Dosing metric in cellular experiments: The mol/cell metric has its limitations.

It has been argued that the mol/cell metric is more universal than concentration of the toxic agent since in many cases the effect of dose expressed as mol/cell is independent of ex-perimental setup. We confirmed it for hemolysis of erythrocytes in phosphate-buffered saline induced by hypochlorite where the amount of femtomoles/cell of hypochlorite needed for 50% hemolysis was independent of erythrocyte concentration. However, in the presence of blood plasma this metric became dependent on cell concentration. Similarly, the effect of 3-bromopyruvic acid (3-BP) on PEO1 cells as a function of mol/cell ratio depended on the volume of the 3-BP containing medium, due to the reaction of 3-BP with components of the medium. Hemolytic amounts of sodium dodecyl sulfate and Triton X-100 expressed as mol/cell decreased with increasing cell concentration while the effect of DMSO on the viability of a constant number of fibroblasts was independent of the volume of DMSO-containing medium. These results demonstrate that the mol/cell metric is still dependent on experimental conditions when the toxic agent interacts with components of the medium or when its physical state is modified by the target cells, and the effect is independent of the mol/per cell ratio for high excess of a cell damaging agent.

Inhibiting Src-mediated PARP1 tyrosine phosphorylation confers synthetic lethality to PARP1 inhibition in HCC.

Hepatocellular carcinoma (HCC), a heterogeneous cancer with high mortality, is resistant to single targeted therapy; thus, combination therapy based on synthetic lethality is a promising therapeutic strategy for HCC. Poly (adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP1) is the most recognized target for synthetic lethality; however, the therapeutic effect of PARP1 inhibition on HCC is disappointing. Therefore, exploring new synthetic lethal partners for the efficient manipulation of HCC is urgently required. In this study, we identified Src and PARP1 as novel synthetic lethal partners, and the combination therapy produced significant anti-tumor effects without causing obvious side effects. Mechanistically, Src interacted with PARP1 and phosphorylated PARP1 at the Y992 residue, which further mediated resistance to PARP1 inhibition. Overall, this study revealed that Src-mediated PARP1 phosphorylation induced HCC resistance to PARP1 inhibitors and indicated a therapeutic window of the Y992 phosphorylation of PARP1 for HCC patients. Moreover, synthetic lethal therapy by co-targeting PARP1 and Src have the potential to broaden the strategies for HCC and might benefit HCC patients with high Src activation and resistance to PARP1 inhibitors alone.

Detection of cancer stem cells by EMT-specific biomarker-based peptide ligands.

The occurrence of epithelial-mesenchymal transition (EMT) within tumors, which enables invasion and metastasis, is linked to cancer stem cells (CSCs) with drug and radiation resistance. We used two specific peptides, F7 and SP peptides, to detect EMT derived cells or CSCs. Human tongue squamous carcinoma cell line-SAS transfected with reporter genes was generated and followed by spheroid culture. A small molecule inhibitor-Unc0642 and low-dose ionizing radiation (IR) were used for induction of EMT. Confocal microscopic imaging and fluorescence-activated cell sorting analysis were performed to evaluate the binding ability and specificity of peptides. A SAS xenograft mouse model with EMT induction was established for assessing the binding affinity of peptides. The results showed that F7 and SP peptides not only specifically penetrated into cytoplasm of SAS cells but also bound to EMT derived cells and CSCs with high nucleolin and vimentin expression. In addition, the expression of CSC marker and the binding of peptides were increased in tumors isolated from Unc0642/IR-treated groups. Our study demonstrates the potential of these peptides for detecting EMT derived cells or CSCs and might provide an alternative isolation method for these subpopulations within the tumor in the future.

Systematic review of embolization of type I endoleaks using liquid embolic agents.

OBJECTIVE: The long-term success of endovascular aneurysm repair (EVAR) is limited by complications, most importantly endoleaks. In case of (persistent) type I endoleak (T1EL), secondary intervention is indicated to prevent secondary aneurysm rupture. Different treatment options are suggested for T1ELs, such as endo anchors, (fenestrated) cuffs, embolization, or open conversion. Currently, the treatment of T1EL with liquid embolic agents is available; however, results are not yet addressed. This review presents the safety and efficacy of embolization with liquid embolic agents for treatment of T1ELs after EVAR. METHODS: A systematic literature search was performed for all studies reporting the use of liquid embolic agents as monotherapy for treatment of T1ELs after EVAR. Patient numbers, technical success (successful delivery of liquid embolics in the T1EL) and clinical success (absence of aneurysm related death, endoleak recurrence or additional interventions during follow-up) were examined. RESULTS: Of 1604 articles, 10 studies met the selection criteria, including 194 patients treated with liquid embolics; 73.2% of the patients were male with a median age of 71 years. The overall technical success was 97.9%. Clinical success was 87.6%. Because the median follow-up was only 13.0 months (range, 1-89 months), data on long-term success are almost absent. Four cases (2.1%) of secondary aneurysm rupture after embolization owing to endoleak recurrence were reported. All ruptures occurred in aneurysms exceeding initial treatment diameter of 70 mm. CONCLUSIONS: Initial technical success after liquid embolization for T1EL is high, although long-term clinical success rates are lacking. Within this review, the risk of secondary rupture is comparable with untreated T1EL at 2% with a median follow-up of 13 months, regardless of the initial success of embolization. In general, no decrease in secondary aneurysm rupture after embolization of T1EL after EVAR is demonstrated, although the results of late embolization are debated.

Electrocoagulation for liver metastases.

BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma are two of the most common malignant tumours to affect the liver. The liver is second only to the lymph nodes as the most common site for metastatic disease. More than half of the people with metastatic liver disease will die from metastatic complications. Electrocoagulation by diathermy is a method used to destroy tumour tissue, using a high-frequency electric current generating high temperatures, applied locally with an electrode (needle, blade, or ball). The objective of this method is to destroy the tumour completely, if possible, in a single session. With the time, electrocoagulation by diathermy has been replaced by other techniques, but the evidence is unclear. OBJECTIVES: To assess the beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, CINAHL, ClinicalTrials.gov, ICTRP, and FDA to October 2020. SELECTION CRITERIA: We considered all randomised trials that assessed beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus comparators, in people with liver metastases, regardless of the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed risk of bias of the included trial using predefined risk of bias domains, and presented the review results incorporating the certainty of the evidence using GRADE. MAIN RESULTS: We included one randomised clinical trial with 306 participants (175 males; 131 females) who had undergone resection of the sigmoid colon, and who had five or more visible and palpable hepatic metastases. The diagnosis was confirmed by histological assessment (biopsy) and by carcinoembryonic antigen (CEA) level. The trial was conducted in Iraq. The age of participants ranged between 38 and 79 years. The participants were randomised to four different study groups. The liver metastases were biopsied and treated (only once) in three of the groups: 75 received electrocoagulation by diathermy alone, 76 received electrocoagulation plus allopurinol, 78 received electrocoagulation plus dimethyl sulphoxide. In the fourth intervention group, 77 participants functioning as controls received a vehicle solution of allopurinol 5 mL 4 x a day by mouth; the metastases were left untouched. The status of the liver and lungs was followed by ultrasound investigations, without the use of a contrast agent. Participants were followed for five years. The analyses are based on per-protocol data only analysing 223 participants. We judged the trial to be at high risk of bias. After excluding 'nonevaluable patients', the groups seemed comparable for baseline characteristics. Mortality due to disease spread at five-year follow-up was 98% in the electrocoagulation group (57/58 evaluable people); 87% in the electrocoagulation plus allopurinol group (46/53 evaluable people); 86% in the electrocoagulation plus dimethyl sulphoxide group (49/57 evaluable people); and 100% in the control group (55/55 evaluable people). We observed no difference in mortality between the electrocoagulation alone group versus the control group (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.94 to 1.03; 113 participants; very low-certainty evidence). We observed lower mortality in the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus the control group (RR 0.87, 95% CI 0.80 to 0.95; 165 participants; low-certainty evidence). We are very uncertain regarding post-operative deaths between the electrocoagulation alone group versus the control group (RR 1.03, 95% CI 0.07 to 16.12; 152 participants; very low-certainty evidence) and between the electrocoagulation combined with allopurinol or dimethyl sulphoxide groups versus the control group (RR 1.00, 95% CI 0.09 to 10.86; 231 participants; very low-certainty evidence). The trial authors did not report data on number of participants with other adverse events and complications, recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life. Data on failure to clear liver metastases were not provided for the control group. There was no information on funding or conflict of interest. We identified no ongoing trials. AUTHORS' CONCLUSIONS: The evidence on the beneficial and harmful effects of electrocoagulation alone or in combination with allopurinol or dimethyl sulphoxide in people with liver metastases is insufficient, as it is based on one randomised clinical trial at low to very low certainty. It is very uncertain if there is a difference in all-cause mortality and post-operative mortality between electrocoagulation alone versus control. It is also uncertain if electrocoagulation in combination with allopurinol or dimethyl sulphoxide may result in a slight reduction of all-cause mortality in comparison with a vehicle solution of allopurinol (control). It is very uncertain if there is a difference in post-operative mortality between the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus control. Data on other adverse events and complications, failure to clear liver metastases or recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life were most lacking or insufficiently reported for analysis. Electrocoagulation by diathermy is no longer used in the described way, and this may explain the lack of further trials.

Common sense and tumor treatment. A case of pilomatrical carcinoma in a 21-year-old patient with surprisingly rapid tumor progression.

Pilomatrical carcinoma is a rare tumor originating from skin appendages, usually occurring between the 5th and 7th decade of life. We present a case of an exceptionally young, 21-year-old patient with surprisingly rapid tumor progression and answer the question, what was the reason for such uncontrolled tumor growth. The main concern is the diagnostic challenge and a peculiar, one week race against time and tumor progression so that the least disfiguring surgery could be done.

Onyx versus coil embolization for the treatment of type II endoleaks.

OBJECTIVE: Little evidence is available supporting the optimal treatment of type II endoleaks associated with aortic sac growth. Previous studies have lacked comparisons between treatment methods and long-term follow-up. The purpose of the present study was to review our center's experience with the treatment of type II endoleaks comparing Onyx (a liquid embolization agent consisting of ethylene vinyl alcohol; Medtronic, Minneapolis, Minn) embolization and coil embolization. METHODS: A retrospective review of prospectively collected data from a vascular surgery database was performed to identify all patients who had undergone embolization of a type II endoleak for aortic sac growth after endovascular aneurysm repair from 2005 to 2018. The Onyx and coil embolization groups were compared using univariate statistics. RESULTS: A total of 58 patients had undergone 77 embolization procedures for type II endoleaks with either Onyx (27 patients; 37 procedures) or coils (31 patients; 40 procedures). The average aneurysm size at embolization was larger in the Onyx group (77.9 ± 15.1 mm) compared with coil embolization (73.4 ± 11.9 mm). The mean follow-up was 57 months for the Onyx group and 74 months for the coil embolization group. Of the 27 patients who had undergone Onyx embolization, 2 (7.4%) had required graft explantation compared with 5 of the 31 patients (16.1%) who had undergone coil embolization (P = .33). The results of the per-patient analysis showed that the coil embolization group had a significantly greater rate of the need for further reintervention compared with the Onyx group (55% vs 19%; P < .01). Clinical success was observed in 13 patients (48%) in the Onyx embolization group compared with 10 patients (32%) in the coil embolization group (P = .04). Two patients in each group had presented with secondary rupture of the aneurysm sac after attempted embolization. CONCLUSIONS: Type II endoleaks associated with sac growth treated with Onyx were less likely to require further reinterventions than were those treated with coil embolization. A trend was found toward a greater need for endovascular aneurysm repair explant after coil embolization. With a high rate of further reintervention and potential for sac rupture, diligent follow-up is required after attempted type II embolization, regardless of the technique used.

Management of distal aneurysm of the superior mesenteric artery by percutaneous ultrasound-guided Onyx injection: A case report.

OBJECTIVES: The aim of this article is to report an alternative approach for the management of a distal aneurysm of superior mesenteric artery using direct percutaneous ultrasound-guided Onyx injection. METHODS: We report a rare case of symptomatic superior mesenteric artery aneurysm. A 78-year-old man presents with pain and pulsating mass in the right umbilical region of the abdomen. The patient was treated by percutaneous ultrasound-guided Onyx injection after several failing transarterial embolization attempts. RESULTS: The procedure was successful without any complication, and the patient wasdischarged to home the day after procedure. Follow-up at 60 months confirmed the complete thrombosis of the aneurysm sac. Ultrasound-guided Onyx injection for distal superior mesenteric artery aneurysm could provide an alternative to transcatheter arterial embolization or open surgery. Anatomical assessment of collaterals and knowledge of abdomen anatomy could play important roles in preventing bowel ischemia and minimizing the risk of procedural complication. CONCLUSION: Ultrasound-guided Onyx injection of superior mesenteric artery aneurysm is a feasible, effective, and cost-saving technique that can be used when endovascular approach is not possible or has failed.

Liquid Nitrogen Storage of Hybridoma Cells.

Hybridoma and myeloma cell lines can be stored by slowly freezing cells in an appropriate solution of nutrients and a cryoprotectant such as glycerol or dimethyl sulfoxide (DMSO). In this protocol, cells are centrifuged at 4°C, resuspended in cold freezing solution (10% DMSO in FBS), and then transferred to an appropriate freezing vial. The vials are slowly frozen to -70°C in Styrofoam racks and then stored in liquid nitrogen (LN2). Cells stored in LN2 will remain viable for years. Once a frozen vial has been removed from LN2 storage, it should be thawed as described, grown out into log phase, and refrozen.

Comparison of passive-dosed and solvent spiked exposures of pro-carcinogen, benzo[a]pyrene, to human lymphoblastoid cell line, MCL-5.

Genotoxicity testing methods in vitro provide a means to predict the DNA damaging effects of chemicals on human cells. This is hindered in the case of hydrophobic test compounds, however, which will partition to in vitro components such as plastic-ware and medium proteins, in preference to the aqueous phase of the exposure medium. This affects the freely available test chemical concentration, and as this freely dissolved aqueous concentration is that bioavailable to cells, it is important to define and maintain this exposure. Passive dosing promises to have an advantage over traditional 'solvent spiking' exposure methods and involves the establishment and maintenance of known chemical concentrations in the in vitro medium, and therefore aqueous phase. Passive dosing was applied in a novel format to expose the MCL-5 human lymphoblastoid cell line to the pro-carcinogen, benzo[a]pyrene (B[a]P) and was compared to solvent (dimethyl sulphoxide) spiked B[a]P exposures over 48 h. Passive dosing induced greater changes, at lower concentrations, to micronucleus frequency, p21 mRNA expression, cell cycle abnormalities, and cell and nuclear morphology. This was attributed to a maintained, definable, free chemical concentration using passive dosing and the presence or absence of solvent, and highlights the influence of exposure choice on genotoxic outcomes.

Step by step optimization of a sperm cryopreservation protocol for spotted wolffish (Anarhichas minor Olafsen, 1772).

Spotted wolffish Anarhichas minor reproduction in captivity is dependent on in vitro fertilization. However, low sperm volume with relatively low cell concentration and the lack of gametes synchronization (simultaneous availability of mature eggs and sperm) represent a challenge for the industry. Thus, the development of protocols for sperm storage are crucial. Four sequential experiments were conducted to optimize a sperm cryopreservation protocol for this species. First, three different cryoprotectants (DMSO; 1, 2-propanediol; and methanol) at different concentrations (5, 10, and 20%) were tested for their toxicity. No significant differences (p > 0.05) were detected between the control samples and cryoprotectants at concentration up to 10% DMSO, 10% propanediol, and 20% methanol in terms of motility parameters. Second, using the highest non-toxic concentrations of cryoprotectants, sperm was cryopreserved in 0.5 mL straws, at different distances from the liquid nitrogen (1.5, 2.5, 4.5, and 7.5 cm) that correspond to different freezing rates. Motility parameters after freezing/thawing decreased for all the cryoprotectants (p < 0.001), however, methanol had the lowest protective capacity while DMSO the highest. Afterwards, two different thawing rates (1 min at 5 °C; and 25 s at 10 °C) were tested using only 10% DMSO and 10% propanediol. Both for the DMSO and propanediol, there were no significant differences (p > 0.05) between the two thawing rates. The best results were obtained using 10% DMSO. Finally, the fertilization capacity of cryopreserved sperm (10% DMSO and thawed at 5 °C for 1 min) was tested against fresh sperm using two spermatozoa:egg ratios and 4 h gametes contact time. The ratio of eggs with normal cell cleavage, abnormal cleavage or undeveloped were counted at the 2-4 cell stage. Cryopreserved sperm showed lower fertilization capacity at a concentration of 5 × 104 spermatozoa:egg compared with fresh sperm (p < 0.001). At a concentration of 5 × 105 spermatozoa:egg, similar fertilizations rates to the fresh sperm were obtained. The presence of the cryoprotectant DMSO during the 4 h contact time did not affect the fertilization rate or the percentage of embryos with abnormal cleavage (p > 0.05). To cryopreserve spotted wolffish sperm it is recommended to use 10% DMSO, loaded in 0.5 mL straws, freeze at a height between 4.5 (-14.05 °C/min) and 7.5 cm (-5.9 °C/min) from liquid nitrogen for 10 min and thaw for 1 min at 5 °C (177.9 °C/min). In vitro fertilization with cryopreserved sperm should be performed with a concentration of at least 5 × 105 spermatozoa per egg.

DMSO supplementation during in vitro maturation of bovine oocytes improves blastocyst rate and quality.

The molecule Dimethyl sulfoxide is widely used as drug solvent. However, its antioxidant property was poorly explored. In this study, we evaluated the effect of DMSO supplementation during oocyte in vitro maturation (IVM) on embryo development and quality. Bovine oocytes were matured with different DMSO concentrations (0, 0.1, 0.25, 0.5, 0.75, 1 and 10% v:v) followed by in vitro fertilization. Subsequently, quality indicators such as gene expression of SOX2, OCT4, CDX2, SOD1, oocyte and embryo redox status and DNA damage were evaluated. Polar body extrusion and blastocyst rates increased with 0.5% v:v DMSO. Moreover, first polar body extrusion and blastocyst rates did not increase with 1%, and 10% of DMSO reduced polar body extrusion and did not produce blastocyst. Optimal concentration of DMSO for the use on the maturation was estimated at around 0.45% v:v. Supplementation with 0.5% v:v DMSO has not affected mRNA abundance of genes key in blastocyst, however 0.75% increased gene expression of OCT4 and SOX2. Oocytes matured with 0.5% v:v DMSO and blastocyst from DMSO group showed reduced lipid peroxidation respect control. Total Glutathione concentrations increased in blastocyst stage in DMSO group. DMSO increased the total cell number of blastocysts but not TUNEL positive cells. In conclusion, our results suggest that low DMSO concentrations used during bovine oocytes in vitro maturation increases the maturation, as well as the blastocyst rate and its quality, without demonstrating deleterious effect on embryo cells.

Outcomes of Onyx® Embolization of Type II Endoleaks After Endovascular Repair of Abdominal Aortic Aneurysms.

BACKGROUND: Type II endoleaks (T2ELs) are common following endovascular repair of abdominal aortic aneurysms (EVAR). Embolization with ethylene vinyl alcohol copolymer (Onyx) may present an effective treatment alternative for T2ELs. Due to limited data supporting its use, we sought to analyze outcomes of Onyx embolization for T2ELs. METHODS: Retrospective review of consecutive patients treated for T2ELs utilizing Onyx embolization agent from 2009-2018. All pre- and post-Onyx intervention CT scans were analyzed for diameter and volume changes with 3D reconstruction software. The primary outcomes were change in maximum AAA diameter and volume. Secondary outcomes included additional interventions, rupture, and mortality. A subset analysis was performed with patients with isolated T2ELs (no other types of endoleaks present). RESULTS: We identified 85 patients (73 males, mean age 77.6 ± 7.6 years) who underwent 112 Onyx interventions. Average time to first Onyx intervention after index EVAR was 3.3 ± 2.6 years and average sac growth was 6.3 ± 6.7 mm. Patients underwent mean 1.3 Onyx interventions using a mean of 4.9 ± 4.7 ml for treatment. Three complications occurred (Onyx extravasation, colon ischemia, and access site hematoma). Mean follow-up was 2.5 ± 2.1 years after initial Onyx treatment. At the most recent follow-up, sac diameter stabilization was seen in 47% and reduction >5 mm was seen in 19%. Sac growth of >5 mm was seen in 34% of patients following the first Onyx intervention. In our subset of isolated T2EL, 72% had sac stabilization or reduction >5 mm. Four patients experienced a ruptured aneurysm (3 had active type 1 endoleaks). Rupture-free survival was 95% at 5 years, and overall survival was 54% at 5 years. Notably, increasing Onyx interventions were not associated with sac stabilization or reduction (OR 0.6, P = 0.1). On multivariable analysis, AAA sac diameter stabilization or reduction was independently associated with BMI >30 kg/m2 (OR 4.2, P = 0.01) and having only 1 Onyx intervention (OR 3.8, P = 0.02). CONCLUSIONS: Onyx for embolization of T2ELs resulted in AAA sac diameter stabilization or reduction in 66% of patients, and up to 72% in isolated T2ELs. Further, increasing Onyx interventions were not associated with either aneurysm sac stabilization or reduction. Given its similar outcomes to other embolization strategies in the literature, Onyx embolization for management of T2ELs needs to be judiciously considered, particularly for T2ELs persisting after an initial Onyx embolization intervention.

Introducing PHIL (precipitating hydrophobic injectable liquid) - a new embolic agent for the body interventional radiologist.

A number of embolic agents are currently available each with their own properties. Precipitating hydrophobic injectable liquid (PHIL) is a new dimethyl sulfoxide (DMSO) compatible embolic agent with a number of specific properties which make it of interest to interventional radiologists. We review the use of PHIL in a non-neurointerventional setting, describing its use in a range of procedures such as trauma embolization, pseudoaneurysm embolization, and tumor embolization. PHIL's properties include a lack of skin discoloration, the possibility of rapid injection and a lack of glare artifact on follow-up computed tomography imaging. These properties make it an important new tool in the armamentarium of the body interventional radiologist.

Effects of methylsulfonylmethane on growth performance, immunity, antioxidant capacity, and meat quality in Pekin ducks.

This study was conducted to determine the effect of methylsulfonylmethane (MSM) on growth performance, immune function, antioxidant capacity, and meat quality in Pekin ducks. A total of 960 female 1-day-old Pekin ducklings (53.3 ± 0.4 g) were randomly allotted to 3 treatments with 8 replicates of 40 birds, based on their body weight (BW). The experiment lasted 6 wks, and dietary treatments included a corn-soybean meal-based diet supplemented with 0%, 0.15%, and 0.3% MSM, that is, CON, MSM1, and MSM2, respectively. Growth performance, serum profiles, and meat quality were determined. During the period of days 22-42, BW gain (BWG) in MSM2 treatment was higher (P < 0.05) and feed-to-gain ratio (F/G) was lower (P < 0.05) than those of CON and MSM1 treatments. BW gain and final BW in MSM2 treatment were increased (P < 0.05) compared with CON and MSM1 treatments during the period of days 1-42. Serum activities of superoxide dismutase and glutathione peroxidase, total antioxidative capacity, and concentrations of interleukin-2 and interleukin-6 were higher (P < 0.05) in MSM2 than in CON treatment. Ducks in the MSM2 treatment group had lower (P < 0.05) serum malondialdehyde, interferon gamma, and tumor necrosis factor-α levels than those in the CON treatment group. The supplementation of MSM increased (P < 0.05) water-holding capacity and redness (a*) and decreased (P < 0.05) values for 2-thiobarbituric acid and drip loss on day 5. Ducks in the MSM2 treatment group had higher (P < 0.05) pH24h than those in the CON treatment group. Taken together, the inclusion of MSM (0.3%) increased final BW and BWG during periods of days 22-42 and days 1-42, reduced feed-to-gain ratio during the period of days 22-42, and resulted in positive effects on immunity, antioxidant capacity, and meat quality.

Transvenous arteriovenous malformation embolization.

Transvenous embolization of arteriovenous malformations has emerged as a safe and effective intervention. In carefully selected patients the transvenous approach has shown efficacy similar to that of conventional transarterial routes. The optimal lesions amenable to the transvenous approach have not been robustly delineated; however, the approach is reserved for small, deep seeded, single venous drainage lesions with poorly amenable arterial vascular supply. In this video we demonstrate a case of transvernous Onyx embolization of a Spetzler-Martin grade 3 (SM3) left hemispheric, ruptured arteriovenous malformation. The patient underwent successful, single session, complete embolization of the arteriovenous malformation through a venous route without further complications or repeat treatment.

Phase I study of KRP-116D, a 50% w/w dimethyl sulfoxide aqueous solution, on the systemic absorption from bladder by intravesical instillation in healthy Japanese subjects.

OBJECTIVE: This was a single-institution, single-dose, single-arm phase 1 study in healthy adult males to evaluate the safety and absorption of dimethyl sulfoxide (DMSO) from the bladder into the body when KRP-116D (a 50% w/w DMSO solution) was intravesically administered and allowed to remain in the bladder for 15 minutes. METHODS: Six healthy adult males were enrolled in this study. KRP-116D (50 mL) was instilled directly into the bladder via a catheter where it was allowed to remain for 15 minutes under lidocaine anesthesia in accordance with the usage of RIMSO-50 (50% w/w DMSO solution) approved in the USA. The residual DMSO solution in the bladder was collected 15 minutes after instillation. The concentrations of DMSO in the plasma and the recovered solution were analyzed by a validated high-performance liquid chromatography (HPLC) method. The concentration in the residual DMSO solution was multiplied by the solution volume and divided by the dosage to calculate the recovery rate of DMSO. RESULTS: Plasma DMSO was detected in one of six subjects, and in the remaining five subjects DMSO was not detected (<19.6 µg/mL). The recovery rate of DMSO from the bladder was 60.7% to 93.7%. The only drug-related adverse event was breath odor (garlic-like breath) observed in four of six subjects (66.7%). CONCLUSION: Absorption of DMSO from the bladder was low (16.3%), and the systemic exposure was limited. Most of the DMSO was recovered from the bladder. KRP-116D 50 mL was well tolerated and safe.