Pharmacokinetics and bioavailability of chromium malate and its influence on trace metals absorption after oral or intravenous administration.

OBJECTIVES: In our preliminary study, chromium malate could decrease the blood glucose level in mice with diabetes and exhibits good benefits in treating glycometabolism and adipose metabolization obstacle in rats with type 2 diabetes. This study was aimed at assessing the pharmacokinetics and bioavailability of chromium malate and influence on trace metals absorption in rats. METHODS: BAPP 2.3 pharmacokinetic calculating program (China Pharmaceutical University Medicine Center) was used to calculate the pharmacokinetic parameters. Models of type 2 diabetic mellitus rats were applied to analyzed Ca, Mg, Fe, Cu, and Zn contents. RESULTS: The results showed that mean retention time (MRT) in chromium malate group was significantly prolonged and the area under the curve (AUC) and relative bioavailability of chromium malate (male) group were significant increase compared to chromium picolinate group. The serum Ca, Mg, Fe, Cu, and Zn contents in chromium malate (at doses of 15 and 20 µg Cr/kg bw) groups were significantly increased compared to control group, chromium trichloride group, and chromium picolinate group in type 2 diabetes mellitus rats. CONCLUSIONS: Those results indicated that chromium malate can significantly prolong MRT and increase AUC (male). Moreover, chromium malate is more effective at treating increased serum Ca, Mg, Fe, Cu, and Zn contents compared to chromium trichloride and chromium picolinate.

Chromic oxide and acid-insoluble ash as markers in digestibility studies with growing pigs and sows.

The results of three experiments, focused on the determination of endogenous ileal flow (EIF) of amino acids (AA) and nitrogen (N) (Exp. 1), apparent ileal digestibility (AID) of AA and N (Exp. 2), and apparent total tract digestibility (ATTD) of dry matter (DM), organic matter (OM), N, calcium (Ca) and phosphorus (P) (Exps. 2 and 3), were used to compare chromic oxide (Cr2 O3 ) and acid-insoluble ash (AIA) as digestibility markers. In Exps. 1 and 2, a total of six gilts fitted with T-cannula in terminal ileum, and in Exp. 3, a total of 24 pregnant sows were used. In Exps. 1 and 2, the pigs were assigned into four dietary treatments according to 4 × 6 crossover design (Exp. 1; diets with 0%, 4%, 8% and 12% of casein; Exp. 2 basal diet with different levels of phytase). In Exp. 3, the sows were assigned to four dietary treatments (basal diet with different levels of phytase) of six sows. In Exps. 1 and 2 ileal digesta and in Exps. 2 and 3 faeces were collected for the determination of EIF, AID and ATTD. Differences in EIF of AA determined by Cr2 O3 and AIA ranged (p Ëƒ 0.05) from -4.62 to 4.54%. The lowest EIF was for methionine and the greatest one for proline, determined by both markers. Apparent ileal digestibility determined by Cr2 O3 was slightly greater (p Ëƒ 0.05) in comparison with AIA. Differences ranged from 1.88% (Arg) to 7.08% (Gly). The greatest AID was for arginine and the lowest one for glycine, determined by both Cr2 O3 and AIA. Similarly for ATTD of DM, OM, N, Ca and P, there were no differences in digestibility determined by Cr2 O3 and AIA. Both, Cr2 O3 and AIA, are suitable and comparable markers for digestibility studies in pigs.

Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

Patient-specific dosimetry for intracavitary 32P-chromic phosphate colloid therapy of cystic brain tumours.

PURPOSE: (32)P-chromic phosphate colloid treatments of astrocytoma and craniopharyngioma cystic brain tumours in paediatric patients are conventionally based on a sphere model under the assumption of uniform uptake. The aims of this study were to determine the distribution of the absorbed dose delivered by (32)P on a patient-specific basis and to evaluate the accuracy with which this can be predicted from a pretherapy administration of (99m)Tc-Sn colloid. METHODS: Three patients were treated with (32)P-chromic phosphate colloid following (99m)Tc-Sn colloid administrations. Convolution dosimetry was performed using pretherapy and posttherapy sequential SPECT imaging, and verified with EGSnrc Monte Carlo radiation transport simulations. Mean absorbed doses to the cyst wall and dose-volume histograms were also calculated and compared with those obtained by the sphere model approach. RESULTS: Highly nonuniform uptake distributions of both the (99m)Tc and (32)P colloids were observed and characterized by dose-volume histograms to the cyst wall. Mean absorbed doses delivered to the cyst wall, obtained with the convolution method, were on average 21 % (SD 18 %) and 50 % (SD 30 %) lower than those predicted by the (99m)Tc distribution and the uniform assumption of the sphere model, respectively. CONCLUSION: Absorbed doses delivered to the cyst wall by (32)P are more accurately predicted from image-based patient-specific convolution dosimetry than from simple sphere models. These results indicate the necessity to perform personalized treatment planning and verification for intracavitary irradiation of cystic brain tumours treated with radiocolloids. Patient-specific dosimetry can be used to guide the frequency and levels of repeated administrations and would facilitate data collection and comparison to support the multicentre trials necessary to progress this therapy.

Preliminary study of the biodegradation and the correlation between in vitro and in vivo release of (32)P-chromic phosphate-poly(L-lactide) seeds.

OBJECTIVE: To investigate the drug release kinetic of (32)P-chromic phosphate-poly(L-lactide) ((32)P-CP-PLLA). METHODS: (32)P-CP-PLLA were placed into physiological saline and H22 solid tumor mass, respectively. The weight loss rate and radioactivity release rate were evaluated. The release of the microparticles was evaluated using fitting curves. The correlation of the release of the microparticles between physiological saline and H22 solid tumor mass was analyzed. RESULTS: Close correlation was noted in the release of the microparticles between physiological saline and H22 solid tumor mass. The Weibull equation showed the best fitting of (32)P-CP-PLLA in physiological saline. CONCLUSIONS: The Weibull equation could be used for the predictive release of microparticles in vitro. The parameters obtained from the drug release kinetics could be used to estimate the dose of radiopharmaceuticals within the tumors and the surrounding tissues.

The effect of ascorbic acid on the distribution of soluble Cr and Co ions in the blood and organs of rats.

Metal ions (Cr and Co) are released from metal orthopaedic implants in situ. We investigated tissue dissemination of Cr III, Cr VI and Co II ions in the body, and determined if administration of ascorbic acid (AA) affected their in vivo distribution using rats as a model system. Organs of rats treated with both Cr (VI) and Co (II) have higher metal ion levels when compared with control levels in the organs of rats without metal treatment. The reduced form of chromium, Cr III, is reported to be relatively impermeant to cell membranes in vitro, and in line with this, Cr III did not distribute into the organs of the rats after administration in vivo. Potent in vitro reduction of Cr (VI) to Cr III by AA was observed in this study. Prior intraperitoneal injection of AA lowered tissue uptake of both Cr VI and Co II, and increased faecal excretion, but not to a significant extent. AA may only be effective in increasing elimination of Cr VI at high concentrations when plasma reduction is saturated, and may be of limited therapeutic use in patients with orthopaedic implants.

High doses of cobalt induce optic and auditory neuropathy.

The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined.

Evaluation of RbCl and CrCl3 as markers of Triatoma brasiliensis (Hemiptera: Reduviidae) nymphs: persistence and influence of Rb and Cr on triatomine biology.

In order to mark Triatoma brasiliensis, the vector of Chagas disease in Brazil, two chemical compounds, rubidium chloride (RbCl) and chromium chloride (CrCl3), were tested. First, 199 N2-N5 nymphs were fed on blood with 0.025M RbCl. Rb marker positivity ranged from 2.5% (N3)-70% (N2), with a maximum persistence of 98 days. Second, 265 N2-N5 nymphs were fed on blood containing 0.0015M CrCl3. Cr marker positivity ranged up to 93% (N5), with a maximum persistence of 119 days. Finally, we blood fed 213 T. brasiliensis to investigate whether CrCl3 altered the biology of this insect. The developmental time of T. brasiliensis was unaltered, but the survival of the Cr-marked group was lower than that of the control group. Differences in the mean fecundity of the control (mean of 156.1) and experimental (mean of 135.6) groups were not statistically significant and 100% of the egg batches of females Cr-marked as nymphs were positive. In conclusion, CrCl3 is a useful tool for marking T. brasiliensis nymphs due to its high positivity and persistence.

Evaluation of RbCl and CrCl3 as markers of Triatoma brasiliensis (Hemiptera: Reduviidae) nymphs: persistence and influence of Rb and Cr on triatomine biology

In order to mark Triatoma brasiliensis, the vector of Chagas disease in Brazil, two chemical compounds, rubidium chloride (RbCl) and chromium chloride (CrCl3), were tested. First, 199 N2-N5 nymphs were fed on blood with 0.025M RbCl. Rb marker positivity ranged from 2.5 percent (N3)-70 percent (N2), with a maximum persistence of 98 days. Second, 265 N2-N5 nymphs were fed on blood containing 0.0015M CrCl3. Cr marker positivity ranged up to 93 percent (N5), with a maximum persistence of 119 days. Finally, we blood fed 213 T. brasiliensis to investigate whether CrCl3 altered the biology of this insect. The developmental time of T. brasiliensis was unaltered, but the survival of the Cr-marked group was lower than that of the control group. Differences in the mean fecundity of the control (mean of 156.1) and experimental (mean of 135.6) groups were not statistically significant and 100 percent of the egg batches of females Cr-marked as nymphs were positive. In conclusion, CrCl3 is a useful tool for marking T. brasiliensis nymphs due to its high positivity and persistence.

Determination of internalization of chromium oxide nano-particles in Escherichia coli by flow cytometry.

In this study, Escherichia coil DH5alpha (ATCC 35218) were exposed to 0-100 microg/mL chromium oxide nanoparticles (Cr2O3, Nps) for 15-120 min to study the internalization of Nps by flowcytometry. A concentration-duration dependent increased side scatter (SSC) confirmed the internalization of Cr2O3 NPs by the E. coli. This study suggests that the uptake of Nps by bacterial cells can be rapidly monitored with flow cytometry for toxicity and risk assessment.

Hexavalent chromium inhibited the expression of RKIP of heart in vivo and in vitro.

BACKGROUND: Chromium (Cr) is considered to be a risk factor to the cardiovascular effects of fine particulate matter components to PM2.5 from traffic in highway patrol officers. RKIP (raf kinase inhibitor protein) is a physiological inhibitor of GRK-2 (G-protein-coupled receptor kinase 2) and affects ß-adrenergic signaling and contractile activity in cardiomyocytes. OBJECTIVES: In this study, we explored the change of RKIP in heart of chromium (VI)-exposed rats and cultured myocardial cells with chromium (VI) treatment. METHOD: Wistar rats were divided into six groups which were chronically fed with 250, 500, 750, 1000, and 1250 ppm Na(2)Cr(2)O(7) and water for 60 days, respectively. Na(2)Cr(2)O(7) dose of 0.25, 0.5, 1.5, 3, 4.5, and 0 ppm (control group) was applied in cultured myocardial cells. The level of heart Cr (VI) was determined by electrothermal atomic absorption spectrometry. The expression of RKIP was measured by Western blot method. The MTT assay was used to measure the toxicity of myocardial cells with Cr (VI) treatment. The apoptosis test of myocardial cells was determined by caspase-3 colorimetric assay kit. RESULT: The result showed that the expression of RKIP in heart (in vivo) and myocardial cells (in vitro) was decreased following Cr (VI) dose-dependent treatment. CONCLUSION: We suggested that the decrement of RKIP of heart and myocardial cells with Cr (VI) treatment resulted in the function of cardiovascular system decreased.

Bacillus species enhance growth parameters of chickpea (Cicer arietinum L.) in chromium stressed soils.

Pollution of the agricultural land by the toxic chromium is a global threat that has accelerated dramatically since the beginning of industrial revolution. Toxic chromium affects both the microbial diversity as well as reduces the growth of the plants. Understanding the effect of the chromium reducing and plant growth promoting rhizobacteria on chickpea crop will be useful. Chromium reducing and plant growth promoting Bacillus species PSB10 significantly improved growth, nodulation, chlorophyll, leghaemoglobin, seed yield and grain protein of chickpea crop grown in the presence of different concentrations of chromium compared to the plants grown in the absence of bio-inoculant. The strain also reduced the uptake of chromium in roots, shoots and grains of chickpea crop compared to plants grown in the absence of bio-inoculant. This study thus suggested that the Bacillus species PSB10 due to its intrinsic abilities of growth promotion and attenuation of the toxic effects of chromium could be exploited for remediation of chromium from chromium contaminated sites.

Tissue accumulation and urinary excretion of chromium in rats fed diets containing graded levels of chromium chloride or chromium picolinate.

To attempt a risk assessment of the excess intake of trivalent chromium (Cr), tissue Cr accumulation and urinary Cr excretion were examined in weanling rats fed experimental diets containing graded levels of Cr chloride (CrCl3) or Cr picolinate (CrPic). Thirty-six male weanling 4-weeks-old Wistar rats were divided into six groups and fed a casein-based semi-purified diet (Cr content: <0.02 microg/g) supplemented with 1, 10, or 100 microg Cr/g as CrCl3 or CrPic for 28 days. Among the experimental groups, no significant difference was observed in body weight; however, supplementation of 100 microg Cr/g to the diets caused a significant low liver weight irrespective of the chemical species of Cr. Activities of serum aspartate aminotransferase and alanine aminotransferase were significantly elevated in rats given CrPic at 100 microg Cr/g. In the liver, kidney and femur, Cr accumulation increased with elevation of the dietary Cr level. No influence of the difference in the chemical species of supplemented Cr was observed in the liver and kidney, but CrCl3 caused significantly higher Cr accumulation than CrPic in the femur of rats given 100 microg Cr/g. Daily urinary Cr excretion elevated with the increase of the dietary Cr level. Rats given CrPic showed significantly higher daily urinary Cr excretion than those given CrCl3, particularly at a dietary Cr level of 100 microg/g. The rate of urinary Cr excretion in rats given CrPic was constant, irrespective of the dietary Cr level, but that of rats given CrCl3 fell with the increase of the dietary Cr level. These results indicate that the lowest adverse effect level of dietary Cr is less than 100 microg/g, irrespective of the chemical species of Cr.

Intratumoral injection of 32P-chromic phosphate in the treatment of implanted pancreatic carcinoma.

AIM: The aim of this study was to observe the biological distribution and anticancer effect of (32)P-chromic phosphate colloid (Cr(32)PO(4), (32)P-CP) after intratumoral injection to Pc-3 human pancreatic carcinoma-bearing nude mice. METHODS: Eighty-four (84) BALB/c nude mice with transplanted tumor were allocated to 11 groups. Groups 1-5 (n = 6) were intratumorally injected with 14.8 MBq of (32)P-CP and sacrificed at 2, 24, 48, 72, and 168 hours, respectively. Groups 6-11 (n = 9) received injections of 3.7, 7.4, 14.8, 18.5, 29.6, and 0 MBq of (32)P-CP, respectively, and the tumor volume on body surface was measured daily. The animals (n = 6) were sacrificed at 14 days after administration. The dynamic distribution of radioactivity in body (percentage of injected dose per g), morphological changes, the tumor-inhibiting rate (TIR), proliferating index (PI), proliferating cell nuclear antigen (PCNA) tumor microvascular density (MVD), continuous counting of white blood cells (WBCs) and platelets (PLTs) in venous blood, body weight, and toxic reactions were observed. RESULTS: The injected (32)P-CP mainly accumulated in the tumor mass and was retained for a long time. The TIR of each dosage group in order was 21.68%, 39.73%, 50.43%, 71.18%, and 74.09% (F = 159.74; p < 0.001), PI was 70.85, 67.90, 46.70, 20.66, 10.75, and 90.11 (F = 509.54; p < 0.001), and MVD count was 39.19, 28.33, 17.45, 8.89, 8.10, and 64.80 (F = 643.26; p < 0.001), respectively. The data for WBC, PLT, and body weight observed for 28 days in the treatment groups did not indicate significant differences compared with those of the control group. CONCLUSIONS: Interstitial injection of (32)P-CP seems to be a safe and effective interventional nuclide therapy for pancreatic carcinoma-bearing nude mice.

Use of synchrotron- and plasma-based spectroscopic techniques to determine the uptake and biotransformation of chromium(III) and chromium(VI) by Parkinsonia aculeata.

In this study, a combination of inductively coupled plasma optical emission spectroscopy and X-ray absorption spectroscopy (XAS) was used to study the uptake and speciation of chromium in Parkinsonia aculeata, commonly known as Mexican Palo Verde. Plants were treated for 14 days in a modified Hoagland solution containing chromium(III) or chromium(VI) at several concentrations. The results showed that plants treated with 70 mg Cr(III) L(-1) and 30 mg Cr(VI) L(-1) had similar Cr concentrations in leaves (∼200 mg kg(-1) dry weight, DW). The results also showed that neither Cr(III) nor Cr(VI) affected the uptake of phosphorus and sulfur. However, the concentration of calcium in the stems of plants treated with Cr(VI) at 40 mg L(-1) (about 6000 mg Ca kg(-1) DW) was significantly higher compared to the Ca concentration (about 3000 mg kg(-1) DW) found in the stems of plants treated with 150 mg Cr(III) L(-1). However, no differences were observed in potassium and magnesium concentrations. The iron concentration (about 1000 mg kg(-1) DW) in roots treated with 40 mg Cr(VI) L(-1) was similar to the iron concentration found in the roots of plants treated with 110 mg Cr(III) L(-1). The XAS data showed that Cr(VI) was reduced to Cr(III) in/on the plant roots and transported as Cr(III) to the stems and leaves. The XAS studies also showed that Cr(III) within plants was present as an octahedral complex.

Carcinogenic chromium(VI)-induced protein oxidation and lipid peroxidation: implications in DNA-protein crosslinking.

Hexavalent chromium [Cr(VI)] compounds are Group-I human carcinogens. Cr(VI)-induced DNA-protein crosslinks (DPCs) have been implicated in the mutagenic and carcinogenic effects of Cr(VI). Although multiple mechanisms have been suggested for Cr(VI)-induced DNA-protein crosslinking, the mechanism of formation of DNA-protein crosslinks is not well understood. In this study, we explored the hypothesis that Cr(VI)-induced DPCs could be formed via generation of protein carbonyls and malonaldehyde (MDA) through protein oxidation and lipid peroxidation, respectively. Treatment of human leukemic T-lymphocyte MOLT4 cells with potassium chromate induced the formation of protein carbonyls and DPCs within 2 h, but increased the level of MDA only after 4 h, in a dose-dependent manner. Chromate treatment of MOLT4 cell homogenates also resulted in increased formation of MDA and protein carbonyls in a dose-dependent manner. EPR spectrometry in combination with spin trapping techniques revealed that reaction of Cr(VI) with biological reductants such as NADPH, glutathione reductase or H(2)O(2) generates Cr(V) and (*)OH radicals. Pretreatment of cells with antioxidants such as alpha-tocopherol or Tiron inhibited chromate-induced increase in formation of protein carbonyls, MDA and DPCs, but pretreatment of cells with riboflavin or 3-aminotriazole, a catalase inhibitor, had the opposite effect. Our results, for the first time, demonstrate that Cr(VI) exposure increases the cellular level of protein carbonyls and that Cr(VI)-induced DPCs may be formed, at least in part, via generation of protein carbonyls.

Chromium nanoparticle exhibits higher absorption efficiency than chromium picolinate and chromium chloride in Caco-2 cell monolayers.

This study was conducted to determine whether chromium nanoparticle (CrNano) exhibited higher absorption efficiency and possessed unique absorption mechanism in comparison to chromium picolinate (CrPic) and chromium chloride (CrCl(3)), as was postulated by previous reports. Twenty-one-day-old Caco-2 cell monolayers grown on semipermeable membranes in Snapwell tissue culture bichambers were incubated with CrNano, CrPic or CrCl(3) to examine their transport and uptake respectively. In the concentration range of 0.2-20 micromol/l, transport of CrNano, CrPic and CrCl(3) across Caco-2 monolayers both in apical-to-basolateral and basolateral-to-apical direction was concentration-, and time-dependent, and temperature independent. The apparent permeability coefficient (P(app)) of CrNano was between 5.89 and 7.92 x 10(-6) cm/s and that of CrPic and CrCl(3) was between 3.52 and 5.31 x 10(-6) cm/s and between 0.97 and 1.37 x 10(-6) cm/s respectively. Uptake of CrNano, CrPic and CrCl(3) by both apical and basolateral membranes was concentration- and time-dependent. Uptake of CrNano by apical membrane was significantly (p < 0.05) decreased when the incubation temperature was reduced from 37 degrees C to 4 degrees C. The transport efficiency of CrNano, CrPic and CrCl(3) after incubation for 120 min at 37 degrees C was 15.83% +/- 0.76%, 9.08% +/- 0.25% and 2.11% +/- 0.53% respectively. The uptake efficiency of CrNano, CrPic and CrCl(3) was 10.08% +/- 0.76%, 4.73% +/- 0.60% and 0.88% +/- 0.08% respectively. It was concluded that the epithelial transport of CrNano, CrPic and CrCl(3) across the Caco-2 cell monolayers was mainly via passive transport pathways. In addition, CrNano exhibited considerably higher absorption efficiency than both CrPic and CrCl(3) in Caco-2 cell monolayers.

Effects of intralesional 32-P chromic phosphate in refractory patients with head and neck tumours.

BACKGROUND: The clinical outcome of refractory head and neck (H&N) cancer patients remains poor despite novel treatment strategies. In this pilot study the efficacy of intratumoral injection of 32-P chromic phosphate in 14 patiehts with refractory H&N carcinomas was investigated in terms of response rates and overall survival. PATIENTS AND METHODS: Fourteen patients (median age: 59 years) with either cytostatic drug-resistant tumours or tumours known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumour volume, 32-P chromic phosphate (74-444 MBq) was injected into the central part of the tumour under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations and hematological studies. RESULTS: Injection of 32-P chromic phosphate into refractory H&N tumours resulted in remarkable regression. The median survival of all patients was 7.8 months (range: 4-16). Eight patients exhibited a partial response, while 6 patients did not respond to the treatment. In 3 patients thrombocytopenia (grade I/II) was observed, but no other significant side-effects were apparent. Significant pathological and anatomical changes within the tumour tissue were demonstrated. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found. CONCLUSION: A lack of persistent systematic or local side-effects, as well as noteworthy efficacy, are properties of this novel regional treatment modality with 32-P chromic phosphate. This modality deserves consideration for further clinical trials.

Long-term safety evaluation of a novel oxygen-coordinated niacin-bound chromium (III) complex.

Chromium (III) is an essential micronutrient required for normal protein, fat and carbohydrate metabolism, as well as helps insulin metabolize fat, turn protein into muscle and convert sugar into energy. A broad spectrum of research investigations including in vitro, in vivo and clinical studies demonstrated the beneficial effects of novel oxygen- coordinated niacin-bound chromium (III) complex (NBC) in promoting glucose-insulin sensitivity, lipid profile, cardioprotective ability and lean body mass. This study examined the long-term safety of NBC by orally administering either 0 or 25 ppm or the human equivalency dose of 1000 microg elemental chromium (III) as NBC per day for 52 consecutive weeks to male and female Sprague-Dawley rats. Animals of each group and each gender were sacrificed on 26, 39, or 52 weeks of treatment. Body weight, physical and ocular health, feed and water intake, selected organ weights as such and as a percentage of liver and brain weight, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluations were conducted. At 26, 39, or 52 weeks of treatment, body weight gain was significantly reduced by 7.7%, 8.1% and 14.9% in male rats, and 5.5%, 11.4% and 9.6% in female rats, respectively, in the NBC treatment groups. No significant changes were observed in hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluation between control and NBC groups at these time points. These findings, thus far, are in agreement with the subchronic studies in terms of the safety of NBC.