Analgesic and anti-inflammatory articular effects of essential oil and camphor isolated from Ocimum kilimandscharicum Gürke leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from Ocimum kilimandscharicum Gürke (Lamiaceae) are popularly used against articular pain. AIM OF STUDY: The aim of this study was to test the anti-inflammatory and anti-hyperalgesic (analgesic) properties of the essential oil and camphor isolated from O. Kilimandscharicum leaves (EOOK) in 4 models including zymosan induced-articular inflammation model in mice. MATERIAL AND METHODS: For in vivo models, EOOK was tested in carrageenan-induced paw edema model with oral doses of 30, 100, and 300 mg/kg (oral administration = p.o.) and in zymosan-induced articular inflammation (including knee edema, leukocyte infiltration, mechanical hyperalgesia and nitric oxide), EOOK (100 mg/kg, p. o.) and camphor (30 mg/kg, p. o.) were tested. EOOK (100 mg/kg, p. o.) was tested in the rolling and also in the adhesion of leukocytes to the mesenteric microcirculation in situ model of carrageenan induced inflammation and EOOK (1, 3, 10, 30, and 60 µg/mL) was tested in vitro against neutrophils chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP). RESULTS: The treatment with EOOK significantly inhibited the carrageenan-induced edema, mechanical and cold hyperalgesia. Both, EOOK and camphor inhibited all articular parameters induced by zymosan. In situ intravitral microscopy analysis, EOOK significantly inhibited carrageenan-induced leukocyte rolling and adhesion. In vitro neutrophils chemotaxis, EOOK inhibited the leukocyte chemotaxis induced by fMLP. CONCLUSIONS: The present study showed that EOOK inhibited pain and inflammatory parameters contributing, at least in part, to explain the popular use of this plant as analgesic natural agent. This study also demonstrates that camphor and some known anti-inflammatory compounds present in EOOK could contribute for analgesic and anti-inflammatory articular properties.

Oral pharmacological treatment for patent ductus arteriosus in premature neonates with hemodynamic repercussions.

OBJECTIVE: To evaluate the efficacy of oral indomethacin, ibuprofen, and paracetamol in oral dosage form on patent ductus arteriosus (PDA) in premature neonates with significant clinical and hemodynamic repercussions (CHRs) and to determine the effect of these respective treatments on renal function. METHODS: A retrospective study of cases of PDA in premature neonates in the Neonatal Intensive Care Unit was conducted. The treatments consisted of indomethacin [0.2 mg/(kg·d), 3-day cycle], ibuprofen [10 mg/(kg·d) followed by 5 mg/(kg·d), 3-day cycle], and paracetamol (15 mg/kg every 6 h, 5-day cycle). The drugs were administered as an oral solution. The following variables were considered: gestational age, newborn weight at birth, Apgar score, diuresis, serum creatinine and urea levels, and serum electrolyte levels (sodium and potassium). RESULTS: Treatment with indomethacin presented efficacy of 87.5% in closure of the ductus with a mean outcome period of 3.5 d. In premature neonates with CHRs and contraindications for indomethacin, the initial treatment with either ibuprofen or paracetamol failed to close the ductus. However, when this treatment was followed by indomethacin, closure occurred in 66.7% of the neonates, with an outcome period of 9.66 d. The initial treatment with one cycle of ibuprofen followed by one or two cycles of paracetamol failed to close the ductus. CONCLUSIONS: Oral indomethacin was effective for closure of the PDA in premature neonates with severe CHRs. Oral paracetamol or ibuprofen for PDA closure in premature neonates with severe CHRs and contraindications for indomethacin was ineffective. However, results in clinical improvements of neonates allowed the subsequent use of indomethacin and successful closure of the ductus. A significant reduction of diuresis occurred in neonates who were treated with indomethacin, either as a first-line treatment or after the failure of ibuprofen or paracetamol.

Comparative study of tissue reactivity to n-butyl-2-cyanoacrylate and nylon monofilament thread on pericranium-cutaneous flaps in rats.

PURPOSE: To study the repair of pericranium-cutaneous flaps fixed with suture anchored in a skull bone tunnel or N-butyl-2-cyanoacrylate adhesive in Wistar rats with emphasis on the cellular inflammatory response and the production of types I and III collagen. METHODS: The operated region in the cephalic region of Wistar rats was removed minutes before euthanasia, fixed in formalin, and subjected to histological preparation. Slides were stained with hematoxylin-eosin and Picrosirius. Standardized counts of polymorphonuclear and mononuclear cells, fibroblasts, and macrophages were performed, and the percentages of types I and III collagen were determined. Data collection occurred on days 3, 7, 14, 21, and 45 postoperatively. A value of p<0.05 was considered statistically significant. RESULTS: Quantitative analysis of the data showed more fibroblasts in the surgical adhesive group than in the nylon monofilament thread groups (p=0.0211). Qualitative analysis showed higher reactivity in the adhesive group, with a predominance of polymorphonuclear cells from days 3-45 and macrophages from days 3-7. The amount of type I collagen exceeded 80% in the treated and control groups at the end of the experiment. CONCLUSIONS: Subperiosteal detachment triggers a cellular inflammatory response that is amplified using soft tissue fixation methods. The adhesive n-butyl-2-cyanoacrylate was more reactive than the nylon monofilament thread anchored in the skull bone tunnel.

Incidence and predictors of adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study.

PURPOSE: The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs. METHODS: A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors. RESULTS: A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval [CI] = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 [95% CI = 0.68-1.18, p = 0.08]) than patients who presented six or more diseases (OR = 1.12 [95% CI = 1.02-2.01, p < 0.01]). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 [95% CI = 1.92-3.12, p < 0.01]) than patients who took three to four drugs (OR = 0.93 [95% CI = 0.74-1.11, p = 0.06]). No significant difference was found with regard to sex (OR = 1.08 [95% CI 0.48-2.02, p = 0.44]). CONCLUSION: The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.

Effect of teriparatide on induced tooth displacement in ovariectomized rats: a histomorphometric analysis.

INTRODUCTION: The aim of this study was to evaluate morphologically the effect of teriparatide on induced orthodontic movement of the maxillary first molars in ovariectomized rats. METHODS: Ovariectomized Wistar rats (n = 16), ovariectomized rats treated with teriparatide (n = 16), and nonovariectomized rats (n = 16) had orthodontic tooth movement for 5 and 7 days. The group treated with teriparatide received a subcutaneous injection (Forteo, Eli Lilly, Indianapolis, Ind; 30 µg/kg/day) for 90 days after the ovariectomy. Histologic sections obtained from the maxilla were prepared for the morphometric analysis of dental movement, the thickness of the periodontal ligament, and the number of osteoclasts in the pressure and tension areas of the apex of the root and alveolar crest in the distal root of the maxillary first molars. RESULTS: The ovariectomized rats treated with teriparatide had similar responses at 5 and 7 days after the induced dental movements compared with the untreated ovariectomized group. Both ovariectomized groups had greater molar movement on day 7 day compared with the controls (P <0.05). There were no statistically significant differences between groups in the spacing of the periodontal ligament or the number of osteoclasts in the areas studied. CONCLUSIONS: These data suggest that the treatment of osteoporosis with teriparatide is a good alternative for patients undergoing orthodontic treatment.