RESET-PKD: a pilot trial on short-term ketogenic interventions in autosomal dominant polycystic kidney disease.

BACKGROUND: Ketogenic dietary interventions (KDI) have been shown to be effective in animal models of polycystic kidney disease (PKD), but data from clinical trials are lacking. METHODS: Ten autosomal dominant PKD (ADPKD) patients with rapid disease progression were enrolled at visit V1 and initially maintained a carbohydrate-rich diet. At V2, patients entered one of the two KDI arms: a 3-day water fast (WF) or a 14-day ketogenic diet (KD). At V3, they resumed their normal diet for 3-6 weeks until V4. At each visit, magnetic resonance imaging kidney and liver volumetry was performed. Ketone bodies were evaluated to assess metabolic efficacy and questionnaires were used to determine feasibility. RESULTS: All participants [KD n = 5, WF n = 5; age 39.8 ± 11.6 years; estimated glomerular filtration rate 82 ± 23.5 mL/min/1.73 m2; total kidney volume (TKV) 2224 ± 1156 mL] were classified as Mayo Class 1C-1E. Acetone levels in breath and beta-hydroxybutyrate (BHB) blood levels increased in both study arms (V1 to V2 average acetone: 2.7 ± 1.2 p.p.m., V2 to V3: 22.8 ± 11.9 p.p.m., P = .0006; V1 to V2 average BHB: 0.22 ± 0.08 mmol/L, V2 to V3: 1.88 ± 0.93 mmol/L, P = .0008). Nine of 10 patients reached a ketogenic state and 9/10 evaluated KDIs as feasible. TKV did not change during this trial. However, we found a significant impact on total liver volume (ΔTLV V2 to V3: -7.7%, P = .01), mediated by changes in its non-cystic fraction. CONCLUSIONS: RESET-PKD demonstrates that short-term KDIs potently induce ketogenesis and are feasible for ADPKD patients in daily life. While TLV quickly changed upon the onset of ketogenesis, changes in TKV may require longer-term interventions.

Potential effect of Turbinaria decurrens acetone extract on the biochemical and histological parameters of alloxan-induced diabetic rats.

Upon Seeking natural and safe alternatives for synthetic medicines to treat many chronic diseases, seaweeds have offered a promising resource to produce numerous bioactive secondary metabolites. Through in vivo investigations, Turbinaria decurrens acetone extract (AE) revealed its antidiabetic activity against alloxan-induced diabetic rats. Treatment of rats with T. decurrens AE at 300 and 150 mg/Kg doses revealed antihyperglycemic activity by reducing the elevated blood glucose level. A remarkable decrease in the liver, kidney functions, and hyperlipidemia related to diabetes were also detected. Administration of the same extract also showed a recovery in body weight loss, total protein, albumin, and haemoglobin levels compared with untreated diabetic rats. Furthermore, treatment of rats with the same extract improved liver and pancreas histopathological disorders related to diabetes. These effects may be attributed to the presence of bioactive phytochemicals and antioxidant components in T. decurrens AE mainly cyclotrisiloxane, hexamethyl, and cyclic diterpene 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol alcohol). Besides, other valuable secondary metabolites, as phenols, flavonoids, alkaloids, terpenoids, steroid and glycosides, which were documented and published by the same authors in a previous study. The obtained results in the present study recommended using T. decurrens AE in developing medicinal preparations for treatment of diabetes and its related symptoms.

Modular Acid-Activatable Acetone-Based Ketal-Linked Nanomedicine by Dexamethasone Prodrugs for Enhanced Anti-Rheumatoid Arthritis with Low Side Effects.

Given the physically encapsulated payloads with drug burst release and/or low drug loading, it is critical to initiate an innovative prodrug strategy to optimize the design of modular nanomedicines. Here, we designed modular pH-sensitive acetone-based ketal-linked prodrugs of dexamethasone (AKP-dexs) and formulated them as nanoparticles. We comprehensively studied the relationships between AKP-dex structure and properties, and we selected two types of AKP-dex-loaded nanoparticles for in vivo studies on the basis of their size, drug loading, and colloidal stability. In a collagen-induced arthritis rat model, these AKP-dex-loaded nanoparticles showed higher accumulation in inflamed joints and better therapeutic efficacy than free dexamethasone phosphate with less-severe side effects. AKP-dex-loaded nanoparticles may be useful for treating other inflammatory diseases and thus have great translational potential. Our findings represent an important step toward the development of practical applications for acetone-based ketal-linked prodrugs and are useful in the design of modular nanomedicines.

Acetone clearance of mesocolic or mesorectal fat increases lymph node yield and may improve detection of high-risk Stage II colorectal cancer patients.

AIM: Lymph node (LN) status is key to determining the need for adjuvant therapy in colorectal cancer (CRC) and for disease which has progressed to Stage II (T3-T4, N0, M0). A yield of fewer than 12 LNs is considered a risk factor similar to high-grade histology and vascular, lymphatic and perineural invasion. The aim of this retrospective study was to investigate the effect of acetone fat clearance of the mesocolon or mesorectum on LN yield and the identification of patients with high-risk Stage II CRC. METHOD: After conventional LN retrieval, fatty tissue derived from the mesocolon or mesorectum of 80 CRC specimens was incubated in acetone for 24 h. A second dissection was then performed by a trained technician. The total number of LNs as well as tumour involvement (LNpositive and LNnegative) were assessed at each stage. In addition, LN morphology was assessed and clinicopathological data were extracted from existing pathology reports. RESULTS: Eighty CRC specimens were available for study. 1548 (94%) LN were negative and 96 (6%) were positive. The median (range) LN yield per specimen was 12 (3-41) LN increasing to 18 (4-48) LN after fat clearance (P < 0.001). After fat clearance, 534 additional LNs were identified in 75 (94%) of the specimens, and all but 10 were negative. The pN stage did not change in six patients who were found to be LN positive after fat clearance. However, the number of high-risk Stage II CRC patients decreased from 11 to 7. Although important for these patients, this downstaging did not reach statistical significance (P = 0.125). CONCLUSION: Acetone clearance of mesocolic or mesorectal fat increases median LN yield and may in a larger study decrease the number of patients classified as having high-risk Stage II CRC.

Effect of prolonged air drying on the bond strength of adhesive systems to dentin.

This in vitro study evaluated the effect of air-drying time on degree of solvent evaporation (DE), dentin microtensile bond strength (µTBS), and degree of conversion (DC) of 5 adhesive systems: Adper Single Bond 2, XP Bond, Prime & Bond 2.1, OptiBond Solo, and Adper Easy One. For DE testing, 20 µL of each material was submitted to measurements in a digital balance after an air stream of 3, 5, 10, 20, 30, or 60 seconds; the weight loss was computed and converted to a percentage (DE). For µTBS testing, 50 sound human molars were divided into groups (n = 5). The 5 adhesive systems were applied either in accordance with manufacturers' instructions for solvent drying time (control) or with a prolonged drying time (20-30 seconds). After composite resin was built up on the hybridized surfaces, the teeth were stored for 24 hours and then sectioned to obtain beams that were loaded until fracture. For DC testing, specimens of each adhesive and air-drying condition (n = 3) were evaluated by means of attenuated total reflectance Fourier transform infrared spectroscopy. Data were submitted to 2-way analysis of variance, t test, and Spearman test for correlation analysis. Prolonged air drying resulted in significantly greater DE than did the time suggested by the manufacturers. The adhesives XP Bond and Adper Easy One showed significantly greater µTBS with prolonged air drying. The DC was not affected by air-drying time. No statistically significant correlation was found between DC and µTBS values. Depending on the material, bond strength can be improved by prolonged air-drying times.

Acetone extract from Streptoverticillium sp., a bacterium isolated from Brazilian Cerrado soil, induces anti-inflammatory activity in mice.

The Streptoverticillium sp. Z1 is an actinomycete isolated from the soil under Cerrado vegetation, the extract of this strain was investigated in nociceptive and inflammatory models. The Streptoverticillium extract (ExS) 50 and 100 mg/kg (s.c.) produced a significant inhibition of acetic acid-induced abdominal writhings thereby demonstrating an anti-nociceptive effect. In the tail flick test the ExS (s.c.) was inactive. This result implited that ExS does not contain opioid-like compounds with central analgesic properties. In the inflammatory models, ExS 100 and 200 mg/kg (s.c.) were able to inhibit the croton oil-induced ear edema and, ExS 200 and 500 mg/kg (s.c.) inhibited the leukocyte migration on the carrageenan-induced peritonitis. The phospholipase A2 enzymatic assay showed that the anti-inflammatory activity of ExS was not due to direct effect on phospholipase A2 activity. These data suggest that Streptoverticillium sp. produces metabolites with anti-inflammatory effect and that these metabolites are unable to directly inhibit phospholipase A2 enzyme.

The interplay of solvent-drug-protein interactions during albumin nanoparticles formulations for temozolomide delivery to brain cancer cells.

OBJECTIVES: Temozolomide (TMZ), the first line for glioma therapy, suffers from stability at physiological pH. TMZ was selected as a challenging model drug for loading into human serum albumin nanoparticles (HSA NPs). Our aim is to optimise the conditions for TMZ loading into HSA NPs while ensuring TMZ stability. METHODS: Blank and TMZ-HSA NPs were fabricated using the de-solvation technique and the effect of different formulation parameters was evaluated. KEY FINDINGS: For blank NPs, crosslinking time had no significant effect on NPs' size while acetone produced significantly smaller particles than ethanol. Upon drug loading, though TMZ was stable in acetone and ethanol as single agents yet, ethanol-based NPs showed misleadingly high EE% due to drug instability in ethanol formulations as evident by the UV spectrum.The optimum conditions for drug-loaded particles were: 10 mg/ml HSA, 4 mg TMZ using acetone, yielded NPs with 145 nm in diameter, ξ of -16.98 mV and 0.16% DL. The selected formula reduced the cell viabilities of GL261 glioblastoma cells and BL6 glioblastoma stem cells to 61.9% and 38.3%, respectively. CONCLUSIONS: Our results corroborated that careful manipulation of TMZ formulation processing parameters is crucial for encapsulating such chemically unstable dug while simultaneously ensuring its chemical stability.

Treadmill workouts alleviate neuropathic allodynia and scratching behavior in rats following thoracotomy.

BACKGROUND: The aim of the experiment was to investigate the effects of treadmill exercise on postthoracotomy pain and the expression of spinal pro-inflammatory and anti-inflammatory cytokines. METHODS: Animals were randomly distributed into four groups: (a) sham surgery, (b) rats following 60 min thoracotomy and rib retraction (thoracotomy), (c) thoracotomy rats received treadmill training (thoracotomy+treadmill), and (d) sham surgery rats received treadmill training (sham surgery+treadmill). Treadmill workouts were started on postoperative day 10 (POD10) and lasted for 6 weeks (5 days per week). Rats were examined for cold allodynia using acetone and mechanical allodynia using von Frey hairs (in grams) at the surgical site. Spinal pro-inflammatory and anti-inflammatory cytokines were analyzed on PODs 28 and 49. RESULTS: Both thoracotomy and thoracotomy+treadmill groups exhibited a decrease in mechanical force thresholds (g) and an increase in scratches per min on POD10. Mechanical hypersensitivity and incremental scratches lasted from POD14 and POD49 in the thoracotomy group. Although force thresholds and scratches remained not return to baseline, incremental force thresholds (p < 0.001) and diminutive scratches (p < 0.001) occurred after 6-week treadmill workouts. The rise in spinal interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) concentrations or the decline in spinal IL-10 concentration in thoracotomy+treadmill rats was less (p < 0.05) than thoracotomy rats without exercise. CONCLUSIONS: Mechanical allodynia using von Frey filament testing and cold allodynia by acetone testing were improved in thoracotomy rats after treadmill workouts.. Treadmill exercise restrained excess pro-inflammatory cytokine expression but increased anti-inflammatory cytokine level in a rib retraction model.

Mechanistic efficacy assessment of selected novel methanimine derivatives against vincristine induced Neuropathy: In-vivo, Ex-vivo and In-silico correlates.

Vincristine induced peripheral neuropathy (VIPN) is a serious untoward side effect suffered by cancer patients, which still lacks an adequate therapeutic approach. This study examined the alleviating potential of novel methanimine derivatives i.e. (E)-N-(4-nitrobenzylidene)-4-chloro-2-iodobenzamine (KB 9) and (E)-N-(2-methylbenzylidene)-4-chloro-2-iodobenzamine (KB 10) in VIPN. Vincristine was injected in BALB/c mice for 10 days to instigate nociceptive neuropathy. Dynamic and static allodynia, thermal (hot and cold) hyperalgesia were evaluated at 0, 5, 10 and 14 days using cotton brush, Von Frey filament application, hot plate test, acetone drop and cold water respectively. Tumour necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), lipid peroxide (LPO), glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and reactive oxygen species (ROS) assays were performed to assess the efficacy of KB9 and KB10 against neuroinflammation and oxidative stress utilizing ELISA, immunohistochemistry and western blot analysis in brain and sciatic nerve tissues. Computational studies were executed to determine the stable binding conformation of both compounds with respect to COX-2 and NF-κB. Interestingly, both compounds substantially reduced protein expression related to neuroinflammation, oxidative stress (LPO, GST, SOD, CAT) and pain (NF-κB, COX-2, IL-1ß and TNF-α). This molecular analysis suggested that the neuroprotective effect of KB9 and KB10 was mediated via regulation of inflammatory signaling pathways. Overall, this study demonstrated that KB9 and KB10 ameliorated vincristine induced neuropathy, through anti-inflammatory, anti-nociceptive and antioxidant mechanisms.

Neuron-restrictive silencer factor is not required for the antiepileptic effect of the ketogenic diet.

PURPOSE: The ketogenic diet (KD) has been used as an effective antiepileptic treatment for nearly a century. Inhibition of glycolysis and increased levels of ketone bodies are both known to contribute to the antiepileptic effects of the KD. Neuron-restrictive silencer factor (NRSF), also known as RE-1 silencing transcription factor (REST), is implicated in the antiepileptic effects of the glycolytic inhibitor 2-deoxy-d-glucose (2DG). Glycolytic inhibition is a common feature of the KD and 2DG treatment, leading to the hypothesis that NRSF might also be involved in the antiepileptic effect of the KD. To test this hypothesis, the present study was designed to investigate the role of NRSF in the antiepileptic effect of 2DG, the KD, and acetone in vivo. METHODS: Kindling was used as a model to test the antiepileptic effects of 2DG, the KD, and acetone on control and NRSF conditional knockout mice (NRSF-cKO; from the intercross of CamKIIα-iCre and NRSF exon 2 floxed mice). After recovery from electrode implantation, adult mice were stimulated twice a day at afterdischarge threshold (ADT) current intensity. In the 2DG- (500 mg/kg) and acetone- (10 mmol/kg) treated groups, drugs were injected intraperitoneally 20 min before each stimulus. In the 2DG group, mice were pretreated with intraperitoneal injections for 3 days in addition to the injections administered before the regular kindling stimulation. In the KD group, mice were fed the KD instead of a control diet until the end of stimulations. KEY FINDINGS: Compared with control mice, the antiepileptic effect of 2DG was abolished in NRSF-cKO mice, indicating that NRSF is required for the antiepileptic effect of 2DG. In the KD-fed group, kindling development was retarded in both control and NRSF-cKO mice. In the acetone-treated group, inhibition of kindling-induced epileptogenesis was observed in both control and NRSF-cKO mice, similar to the action of the KD. SIGNIFICANCE: These findings imply that NRSF repression complex is not essential for the antiepileptic effect of the ketogenic diet.

Antioxidant potential of Xylopia aethiopica fruit acetone fraction in a type 2 diabetes model of rats.

The fruit decoction of Xylopia aethiopica (Dunal) A. Rich. is widely used for the treatment of diseases associated with oxidative stress such as diabetes, particularly in Africa. The present study was aimed to investigate the effects of X. aethiopica fruit acetone (XAFA) fraction in ameliorating oxidative stress in a type 2 diabetes (T2D) model of rats. The crude X. aethiopica fruit ethanolic extract was fractionated using solvents with increasing polarity and acetone fraction showed significantly (p<0.05) higher in vitro antioxidant potentials which were measured by (1,1-diphenyl-2-picrylhydrazyl radical (DPPH), hydroxyl radical (HRS) and nitric oxide (NO) assays compared to other fractions. It was then subjected to in vivo antioxidant study in a T2D rat model. Acetone fraction depicted potent in vitro antioxidant actions (IC50: DPPH: 19.82±0.73µg/mL; HRS: 25.34±6.19µg/mL; NO: 14.45±2.44µg/mL) compared to other fractions. Additionally, a significant (p<0.05) and dose-dependent improvement on the in vivo antioxidant status was observed in the animals in diabetic treated groups (DXAL, DXAH) compared to the diabetic control (DBC) group. The results of our study suggest that XAFA possesses potent antioxidant potential and could be used to ameliorate oxidative stress associated metabolic complications such as T2D.

Inhibition of root caries progression by an antibacterial adhesive.

A dentin primer containing the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) has been shown to penetrate and kill the bacteria in artificially demineralized dentin. We hypothesized that an experimental adhesive system, which incorporates the MDPB-containing primer, would be effective in inhibiting the progression of root caries in vitro. Artificial caries lesions were prepared by either an acid-gel or a Streptococcus mutans culture technique on the roots of extracted human teeth. The progression of these lesions after the application of the experimental or proprietary adhesive system was examined. Further demineralization was completely prevented by the experimental adhesive system, while lesions managed with the proprietary materials showed limited ability to inhibit further demineralization. We conclude that the experimental adhesive system can inhibit the progression of root-surface caries in vitro, through a combination of its antimicrobial activity and sealing of the demineralized dentin.

Scanning electron microscopy examination of 3 different adhesive systems.

OBJECTIVES: The aim of this study was to compare the interaction of dentin with 2 different self-etch resin bonding systems, as well as with a total-etch resin bonding system. METHOD AND MATERIALS: Nine recently extracted, unerupted third molars, roots, and occlusal thirds were used. A standardized smear layer was produced on the occlusal dentin surface exposed. The specimens were split into 3 groups of 3 specimens each, 1 group for each bonding agent: Clearfil Liner Bond 2, Prime & Bond 2.1, and Scotchbond Multipurpose (control group). After the tooth was briefly sprayed with an air/water mixture, 1 of the experimental adhesive systems was applied on the dentin surface. A 2-mm layer of composite was applied over the adhesive system layer. After 7 days in distilled water at 37 degrees C, the specimens were cross-sectioned perpendicular to the resin-dentin interface. The crosssections were mounted on aluminum stubs, etched with 2% hydrochloridric acid, and studied using scanning electron microscopy. A descriptive analysis of the images of the interdiffusion zone characteristics was done first. Afterwards, statistical analyses of the measurements of the interdiffusion zone structures-hybrid layer thickness, resin tags penetration, and adhesive layer thickness using analysis of variance, followed by "post hoc" test-were carried out to compare the bonding systems' interactions. RESULTS: The descriptive analysis of the self-etch bonding systems studied showed a good interlocking of Clearfil Liner Bond 2 with dentin, similar to Scotchbond Multipurpose and better than Prime & Bond 2.1. The analysis of variance, followed by the "post hoc" test, identified statistical differences just for the adhesive layer thickness that was thicker for Scotchbond than for Prime & Bond (P = .020). The "post hoc" test also showed a strong tendency to identify differences between the Scotchbond and the Prime & Bond groups (P = .062), and the Clearfil and the Prime & Bond groups (P = .069). CONCLUSION: Within the limitations of this study, Clearfil Liner Bond 2 produced the thickest hybrid layer with deepest tag formation and good interlocking with dentin, similar to the control. Statistical differences among the interdiffusion zone of the 3 bonding systems studied were identified just for the adhesive layer thickness, which was thicker for Scotchbond than for Prime & Bond.

The comparison of a dentin adhesive with calcium hydroxide as a pulp-capping agent on the exposed pulps of human and sheep teeth.

OBJECTIVE: This study evaluated the biocompatibility of a one-step dentin bonding agent (Prime&Bond 2.1) in pulp capping compared with calcium hydroxide [Ca(OH)2]. METHOD AND MATERIALS: Thirty sheep teeth and 20 intact human premolars were used. After cavity preparation, pulp exposure was achieved with a bur (#390). Adhesive pulp capping was performed in 25 teeth (15 sheep and 10 human). In the control group (12 sheep and 10 human teeth), pulps were capped with Ca(OH)2 and all of the cavities in both groups were sealed with resin composite. Three of the sheep teeth were used as intact controls. Teeth were extracted 7 or 90 days following treatment and prepared for histological examination and bacterial detection. RESULTS: At 7 days, severe inflammatory responses underlying the bonding agent and in the coronal pulp were observed with soft tissue disorganization in both human and sheep teeth capped with Prime&Bond 2.1. All of the teeth capped with Ca(OH)2 exhibited mild inflammatory reactions limited with the perforation area. After 90 days with the bonding agent, in 3 of 9 sheep teeth, chronic inflammatory reactions were significant, while slight pulpal reactions were observed in the others and dentin bridge formation in all of the sheep teeth was found. However, in human pulps, persistent, unresolved inflammation with the lack of dentin bridge formation was observed. In the Ca(OH)2 group, pulp repair with dentin bridging was found in all of the teeth, both sheep and human. No correlation was found between the presence of inflammation and bacterial staining using Spearman rank correlation test (P > .05). CONCLUSION: Prime&Bond 2.1 facilitates enhanced pulp healing and bridge formation in sheep teeth, but in human teeth it was not as successful as Ca(OH)2 as a pulp capping agent.

3-Fluoro-1-hydroxypropan-2-one (fluorohydroxyacetone) and some esters. Syntheses and effects in BDF mice.

1-(Benzoyloxy), 1-(4-nitrobenzoyloxy), and 1-(3,5-dinitrobenzoyloxy) derivatives of 3-fluoro-, 3-chloro-, and 3-bromopropan-2-one were prepared by oxidation of the 1-benzoyloxy-3-halopropan-2-ols in turn prepared from the appropriate benzoyl chloride and 3-halo-1,2-propanediols, 1-Benzoyloxy-3-fluoropropan-2-one was allowed to react with acidic trimethyl orthoformate to yeild 1-benzoyloxy-2,2-dimethoxy-3-fluoropropane which upon basic hydrolysis afforded 2, 2-dimethoxy-3-fluoropropan-1-ol (fluorohydroxyacetone dimethyl ketal). This was deketalized with aqueous HCL to afford 3-fluoro-1-hydroxypropan-2-one (fluorohydroxyacetone), the title compound. By reacting 1-chloro-3-fluoropropan-2-one and 1, 3-dichloropropan-2-one with potassium acetate, 1-acetoxy-3-fluoropropan-2-one and 1-acetoxy-3-chloropropan-2-one (fluoro- and chlorohydroxyacetone acetate, respectively) were obtained. Similarly, sodium benzoate and 1-chloropropan-2-one produced 1-benzoyloxypropan-2-one. Stucture-activity relationships are discussed which relate chemical structure, alkylating ability, toxicity, and antitumor effects. Comparative toxicities in mice showed decreasing toxicity, on a molar basis, in the 1-benzoyloxy-3-halopropan-2-one series of bromo greater than fluoro greater than chloro. Ketones were much more toxic than the corresponding alcohols. In general the phosphate and benzoyloxy derivatives are more toxic than acetoxy compounds, with nitro-substituted benzoyloxy derivatives being much less toxic.

Evaluation of the anticonvulsant activity of the seed acetone extract of Ferula gummosa Boiss. against seizures induced by pentylenetetrazole and electroconvulsive shock in mice.

Ferula gummosa Boiss. (Apiaceae) which has been used as an antiepileptic remedy in Iranian traditional medicine was evaluated for anticonvulsant activity against experimental seizures. The seed acetone extract of F. gummosa protected mice against tonic convulsions induced by maximal electroshock (the median effective dose [ED(50)]=198.3 mg/kg) and especially by pentylenetetrazole (ED(50)=55 mg/kg). Neurotoxicity (sedation and motor impairment) of the extract was assessed by the rotarod test and the median toxic dose (TD(50)) value of 375.8 mg/kg was obtained. Preliminary phytochemical analysis showed the presence of terpenoids and alkaloids in the extract. The acceptable acute toxicity of the extract recommends further studies to determine the mechanism(s) and compound(s) involved in the anticonvulsant activity.

Inhibition of chemically-induced skin carcinogenesis in mice by peanut oil preparations.

Epidermal hyperplasia and sebaceous gland destruction - good indicators of carcinogenic potential - were studied in short-term mouse skin experiments following application of BaP and TPA dissolved either in a peanut oil mixture or in acetone. Subsequently, the carcinogenicity of BaP and DMBA alone or in association with TPA was dissolved in the same vehicles, and determined in mouse long-term skin tests. In parallel, ODC activity and binding to DNA, RNA and proteins were examined in epidermal cells after exposure to TPA and BaP respectively. When the peanut oil excipient was used as a solvent, a complete inhibition of BaP and TPA activities was observed in short-term skin tests, as well as a complete inhibition of BaP, DMBA and TPA carcinogenicity in long-term tests. TPA-induced ODC activity was suppressed by the peanut oil mixture while BaP binding to nucleic acids and proteins of epidermal cells was only slightly inhibited. These results indicate that the excipient possesses anti-carcinogenic potentials for epidermal cells. The persistence of BaP binding to macromolecules in epidermal cells without tumor development suggests that the carcinogenic action of BaP may include both genotoxic and epigenetic mechanisms.

Topical acetone for control of life-threatening vaginal hemorrhage from recurrent gynecologic cancer.

Two patients with intractable, life-threatening vaginal bleeding from recurrent gynecologic cancer were successfully treated with application of topical acetone or placement of an acetone-soaked pack, with immediate control of hemorrhage and no immediate side effects other than pain. No long-term adverse effects were noted. Acetone application may control vaginal bleeding from recurrent pelvic malignancy, particularly in previously radiated patients who cannot safely be treated with additional radiotherapy or when embolic techniques are not immediately available or practical.

Clinical evaluation of Prime & Bond 2.1 for treating cervical dentin hypersensitivity.

PURPOSE: To evaluate the effectiveness of a "one-bottle" dentin adhesive for reducing or eliminating hypersensitivity in exposed cervical dentin. MATERIALS AND METHODS: Eight patients with hypersensitive teeth were enrolled in this clinical trial. The hypersensitive teeth included a total of 22 premolars and anterior teeth with exposed cervical dentin that was sensitive to cold or other stimuli. A single layer of Prime & Bond 2.1, an acetone-based "one-bottle" adhesive, was applied to the cervical dentin and was light-cured. Sensitivity to compressed air and cold stimuli was determined immediately before and after treatment, and at periods ranging to 24 wks after treatment. Patient responses to the stimuli were timed, and were also evaluated by the use of a visual analogue scale. RESULTS: Application of a single coat of Prime & Bond 2.1 significantly reduced cervical dentin hypersensitivity to both compressed air and cold stimuli immediately after treatment. The reduction in hypersensitivity remained significant at 24 wks after treatment.

Decontamination of human skin exposed to 2,3,7,8-tetrachlorodibenzo-p-Dioxin (TCDD) in vitro.

Human post-mortem skin was exposed in vitro to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 32 degrees C, under controlled humidity. In one-half of the samples, damage to the surface of the skin was simulated by stripping of the stratum corneum. After incubation with TCDD for 100 min, four different decontamination protocols were performed: (1) the sample was wiped with dry, adsorbent material (cotton balls); (2) a 10-min topical treatment with mineral oil was followed by dry wiping with cotton balls; (3) a 10-min topical treatment with mineral oil was followed by wiping with acetone-soaked cotton balls; and (4) the sample was washed with water and soap. After decontamination, skin samples were incubated (up to 300 min) again at 32 degrees C. One set of both intact and stripped TCDD-exposed skin samples was incubated for 300 min--absent decontamination--and was used as a control. Mineral oil treatment and acetone wipes, or water and soap, were effective in reducing (i.e., about two-fold) the amount of TCDD in the stratum corneum of intact skin. Mineral oil plus dry wipes reduced the amount of TCDD in the stratum corneum by about one-third, whereas dry wiping alone was ineffective. All protocols, however, were similarly effective in reducing the amount of TCDD in the epidermis and upper dermis; TCDD concentrations were decreased locally by factors of up to ten. In the lower dermis, a minimal effect of the decontamination procedures was observed.(ABSTRACT TRUNCATED AT 250 WORDS)