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Pharmacokinetics and tissue distribution of hydrazinocurcumin in rats

Satyavert, Gupta S, Choudhury H, Jacob S, Nair AB, Dhanawat M, et al.

Pharmacol Rep, 2021 Dec;73(6):1734-1743.
PMID: 34283375 DOI: 10.1007/s43440-021-00312-5

BACKGROUND: Curcumin, a natural polyphenol from Curcuma longa, is known to possess diversified pharmacological roles including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic properties; however, its bioavailability is severely limited due to its poor solubility, poor absorption, rapid metabolism, and significant elimination. Hydrazinocurcumin (HZC), a novel analogue of curcumin has been reported to overcome the limitations of curcumin and also possesses multiple pharmacological activities. The present study aimed to evaluate the unexplored pharmacokinetic profile of this agent in experimental rats.
METHODS: Drug formulations were administered to the experimental animals via oral, intravenous and intraperitoneal routes. Blood samples were collected at different pre-determined time intervals to determine the pharmacokinetic parameters. To understand the biodistribution profile of HCZ, tissue samples were isolated from different groups of Sprague-Dawley rats at different time points. The pharmacokinetic parameters of HZC were evaluated after administration through oral (100 mg/kg), intraperitoneal (100 mg/kg) and intravenous (10 mg/kg) routes.
RESULTS: Significantly (p

Matched MeSH terms: Injections, Intraperitoneal
Bioavailability and pharmacokinetic studies of eurycomanone from Eurycoma longifolia

Low BS, Ng BH, Choy WP, Yuen KH, Chan KL

Planta Med, 2005 Sep;71(9):803-7.
PMID: 16206032

A validated HPLC analysis of eurycomanone (1), a bioactive quassinoid, in rat plasma following oral and intravenous administration of Eurycoma longifolia Jack extract was developed for pharmacokinetic and bioavailability studies. Relatively high plasma eurycomanone concentrations were detected after an intravenous injection of 10 mg/kg extract F2 containing 1.96 mg/kg of the quassinoid. However, it declined rapidly to zero after 8 h. Its mean elimination rate constant (k(e)), biological half-life (t(1/2)), volume of distribution (V(d)) and clearance (CL) were 0.88 +/- 0.19 h (-1), 1.00 +/- 0.26 h, 0.68 +/- 0.30 L/kg and 0.39 +/- 0.08 L/h/kg, respectively. Following oral administration of eurycomanone, its Cmax and Tmax values were detected as 0.33 +/- 0.03 microg/mL and 4.40 +/- 0.98 h, respectively. The plasma concentration of the quassinoid after oral administration was much lower than after intravenous application in spite of the oral dose being 5 times higher. The results indicate that eurycomanone is poorly bioavailable when given orally. A comparison of the AUC (0-->infinity) obtained orally to that obtained after an intravenous administration (normalized for dose differences) revealed that the absolute bioavailability of the compound was low with 10.5 %. Furthermore, the compound appeared to be well distributed in the extravascular fluids because of its relatively high V(d) value. The poor oral bioavailability was not attributed to instability problems because eurycomanone has been shown to be stable under different pH conditions. Thus, its poor oral bioavailability may be due to poor membrane permeability in view of its low P value and/or high first-pass metabolism.

Matched MeSH terms: Injections, Intravenous
Fulltext Randomized controlled trial comparing efficacy of conventional and new single larger dose of intra-articular viscosupplementation in management of knee osteoarthritis

Suppan VKL, Wei CY, Siong TC, Mei TM, Chern WB, Nanta Kumar VK, et al.

J Orthop Surg (Hong Kong), 2017 9 28;25(3):2309499017731627.
PMID: 28946838 DOI: 10.1177/2309499017731627

BACKGROUND: Intra-articular hyaluronic acid (HA) injection is used in management of knee, hand and hip osteoarthritis. While HA injection is included in the list of evaluated therapies, its efficacy and optimum dosing still have no consensus. This study was conducted to explore the possibility of using single injection HA to increase patient convenience while maintaining the therapeutic efficacy.

METHODS: We present a prospective, open label, non-blinded, randomized controlled trial performed in accordance with guidelines in principles of good clinical practice. Block randomization was done for patients to receive either single 5 ml GO-ON injection or the conventional three injections of 2.5 ml GO-ON at weekly interval. Baseline Western Ontario McMaster University Osteoarthritis (WOMAC) scores were evaluated and recorded. All subjects were re-evaluated at 3 months and the WOMAC score recorded again as primary end points. Data analyses were performed with IBM SPSS Statistics for Windows software (version 21.0, IBM Corp, Armonk, New York, USA).

RESULTS: In the cohort of 127 patients, 33 were males and 94 females. The mean age was 59.1 years (standard deviation (SD) = 7.25) in single injection arm and 60.1 years (SD = 7.72) in triple injection arm. The two groups were recorded to have no significant difference in age ( p = 0.46) and Kellgren-Lawrence radiological grade ( p = 0.694). There was significant increase in the WOMAC scores from the baseline (pre-injection) to that recorded 3 months after injection ( p < 0.001) in patients of both groups. However, there was no statistically significant difference noticed in this clinical improvement between the two arms ( p = 0.889).

CONCLUSION: The study shows single 5 ml dose regime comparing well with conventional three doses of 2.5 ml of intra-articular GO-ON HA injected at weekly intervals and confirms good efficacy, tolerability and safety of single larger dose of GO-ON knee intra-articular injection.

Matched MeSH terms: Injections, Intra-Articular
Fulltext Continuous infusion vs. intermittent bolus injection of furosemide in acute decompensated heart failure: systematic review and meta-analysis of randomised controlled trials

Ng KT, Yap JLL

Anaesthesia, 2018 Feb;73(2):238-247.
PMID: 28940440 DOI: 10.1111/anae.14038

Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent randomised controlled trials have examined the clinical benefit of continuous vs. bolus furosemide in acute decompensated heart failure, but have reported conflicting findings. The aim of this review was to compare the effects of continuous and bolus furosemide with regard to mortality, length of hospital stay and its efficacy profile in acute decompensated heart failure. All parallel-arm randomised controlled trials from MEDLINE, EMBASE, PubMed and the Cochrane Database of Systematic Reviews from inception until May 2017 were included. Cross-over randomised controlled trials, observational studies, case reports, case series and non-systematic reviews that involved children were excluded. Eight trials (n = 669) were eligible for inclusion. There was no difference between furosemide continuous infusion and bolus administration for all-cause mortality (four studies; n = 491; I2 = 0%; OR 1.65; 95%CI 0.93-2.91; p = 0.08) or duration of hospitalisation (six studies; n = 576; I2 = 71%; mean difference 0.27; 95%CI -1.35 to 1.89 days; p = 0.74). Continuous infusion of intravenous furosemide was associated with increased weight reduction (five studies; n = 516; I2 = 0%; mean difference 0.70; 95%CI 0.12-1.28 kg; p = 0.02); increased total urine output in 24 h (four studies; n = 390; I2 = 33%; mean difference 461.5; 95%CI 133.7-789.4 ml; p < 0.01); and reduced brain natriuretic peptide (two studies; n = 390; I2 = 0%; mean difference 399.5; 95%CI 152.7-646.3 ng.l-1 ; p < 0.01), compared with the bolus group. There was no difference in the incidence of raised creatinine and hypokalaemia between the two groups. In summary, there was no difference between continuous infusion and bolus of furosemide for all-cause mortality, length of hospital stay and electrolyte disturbance, but continuous infusion was superior to bolus administration with regard to diuretic effect and reduction in brain natriuretic peptide.

Matched MeSH terms: Injections, Intravenous
Allergic contact dermatitis caused by polymethylmethacrylate following intradermal filler injection

Shah V, Chaubal TV, Bapat RA, Shetty D

Contact Derm., 2017 Dec;77(6):407-408.
PMID: 29164691 DOI: 10.1111/cod.12779
Matched MeSH terms: Injections, Intradermal
Delusional infestation successfully controlled with typical antipsychotic depot injection: An illustrative case report

Jamaluddin R

Asian J Psychiatr, 2018 Jan;31:69-70.
PMID: 29438922 DOI: 10.1016/j.ajp.2018.02.002
Matched MeSH terms: Injections
Fulltext When dermatomyositis patient has blurring of vision - what goes wrong?

Ng CWK, Hanizasurana H, Nor Azita AT, Nor Fariza N, Zabri K

Medicine & Health, 2016;11(2):313-318.
MyJurnal

Cytomegalovirus (CMV) retinitis occurs predominantly in Human Immunodeficiency Virus (HIV) -infected patients. It was also reported in HIV-seronegative patients with systemic autoimmune disorder requiring systemic immunosuppression, organ or bone marrow transplantation, haematological or breast malignancy receiving chemotherapy, ocular diseases following intraocular or periocular corticosteroid injection, diabetes mellitus and Good syndrome. However, CMV retinitis in patients with concurrent dermatomyositis and malignancy has not been previously reported. It has not been reported in cancer other than haematological or breast malignancy, or in cancer patient prior to chemotherapy. We report a case of 40-year-old HIV-seronegative woman with underlying dermatomyositis and lung malignancy who developed right CMV retinitis which relapsed after recommencement of immunosuppressant. Both episodes of CMV retinitis were successfully treated after taken her immunocompromised state into consideration.

Matched MeSH terms: Injections, Intraocular
Embryo culture conditions are significantly improved during uninterrupted incubation: A randomized controlled trial

Alhelou Y, Mat Adenan NA, Ali J

Reprod Biol, 2018 Mar;18(1):40-45.
PMID: 29279181 DOI: 10.1016/j.repbio.2017.12.003

A parallel group superiority prospective randomised controlled trial was devised to compare the culture characteristics of human pre-implantation stage embryos during uninterrupted culture in a time lapse incubator (TLI) versus the conventional model of interrupted culture in a standard incubator (SI) under low oxygen tension using a single step medium. 221 patients aged 35-and-under, 124 patients aged between 36 and 39 and 86 patients aged 40-and-over years were randomised and cultured either in a SI or in a TLI. Patients in the three age groups were distributed between the TLI and SI in a 1:1 ratio. The development of embryos on days 2, 3 and 5, and the clinical pregnancy and implantation rates were recorded. The fertilisation rate, development of day 2 and clinical pregnancy rates were similar in both treatments but the 8-cell development rate in all age groups combined (p = 0.016), blastocyst development rate (p = 0.0022) and the implantation rate (p = 0.0022) was significantly higher for the uninterrupted culture. These findings demonstrated significant differences between the two incubation groups. It also indicated less efficacious embryonic development with age in both treatments which appeared more pronounced in the conventional incubator. In conclusion uninterrupted culture is superior compared to the interrupted incubation culture system.

Matched MeSH terms: Sperm Injections, Intracytoplasmic
Fulltext True hermaphrodite--a case report

Yip CH, Pathmanathan R

Singapore Med J, 1996 Feb;37(1):117-8.
PMID: 8783930

A case report of a male true hermaphrodite with 46XX/46XY karyotype is presented. He was first diagnosed at the age of 9 years when he presented with hypospadias and a left undescended testis. He was lost to follow-up until he presented at the age of 23 years with bilateral gynaecomastia. A hormonal profile showed a low testosterone level, while a seminal assay showed very few sperms. However he claimed to be sexually active. A year later, after he got married, he began to complain of impotence. A review of the condition is presented.

Matched MeSH terms: Injections, Intramuscular
Factors affecting central macular thickness of diabetic macular oedema patients after an induction treatment of intravitreal ranibizumab

Nursyafiqah MT, Siti-Azrin AH, Yaacob NM, Wan-Nor-Asyikeen WA, Zunaina E

Trop Med Int Health, 2023 Apr;28(4):300-307.
PMID: 36787961 DOI: 10.1111/tmi.13862

OBJECTIVE: Intravitreal ranibizumab is one of the anti-vascular endothelial growth factors used for the treatment of diabetic macular oedema, not always successfully. We aimed to identify the factors affecting the changes of central macular thickness after induction treatment with intravitreal ranibizumab, to predict the treatment effect and facilitate early treatment decisions.
METHODS: Cross-sectional study involving a retrospective record review of diabetic macular oedema patients who received an induction treatment of three monthly 0.5 mg intravitreal ranibizumab injections between 2016 and 2019. Central macular thickness was measured at baseline and 3 months post-treatment. Linear regression was applied to identify the factors associated with the changes of central macular thickness.
RESULTS: A total of 153 diabetic macular oedema patients were involved in this study. Their mean age was 57.5 ± 7.7 years, 54.9% were female. The mean change of central macular thickness from baseline to 3 months after completed induction treatment of intravitreal ranibizumab was 155.5 ± 137.8 μm. Factors significantly associated with changes of central macular thickness were baseline central macular thickness [b = 0.73; 95% (CI): 0.63, 0.84; p = <0.001] and presence of subretinal fluid [b = 35.43; 95% CI: 3.70, 67.16; p = 0.029].
CONCLUSION: Thicker baseline central macular thickness and presence of subretinal fluid were the factors significantly associated with greater changes of central macular thickness in diabetic macular oedema patients after receiving three injections of intravitreal ranibizumab.

Matched MeSH terms: Intravitreal Injections
Method development and validation of a high-performance liquid chromatographic method for tramadol in human plasma using liquid-liquid extraction

Gan SH, Ismail R, Wan Adnan WA, Wan Z

J Chromatogr B Analyt Technol Biomed Life Sci, 2002 May 25;772(1):123-9.
PMID: 12016023

An HPLC system using a simple liquid-liquid extraction and HPLC with UV detection has been validated to determine tramadol concentration in human plasma. The method developed was selective and linear for concentrations ranging from 10 to 2000 ng/ml with average recovery of 98.63%. The limit of quantitation (LOQ) was 10 ng/ml and the percentage recovery of the internal standard phenacetin was 76.51%. The intra-day accuracy ranged from 87.55 to 105.99% and the inter-day accuracy, 93.44 to 98.43% for tramadol. Good precision (5.32 and 6.67% for intra- and inter-day, respectively) was obtained at LOQ. The method has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.

Matched MeSH terms: Injections, Intravenous
Fulltext Infographic: "Planet Trial: Intravitreal aflibercept monotherapy for polypoidal choroidal vasculopathy (PCV)"

Sim SS, Vyas CH, Gunatheesan R, Lott PW, Sun CZ, Teo KYC, et al.

Eye (Lond), 2022 Jun;36(6):1142.
PMID: 35001091 DOI: 10.1038/s41433-021-01874-7
Matched MeSH terms: Intravitreal Injections
A comparative histopathological study of systemic candidiasis in association with experimentally induced breast cancer

Choo ZW, Chakravarthi S, Wong SF, Nagaraja HS, Thanikachalam PM, Mak JW, et al.

Oncol Lett, 2010 Jan;1(1):215-222.
PMID: 22966285

Systemic candidiasis is a fungal infection which coupled with solid malignancies places patients at high risk of succumbing to the disease. Few studies have shown evidence of the relationship between systemic candidiasis and malignancy-induced immunosuppression disease especially in breast cancer. At present, animal studies that exclusively demonstrate this relationship have yet to be conducted. The exact causative mechanism of systemic candidiasis is currently under much speculation. This study therefore aimed to demonstrate this relationship by observing the histopathological changes of organs harvested from female Balb/c mice which were experimentally induced with breast cancer and inoculated with systemic candidiasis. The mice were randomly assigned to five different groups (n=12). The first group (group 1) was injected with phosphate buffer solution, the second (group 2) with systemic candidiasis, the third (group 3) with breast cancer and the final two groups (groups 4 and 5) had both candidiasis and breast cancer at two different doses of candidiasis, respectively. Inoculation of mice with systemic candidiasis was performed by an intravenous injection of Candida albicans via the tail vein following successful culture methods. Induction of mice with breast cancer occurred via injection of 4T1 cancer cells at the right axillary mammary fatpad after effective culture methods. The prepared slides with organ tissues were stained with hematoxylin and eosin, periodic acidic schiff and gomori methenamine silver stains for a histopathological analysis. Grading of primary tumour and identification of metastatic deposits, as well as scoring of inflammation and congestion in all the respective organs was conducted. Statistical tests performed to compare groups 2 and 4 showed that group 4 exhibited a highly statistically significant increase in organ inflammation and congestion (p<0.01). The median severity of candidiasis in the kidneys and liver also increased in group 4 as compared to group 2. In conclusion, based on the above evidence, systemic candidiasis significantly increased in mice with breast cancer.

Matched MeSH terms: Injections, Intravenous
Fulltext Pasteurella canis Isolation following Penetrating Eye Injury: A Case Report

Rashid NK, Zam Z, Mdnoor SS, Siti-Raihan I, Azhany Y

Case Rep Ophthalmol Med, 2012;2012:362369.
PMID: 22606491 DOI: 10.1155/2012/362369

A 3-year-old boy presented with history of trauma to the left eye after he accidentally injured his eye with a broom stick made up from coconut skewers. There was history of cats as their pets but not dogs. Ocular examination revealed left superonasal conjunctival laceration and scleral perforation with prolapsed vitreous. Fundus examination showed minimal vitreous haemorrhage and flat retina. Conjunctiva swab at the wound site was sent for gram staining, culture, and sensitivity. He underwent scleral suturing, vitreous tap, and intravitreal injection of Ceftazidime and Amikacin. Vitreous tap was sent for gram stained, culture and sensitivity. Postoperatively, he was started empirically on IV Ciprofloxacin 160 mg BD, Guttae Ciprofloxacin, and Guttae Ceftazidime. Conjunctiva swab grew Pasteurella canis which was sensitive to all Beta lactams, Ciprofloxacin, Chloramphenicol, and Aminoglycoside. Post-operative was uneventful, absent signs of endophthalmitis or orbital cellulitis.

Matched MeSH terms: Intravitreal Injections
Fulltext Effects of repeated comparative intradermal tuberculin testing on test results: a longitudinal study in TB-free red deer

Che-Amat A, Risalde MÁ, González-Barrio D, Ortíz JA, Gortázar C

BMC Vet Res, 2016 Sep 05;12(1):184.
PMID: 27596591 DOI: 10.1186/s12917-016-0825-2

Diagnosing tuberculosis (TB) in farmed red deer (Cervus elaphus) is challenging and might require combining cellular and humoral diagnostic tests. Repeated skin-testing with mycobacterial purified protein derivatives (PPDs) might sensitize or desensitize the subjects to both kinds of diagnostic tools. We evaluated the effect of repeated (every 6 months) comparative tuberculin skin testing on skin test and ELISA responsiveness in farmed red deer hinds from a TB-free herd. Eighteen 8-month old hinds were inoculated with bovine and avian PPDs and the mitogen phytohaemagglutinin (PHA), as positive control and concurrently tested by ELISA for antibodies against avian (avian PPD, aPPD and protoplasmatic antigen 3, PPA3) and bovine antigens (bPPD and MPB70). Blood serum was also sampled three weeks after each skin testing round and tested for antibodies against aPPD and bPPD, in order to detect eventual antibody level boosts. Testing took place every six months from winter 2012 until winter 2015.

Matched MeSH terms: Injections, Intradermal
Fulltext Effect of Piper sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study

Thent ZC, Seong Lin T, Das S, Zakaria Z

Evid Based Complement Alternat Med, 2012;2012:628750.
PMID: 23304208 DOI: 10.1155/2012/628750

Although Piper sarmentosum (PS) is known to possess the antidiabetic properties, its efficacy towards diabetic cardiovascular tissues is still obscured. The present study aimed to observe the electron microscopic changes on the cardiac tissue and proximal aorta of experimental rats treated with PS extract. Thirty-two male Sprague-Dawley rats were divided into four groups: untreated control group (C), PS-treated control group (CTx), untreated diabetic group (D), and PS-treated diabetic group (DTx). Intramuscular injection of streptozotocin (STZ, 50 mg/kg body weight) was given to induce diabetes. Following 28 days of diabetes induction, PS extract (0.125 g/kg body weight) was administered orally for 28 days. Body weight, fasting blood glucose, and urine glucose levels were measured at 4-week interval. At the end of the study, cardiac tissues and the aorta were viewed under transmission electron microscope (TEM). DTx group showed increase in body weight and decrease in fasting blood glucose and urine glucose level compared to the D group. Under TEM study, DTx group showed lesser ultrastructural degenerative changes in the cardiac tissues and the proximal aorta compared to the D group. The results indicate that PS restores ultrastructural integrity in the diabetic cardiovascular tissues.

Matched MeSH terms: Injections, Intramuscular
Authors' response to comments on 'Subcutaneous versus intravenous tramadol for extremity injury with moderate pain in the emergency department: a randomised controlled noninferiority trial'

Bustam A, Poh K, Zambri A, Noor Azhar AM

Eur J Emerg Med, 2024 Jun 01;31(3):226-227.
PMID: 38661509 DOI: 10.1097/MEJ.0000000000001132
Matched MeSH terms: Injections, Subcutaneous
Exogenous leptin administration decreases sperm count and increases the fraction of abnormal sperm in adult rats

Haron MN, D'Souza UJ, Jaafar H, Zakaria R, Singh HJ

Fertil Steril, 2010 Jan;93(1):322-4.
PMID: 19709655 DOI: 10.1016/j.fertnstert.2009.07.995

Daily intraperitoneal injection of 5-30 microg/kg body weight of leptin for 42 days to adult rats decreases sperm count and increases the fraction of abnormal sperm.

Matched MeSH terms: Injections, Intraperitoneal
Treatment of macular hole retinal detachment

Lai YK

Br J Ophthalmol, 1990 Apr;74(4):201-2.
PMID: 2337542

Seven patients with macular hole retinal detachment were treated by intravitreal gas injection with or without release of subretinal fluid. Macular buckling, diathermy, cryopexy, or vitrectomy were not used. The patients were placed prone for eight hours a day until the gas had absorbed. In five of the seven patients the retina became reattached within three days and remained reattached with follow-up periods of three to 22 months (average nine months). It is believed that such detachments are due to vitreoretinal traction and the intravitreal gas bubble relieves this traction. This technique is simple, safe, and does not require costly or sophisticated instruments. It has an added advantage in preserving macular function.

Matched MeSH terms: Injections
Cost analysis of risperidone long-acting injection in the treatment of schizophrenia and schizoaffective disorders in Hong Kong: an approach using generalised estimating equations

Wu DB, Lee EH, Chung WS, Chow DP, Lee VW, Wong MC, et al.

Psychiatry Res, 2013 Dec 30;210(3):745-50.
PMID: 24012164 DOI: 10.1016/j.psychres.2013.07.012

Schizophrenia is one of the most expensive psychiatric illnesses. This study compared retrospectively health-care resources consumed 12 months before and 24 months after risperidone long-acting injection (RLAI) treatment in Hong Kong. A mirror-image analysis was conducted using data (N=191) from three public hospitals in Hong Kong from 2003 to 2007. The main outcome measure was hospitalisation cost. Other secondary outcomes such as hospitalisation episodes, outpatient visits and adverse events were also compared. A predictive model was established using linear regression based on generalised estimating equations. Analysis showed that RLAI was associated with a reduction in hospitalisation cost by HK$10,001,390 (24.7%) (HK$40,418,694 vs. HK$30,417,303; P-value <0.05). Days of hospitalisation were reduced by 1538 days (10.1%) (15,271 vs. 13,733; P-value <0.05). The predictive model estimated that the hospitalisation cost of patients using RLAI was only 11.1% (3.1-3.93%, 95% confidence interval (CI)) compared to those receiving conventional antipsychotics combined with oral risperidone. Cost of hospitalisation was significantly reduced after RLAI therapy. However, results should be considered as indicative or suggestive only, due to potential channelling bias where certain drug regimens are preferentially prescribed to patients with particular conditions. The findings from our study may be useful in health-care decision making considering treatment options for schizophrenia in resource-limited settings.

Matched MeSH terms: Injections/economics

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