Currently we are faced with an ever-growing use of Δ9-tetrahydrocannabinol (THC) preparations, often used as supportive therapies for various malignancies and neurological disorders. As some of ...illegally distributed forms of such preparations, like cannabis oils and butane hash oil, might contain over 80% of THC, their consumers can become intoxicated or experience various detrimental effects. This fact motivated us for the assessments of THC toxicity in vivo on a Wistar rat model, at a daily oral dose of 7 mg/kg which is comparable to those found in illicit preparations. The main objective of the present study was to establish the magnitude and dynamics of DNA breakage associated with THC exposure in white blood and brain cells of treated rats using the alkaline comet assay. The extent of oxidative stress after acute 24 h exposure to THC was also determined as well as changes in activities of plasma and brain cholinesterases (ChE) in THC-treated and control rats. The DNA of brain cells was more prone to breakage after THC treatment compared to DNA in white blood cells. Even though DNA damage quantified by the alkaline comet assay is subject to repair, its elevated level detected in the brain cells of THC-treated rats was reason for concern. Since neurons do not proliferate, increased levels of DNA damage present threats to these cells in terms of both viability and genome stability, while inefficient DNA repair might lead to their progressive loss. The present study contributes to existing knowledge with evidence that acute exposure to a high THC dose led to low-level DNA damage in white blood cells and brain cells of rats and induced oxidative stress in brain, but did not disturb ChE activities.
There is growing interest regarding the use of herbal preparations based on Cannabis sativa for medicinal purposes, despite the poorly understood interactions of their main constituent ...Δ9-tetrahydrocannabinol (THC) with conventional drugs, especially cytostatics. The objective of this pilot study was to prove whether the concomitant intake of THC impaired liver function in male Wistar rats treated with the anticancer drug irinotecan (IRI), and evaluate the toxic effects associated with this exposure. IRI was administered once intraperitoneally (at 100 mg/kg of the body weight (b.w.)), while THC was administered per os repeatedly for 1, 3, and 7 days (at 7 mg/kg b.w.). Functional liver impairments were studied using biochemical markers of liver function (aspartate aminotransferase—AST, alanine aminotransferase—ALP, alkaline phosphatase—AP, and bilirubin) in rats given a combined treatment, single IRI, single THC, and control groups. Using common oxidative stress biomarkers, along with measurement of primary DNA damage in hepatocytes, the degree of impairments caused at the cellular level was also evaluated. THC caused a time-dependent enhancement of acute toxicity in IRI-treated rats, which was confirmed by body and liver weight reduction. Although single THC affected ALP and AP levels more than single IRI, the levels of liver function markers measured after the administration of a combined treatment mostly did not significantly differ from control. Combined exposure led to increased oxidative stress responses in 3- and 7-day treatments, compared to single IRI. Single IRI caused the highest DNA damage at all timepoints. Continuous 7-day oral exposure to single THC caused an increased mean value of comet tail length compared to its shorter treatments. Concomitant intake of THC slightly affected the levels of IRI genotoxicity at all timepoints, but not in a consistent manner. Further studies are needed to prove our preliminary observations, clarify the underlying mechanisms behind IRI and THC interactions, and unambiguously confirm or reject the assumptions made herein.
Fizikalna svojstva sadrenih zavoja bitan su čimbenik u ostvarenju osnovne funkcije sadrenih imobilizacija (zadržavanje ulomaka kosti u dobrom položaju), a time izravno utječu na brzinu i kvalitetu ...cijeljenja prijeloma. U ovom radu mjere se fizikalna svojstva (masa, specifična težina, brzina sušenja, krutost i čvrstoća) i bilježe razlike sadrenog postupka, brzovežućih sadrenih zavoja širine 10 cm triju različitih proizvođača: Safix plus (Hartmann, Njemačka), Cellona (Lohman Rauscher, Austrija) i Gipsan (Ivo Lola Ribar d. o. o., Hrvatska). Sadreno je deset slojeva zavoja u pločice dimenzija 10 × 10 cm. Od svakog proizvoda načinjene su 24 pločice sadrene u vodi temperature 22 °C i isto toliko u vodi temperature 34 °C. Prosječna specifična težina originalnog pakiranja zavoja bila je: Cellona 0,52 g/cm3, Gipsan 0,50 g/cm3, Safix plus 0,38 g/cm3. Tri dana nakon sadrenja prosječna specifična težina pločica bila je: Gipsan 1,15 g/cm3, Safix plus 1,00 g/cm3, Cellona 1,10 g/cm3. Prosječna vlažnost od 50% pločicâ Safix i Cellona trajala je 18 sati, a pločicâ Gipsan 48 sati nakon sadrenja. Treći dan nakon sadrenja prosječna vlažnost pločica Gipsan bila je 30%, Safixa 24%, a Cellone 16%. Najveću krutost imale su pločice sadrenog zavoja Cellona sadrene vodom temperature 34 °C (11,75 ± 3,18 MPa), a najmanju (7,21 ± 0,9 MPa) pločice sadrenog zavoja Gipsan sadrene vodom temperature 22 °C. Sadreni zavoj Cellona, sadren vodom temperature 34 °C, pokazuje najveću čvrstoću materijala (4390 ± 838 MPa), a najmanju (771 ± 367 MPa) pločice sadrenog zavoja Gipsan sadrene vodom temperature 22 °C. Sadrenjem zavoja Cellona i Gipsan u toplijoj vodi (34 °C) pločice su bile veće krutosti i čvrstoće. Pločice Safix plus nemaju ovo svojstvo. Sve tri vrste sadrenih zavoja razlikuju se prema fizikalnim svojstvima. S obzirom na masu i specifičnu težinu prije i nakon sadrenja razlike su minimalne. Prema brzini sušenja, čvrstoći i krutosti postoje veće razlike.
Plaster splints are used daily in surgical and orthopedic fields in order to immobilize injured children and adults. The aim of this study was to measure the aerodynamic diameter and concentration of ...dust particles in the air caused by sawing plaster splints (calcium sulfate dehy-drate). We performed fractional measurements of airborne dust particles. The measured particles, which can potentially be inhaled, may have a specific negative effect on human health. Measurements were conducted in laboratory research facilities that simulated hospital conditions within a casting room and the associated waiting room. Measurements within the casting room were made using two particle collector devices and one laser photometer. The measurement for the simulated waiting room was performed using the same principles and devices. The collected plaster dust particles differed in aerodynamic diameter and concentration according to the various locations observed. The highest concentration of particles of all sizes was recorded at the site of cast sawing. There was direct correlation between distance from the source and concentration of airborne particles; this concentration was lowest in the waiting room. The concentrations of plaster dust recorded were lower than the recommended minimal limit values for total and respiratory fractions in Croatia. Accordingly, it can be assumed that sawing of plaster splints has no harmful health effects on the exposed patients and health personnel.
Treatment of clavicle fracture is principally outpatient. Operative treatment is accompanied by the need for more x-rays and possible complications. Fractures with absolute indications for operative ...treatment occur only sporadically and these indications are relatively clear, but children often undergo surgery because of relative indications (shortening, fragment displacement, multifragmentary fractures), which are open to debate. In a retrospective study on 256 children, of 44 (17%) patients that received operative treatment only one 17-year-old boy had an absolute indication for surgical intervention. Other indications were fragment distraction (22 mm on average), age, associated injuries, and multifragmentary fracture. The placement of K-wire of appropriate thickness is often difficult, since the wire tends to bend and break, and patients have to undergo two additional operations of plate and screw fixation and later removal. In this retrospective study, we considered the advantages of using titanium or an elastic steel pin. All patients had favorable outcome, although some experienced numbness around the operation scar (4.5%), skin infections around the wire (15%), and/or the implanted K-wire damage (7%).
Because of the great interest for research on the potential use of cannabis preparations as co-medication for alleviation of toxic effects in cancer management, we investigated the influence of ...Δ9-tetrahydrocannabinol (Δ9-THC) to modulate irinotecan (CPT-11)-induced toxicity. Male Wistar rats were treated either with a single irinotecan intraperitoneal dose, 100 mg/kg body-weight (b.w.), or with irinotecan in combination with THC (7 mg/kg b.w., p.o., administered repeatedly for 1, 3 and 7 days). Serial blood samples were obtained up to seven days after dosing and were analyzed for complete blood count and biochemical parameters (liver enzymes, creatinine, inflammatory markers, and lipid status). Serial urine samples were collected in the first 24 h to monitor the time-course of THC metabolite 11-nor-9-carboxy-Δ9-THC (THC-COOH) excretion with concomitant irinotecan treatment or without. Both irinotecan and irinotecan + Δ9-THC administration caused moderate leukopenia but a greater decrease in leukocyte count was observed in the irinotecan + Δ9-THC treated compared to the single irinotecan suggesting higher cytotoxic effects in combined treatment. Irinotecan treatment induced elevation of aspartate aminotransferase (AST) in rats without diarrheal symptoms and without an increase in circulating pro-inflammatory mediators. Interestingly, the elevation of AST was not observed in the irinotecan + Δ9-THC group. The median creatinine-corrected urinary THC-COOH concentration was higher in the irinotecan + THC group compared to the THC-only group in a time-dependent manner, suggesting a possible early interaction between cannabinoids and irinotecan. Further studies are needed to investigate the role of cannabinoids particularly on hematological toxicity, irinotecan metabolism and their role as a possible modifiable factor among irinotecan-treated hosts.
•The clinical effects of irinotecan can be modulated by Δ9-THC in rats.•The lowest leukocytes count was observed in combined treatment at day 3.•Hepatic toxicity after irinotecan injection was alleviated in the presence of THC.•The urinary THC-COOH was significantly increased in combined treatment.
In order to evaluate the effect of irinotecan (IRI) on urinary elimination of delta-9-tetrahydrocannabinol (THC) in a rat experimental model, we developed an analytical method for the determination ...of the mass concentration of THC and its metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in the urine of rats treated only with THC and treated simultaneously with THC and irinotecan. For this purpose, hydrolysis and solid phase extraction conditions of the investigated analytes were optimised and a gas chromatography-mass spectrometry (GC-MS) method was developed to determine all three analytes in rat urine. The most effective hydrolysis method for THC, THC-OH, and THC-COOH conjugates was so-called tandem hydrolysis by the β-glucuronidase enzyme from
at 50 °C for 2 hours and followed by alkaline hydrolysis. The proposed method was then applied for determining concentrations of analytes in 24-hour rat urine. THC was not detected in either sample, THC-OH was detected in 50 % of samples, and THC-COOH in all of the samples. Enhanced urinary THC-COOH excretion was noted in rats administered combined treatment compared to single THC treatment. The method described herein was suitable for determining the mass concentration of THC metabolites in the rat urine due to its sensitivity (detection limits: 0.8-1.0 μg/L), accuracy (>96 %), and precision (RSD <6 %).
Abstract Background The importance of the periosteum in fracture healing is well-known. Preserving periosteal vascularisation is essential during internal plate fixation of fractures. Methods This ...was an experimental randomised, controlled animal study on nine sheep. Standard dynamic compression plate (DCP) and four different newly designed reefed plates, with different plate-bone contact surface areas and different reef directions, were fixated on to the tibia or radius. After two weeks the plates were removed and the underlying periosteum was analysed. Blood vessels were marked by immunohistochemical staining (CD31 and CD34), microphotographs were taken and blood vessels counted to calculate blood vessel density. Results Median blood vessel density beneath the standard plate was significantly lower than in the intact periosteum (18.0 vs 27.7 mm3 /cm3 ). Blood vessel density in the periosteum beneath plates with reefs was significantly increased compared with the intact periosteum, and was highest beneath the plate with the lowest bone-plate contact area and crosswise reefs (51.5 mm3 /cm3 ), followed by plates with transverse, oblique and longitudinal reefs, respectively. The direction of the reefs did not have much influence on the periosteal capillary network. Lower contact surface area seems to be the main factor that increases blood vessel density beneath the plates. Conclusions The results show that plates with lower contact surface area stimulate angiogenesis in the underlying periosteum, which results in much higher blood vessel density compared with standard DCP. A randomised clinical trial is needed to prove the clinical relevance of these findings.
There is growing interest regarding the use of herbal preparations based on
for medicinal purposes, despite the poorly understood interactions of their main constituent Δ⁸-tetrahydrocannabinol (THC) ...with conventional drugs, especially cytostatics. The objective of this pilot study was to prove whether the concomitant intake of THC impaired liver function in male Wistar rats treated with the anticancer drug irinotecan (IRI), and evaluate the toxic effects associated with this exposure. IRI was administered once intraperitoneally (at 100 mg/kg of the body weight (b.w.)), while THC was administered per os repeatedly for 1, 3, and 7 days (at 7 mg/kg b.w.). Functional liver impairments were studied using biochemical markers of liver function (aspartate aminotransferase-AST, alanine aminotransferase-ALP, alkaline phosphatase-AP, and bilirubin) in rats given a combined treatment, single IRI, single THC, and control groups. Using common oxidative stress biomarkers, along with measurement of primary DNA damage in hepatocytes, the degree of impairments caused at the cellular level was also evaluated. THC caused a time-dependent enhancement of acute toxicity in IRI-treated rats, which was confirmed by body and liver weight reduction. Although single THC affected ALP and AP levels more than single IRI, the levels of liver function markers measured after the administration of a combined treatment mostly did not significantly differ from control. Combined exposure led to increased oxidative stress responses in 3- and 7-day treatments, compared to single IRI. Single IRI caused the highest DNA damage at all timepoints. Continuous 7-day oral exposure to single THC caused an increased mean value of comet tail length compared to its shorter treatments. Concomitant intake of THC slightly affected the levels of IRI genotoxicity at all timepoints, but not in a consistent manner. Further studies are needed to prove our preliminary observations, clarify the underlying mechanisms behind IRI and THC interactions, and unambiguously confirm or reject the assumptions made herein.
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