Effects of chronic administration of D-003, a mixture of sugar cane wax high molecular acids, in beagle dogs

D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar cane wax (Saccharum officinarum, L) with cholesterol-lowering and antiplatelet effects. Previous studies, including a 6-month study conducted in rats, have shown no D-003-related toxicity. The present study was undertaken to investigate the effects of D-003 orally administered for 9 months in beagle dogs. The animals were randomly distributed in three groups: a control group receiving the vehicle only and two groups orally administered D-003 (200 and 400 mg/kg). Body weight gain, food consumption and clinical signs were controlled throughout the study. The effects of D-003 on collagen-induced platelet aggregation, bleeding time (BT) and coagulation parameters (prothrombin time and kaolin-activated thromboplastin time) were also investigated. Most blood biochemistry and hematological parameters were assessed at baseline and after 6 and 9 months of treatment, while total cholesterol (TC), triglycerides, platelet aggregation, BT and coagulation parameters were determined at baseline and after 9 months of treatment. At study completion, the animals were sacrificed. D-003 at a dose of 200 and 400 mg/kg significantly reduced TC (p < 0.05), significantly inhibited platelet aggregation and increased BT compared with levels in controls. Data analyses of body weight gain, food consumption, clinical observations, the remaining blood biochemistry and hematology indicators (including coagulation parameters, organ weight ratios and histopathological findings) showed no trends with D-003 doses or significant differences between control animals and treated groups. In conclusion, D-003 administered for 9 months to beagle dogs induced the expected effects with no evidence of drug-related toxicity.     

Preservation of tubal function following methotrexate treatment for ectopic pregnancy

To evaluate methotrexate (MTX) administration as a conservative treatment for ectopic pregnancy, we reviewed the medical records of 248 cases (210 patients) of MTX treatment for tubal pregnancies at our department between December 1985 and December 2003, and compared its pregnancy prognosis with that of laparoscopic salpigotomy (59 patients). With the MTX treatment, 185 patients were successfully treated, and the subsequent pregnancy rate and ectopic pregnancy rate were 48.4 % and 18.4 %, respectively, while those rates were 49.2 % and 18.6 %, respectively, after the salpigotomy. These results suggest that MTX treatment is comparable to the more conservative operation. To clarify the (dys/) function of the ectopic implantation tubes and MTX-treated tube (s), we excluded patients who had a contra-lateral healthy tube, and extracted 40 patients as "the affected tube group", where the pregnancy-related parameters were not adversely affected. The findings suggest that MTX is not necessary to preserve tubal function.     

Effect of D-003 on isoproterenol-induced myocardial necrosis in rats

D-003 is a mixture of high-molecular-weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Cardiac lesions induced by isoproterenol (ISO) are characterized by myocardial necrosis and exudative infiltration. The objective of this study was to determine whether D-003 shows protective effects against ISO-induced myocardial necrosis in rats. Effects of orally administered single doses of D-003 (25-400 mg/kg) and acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5-200 mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were investigated. D-003 administered as single doses dose-dependently decreased necrosis area, percent of infarct area, and the presence of polymorphonuclear cells (PMNs) in myocardial tissue, but only the reductions induced by 200 and 400 mg/kg were significant. Oral acute treatment with ASA also decreased necrosis area and percent of infarct area, but the occurrence of PMNs was unchanged. D-003 administered repeatedly for 10 days also decreased all myocardial necrosis indicators in a dose-dependent manner, with results effective from 25 mg/kg to the highest dose tested, indicating that the repeated dose scheme was more effective to prevent the damage. It is concluded that D-003 shows a protective effect on the myocardial necrosis induced by ISO in rats.     

Comparison of Botulinum Toxin Types A And B: A Bilateral and Double-Blind Randomized Evaluation in the Treatment of Canthal Rhytides

BACKGROUND: The obligate bacterium Clostridium botulinum produces exotoxins (A, B, C-1, C-2, D, E, F, G) that are serologically and antigenically distinct. All serotypes have similar neurotoxic properties resulting in flaccid muscle paralysis. Types A and B are commercially available and are used widely for the reduction of dynamic facial rhytides. Although extensive information is known about type A, type B has recently become available; however, there is a limited clinical familiarity. Some of the remaining unknown distinctions between the two subtypes are the extent of toxin diffusion from the site of injection, the onset of action, the dose equivalency, and the duration of effect. OBJECTIVE: The purpose of this preliminary double-blind study was to compare the duration of muscle paralysis and rhytid reduction of botulinum toxin types A and B. Additional relevant information was obtained, all of which can be useful in toxin selection. METHOD: Ten women, ages 28 through 60, voluntarily consented to undergo a double-blind trial and were randomly assigned to have botulinum toxin type A injected into one set of lateral canthal rhytides and toxin type B into the contralateral periocular region. Based on dose-ranging investigations performed in patients with cervical dystonia, participants received treatment at the lowest reported effective ratio of 1:50 (1 U of toxin type A to 50 U of toxin type B). Three injections of 5 U of type A (total 15 U) and three injections of 250 U of undiluted type B (total 750 U) were injected into the lateral fibers of the orbicularis oculi muscle. RESULTS: Patients were evaluated at 7, 30, 60, and 90 days. Findings were compared by the treating physician, patient self-assessment, and photographic images. CONCLUSION: All patients noted rapid and satisfactory reduction in the rhytides in both periocular areas. However, upon unblinding of the solutions at the same volumes with a 1:50 ratio, type B toxin was found to be associated with slightly more discomfort upon injection, quicker onset of action, a sensation of "tightness" of the treated area, and a briefer duration of muscle paralysis.     

Long-term carcinogenicity of D-003, a mixture of high molecular weight acids from sugarcane wax, in Sprague Dawley rats: A 24 months study

D-003 is a mixture of high molecular weight sugarcane wax aliphatic primary acids with cholesterol-lowering, anti-platelet and antioxidant effects. This study investigated the long-term oral toxicity and carcinogenicity of D-003 in Sprague Dawley rats of both sexes, randomly distributed into four groups: a control group, treated only with the vehicle, and three treated with D-003 (50, 500 and 1500 mg/kg). All treatments were given orally for 24 months. Mortality (survival analysis), clinical symptoms, weight gain, food consumption, organ weights, time-to-tumour or tumour incidence data were not shown between group differences or trends. With the exception of serum cholesterol levels, lower in D-003-treated groups (500 and 1500 mg/kg) than in the controls, no other difference in blood indicators was found. D-003 did not increase the frequency of neoplastic and non-neoplastic lesions compared with the controls. The occurrence of all malignant and mammary tumours in D-003-treated females was lower than in the controls. The lesions observed were consistent with spontaneous lesions reported in this species. In conclusion, D-003 is not toxic or carcinogenic when given orally to Sprague Dawley rats up to 1500 mg/kg for 2 years, and 1500 mg/kg was a not-observable effect dose.     

The role of chemical peeling in the treatment of photodamaged skin

Management of the aging face involves evaluation of the degree of solar elastosis, rhytidosis, and the structural changes associated with senescent skin. Chemical facial exfoliation is divided into deep, medium, and superficial based upon depth of penetration of the caustic agent used. Knowledge of the appropriate indications and technique are essential in obtaining optimal clinical results.     

SIRT1/HERC4 Locus Associated With Bisphosphonate‐Induced Osteonecrosis of the Jaw: An Exome‐Wide Association Analysis

Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole‐exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors. Multivariable logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and principal components for ancestry. Meta‐analysis of WES phase 1 and 2 was performed to estimate the combined ORs. In silico analyses were then performed to identify expression quantitative loci (eQTL) single‐nucleotide polymorphisms (SNPs) that are in high linkage disequilibrium (LD) with the top SNPs. The associations of the potentially functional SNPs were replicated and validated in an independent case‐control study of 48 patients of European ancestry treated with iv BPs (19 ONJ cases and 29 controls). The top SNPs in the exome‐wide association meta‐analysis were two SNPs on chromosome 10: SIRT1 SNP rs7896005 and HERC4 SNP rs3758392 with identical OR of 0.07 (0.01–0.46; p = 3.83 × 10^?5). In the in silico functional analyses, two promoter region SNPs (rs7894483 and rs3758391) were identified to be in high LD with the index SNPs and are eQTLs for SIRT1 gene in whole blood in the GTEx database. The ORs were 0.30 (0.10–0.88), 0.26 (0.12–0.55), and 0.26 (0.12–0.55) for the WES top SNP rs7896005 and two promoter SNPs rs7894483 and rs3758391, respectively, in the replication sample. In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP‐induced ONJ and two promoter SNPs that might be the potential genetic markers for this association. © 2017 The Authors.Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.     

One year oral Toxicity of D-004, a lipid extract from Roystonea regia fruits, in Sprague Dawley rats

D-004, a lipid extract of royal palm (Roystonea regia) fruits that contains a reproducible mixture of fatty acids, has been shown to prevent testosterone and phenylephrine-induced prostate hyperplasia in rodents. This study investigated the long-term oral toxicity of D-004 in rats. Rats from both sexes were randomized into four groups (20 rats sex/group): a control and three treated with D-004 (800, 1500 or 2000 mg/kg/day, respectively). At study completion, rats were sacrificed under anaesthesia. Determinations of blood biochemical and haematological parameters and organ weight were done. Also, necropsy and histopathological studies were performed. Four of 160 rats died before study completion. No clinical signs of toxicity were observed throughout the study. Food and water consumption, bodyweight, blood biochemical and haematological parameters, organ weight ratios and histopathological findings were similar in control and treated groups. The histological lesions found in treated animals are commonly present in this specie and strain according to literature and our historical data. In conclusion, long-term (12 months) oral treatment of rats with D-004 (800–2000 mg/kg/day) did not show evidences of D-004-related toxicity under our conditions. The highest dose tested (2000 mg/kg) was a no-observed adverse effect level in this study.