Cutaneous anaphylactoid reaction to polyoxyethylene hydrogenated castor oil in dogs.

BACKGROUND: Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs. OBJECTIVE: To determine the potential for HCO-ethoxylate-containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO-25, -40, -60 and -80). ANIMALS: Four healthy male laboratory dogs. MATERIALS AND METHODS: We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre-treatment with an antihistamine. RESULTS: All HCO-ethoxylate-containing drugs caused a wheal-and-flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO-ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO-60-induced reaction was suppressed by an oral antihistamine. CONCLUSIONS AND CLINICAL RELEVANCE: The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision-making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect.

Anti-diarrheal effect of piperine possibly through the interaction with inflammation inducing enzymes: In vivo and in silico studies.

Piperine is a natural alkaloid that possesses a variety of therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and anticarcinogenic activities. The present study aims to assess the medicinal benefits of piperine as an anti-diarrheal agent in a chick model by utilizing in vivo and in silico techniques. For this, castor oil was administered orally to 2-day-old chicks to cause diarrhea. Bismuth subsalicylate (10 mg/kg), loperamide (3 mg/kg), and nifedipine (2.5 mg/kg) were used as positive controls, while the vehicle was utilized as a negative control. Two different doses (25 and 50 mg/kg b.w.) of the test sample (piperine) were administered orally, and the highest dose was tested with standards to investigate the synergistic activity of the test sample. In our findings, piperine prolonged the latent period while reducing the number of diarrheal feces in the experimental chicks during the monitoring period (4 h). At higher doses, piperine appears to reduce diarrheal secretion while increasing latency in chicks. Throughout the combined pharmacotherapy, piperine outperformed bismuth subsalicylate and nifedipine in terms of anti-diarrheal effects with loperamide. In molecular docking, piperine exhibited higher binding affinities towards different inflammatory enzymes such as cyclooxygenase 1 (-7.9 kcal/mol), cyclooxygenase 2 (-8.4 kcal/mol), nitric oxide synthases (-8.9 kcal/mol), and L-type calcium channel (-8.8 kcal/mol), indicating better interaction of PP with these proteins. In conclusion, piperine showed a potent anti-diarrheal effect in castor oil-induced diarrheal chicks by suppressing the inflammation and calcium ion influx induced by castor oil.

CYX-5, a G-protein biassed MOP receptor agonist, DOP receptor antagonist and KOP receptor agonist, evokes constipation but not respiratory depression relative to morphine in rats.

BACKGROUND: Strong opioid analgesics such as morphine alleviate moderate to severe acute nociceptive pain (e.g. post-surgical or post-trauma pain) as well as chronic cancer pain. However, they evoke many adverse effects and so there is an unmet need for opioid analgesics with improved tolerability. Recently, a prominent hypothesis has been that opioid-related adverse effects are mediated by ß-arrestin2 recruitment at the µ-opioid (MOP) receptor and this stimulated research on discovery of G-protein biassed opioid analgesics. In other efforts, opioids with MOP agonist and δ-opioid (DOP) receptor antagonist profiles are promising for reducing side effects c.f. morphine. Herein, we report on the in vivo pharmacology of a novel opioid peptide (CYX-5) that is a G-protein biassed MOP receptor agonist, DOP receptor antagonist and kappa opioid (KOP) receptor agonist. METHODS: Male Sprague-Dawley received intracerebroventricular bolus doses of CYX-5 (3, 10, 20 nmol), morphine (100 nmol) or vehicle, and antinociception (tail flick) was assessed relative to constipation (charcoal meal and castor oil-induced diarrhoea tests) and respiratory depression (whole body plethysmography). RESULTS: CYX-5 evoked naloxone-sensitive, moderate antinociception, at the highest dose tested. Although CYX-5 did not inhibit gastrointestinal motility, it reduced stool output markedly in the castor oil-induced diarrhoea test. In contrast to morphine that evoked respiratory depression, CYX-5 increased tidal volume, thereby stimulating respiration. CONCLUSION: Despite its lack of recruitment of ß-arrestin2 at MOP, DOP and KOP receptors, CYX-5 evoked constipation, implicating a mechanism other than ß-arrestin2 recruitment at MOP, DOP and KOP receptors, mediating constipation evoked by CYX-5 and potentially other opioid ligands.

In vivo anti-diarrheal activity of jujube honey on castor oil-induced diarrhea in mice.

OBJECTIVE: To evaluate the antidiarrheal effect of jujube honey on experimentally castor oil-induced diarrhea in mice by using different testing models (diarrhea, enteropooling and gastrointestinal motility). METHODS: The mice intragastric administration castor oil was post-treated after 30 min with jujube honey, diluted jujube honey and loperamide or vehicles in different experimental groups. The onset and number of wet defecation on the absorbent paper was recorded for each animal for 4 h. Plasma was examined for C-reactive protein (CRP) and nitric oxide (NO) for clinical inflammation evaluation. The oxidative stress was investigated by superoxide dismutase (SOD) and catalase levels. RESULTS: The diluted jujube honey exhibited an important antidiarrheal activity manifested by significant delay in onset of diarrhea (P < 0.05), loss in number of wet stools (P < 0.001), total number of stools (P < 0.001) and total stool weight of fecal output (P < 0.001) in 4 h in castor oil-induced diarrheal groups. The inhibition of intestinal transit of charcoal meal (P < 0.01) is a most likely mechanism that may account for antidiarrheal effect of jujube honey. It also significantly increased SOD and catalase levels (P < 0.001) and significantly decreased CRP and NO in plasma diarrheic mice (P < 0.01). CONCLUSION: The results of this research reveal that the jujube honey contains pharmacologically active compounds with antidiarrheal properties. However, diluted honey is more effective in the treatment of diarrhea and imbalance of intestinal motility. In conclusion, these findings illustrated the antidiarrheal activity effect of jujube honey and which has the strongest evidence supporting its use in the treatment of diarrhea in traditional medicine.

Anaphylaxis Induced by Intravenous Tacrolimus Administration During Kidney Transplant Surgery: A Case Report.

A 35-year-old male patient with end-stage renal disease due to vesicoureteral reflux preemptively received a renal graft from his father. The patient had a history of allergy to contrast-enhancing media. He received oral tacrolimus (TAC) and mycophenolate mofetil without any problems for 2 days before kidney transplantation. During the induction period of the surgery, his systolic blood pressure (sBP) decreased to 60 mmHg approximately 1 hour after initiating intravenous tacrolimus (TAC-IV) and intravenous piperacillin (PIPC), and the anesthesiologist suspected drug-induced anaphylaxis and stopped administration of the medications. Because TAC had been administered preoperatively without any adverse events, PIPC was suspected as the causative agent of the anaphylaxis. After the patient's hemodynamics returned to baseline, TAC-IV was restarted. However, his sBP rapidly decreased to 40 mmHg and the patient developed wheezing. He was diagnosed with drug-induced anaphylaxis due to castor oil derivatives in the TAC-IV formulation. The patient's sBP was restored with the administration of some vasopressors, and kidney transplantation was then performed without difficulty. Two days after kidney transplantation, oral TAC was administered without anaphylaxis. Clinicians should consider that not only the drug itself but also its additives or metabolites could induce anaphylaxis.

Protective effect of SKB_Gutbiotic against castor oil and E.coli induced diarrhea in laboratory animals.

The aim of this study is to evaluate antidiarrheal activity of SKB_Gutbiotic against Castor oil and E.coli induced diarrhea in Swiss albino mice and Sprague Dawley rats. In present study three doses of SKB_Gutbiotic were tested against castor oil induced diarrhea in mice. Its effect on co-administration with l-arginine was studied. SKB_Gutbiotic delayed onset of diarrhea, reduced fecal output and fecal weight. In Gastrointestinal transit time and Castor oil induced enteropooling, SKB_Gutbiotic significantly reduced peristaltic index and volume of intestinal content respectively. In E.coli induced diarrhea model, E.coli suspension was administered for 3 days for inducing diarrhea. SKB_Gutbiotic significantly and dose dependently reduced fecal output, improved fecal consistency, reduced fecal water content and improved WBC count. Histopathological images showed improvement in damage caused to the mucosal epithelium due to E.coli and also improved complete crypt cell architecture and integrity of goblet cells. These results indicated that SKB_Gutbiotic can be used as an antidiarrheal agent against castor oil and E.coli induced diarrhea. It inhibits colonization of E.coli bacteria on colonic epithelium which results into decreased intestinal hypersecretion and motility which is very useful in the management of infectious diarrhea. Thus SKB_Gutbiotic could be an effective alternative to standard antidiarrheal drugs.

Pharmacological and computational evaluation of fig for therapeutic potential in hyperactive gastrointestinal disorders.

BACKGROUND: Ficus palmata (Fig), are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including inflammation, tumor, epilepsy, jaundice, influenza and bacillary dysentery. The present study aimed to evaluate the antidiarrheal, antisecretary, antispasmodic, antiulcer and anti motility properties of Ficus palmata. METHODS: In-vivo, in-vitro and in-silico techniques were used to investigate various gastrointestinal effects of Ficus palmata. Antidiarrheal, antisecretary, antispasmodic, antiulcer, anti motility and molecular docking were performed using castor oil induced diarrhea and fluid accumulation, isolated tissue preparations, ethanol-HCl induced ulcer assay, charcoal meal transit time and Auto Doc Vina. RESULTS: Ficus palmata crude extract (Fp.Cr) exhibited protection against castor oil-induced diarrhea in mice and dose-dependently inhibited intestinal fluid secretions. Fp.Cr caused relaxation of spontaneous and K+ (80 Mm)-induced contractions in isolated rabbit jejunum preparations. It showed protective effect against gastric ulcers induced by ethanol-hydrochloric acid in rats. Fp.Cr reduced distance travelled by charcoal meal in the gastrointestinal transit model in mice. The plant constituents: psoralenoside and bergapten showed high binding affinities (E-value ≥ - 6.5 Kcal/mol) against histaminergic H1, calmodulin and voltage gated L-type calcium channels, while showed moderate affinities (E-value ≥7 Kcal/mol) against dopaminergic D2, adrenergic α1, muscranic M3, mu-opioid, whereas revealed lower affinities (E-value ≥9.5 Kcal/mol) vs. muscranic M1, histaminergic H2 and H+/K+ ATPase pump. Germanicol acetate and psoralene exhibited weak affinities against aforementioned targets. CONCLUSION: This study reveals that Ficus palmata possesses anti-diarrheal, anti-secretory, anti-spasmodic, anti-motility and anti-ulcer activities. The various constituents reveal different binding affinities against target proteins, which mediate the gastrointestinal functions.

In Vivo, Proteomic, and In Silico Investigation of Sapodilla for Therapeutic Potential in Gastrointestinal Disorders.

This study aims to delineate the effects of Manilkara zapota Linn. (Sapodilla) fruit chloroform (Mz.CHCl3) and aqueous (Mz.Aq) extracts tested through different techniques. Antidiarrheal activity and intestinal fluid accumulation were examined by using castor oil-induced diarrhea and castor oil fluid accumulation models. Isolated rabbit jejunum tissues were employed for in vitro experiments. Antimotility and antiulcer were performed through charcoal meal transient time and ethanol-induced ulcer assay, molecular studies were conducted through proteomic analysis, and virtual screening was performed by using a discovery studio visualizer (DSV). Mz.CHCl3 and Mz.Aq extracts attributed dose-dependent (50-300 mg/kg) protection (20-100%) against castor oil-induced diarrhea and dose-dependently (50-300 mg/kg) inhibited intestinal fluid secretions in mice. Mz.CHCl3 and Mz.Aq extracts produce relaxation of spontaneous and K+ (80 Mm) induced contractions in isolated tissue preparations and decreased the distance moved by charcoal in the gastrointestinal transit model in rats. It showed gastroprotective effect in ulcerative stomach of rats and decreased levels of IL-18 quantified by proteomic analysis. Histopathological results showed ethanol-induced significant gastric injury, leading to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all gastric zones using hematoxylin and eosin (H&E) staining. Moreover, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), cyclooxygenase (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (p-NFκB). In silico results were comparative to in vitro results evaluated through virtual screening. Moreover, ethanol increased the activation and expression of tumor necrotic factor, cyclooxygenase, and nuclear factor kappa-light-chain-enhancer of activated B cells. This study exhibits the gastroprotective effect of Manilkara zapota extracts in the peritoneal cavity using a proteomic and in silico approach which reveals different energy values against target proteins, which mediate the gastrointestinal functions.

Evaluation of the antidiarrheal activity of the leaf extracts of Myrtus communis Linn (Myrtaceae) in mice model.

BACKGROUND: Myrtus communis L. has a folkloric repute for the management of diarrhea and dysentery in different parts of the world. However, the safety and efficacy of the leaf extract have not been scientifically validated in animal model. This study was, therefore, aimed to investigate the antidiarrheal effect of 80% methanol extract (80ME) and solvent fractions of the leaves of Myrtus communis L. in mice. METHODS: The antidiarrheal activity of the 80ME and solvent fractions was evaluated against castor oil induced diarrheal model, charcoal meal and enteropooling tests. For the 80%ME, the test groups received 100, 200 and 400 mg/kg of the extract. In case of fractions, the test groups received various doses of fractions (200, 300, 400 mg/kg and an additional dose of 800 mg/kg for the aqueous fraction (AF)), where as negative controls received the vehicle (10 ml/kg) and positive controls received loperamide (3 mg/kg). RESULTS: The 80ME at 200 mg/kg (p < 0.05) & 400 mg/kg (p < 0.01) as well as the chloroform fraction (CF) and methanol fraction (MF) at 400 mg/kg (p < 0.05) significantly delayed the onset of diarrhea. Besides, the 80ME (at all tested doses) and both of these fractions (at 300 & 400 mg/kg) significantly decreased the frequency and weight of fecal outputs. Results from the charcoal meal test revealed that the 80ME, at all doses, (p < 0.001) as well as the CF and MF at 300 mg/kg (p < 0.05) & 400 mg/kg (p < 0.001) produced a significant anti-motility effect. Similarly, in the entero-pooling test, the 80ME (at all tested doses) (p < 0.01) as well as the CF and MF (at 300 & 400 mg/kg, p < 0.05) produced a significant decline in the weight and volume of intestinal contents, whereas the AF revealed significant effect (p < 0.05) at dose of 800 mg/kg only. CONCLUSION: The study demonstrated that the 80ME and solvent fractions contain bioactive constituents that have antidiarrheal activity. Therefore, this study provides a scientific support for the acclaimed traditional use of Myrtus communis L for the treatment of diarrheal diseases.

Effect of the incorporation of chitosan on the physico-chemical, mechanical properties and biological activity on a mixture of polycaprolactone and polyurethanes obtained from castor oil.

In the present study, polyurethane materials were obtained from castor oil, polycaprolactone and isophorone diisocyanate by incorporating different concentrations of chitosan (0.5, 1.0 and 2.0% w/w) as an additive to improve the mechanical properties and the biological activity of polyurethanes. The polyurethanes were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, stress/strain fracture tests and swelling analysis, and the hydrophilic character of the surface was determined by contact angle trials. The objectives of the study were to evaluate the effect of the incorporation of chitosan on the changes of the physico-chemical and mechanical properties and the in vitro biological activity of the polyurethanes. It was found that the incorporation of chitosan enhances the ultimate tensile strength of the polyurethanes and does not affect the strain at fracture in polyurethanes with 5% w/w of polycaprolactone and concentrations of chitosan ranging from 0 to 2% w/w. In addition, PCL5-Q-PU formulations and their degradation products did not affect cell viability of L929 mouse fibroblast and 3T3, respectively. Polyurethane formulations showed antibacterial activities against Staphylococcus aureus and Escherichia coli bacteria. The results of this study have highlighted the potential biomedical application of this polyurethanes related to soft and cardiovascular tissues.

The efficacy of a sulphated polysaccharide fraction from Hypnea musciformis against diarrhea in rodents.

Seaweeds are sources of diverse bioactive compounds, such as sulphated polysaccharides. This study was designed to evaluate the chemical composition and anti-diarrheal activity of a fraction of sulphated polysaccharide (PLS) obtained from the red seaweed Hypnea musciformis in different animal models, and to elucidate the underlying mechanisms. PLS was obtained by aqueous extraction, with a yield of 31.8% of the seaweed dry weight. The total carbohydrate content accounted for 99% of the sample. The sulfate content of the polysaccharide was 5.08% and the percentage of carbon was 25.98%. Pretreatment with all doses of PLS inhibited castor oil-induced diarrhea, with reduction of the total amount of stool, diarrheal stools, and the severity of diarrhea. PLS (90 mg/Kg) decreased castor oil- and PGE2-induced enteropooling. In addition, PLS (90 mg/Kg) increased the Na(+)/K(+)-ATPase activity in the small intestine and reduced gastrointestinal transit, possibly via activation of cholinergic receptors. Interestingly, the cholera toxin-induced fluid secretion and Cl(-) ion levels decreased in the intestinal contents of the animals pretreated with PLS (90 mg/kg), probably via reduction of toxin-GM1 receptor binding. In conclusion, PLS exerts anti-diarrheal activity by increasing Na(+)/K(+)-ATPase activity, inhibiting gastrointestinal motility, and blocking the toxin-GM1 receptor binding.

Antidiarrhoeic effect of Eugenia dysenterica DC (Myrtaceae) leaf essential oil.

Essential oil from Eugenia dysenterica leaves was able to inhibit both the diarrhoea and enteropooling induced by castor oil; however, the distance travelled by charcoal meal in the intestine was not change. These data suggest that the antidiarrhoeic effect of the essential oil from E. dysenterica leaves is related to its ability to inhibit intestinal secretion and/or to increase intestinal absorption.

Infectious Complication Following Midface Reconstruction With Calcified Triglyceride.

This case report describes an infectious complication related to the use of calcified triglyceride (Kryptonite Bone Cement) in post-traumatic midface reconstruction. Ultimately, the infected material required removal, and the facial deformity was repaired with subsequent procedures. The literature suggests that bone cement products should be used with caution when in contact with the paranasal sinuses.

Vertebroplasty Using Calcium Triglyceride Bone Cement (Kryptonite™) for Vertebral Compression Fractures. A Single-Centre Preliminary Study of Outcomes at One-Year Follow-up.

This study assessed the one-year clinical and radiographic outcomes, in terms of pain-relief, vertebral re-fracture and complications, after vertebroplasty (VP) using a new osteoconductive cement (calcium triglyceride bone cement - Kryptonite™ bone cement, Doctors Research Group Inc., Southbury, CT, USA) to treat osteoporotic vertebral compression fractures. Sixteen consecutive osteoporotic patients (12 women and four men, mean age 68+/-10.5) were treated with VP using Kryptonite™ bone cement for a total of 20 vertebral fractures. All the patients complained of a pain syndrome resistant to medical therapy and all procedures were performed under fluoroscopy control with neuroleptoanalgesia using a monopedicular approach in 12 patients and bipedicular approach in four patients. All patients were studied by MR and MDCT and were evaluated with the visual analogue scale (VAS) and the Oswestry disability index (ODI) before treatment and at one and 12 months after the procedure. A successful outcome was observed in 80% of patients, with a complete resolution of pain. Differences in pre and post treatment VAS and ODI at one-year follow-up were significant (P<0.0001). We observed a disk and venous leakage in 66% of patients but only in one case did an asymptomatic pulmonary embolism occur during cement injection. Two cases of vertebral re-fractures at distant metamers were observed during follow-up. VP using Kryptonite bone cement is a helpful procedure that allows complete and long-lasting resolution of painful vertebral symptoms. The cost of the material is very high and the rate of disk and venous leakage is too high compared to standard cement.

Castor oil, bath and/or enema for cervical priming and induction of labour.

BACKGROUND: Castor oil, a potent cathartic, is derived from the bean of the castor plant. Anecdotal reports, which date back to ancient Egypt have suggested the use of castor oil to stimulate labour. Castor oil has been widely used as a traditional method of initiating labour in midwifery practice. Its role in the initiation of labour is poorly understood and data examining its efficacy within a clinical trial are limited. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of castor oil or enemas for third trimester cervical ripening or induction of labour in comparison with other methods of cervical ripening or induction of labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing castor oil, bath or enemas used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. MAIN RESULTS: Three trials, involving 233 women, are included. There was no evidence of differences in caesarean section rates between the two interventions in the two trials reporting this outcome (risk ratio (RR) 2.04, 95% confidence interval (CI) 0.92 to 4.55). There were no data presented on neonatal or maternal mortality or morbidity.There was no evidence of a difference between castor oil and placebo/no treatment for the rate of instrumental delivery, meconium-stained liquor, or Apgar score less than seven at five minutes. The number of participants was too small to detect all but large differences in outcome. All women who ingested castor oil felt nauseous (RR 59.92, 95% CI 8.46 to 424.52). AUTHORS' CONCLUSIONS: The three trials included in the review contain small numbers of women. All three studies used single doses of castor oil. The results from these studies should be interpreted with caution due to the risk of bias introduced due to poor methodological quality. Further research is needed to attempt to quantify the efficacy of castor oil as an cervical priming and induction agent.

Allergic contact dermatitis from 12-hydroxystearic Acid and hydrogenated castor oil.

A 34-year-old male experienced severe allergic contact dermatitis from 12-hydroxystearic acid in a lip balm and from hydrogenated castor oil in an underarm deodorant. He also had a positive patch-test reaction to bis-diglyceryl polyacyladipate-2, which is present in the implicated lip balm and which itself contains 12-hydroxystearic acid. He was also incidentally found to have contact allergy to ricinoleic acid and castor oil. Ricinoleic acid is the principal fatty acid in castor oil, whereas 12-hydroxystearic acid is the principal fatty acid in hydrogenated castor oil. These two fatty acids are each 18-carbon 12-hydroxylated fatty acids, differing only in degree of saturation. The lack of patch-test reactivity to the analogous nonhydroxylated fatty acids, stearic acid (C18:0), and oleic acid (C18:1) indicates that 12-hydroxylation was required for allergenicity in this patient. In addition, serial dilution testing demonstrated that saturation of the hydroxylated C18 fatty acid enhanced its allergenicity.