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Therapeutic potential of selenium and tellurium compounds: opportunities yet unrealised

Tiekink ER

Dalton Trans, 2012 Jun 7;41(21):6390-5.
PMID: 22252404 DOI: 10.1039/c2dt12225a

Despite being disparaged for their malodorous and toxic demeanour, compounds of selenium, a bio-essential element, and tellurium, offer possibilities as therapeutic agents. Herein, their potential use as drugs, for example, as anti-viral, anti-microbial, anti-inflammatory agents, etc., will be surveyed along with a summary of the established biological functions of selenium. The natural biological functions of tellurium remain to be discovered.

Matched MeSH terms: Organometallic Compounds/therapeutic use*
Occupational and ambient radiation exposures from Lu-177 DOTATATE during targeted therapy

Sulieman A, Mayhoub FH, Salah H, Al-Mohammed HI, Alkhorayef M, Moftah B, et al.

Appl Radiat Isot, 2020 Oct;164:109240.
PMID: 32819499 DOI: 10.1016/j.apradiso.2020.109240

Lutetium-177 (DOTATATE) (177Lu; T1/2 6.7 days), a labelled β- and Auger-electron emitter, is widely used in treatment of neuroendocrine tumours. During performance of the procedure, staff and other patients can potentially receive significant doses in interception of the gamma emissions [113 keV (6.4%) and 208 keV (11%)] that are associated with the particle decays. While radiation protection and safety assessment are required in seeking to ensure practices comply with international guidelines, only limited published studies are available. The objectives of present study are to evaluate patient and occupational exposures, measuring ambient doses and estimating the radiation risk. The results, obtained from studies carried out in Riyadh over an 11 month period, at King Faisal Specialist Hospital and Research Center, concerned a total of 33 177Lu therapy patients. Patient exposures were estimated using a calibrated Victoreen 451P survey meter (Fluke Biomedical), for separations of 30 cm, 100 cm and 300 cm, also behind a bed shield that was used during hospitalization of the therapy patients. Occupational and ambient doses were also measured through use of calibrated thermoluminescent dosimeters and an automatic TLD reader (Harshaw 6600). The mean and range of administered activity (in MBq)) was 7115.2 ± 917.2 (4329-7955). The ambient dose at corridors outside of therapy isolation rooms was 1.2 mSv over the 11 month period, that at the nursing station was below the limit of detection and annual occupational doses were below the annual dose limit of 20 mSv. Special concern needs to be paid to comforters (carers) and family members during the early stage of radioisotope administration.

Matched MeSH terms: Organometallic Compounds/therapeutic use*
Helicobacter pylori infection and non-ulcer dyspepsia: the effect of treatment with colloidal bismuth subcitrate

Goh KL, Parasakthi N, Peh SC, Wong NW, Lo YL, Puthucheary SD

Scand. J. Gastroenterol., 1991 Nov;26(11):1123-31.
PMID: 1754846

A study was undertaken to determine the role of Helicobacter pylori in non-ulcer dyspepsia (NUD) and to determine the efficacy of colloidal bismuth subcitrate (CBS) in the treatment of NUD. Seventy-one patients were randomly allocated (double blind) to CBS or placebo, two tablets twice daily for 4 weeks. The severity of dyspepsia was scored and endoscopies performed before and after treatment, and antral biopsy specimens were taken for bacteriologic and histologic examination. Forty patients had H. pylori infection, and all had changes of chronic active gastritis. H. pylori was cleared from 17 to 21 patients (81%) treated with CBS, whereas none of the 19 patients treated with placebo cleared the bacteria. Improvement in histology was noted in 15 of 21 patients (71.4%) treated with CBS, whereas no improvement was noted in any of the placebo controls. Thirty-one patients were negative for H. pylori. All had either normal gastric histology or minor degrees of inflammation. Seventeen of these patients received CBS, and 14 received placebo. All groups reported improvement in the symptom score; however, the H. pylori-positive, CBS-treated group recorded a significantly higher improvement than the other groups (p less than 0.001). Relapse of H. pylori infection after initial clearance of the bacteria was high. Twelve of 16 patients evaluated relapsed 1 month after withdrawal of CBS.

Matched MeSH terms: Organometallic Compounds/therapeutic use*
Fulltext Evaluation of therapies in the treatment of Helicobacter pylori associated non-ulcer dyspepsia

Nafeeza MI, Shahimi MM, Kudva MV, Ahmad H, Isa MR, Sood IM, et al.

Singapore Med J, 1992 Dec;33(6):570-4.
PMID: 1488663

This randomised double blind placebo controlled study evaluated the effectiveness of colloidal bismuth subcitrate (CBS), ampicillin and their combination in the treatment of Helicobacter Pylori in non-ulcer dyspepsia (NUD) and assessed if elimination of this organism is associated with improvement of gastritis and the symptoms. Forty-eight NUD patients with H. pylori and histologic gastritis were randomly allocated to one of the three regimens for 28 days. Symptoms were assessed before and after treatment. Forty-three patients completed the trial. Repeat endoscopy within 48 hours of completing treatment showed suppression of H. pylori in 6 of 7 patients (85.7%) on combined therapy and one of 8 patients (12.5%) on CBS therapy (p = 0.0205). There was no suppression of the bacteria in patients treated with ampicillin. Repeat endoscopy performed 2 weeks after completing treatment showed suppression of H. pylori in 3 of 7 patients (42.9%) on combined therapy and none in the other two groups. Patients on combined therapy who had suppression of H. pylori, 48 hours or 2 weeks after completing treatment were noted to have historical improvement of their gastritis (p = 0.0001 and p = 0.05 respectively). This was also associated with improvement of symptoms in these patients.

Matched MeSH terms: Organometallic Compounds/therapeutic use
Fulltext Enhanced blood compatibility of metallocene polyethylene subjected to hydrochloric acid treatment for cardiovascular implants

Jaganathan SK, Mohandas H, Sivakumar G, Kasi P, Sudheer T, Avineri Veetil S, et al.

Biomed Res Int, 2014;2014:963149.
PMID: 24955370 DOI: 10.1155/2014/963149

Blood compatibility of metallocene polyethylene (mPE) was investigated after modifying the surface using hydrochloric acid. Contact angle of the mPE exposed to HCl poses a decrease in its value which indicates increasing wettability and better blood compatibility. Surface of mPE analyzed by using FTIR revealed no significant changes in its functional groups after treatment. Furthermore, scanning electron microscope images supported the increasing wettability through the modifications like pit formations and etching on the acid rendered surface. To evaluate the effect of acid treatment on the coagulation cascade, prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Both PT and APTT were delayed significantly (P < 0.05) after 60 min exposure implying improved blood compatibility of the surfaces. Hemolysis assay of the treated surface showed a remarkable decrease in the percentage of lysis of red blood cells when compared with untreated surface. Moreover, platelet adhesion assay demonstrated that HCl exposed surfaces deter the attachment of platelets and thereby reduce the chances of activation of blood coagulation cascade. These results confirmed the enhanced blood compatibility of mPE after HCl exposure which can be utilized for cardiovascular implants like artificial vascular prostheses, implants, and various blood contacting devices.

Matched MeSH terms: Organometallic Compounds/therapeutic use*
Efficacy and safety of 2 g/day of strontium ranelate in Asian women with postmenopausal osteoporosis

Liu JM, Wai-Chee Kung A, Chan SP, Zhu HM, Zhang ZL, Wu YY, et al.

Bone, 2009 Sep;45(3):460-5.
PMID: 19464401 DOI: 10.1016/j.bone.2009.05.014

Strontium ranelate is a new effective anti-osteoporotic treatment having a unique mode of action, reducing bone resorption while promoting continued bone formation, with a broad range of anti-fracture efficacy at vertebral as well as peripheral sites. In Phase III studies, it has proven its early and sustained efficacy against vertebral fractures in Caucasians along with a significant increase in lumbar bone mineral density (BMD). The aim of this randomized double-blind study was to demonstrate the efficacy of strontium ranelate (2 g/day) on lumbar spine bone mineral density and the clinical and biological safety in Asian postmenopausal osteoporotic patients compared to placebo over 1 year. Three hundred and twenty-nine eligible women from mainland China, Hong Kong and Malaysia were randomized into the study. The baseline characteristics were similar in the treatment and placebo groups: mean age of 66.2+/-6.5 years, time since menopause 17.6+/-7.2 years. In the Full Analysis Set (FAS, N=302), the mean baseline lumbar L2-L4 BMD was 0.715+/-0.106 g/cm(2) in the strontium ranelate group and 0.708 +/- 0.109 g/cm2 in the placebo group. The mean baseline femoral neck BMD was 0.575+/-0.074 g/cm2 and 0.566+/-0.069 g/cm2 respectively and mean total hip BMD was 0.642+/-0.080 g/cm2 and 0.631 +/-0.088 g/cm2 respectively. The overall compliance was 91.4% in the study drug group, and 97.4% in the placebo group. After 1 year of treatment, the lumbar spine, femoral neck and total hip BMD in the treated group was significantly increased by 3-5% as compared to placebo. Strontium ranelate was well tolerated. The most frequently reported emergent adverse events were comparable in both groups (60.4% versus 60.0%), with majority of them being mild gastrointestinal disorders. There were no clinically relevant changes in laboratory tests, such as blood routine, hepatic and renal function. It is thus concluded that the effects of 2 g/day strontium ranelate on BMD and its safety profile in this cohort of postmenopausal osteoporotic Asian women were consistent with results obtained from Caucasian women in which the efficacy on the reduction in risk of fracture has been proven.

Matched MeSH terms: Organometallic Compounds/therapeutic use*
Reinfection and duodenal ulcer relapse in south-east Asian patients following successful Helicobacter pylori eradication: results of a 2-year follow-up

Goh KL, Navaratnam P, Peh SC

Eur J Gastroenterol Hepatol, 1996 Dec;8(12):1157-60.
PMID: 8980932

OBJECTIVES: To determine the reinfection rate of Helicobacter pylori and duodenal ulcer relapse rate in a group of patients followed up long term.
DESIGN: Prospective study.
PATIENTS AND METHODS: Patients were followed up endoscopically at 3, 6, 12 and 24 months after successful H. pylori eradication and duodenal ulcer healing. H. pylori status was determined by culture, rapid urease test, Gram's stain of a fresh tissue smear and histological examination of antral biopsies and rapid urease test and histological examination of corpus biopsies.
MAIN OUTCOME MEASURES: Duodenal ulcer healing, H. pylori reinfection.
RESULTS: Thirty-eight patients with duodenal ulcer disease (35 active, 3 healed) had successfully eradicated H. pylori following treatment with omeprazole/amoxycillin (n = 11), omeprazole/amoxycillin/metronidazole (n = 16) and colloidal bismuth subcitrate/ amoxycillin/metronidazole (n = 11). All patients with active duodenal ulcer had healed ulcers at the end of therapy. Thirty-five of 38 patients were seen according to schedule up to 2 years; two patients were seen up to 12 months and one up to 6 months only. Reinfection with H. pylori was not recorded in any of our patients. Shallow duodenal ulcers were noted in three patients at 1-year follow-up, two of whom admitted to taking non-steroidal anti-inflammatory drugs (NSAIDs); H. pylori status was negative in all three. Subsequent follow-up revealed spontaneous healing of the ulcers in all three patients. At 2 years, one patient whose H. pylori status was negative had recurrence of duodenal ulcer. All of the three patients who defaulted subsequent to follow-up were negative for H. pylori and had healed ulcers on follow-up endoscopy at 6 and 12 months.
CONCLUSION: Reinfection rate with H. pylori was zero in a group of South-East Asian patients who had successfully eradicated the infection. Duodenal ulcer relapse was also low (2.9%) in this group of patients at 2 years.

Matched MeSH terms: Organometallic Compounds/therapeutic use
Gastroprotective activity and mechanism of novel dichlorido-zinc(II)-4-(2-(5-methoxybenzylideneamino)ethyl)piperazin-1-iumphenolate complex on ethanol-induced gastric ulceration

Salga MS, Ali HM, Abdulla MA, Abdelwahab SI

Chem Biol Interact, 2012 Jan 25;195(2):144-53.
PMID: 22178775 DOI: 10.1016/j.cbi.2011.11.008

Zinc complexes were reported to have anti-ulcer activity and used as drug for the treatment of gastrointestinal disorders. A novel compound dichlorido-zinc(II)-4-(2-(5-methoxybenzylidene amino)ethyl)piperazin-1-iumphenolate (ZnHMS) was synthesized, characterized and evaluated for its gastroprotective activity against ethanol-induced ulcer in rats. Gross and microscopic lesions, histochemical staining of glycogen storage, biochemical and immunological parameters were taken into consideration. Oral administration of ZnHMS (30 and 60 mg/kg; 14 days) dose-dependently inhibited gastric lesions. It significantly increased the mucus content and total acidity compared to the control group (P<0.01). Serum levels of aspartate (AST), alanine (ALT) transaminases, pro-inflammatory interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and anti-inflammatory interleukin-10 (IL-10) in the rats exposed to ethanol induced ulceration have been altered. ZnHMS considerably enhances (P<0.05) the protection of gastric epithelia by modulating the acute alterations of AST, ALT, IL-6, IL-10, TNF-α and stomach glycogen. Interestingly, ZnHMS did interfere with the natural release of nitric oxide. In addition, acute toxicity study revealed no abnormal sign to the rats treated with ZnHMS (2000 mg/kg). These findings suggest that the gastroprotective activity of ZnHMS might contribute in adjusting the inflammatory cytokine-mediated oxidative damage to the gastric mucosa.

Matched MeSH terms: Organometallic Compounds/therapeutic use*