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Use of prednisolone to aid propagation of Toxoplasma gondii in mice

Puvanesuaran VR, Nowroji K, Sreenivasan S, Noordin R, Balakrishnan V

Eur Rev Med Pharmacol Sci, 2012 Aug;16(8):1028-32.
PMID: 22913152

AIM: To determine the usefulness of prednisolone in increasing the number of Toxoplasma (T.) gondii tachyzoites and bradyzoites in mice.
MATERIALS AND METHODS: The mice were water-fasted prior to being immunosuppressed with oral inoculation of prednisolone. Tachyzoites of 7T gondii RH strain were inoculated into mice and the number of the parasites in the intraperitoneal fluids was then determined at 96 hs post-infection. In addition, tachyzoites of T. gondii ME49 strains were orally introduced into mice and the number of brain cysts formed was observed by microscopic observation at 45 days post-infection.
RESULTS: T. gondii propagation was found to be significantly improved by introduction of the prednisolone (p = 0.0004); and the number of parasite showed positive correlation with the increment in dosage of prednisolone (r = 0.9051).
CONCLUSIONS: The use of prednisolone greatly improved the number of parasite formed in mice: both tachyzoite and cyst forms.
Fulltext Methadone, Buprenorphine, and Clonidine Attenuate Mitragynine Withdrawal in Rats

Hassan R, Sreenivasan S, Müller CP, Hassan Z

Front Pharmacol, 2021;12:708019.
PMID: 34322028 DOI: 10.3389/fphar.2021.708019

Background: Kratom or Mitragyna speciosa Korth has been widely used to relieve the severity of opioid withdrawal in natural settings. However, several studies have reported that kratom may by itself cause dependence following chronic consumption. Yet, there is currently no formal treatment for kratom dependence. Mitragynine, is the major psychoactive alkaloid in kratom. Chronic mitragynine treatment can cause addiction-like symptoms in rodent models including withdrawal behaviour. In this study we assessed whether the prescription drugs, methadone, buprenorphine and clonidine, could mitigate mitragynine withdrawal effects. In order to assess treatment safety, we also evaluated hematological, biochemical and histopathological treatment effects. Methods: We induced mitragynine withdrawal behaviour in a chronic treatment paradigm in rats. Methadone (1.0 mg/kg), buprenorphine (0.8 mg/kg) and clonidine (0.1 mg/kg) were i.p. administered over four days during mitragynine withdrawal. These treatments were stopped and withdrawal sign assessment continued. Thereafter, toxicological profiles of the treatments were evaluated in the blood and in organs. Results: Chronic mitragynine treatment caused significant withdrawal behaviour lasting at least 5 days. Methadone, buprenorphine, as well as clonidine treatments significantly attenuated these withdrawal signs. No major effects on blood or organ toxicity were observed. Conclusion: These data suggest that the already available prescription medications methadone, buprenorphine, and clonidine are capable to alleviate mitragynine withdrawal signs rats. This may suggest them as treatment options also for problematic mitragynine/kratom use in humans.
Fulltext Chemical Composition and Biological Activity of the Centipeda minima (Asteraceae)

Soetardjo S, Jong PC, Ahmad MN, Lachimanan YL, Sreenivasan S

Malays J Nutr, 2007 Mar;13(1):81-7.
PMID: 22692191 MyJurnal

The antimicrobial activity of the Centipeda minima L. (Asteraceae) extract was evaluated against seven microorganisms using the disc diffusion method. The extract showed a broad spectrum of antimicrobial activity against all the tested bacterial strains, especially Enterobacter aerogenes, Klebsiella pneumonia, Staphylococcus aureus and Yersinia enterocolitica. The chemical composition of the extract obtained from Centipeda minima was analysed by GC-MS. Twentythree compounds, constituting about 84.75 % of the total extract, were identified. The main constituents were palmitic acid (7.47%), (Z,Z)-9-,12-octadecatrienoic acid (6.52%), (Z,Z,Z)-9-,12-octadecatrienoic acid (7.01%), phytol (7.01%), naptho[2.3-b]furan-2-(3H)-on (6.21%), 1-(1,2,3,4,7,7a-hexahydro-1,4,4,5-tetramethyl-1,3a-ethano-3aH-inden-6-yl)etanon (7.95%), 1,3,5-tri-tertbutyl- benzene (4.52%), (3Z)-2-methyl-3-octen-2-ol (5.95%) and artemisia ketone (4.98%). The extract was also tested against brine shrimp for toxicity. There was no significant toxicity as it only recorded a LC50 value of 4.92 mg/ml. The study shows that the extract is a good antimicrobial agent with potential applications in public health against diseases.
Fulltext Isolation and identification of salmonella from curry samples and its sensitivity to commercial antibiotics and aqueous extracts of Camelia sinensis (L.) and Trachyspermum ammi (L.)

Gunasegaran T, Rathinam X, Kasi M, Sathasivam K, Sreenivasan S, Subramaniam S

Asian Pac J Trop Biomed, 2011 Aug;1(4):266-9.
PMID: 23569772 DOI: 10.1016/S2221-1691(11)60040-3

To isolate Salmonella from curry samples and to evaluate the drug sensitivity of the food-borne Salmonella and its susceptibility to specific plant extracts.
Fulltext Lactobacillus plantarum DR7 Reduces Cholesterol via Phosphorylation of AMPK That Down-regulated the mRNA Expression of HMG-CoA Reductase

Lew LC, Choi SB, Khoo BY, Sreenivasan S, Ong KL, Liong MT

Korean J Food Sci Anim Resour, 2018 Apr;38(2):350-361.
PMID: 29805284 DOI: 10.5851/kosfa.2018.38.2.350

Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells. Cell free supernatant (CFS) from Lactobacillus plantarum DR7 showed a higher ability to assimilate cholesterol, reduction in cholesterol accumulation in both HepG2 and HT-29 cells, accompanied by reduced mRNA expression of HMG-CoA reductase (HMGCR) in HepG2 (p<0.05), compared to other lactobacilli. The reduction of HMGCR expression was also diminished in the presence of an AMPK inhibitor (Compound C), suggesting that L. plantarum DR7 exerted its effect via the AMPK pathway, typically via the phosphorylation of AMPK instead of the AMPK mRNA expression in HepG2 (p<0.05). Altogether, our present study illustrated that lactobacilli could exert cholesterol lowering properties along the AMPK pathway, specifically via phosphorylation of AMPK that led to reduced expression of HMGCR.
Methadone hydrochloride and leukemia cells: Effects on cell viability, DNA fragmentation and apoptotic proteins expression level

Kua VMD, Rasul A, Sreenivasan S, Rasool B, Younis T, Lai NS

Pak J Pharm Sci, 2019 Jul;32(4(Supplementary)):1797-1803.
PMID: 31680075

Leukemia is a type of blood cancer where abnormal and immature leucocytes are produced in the bone marrow. Methadone hydrochloride is a man-made drug that is commonly used in the maintenance treatment for drug addiction. The objective of this research was to determine the cytotoxic activity and apoptotic effects of methadone hydrochloride treatment towards two leukemia cell lines which are CCRF-CEM and HL-60. CCRF-CEM and HL-60 cells were treated with methadone hydrochloride for 24 and 48 hours to determine the cytotoxic activity. IC50 at 24 hours obtained for CCRF-CEM was 121.6μmol/L while IC50 for HL-60 cells was 97.18μmol/L. Result obtained from DNA fragmentation assay showed no characteristic DNA ladder pattern in CCRF-CEM leukemia cells treated with methadone hydrochloride. Characteristics DNA ladder pattern was observed in methadone hydrochloride treated HL-60 cells. Formation of comets was seen in methadone hydrochloride treated CCRF-CEM and HL-60 cells with varying degree of DNA damage. The comets formed by methadone hydrochloride treated HL-60 cells were more prominent as compared to methadone-treated CCRF-CEM cells. The expression of apoptotic-related proteins in methadone-treated CCRF-CEM and HL-60 cells were checked by incubating the cell lysate with Raybio® Human Apoptosis Antibody Array. Significant alterations in expression level of apoptosis-related proteins in methadone hydrochloride treated CCRF-CEM cells were found involving upregulation of caspase-8 expression and downregulation of survivin expression. Methadone hydrochloride induced apoptosis in HL-60 cells involved upregulation of Bid and caspase-8 expression and downregulation of Bcl-2, p21 and survivin expression.
Fulltext Mitragynine Attenuates Morphine Withdrawal Effects in Rats-A Comparison With Methadone and Buprenorphine

Hassan R, Pike See C, Sreenivasan S, Mansor SM, Müller CP, Hassan Z

Front Psychiatry, 2020;11:411.
PMID: 32457670 DOI: 10.3389/fpsyt.2020.00411

Background: Opiate addiction is a major health problem in many countries. A crucial component of the medical treatment is the management of highly aversive opiate withdrawal signs, which may otherwise lead to resumption of drug taking. In a medication-assisted treatment (MAT), methadone and buprenorphine have been implemented as substitution drugs. Despite MAT effectiveness, there are still limitations and side effects of using methadone and buprenorphine. Thus, other alternative therapies with less side effects, overdosing, and co-morbidities are desired. One of the potential pharmacotherapies may involve kratom's major indole alkaloid, mitragynine, since kratom (Mitragyna speciosa Korth.) preparations have been reported to alleviate opiate withdrawal signs in self-treatment in Malaysian opiate addicts.
Methods: Based on the morphine withdrawal model, rats were morphine treated with increasing doses from 10 to 50 mg/kg twice daily over a period of 6 days. The treatment was discontinued on day 7 in order to induce a spontaneous morphine abstinence. The withdrawal signs were measured daily after 24 h of the last morphine administration over a period of 28 abstinence days. In rats that developed withdrawal signs, a drug replacement treatment was given using mitragynine, methadone, or buprenorphine and the global withdrawal score was evaluated.
Results: The morphine withdrawal model induced profound withdrawal signs for 16 days. Mitragynine (5-30 mg/kg; i.p.) was able to attenuate acute withdrawal signs in morphine dependent rats. On the other hand, smaller doses of methadone (0.5-2 mg/kg; i.p.) and buprenorphine (0.4-1.6 mg/kg; i.p.) were necessary to mitigate these effects.
Conclusions: These data suggest that mitragynine may be a potential drug candidate for opiate withdrawal treatment.
Fulltext Breast milk from healthy women has higher anti-Candida properties than women with vaginal infections during pregnancy

Nisaa AA, Oon CE, Sreenivasan S, Balakrishnan V, Tan JJ, Teh CS, et al.

Food Sci Biotechnol, 2023 Mar;32(4):471-480.
PMID: 36911325 DOI: 10.1007/s10068-022-01088-x

The aim of this study was to investigate the different immunological and antimicrobial properties of breast milk from women with (W) or without (WO) vaginal yeast infections during pregnancy in 85 lactating women (W, n = 43; WO, n = 42). Concentrations of IL-10, IgA, IgM, IgG, EGF, and TGF-α were similar in both groups. However, breast milk of women aged below 31 years old from the W-group showed higher concentration of EGF than the WO-group (p = 0.031). Breast milk from WO-group exhibited higher anti-Candida properties than W-group, both via growth inhibition and aggregation of yeast cells (p
Fulltext Probiotic Bifidobacterium lactis Probio-M8 treated and prevented acute RTI, reduced antibiotic use and hospital stay in hospitalized young children: a randomized, double-blind, placebo-controlled study

Mageswary MU, Ang XY, Lee BK, Chung YF, Azhar SNA, Hamid IJA, et al.

Eur J Nutr, 2021 Nov 26.
PMID: 34825264 DOI: 10.1007/s00394-021-02689-8

PURPOSE: The development of probiotics has seen tremendous growth over the years, with health benefits ranging from gut health to respiratory. We thus aimed to investigate the effects of probiotic Bifidobacterium lactis Probio-M8 (2 × 1010 log CFU/day) against acute respiratory tract infections (RTI), use of antibiotics, hospitalization period and elucidate the possible mechanisms of action in hospitalized young children.
METHOD: A prospective, randomized, double-blind and placebo-controlled study was performed in RTI-hospitalized children. Patients were randomized to either the probiotic (n = 60, mean age 13.81 ± 0.90 months) or placebo (n = 60, mean age 12.11 ± 0.73 months) which were administered upon admission, continued during hospitalization and 4-week post-discharged. RTI and gut health parameters were assessed at these time points using validated questionnaires while concentrations of inflammatory cytokines were assessed via oral swabs.
RESULTS: Probio-M8 reduced the duration of nasal, pharyngeal and general flu-like symptoms compared to the placebo during the hospitalization period and 4-week post-discharged (P
Correction to: Probiotic Bifidobacterium lactis Probio-M8 treated and prevented acute RTI, reduced antibiotic use and hospital stay in hospitalized young children: a randomized, double-blind, placebo-controlled study

Mageswary MU, Ang XY, Lee BK, Chung YF, Azhar SNA, Hamid IJA, et al.

Eur J Nutr, 2022 Feb 05.
PMID: 35122153 DOI: 10.1007/s00394-022-02818-x
Fulltext Vaginal Infections during Pregnancy Increase Breast Milk Microbiome Alpha Diversity and Alter Taxonomic Composition

Nisaa AA, Oon CE, Sreenivasan S, Balakrishnan V, Rajendran D, Tan JJ, et al.

Prev Nutr Food Sci, 2023 Mar 31;28(1):1-9.
PMID: 37066035 DOI: 10.3746/pnf.2023.28.1.1

We previously reported that breast milk from women with (W) or without (WO) vaginal yeast infection during pregnancy differs in its immunological and antimicrobial properties, especially against pathogenic vaginal Candida sp.. Here, we investigated the differences in microbiota profiles of breast milk from these groups. Seventy-two breast milk samples were collected from lactating mothers (W, n=37; WO, n=35). The DNA of bacteria was extracted from each breast milk sample for microbiota profiling by 16S rRNA gene sequencing. Breast milk from the W-group exhibited higher alpha diversity than that from the WO-group across different taxonomic levels of class (P=0.015), order (P=0.011), family (P=0.020), and genus (P=0.030). Compositional differences between groups as determined via beta diversity showed marginal differences at taxonomic levels of phylum (P=0.087), family (P=0.064), and genus (P=0.067). The W-group showed higher abundances of families Moraxellaceae (P=0.010) and Xanthomonadaceae (P=0.008), and their genera Acinetobacter (P=0.015), Enhydrobacter (P=0.015), and Stenotrophomonas (P=0.007). Meanwhile, the WO-group showed higher abundances of genus Staphylococcus (P=0.046) and species Streptococcus infantis (P=0.025). This study shows that, although breast milk composition is affected by vaginal infection during pregnancy, this may not pose a threat to infant growth and development.