Chemotherapeutical effects of the herbal medicine Uncaria tomentosa (Willd.) DC.

The use of medicinal plants dates back to the beginning of humanity, and today their application as complementary therapy has been widely disseminated as an alternative to conventional therapy. The medicinal plant named Uncaria tomentosa (Willd.) DC. (known as cat's claw) is a common woody vine of the Amazon forest that has traditionally been used in the treatment of arthritis because of its anti-inflammatory properties. This study aimed to evaluate the cytotoxic, mutagenic, and antimutagenic potentials of this medicinal plant. The biological activities of U. tomentosa were determined on bone marrow cells of Wistar rats that were treated in vivo. For the cytotoxic and mutagenic analyses, aqueous plant extract solutions were administered by gavage (1, 2, or 3 mg/mL) for 24 h (an acute treatment) or 7 days (a subchronic treatment). For the antimutagenic analyses, aqueous plant extract solutions (1 mg/mL) were administered by gavage before (pretreatment), simultaneous to (simultaneous treatment), or after (post-treatment), the administration of cyclophosphamide (1.5 mg/mL). U. tomentosa did not show any cytotoxic or mutagenic effects in any of the cytological or chromosomal analyses. Besides, the antimutagenic tests showed that the plant extracts displayed antimutagenic activities, which significantly reduced the percentages of the chromosomal aberrations that were induced by cyclophosphamide at 53.91, 58.60, and 57.03%, respectively, for the simultaneous treatment, pretreatment, and post-treatment. The results suggested a safe use of this herbal medicine that is available free of charge from the Brazilian Public Health System for the treatment of arthritis. This medicinal plant can also effectively contribute to improving the quality of life and the recovery of people undergoing chemotherapeutical treatments.

In vivo antimutagenic activity of the medicinal plants Pfaffia glomerata (Brazilian ginseng) and Ginkgo biloba.

Complementary and alternative therapies, including the use of medicinal plants, have become almost standard among the world's population. Pfaffia glomerata (PG), popularly known as Brazilian ginseng, is widely used as a restorer of vital functions, increasing mental balance, and is used for the treatment of diabetes and rheumatism. Ginkgo biloba (GB) is one of the oldest known gymnosperms, whose leaves are widely used for its potentiating action on the nervous system. The biological activities of these plants were determined on bone marrow cells of Wistar rats treated in vivo. For cytotoxic and mutagenic acute analysis, plant extracts were administered by gavage at concentrations of 0.15, 1.5, and 15 mg PG/mL water and 1, 2, and 3 mg GB/mL water. For antimutagenic analysis, plant extracts aqueous solution (PG, 1.5 mg/mL or GB, 2 mg/mL) were administered by gavage before (pretreatment), simultaneous to (simultaneous treatment), or after (post-treatment) the administration of cyclophosphamide (1.5 mg/mL, intraperitoneally). Both plant extracts have no cytotoxic or mutagenic potential, and they significantly reduce the percentage of chromosomal aberrations induced by the cyclophosphamide given simultaneously (PG, 87%; GB, 75%), pretreatment (PG, 98%, GB, 78%) and post-treatment (PG, 99%, GB, 75%). This beneficial antimutagenic property of the medicinal plants P. glomerata and G. biloba presented here, with no cytotoxic or mutagenic activity, can efficiently contribute to improvements in quality of life and recovery for people undergoing chemotherapeutic treatment, or those looking for health and preventive habits.

Degenerative effects of cobalt-chloride treatment on neurons and microglia in a porcine retina organ culture model.

In order to understand the pathological processes of retinal diseases, experimental models are necessary. Cobalt, as part of the vitamin B12 complex, is important for neuronal integrity. However, it is known that high quantities of cobalt induce cytotoxic mechanisms via hypoxia mimicry. Therefore, we tested the degenerative effect of cobalt chloride (CoCl2) on neurons and microglia in a porcine retina organ culture model. Organotypic cultures of porcine retinas were cultured and treated with different concentrations of CoCl2 (0, 100, 300 and 500 µM) for 48 h. After four and eight days, CoCl2 induced a strong degeneration of the porcine retina, starting at 300 µM. A loss of retinal ganglion cells (RGCs, Brn-3a), amacrine cells (calretinin) and bipolar cells (PKCα) was observed. Additionally, a high expression of hypoxia induced factor-1a (HIF-1a) and heat shock protein 70 (HSP70) was noted at both points in time. Also, the Caspase 3 protein was activated and P21 expression was induced. However, only at day four, the Bax/Bcl-2 ratio was increased. The effect of CoCl2 was not restricted to neurons. CoCl2 concentrations reduced the microglia amount (Iba1) and activity (Iba1 + Fcγ-Receptor) at both points in time. These damaging effects on microglia were surprising, since CoCl2 causes hypoxia and a pro-inflammatory environment. However, high concentrations of CoCl2 also seem to be toxic to these cells. Similar degenerative mechanisms as in comparison to retinal ischemia animal models were observed. In summary, an effective and reproducible hypoxia-mimicking organotypic model for retinal degeneration was established, which is easy to handle and ready for drug studies.

Interferon-α combined with lamivudine versus lamivudine monotherapy for the emergence of YMDD mutations in chronic hepatitis B infection: a meta-analysis of randomized controlled trials.

BACKGROUND/AIMS: Tyrosine-methionine-aspartate-aspartate (YMDD) mutations were the main limitation of lamivudine (LAM) for treating chronic hepatitis B (CHB). The aim of this study was to evaluate whether LAM combined with IFN-α offer advantage over lamivudine monotherapy for the occurrence of YMDD mutations in CHB using a meta-analysis. METHODOLOGY: We searched electronic databases and calculated the odds ratios (OR) with their 95% confidence intervals (CI) and pooled the results. RESULTS: Our meta-analysis indicated that the difference of YMDD mutation rates between the combination therapy of IFN-α2b, IFN-α2a and Peg-IFN-α2a respectively plus LAM and LAM monotherapy (95% CI, 3.25-9.70, 95% CI, 5.77-17.51, 95% CI, 6.79-26.13, respectively). The rate of YMDD mutations in LAM monotherapy was increased when compared with combination and sequential combination group (95% CI, 6.79-22.16, and 95% CI, 2.69-7.75, respectively). The YMDD mutation rate in combination therapy was lower than that of LAM monotherapy in HBeAg positive patients (95% CI, 4.98-13.23). CONCLUSIONS: Our present meta-analysis suggests that different types of IFN-a in combination with LAM can significantly reduce the rate of YMDD mutation compared to LAM monotherapy.

A visible response to an invisible tattoo.

Invisible (or blacklight) tattoos are fast becoming the trend in the world of tattoo art, and with their rise comes the onset of associated complications. Though there have been many reports of cutaneous reactions to traditional tattoo pigments, literature regarding reactions to invisible tattoos is scarce. We report the case of a 28-year-old man who presented with an inflammatory eruption of 2 months' duration confined to the area of a recently placed invisible tattoo; the eruption was diagnosed as granulomatous dermatitis to a foreign material. Under fluorescent light, a refractile foreign material was identified in the biopsy specimen, which we believe to be melamine, one of the invisible tattoo's five ingredients. Previous cases of cutaneous reactions to invisible tattoos were attributed to polymethylmethacrylate, not a component of the tattoo in this case. To our knowledge, this is the first case implicating melamine as the cause of a granulomatous tattoo reaction. Given the rising popularity of invisible tattoos, we present this case to raise awareness of the risks associated with this alternative tattoo trend.

Conventional (MG-BR46 Conquista) and transgenic (BRS Valiosa RR) soybeans have no mutagenic effects and may protect against induced-DNA damage in vivo.

In the present study, we evaluated the pesticide and metal concentrations as well as the antimutagenic and mutagenic properties of commercial soybeans (Glycine max). Male Swiss mice were fed diets containing 1%, 10%, or 20% (w/w) transgenic soybeans (BRS Valiosa RR) or parental isogenic conventional soybeans (MG-BR46 Conquista). Cyclophosphamide (50 mg kg⁻¹ b.w.) was added in a single dose 24 h before euthanasia as an induction agent. There was no difference in the composition (ash, total fat, protein, moisture, and carbohydrates) of the diets containing the same soybean concentration. The results show that the commercially available Brazilian soybeans tested are free of organochlorine, organophosphate, and carbamate pesticides and contain acceptable heavy metal concentrations. Both cyclophosphamide and soybean treatments were not sufficient to cause detectable oxidative damage on liver by the levels of malondialdehyde and protein carbonyl. The transgenic soybeans are also nonmutagenic and have protective effects against DNA damage similar to those of conventional soybeans but to a lesser percentage (64%-101% for conventional and 23%-33% for transgenic diets).

Protective effect of zinc chloride against cobalt chloride-induced cytotoxicity on vero cells: preliminary results.

The aim of this study was to investigate the possible time- and dose-dependent cytotoxic effects of cobalt chloride on Vero cells. The cultured cells were incubated with different concentrations of cobalt chloride ranging from 0.5 to 1,000 µM, and cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and resazurin assays. Possible protective effects of vitamin E, coenzyme Q(10), and zinc chloride were also tested in this system. A gradual decrease in cell proliferation was observed at concentrations ~≥ 200 µM in incubation periods of 24, 48, 72, and 96 h with MTT assay. Exposure of cells to 500 and 1,000 µM cobalt chloride caused significant decrease in cell survival. A biphasic survival profile of cells was observed at 1-25 µM concentration range following 96 h of incubation. With resazurin assay, cytotoxicity profile of CoCl(2) was found comparable to the results of MTT assay, particularly at high concentrations and long incubation periods. Dose-dependent cytotoxicity was noted following exposure of cells to ≥ 250 µM of CoCl(2) for 24 h and ≥ 100 µM concentrations of CoCl(2) for 48-96 h. Pretreatment of cells with ZnCl(2) for 4 or 24 h provided significant protection against cobalt chloride-induced cytotoxicity when measured with MTT assay. However, vitamin E or coenzyme Q(10) was not protective. CoCl(2) had dose- and time-dependent cytotoxic effects in Vero cells. Preventive effect of ZnCl(2) against CoCl(2)-induced cytotoxicity should be considered in detail to define exact mechanism of toxicity in Vero cells.

Analytical constraints for the analysis of human cell line secretomes by shotgun proteomics.

Human cell line secretome represents a valuable source of therapeutic targets and candidate biomarkers. Secreted proteins found in biological fluids or culture media are by essence highly diluted. Secretome investigation with proteomic approaches is hardly compatible with the high content of proteins found in complete cell culture media. Therefore, many studies are currently done with media containing few or no protein. Such conditions may perturb cell metabolism and proliferation. Here, we compared seventeen different compositions of culture media for the human bronchial epithelial BEAS-2B cell line. Cell viability, proliferation rate and initial protein charge were systematically compared. We have shown that an important difficulty for the proteomic analysis is due to the presence of detergents such as Pluronic F-68 which hinders peptide mass spectrometry. The high glucose containing DMEM medium which is free of proteins was shown to preserve a good viability and proliferation of cells. With this conditioning medium, we identified 81 extracellular proteins in the secretome of BEAS-2B cells. Moreover, to illustrate this approach, we exposed BEAS-2B cells to a low toxic dose of CoCl(2,) and found 24 extracellular proteins modulated by cobalt. This study highlights the possible contribution of such proteomic approach in the field of toxicology.

Egyptian sweet marjoram leaves protect against genotoxicity, immunosuppression and other complications induced by cyclophosphamide in albino rats.

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs that show a high therapeutic index, despite the widespread side effects and toxicity particularly in high-dose regimens and long-term use. Here, we evaluated and compared the efficacy of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) in alleviating the genotoxicity, immunosuppression and other complications induced by CP in non-tumour-bearing albino rats. The present study showed (probably for the first time) that both MLP and MLE significantly alleviated (P < 0·05-0·001) most side effects and toxicity of CP-treated rats including the increase in chromosomal aberrations of bone marrow cells and serum malondialdehyde level, the decrease in the level of serum Ig, the delayed type of hypersensitivity response as also the weights and cellularity of lymphoid organs, and myelosuppression, leucopenia, macrocytic normochromic anaemia as well as thrombocytopenia by reactivating the non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant system and increasing the mitotic index of bone marrow cells. The modulatory effects of marjoram leaves shown in the present study were dose dependent in most cases and much higher in MLE (21-23 % for all parameters taken together). In addition, the doses used in the present study were considered safe. In conclusion, sweet marjoram leaves (especially in the form of a herbal tea) may be useful as an immunostimulant and in reducing genotoxicity in patients under chemotherapeutic interventions.

Protective effect of Enicostema axillare on mutagenicity of Salmonella typhimurium by increasing free radical scavenging abilities.

CONTEXT: Enicostema axillare A. Raynal (Gentianaceae) has been used in the traditional Indian system of medicine as a depurative and for the treatment of skin diseases, tumors, intermittent fever, and helminthiasis. OBJECTIVE: E. axillare was investigated for antimutagenic and antioxidant effects. MATERIALS AND METHODS: The antioxidant and antimutagenic activities of E. axillare fractions were determined by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging assay and Ames test using Salmonella typhimurium tester strains TA98 and TA100 against direct-acting mutagens, such as sodium azide (NaN3), 4-nitro-O-phenylene diamine (NPD), and mutagen needing activation, such as 2-aminofluorene (2AF). Toxicity study of these fractions was also performed. RESULTS AND DISCUSSION: The ethyl acetate fraction showed maximum antimutagenic effect by 88.25 and 84.46% (preincubation) and 85.13 and 84.47% (coincubation) of inhibition against NaN3 and NPD-induced mutagenicity, respectively. Inhibition of S9-dependent mutagens such as 2AF was higher than direct-acting mutagens by the ethyl acetate fraction of E. axillare. It showed 90.25 and 92.00% of inhibition in the preincubation and coincubation experiments. The ethyl acetate fraction showed higher total antioxidant capacity (24.79 ± 0.29 µg) and low IC50 value for DPPH radical scavenging assay (192.27 ± 3.67 µg). The overall effect of E. axillare fractions was found to be in the order: ethyl acetate > methanol > hexane in these assays. In subacute toxicity study, with oral administration of these fractions, no marked biochemical and histopathologic changes were observed. CONCLUSION: The significant antimutagenic and antioxidant activities of E. axillare might provide a scientific validation for the traditional use of this plant.

Polyubiquitination events mediate polymethylmethacrylate (PMMA) particle activation of NF-kappaB pathway.

The pathologic response to implant wear-debris constitutes a major component of inflammatory osteolysis and remains under intense investigation. Polymethylmethacrylate (PMMA) particles, which are released during implant wear and loosening, constitute a major culprit by virtue of inducing inflammatory and osteolytic responses by macrophages and osteoclasts, respectively. Recent work by several groups has identified important cellular entities and secreted factors that contribute to inflammatory osteolysis. In previous work, we have shown that PMMA particles contribute to inflammatory osteolysis through stimulation of major pathways in monocytes/macrophages, primarily NF-κB and MAP kinases. The former pathway requires assembly of large IKK complex encompassing IKK1, IKK2, and IKKγ/NEMO. We have shown recently that interfering with the NF-κB and MAPK activation pathways, through introduction of inhibitors and decoy molecules, impedes PMMA-induced inflammation and osteolysis in mouse models of experimental calvarial osteolysis and inflammatory arthritis. In this study, we report that PMMA particles activate the upstream transforming growth factor ß-activated kinase-1 (TAK1), which is a key regulator of signal transduction cascades leading to activation of NF-κB and AP-1 factors. More importantly, we found that PMMA particles induce TAK1 binding to NEMO and UBC13. In addition, we show that PMMA particles induce TRAF6 and UBC13 binding to NEMO and that lack of TRAF6 significantly attenuates NEMO ubiquitination. Altogether, these observations suggest that PMMA particles induce ubiquitination of NEMO, an event likely mediated by TRAF6, TAK1, and UBC13. Our findings provide important information for better understanding of the mechanisms underlying PMMA particle-induced inflammatory responses.

[Lipid peroxidation, activity of Na+,k(+) -ATPase and exzymes of antioxidant defence in rats with nephropathy induced by cobalt chloride].

Chronic parenteral administration of cobalt chloride (6 mg/kg) to male rats for 2 weeks or 1 month was accompanied by activation of lipid peroxidation (LPO), a decrease of superoxide dismutase activity and an increase of catalase activity. The membrane toxic action also resulted in a decrease of cortical and medullar Na+,K(+)-ATPase activity of kidneys, and the decrease in renal functions (glomerular filtration, renal water reabsorption, spontaneous diuresis, electrolyte excretion).

Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study.

AIMS: To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment. METHODS: This was a 12-week, open-label, flexible-dose study of adults with OAB (> or = 8 micturitions and > or = 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject's and physician's subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed. RESULTS: Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p < 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement > or = 2 points. Significant improvements from baseline (p < 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified. CONCLUSION: Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.

Anti- and pro-mutagenic effects of silymarin in the Ames bacterial reverse mutation assay.

Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), is being used clinically in Europe and Asia for the treatment of liver diseases. Silymarin has a strong antioxidative action capable of scavenging both free radicals and reactive oxygen species responsible for cancer. Silymarin, a powerful hepatoprotective and antioxidant, was chosen in the present study and was tested for its antimutagenic activity using an in vitro test, the Ames bacterial reverse mutation assay. The results indicated that silymarin showed a significant mutagenicity in frame shift mutant strains (TA97a and TA98) with metabolic activation. This compound also showed stronger antimutagenic effect against 2-aminofluorene and 4-nitroquinoline N-oxide induced mutation. When pre-, co- and post-treatment of silymarin was carried out, it showed stronger antimutagenic activity in the post-treatment with 2-aminofluorene and 4-nitroquinoline N-oxide in TA97a and TA98 strains.

Cellular mechanisms of cobalt-induced hippocampal epileptiform discharges.

PURPOSE: To explore the cellular mechanisms of cobalt-induced epileptiform discharges in mouse hippocampal slices. METHODS: Hippocampal slices were prepared from adult mice and briefly exposed to a CoCl(2)-containing external solution. Population and single cell activities were examined via extracellular and whole-cell patch recordings. RESULTS: Brief cobalt exposure induced spontaneous, ictal-like discharges originating from the CA3 area. These discharges were suppressed by anticonvulsants, gap junction blockers, or by raising extracellular Ca(2+), but their generation was not associated with overall hyperexcitability or impairment in GABAergic inhibition in the CA3 circuit. Electroencephalographic ictal discharges of similar waveforms were observed in behaving rats following intrahippocampal cobalt infusion. DISCUSSION: Mechanisms involving activity-dependent facilitation of gap junctional communication may play a major role in cobalt-induced epileptiform discharges.

In vitro safety evaluation and anticlastogenic effect of BacoMind on human lymphocytes.

OBJECTIVE: BacoMind (BM) is a standardized extract of Bacopa monnieri, which belongs to the family Scrophulariaceae and is a creeping annual plant found throughout the Indian subcontinent. It has been used by Ayurvedic medicinal practitioners in India for almost 3000 years and is classified as a medharasayana, a substance which improves memory and intellect. With the widespread traditional use as well as scientific validation of Bacopa monnieri for nootropic activity, a bioactive-rich unique phytochemical composition-BacoMind was developed from B. monnieri for use as a cognition and memory enhancing agent. The present study aimed to investigate the in vitro toxicity of this formulation of BacoMind on human lymphocytes and to rule out its possible contribution to mutagenicity. METHODS: In the present investigation the active ingredients present in BM were identified and quantified by high performance liquid chromatography (HPLC) and high performance thin-layer chromatography (HPTLC). Antioxidant and anticlastogenic properties of BM were studied in vitro with and without metabolic activation. Doses of BM were chosen on the basis of mitotic index (MI) and cytokinesis-block proliferation index (CBPI). Clastogenicity assays were performed at 31.2 microg/mL, 62.5 microg/mL, and 125 microg/mL, while the Salmonella reverse mutation assay (Ames test) was performed at doses of 61.72, 185.18, 555.55, 1666.67, and 5000.00 microg/plate. RESULTS: HPLC and HPTLC analysis of BM revealed the presence of bacoside A3, bacopaside I, bacopaside II, jujubogenin isomer of bacopasaponin C, bacosine, luteolin, apigenin, bacosine, and beta-sitosterol D glucoside. BM demonstrated significant antioxidant activity. The number of chromosomal aberrations and the frequency of micronuclei induced by BM were not statistically significant up to a dose of 62.5 microg/mL. A subsequent dose of 125 microg/mL prior to metabolic activation induced mild clastogenicity, but it was found to be biologically insignificant as this effect was not seen post metabolic activation. BM also demonstrated a dose-dependent protection against the clastogens used in this study using the above tests for clastogenicity. Maximum protection was observed in presence of metabolic activation. Moreover, BM demonstrated no mutagenic effect on the tested strains, as observed in the Ames test. CONCLUSION: BM protected human lymphocytes against various clastogens. BM also exhibited high antioxidant activity which might be responsible for the observed protective effects against the clastogens since the used clastogens are known to induce their clastogenic effects via production of oxidative radicals.

A retrospective study of 2585 patients patch tested with the European standard series in Hong Kong (1995-99).

BACKGROUND: Data on patch test findings in Hong Kong are scarce, with the last survey performed more than 10 years ago. A retrospective analysis of results from all patch tests performed on patients with suspected allergic contact dermatitis from January 1995 to December 1999 in the Social Hygiene Service, which provides a public dermatology service in Hong Kong, was undertaken. We aimed to explore the demographic data associated with positive reactions and the profile of contact sensitizing allergens in Hong Kong. METHODS: A total of 2585 patients were patch tested with the European standard series during the period. Most were Chinese, with a female-to-male ratio of 3 : 2. RESULTS: One or more positive responses were noted in 1415 patients (54.7%). The most common allergen was nickel sulfate (24.4%), followed by fragrance mix (13.7%), cobalt chloride (8.7%), p-phenylenediamine (6.0%), and balsam of Peru (5.7%). Nickel sensitivity was more common in female patients, and dichromate sensitivity was more common in male patients (P < 0.001). Female gender, an age of 40 years or below, truncal and upper limb involvement, absence of lower limb involvement, and a positive atopy history were significant risk factors for nickel sensitivity. CONCLUSIONS: This study provides a profile of allergens responsible for allergic contact dermatitis in the public dermatology service in Hong Kong. A prospective study, using a larger panel of allergens, involving patients from both the private and public sectors, would provide a more comprehensive profile of contact allergens in Hong Kong and contribute to the establishment of a local standard series.

Cutaneous sarcoidal granulomas developing after Artecoll facial cosmetic filler in a patient with newly diagnosed systemic sarcoidosis.

Artecoll is a recently developed permanent synthetic cosmetic filler substance, composed of 80% bovine collagen and 20% polymethylacrylate (PMMA) microspheres of 32-40 mum in diameter. It is used for the augmentation of deep wrinkles and is to be injected subdermally. We report the development of granulomas at the site of Artecoll injections in the face in a 48-year-old woman who had pulmonary sarcoidosis. There were features consistent of both sarcoid and foreign-body granuloma, typical of those reported previously with Artecoll. We postulate that the PMMA foreign material contained within Artecoll acted as a stimulus for the development of the cutaneous sarcoid granulomas.