared between baseline (pre-intervention) and endline (post-intervention) cycles for documenting impact. RESULTS: The interventions closed 50% of gaps identified, increased the number of deliveries (1562 to 1631 monthly), improved care of pregnant women in labour with hypertension (1.2% to 3.9%, p<0.01) and essential newborn care services at birth (achieved ≥90% at most facilities). Antenatal identification of high-risk pregnancies increased from 4.1% to 8.8% (p<0.01). Hand hygiene practices improved from 35.7% to 58.7% (p<0.01). The case record completeness improved from 66% to 87% (p<0.01). The time spent in antenatal clinics declined by 19-42 minutes (p<0.01). The pooled patient satisfaction scores improved from 82.5% to 95.5% (p<0.01). Key challenges included manpower shortage, staff transfers, leadership change and limited orientation for QoC. CONCLUSION: This multipronged quality improvement strategy improved the maternal and newborn services, case documentation and patient satisfaction at district and sub-district hospitals. The processes and lessons learned shall be useful for replicating and scaling up.

Lipid Lowering Activity of Anthocephalus indicus Root in Hyperlipidemic Rats.

The lipid lowering activity of Anthocephalus indicus (family Rubiaceae; Hindi name Kadamba) root extract has been studied in triton WR-1339 induced hyperlipidemia in rats. In this model, feeding with root extract (500 mg kg(-1) b.w.) lowered plasma lipids and reactivated post-heparin lipolytic activity in hyperlipidemic rats. Furthermore, the root extract (50-500 µM) inhibited the generation of superoxide anions and hydroxyl radicals, in both enzymic and non-enzymic systems, in vitro. The results of the present study demonstrated both lipid lowering and antioxidant activities in root extract of A. indicus, which could help prevention of hyperlipidemia and related diseases.

Hypolipidemic and antioxidant activity of Anthocephalus indicus (Kadam) root extract.

The present study was carried out to explore the anti-diabetic, anti-dyslipoproteinemic and anti-oxidant activities of Anthocephalus indicus root extract in alloxan-induced (150 mg/kg body wt.) diabetic rats. A marked increase in plasma levels of glucose and lipid peroxides accompanied with an elevation in the lipids and apoprotein levels of serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) following decrease in lipid and protein constituents of high density lipoprotein (HDL) were observed. The alterations in lipoprotein pattern was associated with inhibition of lipolytic and antioxidant enzymes. Oral administration of root extract (500 mg/kg body wt.) for 30 days in dyslipidemic animals resulted in significant decrease in plasma glucose, total cholesterol, phospholipids, triglyceride and lipid peroxides. The decrease of lipids and apoprotein levels of VLDL and LDL were followed by stimulation of plasma post-heparin lipolytic activity and lecithin cholesterol acyltransferase as well as hepatic superoxide dismutase and catalase activities. Lipid and apoprotein levels of HDL were also recovered partially on treatment with root extract.

Hypolipidemic activity of Hibiscus rosa sinensis root in rats.

The hypolipidemic activity of Hibiscus rosa sinensis (family Malvaceae) root extract was studied on triton and cholesterol-rich high fat diet (HFD) induced models of hyperlipidemia in rats. In triton WR-1339-induced hyperlipidemia, feeding with root extract (500 mg/kg body wt/day p.o.) exerted lipid-lowering effect, as assessed by reversal of plasma levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG) and reactivation of post-heparin lipolytic activity (PHLA) of plasma. The other model was fed with cholesterol-rich HFD and root extract (500 mg/kg body wt/ day p.o.) simultaneously for 30 days. This also caused lowering of lipid levels in plasma and liver homogenate and reactivation of plasma PHLA and hepatic total lipoprotein lipase activity. The hypolipidemic activity of Hibiscus rosa sinensis root was compared with a standard drug guggulipid (200 mg/kg body wt/day p.o.), a known lipid- lowering agent in both models. Histopathological findings in rat liver supported the protective role of H. rosa sinensis root extract in preventing cholesterol-rich HFD-induced hepatic steatosis.

Hypoglycemic, lipid lowering and antioxidant activities in root extract of Anthocephalus indicus in alloxan induced diabetic rats.

The present study was carried out to evaluate the hypoglycemic, lipid lowering and antioxidant activities in root extract of Anthocephalus indicus (A indicus) in alloxan inducd diabetic rats. Oral administration of ethanol extract of root (500mg/ kg body weight) for 21 days resulted in significant decrease in the levels of blood glucose, triglycerides, total cholesterol, phospholipid and free fatty acids. Furthermore, the root extract (100-400µg) inhibited the generation of superoxide anions and hydroxyl radicals, in both enzymic and non-enzymic systems, in vitro. The result of the present study demonstrated hypoglycemic, lipid lowering and antioxidant activities in root extract of A indicus, which could help in prevention of diabetic dyslipidemia and related diseases.

Involvement of cytoplasmic membrane damage in the copper (II)-dependent cytotoxicity of a novel naturally occurring tripyrrole.

In the presence of a nonlethal concentration of Cu(II), washed Escherichia coli ATCC8739 cells were killed by a novel tripyrrole 1, isolated as a red pigment from the Serratia sp. Cell killing was accompanied by a depletion in the potassium pools of the cells due to the damage to the cytoplasmic membrane, without any detectable DNA damage as revealed by the transformed plasmid DNA and phage induction assay. This revealed that the bactericidal activity of compound 1 in the presence of Cu(II) results from membrane damage. Induction of endogenous catalase in the E. coli cells increased their resistance against the combination of compound 1 and Cu(II). Although compound 1 alone generated large amount of reactive oxygen species (ROS), it did not show any cell killing against E. coli in the absence of Cu(II). The Cu(II)-dependent bactericidal activity of compound 1 was suppressed by ethylenediaminetetraacetate, bathocuproine, catalase and superoxide disumutase (SOD), but not by dimethyl sulfoxide. These findings suggest that recycling redox reactions between Cu(II) and Cu(I), involving compound 1 and hydrogen peroxide on the cell surface, must be important in the mechanism of the killing. Compound 1 alone showed selective bactericidal activity against the gram positive bacterium, Bacillus cereus ATCC 6630, possibly due to its differential cellular transport.

A novel N-alkylated prodigiosin analogue induced death in tumour cell through apoptosis or necrosis depending upon the cell type.

PURPOSE: To investigate the mechanism of cell death induced by the N-alkylated prodigiosin analogue, 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1''-pyrryl)] dipyrryl-methene (MAMPDM) in S-180 and EL-4 tumour cell lines. METHODS: Effect of MAMPDM on cell viability was assessed by MTT dye conversion. Induction of apoptosis was assessed by monitoring caspase 3 activity using a fluorogenic substrate, fragmentation of DNA by gel electrophoresis and sub-diploid DNA containing cells by flowcytometry. Necrosis was estimated by flowcytometric analysis of the uptake of propidium iodide. RESULTS: MAMPDM inhibited the proliferation of murine fibrosarcoma, S-180 cells and induced cell death. Investigations into the mechanism of cell death by MAMPDM in S-180 cells showed absence of hallmarks of apoptotic cell death such as activation of caspase 3, DNA fragmentation and presence of cells with sub-diploid DNA content. However, there was a rapid loss of membrane integrity as assessed by uptake of propidium iodide, which is characteristic of necrosis. In contrast to induction of necrosis in S-180 cells, MAMPDM induced apoptotic cell death in EL-4 cells as evident by activation of caspase 3, fragmentation of DNA and sub-diploid DNA containing cells. CONCLUSIONS: MAMPDM could induce cell death by either apoptosis or necrosis depending upon the cell type. This would be of advantage in elimination of tumor cells defective in apoptotic pathway and therefore, refractory to the conventional therapies.

Omega-(2-Naphthyloxy) amino alkanes as a novel class of anti-hyperglycemic and lipid lowering agents.

omega-(2-Naphthyloxy) amino alkanes, obtained as major by-product during course of synthesis of carbamate esters from omega-(2-naphthyloxy) alkyl halides and amines, showed significant anti-hyperglycemic and lipid lowering activities in various test models as a novel class of compounds. Compounds were tested in rat GLM, SLM, STZ, and STZ-S models at 100mg/kg dose. Of these compound 13 was found to be the most active which caused lowering of sugar by 33.6%, 31.0%, 28.5%, and 73.8% in GLM, SLM, STZ, STZ-S, and db/db mice models, respectively. It also significantly effected lowering of LDL in rat model and also in Hamster model without reducing HDL. Most of the compounds showing anti-diabetic and lipid lowering activity have shown promising PPAR-alpha/gamma/delta-activity. Compounds 6, 13, and 19 have shown very good PPAR-alpha/gamma/delta activity.

Identification of a red-pigmented bacterium producing a potent anti-tumor N-alkylated prodigiosin as Serratia marcescens.

A bacterial strain producing a novel prodigiosin analogue 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1''-pyrryl)] dipyrrylmethene (MAMPDM) possessing potent cytotoxic activity towards cancer cells was isolated and identified. The bacterial cells were spherical and occurred singly, and some of the biochemical tests matched with Micrococcus. Therefore, the isolate was earlier tentatively reported to be Micrococcus sp. In the present studies, analytical profile index (API) suggested this organism to be Klebsiella. However, Klebsiella is not known to produce the red pigment prodigiosin, which is produced by Serratia species and some other bacteria. Based on other biochemical characteristics, particularly DNase, gelatinase, lipase, ornithine decarboxylase, presence of a cell-associated N-alkylated prodigiosin (MAMPDM) and organic solvent tolerance, the strain has now been identified as a variant of Serratia marcescens. 16S rRNA gene analysis conclusively established this organism as S. marcescens ost3. The red pigment (MAMPDM) of this organism showed selective cytotoxic activity in cancer cell lines of different origin (LS-A and U937) and reduced toxicity to non-malignant cells. The LC50 of MAMPDM was 1.59 microM and 0.176 microM for U937 and LS-A cells, respectively, while there was no effect on the viability of L929, a non-malignant cell line, at these concentrations. Thus, S. marcescens ost3 may serve as a source of a new anti-cancer compound.

Role of interleukin-2 regulated proteins in immunosuppression by the N-alkylated prodigiosin analogue.

Prodigiosins have emerged as a novel family of tripyrrole compounds with significant T cell specific immunosuppressive potential. We had previously reported the immunosuppressive activity of a novel N-alkylated prodigiosin analogue, 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1''-pyrryl)] dipyrryl-methene (MAMPDM) in mitogen stimulated spleen cells. There was an increase in the accumulation of IL-2 and induction of apoptotic cell death. Since IL-2 regulates both cellular proliferation and activation induced cell death (AICD), we have investigated the effect of MAMPDM on the expression of IL-2 regulated genes that are involved in these two opposite processes. The mitogen stimulated mouse spleen cells did not undergo a single division in presence of proliferation inhibitory concentrations of MAMPDM. An increase in the percentage of apoptotic cells was observed in the undivided cell population. The cells were arrested in G1 phase independent of the p53 expression. Expression of IL-2 regulated genes such as CD71, proliferating cell nuclear antigen (PCNA) and cyclin D was suppressed while that of Fas was not. Thus, in the presence of MAMPDM there was selective inhibition of only the pro-mitogenic signaling and not that of pro-apoptotic signaling by IL-2. The induction of apoptosis in presence of MAMPDM was the effect rather than cause for the anti-proliferative activity.

Prodigiosins: a novel family of immunosuppressants with anti-cancer activity.

Prodigiosins (PrGs) are a family of promising therapeutic molecules, isolated mostly from Gram-negative bacteria and characterized by a common pyrryldipyrrylmethene structure with varying side chains. They show a broad spectrum of activities such as anti-microbial, anti-malarial, anti-cancer and immunosuppressive. PrGs are attracting increasing attention due to the ongoing research for less toxic, but effective agents for cancer chemotherapy and immunosuppression for preventing allograft rejection and autoimmunity. Different analogues have been synthesized and evaluated. This review discusses the immunosuppressive and anti-cancer activities of this class of compounds, as both involve inhibition of cell proliferation. The main focus is on the in vitro and in vivo immunosuppressive activity of the different PrGs and the mechanisms involved. PrGs primarily target the T cells, though some effects are observed on other cell types also. Unlike the well-known immunosuppressant cyclosporin A, PrGs do not inhibit the secretion of IL-2 but inhibit the mitogenic signaling from IL-2, suggesting a different mechanism of action. Janus tyrosine kinase 3 (Jak3) that associates with IL-2R upon activation is considered as the molecular target for PrGs. Its restricted expression makes Jak3 as an attractive target for immunosuppressive therapy. However, the available literature suggests that some other pathways are also influenced by the PrGs. These may be important for the anti-cancer activity, as well as immunosuppressive action. Therefore, PrGs appear to be potential candidates for pharmaceutical development as immunosuppressants and also as anti-cancer agents.

Potato peel extract-a natural antioxidant for retarding lipid peroxidation in radiation processed lamb meat.

The effective utilization of potato peel, a waste generated in large quantities by the food industry, as an antioxidant was investigated. Potato peel extract (PPE) exhibited high phenolic content (70.82 mg of catechin equivalent/100 g), chlorogenic acid (27.56 mg/100 g of sample) being the major component. The yield of total phenolics and chlorogenic acid increased by 26 and 60%, respectively, when the extract was prepared from gamma irradiated (150 Gy) potatoes. PPE showed excellent antioxidant activity as determined by beta-carotene bleaching and radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH). The suitability of PPE for controlling lipid oxidation of radiation processed lamb meat was also investigated. PPE (0.04%) when added to meat before radiation processing was found to retard lipid peroxidation of irradiated meat as measured by TBA number and carbonyl content. The antioxidant activity of PPE was found to be comparable to butylated hydroxytoluene (BHT).

Effect of radiation processing on the quality of chilled meat products.

Effect of radiation processing on the shelf-life and safety of some ethnic Indian meat products like chicken chilly, mutton shammi kababs and pork salami during chilled storage was investigated. Radiation processing resulted in dose dependent reduction in microbial counts. A dose of 3 kGy was found to be optimal for the shelf-life extension. In all the three irradiated (3 kGy) meat products the shelf-life was extended by more than 2 weeks at 0-3 °C compared to the corresponding non-irradiated samples. Staphylococcus spp. were completely eliminated by irradiation at a dose of 2 kGy. Some increase in lipid peroxidation on irradiation was observed as measured by TBA assay but it did not affect the sensory attributes of the product.

Antioxidant and lipid lowering activities of Indian black tea.

Indian black tea; CTC leaf and dust, produced by Tata Tea Limited, Kolkata, (India) was studiedin vitro as potential scavenger of oxygen free radicals. Super oxide anions were generated in a system containing xanthine-xanthine oxidase (enzymic system) and by NADH- phenozine methosulphate (non enzymic system). Anions were assayed in terms of uric acid formation and reduction of nitroblue tetrazolium salt, which were shown to be suppressed by tea extracts. Extracts from both leaf and dust also inhibted the formation of hydroxyl radicalsin vitro in the enzymic system comprising hypoxanthine-Cu(+2)-sodium ascorbate and xanthine oxidase and in non enzymic system of deoxyribose-Cu(+2)-sodium ascorbate and H(2)O(2) as well as the Cu(+2) induced lipid peroxidation in human low density lipoprotein. Feeding with black tea in normal rats for sixty days increased their antioxidant activity and their liver microsomes were shown to be protected against peroxidation of lipids as stimulated by metal ions with enzymic or non enzymic reactants. Furthermore feeding with tea extracts in normal as well as triton WR-1339 induced hyperlipidemic rats caused decrease in their plasma levels of total cholesterol, phospholipids and triglycerides. The antioxidant and lipid lowering activities of both extracts from CTC leaf and dust tea was comparable and may be due to the presence of natural products like catechin and others.

A novel prodigiosin-like immunosuppressant from an alkalophilic Micrococcus sp.

A novel red pigment, 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1-pyrryl)] dipyrryl-methene (MAMPDM), which has properties similar to those of prodigiosins, has been isolated for the first time from a bacterium putatively identified as Micrococcus sp. Our studies showed that MAMPDM inhibited proliferation of both human T as well as B cells and murine T cells, in response to polyclonal mitogens, in a concentration-dependent manner while murine B cell proliferation induced by lipopolysaccharide was inhibited only at high concentration. The effect of MAMPDM on constitutive cell cycling was ascertained using four mouse and human tumour cell lines. At 100 nM, the concentration that inhibited con A induced proliferation of mouse spleen cells, the viability of these cell lines was not affected. At 10-100-fold higher concentration of MAMPDM, however, there was a decrease in cell viability with T cell-derived cell lines being more sensitive. MAMPDM did not block the secretion of IL-2 or expression of CD25 though it inhibited the proliferation of con A stimulated T cells. The higher amount of IL-2 in the supernatant of the con A stimulated T cells, cultured in the presence of the immunomodulator, indicated accumulation of IL-2 due to its reduced utilisation. At inhibitory concentration, MAMPDM induced apoptosis in con A stimulated cells. Thus, MAMPDM may have considerable and selective T cell immunosuppressive potential and appears to act by a mechanism distinct from that of other known immunosuppressors.

Shelf-stable and safe intermediate-moisture meat products using hurdle technology.

A number of ready-to-use shelf-stable intermediate-moisture (IM) spiced mutton and spiced chicken products were developed with a combination of hurdles (reduced moisture, vacuum packing, and irradiation). The water activity of the products was reduced to about 0.80 either by grilling or by hot-air drying. These IM products were vacuum packed and subjected to gamma radiation processing at 0 to 10 kGy. Microbiological analyses revealed a radiation dose-dependent reduction in total viable counts and in numbers of Staphylococcus species. IM meat products that did not undergo radiation treatment showed visible mold growth within 2 months. The products subjected to irradiation at 10 kGy showed an absence of viable microorganisms and also retained high sensory acceptability for up to 9 months at ambient temperatures.